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Sample records for noninvasive photoacoustic imaging

  1. Preclinical Evaluation of Photoacoustic Imaging as a Novel Noninvasive Approach to Detect an Orthopaedic Implant Infection

    NARCIS (Netherlands)

    Wang, Yu; Thompson, John M; Ashbaugh, Alyssa G; Khodakivskyi, Pavlo; Budin, Ghyslain; Sinisi, Riccardo; Heinmiller, Andrew; van Oosten, Marleen; van Dijl, Jan M; van Dam, Gooitzen M; Francis, Kevin P; Bernthal, Nicholas M; Dubikovskaya, Elena A; Miller, Lloyd S

    2016-01-01

    INTRODUCTION: Diagnosing prosthetic joint infection (PJI) poses significant challenges, and current modalities are fraught with low sensitivity and/or potential morbidity. Photoacoustic imaging (PAI) is a novel ultrasound-based modality with potential for diagnosing PJI safely and noninvasively. MAT

  2. Non-invasive imaging of epileptic seizures in vivo using photoacoustic tomography

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Qizhi; Carney, Paul R; Yuan Zhen; Jiang Huabei [J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611 (United States); Liu Zhao [Department of Pediatrics, Division of Pediatric Neurology, University of Florida, Gainesville, FL 32610 (United States); Chen Huanxin; Roper, Steven N [Department of Neurosurgery, University of Florida, Gainesville, FL 32610-0265 (United States)], E-mail: hjiang@bme.ufl.edu

    2008-04-07

    Non-invasive laser-induced photoacoustic tomography (PAT) is an emerging imaging modality that has the potential to image the dynamic function of the brain due to its unique ability of imaging biological tissues with high optical contrast and ultrasound resolution. Here we report the first application of our finite-element-based PAT for imaging of epileptic seizures in an animal model. In vivo photoacoustic images were obtained in rats with focal seizures induced by microinjection of bicuculline, a GABA{sub A} antagonist, into the neocortex. The seizure focus was accurately localized by PAT as confirmed with gold-standard electroencephalogram (EEG). Compared to the existing neuroimaging modalities, PAT not only has the unprecedented advantage of high spatial and temporal resolution in a single imaging modality, but also is portable and low in cost, making it possible to bring brain imaging to the bedside.

  3. Photoacoustic imaging and spectroscopy

    CERN Document Server

    Wang, Lihong

    2009-01-01

    Photoacoustics promises to revolutionize medical imaging and may well make as dramatic a contribution to modern medicine as the discovery of the x-ray itself once did. Combining electromagnetic and ultrasonic waves synergistically, photoacoustics can provide deep speckle-free imaging with high electromagnetic contrast at high ultrasonic resolution and without any health risk. While photoacoustic imaging is probably the fastest growing biomedical imaging technology, this book is the first comprehensive volume in this emerging field covering both the physics and the remarkable noninvasive applic

  4. Detection of Melanoma Metastases in Resected Human Lymph Nodes by Noninvasive Multispectral Photoacoustic Imaging

    Directory of Open Access Journals (Sweden)

    Gerrit Cornelis Langhout

    2014-01-01

    Full Text Available Objective. Sentinel node biopsy in patients with cutaneous melanoma improves staging, provides prognostic information, and leads to an increased survival in node-positive patients. However, frozen section analysis of the sentinel node is not reliable and definitive histopathology evaluation requires days, preventing intraoperative decision-making and immediate therapy. Photoacoustic imaging can evaluate intact lymph nodes, but specificity can be hampered by other absorbers such as hemoglobin. Near infrared multispectral photoacoustic imaging is a new approach that has the potential to selectively detect melanin. The purpose of the present study is to examine the potential of multispectral photoacoustic imaging to identify melanoma metastasis in human lymph nodes. Methods. Three metastatic and nine benign lymph nodes from eight melanoma patients were scanned ex vivo using a Vevo LAZR© multispectral photoacoustic imager and were spectrally analyzed per pixel. The results were compared to histopathology as gold standard. Results. The nodal volume could be scanned within 20 minutes. An unmixing procedure was proposed to identify melanoma metastases with multispectral photoacoustic imaging. Ultrasound overlay enabled anatomical correlation. The penetration depth of the photoacoustic signal was up to 2 cm. Conclusion. Multispectral three-dimensional photoacoustic imaging allowed for selective identification of melanoma metastases in human lymph nodes.

  5. Detection of melanoma metastases in resected human lymph nodes by noninvasive multispectral photoacoustic imaging.

    Science.gov (United States)

    Langhout, Gerrit Cornelis; Grootendorst, Diederik Johannes; Nieweg, Omgo Edo; Wouters, Michel Wilhelmus Jacobus Maria; van der Hage, Jos Alexander; Jose, Jithin; van Boven, Hester; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theodoor Jacques Marie

    2014-01-01

    Objective. Sentinel node biopsy in patients with cutaneous melanoma improves staging, provides prognostic information, and leads to an increased survival in node-positive patients. However, frozen section analysis of the sentinel node is not reliable and definitive histopathology evaluation requires days, preventing intraoperative decision-making and immediate therapy. Photoacoustic imaging can evaluate intact lymph nodes, but specificity can be hampered by other absorbers such as hemoglobin. Near infrared multispectral photoacoustic imaging is a new approach that has the potential to selectively detect melanin. The purpose of the present study is to examine the potential of multispectral photoacoustic imaging to identify melanoma metastasis in human lymph nodes. Methods. Three metastatic and nine benign lymph nodes from eight melanoma patients were scanned ex vivo using a Vevo LAZR(©) multispectral photoacoustic imager and were spectrally analyzed per pixel. The results were compared to histopathology as gold standard. Results. The nodal volume could be scanned within 20 minutes. An unmixing procedure was proposed to identify melanoma metastases with multispectral photoacoustic imaging. Ultrasound overlay enabled anatomical correlation. The penetration depth of the photoacoustic signal was up to 2 cm. Conclusion. Multispectral three-dimensional photoacoustic imaging allowed for selective identification of melanoma metastases in human lymph nodes.

  6. Noninvasive tumor oxygen imaging by photoacoustic lifetime imaging integrated with photodynamic therapy

    Science.gov (United States)

    Shao, Qi; Biel, Merrill A.; Ashkenazi, Shai

    2014-03-01

    Oxygen plays a major role in cancer biology and tumor progression. In PDT, the reduction in efficacy is directly related to lack of oxygen because its molecular mechanism relies on oxygen as an energy mediator. Measuring tumor oxygenation can provide physicians with better diagnosis and optimization of treatment plans. However, clinical tools for directly assessing tissue oxygenation are limited. The gold standard is oxygen needle electrode, which is invasive and measures oxygen level at a single location. We present our work on developing a combined treatment-imaging modality that integrates PDT and photoacoustic oxygen imaging. We propose a system designed for clinical treatments of cancer of the oral cavity. Tissue oxygen imaging is performed by applying Photoacoustic Lifetime Imaging (PALI). This technology relies on photoacoustic probing of oxygen-dependent excitation lifetime of Methylene Blue. The dye is excited by the same wavelength of illumination source for PDT. Once excited, the population of photosensitizer molecules at triplet state has a lifetime depending on the oxygen level. The transition from excited triplet state to ground state can be probe by another laser, which generate photoacoustic signal that is used to map the lifetime. The lifetime map is then converted to pO2 distribution. We expect that PDT efficacy can be improved by applying PALI imaging feedback in real-time to determine, and individually optimize, O2-enriched gas breathing parameters and PDT light-dose during treatment. Successful implementation of PALI in PDT can also drive its application in guiding other cancer treatments that are affected by hypoxia.

  7. Molecular photoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Frogh Jafarian Dehkordi

    2015-04-01

    Full Text Available Background: Hybrid imaging modalities which simultaneously benefit from capabilities of combined modalities provides an opportunity to modify quality of the images which can be obtained by each of the combined imaging systems. One of the imaging modalities, emerged in medical research area as a hybrid of ultrasound imaging and optical imaging, is photoacoustic imaging which apply ultrasound wave generated by tissue, after receiving laser pulse, to produce medical images. Materials and Methods: In this review, using keywords such as photoacoustic, optoacoustic, laser-ultrasound, thermoacoustic at databases such as PubMed and ISI, studies performed in the field of photoacoustic and related findings were evaluated. Results: Photoacoustic imaging, acquiring images with high contrast and desired resolution, provides an opportunity to perform physiologic and anatomic studies. Because this technique does not use ionizing radiation, it is not restricted by the limitation of the ionizing-based imaging systems therefore it can be used noninvasively to make images from cell, vessels, whole body imaging of the animal and distinguish tumor from normal tissue. Conclusion: Photoacoustic imaging is a new method in preclinical researches which can be used in various physiologic and anatomic studies. This method, because of application of non-ionizing radiation, may resolve limitation of radiation based method in diagnostic assessments.

  8. Quantitative, Noninvasive Imaging of DNA Damage in Vivo of Prostate Cancer Therapy by Transurethral Photoacoustic (TUPA) Imaging

    Science.gov (United States)

    2014-10-01

    Photoacoustic (TUPA) Imaging PRINCIPAL INVESTIGATOR: Liangzhong Xiang CONTRACTING ORGANIZATION: The Leland Stanford Junior University Stanford, CA...NUMBER Prostate Cancer Therapy by Transurethral Photoacoustic Imaging 5b. GRANT NUMBER W81XWH-13-1-0481 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S... Photoacoustic (TUPA) Imaging, which utilizing a small catheter into the urethra enabling imaging molecular marker of DNA Damage during prostate radiation

  9. A dual-modality photoacoustic and ultrasound imaging system for noninvasive sentinel lymph node detection: preliminary clinical results

    Science.gov (United States)

    Erpelding, Todd N.; Garcia-Uribe, Alejandro; Krumholz, Arie; Ke, Haixin; Maslov, Konstantin; Appleton, Catherine; Margenthaler, Julie; Wang, Lihong V.

    2014-03-01

    Sentinel lymph node biopsy (SLNB) has emerged as an accurate, less invasive alternative to axillary lymph node dissection, and it has rapidly become the standard of care for patients with clinically node-negative breast cancer. The sentinel lymph node (SLN) hypothesis states that the pathological status of the axilla can be accurately predicted by determining the status of the first (i.e., sentinel) lymph nodes that drain from the primary tumor. Physicians use radio-labeled sulfur colloid and/or methylene blue dye to identify the SLN, which is most likely to contain metastatic cancer cells. However, the surgical procedure causes morbidity and associated expenses. To overcome these limitations, we developed a dual-modality photoacoustic and ultrasound imaging system to noninvasively detect SLNs based on the accumulation of methylene blue dye. Ultimately, we aim to guide percutaneous needle biopsies and provide a minimally invasive method for axillary staging of breast cancer. The system consists of a tunable dye laser pumped by a Nd:YAG laser, a commercial ultrasound imaging system (Philips iU22), and a multichannel data acquisition system which displays co-registered photoacoustic and ultrasound images in real-time. Our clinical results demonstrate that real-time photoacoustic imaging can provide sensitive and specific detection of methylene blue dye in vivo. While preliminary studies have shown that in vivo detection of SLNs by using co-registered photoacoustic and ultrasound imaging is feasible, further investigation is needed to demonstrate robust SLN detection.

  10. Noninvasive Label-Free Detection of Micrometastases in the Lymphatics with Ultrasound-Guided Photoacoustic Imaging

    Science.gov (United States)

    2015-10-01

    Ultrasound and Photoacoustic Imaging of Anatomical and Functional Indicators of Lymph Node Metastasis,” Biomedical Engineering Society Annual Meeting...imaging system that will detect functional changes associated with lymph node metastasis in breast cancer patients. Our efforts in the first year have...imaging can be used to guide dissection . We have also successfully integrated a programmable ultrasound machine (Verasonics Vantage) and tunable pulsed

  11. Wavelength-Modulated Differential Photoacoustic (WM-DPA) imaging: a high dynamic range modality towards noninvasive diagnosis of cancer

    Science.gov (United States)

    Dovlo, Edem; Lashkari, Bahman; Choi, Sung soo Sean; Mandelis, Andreas

    2016-03-01

    This study explores wavelength-modulated differential photo-acoustic (WM-DPA) imaging for non-invasive early cancer detection via sensitive characterization of functional information such as hemoglobin oxygenation (sO2) levels. Well-known benchmarks of tumor formation such as angiogenesis and hypoxia can be addressed this way. While most conventional photo-acoustic imaging has almost entirely employed high-power pulsed lasers, frequency-domain photo-acoustic radar (FD-PAR) has seen significant development as an alternative technique. It employs a continuous wave laser source intensity-modulated and driven by frequency-swept waveforms. WM-DPA imaging utilizes chirp modulated laser beams at two distinct wavelengths for which absorption differences between oxy- and deoxygenated hemoglobin are minimum (isosbestic point, 805 nm) and maximum (680 nm) to simultaneously generate two signals detected using a standard commercial array transducer as well as a single-element transducer that scans the sample. Signal processing is performed using Lab View and Matlab software developed in-house. Minute changes in total hemoglobin concentration (tHb) and oxygenation levels are detectable using this method since background absorption is suppressed due to the out-of-phase modulation of the laser sources while the difference between the two signals is amplified, thus allowing pre-malignant tumors to become identifiable. By regulating the signal amplitude ratio and phase shift the system can be tuned to applications like cancer screening, sO2 quantification and hypoxia monitoring in stroke patients. Experimental results presented demonstrate WM-DPA imaging of sheep blood phantoms in comparison to single-wavelength FD-PAR imaging. Future work includes the functional PA imaging of small animals in vivo.

  12. Non-invasive parenchymal, vascular and metabolic high-frequency ultrasound and photoacoustic rat deep brain imaging.

    Science.gov (United States)

    Giustetto, Pierangela; Filippi, Miriam; Castano, Mauro; Terreno, Enzo

    2015-03-02

    Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive

  13. Molecular photoacoustic imaging

    OpenAIRE

    Frogh Jafarian Dehkordi; Ali Mahmoud Pashazadeh; Majid Assadi

    2015-01-01

    Background: Hybrid imaging modalities which simultaneously benefit from capabilities of combined modalities provides an opportunity to modify quality of the images which can be obtained by each of the combined imaging systems. One of the imaging modalities, emerged in medical research area as a hybrid of ultrasound imaging and optical imaging, is photoacoustic imaging which apply ultrasound wave generated by tissue, after receiving laser pulse, to produce medical images. Materials and Methods...

  14. Molecular photoacoustic imaging of follicular thyroid carcinoma

    DEFF Research Database (Denmark)

    Levi, Jelena; Kothapalli, Sri-Rajashekar; Bohndiek, Sarah

    2013-01-01

    Purpose To evaluate the potential of targeted photoacoustic imaging as a non-invasive method for detection of follicular thyroid carcinoma. Experimental Design We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers...... for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP activatable agent was imaged after intratumoral and intravenous injections...... With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas....

  15. 3D photoacoustic imaging

    Science.gov (United States)

    Carson, Jeffrey J. L.; Roumeliotis, Michael; Chaudhary, Govind; Stodilka, Robert Z.; Anastasio, Mark A.

    2010-06-01

    Our group has concentrated on development of a 3D photoacoustic imaging system for biomedical imaging research. The technology employs a sparse parallel detection scheme and specialized reconstruction software to obtain 3D optical images using a single laser pulse. With the technology we have been able to capture 3D movies of translating point targets and rotating line targets. The current limitation of our 3D photoacoustic imaging approach is its inability ability to reconstruct complex objects in the field of view. This is primarily due to the relatively small number of projections used to reconstruct objects. However, in many photoacoustic imaging situations, only a few objects may be present in the field of view and these objects may have very high contrast compared to background. That is, the objects have sparse properties. Therefore, our work had two objectives: (i) to utilize mathematical tools to evaluate 3D photoacoustic imaging performance, and (ii) to test image reconstruction algorithms that prefer sparseness in the reconstructed images. Our approach was to utilize singular value decomposition techniques to study the imaging operator of the system and evaluate the complexity of objects that could potentially be reconstructed. We also compared the performance of two image reconstruction algorithms (algebraic reconstruction and l1-norm techniques) at reconstructing objects of increasing sparseness. We observed that for a 15-element detection scheme, the number of measureable singular vectors representative of the imaging operator was consistent with the demonstrated ability to reconstruct point and line targets in the field of view. We also observed that the l1-norm reconstruction technique, which is known to prefer sparseness in reconstructed images, was superior to the algebraic reconstruction technique. Based on these findings, we concluded (i) that singular value decomposition of the imaging operator provides valuable insight into the capabilities of

  16. Integrative System of Fast Photoacoustic Imaging

    Science.gov (United States)

    Yi, Tan

    An integrative fast (Photoacoustic) PA imaging system based on multi-element linear ultrasonic transducer array was developed, which integrates laser delivery, photoacoustic excitation and photoacoustic detection into a portable system. It collects PA signals by a multi-element linear transducer array in a reflection mode. The PA images with high spatial resolution and high contrast were obtained. Compared to other existing PA imaging methods, the integrative PA imaging system is characterized by rapidness, convenience and high practicality. The integrative system is mobile and portable, and it is suitable for imaging samples in natural condition with various different shapes. It will provide a novel and effective PA imaging approach for clinic diagnosis of neoplasm and tissue functional imaging in vivo, and has potential to be developed into a practical apparatus used in the early non-invasive detection of breast-cancer.

  17. Quantitative imaging of bilirubin by photoacoustic microscopy

    Science.gov (United States)

    Zhou, Yong; Zhang, Chi; Yao, Da-Kang; Wang, Lihong V.

    2013-03-01

    Noninvasive detection of both bilirubin concentration and its distribution is important for disease diagnosis. Here we implemented photoacoustic microscopy (PAM) to detect bilirubin distribution. We first demonstrate that our PAM system can measure the absorption spectra of bilirubin and blood. We also image bilirubin distributions in tissuemimicking samples, both without and with blood mixed. Our results show that PAM has the potential to quantitatively image bilirubin in vivo for clinical applications.

  18. Photoacoustic tomography: applications for atherosclerosis imaging

    Science.gov (United States)

    Sangha, Gurneet S.; Goergen, Craig J.

    2016-08-01

    Atherosclerosis is a debilitating condition that increases a patient’s risk for intermittent claudication, limb amputation, myocardial infarction, and stroke, thereby causing approximately 50% of deaths in the western world. Current diagnostic imaging techniques, such as ultrasound, digital subtraction angiography, computed tomography angiography, magnetic resonance angiography, and optical imaging remain suboptimal for detecting development of early stage plaques. This is largely due to the lack of compositional information, penetration depth, and/or clinical efficiency of these traditional imaging techniques. Photoacoustic imaging has emerged as a promising modality that could address some of these limitations to improve the diagnosis and characterization of atherosclerosis-related diseases. Photoacoustic imaging uses near-infrared light to induce acoustic waves, which can be used to recreate compositional images of tissue. Recent developments in photoacoustic techniques show its potential in noninvasively characterizing atherosclerotic plaques deeper than traditional optical imaging approaches. In this review, we discuss the significance and development of atherosclerosis, current and novel clinical diagnostic methods, and recent works that highlight the potential of photoacoustic imaging for both experimental and clinical studies of atherosclerosis.

  19. Imaging acute thermal burns by photoacoustic microscopy

    OpenAIRE

    Zhang, Hao F.; Maslov, Konstantin; Stoica, George; Wang, Lihong V.

    2006-01-01

    The clinical significance of a burn depends on the percentage of total body involved and the depth of the burn. Hence a noninvasive method that is able to evaluate burn depth would be of great help in clinical evaluation. To this end, photoacoustic microscopy is used to determine the depth of acute thermal burns by imaging the total hemoglobin concentration in the blood that accumulates along the boundaries of injuries as a result of thermal damage to the vasculature. We induce acute thermal ...

  20. Clinical photoacoustic imaging of cancer

    Science.gov (United States)

    2016-01-01

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented. PMID:27669961

  1. Clinical photoacoustic imaging of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Valluru, Keerthi S.; Willmann, Juergen K. [Dept. of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford (United States)

    2016-08-15

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.

  2. Clinical photoacoustic imaging of cancer

    Directory of Open Access Journals (Sweden)

    Keerthi S. Valluru

    2016-10-01

    Full Text Available Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.

  3. Clinical photoacoustic imaging of cancer.

    Science.gov (United States)

    Valluru, Keerthi S; Willmann, Juergen K

    2016-10-01

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.

  4. Organosilicon phantom for photoacoustic imaging.

    Science.gov (United States)

    Avigo, Cinzia; Di Lascio, Nicole; Armanetti, Paolo; Kusmic, Claudia; Cavigli, Lucia; Ratto, Fulvio; Meucci, Sandro; Masciullo, Cecilia; Cecchini, Marco; Pini, Roberto; Faita, Francesco; Menichetti, Luca

    2015-04-01

    Photoacoustic imaging is an emerging technique. Although commercially available photoacoustic imaging systems currently exist, the technology is still in its infancy. Therefore, the design of stable phantoms is essential to achieve semiquantitative evaluation of the performance of a photoacoustic system and can help optimize the properties of contrast agents. We designed and developed a polydimethylsiloxane (PDMS) phantom with exceptionally fine geometry; the phantom was tested using photoacoustic experiments loaded with the standard indocyanine green dye and compared to an agar phantom pattern through polyethylene glycol-gold nanorods. The linearity of the photoacoustic signal with the nanoparticle number was assessed. The signal-tonoiseratio and contrast were employed as image quality parameters, and enhancements of up to 50 and up to 300%, respectively, were measured with the PDMS phantom with respect to the agar one. A tissue-mimicking (TM)-PDMS was prepared by adding TiO2 and India ink; photoacoustic tests were performed in order to compare the signal generated by the TM-PDMS and the biological tissue. The PDMS phantom can become a particularly promising tool in the field of photoacoustics for the evaluation of the performance of a PA system and as a model of the structure of vascularized soft tissues.

  5. Photoacoustic Imaging in Oncology: Translational Preclinical and Early Clinical Experience.

    Science.gov (United States)

    Valluru, Keerthi S; Wilson, Katheryne E; Willmann, Jürgen K

    2016-08-01

    Photoacoustic imaging has evolved into a clinically translatable platform with the potential to complement existing imaging techniques for the management of cancer, including detection, characterization, prognosis, and treatment monitoring. In photoacoustic imaging, tissue is optically excited to produce ultrasonographic images that represent a spatial map of optical absorption of endogenous constituents such as hemoglobin, fat, melanin, and water or exogenous contrast agents such as dyes and nanoparticles. It can therefore provide functional and molecular information that allows noninvasive soft-tissue characterization. Photoacoustic imaging has matured over the years and is currently being translated into the clinic with various clinical studies underway. In this review, the current state of photoacoustic imaging is presented, including techniques and instrumentation, followed by a discussion of potential clinical applications of this technique for the detection and management of cancer. (©) RSNA, 2016.

  6. Reconstruction Formulas for Photoacoustic Sectional Imaging

    CERN Document Server

    Elbau, Peter; Schulze, Rainer

    2011-01-01

    The literature on reconstruction formulas for photoacoustic tomography (PAT) is vast. The various reconstruction formulas differ by used measurement devices and geometry on which the data are sampled. In standard photoacoustic imaging (PAI), the object under investigation is illuminated uniformly. Recently, sectional photoacoustic imaging techniques, using focusing techniques for initializing and measuring the pressure along a plane, appeared in the literature. This paper surveys existing and provides novel exact reconstruction formulas for sectional photoacoustic imaging.

  7. Acoustic property measurements in a photoacoustic imager

    NARCIS (Netherlands)

    Willemink, Rene; Manohar, Srirang; Slump, Cornelis H.; van der Heijden, Ferdinand; van Leeuwen, Ton; Depeursinge, C.D.

    2007-01-01

    Photoacoustics is a hybrid imaging technique that combines the contrast available to optical imaging with the resolution that is possessed by ultrasound imaging. The technique is based on generating ultrasound from absorbing structures in tissue using pulsed light. In photoacoustic (PA) computerized

  8. Acoustic property measurements in a photoacoustic imager

    NARCIS (Netherlands)

    Willemink, G.H.; Manohar, S.; Slump, C.H.; Heijden, van der F.; Leeuwen, van T.G.; Depeursinge, C.D.

    2007-01-01

    Photoacoustics is a hybrid imaging technique that combines the contrast available to optical imaging with the resolution that is possessed by ultrasound imaging. The technique is based on generating ultrasound from absorbing structures in tissue using pulsed light. In photoacoustic (PA) computerized

  9. Coherent photoacoustic-ultrasound correlation and imaging.

    Science.gov (United States)

    Gao, Fei; Feng, Xiaohua; Zheng, Yuanjin

    2014-09-01

    Both photoacoustics and ultrasound have been researched extensively but separately. In this letter, we report an initial study on the coherent correlation between pulsed photoacoustic wave and pulse-echo ultrasound wave. By illuminating an object with a pulsed laser and external ultrasound sequentially, both the endogenous photoacoustic wave and pulse-echo ultrasound wave are received and coherently correlated, demonstrating enhanced signal-to-noise ratio. Image contrast of the proposed coherent photoacoustic-ultrasound imaging is also demonstrated to be improved significantly on vessel-mimicking phantom, due to fusion of the optical absorption and ultrasound reflection contrasts by coherent correlation of either conventional laser-induced photoacoustic imaging or pulse-echo ultrasound imaging separately.

  10. Photoacoustic-guided focused ultrasound (PAFUSion for identifying reflection artifacts in photoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Mithun Kuniyil Ajith Singh

    2015-12-01

    Full Text Available Influence of acoustic inhomogeneities and resulting reflection artifacts is an important problem in reflection-mode photoacoustic imaging. Absorption of light by skin and superficial optical absorbers will generate photoacoustic transients, which traverse into the tissue and get reflected from structures having different acoustic impedance. These reflected photoacoustic signals, when reconstructed, may appear in the region of interest, which causes difficulties in image interpretation. We propose a novel method to identify and potentially eliminate reflection artifacts in photoacoustic images using photoacoustic-guided focused ultrasound [PAFUSion]. Our method uses focused ultrasound pulses to mimic the wave field produced by photoacoustic sources and thus provides a way to identify reflection artifacts in clinical combined photoacoustic and pulse-echo ultrasound. Simulation and phantom results are presented to demonstrate the validity and impact of this method. Results show that PAFUSion can identify reflections in photoacoustic images and thus envisages potential for improving photoacoustic imaging of acoustically inhomogeneous tissue.

  11. Photoacoustic phasoscopy super-contrast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Fei; Feng, Xiaohua; Zheng, Yuanjin, E-mail: yjzheng@ntu.edu.sg [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2014-05-26

    Phasoscopy is a recently proposed concept correlating electromagnetic (EM) absorption and scattering properties based on energy conservation. Phase information can be extracted from EM absorption induced acoustic wave and scattered EM wave for biological tissue characterization. In this paper, an imaging modality, termed photoacoustic phasoscopy imaging (PAPS), is proposed and verified experimentally based on phasoscopy concept with laser illumination. Both endogenous photoacoustic wave and scattered photons are collected simultaneously to extract the phase information. The PAPS images are then reconstructed on vessel-mimicking phantom and ex vivo porcine tissues to show significantly improved contrast than conventional photoacoustic imaging.

  12. Photoacoustic imaging in both soft and hard biological tissue

    Energy Technology Data Exchange (ETDEWEB)

    Li, T; Dewhurst, R J, E-mail: richard.dewhurst@manchester.ac.u [Photon Science Institute, University of Manchester, Alan Turing Building, Oxford road, Manchester, M13 9PL (United Kingdom)

    2010-03-01

    To date, most Photoacoustic (PA) imaging results have been from soft biotissues. In this study, a PA imaging system with a near-infrared pulsed laser source has been applied to obtain 2-D and 3-D images from both soft tissue and post-mortem dental samples. Imaging results showed that the PA technique has the potential to image human oral disease, such as early-stage teeth decay. For non-invasive photoacoustic imaging, the induced temperature and pressure rises within biotissues should not cause physical damage to the tissue. Several simulations based on the thermoelastic effect have been applied to predict initial temperature and pressure fields within a tooth sample. Predicted initial temperature and pressure rises are below corresponding safety limits.

  13. Near-Infrared Squaraine Dye Encapsulated Micelles for in Vivo Fluorescence and Photoacoustic Bimodal Imaging.

    Science.gov (United States)

    Sreejith, Sivaramapanicker; Joseph, James; Lin, Manjing; Menon, Nishanth Venugopal; Borah, Parijat; Ng, Hao Jun; Loong, Yun Xian; Kang, Yuejun; Yu, Sidney Wing-Kwong; Zhao, Yanli

    2015-06-23

    Combined near-infrared (NIR) fluorescence and photoacoustic imaging techniques present promising capabilities for noninvasive visualization of biological structures. Development of bimodal noninvasive optical imaging approaches by combining NIR fluorescence and photoacoustic tomography demands suitable NIR-active exogenous contrast agents. If the aggregation and photobleaching are prevented, squaraine dyes are ideal candidates for fluorescence and photoacoustic imaging. Herein, we report rational selection, preparation, and micelle encapsulation of an NIR-absorbing squaraine dye (D1) for in vivo fluorescence and photoacoustic bimodal imaging. D1 was encapsulated inside micelles constructed from a biocompatible nonionic surfactant (Pluoronic F-127) to obtain D1-encapsulated micelles (D1(micelle)) in aqueous conditions. The micelle encapsulation retains both the photophysical features and chemical stability of D1. D1(micelle) exhibits high photostability and low cytotoxicity in biological conditions. Unique properties of D1(micelle) in the NIR window of 800-900 nm enable the development of a squaraine-based exogenous contrast agent for fluorescence and photoacoustic bimodal imaging above 820 nm. In vivo imaging using D1(micelle), as demonstrated by fluorescence and photoacoustic tomography experiments in live mice, shows contrast-enhanced deep tissue imaging capability. The usage of D1(micelle) proven by preclinical experiments in rodents reveals its excellent applicability for NIR fluorescence and photoacoustic bimodal imaging.

  14. Combined ultrasonic and photoacoustic system for deep tissue imaging

    Science.gov (United States)

    Kim, Chulhong; Erpelding, Todd N.; Jankovic, Ladislav; Wang, Lihong V.

    2011-03-01

    A combined ultrasonic and photoacoustic imaging system is presented that is capable of deep tissue imaging. The system consists of a modified clinical ultrasound array system and tunable dye laser pumped by a Nd:YAG laser. The system is designed for noninvasive detection of sentinel lymph nodes and guidance of needle biopsies for axillary lymph node staging in breast cancer patients. Using a fraction of the American National Standards Institute (ANSI) safety limit, photoacoustic imaging of methylene blue achieved penetration depths of greater than 5 cm in chicken breast tissue. Photoacoustic imaging sensitivity was measured by varying the concentration of methylene blue dye placed at a depth of 3 cm within surrounding chicken breast tissue. Signal-to-noise ratio, noise equivalent sensitivity, and axial spatial resolution were quantified versus depth based on in vivo and chicken breast tissue experiments. The system has been demonstrated in vivo for detecting sentinel lymph nodes in rats following intradermal injection of methylene blue. These results highlight the clinical potential of photoacoustic image-guided identification and needle biopsy of sentinel lymph nodes for axillary staging in breast cancer patients.

  15. Photoacoustic lifetime imaging of dissolved oxygen using methylene blue

    Science.gov (United States)

    Ashkenazi, Shai

    2010-07-01

    Measuring distribution of dissolved oxygen in biological tissue is of prime interest for cancer diagnosis, prognosis, and therapy optimization. Tumor hypoxia indicates poor prognosis and resistance to radiotherapy. Despite its major clinical significance, no current imaging modality provides direct imaging of tissue oxygen. We present preliminary results demonstrating the potential of photoacoustic lifetime imaging (PALI) for noninvasive, 3-D imaging of tissue oxygen. The technique is based on photoacoustic probing of the excited state lifetime of methylene blue (MB) dye. MB is an FDA-approved water soluble dye with a peak absorption at 660 nm. A double pulse laser system (pump probe) is used to excite the dye and probe its transient absorption by detecting photoacoustic emission. The relaxation rate of MB depends linearly on oxygen concentration. Our measurements show high photoacoustic signal contrast at a probe wavelength of 810 nm, where the excited state absorption is more than four times higher than the ground state absorption. Imaging of a simple phantom is demonstrated. We conclude by discussing possible implementations of the technique in clinical settings and combining it with photodynamic therapy (PDT) for real-time therapy monitoring.

  16. Controlling light in scattering media noninvasively using the photo-acoustic transmission-matrix

    CERN Document Server

    Chaigne, T; Boccara, A C; Fink, M; Bossy, E; Gigan, S

    2013-01-01

    Optical wavefront-shaping has emerged as a powerful tool to manipulate light in strongly scattering media. It enables diffraction-limited focusing and imaging at depths where conventional microscopy techniques fail. However, while most wavefront-shaping works to-date exploited direct access to the target or implanted probes, the challenge is to apply it non-invasively inside complex samples. Ultrasonic-tagging techniques have been recently demonstrated but these require a sequential point-by- point acquisition, a major drawback for imaging applications. Here, we introduce a novel approach to non-invasively measure the optical transmission-matrix inside a scattering medium, exploiting the photo-acoustic effect. Our approach allows for the first time to simultaneously discriminate, localize, and selectively focus light on multiple targets inside a scattering sample, as well as to recover and exploit the scattering medium properties. Combining the powerful approach of the transmission-matrix with the advantages ...

  17. Lifetime-weighted photoacoustic imaging

    Science.gov (United States)

    Forbrich, A.; Shao, P.; Shi, W.; Zemp, Roger J.

    2016-12-01

    Photoacoustic (PA) imaging has been utilized to quantify the lifetime profile of exogenous agents using a series of pump-probe pulses with a varying time delay; however, current techniques typically lead to long acquisition times which are sensitive to motion and cause absorption or photobleaching. We introduce a technique called lifetime-weighted imaging, which uses only three laser pulses to preferentially weight signals from chromophores with long lifetimes (including exogenous contrast agents with triplet excited states such as methylene blue and porphyrins) while nulling chromophores with short picosecond- to nanosecond-scale lifetimes (including hemoglobin). This technique detects the PA signal from a probe pulse either with or without a pump pulse. By subtracting the probe-only signal from the pump-present probe signal, we effectively eliminate signals from chromophores with short lifetimes while preserving PA signals from chromophores with long-lifetimes. We demonstrate the oxygen-dependent lifetime of both methylene blue and porphyrin-lipids and demonstrate both ground-state recovery and excited-state lifetime-weighted imaging. Lifetime-weighted PA imaging may have applications in many molecular imaging application including: photodynamic therapy dosimetry guidance and oxygen sensing.

  18. Acoustic property measurements in a photoacoustic imager

    Science.gov (United States)

    Willemink, René G. H.; Manohar, Srirang; Slump, Cornelis H.; van der Heijden, Ferdi; van Leeuwen, Ton

    2007-07-01

    Photoacoustics is a hybrid imaging technique that combines the contrast available to optical imaging with the resolution that is possessed by ultrasound imaging. The technique is based on generating ultrasound from absorbing structures in tissue using pulsed light. In photoacoustic (PA) computerized tomography (CT) imaging, reconstruction of the optical absorption in a subject, is performed for example by filtered backprojection. The backprojection is performed along circular paths in image space instead of along straight lines as in X-ray CT imaging. To achieve this, the speed-of-sound through the subject is usually assumed constant. An unsuitable speed-of-sound can degrade resolution and contrast. We discuss here a method of actually measuring the speed-of- sound distribution using ultrasound transmission through the subject under photoacoustic investigation. This is achieved in a simple approach that does not require any additional ultrasound transmitter. The method uses a passive element (carbon fiber) that is placed in the imager in the path of the illumination which generates ultrasound by the photoacoustic effect and behaves as an ultrasound source. Measuring the time-of-flight of this ultrasound transient by the same detector used for conventional photoacoustics, allows a speed-of-sound image to be reconstructed. This concept is validated on phantoms.

  19. Photoacoustic imaging: a potential new tool for arthritis

    Science.gov (United States)

    Wang, Xueding

    2012-12-01

    The potential application of photoacoustic imaging (PAI) technology to diagnostic imaging and therapeutic monitoring of inflammatory arthritis has been explored. The feasibility of our bench-top joint imaging systems in delineating soft articular tissue structures in a noninvasive manner was validated first on rat models and then on human peripheral joints. Based on the study on commonly used arthritis rat models, the capability of PAI to differentiate arthritic joints from the normal was also examined. With sufficient imaging depth, PAI can realize tomographic imaging of a human peripheral joint or a small-animal joint as a whole organ noninvasively. By presenting additional optical contrast and tissue functional information such as blood volume and blood oxygen saturation, PAI may provide an opportunity for early diagnosis of inflammatory joint disorders, e.g. rheumatoid arthritis, and for monitoring of therapeutic outcomes with improved sensitivity and accuracy.

  20. Potential for photoacoustic imaging of the neonatal brain

    Science.gov (United States)

    Tavakolian, Pantea; Kosik, Ivan; Chamson-Reig, Astrid; St. Lawrence, Keith; Carson, Jeffrey J. L.

    2013-03-01

    Photoacoustic imaging (PAI) has been proposed as a non-invasive technique for imaging neonatal brain injury. Since PAI combines many of the merits of both optical and ultrasound imaging, images with high contrast, high resolution, and a greater penetration depth can be obtained when compared to more traditional optical methods. However, due to the strong attenuation and reflection of photoacoustic pressure waves at the skull bone, PAI of the brain is much more challenging than traditional methods (e.g. near infrared spectroscopy) for optical interrogation of the neonatal brain. To evaluate the potential limits the skull places on 3D PAI of the neonatal brain, we constructed a neonatal skull phantom (1.4-mm thick) with a mixture of epoxy and titanium dioxide powder that provided acoustic insertion loss (1-5MHz) similar to human infant skull bone. The phantom was molded into a realistic infant skull shape by means of a CNCmachined mold that was based upon a 3D CAD model. To evaluate the effect of the skull bone on PAI, a photoacoustic point source was raster scanned within the phantom brain cavity to capture the imaging operator of the 3D PAI system (128 ultrasound transducers in a hemispherical arrangement) with and without the intervening skull phantom. The resultant imaging operators were compared to determine the effect of the skull layer on the PA signals in terms of amplitude loss and time delay.

  1. Noninvasive Assessment of Early Dental Lesion Using a Dual-Contrast Photoacoustic Tomography

    Science.gov (United States)

    Cheng, Renxiang; Shao, Jiaojiao; Gao, Xiaoxiang; Tao, Chao; Ge, Jiuyu; Liu, Xiaojun

    2016-02-01

    Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro-structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion.

  2. Whole-body and multispectral photoacoustic imaging of adult zebrafish

    Science.gov (United States)

    Huang, Na; Xi, Lei

    2016-10-01

    Zebrafish is a top vertebrate model to study developmental biology and genetics, and it is becoming increasingly popular for studying human diseases due to its high genome similarity to that of humans and the optical transparency in embryonic stages. However, it becomes difficult for pure optical imaging techniques to volumetric visualize the internal organs and structures of wild-type zebrafish in juvenile and adult stages with excellent resolution and penetration depth. Even with the establishment of mutant lines which remain transparent over the life cycle, it is still a challenge for pure optical imaging modalities to image the whole body of adult zebrafish with micro-scale resolution. However, the method called photoacoustic imaging that combines all the advantages of the optical imaging and ultrasonic imaging provides a new way to image the whole body of the zebrafish. In this work, we developed a non-invasive photoacoustic imaging system with optimized near-infrared illumination and cylindrical scanning to image the zebrafish. The lateral and axial resolution yield to 80 μm and 600 μm, respectively. Multispectral strategy with wavelengths from 690 nm to 930 nm was employed to image various organs inside the zebrafish. From the reconstructed images, most major organs and structures inside the body can be precisely imaged. Quantitative and statistical analysis of absorption for organs under illumination with different wavelengths were carried out.

  3. Multifunctional polyelectrolyte microcapsules as a contrast agent for photoacoustic imaging in blood.

    Science.gov (United States)

    Yashchenok, Alexey M; Jose, Jithin; Trochet, Philippe; Sukhorukov, Gleb B; Gorin, Dmitry A

    2016-08-01

    The polyelectrolyte microcapsules that can be accurate either visualized in biological media or in tissue would enhance their further in vivo application both as a carrier of active payloads and as a specific sensor. The immobilization of active species, for instance fluorescent dyes, quantum dots, metal nanoparticles, in polymeric shell enables visualization of capsules by optical imaging techniques in aqueous solution. However, for visualization of capsules in complex media an instrument with high contrast modality requires. Herein, we show for the first time photoacoustic imaging (PAI) of multifunctional microcapsules in water and in blood. The microcapsules exhibit greater photoacoustic intensity compare to microparticles with the same composition of polymeric shell presumably their higher thermal expansion. Photoacoustic intensity form microcapsules dispersed in blood displays an enhancement (2-fold) of signal compare to blood. Photoacoustic imaging of microcapsules might contribute to non-invasive carrier visualization and further their in vivo distribution.

  4. Improving photoacoustic imaging contrast of brachytherapy seeds

    Science.gov (United States)

    Pan, Leo; Baghani, Ali; Rohling, Robert; Abolmaesumi, Purang; Salcudean, Septimiu; Tang, Shuo

    2013-03-01

    Prostate brachytherapy is a form of radiotherapy for treating prostate cancer where the radiation sources are seeds inserted into the prostate. Accurate localization of seeds during prostate brachytherapy is essential to the success of intraoperative treatment planning. The current standard modality used in intraoperative seeds localization is transrectal ultrasound. Transrectal ultrasound, however, suffers in image quality due to several factors such speckle, shadowing, and off-axis seed orientation. Photoacoustic imaging, based on the photoacoustic phenomenon, is an emerging imaging modality. The contrast generating mechanism in photoacoustic imaging is optical absorption that is fundamentally different from conventional B-mode ultrasound which depicts changes in acoustic impedance. A photoacoustic imaging system is developed using a commercial ultrasound system. To improve imaging contrast and depth penetration, absorption enhancing coating is applied to the seeds. In comparison to bare seeds, approximately 18.5 dB increase in signal-to-noise ratio as well as a doubling of imaging depth are achieved. Our results demonstrate that the coating of the seeds can further improve the discernibility of the seeds.

  5. Hybrid photoacoustic - ultrasound transmission parameter imaging in a miniature photoacoustic imager

    NARCIS (Netherlands)

    Manohar, Srirang; Willemink, Rene; van Hespen, Johannes C.G.; van Leeuwen, Ton

    2008-01-01

    Photoacoustic imaging is based on detecting laser pulse induced ultrasound transients from absorbing structures in tissue. The technique combines the advantages of a high optical absorption exhibited by tumors for example with the high resolution possible with ultrasound. A conventional

  6. Rationally encapsulated gold nanorods improving both linear and nonlinear photoacoustic imaging contrast in vivo.

    Science.gov (United States)

    Gao, Fei; Bai, Linyi; Liu, Siyu; Zhang, Ruochong; Zhang, Jingtao; Feng, Xiaohua; Zheng, Yuanjin; Zhao, Yanli

    2017-01-07

    Photoacoustic tomography has emerged as a promising non-invasive imaging technique that integrates the merits of high optical contrast with high ultrasound resolution in deep scattering medium. Unfortunately, the blood background in vivo seriously impedes the quality of imaging due to its comparable optical absorption with contrast agents, especially in conventional linear photoacoustic imaging modality. In this study, we demonstrated that two hybrids consisting of gold nanorods (Au NRs) and zinc tetra(4-pyridyl)porphyrin (ZnTPP) exhibited a synergetic effect in improving optical absorption, conversion efficiency from light to heat, and thermoelastic expansion, leading to a notable enhancement in both linear (four times greater) and nonlinear (more than six times) photoacoustic signals as compared with conventional Au NRs. Subsequently, we carefully investigated the interesting factors that may influence photoacoustic signal amplification, suggesting that the coating of ZnTPP on Au NRs could result in the reduction of gold interfacial thermal conductance with a solvent, so that the heat is more confined within the nanoparticle clusters for a significant enhancement of local temperature. Hence, both the linear and nonlinear photoacoustic signals are enhanced on account of better thermal confinement. The present work not only shows that ZnTPP coated Au NRs could serve as excellent photoacoustic nanoamplifiers, but also brings a perspective for photoacoustic image-guided therapy.

  7. Oscillatory Dynamics and In Vivo Photoacoustic Imaging Performance of Plasmonic Nanoparticle-Coated Microbubbles.

    Science.gov (United States)

    Dixon, Adam J; Hu, Song; Klibanov, Alexander L; Hossack, John A

    2015-07-01

    Microbubbles bearing plasmonic nanoparticles on their surface provide contrast enhancement for both photoacoustic and ultrasound imaging. In this work, the responses of microbubbles with surface-bound gold nanorods-termed AuMBs-to nanosecond pulsed laser excitation are studied using high-speed microscopy, photoacoustic imaging, and numerical modeling. In response to laser fluences below 5 mJ cm(-2) , AuMBs produce weak photoacoustic emissions and exhibit negligible microbubble wall motion. However, in reponse to fluences above 5 mJ cm(-2) , AuMBs undergo dramatically increased thermal expansion and emit nonlinear photoacoustic waves of over 10-fold greater amplitude than would be expected from freely dispersed gold nanorods. Numerical modeling suggests that AuMB photoacoustic responses to low laser fluences result from conductive heat transfer from the surface-bound nanorods to the microbubble gas core, whereas at higher fluences, explosive boiling may occur at the nanorod surface, producing vapor nanobubbles that contribute to rapid AuMB expansion. The results of this study indicate that AuMBs are capable of producing acoustic emissions of significantly higher amplitude than those produced by conventional sources of photoacoustic contrast. In vivo imaging performance of AuMBs in a murine kidney model suggests that AuMBs may be an effective alternative to existing contrast agents for noninvasive photoacoustic and ultrasound imaging applications.

  8. Monkey brain cortex imaging by photoacoustic tomography

    OpenAIRE

    Yang, Xinmai; Wang, Lihong V.

    2008-01-01

    Photoacoustic tomography (PAT) is applied to image the brain cortex of a monkey through the intact scalp and skull ex vivo. The reconstructed PAT image shows the major blood vessels on the monkey brain cortex. For comparison, the brain cortex is imaged without the scalp, and then imaged again without the scalp and skull. Ultrasound attenuation through the skull is also measured at various incidence angles. This study demonstrates that PAT of the brain cortex is capable of surviving the ultras...

  9. Photoacoustic imaging of port-wine stains

    NARCIS (Netherlands)

    Kolkman, Roy G.M.; Mulder, Miranda J.; Glade, Conrad P.; Steenbergen, Wiendelt; Leeuwen, van Ton G.

    2008-01-01

    Background and Objective: To optimize laser therapy of port-wine stains (PWSs), information about the vasculature as well as lesion depth is valuable. In this study we investigated the use of photoacoustic imaging (PAI) to obtain this information. - Study Design/Materials and Methods: PAI uses puls

  10. Photoacoustic elastography.

    Science.gov (United States)

    Hai, Pengfei; Yao, Junjie; Li, Guo; Li, Chiye; Wang, Lihong V

    2016-02-15

    Elastography can noninvasively map the elasticity distribution in biological tissue, which can potentially be used to reveal disease conditions. In this Letter, we have demonstrated photoacoustic elastography by using a linear-array photoacoustic computed tomography system. The feasibility of photoacoustic elastography was first demonstrated by imaging the strains of single-layer and bilayer gelatin phantoms with various stiffness values. The measured strains agreed well with theoretical values, with an average error of less than 5.2%. Next, in vivo photoacoustic elastography was demonstrated on a mouse leg, where the fat and muscle distribution was mapped based on the elasticity contrast. We confirmed the photoacoustic elastography results by ultrasound elastography performed simultaneously.

  11. In vivo photoacoustic lipid imaging in mice using the second near-infrared window

    Science.gov (United States)

    Sangha, Gurneet S.; Phillips, Evan H.; Goergen, Craig J.

    2017-01-01

    Photoacoustic imaging has emerged as a promising technique to improve preclinical and clinical imaging by providing users with label-free optical contrast of tissue. Here, we present a proof-of-concept study for noninvasive in vivo murine lipid imaging using 1210 nm light to investigate differences in periaortic fat among mice of different gender, genotypes, and maturation. Acquired lipid signals suggest that adult male apoE−/− mice have greater periaortic fat accumulation compared to adolescent males, apoE−/− females, and wild-type mice. These results demonstrate the potential of photoacoustic tomography for studying vascular pathophysiology and improving the diagnosis of lipid-based diseases. PMID:28270980

  12. Acoustic and Photoacoustic Molecular Imaging of Cancer

    Science.gov (United States)

    Wilson, Katheryne E.; Wang, Tzu Yin; Willmann, Jürgen K.

    2014-01-01

    Ultrasound and combined optical and ultrasonic (photoacoustic) molecular imaging have shown great promise in the visualization and monitoring of cancer through imaging of vascular and extravascular molecular targets. Contrast-enhanced ultrasound with molecularly targeted microbubbles can detect early-stage cancer through the visualization of targets expressed on the angiogenic vasculature of tumors. Ultrasonic molecular imaging can be extended to the imaging of extravascular targets through use of nanoscale, phase-change droplets and photoacoustic imaging, which provides further molecular information on cancer given by the chemical composition of tissues and by targeted nanoparticles that can interact with extravascular tissues at the receptor level. A new generation of targeted contrast agents goes beyond merely increasing imaging signal at the site of target expression but shows activatable and differential contrast depending on their interactions with the tumor microenvironment. These innovations may further improve our ability to detect and characterize tumors. In this review, recent developments in acoustic and photoacoustic molecular imaging of cancer are discussed. PMID:24187042

  13. Acoustic and photoacoustic molecular imaging of cancer.

    Science.gov (United States)

    Wilson, Katheryne E; Wang, Tzu Yin; Willmann, Jürgen K

    2013-11-01

    Ultrasound and combined optical and ultrasonic (photoacoustic) molecular imaging have shown great promise in the visualization and monitoring of cancer through imaging of vascular and extravascular molecular targets. Contrast-enhanced ultrasound with molecularly targeted microbubbles can detect early-stage cancer through the visualization of targets expressed on the angiogenic vasculature of tumors. Ultrasonic molecular imaging can be extended to the imaging of extravascular targets through use of nanoscale, phase-change droplets and photoacoustic imaging, which provides further molecular information on cancer given by the chemical composition of tissues and by targeted nanoparticles that can interact with extravascular tissues at the receptor level. A new generation of targeted contrast agents goes beyond merely increasing imaging signal at the site of target expression but shows activatable and differential contrast depending on their interactions with the tumor microenvironment. These innovations may further improve our ability to detect and characterize tumors. In this review, recent developments in acoustic and photoacoustic molecular imaging of cancer are discussed.

  14. Phthalocyanine photosensitizers as contrast agents for in vivo photoacoustic tumor imaging.

    Science.gov (United States)

    Attia, Amalina Bte Ebrahim; Balasundaram, Ghayathri; Driessen, Wouter; Ntziachristos, Vasilis; Olivo, Malini

    2015-02-01

    There is a need for contrast agents for non-invasive diagnostic imaging of tumors. Herein, Multispectral Optoacoustic Tomography (MSOT) was employed to evaluate phthalocyanines commonly used in photodynamic therapy as photoacoustic contrast agents. We studied the photoacoustic activity of three water-soluble phthalocyanine photosensitizers: phthalocyanine tetrasulfonic acid (PcS4), Zn(II) phthalocyanine tetrasulfonic acid (ZnPcS4) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) in phantom and in tumor-bearing mice to investigate the biodistribution and fate of the phthalocyanines in the biological tissues. PcS4 was observed to grant good contrast between the different reticuloendothelial organs and accumulate in the tumor within an hour of post-administration. ZnPcS4 and AlPcS4 offered little contrast in photoacoustic signals between the organs. PcS4 is a promising photoacoustic contrast agent and can be exploited as a photodiagnostic agent.

  15. Super-resolution photoacoustic fluctuation imaging with multiple speckle illumination

    CERN Document Server

    Chaigne, Thomas; Allain, Marc; Katz, Ori; Gigan, Sylvain; Sentenac, Anne; Bossy, Emmanuel

    2015-01-01

    In deep tissue photoacoustic imaging, the spatial resolution is inherently limited by acoustic diffraction. Moreover, as the ultrasound attenuation increases with frequency, resolution is often traded-off for penetration depth. Here we report on super-resolution photoacoustic imaging by use of multiple speckle illumination. Specifically, we show that the analysis of second-order fluctuations of the photoacoustic images combined with image deconvolution enables resolving optically absorbing structures beyond the acoustic diffraction limit. A resolution increase of almost a factor 2 is demonstrated experimentally. Our method introduces a new framework that could potentially lead to deep tissue photoacoustic imaging with sub-acoustic resolution.

  16. Photoacoustic imaging of the bladder: a pilot study.

    Science.gov (United States)

    Kamaya, Aya; Vaithilingam, Srikant; Chung, Benjamin I; Oralkan, Omer; Khuri-Yakub, Butrus T

    2013-07-01

    Photoacoustic imaging is a promising new technology that combines tissue optical characteristics with ultrasound transmission and can potentially visualize tumor depth in bladder cancer. We imaged simulated tumors in 5 fresh porcine bladders with conventional pulse-echo sonography and photoacoustic imaging. Isoechoic biomaterials of different optical qualities were used. In all 5 of the bladder specimens, photoacoustic imaging showed injected biomaterials, containing varying degrees of pigment, better than control pulse-echo sonography. Photoacoustic imaging may be complementary to diagnostic information obtained by cystoscopy and urine cytologic analysis and could potentially obviate the need for biopsy in some tumors before definitive treatment.

  17. In vivo photoacoustic imaging of osteosarcoma on animal model

    Energy Technology Data Exchange (ETDEWEB)

    Yu Menglei; Hu Jun [Department of Orthopaedics, The First Affiliated Hospital, Shantou University Medical College, Shantou 515041 (China); Ye Fei, E-mail: hjzkm@yahoo.com.cn [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631 (China)

    2011-01-01

    Osteosarcoma is the commonest primary malignant tumor of bone, and the second highest cause of cancer-related death in the paediatric age group. Although there are several methods for osteosarcoma detection, e.g. X-ray, CT, MRI and bone scan, they are not satisfied methods because they can hardly detect osteosarcoma in early stage. Photoacoustic imaging (PAI) is an emerging hybrid imaging modality that is noninvasive, nonionizing, with high sensitivity, satisfactory imaging depth and good temporal and spatial resolution. In order to explore this new method to detect osteosarcoma, we established SD rat models with osteosarcoma and utilized PAI to reconstruct the osteosarcoma image in vivo. This is the first time detecting osteosarcoma in vivo using PAI, and the results suggested that PAI has potential clinical application for detecting osteosarcoma in the early stage.

  18. Real-time in vivo photoacoustic and ultrasound imaging

    NARCIS (Netherlands)

    Kolkman, Roy G.M.; Brands, Peter J.; Steenbergen, Wiendelt; Leeuwen, van Ton G.

    2008-01-01

    A real-time photoacoustic imaging system is designed and built. This system is based on a commercially available ultrasound imaging system. It can achieve a frame rate of 8 frames/sec. Vasculature in the hand of a human volunteer is imaged, and the resulting photoacoustic image is combined with the

  19. Handheld probe integrating laser diode and ultrasound transducer array for ultrasound/photoacoustic dual modality imaging

    NARCIS (Netherlands)

    Daoudi, K.; Berg, van den P.J.; Rabot, O.; Kohl, A.; Tisserand, S.; Brands, P.J.; Steenbergen, W.

    2014-01-01

    Ultrasound and photoacoustics can be utilized as complementary imaging techniques to improve clinical diagnoses. Photoacoustics provides optical contrast and functional information while ultrasound provides structural and anatomical information. As of yet, photoacoustic imaging uses large and expens

  20. Photoacoustic Detection of Terahertz Radiation for Chemical Sensing and Imaging Applications

    Science.gov (United States)

    2013-03-01

    PHOTOACOUSTIC ... PHOTOACOUSTIC DETECTION OF TERAHERTZ RADIATION FOR CHEMICAL SENSING AND IMAGING THESIS Presented to the Faculty...AFIT-ENG-13-M-08 PHOTOACOUSTIC DETECTION OF TERAHERTZ RADIATION FOR CHEMICAL SENSING AND IMAGING Stjepan Blazevic, B. E. E

  1. Photoacoustic Imaging: Opening New Frontiers in Medical Imaging

    Directory of Open Access Journals (Sweden)

    Keerthi S Valluru

    2011-01-01

    Full Text Available In today′s world, technology is advancing at an exponential rate and medical imaging is no exception. During the last hundred years, the field of medical imaging has seen a tremendous technological growth with the invention of imaging modalities including but not limited to X-ray, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. These tools have led to better diagnosis and improved patient care. However, each of these modalities has its advantages as well as disadvantages and none of them can reveal all the information a physician would like to have. In the last decade, a new diagnostic technology called photoacoustic imaging has evolved which is moving rapidly from the research phase to the clinical trial phase. This article outlines the basics of photoacoustic imaging and describes our hands-on experience in developing a comprehensive photoacoustic imaging system to detect tissue abnormalities.

  2. Modelling, verification, and calibration of a photoacoustics based continuous non-invasive blood glucose monitoring system.

    Science.gov (United States)

    Pai, Praful P; Sanki, Pradyut K; Sarangi, Satyabrata; Banerjee, Swapna

    2015-06-01

    This paper examines the use of photoacoustic spectroscopy (PAS) at an excitation wavelength of 905 nm for making continuous non-invasive blood glucose measurements. The theoretical background of the measurement technique is verified through simulation. An apparatus is fabricated for performing photoacoustic measurements in vitro on glucose solutions and in vivo on human subjects. The amplitude of the photoacoustic signals measured from glucose solutions is observed to increase with the solution concentration, while photoacoustic amplitude obtained from in vivo measurements follows the blood glucose concentration of the subjects, indicating a direct proportionality between the two quantities. A linear calibration method is applied separately on measurements obtained from each individual in order to estimate the blood glucose concentration. The estimated glucose values are compared to reference glucose concentrations measured using a standard glucose meter. A plot of 196 measurement pairs taken over 30 normal subjects on a Clarke error grid gives a point distribution of 82.65% and 17.35% over zones A and B of the grid with a mean absolute relative deviation (MARD) of 11.78% and a mean absolute difference (MAD) of 15.27 mg/dl (0.85 mmol/l). The results obtained are better than or comparable to those obtained using photoacoustic spectroscopy based methods or other non-invasive measurement techniques available. The accuracy levels obtained are also comparable to commercially available continuous glucose monitoring systems.

  3. Monkey brain cortex imaging by photoacoustic tomography.

    Science.gov (United States)

    Yang, Xinmai; Wang, Lihong V

    2008-01-01

    Photoacoustic tomography (PAT) is applied to image the brain cortex of a monkey through the intact scalp and skull ex vivo. The reconstructed PAT image shows the major blood vessels on the monkey brain cortex. For comparison, the brain cortex is imaged without the scalp, and then imaged again without the scalp and skull. Ultrasound attenuation through the skull is also measured at various incidence angles. This study demonstrates that PAT of the brain cortex is capable of surviving the ultrasound signal attenuation and distortion caused by a relatively thick skull.

  4. In vivo carbon nanotube-enhanced non-invasive photoacoustic mapping of the sentinel lymph node

    Science.gov (United States)

    Pramanik, Manojit; Song, Kwang Hyun; Swierczewska, Magdalena; Green, Danielle; Sitharaman, Balaji; Wang, Lihong V.

    2009-06-01

    Sentinel lymph node biopsy (SLNB), a less invasive alternative to axillary lymph node dissection (ALND), has become the standard of care for patients with clinically node-negative breast cancer. In SLNB, lymphatic mapping with radio-labeled sulfur colloid and/or blue dye helps identify the sentinel lymph node (SLN), which is most likely to contain metastatic breast cancer. Even though SLNB, using both methylene blue and radioactive tracers, has a high identification rate, it still relies on an invasive surgical procedure, with associated morbidity. In this study, we have demonstrated a non-invasive single-walled carbon nanotube (SWNT)-enhanced photoacoustic (PA) identification of SLN in a rat model. We have successfully imaged the SLN in vivo by PA imaging (793 nm laser source, 5 MHz ultrasonic detector) with high contrast-to-noise ratio (=89) and good resolution (~500 µm). The SWNTs also show a wideband optical absorption, generating PA signals over an excitation wavelength range of 740-820 nm. Thus, by varying the incident light wavelength to the near infrared region, where biological tissues (hemoglobin, tissue pigments, lipids and water) show low light absorption, the imaging depth is maximized. In the future, functionalization of the SWNTs with targeting groups should allow the molecular imaging of breast cancer.

  5. Multifunctional photosensitizer-based contrast agents for photoacoustic imaging.

    Science.gov (United States)

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U S; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-06-18

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

  6. Multifunctional Photosensitizer-Based Contrast Agents for Photoacoustic Imaging

    Science.gov (United States)

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U. S.; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-06-01

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

  7. Programmable Real-time Clinical Photoacoustic and Ultrasound Imaging System.

    Science.gov (United States)

    Kim, Jeesu; Park, Sara; Jung, Yuhan; Chang, Sunyeob; Park, Jinyong; Zhang, Yumiao; Lovell, Jonathan F; Kim, Chulhong

    2016-10-12

    Photoacoustic imaging has attracted interest for its capacity to capture functional spectral information with high spatial and temporal resolution in biological tissues. Several photoacoustic imaging systems have been commercialized recently, but they are variously limited by non-clinically relevant designs, immobility, single anatomical utility (e.g., breast only), or non-programmable interfaces. Here, we present a real-time clinical photoacoustic and ultrasound imaging system which consists of an FDA-approved clinical ultrasound system integrated with a portable laser. The system is completely programmable, has an intuitive user interface, and can be adapted for different applications by switching handheld imaging probes with various transducer types. The customizable photoacoustic and ultrasound imaging system is intended to meet the diverse needs of medical researchers performing both clinical and preclinical photoacoustic studies.

  8. Quantitative photoacoustic imaging of nanoparticles in cells and tissues.

    Science.gov (United States)

    Cook, Jason R; Frey, Wolfgang; Emelianov, Stanislav

    2013-02-26

    Quantitative visualization of nanoparticles in cells and tissues, while preserving the spatial information, is very challenging. A photoacoustic imaging technique to depict the presence and quantity of nanoparticles is presented. This technique is based on the dependence of the photoacoustic signal on both the nanoparticle quantity and the laser fluence. Quantitative photoacoustic imaging is a robust technique that does not require knowledge of the local fluence, but a relative change in the fluence. This eliminates the need for sophisticated methods or models to determine the energy distribution of light in turbid media. Quantitative photoacoustic imaging was first applied to nanoparticle-loaded cells, and quantitation was validated by inductively coupled plasma mass spectrometry. Quantitative photoacoustic imaging was then extended to xenograft tumor tissue sections, and excellent agreement with traditional histopathological analysis was demonstrated. Our results suggest that quantitative photoacoustic imaging may be used in many applications including the determination of the efficiency and effectiveness of molecular targeting strategies for cell studies and animal models, the quantitative assessment of photoacoustic contrast agent biodistribution, and the validation of in vivo photoacoustic imaging.

  9. Functional photoacoustic tomography for neonatal brain imaging: developments and challenges

    Science.gov (United States)

    Hariri, Ali; Tavakoli, Emytis; Adabi, Saba; Gelovani, Juri; Avanaki, Mohammad R. N.

    2017-03-01

    Transfontanelle ultrasound imaging (TFUSI) is a routine diagnostic brain imaging method in infants who are born prematurely, whose skull bones have not completely fused together and have openings between them, so-called fontanelles. Open fontanelles in neonates provide acoustic windows, allowing the ultrasound beam to freely pass through. TFUSI is used to rule out neurological complications of premature birth including subarachnoid hemorrhage (SAH), intraventricular (IVH), subependimal (SEPH), subdural (SDH) or intracerebral (ICH) hemorrhages, as well as hypoxic brain injuries. TFUSI is widely used in the clinic owing to its low cost, safety, accessibility, and noninvasive nature. Nevertheless, the accuracy of TFUSI is limited. To address several limitations of current clinical imaging modalities, we develop a novel transfontanelle photoacoustic imaging (TFPAI) probe, which, for the first time, should allow for non-invasive structural and functional imaging of the infant brain. In this study, we test the feasibility of TFPAI for detection of experimentally-induced intra ventricular and Intraparenchymal hemorrhage phantoms in a sheep model with a surgically-induced cranial window which will serve as a model of neonatal fontanelle. This study is towards using the probe we develop for bedside monitoring of neonates with various disease conditions and complications affecting brain perfusion and oxygenation, including apnea, asphyxia, as well as for detection of various types of intracranial hemorrhages (SAH, IVH, SEPH, SDH, ICH).

  10. Transurethral light delivery for prostate photoacoustic imaging

    Science.gov (United States)

    Lediju Bell, Muyinatu A.; Guo, Xiaoyu; Song, Danny Y.; Boctor, Emad M.

    2015-03-01

    Photoacoustic imaging has broad clinical potential to enhance prostate cancer detection and treatment, yet it is challenged by the lack of minimally invasive, deeply penetrating light delivery methods that provide sufficient visualization of targets (e.g., tumors, contrast agents, brachytherapy seeds). We constructed a side-firing fiber prototype for transurethral photoacoustic imaging of prostates with a dual-array (linear and curvilinear) transrectal ultrasound probe. A method to calculate the surface area and, thereby, estimate the laser fluence at this fiber tip was derived, validated, applied to various design parameters, and used as an input to three-dimensional Monte Carlo simulations. Brachytherapy seeds implanted in phantom, ex vivo, and in vivo canine prostates at radial distances of 5 to 30 mm from the urethra were imaged with the fiber prototype transmitting 1064 nm wavelength light with 2 to 8 mJ pulse energy. Prebeamformed images were displayed in real time at a rate of 3 to 5 frames per second to guide fiber placement and beamformed offline. A conventional delay-and-sum beamformer provided decreasing seed contrast (23 to 9 dB) with increasing urethra-to-target distance, while the short-lag spatial coherence beamformer provided improved and relatively constant seed contrast (28 to 32 dB) regardless of distance, thus improving multitarget visualization in single and combined curvilinear images acquired with the fiber rotating and the probe fixed. The proposed light delivery and beamforming methods promise to improve key prostate cancer detection and treatment strategies.

  11. High resolution ultrasound and photoacoustic imaging of single cells.

    Science.gov (United States)

    Strohm, Eric M; Moore, Michael J; Kolios, Michael C

    2016-03-01

    High resolution ultrasound and photoacoustic images of stained neutrophils, lymphocytes and monocytes from a blood smear were acquired using a combined acoustic/photoacoustic microscope. Photoacoustic images were created using a pulsed 532 nm laser that was coupled to a single mode fiber to produce output wavelengths from 532 nm to 620 nm via stimulated Raman scattering. The excitation wavelength was selected using optical filters and focused onto the sample using a 20× objective. A 1000 MHz transducer was co-aligned with the laser spot and used for ultrasound and photoacoustic images, enabling micrometer resolution with both modalities. The different cell types could be easily identified due to variations in contrast within the acoustic and photoacoustic images. This technique provides a new way of probing leukocyte structure with potential applications towards detecting cellular abnormalities and diseased cells at the single cell level.

  12. High resolution ultrasound and photoacoustic imaging of single cells

    Directory of Open Access Journals (Sweden)

    Eric M. Strohm

    2016-03-01

    Full Text Available High resolution ultrasound and photoacoustic images of stained neutrophils, lymphocytes and monocytes from a blood smear were acquired using a combined acoustic/photoacoustic microscope. Photoacoustic images were created using a pulsed 532 nm laser that was coupled to a single mode fiber to produce output wavelengths from 532 nm to 620 nm via stimulated Raman scattering. The excitation wavelength was selected using optical filters and focused onto the sample using a 20× objective. A 1000 MHz transducer was co-aligned with the laser spot and used for ultrasound and photoacoustic images, enabling micrometer resolution with both modalities. The different cell types could be easily identified due to variations in contrast within the acoustic and photoacoustic images. This technique provides a new way of probing leukocyte structure with potential applications towards detecting cellular abnormalities and diseased cells at the single cell level.

  13. Single laser pulse generates dual photoacoustic signals for differential contrast photoacoustic imaging.

    Science.gov (United States)

    Gao, Fei; Feng, Xiaohua; Zhang, Ruochong; Liu, Siyu; Ding, Ran; Kishor, Rahul; Zheng, Yuanjin

    2017-04-04

    Photoacoustic sensing and imaging techniques have been studied widely to explore optical absorption contrast based on nanosecond laser illumination. In this paper, we report a long laser pulse induced dual photoacoustic (LDPA) nonlinear effect, which originates from unsatisfied stress and thermal confinements. Being different from conventional short laser pulse illumination, the proposed method utilizes a long square-profile laser pulse to induce dual photoacoustic signals. Without satisfying the stress confinement, the dual photoacoustic signals are generated following the positive and negative edges of the long laser pulse. More interestingly, the first expansion-induced photoacoustic signal exhibits positive waveform due to the initial sharp rising of temperature. On the contrary, the second contraction-induced photoacoustic signal exhibits exactly negative waveform due to the falling of temperature, as well as pulse-width-dependent signal amplitude. An analytical model is derived to describe the generation of the dual photoacoustic pulses, incorporating Gruneisen saturation and thermal diffusion effect, which is experimentally proved. Lastly, an alternate of LDPA technique using quasi-CW laser excitation is also introduced and demonstrated for both super-contrast in vitro and in vivo imaging. Compared with existing nonlinear PA techniques, the proposed LDPA nonlinear effect could enable a much broader range of potential applications.

  14. Development of a neonatal skull phantom for photoacoustic imaging

    Science.gov (United States)

    Tavakolian, Pantea; Todd, Rhiannon; Kosik, Ivan; Chamson-Reig, Astrid; Vasefi, Fartash; St. Lawrence, Keith; Carson, Jeffrey J. L.

    2013-03-01

    Photoacoustic imaging (PAI) has been proposed as a non-invasive technique for the diagnosis and monitoring of disorders in the neonatal brain. However, PAI of the brain through the intact skull is challenging due to reflection and attenuation of photoacoustic pressure waves by the skull bone. The objective of this work was to develop a phantom for testing the potential limits the skull bone places on PAI of the neonatal brain. Our approach was to make acoustic measurements on materials designed to mimic the neonatal skull bone and construct a semi-realistic phantom. A water tank and two ultrasound transducers were utilized to measure the ultrasound insertion loss (100 kHz to 5MHz) of several materials. Cured mixtures of epoxy and titanium dioxide powder provided the closest acoustic match to neonatal skull bone. Specifically, a 1.4-mm thick sample composed of 50% (by mass) titanium dioxide powder and 50% epoxy was closest to neonatal skull bone in terms of acoustic insertion loss. A hemispherical skull phantom (1.4 mm skull thickness) was made by curing the epoxy/titanium dioxide powder mixture inside a mold. The mold was constructed using 3D prototyping techniques and was based on the hairless head of a realistic infant doll. The head was scanned to generate a 3D model, which in turn was used to build a 3D CAD version of the mold. The mold was CNC machined from two solid blocks of Teflon®. The neonatal skull phantom will enable the study of the propagation of photoacoustic pressure waves under a variety of experimental conditions.

  15. Multiplane spectroscopic whole-body photoacoustic imaging of small animals in vivo.

    Science.gov (United States)

    Jeon, Mansik; Kim, Jeesu; Kim, Chulhong

    2016-03-01

    We have successfully developed a multiscale acoustic-resolution photoacoustic tomography system in a single imaging platform. By switching between ultrasound transducers (center frequencies 5 and 40 MHz) and optical condensers, we have photoacoustically imaged microvasculatures of small animals in vivo at different scales. Further, we have extended the field of view of our imaging system to entire bodies of small animals. At different imaging planes, we have noninvasively imaged the major blood vessels (e.g., descending aorta, intercostal vessels, cephalic vessels, brachial vessels, femoral vessels, popliteal vessels, lateral marginal vessels, cranial mesenteric vessels, mammalian vessels, carotid artery, jugular vein, subclavian vessels, iliac vessels, and caudal vessels) as well as intact internal organs (e.g., spleen, liver, kidney, intestine, cecum, and spinal cord) of the animals in vivo. The spectroscopic whole-body photoacoustic imaging clearly reveals the spectral responses of the internal structures. Similar to other existing preclinical whole-body imaging systems, this whole-body photoacoustic tomography can be a useful tool for small-animal research.

  16. Photoacoustic lymphatic imaging with high spatial-temporal resolution

    Science.gov (United States)

    Martel, Catherine; Yao, Junjie; Huang, Chih-Hsien; Zou, Jun; Randolph, Gwendalyn J.; Wang, Lihong V.

    2014-11-01

    Despite its critical function in coordinating the egress of inflammatory and immune cells out of tissues and maintaining fluid balance, the causative role of lymphatic network dysfunction in pathological settings is still understudied. Engineered-animal models and better noninvasive high spatial-temporal resolution imaging techniques in both preclinical and clinical studies will help to improve our understanding of different lymphatic-related pathologic disorders. Our aim was to take advantage of our newly optimized noninvasive wide-field fast-scanning photoacoustic (PA) microcopy system to coordinately image the lymphatic vasculature and its flow dynamics, while maintaining high resolution and detection sensitivity. Here, by combining the optical-resolution PA microscopy with a fast-scanning water-immersible microelectromechanical system scanning mirror, we have imaged the lymph dynamics over a large field-of-view, with high spatial resolution and advanced detection sensitivity. Depending on the application, lymphatic vessels (LV) were spectrally or temporally differentiated from blood vessels. Validation experiments were performed on phantoms and in vivo to identify the LV. Lymphatic flow dynamics in nonpathological and pathological conditions were also visualized. These results indicate that our newly developed PA microscopy is a promising tool for lymphatic-related biological research.

  17. Improving visibility in photoacoustic imaging using dynamic speckle illumination

    CERN Document Server

    Gateau, Jérôme; Katz, Ori; Gigan, Sylvain; Bossy, Emmanuel

    2013-01-01

    In high-frequency photoacoustic imaging with uniform illumination, homogenous photo-absorbing structures may be invisible because of their large size or limited-view issues. Here we show that it is possible to reveal features, which are normally invisible with a photoacoustic system comprised of a 20MHz linear ultrasound array, by exploiting dynamic speckle illumination. We demonstrate imaging of a \\emptyset 5mm absorbing cylinder and a 30 \\mu m black thread arranged in a complex shape. The hidden structures are directly retrieved from photoacoustic images recorded for different random speckle illuminations of the phantoms by assessing the variation in the value of each pixel over the illumination patterns.

  18. PHOTOACOUSTIC IMAGING: AN ORCHESTRA OF LIGHT AND SOUND

    Directory of Open Access Journals (Sweden)

    Namitha

    2013-11-01

    Full Text Available ABSTRACT: Photoacoustic imaging, also called optoacoustic imaging, is a new biomedical i maging modality based on the use of laser - generated ultrasound. It is a hybrid modality, combining the high - contrast and spectroscopy based specificity of optical imaging with the high spatial resolution of ultrasound imaging. In essence, a Photoacoustic i mage can be regarded as an ultrasound image in which the contrast depends not on the mechanical and elastic properties of the tissue, but its optical properties, specifically optical absorption. As a result, it offers greater specificity than conventional sonographic imaging with the ability to detect haemoglobin, lipids, water and other light - absorbing chromophores, but with greater penetration depth than purely optical imaging modalities that rely on ballistic photons. In addition to visualizing anatomica l structures such as the microvasculature, it can also provide functional information such as blood oxygenation, blood flow and temperature. These attributes make photoacoustic imaging applicable in clinical medicine, preclinical research and early detecti on of cancer, cardiovascular disease and abnormalities of microcirculation. Photoacoustic microscopy is a promising tool for imaging both dental decay and dental pulp. Using photoacoustics, near - infrared optical contrast between sound and carious dental ti ssues can be detected relatively easily and accurately at ultrasound resolution and may ultimately allow for continuous monitoring of caries before and during treatment. Photoacousting imaging compares favorably to other imaging modalities with its precise depth information, submillimeter resolution, and nanomolar sensitivity. With further improvement in background reduction, as well as the use of lasers with high - repetition rates, it is likely that Photoacoustic imaging will find wide use in the future in both basic research and clinical care. It is a highly vibrant research field in the

  19. Tissue oxygen monitoring by photoacoustic lifetime imaging (PALI) and its application to image-guided photodynamic therapy (PDT)

    Science.gov (United States)

    Shao, Qi; Morgounova, Ekaterina; Ashkenazi, Shai

    2015-03-01

    The oxygen partial pressure (pO2), which results from the balance between oxygen delivery and its consumption, is a key component of the physiological state of a tissue. Images of oxygen distribution can provide essential information for identifying hypoxic tissue and optimizing cancer treatment. Previously, we have reported a noninvasive in vivo imaging modality based on photoacoustic lifetime. The technique maps the excited triplet state of oxygen-sensitive dye, thus reflects the spatial and temporal distribution of tissue oxygen. We have applied PALI on tumor on small animals to identify hypoxia area. We also showed that PALI is able monitor changes of tissue oxygen, in an acute ischemia and breathing modulation model. Here we present our work on developing a treatment/imaging modality (PDT-PALI) that integrates PDT and a combined ultrasound/photoacoustic imaging system. The system provides real-time feedback of three essential parameters namely: tissue oxygen, light penetration in tumor location, and distribution of photosensitizer. Tissue oxygen imaging is performed by applying PALI, which relies on photoacoustic probing of oxygen-dependent, excitation lifetime of Methylene Blue (MB) photosensitizer. Lifetime information can also be used to generate image showing the distribution of photosensitizer. The level and penetration depth of PDT illumination can be deduced from photoacoustic imaging at the same wavelength. All images will be combined with ultrasound B-mode images for anatomical reference.

  20. Non-invasive assessment of the liver using imaging

    Science.gov (United States)

    Thorling Thompson, Camilla; Wang, Haolu; Liu, Xin; Liang, Xiaowen; Crawford, Darrell H.; Roberts, Michael S.

    2016-12-01

    Chronic liver disease causes 2,000 deaths in Australia per year and early diagnosis is crucial to avoid progression to cirrhosis and end stage liver disease. There is no ideal method to evaluate liver function. Blood tests and liver biopsies provide spot examinations and are unable to track changes in function quickly. Therefore better techniques are needed. Non-invasive imaging has the potential to extract increased information over a large sampling area, continuously tracking dynamic changes in liver function. This project aimed to study the ability of three imaging techniques, multiphoton and fluorescence lifetime imaging microscopy, infrared thermography and photoacoustic imaging, in measuring liver function. Collagen deposition was obvious in multiphoton and fluorescence lifetime imaging in fibrosis and cirrhosis and comparable to conventional histology. Infrared thermography revealed a significantly increased liver temperature in hepatocellular carcinoma. In addition, multiphoton and fluorescence lifetime imaging and photoacoustic imaging could both track uptake and excretion of indocyanine green in rat liver. These results prove that non-invasive imaging can extract crucial information about the liver continuously over time and has the potential to be translated into clinic in the assessment of liver disease.

  1. Regularized Iterative Weighted Filtered Back-Projection for Few-View Data Photoacoustic Imaging

    Science.gov (United States)

    Peng, Dong

    2016-01-01

    Photoacoustic imaging is an emerging noninvasive imaging technique with great potential for a wide range of biomedical imaging applications. However, with few-view data the filtered back-projection method will create streak artifacts. In this study, the regularized iterative weighted filtered back-projection method was applied to our photoacoustic imaging of the optical absorption in phantom from few-view data. This method is based on iterative application of a nonexact 2DFBP. By adding a regularization operation in the iterative loop, the streak artifacts have been reduced to a great extent and the convergence properties of the iterative scheme have been improved. Results of numerical simulations demonstrated that the proposed method was superior to the iterative FBP method in terms of both accuracy and robustness to noise. The quantitative image evaluation studies have shown that the proposed method outperforms conventional iterative methods. PMID:27594896

  2. Quantitative photoacoustic image reconstruction improves accuracy in deep tissue structures.

    Science.gov (United States)

    Mastanduno, Michael A; Gambhir, Sanjiv S

    2016-10-01

    Photoacoustic imaging (PAI) is emerging as a potentially powerful imaging tool with multiple applications. Image reconstruction for PAI has been relatively limited because of limited or no modeling of light delivery to deep tissues. This work demonstrates a numerical approach to quantitative photoacoustic image reconstruction that minimizes depth and spectrally derived artifacts. We present the first time-domain quantitative photoacoustic image reconstruction algorithm that models optical sources through acoustic data to create quantitative images of absorption coefficients. We demonstrate quantitative accuracy of less than 5% error in large 3 cm diameter 2D geometries with multiple targets and within 22% error in the largest size quantitative photoacoustic studies to date (6cm diameter). We extend the algorithm to spectral data, reconstructing 6 varying chromophores to within 17% of the true values. This quantitiative PA tomography method was able to improve considerably on filtered-back projection from the standpoint of image quality, absolute, and relative quantification in all our simulation geometries. We characterize the effects of time step size, initial guess, and source configuration on final accuracy. This work could help to generate accurate quantitative images from both endogenous absorbers and exogenous photoacoustic dyes in both preclinical and clinical work, thereby increasing the information content obtained especially from deep-tissue photoacoustic imaging studies.

  3. Resolution enhancement in nonlinear photoacoustic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goy, Alexandre S.; Fleischer, Jason W. [Department of Electrical Engineering, Princeton University, Olden St., Princeton, New Jersey 08544 (United States)

    2015-11-23

    Nonlinear processes can be exploited to gain access to more information than is possible in the linear regime. Nonlinearity modifies the spectra of the excitation signals through harmonic generation, frequency mixing, and spectral shifting, so that features originally outside the detector range can be detected. Here, we present an experimental study of resolution enhancement for photoacoustic imaging of thin metal layers immersed in water. In this case, there is a threshold in the excitation below which no acoustic signal is detected. Above threshold, the nonlinearity reduces the width of the active area of the excitation beam, resulting in a narrower absorption region and thus improved spatial resolution. This gain is limited only by noise, as the active area of the excitation can be arbitrarily reduced when the fluence becomes closer to the threshold. Here, we demonstrate a two-fold improvement in resolution and quantify the image quality as the excitation fluence goes through threshold.

  4. Three-dimensional photoacoustic endoscopic imaging of the rabbit esophagus.

    Science.gov (United States)

    Yang, Joon Mo; Favazza, Christopher; Yao, Junjie; Chen, Ruimin; Zhou, Qifa; Shung, K Kirk; Wang, Lihong V

    2015-01-01

    We report photoacoustic and ultrasonic endoscopic images of two intact rabbit esophagi. To investigate the esophageal lumen structure and microvasculature, we performed in vivo and ex vivo imaging studies using a 3.8-mm diameter photoacoustic endoscope and correlated the images with histology. Several interesting anatomic structures were newly found in both the in vivo and ex vivo images, which demonstrates the potential clinical utility of this endoscopic imaging modality. In the ex vivo imaging experiment, we acquired high-resolution motion-artifact-free three-dimensional photoacoustic images of the vasculatures distributed in the walls of the esophagi and extending to the neighboring mediastinal regions. Blood vessels with apparent diameters as small as 190 μm were resolved. Moreover, by taking advantage of the dual-mode high-resolution photoacoustic and ultrasound endoscopy, we could better identify and characterize the anatomic structures of the esophageal lumen, such as the mucosal and submucosal layers in the esophageal wall, and an esophageal branch of the thoracic aorta. In this paper, we present the first photoacoustic images showing the vasculature of a vertebrate esophagus and discuss the potential clinical applications and future development of photoacoustic endoscopy.

  5. Three-dimensional photoacoustic endoscopic imaging of the rabbit esophagus.

    Directory of Open Access Journals (Sweden)

    Joon Mo Yang

    Full Text Available We report photoacoustic and ultrasonic endoscopic images of two intact rabbit esophagi. To investigate the esophageal lumen structure and microvasculature, we performed in vivo and ex vivo imaging studies using a 3.8-mm diameter photoacoustic endoscope and correlated the images with histology. Several interesting anatomic structures were newly found in both the in vivo and ex vivo images, which demonstrates the potential clinical utility of this endoscopic imaging modality. In the ex vivo imaging experiment, we acquired high-resolution motion-artifact-free three-dimensional photoacoustic images of the vasculatures distributed in the walls of the esophagi and extending to the neighboring mediastinal regions. Blood vessels with apparent diameters as small as 190 μm were resolved. Moreover, by taking advantage of the dual-mode high-resolution photoacoustic and ultrasound endoscopy, we could better identify and characterize the anatomic structures of the esophageal lumen, such as the mucosal and submucosal layers in the esophageal wall, and an esophageal branch of the thoracic aorta. In this paper, we present the first photoacoustic images showing the vasculature of a vertebrate esophagus and discuss the potential clinical applications and future development of photoacoustic endoscopy.

  6. Photoacoustic imaging using acoustic reflectors to enhance planar arrays.

    Science.gov (United States)

    Ellwood, Robert; Zhang, Edward; Beard, Paul; Cox, Ben

    2014-12-01

    Planar sensor arrays have advantages when used for photoacoustic imaging: they do not require the imaging target to be enclosed, and they are easier to manufacture than curved arrays. However, planar arrays have a limited view of the acoustic field due to their finite size; therefore, not all of the acoustic waves emitted from a photoacoustic source can be recorded. This loss of data results in artifacts in the reconstructed photoacoustic image. A detection array configuration which combines a planar Fabry–Pérot sensor with perpendicular acoustic reflectors is described and experimentally implemented. This retains the detection advantages of the planar sensor while increasing the effective detection aperture in order to improve the reconstructed photoacoustic image.

  7. Water-soluble dopamine-based polymers for photoacoustic imaging

    NARCIS (Netherlands)

    Repenko, T.; Fokong, S.; De Laporte, L.; Go, D.; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria; Kuehne, A.

    2015-01-01

    Here we present a facile synthetic method yielding a linear form of polydopamine via Kumada-coupling, which can be converted into water-soluble melanin, generating high contrast in photoacoustic imaging.

  8. Whole-body multispectral photoacoustic imaging of adult zebrafish

    Science.gov (United States)

    Huang, Na; Guo, Heng; Qi, Weizhi; Zhang, Zhiwei; Rong, Jian; Yuan, Zhen; Ge, Wei; Jiang, Huabei; Xi, Lei

    2016-01-01

    The zebrafish, an ideal vertebrate for studying developmental biology and genetics, is increasingly being used to understand human diseases, due to its high similarity to the human genome and its optical transparency during embryonic stages. Once the zebrafish has fully developed, especially wild-type breeds, conventional optical imaging techniques have difficulty in imaging the internal organs and structures with sufficient resolution and penetration depth. Even with established mutant lines that remain transparent throughout their life cycle, it is still challenging for purely optical imaging modalities to visualize the organs of juvenile and adult zebrafish at a micro-scale spatial resolution. In this work, we developed a non-invasive three-dimensional photoacoustic imaging platform with an optimized illumination pattern and a cylindrical-scanning-based data collection system to image entire zebrafish with micro-scale resolutions of 80 μm and 600 μm in the lateral and axial directions, respectively. In addition, we employed a multispectral strategy that utilized excitation wavelengths from 690 nm to 930 nm to statistically quantify the relative optical absorption spectrum of major organs. PMID:27699119

  9. Technique development for photoacoustic imaging guided interventions

    Science.gov (United States)

    Cheng, Qian; Zhang, Haonan; Yuan, Jie; Feng, Ting; Xu, Guan; Wang, Xueding

    2015-03-01

    Laser-induced thermotherapy (LITT), i.e. tissue destruction induced by a local increase of temperature by means of laser light energy transmission, has been frequently used for minimally invasive treatments of various diseases such as benign thyroid nodules and liver cancer. The emerging photoacoustic (PA) imaging, when integrated with ultrasound (US), could contribute to LITT procedure. PA can enable a good visualization of percutaneous apparatus deep inside tissue and, therefore, can offer accurate guidance of the optical fibers to the target tissue. Our initial experiment demonstrated that, by picking the strong photoacoustic signals generated at the tips of optical fibers as a needle, the trajectory and position of the fibers could be visualized clearly using a commercial available US unit. When working the conventional US Bscan mode, the fibers disappeared when the angle between the fibers and the probe surface was larger than 60 degree; while working on the new PA mode, the fibers could be visualized without any problem even when the angle between the fibers and the probe surface was larger than 75 degree. Moreover, with PA imaging function integrated, the optical fibers positioned into the target tissue, besides delivering optical energy for thermotherapy, can also be used to generate PA signals for on-line evaluation of LITT. Powered by our recently developed PA physio-chemical analysis, PA measurements from the tissue can provide a direct and accurate feedback of the tissue responses to laser ablation, including the changes in not only chemical compositions but also histological microstructures. The initial experiment on the rat liver model has demonstrated the excellent sensitivity of PA imaging to the changes in tissue temperature rise and tissue status (from native to coagulated) when the tissue is treated in vivo with LITT.

  10. Self-assembled nanomaterials for photoacoustic imaging.

    Science.gov (United States)

    Wang, Lei; Yang, Pei-Pei; Zhao, Xiao-Xiao; Wang, Hao

    2016-02-07

    In recent years, extensive endeavors have been paid to construct functional self-assembled nanomaterials for various applications such as catalysis, separation, energy and biomedicines. To date, different strategies have been developed for preparing nanomaterials with diversified structures and functionalities via fine tuning of self-assembled building blocks. In terms of biomedical applications, bioimaging technologies are urgently calling for high-efficient probes/contrast agents for high-performance bioimaging. Photoacoustic (PA) imaging is an emerging whole-body imaging modality offering high spatial resolution, deep penetration and high contrast in vivo. The self-assembled nanomaterials show high stability in vivo, specific tolerance to sterilization and prolonged half-life stability and desirable targeting properties, which is a kind of promising PA contrast agents for biomedical imaging. Herein, we focus on summarizing recent advances in smart self-assembled nanomaterials with NIR absorption as PA contrast agents for biomedical imaging. According to the preparation strategy of the contrast agents, the self-assembled nanomaterials are categorized into two groups, i.e., the ex situ and in situ self-assembled nanomaterials. The driving forces, assembly modes and regulation of PA properties of self-assembled nanomaterials and their applications for long-term imaging, enzyme activity detection and aggregation-induced retention (AIR) effect for diagnosis and therapy are emphasized. Finally, we conclude with an outlook towards future developments of self-assembled nanomaterials for PA imaging.

  11. Multispectral photoacoustic imaging of nerves with a clinical ultrasound system

    Science.gov (United States)

    Mari, Jean Martial; West, Simeon; Beard, Paul C.; Desjardins, Adrien E.

    2014-03-01

    Accurate and efficient identification of nerves is of great importance during many ultrasound-guided clinical procedures, including nerve blocks and prostate biopsies. It can be challenging to visualise nerves with conventional ultrasound imaging, however. One of the challenges is that nerves can have very similar appearances to nearby structures such as tendons. Several recent studies have highlighted the potential of near-infrared optical spectroscopy for differentiating nerves and adjacent tissues, as this modality can be sensitive to optical absorption of lipids that are present in intra- and extra-neural adipose tissue and in the myelin sheaths. These studies were limited to point measurements, however. In this pilot study, a custom photoacoustic system with a clinical ultrasound imaging probe was used to acquire multi-spectral photoacoustic images of nerves and tendons from swine ex vivo, across the wavelength range of 1100 to 1300 nm. Photoacoustic images were processed and overlaid in colour onto co-registered conventional ultrasound images that were acquired with the same imaging probe. A pronounced optical absorption peak centred at 1210 nm was observed in the photoacoustic signals obtained from nerves, and it was absent in those obtained from tendons. This absorption peak, which is consistent with the presence of lipids, provides a novel image contrast mechanism to significantly enhance the visualization of nerves. In particular, image contrast for nerves was up to 5.5 times greater with photoacoustic imaging (0.82 +/- 0.15) than with conventional ultrasound imaging (0.148 +/- 0.002), with a maximum contrast of 0.95 +/- 0.02 obtained in photoacoustic mode. This pilot study demonstrates the potential of photoacoustic imaging to improve clinical outcomes in ultrasound-guided interventions in regional anaesthesia and interventional oncology.

  12. Photoacoustic image reconstruction based on Bayesian compressive sensing algorithm

    Institute of Scientific and Technical Information of China (English)

    Mingjian Sun; Naizhang Feng; Yi Shen; Jiangang Li; Liyong Ma; Zhenghua Wu

    2011-01-01

    The photoacoustic tomography (PAT) method, based on compressive sensing (CS) theory, requires that,for the CS reconstruction, the desired image should have a sparse representation in a known transform domain. However, the sparsity of photoacoustic signals is destroyed because noises always exist. Therefore,the original sparse signal cannot be effectively recovered using the general reconstruction algorithm. In this study, Bayesian compressive sensing (BCS) is employed to obtain highly sparse representations of photoacoustic images based on a set of noisy CS measurements. Results of simulation demonstrate that the BCS-reconstructed image can achieve superior performance than other state-of-the-art CS-reconstruction algorithms.%@@ The photoacoustic tomography (PAT) method, based on compressive sensing (CS) theory, requires that,for the CS reconstruction, the desired image should have a sparse representation in a known transform domain.However, the sparsity of photoacoustic signals is destroyed because noises always exist.Therefore,the original sparse signal cannot be effectively recovered using the general reconstruction algorithm.In this study, Bayesian compressive sensing (BCS) is employed to obtain highly sparse representations of photoacoustic inages based on a set of noisy CS measurements.Results of simulation demonstrate that the BCS-reconstructed image can achieve superior performance than other state-of-the-art CS-reconstruction algorithms.

  13. Pulsed photoacoustic flow imaging with a handheld system.

    Science.gov (United States)

    van den Berg, Pim J; Daoudi, Khalid; Steenbergen, Wiendelt

    2016-02-01

    Flow imaging is an important technique in a range of disease areas, but estimating low flow speeds, especially near the walls of blood vessels, remains challenging. Pulsed photoacoustic flow imaging can be an alternative since there is little signal contamination from background tissue with photoacoustic imaging. We propose flow imaging using a clinical photoacoustic system that is both handheld and portable. The system integrates a linear array with 7.5 MHz central frequency in combination with a high-repetition-rate diode laser to allow high-speed photoacoustic imaging--ideal for this application. This work shows the flow imaging performance of the system in vitro using microparticles. Both two-dimensional (2-D) flow images and quantitative flow velocities from 12 to 75  mm/s were obtained. In a transparent bulk medium, flow estimation showed standard errors of ∼7% the estimated speed; in the presence of tissue-realistic optical scattering, the error increased to 40% due to limited signal-to-noise ratio. In the future, photoacoustic flow imaging can potentially be performed in vivo using fluorophore-filled vesicles or with an improved setup on whole blood.

  14. Aortic atherosclerotic plaque detection using a multiwavelength handheld photoacoustic imaging system

    Science.gov (United States)

    Hirano, Susumu; Namita, Takeshi; Kondo, Kengo; Yamakawa, Makoto; Shiina, Tsuyoshi

    2016-03-01

    Patients affected by diseases caused by arteriosclerosis are increasing. Atherosclerosis, which is becoming an especially difficult health problem, forms plaques from lipids such as cholesterol located in walls of the aorta, cerebral artery, and coronary artery. Because lipid-rich plaques are vulnerable and because arterial rupture causes acute vascular occlusion, early detection is crucially important to prevent plaque growth and rupture. Ultrasound systems can detect plaques but cannot discriminate between vulnerable and equable plaques. To evaluate plaques non-invasively and easily, we developed a handheld photoacoustic imaging device. Its usefulness was verified in phantom experiments with a bovine aorta in which mimic plaque had been embedded. Photoacoustic images taken at wavelengths that produce high light absorbance by lipids show strong photoacoustic signals from the boundary of the mimic plaque. Results confirmed that our system can evaluate plaque properties by analysis with the photoacoustic spectrum. The effects of surrounding tissues and tissue components on plaque evaluation were investigated using a layered phantom. The mimic plaque located under a 6 mm blood layer was also evaluated. Results of these analyses demonstrate the system's usefulness.

  15. In vivo photoacoustic and ultrasonic mapping of rat sentinel lymph nodes with a modified commercial ultrasound imaging system

    Science.gov (United States)

    Erpelding, Todd N.; Kim, Chulhong; Pramanik, Manojit; Guo, Zijian; Dean, John; Jankovic, Ladislav; Maslov, Konstantin; Wang, Lihong V.

    2010-02-01

    Sentinel lymph node biopsy (SLNB) has become the standard method for axillary staging in breast cancer patients, relying on invasive identification of sentinel lymph nodes (SLNs) following injection of blue dye and radioactive tracers. While SLNB achieves a low false negative rate (5-10%), it is an invasive procedure requiring ionizing radiation. As an alternative to SLNB, ultrasound-guided fine needle aspiration biopsy has been tested clinically. However, ultrasound alone is unable to accurately identify which lymph nodes are sentinel. Therefore, a non-ionizing and noninvasive detection method for accurate SLN mapping is needed. In this study, we successfully imaged methylene blue dye accumulation in vivo in rat axillary lymph nodes using a Phillips iU22 ultrasound imaging system adapted for photoacoustic imaging with an Nd:YAG pumped, tunable dye laser. Photoacoustic images of rat SLNs clearly identify methylene blue dye accumulation within minutes following intradermal dye injection and co-registered photoacoustic/ultrasound images illustrate lymph node position relative to surrounding anatomy. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding chicken breast tissue on top of the rat skin surface. These results raise confidence that photoacoustic imaging can be used clinically for accurate, noninvasive SLN mapping.

  16. Photoacoustic Imaging: Semiconducting Oligomer Nanoparticles as an Activatable Photoacoustic Probe with Amplified Brightness for In Vivo Imaging of pH (Adv. Mater. 19/2016).

    Science.gov (United States)

    Miao, Qingqing; Lyu, Yan; Ding, Dan; Pu, Kanyi

    2016-05-01

    Despite the great potential of photoacoustic imaging in the life sciences, the development of smart activatable photoacoustic probes remains elusive. On page 3662, K. Pu and co-workers report a facile nanoengineering approach based on semiconducting oligomer nano-particles to develop ratiometric photoacoustic probes with amplified brightness and enhanced sensing capability for accurate photoacoustic mapping of pH in the tumors of living mice.

  17. Feasibility of using RH795 dye for photoacoustic imaging of neuro-electrical activity

    Science.gov (United States)

    Rasheed, Nashaat; Cressman, John R.; Chitnis, Parag V.

    2017-02-01

    Currently, the most researched noninvasive approach for monitoring neuro-electrical activity involves opticalfluorescence imaging, which suffers from limited imaging penetration. We propose an alternative approach, photoacoustic imaging (PAI) of biopotentials, that relies on transient absorption of light by voltage-sensitive probes and subsequent generation/detection of ultrasound. PAI-based voltage imaging approach can offer the same advantages as the fluorescence imaging in terms of sensitivity and molecular specificity, but it also can significantly extend the imaging depth. In this pilot study we are investigating the feasibility of photoacoustically visualizing biopotentials in rat pheochromocytoma (PC12) cells tagged with voltage-sensitive styrylpyridinium dye, RH795. A change in the intramembrane potential was induced in PC12 cells by adding tetraphenylborate (TPB) to the cell culture. A custommade absorption spectrophotometer was used to verify the change in optical absorption of RH795 dye as a result of TPBinduced electrical fields. Absorption spectra recorded before and after the addition of 100 μM TPB exhibited a wavelength shift of the absorption peak (approximately 510 nm to 550 nm) as well as an increase in the overall magnitude of absorption in the wavelength range of 500-1000 nm. The absorption spectral measurements indicated that RH795 is a good candidate as a voltage-sensitive dye for photoacoustically tracking changes in cell-membrane potential.

  18. Characterizing intraocular tumors with photoacoustic imaging

    Science.gov (United States)

    Xu, Guan; Xue, Yafang; Gursel, Zeynep; Slimani, Naziha; Wang, Xueding; Demirci, Hakan

    2016-03-01

    Intraocular tumors are life-threatening conditions. Long-term mortality from uveal melanoma, which accounts for 80% of primary intraocular tumors, could be as high as 25% depending on the size, ciliary body involvement and extraocular extension. The treatments of intraocular tumors include eye-sparing approaches such as radiotherapy and thermotherapy, and the more aggressive enucleation. The accurate diagnosis of intraocular tumors is thereby critical in the management and follow-up of the patients. The diagnosis of intraocular tumors is usually based on clinical examination with acoustic backscattering based ultrasonography. By analyzing the high frequency fluctuations within the ultrasound (US) signals, microarchitecture information inside the tumor can be characterized. However, US cannot interrogate the histochemical components formulating the microarchitecture. One representative example is the inability of US imaging (and other contemporary imaging modalities as well) in differentiating nevoid and melanoma cells as the two types of cells possesses similar acoustic backscattering properties. Combining optical and US imaging, photoacoustic (PA) measurements encode both the microarchitecture and histochemical component information in biological tissue. This study attempts to characterize ocular tumors by analyzing the high frequency signal components in the multispectral PA images. Ex vivo human eye globes with melanoma and retinoblastoma tumors were scanned using less than 6 mJ per square centimeters laser energy with tunable range of 600-1700 nm. A PA-US parallel imaging system with US probes CL15-7 and L22-14 were used to acquire the high frequency PA signals in real time. Preliminary results show that the proposed method can identify uveal melanoma against retinoblastoma tumors.

  19. Identification and elimination of reflection artifacts in biomedical photoacoustic imaging

    NARCIS (Netherlands)

    Kuniyil Ajith Singh, Mithun

    2016-01-01

    Photoacoustic (PA) or optoacoustic imaging is a hybrid imaging modality that acoustically detects optical absorption contrast via the PA effect, a physical phenomenon that converts absorbed optical energy into acoustic energy. PA imaging is one of the fastest growing fields in biomedical optics, and

  20. Skeletonization algorithm-based blood vessel quantification using in vivo 3D photoacoustic imaging

    Science.gov (United States)

    Meiburger, K. M.; Nam, S. Y.; Chung, E.; Suggs, L. J.; Emelianov, S. Y.; Molinari, F.

    2016-11-01

    Blood vessels are the only system to provide nutrients and oxygen to every part of the body. Many diseases can have significant effects on blood vessel formation, so that the vascular network can be a cue to assess malicious tumor and ischemic tissues. Various imaging techniques can visualize blood vessel structure, but their applications are often constrained by either expensive costs, contrast agents, ionizing radiations, or a combination of the above. Photoacoustic imaging combines the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging, and image contrast depends on optical absorption. This enables the detection of light absorbing chromophores such as hemoglobin with a greater penetration depth compared to purely optical techniques. We present here a skeletonization algorithm for vessel architectural analysis using non-invasive photoacoustic 3D images acquired without the administration of any exogenous contrast agents. 3D photoacoustic images were acquired on rats (n  =  4) in two different time points: before and after a burn surgery. A skeletonization technique based on the application of a vesselness filter and medial axis extraction is proposed to extract the vessel structure from the image data and six vascular parameters (number of vascular trees (NT), vascular density (VD), number of branches (NB), 2D distance metric (DM), inflection count metric (ICM), and sum of angles metric (SOAM)) were calculated from the skeleton. The parameters were compared (1) in locations with and without the burn wound on the same day and (2) in the same anatomic location before (control) and after the burn surgery. Four out of the six descriptors were statistically different (VD, NB, DM, ICM, p  approach to obtain quantitative characterization of the vascular network from 3D photoacoustic images without any exogenous contrast agent which can assess microenvironmental changes related to

  1. Super-resolution photoacoustic imaging of single gold nanoparticles

    Science.gov (United States)

    Lee, Seunghyun; Kwon, Owoong; Jeon, Mansik; Song, Jaejung; Jo, Minguk; Kim, Sungjee; Son, Junwoo; Kim, Yunseok; Kim, Chulhong

    2016-03-01

    Photoacoustic imaging (PAI) is an emerging hybrid imaging modality that can provide a strong optical absorption contrast using the photoacoustic (PA) effect, and breaks through the fundamental imaging depth limit of existing optical microscopy such as optical coherence tomography (OCT), confocal or two-photon microscopy. In PAI, a short-pulsed laser is illuminated to the tissue, and the PA waves are generated by thermoelastic expansion. Despite the high lateral resolution of optical-resolution photoacoustic microscopy (OR-PAM) thanks to the tight optical focus, the lateral resolution of OR-PAM is limited to the optical diffraction limit, which is approximately a half of the excitation wavelength. Here, we demonstrate a new super-resolution photoacoustic microscopy (SR-PAM) system by breaking the optical diffraction limit. The conventional microscopes with nanoscale resolutions such as a scanning electron microscope (SEM) and transmission electron microscope (TEM) are typically used to image the structures of nanomaterials, but these systems should work in a high vacuum environment and cannot provide the optical properties of the materials. Our newly developed SR-PAM system provides the optical properties with a nanoscale resolution in a normal atmosphere. We have photoacoustically imaged single gold nanoparticles with an average size of 80 nm in diameter and shown their PA expansion properties individually. The lateral resolution of this system was approximately 20 nm. Therefore, this tool will provide an unprecedented optical absorption property with an accurate nanoscale resolution and greatly impact on materials science and nanotechnology field.

  2. Imaging thermal fields in nonlinear photoacoustics

    NARCIS (Netherlands)

    Oshurko, V. B.

    2006-01-01

    It is demonstrated that the shape of a photoacoustic response in systems with a temperature-dependent thermal expansion coefficient (thermononlinear case) represents a wavelet transform of the spatial distribution of heat sources.

  3. Photoacoustic imaging of hidden dental caries by using a fiber-based probing system

    Science.gov (United States)

    Koyama, Takuya; Kakino, Satoko; Matsuura, Yuji

    2017-04-01

    Photoacoustic method to detect hidden dental caries is proposed. It was found that high frequency ultrasonic waves are generated from hidden carious part when radiating laser light to occlusal surface of model tooth. By making a map of intensity of these high frequency components, photoacoustic images of hidden caries were successfully obtained. A photoacoustic imaging system using a bundle of hollow optical fiber was fabricated for using clinical application, and clear photoacoustic image of hidden caries was also obtained by this system.

  4. Detecting inflammation and fibrosis in bowel wall with photoacoustic imaging in a Crohn's disease animal model

    Science.gov (United States)

    Xu, Guan; Johnson, Laura A.; Hu, Jack; Dillman, Jonathan R.; Higgins, Peter D. R.; Wang, Xueding

    2015-03-01

    Crohn's disease (CD) is an autoimmune disease affecting 700,000 people in the United States. This condition may cause obstructing intestinal narrowings (strictures) due to inflammation, fibrosis (deposition of collagen), or a combination of both. Utilizing the unique strong optical absorption of hemoglobin at 532 nm and collagen at 1370 nm, this study investigated the feasibility of non-invasively characterizing intestinal strictures using photoacoustic imaging (PAI). Three normal controls, ten pure inflammation and 9 inflammation plus fibrosis rat bowel wall samples were imaged. Statistical analysis of the PA measurements has shown the capability of discriminating the purely inflammatory from mixed inflammatory and fibrotic strictures.

  5. Photoacoustic imaging taking into account thermodynamic attenuation

    Science.gov (United States)

    Acosta, Sebastián; Montalto, Carlos

    2016-11-01

    In this paper we consider a mathematical model for photoacoustic imaging which takes into account attenuation due to thermodynamic dissipation. The propagation of acoustic (compressional) waves is governed by a scalar wave equation coupled to the heat equation for the excess temperature. We seek to recover the initial acoustic profile from knowledge of acoustic measurements at the boundary. We recognize that this inverse problem is a special case of boundary observability for a thermoelastic system. This leads to the use of control/observability tools to prove the unique and stable recovery of the initial acoustic profile in the weak thermoelastic coupling regime. This approach is constructive, yielding a solvable equation for the unknown acoustic profile. Moreover, the solution to this reconstruction equation can be approximated numerically using the conjugate gradient method. If certain geometrical conditions for the wave speed are satisfied, this approach is well-suited for variable media and for measurements on a subset of the boundary. We also present a numerical implementation of the proposed reconstruction algorithm.

  6. In vivo demonstration of reflection artifact reduction in photoacoustic imaging using synthetic aperture photoacoustic-guided focused ultrasound (PAFUSion)

    NARCIS (Netherlands)

    Kuniyil Ajith Singh, M.; Jaeger, M.; Frenz, M.; Steenbergen, W.

    2016-01-01

    Reflection artifacts caused by acoustic inhomogeneities are a critical problem in epi-mode biomedical photoacoustic imaging. High light fluence beneath the probe results in photoacoustic transients, which propagate into the tissue and reflect back from echogenic structures. These reflection artifact

  7. Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early

    Science.gov (United States)

    2013-07-01

    10-1-0422 TITLE: Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early PRINCIPAL...DATES COVERED 1 July 2010 - 30 June 2013 4. TITLE AND SUBTITLE Targeting Cell Surface Proteins in Molecular 5a. CONTRACT NUMBER Photoacoustic ...upon request). Aim 2) Prioritize ovarian cancer-associated surface proteins for their utility as molecular photoacoustic imaging targets and

  8. Ratiometric Photoacoustic Molecular Imaging for Methylmercury Detection in Living Subjects.

    Science.gov (United States)

    Liu, Yi; Wang, Sheng; Ma, Ying; Lin, Jing; Wang, Hai-Yan; Gu, Yueqing; Chen, Xiaoyuan; Huang, Peng

    2017-02-22

    Photoacoustic molecular imaging is an emerging and promising diagnostic tool for heavy metal ions detection. Methylmercury (MeHg(+) ) is one of the most potent neurotoxins, which damages the brain and nervous system of human beings through fish consumption. The development of a selective and sensitive method for MeHg(+) detection is highly desirable. In this Communication, we develope a chemoselective photoacoustic sensor (LP-hCy7) composed of the liposome (LP) and MeHg(+) -responsive near-infrared (NIR) cyanine dye (hCy7) for MeHg(+) detection within living subjects, such as zebrafish and mouse. The as-prepared LP-hCy7 nanoprobe displays unique dual-shift NIR absorbance peaks and produces a normalized turn-on response after the reaction of MeHg(+) and hCy7 through a mercury-promoted cyclization reaction. The absorbance intensities of LP-hCy7 nanoprobe at 690 and 860 nm are decreased and increased, respectively. The ratiometric photoacoustic signal (PA860/PA690) is noticeably increased in the presence of MeHg(+) . These findings not only provide a ratiometric photoacoustic molecular imaging probe for the detection of metal ions in vivo, but also provides a tool for spectroscopic photoacoustic molecular imaging.

  9. Contrast Agents for Photoacoustic and Thermoacoustic Imaging: A Review

    Directory of Open Access Journals (Sweden)

    Dan Wu

    2014-12-01

    Full Text Available Photoacoustic imaging (PAI and thermoacoustic imaging (TAI are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.

  10. Contrast agents for photoacoustic and thermoacoustic imaging: a review.

    Science.gov (United States)

    Wu, Dan; Huang, Lin; Jiang, Max S; Jiang, Huabei

    2014-12-18

    Photoacoustic imaging (PAI) and thermoacoustic imaging (TAI) are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.

  11. Noninvasive imaging technologies for cutaneous wound assessment: A review.

    Science.gov (United States)

    Paul, Dereck W; Ghassemi, Pejhman; Ramella-Roman, Jessica C; Prindeze, Nicholas J; Moffatt, Lauren T; Alkhalil, Abdulnaser; Shupp, Jeffrey W

    2015-01-01

    The ability to phenotype wounds for the purposes of assessing severity, healing potential and treatment is an important function of evidence-based medicine. A variety of optical technologies are currently in development for noninvasive wound assessment. To varying extents, these optical technologies have the potential to supplement traditional clinical wound evaluation and research, by providing detailed information regarding skin components imperceptible to visual inspection. These assessments are achieved through quantitative optical analysis of tissue characteristics including blood flow, collagen remodeling, hemoglobin content, inflammation, temperature, vascular structure, and water content. Technologies that have, to this date, been applied to wound assessment include: near infrared imaging, thermal imaging, optical coherence tomography, orthogonal polarization spectral imaging, fluorescence imaging, laser Doppler imaging, microscopy, spatial frequency domain imaging, photoacoustic detection, and spectral/hyperspectral imaging. We present a review of the technologies in use or development for these purposes with three aims: (1) providing basic explanations of imaging technology concepts, (2) reviewing the wound imaging literature, and (3) providing insight into areas for further application and exploration. Noninvasive imaging is a promising advancement in wound assessment and all technologies require further validation.

  12. Toward the detection of intraplaque hemorrhage in carotid artery lesions using photoacoustic imaging

    Science.gov (United States)

    Arabul, Mustafa Umit; Heres, Maarten; Rutten, Marcel C. M.; van Sambeek, Marc R.; van de Vosse, Frans N.; Lopata, Richard G. P.

    2017-04-01

    Photoacoustic imaging (PAI) may have the ability to reveal the composition and the anatomical structure of carotid plaques, which determines its mechanical properties and vulnerability. We used PAI and plane wave ultrasound (PUS) imaging to obtain three-dimensional (3-D) images of endarterectomy samples ex vivo and compared the results with histology to investigate the potential of PAI-based identification of intraplaque hemorrhage. Seven carotid plaque samples were obtained from patients undergoing carotid endarterectomy and imaged with a fully integrated hand-held photoacoustic (PA) probe, consisting of a pulsed diode laser (tpulse=130 ns, Epulse=1 mJ, λ=808 nm) and a linear array transducer (fc=7.5 MHz). The samples were rotated 360 deg with 10 deg steps, and data were spatially compounded to obtain complete 3-D images of the plaques. Areas of high absorption in the 3-D datasets were identified and compared to histological data of the plaques. Data in six out of seven endarterectomy samples revealed the presence of intraplaque hemorrhages that were not visible in the PUS images. Due to the noninvasive nature of PAI, this ex vivo study may elucidate preclinical studies toward the in vivo, noninvasive, vulnerability assessment of the atherosclerotic carotid plaque.

  13. Microwave-heating-coupled photoacoustic radar for tissue diagnostic imaging

    Science.gov (United States)

    Wang, Wei; Mandelis, Andreas

    2016-06-01

    An investigation of microwave (MW) heating effects on biotissue for enhancing photoacoustic radar (PAR) signals was conducted. Localized tissue heating generated by MWs was used to improve PAR imaging depth and signal-to-noise ratio (SNR). Elevated temperatures were measured with thermocouples in ex vivo bovine muscle. The measured temperature rise on the heated spot surface by MWs was in agreement with theoretical predictions. The study showed localized MW heating can increase the photoacoustic imaging depth by 11%, and the SNR by 5% in ex vivo bovine muscle.

  14. In vivo demonstration of reflection artifact reduction in photoacoustic imaging using synthetic aperture photoacoustic-guided focused ultrasound (PAFUSion).

    Science.gov (United States)

    Singh, Mithun Kuniyil Ajith; Jaeger, Michael; Frenz, Martin; Steenbergen, Wiendelt

    2016-08-01

    Reflection artifacts caused by acoustic inhomogeneities are a critical problem in epi-mode biomedical photoacoustic imaging. High light fluence beneath the probe results in photoacoustic transients, which propagate into the tissue and reflect back from echogenic structures. These reflection artifacts cause problems in image interpretation and significantly impact the contrast and imaging depth. We recently proposed a method called PAFUSion (Photoacoustic-guided focused ultrasound) to identify such reflection artifacts in photoacoustic imaging. In its initial version, PAFUSion mimics the inward-travelling wavefield from small blood vessel-like PA sources by applying ultrasound pulses focused towards these sources, and thus provides a way to identify the resulting reflection artifacts. In this work, we demonstrate reduction of reflection artifacts in phantoms and in vivo measurements on human volunteers. In view of the spatially distributed PA sources that are found in clinical applications, we implemented an improved version of PAFUSion where photoacoustic signals are backpropagated to imitate the inward travelling wavefield and thus the reflection artifacts. The backpropagation is performed in a synthetic way based on the pulse-echo acquisitions after transmission on each single element of the transducer array. The results provide a direct confirmation that reflection artifacts are prominent in clinical epi-photoacoustic imaging, and that PAFUSion can strongly reduce these artifacts to improve deep-tissue photoacoustic imaging.

  15. High-efficiency FRET-enhanced photoacoustic probes for in vivo tumor imaging

    Science.gov (United States)

    Qin, Huan; Liu, Liming

    2017-01-01

    Photoacoustic imaging can provide high-resolution and high-contrast image under unprecedented depth compared with pure optical imaging techniques by making use of laser-induced ultrasound waves. Although a series of absorption-enhanced optical contrast agents for photoacoustic imaging were developed, the probe with fully conversion from absorbed light energy to acoustic energy has not been achieved so far. Here we develop a high-efficiency photoacoustic probes with fluorescence resonance energy transfer (FRET) effect for enhancement of nonradiative energy. Graphene oxide (GO) binding optical dyes (GO-dyes) were achieved to show highly fluorescence quenching and violently increased photoacoustic signal intensity. GO-dyes were constructed and testified for multi-spectral photoacoustic imaging. As a representative probe, GO-Cy7 nanoparticles were used to validate the feasibility of photoacoustic tumor molecular imaging in vivo. Our work demonstrated a new approach to construct high-efficiency FRET-enhanced multi-spectrum probes for photoacoustic molecular imaging.

  16. In vivo photoacoustic imaging of nude mice vasculature using a photoacoustic imaging system based on a commercial ultrasound scanner

    Science.gov (United States)

    Jankovic, Ladislav; Shahzad, Khalid; Wang, Yao; Burcher, Michael; Scholle, Frank-Detlef; Hauff, Peter; Mofina, Sabine; Skobe, Mihaela

    2008-02-01

    In-vivo photoacoustic/ultrasound (PA/US) imaging of nude mice was investigated using a photoacoustic imaging system based on a commercial ultrasound scanner HDI-5000. Raw per-channel data was captured and beamformed to generate each individual photoacoustic image with a single laser shot. An ultra-broadband CL15-7 linear array with a center frequency of 8 MHz, combined with a Schott Glass fiber bundle, was used as a compact high resolution imaging probe, with lateral and axial PA resolutions of about 300µm and 200µm, respectively. The imaging system worked in a dual PA-US mode, with the ultrasound outlining the tissue structure and the photoacoustic image showing the blood vessels. PA signals were generated by exposing mice to ultra-short optical pulses from a Nd:YAG-pumped OPO laser operating in a wavelength range of 700-950nm. The corresponding ultrasound images were generated in the regular B-mode with standard delay-and-sum beamforming algorithm. The system resolution was sufficiently high to identify and clearly distinguish the dorsal artery and the two lateral veins in the mouse tail. Both the saphena artery and the ischiatic vein on the cross-section of the mouse leg were clearly outlined in the PA images and correctly overlaid on the ultrasound image of the tissue structure. Similarly, cross-section PA images of the mouse abdomen revealed mesenteric vasculatures located below the abdominal wall. Finally, a successful PA imaging of the mouse thoracic cavity unveiled the ascending and descending aorta. These initial results demonstrate a great potential for a dual photoacoustic/ultrasound imaging modality implemented on a commercial ultrasound imaging scanner.

  17. Noninvasive photoacoustic and fluorescence sentinel lymph node identification using dye-loaded perfluorocarbon nanoparticles.

    Science.gov (United States)

    Akers, Walter J; Kim, Chulhong; Berezin, Mikhail; Guo, Kevin; Fuhrhop, Ralph; Lanza, Gregory M; Fischer, Georg M; Daltrozzo, Ewald; Zumbusch, Andreas; Cai, Xin; Wang, Lihong V; Achilefu, Samuel

    2011-01-25

    The contrast mechanisms used for photoacoustic tomography (PAT) and fluorescence imaging differ in subtle, but significant, ways. The design of contrast agents for each or both modalities requires an understanding of the spectral characteristics as well as intra- and intermolecular interactions that occur during formulation. We found that fluorescence quenching that occurs in the formulation of near-infrared (NIR) fluorescent dyes in nanoparticles results in enhanced contrast for PAT. The ability of the new PAT method to utilize strongly absorbing chromophores for signal generation allowed us to convert a highly fluorescent dye into an exceptionally high PA contrast material. Spectroscopic characterization of the developed NIR dye-loaded perfluorocarbon-based nanoparticles for combined fluorescence and PA imaging revealed distinct dye-dependent photophysical behavior. We demonstrate that the enhanced contrast allows detection of regional lymph nodes of rats in vivo with time-domain optical and photoacoustic imaging methods. The results further show that the use of fluorescence lifetime imaging, which is less dependent on fluorescence intensity, provides a strategic approach to bridge the disparate contrast reporting mechanisms of fluorescence and PA imaging methods.

  18. Photoacoustic imaging of prostate brachytherapy seeds in ex vivo prostate

    Science.gov (United States)

    Kuo, Nathanael; Kang, Hyun Jae; DeJournett, Travis; Spicer, James; Boctor, Emad

    2011-03-01

    The localization of brachytherapy seeds in relation to the prostate is a key step in intraoperative treatment planning (ITP) for improving outcomes in prostate cancer patients treated with low dose rate prostate brachytherapy. Transrectal ultrasound (TRUS) has traditionally been the modality of choice to guide the prostate brachytherapy procedure due to its relatively low cost and apparent ease of use. However, TRUS is unable to visualize seeds well, precluding ITP and producing suboptimal results. While other modalities such as X-ray and magnetic resonance imaging have been investigated to localize seeds in relation to the prostate, photoacoustic imaging has become an emerging and promising modality to solve this challenge. Moreover, photoacoustic imaging may be more practical in the clinical setting compared to other methods since it adds little additional equipment to the ultrasound system already adopted in procedure today, reducing cost and simplifying engineering steps. In this paper, we demonstrate the latest efforts of localizing prostate brachytherapy seeds using photoacoustic imaging, including visualization of multiple seeds in actual prostate tissue. Although there are still several challenges to be met before photoacoustic imaging can be used in the operating room, we are pleased to present the current progress in this effort.

  19. Dynamic contrast-enhanced 3D photoacoustic imaging

    Science.gov (United States)

    Wong, Philip; Kosik, Ivan; Carson, Jeffrey J. L.

    2013-03-01

    Photoacoustic imaging (PAI) is a hybrid imaging modality that integrates the strengths from both optical imaging and acoustic imaging while simultaneously overcoming many of their respective weaknesses. In previous work, we reported on a real-time 3D PAI system comprised of a 32-element hemispherical array of transducers. Using the system, we demonstrated the ability to capture photoacoustic data, reconstruct a 3D photoacoustic image, and display select slices of the 3D image every 1.4 s, where each 3D image resulted from a single laser pulse. The present study aimed to exploit the rapid imaging speed of an upgraded 3D PAI system by evaluating its ability to perform dynamic contrast-enhanced imaging. The contrast dynamics can provide rich datasets that contain insight into perfusion, pharmacokinetics and physiology. We captured a series of 3D PA images of a flow phantom before and during injection of piglet and rabbit blood. Principal component analysis was utilized to classify the data according to its spatiotemporal information. The results suggested that this technique can be used to separate a sequence of 3D PA images into a series of images representative of main features according to spatiotemporal flow dynamics.

  20. Using high-power light emitting diodes for photoacoustic imaging

    DEFF Research Database (Denmark)

    Hansen, René Skov

    The preliminary result of using a high-power light emitting diode, LED, for photoacoustic imaging is presented. The pulsed light source is created by a 1Watt red Luxeon LED. The LED delivers light pulses with 25W peak power when supplied by 40A peak, 60ns wide current pulses. The phantom used...... for the experiment consists of a 3mm high x 5mm wide slice of green colored gelatine overlaid by a 3cm layer of colorless gelatine. The light pulses from the LED is focused on the green gelatine. The photoacoustic response from the green gelatine is detected by a single transducer on the opposite (top) surface...

  1. Quantitative phase-filtered wavelength-modulated differential photoacoustic radar tumor hypoxia imaging toward early cancer detection.

    Science.gov (United States)

    Dovlo, Edem; Lashkari, Bahman; Soo Sean Choi, Sung; Mandelis, Andreas; Shi, Wei; Liu, Fei-Fei

    2016-10-19

    Overcoming the limitations of conventional linear spectroscopy used in multispectral photoacoustic imaging, wherein a linear relationship is assumed between the absorbed optical energy and the absorption spectra of the chromophore at a specific location, is crucial for obtaining accurate spatially-resolved quantitative functional information by exploiting known chromophore-specific spectral characteristics. This study introduces a non-invasive phase-filtered differential photoacoustic technique, wavelength-modulated differential photoacoustic radar (WM-DPAR) imaging that addresses this issue by eliminating the effect of the unknown wavelength-dependent fluence. It employs two laser wavelengths modulated out-of-phase to significantly suppress background absorption while amplifying the difference between the two photoacoustic signals. This facilitates pre-malignant tumor identification and hypoxia monitoring, as minute changes in total hemoglobin concentration and hemoglobin oxygenation are detectable. The system can be tuned for specific applications such as cancer screening and SO2 quantification by regulating the amplitude ratio and phase shift of the signal. The WM-DPAR imaging of a head and neck carcinoma tumor grown in the thigh of a nude rat demonstrates the functional PA imaging of small animals in vivo. The PA appearance of the tumor in relation to tumor vascularity is investigated by immunohistochemistry. Phase-filtered WM-DPAR imaging is also illustrated, maximizing quantitative SO2 imaging fidelity of tissues. Oxygenation levels within a tumor grown in the thigh of a nude rat using the two-wavelength phase-filtered differential PAR method.

  2. Indocyanine Green Loaded Reduced Graphene Oxide for In Vivo Photoacoustic/Fluorescence Dual-Modality Tumor Imaging.

    Science.gov (United States)

    Chen, Jingqin; Liu, Chengbo; Zeng, Guang; You, Yujia; Wang, Huina; Gong, Xiaojing; Zheng, Rongqin; Kim, Jeesu; Kim, Chulhong; Song, Liang

    2016-12-01

    Multimodality imaging based on multifunctional nanocomposites holds great promise to fundamentally augment the capability of biomedical imaging. Specifically, photoacoustic and fluorescence dual-modality imaging is gaining much interest because of their non-invasiveness and the complementary nature of the two modalities in terms of imaging resolution, depth, sensitivity, and speed. Herein, using a green and facile method, we synthesize indocyanine green (ICG) loaded, polyethylene glycol (PEG)ylated, reduced nano-graphene oxide nanocomposite (rNGO-PEG/ICG) as a new type of fluorescence and photoacoustic dual-modality imaging contrast. The nanocomposite is shown to have minimal toxicity and excellent photoacoustic/fluorescence signals both in vitro and in vivo. Compared with free ICG, the nanocomposite is demonstrated to possess greater stability, longer blood circulation time, and superior passive tumor targeting capability. In vivo study shows that the circulation time of rNGO-PEG/ICG in the mouse body can sustain up to 6 h upon intravenous injection; while after 1 day, no obvious accumulation of rNGO-PEG/ICG is found in any major organs except the tumor regions. The demonstrated high fluorescence/photoacoustic dual contrasts, together with its low toxicity and excellent circulation life time, suggest that the synthesized rNGO-PEG/ICG can be a promising candidate for further translational studies on both the early diagnosis and image-guided therapy/surgery of cancer.

  3. Indocyanine Green Loaded Reduced Graphene Oxide for In Vivo Photoacoustic/Fluorescence Dual-Modality Tumor Imaging

    Science.gov (United States)

    Chen, Jingqin; Liu, Chengbo; Zeng, Guang; You, Yujia; Wang, Huina; Gong, Xiaojing; Zheng, Rongqin; Kim, Jeesu; Kim, Chulhong; Song, Liang

    2016-02-01

    Multimodality imaging based on multifunctional nanocomposites holds great promise to fundamentally augment the capability of biomedical imaging. Specifically, photoacoustic and fluorescence dual-modality imaging is gaining much interest because of their non-invasiveness and the complementary nature of the two modalities in terms of imaging resolution, depth, sensitivity, and speed. Herein, using a green and facile method, we synthesize indocyanine green (ICG) loaded, polyethylene glycol (PEG)ylated, reduced nano-graphene oxide nanocomposite (rNGO-PEG/ICG) as a new type of fluorescence and photoacoustic dual-modality imaging contrast. The nanocomposite is shown to have minimal toxicity and excellent photoacoustic/fluorescence signals both in vitro and in vivo. Compared with free ICG, the nanocomposite is demonstrated to possess greater stability, longer blood circulation time, and superior passive tumor targeting capability. In vivo study shows that the circulation time of rNGO-PEG/ICG in the mouse body can sustain up to 6 h upon intravenous injection; while after 1 day, no obvious accumulation of rNGO-PEG/ICG is found in any major organs except the tumor regions. The demonstrated high fluorescence/photoacoustic dual contrasts, together with its low toxicity and excellent circulation life time, suggest that the synthesized rNGO-PEG/ICG can be a promising candidate for further translational studies on both the early diagnosis and image-guided therapy/surgery of cancer.

  4. Quantification of photoacoustic microscopy images for ovarian cancer detection

    Science.gov (United States)

    Wang, Tianheng; Yang, Yi; Alqasemi, Umar; Kumavor, Patrick D.; Wang, Xiaohong; Sanders, Melinda; Brewer, Molly; Zhu, Quing

    2014-03-01

    In this paper, human ovarian tissues with malignant and benign features were imaged ex vivo by using an opticalresolution photoacoustic microscopy (OR-PAM) system. Several features were quantitatively extracted from PAM images to describe photoacoustic signal distributions and fluctuations. 106 PAM images from 18 human ovaries were classified by applying those extracted features to a logistic prediction model. 57 images from 9 ovaries were used as a training set to train the logistic model, and 49 images from another 9 ovaries were used to test our prediction model. We assumed that if one image from one malignant ovary was classified as malignant, it is sufficient to classify this ovary as malignant. For the training set, we achieved 100% sensitivity and 83.3% specificity; for testing set, we achieved 100% sensitivity and 66.7% specificity. These preliminary results demonstrate that PAM could be extremely valuable in assisting and guiding surgeons for in vivo evaluation of ovarian tissue.

  5. Advanced photoacoustic image reconstruction using the k-Wave toolbox

    Science.gov (United States)

    Treeby, B. E.; Jaros, J.; Cox, B. T.

    2016-03-01

    Reconstructing images from measured time domain signals is an essential step in tomography-mode photoacoustic imaging. However, in practice, there are many complicating factors that make it difficult to obtain high-resolution images. These include incomplete or undersampled data, filtering effects, acoustic and optical attenuation, and uncertainties in the material parameters. Here, the processing and image reconstruction steps routinely used by the Photoacoustic Imaging Group at University College London are discussed. These include correction for acoustic and optical attenuation, spatial resampling, material parameter selection, image reconstruction, and log compression. The effect of each of these steps is demonstrated using a representative in vivo dataset. All of the algorithms discussed form part of the open-source k-Wave toolbox (available from http://www.k-wave.org).

  6. Design of a portable noninvasive photoacoustic glucose monitoring system integrated laser diode excitation with annular array detection

    Science.gov (United States)

    Zeng, Lvming; Liu, Guodong; Yang, Diwu; Ren, Zhong; Huang, Zhen

    2008-12-01

    A near-infrared photoacoustic glucose monitoring system, which is integrated dual-wavelength pulsed laser diode excitation with eight-element planar annular array detection technique, is designed and fabricated during this study. It has the characteristics of nonivasive, inexpensive, portable, accurate location, and high signal-to-noise ratio. In the system, the exciting source is based on two laser diodes with wavelengths of 905 nm and 1550 nm, respectively, with optical pulse energy of 20 μJ and 6 μJ. The laser beam is optically focused and jointly projected to a confocal point with a diameter of 0.7 mm approximately. A 7.5 MHz 8-element annular array transducer with a hollow structure is machined to capture photoacoustic signal in backward mode. The captured signals excitated from blood glucose are processed with a synthetic focusing algorithm to obtain high signal-to-noise ratio and accurate location over a range of axial detection depth. The custom-made transducer with equal area elements is coaxially collimated with the laser source to improve the photoacoustic excite/receive efficiency. In the paper, we introduce the photoacoustic theory, receive/process technique, and design method of the portable noninvasive photoacoustic glucose monitoring system, which can potentially be developed as a powerful diagnosis and treatment tool for diabetes mellitus.

  7. Photoacoustic imaging using an 8-beam Fabry-Perot scanner

    Science.gov (United States)

    Huynh, Nam; Ogunlade, Olumide; Zhang, Edward; Cox, Ben; Beard, Paul

    2016-03-01

    The planar Fabry Perot (FP) photoacoustic scanner has been shown to provide exquisite high resolution 3D images of soft tissue structures in vivo to depths up to approximately 10mm. However a significant limitation of current embodiments of the concept is low image acquisition speed. To increase acquisition speed, a novel multi-beam scanner architecture has been developed. This enables a line of equally spaced 8 interrogation beams to be scanned simultaneously across the FP sensor and the photoacoustic signals detected in parallel. In addition, an excitation laser operating at 200Hz was used. The combination of parallelising the detection and the high pulse repetition frequency (PRF) of the excitation laser has enabled dramatic reductions in image acquisition time to be achieved. A 3D image can now be acquired in 10 seconds and 2D images at video rates are now possible.

  8. Initial results of finger imaging using Photoacoustic Computed Tomography

    CERN Document Server

    van Es, Peter; Moens, Hein J Bernelot; Steenbergen, Wiendelt; Manohar, Srirang

    2014-01-01

    We present a photoacoustic computed tomography investigation on a healthy human finger, to image blood vessels with a focus on vascularity across the interphalangeal joints. The cross-sectional images were acquired using an imager specifically developed for this purpose. The images show rich detail of the digital blood vessels with diameters between 100 $\\mu$m and 1.5 mm in various orientations and at various depths. Different vascular layers in the skin including the subpapillary plexus could also be visualized. Acoustic reflections on the finger bone of photoacoustic signals from skin were visible in sequential slice images along the finger except at the location of the joint gaps. Not unexpectedly, the healthy synovial membrane at the joint gaps was not detected due to its small size and normal vascularization. Future research will concentrate on studying digits afflicted with rheumatoid arthritis to detect the inflamed synovium with its heightened vascularization, whose characteristics are potential marke...

  9. Photoacoustic imaging of inflammatory arthritis in human joints

    Science.gov (United States)

    Jo, Janggun; Xu, Guan; Marquardt, April; Francis, Sheeja; Yuan, Jie; Girish, Dhanuj; Girish, Gandikota; Wang, Xueding

    2016-02-01

    The ducal imaging with photoacoustic imaging (PAI) that is an emerging technology and clinical ultrasound imaging that is an established modality is developed for the imaging of early inflammatory arthritis. PAI is sensitive to blood volume, not limited by flow like ultrasound, holding great promise for the earliest detection of increase in blood volume and angiogenesis - a key early finding inflammation PAI has the capability of assessing inflammation in superficial human soft tissues, offering potential benefits in diagnosis, treatment and monitoring of inflammatory arthritis. PAI combined with ultrasonography (US), is a real time dual-modality system developed and tested to identify active synovitis in metacarpophalangeal (MCP) joints of 10 arthritis patients and 10 normal volunteers. Photoacoustic images of the joints were acquired at 580-nm laser wavelength, which provided the desired balance between the optical contrast of hemoglobin over bone cortex and the imaging depth. Confirmed by US Doppler imaging, the results from ten patients and ten normal volunteers demonstrated satisfactory sensitivity of PAI in assessing enhanced blood flow due to active synovitis. This preliminary study suggests that photoacoustic imaging, by identifying early increase in blood volume, related to increased vascularity, a hallmark of joint inflammation, could be a valuable supplement to musculoskeletal US.

  10. Fiber-Laser-Based Ultrasound Sensor for Photoacoustic Imaging

    Science.gov (United States)

    Liang, Yizhi; Jin, Long; Wang, Lidai; Bai, Xue; Cheng, Linghao; Guan, Bai-Ou

    2017-01-01

    Photoacoustic imaging, especially for intravascular and endoscopic applications, requires ultrasound probes with miniature size and high sensitivity. In this paper, we present a new photoacoustic sensor based on a small-sized fiber laser. Incident ultrasound waves exert pressures on the optical fiber laser and induce harmonic vibrations of the fiber, which is detected by the frequency shift of the beating signal between the two orthogonal polarization modes in the fiber laser. This ultrasound sensor presents a noise-equivalent pressure of 40 Pa over a 50-MHz bandwidth. We demonstrate this new ultrasound sensor on an optical-resolution photoacoustic microscope. The axial and lateral resolutions are 48 μm and 3.3 μm. The field of view is up to 1.57 mm2. The sensor exhibits strong resistance to environmental perturbations, such as temperature changes, due to common-mode cancellation between the two orthogonal modes. The present fiber laser ultrasound sensor offers a new tool for all-optical photoacoustic imaging.

  11. Fiber-Laser-Based Ultrasound Sensor for Photoacoustic Imaging

    Science.gov (United States)

    Liang, Yizhi; Jin, Long; Wang, Lidai; Bai, Xue; Cheng, Linghao; Guan, Bai-Ou

    2017-01-01

    Photoacoustic imaging, especially for intravascular and endoscopic applications, requires ultrasound probes with miniature size and high sensitivity. In this paper, we present a new photoacoustic sensor based on a small-sized fiber laser. Incident ultrasound waves exert pressures on the optical fiber laser and induce harmonic vibrations of the fiber, which is detected by the frequency shift of the beating signal between the two orthogonal polarization modes in the fiber laser. This ultrasound sensor presents a noise-equivalent pressure of 40 Pa over a 50-MHz bandwidth. We demonstrate this new ultrasound sensor on an optical-resolution photoacoustic microscope. The axial and lateral resolutions are 48 μm and 3.3 μm. The field of view is up to 1.57 mm2. The sensor exhibits strong resistance to environmental perturbations, such as temperature changes, due to common-mode cancellation between the two orthogonal modes. The present fiber laser ultrasound sensor offers a new tool for all-optical photoacoustic imaging. PMID:28098201

  12. In vivo photoacoustic imaging of osteosarcoma in a rat model

    Science.gov (United States)

    Hu, Jun; Yu, Menglei; Ye, Fei; Xing, Da

    2011-02-01

    Osteosarcoma is one of the most common primary malignant tumors of the bone and the second leading cause of cancer-related deaths in the pediatric age group. Confirmed diagnosis and prompt treatment of osteosarcoma are critical for effective prognosis. In this study, we investigate the application of photoacoustic imaging (PAI) for the detection of osteosarcoma in an animal model. Cross-section images of a normal rat leg and a tumorous rat leg were successfully reconstructed in vivo. Morphological changes and the development of the implanted osteosarcoma were accurately mapped with time-dependent photoacoustic images. Furthermore, we evaluate the use of gold nanorods as contrast agents for imaging osteosarcoma with PAI. This is the first study that uses PAI to detect osteosarcoma in vivo, and the results suggest that PAI has the potential clinical application for detecting osteosarcoma in the early stage.

  13. Super-resolution photoacoustic imaging through a scattering wall

    Science.gov (United States)

    Conkey, Donald B.; Caravaca-Aguirre, Antonio M.; Dove, Jake D.; Ju, Hengyi; Murray, Todd W.; Piestun, Rafael

    2015-08-01

    The use of wavefront shaping to compensate for scattering has brought a renewed interest as a potential solution to imaging through scattering walls. A key to the practicality of any imaging through scattering technique is the capability to focus light without direct access behind the scattering wall. Here we address this problem using photoacoustic feedback for wavefront optimization. By combining the spatially non-uniform sensitivity of the ultrasound transducer to the generated photoacoustic waves with an evolutionary competition among optical modes, the speckle field develops a single, high intensity focus significantly smaller than the acoustic focus used for feedback. Notably, this method is not limited by the size of the absorber to form a sub-acoustic optical focus. We demonstrate imaging behind a scattering medium using two different imaging modalities with up to ten times improvement in signal-to-noise ratio and five to six times sub-acoustic resolution.

  14. Wavelength-Modulated Differential Photoacoustic Spectroscopy (WM-DPAS) for noninvasive early cancer detection and tissue hypoxia monitoring.

    Science.gov (United States)

    Choi, Sung Soo Sean; Mandelis, Andreas; Guo, Xinxin; Lashkari, Bahman; Kellnberger, Stephan; Ntziachristos, Vasilis

    2016-04-01

    This study introduces a novel noninvasive differential photoacoustic method, Wavelength Modulated Differential Photoacoustic Spectroscopy (WM-DPAS), for noninvasive early cancer detection and continuous hypoxia monitoring through ultrasensitive measurements of hemoglobin oxygenation levels (StO2 ). Unlike conventional photoacoustic spectroscopy, WM-DPAS measures simultaneously two signals induced from square-wave modulated laser beams at two different wavelengths where the absorption difference between maximum deoxy- and oxy-hemoglobin is 680 nm, and minimum (zero) 808 nm (the isosbestic point). The two-wavelength measurement efficiently suppresses background, greatly enhances the signal to noise ratio and thus enables WM-DPAS to detect very small changes in total hemoglobin concentration (CHb ) and oxygenation levels, thereby identifying pre-malignant tumors before they are anatomically apparent. The non-invasive nature also makes WM-DPAS the best candidate for ICU bedside hypoxia monitoring in stroke patients. Sensitivity tunability is another special feature of the technology: WM-DPAS can be tuned for different applications such as quick cancer screening and accurate StO2 quantification by selecting a pair of parameters, signal amplitude ratio and phase shift. The WM-DPAS theory has been validated with sheep blood phantom measurements. Sensitivity comparison between conventional single-ended signal and differential signal.

  15. Acoustic and photoacoustic microscopy imaging of single leukocytes

    Science.gov (United States)

    Strohm, Eric M.; Moore, Michael J.; Kolios, Michael C.

    2016-03-01

    An acoustic/photoacoustic microscope was used to create micrometer resolution images of stained cells from a blood smear. Pulse echo ultrasound images were made using a 1000 MHz transducer with 1 μm resolution. Photoacoustic images were made using a fiber coupled 532 nm laser, where energy losses through stimulated Raman scattering enabled output wavelengths from 532 nm to 620 nm. The laser was focused onto the sample using a 20x objective, and the laser spot co-aligned with the 1000 MHz transducer opposite the laser. The blood smear was stained with Wright-Giemsa, a common metachromatic dye that differentially stains the cellular components for visual identification. A neutrophil, lymphocyte and a monocyte were imaged using acoustic and photoacoustic microscopy at two different wavelengths, 532 nm and 600 nm. Unique features in each imaging modality enabled identification of the different cell types. This imaging method provides a new way of imaging stained leukocytes, with applications towards identifying and differentiating cell types, and detecting disease at the single cell level.

  16. Dual Modality Noncontact Photoacoustic and Spectral Domain OCT Imaging.

    Science.gov (United States)

    Leiss-Holzinger, Elisabeth; Bauer-Marschallinger, Johannes; Hochreiner, Armin; Hollinger, Philipp; Berer, Thomas

    2016-01-01

    We developed a multimodal imaging system, combining noncontact photoacoustic imaging and optical coherence tomography (OCT). Photoacoustic signals are recorded without contact to the specimens' surface by using an interferometric technique. The interferometer is realized within a fiber-optic network using a fiber laser at 1550 nm as source. The fiber-optic network allows the integration of a fiber-based OCT system operating at a wavelength region around 1310 nm. Light from the fiber laser and the OCT source are multiplexed into one fiber using wavelength-division multiplexing. The same focusing optics is used for both modalities. Back-reflected light from the sample is demultiplexed and guided to the respective imaging systems. As the same optical components are used for OCT and photoacoustic imaging, the obtained images are co-registered intrinsically in lateral direction. Three-dimensional imaging is implemented by hybrid galvanometer and mechanical scanning. To allow fast B-scan measurements, scanning of the interrogation beam along one dimension is executed by a galvanometer scanner. Slow-axis scanning, perpendicular to the fast axis, is performed utilizing a linear translational stage. We demonstrate two-dimensional and three-dimensional imaging on agarose phantoms.

  17. High frame rate photoacoustic imaging at 7000 frames per second using clinical ultrasound system.

    Science.gov (United States)

    Sivasubramanian, Kathyayini; Pramanik, Manojit

    2016-02-01

    Photoacoustic tomography, a hybrid imaging modality combining optical and ultrasound imaging, is gaining attention in the field of medical imaging. Typically, a Q-switched Nd:YAG laser is used to excite the tissue and generate photoacoustic signals. But, such photoacoustic imaging systems are difficult to translate into clinical applications owing to their high cost, bulky size often requiring an optical table to house such lasers. Moreover, the low pulse repetition rate of few tens of hertz prevents them from being used in high frame rate photoacoustic imaging. In this work, we have demonstrated up to 7000 Hz photoacoustic imaging (B-mode) and measured the flow rate of a fast moving object. We used a ~140 nanosecond pulsed laser diode as an excitation source and a clinical ultrasound imaging system to capture and display the photoacoustic images. The excitation laser is ~803 nm in wavelength with ~1.4 mJ energy per pulse. So far, the reported 2-dimensional photoacoustic B-scan imaging is only a few tens of frames per second using a clinical ultrasound system. Therefore, this is the first report on 2-dimensional photoacoustic B-scan imaging with 7000 frames per second. We have demonstrated phantom imaging to view and measure the flow rate of ink solution inside a tube. This fast photoacoustic imaging can be useful for various clinical applications including cardiac related problems, where the blood flow rate is quite high, or other dynamic studies.

  18. Light Focusing and Two-Dimensional Imaging Through Scattering Media using the Photoacoustic Transmission-Matrix with an Ultrasound Array

    CERN Document Server

    Chaigne, Thomas; Katz, Ori; Bossy, Emmanuel; Gigan, Sylvain

    2014-01-01

    We implement the photoacoustic transmission-matrix approach on a two-dimensional photoacoustic imaging system, using a 15 MHz linear ultrasound array. Using a black leaf skeleton as a complex absorbing structure, we demonstrate that the photoacoustic transmission-matrix approach allows to reveal structural features that are invisible in conventional photoacoustic images, as well as to selectively control light focusing on absorbing targets, leading to a local enhancement of the photoacoustic signal.

  19. Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors.

    Science.gov (United States)

    Kanazaki, Kengo; Sano, Kohei; Makino, Akira; Homma, Tsutomu; Ono, Masahiro; Saji, Hideo

    2016-09-26

    Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging.

  20. Photoacoustic and Ultrasonic Image-Guided Needle Biopsy of the Prostate

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0024 TITLE: Photoacoustic and Ultrasonic Image-Guided Needle Biopsy of the Prostate PRINCIPAL INVESTIGATOR: Richard...light sources to yield multi-spectral photoacoustic (PA) imaging data in excised prostate tissue. Two types of interstitial sources – a directional...ANSI Std. Z39.18 Photoacoustic and Ultrasonic Image-Guided Needle Biopsy of the Prostate 34 Table of Contents Page 1. Introduction

  1. In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

    Science.gov (United States)

    2015-09-01

    AD______________ AWARD NUMBER: W81XWH-14-1-0242 TITLE: In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent...2015 4. TITLE AND SUBTITLE In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent 5a. CONTRACT NUMBER W81XWH-14-1-0242 5b...men with false positive PSA elevation and to ensure successful biopsy for those with small cancers. Photoacoustic imaging is an emerging functional

  2. Pharmacokinetic Monitoring of Indocyanine Green for Tumor Detection Using Photoacoustic Imaging

    Institute of Scientific and Technical Information of China (English)

    YANG Si-Hua; YIN Guang-Zhi; XING Da

    2010-01-01

    @@ We report tumor detection using a photoacoustic technique for the imaging of angiogenesis and monitoring of agent pharmacokinetics on an animal model.We take 532-nm laser pulses to excite photoacoustic signals of blood vessels with acquisition by a broadband hydrophone,and the morphological characteristics of tumor angiogenesis are successfully image depicted.Furthermore,tumor pharmacokinetics is preformed and analyzed with fast multielement photoacoustic imaging of the intravenous-injected indocyanine green (ICG).

  3. Gold nanoflowers for 3D volumetric molecular imaging of tumors by photoacoustic tomography

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Jiang[1,4; Zijian Deng[2,4; Dan Yang[3; Xin Deng[1; Qi Li[1; Yinlin Sha[3; Changhui Li[2; Dongsheng Xu[1

    2015-01-01

    By binding molecular probes that target tumor cells, gold nanoparticles (AuNPs) with superior characteristics have shown great potential in tumor molecular imaging studies. The non-invasive, high-resolution, and three-dimensional imaging of the targeted AuNPs within the tumor is desirable for both diagnosis and therapy. In this study, gold nanoflowers (AuNFs) are presented as a novel contrast agent for photoacoustic tomography (PAT). By binding to folic acid, the molecular probe, the tail-vein injected AuNFs concentrated within the tumor site in mice; this was clearly visualized by three-dimensional (3D) PAT imaging. In addition, toxicity assay proved that AuNFs were harmless to living cells and animals. Our results demonstrate that AuNFs have great potential in tumor molecular imaging.

  4. Photoacoustic molecular imaging for in vivo liver iron quantitation

    Science.gov (United States)

    Maccarinelli, Federica; Carmona, Fernando; Regoni, Maria; Arosio, Paolo

    2016-05-01

    A recent study showed that ferritin is a suitable endogenous contrast agent for photoacoustic molecular imaging in cultured mammalian cells. We have therefore tested whether this imaging technique can be used for in vivo quantification of iron in mouse livers. To verify this hypothesis, we used multispectral optoacoustic tomography (MSOT) to image albino CD1 mice before and after experimental iron loading. Postmortem assays showed that the iron treatment caused a 15-fold increase in liver iron and a 40-fold increase in liver ferritin levels, while in vivo longitudinal analysis using MSOT revealed just a 1.6-fold increase in the ferritin/iron photoacoustic signal in the same animals. We conclude that MSOT can monitor changes in ferritin/iron levels in vivo, but its sensitivity is much lower than that of ex vivo iron assays.

  5. Photoacoustic imaging of vascular networks in transgenic mice

    Science.gov (United States)

    Laufer, J. G.; Cleary, J. O.; Zhang, E. Z.; Lythgoe, M. F.; Beard, P. C.

    2010-02-01

    The preferential absorption of near infrared light by blood makes photoacoustic imaging well suited to visualising vascular structures in soft tissue. In addition, the spectroscopic specificity of tissue chromophores can be exploited by acquiring images at multiple excitation wavelengths. This allows the quantification of endogenous chromophores, such as oxy- and deoxyhaemoglobin, and hence blood oxygenation, and the detection of exogenous chromophores, such as functionalised contrast agents. More importantly, this approach has the potential to visualise the spatial distribution of low concentrations of functionalised contrast agents against the strong background absorption of the endogenous chromophores. This has a large number of applications in the life sciences. One example is the structural and functional phenotyping of transgenic mice for the study of the genetic origins of vascular malformations, such as heart defects. In this study, photoacoustic images of mouse embryos have been acquired to study the development of the vasculature following specific genetic knockouts.

  6. Non-destructive photoacoustic imaging of metal surface defects

    Science.gov (United States)

    Jeon, Seungwan; Kim, Jeesu; Yun, Jong Pil; Kim, Chulhong

    2016-11-01

    The detection of metal surface defects is important in achieving the goals of product quality enhancement and manufacturing cost reduction. Identifying the defects with visual inspection is difficult, inaccurate, and time-consuming. Thus, several inspection methods using line cameras, magnetic field, and ultrasound have been proposed. However, identifying small defects on metal surfaces remains a challenge. To deal with this problem, we propose the use of photoacoustic imaging (PAI) as a new non-destructive imaging tool to detect metal surface defects. We successfully visualized two types of cracks (i.e., unclassified and seam cracks) in metal plate samples using PAI. In addition, we successfully extracted cracked edges from height-encoded photoacoustic maximum amplitude projection images using the Laplacian of Gaussian filtering method, and then, quantified the detected edges for a statistical analysis. We concluded that PAI can be useful in detecting metal surface defects reducing the defect rate and manufacturing cost during metal production.

  7. Engineering Dark Chromoprotein Reporters for Photoacoustic Microscopy and FRET Imaging

    Science.gov (United States)

    Li, Yan; Forbrich, Alex; Wu, Jiahui; Shao, Peng; Campbell, Robert E.; Zemp, Roger

    2016-03-01

    A subset of the family of fluorescent proteins are the non-fluorescent chromoproteins which are promising probe molecules for use in photoacoustic imaging and as acceptor chromophores in Förster resonance energy transfer (FRET)-based biosensors. Typical approaches for fluorescent protein optimization by screening of large libraries of variants cannot be effectively applied to chromoproteins due to their characteristic lack of fluorescence. To address this challenge, we have developed a directed evolution method to iteratively screen large libraries of protein variants on the basis of their photoacoustic signal levels. By applying this procedure to the promising Ultramarine and cjBlue chromoprotein templates, we were able to identify improved variants with a 02-04 fold increase in photoacoustic signal-to-noise ratio after only a few evolutionary steps. These improved variants enable more accurate spectral de-mixing and localization of protein-producing bacteria in vivo and serve as effective FRET acceptors for both fluorescence- and photoacoustic-based detection of protease activity.

  8. Photoacoustic imaging of blood vessels in tissues

    Science.gov (United States)

    de Mul, Frits F. M.; Pilatou, Magdalena C.; Kolkman, Roy G. M.; Hondebrink, Erwin; Steenbergen, Wiendelt

    2002-10-01

    To localize and monitor the blood content in tissue we developed very sensitive photoacoustical detectors. In these detectors a PVdF-layer has been used as piezo-electric material and also fibers for the illumination of the sample are integrated. The resolution is about 20 im in depth and about 50-100 im laterally. The wavelengths ofthe laser light were 532and 1064 nm. With these colors we can measure at different depths in tissue. We will report measurements on real tissue: vessels in chicken breast, in the human arm, and in test animals at various positions.

  9. Multispectral photoacoustic imaging of tumours in mice injected with an enzyme-activatable photoacoustic probe

    Science.gov (United States)

    Hirasawa, Takeshi; Iwatate, Ryu J.; Kamiya, Mako; Okawa, Shinpei; Urano, Yasuteru; Ishihara, Miya

    2017-01-01

    Photoacoustic (PA) imaging offers depth-resolved images of optical absorbers with the spatial resolution of ultrasound imaging. To enhance tumour contrast, tumour-specific probes are used as contrast agents. We synthesised a colourless PA probe that is activated in the presence of γ-glutamyltranspeptidase, a cancer-associated enzyme, to show its original colour and fluorescence. We have acquired high specificity fluorescence images of small tumours, using a fluorescent probe based on similar enzymatic reactions. Here, we developed a PA imaging technique to detect the PA probe. In PA imaging, depending on the concentration and excitation wavelength of the probe, the intensities of the probe signals may be lower than those of the background signals produced by intrinsic optical absorbers such as haemoglobin. For probe imaging in the presence of strong background signals, multispectral photoacoustic (MS-PA) imaging was evaluated. In MS-PA imaging, the spectral fitting method, which distinguishes the probe signals from background signals using reference spectra, has been widely used. To compensate for the decrease of fluence due to optical attenuation in biological tissue, we used a simplified compensation method that calculates fluence inside biological tissues by the Monte-Carlo model using published data on optical properties of biological tissues. The validity of the method was confirmed using tissue-mimicking phantoms. Finally, MS-PA imaging of a mouse subcutaneous tumour injected with the activatable probe was demonstrated. In conclusion, our MS-PA imaging technique afforded successful detection of the activated probe in the tumour, and time-increase of PA signals were successfully observed.

  10. Functional connectivity in the mouse brain imaged by B-mode photoacoustic microscopy

    Science.gov (United States)

    Nasiriavanaki, Mohammadreza; Xing, Wenxin; Xia, Jun; Wang, Lihong V.

    2014-03-01

    The increasing use of mouse models for human brain disease studies, coupled with the fact that existing functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing acoustic-resolution photoacoustic microscopy (AR-PAM), we imaged spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images were acquired noninvasively in B-scan mode with a fast frame rate, a large field of view, and a high spatial resolution. At a location relative to the bregma 0, correlations were investigated inter-hemispherically between bilaterally homologous regions, as well as intra-hemispherically within the same functional regions. The functional connectivity in different functional regions was studied. The locations of these regions agreed well with the Paxinos mouse brain atlas. The functional connectivity map obtained in this study can then be used in the investigation of brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy. Our experiments show that photoacoustic microscopy is capable to detect connectivities between different functional regions in B-scan mode, promising a powerful functional imaging modality for future brain research.

  11. In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy.

    Science.gov (United States)

    Laufer, Jan; Johnson, Peter; Zhang, Edward; Treeby, Bradley; Cox, Ben; Pedley, Barbara; Beard, Paul

    2012-05-01

    The use of a novel all-optical photoacoustic scanner for imaging the development of tumor vasculature and its response to a therapeutic vascular disrupting agent is described. The scanner employs a Fabry-Perot polymer film ultrasound sensor for mapping the photoacoustic waves and an image reconstruction algorithm based upon attenuation-compensated acoustic time reversal. The system was used to noninvasively image human colorectal tumor xenografts implanted subcutaneously in mice. Label-free three-dimensional in vivo images of whole tumors to depths of almost 10 mm with sub-100-micron spatial resolution were acquired in a longitudinal manner. This enabled the development of tumor-related vascular features, such as vessel tortuosity, feeding vessel recruitment, and necrosis to be visualized over time. The system was also used to study the temporal evolution of the response of the tumor vasculature following the administration of a therapeutic vascular disrupting agent (OXi4503). This revealed the well-known destruction and recovery phases associated with this agent. These studies illustrate the broader potential of this technology as an imaging tool for the preclinical and clinical study of tumors and other pathologies characterized by changes in the vasculature.

  12. Photoacoustic image patterns of breast carcinoma and comparisons with Magnetic Resonance Imaging and vascular stained histopathology.

    Science.gov (United States)

    Heijblom, M; Piras, D; Brinkhuis, M; van Hespen, J C G; van den Engh, F M; van der Schaaf, M; Klaase, J M; van Leeuwen, T G; Steenbergen, W; Manohar, S

    2015-07-10

    Photoacoustic (optoacoustic) imaging can visualize vasculature deep in tissue using the high contrast of hemoglobin to light, with the high-resolution possible with ultrasound detection. Since angiogenesis, one of the hallmarks of cancer, leads to increased vascularity, photoacoustics holds promise in imaging breast cancer as shown in proof-of-principle studies. Here for the first time, we investigate if there are specific photoacoustic appearances of breast malignancies which can be related to the tumor vascularity, using an upgraded research imaging system, the Twente Photoacoustic Mammoscope. In addition to comparisons with x-ray and ultrasound images, in subsets of cases the photoacoustic images were compared with MR images, and with vascular staining in histopathology. We were able to identify lesions in suspect breasts at the expected locations in 28 of 29 cases. We discovered generally three types of photoacoustic appearances reminiscent of contrast enhancement types reported in MR imaging of breast malignancies, and first insights were gained into the relationship with tumor vascularity.

  13. Photoacoustic image patterns of breast carcinoma and comparisons with Magnetic Resonance Imaging and vascular stained histopathology

    Science.gov (United States)

    Heijblom, M.; Piras, D.; Brinkhuis, M.; van Hespen, J. C. G.; van den Engh, F. M.; van der Schaaf, M.; Klaase, J. M.; van Leeuwen, T. G.; Steenbergen, W.; Manohar, S.

    2015-07-01

    Photoacoustic (optoacoustic) imaging can visualize vasculature deep in tissue using the high contrast of hemoglobin to light, with the high-resolution possible with ultrasound detection. Since angiogenesis, one of the hallmarks of cancer, leads to increased vascularity, photoacoustics holds promise in imaging breast cancer as shown in proof-of-principle studies. Here for the first time, we investigate if there are specific photoacoustic appearances of breast malignancies which can be related to the tumor vascularity, using an upgraded research imaging system, the Twente Photoacoustic Mammoscope. In addition to comparisons with x-ray and ultrasound images, in subsets of cases the photoacoustic images were compared with MR images, and with vascular staining in histopathology. We were able to identify lesions in suspect breasts at the expected locations in 28 of 29 cases. We discovered generally three types of photoacoustic appearances reminiscent of contrast enhancement types reported in MR imaging of breast malignancies, and first insights were gained into the relationship with tumor vascularity.

  14. Photoacoustic and ultrasound imaging using dual contrast perfluorocarbon nanodroplets triggered by laser pulses at 1064 nm.

    Science.gov (United States)

    Hannah, Alexander S; VanderLaan, Donald; Chen, Yun-Sheng; Emelianov, Stanislav Y

    2014-09-01

    Recently, a dual photoacoustic and ultrasound contrast agent-named photoacoustic nanodroplet-has been introduced. Photoacoustic nanodroplets consist of a perfluorocarbon core, surfactant shell, and encapsulated photoabsorber. Upon pulsed laser irradiation the perfluorocarbon converts to gas, inducing a photoacoustic signal from vaporization and subsequent ultrasound contrast from the resulting gas microbubbles. In this work we synthesize nanodroplets which encapsulate gold nanorods with a peak absorption near 1064 nm. Such nanodroplets are optimal for extended photoacoustic imaging depth and contrast, safety and system cost. We characterized the nanodroplets for optical absorption, image contrast and vaporization threshold. We then imaged the particles in an ex vivo porcine tissue sample, reporting contrast enhancement in a biological environment. These 1064 nm triggerable photoacoustic nanodroplets are a robust biomedical tool to enhance image contrast at clinically relevant depths.

  15. Polyacrylamide based ICG nanocarriers for enhanced fluorescence and photoacoustic imaging

    Science.gov (United States)

    Ray, Aniruddha; Yoon, Hyung Ki; Ryu, HeeJu; Koo Lee, Yong-Eun; Kim, Gwangseong; Wang, Xueding; Kopelman, Raoul

    2013-02-01

    Indocyanine green (ICG) is an FDA approved tricarbocyanine dye. This dye, with a strong absorbance in the near infrared (NIR) region, has been extensively used for fluorescence and photoacoustic imaging in vivo. ICG in its free form, however, has a few drawbacks that limit its in vivo applications, such as non-targetability, tendency to form aggregates which changes its optical properties, fast degradation, short plasma lifetime and reduced fluorescence at body temperature. In order to bypass these inherent drawbacks, we demonstrate a polyacrylamide based nanocarrier that was particularly designed to carry the negatively charged ICG molecules. These nanocarriers are biodegradable, biocompatible and can be specifically targeted to any cell or tissue. Using these nanocarriers we avoid all the problems associated with free ICG, such as degradation, aggregation and short plasma lifetime, and also enhance demonstrate its ability towards photoacoustics and fluorescence imaging.

  16. An algorithm for total variation regularized photoacoustic imaging

    DEFF Research Database (Denmark)

    Dong, Yiqiu; Görner, Torsten; Kunis, Stefan

    2014-01-01

    Recovery of image data from photoacoustic measurements asks for the inversion of the spherical mean value operator. In contrast to direct inversion methods for specific geometries, we consider a semismooth Newton scheme to solve a total variation regularized least squares problem. During the iter...... the iteration, each matrix vector multiplication is realized in an efficient way using a recently proposed spectral discretization of the spherical mean value operator. All theoretical results are illustrated by numerical experiments.......Recovery of image data from photoacoustic measurements asks for the inversion of the spherical mean value operator. In contrast to direct inversion methods for specific geometries, we consider a semismooth Newton scheme to solve a total variation regularized least squares problem. During...

  17. Photoacoustic image-guided navigation system for surgery (Conference Presentation)

    Science.gov (United States)

    Park, Sara; Jang, Jongseong; Kim, Jeesu; Kim, Young Soo; Kim, Chulhong

    2017-03-01

    Identifying and delineating invisible anatomical and pathological details during surgery guides surgical procedures in real time. Various intraoperative imaging modalities have been increasingly employed to minimize such surgical risks as anatomical changes, damage to normal tissues, and human error. However, current methods provide only structural information, which cannot identify critical structures such as blood vessels. The logical next step is an intraoperative imaging modality that can provide functional information. Here, we have successfully developed a photoacoustic (PA) image-guided navigation system for surgery by integrating a position tracking system and a real-time clinical photoacoustic/ultrasound (PA/US) imaging system. PA/US images were acquired in real time and overlaid on pre-acquired cross-sectional magnetic resonance (MR) images. In the overlaid images, PA images represent the optical absorption characteristics of the surgical field, while US and MR images represent the morphological structure of surrounding tissues. To test the feasibility of the system, we prepared a tissue mimicking phantom which contained two samples, methylene blue as a contrast agent and water as a control. We acquired real-time overlaid PA/US/MR images of the phantom, which were well-matched with the optical and morphological properties of the samples. The developed system is the first approach to a novel intraoperative imaging technology based on PA imaging, and we believe that the system can be utilized in various surgical environments in the near future, improving the efficacy of surgical guidance.

  18. Photoacoustic imaging of prostate cancer using cylinder diffuse radiation

    Science.gov (United States)

    Xie, Wenming; Li, Li; Li, Zhifang; Li, Hui

    2012-12-01

    Prostate cancer is one of diseases with high mortality in man. Many clinical imaging modalities are utilized for the detection, grading and staging of prostate cancer, such as ultrasound, CT, MRI, etc. But they lacked adequate sensitivity and specificity for finding cancer in transition or central zone of prostate. To overcome these problems, we propose a photoacoustic imaging modality based on cylinder diffuse radiation through urethra for prostate cancer detection. We measure the related parameters about this system like lateral resolution (~2mm) and axial resolution(~333μm). Finally, simulated sample was imaged by our system. The results demonstrate the feasibility for detecting prostate cancer by our system.

  19. Novel organosilicon phantoms as testing material for photoacoustic imaging

    Science.gov (United States)

    Avigo, Cinzia; Armanetti, Paolo; Masciullo, Cecilia; Di Lascio, Nicole; Cavigli, Lucia; Ratto, Fulvio; Pini, Roberto; Cecchini, Marco; Kusmic, Claudia; Faita, Francesco; Menichetti, Luca

    2016-03-01

    The contrast in photoacoustic (PA) imaging depends on the mechanical and elastic properties of the tissue, as well as on his optical absorption and scatter properties. Thanks to these futures, this novel modality could offer additional specificity compared to conventional ultrasound techniques, being able to reveal the signal of absorbing materials and chomophores, e.g. endogenous molecules like haemoglobin or specific near infrared dyes or plasmonic contrast agents. The development of semi-quantitative protocols for the assessment of the contrast enhancement, is one of the key aspect of the ongoing research, that could open new routes to the use of PA imaging for a variety of applications in preclinical research of cancer and cardiovascular diseases. In this work, we designed and tested a tissue mimicking polydimethylsiloxane (PDMS) phantom for photoacoustic applications, with tailored biomechanical/optical and geometrical properties. In order to modulate the light fluence and penetration, that remains one of the major challenge for this technique, we added titanium dioxide and black ink, rendering the optical absorption and scattering coefficients similar to those of biological tissues. The PDMS phantom can become a particularly promising tool in the field of photoacoustics for the evaluation of the performance of a PA system and as a model of the structure of vascularized soft tissues.

  20. High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

    Science.gov (United States)

    Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

    2016-02-01

    Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

  1. Noninvasively measuring oxygen saturation of human finger-joint vessels by multi-transducer functional photoacoustic tomography

    Science.gov (United States)

    Deng, Zijian; Li, Changhui

    2016-06-01

    Imaging small blood vessels and measuring their functional information in finger joint are still challenges for clinical imaging modalities. In this study, we developed a multi-transducer functional photoacoustic tomography (PAT) system and successfully imaged human finger-joint vessels from ˜1 mm to anatomical and functional information of individual finger-joint vessels with different sizes, which might help the study of finger-joint diseases, such as rheumatoid arthritis.

  2. An adaptive filtered back-projection for photoacoustic image reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Huang, He; Bustamante, Gilbert; Peterson, Ralph; Ye, Jing Yong, E-mail: jingyong.ye@utsa.edu [Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas 78249 (United States)

    2015-05-15

    Purpose: The purpose of this study is to develop an improved filtered-back-projection (FBP) algorithm for photoacoustic tomography (PAT), which allows image reconstruction with higher quality compared to images reconstructed through traditional algorithms. Methods: A rigorous expression of a weighting function has been derived directly from a photoacoustic wave equation and used as a ramp filter in Fourier domain. The authors’ new algorithm utilizes this weighting function to precisely calculate each photoacoustic signal’s contribution and then reconstructs the image based on the retarded potential generated from the photoacoustic sources. In addition, an adaptive criterion has been derived for selecting the cutoff frequency of a low pass filter. Two computational phantoms were created to test the algorithm. The first phantom contained five spheres with each sphere having different absorbances. The phantom was used to test the capability for correctly representing both the geometry and the relative absorbed energy in a planar measurement system. The authors also used another phantom containing absorbers of different sizes with overlapping geometry to evaluate the performance of the new method for complicated geometry. In addition, random noise background was added to the simulated data, which were obtained by using an arc-shaped array of 50 evenly distributed transducers that spanned 160° over a circle with a radius of 65 mm. A normalized factor between the neighbored transducers was applied for correcting measurement signals in PAT simulations. The authors assumed that the scanned object was mounted on a holder that rotated over the full 360° and the scans were set to a sampling rate of 20.48 MHz. Results: The authors have obtained reconstructed images of the computerized phantoms by utilizing the new FBP algorithm. From the reconstructed image of the first phantom, one can see that this new approach allows not only obtaining a sharp image but also showing

  3. Optical drug monitoring: photoacoustic imaging of nanosensors to monitor therapeutic lithium in vivo.

    Science.gov (United States)

    Cash, Kevin J; Li, Chiye; Xia, Jun; Wang, Lihong V; Clark, Heather A

    2015-02-24

    Personalized medicine could revolutionize how primary care physicians treat chronic disease and how researchers study fundamental biological questions. To realize this goal, we need to develop more robust, modular tools and imaging approaches for in vivo monitoring of analytes. In this report, we demonstrate that synthetic nanosensors can measure physiologic parameters with photoacoustic contrast, and we apply that platform to continuously track lithium levels in vivo. Photoacoustic imaging achieves imaging depths that are unattainable with fluorescence or multiphoton microscopy. We validated the photoacoustic results that illustrate the superior imaging depth and quality of photoacoustic imaging with optical measurements. This powerful combination of techniques will unlock the ability to measure analyte changes in deep tissue and will open up photoacoustic imaging as a diagnostic tool for continuous physiological tracking of a wide range of analytes.

  4. Multimodal non-contact photoacoustic and OCT imaging with galvanometer scanning

    Science.gov (United States)

    Berer, Thomas; Hochreiner, Armin; Leiss-Holzinger, Elisabeth; Bauer-Marschallinger, Johannes; Buchsbaum, Andreas

    2015-03-01

    In this paper we present multimodal non-contact photoacoustic and optical coherence tomography (OCT) imaging using a galvanometer scanner. Photoacoustic signals are acquired without contact on the surface of a specimen using an interferometric technique. The interferometer is realized in a fiber-optic network using a fiber laser at 1550 nm as source. In the same fiber-optic network a spectral-domain OCT system is realized, using a broadband light source at 1300 nm. Light from the fiber laser and the OCT source are multiplexed into the same fiber and the same objective is used for both imaging modalities. Fast non-contact photoacoustic and OCT imaging is demonstrated by scanning the detection spot utilizing a galvanometer scanner. Multimodal photoacoustic and OCT imaging is shown on agarose phantoms. As the same fiber network and optical components are used for non-contact photoacoustic and OCT imaging the obtained images are co-registered intrinsically.

  5. Photoacoustic imaging of single circulating melanoma cells in vivo

    Science.gov (United States)

    Wang, Lidai; Yao, Junjie; Zhang, Ruiying; Xu, Song; Li, Guo; Zou, Jun; Wang, Lihong V.

    2015-03-01

    Melanoma, one of the most common types of skin cancer, has a high mortality rate, mainly due to a high propensity for tumor metastasis. The presence of circulating tumor cells (CTCs) is a potential predictor for metastasis. Label-free imaging of single circulating melanoma cells in vivo provides rich information on tumor progress. Here we present photoacoustic microscopy of single melanoma cells in living animals. We used a fast-scanning optical-resolution photoacoustic microscope to image the microvasculature in mouse ears. The imaging system has sub-cellular spatial resolution and works in reflection mode. A fast-scanning mirror allows the system to acquire fast volumetric images over a large field of view. A 500-kHz pulsed laser was used to image blood and CTCs. Single circulating melanoma cells were imaged in both capillaries and trunk vessels in living animals. These high-resolution images may be used in early detection of CTCs with potentially high sensitivity. In addition, this technique enables in vivo study of tumor cell extravasation from a primary tumor, which addresses an urgent pre-clinical need.

  6. Compensation for air voids in photoacoustic computed tomography image reconstruction

    Science.gov (United States)

    Matthews, Thomas P.; Li, Lei; Wang, Lihong V.; Anastasio, Mark A.

    2016-03-01

    Most image reconstruction methods in photoacoustic computed tomography (PACT) assume that the acoustic properties of the object and the surrounding medium are homogeneous. This can lead to strong artifacts in the reconstructed images when there are significant variations in sound speed or density. Air voids represent a particular challenge due to the severity of the differences between the acoustic properties of air and water. In whole-body small animal imaging, the presence of air voids in the lungs, stomach, and gastrointestinal system can limit image quality over large regions of the object. Iterative reconstruction methods based on the photoacoustic wave equation can account for these acoustic variations, leading to improved resolution, improved contrast, and a reduction in the number of imaging artifacts. However, the strong acoustic heterogeneities can lead to instability or errors in the numerical wave solver. Here, the impact of air voids on PACT image reconstruction is investigated, and procedures for their compensation are proposed. The contributions of sound speed and density variations to the numerical stability of the wave solver are considered, and a novel approach for mitigating the impact of air voids while reducing the computational burden of image reconstruction is identified. These results are verified by application to an experimental phantom.

  7. Upconversion nanoparticles as a contrast agent for photoacoustic imaging in live mice.

    Science.gov (United States)

    Maji, Swarup Kumar; Sreejith, Sivaramapanicker; Joseph, James; Lin, Manjing; He, Tingchao; Tong, Yan; Sun, Handong; Yu, Sidney Wing-Kwong; Zhao, Yanli

    2014-08-27

    An inclusion complex of NaYF4 :Yb(3+) ,Er(3+) upconversion nanoparticles with α-cyclodextrin in aqueous conditions exhibits luminescence quenching when excited at 980 nm. This non-radiative relaxation leads to an unprecedented photoacoustic signal enhancement. In vivo localization of α-cyclodextrin-covered NaYF4 :Yb(3+) ,Er(3+) is demonstrated using photoacoustic tomography in live mice, showing its high capability for photoacoustic imaging.

  8. Imaging of an inflammatory injury in the newborn rat brain with photoacoustic tomography.

    Directory of Open Access Journals (Sweden)

    Edgar Guevara

    Full Text Available BACKGROUND: The precise assessment of cerebral saturation changes during an inflammatory injury in the developing brain, such as seen in periventricular leukomalacia, is not well defined. This study investigated the impact of inflammation on locoregional cerebral oxygen saturation in a newborn rodent model using photoacoustic imaging. METHODS: 1 mg/kg of lipopolysaccharide(LPS diluted in saline or saline alone was injected under ultrasound guidance directly in the corpus callosum of P3 rat pups. Coronal photoacoustic images were carried out 24 h after LPS exposure. Locoregional oxygen saturation (SO2 and resting state connectivity were assessed in the cortex and the corpus callosum. Microvasculature was then evaluated on cryosection slices by lectin histochemistry. RESULTS: Significant reduction of SO2 was found in the corpus callosum; reduced SO2 was also found in the cortex ipsilateral to the injection site. Seed-based functional connectivity analysis showed that bilateral connectivity was not affected by LPS exposure. Changes in locoregional oxygen saturation were accompanied by a significant reduction in the average length of microvessels in the left cortex but no differences were observed in the corpus callosum. CONCLUSION: Inflammation in the developing brain induces marked reduction of locoregional oxygen saturation, predominantly in the white matter not explained by microvascular degeneration. The ability to examine regional saturation offers a new way to monitor injury and understand physiological disturbance non-invasively.

  9. Resting-state functional connectivity imaging of the mouse brain using photoacoustic tomography

    Science.gov (United States)

    Nasiriavanaki, Mohammadreza; Xia, Jun; Wan, Hanlin; Bauer, Adam Q.; Culver, Joseph P.; Wang, Lihong V.

    2014-03-01

    Resting-state functional connectivity (RSFC) imaging is an emerging neuroimaging approach that aims to identify spontaneous cerebral hemodynamic fluctuations and their associated functional connections. Clinical studies have demonstrated that RSFC is altered in brain disorders such as stroke, Alzheimer's, autism, and epilepsy. However, conventional neuroimaging modalities cannot easily be applied to mice, the most widely used model species for human brain disease studies. For instance, functional magnetic resonance imaging (fMRI) of mice requires a very high magnetic field to obtain a sufficient signal-to-noise ratio and spatial resolution. Functional connectivity mapping with optical intrinsic signal imaging (fcOIS) is an alternative method. Due to the diffusion of light in tissue, the spatial resolution of fcOIS is limited, and experiments have been performed using an exposed skull preparation. In this study, we show for the first time, the use of photoacoustic computed tomography (PACT) to noninvasively image resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight regions, as well as several subregions. These findings agreed well with the Paxinos mouse brain atlas. This study showed that PACT is a promising, non-invasive modality for small-animal functional brain imaging.

  10. Advanced devices for photoacoustic imaging to improve cancer and cerebrovascular medicine

    Science.gov (United States)

    Montilla Marien, Leonardo Gabriel

    Recent clinical studies have demonstrated that photoacoustic imaging (PAI) provides important diagnostic information for breast cancer staging. Despite these promising studies, PAI remains an unfeasible option for clinics due to the cost to implement, the required large modification in user conduct and the inflexibility of the hardware to accommodate other applications for the incremental enhancement in diagnostic information. The research described in this dissertation addresses these issues by designing attachments to clinical ultrasound probes and incorporating custom detectors into commercial ultrasound scanners. The ultimate benefit of these handheld devices is to expand the capability of current ultrasound systems and facilitate the translation of PAI to enhance cancer diagnostics and neurosurgical outcomes. Photoacoustic enabling devices (PEDs) were designed as attachments to two clinical ultrasound probes optimized for breast cancer diagnostics. PAI uses pulsed laser excitation to create transient heating (detected as an ultrasonic emission. These ultrasonic emissions are remotely sensed to construct noninvasive images with optical contrast at depths much greater than other optical modalities. The PEDs are feasible in terms of cost, user familiarity and flexibility for various applications. Another possible application for PAI is in assisting neurosurgeons treating aneurysms. Aneurysms are often treated by placing a clip to prevent blood flow into the aneurysm. However, this procedure has risks associated with damaging nearby vessels. One of the developed PEDs demonstrated the feasibility to three-dimensionally image tiny microvasculature (2.4mm) in a phantom model. The capability to use this during surgery would suggest decreasing the risks associated with these treatments. However, clinical ultrasound arrays are not clinically feasible for microsurgical applications due to their bulky size and linear scanning requirements for 3D. Therefore, capacitive

  11. Interventional multi-spectral photoacoustic imaging in laparoscopic surgery

    Science.gov (United States)

    Hill, Emma R.; Xia, Wenfeng; Nikitichev, Daniil I.; Gurusamy, Kurinchi; Beard, Paul C.; Hawkes, David J.; Davidson, Brian R.; Desjardins, Adrien E.

    2016-03-01

    Laparoscopic procedures can be an attractive treatment option for liver resection, with a shortened hospital stay and reduced morbidity compared to open surgery. One of the central challenges of this technique is visualisation of concealed structures within the liver, particularly the vasculature and tumourous tissue. As photoacoustic (PA) imaging can provide contrast for haemoglobin in real time, it may be well suited to guiding laparoscopic procedures in order to avoid inadvertent trauma to vascular structures. In this study, a clinical laparoscopic ultrasound probe was used to receive ultrasound for PA imaging and to obtain co-registered B-mode ultrasound (US) images. Pulsed excitation light was delivered to the tissue via a fibre bundle in dark-field mode. Monte Carlo simulations were performed to optimise the light delivery geometry for imaging targets at depths of 1 cm, 2 cm and 3 cm, and 3D-printed mounts were used to position the fibre bundle relative to the transducer according to the simulation results. The performance of the photoacoustic laparoscope system was evaluated with phantoms and tissue models. The clinical potential of hybrid PA/US imaging to improve the guidance of laparoscopic surgery is discussed.

  12. Dual plasmonic gold nanoparticles for multispectral photoacoustic imaging application

    Science.gov (United States)

    Raghavan, Vijay; Subhash, Hrebesh; Breathnach, Aedán.; Leahy, Martin; Dockery, Peter; Olivo, Malini

    2014-03-01

    Nanoparticle contrast agents for molecular targeted imaging have widespread interest in diagnostic applications with cellular resolution, specificity and selectivity for visualization and assessment of various disease processes. Of particular interest is gold nanoparticle owing to its tunability of the surface plasmon resonance (SPR) and its relative inertness. Here we present the synthesis of anisotropic multi-branched star shaped gold nanoparticles exhibiting dual-band plasmon absorption peaks and its application as a contrast agent for multispectral photoacoustic imaging. The transverse plasmon absorption peak of the synthesised dual plasmonic gold nanostar (DPGNS) was around 700 nm and that of longitudinal plasmon absorption in the longer wavelength region around 1050-1150 nm. Unlike most reported PA contrast agent with surface plasmon absorption in the range of 700 to 800 nm showing moderate tissue penetration, 1050-1200 nm range lies in the farther region of the optical window of biological tissue where scattering and the intrinsic optical extinction of endogenous chromophores is at its minimum. We also present a proof of principle demonstration of DPGNS as contrast agent for multispectral photoacoustic animal imaging. Our results show that DPGNS are promising for PA imaging with extended-depth imaging applications.

  13. Photoacoustic imaging using lock-in amplification and pulsed fiber lasers

    Science.gov (United States)

    Shi, Wei; Hajireza, Parsin; Zemp, Roger

    2016-03-01

    Photoacoustic (PA) imaging is a non-invasive, non-ionizing imaging technology with high optical contrast between blood and tissue, and with high sensitivity of hemoglobin concentration and oxygen saturation due to different optical absorption spectra resulting from different oxygenation of hemoglobin. Most PA imaging systems implement a nanosecond pulsed laser source as excitation source to induce PA signal, and rely on broadband amplifiers to record time-domain PA signals [1-6]. Some groups, however, have reported using modulated continuous-wave lasers as an excitation source for frequency-domain imaging [7-9]. Frequency-domain imaging offers the potential of lock-in amplification which has sensitivities as low as nV even in noise orders of magnitude higher than the signal. However, although modulated CW sources works for low cost and compact PA imaging, it does not satisfy thermal and stress confinement conditions required for optimal PA signal strength. Here, we investigate a PA methodology using pulsed fiber lasers as excitation laser source combined with lock-in amplification technology. For comparison, we also studied time-domain PA methodology. Phantom studies show that signal-to-noise ratio (SNR) obtained with frequency domain PA imaging is significantly more sensitive than that obtained using time-domain PA imaging when the laser pulse repetition rate (PRR) matches the bandwidth of ultrasound transducer. Therefore, high sensitive PA imaging technology using pulsed fiber laser sources with lock-in amplification may potentially greatly extend the depth of PA imaging.

  14. Real-time photoacoustic and ultrasound dual-modality imaging system facilitated with graphics processing unit and code parallel optimization.

    Science.gov (United States)

    Yuan, Jie; Xu, Guan; Yu, Yao; Zhou, Yu; Carson, Paul L; Wang, Xueding; Liu, Xiaojun

    2013-08-01

    Photoacoustic tomography (PAT) offers structural and functional imaging of living biological tissue with highly sensitive optical absorption contrast and excellent spatial resolution comparable to medical ultrasound (US) imaging. We report the development of a fully integrated PAT and US dual-modality imaging system, which performs signal scanning, image reconstruction, and display for both photoacoustic (PA) and US imaging all in a truly real-time manner. The back-projection (BP) algorithm for PA image reconstruction is optimized to reduce the computational cost and facilitate parallel computation on a state of the art graphics processing unit (GPU) card. For the first time, PAT and US imaging of the same object can be conducted simultaneously and continuously, at a real-time frame rate, presently limited by the laser repetition rate of 10 Hz. Noninvasive PAT and US imaging of human peripheral joints in vivo were achieved, demonstrating the satisfactory image quality realized with this system. Another experiment, simultaneous PAT and US imaging of contrast agent flowing through an artificial vessel, was conducted to verify the performance of this system for imaging fast biological events. The GPU-based image reconstruction software code for this dual-modality system is open source and available for download from http://sourceforge.net/projects/patrealtime.

  15. Imaging-guided photoacoustic drug release and synergistic chemo-photoacoustic therapy with paclitaxel-containing nanoparticles.

    Science.gov (United States)

    Zhong, Junping; Yang, Sihua; Wen, Liewei; Xing, Da

    2016-03-28

    Here, a novel triggered drug release modality was developed for oncotherapy. Paclitaxel (PTX), perfluorohexane (PFH) and gold nanorods (AuNRs) loaded nanoparticles (PTX-PAnP) were synthesized. Folic acid (FA) conjugated PTX-PAnP (PTX-PAnP-FA) could be selectively taken into folate receptor-overexpressed tumor cells. Upon pulsed laser irradiation, the PTX-PAnP-FA could be rapidly destructed because of the PFH vaporization, resulting in fast drug release, which induced apoptosis of cancer cells efficiently. Stimulated fragmentation of the PTX-PAnP-FA nanoparticles can facilitate multiple mechanisms such as bubble implosion, shockwave generation, and sonoporation that further enhance the therapeutic efficiency. The in vivo therapy study further confirmed this new approach resulted in efficient tumor suppression. The results demonstrate a unique drug release mechanism based on photoacoustic effect. It provides an all-in-one platform for photoacoustic image-guided drug release and synergistic chemo-photoacoustic therapy.

  16. Photoacoustic section imaging with an integrating cylindrical detector

    Science.gov (United States)

    Gratt, Sibylle; Passler, Klaus; Nuster, Robert; Paltauf, Guenther

    2011-07-01

    A piezoelectric detector with cylindrical shape for photoacoustic section imaging is characterized. This detector is larger than the imaging object in direction of the cylinder axis, giving rise to its integrating properties. Its focal volume has the shape of a slice and the acquisition of signals for one section image requires rotation of an object about an axis perpendicular to this slice. Image reconstruction from the signals requires the application of the inverse Radon transform. It is shown that implementing the Abel transform is a suitable step in data processing, allowing speeding up the data acquisition since the scanning angle can be reduced. The resolution of the detector was estimated in directions perpendicular and parallel to the detection plane. An upper limit for the out of plane resolution is given and section images of a zebra fish are shown.

  17. Photoacoustic imaging using genetically encoded reporters: a review

    Science.gov (United States)

    Brunker, Joanna; Yao, Junjie; Laufer, Jan; Bohndiek, Sarah E.

    2017-07-01

    Genetically encoded contrast in photoacoustic imaging (PAI) is complementary to the intrinsic contrast provided by endogenous absorbing chromophores such as hemoglobin. The use of reporter genes expressing absorbing proteins opens the possibility of visualizing dynamic cellular and molecular processes. This is an enticing prospect but brings with it challenges and limitations associated with generating and detecting different types of reporters. The purpose of this review is to compare existing PAI reporters and signal detection strategies, thereby offering a practical guide, particularly for the nonbiologist, to choosing the most appropriate reporter for maximum sensitivity in the biological and technological system of interest.

  18. Photoacoustic imaging of blood vessels with a double-ring sensor featuring a narrow angular aperture

    NARCIS (Netherlands)

    Kolkman, Roy G.M.; Hondebrink, Erwin; Steenbergen, Wiendelt; Leeuwen, van Ton G.; Mul, de Frits F.M.

    2004-01-01

    A photoacoustic double-ring sensor, featuring a narrow angular aperture, is developed for laser-induced photoacoustic imaging of blood vessels. An integrated optical fiber enables reflection-mode detection of ultrasonic waves. By using the cross-correlation between the signals detected by the two ri

  19. Multimodal photoacoustic and optical coherence tomography scanner using an all optical detection scheme for 3D morphological skin imaging.

    Science.gov (United States)

    Zhang, Edward Z; Povazay, Boris; Laufer, Jan; Alex, Aneesh; Hofer, Bernd; Pedley, Barbara; Glittenberg, Carl; Treeby, Bradley; Cox, Ben; Beard, Paul; Drexler, Wolfgang

    2011-08-01

    A noninvasive, multimodal photoacoustic and optical coherence tomography (PAT/OCT) scanner for three-dimensional in vivo (3D) skin imaging is described. The system employs an integrated, all optical detection scheme for both modalities in backward mode utilizing a shared 2D optical scanner with a field-of-view of ~13 × 13 mm(2). The photoacoustic waves were detected using a Fabry Perot polymer film ultrasound sensor placed on the surface of the skin. The sensor is transparent in the spectral range 590-1200 nm. This permits the photoacoustic excitation beam (670-680 nm) and the OCT probe beam (1050 nm) to be transmitted through the sensor head and into the underlying tissue thus providing a backward mode imaging configuration. The respective OCT and PAT axial resolutions were 8 and 20 µm and the lateral resolutions were 18 and 50-100 µm. The system provides greater penetration depth than previous combined PA/OCT devices due to the longer wavelength of the OCT beam (1050 nm rather than 829-870 nm) and by operating in the tomographic rather than the optical resolution mode of photoacoustic imaging. Three-dimensional in vivo images of the vasculature and the surrounding tissue micro-morphology in murine and human skin were acquired. These studies demonstrated the complementary contrast and tissue information provided by each modality for high-resolution 3D imaging of vascular structures to depths of up to 5 mm. Potential applications include characterizing skin conditions such as tumors, vascular lesions, soft tissue damage such as burns and wounds, inflammatory conditions such as dermatitis and other superficial tissue abnormalities.

  20. All-optically integrated multimodality imaging system: combined photoacoustic microscopy, optical coherence tomography, and fluorescence imaging

    Science.gov (United States)

    Chen, Zhongjiang; Yang, Sihua; Xing, Da

    2016-10-01

    We have developed a multimodality imaging system by optically integrating all-optical photoacoustic microscopy (AOPAM), optical coherence tomography (OCT) and fluorescence microscopy (FLM) to provide complementary information including optical absorption, optical back-scattering and fluorescence contrast of biological tissue. By sharing the same low-coherence Michelson interferometer, AOPAM and OCT could be organically optically combined to obtain the absorption and scattering information of the biological tissues. Also, owing to using the same laser source and objective lens, intrinsically registered photoacoustic and fluorescence signals are obtained to present the radiative and nonradiative transition process of absorption. Simultaneously photoacoustic angiography, tissue structure and fluorescence molecular in vivo images of mouse ear were acquired to demonstrate the capabilities of the optically integrated trimodality imaging system, which can present more information to study tumor angiogenesis, vasculature, anatomical structure and microenvironments in vivo.

  1. Super-resolution photoacoustic imaging through a scattering wall

    CERN Document Server

    Conkey, Donald B; Dove, Jacob D; Ju, Hengyi; Murray, Todd W; Piestun, Rafael

    2013-01-01

    Imaging through opaque, highly scattering walls is a long sought after capability with potential applications in a variety of fields. The use of wavefront shaping to compensate for scattering has brought a renewed interest as a potential solution to this problem. A key to the practicality of any imaging technique is the capability to focus light without direct access behind the scattering wall. Here, we address this problem using photoacoustic feedback for wavefront optimization. By combining the spatially non-uniform sensitivity of the ultrasound transducer to the generated photoacoustic waves with an evolutionary competition among optical modes, the speckle field develops a single, high intensity focus significantly smaller than the acoustic focus used for feedback. Notably, this method is not limited by the size of the absorber to form a sub-acoustic optical focus. We demonstrate imaging behind a scattering medium with up to ten times improvement in signal-to-noise ratio (SNR) and five to six times sub-aco...

  2. Photoacoustic imaging driven by an interstitial irradiation source

    Directory of Open Access Journals (Sweden)

    Trevor Mitcham

    2015-06-01

    Full Text Available Photoacoustic (PA imaging has shown tremendous promise in providing valuable diagnostic and therapy-monitoring information in select clinical procedures. Many of these pursued applications, however, have been relatively superficial due to difficulties with delivering light deep into tissue. To address this limitation, this work investigates generating a PA image using an interstitial irradiation source with a clinical ultrasound (US system, which was shown to yield improved PA signal quality at distances beyond 13 mm and to provide improved spectral fidelity. Additionally, interstitially driven multi-wavelength PA imaging was able to provide accurate spectra of gold nanoshells and deoxyhemoglobin in excised prostate and liver tissue, respectively, and allowed for clear visualization of a wire at 7 cm in excised liver. This work demonstrates the potential of using a local irradiation source to extend the depth capabilities of future PA imaging techniques for minimally invasive interventional radiology procedures.

  3. Hyperspectral vibrational photoacoustic imaging of lipids and collagen

    Science.gov (United States)

    Wang, Pu; Wang, Ping; Wang, Han-Wei; Cheng, Ji-Xin

    2012-02-01

    The recently developed vibrational photoacoustic (VPA) microscopy allows bond-selective imaging of deep tissues by taking advantage of intrinsic contrast from harmonic vibration of C-H bonds. Due to the spectral similarity of molecules in the overtone vibration region, the compositional information is not available from VPA images acquired by single wavelength excitation. Here we demonstrate that lipids and collagen, two critical markers in many kinds of diseases, can be distinguished by hyperspectral VPA imaging. A phantom consisted of rat tail tendon (collagen) and fat tissue (lipids) was constructed. Wavelengths between 1650 and 1850 nm were scanned to excite the first overtone/combination vibration of C-H bond. B-scan hyperspectral VPA images, in which each pixel contains a spectrum, was analyzed by a Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS) algorism to recover the spatial distribution of two chemical components in the phantom.

  4. Multimodal non-contact photoacoustic and OCT imaging using a fiber based approach

    Science.gov (United States)

    Berer, T.; Leiss-Holzinger, E.; Hochreiner, A.; Bauer-Marschallinger, J.; Leitner, M.; Buchsbaum, A.

    2014-03-01

    In this paper we present multimodal non-contact photoacoustic and OCT imaging. Photoacoustic signals are acquired remotely on the surface of a specimen with a Mach-Zehnder interferometer. The interferometer is realized in a fiberoptic network using a fiber laser at 1550nm as source. In the same fiber-optic network a spectral-domain OCT system is realized. The OCT system utilizes a superluminescent diode at 1325nm as light source; imaging data are acquired using a spectrometer with an InGaAs line array. Light from the fiber laser and the superluminescent diode are multiplexed into one fiber and the same objective is used for both imaging modalities. Reflected light is demultiplexed and guided to the respective imaging systems. We demonstrate the photoacoustic and OCT imaging modalities on different phantom samples. Finally, we show multimodal imaging with both modalities simultaneously. The resulting photoacoustic and OCT images match perfectly.

  5. Comprehensive vascular imaging using optical coherence tomography-based angiography and photoacoustic tomography

    Science.gov (United States)

    Zabihian, Behrooz; Chen, Zhe; Rank, Elisabet; Sinz, Christoph; Bonesi, Marco; Sattmann, Harald; Ensher, Jason; Minneman, Michael P.; Hoover, Erich; Weingast, Jessika; Ginner, Laurin; Leitgeb, Rainer; Kittler, Harald; Zhang, Edward; Beard, Paul; Drexler, Wolfgang; Liu, Mengyang

    2016-09-01

    Studies have proven the relationship between cutaneous vasculature abnormalities and dermatological disorders, but to image vasculature noninvasively in vivo, advanced optical imaging techniques are required. In this study, we imaged a palm of a healthy volunteer and three subjects with cutaneous abnormalities with photoacoustic tomography (PAT) and optical coherence tomography with angiography extension (OCTA). Capillaries in the papillary dermis that are too small to be discerned with PAT are visualized with OCTA. From our results, we speculate that the PA signal from the palm is mostly from hemoglobin in capillaries rather than melanin, knowing that melanin concentration in volar skin is significantly smaller than that in other areas of the skin. We present for the first time OCTA images of capillaries along with the PAT images of the deeper vessels, demonstrating the complementary effective imaging depth range and the visualization capabilities of PAT and OCTA for imaging human skin in vivo. The proposed imaging system in this study could significantly improve treatment monitoring of dermatological diseases associated with cutaneous vasculature abnormalities.

  6. Photoacoustic tomography of human hepatic malignancies using intraoperative indocyanine green fluorescence imaging.

    Directory of Open Access Journals (Sweden)

    Akinori Miyata

    Full Text Available Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10 under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases, photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical

  7. Photoacoustic tomography of human hepatic malignancies using intraoperative indocyanine green fluorescence imaging.

    Science.gov (United States)

    Miyata, Akinori; Ishizawa, Takeaki; Kamiya, Mako; Shimizu, Atsushi; Kaneko, Junichi; Ijichi, Hideaki; Shibahara, Junji; Fukayama, Masashi; Midorikawa, Yutaka; Urano, Yasuteru; Kokudo, Norihiro

    2014-01-01

    Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed

  8. Non-contact biomedical photoacoustic and ultrasound imaging.

    Science.gov (United States)

    Rousseau, Guy; Gauthier, Bruno; Blouin, Alain; Monchalin, Jean-Pierre

    2012-06-01

    The detection of ultrasound in photoacoustic tomography (PAT) usually relies on ultrasonic transducers in contact with the biological tissue through a coupling medium. This is a major drawback for important potential applications such as surgery. Here we report the use of a remote optical method, derived from industrial laser-ultrasonics, to detect ultrasound in tissues. This approach enables non-contact PAT (NCPAT) without exceeding laser exposure safety limits. The sensitivity of the method is based on the use of suitably shaped detection laser pulses and a confocal Fabry-Perot interferometer in differential configuration. Reliable image reconstruction is obtained by measuring remotely the surface profile of the tissue with an optical coherence tomography system. The proposed method also allows non-contact ultrasound imaging (US) by applying a second reconstruction algorithm to the data acquired for NCPAT. Endogenous and exogenous inclusions exhibiting optical and acoustic contrasts were detected ex vivo in chicken breast and calf brain specimens. Inclusions down to 0.3 mm in size were detected at depths exceeding 1 cm. The method could expand the scope of photoacoustic and US to in-vivo biomedical applications where contact is impractical.

  9. Non-contact biomedical photoacoustic and ultrasound imaging

    Science.gov (United States)

    Rousseau, Guy; Gauthier, Bruno; Blouin, Alain; Monchalin, Jean-Pierre

    2012-06-01

    The detection of ultrasound in photoacoustic tomography (PAT) usually relies on ultrasonic transducers in contact with the biological tissue through a coupling medium. This is a major drawback for important potential applications such as surgery. Here we report the use of a remote optical method, derived from industrial laser-ultrasonics, to detect ultrasound in tissues. This approach enables non-contact PAT (NCPAT) without exceeding laser exposure safety limits. The sensitivity of the method is based on the use of suitably shaped detection laser pulses and a confocal Fabry-Perot interferometer in differential configuration. Reliable image reconstruction is obtained by measuring remotely the surface profile of the tissue with an optical coherence tomography system. The proposed method also allows non-contact ultrasound imaging (US) by applying a second reconstruction algorithm to the data acquired for NCPAT. Endogenous and exogenous inclusions exhibiting optical and acoustic contrasts were detected ex vivo in chicken breast and calf brain specimens. Inclusions down to 0.3 mm in size were detected at depths exceeding 1 cm. The method could expand the scope of photoacoustic and US to in-vivo biomedical applications where contact is impractical.

  10. Coregistered photoacoustic and ultrasound imaging and classification of ovarian cancer: ex vivo and in vivo studies

    Science.gov (United States)

    Salehi, Hassan S.; Li, Hai; Merkulov, Alex; Kumavor, Patrick D.; Vavadi, Hamed; Sanders, Melinda; Kueck, Angela; Brewer, Molly A.; Zhu, Quing

    2016-04-01

    Most ovarian cancers are diagnosed at advanced stages due to the lack of efficacious screening techniques. Photoacoustic tomography (PAT) has a potential to image tumor angiogenesis and detect early neovascular changes of the ovary. We have developed a coregistered PAT and ultrasound (US) prototype system for real-time assessment of ovarian masses. Features extracted from PAT and US angular beams, envelopes, and images were input to a logistic classifier and a support vector machine (SVM) classifier to diagnose ovaries as benign or malignant. A total of 25 excised ovaries of 15 patients were studied and the logistic and SVM classifiers achieved sensitivities of 70.4 and 87.7%, and specificities of 95.6 and 97.9%, respectively. Furthermore, the ovaries of two patients were noninvasively imaged using the PAT/US system before surgical excision. By using five significant features and the logistic classifier, 12 out of 14 images (86% sensitivity) from a malignant ovarian mass and all 17 images (100% specificity) from a benign mass were accurately classified; the SVM correctly classified 10 out of 14 malignant images (71% sensitivity) and all 17 benign images (100% specificity). These initial results demonstrate the clinical potential of the PAT/US technique for ovarian cancer diagnosis.

  11. Development of human serum albumin conjugated with near-infrared dye for photoacoustic tumor imaging

    Science.gov (United States)

    Kanazaki, Kengo; Sano, Kohei; Makino, Akira; Takahashi, Atsushi; Deguchi, Jun; Ohashi, Manami; Temma, Takashi; Ono, Masahiro; Saji, Hideo

    2014-09-01

    Photoacoustic (PA) imaging has emerged as a noninvasive diagnostic method which detects ultrasonic waves thermoelastically induced by optical absorbers irradiated with laser. For tumor diagnosis, PA contrast agent has been proposed to enhance the PA effect for detecting tumors sensitively. Here, we prepared a human serum albumin (HSA) conjugated with indocyanine green (ICG) as a PA contrast agent allowing enhanced permeability and retention effect for sensitive tumor imaging. The feasibility of PA imaging with HSA-ICG to detect allografted tumors was evaluated in tumor-bearing mice. In vivo fluorescence imaging and radiolabeled biodistribution study showed that the biodistribution dramatically changed as the number of ICG bound to HSA increased, and the maximum accumulation of ICG was achieved when around three ICG molecules were loaded on an HSA. In vivo PA imaging demonstrated a tumor-selective and dose-dependent increase of PA signal intensity in mice injected with HSA-ICG (R2=0.88, 387% increase for HSA-ICG, 104 nmol ICG). In conclusion, HSA-ICG clearly visualized the allografted tumors with high tumor-to-background ratios having high quantitative and spatial resolution for the sensitive PA imaging of tumors. HSA-ICG could be useful as a favorable contrast agent for PA tumor imaging for the management of cancer.

  12. Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines

    Science.gov (United States)

    Zhang, Yumiao; Jeon, Mansik; Rich, Laurie J.; Hong, Hao; Geng, Jumin; Zhang, Yin; Shi, Sixiang; Barnhart, Todd E.; Alexandridis, Paschalis; Huizinga, Jan D.; Seshadri, Mukund; Cai, Weibo; Kim, Chulhong; Lovell, Jonathan F.

    2014-08-01

    There is a need for safer and improved methods for non-invasive imaging of the gastrointestinal tract. Modalities based on X-ray radiation, magnetic resonance and ultrasound suffer from limitations with respect to safety, accessibility or lack of adequate contrast. Functional intestinal imaging of dynamic gut processes has not been practical using existing approaches. Here, we report the development of a family of nanoparticles that can withstand the harsh conditions of the stomach and intestine, avoid systemic absorption, and provide good optical contrast for photoacoustic imaging. The hydrophobicity of naphthalocyanine dyes was exploited to generate purified ∼20 nm frozen micelles, which we call nanonaps, with tunable and large near-infrared absorption values (>1,000). Unlike conventional chromophores, nanonaps exhibit non-shifting spectra at ultrahigh optical densities and, following oral administration in mice, passed safely through the gastrointestinal tract. Non-invasive, non-ionizing photoacoustic techniques were used to visualize nanonap intestinal distribution with low background and remarkable resolution, and enabled real-time intestinal functional imaging with ultrasound co-registration. Positron emission tomography following seamless nanonap radiolabelling allowed complementary whole-body imaging.

  13. Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice

    Science.gov (United States)

    Pu, Kanyi; Shuhendler, Adam J.; Jokerst, Jesse V.; Mei, Jianguo; Gambhir, Sanjiv S.; Bao, Zhenan; Rao, Jianghong

    2014-03-01

    Photoacoustic imaging holds great promise for the visualization of physiology and pathology at the molecular level with deep tissue penetration and fine spatial resolution. To fully utilize this potential, photoacoustic molecular imaging probes have to be developed. Here, we introduce near-infrared light absorbing semiconducting polymer nanoparticles as a new class of contrast agents for photoacoustic molecular imaging. These nanoparticles can produce a stronger signal than the commonly used single-walled carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph-node photoacoustic mapping in living mice at a low systemic injection mass. Furthermore, the semiconducting polymer nanoparticles possess high structural flexibility, narrow photoacoustic spectral profiles and strong resistance to photodegradation and oxidation, enabling the development of the first near-infrared ratiometric photoacoustic probe for in vivo real-time imaging of reactive oxygen species--vital chemical mediators of many diseases. These results demonstrate semiconducting polymer nanoparticles to be an ideal nanoplatform for developing photoacoustic molecular probes.

  14. Nonlinear photoacoustic microscopy via a loss modulation technique: from detection to imaging.

    Science.gov (United States)

    Lai, Yu-Hung; Lee, Szu-Yu; Chang, Chieh-Feng; Cheng, Yu-Hsiang; Sun, Chi-Kuang

    2014-01-13

    In order to achieve high-resolution deep-tissue imaging, multi-photon fluorescence microscopy and photoacoustic tomography had been proposed in the past two decades. However, combining the advantages of these two imaging systems to achieve optical-spatial resolution with an ultrasonic-penetration depth is still a field with challenges. In this paper, we investigate the detection of the two-photon photoacoustic ultrasound, and first demonstrate background-free two-photon photoacoustic imaging in a phantom sample. To generate the background-free two-photon photoacoustic signals, we used a high-repetition rate femtosecond laser to induce narrowband excitation. Combining a loss modulation technique, we successfully created a beating on the light intensity, which not only provides pure sinusoidal modulation, but also ensures the spectrum sensitivity and frequency selectivity. By using the lock-in detection, the power dependency experiment validates our methodology to frequency-select the source of the nonlinearity. This ensures our capability of measuring the background-free two-photon photoacoustic waves by detecting the 2nd order beating signal directly. Furthermore, by mixing the nanoparticles and fluorescence dyes as contrast agents, the two-photon photoacoustic signal was found to be enhanced and detected. In the end, we demonstrate subsurface two-photon photoacoustic bio-imaging based on the optical scanning mechanism inside phantom samples.

  15. Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice.

    Science.gov (United States)

    Pu, Kanyi; Shuhendler, Adam J; Jokerst, Jesse V; Mei, Jianguo; Gambhir, Sanjiv S; Bao, Zhenan; Rao, Jianghong

    2014-03-01

    Photoacoustic imaging holds great promise for the visualization of physiology and pathology at the molecular level with deep tissue penetration and fine spatial resolution. To fully utilize this potential, photoacoustic molecular imaging probes have to be developed. Here, we introduce near-infrared light absorbing semiconducting polymer nanoparticles as a new class of contrast agents for photoacoustic molecular imaging. These nanoparticles can produce a stronger signal than the commonly used single-walled carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph-node photoacoustic mapping in living mice at a low systemic injection mass. Furthermore, the semiconducting polymer nanoparticles possess high structural flexibility, narrow photoacoustic spectral profiles and strong resistance to photodegradation and oxidation, enabling the development of the first near-infrared ratiometric photoacoustic probe for in vivo real-time imaging of reactive oxygen species--vital chemical mediators of many diseases. These results demonstrate semiconducting polymer nanoparticles to be an ideal nanoplatform for developing photoacoustic molecular probes.

  16. Photoacoustic image reconstruction: material detection and acoustical heterogeneities

    Science.gov (United States)

    Schoeder, S.; Kronbichler, M.; Wall, W. A.

    2017-05-01

    The correct consideration of acoustical heterogeneities in the context of photoacoustic image reconstruction is an open topic. In this publication a physically motivated algorithm is proposed that reconstructs the optical absorption and diffusion coefficients using a gradient-based scheme. The simultaneous reconstruction of both material properties allows for a subsequent material identification and an accordant update of the acoustical material properties. The algorithm is general in terms of illumination scenarios, detection geometries and applications. No prior knowledge on material distributions needs to be provided, only expected materials have to be specified. Numerical experiments are performed to gain insight into the complex inverse problem and to validate the proposed method. Results show that acoustical heterogeneities are correctly detected improving the optical images.

  17. Speed-of-sound compensated photoacoustic tomography for accurate imaging

    CERN Document Server

    Jose, Jithin; Steenbergen, Wiendelt; Slump, Cornelis H; van Leeuwen, Ton G; Manohar, Srirang

    2012-01-01

    In most photoacoustic (PA) measurements, variations in speed-of-sound (SOS) of the subject are neglected under the assumption of acoustic homogeneity. Biological tissue with spatially heterogeneous SOS cannot be accurately reconstructed under this assumption. We present experimental and image reconstruction methods with which 2-D SOS distributions can be accurately acquired and reconstructed, and with which the SOS map can be used subsequently to reconstruct highly accurate PA tomograms. We begin with a 2-D iterative reconstruction approach in an ultrasound transmission tomography (UTT) setting, which uses ray refracted paths instead of straight ray paths to recover accurate SOS images of the subject. Subsequently, we use the SOS distribution in a new 2-D iterative approach, where refraction of rays originating from PA sources are accounted for in accurately retrieving the distribution of these sources. Both the SOS reconstruction and SOS-compensated PA reconstruction methods utilize the Eikonal equation to m...

  18. All-optical photoacoustic imaging and detection of early-stage dental caries

    Science.gov (United States)

    Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

    2015-02-01

    Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

  19. Development of catheters for combined intravascular ultrasound and photoacoustic imaging

    Science.gov (United States)

    Karpiouk, Andrei B.; Wang, Bo; Emelianov, Stanislav Y.

    2009-02-01

    Coronary atherosclerosis is a complex disease accompanied by the development of plaques in the arterial wall. Since the vulnerability of the plaques depends on their composition, the appropriate treatment of the arteriosclerosis requires a reliable characterization of the plaques' geometry and content. The intravascular ultrasound (IVUS) imaging is capable of providing structural details of the plaques as well as some functional information. In turn, more functional information about the same plaques can be obtained from intravascular photoacoustic (IVPA) images since the optical properties of the plaque's components differ from that of their environment. The combined IVUS/IVPA imaging is capable of simultaneously detecting and differentiating the plaques, thus determining their vulnerability. The potential of combined IVUS/IVPA imaging has already been demonstrated in phantoms and ex-vivo experiments. However, for in-vivo or clinical imaging, an integrated IVUS/IVPA catheter is required. In this paper, we introduce two prototypes of integrated IVUS/IVPA catheters for in-vivo imaging based on a commercially available single-element IVUS imaging catheter. The light delivery systems are developed using multimode optical fibers with custom-designed distal tips. Both prototypes were tested and compared using an arterial mimicking phantom. The advantages and limitations of both designs are discussed. Overall, the results of our studies suggest that both designs of integrated IVUS/IVPA catheter have a potential for in-vivo IVPA/IVUS imaging of atherosclerotic plaques.

  20. Family of enhanced photoacoustic imaging agents for high-sensitivity and multiplexing studies in living mice.

    Science.gov (United States)

    de la Zerda, Adam; Bodapati, Sunil; Teed, Robert; May, Salomón Y; Tabakman, Scott M; Liu, Zhuang; Khuri-Yakub, Butrus T; Chen, Xiaoyuan; Dai, Hongjie; Gambhir, Sanjiv S

    2012-06-26

    Photoacoustic imaging is a unique modality that overcomes to a great extent the resolution and depth limitations of optical imaging while maintaining relatively high contrast. However, since many diseases will not manifest an endogenous photoacoustic contrast, it is essential to develop exogenous photoacoustic contrast agents that can target diseased tissue(s). Here we present a family of novel photoacoustic contrast agents that are based on the binding of small optical dyes to single-walled carbon nanotubes (SWNT-dye). We synthesized five different SWNT-dye contrast agents using different optical dyes, creating five "flavors" of SWNT-dye nanoparticles. In particular, SWNTs that were coated with either QSY(21) (SWNT-QSY) or indocyanine green (SWNT-ICG) exhibited over 100-times higher photoacoustic contrast in living animals compared to plain SWNTs, leading to subnanomolar sensitivities. We then conjugated the SWNT-dye conjugates with cyclic Arg-Gly-Asp peptides to molecularly target the α(v)β(3) integrin, which is associated with tumor angiogenesis. Intravenous administration of these tumor-targeted imaging agents to tumor-bearing mice showed significantly higher photoacoustic signal in the tumor than in mice injected with the untargeted contrast agent. Finally, we were able to spectrally separate the photoacoustic signals of SWNT-QSY and SWNT-ICG in living animals injected subcutaneously with both particles in the same location, opening the possibility for multiplexing in vivo studies.

  1. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes.

    Science.gov (United States)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-06

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  2. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes

    Science.gov (United States)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  3. Frequency-domain photoacoustic phased array probe for biomedical imaging applications.

    Science.gov (United States)

    Telenkov, Sergey; Alwi, Rudolf; Mandelis, Andreas; Worthington, Arthur

    2011-12-01

    We report the development of a frequency-domain biomedical photoacoustic imaging system that utilizes a continuous-wave laser source with a custom intensity modulation pattern, ultrasonic phased array for signal detection, and processing coupled with a beam-forming algorithm for reconstruction of photoacoustic correlation images. Sensitivity to optical contrast was demonstrated using tissue-mimicking phantoms and in-vivo tissue samples.

  4. Photoacoustic and ultrasound dual-modality imaging for inflammatory arthritis

    Science.gov (United States)

    Xu, Guan; Chamberland, David; Girish, Gandikota; Wang, Xueding

    2014-03-01

    Arthritis is a leading cause of disability, affecting 46 million of the population in the U.S. Rendering new optical contrast in articular tissues at high spatial and temporal resolution, emerging photoacoustic imaging (PAI) combined with more established ultrasound (US) imaging technologies provides unique opportunities for diagnosis and treatment monitoring of inflammatory arthritis. In addition to capturing peripheral bone and soft tissue images, PAI has the capability to quantify hemodynamic properties including regional blood oxygenation and blood volume, both abnormal in synovial tissues affected by arthritis. Therefore, PAI, especially when performed together with US, should be of considerable help for further understanding the pathophysiology of arthritis as well as assisting in therapeutic decisions, including assessing the efficacy of new pharmacological therapies. In this paper, we will review our recent work on the development of PAI for application to the diagnostic imaging and therapeutic monitoring of inflammatory arthritis. We will present the imaging results from a home-built imaging system and another one based on a commercial US. The performance of PAI in evaluating pharmacological therapy on animal model of arthritis will be shown. Moreover, our resent work on PAI and US dual-modality imaging of human peripheral joints in vivo will also be presented.

  5. Visualization of tumor-related blood vessels in human breast by photoacoustic imaging system with a hemispherical detector array

    Science.gov (United States)

    Toi, M.; Asao, Y.; Matsumoto, Y.; Sekiguchi, H.; Yoshikawa, A.; Takada, M.; Kataoka, M.; Endo, T.; Kawaguchi-Sakita, N.; Kawashima, M.; Fakhrejahani, E.; Kanao, S.; Yamaga, I.; Nakayama, Y.; Tokiwa, M.; Torii, M.; Yagi, T.; Sakurai, T.; Togashi, K.; Shiina, T.

    2017-01-01

    Noninvasive measurement of the distribution and oxygenation state of hemoglobin (Hb) inside the tissue is strongly required to analyze the tumor-associated vasculatures. We developed a photoacoustic imaging (PAI) system with a hemispherical-shaped detector array (HDA). Here, we show that PAI system with HDA revealed finer vasculature, more detailed blood-vessel branching structures, and more detailed morphological vessel characteristics compared with MRI by the use of breast shape deformation of MRI to PAI and their fused image. Morphologically abnormal peritumoral blood vessel features, including centripetal photoacoustic signals and disruption or narrowing of vessel signals, were observed and intratumoral signals were detected by PAI in breast cancer tissues as a result of the clinical study of 22 malignant cases. Interestingly, it was also possible to analyze anticancer treatment-driven changes in vascular morphological features and function, such as improvement of intratumoral blood perfusion and relevant changes in intravascular hemoglobin saturation of oxygen. This clinical study indicated that PAI appears to be a promising tool for noninvasive analysis of human blood vessels and may contribute to improve cancer diagnosis. PMID:28169313

  6. Photo-acoustic imaging of coronary arteries with polymer optical fibers

    DEFF Research Database (Denmark)

    Woyessa, Getinet; Broadway, Christian; Lamela, Horacio

    2014-01-01

    less blood to flow through the arteries hence the heart muscle can't get the blood or oxygen it needs. Worse, a plaque can suddenly rupture. As a result, blood clot over the rapture and suddenly cut off the hearts’ blood supply, causing permanent heart dama ge or stroke [1]. Photo-acoustic imaging...... is useful for detection of plaques for prevention of rupture of vulnerable plaques. These vulnerable plaques in the arteries can be distinguished using photo-acoustic imaging based on lipid accumulation with different characteristics of optical absorption. The basic principle of this imaging technique...... relies on exposing lipids to a laser capable of inducing photo-acoustic effect and a sensor affected by the induced pressure. Polymer optical fibre Bragg grating and Fabry-Perot sensors will be developed for detection of photo-acoustic signal in collaboration of Optoelectronics and Laser technology group...

  7. Mapping lipid and collagen by multispectral photoacoustic imaging of chemical bond vibration

    Science.gov (United States)

    Wang, Pu; Wang, Ping; Wang, Han-Wei; Cheng, Ji-Xin

    2012-09-01

    Photoacoustic microscopy using vibrational overtone absorption as a contrast mechanism allows bond-selective imaging of deep tissues. Due to the spectral similarity of molecules in the region of overtone vibration, it is difficult to interrogate chemical components using photoacoustic signal at single excitation wavelength. Here we demonstrate that lipids and collagen, two critical markers for many kinds of diseases, can be distinguished by multispectral photoacoustic imaging of the first overtone of C-H bond. A phantom consisting of rat-tail tendon and fat was constructed to demonstrate this technique. Wavelengths between 1650 and 1850 nm were scanned to excite both the first overtone and combination bands of C-H bonds. B-scan multispectral photoacoustic images, in which each pixel contains a spectrum, were analyzed by a multivariate curve resolution-alternating least squares algorithm to recover the spatial distribution of collagen and lipids in the phantom.

  8. Amplified photoacoustic performance and enhanced photothermal stability of reduced graphene oxide coated gold nanorods for sensitive photoacoustic imaging.

    Science.gov (United States)

    Moon, Hyungwon; Kumar, Dinesh; Kim, Haemin; Sim, Changbeom; Chang, Jin-Ho; Kim, Jung-Mu; Kim, Hyuncheol; Lim, Dong-Kwon

    2015-03-24

    We report a strongly amplified photoacoustic (PA) performance of the new functional hybrid material composed of reduced graphene oxide and gold nanorods. Due to the excellent NIR light absorption properties of the reduced graphene oxide coated gold nanorods (r-GO-AuNRs) and highly efficient heat transfer process through the reduced graphene oxide layer, r-GO-AuNRs exhibit excellent photothermal stability and significantly higher photoacoustic amplitudes than those of bare-AuNRs, nonreduced graphene oxide coated AuNRs (GO-AuNRs), or silica-coated AuNR, as demonstrated in both in vitro and in vivo systems. The linear response of PA amplitude from reduced state controlled GO on AuNR indicates the critical role of GO for a strong photothermal effect of r-GO-AuNRs. Theoretical studies with finite-element-method lab-based simulation reveal that a 4 times higher magnitude of the enhanced electromagnetic field around r-GO-AuNRs can be generated compared with bare AuNRs or GO-AuNRs. Furthermore, the r-GO-AuNRs are expected to be a promising deep-tissue imaging probe because of extraordinarily high PA amplitudes in the 4-11 MHz operating frequency of an ultrasound transducer. Therefore, the r-GO-AuNRs can be a useful imaging probe for highly sensitive photoacoustic images and NIR sensitive therapeutics based on a strong photothermal effect.

  9. Photoacoustic imaging of chemotherapy-induced apoptosis in squamous cell carcinoma

    Science.gov (United States)

    Yang, Quihong; Cui, Huizhong; Cai, Shuang; Yang, Xinmai; Forrest, M. Laird

    2012-02-01

    Anti-cancer drugs typically exert their pharmacological effect on tumors by inducing apoptosis, or programmed cell death, within the cancer cells, with PCD occurring as soon as 4 hours after treatment. Detection of apoptosis in patients could decisively report a response to treatment days or even weeks before MRI, CAT, and ultrasound indicate morphological changes in the tumor. Here we developed a novel near-infrared dye based imaging probe to directly detect apoptosis with high specificity in cancer cells by utilizing a non-invasive photoacoustic imaging technique. Nude mice bearing head and neck tumors received cisplatin chemotherapy were imaged by PAI after tail vein injection of the contrast agent. In vivo PAI indicated a strong apoptotic response to chemotherapy on the peripheral margins of tumors, whereas untreated controls showed no contrast enhancement by PAI. The apoptotic status of the mouse tumor tissue was verified by immunohistochemical techniques staining for cleaved caspase-3 p11 subunit. The results demonstrated the potential of this imaging probe to guide the evaluation of chemotherapy treatment.

  10. Ultrasound and photoacoustic imaging to monitor ocular stem cell delivery and tissue regeneration (Conference Presentation)

    Science.gov (United States)

    Kubelick, Kelsey; Snider, Eric; Yoon, Heechul; Ethier, C. Ross; Emelianov, Stanislav Y.

    2017-03-01

    Glaucoma is associated with dysfunction of the trabecular meshwork (TM), a fluid drainage tissue in the anterior eye. A promising treatment involves delivery of stem cells to the TM to restore tissue function. Currently histology is the gold standard for tracking stem cell delivery and differentiation. To expedite clinical translation, non-invasive longitudinal monitoring in vivo is desired. Our current research explores a technique combining ultrasound (US) and photoacoustic (PA) imaging to track mesenchymal stem cells (MSCs) after intraocular injection. Adipose-derived MSCs were incubated with gold nanospheres to label cells (AuNS-MSCs) for PA imaging. Successful labeling was first verified with in vitro phantom studies. Next, MSC delivery was imaged ex vivo in porcine eyes, while intraocular pressure was hydrostatically clamped to maintain a physiological flow rate through the TM. US/PA imaging was performed before, during, and after AuNS-MSC delivery. Additionally, spectroscopic PA imaging was implemented to isolate PA signals from AuNS-MSCs. In vitro cell imaging showed AuNS-MSCs produce strong PA signals, suggesting that MSCs can be tracked using PA imaging. While the cornea, sclera, iris, and TM region can be visualized with US imaging, pigmented tissues also produce PA signals. Both modalities provide valuable anatomical landmarks for MSC localization. During delivery, PA imaging can visualize AuNS-MSC motion and location, creating a unique opportunity to guide ocular cell delivery. Lastly, distinct spectral signatures of AuNS-MSCs allow unmixing, with potential for quantitative PA imaging. In conclusion, results show proof-of-concept for monitoring MSC ocular delivery, raising opportunities for in vivo image-guided cell delivery.

  11. Precise diagnosis in different scenarios using photoacoustic and fluorescence imaging with dual-modality nanoparticles

    Science.gov (United States)

    Peng, Dong; Du, Yang; Shi, Yiwen; Mao, Duo; Jia, Xiaohua; Li, Hui; Zhu, Yukun; Wang, Kun; Tian, Jie

    2016-07-01

    Photoacoustic imaging and fluorescence molecular imaging are emerging as important research tools for biomedical studies. Photoacoustic imaging offers both strong optical absorption contrast and high ultrasonic resolution, and fluorescence molecular imaging provides excellent superficial resolution, high sensitivity, high throughput, and the ability for real-time imaging. Therefore, combining the imaging information of both modalities can provide comprehensive in vivo physiological and pathological information. However, currently there are limited probes available that can realize both fluorescence and photoacoustic imaging, and advanced biomedical applications for applying this dual-modality imaging approach remain underexplored. In this study, we developed a dual-modality photoacoustic-fluorescence imaging nanoprobe, ICG-loaded Au@SiO2, which was uniquely designed, consisting of gold nanorod cores and indocyanine green with silica shell spacer layers to overcome fluorophore quenching. This nanoprobe was examined by both PAI and FMI for in vivo imaging on tumor and ischemia mouse models. Our results demonstrated that the nanoparticles can specifically accumulate at the tumor and ischemic areas and be detected by both imaging modalities. Moreover, this dual-modality imaging strategy exhibited superior advantages for a precise diagnosis in different scenarios. The new nanoprobe with the dual-modality imaging approach holds great potential for diagnosis and stage classification of tumor and ischemia related diseases.Photoacoustic imaging and fluorescence molecular imaging are emerging as important research tools for biomedical studies. Photoacoustic imaging offers both strong optical absorption contrast and high ultrasonic resolution, and fluorescence molecular imaging provides excellent superficial resolution, high sensitivity, high throughput, and the ability for real-time imaging. Therefore, combining the imaging information of both modalities can provide

  12. Photoacoustic imaging for transvascular drug delivery to the rat brain

    Science.gov (United States)

    Watanabe, Ryota; Sato, Shunichi; Tsunoi, Yasuyuki; Kawauchi, Satoko; Takemura, Toshiya; Terakawa, Mitsuhiro

    2015-03-01

    Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal characteristics of EB that was transvascularly delivered to the target tissue in the brain.

  13. Polymer-encapsulated organic nanoparticles for fluorescence and photoacoustic imaging.

    Science.gov (United States)

    Li, Kai; Liu, Bin

    2014-09-21

    Polymer encapsulated organic nanoparticles have recently attracted increasing attention in the biomedical field because of their unique optical properties, easy fabrication and outstanding performance as imaging and therapeutic agents. Of particular importance is the polymer encapsulated nanoparticles containing conjugated polymers (CP) or fluorogens with aggregation induced emission (AIE) characteristics as the core, which have shown significant advantages in terms of tunable brightness, superb photo- and physical stability, good biocompatibility, potential biodegradability and facile surface functionalization. In this review, we summarize the latest advances in the development of polymer encapsulated CP and AIE fluorogen nanoparticles, including preparation methods, material design and matrix selection, nanoparticle fabrication and surface functionalization for fluorescence and photoacoustic imaging. We also discuss their specific applications in cell labeling, targeted in vitro and in vivo imaging, blood vessel imaging, cell tracing, inflammation monitoring and molecular imaging. We specially focus on strategies to fine-tune the nanoparticle property (e.g. size and fluorescence quantum yield) through precise engineering of the organic cores and careful selection of polymer matrices. The review also highlights the merits and limitations of these nanoparticles as well as strategies used to overcome the limitations. The challenges and perspectives for the future development of polymer encapsulated organic nanoparticles are also discussed.

  14. Quantitative ultrasound and photoacoustic imaging for the assessment of vascular parameters

    CERN Document Server

    Meiburger, Kristen M

    2017-01-01

    This book describes the development of quantitative techniques for ultrasound and photoacoustic imaging in the assessment of architectural and vascular parameters. It presents morphological vascular research based on the development of quantitative imaging techniques for the use of clinical B-mode ultrasound images, and preclinical architectural vascular investigations on quantitative imaging techniques for ultrasounds and photoacoustics. The book is divided into two main parts, the first of which focuses on the development and validation of quantitative techniques for the assessment of vascular morphological parameters that can be extracted from B-mode ultrasound longitudinal images of the common carotid artery. In turn, the second part highlights quantitative imaging techniques for assessing the architectural parameters of vasculature that can be extracted from 3D volumes, using both contrast-enhanced ultrasound (CEUS) imaging and photoacoustic imaging without the addition of any contrast agent. Sharing and...

  15. Time Reversal Reconstruction Algorithm Based on PSO Optimized SVM Interpolation for Photoacoustic Imaging

    Directory of Open Access Journals (Sweden)

    Mingjian Sun

    2015-01-01

    Full Text Available Photoacoustic imaging is an innovative imaging technique to image biomedical tissues. The time reversal reconstruction algorithm in which a numerical model of the acoustic forward problem is run backwards in time is widely used. In the paper, a time reversal reconstruction algorithm based on particle swarm optimization (PSO optimized support vector machine (SVM interpolation method is proposed for photoacoustics imaging. Numerical results show that the reconstructed images of the proposed algorithm are more accurate than those of the nearest neighbor interpolation, linear interpolation, and cubic convolution interpolation based time reversal algorithm, which can provide higher imaging quality by using significantly fewer measurement positions or scanning times.

  16. Aberration correction for transcranial photoacoustic tomography of primates employing adjunct image data

    Science.gov (United States)

    Huang, Chao; Nie, Liming; Schoonover, Robert W.; Guo, Zijian; Schirra, Carsten O.; Anastasio, Mark A.; Wang, Lihong V.

    2012-06-01

    A challenge in photoacoustic tomography (PAT) brain imaging is to compensate for aberrations in the measured photoacoustic data due to their propagation through the skull. By use of information regarding the skull morphology and composition obtained from adjunct x-ray computed tomography image data, we developed a subject-specific imaging model that accounts for such aberrations. A time-reversal-based reconstruction algorithm was employed with this model for image reconstruction. The image reconstruction methodology was evaluated in experimental studies involving phantoms and monkey heads. The results establish that our reconstruction methodology can effectively compensate for skull-induced acoustic aberrations and improve image fidelity in transcranial PAT.

  17. Photoacoustic image-guided drug delivery in the prostate

    Science.gov (United States)

    Tang, Shanshan; Chen, Jian; Samant, Pratik; Xiang, Liangzhong

    2016-03-01

    Image guided drug delivery is a novel strategy that combines the effect of therapy and visibility into one system. Here we apply photoacoustic (PA) imaging to visualize the drug delivery process, and perform a simulation study on monitoring the photosensitizer concentration in a prostate tumor during photodynamic therapy (PDT). A 3D optical model of the human prostate is developed, and the light absorption distribution in the prostate is estimated by the Monte Carlo simulation method. The filtered back-projection algorithm is used to reconstruct PA images. PA images of transurethral laser/transrectal ultrasound are compared to those of transrectal laser/ultrasound. Results show that the transurethral laser has a better penetration depth in the prostate compared with transrectal one. Urethral thermal safety is investigated via COMSOL Multiphysics, and the results show that the proposed pulsed transurethral laser will cause no thermal damage on the urethral surface. Regression analysis for PA signal amplitude and drug concentration demonstrates that the PA technique has the potential to monitor drug distributions in PDT, as well as in other laser-based prostate therapy modalities.

  18. Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging.

    Science.gov (United States)

    Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L; Leung, Ben Y C; Goertz, David E; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F; Kim, Chulhong

    2014-01-01

    Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

  19. Photoacoustic imaging of early gastric cancer diagnosis based on long focal area ultrasound transducer

    Science.gov (United States)

    Wu, Huaqin; Li, Zuoran; Liu, Lantian; Li, Zhifang; Wu, Shulian; Li, Hui

    2017-06-01

    We illustrated a novel imaging method to diagnose gastric neoplasms via photoacoustic tomography (PAT). Depending on the structural characteristics of gastric cavity, we used column diffusion fiber to irradiate the stomach tissue through the esophagus, and the externally placed telecentric focus ultrasonic transducer detected photoacoustic signals from the gastric tissue. We reconstructed the distribution of light energy deposition of the simulated gastric tumor, and obtained the location and size information of gastric tumor.

  20. Photoacoustic Tomography Imaging of the Adult Zebrafish by Using Unfocused and Focused High-Frequency Ultrasound Transducers

    Directory of Open Access Journals (Sweden)

    Yubin Liu

    2016-11-01

    Full Text Available The zebrafish model provides an essential platform for the study of human diseases or disorders due to the possession of about 87% homologous genes with human. However, it is still very challenging to noninvasively visualize the structure and function of adult zebrafish based on available optical imaging techniques. In this study, photoacoustic tomography (PAT was utilized for high-resolution imaging of adult zebrafish by using focused and unfocused high-frequency (10 MHz ultrasound transducers. We examined and compared the imaging results from the two categories of transducers with in vivo experimental tests, in which we discovered that the unfocused transducer is able to identify the inner organs of adult zebrafish with higher contrast but limited regional resolution, whereas the findings from the focused transducer were with high resolution but limited regional contrast for the recovered inner organs.

  1. Validating tyrosinase homologue melA as a photoacoustic reporter gene for imaging Escherichia coli

    Science.gov (United States)

    Paproski, Robert J.; Li, Yan; Barber, Quinn; Lewis, John D.; Campbell, Robert E.; Zemp, Roger

    2015-10-01

    To understand the pathogenic processes for infectious bacteria, appropriate research tools are required for replicating and characterizing infections. Fluorescence and bioluminescence imaging have primarily been used to image infections in animal models, but optical scattering in tissue significantly limits imaging depth and resolution. Photoacoustic imaging, which has improved depth-to-resolution ratio compared to conventional optical imaging, could be useful for visualizing melA-expressing bacteria since melA is a bacterial tyrosinase homologue which produces melanin. Escherichia coli-expressing melA was visibly dark in liquid culture. When melA-expressing bacteria in tubes were imaged with a VisualSonics Vevo LAZR system, the signal-to-noise ratio of a 9× dilution sample was 55, suggesting that ˜20 bacteria cells could be detected with our system. Multispectral (680, 700, 750, 800, 850, and 900 nm) analysis of the photoacoustic signal allowed unmixing of melA-expressing bacteria from blood. To compare photoacoustic reporter gene melA (using Vevo system) with luminescent and fluorescent reporter gene Nano-lantern (using Bruker Xtreme In-Vivo system), tubes of bacteria expressing melA or Nano-lantern were submerged 10 mm in 1% Intralipid, spaced between bioluminescence and fluorescence imaging could not resolve the two tubes of Nano-lantern-expressing bacteria even when the tubes were spaced 10 mm from each other. After injecting 100-μL of melA-expressing bacteria in the back flank of a chicken embryo, photoacoustic imaging allowed visualization of melA-expressing bacteria up to 10-mm deep into the embryo. Photoacoustic signal from melA could also be separated from deoxy- and oxy-hemoglobin signal observed within the embryo and chorioallantoic membrane. Our results suggest that melA is a useful photoacoustic reporter gene for visualizing bacteria, and further work incorporating photoacoustic reporters into infectious bacterial strains is warranted.

  2. Imaging of acoustic attenuation and speed of sound maps using photoacoustic measurements

    NARCIS (Netherlands)

    Willemink, G.H.; Manohar, S.; Purwar, Y.; Slump, C.H.; Heijden, van der F.; Leeuwen, van T.G.; McAleavey, S.A.; D'Hooge, J.

    2008-01-01

    Photoacoustic imaging is an upcoming medical imaging modality with the potential of imaging both optical and acoustic properties of objects. We present a measurement system and outline reconstruction methods to image both speed of sound and acoustic attenuation distributions of an object using only

  3. Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer

    Directory of Open Access Journals (Sweden)

    Balasundaram G

    2015-01-01

    Full Text Available Ghayathri Balasundaram,1,* Chris Jun Hui Ho,1,* Kai Li,2 Wouter Driessen,3 US Dinish,1 Chi Lok Wong,1 Vasilis Ntziachristos,3 Bin Liu,2 Malini Olivo1,41Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC, 2Institute of Materials Research and Engineering (IMRE, Agency for Science, Technology and Research (A*STAR, Singapore; 3Institute of Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany; 4School of Physics, National University of Ireland, Galway, Ireland *These authors contributed equally to this work Abstract: Conjugated polymers (CPs are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used

  4. Optical-thermal light-tissue interactions during photoacoustic imaging

    Science.gov (United States)

    Gould, Taylor; Wang, Quanzeng; Pfefer, T. Joshua

    2014-03-01

    Photoacoustic imaging (PAI) has grown rapidly as a biomedical imaging technique in recent years, with key applications in cancer diagnosis and oximetry. In spite of these advances, the literature provides little insight into thermal tissue interactions involved in PAI. To elucidate these basic phenomena, we have developed, validated, and implemented a three-dimensional numerical model of tissue photothermal (PT) response to repetitive laser pulses. The model calculates energy deposition, fluence distributions, transient temperature and damage profiles in breast tissue with blood vessels and generalized perfusion. A parametric evaluation of these outputs vs. vessel diameter and depth, optical beam diameter, wavelength, and irradiance, was performed. For a constant radiant exposure level, increasing beam diameter led to a significant increase in subsurface heat generation rate. Increasing vessel diameter resulted in two competing effects - reduced mean energy deposition in the vessel due to light attenuation and greater thermal superpositioning due to reduced thermal relaxation. Maximum temperatures occurred either at the surface or in subsurface regions of the dermis, depending on vessel geometry and position. Results are discussed in terms of established exposure limits and levels used in prior studies. While additional experimental and numerical study is needed, numerical modeling represents a powerful tool for elucidating the effect of PA imaging devices on biological tissue.

  5. Photoacoustic imaging features of intraocular tumors: Retinoblastoma and uveal melanoma

    Science.gov (United States)

    Xu, Guan; Xue, Yafang; Özkurt, Zeynep Gürsel; Slimani, Naziha; Hu, Zizhong; Wang, Xueding; Xia, Kewen; Ma, Teng; Zhou, Qifa; Demirci, Hakan

    2017-01-01

    The purpose of this study is to examine the capability of photoacoustic (PA) imaging (PAI) in assessing the unique molecular and architectural features in ocular tumors. A real-time PA and ultrasonography (US) parallel imaging system based on a research US platform was developed to examine retinoblastoma in mice in vivo and human retinoblastoma and uveal melanoma ex vivo. PA signals were generated by optical illumination at 720, 750, 800, 850, 900 and 950 nm delivered through a fiber optical bundle. The optical absorption spectra of the tumors were derived from the PA images. The optical absorption spectrum of each tumor was quantified by fitting to a polynomial model. The microscopic architectures of the tumors were quantified by frequency domain analysis of the PA signals. Both the optical spectral and architectural features agree with the histological findings of the tumors. The mouse and human retinoblastoma showed comparable total optical absorption spectra at a correlation of 0.95 (p<0.005). The quantitative PAI features of human retinoblastoma and uveal melanoma have shown statistically significant difference in two tailed t-tests (p<0.05). Fully compatible with the concurrent procedures, PAI could be a potential tool complementary to other diagnostic modalities for characterizing intraocular tumors. PMID:28231293

  6. Differentiating fatty and non-fatty tissue using photoacoustic imaging

    Science.gov (United States)

    Pan, Leo; Rohling, Robert; Abolmaesumi, Purang; Salcudean, Septimiu; Tang, Shuo

    2014-03-01

    In this paper, we demonstrate a temporal-domain intensity-based photoacoustic imaging method that can differentiate between fatty and non-fatty tissues. PA pressure intensity is partly dependent on the tissue's speed of sound, which increases as temperature increases in non-fatty tissue and decreases in fatty tissue. Therefore, by introducing a temperature change in the tissue and subsequently monitoring the change of the PA intensity, it is possible to distinguish between the two types of tissue. A commercial ultrasound system with a 128-element 5-14 MHz linear array transducer and a tunable ND:YAG laser were used to produce PA images. Ex-vivo bovine fat and porcine liver tissues were precooled to below 10°C and then warmed to room-temperature over ~1 hour period. A thermocouple monitored the temperature rise while PA images were acquired at 0.5°C intervals. The averaged intensity of the illuminated tissue region at each temperature interval was plotted and linearly fitted. Liver samples showed a mean increase of 2.82 %/°C, whereas bovine fat had a mean decrease of 6.24 %/°C. These results demonstrate that this method has the potential to perform tissue differentiation in the temporal-domain.

  7. Non-invasive photoacoustic spectroscopic determination of relative endogenous nitric oxide and ethylene content stoichiometry during the ripening of strawberries Fragaria anannasa (Duch.) and avocados Persea americana (Mill.).

    Science.gov (United States)

    Leshem, Y Y; Pinchasov, Y

    2000-08-01

    Employing non-invasive photoacoustic spectrometry, emissions of nitric oxide (NO) and ethylene in post-harvest strawberries and avocados were monitored. A clear-cut stoichiometric relationship was found between the two gases: unripe fruit manifesting high NO and low ethylene levels-the converse in ripe fruit. Findings are discussed in the light of putative control of ethylene-promoted fruit senescence by endogenous NO.

  8. Photoacoustic Sentinel Lymph Node Imaging with Self-Assembled Copper Neodecanoate Nanoparticles

    Science.gov (United States)

    Pan, Dipanjan; Cai, Xin; Yalaz, Ceren; Senpan, Angana; Omanakuttan, Karthik; Wickline, Samuel A.; Wang, Lihong V.; Lanza, Gregory M.

    2012-01-01

    Photoacoustic tomography (PAT) is emerging as a novel, hybrid, and non ionizing imaging modality, because of its satisfactory spatial resolution and high soft tissue contrast. PAT combines the advantages of both optical and ultrasonic imaging methods. It opens up the possibilities for non-invasive staging of breast cancer and may replace sentinel lymph node (SLN) biopsy in clinic in the near future. In this work, we demonstrate for the first time that Copper can be used as a contrast metal for near infrared detection of SLN using PAT. A unique strategy is adopted to encapsulate multiple copies of Cu as organically soluble small molecule complexes within a phospholipids-entrapped nanoparticle. The nanoparticles assumed a size of 80–90nm, which is the optimum hydrodynamic diameter for its distribution throughout the lymphatic systems. These particles provided at least six times higher signal sensitivity in comparison to blood, which is a natural absorber of light. We also demonstrated that high SLN detection sensitivity with PAT can be achieved in rodent model. This work clearly demonstrates for the first time, the potential use of copper as an optical contrast agent. PMID:22229462

  9. Detecting occlusion inside a ventricular catheter using photoacoustic imaging through skull

    Science.gov (United States)

    Tavakoli, Behnoosh; Guo, Xiaoyu; Taylor, Russell H.; Kang, Jin U.; Boctor, Emad M.

    2014-03-01

    Ventricular catheters are used to treat hydrocephalus by diverting the excess of the cerebrospinal fluid (CSF) to the reabsorption site so as to regulate the intracranial pressure. The failure rate of these shunts is extremely high due to the ingrown tissue that blocks the CSF flow. We have studied a method to image the occlusion inside the shunt through the skull. In this approach the pulsed laser light coupled to the optical fiber illuminate the occluding tissue inside the catheter and an external ultrasound transducer is applied to detect the generated photoacoustic signal. The feasibility of this method is investigated using a phantom made of ovis aries brain tissue and adult human skull. We were able to image the target inside the shunt located 20mm deep inside the brain through about 4mm thick skull bone. This study could lead to the development of a simple, safe and non-invasive device for percutaneous restoration of patency to occluded shunts. This will eliminate the need of the surgical replacement of the occluded catheters which expose the patients to risks including hemorrhage and brain injury.

  10. Precise diagnosis in different scenarios using photoacoustic and fluorescence imaging with dual-modality nanoparticles.

    Science.gov (United States)

    Peng, Dong; Du, Yang; Shi, Yiwen; Mao, Duo; Jia, Xiaohua; Li, Hui; Zhu, Yukun; Wang, Kun; Tian, Jie

    2016-08-14

    Photoacoustic imaging and fluorescence molecular imaging are emerging as important research tools for biomedical studies. Photoacoustic imaging offers both strong optical absorption contrast and high ultrasonic resolution, and fluorescence molecular imaging provides excellent superficial resolution, high sensitivity, high throughput, and the ability for real-time imaging. Therefore, combining the imaging information of both modalities can provide comprehensive in vivo physiological and pathological information. However, currently there are limited probes available that can realize both fluorescence and photoacoustic imaging, and advanced biomedical applications for applying this dual-modality imaging approach remain underexplored. In this study, we developed a dual-modality photoacoustic-fluorescence imaging nanoprobe, ICG-loaded Au@SiO2, which was uniquely designed, consisting of gold nanorod cores and indocyanine green with silica shell spacer layers to overcome fluorophore quenching. This nanoprobe was examined by both PAI and FMI for in vivo imaging on tumor and ischemia mouse models. Our results demonstrated that the nanoparticles can specifically accumulate at the tumor and ischemic areas and be detected by both imaging modalities. Moreover, this dual-modality imaging strategy exhibited superior advantages for a precise diagnosis in different scenarios. The new nanoprobe with the dual-modality imaging approach holds great potential for diagnosis and stage classification of tumor and ischemia related diseases.

  11. A numerical model for the study of photoacoustic imaging of brain tumours

    CERN Document Server

    Firouzi, Kamyar

    2015-01-01

    Photoacoustic imaging has shown great promise for medical imaging, where optical energy absorption by blood haemoglobin is used as the contrast mechanism. A numerical method was developed for the in-silico assessment of the photoacoustic image reconstruction of the brain. Image segmentation techniques were used to prepare a digital phantom from MR images. Light transport through brain tissue was modelled using a Finite Element approach. The resulting acoustic pressure was then estimated by pulsed photoacoustics considerations. The forward acoustic wave propagation was modelled by the linearized coupled first order wave equations and solved by an acoustic k-space method. Since skull bone is an elastic solid and strongly attenuates ultrasound (due to both scattering and absorption), a k-space method was developed for elastic media. To model scattering effects, a new approach was applied based on propagation in random media. In addition, absorption effects were incorporated using a power law. Finally, the acoust...

  12. In vivo three-dimensional photoacoustic imaging based on a clinical matrix array ultrasound probe

    Science.gov (United States)

    Wang, Yu; Erpelding, Todd N.; Jankovic, Ladislav; Guo, Zijian; Robert, Jean-Luc; David, Guillaume; Wang, Lihong V.

    2012-06-01

    We present an integrated photoacoustic and ultrasonic three-dimensional (3-D) volumetric imaging system based on a two-dimensional (2-D) matrix array ultrasound probe. A wavelength-tunable dye laser pumped by a Q-switched Nd:YAG laser serves as the light source and a modified commercial ultrasound imaging system (iU22, Philips Healthcare) with a 2-D array transducer (X7-2, Philips Healthcare) detects both the pulse-echo ultrasound and photoacoustic signals. A multichannel data acquisition system acquires the RF channel data. The imaging system enables rendering of co-registered 3-D ultrasound and photoacoustic images without mechanical scanning. The resolution along the azimuth, elevation, and axial direction are measured to be 0.69, 0.90 and 0.84 mm for photoacoustic imaging. In vivo 3-D photoacoustic mapping of the sentinel lymph node was demonstrated in a rat model using methylene blue dye. These results highlight the clinical potential of 3-D PA imaging for identification of sentinel lymph nodes for cancer staging in humans.

  13. Towards photoacoustic mammography

    NARCIS (Netherlands)

    Kharin, Aleksey Anatolievich

    2005-01-01

    This research deals with developing the photoacoustic imaging technique for breast cancer detection. Photoacoustics brings together the strong aspects of ultrasound and optical imaging. Medical imaging with photoacoustics is relatively new, and promising for a lot of applications, one of which is br

  14. Characterization of tissue-simulating polymers for photoacoustic vascular imaging

    Science.gov (United States)

    Vogt, William C.; Jia, Congxian; Garra, Brian S.; Pfefer, T. Joshua

    2014-05-01

    Photoacoustic tomography (PAT) is a maturing imaging technique which combines optical excitation and acoustic detection to enable deep tissue sensing for biomedical applications. Optical absorption provides biochemical specificity and high optical contrast while ultrasonic detection provides high spatial resolution and penetration depth. These characteristics make PAT highly suitable as an approach for vascular imaging. However, standard testing methods are needed in order to characterize and compare the performance of these systems. Tissue-mimicking phantoms are commonly used as standard test samples for imaging system development and evaluation due to their repeatable fabrication and tunable properties. The multi-domain mechanism behind PAT necessitates development of phantoms that accurately mimic both acoustic and optical properties of tissues. While a wide variety of materials have been used in the literature, from gelatin and agar hydrogels to silicone, published data indicates that poly(vinyl chloride) plastisol (PVCP) is a promising candidate material for simulating tissue optical and acoustic properties while also providing superior longevity and stability. Critical acoustic properties of PVCP phantoms, including sound velocity and attenuation, were measured using acoustic transmission measurements at multiple frequencies relevant to typical PAT systems. Optical absorption and scattering coefficients of PVCP gels with and without biologically relevant absorbers and scatterers were measured over wavelengths from 500 to 1100 nm. A custom PAT system was developed to assess image contrast in PVCP phantoms containing fluid channels filled with absorbing dye. PVCP demonstrates strong potential as the basis of high-fidelity polymer phantoms for developing and evaluating PAT systems for vascular imaging applications.

  15. India ink incorporated multifunctional phase-transition nanodroplets for photoacoustic/ultrasound dual-modality imaging and photoacoustic effect based tumor therapy.

    Science.gov (United States)

    Jian, Jia; Liu, Chengbo; Gong, Yuping; Su, Lei; Zhang, Bin; Wang, Zhigang; Wang, Dong; Zhou, Yu; Xu, Fenfen; Li, Pan; Zheng, Yuanyi; Song, Liang; Zhou, Xiyuan

    2014-01-01

    The in vivo applications of gas-core microbubbles have been limited by gas diffusion, rapid body clearance, and poor vascular permeability. To overcome these limitations, using a modified three-step emulsion process, we have developed a first-of-its-kind India ink incorporated optically-triggerable phase-transition perfluorocarbon nanodroplets (INDs) that can provide not only three types of contrast mechanisms-conventional/thermoelastic photoacoustic, phase-transition/nonlinear photoacoustic, and ultrasound imaging contrasts, but also a new avenue for photoacoustic effect mediated tumor therapy. Upon pulsed laser illumination above a relatively low energy threshold, liquid-gas phase transition of the INDs has been demonstrated both in vitro and in vivo, offering excellent contrasts for photoacoustic and ultrasound dual-modality imaging. With further increased laser energy, the nanodroplets have been shown to be capable of destructing cancer cells in vivo, presumably due to the photoacoustic effect induced shock-wave generation from the carbon particles of the incorporated India ink. The demonstrated results suggest that the developed multifunctional phase-transition nanodroplets have a great potential for many theranostic biomedical applications, including photoacoustic/ultrasound dual-modality molecular imaging and targeted, localized cancer therapy.

  16. Deep in vivo photoacoustic imaging of mammalian tissues using a tyrosinase-based genetic reporter

    Science.gov (United States)

    Jathoul, Amit P.; Laufer, Jan; Ogunlade, Olumide; Treeby, Bradley; Cox, Ben; Zhang, Edward; Johnson, Peter; Pizzey, Arnold R.; Philip, Brian; Marafioti, Teresa; Lythgoe, Mark F.; Pedley, R. Barbara; Pule, Martin A.; Beard, Paul

    2015-04-01

    Photoacoustic imaging allows absorption-based high-resolution spectroscopic in vivo imaging at a depth beyond that of optical microscopy. Until recently, photoacoustic imaging has largely been restricted to visualizing the vasculature through endogenous haemoglobin contrast, with most non-vascularized tissues remaining invisible unless exogenous contrast agents are administered. Genetically encodable photoacoustic contrast is attractive as it allows selective labelling of cells, permitting studies of, for example, specific genetic expression, cell growth or more complex biological behaviours in vivo. In this study we report a novel photoacoustic imaging scanner and a tyrosinase-based reporter system that causes human cell lines to synthesize the absorbing pigment eumelanin, thus providing strong photoacoustic contrast. Detailed three-dimensional images of xenografts formed of tyrosinase-expressing cells implanted in mice are obtained in vivo to depths approaching 10 mm with a spatial resolution below 100 μm. This scheme is a powerful tool for studying cellular and genetic processes in deep mammalian tissues.

  17. Towards quantitative tissue absorption imaging by combining photoacoustics and acousto-optics

    CERN Document Server

    Daoudi, Khalid

    2012-01-01

    We propose a strategy for quantitative photoacoustic mapping of chromophore concentrations that can be performed purely experimentally. We exploit the possibility of acousto-optic modulation using focused ultrasound, and the principle that photons follow trajectories through a turbid medium in two directions with equal probability. A theory is presented that expresses the local absorption coefficient inside a medium in terms of noninvasively measured quantities and experimental parameters. Proof of the validity of the theory is given with Monte Carlo simulations.

  18. Bond-selective photoacoustic imaging by converting molecular vibration into acoustic waves.

    Science.gov (United States)

    Hui, Jie; Li, Rui; Phillips, Evan H; Goergen, Craig J; Sturek, Michael; Cheng, Ji-Xin

    2016-03-01

    The quantized vibration of chemical bonds provides a way of detecting specific molecules in a complex tissue environment. Unlike pure optical methods, for which imaging depth is limited to a few hundred micrometers by significant optical scattering, photoacoustic detection of vibrational absorption breaks through the optical diffusion limit by taking advantage of diffused photons and weak acoustic scattering. Key features of this method include both high scalability of imaging depth from a few millimeters to a few centimeters and chemical bond selectivity as a novel contrast mechanism for photoacoustic imaging. Its biomedical applications spans detection of white matter loss and regeneration, assessment of breast tumor margins, and diagnosis of vulnerable atherosclerotic plaques. This review provides an overview of the recent advances made in vibration-based photoacoustic imaging and various biomedical applications enabled by this new technology.

  19. Bond-selective photoacoustic imaging by converting molecular vibration into acoustic waves

    Science.gov (United States)

    Hui, Jie; Li, Rui; Phillips, Evan H.; Goergen, Craig J.; Sturek, Michael; Cheng, Ji-Xin

    2016-01-01

    The quantized vibration of chemical bonds provides a way of detecting specific molecules in a complex tissue environment. Unlike pure optical methods, for which imaging depth is limited to a few hundred micrometers by significant optical scattering, photoacoustic detection of vibrational absorption breaks through the optical diffusion limit by taking advantage of diffused photons and weak acoustic scattering. Key features of this method include both high scalability of imaging depth from a few millimeters to a few centimeters and chemical bond selectivity as a novel contrast mechanism for photoacoustic imaging. Its biomedical applications spans detection of white matter loss and regeneration, assessment of breast tumor margins, and diagnosis of vulnerable atherosclerotic plaques. This review provides an overview of the recent advances made in vibration-based photoacoustic imaging and various biomedical applications enabled by this new technology. PMID:27069873

  20. Three-dimensional photoacoustic and ultrasonic endoscopic imaging of two rabbit esophagi

    Science.gov (United States)

    Yang, Joon-Mo; Favazza, Christopher P.; Yao, Junjie; Chen, Ruimin; Zhou, Qifa; Shung, K. K.; Wang, Lihong V.

    2015-03-01

    The addition of photoacoustic endoscopy to conventional endoscopic ultrasound offers imaging capabilities that may improve diagnosis and clinical care of gastrointestinal tract diseases. In this study, using a 3.8-mm diameter dual-mode photoacoustic and ultrasonic endoscopic probe, we investigated photoacoustic and ultrasonic image features of rabbit esophagi. Specifically, we performed ex vivo imaging of intact rabbit esophagi and correlated the acquired images with histology. Without motion artifact-based limitations, we were able to utilize the full resolving power of the endoscopic device and acquire the first three-dimensional vasculature map of the esophagus and mediastinum, along with coregistered tissue density information. Here, we present the experimental results and discuss potential clinical applications of the technique.

  1. Bond-selective photoacoustic imaging by converting molecular vibration into acoustic waves

    Directory of Open Access Journals (Sweden)

    Jie Hui

    2016-03-01

    Full Text Available The quantized vibration of chemical bonds provides a way of detecting specific molecules in a complex tissue environment. Unlike pure optical methods, for which imaging depth is limited to a few hundred micrometers by significant optical scattering, photoacoustic detection of vibrational absorption breaks through the optical diffusion limit by taking advantage of diffused photons and weak acoustic scattering. Key features of this method include both high scalability of imaging depth from a few millimeters to a few centimeters and chemical bond selectivity as a novel contrast mechanism for photoacoustic imaging. Its biomedical applications spans detection of white matter loss and regeneration, assessment of breast tumor margins, and diagnosis of vulnerable atherosclerotic plaques. This review provides an overview of the recent advances made in vibration-based photoacoustic imaging and various biomedical applications enabled by this new technology.

  2. Novel compact photoacoustic imaging system to explore the applications in the medical imaging field

    Science.gov (United States)

    Irisawa, Kaku; Wada, Takatsugu; Hayakawa, Toshiro; Ishihara, Miya

    2017-04-01

    PhotoAcoustic (PA) imaging is a promising imaging method using the pulsed-laser light source and ultrasound detector. PA image shows the features of optical contrast in biological tissue with ultrasound-like depth and resolution. In the human body, Hemoglobin of the blood is strong optical absorber, so the high-contrast blood distribution (vascular) image is obtained by PA imaging. Recently, FUJIFILM has developed the PA imaging system to explore its application in medical imaging field. In this system, the fusion of PA and conventional ultrasound image is realized, for example, ultrasound Doppler image is superposed to the PA and B-mode image. The system features and some results of clinical studies will be introduced.

  3. Ultrasound-guided spectral photoacoustic imaging of hemoglobin oxygenation during development

    Science.gov (United States)

    Bayer, Carolyn L.; Wlodarczyk, Bogdan J.; Finnell, Richard H.; Emelianov, Stanislav Y.

    2017-01-01

    Few technologies are capable of imaging in vivo function during development. In this study, we have implemented spectral photoacoustic imaging to estimate tissue oxygenation longitudinally in pregnant mice. We used the spectral photoacoustic signal to estimate hemoglobin oxygen saturation within intact, in vivo mouse concepti from developmental day (E) 8.5 to E16.5—a first step towards functional imaging of the maternal-fetal environment. Future work will apply these methods to compare longitudinal functional changes during normal vs abnormal development of embryos, fetuses, and placentas. PMID:28270982

  4. Porphyrin Nanodroplets: Sub-micrometer Ultrasound and Photoacoustic Contrast Imaging Agents.

    Science.gov (United States)

    Paproski, Robert J; Forbrich, Alexander; Huynh, Elizabeth; Chen, Juan; Lewis, John D; Zheng, Gang; Zemp, Roger J

    2016-01-20

    A novel class of all-organic nanoscale porphyrin nanodroplet agents is presented which is suitable for multimodality ultrasound and photoacoustic molecular imaging. Previous multimodality photoacoustic-ultrasound agents are either not organic, or not yet demonstrated to exhibit enhanced accumulation in leaky tumor vasculature, perhaps because of large diameters. In the current study, porphyrin nanodroplets are created with a mean diameter of 185 nm which is small enough to exhibit the enhanced permeability and retention effect. Porphyrin within the nanodroplet shell has strong optical absorption at 705 nm with an estimated molar extinction coefficient >5 × 10(9) m(-1) cm(-1) , allowing both ultrasound and photoacoustic contrast in the same nanoparticle using all organic materials. The potential of nanodroplets is that they may be phase-changed into microbubbles using high pressure ultrasound, providing ultrasound contrast with single-bubble sensitivity. Multispectral photoacoustic imaging allows visualization of nanodroplets when injected intratumorally in an HT1080 tumor in the chorioallantoic membrane of a chicken embryo. Intravital microscopy imaging of Hep3-GFP and HT1080-GFP tumors in chicken embryos determines that nanodroplets accumulated throughout or at the periphery of tumors, suggesting that porphyrin nanodroplets may be useful for enhancing the visualization of tumors with ultrasound and/or photoacoustic imaging.

  5. Photoacoustic imaging of angiogenesis in subdermal islet transplant sites

    Science.gov (United States)

    Shi, Wei; Pawlick, Rena; Bruni, Antonio; Rafiei, Yasmin; Pepper, Andrew R.; Gala-Lopez, Boris; Choi, Min; Malcolm, Andrew; Zemp, Roger J.; Shapiro, A. M. James

    2016-03-01

    Exogenous insulin administration is the mainstay treatment therapy for patients with Type-1 diabetes mellitus (T1DM). However, for select patients, clinical islet transplantation is an alternative therapeutic treatment. In this procedure, islets are transplanted into the hepatic portal vein, and despite improved success within the last decade, obstacles are still associated with this approach. It has been discovered that the subcutaneous space may be an effective alternative site for islet transplantation, and may provide advantages of easy access and potential for simple monitoring. The ability to monitor islet viability and the transplant microenvironment may be key to future success in islet transplantation. A subcutaneous device-less technique has been developed to facilitate angiogenesis in the islet transplant site, however, a method for monitoring the potential engraftment site have yet to be explored fully. Here we demonstrate the ability to track angiogenesis in mice with 1, 2, 3 and 4 weeks post-catheter implant on both sides of the abdomen using a FujiFilm VisualSonics Vevo-LAZR system. Quantitative analysis on vessel densities exhibited gradual vessel growth successfully induced by catheter implantation. Our study demonstrates the ability of employing photoacoustic and micro-ultrasound imaging to track angiogenesis around the catheter site prior to islet transplantation.

  6. Imaging high-intensity focused ultrasound-induced tissue denaturation by multispectral photoacoustic method: an ex vivo study.

    Science.gov (United States)

    Sun, Yao; O'Neill, Brian

    2013-03-10

    We present an ex vivo study for the first time, to the best of our knowledge, in multispectral photoacoustic imaging (PAI) of tissue denaturation induced by high-intensity focused ultrasound (HIFU) in this paper. Tissue of bovine muscle was thermally treated in a heated water bath and by HIFU, and then was imaged using a multispectral photoacoustic approach. Light at multiple optical wavelengths between 700 and 900 nm was delivered to the treated bovine muscle tissue to excite the photoacoustic signal. Apparent tissue denaturation has been observed in multispectral photoacoustic images after being treated in a water bath and by HIFU. It is interesting that the denaturation is more striking at shorter optical wavelength photoacoustic images than at longer optical wavelength photoacoustic images. Multispectral photoacoustic images of the tissue denaturation were further analyzed and the photoacoustic spectrums of the denaturized tissue were calculated in this paper. This study suggests that a multispectral PAI approach might be a promising tool to evaluate tissue denaturation induced by HIFU treatment.

  7. Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors.

    Science.gov (United States)

    Uthaman, Saji; Bom, Joon-suk; Kim, Hyeon Sik; John, Johnson V; Bom, Hee-Seung; Kim, Seon-Jong; Min, Jung-Joon; Kim, Il; Park, In-Kyu

    2016-05-01

    Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI.

  8. Planoconcave optical microresonator sensors for photoacoustic imaging: pushing the limits of sensitivity (Conference Presentation)

    Science.gov (United States)

    Guggenheim, James A.; Zhang, Edward Z.; Beard, Paul C.

    2016-03-01

    Most photoacoustic scanners use piezoelectric detectors but these have two key limitations. Firstly, they are optically opaque, inhibiting backward mode operation. Secondly, it is difficult to achieve adequate detection sensitivity with the small element sizes needed to provide near-omnidirectional response as required for tomographic imaging. Planar Fabry-Perot (FP) ultrasound sensing etalons can overcome both of these limitations and have proved extremely effective for superficial (heating. Finally, a prototype microresonator based photoacoustic scanner has been developed and applied to the problem of deep-tissue (>1cm) photoacoustic imaging in vivo. Imaging results for second generation microresonator sensors (with R = 99.5% and thickness up to ~800um) are compared to the best achievable with the planar FP sensors and piezoelectric receivers.

  9. Label-free imaging of cellular malformation using high resolution photoacoustic microscopy

    Science.gov (United States)

    Chen, Zhongjiang; Li, Bingbing; Yang, Sihua

    2014-09-01

    A label-free high resolution photoacoustic microscopy (PAM) system for imaging cellular malformation is presented. The carbon fibers were used to testify the lateral resolution of the PAM. Currently, the lateral resolution is better than 2.7 μm. The human normal red blood cells (RBCs) were used to prove the imaging capability of the system, and a single red blood cell was mapped with high contrast. Moreover, the iron deficiency anemia RBCs were clearly distinguished from the cell morphology by using the PAM. The experimental results demonstrate that the photoacoustic microscopy system can accomplish label-free photoacoustic imaging and that it has clinical potential for use in the detection of erythrocytes and blood vessels malformation.

  10. Noninvasive imaging of oral premalignancy and malignancy

    Science.gov (United States)

    Wilder-Smith, Petra; Krasieva, T.; Jung, W.; You, J. S.; Chen, Z.; Osann, K.; Tromberg, B.

    2005-04-01

    Objectives: Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. Despite significant advances in treatment, oral cancer still results in 10,000 U.S. deaths annually, mainly due to the late detection of most oral lesions. Specific aim was to use a combination of non-invasive optical in vivo technologies to test a multi-modality approach to non-invasive diagnostics of oral premalignancy and malignancy. Methods: In the hamster cheek pouch model (120 hamsters), in vivo optical coherence tomography (OCT) and optical Doppler tomography (ODT) mapped epithelial, subepithelial and vascular change throughout carcinogenesis in specific, marked sites. In vivo multi-wavelength multi-photon (MPM) and second harmonic generated (SHG) fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images were diagnosed by 2 blinded, pre-standardized investigators using a standardized scale from 0-6 for all modalities. After sacrifice, histopathological sections were prepared and pathology evaluated on a scale of 0-6. ANOVA techniques compared imaging diagnostics with histopathology. 95% confidence limits of the sensitivity and specificity were established for the diagnostic capability of OCT/ODT+ MPM/SHG using ROC curves and kappa statistics. Results: Imaging data were reproducibly obtained with good accuracy. Carcinogenesis-related structural and vascular changes were clearly visible to tissue depths of 2mm. Sensitivity (OCT/ODT alone: 71-88%; OCT+MPM/SHG: 79-91%) and specificity (OCT alone: 62-83%;OCT+MPM/SHG: 67-90%) compared well with conventional techniques. Conclusions: OCT/ODT and MPM/SHG are promising non-invasive in vivo diagnostic modalities for oral dysplasia and malignancy. Supported by CRFA 30003, CCRP 00-01391V-20235, NIH (LAMMP) RR01192, DOE DE903-91ER 61227, NIH EB-00293 CA91717, NSF BES

  11. Validating tyrosinase homologue melA as a photoacoustic reporter gene for imaging Escherichia coli.

    Science.gov (United States)

    Paproski, Robert J; Li, Yan; Barber, Quinn; Lewis, John D; Campbell, Robert E; Zemp, Roger

    2015-10-01

    To understand the pathogenic processes for infectious bacteria, appropriate research tools are required for replicating and characterizing infections. Fluorescence and bioluminescence imaging have primarily been used to image infections in animal models, but optical scattering in tissue significantly limits imaging depth and resolution. Photoacoustic imaging, which has improved depth-to-resolution ratio compared to conventional optical imaging, could be useful for visualizing melA-expressing bacteria since melA is a bacterial tyrosinase homologue which produces melanin. Escherichia coli-expressing melA was visibly dark in liquid culture. When melA-expressing bacteria in tubes were imaged with a VisualSonics Vevo LAZR system, the signal-to-noise ratio of a 9×dilution sample was 55, suggesting that ∼20 bacteria cells could be detected with our system. Multispectral (680, 700, 750, 800, 850, and 900 nm) analysis of the photoacoustic signal allowed unmixing of melA-expressing bacteria from blood. To compare photoacoustic reporter gene melA (using Vevo system) with luminescent and fluorescent reporter gene Nano-lantern (using Bruker Xtreme In-Vivo system), tubes of bacteria expressing melA or Nano-lantern were submerged 10 mm in 1% Intralipid, spaced between Photoacoustic imaging could resolve the two tubes of melA-expressing bacteria even when the tubes were less than 1 mm from each other, while bioluminescence and fluorescence imaging could not resolve the two tubes of Nano-lantern-expressing bacteria even when the tubes were spaced 10 mm from each other. After injecting 100-μL of melA-expressing bacteria in the back flank of a chicken embryo, photoacoustic imaging allowed visualization of melA-expressing bacteria up to 10-mm deep into the embryo. Photoacoustic signal from melA could also be separated from deoxy- and oxy-hemoglobin signal observed within the embryo and chorioallantoic membrane. Our results suggest that melA is a useful photoacoustic reporter gene

  12. An interventional multispectral photoacoustic imaging platform for the guidance of minimally invasive procedures

    Science.gov (United States)

    Xia, Wenfeng; Nikitichev, Daniil I.; Mari, Jean Martial; West, Simeon J.; Ourselin, Sebastien; Beard, Paul C.; Desjardins, Adrien E.

    2015-07-01

    Precise and efficient guidance of medical devices is of paramount importance for many minimally invasive procedures. These procedures include fetal interventions, tumor biopsies and treatments, central venous catheterisations and peripheral nerve blocks. Ultrasound imaging is commonly used for guidance, but it often provides insufficient contrast with which to identify soft tissue structures such as vessels, tumors, and nerves. In this study, a hybrid interventional imaging system that combines ultrasound imaging and multispectral photoacoustic imaging for guiding minimally invasive procedures was developed and characterized. The system provides both structural information from ultrasound imaging and molecular information from multispectral photoacoustic imaging. It uses a commercial linear-array ultrasound imaging probe as the ultrasound receiver, with a multimode optical fiber embedded in a needle to deliver pulsed excitation light to tissue. Co-registration of ultrasound and photoacoustic images is achieved with the use of the same ultrasound receiver for both modalities. Using tissue ex vivo, the system successfully discriminated deep-located fat tissue from the surrounding muscle tissue. The measured photoacoustic spectrum of the fat tissue had good agreement with the lipid spectrum in literature.

  13. I vivo three-dimensional photoacoustic imaging based on a clinicall matrix array ultrasound probe

    NARCIS (Netherlands)

    Wang, Y.; Erpelding, T.N.; Jankovic, L.; Guo, Z.; Robert, J.L.; David, G.; Wang, L.V.

    2011-01-01

    We present an integrated photoacoustic and ultrasonic three-dimensional (3D) volumetric imaging system based on a two-dimensional (2D) matrix array ultrasound probe. A wavelength-tunable dye laser pumpedby a Q-switched Nd:YAG laser serves as the light source and a modified commercial ultrasound imag

  14. Clinical experiences with photoacoustic breast imaging: the appearance of suspicious lesions

    NARCIS (Netherlands)

    Heijblom, Michelle

    2014-01-01

    This thesis describes photoacoustic (PA) imaging of suspicious breast lesions. In PA imaging, the tissue of interest is illuminated by short pulses of laser light, usually in the near infrared (NIR) regime. Upon absorption by primarily the tumor vasculature, the light causes a small temperature incr

  15. In vivo photoacoustic imaging of blood vessels with a pulsed laser diode

    NARCIS (Netherlands)

    Kolkman, R.G.M.; Steenbergen, Wiendelt; van Leeuwen, Ton

    2006-01-01

    Photoacoustic imaging is a hybrid imaging modality that is based on the detection of acoustic waves generated by absorption of pulsed light by tissue chromophores such as hemoglobin in blood. For this technique, usually large and costly Q-switched Nd:YAG lasers are used. These lasers provide a pulse

  16. Physically-synthesized gold nanoparticles containing multiple nanopores for enhanced photothermal conversion and photoacoustic imaging.

    Science.gov (United States)

    Park, Jisoo; Kang, Heesung; Kim, Young Heon; Lee, Sang-Won; Lee, Tae Geol; Wi, Jung-Sub

    2016-08-25

    Physically-synthesized gold nanoparticles having a narrow size distribution and containing multiple nanopores have been utilized as photothermal converters and imaging contrast agents. Nanopores within the gold nanoparticles make it possible to increase the light-absorption cross-section and consequently exhibit distinct improvements in photothermal conversion and photoacoustic imaging efficiencies.

  17. Performance characterization of an integrated ultrasound, photoacoustic, and thermoacoustic imaging system

    NARCIS (Netherlands)

    Ke, H.; Erpelding, T.; Jankovic, L.; Wang, L.V.

    2012-01-01

    We developed a tri-modality imaging system for breast cancer imagingby integrating photoacoustic (PA) and thermoacoustic (TA) imaging techniques into a modified commercial ultrasound scanner. Laser and microwave excitation pulses were interleaved to enable PA and TA dataacquisition in parallel at th

  18. Noncontact photoacoustic imaging by using a modified optical-fiber Michelson interferometer

    Science.gov (United States)

    Lu, Jiao; Gao, Yingzhe; Ma, Zhenhe; Wang, Bo; Wang, Yi

    2016-03-01

    We demonstrate a noncontact photoacoustic imaging (PAI) system in which an optical interferometer is used for ultrasound detection. The system is based on a modified optical-fiber Michelson interferometer that measures the surface displacement caused by photoacoustic pressure. A synchronization method is utilized to keep its high sensitivity to reduce the influence of ambient vibrations. The system is experimentally verified by imaging of a phantom. The experimental results indicate that the proposed system can be used for noncontact PAI with high resolution and high bandwidth.

  19. Photoacoustic endoscopic imaging study of melanoma tumor growth in a rat colorectum in vivo

    Science.gov (United States)

    Li, Chiye; Yang, Joon-Mo; Chen, Ruimin; Zhang, Yu; Xia, Younan; Zhou, Qifa; Shung, K. Kirk; Wang, Lihong V.

    2013-03-01

    We performed a photoacoustic endoscopic imaging study of melanoma tumor growth in a nude rat in vivo. After inducing the tumor at the colorectal wall of the animal, we monitored the tumor development in situ by using a photoacoustic endoscopic system. This paper introduces our experimental method for tumor inoculation and presents imaging results showing the morphological changes of the blood vasculature near the tumor region according to the tumor progress. Our study could provide insights for future studies on tumor development in small animals.

  20. Identification and removal of laser-induced noise in photoacoustic imaging using singular value decomposition.

    Science.gov (United States)

    Hill, Emma R; Xia, Wenfeng; Clarkson, Matthew J; Desjardins, Adrien E

    2017-01-01

    Singular value decomposition (SVD) was used to identify and remove laser-induced noise in photoacoustic images acquired with a clinical ultrasound scanner. This noise, which was prominent in the radiofrequency data acquired in parallel from multiple transducer elements, was induced by the excitation light source. It was modelled by truncating the SVD matrices so that only the first few largest singular value components were retained, and subtracted prior to image reconstruction. The dependency of the signal amplitude and the number of the largest singular value components used for noise modeling was investigated for different photoacoustic source geometries. Validation was performed with simulated data and measured noise, and with photoacoustic images acquired from the human forearm and finger in vivo using L14-5/38 and L40-8/12 linear array clinical imaging probes. The use of only one singular value component was found to be sufficient to achieve near-complete removal of laser-induced noise from reconstructed images. This method has strong potential to increase image quality for a wide range of photoacoustic imaging systems with parallel data acquisition.

  1. Phase-domain photoacoustic sensing

    Science.gov (United States)

    Gao, Fei; Zhang, Ruochong; Feng, Xiaohua; Liu, Siyu; Ding, Ran; Kishor, Rahul; Qiu, Lei; Zheng, Yuanjin

    2017-01-01

    As one of the fastest-growing imaging modalities in recent years, photoacoustic imaging has attracted tremendous research interest for various applications including anatomical, functional, and molecular imaging. The majority of the photoacoustic imaging systems are based on the time-domain pulsed photoacoustic method, which utilizes a pulsed laser source to induce a wideband photoacoustic signal, revealing optical absorption contrast. An alternative way is the frequency-domain photoacoustic method utilizing the chirping modulation of laser intensity to achieve lower system cost. In this paper, we report another way of the photoacoustic method, called phase-domain photoacoustic sensing, which explores the phase difference between two consequent intensity-modulated laser pulse induced photoacoustic measurements to reveal the optical properties. The basic principle is introduced, modeled, and experimentally validated in this paper, which opens another potential pathway to perform photoacoustic sensing and imaging, eliminating acoustic detection variations beyond the conventional time-domain and frequency-domain photoacoustic methods.

  2. NH4HCO3 gas-generating liposomal nanoparticle for photoacoustic imaging in breast cancer

    Directory of Open Access Journals (Sweden)

    Xia J

    2017-03-01

    Full Text Available Jizhu Xia, Gang Feng, Xiaorong Xia, Lan Hao, Zhigang Wang Chongqing Key Laboratory of Ultrasound Molecular Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Abstract: In this study, we have developed a biodegradable nanomaterial for photoacoustic imaging (PAI. Its biodegradation products can be fully eliminated from a living organism. It is a gas-generating nanoparticle of liposome-encapsulating ammonium bicarbonate (NH4HCO3 solution, which is safe, effective, inexpensive, and free of side effects. When lasers irradiate these nanoparticles, NH4HCO3 decomposes to produce CO2, which can absorb much of the light energy under laser irradiation with a specific wavelength, and then expand under heat to generate a thermal acoustic wave. An acoustic detector can detect this wave and show it as a photoacoustic signal on a display screen. The intensity of the photoacoustic signal is enhanced corresponding to an increase in time, concentration, and temperature. During in vivo testing, nanoparticles were injected into tumor-bearing nude mice through the caudal vein, and photoacoustic signals were detected from the tumor, reaching a peak in 4 h, and then gradually disappearing. There was no damage to the skin or subcutaneous tissue from laser radiation. Our developed gas-generating nanomaterial, NH4HCO3 nanomaterial, is feasible, effective, safe, and inexpensive. Therefore, it is a promising material to be used in clinical PAI. Keywords: Photoacoustic tomography, CO2, NH4HCO3, contrast agent, cancer

  3. Interventional multispectral photoacoustic imaging with a clinical linear array ultrasound probe for guiding nerve blocks

    Science.gov (United States)

    Xia, Wenfeng; West, Simeon J.; Nikitichev, Daniil I.; Ourselin, Sebastien; Beard, Paul C.; Desjardins, Adrien E.

    2016-03-01

    Accurate identification of tissue structures such as nerves and blood vessels is critically important for interventional procedures such as nerve blocks. Ultrasound imaging is widely used as a guidance modality to visualize anatomical structures in real-time. However, identification of nerves and small blood vessels can be very challenging, and accidental intra-neural or intra-vascular injections can result in significant complications. Multi-spectral photoacoustic imaging can provide high sensitivity and specificity for discriminating hemoglobin- and lipid-rich tissues. However, conventional surface-illumination-based photoacoustic systems suffer from limited sensitivity at large depths. In this study, for the first time, an interventional multispectral photoacoustic imaging (IMPA) system was used to image nerves in a swine model in vivo. Pulsed excitation light with wavelengths in the ranges of 750 - 900 nm and 1150 - 1300 nm was delivered inside the body through an optical fiber positioned within the cannula of an injection needle. Ultrasound waves were received at the tissue surface using a clinical linear array imaging probe. Co-registered B-mode ultrasound images were acquired using the same imaging probe. Nerve identification was performed using a combination of B-mode ultrasound imaging and electrical stimulation. Using a linear model, spectral-unmixing of the photoacoustic data was performed to provide image contrast for oxygenated and de-oxygenated hemoglobin, water and lipids. Good correspondence between a known nerve location and a lipid-rich region in the photoacoustic images was observed. The results indicate that IMPA is a promising modality for guiding nerve blocks and other interventional procedures. Challenges involved with clinical translation are discussed.

  4. Automated wavelet denoising of photoacoustic signals for burn-depth image reconstruction

    Science.gov (United States)

    Holan, Scott H.; Viator, John A.

    2007-02-01

    Photoacoustic image reconstruction involves dozens or perhaps hundreds of point measurements, each of which contributes unique information about the subsurface absorbing structures under study. For backprojection imaging, two or more point measurements of photoacoustic waves induced by irradiating a sample with laser light are used to produce an image of the acoustic source. Each of these point measurements must undergo some signal processing, such as denoising and system deconvolution. In order to efficiently process the numerous signals acquired for photoacoustic imaging, we have developed an automated wavelet algorithm for processing signals generated in a burn injury phantom. We used the discrete wavelet transform to denoise photoacoustic signals generated in an optically turbid phantom containing whole blood. The denoising used universal level independent thresholding, as developed by Donoho and Johnstone. The entire signal processing technique was automated so that no user intervention was needed to reconstruct the images. The signals were backprojected using the automated wavelet processing software and showed reconstruction using denoised signals improved image quality by 21%, using a relative 2-norm difference scheme.

  5. All-optical scanhead for ultrasound and photoacoustic imaging-Imaging mode switching by dichroic filtering.

    Science.gov (United States)

    Hsieh, Bao-Yu; Chen, Sung-Liang; Ling, Tao; Guo, L Jay; Li, Pai-Chi

    2014-03-01

    Ultrasound (US) and photoacoustic (PA) multimodality imaging has the advantage of combining good acoustic resolution with high optical contrast. The use of an all-optical scanhead for both imaging modalities can simplify integration of the two systems and miniaturize the imaging scanhead. Herein we propose and demonstrate an all-optical US/PA scanhead using a thin plate for optoacoustic generation in US imaging, a polymer microring resonator for acoustic detection, and a dichroic filter to switch between the two imaging modes by changing the laser wavelength. A synthetic-aperture focusing technique is used to improve the resolution and contrast. Phantom images demonstrate the feasibility of this design, and show that axial and lateral resolutions of 125 μm and 2.52°, respectively, are possible.

  6. Preclinical evaluation of a novel cyanine dye for tumor imaging with in vivo photoacoustic imaging

    Science.gov (United States)

    Temma, Takashi; Onoe, Satoru; Kanazaki, Kengo; Ono, Masahiro; Saji, Hideo

    2014-09-01

    Photoacoustic imaging (PA imaging or PAI) has shown great promise in the detection and monitoring of cancer. Although nanocarrier-based contrast agents have been studied for use in PAI, small molecule contrast agents are required due to their ease of preparation, cost-effectiveness, and low toxicity. Here, we evaluated the usefulness of a novel cyanine dye IC7-1-Bu as a PAI contrast agent without conjugated targeting moieties for in vivo tumor imaging in a mice model. Basic PA characteristics of IC7-1-Bu were compared with indocyanine green (ICG), a Food and Drug Administration approved dye, in an aqueous solution. We evaluated the tumor accumulation profile of IC7-1-Bu and ICG by in vivo fluorescence imaging. In vivo PAI was then performed with a photoacoustic tomography system 24 and 48 h after intravenous injection of IC7-1-Bu into tumor bearing mice. IC7-1-Bu showed about a 2.3-fold higher PA signal in aqueous solution compared with that of ICG. Unlike ICG, IC7-1-Bu showed high tumor fluorescence after intravenous injection. In vivo PAI provided a tumor to background PA signal ratio of approximately 2.5 after intravenous injection of IC7-1-Bu. These results indicate that IC7-1-Bu is a promising PAI contrast agent for cancer imaging without conjugation of targeting moieties.

  7. NOTE: Automated wavelet denoising of photoacoustic signals for circulating melanoma cell detection and burn image reconstruction

    Science.gov (United States)

    Holan, Scott H.; Viator, John A.

    2008-06-01

    Photoacoustic image reconstruction may involve hundreds of point measurements, each of which contributes unique information about the subsurface absorbing structures under study. For backprojection imaging, two or more point measurements of photoacoustic waves induced by irradiating a biological sample with laser light are used to produce an image of the acoustic source. Each of these measurements must undergo some signal processing, such as denoising or system deconvolution. In order to process the numerous signals, we have developed an automated wavelet algorithm for denoising signals. We appeal to the discrete wavelet transform for denoising photoacoustic signals generated in a dilute melanoma cell suspension and in thermally coagulated blood. We used 5, 9, 45 and 270 melanoma cells in the laser beam path as test concentrations. For the burn phantom, we used coagulated blood in 1.6 mm silicon tube submerged in Intralipid. Although these two targets were chosen as typical applications for photoacoustic detection and imaging, they are of independent interest. The denoising employs level-independent universal thresholding. In order to accommodate nonradix-2 signals, we considered a maximal overlap discrete wavelet transform (MODWT). For the lower melanoma cell concentrations, as the signal-to-noise ratio approached 1, denoising allowed better peak finding. For coagulated blood, the signals were denoised to yield a clean photoacoustic resulting in an improvement of 22% in the reconstructed image. The entire signal processing technique was automated so that minimal user intervention was needed to reconstruct the images. Such an algorithm may be used for image reconstruction and signal extraction for applications such as burn depth imaging, depth profiling of vascular lesions in skin and the detection of single cancer cells in blood samples.

  8. Non-invasive Imaging of Human Embryonic Stem Cells

    OpenAIRE

    Hong, Hao; Yang, Yunan; Zhang, Yin; Cai, Weibo

    2010-01-01

    Human embryonic stem cells (hESCs) hold tremendous therapeutic potential in a variety of diseases. Over the last decade, non-invasive imaging techniques have proven to be of great value in tracking transplanted hESCs. This review article will briefly summarize the various techniques used for non-invasive imaging of hESCs, which include magnetic resonance imaging (MRI), bioluminescence imaging (BLI), fluorescence, single-photon emission computed tomography (SPECT), positron emission tomography...

  9. Using high-power light emitting diodes for photoacoustic imaging

    DEFF Research Database (Denmark)

    Hansen, René Skov

    for the experiment consists of a 3mm high x 5mm wide slice of green colored gelatine overlaid by a 3cm layer of colorless gelatine. The light pulses from the LED is focused on the green gelatine. The photoacoustic response from the green gelatine is detected by a single transducer on the opposite (top) surface...... of the colorless gelatine layer....

  10. Speed-of-sound compensated photoacoustic tomography for accurate imaging

    NARCIS (Netherlands)

    Jose, J.; Willemink, G.H.; Steenbergen, W.; Leeuwen, van A.G.J.M.; Manohar, S.

    2012-01-01

    Purpose: In most photoacoustic (PA) tomographic reconstructions, variations in speed-of-sound (SOS) of the subject are neglected under the assumption of acoustic homogeneity. Biological tissue with spatially heterogeneous SOS cannot be accurately reconstructed under this assumption. The authors pres

  11. All-optical photoacoustic imaging system using fiber ultrasound probe and hollow optical fiber bundle.

    Science.gov (United States)

    Miida, Yusuke; Matsuura, Yuji

    2013-09-23

    An all-optical 3D photoacoustic imaging probe that consists of an optical fiber probe for ultrasound detection and a bundle of hollow optical fibers for excitation of photoacoustic waves was developed. The fiber probe for ultrasound is based on a single-mode optical fiber with a thin polymer film attached to the output end surface that works as a Fabry Perot etalon. The input end of the hollow fiber bundle is aligned so that each fiber in the bundle is sequentially excited. A thin and flexible probe can be obtained because the probe system does not have a scanning mechanism at the distal end.

  12. Handheld probe integrating laser diode and ultrasound transducer array for ultrasound/photoacoustic dual modality imaging.

    Science.gov (United States)

    Daoudi, K; van den Berg, P J; Rabot, O; Kohl, A; Tisserand, S; Brands, P; Steenbergen, W

    2014-10-20

    Ultrasound and photoacoustics can be utilized as complementary imaging techniques to improve clinical diagnoses. Photoacoustics provides optical contrast and functional information while ultrasound provides structural and anatomical information. As of yet, photoacoustic imaging uses large and expensive systems, which limits their clinical application and makes the combination costly and impracticable. In this work we present and evaluate a compact and ergonomically designed handheld probe, connected to a portable ultrasound system for inexpensive, real-time dual-modality ultrasound/photoacoustic imaging. The probe integrates an ultrasound transducer array and a highly efficient diode stack laser emitting 130 ns pulses at 805 nm wavelength and a pulse energy of 0.56 mJ, with a high pulse repetition frequency of up to 10 kHz. The diodes are driven by a customized laser driver, which can be triggered externally with a high temporal stability necessary to synchronize the ultrasound detection and laser pulsing. The emitted beam is collimated with cylindrical micro-lenses and shaped using a diffractive optical element, delivering a homogenized rectangular light intensity distribution. The system performance was tested in vitro and in vivo by imaging a human finger joint.

  13. Plasmonic Nanoparticles with Quantitatively Controlled Bioconjugation for Photoacoustic Imaging of Live Cancer Cells.

    Science.gov (United States)

    Tian, Chao; Qian, Wei; Shao, Xia; Xie, Zhixing; Cheng, Xu; Liu, Shengchun; Cheng, Qian; Liu, Bing; Wang, Xueding

    2016-12-01

    Detection and imaging of single cancer cells is critical for cancer diagnosis and understanding of cellular dynamics. Photoacoustic imaging (PAI) provides a potential tool for the study of cancer cell dynamics, but faces the challenge that most cancer cells lack sufficient endogenous contrast. Here, a type of colloidal gold nanoparticles (AuNPs) are physically fabricated and are precisely functionalized with quantitative amounts of functional ligands (i.e., polyethyleneglycol (PEG) and (Arginine(R)-Glycine(G)-Aspartic(D))4 (RGD) peptides) to serve as an exogenous contrast agent for PAI of single cells. The functionalized AuNPs, with a fixed number of PEG but different RGD densities, are delivered into human prostate cancer cells. Radioactivity and photoacoustic analyses show that, although cellular uptake efficiency of the AuNPs linearly increases along with RGD density, photoacoustic signal generation efficiency does not and only maximize at a moderate RGD density. The functionalization of the AuNPs is in turn optimized based on the experimental finding, and single cancer cells are imaged using a custom photoacoustic microscopy with high-resolution. The quantitatively functionalized AuNPs together with the high-resolution PAI system provide a unique platform for the detection and imaging of single cancer cells, and may impact not only basic science but also clinical diagnostics on a range of cancers.

  14. A new approach to depict bone surfaces in finger imaging using photoacoustic tomography

    NARCIS (Netherlands)

    Biswas, Samir Kumar; van Es, Peter; Steenbergen, Wiendelt; Manohar, Srirang; Oraevsky, Alexander A.; Wang, Lihong V.

    2015-01-01

    Imaging the vasculature close around the finger joints is of interest in the field of rheumatology. Locally increased vasculature in the synovial membrane of these joints can be a marker for rheumatoid arthritis. In previous work we showed that part of the photoacoustically induced ultrasound from t

  15. Photoacoustic imaging of mesenchymal stem cells in living mice via silica-coated gold nanorods

    Science.gov (United States)

    Jokerst, Jesse V.; Thangaraj, Mridhula; Gambhir, Sanjiv S.

    2014-03-01

    Imaging is crucial for stem cell therapy to monitor the location(s), numbers, and state of the implanted cells. Real-time imaging in particular can ensure proper cell delivery for best engraftment. However, established imaging tools such as MRI are limited by their temporal resolution for guidance during delivery. In contrast, photoacoustic imaging is ideally suited for real time, image-guided therapy. Here, we use silica-coated gold nanorods as photoacoustic contrast agents and deploy them to image and quantitate mesenchymal stem cells during implant into the muscle tissue of live mice. Silica-coated gold nanorods (SiGNRs) were created with standard methods and loaded into mesenchymal stem cells (MSCs) without transfection agents. There was no significant (pcytokines should only minor upregulation of inflammatory markers including interleukin-6. We used electron microscopy to illustrate vacuole-bound SiGNRs inside the cells. This cell staining increased photoacoustic signal 175% relative to MSCs without contrast agent—the silica coat itself increased signal 55% relative to uncoated GNRs. Using inductively coupled plasma spectroscopy, we found that there were 100,000 SiGNRs per MSC. This value was 5-fold higher than a MSC population stained with GNRs in the absence of silica coat. After labeling, cells were washed and injected into murine muscle tissue to simulate a muscular dystrophy patient. Mice (N=5) treated with these SiGNRlabeled MSCs exhibited no adverse events and implants up to 5 mm deep were easily visualized. The in vivo detection limit was 90,000 cells in a 100 uL bolus in mouse thigh muscle. Here, the B-mode signal is useful for orienting the treatment area and visualizing the delivery catheter while the photoacoustic mode offers cell-specific content. The photoacoustic signal was validated with histology a long-term fluorescent tracking dye after MSC transplant.

  16. Multi-parameter photoacoustic imaging and its application in biomedicine%多参量光声成像及其在生物医学领域的应用∗

    Institute of Scientific and Technical Information of China (English)

    殷杰; 陶超; 刘晓峻

    2015-01-01

    Photoacoustic imaging is a hybrid imaging technique based on the photoacoustic effect. As a non-invasive and non-ionizing modality, photoacoustic imaging takes the both merits of the conventional acoustic imaging and optical imaging. Firstly, the contrast of photoacoustic imaging primarily depends on the optical absorption. The unique optical spectra of atoms and molecules makes optical methods to be a widely used modality to probe the molecular and chemical information of biological tissue. Therefore, photoacoustic imaging has its inherent advantage in high-contrast functional and physiological imaging of biological tissue, as well as the optical imaging method. Secondly, photoacoustic imaging has the high spatial resolution in deep tissue in comparison with the pure optical imaging method. Since the strongly optical scattering in biological tissue, pure optical imaging method is difficult to obtain the high-resolution image in the tissue deeper than∼1 mm. Whereas, acoustic wave suffers much less from scattering than optical wave, the acoustic scattering coefficient is about 2–3 orders of magnitude less than the optical scattering coefficient. Photoacoustic imaging can achieve a fine resolution in deep tissue, which equivalent to 1/200 of the imaging depth. Thirdly, non-ionizing radiation used for photoacoustic imaging is much safer than X-ray. Moreover, the low-temperature rises make photoacoustic imaging be safely used in live tissue. A laser-induced temperature rise of 1 mK yields an initial pressure of ∼800 Pa in soft tissue. Such a sound pressure level has reached the sensitivities of typical ultrasonic transducers. Fourthly, photoacoustic imaging has the ability of extracting multiple contrasts, including biochemical parameter, biomechanical parameter, blood velocity distribution, tissue temperature, and microstructure information. Photoacoustic imaging can capture more specific and reliable information about the tissue structure, function, metabolism

  17. Intravascular photoacoustic detection of vulnerable plaque based on constituent selected imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jian; Xing Da, E-mail: xingda@scnu.edu.cn [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631 (China)

    2011-01-01

    Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. Over decades, atherosclerosis is characterized by thickening of the walls of the arteries, only advanced atherosclerotic disease could be observed. Photoacoustic imaging is a hybrid imaging technique that combines the advantages of high spatial resolution of ultrasound with contrast of optical absorption. In this paper, we present an intravascular photoacoustic (IVPA) imaging system to characterize vulnerable plaques by using the optical absorption contrast between different constituents. Epidemiological studies have revealed several important plaque constituents associated with early atherosclerosis, such as macrophage, cholesterol, lipid, calcification, and so on. We chose a section of lipid rich atherosclerosis artery and a section of normal artery as the phantom. Two IVPA images of them are given to show the difference between sick and normal. As a new method of detecting vulnerable plaque, IVPA constituents imaging will provide more details for diagnosis that offer an enticing prospect in early detecting of atherosclerosis.

  18. Photoacoustic microscopy in tissue engineering

    Directory of Open Access Journals (Sweden)

    Xin Cai

    2013-03-01

    Full Text Available Photoacoustic tomography (PAT is an attractive modality for noninvasive, volumetric imaging of scattering media such as biological tissues. By choosing the ultrasonic detection frequency, PAT enables scalable spatial resolution with an imaging depth of up to ∼7 cm while maintaining a high depth-to-resolution ratio of ∼200 and consistent optical absorption contrasts. Photoacoustic microscopy (PAM, the microscopic embodiment of PAT, aims to image at millimeter depth and micrometer-scale resolution. PAM is well-suited for characterizing three-dimensional scaffold-based samples, including scaffolds themselves, cells, and blood vessels, both qualitatively and quantitatively. Here we review our previous work on applications of PAM in tissue engineering and then discuss its future developments.

  19. Two-photon absorption-induced photoacoustic imaging of Rhodamine B dyed polyethylene spheres using a femtosecond laser.

    Science.gov (United States)

    Langer, Gregor; Bouchal, Klaus-Dieter; Grün, Hubert; Burgholzer, Peter; Berer, Thomas

    2013-09-23

    In the present paper we demonstrate the possibility to image dyed solids, i.e. Rhodamine B dyed polyethylene spheres, by means of two-photon absorption-induced photoacoustic scanning microscopy. A two-photon luminescence image is recorded simultaneously with the photoacoustic image and we show that location and size of the photoacoustic and luminescence image match. In the experiments photoacoustic signals and luminescence signals are generated by pulses from a femtosecond laser. Photoacoustic signals are acquired with a hydrophone; luminescence signals with a spectrometer or an avalanche photo diode. In addition we derive the expected dependencies between excitation intensity and photoacoustic signal for single-photon absorption, two-photon absorption and for the combination of both. In order to verify our setup and evaluation method the theoretical predictions are compared with experimental results for liquid and solid specimens, i.e. a carbon fiber, Rhodamine B solution, silicon, and Rhodamine B dyed microspheres. The results suggest that the photoacoustic signals from the Rhodamine B dyed microspheres do indeed stem from two-photon absorption.

  20. Photoacoustic imaging of blood perfusion in tissue and phantoms

    Science.gov (United States)

    Pilatou, Magdalena C.; Kolkman, Roy G. M.; Hondebrink, Erwin; Bolt, Rene A.; de Mul, Frits F. M.

    2001-06-01

    To localize and monitor the blood content in tissue we developed a very sensitive photo-acoustical detector. PVDF has been used as piezo-electric material. In this detector also fibers for the illumination of the sample are integrated. Resolution is about 20 (m in depth and about 50-100 m laterally). We use 532 nm light. We will show how photoacoustics can be used for measuring the thickness of tissue above bone. We will also report measurements on tissue phantoms: e.g. a vessel delta from the epigastric artery branching of a Wistar rat, filled with an artificial blood-resembling absorber. The measurements have been carried out on phantoms containing vessels at several depths. Signal processing was enhanced by Fourier processing of the data.

  1. Reflection-mode photoacoustic microscopy using a hollow focused ultrasound transducer for in vivo imaging of blood vessels

    Institute of Scientific and Technical Information of China (English)

    Yuan Yi; Yang Si-Hua

    2012-01-01

    A reflection-mode photoacoustic microscope using a hollow focused ultrasound transducer is developed for highresolution in vivo imaging.A confocal structure of the laser and the ultrasound is used to improve the system resolution.The axial and lateral resolutions of the system are measured to be~32 μm and~58 μm,respectively.Ex vivo and in vivo modes are tested to validate the imaging capability of the photoacoustic microscope.The adjacent vein and artery can be seen clearly from the reconstructed photoacoustic images.The results demonstrate that the reflectionmode photoacoustic microscope can be used for high-resolution imaging of micro-blood vessels,which would be of great benefit for monitoring the neovascularization in tumor angiogenesis.

  2. Full-Wave Iterative Image Reconstruction in Photoacoustic Tomography with Acoustically Inhomogeneous Media

    CERN Document Server

    Huang, Chao; Nie, Liming; Wang, Lihong V; Anastasio, Mark A

    2013-01-01

    Existing approaches to image reconstruction in photoacoustic computed tomography (PACT) with acoustically heterogeneous media are limited to weakly varying media, are computationally burdensome, and/or cannot effectively mitigate the effects of measurement data incompleteness and noise. In this work, we develop and investigate a discrete imaging model for PACT that is based on the exact photoacoustic (PA) wave equation and facilitates the circumvention of these limitations. A key contribution of the work is the establishment of a procedure to implement a matched forward and backprojection operator pair associated with the discrete imaging model, which permits application of a wide-range of modern image reconstruction algorithms that can mitigate the effects of data incompleteness and noise. The forward and backprojection operators are based on the k-space pseudospectral method for computing numerical solutions to the PA wave equation in the time domain. The developed reconstruction methodology is investigated...

  3. In vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

    Science.gov (United States)

    2016-11-01

    prostate biopsy is only 52% due to either the absence of tumor or the inability to precisely sample small tumors with the biopsy needles. Thus, there is...ensure successful biopsy for those with small cancers. Photoacoustic imaging is an emerging functional imaging technique that can detect and...no reliable technology to identify the rare aggressive cancers among the mass of indolent screen-detected PrCa, which has lead to frequent over

  4. Palladium nanosheets as highly stable and effective contrast agents for in vivo photoacoustic molecular imaging

    Science.gov (United States)

    Nie, Liming; Chen, Mei; Sun, Xiaolian; Rong, Pengfei; Zheng, Nanfeng; Chen, Xiaoyuan

    2014-01-01

    A stable and efficient contrast agent is highly desirable for photoacoustic (PA) imaging applications. Recently gold nanostructures have been widely reported and studied for PA imaging and photothermal therapy. However, the structures of the nonspherical gold nanoparticles are easily destroyed after laser irradiation and thus may fail to complete the intended tasks. In this study, we propose to apply palladium nanosheets (PNSs), with strong optical absorption in the near-infrared (NIR) region, as a new class of exogenous PA contrast agents. PA and ultrasound (US) images were acquired sequentially by a portable and fast photoacoustic tomography (PAT) system with a hand-held transducer. Significant and long-lasting imaging enhancement in SCC7 head and neck squamous cell carcinoma was successfully observed in mice by PAT over time after tail vein administration of PNSs. The morphology and functional perfusion of the tumors were delineated in PA images due to the nanoparticle accumulation. PAT of the main organs was also conducted ex vivo to trace the fate of PNSs, which was further validated by inductively coupled plasma atomic emission spectrometry (ICP-AES). No obvious toxic effect was observed by in vitro MTT assay and ex vivo histological examination 7 days after PNS administration. With the combination of a portable imaging instrument and signal specificity, PNSs might be applied as stable and effective agents for photoacoustic cancer detection, diagnosis and treatment guidance.

  5. Imaging breast lesions using the Twente photoacoustic mammoscope: ongoing clinical experience

    Science.gov (United States)

    Heijblom, M.; Piras, D.; Xia, W.; van Hespen, J. C. G.; van den Engh, F. M.; Klaase, J. M.; van Leeuwen, T. G.; Steenbergen, W.; Manohar, S.

    2012-02-01

    Current imaging modalities are often not able to detect early stages of breast cancer with high imaging contrast. Visualizing malignancy-associated increased hemoglobin concentrations might improve breast cancer diagnosis. Photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound resolution, which makes it potentially ideal for breast imaging. The Twente Photoacoustic Mammoscope (PAM) has been designed specifically for this purpose. Based on a successful pilot study in 2007, a large clinical study using PAM has been started in December 2010. PAM uses a pulsed Q-switched Nd:YAG laser at 1064 nm to illuminate a region of interest on the breast. Photoacoustic signals are detected with a 1MHz, unfocused ultrasound detector array. Three dimensional data are reconstructed using an acoustic backprojection algorithm. Those reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study, the goal was to optimize the visualization of malignancies. We performed sixteen technically acceptable measurements on confined breast malignancies. In the reconstructed volumes of all malignancies, a confined high contrast region could be identified at the expected lesion depth. After ten successful measurements, the illumination area was increased and the fluence was substantially decreased. This caused a further significant increase in PAM lesion contrast.

  6. Breast imaging using the Twente photoacoustic mammoscope (PAM): new clinical measurements

    Science.gov (United States)

    Heijblom, Michelle; Piras, Daniele; Ten Tije, Ellen; Xia, Wenfeng; van Hespen, Johan; Klaase, Joost; van den Engh, Frank; van Leeuwen, Ton; Steenbergen, Wiendelt; Manohar, Srirang

    2011-07-01

    Worldwide, yearly about 450,000 women die from the consequences of breast cancer. Current imaging modalities are not optimal in discriminating benign from malignant tissue. Visualizing the malignancy-associated increased hemoglobin concentration might significantly improve early diagnosis of breast cancer. Since photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound-like resolution, it is potentially an ideal method for early breast cancer imaging. The Twente Photoacoustic Mammoscope (PAM) has been developed specifically for breast imaging. Recently, a large clinical study has been started in the Medisch Spectrum Twente in Oldenzaal using PAM. In PAM, the breast is slightly compressed between a window for laser light illumination and a flat array ultrasound detector. The measurements are performed using a Q-switched Nd:YAG laser, pulsed at 1064 nm and a 1 MHz unfocused ultrasound detector array. Three-dimensional data are reconstructed using a delay and sum reconstruction algorithm. Those reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study 12 patients with a malignant lesion and 2 patients with a benign cyst have been measured. The results are used to guide developments in photoacoustic mammography in order to pave the way towards an optimal technique for early diagnosis of breast cancer.

  7. Photoacoustic imaging system for peripheral small-vessel imaging based on clinical ultrasound technology

    Science.gov (United States)

    Irisawa, Kaku; Hirota, Kazuhiro; Hashimoto, Atsushi; Murakoshi, Dai; Ishii, Hiroyasu; Tada, Takuji; Wada, Takatsugu; Hayakawa, Toshiro; Azuma, Ryuichi; Otani, Naoki; Itoh, Kenji; Ishihara, Miya

    2016-03-01

    One of the features of photoacoustic (PA) imaging is small-vessel visualization realized without injection of a contrast agent or exposure to X-rays. For carrying out clinical studies in this field, a prototype PA imaging system has been developed. The PA imaging system utilizes a technological platform of FUJIFILM's clinical ultrasound (US) imaging system mounting many-core MPU for enhancing the image quality of US B-mode and US Doppler mode, which can be superposed onto PA images. By evaluating the PA and US Doppler images of the prototyped system, the applicability of the prototype system to small-vessel visualization has been discussed. The light source for PA imaging was on a compact cart of a US unit and emitted 750 nm wavelength laser pulses. The laser light was transferred to illumination optics in a handheld US transducer, which was connected to the US unit. Obtained PA rf data is reconstructed into PA images in the US unit. 3D images were obtained by scanning a mechanical stage, which the transducer is attached to. Several peripheral parts such as fingers, palms and wrists were observed by PA and US Doppler imaging. As for small arteries, US Doppler images were able to visualize the bow-shaped artery in the tip of the finger. Though PA images cannot distinguish arteries and veins, it could visualize smaller vessels and showed good resolution and vascular connectivity, resulting in a complementary image for the US Doppler images. Therefore, superposed images of the PA, US B-mode and US Doppler can visualize from large to small vessels without a contrast agent, which should be a differentiating feature of US/PA combined technology from other clinical vascular imaging modalities.

  8. NH4HCO3 gas-generating liposomal nanoparticle for photoacoustic imaging in breast cancer.

    Science.gov (United States)

    Xia, Jizhu; Feng, Gang; Xia, Xiaorong; Hao, Lan; Wang, Zhigang

    2017-01-01

    In this study, we have developed a biodegradable nanomaterial for photoacoustic imaging (PAI). Its biodegradation products can be fully eliminated from a living organism. It is a gas-generating nanoparticle of liposome-encapsulating ammonium bicarbonate (NH4HCO3) solution, which is safe, effective, inexpensive, and free of side effects. When lasers irradiate these nanoparticles, NH4HCO3 decomposes to produce CO2, which can absorb much of the light energy under laser irradiation with a specific wavelength, and then expand under heat to generate a thermal acoustic wave. An acoustic detector can detect this wave and show it as a photoacoustic signal on a display screen. The intensity of the photoacoustic signal is enhanced corresponding to an increase in time, concentration, and temperature. During in vivo testing, nanoparticles were injected into tumor-bearing nude mice through the caudal vein, and photoacoustic signals were detected from the tumor, reaching a peak in 4 h, and then gradually disappearing. There was no damage to the skin or subcutaneous tissue from laser radiation. Our developed gas-generating nanomaterial, NH4HCO3 nanomaterial, is feasible, effective, safe, and inexpensive. Therefore, it is a promising material to be used in clinical PAI.

  9. NH4HCO3 gas-generating liposomal nanoparticle for photoacoustic imaging in breast cancer

    Science.gov (United States)

    Xia, Jizhu; Feng, Gang; Xia, Xiaorong; Hao, Lan; Wang, Zhigang

    2017-01-01

    In this study, we have developed a biodegradable nanomaterial for photoacoustic imaging (PAI). Its biodegradation products can be fully eliminated from a living organism. It is a gas-generating nanoparticle of liposome-encapsulating ammonium bicarbonate (NH4HCO3) solution, which is safe, effective, inexpensive, and free of side effects. When lasers irradiate these nanoparticles, NH4HCO3 decomposes to produce CO2, which can absorb much of the light energy under laser irradiation with a specific wavelength, and then expand under heat to generate a thermal acoustic wave. An acoustic detector can detect this wave and show it as a photoacoustic signal on a display screen. The intensity of the photoacoustic signal is enhanced corresponding to an increase in time, concentration, and temperature. During in vivo testing, nanoparticles were injected into tumor-bearing nude mice through the caudal vein, and photoacoustic signals were detected from the tumor, reaching a peak in 4 h, and then gradually disappearing. There was no damage to the skin or subcutaneous tissue from laser radiation. Our developed gas-generating nanomaterial, NH4HCO3 nanomaterial, is feasible, effective, safe, and inexpensive. Therefore, it is a promising material to be used in clinical PAI. PMID:28293107

  10. Photo-imprint Photoacoustic Microscopy for Three-dimensional Label-free Sub-diffraction Imaging

    Science.gov (United States)

    Yao, Junjie; Wang, Lidai; Li, Chiye; Zhang, Chi; Wang, Lihong V.

    2014-01-01

    Sub-diffraction optical microscopy allows the imaging of cellular and subcellular structures with resolution finer than the diffraction limit. Here, combining the absorption-based photoacoustic effect and intensity-dependent photobleaching effect, we demonstrate a simple method for sub-diffraction photoacoustic imaging of both fluorescent and non-fluorescent samples. Our method is based on a double-excitation process, where the first excitation pulse partially and inhomogeneously bleaches the molecules in the diffraction-limited excitation volume, thus biasing the signal contributions from a second excitation pulse striking the same region. The differential signal between the two excitations preserves the signal contribution mostly from the center of the excitation volume, and dramatically sharpens the lateral resolution. Moreover, due to the nonlinear nature of the signal, our method offers inherent optical sectioning capability, which is lacking in conventional photoacoustic microscopy. By scanning the excitation beam, we performed three-dimensional sub-diffraction imaging of varied fluorescent and non-fluorescent species. As any molecules have absorption, this technique has the potential to enable label-free sub-diffraction imaging, and can be transferred to other optical imaging modalities or combined with other sub-diffraction methods. PMID:24483902

  11. Dynamic contrast-enhanced photoacoustic imaging using photothermal stimuli-responsive composite nanomodulators

    Science.gov (United States)

    Chen, Yun-Sheng; Yoon, Soon Joon; Frey, Wolfgang; Dockery, Mary; Emelianov, Stanislav

    2017-06-01

    Molecular photoacoustic imaging has shown great potential in medical applications; its sensitivity is normally in pico-to-micro-molar range, dependent on exogenous imaging agents. However, tissue can produce strong background signals, which mask the signals from the imaging agents, resulting in orders of magnitude sensitivity reduction. As such, an elaborate spectral scan is often required to spectrally un-mix the unwanted background signals. Here we show a new single-wavelength photoacoustic dynamic contrast-enhanced imaging technique by employing a stimuli-responsive contrast agent. Our technique can eliminate intrinsic background noises without significant hardware or computational resources. We show that this new contrast agent can generate up to 30 times stronger photoacoustic signals than the concentration-matched inorganic nanoparticle counterparts. By dynamically modulating signals from the contrast agents with an external near-infrared optical stimulus, we can further suppress the background signals leading to an additional increase of more than five-fold in imaging contrast in vivo.

  12. Application of laser pulse stretching scheme for efficiently delivering laser energy in photoacoustic imaging

    Science.gov (United States)

    Wang, Tianheng; Kumavor, Patrick D.; Zhu, Quing

    2012-06-01

    High-energy and short-duration laser pulses are desirable to improve the photoacoustic image quality when imaging deeply seated lesions. In many clinical applications, the high-energy pulses are coupled to tissue using optical fibers. These pulses can damage fibers if the damage threshold is exceeded. While keeping the total energy under the Food and Drug Administration limit for avoiding tissue damage, it is necessary to reduce the peak intensity and increase the pulse duration for minimizing fiber damage and delivering sufficient light for imaging. We use laser-pulse-stretching to address this problem. An initial 17-ns pulse was stretched to 27 and 37 ns by a ring-cavity laser-pulse-stretching system. The peak power of the 37-ns stretched pulse reduced to 42% of the original, while the fiber damage threshold was increased by 1.5-fold. Three ultrasound transducers centered at 1.3-, 3.5-, and 6-MHz frequencies were simulated, and the results showed that the photoacoustic signal of a 0.5-mm-diameter target obtained with 37-ns pulse was about 98, 91, and 80%, respectively, using the same energy as the 17-ns pulse. Simulations were validated using a broadband hydrophone. Quantitative comparisons of photoacoustic images obtained with three corresponding transducers showed that the image quality was not affected by stretching the pulse.

  13. Photoacoustic monitoring and imaging of blood vessels in tissue

    Science.gov (United States)

    Kolkman, Roy G. M.; Pilatou, Magdalena C.; Steenbergen, Wiendelt; de Mul, Frits F. M.

    2002-06-01

    Using very sensitive photoacoustical detectors we localized and monitored the blood content in tissue. In these detectors a PVdF-layer has been used as piezo-electric material and also fibers for the illumination of the sample are integrated. The resolution is about 20micrometers in depth and about 50-100micrometers laterally. The wavelengths of the laser light were 532 and 1064 nm. With these colors we can measure at different depths in tissue. The measurements concerned blood perfusion in real tissue: vessels in chicken breast, in test animals at various positions and in the human arm.

  14. Frequency-domain photoacoustic imaging system%频率域光声成像系统的研究

    Institute of Scientific and Technical Information of China (English)

    杨虹; 黄远辉; 苗少峰; 宫睿; 邵晓鹏; 毕祥丽

    2016-01-01

    Frequency-domain photoacoustic imaging is a new imaging modality, which uses the output amplitude information periodically modulated by a continuous-wave laser as a light source to stimulate biological tissues and to produce photoacoustic signals processed at frequency-domain and used to image the tissues. Firstly, the principles, developments and research status of photoacoustic imaging and frequency-domain photoacoustic imaging were introduced, and then the specific test methods and basic reconstruction algorithms of the frequency-domain photoacoustic imaging filed were described. In order to make up for time domain photoacoustic imaging with high costs, great harmful, poor portability and so on shortcomings, two imaging modalities were proposed and two complete experimental system structure diagrams were exhibited, showing different features and developing directions of photoacoustic imaging with respect to the traditional domain-photoacoustic imaging. At last, the outlook of the frequency-domain photoacoustic imaging was made to provide some references and guidance for our research and development about photoacoustic imaging.%频率域光声成像是指使用连续波激光器输出激光光源,利用该调制后的激光信号辐射组织,在频率域对激励的光声信号进行处理并成像的方式.首先阐述光声成像和频率域光声成像的原理、发展以及研究现状,然后介绍频率域光声成像的具体实验方法和基本重建算法.为了弥补时域光声成像成本高、伤害性大、便携性差等缺点,提出了频率域光声成像的两种成像方式,给出了完整的实验系统结构图,展示其相对于传统时域光声成像不同的研究特点与方向.最后对频率域光声成像进行展望,为光声成像在国内的研究和发展提供一定的借鉴和引导.

  15. Development of a high-sensitivity and portable cell using Helmholtz resonance for noninvasive blood glucose-level measurement based on photoacoustic spectroscopy.

    Science.gov (United States)

    Tachibana, K; Okada, K; Kobayashi, R; Ishihara, Y

    2016-08-01

    We describe the possibility of high-sensitivity noninvasive blood glucose measurement based on photoacoustic spectroscopy (PAS). The demand for noninvasive blood glucose-level measurement has increased due to the explosive increase in diabetic patients. We have developed a noninvasive blood glucose-level measurement based on PAS. The conventional method uses a straight-type resonant cell. However, the cell volume is large, which results in a low detection sensitivity and difficult portability. In this paper, a small-sized Helmholtz-type resonant cell is proposed to improve detection sensitivity and portability by reducing the cell dead volume. First, the acoustic property of the small-sized Helmholtz-type resonant cell was evaluated by performing an experiment using a silicone rubber. As a result, the detection sensitivity of the small-sized Helmholtz-type resonant cell was approximately two times larger than that of the conventional straight-type resonant cell. In addition, the inside volume was approximately 30 times smaller. Second, the detection limits of glucose concentration were estimated by performing an experiment using glucose solutions. The experimental results showed that a glucose concentration of approximately 1% was detected by the small-sized Helmholtz-type resonant cell. Although these results on the sensitivity of blood glucose-level measurement are currently insufficient, they suggest that miniaturization of a resonance cell is effective in the application of noninvasive blood glucose-level measurement.

  16. Gold nanorods combine photoacoustic and Raman imaging for detection and treatment of ovarian cancer

    Science.gov (United States)

    Jokerst, Jesse V.; Cole, Adam J.; Bohndiek, Sarah E.; Gambhir, Sanjiv S.

    2014-03-01

    Gold nanorods (GNRs) were synthesized with surfactant templating and coated with IR792 to produce surface-enhanced Raman signal (SERS). Subcutaneous and orthotopic tumor models were created in nude mice using the OV2008 cell line, and a Nexus128 scanner from Endra LifeSciences was used to collect the photoacoustic data. We used GNRs with resonance at 756 nm, and the Raman signal was 10-fold larger than 60 nm gold core/silica shell nanoparticles. This signal was stable for over 24 hours in 50% serum. The batch-to-batch reproducibility was 15.5% and 3.6% in the SERS and photoacoustic modalities for n=4 batches. Animals were injected with 200 μL of 2.5, 5.4, and 16.8 nM GNRs. Relative to baseline photoacoustic signal, these concentrations increased tumor signal 1.3-, 1.6-, and 2.5-fold, respectively. The maximum signal increase occurred within 2 hours of injection persisted for at least 24 hours and was significant at p0.90) between tumor gold concentration and photoacoustic signal. By 24 hours, free GNRs had been sequestered to the liver and spleen with 2%ID/g immobilized in the tumor. The same GNRs produced SERS signal, and Raman maps were created with least squares analysis. We used the Raman signal to identify tumor margins and also to monitor resection and ensure complete removal of tumor tissue. Thus, the GNRs allow pre-surgical photoacoustic visualization for tumor staging and intra-operative Raman imaging to guide resection. Future work will study GNRs targeted to cell surface proteins to increase tumor accumulation.

  17. Noncontact photoacoustic imaging achieved by using a low-coherence interferometer as the acoustic detector.

    Science.gov (United States)

    Wang, Yi; Li, Chunhui; Wang, Ruikang K

    2011-10-15

    We report on a noncontact photoacoustic imaging (PAI) technique in which a low-coherence interferometer [(LCI), optical coherence tomography (OCT) hardware] is utilized as the acoustic detector. A synchronization approach is used to lock the LCI system at its highly sensitive region for photoacoustic detection. The technique is experimentally verified by the imaging of a scattering phantom embedded with hairs and the blood vessels within a mouse ear in vitro. The system's axial and lateral resolutions are evaluated at 60 and 30 μm, respectively. The experimental results indicate that PAI in a noncontact detection mode is possible with high resolution and high bandwidth. The proposed approach lends itself to a natural integration of PAI with OCT, rather than a combination of two separate and independent systems.

  18. Co-registration of ultrasound and frequency-domain photoacoustic radar images and image improvement for tumor detection

    Science.gov (United States)

    Dovlo, Edem; Lashkari, Bahman; Choi, Sung soo Sean; Mandelis, Andreas

    2015-03-01

    This paper demonstrates the co-registration of ultrasound (US) and frequency domain photoacoustic radar (FD-PAR) images with significant image improvement from applying image normalization, filtering and amplification techniques. Achieving PA imaging functionality on a commercial Ultrasound instrument could accelerate clinical acceptance and use. Experimental results presented demonstrate live animal testing and show enhancements in signal-to-noise ratio (SNR), contrast and spatial resolution. The co-registered image produced from the US and phase PA images, provides more information than both images independently.

  19. Biological tissue component evaluation by measuring photoacoustic spectrum

    Science.gov (United States)

    Namita, Takeshi; Murata, Yuya; Tokuyama, Junji; Kondo, Kengo; Yamakawa, Makoto; Shiina, Tsuyoshi

    2017-03-01

    Photoacoustic imaging has garnered constant attention as a non-invasive modality for visualizing details of the neovascularization structure of tumors, or the distribution of oxygen saturation, which is related to the tumor grade. However, photoacoustic imaging is applicable not only for vascular imaging but also for diagnosing properties of various tissues such as skin or muscle diseases, fat related to arteriosclerosis or fatty liver, cartilage related to arthritis, and fibrous tissues related to hepatitis. The photoacoustic signal intensity is wavelength-dependent and proportional to the absorption coefficient and thermal acoustic conversion efficiency (i.e. Grüneisen parameter) of the target biological tissue. To ascertain the appropriate wavelength range for biological tissue imaging and to evaluate tissue properties, photoacoustic spectra of various tissues (e.g., skin, muscle, and adipose tissue) were measured using a hydrophone (9 mm diameter) at 680-1600 nm wavelengths. Results confirmed that respective tissues have unique photoacoustic spectra. However, almost all samples have peaks around 1200 nm and 1400-1500 nm for wavelengths where the light absorbance of lipid or water is high. The main components of biological tissues are water, protein, and lipid. Results confirmed that photoacoustic spectra reflect the tissue components well. To evaluate the feasibility of the tissue characterization using photoacoustic methods, the photoacoustic signal intensity ratio between two wavelength regions was calculated as described above. Signal intensity ratios agreed well with the composition ratio between water and lipid in samples. These analyses verified the feasibility of evaluating tissue properties using photoacoustic methods.

  20. Hybrid Photoacoustic/Ultrasound Tomograph for Real-Time Finger Imaging.

    Science.gov (United States)

    Oeri, Milan; Bost, Wolfgang; Sénégond, Nicolas; Tretbar, Steffen; Fournelle, Marc

    2017-10-01

    We report a target-enclosing, hybrid tomograph with a total of 768 elements based on capacitive micromachined ultrasound transducer technology and providing fast, high-resolution 2-D/3-D photoacoustic and ultrasound tomography tailored to finger imaging. A freely programmable ultrasound beamforming platform sampling data at 80 MHz was developed to realize plane wave transmission under multiple angles. A multiplexing unit enables the connection and control of a large number of elements. Fast image reconstruction is provided by GPU processing. The tomograph is composed of four independent and fully automated movable arc-shaped transducers, allowing imaging of all three finger joints. The system benefits from photoacoustics, yielding high optical contrast and enabling visualization of finger vascularization, and ultrasound provides morphologic information on joints and surrounding tissue. A diode-pumped, Q-switched Nd:YAG laser and an optical parametric oscillator are used to broaden the spectrum of emitted wavelengths to provide multispectral imaging. Custom-made optical fiber bundles enable illumination of the region of interest in the plane of acoustic detection. Precision in positioning of the probe in motion is ensured by use of a motor-driven guide slide. The current position of the probe is encoded by the stage and used to relate ultrasound and photoacoustic signals to the corresponding region of interest of the suspicious finger joint. The system is characterized in phantoms and a healthy human finger in vivo. The results obtained promise to provide new opportunities in finger diagnostics and establish photoacoustic/ultrasound-tomography in medical routine. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  1. Imaging a spatially confined photoacoustic source defined by a distribution of plasmonic nanoparticles

    Science.gov (United States)

    Norton, Stephen J.; Vo-Dinh, Tuan

    2012-05-01

    This paper describes the use of plasmonic nanoparticles in photoacoustic imaging. When acoustic waves are generated by thermoacoustic expansion in the fluid medium surrounding a distribution of these particles and the acoustic signals are recorded over a planar aperture, a bandlimited image of this distribution can be reconstructed. It is shown that the accessible portion of the three-dimensional spatial Fourier transform of the unknown source distribution is a spherical shell in k-space, with the core representing missing low-frequency Fourier components of the source density. When the source arises from an isolated distribution of nanoparticles, the iterative Gerchberg-Papoulis procedure can be applied to recover the low-frequency Fourier components. It is shown that this version of the photoacoustic source reconstruction problem is well suited for the use of this procedure. In this way, the fidelity of the image of the photoacoustic-generated source defined by the particle concentration can be enhanced. The procedure is illustrated using simulated data derived from a hypothetical source distribution.

  2. Forward and adjoint radiance Monte Carlo models for quantitative photoacoustic imaging

    Science.gov (United States)

    Hochuli, Roman; Powell, Samuel; Arridge, Simon; Cox, Ben

    2015-03-01

    In quantitative photoacoustic imaging, the aim is to recover physiologically relevant tissue parameters such as chromophore concentrations or oxygen saturation. Obtaining accurate estimates is challenging due to the non-linear relationship between the concentrations and the photoacoustic images. Nonlinear least squares inversions designed to tackle this problem require a model of light transport, the most accurate of which is the radiative transfer equation. This paper presents a highly scalable Monte Carlo model of light transport that computes the radiance in 2D using a Fourier basis to discretise in angle. The model was validated against a 2D finite element model of the radiative transfer equation, and was used to compute gradients of an error functional with respect to the absorption and scattering coefficient. It was found that adjoint-based gradient calculations were much more robust to inherent Monte Carlo noise than a finite difference approach. Furthermore, the Fourier angular discretisation allowed very efficient gradient calculations as sums of Fourier coefficients. These advantages, along with the high parallelisability of Monte Carlo models, makes this approach an attractive candidate as a light model for quantitative inversion in photoacoustic imaging.

  3. Zwitterion functionalized gold nanoclusters for multimodal near infrared fluorescence and photoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Danjin Shen

    2017-05-01

    Full Text Available Gold nanoclusters (Au NCs are an emerging type of theranostic agents combining therapeutic and imaging features with reduced toxicity. Au NCs stabilized by a zwitterion ligand with a fine control of the metal core size and the ligand coverage were synthesized by wet chemistry. Intense fluorescence signal is reported for the highest ligand coverage, whereas photoacoustic signal is stronger for the largest metal core. The best Au NC candidate with an average molecular weight of 17 kDa could be detected with high sensitivity on a 2D-near-infrared imaging instrument (limit of detection (LOD = 2.3 μM and by photoacoustic imaging. In vitro and in vivo experiments demonstrate an efficient cell uptake in U87 cell lines, a fast renal clearance (t1/2α = 6.5 ± 1.3 min, and a good correlation between near infrared fluorescence and photoacoustic measurements to follow the early uptake of Au NCs in liver.

  4. Transparent Fabry-Perot polymer film ultrasound array for backward-mode photoacoustic imaging

    Science.gov (United States)

    Beard, Paul C.; Zhang, Edward Z. Y.; Cox, Benjamin T.

    2004-07-01

    A novel optical ultrasound sensor has been developed for backward-mode photoacoustic imaging. The sensor is based on a Fabry Perot polymer film interferometer, the mirrors of which are transparent to 1064nm, but highly reflective at 850nm. When illuminated by a CW interrogating laser source at the latter wavelength, the system acts as a resonant Fabry Perot (FP) sensing cavity, the reflected intensity output of which is dependent upon acoustically-induced changes in the optical thickness of the polymer film. By optically addressing different regions of the sensor, a notional ultrasound array of arbitrary aperture and dimensionality can be synthesised. The system was demonstrated in backward mode by transmitting 1064nm excitation laser pulses through the sensor into an Intralipid scattering solution (μa=0.03mm-1, μs'=1mm-1) containing various absorbing structures and detecting the resulting photoacoustic signals over a line. A 1D depth profile of a 1.3mm thick absorbing polymer sheet (´a=0.8mm-1) immersed to a depth of 12mm in the Intralipid solution was obtained by performing an 11mm linescan. In another experiment, a 3-layer structure consisting of 0.076mm thick line absorbers was immersed in Intralipid and a 2D image reconstructed from the detected photoacoustic signals using an inverse k-space reconstruction algorithm. Lateral resolution was 0.4mm and the vertical resolution 0.1mm. The ability of this system to map wideband photoacoustic signals with high sensitivity in backward mode may provide a useful tool for high resolution imaging of superficial tissue structures such as the skin microvasculature.

  5. Photoacoustic-based nanomedicine for cancer diagnosis and therapy.

    Science.gov (United States)

    Sim, Changbeom; Kim, Haemin; Moon, Hyungwon; Lee, Hohyeon; Chang, Jin Ho; Kim, Hyuncheol

    2015-04-10

    Photoacoustic imaging is the latest promising diagnostic modality that has various advantages such as high spatial resolution, deep penetration depth, and use of non-ionizing radiation. It also employs a non-invasive imaging technique and optically functionalized imaging. The goal of this study was to develop a nanomedicine for simultaneous cancer therapy and diagnosis based on photoacoustic imaging. Human serum albumin nanoparticles loaded with melanin and paclitaxel (HMP-NPs) were developed using the desolvation technique. The photoacoustic-based diagnostic and chemotherapeutic properties of HMP-NPs were evaluated through in vitro and in vivo experiments. The size and zeta potential of the HMP-NPs were found to be 192.8±21.11nm and -22.2±4.39mV, respectively. In in vitro experiments, HMP-NPs produced increased photoacoustic signal intensity because of the loaded melanin and decreased cellular viability because of the encapsulated paclitaxel, compared to the free human serum albumin nanoparticles (the control). In vivo experiments showed that the HMP-NPs efficiently accumulated inside the tumor, resulting in the enhanced photoacoustic signal intensity in the tumor site, compared to the normal tissues. The in vivo chemotherapy study demonstrated that HMP-NPs had the capability to treat cancer for an extended period. In conclusion, HMP-NPs were simultaneously capable of photoacoustic diagnostic and chemotherapy against cancer.

  6. Photoacoustic and ultrasound dual-modality imaging of human peripheral joints

    Science.gov (United States)

    Xu, Guan; Rajian, Justin R.; Girish, Gandikota; Kaplan, Mariana J.; Fowlkes, J. Brian; Carson, Paul L.; Wang, Xueding

    2013-01-01

    A photoacoustic (PA) and ultrasound (US) dual modality system, for imaging human peripheral joints, is introduced. The system utilizes a commercial US unit for both US control imaging and PA signal acquisition. Preliminary in vivo evaluation of the system, on normal volunteers, revealed that this system can recover both the structural and functional information of intra- and extra-articular tissues. Confirmed by the control US images, the system, on the PA mode, can differentiate tendon from surrounding soft tissue based on the endogenous optical contrast. Presenting both morphological and pathological information in joint, this system holds promise for diagnosis and characterization of inflammatory joint diseases such as rheumatoid arthritis.

  7. Nonlinear contrast enhancement in photoacoustic molecular imaging with gold nanosphere encapsulated nanoemulsions

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Chen-wei; Lombardo, Michael; Larson-Smith, Kjersta; Perez, Camilo; Xia, Jinjun; Matula, Thomas; Pozzo, Danilo; O' Donnell, Matthew [Departments of Bioengineering and Chemical Engineering, and Applied Physics Lab, University of Washington, Seattle, Washington 98195 (United States); Pelivanov, Ivan [Departments of Bioengineering and Chemical Engineering, and Applied Physics Lab, University of Washington, Seattle, Washington 98195 (United States); International Laser Center, Moscow State University, Moscow (Russian Federation)

    2014-01-20

    A composite contrast agent, a nanoemulsion bead with assembled gold nanospheres at the interface, is proposed to improve the specific contrast of photoacoustic molecular imaging. A phase transition in the bead's core is induced by absorption of a nanosecond laser pulse with a fairly low laser fluence (∼3.5 mJ/cm{sup 2}), creating a transient microbubble through dramatically enhanced thermal expansion. This generates nonlinear photoacoustic signals with more than 10 times larger amplitude compared to that of a linear agent with the same optical absorption. By applying a differential scheme similar to ultrasound pulse inversion, more than 40 dB contrast enhancement is demonstrated with suppression of background signals.

  8. Stable J-aggregation enabled dual photoacoustic and fluorescence nanoparticles for intraoperative cancer imaging.

    Science.gov (United States)

    Shakiba, Mojdeh; Ng, Kenneth K; Huynh, Elizabeth; Chan, Harley; Charron, Danielle M; Chen, Juan; Muhanna, Nidal; Foster, F Stuart; Wilson, Brian C; Zheng, Gang

    2016-07-07

    J-aggregates display nanoscale optical properties which enable their use in fluorescence and photoacoustic imaging applications. However, control over their optical properties in an in vivo setting is hampered by the conformational lability of the J-aggregate structure in complex biological environments. J-aggregating nanoparticles (JNP) formed by self-assembly of bacteriopheophorbide-lipid (Bchl-lipid) in lipid nanovesicles represents a novel strategy to stabilize J-aggregates for in vivo bioimaging applications. We find that 15 mol% Bchl-lipid embedded within a saturated phospholipid bilayer vesicle was optimal in terms of maximizing Bchl-lipid dye loading, while maintaining a spherical nanoparticle morphology and retaining spectral properties characteristic of J-aggregates. The addition of cholesterol maintains the stability of the J-aggregate absorption band for up to 6 hours in the presence of 90% FBS. In a proof-of-concept experiment, we successfully applied JNPs as a fluorescence contrast agent for real-time intraoperative detection of metastatic lymph nodes in a rabbit head-and-neck cancer model. Lymph node metastasis delineation was further verified by visualizing the JNP within the excised lymph node using photoacoustic imaging. Using JNPs, we demonstrate the possibility of using J-aggregates as fluorescence and photoacoustic contrast agents and may potentially spur the development of other nanomaterials that can stably induce J-aggregation for in vivo cancer bioimaging applications.

  9. Tunable Semiconducting Polymer Nanoparticles with INDT-Based Conjugated Polymers for Photoacoustic Molecular Imaging.

    Science.gov (United States)

    Stahl, Thomas; Bofinger, Robin; Lam, Ivan; Fallon, Kealan J; Johnson, Peter; Ogunlade, Olumide; Vassileva, Vessela; Pedley, R Barbara; Beard, Paul C; Hailes, Helen C; Bronstein, Hugo; Tabor, Alethea B

    2017-06-21

    Photoacoustic imaging combines both excellent spatial resolution with high contrast and specificity, without the need for patients to be exposed to ionizing radiation. This makes it ideal for the study of physiological changes occurring during tumorigenesis and cardiovascular disease. In order to fully exploit the potential of this technique, new exogenous contrast agents with strong absorbance in the near-infrared range, good stability and biocompatibility, are required. In this paper, we report the formulation and characterization of a novel series of endogenous contrast agents for photoacoustic imaging in vivo. These contrast agents are based on a recently reported series of indigoid π-conjugated organic semiconductors, coformulated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, to give semiconducting polymer nanoparticles of about 150 nm diameter. These nanoparticles exhibited excellent absorption in the near-infrared region, with good photoacoustic signal generation efficiencies, high photostability, and extinction coefficients of up to three times higher than those previously reported. The absorption maximum is conveniently located in the spectral region of low absorption of chromophores within human tissue. Using the most promising semiconducting polymer nanoparticle, we have demonstrated wavelength-dependent differential contrast between vasculature and the nanoparticles, which can be used to unambiguously discriminate the presence of the contrast agent in vivo.

  10. Feasibility of transcranial photoacoustic imaging for interventional guidance of endonasal surgeries

    Science.gov (United States)

    Lediju Bell, Muyinatu A.; Ostrowski, Anastasia K.; Kazanzides, Peter; Boctor, Emad

    2014-03-01

    Endonasal surgeries to remove pituitary tumors incur the deadly risk of carotid artery injury due to limitations with real-time visualization of blood vessels surrounded by bone. We propose to use photoacoustic imaging to overcome current limitations. Blood vessels and surrounding bone would be illuminated by an optical fiber attached to the endonasal drill, while a transducer placed on the pterional region outside of the skull acquires images. To investigate feasibility, a plastisol phantom embedded with a spherical metal target was submerged in a water tank. The target was aligned with a 1-mm optical fiber coupled to a 1064nm Nd:YAG laser. An Ultrasonix L14-5W/60 linear transducer, placed approximately 1 cm above the phantom, acquired photoacoustic and ultrasound images of the target in the presence and absence of 2- and 4-mm-thick human adult cadaveric skull specimens. Though visualized at 18 mm depth when no bone was present, the target was not detectable in ultrasound images when the 4-mm thick skull specimen was placed between the transducer and phantom. In contrast, the target was visible in photoacoustic images at depths of 17-18 mm with and without the skull specimen. To mimic a clinical scenario where cranial bone in the nasal cavity reduces optical transmission prior to drill penetration, the 2-mm-thick specimen was placed between the phantom and optical fiber, while the 4-mm specimen remained between the phantom and transducer. In this case, the target was present at depths of 15-17 mm for energies ranging 9-18 mJ. With conventional delay-and-sum beamforming, the photoacoustic signal-tonoise ratios measured 15-18 dB and the contrast measured 5-13 dB. A short-lag spatial coherence beamformer was applied to increase signal contrast by 11-27 dB with similar values for SNR at most laser energies. Results are generally promising for photoacoustic-guided endonasal surgeries.

  11. Melanin-originated carbonaceous dots for triple negative breast cancer diagnosis by fluorescence and photoacoustic dual-mode imaging.

    Science.gov (United States)

    Xiao, Wei; Li, Yuan; Hu, Chuan; Huang, Yuan; He, Qin; Gao, Huile

    2017-07-01

    Carbonaceous dots exhibit increasing applications in diagnosis and drug delivery due to excellent photostability and biocompatibility properties. However, relative short excitation and emission of melanin carbonaceous dots (MCDs) limit the applicability in fluorescence bioimaging. Furthermore, the generally poor spatial resolution of fluorescence imaging limits potential in vivo applications. Due to a variety of beneficial properties, in this study, MCDs were prepared exhibiting great potential in fluorescence and photoacoustic dual-mode bioimaging. The MCDs exhibited a long excitation peak at 615nm and emission peak at 650nm, further highlighting the applicability in fluorescence imaging, while the absorbance peak at 633nm renders MCDs suitable for photoacoustic imaging. In vivo, the photoacoustic signal of MCDs was linearly correlated with the concentration of MCDs. Moreover, the MCDs were shown to be taken up into triple negative breast cancer cell line 4T1 in both a time- and concentration-dependent manner. In vivo fluorescence and photoacoustic imaging of subcutaneous 4T1 tumor demonstrated that MCDs could passively target triple negative breast cancer tissue by enhanced permeability and retention effects and may therefore be used for tumor dual-mode imaging. Furthermore, fluorescence distribution in tissue slices suggested that MCDs may distribute in 4T1 tumor with high efficacy. In conclusion, the MCDs studied offer potential application in fluorescence and photoacoustic dual-mode imaging.

  12. Non-invasive imaging of human embryonic stem cells.

    Science.gov (United States)

    Hong, Hao; Yang, Yunan; Zhang, Yin; Cai, Weibo

    2010-09-01

    Human embryonic stem cells (hESCs) hold tremendous therapeutic potential in a variety of diseases. Over the last decade, non-invasive imaging techniques have proven to be of great value in tracking transplanted hESCs. This review article will briefly summarize the various techniques used for non-invasive imaging of hESCs, which include magnetic resonance imaging (MRI), bioluminescence imaging (BLI), fluorescence, single-photon emission computed tomography (SPECT), positron emission tomography (PET), and multimodality approaches. Although the focus of this review article is primarily on hESCs, the labeling/tracking strategies described here can be readily applied to other (stem) cell types as well. Non-invasive imaging can provide convenient means to monitor hESC survival, proliferation, function, as well as overgrowth (such as teratoma formation), which could not be readily investigated previously. The requirement for hESC tracking techniques depends on the clinical scenario and each imaging technique will have its own niche in preclinical/clinical research. Continued evolvement of non-invasive imaging techniques will undoubtedly contribute to significant advances in understanding stem cell biology and mechanisms of action.

  13. Ex vivo detection of macrophages in atherosclerotic plaques using intravascular ultrasonic-photoacoustic imaging

    Science.gov (United States)

    Quang Bui, Nhat; Hlaing, Kyu Kyu; Lee, Yong Wook; Kang, Hyun Wook; Oh, Junghwan

    2017-01-01

    Macrophages are excellent imaging targets for detecting atherosclerotic plaques as they are involved in all the developmental stages of atherosclerosis. However, no imaging technique is currently capable of visualizing macrophages inside blood vessel walls. The current study develops an intravascular ultrasonic-photoacoustic (IVUP) imaging system combined with indocyanine green (ICG) as a contrast agent to provide morphological and compositional information about the targeted samples. Both tissue-mimicking vessel phantoms and atherosclerotic plaque-mimicking porcine arterial tissues are used to demonstrate the feasibility of mapping macrophages labeled with ICG by endoscopically applying the proposed hybrid technique. A delay pulse triggering technique is able to sequentially acquire photoacoustic (PA) and ultrasound (US) signals from a single scan without using any external devices. The acquired PA and US signals are used to reconstruct 2D cross-sectional and 3D volumetric images of the entire tissue with the ICG-loaded macrophages injected. Due to high imaging contrast and sensitivity, the IVUP imaging vividly reveals structural information and detects the spatial distribution of the ICG-labeled macrophages inside the samples. ICG-assisted IVUP imaging can be a feasible imaging modality for the endoscopic detection of atherosclerotic plaques.

  14. SU-E-J-44: Design a Platform and Phantom Model for Photoacoustic Imaging in Combination with CT

    Energy Technology Data Exchange (ETDEWEB)

    Sick, J; Alsanea, F; Rancilio, N; Stantz, K [Purdue University, West Lafayette, IN (United States)

    2014-06-01

    Purpose: Our (long-term) objective is to develop a US manipulator that will provide in situ radiation response and image-guided therapy for bladder cancer based on photoacoustic molecular imaging. Methods: A platform was devised to provide a reproducible positional frame of reference for targeting anatomic structure between MDCT and US scans, in lieu of CBCT, and to fuse photoacoustic molecular imaging. US and photoacoustic scans are taken of a patient while in the CT scanner and IRMT. Through co-registration, based on anatomical positions, we identified a common coordinate system to be used in Eclipse. A bladder phantom was constructed to validate anatomical tracking via US and photoacoustic imaging. We tested the platform using phantom model to demonstrate validity once moved from the CT couch to the linear accelerator couch. Results: This platform interlocks with Varian exact couch index points for reproducibility of positioning. Construction from low Z material and sized appropriately to fit in CT/IMRT gantry. Error in conversion from cylindrical coordinates of the manipulator to X, Y, Z coordinates of the treatment couch was less than 1mm. We measured the bladder size in 3 different directions in both Eclipse from the CT and Acuson from US. The error was less than 2mm in all directions. CT and US images were co-registered in MATLAB. Co-registration of photoacoustic images is still being developed. Conclusion: For Linear Accelerators without on board imaging, MV portal images are not a viable option for the localization of soft tissue anatomy. We believe our manipulator provides an alternative using US imaging, which will be examined in an upcoming clinical trial. We plan to examine the value of hypoxia guided treatment through photoacoustic imaging during this trial.

  15. Improving image quality by accounting for changes in water temperature during a photoacoustic tomography scan.

    Directory of Open Access Journals (Sweden)

    Dominique Van de Sompel

    Full Text Available The emerging field of photoacoustic tomography is rapidly evolving with many new system designs and reconstruction algorithms being published. Many systems use water as a coupling medium between the scanned object and the ultrasound transducers. Prior to a scan, the water is heated to body temperature to enable small animal imaging. During the scan, the water heating system of some systems is switched off to minimize the risk of bubble formation, which leads to a gradual decrease in water temperature and hence the speed of sound. In this work, we use a commercially available scanner that follows this procedure, and show that a failure to model intra-scan temperature decreases as small as 1.5°C leads to image artifacts that may be difficult to distinguish from true structures, particularly in complex scenes. We then improve image quality by continuously monitoring the water temperature during the scan and applying variable speed of sound corrections in the image reconstruction algorithm. While upgrading to an air bubble-free heating pump and keeping it running during the scan could also solve the changing temperature problem, we show that a software correction for the temperature changes provides a cost-effective alternative to a hardware upgrade. The efficacy of the software corrections was shown to be consistent across objects of widely varying appearances, namely physical phantoms, ex vivo tissue, and in vivo mouse imaging. To the best of our knowledge, this is the first study to demonstrate the efficacy of modeling temporal variations in the speed of sound during photoacoustic scans, as opposed to spatial variations as focused on by previous studies. Since air bubbles pose a common problem in ultrasonic and photoacoustic imaging systems, our results will be useful to future small animal imaging studies that use scanners with similarly limited heating units.

  16. Combined multi-modal photoacoustic tomography, optical coherence tomography (OCT) and OCT angiography system with an articulated probe for in vivo human skin structure and vasculature imaging.

    Science.gov (United States)

    Liu, Mengyang; Chen, Zhe; Zabihian, Behrooz; Sinz, Christoph; Zhang, Edward; Beard, Paul C; Ginner, Laurin; Hoover, Erich; Minneman, Micheal P; Leitgeb, Rainer A; Kittler, Harald; Drexler, Wolfgang

    2016-09-01

    Cutaneous blood flow accounts for approximately 5% of cardiac output in human and plays a key role in a number of a physiological and pathological processes. We show for the first time a multi-modal photoacoustic tomography (PAT), optical coherence tomography (OCT) and OCT angiography system with an articulated probe to extract human cutaneous vasculature in vivo in various skin regions. OCT angiography supplements the microvasculature which PAT alone is unable to provide. Co-registered volumes for vessel network is further embedded in the morphologic image provided by OCT. This multi-modal system is therefore demonstrated as a valuable tool for comprehensive non-invasive human skin vasculature and morphology imaging in vivo.

  17. Combined multi-modal photoacoustic tomography, optical coherence tomography (OCT) and OCT angiography system with an articulated probe for in vivo human skin structure and vasculature imaging

    Science.gov (United States)

    Liu, Mengyang; Chen, Zhe; Zabihian, Behrooz; Sinz, Christoph; Zhang, Edward; Beard, Paul C.; Ginner, Laurin; Hoover, Erich; Minneman, Micheal P.; Leitgeb, Rainer A.; Kittler, Harald; Drexler, Wolfgang

    2016-01-01

    Cutaneous blood flow accounts for approximately 5% of cardiac output in human and plays a key role in a number of a physiological and pathological processes. We show for the first time a multi-modal photoacoustic tomography (PAT), optical coherence tomography (OCT) and OCT angiography system with an articulated probe to extract human cutaneous vasculature in vivo in various skin regions. OCT angiography supplements the microvasculature which PAT alone is unable to provide. Co-registered volumes for vessel network is further embedded in the morphologic image provided by OCT. This multi-modal system is therefore demonstrated as a valuable tool for comprehensive non-invasive human skin vasculature and morphology imaging in vivo. PMID:27699106

  18. Photoacoustic image reconstruction from ultrasound post-beamformed B-mode image

    Science.gov (United States)

    Zhang, Haichong K.; Guo, Xiaoyu; Kang, Hyun Jae; Boctor, Emad M.

    2016-03-01

    A requirement to reconstruct photoacoustic (PA) image is to have a synchronized channel data acquisition with laser firing. Unfortunately, most clinical ultrasound (US) systems don't offer an interface to obtain synchronized channel data. To broaden the impact of clinical PA imaging, we propose a PA image reconstruction algorithm utilizing US B-mode image, which is readily available from clinical scanners. US B-mode image involves a series of signal processing including beamforming, followed by envelope detection, and end with log compression. Yet, it will be defocused when PA signals are input due to incorrect delay function. Our approach is to reverse the order of image processing steps and recover the original US post-beamformed radio-frequency (RF) data, in which a synthetic aperture based PA rebeamforming algorithm can be further applied. Taking B-mode image as the input, we firstly recovered US postbeamformed RF data by applying log decompression and convoluting an acoustic impulse response to combine carrier frequency information. Then, the US post-beamformed RF data is utilized as pre-beamformed RF data for the adaptive PA beamforming algorithm, and the new delay function is applied by taking into account that the focus depth in US beamforming is at the half depth of the PA case. The feasibility of the proposed method was validated through simulation, and was experimentally demonstrated using an acoustic point source. The point source was successfully beamformed from a US B-mode image, and the full with at the half maximum of the point improved 3.97 times. Comparing this result to the ground-truth reconstruction using channel data, the FWHM was slightly degraded with 1.28 times caused by information loss during envelope detection and convolution of the RF information.

  19. Three-dimensional photoacoustic imaging system with a 4f aspherical acoustic lens

    Science.gov (United States)

    Jen, En; Lin, Hsintien; Chiang, Huihua Kenny

    2016-08-01

    Photoacoustic (PA) imaging is a modality for achieving high-contrast images of blood vessels or tumors. Most PA imaging systems use complex reconstruction algorithms under conventional linear array transducers. We introduced the optical simulating method to improve the acoustic lens design and obtain a PA imaging system with improved spatial revolution (a 0.5-mm point spread function and a lateral image resolution of more than 1 mm) is realized using a 4f aspherical acoustic lens. The acoustic lens approach improved the image resolution and enabled direct reconstruction of three-dimensional (3-D) PA images. The system demonstrated a lateral resolution of more than 1 mm, a field of view of 8.5 deg, and a depth of focus of 10 mm. The system displays great potential for developing a real-time 3-D PA camera system for biomedical ultrasound imaging applications.

  20. A dual function theranostic agent for near-infrared photoacoustic imaging and photothermal therapy

    Science.gov (United States)

    Upputuri, Paul Kumar; Huang, Shuo; Wang, Mingfeng; Pramanik, Manojit

    2016-03-01

    Theranostic, defined as combining diagnostic and therapeutic agents, has attracted more attention in biomedical application. It is essential to monitor diseased tissue before treatment. Photothermal therapy (PTT) is a promising treatment of cancer tissue due to minimal invasion, unharmful to normal tissue and high efficiency. Photoacoustic tomography (PAT) is a hybrid nonionizing biomedical imaging modality that combines rich optical contrast and high ultrasonic resolution in a single imaging modality. The near infra-red (NIR) wavelengths, usually used in PAT, can provide deep penetration at the expense of reduced contrast, as the blood absorption drops in the NIR range. Exogenous contrast agents with strong absorption in the NIR wavelength range can enhance the photoacoustic imaging contrast as well as imaging depth. Most theranostic agents incorporating PAT and PTT are inorganic nanomaterials that suffer from poor biocompatibility and biodegradability. Herein, we present an benzo[1,2-c;4,5-c'] bis[1,2,5] thiadiazole (BBT), based theranostic agent which not only acts as photoacoustic contrast agent but also a photothermal therapy agent. Experiments were performed on animal blood and organic nanoparticles embedded in a chicken breast tissue using PAT imaging system at ~803 nm wavelengths. Almost ten time contrast enhancement was observed from the nanoparticle in suspension. More than 6.5 time PA signal enhancement was observed in tissue at 3 cm depth. HeLa cell lines was used to test photothermal effect showing 90% cells were killed after 10 min laser irradiation. Our results indicate that the BBT - based naoparticles are promising theranostic agents for PAT imaging and cancer treatment by photothermal therapy.

  1. Development of photoacoustic imaging technology overlaid on ultrasound imaging and its clinical application

    Science.gov (United States)

    Ishihara, Miya; Tsujita, Kazuhiro; Horiguchi, Akio; Irisawa, Kaku; Komatsu, Tomohiro; Ayaori, Makoto; Hirasawa, Takeshi; Kasamatsu, Tadashi; Hirota, Kazuhiro; Tsuda, Hitoshi; Ikewaki, Katsunori; Asano, Tomohiko

    2015-03-01

    Purpose: Photoacoustic imaging (PAI) enables one to visualize the distribution of hemoglobin and acquire a map of microvessels without using contrast agents. The purpose of our study is to develop a clinically applicable PAI system integrated with a clinical ultrasound (US) array system with handheld PAI probes providing coregistered PAI and US images. Clinical research trials were performed to evaluate the performance and feasibility of clinical value. Materials and Methods: We developed two types of handheld PAI probes: a linear PAI probe combining a conventional linear-array US probe with optical illumination and a transrectal ultrasonography (TRUS)-type PAI probe. We performed experiments with Japanese white rabbits and conducted clinical research trials of urology and vascular medicine with the approval of the medical human ethics committee of the National Defense Medical College. Results: We successfully acquired high-dynamic-range images of the vascular network ranging from capillaries to landmark arteries and identified the femoral vein, deep femoral vein, and great saphenous vein of rabbits. These major vessels in the rabbits groin are surrounded with microvessels connected to each other. Periprostatic microvessels were monitored during radical prostatectomy for localized prostate cancer and they were colocalized with nerve fibers, and their distribution was consistent with the corresponding PAI. The TRUS-type PAI probe clearly demonstrated the location and extent of the neurovascular bundle (NVB) better than does TRUS alone. Conclusions: The system, which can obtain a PAI, a US image, and a merged image, was innovatively designed so that medical doctors can easily find the location without any prior knowledge or extended skills to analyze the obtained images. Our pilot feasibility study confirms that PAI could be an imaging modality useful in the screening study and diagnostic biopsy.

  2. Salt-induced aggregation of gold nanoparticles for photoacoustic imaging and photothermal therapy of cancer

    Science.gov (United States)

    Sun, Mengmeng; Liu, Fei; Zhu, Yukun; Wang, Wansheng; Hu, Jin; Liu, Jing; Dai, Zhifei; Wang, Kun; Wei, Yen; Bai, Jing; Gao, Weiping

    2016-02-01

    The challenge in photothermal therapy (PTT) is to develop biocompatible photothermal transducers that can absorb and convert near-infrared (NIR) light into heat with high efficiency. Herein, we report salt-induced aggregation of gold nanoparticles (GNPs) in biological media to form highly efficient and biocompatible NIR photothermal transducers for PTT and photothermal/photoacoustic (PT/PA) imaging of cancer. The GNP depots in situ formed by salt-induced aggregation of GNPs show strong NIR absorption induced by plasmonic coupling between adjacent GNPs and very high photothermal conversion efficiency (52%), enabling photothermal destruction of tumor cells. More interestingly, GNPs in situ aggregate in tumors to form GNP depots, enabling simultaneous PT/PA imaging and PTT of the tumors. These findings may provide a simple and effective way to develop a new class of intelligent and biocompatible NIR photothermal transducers with high efficiency for PT/PA imaging and PTT.The challenge in photothermal therapy (PTT) is to develop biocompatible photothermal transducers that can absorb and convert near-infrared (NIR) light into heat with high efficiency. Herein, we report salt-induced aggregation of gold nanoparticles (GNPs) in biological media to form highly efficient and biocompatible NIR photothermal transducers for PTT and photothermal/photoacoustic (PT/PA) imaging of cancer. The GNP depots in situ formed by salt-induced aggregation of GNPs show strong NIR absorption induced by plasmonic coupling between adjacent GNPs and very high photothermal conversion efficiency (52%), enabling photothermal destruction of tumor cells. More interestingly, GNPs in situ aggregate in tumors to form GNP depots, enabling simultaneous PT/PA imaging and PTT of the tumors. These findings may provide a simple and effective way to develop a new class of intelligent and biocompatible NIR photothermal transducers with high efficiency for PT/PA imaging and PTT. Electronic supplementary

  3. Adaptive multi-sample-based photoacoustic tomography with imaging quality optimization

    Institute of Scientific and Technical Information of China (English)

    Yuxin Wang; Jie Yuan; Sidan Du; Xiaojun Liu; Guan Xu; Xueding Wang

    2015-01-01

    The energy of light exposed on human skin is compulsively limited for safety reasons which affects the power of photoacoustic (PA) signal and its signal-to-noise ratio (SNR) level.Thus,the final reconstructed PA image quality is degraded.This Letter proposes an adaptive multi-sample-based approach to enhance the SNR of PA signals and in addition,detailed information in rebuilt PA images that used to be buried in the noise can be distinguished.Both ex vivo and in vivo experiments are conducted to validate the effectiveness of our proposed method which provides its potential value in clinical trials.

  4. Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography

    Science.gov (United States)

    Chatni, Muhammad Rameez; Xia, Jun; Sohn, Rebecca; Maslov, Konstantin; Guo, Zijian; Zhang, Yu; Wang, Kun; Xia, Younan; Anastasio, Mark; Arbeit, Jeffrey; Wang, Lihong V.

    2012-07-01

    With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.

  5. Photoacoustic imaging of an inflammatory lesion model in the neonatal rat brain

    Science.gov (United States)

    Guevara, Edgar; Berti, Romain; Londono, Irène; Xie, Ningshi; Bellec, Pierre; Lesage, Frédéric; Lodygensky, G. A.

    2014-09-01

    Periventricular leukomalacia (PVL) is a condition that may cause significant neurodevelopmental handicap in premature newborns. It is characterized by white matter injury, associated with inflammation. This work aimed to assess the impact of inflammation on cerebral oxygen saturation (sO2) using depth-sensitive photoacoustic tomography (PAT). The aspects of PVL were reproduced in a rodent model by injection of lipopolysaccharide (LPS) into the corpus callosum. The results of this exploratory work reveal lower sO2 values in LPS group, as compared to sham controls; showing decreased values in the corpus callosum and in the left cortex, ipsilateral to the injection site. Interhemispherical connectivity was not affected by LPS injection, as shown by functional connectivity analysis. This study supports the use of PAT as a non-invasive tool to assess oxygenation values in vivo in the newborn brain.

  6. MRI Reporter Genes for Noninvasive Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Caixia Yang

    2016-05-01

    Full Text Available Magnetic resonance imaging (MRI is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific microenvironments. Commonly used reporter genes for MRI usually include genes encoding the enzyme (e.g., tyrosinase and β-galactosidase, the receptor on the cells (e.g., transferrin receptor, and endogenous reporter genes (e.g., ferritin reporter gene. However, low sensitivity limits the application of MRI and reporter gene-based multimodal imaging strategies are common including optical imaging and radionuclide imaging. These can significantly improve diagnostic efficiency and accelerate the development of new therapies.

  7. FPGA-Based Reconfigurable Processor for Ultrafast Interlaced Ultrasound and Photoacoustic Imaging

    Science.gov (United States)

    Alqasemi, Umar; Li, Hai; Aguirre, Andrés; Zhu, Quing

    2016-01-01

    In this paper, we report, to the best of our knowledge, a unique field-programmable gate array (FPGA)-based reconfigurable processor for real-time interlaced co-registered ultrasound and photoacoustic imaging and its application in imaging tumor dynamic response. The FPGA is used to control, acquire, store, delay-and-sum, and transfer the data for real-time co-registered imaging. The FPGA controls the ultrasound transmission and ultrasound and photoacoustic data acquisition process of a customized 16-channel module that contains all of the necessary analog and digital circuits. The 16-channel module is one of multiple modules plugged into a motherboard; their beamformed outputs are made available for a digital signal processor (DSP) to access using an external memory interface (EMIF). The FPGA performs a key role through ultrafast reconfiguration and adaptation of its structure to allow real-time switching between the two imaging modes, including transmission control, laser synchronization, internal memory structure, beamforming, and EMIF structure and memory size. It performs another role by parallel accessing of internal memories and multi-thread processing to reduce the transfer of data and the processing load on the DSP. Furthermore, because the laser will be pulsing even during ultrasound pulse-echo acquisition, the FPGA ensures that the laser pulses are far enough from the pulse-echo acquisitions by appropriate time-division multiplexing (TDM). A co-registered ultrasound and photoacoustic imaging system consisting of four FPGA modules (64-channels) is constructed, and its performance is demonstrated using phantom targets and in vivo mouse tumor models. PMID:22828830

  8. FPGA-based reconfigurable processor for ultrafast interlaced ultrasound and photoacoustic imaging.

    Science.gov (United States)

    Alqasemi, Umar; Li, Hai; Aguirre, Andrés; Zhu, Quing

    2012-07-01

    In this paper, we report, to the best of our knowledge, a unique field-programmable gate array (FPGA)-based reconfigurable processor for real-time interlaced co-registered ultrasound and photoacoustic imaging and its application in imaging tumor dynamic response. The FPGA is used to control, acquire, store, delay-and-sum, and transfer the data for real-time co-registered imaging. The FPGA controls the ultrasound transmission and ultrasound and photoacoustic data acquisition process of a customized 16-channel module that contains all of the necessary analog and digital circuits. The 16-channel module is one of multiple modules plugged into a motherboard; their beamformed outputs are made available for a digital signal processor (DSP) to access using an external memory interface (EMIF). The FPGA performs a key role through ultrafast reconfiguration and adaptation of its structure to allow real-time switching between the two imaging modes, including transmission control, laser synchronization, internal memory structure, beamforming, and EMIF structure and memory size. It performs another role by parallel accessing of internal memories and multi-thread processing to reduce the transfer of data and the processing load on the DSP. Furthermore, because the laser will be pulsing even during ultrasound pulse-echo acquisition, the FPGA ensures that the laser pulses are far enough from the pulse-echo acquisitions by appropriate time-division multiplexing (TDM). A co-registered ultrasound and photoacoustic imaging system consisting of four FPGA modules (64-channels) is constructed, and its performance is demonstrated using phantom targets and in vivo mouse tumor models.

  9. High repetition rate passively Q-switched fiber and microchip lasers for optical resolution photoacoustic imaging

    Science.gov (United States)

    Shi, Wei; Utkin, Ilya; Ranasinghesagara, Janaka; Pan, Lei; Godwal, Yogesh; Kerr, Shaun; Zemp, Roger J.; Fedosejevs, Robert

    2010-02-01

    Optical-resolution photoacoustic microscopy is a novel imaging technology for visualizing optically-absorbing superficial structures in vivo with lateral spatial resolution determined by optical focusing rather than acoustic detection. Since scanning of the illumination spot is required, the imaging speed is limited by the scanning speed and the laser pulse repetition rate. Unfortunately, lasers with high-repetition rate and suitable pulse durations and energies are difficult to find. We are developing compact laser sources for this application. Passively Q-switched fiber and microchip lasers with pulse repetition rates up to 300 kHz are demonstrated. Using a diode-pumped microchip laser fiber-coupled to a large mode-area Yb-doped fiber amplifier we obtained 60μJ 1-ns pulses at the frequency-doubled 532-nm wavelength. The pulse-repetition rate was determined by the power of the microchip laser pump source at 808nm and may exceed 10 kHz. Additionally, a passively Q-switched fiber laser utilizing a Yb-doped double-cladding fiber and an external saturable absorber has shown to produce 250ns pulses at repetition rates of 100-300 KHz. A photoacoustic probe enabling flexible scanning of the focused output of these lasers consisted of a 45-degree glass prism in an optical index-matching fluid. Photoacoustic signals exiting the sample are deflected by the prism to an ultrasound transducer. Phantom studies with a 7.5-micron carbon fiber demonstrate the ability to image with optical rather than acoustic resolution. We believe that the high pulse-repetition rates and the potentially compact and fiber-coupled nature of these lasers will prove important for clinical imaging applications where realtime imaging performance is essential.

  10. Photoacoustic projection imaging using a 64-channel fiber optic detector array

    Science.gov (United States)

    Bauer-Marschallinger, Johannes; Felbermayer, Karoline; Bouchal, Klaus-Dieter; Veres, Istvan A.; Grün, Hubert; Burgholzer, Peter; Berer, Thomas

    2015-03-01

    In this work we present photoacoustic projection imaging with a 64-channel integrating line detector array, which average the pressure over cylindrical surfaces. For imaging, the line detectors are arranged parallel to each other on a cylindrical surface surrounding a specimen. Thereby, the three-dimensional imaging problem is reduced to a twodimensional problem, facilitating projection imaging. After acquisition of a dataset of pressure signals, a twodimensional photoacoustic projection image is reconstructed. The 64 channel line detector array is realized using optical fibers being part of interferometers. The parts of the interferometers used to detect the ultrasonic pressure waves consist of graded-index polymer-optical fibers (POFs), which exhibit better sensitivity than standard glass-optical fibers. Ultrasonic waves impinging on the POFs change the phase of light in the fiber-core due to the strain-optic effect. This phase shifts, representing the pressure signals, are demodulated using high-bandwidth balanced photo-detectors. The 64 detectors are optically multiplexed to 16 detection channels, thereby allowing fast imaging. Results are shown on a Rhodamine B dyed microsphere.

  11. Comparison of transrectal photoacoustic, Doppler, and magnetic resonance imaging for prostate cancer detection

    Science.gov (United States)

    Ishihara, Miya; Horiguchi, Akio; Shinmoto, Hiroshi; Tsuda, Hitoshi; Irisawa, Kaku; Wada, Takatsugu; Asano, Tomohiko

    2016-03-01

    Transrectal ultrasonography (TRUS) is the most popular imaging modality for diagnosing and treating prostate cancer. TRUS-guided prostate biopsy is mandatory for the histological diagnosis of patients with elevated serum prostatespecific antigen (PSA), but its diagnostic accuracy is not satisfactory due to TRUS's low resolution. As a result, a considerable number of patients are required to undergo an unnecessary repeated biopsy. Photoacoustic imaging (PAI) can be used to provide microvascular network imaging using hemoglobin as an intrinsic, optical absorption molecule. We developed an original TRUS-type PAI probe consisting of a micro-convex array transducer with an optical illumination system to provide superimposed PAI and ultrasound images. TRUS-type PAI has the advantage of having much higher resolution and greater contrast than does Doppler TRUS. The purpose of this study was to demonstrate the clinical feasibility of the transrectal PAI system. We performed a clinical trial to compare the image of the cancerous area obtained by transrectal PAI with that obtained by TRUS Doppler during prostate biopsy. The obtained prostate biopsy cores were stained with anti-CD34 antibodies to provide a microvascular distribution map. We also confirmed its consistency with PAI and pre-biopsy MRI findings. Our study demonstrated that transrectal identification of tumor angiogenesis under superimposed photoacoustic and ultrasound images was easier than that under TRUS alone. We recognized a consistent relationship between PAI and MRI findings in most cases. However, there were no correspondences in some cases.

  12. Photoacoustic molecular imaging of angiogenesis using theranostic ανβ3-targeted copper nanoparticles incorporating a sn-2 lipase-labile fumagillin prodrug

    Science.gov (United States)

    Zhang, Ruiying; Cai, Xin; Yang, Xiaoxia; Senpan, Angana; Allen, John S.; Pan, Dipanjan; Lanza, Gregory M.; Wang, Lihong V.

    2014-03-01

    Photoacoustic (PA) tomography imaging is an emerging, versatile, and noninvasive imaging modality, which combines the advantages of both optical imaging and ultrasound imaging. It opens up opportunities for noninvasive imaging of angiogenesis, a feature of skin pathologies including cancers and psoriasis. In this study, high-density copper oleate encapsulated within a phospholipid surfactant (CuNPs) generated a soft nanoparticle with PA contrast comparable to gold. Within the near-infrared window, the copper nanoparticles can provide a signal more than 7 times higher that of blood. ανβ3-targeted of CuNPs in a Matrigel mouse model demonstrated prominent PA contrast enhancement of the neovasculature compared to mice given nontargeted or competitively inhibited CuNPs. Incorporation of a sn-2 lipase-labile fumagillin prodrug into the CuNPs produced marked antiangiogenesis in the same model, demonstrating the theranostic potential of a PA agent for the first time in vivo. With a PA signal comparable to gold-based nanoparticles yet a lower cost and demonstrated drug delivery potential, ανβ3-targeted CuNPs hold great promise for the management of skin pathologies with neovascular features.

  13. Noninvasive bioluminescence imaging in small animals.

    Science.gov (United States)

    Zinn, Kurt R; Chaudhuri, Tandra R; Szafran, April Adams; O'Quinn, Darrell; Weaver, Casey; Dugger, Kari; Lamar, Dale; Kesterson, Robert A; Wang, Xiangdong; Frank, Stuart J

    2008-01-01

    There has been a rapid growth of bioluminescence imaging applications in small animal models in recent years, propelled by the availability of instruments, analysis software, reagents, and creative approaches to apply the technology in molecular imaging. Advantages include the sensitivity of the technique as well as its efficiency, relatively low cost, and versatility. Bioluminescence imaging is accomplished by sensitive detection of light emitted following chemical reaction of the luciferase enzyme with its substrate. Most imaging systems provide 2-dimensional (2D) information in rodents, showing the locations and intensity of light emitted from the animal in pseudo-color scaling. A 3-dimensional (3D) capability for bioluminescence imaging is now available, but is more expensive and less efficient; other disadvantages include the requirement for genetically encoded luciferase, the injection of the substrate to enable light emission, and the dependence of light signal on tissue depth. All of these problems make it unlikely that the method will be extended to human studies. However, in small animal models, bioluminescence imaging is now routinely applied to serially detect the location and burden of xenografted tumors, or identify and measure the number of immune or stem cells after an adoptive transfer. Bioluminescence imaging also makes it possible to track the relative amounts and locations of bacteria, viruses, and other pathogens over time. Specialized applications of bioluminescence also follow tissue-specific luciferase expression in transgenic mice, and monitor biological processes such as signaling or protein interactions in real time. In summary, bioluminescence imaging has become an important component of biomedical research that will continue in the future.

  14. Muscle perfusion and metabolic heterogeneity: insights from noninvasive imaging techniques

    DEFF Research Database (Denmark)

    Kalliokoski, Kari K; Scheede-Bergdahl, Celena; Kjaer, Michael

    2006-01-01

    Recent developments in noninvasive imaging techniques have enabled the study of local changes in perfusion and metabolism in skeletal muscle as well as patterns of heterogeneity in these variables in humans. In this review, the principles of these techniques along with some recent findings on fun...

  15. Non-invasive terahertz field imaging inside parallel plate waveguides

    DEFF Research Database (Denmark)

    Iwaszczuk, Krzysztof; Andryieuski, Andrei; Lavrinenko, Andrei

    2011-01-01

    We present a non-invasive broadband air photonic method of imaging of the electric field of THz pulses propagating inside a tapered parallel plate waveguide. The method is based on field-enhanced second harmonic generation of the fundamental laser beam in an external electric field. We apply...

  16. Clinical study of ex vivo photoacoustic imaging in endoscopic mucosal resection tissues

    Science.gov (United States)

    Lim, Liang; Streutker, Catherine J.; Marcon, Norman; Cirocco, Maria; Lakovlev, Vladimir V.; DaCosta, Ralph; Foster, F. S.; Wilson, Brian C.

    2015-03-01

    Accurate endoscopic detection and dysplasia in patients with Barrett's esophagus (BE) remains a major unmet clinical need. Current diagnosis use multiple biopsies under endoscopic image guidance, where up to 99% of the tissue remains unsampled, leading to significant risk of missing dysplasia. We conducted an ex vivo clinical trial using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) with known high-grade dysplasia for the purpose of characterizing the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. EMR tissues were mounted immediately on an agar layer and covered with ultrasound gel. Digital photography guided the placement of the PAI transducer (40 MHz center frequency). The luminal side of the specimen was scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, 824, 850 and 970 nm. Acoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with H and E staining. Analysis consisted of co-registration and correlation between the intrinsic PAI features and the histological images. The initial PAI + ultrasound images from 8 BE patients have demonstrated the technical feasibility of this approach and point to the potential of PAI to reveal the microvascular pattern within EMR specimens. There are several technical factors to be considered in rigorous interpretation of the PAI characteristics, including the loss of blood from the ex vivo specimens and the limited depth penetration of the photoacoustic signal.

  17. Label-free photoacoustic microscopy of peripheral nerves

    Science.gov (United States)

    Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

    2014-01-01

    Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies.

  18. Engineering a near-infrared dark chromoprotein optimized for photoacoustic imaging (Conference Presentation)

    Science.gov (United States)

    Li, Yan; Barber, Quinn; Paproski, Robert J.; Enterina, Jhon R.; Rodriguez, Erik A.; Tsien, Roger Y.; Campbell, Robert E.; Zemp, Roger J.

    2016-03-01

    An optimal genetically-encoded probe for photoacoustic (PA) imaging should exhibit high optical absorption, low fluorescence quantum yield, and an absorption maxima within the near-infrared (NIR) window. One promising candidate is a newly engineered chromoprotein (CP), designated dark small ultra-red fluorescent protein (dsmURFP), which is based on a cyanobacterial phycobiliprotein. To optimize dsmURFP characteristics for PA imaging, we have developed a directed evolution method to iteratively screen libraries of protein variants with three different screening systems. Firstly, we took inspiration from dark-acceptor (also known as dark-quencher)-based Förster resonance energy transfer (FRET) constructs, and used dsmURFP as a dark acceptor from a mCardinal fluorescent donor. The rationale for this design was that the higher the extinction coefficient of the dsmURFP, the more the emission of the donor would be quenched. In addition, more energy transferred to the dark acceptor would lead to more thermoelastic expansion and a stronger PA signal. Three rounds of evolution using this first strategy resulted in dsmURFP1.3 that quenched the emission of mCardinal ~2-fold more efficiently than dsmURFP. Secondly, an absorption-based screening based on visual inspection of plates led to identification of the variant dsmURFP1.4, which exhibited a 2-fold higher absorbance and a 5 nm red shift. Thirdly, we developed a colony-based photoacoustic screening method. To demonstrate the utility of our optimized variants, we used photoacoustic imaging to visualize dsmURFP and its variants in phantom and in vivo experiments using chicken embryo models and murine bacterial bladder infection models.

  19. Optimizing the optical wavelength for the photoacoustic imaging of inflammatory arthritis

    Science.gov (United States)

    Jo, Janggun; Xu, Guan; Hu, Jack; Francis, Sheeja; Marquardt, April; Yuan, Jie; Girish, Gandikota; Wang, Xueding

    2015-03-01

    With the capability of assessing high resolution optical information in soft tissues at imaging depth up to several centimeters, innovative biomedical photoacoustic imaging (PAI) offers benefits to diagnosis and treatment monitoring of inflammatory arthritis, particularly in combination with more established ultrasonography (US). In this work, a PAI and US dual-modality system facilitating both imaging functions in a real-time fashion was developed and initially tested for its clinical performance on patients with active inflammatory arthritis. Photoacoustic (PA) images of metacarpophalangeal (MCP) joints were acquired at 580-nm wavelength that provides a desired balance between optical absorption of blood and attenuation in background tissue. The results from six patients and six normal volunteers used as a control demonstrated the satisfactory sensitivity of PAI in assessing the physiological changes in the joints, specifically enhanced blood flow as a result of active synovitis. This preliminary study suggests that PAI, by revealing vascular features suggestive of joint inflammation, could be a valuable supplement to musculoskeletal US for rheumatology clinic.

  20. Imaging and detection of early stage dental caries with an all-optical photoacoustic microscope

    Science.gov (United States)

    Hughes, D. A.; Sampathkumar, A.; Longbottom, C.; Kirk, K. J.

    2015-01-01

    Tooth decay, at its earliest stages, manifests itself as small, white, subsurface lesions in the enamel. Current methods for detection in the dental clinic are visual and tactile investigations, and bite-wing X-ray radiographs. These techniques suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease due to the small size (<100μm) of the lesion. A fine-resolution (600 nm) ultra-broadband (200 MHz) all-optical photoacoustic microscopy system was is used to image the early signs of tooth decay. Ex-vivo tooth samples exhibiting white spot lesions were scanned and were found to generate a larger (one order of magnitude) photoacoustic (PA) signal in the lesion regions compared to healthy enamel. The high contrast in the PA images potentially allows lesions to be imaged and measured at a much earlier stage than current clinical techniques allow. PA images were cross referenced with histology photographs to validate our experimental results. Our PA system provides a noncontact method for early detection of white-spot lesions with a high detection bandwidth that offers advantages over previously demonstrated ultrasound methods. The technique provides the sensing depth of an ultrasound system, but with the spatial resolution of an optical system.

  1. Dual modality of non-contact photoacoustic tomography and fluorescence imaging using double cladding fiber

    Science.gov (United States)

    Eom, Jonghyun; Park, Seong Jun; Kim, Ju Wan; Park, Soongho; Lee, Byeong Ha

    2015-03-01

    We present a fiber-based dual-modal imaging system that combines non-contact photoacoustic tomography (NCPAT) and fluorescence imaging by using double cladding fiber (DCF). The NCPAT system utilizing an all-fiber heterodyne interferometer as an ultrasound detector measures the photoacoustic signal at the sample surface without physical contact. Fluorescence imaging system is composed of fiber-optics to deliver the excitation light and the emission light. For combined system the probe consists of a specially fabricated DCF coupler and a lensed fiber so that we can simultaneously acquire the signals of two systems with the same probe. The DCF has a core and two claddings, inner and outer, which allows two concentric light-guiding channels via the core and the inner cladding. The lensed fiber of the DCF probe is compactly fabricated to focus the interferometer light and the excitation light, and to efficiently collect the fluorescence signal. To demonstrate the feasibility of the proposed dual-modal system, we have conducted phantom experiments using tissue mimicking phantoms which contained a couple of tubes filled with fluorescein solution and black ink, respectively. The proposed imaging system is implanted with fiber-optic configurations so that it has the potential for minimally invasive and improved diagnosis and guided treatment of diseases.

  2. Real-time volumetric lipid imaging in vivo by intravascular photoacoustics at 20 frames per second

    Science.gov (United States)

    Wu, Min; Springeling, Geert; Lovrak, Matija; Mastik, Frits; Iskander-Rizk, Sophinese; Wang, Tianshi; van Beusekom, Heleen M. M.; van der Steen, A. F. W.; Van Soest, Gijs

    2017-01-01

    Lipid deposition can be assessed with combined intravascular photoacoustic/ultrasound (IVPA/US) imaging. To date, the clinical translation of IVPA/US imaging has been stalled by a low imaging speed and catheter complexity. In this paper, we demonstrate imaging of lipid targets in swine coronary arteries in vivo, at a clinically useful frame rate of 20 s−1. We confirmed image contrast for atherosclerotic plaque in human samples ex vivo. The system is on a mobile platform and provides real-time data visualization during acquisition. We achieved an IVPA signal-to-noise ratio of 20 dB. These data show that clinical translation of IVPA is possible in principle. PMID:28270995

  3. Noninvasive Imaging of Administered Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    The objective of this research grant was to develop an approach for labeling progenitor cells, specifically those that we had identified as being able to replace ischemic heart cells, so that the distribution could be followed non-invasively. In addition, the research was aimed at determining whether administration of progenitor cells resulted in improved myocardial perfusion and function. The efficiency and toxicity of radiolabeling of progenitor cells was to be evaluated. For the proposed clinical protocol, subjects with end-stage ischemic coronary artery disease were to undergo a screening cardiac positron emission tomography (PET) scan using N-13 ammonia to delineate myocardial perfusion and function. If they qualified based on their PET scan, they would undergo an in-hospital protocol whereby CD34+ cells were stimulated by the administration of granulocytes-colony stimulating factor (G-CSF). CD34+ cells would then be isolated by apharesis, and labeled with indium-111 oxine. Cells were to be re-infused and subjects were to undergo single photon emission computed tomography (SPECT) scanning to evaluate uptake and distribution of labeled progenitor cells. Three months after administration of progenitor cells, a cardiac PET scan was to be repeated to evaluate changes in myocardial perfusion and/or function. Indium oxine is a radiopharmaceutical for labeling of autologous lymphocytes. Indium-111 (In-111) decays by electron capture with a t{sub ½} of 67.2 hours (2.8 days). Indium forms a saturated complex that is neutral, lipid soluble, and permeates the cell membrane. Within the cell, the indium-oxyquinolone complex labels via indium intracellular chelation. Following leukocyte labeling, ~77% of the In-111 is incorporated in the cell pellet. The presence of red cells and /or plasma reduces the labeling efficacy. Therefore, the product needed to be washed to eliminate plasma proteins. This repeated washing can damage cells. The CD34 selected product was a 90

  4. Non-Invasive in vivo Imaging in Small Animal Research

    Directory of Open Access Journals (Sweden)

    V. Koo

    2006-01-01

    Full Text Available Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI, Computed Tomography (CT, Positron Emission Tomography (PET, bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

  5. Multimodality Noninvasive Imaging in the Monitoring of Pediatric Heart Transplantation.

    Science.gov (United States)

    Kindel, Steven J; Hsu, Hao H; Hussain, Tarique; Johnson, Jonathan N; McMahon, Colin J; Kutty, Shelby

    2017-09-01

    Orthotopic heart transplantation is a well-established and effective therapeutic option for children with end-stage heart failure. Multiple modalities, including noninvasive cardiac imaging, cardiac catheterization, angiography, and endomyocardial biopsy, are helpful to monitor these patients for graft dysfunction, rejection, and vasculopathy. Because of morbidities associated with invasive monitoring, noninvasive imaging plays a key role in the surveillance and evaluation of symptoms in pediatric transplant recipients. Echocardiography with or without stress augmentation may provide serial data on systolic and diastolic function, ventricular deformation, and tissue characteristics in children after transplantation. Although not perfectly sensitive or specific, advanced two- and three-dimensional echocardiographic detection of functional changes in cardiac grafts may allow early recognition of allograft rejection. Magnetic resonance imaging has shown promise for characterization of edema and scar and myocardial perfusion reserve, as well as potential application for the detection of microvasculopathic changes in the transplanted heart. Cardiac computed tomography is particularly well suited for the demonstration of coronary artery dimensions and anatomic residual lesions. In combination, these noninvasive imaging techniques help the transplantation cardiologist screen for graft dysfunction, detect critical graft events, and identify situations that require invasive testing of the transplanted heart. Advanced multimodality imaging techniques are likely to increasingly shape the monitoring practices for children following heart transplantation. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  6. Stable J-aggregation enabled dual photoacoustic and fluorescence nanoparticles for intraoperative cancer imaging

    Science.gov (United States)

    Shakiba, Mojdeh; Ng, Kenneth K.; Huynh, Elizabeth; Chan, Harley; Charron, Danielle M.; Chen, Juan; Muhanna, Nidal; Foster, F. Stuart; Wilson, Brian C.; Zheng, Gang

    2016-06-01

    J-aggregates display nanoscale optical properties which enable their use in fluorescence and photoacoustic imaging applications. However, control over their optical properties in an in vivo setting is hampered by the conformational lability of the J-aggregate structure in complex biological environments. J-aggregating nanoparticles (JNP) formed by self-assembly of bacteriopheophorbide-lipid (Bchl-lipid) in lipid nanovesicles represents a novel strategy to stabilize J-aggregates for in vivo bioimaging applications. We find that 15 mol% Bchl-lipid embedded within a saturated phospholipid bilayer vesicle was optimal in terms of maximizing Bchl-lipid dye loading, while maintaining a spherical nanoparticle morphology and retaining spectral properties characteristic of J-aggregates. The addition of cholesterol maintains the stability of the J-aggregate absorption band for up to 6 hours in the presence of 90% FBS. In a proof-of-concept experiment, we successfully applied JNPs as a fluorescence contrast agent for real-time intraoperative detection of metastatic lymph nodes in a rabbit head-and-neck cancer model. Lymph node metastasis delineation was further verified by visualizing the JNP within the excised lymph node using photoacoustic imaging. Using JNPs, we demonstrate the possibility of using J-aggregates as fluorescence and photoacoustic contrast agents and may potentially spur the development of other nanomaterials that can stably induce J-aggregation for in vivo cancer bioimaging applications.J-aggregates display nanoscale optical properties which enable their use in fluorescence and photoacoustic imaging applications. However, control over their optical properties in an in vivo setting is hampered by the conformational lability of the J-aggregate structure in complex biological environments. J-aggregating nanoparticles (JNP) formed by self-assembly of bacteriopheophorbide-lipid (Bchl-lipid) in lipid nanovesicles represents a novel strategy to stabilize J

  7. In vivo spectroscopic photoacoustic tomography imaging of a far red fluorescent protein expressed in the exocrine pancreas of adult zebrafish

    Science.gov (United States)

    Liu, Mengyang; Schmitner, Nicole; Sandrian, Michelle G.; Zabihian, Behrooz; Hermann, Boris; Salvenmoser, Willi; Meyer, Dirk; Drexler, Wolfgang

    2014-03-01

    Fluorescent proteins brought a revolution in life sciences and biological research in that they make a powerful tool for researchers to study not only the structural and morphological information, but also dynamic and functional information in living cells and organisms. While green fluorescent proteins (GFP) have become a common labeling tool, red-shifted or even near infrared fluorescent proteins are becoming the research focus due to the fact that longer excitation wavelengths are more suitable for deep tissue imaging. In this study, E2-Crimson, a far red fluorescent protein whose excitation wavelength is 611 nm, was genetically expressed in the exocrine pancreas of adult zebrafish. Using spectroscopic all optical detection photoacoustic tomography, we mapped the distribution of E2-Crimson in 3D after imaging the transgenic zebrafish in vivo using two different wavelengths. With complementary morphological information provided by imaging the same fish using a spectral domain optical coherence tomography system, the E2-Crimson distribution acquired from spectroscopic photoacoustic tomography was confirmed in 2D by epifluorescence microscopy and in 3D by histology. To the authors' knowledge, this is the first time a far red fluorescent protein is imaged in vivo by spectroscopic photoacoustic tomography. Due to the regeneration feature of zebrafish pancreas, this work preludes the longitudinal studies of animal models of diseases such as pancreatitis by spectroscopic photoacoustic tomography. Since the effective penetration depth of photoacoustic tomography is beyond the transport mean free path length, other E2-Crimson labeled inner organs will also be able to be studied dynamically using spectroscopic photoacoustic tomography.

  8. Intravascular ultrasonic-photoacoustic (IVUP) endoscope with 2.2-mm diameter catheter for medical imaging.

    Science.gov (United States)

    Bui, Nhat Quang; Hlaing, Kyu Kyu; Nguyen, Van Phuc; Nguyen, Trung Hau; Oh, Yun-Ok; Fan, Xiao Feng; Lee, Yong Wook; Nam, Seung Yun; Kang, Hyun Wook; Oh, Junghwan

    2015-10-01

    Intravascular ultrasound (IVUS) imaging is extremely important for detection and characterization of high-risk atherosclerotic plaques as well as gastrointestinal diseases. Recently, intravascular photoacoustic (IVPA) imaging has been used to differentiate the composition of biological tissues with high optical contrast and ultrasonic resolution. The combination of these imaging techniques could provide morphological information and molecular screening to characterize abnormal tissues, which would help physicians to ensure vital therapeutic value and prognostic significance for patients before commencing therapy. In this study, integration of a high-frequency IVUS imaging catheter (45MHz, single-element, unfocused, 0.7mm in diameter) with a multi-mode optical fiber (0.6mm in core diameter, 0.22 NA), an integrated intravascular ultrasonic-photoacoustic (IVUP) imaging catheter, was developed to provide spatial and functional information on light distribution in a turbid sample. Simultaneously, IVUS imaging was co-registered to IVPA imaging to construct 3D volumetric sample images. In a phantom study, a polyvinyl alcohol (PVA) tissue-mimicking arterial vessel phantom with indocyanine green (ICG) and methylene blue (MB) inclusion was used to demonstrate the feasibility of mapping the biological dyes, which are used in cardiovascular and cancer diagnostics. For the ex vivo study, an excised sample of pig intestine with ICG was utilized to target the biomarkers present in the gastrointestinal tumors or the atherosclerotic plaques with the proposed hybrid technique. The results indicated that IVUP endoscope with the 2.2-mm diameter catheter could be a useful tool for medical imaging. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Assessment of disease activity in muscular dystrophies by noninvasive imaging.

    Science.gov (United States)

    Maguire, Katie K; Lim, Leland; Speedy, Sedona; Rando, Thomas A

    2013-05-01

    Muscular dystrophies are a class of disorders that cause progressive muscle wasting. A major hurdle for discovering treatments for the muscular dystrophies is a lack of reliable assays to monitor disease progression in animal models. We have developed a novel mouse model to assess disease activity noninvasively in mice with muscular dystrophies. These mice express an inducible luciferase reporter gene in muscle stem cells. In dystrophic mice, muscle stem cells activate and proliferate in response to muscle degeneration, resulting in an increase in the level of luciferase expression, which can be monitored by noninvasive, bioluminescence imaging. We applied this noninvasive imaging to assess disease activity in a mouse model of the human disease limb girdle muscular dystrophy 2B (LGMD2B), caused by a mutation in the dysferlin gene. We monitored the natural history and disease progression in these dysferlin-deficient mice up to 18 months of age and were able to detect disease activity prior to the appearance of any overt disease manifestation by histopathological analyses. Disease activity was reflected by changes in luciferase activity over time, and disease burden was reflected by cumulative luciferase activity, which paralleled disease progression as determined by histopathological analysis. The ability to monitor disease activity noninvasively in mouse models of muscular dystrophy will be invaluable for the assessment of disease progression and the effectiveness of therapeutic interventions.

  10. Multi-modality analysis of glucose aqueous solution using photoacoustic and dielectric spectroscopy for non-invasive glucose monitoring

    Science.gov (United States)

    Tajima, Takuro; Tanaka, Yujiro; Nakamura, Masahito; Seyama, Michiko

    2017-03-01

    Quantitative analysis of glucose using conventional optical spectroscopy suffers from a lack of repeatability due to high optical scattering in skin tissue. Here we present a multi-modality analysis of glucose aqueous solution using photoacoustic spectroscopy (PAS) and broadband dielectric spectroscopy (BDS). These techniques involve the direct detection of the acoustic and electromagnetic waves propagating through or reflecting from tissue without their being scattered. They therefore have potential for better tolerance to the variation of scattering. For PAS, to differentiate signals induced by water absorption, we select another laser wavelength (1.38 μm) that exhibits the same absorbance for water at 1.61 μm. Furthermore, one of the two photoacoustic signals is used to normalize the variations of acoustic properties in differential signal. Measured results for glucose solutions (0-2 g/dL) showed that the differential signal has a sensitivity of 1.61%/g·dL-1 and a detection limit of 120 mg/dL. We also tested glucose detection with BDS (500 MHz to 50 GHz) by detecting glucose hydration bonding at around 10-20 GHz. Using a partial least square analysis and first derivation on broadband spectra, we obtained an RMS error 19 mg/dL and a detection limit of 59 mg/dL. Using both the low-scattering ultrasonic and microwave detection techniques, we successfully captured the glucose footprint in the physiological range.

  11. Reflection-mode Bessel-beam photoacoustic microscopy for in vivo imaging of cerebral capillaries.

    Science.gov (United States)

    Jiang, Bowen; Yang, Xiaoquan; Luo, Qingming

    2016-09-05

    A reflection-mode Bessel-beam photoacoustic microscope (BB-PAM) is developed for the in vivo imaging of cerebral capillaries with extended depth of field (DoF). The non-diffraction characteristic of Bessel beams means that a larger DoF can be expected in the PAM compared to that using a Gaussian beam (GB). In our system, we generate the Bessel beam using an axicon and an annular mask. The lateral resolution of the system is estimated to be 1.6 μm. The DoF is measured to be 483 μm, and this is verified by imaging a carbon fiber network. The DoF of BB-PAM is about 7 times that of a GB-PAM. The cerebral vasculature of an open-skull mouse is imaged using the developed BB-PAM to demonstrate its in vivo imaging capability and advantages over GB-PAM.

  12. Non-invasive diagnostic imaging of colorectal liver metastases

    Institute of Scientific and Technical Information of China (English)

    Pier; Paolo; Mainenti; Federica; Romano; Laura; Pizzuti; Sabrina; Segreto; Giovanni; Storto; Lorenzo; Mannelli; Massimo; Imbriaco; Luigi; Camera; Simone; Maurea

    2015-01-01

    Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases(CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liverdirected therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs.

  13. Non-invasive diagnostic imaging of colorectal liver metastases.

    Science.gov (United States)

    Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone

    2015-07-28

    Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs.

  14. VCAM-1-targeting gold nanoshell probe for photoacoustic imaging of atherosclerotic plaque in mice.

    Science.gov (United States)

    Rouleau, Leonie; Berti, Romain; Ng, Vanessa W K; Matteau-Pelletier, Carl; Lam, Tina; Saboural, Pierre; Kakkar, Ashok K; Lesage, Frédéric; Rhéaume, Eric; Tardif, Jean-Claude

    2013-01-01

    The development of molecular probes and novel imaging modalities, allowing better resolution and specificity, is associated with an increased potential for molecular imaging of atherosclerotic plaques especially in basic and pre-clinical research applications. In that context, a photoacoustic molecular probe based on gold nanoshells targeting VCAM-1 in mice (immunonanoshells) was designed. The molecular probe was validated in vitro and in vivo, showing no noticeable acute toxic effects. We performed the conjugation of gold nanoshells displaying near-infrared absorption properties with VCAM-1 antibody molecules and PEG to increase their biocompatibility. The resulting immunonanoshells obtained under different conditions of conjugation were then assessed for specificity and sensitivity. Photoacoustic tomography was performed to determine the ability to distinguish gold nanoshells from blood both in phantoms and in vivo. Ex vivo optical projection tomography of hearts and aortas from atherosclerotic and control mice confirmed the selective accumulation of the immunonanoshells in atherosclerotic-prone regions in mice, thus validating the utility of the probe in vivo in small animals for pre-clinical research. These immunonanoshells represent an adequate mean to target atherosclerotic plaques in small animals, leading to new tools to follow the effect of therapies on the progression or regression of the disease.

  15. Polypyrrole coated phase-change contrast agents for sono-photoacoustic imaging (Conference Presentation)

    Science.gov (United States)

    Li, David S.; Yoon, Soon Joon; Matula, Thomas J.; O'Donnell, Matthew; Pozzo, Lilo D.

    2017-03-01

    A new light and sound sensitive nanoemulsion contrast agent is presented. The agents feature a low boiling point liquid perfluorocarbon core and a broad light spectrum absorbing polypyrrole (PPy) polymer shell. The PPy coated nanoemulsions can reversibly convert from liquid to gas phase upon cavitation of the liquid perfluorocarbon core. Cavitation can be initiated using a sufficiently high intensity acoustic pulse or from heat generation due to light absorption from a laser pulse. The emulsions can be made between 150 and 350 nm in diameter and PPy has a broad optical absorption covering both the visible spectrum and extending into the near-infrared spectrum (peak absorption 1053 nm). The size, structure, and optical absorption properties of the PPy coated nanoemulsions were characterized and compared to PPy nanoparticles (no liquid core) using dynamic light scattering, ultraviolet-visible spectrophotometry, transmission electron microscopy, and small angle X-ray scattering. The cavitation threshold and signal intensity were measured as a function of both acoustic pressure and laser fluence. Overlapping simultaneous transmission of an acoustic and laser pulse can significantly reduce the activation energy of the contrast agents to levels lower than optical or acoustic activation alone. We also demonstrate that simultaneous light and sound cavitation of the agents can be used in a new sono-photoacoustic imaging method, which enables greater sensitivity than traditional photoacoustic imaging.

  16. Influence of limited-view scanning on depth imaging of photoacoustic tomography

    Institute of Scientific and Technical Information of China (English)

    Wu Dan; Tao Chao; Liu Xiao-Jun; Wang Xue-Ding

    2012-01-01

    We study the influence of limited-view scanning on the depth imaging of photoacoustic tomography.The situation,in which absorbers are located at different depths with respect to the limited-view scanning trajectory,is called depth imaging and is investigated in this paper.The results show that limited-view scanning causes the reconstructed intensity of deep absorbers to be weaker than that of shallow ones and that deep absorbers will be invisible if the scanning range is too small.The concept of effective scanning angle is proposed to analyse that phenomenon.We find that an effective scanning angle can well predict the relationship between scanning angle and the intensity ratio of absorbers.In addition,limited-view scanning is employed to improve image quality.

  17. High-throughput fiber-array transvaginal ultrasound/photoacoustic probe for ovarian cancer imaging

    Science.gov (United States)

    Salehi, Hassan S.; Kumavor, Patrick D.; Alqasemi, Umar; Li, Hai; Wang, Tianheng; Zhu, Quing

    2014-03-01

    A high-throughput ultrasound/photoacoustic probe for delivering high contrast and signal-to-noise ratio images was designed, constructed, and tested. The probe consists of a transvaginal ultrasound array integrated with four 1mm-core optical fibers and a sheath. The sheath encases transducer and is lined with highly reflecting aluminum for high intensity light output and uniformity while at the same time remaining below the maximum permissible exposure (MPE) recommended by the American National Standards Institute (ANSI). The probe design was optimized by simulating the light fluence distribution in Zemax. The performance of the probe was evaluated by experimental measurements of the fluence and real-time imaging of polyethylene-tubing filled with blood. These results suggest that our probe has great potential for in vivo imaging and characterization of ovarian cancer.

  18. Targeted lipid-polyaniline hybrid nanoparticles for photoacoustic imaging guided photothermal therapy of cancer

    Science.gov (United States)

    Wang, Jinping; Yan, Ran; Guo, Fang; Yu, Meng; Tan, Fengping; Li, Nan

    2016-07-01

    Designing a targeted and versatile photothermal agent for the integration of precise diagnosis and effective photothermal treatment of tumors is desirable but remains a great challenge. In this study, folic acid ligand conjugated lipid-coated polyaniline hybrid nanoparticles (FA-Lipid-PANI NPs) were successfully fabricated by a distinctive technology. The obtained hybrid FA-Lipid-PANI NPs with small size exhibited not only significant photoacoustic (PA) imaging signals, but also a remarkable photothermal effect for tumor treatment. With PA imaging and photothermal therapy (PTT), the tumor could be accurately positioned and thoroughly eradicated in vivo after intravenous injection of FA-Lipid-PANI NPs. These multifunctional nanoparticles could play an important role in simultaneously facilitating imaging and PTT to achieve better therapeutic efficacy.

  19. Passive element enriched photoacoustic computed tomography (PER PACT) for simultaneous imaging of acoustic propagation properties and light absorption.

    Science.gov (United States)

    Jose, Jithin; Willemink, Rene G H; Resink, Steffen; Piras, Daniele; van Hespen, J C G; Slump, Cornelis H; Steenbergen, Wiendelt; van Leeuwen, Ton G; Manohar, Srirang

    2011-01-31

    We present a 'hybrid' imaging approach which can image both light absorption properties and acoustic transmission properties of an object in a two-dimensional slice using a computed tomography (CT) photoacoustic imager. The ultrasound transmission measurement method uses a strong optical absorber of small cross-section placed in the path of the light illuminating the sample. This absorber, which we call a passive element acts as a source of ultrasound. The interaction of ultrasound with the sample can be measured in transmission, using the same ultrasound detector used for photoacoustics. Such measurements are made at various angles around the sample in a CT approach. Images of the ultrasound propagation parameters, attenuation and speed of sound, can be reconstructed by inversion of a measurement model. We validate the method on specially designed phantoms and biological specimens. The obtained images are quantitative in terms of the shape, size, location, and acoustic properties of the examined heterogeneities.

  20. Phase Difference Optimization of Dual-Wavelength Excitation for the CW-Photoacoustic-Based Noninvasive and Selective Investigation of Aqueous Solutions of Glucose

    Directory of Open Access Journals (Sweden)

    Serge Camou

    2015-07-01

    Full Text Available Towards the noninvasive and continuous monitoring of blood glucose levels, we chose the continuous-wave photoacoustic (CW-PA technique and developed the optical power balance shift (OPBS method. However, operating with optical wavelengths in the near-infrared (NIR region ensures deep penetration inside human soft-tissue, but also leads to two serious issues: strong background level noise from water molecules in this wavelength range and small differences between the absorbance spectra of diluted compounds. To resolve them, the OPBS method relies on simultaneous optical excitation at two wavelengths for differential measurements. However, the first validation in vitro with calibrated aqueous solutions of glucose and albumin revealed strong dependence on the phase difference between the two lights sources. In this paper, we report a systematic investigation of this parameter, from PA-based measurements over a wide range of phase differences and an extensive characterization in the frequency domain. The process of maintaining the phase quadrature of the two optical signals is demonstrated in real time through an analysis of the PA signal and therefore does not require any additional equipment. Finally, a comparison of aqueous glucose solution characterizations at high concentration levels with the two methods was performed and consistent results were obtained.

  1. Experimental investigation of target and transducer effects on quantitative image reconstruction in photoacoustic tomography

    Science.gov (United States)

    Gamelin, John K.; Aguirre, Andres C.; Huang, Fei; Maurudis, Anastasios; Castillo, Diego; Wang, Lihong V.; Zhu, Quing

    2007-02-01

    In principle, absorbed energy profiles can be exactly reconstructed from photoacoustic measurements on a closed surface. Clinical applications, however, involve compromises due to transducer focus, frequency characteristics, and incomplete measurement apertures. These tradeoffs introduce artifacts and errors in reconstructed absorption distributions that affect quantitative interpretations as well as qualitative contrast between features. The quantitative effects of target geometry, limited measurement surfaces, and bandpass transducer frequency response have been investigated using a ring transducer system designed for small animal imaging. The directionality of photoacoustic radiation is shown to increase with target aspect ratio, producing proportionate overestimates of absorption values for two-dimension apertures less than approximately 150 degrees. For all target geometries and orientations, mean absorption values approach the full view values for hemicircular measurement surfaces although the true spatial uniformity is recovered only with the complete surface. The bandpass transducer frequency spectrum produces a peaked amplitude response biased toward spatial features ranging from 1 to 8 times the system resolution. We discuss the implications of these results for design of clinical systems.

  2. A Broadband Polyvinylidene Difluoride-Based Hydrophone with Integrated Readout Circuit for Intravascular Photoacoustic Imaging.

    Science.gov (United States)

    Daeichin, Verya; Chen, Chao; Ding, Qing; Wu, Min; Beurskens, Robert; Springeling, Geert; Noothout, Emile; Verweij, Martin D; van Dongen, Koen W A; Bosch, Johan G; van der Steen, Antonius F W; de Jong, Nico; Pertijs, Michiel; van Soest, Gijs

    2016-05-01

    Intravascular photoacoustic (IVPA) imaging can visualize the coronary atherosclerotic plaque composition on the basis of the optical absorption contrast. Most of the photoacoustic (PA) energy of human coronary plaque lipids was found to lie in the frequency band between 2 and 15 MHz requiring a very broadband transducer, especially if a combination with intravascular ultrasound is desired. We have developed a broadband polyvinylidene difluoride (PVDF) transducer (0.6 × 0.6 mm, 52 μm thick) with integrated electronics to match the low capacitance of such a small polyvinylidene difluoride element (<5 pF/mm(2)) with the high capacitive load of the long cable (∼100 pF/m). The new readout circuit provides an output voltage with a sensitivity of about 3.8 μV/Pa at 2.25 MHz. Its response is flat within 10 dB in the range 2 to 15 MHz. The root mean square (rms) output noise level is 259 μV over the entire bandwidth (1-20 MHz), resulting in a minimum detectable pressure of 30 Pa at 2.25 MHz.

  3. Feasibility of Prostate Cancer Diagnosis by Transrectal Photoacoustic Imaging

    Science.gov (United States)

    2014-05-01

    DOT. PA techniques can potentially be used for imaging cancers in human breast, prostate, skin , thyroid, neck, head, and others areas.4 PA techniques...Cole, Cengage Learning, 2013). 30. G. Zonios and A. Dimou, “Light scattering spectroscopy of human skin in vivo,” Opt. Express 17(3), 1256–1267...this pair is directly linked to the oxidized form of nicotinamide adenine dinucleotide, which is a major electron acceptor. In its reduced form, it

  4. In vivo tumor detection with combined MR–Photoacoustic-Thermoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Lin Huang

    2016-09-01

    Full Text Available Here, we report a new method using combined magnetic resonance (MR–Photoacoustic (PA–Thermoacoustic (TA imaging techniques, and demonstrate its unique ability for in vivo cancer detection using tumor-bearing mice. Circular scanning TA and PA imaging systems were used to recover the dielectric and optical property distributions of three colon carcinoma bearing mice While a 7.0-T magnetic resonance imaging (MRI unit with a mouse body volume coil was utilized for high resolution structural imaging of the same mice. Three plastic tubes filled with soybean sauce were used as fiducial markers for the co-registration of MR, PA and TA images. The resulting fused images provided both enhanced tumor margin and contrast relative to the surrounding normal tissues. In particular, some finger-like protrusions extending into the surrounding tissues were revealed in the MR/TA infused images. These results show that the tissue functional optical and dielectric properties provided by PA and TA images along with the anatomical structure by MRI in one picture make accurate tumor identification easier. This combined MR–PA–TA-imaging strategy has the potential to offer a clinically useful triple-modality tool for accurate cancer detection and for intraoperative surgical navigation.

  5. Generation of anatomically realistic numerical phantoms for photoacoustic and ultrasonic breast imaging.

    Science.gov (United States)

    Lou, Yang; Zhou, Weimin; Matthews, Thomas P; Appleton, Catherine M; Anastasio, Mark A

    2017-04-01

    Photoacoustic computed tomography (PACT) and ultrasound computed tomography (USCT) are emerging modalities for breast imaging. As in all emerging imaging technologies, computer-simulation studies play a critically important role in developing and optimizing the designs of hardware and image reconstruction methods for PACT and USCT. Using computer-simulations, the parameters of an imaging system can be systematically and comprehensively explored in a way that is generally not possible through experimentation. When conducting such studies, numerical phantoms are employed to represent the physical properties of the patient or object to-be-imaged that influence the measured image data. It is highly desirable to utilize numerical phantoms that are realistic, especially when task-based measures of image quality are to be utilized to guide system design. However, most reported computer-simulation studies of PACT and USCT breast imaging employ simple numerical phantoms that oversimplify the complex anatomical structures in the human female breast. We develop and implement a methodology for generating anatomically realistic numerical breast phantoms from clinical contrast-enhanced magnetic resonance imaging data. The phantoms will depict vascular structures and the volumetric distribution of different tissue types in the breast. By assigning optical and acoustic parameters to different tissue structures, both optical and acoustic breast phantoms will be established for use in PACT and USCT studies.

  6. Generation of anatomically realistic numerical phantoms for photoacoustic and ultrasonic breast imaging

    Science.gov (United States)

    Lou, Yang; Zhou, Weimin; Matthews, Thomas P.; Appleton, Catherine M.; Anastasio, Mark A.

    2017-04-01

    Photoacoustic computed tomography (PACT) and ultrasound computed tomography (USCT) are emerging modalities for breast imaging. As in all emerging imaging technologies, computer-simulation studies play a critically important role in developing and optimizing the designs of hardware and image reconstruction methods for PACT and USCT. Using computer-simulations, the parameters of an imaging system can be systematically and comprehensively explored in a way that is generally not possible through experimentation. When conducting such studies, numerical phantoms are employed to represent the physical properties of the patient or object to-be-imaged that influence the measured image data. It is highly desirable to utilize numerical phantoms that are realistic, especially when task-based measures of image quality are to be utilized to guide system design. However, most reported computer-simulation studies of PACT and USCT breast imaging employ simple numerical phantoms that oversimplify the complex anatomical structures in the human female breast. We develop and implement a methodology for generating anatomically realistic numerical breast phantoms from clinical contrast-enhanced magnetic resonance imaging data. The phantoms will depict vascular structures and the volumetric distribution of different tissue types in the breast. By assigning optical and acoustic parameters to different tissue structures, both optical and acoustic breast phantoms will be established for use in PACT and USCT studies.

  7. Lipid detection by intravascular photoacoustic imaging with flexible catheter at 20 fps (Conference Presentation)

    Science.gov (United States)

    Wu, Min; Daeichin, Verya; Springeling, Geert; van der Steen, Antonius F. W.; van Soest, Gijs

    2016-02-01

    Intravascular Photoacoustic (IVPA) imaging is a promising new technology to assess lipid content of coronary atherosclerotic plaque, an important determinant of the risk associated with the plaque triggering a heart attack. Clinical translation of IVPA imaging requires real-time image acquisition, which has been a technological challenge. In this work, we demonstrate a high-speed, dual-wavelength IVPA imaging system at 1.7 µm wavelength, operating with a flexible catheter of 1.2 mm outer diameter (including outer sheath). The catheter was custom designed and fabricated, and used a 40 MHz transducer for intravascular ultrasound (IVUS) and IVPA imaging. The optical excitation is provided by a dual OPO system, pumped by CW diode-pumped Q-switched Nd:YAG lasers, with a repetition rate of 5 kHz. Each OPO can be tuned to a custom wavelength between 1690 and 1750 nm; two wavelengths only are needed to discriminate between plaque lipids and adipose tissue. The pulse energy is about 80 µJ. We tested the imaging performance of the presented system in a polyvinyl-alcohol (PVA) vessel mimicking phantom and human coronary arteries ex vivo. IVPA identified lipid deposits inside atherosclerotic plaque, while IVUS showed tissue structure. We demonstrated IVPA imaging at a speed of 20 frames per second, with 250 A-scans per frame. This is significantly faster than previous IVPA imaging systems, and will enable the translation of IVPA imaging into clinical practice.

  8. Real-time intravascular ultrasound/photoacoustic imaging system with omni-directional light excitation

    Science.gov (United States)

    Hsieh, Bao-Yu; Li, Pai-Chi

    2012-02-01

    Photoacoustic (PA) imaging has been investigated for intravascular applications. One of the main challenges is that the imaging frame rate is limited by the pulse repetition frequency (PRF), thus making real-time imaging difficult with most high-power solid-state pulse lasers. The goal of this study is to combine omni-directional optical excitation with a ring array transducer for high-frame-rate imaging, so that the image frame rate is the same as the laser PRF. In the preliminary study, we developed a real-time integrated IVUS/IVPA imaging system by modifying an IVUS system in combination with a high-speed Nd:YLF pulsed laser. In addition, an optical fiber with axicon-like distal tip is designed for omni-directional excitation. In this design, a PA image is acquired without rotating the laser light. The imaging frame rate of this integrated imaging system is 19 fps. Both US and PA images are recorded at the same time and co-registered in the fusion image. The US/PA images of tungsten wire, black tube and rabbit's atherosclerotic aorta were acquired with this integrated system to evaluate its imaging performance. The lateral/axial -6 dB resolution of US image is 2.56°/62.4μm. Resolution of PA imaging is 3.76°/91.5μm. The imaging system was also utilized to acquire IVUS/IVPA images of atherosclerotic rabbit's aorta in ex vivo study.

  9. Cytotoxic Induction and Photoacoustic Imaging of Breast Cancer Cells Using Astaxanthin-Reduced Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Subramaniyan Bharathiraja

    2016-04-01

    Full Text Available Astaxanthin, a kind of photosynthetic pigment, was employed for gold nanoparticle formation. Nanoparticles were characterized using Ulteraviolet-Visible (UV-Vis spectroscopy, transmission electron microscopy, and X-ray diffraction, and the possible presence of astaxanthin functional groups were analyzed by Fourier transform infrared spectroscopy (FTIR. The cytotoxic effect of synthesized nanoparticles was evaluated against MDA-MB-231 (human breast cancer cells using a tetrazolium-based assay, and synthesized nanoparticles exhibited dose-dependent toxicity. The morphology upon cell death was differentiated through fluorescent microscopy using different stains that predicted apoptosis. The synthesized nanoparticles were applied in ultrasound-coupled photoacoustic imaging to obtain good images of treated cells. Astaxanthin-reduced gold nanoparticle has the potential to act as a promising agent in the field of photo-based diagnosis and therapy.

  10. Combined photoacoustic and ultrasound imaging of human breast in vivo in the mammographic geometry

    Science.gov (United States)

    Xie, Zhixing; Lee, Won-Mean; Hooi, Fong Ming; Fowlkes, J. Brian; Pinsky, Renee W.; Mueller, Dean; Wang, Xueding; Carson, Paul L.

    2013-03-01

    This photoacoustic volume imaging (PAVI) system is designed to study breast cancer detection and diagnosis in the mammographic geometry in combination with automated 3D ultrasound (AUS). The good penetration of near-infrared (NIR) light and high receiving sensitivity of a broad bandwidth, 572 element, 2D PVDF array at a low center-frequency of 1MHz were utilized with 20 channel simultaneous acquisition. The feasibility of this system in imaging optically absorbing objects in deep breast tissues was assessed first through experiments on ex vivo whole breasts. The blood filled pseudo lesions were imaged at depths up to 49 mm in the specimens. In vivo imaging of human breasts has been conducted. 3D PAVI image stacks of human breasts were coregistered and compared with 3D ultrasound image stacks of the same breasts. Using the designed system, PAVI shows satisfactory imaging depth and sensitivity for coverage of the entire breast when imaged from both sides with mild compression in the mammographic geometry. With its unique soft tissue contrast and excellent sensitivity to the tissue hemodynamic properties of fractional blood volume and blood oxygenation, PAVI, as a complement to 3D ultrasound and digital tomosynthesis mammography, might well contribute to detection, diagnosis and prognosis for breast cancer.

  11. Fabricating multifunctional microbubbles and nanobubbles for concurrent ultrasound and photoacoustic imaging

    Science.gov (United States)

    Qin, Ruogu; Xu, Jeff; Xu, Ronald; Kim, Chulhong; Wang, Lihong V.

    2010-02-01

    Background: Clinical ultrasound (US) uses ultrasonic scattering contrast to characterize subcutaneous anatomic structures. Photoacoustic (PA) imaging detects the functional properties of thick biological tissue with high optical contrast. In the case of image-guided cancer ablation therapy, simultaneous US and PA imaging can be useful for intraoperative assessment of tumor boundaries and ablation margins. In this regard, accurate co-registration between imaging modalities and high sensitivity to cancer cells are important. Methods: We synthesized poly-lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) encapsulating India ink or indocyanine green (ICG). Multiple tumor simulators were fabricated by entrapping ink MBs or NBs at various concentrations in gelatin phantoms for simultaneous US and PA imaging. MBs and NBs were also conjugated with CC49 antibody to target TAG-72, a human glycoprotein complex expressed in many epithelial-derived cancers. Results: Accurate co-registration and intensity correlation were observed in US and PA images of MB and NB tumor simulators. MBs and NBs conjugating with CC49 effectively bound with over-expressed TAG-72 in LS174T colon cancer cell cultures. ICG was also encapsulated in MBs and NBs for the potential to integrate US, PA, and fluorescence imaging. Conclusions: Multifunctional MBs and NBs can be potentially used as a general contrast agent for multimodal intraoperative imaging of tumor boundaries and therapeutic margins.

  12. Non-invasive imaging of microcirculation: a technology review

    Directory of Open Access Journals (Sweden)

    Eriksson S

    2014-12-01

    Full Text Available Sam Eriksson,1,2 Jan Nilsson,1,2 Christian Sturesson1,2 1Department of Surgery, Clinical Sciences Lund, Lund University, 2Skåne University Hospital, Lund, Sweden Abstract: Microcirculation plays a crucial role in physiological processes of tissue oxygenation and nutritional exchange. Measurement of microcirculation can be applied on many organs in various pathologies. In this paper we aim to review the technique of non-invasive methods for imaging of the microcirculation. Methods covered are: videomicroscopy techniques, laser Doppler perfusion imaging, and laser speckle contrast imaging. Videomicroscopy techniques, such as orthogonal polarization spectral imaging and sidestream dark-field imaging, provide a plentitude of information and offer direct visualization of the microcirculation but have the major drawback that they may give pressure artifacts. Both laser Doppler perfusion imaging and laser speckle contrast imaging allow non-contact measurements but have the disadvantage of their sensitivity to motion artifacts and that they are confined to relative measurement comparisons. Ideal would be a non-contact videomicroscopy method with fully automatic analysis software. Keywords: laser speckle contrast imaging, sidestream dark-field, orthogonal polarization spectral imaging, laser Dopplerimaging

  13. Biologically relevant photoacoustic imaging phantoms with tunable optical and acoustic properties

    Science.gov (United States)

    Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Joshua Pfefer, T.

    2016-10-01

    Established medical imaging technologies such as magnetic resonance imaging and computed tomography rely on well-validated tissue-simulating phantoms for standardized testing of device image quality. The availability of high-quality phantoms for optical-acoustic diagnostics such as photoacoustic tomography (PAT) will facilitate standardization and clinical translation of these emerging approaches. Materials used in prior PAT phantoms do not provide a suitable combination of long-term stability and realistic acoustic and optical properties. Therefore, we have investigated the use of custom polyvinyl chloride plastisol (PVCP) formulations for imaging phantoms and identified a dual-plasticizer approach that provides biologically relevant ranges of relevant properties. Speed of sound and acoustic attenuation were determined over a frequency range of 4 to 9 MHz and optical absorption and scattering over a wavelength range of 400 to 1100 nm. We present characterization of several PVCP formulations, including one designed to mimic breast tissue. This material is used to construct a phantom comprised of an array of cylindrical, hemoglobin-filled inclusions for evaluation of penetration depth. Measurements with a custom near-infrared PAT imager provide quantitative and qualitative comparisons of phantom and tissue images. Results indicate that our PVCP material is uniquely suitable for PAT system image quality evaluation and may provide a practical tool for device validation and intercomparison.

  14. Advances in noninvasive cardiovascular imaging: implications for the anesthesiologist.

    Science.gov (United States)

    Cahalan, M K; Litt, L; Botvinick, E H; Schiller, N B

    1987-03-01

    We have presented a review of recent advances in medical imaging which are relevant to the practice of anesthesia and associated research. The appropriate interpretation and use of the information derived from these noninvasive technologies can prevent unnecessary morbidity and mortality. Echocardiography remains the most advanced tool for noninvasive cardiac imaging because of its applicability for most cardiac disorders and its exquisite spatial resolution. Two-dimensional systems produce real time, dynamic, qualitative assessments of cardiac chamber morphology, size, thickness, and performance. The development of transesophageal echocardiography has brought this imaging power into the operating room for use by anesthesiologists. Recently developed quantitative and color-coded Doppler techniques will reveal intracardiac flow patterns and their alterations by anesthetics and surgery. These advantages are partially offset by inherent difficulties in quantifying echocardiographic data, and the need for highly trained operators for image reproduction. Nuclear cardiology and echocardiology are highly complementary. The scintigraphic methods identify myocardium at risk for infarction, confirm infarction when present, and produce quantitative, highly reproducible estimates of ventricular filling and performance. Time required to obtain data can be very brief for first-pass techniques, and these data are ideally suited for computer processing. Equilibrium studies require a larger dose of radioactive material, but provide excellent assessment of segmental wall motion. Preoperative studies with dipyridamole and Tl can indicate the patients truly at high risk for perioperative myocardial infarction. Monitoring and intensive care efforts may be better allocated with this information. No new technology in the past decade has stirred as much interest among clinicians as magnetic resonance imaging. Like echocardiography, it uses no ionizing radiation and is entirely noninvasive

  15. Folding Up of Gold Nanoparticle Strings into Plasmonic Vesicles for Enhanced Photoacoustic Imaging

    KAUST Repository

    Liu, Yijing

    2015-11-11

    The stepwise self-assembly of hollow plasmonic vesicles with vesicular membranes containing strings of gold nanoparticles (NPs) is reported. The formation of chain vesicles can be controlled by tuning the density of the polymer ligands on the surface of the gold NPs. The strong absorption of the chain vesicles in the near-infrared (NIR) region leads to a much higher efficiency in photoacoustic (PA) imaging than for non-chain vesicles. The chain vesicles were further employed for the encapsulation of drugs and the NIR light triggered release of payloads. This work not only offers a new platform for controlling the hierarchical self-assembly of NPs, but also demonstrates that the physical properties of the materials can be tailored by controlling the spatial arrangement of NPs within assemblies to achieve a better performance in biomedical applications.

  16. Photoacoustics with coherent light

    Directory of Open Access Journals (Sweden)

    Emmanuel Bossy

    2016-03-01

    Full Text Available Since its introduction in the mid-nineties, photoacoustic imaging of biological tissue has been one of the fastest growing biomedical imaging modality, and its basic principles are now considered as well established. In particular, light propagation in photoacoustic imaging is generally considered from the perspective of transport theory. However, recent breakthroughs in optics have shown that coherent light propagating through optically scattering medium could be manipulated towards novel imaging approaches. In this article, we first provide an introduction to the relevant concepts in the field, and then review the recent works showing that it is possible to exploit the coherence of light in conjunction with photoacoustics. We illustrate how the photoacoustic effect can be used as a powerful feedback mechanism for optical wavefront shaping in complex media, and conversely show how the coherence of light can be exploited to enhance photoacoustic imaging, for instance in terms of spatial resolution or for designing minimally invasive endoscopic devices. Finally, we discuss the current challenges and perspectives down the road towards practical applications in the field of photoacoustic imaging.

  17. Possibility of transrectal photoacoustic imaging-guided biopsy for detection of prostate cancer

    Science.gov (United States)

    Ishihara, Miya; Shinchi, Masayuki; Horiguchi, Akio; Shinmoto, Hiroshi; Tsuda, Hitoshi; Irisawa, Kaku; Wada, Takatsugu; Asano, Tomohiko

    2017-03-01

    A transrectral ultrasonography (TRUS) guided prostate biopsy is mandatory for histological diagnosis in patients with an elevated serum prostate-specific antigen (PSA), but its diagnostic accuracy is not satisfactory; therefore, a considerable number of patients are forced to have an unnecessary repeated biopsy. Photoacoustic (PA) imaging has the ability to visualize the distribution of hemoglobin clearly. Thus, there is the potential to acquire different maps of small vessel networks between cancerous and normal tissue. We developed an original TRUS-type PA probe consisting of a microconvex array transducer with an optical illumination system providing coregistered PA and ultrasound images. The purpose of this study is to demonstrate the clinical possibility of a transrectral PA image. The prostate biopsy cores obtained by transrectal systemic biopsies under TRUS guidance were stained with HE staining and anti-CD34 antibodies as a marker of the endothelium of the blood vessel in order to find a pattern in the map of a small vessel network, which allows for imaging-based identification of prostate cancer. We analyzed the association of PA signal patterns, the cancer location by a magnetic resonance imaging (MRI) study, and the pathological diagnosis with CD34 stains as a prospective intervention study. In order to demonstrate the TRUS-merged-with-PA imaging guided targeted biopsy combined with a standard biopsy for capturing the clinically significant tumors, we developed a puncture needle guide attachment for the original TRUS-type PA probe.

  18. A Cystine Knot Peptide Targeting Integrin αvβ6 for Photoacoustic and Fluorescence Imaging of Tumors in Living Subjects.

    Science.gov (United States)

    Zhang, Chao; Kimura, Richard; Abou-Elkacem, Lotfi; Levi, Jelena; Xu, Lingyun; Gambhir, Sanjiv Sam

    2016-10-01

    Photoacoustic imaging is a nonionizing biomedical imaging modality with higher resolution and imaging depth than fluorescence imaging, which has greater sensitivity. The combination of the 2 imaging modalities could improve the detection of cancer. Integrin αvβ6 is a cell surface marker overexpressed in many different cancers. Here, we report the development and evaluation of a dye-labeled cystine knot peptide, which selectively recognizes integrin αvβ6 with high affinity, for photoacoustic and fluorescence imaging. The new dual-modality probe may find clinical application in cancer diagnosis and intraoperative imaging of integrin αvβ6-positive tumors.

  19. In vivo photoacoustic imaging of chemotherapy-induced apoptosis in squamous cell carcinoma using a near-infrared caspase-9 probe

    Science.gov (United States)

    Yang, Qiuhong; Cui, Huizhong; Cai, Shuang; Yang, Xinmai; Forrest, M. Laird

    2011-11-01

    Anti-cancer drugs typically exert their pharmacological effect on tumors by inducing apoptosis, or programmed cell death, within the cancer cells. However, no tools exist in the clinic for detecting apoptosis in real time. Microscopic examination of surgical biopsies and secondary responses, such as morphological changes, are used to verify efficacy of a treatment. Here, we developed a novel near-infrared dye-based imaging probe to directly detect apoptosis with high specificity in cancer cells by utilizing a noninvasive photoacoustic imaging (PAI) technique. Nude mice bearing head and neck tumors received cisplatin chemotherapy (10 mg/kg) and were imaged by PAI after tail vein injection of the contrast agent. In vivo PAI indicated a strong apoptotic response to chemotherapy on the peripheral margins of tumors, whereas untreated controls showed no contrast enhancement by PAI. The apoptotic status of the mouse tumor tissue was verified by immunohistochemical techniques staining for cleaved caspase-3 p11 subunit. The results demonstrated the potential of this imaging probe to guide the evaluation of chemotherapy treatment.

  20. Label-free imaging of gold nanoparticles in single live cells by photoacoustic microscopy

    Science.gov (United States)

    Tian, Chao; Qian, Wei; Shao, Xia; Xie, Zhixing; Cheng, Xu; Liu, Shengchun; Cheng, Qian; Liu, Bing; Wang, Xueding

    2016-03-01

    Gold nanoparticles (AuNPs) have been extensively explored as a model nanostructure in nanomedicine and have been widely used to provide advanced biomedical research tools in diagnostic imaging and therapy. Due to the necessity of targeting AuNPs to individual cells, evaluation and visualization of AuNPs in the cellular level is critical to fully understand their interaction with cellular environment. Currently imaging technologies, such as fluorescence microscopy and transmission electron microscopy all have advantages and disadvantages. In this paper, we synthesized AuNPs by femtosecond pulsed laser ablation, modified their surface chemistry through sequential bioconjugation, and targeted the functionalized AuNPs with individual cancer cells. Based on their high optical absorption contrast, we developed a novel, label-free imaging method to evaluate and visualize intracellular AuNPs using photoacoustic microscopy (PAM). Preliminary study shows that the PAM imaging technique is capable of imaging cellular uptake of AuNPs in vivo at single-cell resolution, which provide an important tool for the study of AuNPs in nanomedicine.

  1. Performance characterization of an integrated ultrasound, photoacoustic, and thermoacoustic imaging system

    Science.gov (United States)

    Ke, Haixin; Erpelding, Todd N.; Jankovic, Ladislav; Liu, Changjun; Wang, Lihong V.

    2012-05-01

    We developed a novel trimodality system for human breast imaging by integrating photoacoustic (PA) and thermoacoustic (TA) imaging techniques into a modified commercial ultrasound scanner. Because light was delivered with an optical assembly placed within the microwave antenna, no mechanical switching between the microwave and laser sources was needed. Laser and microwave excitation pulses were interleaved to enable PA and TA data acquisition in parallel at a rate of 10 frames per second. A tube (7 mm inner diameter) filled with oxygenated bovine blood or 30 mM methylene blue dye was successfully detected in PA images in chicken breast tissue at depths of 6.6 and 8.4 cm, respectively, for the first time. The SNRs at these depths reached ˜24 and ˜15 dB, respectively, by averaging 200 signal acquisitions. Similarly, a tube (13 mm inner diameter) filled with saline solution (0.9%) at a depth of 4.4 cm in porcine fat tissue was successfully detected in TA images. The PA axial, lateral, and elevational resolutions were 640 μm, 720 μm, and 3.5 mm, respectively, suitable for breast cancer imaging. A PA noise-equivalent sensitivity to methylene blue solution of 260 nM was achieved in chicken tissue at a depth of 3.4 cm.

  2. Combined photoacoustic and ultrasound biomicroscopy.

    Science.gov (United States)

    Harrison, Tyler; Ranasinghesagara, Janaka C; Lu, Huihong; Mathewson, Kory; Walsh, Andrew; Zemp, Roger J

    2009-11-23

    We report on the development of an imaging system capable of combined ultrasound and photoacoustic imaging based on a fast-scanning single-element 25-MHz ultrasound transducer and a unique light-delivery system. The system is capable of 20 ultrasound frames per second and slower photoacoustic frame rates limited by laser pulse-repetition rates. Laser and ultrasound pulses are interlaced for co-registration of photoacoustic and ultrasound images. In vivo imaging of a human finger permits ultrasonic visualization of vessel structures and speckle changes indicative of blood flow, while overlaid photoacoustic images highlight some small vessels that are not clear from the ultrasound scan. Photoacoustic images provide optical absorption contrast co-registered in the structural and blood-flow context of ultrasound with high-spatial resolution and may prove important for clinical diagnostics and basic science of the microvasculature.

  3. Multifunctional biocompatible chitosan-polypyrrole nanocomposites as novel agents for photoacoustic imaging-guided photothermal ablation of cancer

    Science.gov (United States)

    Manivasagan, Panchanathan; Quang Bui, Nhat; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Oh, Yun-Ok; Song, Kyeongeun; Seo, Hansu; Yoon, Min; Oh, Junghwan

    2017-01-01

    Cancer nanotechnology is emerging as one of the promising strategies combining photothermal therapy (PTT) and photoacoustic imaging (PAI) for the treatment of breast cancer and it has received considerable attention in the recent years because it is minimally invasive, prevents damage to non-targeted regions, permits fast recovery, and involves breast cancer imaging. The present study demonstrates multifunctional biocompatible chitosan-polypyrrole nanocomposites (CS-PPy NCs) as novel agents for photoacoustic imaging-guided photothermal ablation of cancer because of their biocompatibility, conductivity, stability, and strong near-infrared (NIR) absorbance. The CS-PPy NCs are spherical in shape and range 26–94 nm in size with a mean value of 50.54 ± 2.56 nm. The in vitro results demonstrated good biocompatibility of CS-PPy NCs, which can be used in PTT for cancer cells under 808-nm NIR laser irradiation. Tumor-bearing mice fully recovered after treatment with CS-PPy NCs and NIR 808-nm laser irradiation compared to the corresponding control groups. Our research highlights the promising potential of using CS-PPy NCs for photoacoustic imaging-guided photothermal ablation of cancer in preclinical animals, which should be verified in future clinical trials. PMID:28252638

  4. Intraparticle Molecular Orbital Engineering of Semiconducting Polymer Nanoparticles as Amplified Theranostics for in Vivo Photoacoustic Imaging and Photothermal Therapy.

    Science.gov (United States)

    Lyu, Yan; Fang, Yuan; Miao, Qingqing; Zhen, Xu; Ding, Dan; Pu, Kanyi

    2016-04-26

    Optical theranostic nanoagents that seamlessly and synergistically integrate light-generated signals with photothermal or photodynamic therapy can provide opportunities for cost-effective precision medicine, while the potential for clinical translation requires them to have good biocompatibility and high imaging/therapy performance. We herein report an intraparticle molecular orbital engineering approach to simultaneously enhance photoacoustic brightness and photothermal therapy efficacy of semiconducting polymer nanoparticles (SPNs) for in vivo imaging and treatment of cancer. The theranostic SPNs have a binary optical component nanostructure, wherein a near-infrared absorbing semiconducting polymer and an ultrasmall carbon dot (fullerene) interact with each other to induce photoinduced electron transfer upon light irradiation. Such an intraparticle optoelectronic interaction augments heat generation and consequently enhances the photoacoustic signal and maximum photothermal temperature of SPNs by 2.6- and 1.3-fold, respectively. With the use of the amplified SPN as the theranostic nanoagent, it permits enhanced photoacoustic imaging and photothermal ablation of tumor in living mice. Our study thus not only introduces a category of purely organic optical theranostics but also highlights a molecular guideline to amplify the effectiveness of light-intensive imaging and therapeutic nanosystems.

  5. Advanced contrast nanoagents for photoacoustic molecular imaging, cytometry, blood test and photothermal theranostics.

    Science.gov (United States)

    de la Zerda, Adam; Kim, Jin-Woo; Galanzha, Ekaterina I; Gambhir, Sanjiv S; Zharov, Vladimir P

    2011-01-01

    Various nanoparticles have raised significant interest over the past decades for their unique physical and optical properties and biological utilities. Here we summarize the vast applications of advanced nanoparticles with a focus on carbon nanotube (CNT)-based or CNT-catalyzed contrast agents for photoacoustic (PA) imaging, cytometry and theranostics applications based on the photothermal (PT) effect. We briefly review the safety and potential toxicity of the PA/PT contrast nanoagents, while showing how the physical properties as well as multiple biological coatings change their toxicity profiles and contrasts. We provide general guidelines needed for the validation of a new molecular imaging agent in living subjects, and exemplify these guidelines with single-walled CNTs targeted to α(v) β(3) , an integrin associated with tumor angiogenesis, and golden carbon nanotubes targeted to LYVE-1, endothelial lymphatic receptors. An extensive review of the potential applications of advanced contrast agents is provided, including imaging of static targets such as tumor angiogenesis receptors, in vivo cytometry of dynamic targets such as circulating tumor cells and nanoparticles in blood, lymph, bones and plants, methods to enhance the PA and PT effects with transient and stationary bubble conjugates, PT/PA Raman imaging and multispectral histology. Finally, theranostic applications are reviewed, including the nanophotothermolysis of individual tumor cells and bacteria with clustered nanoparticles, nanothrombolysis of blood clots, detection and purging metastasis in sentinel lymph nodes, spectral hole burning and multiplex therapy with ultrasharp rainbow nanoparticles.

  6. Photoacoustic imaging of intestinal strictures: microscopic and macroscopic assessment in vivo (Conference Presentation)

    Science.gov (United States)

    Xu, Guan; Lei, Hao; Johnson, Laura A.; Moons, David S.; Ma, Teng; Zhou, Qifa; Rice, Michael D.; Ni, Jun; Wang, Xueding; Higgins, Peter D. R.

    2017-03-01

    The pathology of Crohn's disease (CD) is characterized by obstructing intestinal strictures because of inflammation (with high levels of hemoglobin), fibrosis (high levels of collagen), or a combination of both. Inflammatory strictures are medically treated. Fibrotic strictures have to be removed surgically. The accurate characterization of the strictures is therefore critical for the management of CD. Currently the comprehensive assessment of a stricture is difficult, as the standard diagnostic procedure, endoscopic biopsy, is superficial and with limited locations as well as depth. In our previous studies, photoacoustic imaging (PAI) has recovered the layered architectures and the relative content of the molecular components in human and animal tissues ex vivo. This study will investigate the capability of multispectral PAI in resolving the architecture and the molecular components of intestinal strictures in rats in vivo. PA images at 532, 1210 and 1310 nm targeting the strong optical absorption of hemoglobin, lipid and collagen were acquired using two approaches. A compact linear array, CL15-7, was used to transcutaneously acquire PA signals generated by the a fiber optics diffuser positioned within the inner lumen of the strictures. Another approach was to use an endoscopic capsule probe for acoustic resolution PA microscopy. The capsule probe is designed for human and therefore cannot fit into rat colon. The inner surface of the intestinal stricture was exposed and the probe was attached to the diseased location for imaging. The findings in PA images were confirmed by histology results.

  7. Enhanced near-infrared photoacoustic imaging of silica-coated rare-earth doped nanoparticles.

    Science.gov (United States)

    Sheng, Yang; Liao, Lun-De; Bandla, Aishwarya; Liu, Yu-Hang; Yuan, Jun; Thakor, Nitish; Tan, Mei Chee

    2017-01-01

    Near-infrared photoacoustic (PA) imaging is an emerging diagnostic technology that utilizes the tissue transparent window to achieve improved contrast and spatial resolution for deep tissue imaging. In this study, we investigated the enhancement effect of the SiO2 shell on the PA property of our core/shell rare-earth nanoparticles (REs) consisting of an active rare-earth doped core of NaYF4:Yb,Er (REDNPs) and an undoped NaYF4 shell. We observed that the PA signal amplitude increased with SiO2 shell thickness. Although the SiO2 shell caused an observed decrease in the integrated fluorescence intensity due to the dilution effect, fluorescence quenching of the rare earth emitting ions within the REDNPs cores was successfully prevented by the undoped NaYF4 shell. Therefore, our multilayer structure consisting of an active core with successive functional layers was demonstrated to be an effective design for dual-modal fluorescence and PA imaging probes with improved PA property. The result from this work addresses a critical need for the development of dual-modal contrast agent that advances deep tissue imaging with high resolution and signal-to-noise ratio. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. alphaVbeta3-targeted copper nanoparticles incorporating an Sn 2 lipase-labile fumagillin prodrug for photoacoustic neovascular imaging and treatment.

    Science.gov (United States)

    Zhang, Ruiying; Pan, Dipanjan; Cai, Xin; Yang, Xiaoxia; Senpan, Angana; Allen, John S; Lanza, Gregory M; Wang, Lihong V

    2015-01-01

    Photoacoustic (PA) tomography enables multiscale, multicontrast and high-resolution imaging of biological structures. In particular, contrast-enhanced PA imaging offers high-sensitivity noninvasive imaging of neovessel sprout formation and nascent tubules, which are important biomarkers of malignant tumors and progressive atherosclerotic disease. While gold nanoparticles or nanorods have been used as PA contrast agents, we utilized high-density copper oleate small molecules encapsulated within a phospholipid surfactant (CuNPs) to generate a soft nanoparticle with PA contrast comparable to that from gold. Within the NIR window, the copper nanoparticles provided a 4-fold higher signal than that of blood. ανβ3-integrin targeting of CuNPs in a Matrigel(TM) angiogenesis mouse model demonstrated prominent (p<0.05) PA contrast enhancement of the neovasculature compared with mice given nontargeted or competitively inhibited CuNPs. Furthermore, incorporation of a Sn 2 lipase-labile fumagillin prodrug into the CuNP outer lipid membrane produced marked antiangiogenesis in the same model when targeted to the ανβ3-integrin, providing proof of concept in vivo for the first targeted PA - drug delivery agent.

  9. ανβ3-targeted Copper Nanoparticles Incorporating an Sn 2 Lipase-Labile Fumagillin Prodrug for Photoacoustic Neovascular Imaging and Treatment

    Science.gov (United States)

    Zhang, Ruiying; Pan, Dipanjan; Cai, Xin; Yang, Xiaoxia; Senpan, Angana; Allen, John S.; Lanza, Gregory M.; Wang, Lihong V.

    2015-01-01

    Photoacoustic (PA) tomography enables multiscale, multicontrast and high-resolution imaging of biological structures. In particular, contrast-enhanced PA imaging offers high-sensitivity noninvasive imaging of neovessel sprout formation and nascent tubules, which are important biomarkers of malignant tumors and progressive atherosclerotic disease. While gold nanoparticles or nanorods have been used as PA contrast agents, we utilized high-density copper oleate small molecules encapsulated within a phospholipid surfactant (CuNPs) to generate a soft nanoparticle with PA contrast comparable to that from gold. Within the NIR window, the copper nanoparticles provided a 4-fold higher signal than that of blood. ανβ3-integrin targeting of CuNPs in a MatrigelTM angiogenesis mouse model demonstrated prominent (p<0.05) PA contrast enhancement of the neovasculature compared with mice given nontargeted or competitively inhibited CuNPs. Furthermore, incorporation of a Sn 2 lipase-labile fumagillin prodrug into the CuNP outer lipid membrane produced marked antiangiogenesis in the same model when targeted to the ανβ3-integrin, providing proof of concept in vivo for the first targeted PA - drug delivery agent. PMID:25553103

  10. Double Stage Delay Multiply and Sum Beamforming Algorithm: Application to Linear-Array Photoacoustic Imaging.

    Science.gov (United States)

    Mozaffarzadeh, Moein; Mahloojifar, Ali; Orooji, Mahdi; Adabi, Saba; Nasiriavanaki, Mohammadreza

    2017-04-05

    Photoacoustic imaging (PAI) is an emerging medical imaging modality capable of providing high spatial resolution of Ultrasound (US) imaging and high contrast of optical imaging. Delay-and-Sum (DAS) is the most common beamforming algorithm in PAI. However, using DAS beamformer leads to low resolution images and considerable contribution of offaxis signals. A new paradigm namely Delay-Multiply-and-Sum (DMAS), which was originally used as a reconstruction algorithm in confocal microwave imaging, was introduced to overcome the challenges in DAS. DMAS was used in PAI systems and it was shown that this algorithm results in resolution improvement and sidelobe degrading. However, DMAS is still sensitive to high levels of noise, and resolution improvement is not satisfying. Here, we propose a novel algorithm based on DAS algebra inside DMAS formula expansion, Double Stage DMAS (DSDMAS), which improves the image resolution and levels of sidelobe, and is much less sensitive to high level of noise compared to DMAS. The performance of DS-DMAS algorithm is evaluated numerically and experimentally. The resulted images are evaluated qualitatively and quantitatively using established quality metrics including signal-to-noise ratio (SNR), full-widthhalf- maximum (FWHM) and contrast ratio (CR). It is shown that DS-DMAS outperforms DAS and DMAS at the expense of higher computational load. DS-DMAS reduces the lateral valley for about 15 dB and improves the SNR and FWHM better than 13% and 30%, respectively. Moreover, the levels of sidelobe are reduced for about 10 dB in comparison with those in DMAS.

  11. Noninvasive imaging of islet grafts using positron-emission tomography

    Science.gov (United States)

    Lu, Yuxin; Dang, Hoa; Middleton, Blake; Zhang, Zesong; Washburn, Lorraine; Stout, David B.; Campbell-Thompson, Martha; Atkinson, Mark A.; Phelps, Michael; Gambhir, Sanjiv Sam; Tian, Jide; Kaufman, Daniel L.

    2006-07-01

    Islet transplantation offers a potential therapy to restore glucose homeostasis in type 1 diabetes patients. However, islet transplantation is not routinely successful because most islet recipients gradually lose graft function. Furthermore, serological markers of islet function are insensitive to islet loss until the latter stages of islet graft rejection. A noninvasive method of monitoring islet grafts would aid in the assessment of islet graft survival and the evaluation of interventions designed to prolong graft survival. Here, we show that recombinant adenovirus can engineer isolated islets to express a positron-emission tomography (PET) reporter gene and that these islets can be repeatedly imaged by using microPET after transplantation into mice. The magnitude of signal from engineered islets implanted into the axillary cavity was directly related to the implanted islet mass. PET signals attenuated over the following weeks because of the transient nature of adenovirus-mediated gene expression. Because the liver is the preferred site for islet implantation in humans, we also tested whether islets could be imaged after transfusion into the mouse liver. Control studies revealed that both intrahepatic islet transplantation and hyperglycemia altered the biodistribution kinetics of the PET probe systemically. Although transplanted islets were dispersed throughout the liver, clear signals from the liver region of mice receiving PET reporter-expressing islets were detectable for several weeks. Viral transduction, PET reporter expression, and repeated microPET imaging had no apparent deleterious effects on islet function after implantation. These studies lay a foundation for noninvasive quantitative assessments of islet graft survival using PET. diabetes | transplantation

  12. Photoacoustic pump-probe tomography of fluorophores in vivo using interleaved image acquisition for motion suppression

    Science.gov (United States)

    Märk, Julia; Wagener, Asja; Zhang, Edward; Laufer, Jan

    2017-01-01

    In fluorophores, the excited state lifetime can be modulated using pump-probe excitation. By generating photoacoustic (PA) signals using simultaneous and time-delayed pump and probe excitation pulses at fluences below the maximum permissible exposure, a modulation of the signal amplitude is observed in fluorophores but not in endogenous chromophores. This provides a highly specific contrast mechanism that can be used to recover the location of the fluorophore using difference imaging. The practical challenges in applying this method to in vivo PA tomography include the typically low concentrations of fluorescent contrast agents, and tissue motion. The former results in smaller PA signal amplitudes compared to those measured in blood, while the latter gives rise to difference image artefacts that compromise the unambiguous and potentially noise-limited detection of fluorescent contrast agents. To address this limitation, a method based on interleaved pump-probe image acquisition was developed. It relies on fast switching between simultaneous and time-delayed pump-probe excitation to acquire PA difference signals in quick succession, and to minimise the effects of tissue motion. The feasibility of this method is demonstrated in tissue phantoms and in initial experiments in vivo. PMID:28091571

  13. MoO3-x quantum dots for photoacoustic imaging guided photothermal/photodynamic cancer treatment.

    Science.gov (United States)

    Ding, Dandan; Guo, Wei; Guo, Chongshen; Sun, Jianzhe; Zheng, Nannan; Wang, Fei; Yan, Mei; Liu, Shaoqin

    2017-02-02

    A theranostic system of image-guided phototherapy is considered as a potential technique for cancer treatment because of the ability to integrate diagnostics and therapies together, thus enhancing accuracy and visualization during the treatment. In this work, we realized photoacoustic (PA) imaging-guided photothermal (PT)/photodynamic (PD) combined cancer treatment just via a single material, MoO3-x quantum dots (QDs). Due to their strong NIR harvesting ability, MoO3-x QDs can convert incident light into hyperthermia and sensitize the formation of singlet oxygen synchronously as evidenced by in vitro assay, hence, they can behave as both PT and PD agents effectively and act as a "dual-punch" to cancer cells. In a further study, elimination of solid tumors from HeLa-tumor bearing mice could be achieved in a MoO3-x QD mediated phototherapeutic group without obvious lesions to the major organs. In addition, the desired PT effect also makes MoO3-x QDs an exogenous PA contrast agent for in vivo live-imaging to depict tumors. Compared with previously reported theranostic systems that put several components into one system, our multifunctional agent of MoO3-x QDs is exempt from unpredictable mutual interference between components and ease of leakage of virtual components from the composited system.

  14. Photoacoustic pump-probe tomography of fluorophores in vivo using interleaved image acquisition for motion suppression

    Science.gov (United States)

    Märk, Julia; Wagener, Asja; Zhang, Edward; Laufer, Jan

    2017-01-01

    In fluorophores, the excited state lifetime can be modulated using pump-probe excitation. By generating photoacoustic (PA) signals using simultaneous and time-delayed pump and probe excitation pulses at fluences below the maximum permissible exposure, a modulation of the signal amplitude is observed in fluorophores but not in endogenous chromophores. This provides a highly specific contrast mechanism that can be used to recover the location of the fluorophore using difference imaging. The practical challenges in applying this method to in vivo PA tomography include the typically low concentrations of fluorescent contrast agents, and tissue motion. The former results in smaller PA signal amplitudes compared to those measured in blood, while the latter gives rise to difference image artefacts that compromise the unambiguous and potentially noise-limited detection of fluorescent contrast agents. To address this limitation, a method based on interleaved pump-probe image acquisition was developed. It relies on fast switching between simultaneous and time-delayed pump-probe excitation to acquire PA difference signals in quick succession, and to minimise the effects of tissue motion. The feasibility of this method is demonstrated in tissue phantoms and in initial experiments in vivo.

  15. Noninvasive imaging of protein-protein interactions in living animals

    Science.gov (United States)

    Luker, Gary D.; Sharma, Vijay; Pica, Christina M.; Dahlheimer, Julie L.; Li, Wei; Ochesky, Joseph; Ryan, Christine E.; Piwnica-Worms, Helen; Piwnica-Worms, David

    2002-05-01

    Protein-protein interactions control transcription, cell division, and cell proliferation as well as mediate signal transduction, oncogenic transformation, and regulation of cell death. Although a variety of methods have been used to investigate protein interactions in vitro and in cultured cells, none can analyze these interactions in intact, living animals. To enable noninvasive molecular imaging of protein-protein interactions in vivo by positron-emission tomography and fluorescence imaging, we engineered a fusion reporter gene comprising a mutant herpes simplex virus 1 thymidine kinase and green fluorescent protein for readout of a tetracycline-inducible, two-hybrid system in vivo. By using micro-positron-emission tomography, interactions between p53 tumor suppressor and the large T antigen of simian virus 40 were visualized in tumor xenografts of HeLa cells stably transfected with the imaging constructs. Imaging protein-binding partners in vivo will enable functional proteomics in whole animals and provide a tool for screening compounds targeted to specific protein-protein interactions in living animals.

  16. 光声成像技术在生物医学中的研究进展%Development of Photoacoustic Imaging Technology in Biomedical Applications

    Institute of Scientific and Technical Information of China (English)

    常金凤; 李成; 李荧

    2014-01-01

    As a kind of nondestructive testing technology, photoacoustic imaging technology, which is characterized by high resolution and high contrast, has been one of the development directions in the field of biomedical technologies. From the view of photoacoustic imaging systems, photoacoustic detec-tors and image reconstruction algorithms, the photoacoustic imaging technology is analyzed in this paper. Then the current photoacoustic imaging systems are illustrated in accordance with photoacoustic com-puted tomography, photoacoustic microscopy and photoacoustic endoscopy. The research advance of pho-toacoustic detectors, relating to multi-elememnt probes, array probes, MEMS probes and diaphragm-type Fabry-Perot probes, is discussed. Also, the application characteristics of typical image reconstruction algorithms are compared. As a result, the major research orientations of the photoacoustic imaging tech-nology, including higher resolution, greater detective depth, hard real-time, miniaturization technology and low-cost design, are demonstrated in consideration of potential future applications.%光声成像是近年来发展较快的无损检测技术,其高分辨率、高对比度的特点使其成为生物医学检测技术的主要发展方向之一。文中从光声成像系统、光声探测器和图像重建算法的角度,对光声成像技术进行了分析。在此基础上,分别结合光声计算层析成像、光声显微成像和光声内窥成像对光声成像系统进行了阐述,探讨了光声探测器在多探头、阵列式、MEMS微型化和光纤F-P腔等方面的研究进展,比较了典型图像重建算法的应用特点,并指出了基于光声技术的生物医学无损成像系统的高分辨率、大探测深度、实时性强、小型化、低成本的研究方向。

  17. Photoacoustic elastic oscillation and characterization.

    Science.gov (United States)

    Gao, Fei; Feng, Xiaohua; Zheng, Yuanjin

    2015-08-10

    Photoacoustic imaging and sensing have been studied extensively to probe the optical absorption of biological tissue in multiple scales ranging from large organs to small molecules. However, its elastic oscillation characterization is rarely studied and has been an untapped area to be explored. In literature, photoacoustic signal induced by pulsed laser is commonly modelled as a bipolar "N-shape" pulse from an optical absorber. In this paper, the photoacoustic damped oscillation is predicted and modelled by an equivalent mass-spring system by treating the optical absorber as an elastic oscillator. The photoacoustic simulation incorporating the proposed oscillation model shows better agreement with the measured signal from an elastic phantom, than conventional photoacoustic simulation model. More interestingly, the photoacoustic damping oscillation effect could potentially be a useful characterization approach to evaluate biological tissue's mechanical properties in terms of relaxation time, peak number and ratio beyond optical absorption only, which is experimentally demonstrated in this paper.

  18. Photoacoustic elastic oscillation and characterization

    CERN Document Server

    Gao, Fei; Zheng, Yuanjin

    2014-01-01

    Photoacoustic imaging and sensing have been studied extensively to probe the optical absorption of biological tissue in multiple scales ranging from large organs to small molecules. However, its elastic oscillation characterization is rarely studied and has been an untapped area to be explored. In literature, photoacoustic signal induced by pulsed laser is commonly modelled as a bipolar "N-shape" pulse from an optical absorber. In this paper, the photoacoustic damped oscillation is predicted and modelled by an equivalent mass-spring system by treating the optical absorber as an elastic oscillator. The photoacoustic simulation incorporating the proposed oscillation model shows better agreement with the measured signal from an elastic phantom, than conventional photoacoustic simulation model. More interestingly, the photoacoustic damping oscillation effect could potentially be a useful characterization approach to evaluate biological tissue's mechanical properties in terms of relaxation time, peak number and ra...

  19. In Vivo Monitoring of Neovascularization in Tumour Angiogenesis by Photoacoustic Tomography

    Institute of Scientific and Technical Information of China (English)

    XIANG Liang-Zhong; XING Da; GU Huai-Min; ZHOU Fei-Fan; YANG Di-Wu; ZENG Lv-Ming; YANG Si-Hua

    2007-01-01

    Photoacoustic tomography (PAT) is presented to in vivo monitor neovascularization in tumout angiogenesis with high resolution and high contrast images in a rat. With a circular scan system, the photoacoustic signal, generated by laser pulses at a wavelength of 532nm from a Q-switched Nd:YAG laser, is captured by a hydrophone with a diameter of 1 mm and a sensitivity of 850nV/Pa. The vascular structure around the rat tumour is imaged clearly, with optimal contrast, because blood has strong absorption near this wavelength. Serial noninvasive photoacoustic images of neovascularization in tumour angiogenesis are also obtained consecutively from a growing tumour implanted under the skin of a rat over a period of two weeks. This work demonstrates that PAT can potentially provide a powerful tool for tumour angiogenesis detection in cancer research. It will bring us closer to clinical applications for tumour diagnosis and treatment monitoring.

  20. Photoacoustic imaging of small organic molecule-based photoacoustic probe in subcutaneous tumor using P(VDF-TrFE) acoustic sensor

    Science.gov (United States)

    Hirasawa, Takeshi; Okawa, Shinpei; Kamiya, Mako; Urano, Yasuteru; Ishihara, Miya

    2015-03-01

    The P(VDF-TrFE) sensor which had uniform sensitivity in a frequency range of 2.9 - 19.6 MHz was developed for multispectral photoacoustic imaging (MS-PAI). A small organic molecule-based PA probe synthesized by our group had the absorption maximum at 530 nm and was used as a contrast agent. The PA probe was designed to have low quantum yield. Therefore, the PA probe efficiently converted absorbed optical energies to PA signals. The probe was injected in subcutaneous tumor of mice. Then, the subcutaneous tumor was imaged in vivo by using P(VDF-TrFE) sensor. MS-PAI successfully discriminated the probe signals from background signals produced from endogenous optical absorbers such as hemoglobin. The probe detectability of the P(VDF-TrFE) sensor was evaluated and then compared with that of lead zirconium titanate (PZT) sensors. The P(VDF-TrFE) sensor imaged the tumor more clearly than the PZT sensor with central frequency of 20 MHz, especially when the probe was accumulated in the tumor with low concentration. That was because the low-concentrated probe generated PA signals with low frequency. MS-PAI using P(VDF-TrFE) sensor which can detect PA signals with wide range of frequency is able to image various distribution of the probe and is superior to that using PZT sensor which detects PA signals with narrow frequency range.

  1. Stabilizing Two Classical Antiaromatic Frameworks: Demonstration of Photoacoustic Imaging and the Photothermal Effect in Metalla-aromatics.

    Science.gov (United States)

    Zhu, Congqing; Yang, Yuhui; Luo, Ming; Yang, Caixia; Wu, Jingjing; Chen, Lina; Liu, Gang; Wen, Tingbin; Zhu, Jun; Xia, Haiping

    2015-05-18

    Antiaromatic species are substantially less thermodynamically stable than aromatic moieties. Herein, we report the stabilization of two classical antiaromatic frameworks, cyclobutadiene and pentalene, by introducing one metal fragment through the first [2+2] cycloaddition reaction of a late-transition-metal carbyne with alkynes. Experimental observations and theoretical calculations reveal that the metal fragment decreases the antiaromaticity in cyclobutadiene and pentalene simultaneously, leading to air- and moisture-stable products. These molecules show broad absorption from the UV to the near-IR region, resulting in photoacoustic and photothermal effects for metalla-aromatic compounds for the first time. These results will encourage further efforts into the exploration of organometallic compounds for photoacoustic-imaging-guided photothermal therapy.

  2. Photoacoustic and Fluorescence Imaging of Cutaneous Squamous Cell Carcinoma in Living Subjects Using a Probe Targeting Integrin αvβ6

    Science.gov (United States)

    Zhang, Chao; Zhang, Yong; Hong, Kai; Zhu, Shu; Wan, Jie

    2017-01-01

    Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. Today, cSCC is diagnosed by visual inspection followed by invasive skin biopsy. There is a need to develop non-invasive diagnostic tools to achieve early and accurate detection. Photoacoustic imaging (PAI) possesses high ultrasonic resolution and strong optical contrast at new depths (<1–5 cm). Together with exogenous contrast agents, PAI has found promising use in various tumors in living subjects. The expression of integrin αvβ6 is significantly up-regulated in cSCC. We fabricated an anti-integrin αvβ6 antibody and labeled it with indocyanine green (ICG) to form an ICG-αvβ6 antibody. The results showed that the ICG-αvβ6 antibody probe could be used to detect cSCC with high specificity (3-fold over the control by PAI) and deep penetration (approximately 1 cm) by PAI. This suggests that the ICG-αvβ6 antibody is a promising probe targeting the integrin αvβ6 for detection of cSCC tumors by PAI and fluorescence imaging. It may find clinical application in the early diagnosis of cSCC as well as in intraoperative navigation. PMID:28181579

  3. Influence of nanosecond pulsed laser irradiance on the viability of nanoparticle-loaded cells: implications for safety of contrast-enhanced photoacoustic imaging

    Science.gov (United States)

    Bayer, Carolyn L.; Kelvekar, Juili; Emelianov, Stanislav Y.

    2013-11-01

    Photoacoustic imaging, a promising new diagnostic medical imaging modality, can provide high contrast images of molecular features by introducing highly-absorbing plasmonic nanoparticles. Currently, it is uncertain whether the absorption of low fluence pulsed light by plasmonic nanoparticles could lead to cellular damage. In our studies we have shown that low fluence pulsed laser excitation of accumulated nanoparticles at low concentration does not impact cell growth and viability, while we identify thresholds at which higher nanoparticle concentrations and fluences produce clear evidence of cell death. The results provide insights for improved design of photoacoustic contrast agents and for applications in combined imaging and therapy.

  4. Noninvasive dosimetry and monitoring of TTT using spectral imaging

    Science.gov (United States)

    Schuele, G.; Molnar, F. E.; Yellachich, D.; Vitkin, E.; Perelman, L. T.; Palanker, D.

    2006-02-01

    Transpupillary thermo therapy (TTT) is a slow (60 seconds) photothermal treatment of the fundus with a near-infrared (780-810nm) laser irradiating a large spot (0.5- 1. mm) on the retina. Due to high variability in ocular tissue properties and the lack of immediately observable outcome of the therapy, a real-time dosimetry is highly desirable. We found that fundus spectroscopy and spectrally-resolved imaging allow for non-invasive real-time monitoring and dosimetry of TTT. A 795nm laser was applied in rabbit eyes for 60 seconds using a 0.86mm retinal spot diameter. The fundus was illuminated with a broadband polarized light, and its reflectance spectra were measured in parallel and cross-polarizations. The fundus was also imaged in selected spectral domains. At irradiances that do not create ophthalmoscopically visible lesions the fundus reflectance increases at the wavelengths corresponding to absorption of the oxygenated blood indicating the reduced concentration of blood in the choroid. Vasoconstrictive response of the choroidal and retinal vasculature during TTT was also directly observed using spectrally-resolved imaging. At irradiances that produce ophthalmoscopically visible lesions a rapid reduction of the fundus reflectance was observed within the first 5-10 seconds of the exposure even when the visible lesions developed only by the end of the 60 second exposure. No visible lesions were produced where the laser was terminated after detection of the reduced scattering but prior to appearance of the enhanced scattering.

  5. Two-dimensional TiS₂ nanosheets for in vivo photoacoustic imaging and photothermal cancer therapy.

    Science.gov (United States)

    Qian, Xiaoxin; Shen, Sida; Liu, Teng; Cheng, Liang; Liu, Zhuang

    2015-04-14

    Recently, transition metal dichalcogenides (TMDCs) have attracted significant attention in nanomedicine owing to their intriguing properties. In this study, TiS2 nanosheets, a new TMDC nanomaterial, are synthesized by a bottom-up solution-phase method and then modified with polyethylene glycol (PEG), obtaining TiS2-PEG with high stability in physiological solutions and no appreciable in vitro toxicity. Due to their high absorbance in the near-infrared (NIR) region, TiS2-PEG nanosheets could offer a strong contrast in photoacoustic imaging, which uncovers the high tumor uptake and retention of these nanosheets after systemic administration into tumor-bearing mice. We further apply TiS2-PEG nanosheets for in vivo photothermal therapy, which are able to completely eradicate the tumors in mice upon intravenous injection of TiS2-PEG followed by NIR laser irradiation. Our work indicates that TiS2 nanosheets with appropriate surface coating (e.g. PEGylation) would be a promising new class of photothermal agents for imaging-guided cancer therapy.

  6. Real-Time Monitoring of Placental Oxygenation during Maternal Hypoxia and Hyperoxygenation Using Photoacoustic Imaging

    Science.gov (United States)

    Arthuis, Chloé J.; Novell, Anthony; Raes, Florian; Escoffre, Jean-Michel; Lerondel, Stéphanie; Le Pape, Alain; Bouakaz, Ayache; Perrotin, Franck

    2017-01-01

    Purpose This preclinical study aimed to evaluate placental oxygenation in pregnant rats by real-time photoacoustic (PA) imaging on different days of gestation and to specify variations in placental oxygen saturation under conditions of maternal hypoxia and hyperoxygenation. Material and methods Placentas of fifteen Sprague-Dawley rats were examined on days 14, 17, and 20 of pregnancy with a PA imaging system coupled to high-resolution ultrasound imaging. Pregnant rats were successively exposed to hyperoxygenated and hypoxic conditions by changing the oxygen concentration in inhaled gas. Tissue oxygen saturation was quantitatively analyzed by real-time PA imaging in the skin and 3 regions of the placenta. All procedures were performed in accordance with applicable ethical guidelines and approved by the animal care committee. Results Maternal hypoxia was associated with significantly greater decrease in blood oxygen saturation (ΔO2 Saturation) in the skin (70.74% ±7.65) than in the mesometrial triangle (32.66% ±5.75) or other placental areas (labyrinth: 18.58% ± 6.61; basal zone: 13.13% ±5.72) on different days of pregnancy (P<0.001). ΔO2 Saturation did not differ significantly between the labyrinth, the basal zone, and the decidua. After the period of hypoxia, maternal hyperoxygenation led to a significant rise in oxygen saturation, which returned to its initial values in the different placental regions (P<0.001). Conclusions PA imaging enables the variation of blood oxygen saturation to be monitored in the placenta during maternal hypoxia or hyperoxygenation. This first preclinical study suggests that the placenta plays an important role in protecting the fetus against maternal hypoxia. PMID:28081216

  7. Biodegradable polymer based theranostic agents for photoacoustic imaging and cancer therapy

    Science.gov (United States)

    Wang, Yan J.; Strohm, Eric M.; Kolios, Michael C.

    2016-03-01

    In this study, multifunctional theranostic agents for photoacoustic (PA), ultrasound (US), fluorescent imaging, and for therapeutic drug delivery were developed and tested. These agents consisted of a shell made from a biodegradable Poly(lactide-co-glycolic acid) (PLGA) polymer, loaded with perfluorohexane (PFH) liquid and gold nanoparticles (GNPs) in the core, and lipophilic carbocyanines fluorescent dye DiD and therapeutic drug Paclitaxel (PAC) in the shell. Their multifunctional capacity was investigated in an in vitro study. The PLGA/PFH/DiD-GNPs particles were synthesized by a double emulsion technique. The average PLGA particle diameter was 560 nm, with 50 nm diameter silica-coated gold nano-spheres in the shell. MCF7 human breast cancer cells were incubated with PLGA/PFH/DiDGNPs for 24 hours. Fluorescent and PA images were recorded using a fluorescent/PA microscope using a 1000 MHz transducer and a 532 nm pulsed laser. For the particle vaporization and drug delivery test, MCF7 cells were incubated with the PLGA/PFH-GNPs-PAC or PLGA/PFH-GNPs particles for 6, 12 and 24 hours. The effects of particle vaporization and drug delivery inside the cells were examined by irradiating the cells with a laser fluence of 100 mJ/cm2, and cell viability quantified using the MTT assay. The PA images of MCF7 cells containing PLGA/PFH/DiD-GNPs were spatially coincident with the fluorescent images, and confirmed particle uptake. After exposure to the PLGA/PFHGNP- PAC for 6, 12 and 24 hours, the cell survival rate was 43%, 38%, and 36% respectively compared with the control group, confirming drug delivery and release inside the cells. Upon vaporization, cell viability decreased to 20%. The particles show potential as imaging agents and drug delivery vehicles.

  8. Photoacoustic imaging of a near-infrared fluorescent marker based on dual wavelength pump-probe excitation

    Science.gov (United States)

    Märk, Julia; Theiss, Christoph; Schmitt, Franz-Josef; Laufer, Jan

    2014-03-01

    Photoacoustic imaging has been used to determine the spatial distribution of fluorophores, such as exogenous dyes and genetically expressed proteins, from images acquired in phantoms and in vivo. Most methods involve the acquisition of multiwavelength images and rely on differences in the absorption spectra of the tissue chromophores to estimate the spatial distribution and abundance of the latter using spectral decomposition techniques, such as model based inversion schemes. However, the inversion of 3-D images can be computationally expensive. Experimental approaches to localising contrast agents may therefore be useful, especially if quantification is not essential. This work aims to develop a method for determining the spatial distribution of a near-infrared fluorescent cell marker from images acquired using dual wavelength excitation. The excitation wavelengths coincided with the absorption and emission spectrum of the fluorophore. The contrast mechanism relies on reducing the excited state lifetime of the fluorophore by inducing stimulated emission. This changes the amount of energy thermalized by the fluorophore, and hence the photoacoustic signal amplitude. Since this is not observed in endogenous chromophores, the background may be removed by subtracting two images acquired with and without pulse delay between the pump and probe pulses. To characterise the fluorophore, the signal amplitude is measured in a cuvette as a function of pulse delay, concentration, and fluence. The spatial distribution of the fluorophore is determined from images acquired in realistic tissue phantoms. This method may be suitable for in vivo applications, such as imaging of exogenous or genetically expressed fluorescent cell markers.

  9. Imaging the pancreas: from ex vivo to non-invasive technology

    DEFF Research Database (Denmark)

    Holmberg, D; Ahlgren, U

    2008-01-01

    While many recently published reviews have covered non-invasive nuclear imaging techniques, the aim of this review is to focus on current developments in optical imaging technologies for investigating the pancreas. Several of these modalities are being developed into non-invasive, real...

  10. 基于柱弥散光源体内辐照的前列腺扫描光声成像仿体实验%Phantom experimental photoacoustic scanning imaging of prostate based on internal light irradiation using cylindrical diffusing source

    Institute of Scientific and Technical Information of China (English)

    彭东青; 谢文明; 吴淑莲; 唐嘉铭; 李志芳; 李晖

    2015-01-01

    Photoacoustic imaging has recently emerged as a promising imaging modality for prostate cancer. As a usual light illumination model in the previous studies, the external light illumination is diffcult to obtain an accurate reconstructed photoacoustic image. It suffers a great deal of light absorption attenuation by the surrounding scattering tissue and cannot colletct suffcient ultrasound signals for image reconstruction. Some particular methods are required to be considered in the photoacoustic imaging technique for examining prostate, such as a light delivery to prostate with suffcient penetrating depth and minimal invasiveness. According to the structural characteristic of prostate tissue, a photoacoustic imaging system is built by using a novel technique for prostate in this paper. In our photoacoustic imaging system, a cylindrical diffusing source with a 2-cm-long diffuser tip is used for an internal light irradiation through a urethra, and a focused transducer with a 3.5 MHz central frequency and 30.3 mm extended focal zone is located in the rectum for scanning the photoacoustic signal. Phantom experimental imaging is carried out. In the experiment, a transverse resolution of 2.21 mm and an axial resolution of 0.39 mm are obtained. The results demonstrate that the system could achieve the accurate imaging position of the absorber in the tissue sample. Because of the symmetrical emitting of the cylindrical diffusing light source and a relatively better lateral uniformity of light absorption around the light source through the internal irradiation model via urethra, light absorption of the upper side of the light source is almost the same as that of the lower side. Therefore the lengthways and lateral imaging ranges can be improved. In addition, the laser energy is allowed to be increased appropriately to obtain a further imaging result without worrying about heat damages to normal tissues, for the light absorption is less around the cylindrical diffusing light

  11. Joseph F. Keithley Award For Advances in Measurement Science Lecture: Thermophotonic and Photoacoustic Radar Imaging Methods for Biomedical and Dental Imaging

    Science.gov (United States)

    Mandelis, Andreas

    2012-02-01

    In the first part of this presentation I will introduce thermophotonic radar imaging principles and techniques using chirped or binary-phase-coded modulation, methods which can break through the maximum detection depth/depth resolution limitations of conventional photothermal waves. Using matched-filter principles, a methodology enabling parabolic diffusion-wave energy fields to exhibit energy localization akin to propagating hyperbolic wave-fields has been developed. It allows for deconvolution of individual responses of superposed axially discrete sources, opening a new field: depth-resolved thermal coherence tomography. Several examples from dental enamel caries diagnostic imaging to metal subsurface defect thermographic imaging will be discussed. The second part will introduce the field of photoacoustic radar (or sonar) biomedical imaging. I will report the development of a novel biomedical imaging system that utilizes a continuous-wave laser source with a custom intensity modulation pattern, ultrasonic phased array for signal detection and processing coupled with a beamforming algorithm for reconstruction of photoacoustic correlation images. Utilization of specific chirped modulation waveforms (``waveform engineering'') achieves dramatic signal-to-noise-ratio increase and improved axial resolution over pulsed laser photoacoustics. The talk will conclude with aspects of instrumental sensitivity of the PA Radar to optical contrast using cancerous breast tissue-mimicking phantoms, super paramagnetic iron oxide nanoparticles as contrast enhancement agents and in-vivo tissue samples.

  12. Physical And Medical Attributes Of Six Contemporary Noninvasive Imaging Techniques

    Science.gov (United States)

    Budinger, Thomas F.

    1981-11-01

    Digital subtraction angiography(DSA)is compared to five other noninvasive imaging methods with respect to physical attributes and medical applications. 1) Digital subtraction angiography measures flow channel (vessel) anatomy and vascular leaks in regions where signals from under and overlying vascular pools do not conflict in strength with the vessel or tissue of interest. 2) X-ray computed tomography, in principle, can separate the under and overlying signals, yet presently it is limited in speed, axial coverage, and computational burden for tasks DSA can efficiently perform. Possible exceptions are the dynamic spatial reconstructor (DSR) of Mayo Clinic and the system under construction at the University of California, San Francisco. 3) Heavy ion imaging measures electron density and is less sensitive to injected contrast than x-ray imaging which has the advantage of the photoelectric effect. A unique attribute of heavy ion imaging is its potential for treatment planning and the fact that beam hardening is not a physical problem. 4) Ultrasound detects surfaces, bulk tissue characteristics, and blood velocity. Doppler ultrasound competes with DSA in some regions of the body and generally involves less equipment and patient procedures. Ultrasound vessel imaging and range-gated Doppler have limitations due to sound absorption by atheromatous tissue and available imaging windows. 5) Emission tomography measures receptor site distribution, metabolism, permeability, and tissue perfusion. Resolution is limited to 7mm full width half maximum (FWHM) in the near future, and extraction of metabolic and perfusion information usually requires kinetic analyses with statistically poor data. The ability of positron tomography to measure metabolism (sugar, fatty acid, and oxygen utilization) and the ability to measure tissue perfusion with single photon tomography (17 mm FWHM) or PET (7 mm FWHM) using non-cyclotron produced radionuclides are the major unique features of emission

  13. Photoacoustic imaging of angiogenesis in a subcutaneous islet transplant site in a murine model

    Science.gov (United States)

    Shi, Wei; Pawlick, Rena; Bruni, Antonio; Rafiei, Yasmin; Pepper, Andrew R.; Gala-Lopez, Boris; Choi, Min; Malcolm, Andrew; Zemp, Roger J.; Shapiro, A. M. James

    2016-06-01

    Islet transplantation (IT) is an established clinical therapy for select patients with type-1 diabetes. Clinically, the hepatic portal vein serves as the site for IT. Despite numerous advances in clinical IT, limitations remain, including early islet cell loss posttransplant, procedural complications, and the inability to effectively monitor islet grafts. Hence, alternative sites for IT are currently being explored, with the subcutaneous space as one potential option. When left unmodified, the subcutaneous space routinely fails to promote successful islet engraftment. However, when employing the previously developed subcutaneous "deviceless" technique, a favorable microenvironment for islet survival and function is established. In this technique, an angiocatheter was temporarily implanted subcutaneously, which facilitated angiogenesis to promote subsequent islet engraftment. This technique has been employed in preclinical animal models, providing a sufficient means to develop techniques to monitor functional aspects of the graft such as angiogenesis. Here, we utilize photoacoustic imaging to track angiogenesis during the priming of the subcutaneous site by the implanted catheter at 1 to 4 weeks postcatheter. Quantitative analysis on vessel densities shows gradual growth of vasculature in the implant position. These results demonstrate the ability to track angiogenesis, thus facilitating a means to optimize and assess the pretransplant microenvironment.

  14. In-vivo photoacoustic microscopy of nanoshell extravasation from solid tumor vasculature

    OpenAIRE

    Li, Meng-Lin; Wang, James Chunjay; Schwartz, Jon A.; Gill-Sharp, Kelly L.; Stoica, George; Lihong V. Wang

    2009-01-01

    In this study, high resolution backward-mode photoacoustic microscopy (PAM) is used to noninvasively image progressive extravasation and accumulation of nanoshells within a solid tumor in vivo. PAM takes advantage of the strong near-infrared absorption of nanoshells and their extravasation tendency from leaky tumor vasculatures for imaging. Subcutaneous tumors are grown on immunocompetent BALB/c mice. Polyethylene glycol (PEGylated) nanoshells with a peak optical absorption at ∼800nm are intr...

  15. Molecular imaging of neutropilin-1 receptor using photoacoustic spectroscopy in breast tumors

    Science.gov (United States)

    Stantz, Keith M.; Cao, Minsong; Liu, Bo; Miller, Kathy D.; Guo, Lili

    2010-02-01

    Purpose: Our purpose is to develop and test a molecular probe that can detect the expression of neutropilin-1 receptor (NPR-1) in vivo using fluorescence imaging and photoacoustic spectroscopy. Introduction: NPR-1 is expressed on endothelial cells and some breast cancer cells, and binds to vascular endothelial growth factor VEGF165, a growth factor associated with pathological tumor angiogenesis. This receptor is coexpressed with VEGFR2 and shown to enhance the binding of VEGF165; therefore, it has the potential to be used as a marker of angiogenic activity and targeted for therapy. Material and Methods: A peptide specific to NPR-1 receptor was synthesized and conjugated to a NIR fluorochrome (IRDye800CW) and was intravenously injected into mice with breast tumors (MCF7VEGF). Probe kinetics was monitored in vivo via near infrared fluorescence (NIRF) within an optical imager for up to 72 hours within the tumor and compared to other organs (liver, muscle) for binding specificity. A multivariate fitting algorithm was used to spectrally deconvolve the IRDye800CW from endogenous hemoglobin signature (hemoglobin concentration and oxygen saturation). Results: Dynamics of the NIR fluorescence signal within the first hour after injection indicates specific binding compared to muscle, with an average tumor-to-muscle ration of 2.00 (+/- 0.27). Spectral analysis clearly indentified the presence of the NPR-1 probe. Based on calibration data, the average tumor concentration from both NIRF and PCT-S was measured to be ~200-300nM. Conclusion: These preliminary results show the capability of PCT to image an exogenous probe in vivo in addition to its hemoglobin state.

  16. In vivo photoacoustic (PA) mapping of sentinel lymph nodes (SLNs) using carbon nanotubes (CNTs) as a contrast agent

    Science.gov (United States)

    Pramanik, Manojit; Song, Kwang Hyun; Swierczewska, Magdalena; Green, Danielle; Sitharaman, Balaji; Wang, Lihong V.

    2009-02-01

    Sentinel lymph node biopsy (SLNB), a less invasive alternative to axillary lymph node dissection (ALND), is routinely used in clinic for staging breast cancer. In SLNB, lymphatic mapping with radio-labeled sulfur colloid and/or blue dye helps identify the sentinel lymph node (SLN), which is most likely to contain metastatic breast cancer. Even though SLNB, using both methylene blue and radioactive tracers, has a high identification rate, it still relies on an invasive surgical procedure, with associated morbidity. In this study, we have demonstrated a non-invasive single-walled carbon nanotube (SWNT)-enhanced photoacoustic (PA) identification of SLN in a rat model. We have used single-walled carbon nanotubes (SWNTs) as a photoacoustic contrast agent to map non-invasively the sentinel lymph nodes (SLNs) in a rat model in vivo. We were able to identify the SLN non-invasively with high contrast to noise ratio (~90) and high resolution (~500 μm). Due to the broad photoacoustic spectrum of these nanotubes in the near infrared wavelength window we could easily choose a suitable light wavelength to maximize the imaging depth. Our results suggest that this technology could be a useful clinical tool, allowing clinicians to identify SLNs non-invasively in vivo. In the future, these contrast agents could be functionalized to do molecular photoacoustic imaging.

  17. 3-Dimensional stereo implementation of photoacoustic imaging based on a new image reconstruction algorithm without using discrete Fourier transform

    Science.gov (United States)

    Ham, Woonchul; Song, Chulgyu

    2017-05-01

    In this paper, we propose a new three-dimensional stereo image reconstruction algorithm for a photoacoustic medical imaging system. We also introduce and discuss a new theoretical algorithm by using the physical concept of Radon transform. The main key concept of proposed theoretical algorithm is to evaluate the existence possibility of the acoustic source within a searching region by using the geometric distance between each sensor element of acoustic detector and the corresponding searching region denoted by grid. We derive the mathematical equation for the magnitude of the existence possibility which can be used for implementing a new proposed algorithm. We handle and derive mathematical equations of proposed algorithm for the one-dimensional sensing array case as well as two dimensional sensing array case too. A mathematical k-wave simulation data are used for comparing the image quality of the proposed algorithm with that of general conventional algorithm in which the FFT should be necessarily used. From the k-wave Matlab simulation results, we can prove the effectiveness of the proposed reconstruction algorithm.

  18. Retinal functional imager (RFI): non-invasive functional imaging of the retina.

    Science.gov (United States)

    Ganekal, S

    2013-01-01

    Retinal functional imager (RFI) is a unique non-invasive functional imaging system with novel capabilities for visualizing the retina. The objective of this review was to show the utility of non-invasive functional imaging in various disorders. Electronic literature search was carried out using the websites www.pubmed.gov and www.google.com. The search words were retinal functional imager and non-invasive retinal imaging used in combination. The articles published or translated into English were studied. The RFI directly measures hemodynamic parameters such as retinal blood-flow velocity, oximetric state, metabolic responses to photic activation and generates capillary perfusion maps (CPM) that provides retinal vasculature detail similar to flourescein angiography. All of these parameters stand in a direct relationship to the function and therefore the health of the retina, and are known to be degraded in the course of retinal diseases. Detecting changes in retinal function aid early diagnosis and treatment as functional changes often precede structural changes in many retinal disorders.

  19. Magnetic resonance imaging based noninvasive measurements of brain hemodynamics in neonates

    DEFF Research Database (Denmark)

    De Vis, Jill B; Alderliesten, Thomas; Hendrikse, Jeroen

    2016-01-01

    Perinatal disturbances of brain hemodynamics can have a detrimental effect on the brain's parenchyma with consequently adverse neurodevelopmental outcome. Noninvasive, reliable tools to evaluate the neonate's brain hemodynamics are scarce. Advances in magnetic resonance imaging have provided new...... methods to noninvasively assess brain hemodynamics. More recently these methods have made their transition to the neonatal population. The aim of this review is twofold. Firstly, to describe these newly available noninvasive methods to investigate brain hemodynamics in neonates. Secondly, to discuss...

  20. High speed photoacoustic imaging with fast OPO laser at 1.7 μm (Conference Presentation)

    Science.gov (United States)

    Piao, Zhonglie; Teng, Ma; Li, Jiawen; Qu, Yueqiao; Yu, Mingyue; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

    2016-03-01

    Acute cardiovascular events are mostly due to a blood clot or thrombus induced by the sudden rupture of vulnerable atherosclerotic plaques within coronary artery walls. Based on the high optical absorption contrast of the lipid rich plaques within the vessel wall, intravascular photoacoustic (IVPA) imaging at 1.7 μm spectral band has shown promising capabilities for detecting of lipid composition, but the translation of the technology for in vivo application is limited by the slow imaging speed. In this work, we will present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm (5 nm linewidth). A miniature catheter with 1.0 mm outer diameter was designed with a polished 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. Two optical illumination methods by gradient-index (GRIN) lens and ball lens are introduced and compared for higher spatial resolution. At 1725 nm, atherosclerotic rabbit abdominal aorta was imaged at two frame per second, which is more than one order of magnitude faster than previous reported IVPA imaging. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo.

  1. Grueneisen relaxation photoacoustic microscopy

    Science.gov (United States)

    Wang, Lidai; Zhang, Chi; Wang, Lihong V.

    2014-01-01

    The temperature-dependent property of the Grueneisen parameter has been employed in photoacoustic imaging mainly to measure tissue temperature. Here we explore this property using a different approach and develop Grueneisen-relaxation photoacoustic microscopy (GR-PAM), a technique that images non-radiative absorption with confocal optical resolution. GR-PAM sequentially delivers two identical laser pulses with a micro-second-scale time delay. The first laser pulse generates a photoacoustic signal and thermally tags the in-focus absorbers. Owing to the temperature dependence of the Grueneisen parameter, when the second laser pulse excites the tagged absorbers within the thermal relaxation time, a photoacoustic signal stronger than the first one is produced. GR-PAM detects the amplitude difference between the two co-located photoacoustic signals, confocally imaging the non-radiative absorption. We greatly improved axial resolution from 45 µm to 2.3 µm and at the same time slightly improved lateral resolution from 0.63 µm to 0.41 µm. In addition, the optical sectioning capability facilitates the measurement of the absolute absorption coefficient without fluence calibration. PMID:25379919

  2. In Vivo Photoacoustic and Fluorescence Cystography Using Clinically Relevant Dual Modal Indocyanine Green

    Directory of Open Access Journals (Sweden)

    Sungjo Park

    2014-10-01

    Full Text Available Conventional X-ray-based cystography uses radio-opaque materials, but this method uses harmful ionizing radiation and is not sensitive. In this study, we demonstrate nonionizing and noninvasive photoacoustic (PA and fluorescence (FL cystography using clinically relevant indocyanine green (ICG in vivo. After transurethral injection of ICG into rats through a catheter, their bladders were photoacoustically and fluorescently visualized. A deeply positioned bladder below the skin surface (i.e., ~1.5–5 mm was clearly visible in the PA and FL image using a laser pulse energy of less than 2 mJ/cm2 (1/15 of the safety limit. Then, the in vivo imaging results were validated through in situ studies. Our results suggest that dual modal cystography can provide a nonionizing and noninvasive imaging tool for bladder mapping.

  3. India Ink Incorporated Multifunctional Phase-transition Nanodroplets for Photoacoustic/Ultrasound Dual-modality Imaging and Photoacoustic Effect Based Tumor Therapy

    OpenAIRE

    Jian, Jia; Liu, Chengbo; Gong, Yuping; SU, LEI; Zhang, Bin; Wang, Zhigang; Dong WANG; Zhou, Yu; Xu, Fenfen; Li, Pan; Zheng, Yuanyi; Song, Liang; Zhou, Xiyuan

    2014-01-01

    The in vivo applications of gas-core microbubbles have been limited by gas diffusion, rapid body clearance, and poor vascular permeability. To overcome these limitations, using a modified three-step emulsion process, we have developed a first-of-its-kind India ink incorporated optically-triggerable phase-transition perfluorocarbon nanodroplets (INDs) that can provide not only three types of contrast mechanisms—conventional/thermoelastic photoacoustic, phase-transition/nonlinear photoacoustic,...

  4. Articulated dual modality photoacoustic and optical coherence tomography probe for preclinical and clinical imaging (Conference Presentation)

    Science.gov (United States)

    Liu, Mengyang; Zabihian, Behrooz; Weingast, Jessika; Hermann, Boris; Chen, Zhe; Zhang, Edward Z.; Beard, Paul C.; Pehamberger, Hubert; Drexler, Wolfgang

    2016-03-01

    The combination of photoacoustic tomography (PAT) with optical coherence tomography (OCT) has seen steady progress over the past few years. With the benchtop and semi-benchtop configurations, preclinical and clinical results have been demonstrated, paving the way for wider applications using dual modality PAT/OCT systems. However, as for the most updated semi-benchtop PAT/OCT system which employs a Fabry-Perot polymer film sensor, it is restricted to only human palm imaging due to the limited flexibility of the probe. The passband limit of the polymer film sensor further restricts the OCT source selection and reduces the sensitivity of the combined OCT system. To tackle these issues, we developed an articulated PAT/OCT probe for both preclinical and clinical applications. In the probe design, the sample arm of OCT sub-system and the interrogation part of the PAT sub-system are integrated into one compact unit. The polymer film sensor has a quick release function so that before each OCT scan, the sensor can be taken off to avoid the sensitivity drop and artefacts in OCT. The holding mechanism of the sensor is also more compact compared to previous designs, permitting access to uneven surfaces of the subjects. With the help of the articulated probe and a patient chair, we are able to perform co-registered imaging on human subjects on both upper and lower extremities while they are at rest positions. An increase in performance characteristics is also achieved. Patients with skin diseases are currently being recruited to test its clinical feasibility.

  5. HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy

    Science.gov (United States)

    Yan, Sijing; LU, Min; Ding, Xiaoya; Chen, Fei; He, Xuemei; Xu, Chunyan; Zhou, Hang; Wang, Qi; Hao, Lan; Zou, Jianzhong

    2016-01-01

    This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic. PMID:27535093

  6. HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy

    Science.gov (United States)

    Yan, Sijing; Lu, Min; Ding, Xiaoya; Chen, Fei; He, Xuemei; Xu, Chunyan; Zhou, Hang; Wang, Qi; Hao, Lan; Zou, Jianzhong

    2016-08-01

    This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic.

  7. Rapid and noncontact photoacoustic tomography imaging system using an interferometer with high-speed phase modulation technique

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jun [School of Physics and Telecom Engineering, South China Normal University, Guangzhou 510006 (China); Tang, Zhilie; Wu, Yongbo [School of Physics and Telecom Engineering, South China Normal University, Guangzhou 510006 (China); GuangDong Province Key Laboratory of Quantum Engineering and Quantum Materials, South China Normal University, IMOT, Guangzhou 510006 (China); Wang, Yi [School of Control Engineering, Northeastern University at Qinhuangdao, Qinhuangdao 066004 (China)

    2015-04-15

    We designed, fabricated, and tested a rapid and noncontact photoacoustic tomography (PAT) imaging system using a low-coherence interferometer with high-speed phase modulation technique. Such a rapid and noncontact probing system can greatly decrease the time of imaging. The proposed PAT imaging system is experimentally verified by capturing images of a simulated tissue sample and the blood vessels within the ear flap of a mouse (pinna) in vivo. The axial and lateral resolutions of the system are evaluated at 45 and ∼15 μm, respectively. The imaging depth of the system is 1 mm in a special phantom. Our results show that the proposed system opens a promising way to realize noncontact, real-time PAT.

  8. Optical-resolution photoacoustic imaging through thick tissue with a thin capillary as a dual optical-in acoustic-out waveguide

    CERN Document Server

    Simandoux, Olivier; Gateau, Jerome; Huignard, Jean-Pierre; Moser, Christophe; Psaltis, Demetri; Bossy, Emmanuel

    2015-01-01

    We demonstrate the ability to guide high-frequency photoacoustic waves through thick tissue with a water-filled silica-capillary (150 \\mu m inner diameter and 30 mm long). An optical-resolution photoacoustic image of a 30 \\mu m diameter absorbing nylon thread was obtained by guiding the acoustic waves in the capillary through a 3 cm thick fat layer. The transmission loss through the capillary was about -20 dB, much lower than the -120 dB acoustic attenuation through the fat layer. The overwhelming acoustic attenuation of high-frequency acoustic waves by biological tissue can therefore be avoided by the use of a small footprint capillary acoustic waveguide for remote detection. We finally demonstrate that the capillary can be used as a dual optical-in acoustic-out waveguide, paving the way for the development of minimally invasive optical-resolution photoacoustic endoscopes free of any acoustic or optical elements at their imaging tip.

  9. Ultrasound-heated photoacoustic flowmetry.

    Science.gov (United States)

    Wang, Lidai; Yao, Junjie; Maslov, Konstantin I; Xing, Wenxin; Wang, Lihong V

    2013-11-01

    We report the development of photoacoustic flowmetry assisted by high-intensity focused ultrasound (HIFU). This novel method employs HIFU to generate a heating impulse in the flow medium, followed by photoacoustic monitoring of the thermal decay process. Photoacoustic flowmetry in a continuous medium remains a challenge in the optical diffusive regime. Here, both the HIFU heating and photoacoustic detection can focus at depths beyond the optical diffusion limit (~1 mm in soft tissue). This method can be applied to a continuous medium, i.e., a medium without discrete scatterers or absorbers resolvable by photoacoustic imaging. Flow speeds up to 41 mm·s-1 have been experimentally measured in a blood phantom covered by 1.5-mm-thick tissue.

  10. Irrigant flow during photon-induced photoacoustic streaming (PIPS) using Particle Image Velocimetry (PIV).

    Science.gov (United States)

    Koch, Jon D; Jaramillo, David E; DiVito, Enrico; Peters, Ove A

    2016-03-01

    This study aimed to compare fluid movements generated from photon-induced photoacoustic streaming (PIPS) and passive ultrasonic irrigation (PUI). Particle Image Velocimetry (PIV) was performed using 6-μm melamine spheres in water. Measurement areas were 3-mm-long sections of the canal in the coronal, midroot and apical regions for PIPS (erbium/yttrium-aluminium garnet (Er:YAG) laser set at 15 Hz with 20 mJ), or passive ultrasonic irrigation (PUI, non-cutting insert at 30% unit power) was performed in simulated root canals prepared to an apical size #30/0.04 taper. Fluid movement was analysed directly subjacent to the apical ends of ultrasonic insert or fiber optic tips as well as at midroot and apically. During PUI, measured average velocities were around 0.03 m/s in the immediate vicinity of the sides and tip of the ultrasonic file. Speeds decayed to non-measureable values at a distance of about 2 mm from the sides and tip. During PIPS, typical average speeds were about ten times higher than those measured for PUI, and they were measured throughout the length of the canal, at distances up to 20 mm away. PIPS caused higher average fluid speeds when compared to PUI, both close and distant from the instrument. The findings of this study could be relevant to the debriding and disinfecting stage of endodontic therapy. Irrigation enhancement beyond needle irrigation is relevant to more effectively eradicate microorganisms from root canal systems. PIPS may be an alternative approach due to its ability to create high streaming velocities further away from the activation source compared to ultrasonic activation.

  11. Magnetic resonance imaging based noninvasive measurements of brain hemodynamics in neonates : A review

    NARCIS (Netherlands)

    De Vis, Jill B; Alderliesten, Thomas; Hendrikse, Jeroen; Petersen, Esben T; Benders, Manon Jnl

    2016-01-01

    Perinatal disturbances of brain hemodynamics can have a detrimental effect on the brain's parenchyma with consequently adverse neurodevelopmental outcome. Noninvasive, reliable tools to evaluate the neonate's brain hemodynamics are scarce. Advances in magnetic resonance imaging have provided new met

  12. Development of Molecular Probes Based on Iron Oxide Nanoparticles for in Vivo Magnetic Resonance/Photoacoustic Dual Imaging of Target Molecules in Tumors.

    Science.gov (United States)

    Sano, Kohei

    2017-01-01

     Molecular imaging probes that enable seamless diagnoses of tumors in the preoperative and intraoperative stages could lead to surgical resection of tumors based on highly accurate diagnoses. Because iron oxide nanoparticles (IONPs) have high proton relaxivity and high molar extinction coefficients suitable for magnetic resonance imaging (MRI) and photoacoustic imaging, respectively, we planned to develop molecular imaging probes applicable to the pre- (MRI) and intraoperative (photoacoustic imaging) stages. Human epidermal growth factor receptor 2 (EGFR2; HER2) was selected as a target molecule, and we designed IONPs (20, 50, and 100 nm) conjugated with anti-HER2 moieties [whole IgG (trastuzumab), single-chain fragment variable (scFv), and peptide] for HER2-targeted tumor imaging. Among the probes tested, scFv-conjugated IONPs (scFv-IONPs) (20 nm) exhibited the highest binding affinity to HER2 (Kd=0.01 nM). An in vivo biodistribution study using (111)In-labeled probes demonstrated that more scFv-IONPs (20 nm) accumulated in HER2-positive than in HER2-negative tumors, suggesting that the uptake of scFv-IONPs is HER2 specific. The scFv-IONPs (20 nm) showed high proton relaxivity and a probe concentration-dependent photoacoustic signal. In vivo MR/photoacoustic imaging studies using scFv-IONPs (20 nm) facilitated HER2-specific visualization of tumors. Furthermore, an iron-staining study demonstrated that the uptake of scFv-IONPs was notable only in HER2-positive tumors. These results suggest that scFv-IONPs (20 nm) may be useful for MR/photoacoustic dual imaging, which could achieve seamless diagnoses in the preoperative and intraoperative stages.

  13. Tutorial on photoacoustic tomography

    Science.gov (United States)

    Zhou, Yong; Yao, Junjie; Wang, Lihong V.

    2016-06-01

    Photoacoustic tomography (PAT) has become one of the fastest growing fields in biomedical optics. Unlike pure optical imaging, such as confocal microscopy and two-photon microscopy, PAT employs acoustic detection to image optical absorption contrast with high-resolution deep into scattering tissue. So far, PAT has been widely used for multiscale anatomical, functional, and molecular imaging of biological tissues. We focus on PAT's basic principles, major implementations, imaging contrasts, and recent applications.

  14. Non-invasive imaging of skin cancer with fluorescence lifetime imaging using two photon tomography

    Science.gov (United States)

    Patalay, Rakesh; Talbot, Clifford; Alexandrov, Yuriy; Munro, Ian; Breunig, Hans Georg; König, Karsten; Warren, Sean; Neil, Mark A. A.; French, Paul M. W.; Chu, Anthony; Stamp, Gordon W.; Dunsby, Christopher

    2011-07-01

    Multispectral fluorescence lifetime imaging (FLIM) using two photon microscopy as a non-invasive technique for the diagnosis of skin lesions is described. Skin contains fluorophores including elastin, keratin, collagen, FAD and NADH. This endogenous contrast allows tissue to be imaged without the addition of exogenous agents and allows the in vivo state of cells and tissues to be studied. A modified DermaInspect® multiphoton tomography system was used to excite autofluorescence at 760 nm in vivo and on freshly excised ex vivo tissue. This instrument simultaneously acquires fluorescence lifetime images in four spectral channels between 360-655 nm using time-correlated single photon counting and can also provide hyperspectral images. The multispectral fluorescence lifetime images were spatially segmented and binned to determine lifetimes for each cell by fitting to a double exponential lifetime model. A comparative analysis between the cellular lifetimes from different diagnoses demonstrates significant diagnostic potential.

  15. Photoacoustic measurement of epidermal melanin

    Science.gov (United States)

    Viator, John A.; Svaasand, Lars O.; Aguilar, Guillermo; Choi, Bernard; Nelson, J. Stuart

    2003-06-01

    Most dermatologic laser procedures must consider epidermal melanin, as it is a broadband optical absorber which affects subsurface fluence, effectively limiting the amount of light reaching the dermis and targeted chromophores. An accurate method for quantifying epidermal melanin content would aid clinicians in determining proper light dosage for therapeutic laser procedures. While epidermal melanin content has been quantified non-invasively using optical methods, there is currently no way to determine the melanin distribution in the epidermis. We have developed a photoacoustic probe that uses a Q-switched, frequency doubled Nd:YAG laser operating at 532nm to generate acoustic pulses in skin in vivo. The probe contained a piezoelectric element that detected photoacoustic waves which were then analyzed for epidermal melanin content, using a photoacoustic melanin index (PAMI). We tested 15 human subjects with skin types I--VI using the photoacoustic probe. We also present photoacoustic data for a human subject with vitiligo. Photoacoustic measurement showed melanin in the vitiligo subject was almost completely absent.

  16. In vivo photoacoustic imaging of transverse blood flow using Doppler broadening of bandwidth

    OpenAIRE

    Yao, Junjie; Maslov, Konstantin I.; Shi, Yunfei; Taber, Larry A.; Lihong V. Wang

    2010-01-01

    A new method is proposed to measure transverse blood flow using photoacoustic Doppler broadening of bandwidth. By measuring bovine blood flowing through a plastic tube, the linear dependence of the broadening on the flow speed was validated. The blood flow of the microvasculature in a mouse ear and a chicken embryo (stage 16) was also studied.

  17. In vivo photoacoustic imaging of transverse blood flow by using Doppler broadening of bandwidth

    OpenAIRE

    Yao, Junjie; Maslov, Konstantin I.; Shi, Yunfei; Taber, Larry A.; Lihong V. Wang

    2010-01-01

    A method is proposed to measure transverse blood flow by using photoacoustic Doppler broadening of bandwidth. By measuring bovine blood flowing through a plastic tube, the linear dependence of the broadening on the flow speed was validated. The blood flow of the microvasculature in a mouse ear and a chicken embryo (stage 16) was also studied.

  18. Enlarged acceptance angle of a finite size detector in photoacoustic imaging using acoustic lenses

    NARCIS (Netherlands)

    Xia, W.; Piras, D.; Heijblom, Michelle; van Hespen, Johannes C.G.; Steenbergen, Wiendelt; Manohar, Srirang; van Veldhoven, Spiridon; Prins, Christian; van Leeuwen, Ton

    2011-01-01

    A large surface area transducer is preferable to be used to detect extremely weak photoacoustic signals in mammography due to its high sensitivity. The lateral resolution is limited by the small acceptance angle of such a transducer. We introduce an excellent material for an acoustic lens used to en

  19. Co-registered Frequency-Domain Photoacoustic Radar and Ultrasound System for Subsurface Imaging in Turbid Media

    Science.gov (United States)

    Dovlo, Edem; Lashkari, Bahman; Mandelis, Andreas

    2016-03-01

    Frequency-domain photoacoustic radar (FD-PAR) imaging of absorbers in turbid media and their comparison and/or validation as well as co-registration with their corresponding ultrasound (US) images are demonstrated in this paper. Also presented are the FD-PAR tomography and the effects of reducing the number of scan lines (or angles) on image quality, resolution, and contrast. The FD-PAR modality uses intensity-modulated (coded) continuous wave laser sources driven by frequency-swept (chirp) waveforms. The spatial cross-correlation function between the PA response and the reference signal used for laser source modulation produces the reconstructed image. Live animal testing is demonstrated, and images of comparable signal-to-noise ratio, contrast, and spatial resolution were obtained. Various image improvement techniques to further reduce absorber spread and artifacts in the images such as normalization, filtering, and amplification were also investigated. The co-registered image produced from the combined US and PA images provides more information than both images independently. The significance of this work lies in the fact that achieving PA imaging functionality on a commercial ultrasound instrument could accelerate its clinical acceptance and use. This work is aimed at functional PA imaging of small animals in vivo.

  20. Fluorescence Quenching Nanoprobes Dedicated to In Vivo Photoacoustic Imaging and High-Efficient Tumor Therapy in Deep-Seated Tissue.

    Science.gov (United States)

    Qin, Huan; Zhou, Ting; Yang, Sihua; Xing, Da

    2015-06-10

    Photoacoustic imaging (PAI) and photoacoustic (PA) therapy have promising applications for treating tumors. It is known that the utilization of high-absorption-coefficient probes can selectively enhance the PAI target contrast and PA tumor therapy efficiency in deep-seated tissue. Here, the design of a probe with the highest availability of optical-thermo conversion by using graphene oxide (GO) and dyes via π-π stacking interactions is reported. The GO serves as a base material for loading dyes and quenching dye fluorescence via fluorescence resonance energy transfer (FRET), with the one purpose of maximum of PA efficiency. Experiments verify that the designed fluorescence quenching nanoprobes can produce stronger PA signals than the sum of the separate signals generated in the dye and the GO. Potential applications of the fluorescence quenching nanoprobes are demonstrated, dedicating to enhance PA contrast of targets in deep-seated tissues and tumors in living mice. PA therapy efficiency both in vitro and in vivo by using the fluorescence quenching nanoprobes is found to be higher than with the commonly used PA therapy agents. Taken together, quenching dye fluorescence via FRET will provide a valid means for developing high-efficiency PA probes. Fluorescence quenching nanoprobes are likely to become a promising candidate for deep-seated tumor imaging and therapy.

  1. One-pot synthesis of gold nanostars using plant polyphenols for cancer photoacoustic imaging and photothermal therapy

    Science.gov (United States)

    Zhang, Xiao-Long; Zheng, Cheng; Zhang, Yun; Yang, Huang-Hao; Liu, Xiaolong; Liu, Jingfeng

    2016-07-01

    Branched plasmonic nanostructures have been found to exhibit strong enhancement of the electromagnetic field surrounding their multi-branched petals. This feature endows them with improved performance in catalysis, surface-enhanced Raman scattering, photoacoustic imaging, and photothermal therapy. Albeit several synthesis techniques have been developed, the precisely controlled growth of highly branched nanostructures with a one-pot surfactant-free procedure is still challenging. Herein, we present a simple seedless route to synthesize gold nanostars (AuNSs) using a natural plant polyphenol, gallic acid (GA), as a reducing and stabilizing agent. The size and shape of AuNSs can be tuned by simply adjusting the amount of added GA. Under the optimum condition, the as-prepared AuNSs with diameters about 100 nm exhibit strong near-infrared absorption, good photothermal efficiency, and high biocompatibility. We demonstrate that AuNSs can be utilized for simultaneous photoacoustic imaging and photothermal therapy in living cancer cells. This study highlights facile synthesized AuNSs could serve as a promising platform for cancer diagnosis and therapy.

  2. Simulation of photoacoustic imaging of microcracks in silicon wafers using a structure-changeable multilayered thermal diffusion model.

    Science.gov (United States)

    Nakata, Toshihiko; Kitamori, Takehiko; Sawada, Tsuguo

    2007-03-01

    The detection characteristics for photoacoustic imaging of microcracks in silicon wafers were theoretically and quantitatively investigated using a numerical simulation. The simulation is based on a one-dimensional multilayered thermal diffusion model coupled with the thermal-wave impedance of each layer, the layer structures of which are constructed along the wafer surface and are variable according to the scanning position of the point heat source. As the modulation frequency was reduced, the spatial resolution of the temperature amplitude profile at the cracks decreased, showing good agreement with the experimentally obtained photoacoustic amplitude images. At a modulation frequency of 200 kHz, for cracks with narrow air gaps of up to 20 nm, which is much smaller than both the beam spot size of 1.5 microm and the thermal diffusion length of 12 microm, the temperature amplitude is twice that of regions without cracks, and the temperature contrast increased with an increase in the modulation frequency. These calculation results suggest the effectiveness of using a high modulation frequency, making it possible to detect microcracks of the order of 10 nm.

  3. In vivo acoustic and photoacoustic focusing of circulating cells

    Science.gov (United States)

    Galanzha, Ekaterina I.; Viegas, Mark G.; Malinsky, Taras I.; Melerzanov, Alexander V.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Zharov, Vladimir P.

    2016-03-01

    In vivo flow cytometry using vessels as natural tubes with native cell flows has revolutionized the study of rare circulating tumor cells in a complex blood background. However, the presence of many blood cells in the detection volume makes it difficult to count each cell in this volume. We introduce method for manipulation of circulating cells in vivo with the use of gradient acoustic forces induced by ultrasound and photoacoustic waves. In a murine model, we demonstrated cell trapping, redirecting and focusing in blood and lymph flow into a tight stream, noninvasive wall-free transportation of blood, and the potential for photoacoustic detection of sickle cells without labeling and of leukocytes targeted by functionalized nanoparticles. Integration of cell focusing with intravital imaging methods may provide a versatile biological tool for single-cell analysis in circulation, with a focus on in vivo needleless blood tests, and preclinical studies of human diseases in animal models.

  4. Nonlinear quantitative photoacoustic tomography with two-photon absorption

    CERN Document Server

    Ren, Kui

    2016-01-01

    Two-photon photoacoustic tomography (TP-PAT) is a non-invasive optical molecular imaging modality that aims at inferring two-photon absorption property of heterogeneous media from photoacoustic measurements. In this work, we analyze an inverse problem in quantitative TP-PAT where we intend to reconstruct optical coefficients in a semilinear elliptic PDE, the mathematical model for the propagation of near infra-red photons in tissue-like optical media with two-photon absorption, from the internal absorbed energy data. We derive uniqueness and stability results on the reconstructions of single and multiple optical coefficients, and present some numerical reconstruction results based on synthetic data to complement the theoretical analysis.

  5. Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy.

    Science.gov (United States)

    Liu, Renfa; Jing, Lijia; Peng, Dong; Li, Yong; Tian, Jie; Dai, Zhifei

    2015-01-01

    The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer.

  6. New developments in non-invasive coronary imaging

    NARCIS (Netherlands)

    Dikkers, Riksta

    2008-01-01

    Coronary artery disease, and especially ischemic heart disease, is a major concern in Western society. To reduce mortality and morbidity early detection and treatment is important. Ideally, early detection should be non-invasive, fast and cheap. Coronary angiography (CAG) is a reliable technique to

  7. New developments in non-invasive coronary imaging

    NARCIS (Netherlands)

    Dikkers, Riksta

    2008-01-01

    Coronary artery disease, and especially ischemic heart disease, is a major concern in Western society. To reduce mortality and morbidity early detection and treatment is important. Ideally, early detection should be non-invasive, fast and cheap. Coronary angiography (CAG) is a reliable technique to

  8. Clinical Report on the First Prototype of a Photoacoustic Tomography System with Dual Illumination for Breast Cancer Imaging.

    Directory of Open Access Journals (Sweden)

    Elham Fakhrejahani

    Full Text Available Photoacoustic tomography is a recently developed imaging modality that can provide high spatial-resolution images of hemoglobin distribution in tissues such as the breast. Because breast cancer is an angiogenesis-dependent type of malignancy, we evaluated the clinical acceptability of breast tissue images produced using our first prototype photoacoustic mammography (PAM system in patients with known cancer. Post-excisionally, histological sections of the tumors were stained immunohistochemically (IHC for CD31 (an endothelial marker and carbonic anhydrase IX (CAIX (a marker of hypoxia. Whole-slide scanning and image analyses were used to evaluate the tumor microvessel distribution pattern and to calculate the total vascular perimeter (TVP/area for each lesion. In this clinical study, 42 lesions were primarily scanned using PAM preoperatively, three of which were reported to be benign and were excluded from statistical analysis. Images were produced for 29 out of 39 cancers (visibility rate = 74.4% at the median depth of 26.5 (3.25-51.2 mm. Age, menopausal status, body mass index, history of neoadjuvant treatment, clinical stage and histological tumor angiogenesis markers did not seem to affect the visibility. The oxygen saturation level in all of the measured lesions was lower than in the subcutaneous counterpart vessels (Wilcoxon test, p value<0.001, as well as in the counterpart contralateral normal breast region of interest (ROI (Wilcoxon test, p value = 0.001. Although the oxygen saturation level was not statistically significant between CAIX-positive vs. -negative cases, lesional TVP/area showed a positive correlation with the oxygen saturation level only in the group that had received therapy before PAM. In conclusion, the vascular and oxygenation data obtained by PAM have great potential for identifying functional features of breast tumors.

  9. Towards ultrahigh resting-state functional connectivity in the mouse brain using photoacoustic microscopy

    Science.gov (United States)

    Hariri, Ali; Bely, Nicholas; Chen, Chen; Nasiriavanaki, Mohammadreza

    2016-03-01

    The increasing use of mouse models for human brain disease studies, coupled with the fact that existing high-resolution functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing both mechanical and optical scanning in the photoacoustic microscopy, we can image spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images is going to be acquired noninvasively with a fast frame rate, a large field of view, and a high spatial resolution. We developed an optical resolution photoacoustic microscopy (OR-PAM) with diode laser. Laser light was raster scanned due to XY-stage movement. Images from ultra-high OR-PAM can then be used to study brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy.

  10. Dual in vivo Photoacoustic and Fluorescence Imaging of HER2 Expression in Breast Tumors for Diagnosis, Margin Assessment, and Surgical Guidance

    Directory of Open Access Journals (Sweden)

    Azusa Maeda

    2015-01-01

    Full Text Available Biomarker-specific imaging probes offer ways to improve molecular diagnosis, intraoperative margin assessment, and tumor resection. Fluorescence and photoacoustic imaging probes are of particular interest for clinical applications because the combination enables deeper tissue penetration for tumor detection while maintaining imaging sensitivity compared to a single optical imaging modality. Here we describe the development of a human epidermal growth factor receptor 2 (HER2-targeting imaging probe to visualize differential levels of HER2 expression in a breast cancer model. Specifically, we labeled trastuzumab with Black Hole Quencher 3 (BHQ3 and fluorescein for photoacoustic and fluorescence imaging of HER2 overexpression, respectively. The dual-labeled trastuzumab was tested for its ability to detect HER2 overexpression in vitro and in vivo. We demonstrated an over twofold increase in the signal intensity for HER2-overexpressing tumors in vivo, compared to low–HER2-expressing tumors, using photoacoustic imaging. Furthermore, we demonstrated the feasibility of detecting tumors and positive surgical margins by fluorescence imaging. These results suggest that multimodal HER2-specific imaging of breast cancer using the BHQ3-fluorescein trastuzumab enables molecular-level detection and surgical margin assessment of breast tumors in vivo. This technique may have future clinical impact for primary lesion detection, as well as intraoperative molecular-level surgical guidance in breast cancer.

  11. Photoacoustic microscopy of bilirubin in tissue phantoms

    Science.gov (United States)

    Zhou, Yong; Zhang, Chi; Yao, Da-Kang; Wang, Lihong V.

    2012-12-01

    Determining both bilirubin's concentration and its spatial distribution are important in disease diagnosis. Here, for the first time, we applied quantitative multiwavelength photoacoustic microscopy (PAM) to detect bilirubin concentration and distribution simultaneously. By measuring tissue-mimicking phantoms with different bilirubin concentrations, we showed that the root-mean-square error of prediction has reached 0.52 and 0.83 mg/dL for pure bilirubin and for blood-mixed bilirubin detection (with 100% oxygen saturation), respectively. We further demonstrated the capability of the PAM system to image bilirubin distribution both with and without blood. Finally, by underlaying bilirubin phantoms with mouse skins, we showed that bilirubin can be imaged with consistent accuracy down to >400 μm in depth. Our results show that PAM has potential for noninvasive bilirubin monitoring in vivo, as well as for further clinical applications.

  12. Photoacoustic investigation of a neonatal skull phantom

    Science.gov (United States)

    Volinski, Bridget; Hariri, Ali; Fatima, Afreen; Xu, Qiuyun; Nasiriavanaki, Mohammadreza

    2017-03-01

    There is a need for continued research into the diagnosis, prevention and cure of neonatal brain disease and disorders. These disorders lead to fatalities and developmental disorders in infants. Non-invasive imaging techniques are being researched for this purpose. However, the availability of neonatal skull samples for this work is very low. A phantom can be used to simulate the neonatal skull and brain to improve imaging techniques. This study selects a phantom of polyurethane and titanium dioxide and proves its value as a replacement for neonatal skull in research. The methods used for this proof are validation of choice against the literature, transmissivity and acoustic experimentation compared to existing literature, and finally photoacoustic evaluation of the final choice to show its usefulness as a neonatal skull phantom.

  13. Q-switched Erbium-doped fiber laser at 1600 nm for photoacoustic imaging application.

    Science.gov (United States)

    Piao, Zhonglie; Zeng, Lvming; Chen, Zhongping; Kim, Chang-Seok

    2016-04-04

    We present a nanosecond Q-switched Erbium-doped fiber (EDF) laser system operating at 1600 nm with a tunable repetition rate from 100 kHz to 1 MHz. A compact fiber coupled, acousto-optic modulator-based EDF ring cavity was used to generate a nanosecond seed laser at 1600 nm, and a double-cladding EDF based power amplifier was applied to achieve the maximum average power of 250 mW. In addition, 12 ns laser pulses with the maximum pulse energy of 2.4 μJ were obtained at 100 kHz. Furthermore, the Stokes shift by Raman scattering over a 25 km long fiber was measured, indicating that the laser can be potentially used to generate the high repetition rate pulses at the 1.7 μm region. Finally, we detected the photoacoustic signal from a human hair at 200 kHz repetition rate with a pulse energy of 1.2 μJ, which demonstrates that a Q-switched Er-doped fiber laser can be a promising light source for the high speed functional photoacoustic imaging.

  14. Q-switched Erbium-doped fiber laser at 1600 nm for photoacoustic imaging application

    Energy Technology Data Exchange (ETDEWEB)

    Piao, Zhonglie [Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Beckman Laser Institute, Department of Biomedical Engineering, University of California, Irvine, California 92612 (United States); Zeng, Lvming; Chen, Zhongping, E-mail: z2chen@uci.edu, E-mail: ckim@pusan.ac.kr [Beckman Laser Institute, Department of Biomedical Engineering, University of California, Irvine, California 92612 (United States); Kim, Chang-Seok, E-mail: z2chen@uci.edu, E-mail: ckim@pusan.ac.kr [Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of)

    2016-04-04

    We present a nanosecond Q-switched Erbium-doped fiber (EDF) laser system operating at 1600 nm with a tunable repetition rate from 100 kHz to 1 MHz. A compact fiber coupled, acousto-optic modulator-based EDF ring cavity was used to generate a nanosecond seed laser at 1600 nm, and a double-cladding EDF based power amplifier was applied to achieve the maximum average power of 250 mW. In addition, 12 ns laser pulses with the maximum pulse energy of 2.4 μJ were obtained at 100 kHz. Furthermore, the Stokes shift by Raman scattering over a 25 km long fiber was measured, indicating that the laser can be potentially used to generate the high repetition rate pulses at the 1.7 μm region. Finally, we detected the photoacoustic signal from a human hair at 200 kHz repetition rate with a pulse energy of 1.2 μJ, which demonstrates that a Q-switched Er-doped fiber laser can be a promising light source for the high speed functional photoacoustic imaging.

  15. Anatomical and metabolic small-animal whole-body imaging using ring-shaped confocal photoacoustic computed tomography

    Science.gov (United States)

    Xia, Jun; Chatni, Muhammad; Maslov, Konstantin; Wang, Lihong V.

    2013-03-01

    Due to the wide use of animals for human disease studies, small animal whole-body imaging plays an increasingly important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose metabolic information, leading to higher costs of building dual-modality systems. Even with image coregistration, the spatial resolution of the metabolic imaging modality is not improved. We present a ring-shaped confocal photoacoustic computed tomography (RC-PACT) system that can provide both assessments in a single modality. Utilizing the novel design of confocal full-ring light delivery and ultrasound transducer array detection, RC-PACT provides full-view cross-sectional imaging with high spatial resolution. Scanning along the orthogonal direction provides three-dimensional imaging. While the mouse anatomy was imaged with endogenous hemoglobin contrast, the glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose. Through mouse tumor models, we demonstrate that RC-PACT may be a paradigm shifting imaging method for preclinical research.

  16. All-optical photoacoustic microscopy

    Directory of Open Access Journals (Sweden)

    Sung-Liang Chen

    2015-12-01

    Full Text Available Three-dimensional photoacoustic microscopy (PAM has gained considerable attention within the biomedical imaging community during the past decade. Detecting laser-induced photoacoustic waves by optical sensing techniques facilitates the idea of all-optical PAM (AOPAM, which is of particular interest as it provides unique advantages for achieving high spatial resolution using miniaturized embodiments of the imaging system. The review presents the technology aspects of optical-sensing techniques for ultrasound detection, such as those based on optical resonators, as well as system developments of all-optical photoacoustic systems including PAM, photoacoustic endoscopy, and multi-modality microscopy. The progress of different AOPAM systems and their representative applications are summarized.

  17. Development of a Multi-modal Tissue Diagnostic System Combining High Frequency Ultrasound and Photoacoustic Imaging with Lifetime Fluorescence Spectroscopy

    Science.gov (United States)

    Sun, Yang; Stephens, Douglas N.; Park, Jesung; Sun, Yinghua; Marcu, Laura; Cannata, Jonathan M.; Shung, K. Kirk

    2010-01-01

    We report the development and validate a multi-modal tissue diagnostic technology, which combines three complementary techniques into one system including ultrasound backscatter microscopy (UBM), photoacoustic imaging (PAI), and time-resolved laser-induced fluorescence spectroscopy (TR-LIFS). UBM enables the reconstruction of the tissue microanatomy. PAI maps the optical absorption heterogeneity of the tissue associated with structure information and has the potential to provide functional imaging of the tissue. Examination of the UBM and PAI images allows for localization of regions of interest for TR-LIFS evaluation of the tissue composition. The hybrid probe consists of a single element ring transducer with concentric fiber optics for multi-modal data acquisition. Validation and characterization of the multi-modal system and ultrasonic, photoacoustic, and spectroscopic data coregistration were conducted in a physical phantom with properties of ultrasound scattering, optical absorption, and fluorescence. The UBM system with the 41 MHz ring transducer can reach the axial and lateral resolution of 30 and 65 μm, respectively. The PAI system with 532 nm excitation light from a Nd:YAG laser shows great contrast for the distribution of optical absorbers. The TR-LIFS system records the fluorescence decay with the time resolution of ~300 ps and a high sensitivity of nM concentration range. Biological phantom constructed with different types of tissues (tendon and fat) was used to demonstrate the complementary information provided by the three modalities. Fluorescence spectra and lifetimes were compared to differentiate chemical composition of tissues at the regions of interest determined by the coregistered high resolution UBM and PAI image. Current results demonstrate that the fusion of these techniques enables sequentially detection of functional, morphological, and compositional features of biological tissue, suggesting potential applications in diagnosis of tumors

  18. One laser pulse generates two photoacoustic signals

    OpenAIRE

    Gao, Fei; Feng, Xiaohua; Bai, Linyi; Zhang, Ruochong; Liu, Siyu; Ding, Ran; Kishor, Rahul; Zhao, Yanli; Zheng, Yuanjin

    2016-01-01

    Photoacoustic sensing and imaging techniques have been studied widely to explore optical absorption contrast based on nanosecond laser illumination. In this paper, we report a long laser pulse induced dual photoacoustic (LDPA) nonlinear effect, which originates from unsatisfied stress and thermal confinements. Being different from conventional short laser pulse illumination, the proposed method utilizes a long square-profile laser pulse to induce dual photoacoustic signals. Without satisfying...

  19. Assessment of plaque vulnerability in atherosclerosis via intravascular photoacoustic imaging of targeted liposomal ICG J-aggregates (Conference Presentation)

    Science.gov (United States)

    Harris, Justin T.; Dumani, Diego S.; Cook, Jason R.; Sokolov, Konstantin V.; Emelianov, Stanislav Y.; Homan, Kimberly A.

    2017-03-01

    While molecular and cellular imaging can be used to visualize the conventional morphology characteristics of vulnerable plaques, there is a need to monitor other physiological factors correlated with high rupture rates; a high M1 activated macrophage concentration is one such indicator of high plaque vulnerability. Here, we present a molecularly targeted contrast agent for intravascular photoacoustic (IVPA) imaging consisting of liposomes loaded with indocyanine green (ICG) J-aggregates with high absorption at 890 nm, allowing for imaging in the presence of blood. This "Lipo-ICG" was targeted to a biomarker of M1 activated macrophages in vulnerable plaques: folate receptor beta (FRβ). The targeted liposomes accumulate in plaques through areas of endothelial dysfunction, while the liposome encapsulation prevents nonspecific interaction with lipids and endothelium. Lipo-ICG specifically interacts with M1 activated macrophages, causing a spectral shift and change in the 890/780 nm photoacoustic intensity ratio upon breakdown of J-aggregates. This sensing mechanism enables assessment of the M1 activated macrophage concentration, providing a measure of plaque vulnerability. In a pilot in vivo study utilizing ApoE deficient mouse models of atherosclerosis, diseased mice showed increased uptake of FRβ targeted Lipo-ICG in the heart and arteries vs. normal mice. Likewise, targeted Lipo-ICG showed increased uptake vs. two non-targeted controls. Thus, we successfully synthesized a contrast agent to detect M1 activated macrophages in high risk atherosclerotic plaques and exhibited targeting both in vitro and in vivo. This biocompatible agent could enable M1 macrophage detection, allowing better clinical decision making in treatment of atherosclerosis.

  20. Non-invasive imaging in detecting myocardial viability: Myocardial function versus perfusion

    Directory of Open Access Journals (Sweden)

    Iqbal A. Elfigih

    2014-12-01

    Full Text Available Coronary artery disease (CAD is the most prevalent and single most common cause of morbidity and mortality [1] with the resulting left ventricular (LV dysfunction an important complication. The distinction between viable and non-viable myocardium in patients with LV dysfunction is a clinically important issue among possible candidates for myocardial revascularization. Several available non-invasive techniques are used to detect and assess ischemia and myocardial viability. These techniques include echocardiography, radionuclide images, cardiac magnetic resonance imaging and recently myocardial computed tomography perfusion imaging. This review aims to distinguish between the available non-invasive imaging techniques in detecting signs of functional and perfusion viability and identify those which have the most clinical relevance in detecting myocardial viability in patients with CAD and chronic ischemic LV dysfunction. The most current available studies showed that both myocardial perfusion and function based on non-invasive imaging have high sensitivity with however wide range of specificity for detecting myocardial viability. Both perfusion and function imaging modalities provide complementary information about myocardial viability and no optimum single imaging technique exists that can provide very accurate diagnostic and prognostic viability assessment. The weight of the body of evidence suggested that non-invasive imaging can help in guiding therapeutic decision making in patients with LV dysfunction.

  1. Non-invasive imaging of kupffer cell status using radiolabelled mannosylated albumin

    NARCIS (Netherlands)

    Mahajan, V.; Hartimath, S.; Comley, R.; Stefan-Gueldner, M.; Roth, A.; Poelstra, K.; Reker-Smit, C.; Kamps, J.; Dierckx, R.; de Vries, Erik

    2014-01-01

    Background and Aims: Kupffer cells are responsible for maintaining liver homeostasis and have a vital role in chronic hepatotoxicity and various liver diseases. Positron Imaging Tomography (PET) is a non-invasive imaging technique that allows quantification and visualization of biochemical processes

  2. Non-invasive monitoring of living cell culture by lensless digital holography imaging

    Institute of Scientific and Technical Information of China (English)

    Yunxin Wang; Dayong Wang; Jie Zhao; Yishu Yang; Xiangqian Xiao; Huakun Cui

    2011-01-01

    @@ A non-invasive detection method for the status analysis of cell culture is presented based on digital holography technology.Lensless Fourier transform digital holography (LFTDH) configuration is developed for living cell imaging without prestaining.Complex amplitude information is reconstructed by a single inverse fast Fourier transform, and the phase aberration is corrected through the two-step phase subtraction method.The image segmentation is then applied to the automatic evaluation of confluency.Finally,the cervical cancer cell TZMbl is employed for experimental validation, and the results demonstrate that LFTDH imaging with the corresponding image post-processing can provide an automatic and non-invasive approach for monitoring living cell culture.%A non-invasive detection method for the status analysis of cell culture is presented based on digital holography technology. Lensless Fourier transform digital holography (LFTDH) configuration is developed for living cell imaging without prestaining. Complex amplitude information is reconstructed by a single inverse fast Fourier transform, and the phase aberration is corrected through the two-step phase subtraction method. The image segmentation is then applied to the automatic evaluation of confluency. Finally,the cervical cancer cell TZMbl is employed for experimental validation, and the results demonstrate that LFTDH imaging with the corresponding image post-processing can provide an automatic and non-invasive approach for monitoring living cell culture.

  3. Non-invasive imaging of kupffer cell status using radiolabelled mannosylated albumin

    NARCIS (Netherlands)

    Mahajan, V.; Hartimath, S.; Comley, R.; Stefan-Gueldner, M.; Roth, A.; Poelstra, K.; Reker-Smit, C.; Kamps, J.; Dierckx, R.; de Vries, Erik

    2014-01-01

    Background and Aims: Kupffer cells are responsible for maintaining liver homeostasis and have a vital role in chronic hepatotoxicity and various liver diseases. Positron Imaging Tomography (PET) is a non-invasive imaging technique that allows quantification and visualization of biochemical processes

  4. Cardiovascular dysfunction in obesity and new diagnostic imaging techniques: the role of noninvasive image methods

    Directory of Open Access Journals (Sweden)

    Barbosa JA

    2011-05-01

    Full Text Available José Augusto A Barbosa¹, Alexandre B Rodrigues¹, Cleonice Carvalho C Mota¹, Márcia M Barbosa², Ana C Simões e Silva¹¹Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG, Belo Horizonte, Minas Gerais, Brazil; ²Ecocenter, Socor Hospital, Belo Horizonte, Minas Gerais, BrazilAbstract: Obesity is a major public health problem affecting adults and children in both developed and developing countries. This condition often leads to metabolic syndrome, which increases the risk of cardiovascular disease. A large number of studies have been carried out to understand the pathogenesis of cardiovascular dysfunction in obese patients. Endothelial dysfunction plays a key role in the progression of atherosclerosis and the development of coronary artery disease, hypertension and congestive heart failure. Noninvasive methods in the field of cardiovascular imaging, such as measuring intima-media thickness, flow-mediated dilatation, tissue Doppler, and strain, and strain rate, constitute new tools for the early detection of cardiac and vascular dysfunction. These techniques will certainly enable a better evaluation of initial cardiovascular injury and allow the correct, timely management of obese patients. The present review summarizes the main aspects of cardiovascular dysfunction in obesity and discusses the application of recent noninvasive imaging methods for the early detection of cardiovascular alterations.Keywords: cardiovascular risk, endothelium dysfunction, obesity, strain and strain rate, tissue Doppler

  5. High-speed intravascular spectroscopic photoacoustic imaging at 1000 A-lines per second with a 0.9-mm diameter catheter

    Science.gov (United States)

    Li, Yan; Gong, Xiaojing; Liu, Chengbo; Lin, Riqiang; Hau, William; Bai, Xiaosong; Song, Liang

    2015-06-01

    Intravascular spectroscopic photoacoustic technology can image atherosclerotic plaque composition with high sensitivity and specificity, which is critical for identifying vulnerable plaques. Here, we designed and engineered a catheter of 0.9 mm in diameter for intravascular photoacoustic (IVPA) imaging, smaller than the critical size of 1 mm required for clinical translation. Further, a quasifocusing photoacoustic excitation scheme was developed for the catheter, producing well-detectable IVPA signals from stents and lipids with a laser energy as low as ˜30 μJ/pulse. As a result, this design enabled the use of a low-energy, high-repetition rate, ns-pulsed optical parametric oscillator laser for high-speed spectroscopic IVPA imaging at both the 1.2-μm and 1.7-μm spectral bands for lipid detection. Specifically, for each wavelength, a 1-kHz IVPA A-line rate was achieved, ˜100-fold faster than previously reported IVPA systems offering a similar wavelength tuning range. Using the system, spectroscopic IVPA imaging of peri-adventitial adipose tissue from a porcine aorta segment was demonstrated. The significantly improved imaging speed, together with the reduced catheter size and multiwavelength spectroscopic imaging ability, suggests that the developed high-speed IVPA technology is of great potential to be further translated for in vivo applications.

  6. One laser pulse generates two photoacoustic signals

    CERN Document Server

    Gao, Fei; Zheng, Yuanjin

    2016-01-01

    Photoacoustic sensing and imaging techniques have been studied widely to explore optical absorption contrast based on nanosecond laser illumination. In this paper, we report a long laser pulse induced dual photoacoustic (LDPA) nonlinear effect, which originates from unsatisfied stress and thermal confinements. Being different from conventional short laser pulse illumination, the proposed method utilizes a long square-profile laser pulse to induce dual photoacoustic signals. Without satisfying the stress confinement, the dual photoacoustic signals are generated following the positive and negative edges of the long laser pulse. More interestingly, the first expansion-induced photoacoustic signal exhibits positive waveform due to the initial sharp rising of temperature. On the contrary, the second contraction-induced photoacoustic signal exhibits exactly negative waveform due to the falling of temperature, as well as pulse-width-dependent, signal amplitude which is caused by the concurrent heat accumulation and ...

  7. Endobronchial Photoacoustic Microscopy for Staging of Lung Cancer

    Science.gov (United States)

    2016-08-01

    optical absorber which is important for PA imaging. To image the lymph node, the dye or absorber is necessary to generate the acoustic signals for...SUPPLEMENTARY NOTES Photoacoustic imaging, photoacoustic microscopy, lung cancer 14. ABSTRACT This research is aimed at developing a new endoscopic...imaging approach, called “photoacoustic microscopy (PAM)”, for lung cancer staging. The project will develop imaging hardware and conduct phantom

  8. Nonlinear photoacoustic spectroscopy of hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P.; Xia, Jun; Wang, Lihong V., E-mail: LHWANG@WUSTL.EDU [Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130 (United States)

    2015-05-18

    As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography.

  9. Photoacoustic tomography of small-animal and human peripheral joints

    Science.gov (United States)

    Wang, Xueding; Chamberland, David L.; Fowlkes, J. Brian; Carson, Paul L.; Jamadar, David A.

    2008-02-01

    As an emerging imaging technology that combines the merits of both light and ultrasound, photoacoustic tomography (PAT) holds promise for screening and diagnosis of inflammatory joint diseases such as rheumatoid arthritis. In this study, the feasibility of PAT in imaging small-animal joints and human peripheral joints in a noninvasive manner was explored. Ex vivo rat tail and fresh cadaveric human finger joints were imaged. Based on the intrinsic optical contrast, intra- and extra-articular tissue structures in the joints were visualized successfully. Using light in the near-infrared region, the imaging depth of PAT is sufficient for cross-sectional imaging of a human peripheral joint as a whole organ. PAT, as a novel imaging modality with unique advantages, may contribute significantly to the early diagnosis of inflammatory joint disorders and accurate monitoring of disease progression and response to therapy.

  10. Review of Image Reconstruction for Intravascular Photoacoustic Imaging%血管内光声成像图像重建的研究现状

    Institute of Scientific and Technical Information of China (English)

    孙正; 韩朵朵; 王健健

    2015-01-01

    Acute cardiovascular disease is the leading killer of human health. Intravascular Photoacoustic (IVPA) imaging modality, which combines photoacoustic imaging and medical endoscopic technique, is expected to provide more reliable information about the vessel and plaques for the detection of vulnerable plaques and the interventional treatment of cardiac diseases. Till now, the study of the IVPA imaging has been still in its beginning stages. The study of the IVPA image reconstruction also mainly learns from the reconstruction algorithms of other mature imaging techniques. Based on the introduction of the IVPA imaging principle, two problems to be solved in IVPA image reconstruction are pointed out and some main reconstruction algorithms that can be applied to the IVPA image reconstruction are introduced and analyzed.%急性心脑血管疾病是人类健康的头号杀手,将光声成像与医学内窥技术相结合的血管内光声(IVPA)成像技术有望为心脑血管内易损斑块的检测以及指导介入治疗提供更可靠的参考指标。目前对 IVPA 成像的研究尚处于起步阶段,对其图像重建的研究也主要是借鉴其它比较成熟的成像技术的重建理论。本文在介绍 IVPA 成像原理的基础上,指出在重建IVPA图像中亟待解决的两个问题,并对目前可以应用到IVPA图像重建中的主流算法进行介绍和分析。

  11. Oil/water nano-emulsion loaded with cobalt ferrite oxide nanocubes for photo-acoustic and magnetic resonance dual imaging in cancer: in vitro and preclinical studies.

    Science.gov (United States)

    Vecchione, Raffaele; Quagliariello, Vincenzo; Giustetto, Pierangela; Calabria, Dominic; Sathya, Ayyappan; Marotta, Roberto; Profeta, Martina; Nitti, Simone; Silvestri, Niccolò; Pellegrino, Teresa; Iaffaioli, Rosario V; Netti, Paolo Antonio

    2017-01-01

    Dual imaging dramatically improves detection and early diagnosis of cancer. In this work we present an oil in water (O/W) nano-emulsion stabilized with lecithin and loaded with cobalt ferrite oxide (Co0.5Fe2.5O4) nanocubes for photo-acoustic and magnetic resonance dual imaging. The nanocarrier is responsive in in vitro photo-acoustic and magnetic resonance imaging (MRI) tests. A clear and significant time-dependent accumulation in tumor tissue is shown in in vivo photo-acoustic studies on a murine melanoma xenograft model. The proposed O/W nano-emulsion exhibits also high values of r2/r1 (ranging from 45 to 85, depending on the magnetic field) suggesting a possible use as T2 weighted image contrast agents. In addition, viability and cellular uptake studies show no significant cytotoxicity on the fibroblast cell line. We also tested the O/W nano-emulsion loaded with curcumin against melanoma cancer cells demonstrating a significant cytotoxicity and thus showing possible therapeutic effects in addition to the in vivo imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Backward-mode multiwavelength photoacoustic scanner using a planar Fabry-Perot polymer film ultrasound sensor for high-resolution three-dimensional imaging of biological tissues.

    Science.gov (United States)

    Zhang, Edward; Laufer, Jan; Beard, Paul

    2008-02-01

    A multiwavelength backward-mode planar photoacoustic scanner for 3D imaging of soft tissues to depths of several millimeters with a spatial resolution in the tens to hundreds of micrometers range is described. The system comprises a tunable optical parametric oscillator laser system that provides nanosecond laser pulses between 600 and 1200 nm for generating the photoacoustic signals and an optical ultrasound mapping system based upon a Fabry-Perot polymer film sensor for detecting them. The system enables photoacoustic signals to be mapped in 2D over a 50 mm diameter aperture in steps of 10 microm with an optically defined element size of 64 microm. Two sensors were used, one with a 22 microm thick polymer film spacer and the other with a 38 mum thick spacer providing -3 dB acoustic bandwidths of 39 and 22 MHz, respectively. The measured noise equivalent pressure of the 38 microm sensor was 0.21 kPa over a 20 MHz measurement bandwidth. The instrument line-spread function (LSF) was measured as a function of position and the minimum lateral and vertical LSFs found to be 38 and 15 microm, respectively. To demonstrate the ability of the system to provide high-resolution 3D images, a range of absorbing objects were imaged. Among these was a blood vessel phantom that comprised a network of blood filled tubes of diameters ranging from 62 to 300 microm immersed in an optically scattering liquid. In addition, to demonstrate the applicability of the system to spectroscopic imaging, a phantom comprising tubes filled with dyes of different spectral characteristics was imaged at a range of wavelengths. It is considered that this type of instrument may provide a practicable alternative to piezoelectric-based photoacoustic systems for high-resolution structural and functional imaging of the skin microvasculature and other superficial structures.

  13. Obesity and the challenges of noninvasive imaging for the detection of coronary artery disease.

    Science.gov (United States)

    Lim, Siok P; Arasaratnam, Punitha; Chow, Benjamin J; Beanlands, Rob S; Hessian, Renée C

    2015-02-01

    Obesity is a significant health problem that could potentially lead to increased cardiovascular risk. Noninvasive imaging plays an important role in the evaluation of cardiovascular symptoms and risk of these patients. Selection of the appropriate test in the diagnosis of obstructive coronary artery disease in this unique population is important. In this article, we focus on the strengths, limitations, and recommendations of the various noninvasive cardiac imaging modalities available in the detection of obstructive coronary artery disease. We have suggested an algorithm to help direct investigation. Ultimately, patient management should be individualized based on clinical judgement, test availability, and local expertise.

  14. Non-invasive estimation of the metabolic heat production of breast tumors using digital infrared imaging

    CERN Document Server

    González, Francisco Javier

    2011-01-01

    In this work the metabolic heat generated by breast tumors was estimated indirectly and noninvasively from digital infrared images and numerically simulating a simplified breast model and a cancerous tumor, this parameter can be of clinical importance since it has been related to the doubling volume's time and malignancy for that particular tumor. The results indicate that digital infrared imaging has the potential to estimate in a non-invasive way the malignancy of a tumor by calculating its metabolic heat generation from bioheat thermal transfer models.

  15. Characterization and treatment monitoring of inflammatory arthritis by photoacoustic imaging: a study on adjuvant-induced arthritis rat model

    Science.gov (United States)

    Wang, Xueding; Rajian, Justin; Shao, Xia; Chamberland, David L.; Girish, Gandikota

    2014-03-01

    Neovascularity also known as angiogenesis is an early feature of inflammatory arthritis disease. Therefore, identifying the development of neovascularity is one way to potentially detect and characterize arthritis. Laser-based photoacoustic imaging (PAI) is an emerging biomedical imaging modality which may aid in detection of both early and continued development of neovascularity. In this work, we investigated the feasibility of PAI to measure angiogenesis, for the purpose of evaluating and monitoring inflammatory arthritis after treatment. The imaging results on an arthritis rat model demonstrate that 1) there is noticeable enhancement in image intensity in the arthritic ankle joints when compared to the normal joints, and 2) there is noticeable decrease in image intensity in the arthritic ankle joints after treatment when compared to the untreated arthritic joints. In order to validate the findings from PAI, we performed positron emission tomography (PET) and histology on the same joints. The diameters of the ankle joints, as a clinical score of the arthritis, were also measured at each time point.

  16. High Resolution Ultrasound and Photoacoustic Imaging of Orthotopic Lung Cancer in Mice: New Perspectives for Onco-Pharmacology

    Science.gov (United States)

    Sobilo, Julien; Le Mée, Marilyne; Rétif, Stéphanie; Natkunarajah, Sharuja; Lerondel, Stéphanie; Le Pape, Alain

    2016-01-01

    Objectives We have developed a relevant preclinical model associated with a specific imaging protocol dedicated to onco-pharmacology studies in mice. Materials and Methods We optimized both the animal model and an ultrasound imaging procedure to follow up longitudinally the lung tumor growth in mice. Moreover we proposed to measure by photoacoustic imaging the intratumoral hypoxia, which is a crucial parameter responsible for resistance to therapies. Finally, we compared ultrasound data to x-ray micro computed tomography and volumetric measurements to validate the relevance of this approach on the NCI-H460 human orthotopic lung tumor. Results This study demonstrates the ability of ultrasound imaging to detect and monitor the in vivo orthotopic lung tumor growth by high resolution ultrasound imaging. This approach enabled us to characterize key biological parameters such as oxygenation, perfusion status and vascularization of tumors. Conclusion Such an experimental approach has never been reported previously and it would provide a nonradiative tool for assessment of anticancer therapeutic efficacy in mice. Considering the absence of ultrasound propagation through the lung parenchyma, this strategy requires the implantation of tumors strictly located in the superficial posterior part of the lung. PMID:27070548

  17. Human CIK Cells Loaded with Au Nanorods as a Theranostic Platform for Targeted Photoacoustic Imaging and Enhanced Immunotherapy and Photothermal Therapy.

    Science.gov (United States)

    Yang, Yao; Zhang, Jingjing; Xia, Fangfang; Zhang, Chunlei; Qian, Qirong; Zhi, Xiao; Yue, Caixia; Sun, Rongjin; Cheng, Shangli; Fang, Shan; Jin, Weilin; Yang, Yuming; Cui, Daxiang

    2016-12-01

    How to realize targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer has become a great challenge. Herein, we reported for the first time that human cytokine-induced killer cells (CIK) loaded with gold nanorods were used for targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer. Silica-modified gold nanorods were prepared; then incubated with human cytokine-induced killer cells (CIK), resultant human CIK cells loaded with Au nanorods were evaluated for their cytotoxicity, targeted ability of gastric cancer in vitro and in vivo, immunotherapy, and photothermal therapy efficacy. In vitro cell experiment shows that human CIK cells labeled with gold nanorods actively target gastric cancer MGC803 cells, inhibit growth of MGC803 cells by inducing cell apoptosis, and kill MGC803 cells under low power density near-infrared (NIR) laser treatment (808-nm continuous wave laser, 1.5 W/cm(2), 3 min). In vivo experiment results showed that human CIK cells labeled with gold nanorods could target actively and image subcutaneous gastric cancer vessels via photoacoustic imaging at 4 h post-injection, could enhance immunotherapy efficacy by up-regulating cytokines such as IL-1, IL-12, IL-2, IL-4, IL-17, and IFN-γ, and kill gastric cancer tissues by photothermal therapy via direct injection into tumor site under near-infrared (NIR) laser irradiation. High-performance human CIK cells labeled with Au nanorods are a good novel theranostic platform to exhibit great potential in applications such as tumor-targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy in the near future.

  18. Human CIK Cells Loaded with Au Nanorods as a Theranostic Platform for Targeted Photoacoustic Imaging and Enhanced Immunotherapy and Photothermal Therapy

    Science.gov (United States)

    Yang, Yao; Zhang, Jingjing; Xia, Fangfang; Zhang, Chunlei; Qian, Qirong; Zhi, Xiao; Yue, Caixia; Sun, Rongjin; Cheng, Shangli; Fang, Shan; Jin, Weilin; Yang, Yuming; Cui, Daxiang

    2016-06-01

    How to realize targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer has become a great challenge. Herein, we reported for the first time that human cytokine-induced killer cells (CIK) loaded with gold nanorods were used for targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer. Silica-modified gold nanorods were prepared; then incubated with human cytokine-induced killer cells (CIK), resultant human CIK cells loaded with Au nanorods were evaluated for their cytotoxicity, targeted ability of gastric cancer in vitro and in vivo, immunotherapy, and photothermal therapy efficacy. In vitro cell experiment shows that human CIK cells labeled with gold nanorods actively target gastric cancer MGC803 cells, inhibit growth of MGC803 cells by inducing cell apoptosis, and kill MGC803 cells under low power density near-infrared (NIR) laser treatment (808-nm continuous wave laser, 1.5 W/cm2, 3 min). In vivo experiment results showed that human CIK cells labeled with gold nanorods could target actively and image subcutaneous gastric cancer vessels via photoacoustic imaging at 4 h post-injection, could enhance immunotherapy efficacy by up-regulating cytokines such as IL-1, IL-12, IL-2, IL-4, IL-17, and IFN-γ, and kill gastric cancer tissues by photothermal therapy via direct injection into tumor site under near-infrared (NIR) laser irradiation. High-performance human CIK cells labeled with Au nanorods are a good novel theranostic platform to exhibit great potential in applications such as tumor-targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy in the near future.

  19. RGD-conjugated silica-coated gold nanorods on the surface of carbon nanotubes for targeted photoacoustic imaging of gastric cancer

    Science.gov (United States)

    Wang, Can; Bao, Chenchen; Liang, Shujing; Fu, Hualin; Wang, Kan; Deng, Min; Liao, Qiande; Cui, Daxiang

    2014-05-01

    Herein, we reported for the first time that RGD-conjugated silica-coated gold nanorods on the surface of multiwalled carbon nanotubes were successfully used for targeted photoacoustic imaging of in vivo gastric cancer cells. A simple strategy was used to attach covalently silica-coated gold nanorods (sGNRs) onto the surface of multiwalled carbon nanotubes (MWNTs) to fabricate a hybrid nanostructure. The cross-linked reaction occurred through the combination of carboxyl groups on the MWNTs and the amino group on the surface of sGNRs modified with a silane coupling agent. RGD peptides were conjugated with the sGNR/MWNT nanostructure; resultant RGD-conjugated sGNR/MWNT probes were investigated for their influences on viability of MGC803 and GES-1 cells. The nude mice models loaded with gastric cancer cells were prepared, the RGD-conjugated sGNR/MWNT probes were injected into gastric cancer-bearing nude mice models via the tail vein, and the nude mice were observed by an optoacoustic imaging system. Results showed that RGD-conjugated sGNR/MWNT probes showed good water solubility and low cellular toxicity, could target in vivo gastric cancer cells, and obtained strong photoacoustic imaging in the nude model. RGD-conjugated sGNR/MWNT probes will own great potential in applications such as targeted photoacoustic imaging and photothermal therapy in the near future.

  20. Dual-Modality Imaging of the Human Finger Joint Systems by Using Combined Multispectral Photoacoustic Computed Tomography and Ultrasound Computed Tomography

    Science.gov (United States)

    Liu, Yubin; Wang, Yating

    2016-01-01

    We developed a homemade dual-modality imaging system that combines multispectral photoacoustic computed tomography and ultrasound computed tomography for reconstructing the structural and functional information of human finger joint systems. The fused multispectral photoacoustic-ultrasound computed tomography (MPAUCT) system was examined by the phantom and in vivo experimental tests. The imaging results indicate that the hard tissues such as the bones and the soft tissues including the blood vessels, the tendon, the skins, and the subcutaneous tissues in the finger joints systems can be effectively recovered by using our multimodality MPAUCT system. The developed MPAUCT system is able to provide us with more comprehensive information of the human finger joints, which shows its potential for characterization and diagnosis of bone or joint diseases. PMID:27774453

  1. Dual-Modality Imaging of the Human Finger Joint Systems by Using Combined Multispectral Photoacoustic Computed Tomography and Ultrasound Computed Tomography

    Directory of Open Access Journals (Sweden)

    Yubin Liu

    2016-01-01

    Full Text Available We developed a homemade dual-modality imaging system that combines multispectral photoacoustic computed tomography and ultrasound computed tomography for reconstructing the structural and functional information of human finger joint systems. The fused multispectral photoacoustic-ultrasound computed tomography (MPAUCT system was examined by the phantom and in vivo experimental tests. The imaging results indicate that the hard tissues such as the bones and the soft tissues including the blood vessels, the tendon, the skins, and the subcutaneous tissues in the finger joints systems can be effectively recovered by using our multimodality MPAUCT system. The developed MPAUCT system is able to provide us with more comprehensive information of the human finger joints, which shows its potential for characterization and diagnosis of bone or joint diseases.

  2. Real-time imaging for cerebral ischemia in rats using the multi-wavelength handheld photoacoustic system

    Science.gov (United States)

    Liu, Yu-Hang; Xu, Yu; Chan, Kim Chuan; Mehta, Kalpesh; Thakor, Nitish; Liao, Lun-De

    2017-02-01

    Stroke is the second leading cause of death worldwide. Rapid and precise diagnosis is essential to expedite clinical decision and improve functional outcomes in stroke patients; therefore, real-time imaging plays an important role to provide crucial information for post-stroke recovery analysis. In this study, based on the multi-wavelength laser and 18.5 MHz array-based ultrasound platform, a real-time handheld photoacoustic (PA) system was developed to evaluate cerebrovascular functions pre- and post-stroke in rats. Using this system, hemodynamic information such as cerebral blood volume (CBV) can be acquired for assessment. One rat stroke model (i.e., photothrombotic ischemia (PTI)) was employed for evaluating the effect of local ischemia. For achieving better intrinsic PA contrast, Vantage and COMSOL simulations were applied to optimize the light delivery (e.g., interval between two arms) from customized fiber bundle, while phantom experiment was conducted to evaluate the imaging performance of this system. Results of phantom experiment showed that hairs ( 150 μm diameter) and pencil lead (500 μm diameter) can be imaged clearly. On the other hand, results of in vivo experiments also demonstrated that stroke symptoms can be observed in PTI model poststroke. In the near future, with the help of PA specific contrast agent, the system would be able to achieve blood-brain barrier leakage imaging post-stroke. Overall, the real-time handheld PA system holds great potential in disease models involving impairments in cerebrovascular