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Sample records for flow-sensitive in-vivo 4d

  1. In vivo analysis of physiological 3D blood flow of cerebral veins

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    Schuchardt, Florian; Schroeder, Laure; Baeuerle, Jochen; Harloff, Andreas [University Medical Centre, Department of Neurology, Freiburg (Germany); Anastasopoulos, Constantin [University Medical Center, Department of Neuropaediatrics and Muscle Disorders, Freiburg (Germany); University Medical Centre, Department of Neuroradiology, Freiburg (Germany); Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine and McCormick School of Engineering, Chicago, IL (United States); Hennemuth, Anja; Drexl, Johann [Fraunhofer MEVIS, Bremen (Germany); Valdueza, Jose M. [Neurological Center, Segeberger Kliniken, Bad Segeberg (Germany); Mader, Irina [University Medical Centre, Department of Neuroradiology, Freiburg (Germany)

    2015-08-15

    To visualize and quantify physiological blood flow of intracranial veins in vivo using time-resolved, 3D phase-contrast MRI (4D flow MRI), and to test measurement accuracy. Fifteen healthy volunteers underwent repeated ECG-triggered 4D flow MRI (3 Tesla, 32-channel head coil). Intracranial venous blood flow was analysed using dedicated software allowing for blood flow visualization and quantification in analysis planes at the superior sagittal, straight, and transverse sinuses. MRI was evaluated for intra- and inter-observer agreement and scan-rescan reproducibility. Measurements of the transverse sinuses were compared with transcranial two-dimensional duplex ultrasound. Visualization of 3D blood flow within cerebral sinuses was feasible in 100 % and within at least one deep cerebral vein in 87 % of the volunteers. Blood flow velocity/volume increased along the superior sagittal sinus and was lower in the left compared to the right transverse sinus. Intra- and inter-observer reliability and reproducibility of blood flow velocity (mean difference 0.01/0.02/0.02 m/s) and volume (mean difference 0.0002/-0.0003/0.00003 l/s) were good to excellent. High/low velocities were more pronounced (8 % overestimation/9 % underestimation) in MRI compared to ultrasound. Four-dimensional flow MRI reliably visualizes and quantifies three-dimensional cerebral venous blood flow in vivo and is promising for studies in patients with sinus thrombosis and related diseases. (orig.)

  2. Characterization of cardiac flow in heart disease patients by computational fluid dynamics and 4D flow MRI

    Science.gov (United States)

    Lantz, Jonas; Gupta, Vikas; Henriksson, Lilian; Karlsson, Matts; Persson, Ander; Carhall, Carljohan; Ebbers, Tino

    2017-11-01

    In this study, cardiac blood flow was simulated using Computational Fluid Dynamics and compared to in vivo flow measurements by 4D Flow MRI. In total, nine patients with various heart diseases were studied. Geometry and heart wall motion for the simulations were obtained from clinical CT measurements, with 0.3x0.3x0.3 mm spatial resolution and 20 time frames covering one heartbeat. The CFD simulations included pulmonary veins, left atrium and ventricle, mitral and aortic valve, and ascending aorta. Mesh sizes were on the order of 6-16 million cells, depending on the size of the heart, in order to resolve both papillary muscles and trabeculae. The computed flow field agreed visually very well with 4D Flow MRI, with characteristic vortices and flow structures seen in both techniques. Regression analysis showed that peak flow rate as well as stroke volume had an excellent agreement for the two techniques. We demonstrated the feasibility, and more importantly, fidelity of cardiac flow simulations by comparing CFD results to in vivo measurements. Both qualitative and quantitative results agreed well with the 4D Flow MRI measurements. Also, the developed simulation methodology enables ``what if'' scenarios, such as optimization of valve replacement and other surgical procedures. Funded by the Wallenberg Foundation.

  3. 4D flow mri post-processing strategies for neuropathologies

    Science.gov (United States)

    Schrauben, Eric Mathew

    double-gated flow acquisition and reconstruction scheme demonstrates respiratory-induced changes in internal jugular vein flow. Finally, a semi-automated intracranial vessel segmentation and flow parameter measurement software tool for fast and consistent 4D flow post-processing analysis is developed, validated, and exhibited an in-vivo.

  4. 4D-MR flow analysis in patients after repair for tetralogy of Fallot

    International Nuclear Information System (INIS)

    Geiger, J.; Markl, M.; Jung, B.; Langer, M.; Grohmann, J.; Stiller, B.; Arnold, R.

    2011-01-01

    Comprehensive analysis of haemodynamics by 3D flow visualisation and retrospective flow quantification in patients after repair of tetralogy of Fallot (TOF). Time-resolved flow-sensitive 4D MRI (spatial resolution ∝ 2.5 mm, temporal resolution = 38.4 ms) was acquired in ten patients after repair of TOF and in four healthy controls. Data analysis included the evaluation of haemodynamics in the aorta, the pulmonary trunk (TP) and left (lPA) and right (rPA) pulmonary arteries by 3D blood flow visualisation using particle traces, and quantitative measurements of flow velocity. 3D visualisation of whole heart haemodynamics provided a comprehensive overview on flow pattern changes in TOF patients, mainly alterations in flow velocity, retrograde flow and pathological vortices. There was consistently higher blood flow in the rPA of the patients (rPA/lPA flow ratio: 2.6 ± 2.5 vs. 1.1 ± 0.1 in controls). Systolic peak velocity in the TP was higher in patients (1.9 m/s ± 0.7 m/s) than controls (0.9 m/s ± 0.1 m/s). 4D flow-sensitive MRI permits the comprehensive evaluation of blood flow characteristics in patients after repair of TOF. Altered flow patterns for different surgical techniques in the small patient cohort may indicate its value for patient monitoring and potentially identifying optimal surgical strategies. (orig.)

  5. 4D-MR flow analysis in patients after repair for tetralogy of Fallot

    Energy Technology Data Exchange (ETDEWEB)

    Geiger, J.; Markl, M.; Jung, B.; Langer, M. [University Hospital Freiburg, Department of Radiology, Medical Physics, Freiburg (Germany); Grohmann, J.; Stiller, B.; Arnold, R. [University Hospital Freiburg, Department of Congenital Heart Disease and Pediatric Cardiology, Freiburg (Germany)

    2011-08-15

    Comprehensive analysis of haemodynamics by 3D flow visualisation and retrospective flow quantification in patients after repair of tetralogy of Fallot (TOF). Time-resolved flow-sensitive 4D MRI (spatial resolution {proportional_to} 2.5 mm, temporal resolution = 38.4 ms) was acquired in ten patients after repair of TOF and in four healthy controls. Data analysis included the evaluation of haemodynamics in the aorta, the pulmonary trunk (TP) and left (lPA) and right (rPA) pulmonary arteries by 3D blood flow visualisation using particle traces, and quantitative measurements of flow velocity. 3D visualisation of whole heart haemodynamics provided a comprehensive overview on flow pattern changes in TOF patients, mainly alterations in flow velocity, retrograde flow and pathological vortices. There was consistently higher blood flow in the rPA of the patients (rPA/lPA flow ratio: 2.6 {+-} 2.5 vs. 1.1 {+-} 0.1 in controls). Systolic peak velocity in the TP was higher in patients (1.9 m/s {+-} 0.7 m/s) than controls (0.9 m/s {+-} 0.1 m/s). 4D flow-sensitive MRI permits the comprehensive evaluation of blood flow characteristics in patients after repair of TOF. Altered flow patterns for different surgical techniques in the small patient cohort may indicate its value for patient monitoring and potentially identifying optimal surgical strategies. (orig.)

  6. Improved Diffuse Fluorescence Flow Cytometer Prototype for High Sensitivity Detection of Rare Circulating Cells In Vivo

    Science.gov (United States)

    Pestana, Noah Benjamin

    Accurate quantification of circulating cell populations is important in many areas of pre-clinical and clinical biomedical research, for example, in the study of cancer metastasis or the immune response following tissue and organ transplants. Normally this is done "ex-vivo" by drawing and purifying a small volume of blood and then analyzing it with flow cytometry, hemocytometry or microfludic devices, but the sensitivity of these techniques are poor and the process of handling samples has been shown to affect cell viability and behavior. More recently "in vivo flow cytometry" (IVFC) techniques have been developed where fluorescently-labeled cells flowing in a small blood vessel in the ear or retina are analyzed, but the sensitivity is generally poor due to the small sampling volume. To address this, our group recently developed a method known as "Diffuse Fluorescence Flow Cytometry" (DFFC) that allows detection and counting of rare circulating cells with diffuse photons, offering extremely high single cell counting sensitivity. In this thesis, an improved DFFC prototype was designed and validated. The chief improvements were three-fold, i) improved optical collection efficiency, ii) improved detection electronics, and iii) development of a method to mitigate motion artifacts during in vivo measurements. In combination, these improvements yielded an overall instrument detection sensitivity better than 1 cell/mL in vivo, which is the most sensitive IVFC system reported to date. Second, development and validation of a low-cost microfluidic device reader for analysis of ocular fluids is described. We demonstrate that this device has equivalent or better sensitivity and accuracy compared a fluorescence microscope, but at an order-of-magnitude reduced cost with simplified operation. Future improvements to both instruments are also discussed.

  7. Self-gated golden-angle spiral 4D flow MRI.

    Science.gov (United States)

    Bastkowski, Rene; Weiss, Kilian; Maintz, David; Giese, Daniel

    2018-01-17

    The acquisition of 4D flow magnetic resonance imaging (MRI) in cardiovascular applications has recently made large progress toward clinical feasibility. The need for simultaneous compensation of cardiac and breathing motion still poses a challenge for widespread clinical use. Especially, breathing motion, addressed by gating approaches, can lead to unpredictable and long scan times. The current work proposes a time-efficient self-gated 4D flow sequence that exploits up to 100% of the acquired data and operates at a predictable scan time. A self-gated golden-angle spiral 4D flow sequence was implemented and tested in 10 volunteers. Data were retrospectively binned into respiratory and cardiac states and reconstructed using a conjugate-gradient sensitivity encoding reconstruction. Net flow curves, stroke volumes, and peak flow in the aorta were evaluated and compared to a conventional Cartesian 4D flow sequence. Additionally, flow quantities reconstructed from 50% to 100% of the self-gated 4D flow data were compared. Self-gating signals for respiratory and cardiac motion were extracted for all volunteers. Flow quantities were in agreement with the standard Cartesian scan. Mean differences in stroke volumes and peak flow of 7.6 ± 11.5 and 4.0 ± 79.9 mL/s were obtained, respectively. By retrospectively increasing breathing navigator efficiency while decreasing acquisition times (15:06-07:33 minutes), 50% of the acquired data were sufficient to measure stroke volumes with errors under 9.6 mL. The feasibility to acquire respiratory and cardiac self-gated 4D flow data at a predictable scan time was demonstrated. Magn Reson Med, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

  8. 4D spiral imaging of flows in stenotic phantoms and subjects with aortic stenosis.

    Science.gov (United States)

    Negahdar, M J; Kadbi, Mo; Kendrick, Michael; Stoddard, Marcus F; Amini, Amir A

    2016-03-01

    time = 3:44 min. The conventional sequence achieved TE = 2.9 ms and scan time = 5:23 min. In subjects with aortic stenosis, we also compared both MRI methods with Doppler ultrasound (US) in the measurement of peak velocity, time to peak systolic velocity, and eject time. Bland-Altman analysis revealed that, when comparing peak velocities, the discrepancy between Doppler US and 4D spiral flow was significantly less than the discrepancy between Doppler and 4D Cartesian flow (2.75 cm/s vs. 10.25 cm/s), whereas the two MR methods were comparable (-5.75 s vs. -6 s) for time to peak. However, for the estimation of eject time, relative to Doppler US, the discrepancy for 4D conventional flow was smaller than that of 4D spiral flow (-16.25 s vs. -20 s). Relative to conventional 4D flow, 4D spiral flow achieves substantial reductions in both the TE and scan times; therefore, utility for it should be sought in a variety of in vivo and complex flow imaging applications. © 2015 Wiley Periodicals, Inc.

  9. Assessment of intracardiac flow and vorticity in the right heart of patients after repair of tetralogy of Fallot by flow-sensitive 4D MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hirtler, Daniel [University Hospital Freiburg, Department of Congenital Heart Defects and Pediatric Cardiology (Heart Center, University of Freiburg), Freiburg (Germany); Garcia, Julio; Barker, Alex J. [Northwestern University Feinberg School of Medicine, Department of Radiology, Chicago, IL (United States); Geiger, Julia [University Childrens' Hospital Zurich, Department of Radiology, Zurich (Switzerland)

    2016-10-15

    To comprehensively and quantitatively analyse flow and vorticity in the right heart of patients after repair of tetralogy of Fallot (rTOF) compared with healthy volunteers. Time-resolved flow-sensitive 4D MRI was acquired in 24 rTOF patients and 12 volunteers. Qualitative flow evaluation was based on consensus reading of two observers. Quantitative analysis included segmentation of the right atrium (RA) and ventricle (RV) in a four-chamber view to extract volumes and regional haemodynamic information for computation of regional mean and peak vorticity. Right heart intra-atrial, intraventricular and outflow tract flow patterns differed considerably between rTOF patients and volunteers. Peak RA and mean RV vorticity was significantly higher in patients (p = 0.02/0.05). Significant negative correlations were found between patients' maximum and mean RV and RA vorticity and ventricular volumes (p < 0.05). The main pulmonary artery (MPA) regurgitant flow was associated with higher RA and RV vorticity, which was significant for RA maximum and RV mean vorticity (p = 0.01/0.03). The calculation of vorticity based on 4D flow data is an alternative approach to assess intracardiac flow changes in rTOF patients compared with qualitative flow visualization. Alterations in intracardiac vorticity could be relevant with regard to the development of RV dilation and impaired function. (orig.)

  10. Assessment of intracardiac flow and vorticity in the right heart of patients after repair of tetralogy of Fallot by flow-sensitive 4D MRI

    International Nuclear Information System (INIS)

    Hirtler, Daniel; Garcia, Julio; Barker, Alex J.; Geiger, Julia

    2016-01-01

    To comprehensively and quantitatively analyse flow and vorticity in the right heart of patients after repair of tetralogy of Fallot (rTOF) compared with healthy volunteers. Time-resolved flow-sensitive 4D MRI was acquired in 24 rTOF patients and 12 volunteers. Qualitative flow evaluation was based on consensus reading of two observers. Quantitative analysis included segmentation of the right atrium (RA) and ventricle (RV) in a four-chamber view to extract volumes and regional haemodynamic information for computation of regional mean and peak vorticity. Right heart intra-atrial, intraventricular and outflow tract flow patterns differed considerably between rTOF patients and volunteers. Peak RA and mean RV vorticity was significantly higher in patients (p = 0.02/0.05). Significant negative correlations were found between patients' maximum and mean RV and RA vorticity and ventricular volumes (p < 0.05). The main pulmonary artery (MPA) regurgitant flow was associated with higher RA and RV vorticity, which was significant for RA maximum and RV mean vorticity (p = 0.01/0.03). The calculation of vorticity based on 4D flow data is an alternative approach to assess intracardiac flow changes in rTOF patients compared with qualitative flow visualization. Alterations in intracardiac vorticity could be relevant with regard to the development of RV dilation and impaired function. (orig.)

  11. Magnetic resonance imaging 4-D flow-based analysis of aortic hemodynamics in Turner syndrome.

    Science.gov (United States)

    Arnold, Raoul; Neu, Marie; Hirtler, Daniel; Gimpel, Charlotte; Markl, Michael; Geiger, Julia

    2017-04-01

    Cardiovascular surveillance is important in Turner syndrome because of the increased risk of aortic dilation and dissection with consecutively increased mortality. To compare 4-D flow MRI for the characterization of aortic 3-D flow patterns, dimensions and vessel wall parameters in pediatric patients with Turner syndrome and age-matched controls. We performed 4-D flow MRI measuring in vivo 3-D blood flow with coverage of the thoracic aorta in 25 patients with Turner syndrome and in 16 female healthy controls (age mean ± standard deviation were 16 ± 5 years and 17 ± 4 years, respectively). Blood flow was visualized by time-resolved 3-D path lines. Visual grading of aortic flow in terms of helices and vortices was performed by two independent observers. Quantitative analysis included measurement of aortic diameters, quantification of peak systolic wall shear stress, pulsatility index and oscillatory shear index at eight defined sites. Patients with Turner syndrome had significantly larger aortic diameters normalized to BSA, increased vortices in the ascending aorta and elevated helix flow in the ascending and descending aorta compared to controls (all PTurner patients compared to controls (p=0.02, p=0.002 and p=0.01 respectively). Four-dimensional flow MRI provides new insights into the altered aortic hemodynamics and wall shear stress that could have an impact on the development of aortic dissections.

  12. Cloud-processed 4D CMR flow imaging for pulmonary flow quantification

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    Chelu, Raluca G., E-mail: ralucachelu@hotmail.com [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Department of Cardiology, Erasmus MC, Rotterdam (Netherlands); Wanambiro, Kevin W. [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Department of Radiology, Aga Khan University Hospital, Nairobi (Kenya); Hsiao, Albert [Department of Radiology, University of California, San Diego, CA (United States); Swart, Laurens E. [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Department of Cardiology, Erasmus MC, Rotterdam (Netherlands); Voogd, Teun [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Hoven, Allard T. van den; Kranenburg, Matthijs van [Department of Cardiology, Erasmus MC, Rotterdam (Netherlands); Coenen, Adriaan [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Department of Cardiology, Erasmus MC, Rotterdam (Netherlands); Boccalini, Sara [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Department of Radiology, University Hospital, Genoa (Italy); Wielopolski, Piotr A. [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Vogel, Mika W. [MR Applications and Workflow – Europe, GE Healthcare B.V. Hoevelaken (Netherlands); Krestin, Gabriel P. [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Vasanawala, Shreyas S. [Department of Radiology, Stanford University, Stanford, CA (United States); Budde, Ricardo P.J. [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Department of Cardiology, Erasmus MC, Rotterdam (Netherlands); Roos-Hesselink, Jolien W. [Department of Cardiology, Erasmus MC, Rotterdam (Netherlands); Nieman, Koen [Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Department of Cardiology, Erasmus MC, Rotterdam (Netherlands)

    2016-10-15

    Highlights: • With 4D flow, any plane of interest can be interactively chosen for quantitative measurements. • Anatomical and flow data are obtained during an approximately 10-min free-breathing scan. • 4D CMR flow measurements correlated well with the 2D PC ones. • Eddy current correction is important for good results with 4D flow. - Abstract: Objectives: In this study, we evaluated a cloud-based platform for cardiac magnetic resonance (CMR) four-dimensional (4D) flow imaging, with fully integrated correction for eddy currents, Maxwell phase effects, and gradient field non-linearity, to quantify forward flow, regurgitation, and peak systolic velocity over the pulmonary artery. Methods: We prospectively recruited 52 adult patients during one-year period from July 2014. The 4D flow and planar (2D) phase-contrast (PC) were acquired during same scanning session, but 4D flow was scanned after injection of a gadolinium-based contrast agent. Eddy-currents were semi-automatically corrected using the web-based software. Flow over pulmonary valve was measured and the 4D flow values were compared against the 2D PC ones. Results: The mean forward flow was 92 (±30) ml/cycle measured with 4D flow and 86 (±29) ml/cycle measured with 2D PC, with a correlation of 0.82 and a mean difference of −6 ml/cycle (−41–29). For the regurgitant fraction the correlation was 0.85 with a mean difference of −0.95% (−17–15). Mean peak systolic velocity measured with 4D flow was 92 (±49) cm/s and 108 (±56) cm/s with 2D PC, having a correlation of 0.93 and a mean difference of 16 cm/s (−24–55). Conclusion: 4D flow imaging post-processed with an integrated cloud-based application accurately quantifies pulmonary flow. However, it may underestimate the peak systolic velocity.

  13. Cloud-processed 4D CMR flow imaging for pulmonary flow quantification

    International Nuclear Information System (INIS)

    Chelu, Raluca G.; Wanambiro, Kevin W.; Hsiao, Albert; Swart, Laurens E.; Voogd, Teun; Hoven, Allard T. van den; Kranenburg, Matthijs van; Coenen, Adriaan; Boccalini, Sara; Wielopolski, Piotr A.; Vogel, Mika W.; Krestin, Gabriel P.; Vasanawala, Shreyas S.; Budde, Ricardo P.J.; Roos-Hesselink, Jolien W.; Nieman, Koen

    2016-01-01

    Highlights: • With 4D flow, any plane of interest can be interactively chosen for quantitative measurements. • Anatomical and flow data are obtained during an approximately 10-min free-breathing scan. • 4D CMR flow measurements correlated well with the 2D PC ones. • Eddy current correction is important for good results with 4D flow. - Abstract: Objectives: In this study, we evaluated a cloud-based platform for cardiac magnetic resonance (CMR) four-dimensional (4D) flow imaging, with fully integrated correction for eddy currents, Maxwell phase effects, and gradient field non-linearity, to quantify forward flow, regurgitation, and peak systolic velocity over the pulmonary artery. Methods: We prospectively recruited 52 adult patients during one-year period from July 2014. The 4D flow and planar (2D) phase-contrast (PC) were acquired during same scanning session, but 4D flow was scanned after injection of a gadolinium-based contrast agent. Eddy-currents were semi-automatically corrected using the web-based software. Flow over pulmonary valve was measured and the 4D flow values were compared against the 2D PC ones. Results: The mean forward flow was 92 (±30) ml/cycle measured with 4D flow and 86 (±29) ml/cycle measured with 2D PC, with a correlation of 0.82 and a mean difference of −6 ml/cycle (−41–29). For the regurgitant fraction the correlation was 0.85 with a mean difference of −0.95% (−17–15). Mean peak systolic velocity measured with 4D flow was 92 (±49) cm/s and 108 (±56) cm/s with 2D PC, having a correlation of 0.93 and a mean difference of 16 cm/s (−24–55). Conclusion: 4D flow imaging post-processed with an integrated cloud-based application accurately quantifies pulmonary flow. However, it may underestimate the peak systolic velocity.

  14. Assessment of intracardiac flow and vorticity in the right heart of patients after repair of tetralogy of Fallot by flow-sensitive 4D MRI.

    Science.gov (United States)

    Hirtler, Daniel; Garcia, Julio; Barker, Alex J; Geiger, Julia

    2016-10-01

    To comprehensively and quantitatively analyse flow and vorticity in the right heart of patients after repair of tetralogy of Fallot (rTOF) compared with healthy volunteers. Time-resolved flow-sensitive 4D MRI was acquired in 24 rTOF patients and 12 volunteers. Qualitative flow evaluation was based on consensus reading of two observers. Quantitative analysis included segmentation of the right atrium (RA) and ventricle (RV) in a four-chamber view to extract volumes and regional haemodynamic information for computation of regional mean and peak vorticity. Right heart intra-atrial, intraventricular and outflow tract flow patterns differed considerably between rTOF patients and volunteers. Peak RA and mean RV vorticity was significantly higher in patients (p = 0.02/0.05). Significant negative correlations were found between patients' maximum and mean RV and RA vorticity and ventricular volumes (p tetralogy of Fallot. • Regurgitant flow in the main pulmonary artery is associated with higher right heart vorticity.

  15. Magnetic resonance imaging 4-D flow-based analysis of aortic hemodynamics in Turner syndrome

    International Nuclear Information System (INIS)

    Arnold, Raoul; Neu, Marie; Hirtler, Daniel; Gimpel, Charlotte; Markl, Michael; Geiger, Julia

    2017-01-01

    Cardiovascular surveillance is important in Turner syndrome because of the increased risk of aortic dilation and dissection with consecutively increased mortality. To compare 4-D flow MRI for the characterization of aortic 3-D flow patterns, dimensions and vessel wall parameters in pediatric patients with Turner syndrome and age-matched controls. We performed 4-D flow MRI measuring in vivo 3-D blood flow with coverage of the thoracic aorta in 25 patients with Turner syndrome and in 16 female healthy controls (age mean ± standard deviation were 16 ± 5 years and 17 ± 4 years, respectively). Blood flow was visualized by time-resolved 3-D path lines. Visual grading of aortic flow in terms of helices and vortices was performed by two independent observers. Quantitative analysis included measurement of aortic diameters, quantification of peak systolic wall shear stress, pulsatility index and oscillatory shear index at eight defined sites. Patients with Turner syndrome had significantly larger aortic diameters normalized to BSA, increased vortices in the ascending aorta and elevated helix flow in the ascending and descending aorta compared to controls (all P<0.03). Patients with abnormal helical or vortical flow in the ascending aorta had significantly larger diameters of the ascending aorta (P<0.03). Peak systolic wall shear stress, pulsatility index and oscillatory shear index were significantly lower in Turner patients compared to controls (p=0.02, p=0.002 and p=0.01 respectively). Four-dimensional flow MRI provides new insights into the altered aortic hemodynamics and wall shear stress that could have an impact on the development of aortic dissections. (orig.)

  16. Magnetic resonance imaging 4-D flow-based analysis of aortic hemodynamics in Turner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, Raoul [University Medical Center Heidelberg, Department of Congenital Heart Disease and Pediatric Cardiology, Heidelberg (Germany); Neu, Marie [University Medical Center, Department of Pediatric Hematology/Oncology/Hemostaseology, Mainz (Germany); Hirtler, Daniel [University of Freiburg, Department of Congenital Heart Defects and Pediatric Cardiology, Heart Center, Freiburg im Breisgau (Germany); Gimpel, Charlotte [Center for Pediatrics, Medical Center - University of Freiburg, Department of General Pediatrics, Adolescent Medicine and Neonatology, Freiburg im Breisgau (Germany); Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Chicago, IL (United States); Geiger, Julia [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); University Children' s Hospital, Department of Radiology, Zuerich (Switzerland)

    2017-04-15

    Cardiovascular surveillance is important in Turner syndrome because of the increased risk of aortic dilation and dissection with consecutively increased mortality. To compare 4-D flow MRI for the characterization of aortic 3-D flow patterns, dimensions and vessel wall parameters in pediatric patients with Turner syndrome and age-matched controls. We performed 4-D flow MRI measuring in vivo 3-D blood flow with coverage of the thoracic aorta in 25 patients with Turner syndrome and in 16 female healthy controls (age mean ± standard deviation were 16 ± 5 years and 17 ± 4 years, respectively). Blood flow was visualized by time-resolved 3-D path lines. Visual grading of aortic flow in terms of helices and vortices was performed by two independent observers. Quantitative analysis included measurement of aortic diameters, quantification of peak systolic wall shear stress, pulsatility index and oscillatory shear index at eight defined sites. Patients with Turner syndrome had significantly larger aortic diameters normalized to BSA, increased vortices in the ascending aorta and elevated helix flow in the ascending and descending aorta compared to controls (all P<0.03). Patients with abnormal helical or vortical flow in the ascending aorta had significantly larger diameters of the ascending aorta (P<0.03). Peak systolic wall shear stress, pulsatility index and oscillatory shear index were significantly lower in Turner patients compared to controls (p=0.02, p=0.002 and p=0.01 respectively). Four-dimensional flow MRI provides new insights into the altered aortic hemodynamics and wall shear stress that could have an impact on the development of aortic dissections. (orig.)

  17. In vivo radiation sensitivity of glioblastoma multiforme

    International Nuclear Information System (INIS)

    Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

    1995-01-01

    Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF 2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD 50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD 50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD 50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD 50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 ± 13.1 Gy. The TCD 50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 ± 6.4. The difference between the average TCD 50 of GBM and SCC was not significant. The STS and CC xenografts had TCD 50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD 50 in vivo and the SF 2 or D 0 in vitro. Conclusions: Our data on GBM xenografts showed a wide range of sensitivities to single dose

  18. In vivo radiation sensitivity of glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

    1995-04-30

    Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF{sub 2} values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD{sub 50} (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD{sub 50} of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD{sub 50} assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD{sub 50} values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 {+-} 13.1 Gy. The TCD{sub 50} values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 {+-} 6.4. The difference between the average TCD{sub 50} of GBM and SCC was not significant. The STS and CC xenografts had TCD{sub 50} values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD{sub 50} in vivo and the SF{sub 2} or D{sub 0} in vitro. Conclusions: Our data on GBM

  19. Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15.

    Directory of Open Access Journals (Sweden)

    Angela Cassese

    Full Text Available Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15 causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1. Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4 restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg ped/pea-15 by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance.

  20. Evaluation of a novel 4D in vivo dosimetry system

    International Nuclear Information System (INIS)

    Cherpak, A.; Ding, W.; Hallil, A.; Cygler, J. E.

    2009-01-01

    A prototype of a new 4D in vivo dosimetry system capable of simultaneous real-time position monitoring and dose measurement has been developed. The radiation positioning system (RADPOS) is controlled by a computer and combines two technologies: MOSFET radiation detector coupled with an electromagnetic positioning device. Special software has been developed that allows sampling position and dose either manually or automatically in user-defined time intervals. Preliminary tests of the new device include a dosimetric evaluation of the detector in 60 Co, 6 MV, and 18 MV beams and measurements of spatial position stability and accuracy. In addition, the effect of metals and other materials on the performance of the positioning system has been investigated. Results show that the RADPOS system can measure in-air dose profiles that agree, on average, within 3%-5% of diode measurements for the energies tested. The response of the detector is isotropic within 1.6% (1 SD) with a maximum deviation of ±4.0% over 360 deg. The maximum variation in the calibration coefficient over field sizes from 6x6 to 25x25 cm 2 was 2.3% for RADPOS probe with the high sensitivity MOSFET and 4.6% for the probe with the standard sensitivity MOSFET. Of the materials tested, only aluminum, lead, and brass caused shifts in the RADPOS read position. The magnitude of the shift varied between materials and size of the material sample. Nonmagnetic stainless steel (Grade 304) caused a distortion of less than 2 mm when placed within 10 mm of the detector; therefore, it can provide a reasonable alternative to other metals if required. The results of the preliminary tests indicate that the device can be used for in vivo dosimetry in 60 Co and high-energy beams from linear accelerators.

  1. Comparison of PIV with 4D-Flow in a physiological accurate flow phantom

    Science.gov (United States)

    Sansom, Kurt; Balu, Niranjan; Liu, Haining; Aliseda, Alberto; Yuan, Chun; Canton, Maria De Gador

    2016-11-01

    Validation of 4D MRI flow sequences with planar particle image velocimetry (PIV) is performed in a physiologically-accurate flow phantom. A patient-specific phantom of a carotid artery is connected to a pulsatile flow loop to simulate the 3D unsteady flow in the cardiovascular anatomy. Cardiac-cycle synchronized MRI provides time-resolved 3D blood velocity measurements in clinical tool that is promising but lacks a robust validation framework. PIV at three different Reynolds numbers (540, 680, and 815, chosen based on +/- 20 % of the average velocity from the patient-specific CCA waveform) and four different Womersley numbers (3.30, 3.68, 4.03, and 4.35, chosen to reflect a physiological range of heart rates) are compared to 4D-MRI measurements. An accuracy assessment of raw velocity measurements and a comparison of estimated and measureable flow parameters such as wall shear stress, fluctuating velocity rms, and Lagrangian particle residence time, will be presented, with justification for their biomechanics relevance to the pathophysiology of arterial disease: atherosclerosis and intimal hyperplasia. Lastly, the framework is applied to a new 4D-Flow MRI sequence and post processing techniques to provide a quantitative assessment with the benchmarked data. Department of Education GAANN Fellowship.

  2. 4-D flow magnetic resonance imaging: blood flow quantification compared to 2-D phase-contrast magnetic resonance imaging and Doppler echocardiography

    Energy Technology Data Exchange (ETDEWEB)

    Gabbour, Maya [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging 9, Chicago, IL (United States); Schnell, Susanne [Northwestern University Feinberg School of Medicine, Department of Radiology, Chicago, IL (United States); Jarvis, Kelly [Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Evanston, IL (United States); Robinson, Joshua D. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Pediatrics, Division of Pediatric Cardiology, Chicago, IL (United States); Northwestern University Feinberg School of Medicine, Department of Pediatrics, Chicago, IL (United States); Markl, Michael [Northwestern University Feinberg School of Medicine, Department of Radiology, Chicago, IL (United States); Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Evanston, IL (United States); Rigsby, Cynthia K. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging 9, Chicago, IL (United States); Northwestern University Feinberg School of Medicine, Department of Radiology, Chicago, IL (United States)

    2015-06-15

    Doppler echocardiography (echo) is the reference standard for blood flow velocity analysis, and two-dimensional (2-D) phase-contrast magnetic resonance imaging (MRI) is considered the reference standard for quantitative blood flow assessment. However, both clinical standard-of-care techniques are limited by 2-D acquisitions and single-direction velocity encoding and may make them inadequate to assess the complex three-dimensional hemodynamics seen in congenital heart disease. Four-dimensional flow MRI (4-D flow) enables qualitative and quantitative analysis of complex blood flow in the heart and great arteries. The objectives of this study are to compare 4-D flow with 2-D phase-contrast MRI for quantification of aortic and pulmonary flow and to evaluate the advantage of 4-D flow-based volumetric flow analysis compared to 2-D phase-contrast MRI and echo for peak velocity assessment in children and young adults. Two-dimensional phase-contrast MRI of the aortic root, main pulmonary artery (MPA), and right and left pulmonary arteries (RPA, LPA) and 4-D flow with volumetric coverage of the aorta and pulmonary arteries were performed in 50 patients (mean age: 13.1 ± 6.4 years). Four-dimensional flow analyses included calculation of net flow and regurgitant fraction with 4-D flow analysis planes similarly positioned to 2-D planes. In addition, 4-D flow volumetric assessment of aortic root/ascending aorta and MPA peak velocities was performed and compared to 2-D phase-contrast MRI and echo. Excellent correlation and agreement were found between 2-D phase-contrast MRI and 4-D flow for net flow (r = 0.97, P < 0.001) and excellent correlation with good agreement was found for regurgitant fraction (r = 0.88, P < 0.001) in all vessels. Two-dimensional phase-contrast MRI significantly underestimated aortic (P = 0.032) and MPA (P < 0.001) peak velocities compared to echo, while volumetric 4-D flow analysis resulted in higher (aortic: P = 0.001) or similar (MPA: P = 0.98) peak

  3. Accuracy and Precision of Plane Wave Vector Flow Imaging for Laminar and Complex Flow In Vivo

    DEFF Research Database (Denmark)

    Jensen, Jonas; Traberg, Marie Sand; Villagómez Hoyos, Carlos Armando

    2017-01-01

    In this study, a comparison between velocity fields for a plane wave 2-D vector flow imaging (VFI) method and a computational fluid dynamics (CFD) simulation is made. VFI estimates are obtained from the scan of a flow phantom, which mimics the complex flow conditions in the carotid artery....... Furthermore, the precision of the VFI method is investigated under laminar and complex flow conditions in vivo. The carotid bifurcation of a healthy volunteer was scanned using both fast plane wave ultrasound and magnetic resonance imaging (MRI). The acquired MRI geometry of the bifurcation was used...... difference within 15 %, however, it was 23 % in the external branch. For the in vivo scan, the precision in terms of mean standard deviation (SD) of estimates aligned to the cardiac cycle was highest in the center of the common carotid artery (SD 4.7◦ for angles) and lowest in the external branch and close...

  4. 4D flow MR imaging of the portal venous system: a feasibility study in children

    International Nuclear Information System (INIS)

    Parekh, Keyur; Rose, Michael; Popescu, Andrada; Rigsby, Cynthia K.; Markl, Michael; Schnell, Susanne

    2017-01-01

    To determine the feasibility of 4D flow MRI for visualization and quantification of the portal venous haemodynamics in children and young adults. 4D flow was performed in 28 paediatric patients (median age, 8.5 years; interquartile range, 5.2-16.5), 15 with non-operated native portal system and 13 with surgically created portal shunt. Image quality assessment for 3D flow visualization and flow pattern analyses was performed. Regional 4D flow peak velocity and net flow were compared with 2D-cine phase contrast MRI (2D-PC MR) in the post-surgical patients. Mean 3D flow visualization quality score was excellent (mean ± SD, 4.2 ± 0.9) with good inter-rater agreement (κ,0.67). Image quality in children aged >10 years was better than children ≤10 years (p < 0.05). Flow pattern was defined for portal, superior mesenteric, splenic veins and splenic artery in all patients. 4D flow and 2D-PC MR peak velocity and net flow were similar with good correlation (peak velocity: 4D flow 22.2 ± 9.1 cm/s and 2D-PC MR 25.2 ± 11.2 cm/s, p = 0.46; r = 0.92, p < 0.0001; net flow: 4D flow 9.5 ± 7.4 ml/s and 2D-PC MR 10.1 ± 7.3 ml/s, p = 0.65; r = 0.81, p = 0.0007). 4D flow MRI is feasible and holds promise for the comprehensive 3D visualization and quantification of portal venous flow dynamics in children and young adults. (orig.)

  5. 4D flow MR imaging of the portal venous system: a feasibility study in children

    Energy Technology Data Exchange (ETDEWEB)

    Parekh, Keyur; Rose, Michael; Popescu, Andrada; Rigsby, Cynthia K. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); McCormick School of Engineering, Northwestern University, Department of Biomedical Engineering, Chicago, IL (United States); Schnell, Susanne [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States)

    2017-02-15

    To determine the feasibility of 4D flow MRI for visualization and quantification of the portal venous haemodynamics in children and young adults. 4D flow was performed in 28 paediatric patients (median age, 8.5 years; interquartile range, 5.2-16.5), 15 with non-operated native portal system and 13 with surgically created portal shunt. Image quality assessment for 3D flow visualization and flow pattern analyses was performed. Regional 4D flow peak velocity and net flow were compared with 2D-cine phase contrast MRI (2D-PC MR) in the post-surgical patients. Mean 3D flow visualization quality score was excellent (mean ± SD, 4.2 ± 0.9) with good inter-rater agreement (κ,0.67). Image quality in children aged >10 years was better than children ≤10 years (p < 0.05). Flow pattern was defined for portal, superior mesenteric, splenic veins and splenic artery in all patients. 4D flow and 2D-PC MR peak velocity and net flow were similar with good correlation (peak velocity: 4D flow 22.2 ± 9.1 cm/s and 2D-PC MR 25.2 ± 11.2 cm/s, p = 0.46; r = 0.92, p < 0.0001; net flow: 4D flow 9.5 ± 7.4 ml/s and 2D-PC MR 10.1 ± 7.3 ml/s, p = 0.65; r = 0.81, p = 0.0007). 4D flow MRI is feasible and holds promise for the comprehensive 3D visualization and quantification of portal venous flow dynamics in children and young adults. (orig.)

  6. Comparison of radial 4D Flow-MRI with perivascular ultrasound to quantify blood flow in the abdomen and introduction of a porcine model of pre-hepatic portal hypertension.

    Science.gov (United States)

    Frydrychowicz, A; Roldan-Alzate, A; Winslow, E; Consigny, D; Campo, C A; Motosugi, U; Johnson, K M; Wieben, O; Reeder, S B

    2017-12-01

    Objectives of this study were to compare radial time-resolved phase contrast magnetic resonance imaging (4D Flow-MRI) with perivascular ultrasound (pvUS) and to explore a porcine model of acute pre-hepatic portal hypertension (PHTN). Abdominal 4D Flow-MRI and pvUS in portal and splenic vein, hepatic and both renal arteries were performed in 13 pigs of approximately 60 kg. In six pigs, measurements were repeated after partial portal vein (PV) ligature. Inter- and intra-reader comparisons and statistical analysis including Bland-Altman (BA) comparison, paired Student's t tests and linear regression were performed. PvUS and 4D Flow-MRI measurements agreed well; flow before partial PV ligature was 322 ± 30 ml/min in pvUS and 297 ± 27 ml/min in MRI (p = 0.294), and average BA difference was 25 ml/min [-322; 372]. Inter- and intra-reader results differed very little, revealed excellent correlation (R 2  = 0.98 and 0.99, respectively) and resulted in BA differences of -5 ml/min [-161; 150] and -2 ml/min [-28; 25], respectively. After PV ligature, PV flow decreased from 356 ± 50 to 298 ± 61 ml/min (p = 0.02), and hepatic arterial flow increased from 277 ± 36 to 331 ± 65 ml/min (p = n.s.). The successful in vivo comparison of radial 4D Flow-MRI to perivascular ultrasound revealed good agreement of abdominal blood flow although with considerable spread of results. A model of pre-hepatic PHTN was successfully introduced and acute responses monitored. • Radial 4D Flow-MRI in the abdomen was successfully compared to perivascular ultrasound. • Inter- and intra-reader testing demonstrated excellent reproducibility of upper abdominal 4D Flow-MRI. • A porcine model of acute pre-hepatic portal hypertension was successfully introduced. • 4D Flow-MRI successfully monitored acute changes in a model of portal hypertension.

  7. Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

    Energy Technology Data Exchange (ETDEWEB)

    Galanzha, Ekaterina I. [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Zharov, Vladimir P., E-mail: zharovvladimirp@uams.edu [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2013-12-10

    Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1–10 CTC/mL) due to the small volume of blood samples (5–10 mL). Consequently, they can miss up to 10{sup 3}–10{sup 4} CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 10{sup 2}–10{sup 3} times) by the examination of the entire blood volume in vivo (5 L in adults). We focus on in vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL) and throughput (up to 10 mL/min) than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-resolution PAFC beyond the diffraction and spectral limits.

  8. Comparison of radial 4D Flow-MRI with perivascular ultrasound to quantify blood flow in the abdomen and introduction of a porcine model of pre-hepatic portal hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Frydrychowicz, A. [University of Wisconsin - Madison, Department of Radiology, School of Medicine and Public Health, E3/366 Clinical Science Center, Madison, WI (United States); University Hospital Schleswig-Holstein, Campus Luebeck, Clinic for Radiology and Nuclear Medicine, Luebeck (Germany); University of Luebeck, Luebeck (Germany); Roldan-Alzate, A. [University of Wisconsin - Madison, Department of Radiology, School of Medicine and Public Health, E3/366 Clinical Science Center, Madison, WI (United States); University of Wisconsin, Department of Mechanical Engineering, Madison (United States); Winslow, E. [University of Wisconsin, Department of Surgery, Madison (United States); Consigny, D.; Campo, C.A.; Motosugi, U. [University of Wisconsin - Madison, Department of Radiology, School of Medicine and Public Health, E3/366 Clinical Science Center, Madison, WI (United States); Johnson, K.M. [University of Wisconsin, Department of Medical Physics, Madison (United States); Wieben, O. [University of Wisconsin - Madison, Department of Radiology, School of Medicine and Public Health, E3/366 Clinical Science Center, Madison, WI (United States); University of Wisconsin, Department of Medical Physics, Madison (United States); Reeder, S.B. [University of Wisconsin - Madison, Department of Radiology, School of Medicine and Public Health, E3/366 Clinical Science Center, Madison, WI (United States); University of Wisconsin, Department of Medical Physics, Madison (United States); University of Wisconsin, Department of Biomedical Engineering, Madison (United States); University of Wisconsin, Department of Medicine, Madison (United States); University of Wisconsin, Department of Emergency Medicine, Madison (United States)

    2017-12-15

    Objectives of this study were to compare radial time-resolved phase contrast magnetic resonance imaging (4D Flow-MRI) with perivascular ultrasound (pvUS) and to explore a porcine model of acute pre-hepatic portal hypertension (PHTN). Abdominal 4D Flow-MRI and pvUS in portal and splenic vein, hepatic and both renal arteries were performed in 13 pigs of approximately 60 kg. In six pigs, measurements were repeated after partial portal vein (PV) ligature. Inter- and intra-reader comparisons and statistical analysis including Bland-Altman (BA) comparison, paired Student's t tests and linear regression were performed. PvUS and 4D Flow-MRI measurements agreed well; flow before partial PV ligature was 322 ± 30 ml/min in pvUS and 297 ± 27 ml/min in MRI (p = 0.294), and average BA difference was 25 ml/min [-322; 372]. Inter- and intra-reader results differed very little, revealed excellent correlation (R {sup 2} = 0.98 and 0.99, respectively) and resulted in BA differences of -5 ml/min [-161; 150] and -2 ml/min [-28; 25], respectively. After PV ligature, PV flow decreased from 356 ± 50 to 298 ± 61 ml/min (p = 0.02), and hepatic arterial flow increased from 277 ± 36 to 331 ± 65 ml/min (p = n.s.). The successful in vivo comparison of radial 4D Flow-MRI to perivascular ultrasound revealed good agreement of abdominal blood flow although with considerable spread of results. A model of pre-hepatic PHTN was successfully introduced and acute responses monitored. (orig.)

  9. 4D phase contrast flow imaging for in-stent flow visualization and assessment of stent patency in peripheral vascular stents--a phantom study.

    Science.gov (United States)

    Bunck, Alexander C; Jüttner, Alena; Kröger, Jan Robert; Burg, Matthias C; Kugel, Harald; Niederstadt, Thomas; Tiemann, Klaus; Schnackenburg, Bernhard; Crelier, Gerard R; Heindel, Walter; Maintz, David

    2012-09-01

    4D phase contrast flow imaging is increasingly used to study the hemodynamics in various vascular territories and pathologies. The aim of this study was to assess the feasibility and validity of MRI based 4D phase contrast flow imaging for the evaluation of in-stent blood flow in 17 commonly used peripheral stents. 17 different peripheral stents were implanted into a MR compatible flow phantom. In-stent visibility, maximal velocity and flow visualization were assessed and estimates of in-stent patency obtained from 4D phase contrast flow data sets were compared to a conventional 3D contrast-enhanced magnetic resonance angiography (CE-MRA) as well as 2D PC flow measurements. In all but 3 of the tested stents time-resolved 3D particle traces could be visualized inside the stent lumen. Quality of 4D flow visualization and CE-MRA images depended on stent type and stent orientation relative to the magnetic field. Compared to the visible lumen area determined by 3D CE-MRA, estimates of lumen patency derived from 4D flow measurements were significantly higher and less dependent on stent type. A higher number of stents could be assessed for in-stent patency by 4D phase contrast flow imaging (n=14) than by 2D phase contrast flow imaging (n=10). 4D phase contrast flow imaging in peripheral vascular stents is feasible and appears advantageous over conventional 3D contrast-enhanced MR angiography and 2D phase contrast flow imaging. It allows for in-stent flow visualization and flow quantification with varying quality depending on stent type. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. In vitro and in vivo studies of pharmacokinetics and antitumor efficacy of D07001-F4, an oral gemcitabine formulation.

    Science.gov (United States)

    Hao, Wei-Hua; Wang, Jong-Jing; Hsueh, Shu-Ping; Hsu, Pei-Jing; Chang, Li-Chien; Hsu, Chang-Shan; Hsu, Kuang-Yang

    2013-02-01

    The chemotherapy agent gemcitabine is currently administered intravenously because the drug has poor oral bioavailability. In order to assess the pharmacokinetics and antitumor activity of D07001-F4, a new self-microemulsifying oral drug delivery system preparation of gemcitabine, this study was performed to compare the effect of D07001-F4 with administered gemcitabine in vitro and in vivo. D07001-F4 pharmacokinetics was examined by evaluation of in vitro deamination of D07001-F4 and gemcitabine hydrochloride by recombinant human cytidine deaminase (rhCDA) and in vivo evaluation of D07001-F4 pharmacokinetics in mice. Antitumor activity was evaluated by comparing the effect of D07001-F4 and gemcitabine hydrochloride in inhibiting growth in nine cancer cell lines and by examining the effect of D07001-F4 and gemcitabine in two xenograft tumor models in mice. In vitro deamination of D07001-F4 by rhCDA was 3.3-fold slower than deamination of gemcitabine hydrochloride. Growth inhibition by D07001-F4 of 7 of the 8 cancer cell lines was increased compared with that seen with gemcitabine hydrochloride, and D07001-F4 inhibited the growth of pancreatic and colon cancer xenografts. In vivo pharmacokinetics showed the oral bioavailability of D07001-F4 to be 34%. D07001-F4 was effective against several cancer types, was metabolized more slowly than gemcitabine hydrochloride, and exhibited enhanced oral bioavailability.

  11. 4D phase contrast flow imaging for in-stent flow visualization and assessment of stent patency in peripheral vascular stents – A phantom study

    International Nuclear Information System (INIS)

    Bunck, Alexander C.; Jüttner, Alena; Kröger, Jan Robert; Burg, Matthias C.; Kugel, Harald; Niederstadt, Thomas; Tiemann, Klaus; Schnackenburg, Bernhard; Crelier, Gerard R.

    2012-01-01

    Purpose: 4D phase contrast flow imaging is increasingly used to study the hemodynamics in various vascular territories and pathologies. The aim of this study was to assess the feasibility and validity of MRI based 4D phase contrast flow imaging for the evaluation of in-stent blood flow in 17 commonly used peripheral stents. Materials and methods: 17 different peripheral stents were implanted into a MR compatible flow phantom. In-stent visibility, maximal velocity and flow visualization were assessed and estimates of in-stent patency obtained from 4D phase contrast flow data sets were compared to a conventional 3D contrast-enhanced magnetic resonance angiography (CE-MRA) as well as 2D PC flow measurements. Results: In all but 3 of the tested stents time-resolved 3D particle traces could be visualized inside the stent lumen. Quality of 4D flow visualization and CE-MRA images depended on stent type and stent orientation relative to the magnetic field. Compared to the visible lumen area determined by 3D CE-MRA, estimates of lumen patency derived from 4D flow measurements were significantly higher and less dependent on stent type. A higher number of stents could be assessed for in-stent patency by 4D phase contrast flow imaging (n = 14) than by 2D phase contrast flow imaging (n = 10). Conclusions: 4D phase contrast flow imaging in peripheral vascular stents is feasible and appears advantageous over conventional 3D contrast-enhanced MR angiography and 2D phase contrast flow imaging. It allows for in-stent flow visualization and flow quantification with varying quality depending on stent type

  12. 4D-Fingerprint Categorical QSAR Models for Skin Sensitization Based on Classification Local Lymph Node Assay Measures

    Science.gov (United States)

    Li, Yi; Tseng, Yufeng J.; Pan, Dahua; Liu, Jianzhong; Kern, Petra S.; Gerberick, G. Frank; Hopfinger, Anton J.

    2008-01-01

    Currently, the only validated methods to identify skin sensitization effects are in vivo models, such as the Local Lymph Node Assay (LLNA) and guinea pig studies. There is a tremendous need, in particular due to novel legislation, to develop animal alternatives, eg. Quantitative Structure-Activity Relationship (QSAR) models. Here, QSAR models for skin sensitization using LLNA data have been constructed. The descriptors used to generate these models are derived from the 4D-molecular similarity paradigm and are referred to as universal 4D-fingerprints. A training set of 132 structurally diverse compounds and a test set of 15 structurally diverse compounds were used in this study. The statistical methodologies used to build the models are logistic regression (LR), and partial least square coupled logistic regression (PLS-LR), which prove to be effective tools for studying skin sensitization measures expressed in the two categorical terms of sensitizer and non-sensitizer. QSAR models with low values of the Hosmer-Lemeshow goodness-of-fit statistic, χHL2, are significant and predictive. For the training set, the cross-validated prediction accuracy of the logistic regression models ranges from 77.3% to 78.0%, while that of PLS-logistic regression models ranges from 87.1% to 89.4%. For the test set, the prediction accuracy of logistic regression models ranges from 80.0%-86.7%, while that of PLS-logistic regression models ranges from 73.3%-80.0%. The QSAR models are made up of 4D-fingerprints related to aromatic atoms, hydrogen bond acceptors and negatively partially charged atoms. PMID:17226934

  13. Magnetic particle imaging for in vivo blood flow velocity measurements in mice

    Science.gov (United States)

    Kaul, Michael G.; Salamon, Johannes; Knopp, Tobias; Ittrich, Harald; Adam, Gerhard; Weller, Horst; Jung, Caroline

    2018-03-01

    Magnetic particle imaging (MPI) is a new imaging technology. It is a potential candidate to be used for angiographic purposes, to study perfusion and cell migration. The aim of this work was to measure velocities of the flowing blood in the inferior vena cava of mice, using MPI, and to evaluate it in comparison with magnetic resonance imaging (MRI). A phantom mimicking the flow within the inferior vena cava with velocities of up to 21 cm s‑1 was used for the evaluation of the applied analysis techniques. Time–density and distance–density analyses for bolus tracking were performed to calculate flow velocities. These findings were compared with the calibrated velocities set by a flow pump, and it can be concluded that velocities of up to 21 cm s‑1 can be measured by MPI. A time–density analysis using an arrival time estimation algorithm showed the best agreement with the preset velocities. In vivo measurements were performed in healthy FVB mice (n  =  10). MRI experiments were performed using phase contrast (PC) for velocity mapping. For MPI measurements, a standardized injection of a superparamagnetic iron oxide tracer was applied. In vivo MPI data were evaluated by a time–density analysis and compared to PC MRI. A Bland–Altman analysis revealed good agreement between the in vivo velocities acquired by MRI of 4.0  ±  1.5 cm s‑1 and those measured by MPI of 4.8  ±  1.1 cm s‑1. Magnetic particle imaging is a new tool with which to measure and quantify flow velocities. It is fast, radiation-free, and produces 3D images. It therefore offers the potential for vascular imaging.

  14. Sensitivity Analysis of Unsteady Flow Fields and Impact of Measurement Strategy

    Directory of Open Access Journals (Sweden)

    Takashi Misaka

    2014-01-01

    Full Text Available Difficulty of data assimilation arises from a large difference between the sizes of a state vector to be determined, that is, the number of spatiotemporal mesh points of a discretized numerical model and a measurement vector, that is, the amount of measurement data. Flow variables on a large number of mesh points are hardly defined by spatiotemporally limited measurements, which poses an underdetermined problem. In this study we conduct the sensitivity analysis of two- and three-dimensional vortical flow fields within a framework of data assimilation. The impact of measurement strategy, which is evaluated by the sensitivity of the 4D-Var cost function with respect to measurements, is investigated to effectively determine a flow field by limited measurements. The assimilation experiment shows that the error defined by the difference between the reference and assimilated flow fields is reduced by using the sensitivity information to locate the limited number of measurement points. To conduct data assimilation for a long time period, the 4D-Var data assimilation and the sensitivity analysis are repeated with a short assimilation window.

  15. Sensitivity enhancement of 13C nuclei in 2D J-resolved NMR spectroscopy using a recycled-flow system

    International Nuclear Information System (INIS)

    Ha, S.T.K.; Lee, R.W.K.; Wilkins, C.L.

    1987-01-01

    Recycled-flow nuclear magnetic resonance for sensitivity enhancement in 1/2 spin nuclei has been reported previously, achieving several-fold signal enhancement. The success of the method depends upon premagnetization of nuclei prior to flowing into the detector region, obviating the need for delays following data acquisition to allow spin-lattice relaxation and reduce experiment time. The actual gains of sensitivity enhancement for 13 C- 1 H 2D J-resolved NMR using a recycled-flow method are evaluated. Possible enhancements for two types of J-resolved measurements, namely, one-bond 13 C- 1 H and long range J-resolved spectroscopy, are estimated using a simple Carr-Purcell spin-echo approach to quantify the 13 C signals. The pulse sequence is simply 90 0 -t /sub 1/2/-180 0 -t/sub 1/2/-AT-t/sub d/, where t/sub 1/2/ is half the evolution time, AT is the acquisition time, and t/sub d/ the experiment repetition time. In a static 2D NMR experiment, t/sub d/ usually must be the same order of the longest spin-lattice relaxation time (T 1 ) of nuclei. Quantitative measurements using a recycled-flow system indicate t/dub d/ can be reduced to a fraction of T 1 ; hence significant time savings can be achieved. Time-savings of between 2 and 25 can be anticipated for 2D spectroscopy under flow measurement conditions used in the present study. Other types of 2D NMR spectroscopy (autocorrelation and double quantum NMR) are discussed

  16. Ultrasonic 3-D Vector Flow Method for Quantitative In Vivo Peak Velocity and Flow Rate Estimation

    DEFF Research Database (Denmark)

    Holbek, Simon; Ewertsen, Caroline; Bouzari, Hamed

    2017-01-01

    Current clinical ultrasound (US) systems are limited to show blood flow movement in either 1-D or 2-D. In this paper, a method for estimating 3-D vector velocities in a plane using the transverse oscillation method, a 32×32 element matrix array, and the experimental US scanner SARUS is presented...... is validated in two phantom studies, where flow rates are measured in a flow-rig, providing a constant parabolic flow, and in a straight-vessel phantom ( ∅=8 mm) connected to a flow pump capable of generating time varying waveforms. Flow rates are estimated to be 82.1 ± 2.8 L/min in the flow-rig compared...

  17. Testing of new hypoxic cell sensitizers in vivo

    International Nuclear Information System (INIS)

    Stone, H.B.; Sinesi, M.S.

    1982-01-01

    We tested five agents as potential sensitizers of hypoxic cells in vivo in mammary tumors in C3H mice in comparison with misonidazole. The LD/sub 50/2/ for desmethylmisonidazole was 2.7 mg/g body wt, compared to 1.3 for misonidazole. It was as effective in reducing the TCD 50 of MDAH-MCa-4 as were equitoxic doses of misonidazole. the LD/sub 50/2/ of SR-2508 was 3.3 mg/g and was as effective a sensitizer as misonidazole. Ro 07-0741 was more toxic, with an LD/sub 50/2/ of 0.6 mg/g, but was as effective as misonidazole at equitoxic doses. NP-1 was also more toxic than misonidazole (LA/sub 50/2/ = 04 mg/g) but was a less effective sensitizer. Rotenone, which causes sensitization by inhibiting cellular respiration, thus increasing the diffusion distance of oxygen, was extremely toxic (LD/sub 50/2/ - 0.003 mg/g), and systemic respiratory inhibition and the radioprotective effects of the dimethyl sulfoxide used to dissolve it rendered it totally ineffective as a sensitizer in vivo

  18. Evaluation of blood flow distribution asymmetry and vascular geometry in patients with Fontan circulation using 4-D flow MRI

    International Nuclear Information System (INIS)

    Jarvis, Kelly; Markl, Michael; Schnell, Susanne; Barker, Alex J.; Garcia, Julio; Chowdhary, Varun; Carr, James; Lorenz, Ramona; Rose, Michael; Robinson, Joshua D.; Rigsby, Cynthia K.

    2016-01-01

    Asymmetrical caval to pulmonary blood flow is suspected to cause complications in patients with Fontan circulation. The aim of this study was to test the feasibility of 4-D flow MRI for characterizing the relationship between 3-D blood flow distribution and vascular geometry. We hypothesized that both flow distribution and geometry can be calculated with low interobserver variability and will detect a direct relationship between flow distribution and Fontan geometry. Four-dimensional flow MRI was acquired in 10 Fontan patients (age: 16 ± 4 years [mean ± standard deviation], range: 9-21 years). The Fontan connection was isolated by 3-D segmentation to evaluate flow distribution from the inferior vena cava (IVC) and superior vena cava (SVC) to the left and right pulmonary arteries (LPA, RPA) and to characterize geometry (cross-sectional area, caval offset, vessel angle). Flow distribution results indicated SVC flow tended toward the RPA while IVC flow was more evenly distributed (SVC to RPA: 78% ± 28 [9-100], IVC to LPA: 54% ± 28 [4-98]). There was a significant relationship between pulmonary artery cross-sectional area and flow distribution (IVC to RPA: R"2=0.50, P=0.02; SVC to LPA: R"2=0.81, P=0.0004). Good agreement was found between observers and for flow distribution when compared to net flow values. Four-dimensional flow MRI was able to detect relationships between flow distribution and vessel geometry. Future studies are warranted to investigate the potential of patient specific hemodynamic analysis to improve diagnostic capability. (orig.)

  19. Evaluation of blood flow distribution asymmetry and vascular geometry in patients with Fontan circulation using 4-D flow MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jarvis, Kelly; Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Chicago, IL (United States); Schnell, Susanne; Barker, Alex J.; Garcia, Julio; Chowdhary, Varun; Carr, James [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Lorenz, Ramona [University Medical Center Freiburg, Department of Radiology, Freiburg (Germany); Rose, Michael [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Robinson, Joshua D. [Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Cardiology, Chicago, IL (United States); Rigsby, Cynthia K. [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2016-10-15

    Asymmetrical caval to pulmonary blood flow is suspected to cause complications in patients with Fontan circulation. The aim of this study was to test the feasibility of 4-D flow MRI for characterizing the relationship between 3-D blood flow distribution and vascular geometry. We hypothesized that both flow distribution and geometry can be calculated with low interobserver variability and will detect a direct relationship between flow distribution and Fontan geometry. Four-dimensional flow MRI was acquired in 10 Fontan patients (age: 16 ± 4 years [mean ± standard deviation], range: 9-21 years). The Fontan connection was isolated by 3-D segmentation to evaluate flow distribution from the inferior vena cava (IVC) and superior vena cava (SVC) to the left and right pulmonary arteries (LPA, RPA) and to characterize geometry (cross-sectional area, caval offset, vessel angle). Flow distribution results indicated SVC flow tended toward the RPA while IVC flow was more evenly distributed (SVC to RPA: 78% ± 28 [9-100], IVC to LPA: 54% ± 28 [4-98]). There was a significant relationship between pulmonary artery cross-sectional area and flow distribution (IVC to RPA: R{sup 2}=0.50, P=0.02; SVC to LPA: R{sup 2}=0.81, P=0.0004). Good agreement was found between observers and for flow distribution when compared to net flow values. Four-dimensional flow MRI was able to detect relationships between flow distribution and vessel geometry. Future studies are warranted to investigate the potential of patient specific hemodynamic analysis to improve diagnostic capability. (orig.)

  20. Evaluation of the in vitro and in vivo angiogenic effects of exendin-4

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hye-Min [Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Kang, Yujung; Chun, Hyung J. [Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT (United States); Jeong, Joo-Won [Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Park, Chan, E-mail: psychan@khu.ac.kr [Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul (Korea, Republic of)

    2013-04-26

    Highlights: •We investigated the effects of exendin-4 on the angiogenic process. •Exendin-4 increased migration, sprouting, and tube formation by HUVECs in in vitro. •Exendin-4 increased sprouts in aortic rings and induced new vessels in Matrigel in in vivo. •Exendin-4 may be of potential use for the treatment of vascular complications of diabetes. -- Abstract: Exendin-4, an analog of glucagon-like peptide (GLP)-1, has beneficial effects on cardiovascular disease induced by diabetes mellitus (DM). Recently, exendin-4 was reported to induce the proliferation of endothelial cells. However, its angiogenic effect on endothelial cells has not been clearly evaluated. Therefore, we investigated the effects of exendin-4 on the angiogenic process with respect to migration, sprouting, and neovascularization using in vitro and in vivo assays. Treatment with exendin-4 increased the migration of human umbilical vein endothelial cells (HUVECs) in in vitro scratch wound assays, as well as the number of lumenized vessels sprouting from HUVECs in in vitro 3D bead assays. These responses were abolished by co-treatment with exendin (9–39), a GLP-1 receptor antagonist, which suggests that exendin-4 regulates endothelial cell migration and tube formation in a GLP-1 receptor-dependent manner. In an ex vivo assay, treatment of aortic rings with exendin-4 increased the sprouting of endothelial cells. Exendin-4 also significantly increased the number of new vessels and induced blood flow in Matrigel plugs in in vivo assays. Our results provide clear evidence for the angiogenic effect of exendin-4 in in vitro and in vivo assays and provide a mechanism underlying the cardioprotective effects of exendin-4.

  1. In-vivo synthetic aperture flow imaging in medical ultrasound

    DEFF Research Database (Denmark)

    Nikolov, Svetoslav; Jensen, Jørgen Arendt

    2003-01-01

    A new method for acquiring flow images using synthetic aperture techniques in medical ultrasound is presented. The new approach makes it possible to have a continuous acquisition of flow data throughout the whole image simultaneously, and this can significantly improve blood velocity estimation.......2% and a mean relative bias of 3.4% using 24 pulse emissions at a flow angle of 45 degrees. The 24 emissions can be used for making a full-color flow map image. An in-vivo image of How in the carotid artery for a 29-year-old male also is presented. The full image is acquired using 24 emissions....

  2. Fast interactive exploration of 4D MRI flow data

    Science.gov (United States)

    Hennemuth, A.; Friman, O.; Schumann, C.; Bock, J.; Drexl, J.; Huellebrand, M.; Markl, M.; Peitgen, H.-O.

    2011-03-01

    1- or 2-directional MRI blood flow mapping sequences are an integral part of standard MR protocols for diagnosis and therapy control in heart diseases. Recent progress in rapid MRI has made it possible to acquire volumetric, 3-directional cine images in reasonable scan time. In addition to flow and velocity measurements relative to arbitrarily oriented image planes, the analysis of 3-dimensional trajectories enables the visualization of flow patterns, local features of flow trajectories or possible paths into specific regions. The anatomical and functional information allows for advanced hemodynamic analysis in different application areas like stroke risk assessment, congenital and acquired heart disease, aneurysms or abdominal collaterals and cranial blood flow. The complexity of the 4D MRI flow datasets and the flow related image analysis tasks makes the development of fast comprehensive data exploration software for advanced flow analysis a challenging task. Most existing tools address only individual aspects of the analysis pipeline such as pre-processing, quantification or visualization, or are difficult to use for clinicians. The goal of the presented work is to provide a software solution that supports the whole image analysis pipeline and enables data exploration with fast intuitive interaction and visualization methods. The implemented methods facilitate the segmentation and inspection of different vascular systems. Arbitrary 2- or 3-dimensional regions for quantitative analysis and particle tracing can be defined interactively. Synchronized views of animated 3D path lines, 2D velocity or flow overlays and flow curves offer a detailed insight into local hemodynamics. The application of the analysis pipeline is shown for 6 cases from clinical practice, illustrating the usefulness for different clinical questions. Initial user tests show that the software is intuitive to learn and even inexperienced users achieve good results within reasonable processing

  3. Vortex flow during early and late left ventricular filling in normal subjects: quantitative characterization using retrospectively-gated 4D flow cardiovascular magnetic resonance and three-dimensional vortex core analysis.

    Science.gov (United States)

    Elbaz, Mohammed S M; Calkoen, Emmeline E; Westenberg, Jos J M; Lelieveldt, Boudewijn P F; Roest, Arno A W; van der Geest, Rob J

    2014-09-27

    LV diastolic vortex formation has been suggested to critically contribute to efficient blood pumping function, while altered vortex formation has been associated with LV pathologies. Therefore, quantitative characterization of vortex flow might provide a novel objective tool for evaluating LV function. The objectives of this study were 1) assess feasibility of vortex flow analysis during both early and late diastolic filling in vivo in normal subjects using 4D Flow cardiovascular magnetic resonance (CMR) with retrospective cardiac gating and 3D vortex core analysis 2) establish normal quantitative parameters characterizing 3D LV vortex flow during both early and late ventricular filling in normal subjects. With full ethical approval, twenty-four healthy volunteers (mean age: 20±10 years) underwent whole-heart 4D Flow CMR. The Lambda2-method was used to extract 3D LV vortex ring cores from the blood flow velocity field during early (E) and late (A) diastolic filling. The 3D location of the center of vortex ring core was characterized using cylindrical cardiac coordinates (Circumferential, Longitudinal (L), Radial (R)). Comparison between E and A filling was done with a paired T-test. The orientation of the vortex ring core was measured and the ring shape was quantified by the circularity index (CI). Finally, the Spearman's correlation between the shapes of mitral inflow pattern and formed vortex ring cores was tested. Distinct E- and A-vortex ring cores were observed with centers of A-vortex rings significantly closer to the mitral valve annulus (E-vortex L=0.19±0.04 versus A-vortex L=0.15±0.05; p=0.0001), closer to the ventricle's long-axis (E-vortex: R=0.27±0.07, A-vortex: R=0.20±0.09, p=0.048) and more elliptical in shape (E-vortex: CI=0.79±0.09, A-vortex: CI=0.57±0.06; vortex. The circumferential location and orientation relative to LV long-axis for both E- and A-vortex ring cores were similar. Good to strong correlation was found between vortex shape and

  4. Exploring 4D Flow Data in an Immersive Virtual Environment

    Science.gov (United States)

    Stevens, A. H.; Butkiewicz, T.

    2017-12-01

    Ocean models help us to understand and predict a wide range of intricate physical processes which comprise the atmospheric and oceanic systems of the Earth. Because these models output an abundance of complex time-varying three-dimensional (i.e., 4D) data, effectively conveying the myriad information from a given model poses a significant visualization challenge. The majority of the research effort into this problem has concentrated around synthesizing and examining methods for representing the data itself; by comparison, relatively few studies have looked into the potential merits of various viewing conditions and virtual environments. We seek to improve our understanding of the benefits offered by current consumer-grade virtual reality (VR) systems through an immersive, interactive 4D flow visualization system. Our dataset is a Regional Ocean Modeling System (ROMS) model representing a 12-hour tidal cycle of the currents within New Hampshire's Great Bay estuary. The model data was loaded into a custom VR particle system application using the OpenVR software library and the HTC Vive hardware, which tracks a headset and two six-degree-of-freedom (6DOF) controllers within a 5m-by-5m area. The resulting visualization system allows the user to coexist in the same virtual space as the data, enabling rapid and intuitive analysis of the flow model through natural interactions with the dataset and within the virtual environment. Whereas a traditional computer screen typically requires the user to reposition a virtual camera in the scene to obtain the desired view of the data, in virtual reality the user can simply move their head to the desired viewpoint, completely eliminating the mental context switches from data exploration/analysis to view adjustment and back. The tracked controllers become tools to quickly manipulate (reposition, reorient, and rescale) the dataset and to interrogate it by, e.g., releasing dye particles into the flow field, probing scalar velocities

  5. Categorical QSAR models for skin sensitization based on local lymph node assay measures and both ground and excited state 4D-fingerprint descriptors

    Science.gov (United States)

    Liu, Jianzhong; Kern, Petra S.; Gerberick, G. Frank; Santos-Filho, Osvaldo A.; Esposito, Emilio X.; Hopfinger, Anton J.; Tseng, Yufeng J.

    2008-06-01

    In previous studies we have developed categorical QSAR models for predicting skin-sensitization potency based on 4D-fingerprint (4D-FP) descriptors and in vivo murine local lymph node assay (LLNA) measures. Only 4D-FP derived from the ground state (GMAX) structures of the molecules were used to build the QSAR models. In this study we have generated 4D-FP descriptors from the first excited state (EMAX) structures of the molecules. The GMAX, EMAX and the combined ground and excited state 4D-FP descriptors (GEMAX) were employed in building categorical QSAR models. Logistic regression (LR) and partial least square coupled logistic regression (PLS-CLR), found to be effective model building for the LLNA skin-sensitization measures in our previous studies, were used again in this study. This also permitted comparison of the prior ground state models to those involving first excited state 4D-FP descriptors. Three types of categorical QSAR models were constructed for each of the GMAX, EMAX and GEMAX datasets: a binary model (2-state), an ordinal model (3-state) and a binary-binary model (two-2-state). No significant differences exist among the LR 2-state model constructed for each of the three datasets. However, the PLS-CLR 3-state and 2-state models based on the EMAX and GEMAX datasets have higher predictivity than those constructed using only the GMAX dataset. These EMAX and GMAX categorical models are also more significant and predictive than corresponding models built in our previous QSAR studies of LLNA skin-sensitization measures.

  6. B cell increases and ex vivo IL-2 production as secondary endpoints for the detection of sensitizers in non-radioisotopic local lymph node assay using flow cytometry.

    Science.gov (United States)

    Jung, Kyoung-Mi; Jang, Won-Hee; Lee, Yong-Kyoung; Yum, Young Na; Sohn, Soojung; Kim, Bae-Hwan; Chung, Jin-Ho; Park, Young-Ho; Lim, Kyung-Min

    2012-03-25

    Non-radioisotopic local lymph node assay (LLNA) using 5-bromo-2'-deoxyuridine (BrdU) with flow cytometry (FCM) is gaining attention since it is free from the regulatory issues in traditional LLNA (tLLNA) accompanying in vivo uses of radioisotope, (3)H-thymidine. However, there is also concern over compromised performance of non-radioisotopic LLNA, raising needs for additional endpoints to improve the accuracy. With the full 22 reference substances enlisted in OECD Test Guideline No. 429, we evaluated the performance of LLNA:BrdU-FCM along with the concomitant measurements of B/T cell ratio and ex vivo cytokine production from isolated lymph node cells (LNCs) to examine the utility of these markers as secondary endpoints. Mice (Balb/c, female) were topically treated with substances on both ears for 3 days and then, BrdU was intraperitoneally injected on day 5. After a day, lymph nodes were isolated and undergone FCM to determine BrdU incorporation and B/T cell sub-typing with B220+ and CD3e+. Ex vivo cytokine production by LNCs was measured such as IL-2, IL-4, IL-6, IL-12, IFN-γ, MCP-1, GM-CSF and TNFα. Mice treated with sensitizers showed preferential increases in B cell population and the selective production of IL-2, which matched well with the increases in BrdU incorporation. When compared with guinea pig or human data, BrdU incorporation, B cell increase and IL-2 production ex vivo could successfully identify sensitizers with the accuracy comparable to tLLNA, suggesting that these markers may be useful for improving the accuracy of LLNA:BrdU-FCM or as stand-alone non-radioisotopic endpoints. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Lack of indirect sensitization in vivo

    International Nuclear Information System (INIS)

    Hetzel, F.W.; Avery, K.; Mensinger, M.; Frinak, S.; Tidwell, C.

    1985-01-01

    The possible utility of respiratory inhibiting drugs as indirect radiation sensitizers has been investigated in both in vitro and in vivo systems. In vitro studies were conducted in V79 monolayer and spheroid cultures examining both respiratory inhibition and radiation survival as end points. These drugs (BCNU, Mustargen and Chlorambucil) were found to be potent respiratory inhibitors and, in the spheroid system, to be effective indirect radiation sensitizers with enhancement ratios of approximately 2.0. In vivo studies with these drugs have also been conducted in a C/sub 3/H mouse MCa tumor system to determine if the same reoxygenation effect observed in spheroids could be demonstrated in the solid tumor system. Detailed microelectrode studies, employing each drug at its LD/sub 10/ level, have been unable to demonstrate any drug induced reoxygenation for any of the drugs tested. Complete details are presented

  8. Non-invasive pulmonary blood flow analysis and blood pressure mapping derived from 4D flow MRI

    Science.gov (United States)

    Delles, Michael; Rengier, Fabian; Azad, Yoo-Jin; Bodenstedt, Sebastian; von Tengg-Kobligk, Hendrik; Ley, Sebastian; Unterhinninghofen, Roland; Kauczor, Hans-Ulrich; Dillmann, Rüdiger

    2015-03-01

    In diagnostics and therapy control of cardiovascular diseases, detailed knowledge about the patient-specific behavior of blood flow and pressure can be essential. The only method capable of measuring complete time-resolved three-dimensional vector fields of the blood flow velocities is velocity-encoded magnetic resonance imaging (MRI), often denoted as 4D flow MRI. Furthermore, relative pressure maps can be computed from this data source, as presented by different groups in recent years. Hence, analysis of blood flow and pressure using 4D flow MRI can be a valuable technique in management of cardiovascular diseases. In order to perform these tasks, all necessary steps in the corresponding process chain can be carried out in our in-house developed software framework MEDIFRAME. In this article, we apply MEDIFRAME for a study of hemodynamics in the pulmonary arteries of five healthy volunteers. The study included measuring vector fields of blood flow velocities by phase-contrast MRI and subsequently computing relative blood pressure maps. We visualized blood flow by streamline depictions and computed characteristic values for the left and the right pulmonary artery (LPA and RPA). In all volunteers, we observed a lower amount of blood flow in the LPA compared to the RPA. Furthermore, we visualized blood pressure maps using volume rendering and generated graphs of pressure differences between the LPA, the RPA and the main pulmonary artery. In most volunteers, blood pressure was increased near to the bifurcation and in the proximal LPA, leading to higher average pressure values in the LPA compared to the RPA.

  9. Minimal vascular flows cause strong heat sink effects in hepatic radiofrequency ablation ex vivo.

    Science.gov (United States)

    Lehmann, Kai S; Poch, Franz G M; Rieder, Christian; Schenk, Andrea; Stroux, Andrea; Frericks, Bernd B; Gemeinhardt, Ole; Holmer, Christoph; Kreis, Martin E; Ritz, Jörg P; Zurbuchen, Urte

    2016-08-01

    The present paper aims to assess the lower threshold of vascular flow rate on the heat sink effect in bipolar radiofrequency ablation (RFA) ex vivo. Glass tubes (vessels) of 3.4 mm inner diameter were introduced in parallel to bipolar RFA applicators into porcine liver ex vivo. Vessels were perfused with flow rates of 0 to 1,500 ml/min. RFA (30 W power, 15 kJ energy input) was carried out at room temperature and 37°C. Heat sink effects were assessed in RFA cross sections by the decrease in ablation radius, area and by a high-resolution sector planimetry. Flow rates of 1 ml/min already caused a significant cooling effect (P ≤ 0.001). The heat sink effect reached a maximum at 10 ml/min (18.4 mm/s) and remained stable for flow rates up to 1,500 ml/min. Minimal vascular flows of ≥1 ml/min cause a significant heat sink effect in hepatic RFA ex vivo. A lower limit for volumetric flow rate was not found. The maximum of the heat sink effect was reached at a flow rate of 10 ml/min and remained stable for flow rates up to 1,500 ml/min. Hepatic inflow occlusion should be considered in RFA close to hepatic vessels. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  10. Clinical flow cytometric screening of SAP and XIAP expression accurately identifies patients with SH2D1A and XIAP/BIRC4 mutations.

    Science.gov (United States)

    Gifford, Carrie E; Weingartner, Elizabeth; Villanueva, Joyce; Johnson, Judith; Zhang, Kejian; Filipovich, Alexandra H; Bleesing, Jack J; Marsh, Rebecca A

    2014-07-01

    X-linked lymphoproliferative disease is caused by mutations in two genes, SH2D1A and XIAP/BIRC4. Flow cytometric methods have been developed to detect the gene products, SAP and XIAP. However, there is no literature describing the accuracy of flow cytometric screening performed in a clinical lab setting. We reviewed the clinical flow cytometric testing results for 656 SAP and 586 XIAP samples tested during a 3-year period. Genetic testing was clinically performed as directed by the managing physician in 137 SAP (21%) and 115 XIAP (20%) samples. We included these samples for analyses of flow cytometric test accuracy. SH2D1A mutations were detected in 15/137 samples. SAP expression was low in 13/15 (sensitivity 87%, CI 61-97%). Of the 122 samples with normal sequencing, SAP was normal in 109 (specificity 89%, CI 82-94%). The positive predictive values (PPVs) and the negative predictive values (NPVs) were 50% and 98%, respectively. XIAP/BIRC4 mutations were detected in 19/115 samples. XIAP expression was low in 18/19 (sensitivity 95%, CI 73-100%). Of the 96 samples with normal sequencing, 59 had normal XIAP expression (specificity 61%, CI 51-71%). The PPVs and NPVs were 33% and 98%, respectively. Receiver-operating characteristic analysis was able to improve the specificity to 75%. Clinical flow cytometric screening tests for SAP and XIAP deficiencies offer good sensitivity and specificity for detecting genetic mutations, and are characterized by high NPVs. We recommend these tests for patients suspected of having X-linked lymphoproliferative disease type 1 (XLP1) or XLP2. © 2014 Clinical Cytometry Society.

  11. Systemic-to-pulmonary collateral flow in patients with palliated univentricular heart physiology: measurement using cardiovascular magnetic resonance 4D velocity acquisition

    Directory of Open Access Journals (Sweden)

    Valverde Israel

    2012-04-01

    Full Text Available Abstract Background Systemic-to-pulmonary collateral flow (SPCF may constitute a risk factor for increased morbidity and mortality in patients with single-ventricle physiology (SV. However, clinical research is limited by the complexity of multi-vessel two-dimensional (2D cardiovascular magnetic resonance (CMR flow measurements. We sought to validate four-dimensional (4D velocity acquisition sequence for concise quantification of SPCF and flow distribution in patients with SV. Methods 29 patients with SV physiology prospectively underwent CMR (1.5 T (n = 14 bidirectional cavopulmonary connection [BCPC], age 2.9 ± 1.3 years; and n = 15 Fontan, 14.4 ± 5.9 years and 20 healthy volunteers (age, 28.7 ± 13.1 years served as controls. A single whole-heart 4D velocity acquisition and five 2D flow acquisitions were performed in the aorta, superior/inferior caval veins, right/left pulmonary arteries to serve as gold-standard. The five 2D velocity acquisition measurements were compared with 4D velocity acquisition for validation of individual vessel flow quantification and time efficiency. The SPCF was calculated by evaluating the disparity between systemic (aortic minus caval vein flows and pulmonary flows (arterial and venour return. The pulmonary right to left and the systemic lower to upper body flow distribution were also calculated. Results The comparison between 4D velocity and 2D flow acquisitions showed good Bland-Altman agreement for all individual vessels (mean bias, 0.05±0.24 l/min/m2, calculated SPCF (−0.02±0.18 l/min/m2 and significantly shorter 4D velocity acquisition-time (12:34 min/17:28 min,p 2; Fontan 0.62±0.82 l/min/m2 and not in controls (0.01 + 0.16 l/min/m2, (3 inverse relation of right/left pulmonary artery perfusion and right/left SPCF (Pearson = −0.47,p = 0.01 and (4 upper to lower body flow distribution trend related to the weight (r = 0.742, p  Conclusions 4D

  12. Speckle tracking in a phantom and feature-based tracking in liver in the presence of respiratory motion using 4D ultrasound

    International Nuclear Information System (INIS)

    Harris, Emma J; Miller, Naomi R; Bamber, Jeffrey C; Symonds-Tayler, J Richard N; Evans, Philip M

    2010-01-01

    We have evaluated a 4D ultrasound-based motion tracking system developed for tracking of abdominal organs during therapy. Tracking accuracy and precision were determined using a tissue-mimicking phantom, by comparing tracked motion with known 3D sinusoidal motion. The feasibility of tracking 3D liver motion in vivo was evaluated by acquiring 4D ultrasound data from four healthy volunteers. For two of these volunteers, data were also acquired whilst simultaneously measuring breath flow using a spirometer. Hepatic blood vessels, tracked off-line using manual tracking, were used as a reference to assess, in vivo, two types of automated tracking algorithm: incremental (from one volume to the next) and non-incremental (from the first volume to each subsequent volume). For phantom-based experiments, accuracy and precision (RMS error and SD) were found to be 0.78 mm and 0.54 mm, respectively. For in vivo measurements, mean absolute distance and standard deviation of the difference between automatically and manually tracked displacements were less than 1.7 mm and 1 mm respectively in all directions (left-right, anterior-posterior and superior-inferior). In vivo non-incremental tracking gave the best agreement. In both phantom and in vivo experiments, tracking performance was poorest for the elevational component of 3D motion. Good agreement between automatically and manually tracked displacements indicates that 4D ultrasound-based motion tracking has potential for image guidance applications in therapy.

  13. Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice

    International Nuclear Information System (INIS)

    Jenkins, Darlene E; Hornig, Yvette S; Oei, Yoko; Dusich, Joan; Purchio, Tony

    2005-01-01

    Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. Two clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly luciferase were isolated following transfection of the parental cells with luciferase cDNA. Each subline was passaged once or twice in vivo to enhance primary tumor growth and to increase metastasis. The resulting luciferase-expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent stability, primary tumor growth, and distal metastasis to lymph nodes, lungs, bone and soft tissues by bioluminescent imaging. Cells were injected into the mammary fat pad of nude and nude-beige mice or were delivered systemically via intracardiac injection. Metastasis was also evaluated by ex vivo imaging and histologic analysis postmortem. The D3H1 and D3H2LN cell lines exhibited long-term stable luciferase expression for up to 4–6 months of accumulative tumor growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad tumor development and detected early spontaneous lymph node metastasis in vivo. Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent histologic evaluation of tissue sections from lymph nodes and lung lobes confirmed spontaneous tumor metastasis at these sites. Following intracardiac injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal tissues, lymph nodes, brain and various visceral organs was detected. Weekly in vivo imaging data permitted longitudinal analysis of metastasis at

  14. 3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours

    International Nuclear Information System (INIS)

    Hornblower, V D M; Yu, E; Fenster, A; Battista, J J; Malthaner, R A

    2007-01-01

    The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial 'tumours' were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the 'tumours' were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure 'tumour' volumes both in vivo and ex vivo

  15. 3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours

    Energy Technology Data Exchange (ETDEWEB)

    Hornblower, V D M [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada); Yu, E [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada); Fenster, A [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada); Battista, J J [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada); Malthaner, R A [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada)

    2007-01-07

    The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial 'tumours' were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the 'tumours' were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure 'tumour' volumes both in vivo and ex vivo.

  16. Altered ratio of D1 and D2 dopamine receptors in mouse striatum is associated with behavioral sensitization to cocaine.

    Directory of Open Access Journals (Sweden)

    Dawn Thompson

    Full Text Available BACKGROUND: Drugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R availability in the brain. Such a decrease consequently alters the ratio of D1R:D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified. METHODS AND FINDINGS: ETHICS STATEMENT: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT and G protein coupled receptor associated sorting protein-1 (GASP-1 knock out (KO mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine. CONCLUSIONS: Together, our data suggests that changes in the ratio of the D1:D2R could contribute to cocaine-induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization.

  17. Four-dimensional (4D) flow of the whole heart and great vessels using real-time respiratory self-gating

    DEFF Research Database (Denmark)

    Uribe, Sergio; Beerbaum, Philipp; Sørensen, Thomas Sangild

    2009-01-01

    Four-dimensional (4D) flow imaging has been used to study flow patterns and pathophysiology, usually focused on specific thoracic vessels and cardiac chambers. Whole-heart 4D flow at high measurement accuracy covering the entire thoracic cardiovascular system would be desirable to simplify...... and improve hemodynamic assessment. This has been a challenge because compensation of respiratory motion is difficult to achieve, but it is paramount to limit artifacts and improve accuracy. In this work we propose a self-gating technique for respiratory motion-compensation integrated into a whole-heart 4D...... flow acquisition that overcomes these challenges. Flow components are measured in all three directions for each pixel over the complete cardiac cycle, and 1D volume projections are obtained at certain time intervals for respiratory gating in real time during the acquisition. The technique was tested...

  18. TIPS bilateral noise reduction in 4D CT perfusion scans produces high-quality cerebral blood flow maps

    Energy Technology Data Exchange (ETDEWEB)

    Mendrik, Adrienne M; Van Ginneken, Bram; Viergever, Max A [Image Sciences Institute, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht (Netherlands); Vonken, Evert-jan; De Jong, Hugo W; Riordan, Alan; Van Seeters, Tom; Smit, Ewoud J; Prokop, Mathias, E-mail: a.m.mendrik@gmail.com [Radiology Department, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht (Netherlands)

    2011-07-07

    Cerebral computed tomography perfusion (CTP) scans are acquired to detect areas of abnormal perfusion in patients with cerebrovascular diseases. These 4D CTP scans consist of multiple sequential 3D CT scans over time. Therefore, to reduce radiation exposure to the patient, the amount of x-ray radiation that can be used per sequential scan is limited, which results in a high level of noise. To detect areas of abnormal perfusion, perfusion parameters are derived from the CTP data, such as the cerebral blood flow (CBF). Algorithms to determine perfusion parameters, especially singular value decomposition, are very sensitive to noise. Therefore, noise reduction is an important preprocessing step for CTP analysis. In this paper, we propose a time-intensity profile similarity (TIPS) bilateral filter to reduce noise in 4D CTP scans, while preserving the time-intensity profiles (fourth dimension) that are essential for determining the perfusion parameters. The proposed TIPS bilateral filter is compared to standard Gaussian filtering, and 4D and 3D (applied separately to each sequential scan) bilateral filtering on both phantom and patient data. Results on the phantom data show that the TIPS bilateral filter is best able to approach the ground truth (noise-free phantom), compared to the other filtering methods (lowest root mean square error). An observer study is performed using CBF maps derived from fifteen CTP scans of acute stroke patients filtered with standard Gaussian, 3D, 4D and TIPS bilateral filtering. These CBF maps were blindly presented to two observers that indicated which map they preferred for (1) gray/white matter differentiation, (2) detectability of infarcted area and (3) overall image quality. Based on these results, the TIPS bilateral filter ranked best and its CBF maps were scored to have the best overall image quality in 100% of the cases by both observers. Furthermore, quantitative CBF and cerebral blood volume values in both the phantom and the

  19. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis ‬

    KAUST Repository

    Zeitelhofer, Manuel; Adzemovic, Milena Z.; Gomez-Cabrero, David; Bergman, Petra; Hochmeister, Sonja; N'diaye, Marie; Paulson, Atul; Ruhrmann, Sabrina; Almgren, Malin; Tegner, Jesper; Ekströ m, Tomas J.; Guerreiro-Cacais, André Ortlieb; Jagodic, Maja

    2017-01-01

    Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo. Namely, Jak/Stat, Erk/Mapk, and Pi3K/Akt/mTor signaling pathway genes were down-regulated upon vitamin D supplementation. The protective effect associated with epigenetic mechanisms, such as (i) changed levels of enzymes involved in establishment and maintenance of epigenetic marks, i.e., DNA methylation and histone modifications; (ii) genome-wide reduction of DNA methylation, and (iii) up-regulation of noncoding RNAs, including microRNAs, with concomitant down-regulation of their protein-coding target RNAs involved in T-cell activation and differentiation. We further demonstrate that treatment of myelin-specific T cells with vitamin D reduces frequency of Th1 and Th17 cells, down-regulates genes in key signaling pathways and epigenetic machinery, and impairs their ability to transfer EAE. Finally, orthologs of nearly 50% of candidate MS risk genes and 40% of signature genes of myelin-reactive T cells in MS changed their expression in vivo in EAE upon supplementation, supporting the hypothesis that vitamin D may modulate risk for developing MS.

  20. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis ‬

    KAUST Repository

    Zeitelhofer, Manuel

    2017-02-15

    Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo. Namely, Jak/Stat, Erk/Mapk, and Pi3K/Akt/mTor signaling pathway genes were down-regulated upon vitamin D supplementation. The protective effect associated with epigenetic mechanisms, such as (i) changed levels of enzymes involved in establishment and maintenance of epigenetic marks, i.e., DNA methylation and histone modifications; (ii) genome-wide reduction of DNA methylation, and (iii) up-regulation of noncoding RNAs, including microRNAs, with concomitant down-regulation of their protein-coding target RNAs involved in T-cell activation and differentiation. We further demonstrate that treatment of myelin-specific T cells with vitamin D reduces frequency of Th1 and Th17 cells, down-regulates genes in key signaling pathways and epigenetic machinery, and impairs their ability to transfer EAE. Finally, orthologs of nearly 50% of candidate MS risk genes and 40% of signature genes of myelin-reactive T cells in MS changed their expression in vivo in EAE upon supplementation, supporting the hypothesis that vitamin D may modulate risk for developing MS.

  1. In vivo evaluation of femoral blood flow measured with magnetic resonance

    International Nuclear Information System (INIS)

    Henriksen, O.; Staahlberg, F.; Thomsen, C.; Moegelvang, J.; Persson, B.; Lund Univ.

    1989-01-01

    Quantitative measurements of blood flow based on magnetic resonance imaging (MRI) using conventional multiple spin echo sequences were evaluated in vivo in healthy young volunteers. Blood flow was measured using MRI in the femoral vein. The initial slope of the multiple spin echo decay curve, corrected for the T2 decay of non-flowing blood was used to calculate the blood flow. As a reference, the blood flow in the femoral artery was measured simultaneously with an invasive indicator dilution technique. T2 of non-flowing blood was measured in vivo in popliteal veins during regional circulatory arrest. The mean T2 of non-flowing blood was found to be 105±31 ms. The femoral blood flow ranged between 0 and 643 ml/min measured with MRI and between 280 and 531 ml/min measured by the indicator dilution technique. There was thus poor agreement between the two methods. The results indicate that in vivo blood flow measurements made with MRI based on wash-out effects, commonly used in multiple spin echo imaging, do not give reliable absolute values for blood flow in the femoral artery or vein. (orig.)

  2. Sensitivity of Regulated Flow Regimes to Climate Change in the Western United States

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Tian [Pacific Northwest National Laboratory, Richland, Washington; Voisin, Nathalie [Pacific Northwest National Laboratory, Richland, Washington; Leng, Guoyong [Pacific Northwest National Laboratory, Richland, Washington; Huang, Maoyi [Pacific Northwest National Laboratory, Richland, Washington; Kraucunas, Ian [Pacific Northwest National Laboratory, Richland, Washington

    2018-03-01

    Water management activities or flow regulations modify water fluxes at the land surface and affect water resources in space and time. We hypothesize that flow regulations change the sensitivity of river flow to climate change with respect to unmanaged water resources. Quantifying these changes in sensitivity could help elucidate the impacts of water management at different spatiotemporal scales and inform climate adaptation decisions. In this study, we compared the emergence of significant changes in natural and regulated river flow regimes across the Western United States from simulations driven by multiple climate models and scenarios. We find that significant climate change-induced alterations in natural flow do not cascade linearly through water management activities. At the annual time scale, 50% of the Hydrologic Unit Code 4 (HUC4) sub-basins over the Western U.S. regions tend to have regulated flow regime more sensitive to the climate change than natural flow regime. Seasonality analyses show that the sensitivity varies remarkably across the seasons. We also find that the sensitivity is related to the level of water management. For 35% of the HUC4 sub-basins with the highest level of water management, the summer and winter flows tend to show a heightened sensitivity to climate change due to the complexity of joint reservoir operations. We further demonstrate that the impacts of considering water management in models are comparable to those that arises from uncertainties across climate models and emission scenarios. This prompts further climate adaptation studies research about nonlinearity effects of climate change through water management activities.

  3. Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo.

    Science.gov (United States)

    Zettergren, Eric; Vickers, Dwayne; Runnels, Judith; Murthy, Shashi K; Lin, Charles P; Niedre, Mark

    2012-03-01

    Accurate quantification of circulating cell populations in mice is important in many areas of preclinical biomedical research. Normally, this is done either by extraction and analysis of small blood samples or, more recently, by using microscopy-based in vivo fluorescence flow cytometry. We describe a new technological approach to this problem using detection of diffuse fluorescent light from relatively large blood vessels in vivo. The diffuse fluorescence flow cytometer (DFFC) uses a laser to illuminate a mouse limb and an array of optical fibers coupled to a high-sensitivity photomultiplier tube array operating in photon counting mode to detect weak fluorescence signals from cells. We first demonstrate that the DFFC instrument is capable of detecting fluorescent microspheres and Vybrant-DiD-labeled cells in a custom-made optical flow phantom with similar size, optical properties, linear flow rates, and autofluorescence as a mouse limb. We also present preliminary data demonstrating that the DFFC is capable of detecting circulating cells in nude mice in vivo. In principle, this device would allow interrogation of the whole blood volume of a mouse in minutes, with sensitivity improvement by several orders of magnitude compared to current approaches. © 2012 Society of Photo-Optical Instrumentation Engineers (SPIE).

  4. Extended forward sensitivity analysis of one-dimensional isothermal flow

    International Nuclear Information System (INIS)

    Johnson, M.; Zhao, H.

    2013-01-01

    Sensitivity analysis and uncertainty quantification is an important part of nuclear safety analysis. In this work, forward sensitivity analysis is used to compute solution sensitivities on 1-D fluid flow equations typical of those found in system level codes. Time step sensitivity analysis is included as a method for determining the accumulated error from time discretization. The ability to quantify numerical error arising from the time discretization is a unique and important feature of this method. By knowing the relative sensitivity of time step with other physical parameters, the simulation is allowed to run at optimized time steps without affecting the confidence of the physical parameter sensitivity results. The time step forward sensitivity analysis method can also replace the traditional time step convergence studies that are a key part of code verification with much less computational cost. One well-defined benchmark problem with manufactured solutions is utilized to verify the method; another test isothermal flow problem is used to demonstrate the extended forward sensitivity analysis process. Through these sample problems, the paper shows the feasibility and potential of using the forward sensitivity analysis method to quantify uncertainty in input parameters and time step size for a 1-D system-level thermal-hydraulic safety code. (authors)

  5. Gene flow analysis method, the D-statistic, is robust in a wide parameter space.

    Science.gov (United States)

    Zheng, Yichen; Janke, Axel

    2018-01-08

    We evaluated the sensitivity of the D-statistic, a parsimony-like method widely used to detect gene flow between closely related species. This method has been applied to a variety of taxa with a wide range of divergence times. However, its parameter space and thus its applicability to a wide taxonomic range has not been systematically studied. Divergence time, population size, time of gene flow, distance of outgroup and number of loci were examined in a sensitivity analysis. The sensitivity study shows that the primary determinant of the D-statistic is the relative population size, i.e. the population size scaled by the number of generations since divergence. This is consistent with the fact that the main confounding factor in gene flow detection is incomplete lineage sorting by diluting the signal. The sensitivity of the D-statistic is also affected by the direction of gene flow, size and number of loci. In addition, we examined the ability of the f-statistics, [Formula: see text] and [Formula: see text], to estimate the fraction of a genome affected by gene flow; while these statistics are difficult to implement to practical questions in biology due to lack of knowledge of when the gene flow happened, they can be used to compare datasets with identical or similar demographic background. The D-statistic, as a method to detect gene flow, is robust against a wide range of genetic distances (divergence times) but it is sensitive to population size. The D-statistic should only be applied with critical reservation to taxa where population sizes are large relative to branch lengths in generations.

  6. Evidence for the strongest version of the 4d a-theorem via a-maximization along RG flows

    International Nuclear Information System (INIS)

    Barnes, Edwin; Intriligator, Ken; Wecht, Brian; Wright, Jason

    2004-01-01

    In earlier work, we (KI and BW) gave a two line 'almost proof' (for supersymmetric RG flows) of the weakest form of the conjectured 4d a-theorem, that aIRaUV, using our result that the exact superconformal R-symmetry of 4d SCFTs maximizes a=3TrR3-TrR. The proof was incomplete because of two identified loopholes: theories with accidental symmetries, and the fact that it is only a local maximum of a. Here we discuss and extend a proposal of Kutasov (which helps close the latter loophole) in which a-maximization is generalized away from the endpoints of the RG flow, with Lagrange multipliers that are conjectured to be identified with the running coupling constants. a-maximization then yields a monotonically decreasing 'a-function' along the RG flow to the IR. As we discuss, this proposal in fact suggests the strongest version of the a-theorem: that 4d RG flows are gradient flows of an a-function, with positive-definite metric. In the perturbative limit, the RG flow metric thus obtained is shown to agree precisely with that found by very different computations by Osborn and collaborators. As examples, we discuss a new class of 4d SCFTs, along with their dual descriptions and IR phases, obtained from SQCD by coupling some of the flavors to added singlets

  7. Left Atrial 4D Blood Flow Dynamics and Hemostasis following Electrical Cardioversion of Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Merih Cibis

    2017-12-01

    Full Text Available Background: Electrical cardioversion in patients with atrial fibrillation is followed by a transiently impaired atrial mechanical function, termed atrial stunning. During atrial stunning, a retained risk of left atrial thrombus formation exists, which may be attributed to abnormal left atrial blood flow patterns. 4D Flow cardiovascular magnetic resonance (CMR enables blood flow assessment from the entire three-dimensional atrial volume throughout the cardiac cycle. We sought to investigate left atrial 4D blood flow patterns and hemostasis during left atrial stunning and after left atrial mechanical function was restored.Methods: 4D Flow and morphological CMR data as well as blood samples were collected in fourteen patients at two time-points: 2–3 h (Time-1 and 4 weeks (Time-2 following cardioversion. The volume of blood stasis and duration of blood stasis were calculated. In addition, hemostasis markers were analyzed.Results: From Time-1 to Time-2: Heart rate decreased (61 ± 7 vs. 56 ± 8 bpm, p = 0.01; Maximum change in left atrial volume increased (8 ± 4 vs. 22 ± 15%, p = 0.009; The duration of stasis (68 ± 11 vs. 57 ± 8%, p = 0.002 and the volume of stasis (14 ± 9 vs. 9 ± 7%, p = 0.04 decreased; Thrombin-antithrombin complex (TAT decreased (5.2 ± 3.3 vs. 3.3 ± 2.2 μg/L, p = 0.008. A significant correlation was found between TAT and the volume of stasis (r2 = 0.69, p < 0.001 at Time-1 and between TAT and the duration of stasis (r2 = 0.34, p = 0.04 at Time-2.Conclusion: In this longitudinal study, left atrial multidimensional blood flow was altered and blood stasis was elevated during left atrial stunning compared to the restored left atrial mechanical function. The coagulability of blood was also elevated during atrial stunning. The association between blood stasis and hypercoagulability proposes that assessment of left atrial 4D flow can add to the pathophysiological understanding of thrombus formation during atrial fibrillation

  8. Left Atrial 4D Blood Flow Dynamics and Hemostasis following Electrical Cardioversion of Atrial Fibrillation

    Science.gov (United States)

    Cibis, Merih; Lindahl, Tomas L.; Ebbers, Tino; Karlsson, Lars O.; Carlhäll, Carl-Johan

    2017-01-01

    Background: Electrical cardioversion in patients with atrial fibrillation is followed by a transiently impaired atrial mechanical function, termed atrial stunning. During atrial stunning, a retained risk of left atrial thrombus formation exists, which may be attributed to abnormal left atrial blood flow patterns. 4D Flow cardiovascular magnetic resonance (CMR) enables blood flow assessment from the entire three-dimensional atrial volume throughout the cardiac cycle. We sought to investigate left atrial 4D blood flow patterns and hemostasis during left atrial stunning and after left atrial mechanical function was restored. Methods: 4D Flow and morphological CMR data as well as blood samples were collected in fourteen patients at two time-points: 2–3 h (Time-1) and 4 weeks (Time-2) following cardioversion. The volume of blood stasis and duration of blood stasis were calculated. In addition, hemostasis markers were analyzed. Results: From Time-1 to Time-2: Heart rate decreased (61 ± 7 vs. 56 ± 8 bpm, p = 0.01); Maximum change in left atrial volume increased (8 ± 4 vs. 22 ± 15%, p = 0.009); The duration of stasis (68 ± 11 vs. 57 ± 8%, p = 0.002) and the volume of stasis (14 ± 9 vs. 9 ± 7%, p = 0.04) decreased; Thrombin-antithrombin complex (TAT) decreased (5.2 ± 3.3 vs. 3.3 ± 2.2 μg/L, p = 0.008). A significant correlation was found between TAT and the volume of stasis (r2 = 0.69, p < 0.001) at Time-1 and between TAT and the duration of stasis (r2 = 0.34, p = 0.04) at Time-2. Conclusion: In this longitudinal study, left atrial multidimensional blood flow was altered and blood stasis was elevated during left atrial stunning compared to the restored left atrial mechanical function. The coagulability of blood was also elevated during atrial stunning. The association between blood stasis and hypercoagulability proposes that assessment of left atrial 4D flow can add to the pathophysiological understanding of thrombus formation during atrial fibrillation related

  9. Quantification of complex blood flow using real-time in vivo vector flow ultrasound

    DEFF Research Database (Denmark)

    Pedersen, Mads Møller; Pihl, Michael Johannes; Haugaard, Per

    2010-01-01

    A quantitative method for distinguishing complex from non-complex flow patterns in ultrasound is presented. A new commercial BK Medical ultrasound scanner uses the Transverse Oscillation vector flow technique for visualising flow patterns in real-time. In vivo vector flow data of the blood flow...... patterns of the common carotid artery and the carotid bulb were obtained simultaneously as the basis for quantifying complex flow. The carotid bifurcation of two healthy volunteers were scanned. The presence of complex flow patterns from eight cardiac cycles were evaluated by three experts in medical...... for automatic detection of complex flow patterns....

  10. Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

    Science.gov (United States)

    Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

    2018-05-01

    Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

  11. 4-D OCT in Developmental Cardiology

    Science.gov (United States)

    Jenkins, Michael W.; Rollins, Andrew M.

    Although strong evidence exists to suggest that altered cardiac function can lead to CHDs, few studies have investigated the influential role of cardiac function and biophysical forces on the development of the cardiovascular system due to a lack of proper in vivo imaging tools. 4-D imaging is needed to decipher the complex spatial and temporal patterns of biomechanical forces acting upon the heart. Numerous solutions over the past several years have demonstrated 4-D OCT imaging of the developing cardiovascular system. This chapter will focus on these solutions and explain their context in the evolution of 4-D OCT imaging. The first sections describe the relevant techniques (prospective gating, direct 4-D imaging, retrospective gating), while later sections focus on 4-D Doppler imaging and measurements of force implementing 4-D OCT Doppler. Finally, the techniques are summarized, and some possible future directions are discussed.

  12. The Neopuff's PEEP valve is flow sensitive.

    LENUS (Irish Health Repository)

    Hawkes, Colin Patrick

    2012-01-31

    AIM: The current recommendation in setting up the Neopuff is to use a gas flow of 5-15 L\\/min. We investigated if the sensitivity of the positive end expiratory pressure (PEEP) valve varies at different flow rates within this range. METHODS: Five Neopuffs were set up to provide a PEEP of 5 cm H(2) O. The number of clockwise revolutions to complete occlusion of the PEEP valve and the mean and range of pressures at each quarter clockwise revolution were recorded at gas flow rates between 5 and 15 L\\/min. Results: At 5, 10 and 15 L\\/min, 0.5, 1.7 and 3.4 full clockwise rotations were required to completely occlude the PEEP valve, and pressures rose from 5 to 11.4, 18.4 and 21.5 cm H(2) O, respectively. At a flow rate of 5 L\\/min, half a rotation of the PEEP dial resulted in a rise in PEEP from 5 to 11.4cm H(2) O. At 10 L\\/min, half a rotation resulted in a rise from 5 to 7.7cm H(2) O, and at 15 L\\/min PEEP rose from 5 to 6.8cm H(2) O. CONCLUSION: Users of the Neopuff should be aware that the PEEP valve is more sensitive at lower flow rates and that half a rotation of the dial at 5 L\\/min gas flow can more than double the PEEP.

  13. Sensitivity Analysis of Transonic Flow over J-78 Wings

    Directory of Open Access Journals (Sweden)

    Alexander Kuzmin

    2015-01-01

    Full Text Available 3D transonic flow over swept and unswept wings with an J-78 airfoil at spanwise sections is studied numerically at negative and vanishing angles of attack. Solutions of the unsteady Reynolds-averaged Navier-Stokes equations are obtained with a finite-volume solver on unstructured meshes. The numerical simulation shows that adverse Mach numbers, at which the lift coefficient is highly sensitive to small perturbations, are larger than those obtained earlier for 2D flow. Due to the larger Mach numbers, there is an onset of self-exciting oscillations of shock waves on the wings. The swept wing exhibits a higher sensitivity to variations of the Mach number than the unswept one.

  14. Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes.

    Science.gov (United States)

    Taylor, I Mitch; Robbins, Elaine M; Catt, Kasey A; Cody, Patrick A; Happe, Cassandra L; Cui, Xinyan Tracy

    2017-03-15

    Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Effect of TIPS placement on portal and splanchnic arterial blood flow in 4-dimensional flow MRI

    Energy Technology Data Exchange (ETDEWEB)

    Stankovic, Zoran [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); University Medical Center Freiburg, Department of Diagnostic Radiology and Medical Physics, Freiburg (Germany); Roessle, Martin; Schultheiss, Michael [University Medical Center Freiburg, Department of Gastroenterology, Freiburg (Germany); Euringer, Wulf; Langer, Mathias [University Medical Center Freiburg, Department of Diagnostic Radiology and Medical Physics, Freiburg (Germany); Salem, Riad; Barker, Alex; Carr, James; Collins, Jeremy D. [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Chicago, IL (United States)

    2015-09-15

    To assess changes in portal and splanchnic arterial haemodynamics in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) using four-dimensional (4D) flow MRI, a non-invasive, non-contrast imaging technique. Eleven patients undergoing TIPS implantation were enrolled. K-t GRAPPA accelerated non-contrast 4D flow MRI of the liver vasculature was applied with acceleration factor R = 5 at 3Tesla. Flow analysis included three-dimensional (3D) blood flow visualization using time-resolved 3D particle traces and semi-quantitative flow pattern grading. Quantitative evaluation entailed peak velocities and net flows throughout the arterial and portal venous (PV) systems. MRI measurements were taken within 24 h before and 4 weeks after TIPS placement. Three-dimensional flow visualization with 4D flow MRI revealed good image quality with minor limitations in PV flow. Quantitative analysis revealed a significant increase in PV flow (562 ± 373 ml/min before vs. 1831 ± 965 ml/min after TIPS), in the hepatic artery (176 ± 132 ml/min vs. 354 ± 140 ml/min) and combined flow in splenic and superior mesenteric arteries (770 ml/min vs. 1064 ml/min). Shunt-flow assessment demonstrated stenoses in two patients confirmed and treated at TIPS revision. Four-dimensional flow MRI might have the potential to give new information about the effect of TIPS placement on hepatic perfusion. It may explain some unexpected findings in clinical observation studies. (orig.)

  16. In vivo and 3D visualization of coronary artery development by optical coherence tomography - art. no. 662709

    DEFF Research Database (Denmark)

    Thrane, Lars; Norozi, K.; Männer, J.

    2007-01-01

    . The in vivo images were generated by optical coherence tomography (OCT). The OCT system used in this study is a mobile fiber-based time-domain real-time OCT system operating with a center wavelength of 1330 nm, an A-scan rate of 4 kHz, and a typical frame rate of 8 frames/s. The axial resolution is 17 mu m......One of the most critical but poorly understood processes during cardiovascular development is the establishment of a functioning coronary artery (CA) system. Due to the lack of suitable imaging technologies, it is currently impossible to visualize this complex dynamic process on living human...... (in tissue), and the lateral resolution is 30 mu m. The OCT system is optimized for in vivo chick heart visualization and enables OCT movie recording with 8 frames/s, full-automatic 3D OCT scanning, and blood flow visualization, i.e., Doppler OCT imaging. Using this OCT system, we generated in vivo...

  17. Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig

    International Nuclear Information System (INIS)

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-01-01

    Experiments on the metabolism and excretion of i.v. administered selectively labeled [ 3 H 8 ]leukotriene C 4 in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D 4 . By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D 4 endogenously. Immunological challenge of animals sensitized to ovalbumin was accompanied by an increase of biliary leukotriene D 4 concentrations from 10 +/- 1 to 86 +/- 10 nM. When considering that bile flow was decreased to about half after challenge, the excretion rate of leukotriene D 4 in bile increased from 0.88 +/- 0.16 before 3.18 +/- 0.38 pmol x min -1 x kg -1 after challenge. It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C 4

  18. FLAIR vascular hyperintensities and dynamic 4D angiograms for the estimation of collateral blood flow in posterior circulation occlusion

    International Nuclear Information System (INIS)

    Foerster, Alex; Wenz, Holger; Kerl, Hans Ulrich; Al-Zghloul, Mansour; Habich, Sonia; Groden, Christoph

    2014-01-01

    The objectives of this paper are to assess collateral blood flow in posterior circulation occlusion by MRI-based approaches (fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs), collateralization on dynamic 4D angiograms) and investigate its relation to ischemic lesion size and growth. In 28 patients with posterior cerebral artery (PCA) and 10 patients with basilar artery (BA) occlusion, MRI findings were analyzed, with emphasis on distal FVH and collateralization on dynamic 4D angiograms. In PCA occlusion, distal FVH was observed in 18/29 (62.1 %), in BA occlusion, in 8/10 (80 %) cases. Collateralization on dynamic 4D angiograms was graded 1 in 8 (27.6 %) patients, 2 in 1 (3.4 %) patient, 3 in 12 (41.4 %) patients, and 4 in 8 (27.6 %) patients with PCA occlusion and 0 in 1 (10 %) patient, 2 in 3 (30 %) patients, 3 in 1 (10 %) patient, and 4 in 5 (50 %) patients with BA occlusion. FVH grade showed neither correlation with initial or follow-up diffusion-weighted image (DWI) lesion size nor DWI-perfusion-weighted imaging (PWI) mismatch ratio. Collateralization on dynamic 4D angiograms correlated inversely with initial DWI lesion size and moderately with the DWI-(PWI) mismatch ratio. The combination of distal FVH and collateralization grade on dynamic 4D angiograms correlated inversely with initial as well as follow-up DWI lesion size and highly with the DWI-PWI mismatch ratio. In posterior circulation occlusion, FVH is a frequent finding, but its prognostic value is limited. Dynamic 4D angiograms are advantageous to examine and graduate collateral blood flow. The combination of both parameters results in an improved characterization of collateral blood flow and might have prognostic relevance. (orig.)

  19. 4D cardiovascular magnetic resonance velocity mapping of alterations of right heart flow patterns and main pulmonary artery hemodynamics in tetralogy of Fallot

    Science.gov (United States)

    2012-01-01

    Background To assess changes in right heart flow and pulmonary artery hemodynamics in patients with repaired Tetralogy of Fallot (rTOF) we used whole heart, four dimensional (4D) velocity mapping (VM) cardiovascular magnetic resonance (CMR). Methods CMR studies were performed in 11 subjects with rTOF (5M/6F; 20.1 ± 12.4 years) and 10 normal volunteers (6M/4F; 34.2 ± 13.4 years) on clinical 1.5T and 3.0T MR scanners. 4D VM-CMR was performed using PC VIPR (Phase Contrast Vastly undersampled Isotropic Projection Reconstruction). Interactive streamline and particle trace visualizations of the superior and inferior vena cava (IVC and SVC, respectively), right atrium (RA), right ventricle (RV), and pulmonary artery (PA) were generated and reviewed by three experienced readers. Main PA net flow, retrograde flow, peak flow, time-to-peak flow, peak acceleration, resistance index and mean wall shear stress were quantified. Differences in flow patterns between the two groups were tested using Fisher's exact test. Differences in quantitative parameters were analyzed with the Kruskal-Wallis rank sum test. Results 4D VM-CMR was successfully performed in all volunteers and subjects with TOF. Right heart flow patterns in rTOF subjects were characterized by (a) greater SVC/IVC flow during diastole than systole, (b) increased vortical flow patterns in the RA and in the RV during diastole, and (c) increased helical or vortical flow features in the PA's. Differences in main PA retrograde flow, resistance index, peak flow, time-to-peak flow, peak acceleration and mean wall shear stress were statistically significant. Conclusions Whole heart 4D VM-CMR with PC VIPR enables detection of both normal and abnormal right heart flow patterns, which may allow for comprehensive studies to evaluate interdependencies of post-surgically altered geometries and hemodynamics. PMID:22313680

  20. S36. DIFFERENTIAL ENCODING OF SENSITIZATION AND CROSS SENSITIZATION TO PSYCHOSTIMULANTS AND ANTIPSYCHOTICS IN NUCLEUS ACCUMBENS D1- AND D2- RECEPTOR EXPRESSING MEDIUM SPINY NEURONS

    Science.gov (United States)

    Amato, Davide; Heinsbroek, Jasper; Kalivas, Peter W

    2018-01-01

    Abstract Background Nearly half of all individuals diagnosed with schizophrenia abuse addictive substances such as cocaine. Currently, the neurobiological mechanisms in patients with schizophrenia that lead to cocaine abuse are unknown. A possible explanation for the co-morbidity between schizophrenia and addiction is that the rewarding properties of cocaine reverse the diminished motivational drive caused by chronic antipsychotic regimen. Moreover, chronic antipsychotic treatment can sensitize and amplify cocaine rewarding effects and exacerbate psychoses. Methods The rewarding properties of cocaine are attributed to the differential effects of dopamine on D1 and D2 receptor-expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc). Using in vivo Ca2+ miniature microscopic imaging, we characterize the role of D1 and D2 MSN in mono- and a cross- sensitization paradigms. D1- and D2-Cre mice were injected with a Cre dependent calcium indicator (gCaMP6f) and implanted with a gradient index (GRIN) lens above the nucleus accumbens and calcium activity was recorded using a head mounted miniature microscope. Cocaine sensitization was measured after a classic repeated cocaine regiment and antipsychotic and psychostimulant cross-sensitization was measured by a single cocaine injection after chronic pre-treatment with haloperidol. Results We found that both D1-MSN and D2-MSN populations are modulated by initial cocaine experience and further modulated during the expression of cocaine sensitization. A subpopulation of D1-MSN displayed initial activation, but reduced activity during the expression of sensitization. By contrast, the majority of D2-MSNs were suppressed by initial cocaine experience, but became active during the expression of sensitization. Furthermore, activity of D1- and D2-MSNs bidirectionally related with the observed behavioral responses to cocaine. Cross-sensitization following haloperidol treatment led to increased behavioral responses to

  1. Estimation of left ventricular blood flow parameters: clinical application of patient-specific CFD simulations from 4D echocardiography

    Science.gov (United States)

    Larsson, David; Spühler, Jeannette H.; Günyeli, Elif; Weinkauf, Tino; Hoffman, Johan; Colarieti-Tosti, Massimiliano; Winter, Reidar; Larsson, Matilda

    2017-03-01

    Echocardiography is the most commonly used image modality in cardiology, assessing several aspects of cardiac viability. The importance of cardiac hemodynamics and 4D blood flow motion has recently been highlighted, however such assessment is still difficult using routine echo-imaging. Instead, combining imaging with computational fluid dynamics (CFD)-simulations has proven valuable, but only a few models have been applied clinically. In the following, patient-specific CFD-simulations from transthoracic dobutamin stress echocardiography have been used to analyze the left ventricular 4D blood flow in three subjects: two with normal and one with reduced left ventricular function. At each stress level, 4D-images were acquired using a GE Vivid E9 (4VD, 1.7MHz/3.3MHz) and velocity fields simulated using a presented pathway involving endocardial segmentation, valve position identification, and solution of the incompressible Navier-Stokes equation. Flow components defined as direct flow, delayed ejection flow, retained inflow, and residual volume were calculated by particle tracing using 4th-order Runge-Kutta integration. Additionally, systolic and diastolic average velocity fields were generated. Results indicated no major changes in average velocity fields for any of the subjects. For the two subjects with normal left ventricular function, increased direct flow, decreased delayed ejection flow, constant retained inflow, and a considerable drop in residual volume was seen at increasing stress. Contrary, for the subject with reduced left ventricular function, the delayed ejection flow increased whilst the retained inflow decreased at increasing stress levels. This feasibility study represents one of the first clinical applications of an echo-based patient-specific CFD-model at elevated stress levels, and highlights the potential of using echo-based models to capture highly transient flow events, as well as the ability of using simulation tools to study clinically complex

  2. A sensitive new method of ex vivo platelet deposition

    International Nuclear Information System (INIS)

    Badimon, L.; Fuster, V.; Dewanjee, M.K.; Romero, J.C.

    1982-01-01

    In 1978, an in vivo quantitative method of platelet aggregation based on the increment of weight of a rabbit tendon when superfused with flowing blood (3 ml/min) derived from a carotid artery of a cat and reentering the contralateral jugular vein was reported. TO increase the sensitivity of the method, researches labeled platelets with indium-111 and reinjected them after two hours; then, with a gamma counter, researches quantitated the 111 In-labeled platelets deposited on the superfused rabbit tendon. Results of the radioactivity method and of the weight method were compared. Researchers found that the 111 In-labeling of platelets was more precise and reproducible method, rendering possible the use of a small amount of blood without need for reentry into the venous system

  3. Nonenhanced magnetic resonance angiography (MRA) of the calf arteries at 3 Tesla: intraindividual comparison of 3D flow-dependent subtractive MRA and 2D flow-independent non-subtractive MRA

    Energy Technology Data Exchange (ETDEWEB)

    Knobloch, Gesine; Lauff, Marie-Teres; Hirsch, Sebastian; Hamm, Bernd; Wagner, Moritz [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Schwenke, Carsten [SCO:SSiS Statistical Consulting, Berlin (Germany)

    2016-12-15

    To prospectively compare 3D flow-dependent subtractive MRA vs. 2D flow-independent non-subtractive MRA for assessment of the calf arteries at 3 Tesla. Forty-two patients with peripheral arterial occlusive disease underwent nonenhanced MRA of calf arteries at 3 Tesla with 3D flow-dependent subtractive MRA (fast spin echo sequence; 3D-FSE-MRA) and 2D flow-independent non-subtractive MRA (balanced steady-state-free-precession sequence; 2D-bSSFP-MRA). Moreover, all patients underwent contrast-enhanced MRA (CE-MRA) as standard-of-reference. Two readers performed a per-segment evaluation for image quality (4 = excellent to 0 = non-diagnostic) and severity of stenosis. Image quality scores of 2D-bSSFP-MRA were significantly higher compared to 3D-FSE-MRA (medians across readers: 4 vs. 3; p < 0.0001) with lower rates of non-diagnostic vessel segments on 2D-bSSFP-MRA (reader 1: <1 % vs. 15 %; reader 2: 1 % vs. 29 %; p < 0.05). Diagnostic performance of 2D-bSSFP-MRA and 3D-FSE-MRA across readers showed sensitivities of 89 % (214/240) vs. 70 % (168/240), p = 0.0153; specificities: 91 % (840/926) vs. 63 % (585/926), p < 0.0001; and diagnostic accuracies of 90 % (1054/1166) vs. 65 % (753/1166), p < 0.0001. 2D flow-independent non-subtractive MRA (2D-bSSFP-MRA) is a robust nonenhanced MRA technique for assessment of the calf arteries at 3 Tesla with significantly higher image quality and diagnostic accuracy compared to 3D flow-dependent subtractive MRA (3D-FSE-MRA). (orig.)

  4. In vivo evaluation of femoral blood flow measured with magnetic resonance

    DEFF Research Database (Denmark)

    Henriksen, O; Ståhlberg, F; Thomsen, C

    1989-01-01

    , corrected for the T2 decay of non-flowing blood was used to calculate the blood flow. As a reference, the blood flow in the femoral artery was measured simultaneously with an invasive indicator dilution technique. T2 of non-flowing blood was measured in vivo in popliteal veins during regional circulatory...... arrest. The mean T2 of non-flowing blood was found to be 105 +/- 31 ms. The femoral blood flow ranged between 0 and 643 ml/min measured with MRI and between 280 and 531 ml/min measured by the indicator dilution technique. There was thus poor agreement between the two methods. The results indicate......Quantitative measurements of blood flow based on magnetic resonance imaging (MRI) using conventional multiple spin echo sequences were evaluated in vivo in healthy young volunteers. Blood flow was measured using MRI in the femoral vein. The initial slope of the multiple spin echo decay curve...

  5. Fast Blood Vector Velocity Imaging using ultrasound: In-vivo examples of complex blood flow in the vascular system

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Lindskov; Udesen, Jesper; Gran, Fredrik

    2008-01-01

    Conventional ultrasound methods for acquiring color flow images of the blood motion are restricted by a relatively low frame rate and angle dependent velocity estimates. The Plane Wave Excitation (PWE) method has been proposed to solve these limitations. The frame rate can be increased, and the 2-D...... vector velocity of the blood motion can be estimated. The transmitted pulse is not focused, and a full speckle image of the blood can be acquired for each emission. A 13 bit Barker code is transmitted simultaneously from each transducer element. The 2-D vector velocity of the blood is found using 2-D...... speckle tracking between segments in consecutive speckle images. The flow patterns of six bifurcations and two veins were investigated in-vivo. It was shown: 1) that a stable vortex in the carotid bulb was present opposed to other examined bifurcations, 2) that retrograde flow was present...

  6. Comparative studies of D2 receptors and cerebral blood flow in hemi-parkinsonism rats

    International Nuclear Information System (INIS)

    Lin, Y.; Lin, X.

    2000-01-01

    To study the relationship between dopamine (DA) D 2 receptors and cerebral blood flow in hemiparkinsonism rats. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat rotates toward the intact side was used to screen that rats, 125 I-IBZM in vivo autoradiography and 99m Tc-HM-PAO regional brain biodistribution were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD were used to measure the concentration of DA and it metabolites homovanillic acid (HVA), 3,4-dehydroxyphenyl acetic acid (DOPAC) in bilateral striatum (ST). The lesioned side ST DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and pseudo-operated control group, ST/cerebellum (CB) 125 I-IBZM uptake ratio was 8.04 ±0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (p 99m Tc 30.1±4.53% enhancement as compared to the intact side, and also show good correlation with 30 min Apo induced rotation numbers (r=0.98), the regional cerebral blood flow study didn't show significant difference between bilateral brain cortex area (p>0.05). The DA content decreased significantly and induced an up-regulation of ST D 2 receptor binding sites in 6-OH-DA lesioned side in hemi-parkinsonism rats, the increased percentage of lesioned-intact side ST/CB 125 I-IBZM uptake ratio showed good correlation with rotation behavior induced by Apo. Compare with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-parkinsonism

  7. Financial Development and Investment-Cash Flow Sensitivity

    Directory of Open Access Journals (Sweden)

    Jungwon Suh

    2007-06-01

    Full Text Available Using firm-level data from thirty-five countries around the world, this paper empirically examines whether investment-cash flow sensitivity reflects financial constraints. Recent US studies have raised questions on the prediction that investment-cash flow sensitivity is a measure of financial constraints. Looking at thirty-five countries with varying degrees of financial development, this study tests whether investment-cash flow sensitivity is in fact related to financial constraints. In most countries, the evidence supporting the argument that firms likely facing financially constraints display high investment-cash flow sensitivity is weak. Moreover, the evidence that firms in the absence of developed financial markets display high investment-cash flow sensitivity is also weak. Overall, the results from this international investigation do not support the prediction that investment-cash flow sensitivity reflects financial constraints.

  8. Evaluation of Marfan patients status post valve-sparing aortic root replacement with 4D flow.

    Science.gov (United States)

    Hope, Thomas A; Kvitting, John-Peder Escobar; Hope, Michael D; Miller, D Craig; Markl, Michael; Herfkens, Robert J

    2013-11-01

    Over the past two decades elective valve-sparing aortic root replacement (V-SARR) has become more common in the treatment of patients with aortic root and ascending aortic aneurysms. Currently there are little data available to predict complications in the post-operative population. The study goal was to determine if altered flow patterns in the thoracic aorta, as measured by MRI, are associated with complications after V-SARR. Time-resolved three-dimensional phase-contrast MRI (4D flow) was used to image 12 patients with Marfan syndrome after V-SARR. The patients were followed up for an average of 5.8 years after imaging and 8.2 years after surgery. Additionally 5 volunteers were imaged for comparison. Flow profiles were visualized during peak systole using streamlines. Wall shear stress estimates and normalized flow displacement were evaluated at multiple planes in the thoracic aorta. During the follow-up period, a single patient developed a Stanford Type B aortic dissection. At initial imaging, prior to the development of the dissection, the patient had altered flow patterns, wall shear stress estimates, and increased normalized flow displacement in the thoracic aorta in comparison to the remaining V-SARR patients and volunteers. This is the first follow-up study of patients after 4D flow imaging. An aortic dissection developed in one patient with altered flow patterns and hemodynamic stresses in the thoracic aorta. These results suggest that flow and altered hemodynamics may play a role in the development of post-operative intramural hematomas and dissections. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 vs. D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

    Science.gov (United States)

    Li, Jing Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

    2018-04-23

    Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well-established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder (PTSD) and opioid addiction. Transmission through PFC DA D4 receptors (D4R) has been shown to potentiate the emotional salience of normally non-salient emotional memories whereas transmission through PFC DA D1 receptors (D1R) has been demonstrated to selectively block recall of reward or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally sub-threshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II (CaMKII-α) or extracellular-signal-related-kinase 1-2 (ERK 1/2), following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. Significance Statement: Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex

  10. [Relationship between sensitivity of tumor cells to chemotherapeutic agent in vivo and in vitro: experiment with mouse lymphoma cells].

    Science.gov (United States)

    Li, Chuan-gang; Li, Mo-lin; Shu, Xiao-hong; Jia, Yu-jie; Liu, Yong-ji; Li, Ming

    2007-06-12

    To study the relationship of the sensitivity of tumor cells to chemotherapeutic agent between in vivo and in vitro. Mouse lymphoma cells of the line E14 were cultured and melphalan resistant EL4 cell line (EL4/melphalan) was established by culturing EL4 cells with continuous low-concentration and intermittent gradually-increasing-concentration of melphalan in vitro. MTT assay was used to evaluate the drug sensitivity and the resistance index of the EL4/melphalan cells to melphalan was calculated. EL4/melphalan and EL4 cells of the concentration of 5 x 10(8)/L were inoculated separately into 20 C57BL/6 mice subcutaneously. 12 days later, the EL4 and EL4/melphalan tumor-bearing mice were randomly divided into 2 groups respectively, 5 mice in each group. Treatment groups were given 7.5 mg/kg melphalan intraperitoneally, and control groups were given the same volume of normal saline. The tumor size was observed every other day. Compared with the EL4 cells, the EL4/melphalan cells had no obvious changes morphologically. They could grow in RPMI 1640 medium containing 5 mg/ml melphalan. The resistance index was 2.87 against melphalan. After the treatment of melphalan of the dose 7.5 mg/kg, the tumor sizes of the treatment groups and control groups inoculated with both EL4 cells and the EL4/melphalan cells gradually decreased at the similar speed, and about one week later all tumors disappeared. However, the tumors of the control groups grew progressively and all the mice died at last. The chemotherapeutic effects of tumors in vivo have nothing to do with the effects of the chemotherapeutic agents on tumor cells in vitro. The tumor cells resistant to melphalan in vitro remain sensitive to the drug in vivo.

  11. Convergence acceleration of two-phase flow calculations in FLICA-4. A thermal-hydraulic 3D computer code

    International Nuclear Information System (INIS)

    Toumi, I.

    1995-01-01

    Time requirements for 3D two-phase flow steady state calculations are generally long. Usually, numerical methods for steady state problems are iterative methods consisting in time-like methods that are marched to a steady state. Based on the eigenvalue spectrum of the iteration matrix for various flow configuration, two convergence acceleration techniques are discussed; over-relaxation and eigenvalue annihilation. This methods were applied to accelerate the convergence of three dimensional steady state two-phase flow calculations within the FLICA-4 computer code. These acceleration methods are easy to implement and no extra computer memory is required. Successful results are presented for various test problems and a saving of 30 to 50 % in CPU time have been achieved. (author). 10 refs., 4 figs

  12. Complex blood flow quantification using real-time in vivo vector flow ultrasound

    DEFF Research Database (Denmark)

    Pedersen, Mads Møller; Pihl, Michael Johannes; Per, Haugaard

    A new method to define and quantify complex blood flow is presented. The standard deviations of real-time in vivo vector flow angle estimates are used. Using vector flow ultrasound imaging both carotid bifurcations of two healthy volunteers were scanned. Scanning was performed with a 7.6 MHz linear...... transducer (8670, B-K Medical, Denmark) and a commercial vector flow ultrasound scanner (ProFocus 2202, B-K Medical). Eight video sequences of one cardiac cycle were obtained. In every frame boxes were placed to define the common carotid artery(box1) and the carotid bulb(box2). The standard deviation...... for the vector angle estimates was calculated for each box in every frame. For comparison three ultrasound experts evaluated the presence of complex flow in every box. The trial was blinded. For every sequence the mean standard deviation of the vector angle estimates were calculated for box1 {39...

  13. 3-D Velocity Estimation for Two Planes in vivo

    DEFF Research Database (Denmark)

    Holbek, Simon; Pihl, Michael Johannes; Ewertsen, Caroline

    2014-01-01

    3-D velocity vectors can provide additional flow information applicable for diagnosing cardiovascular diseases e.g. by estimating the out-of-plane velocity component. A 3-D version of the Transverse Oscillation (TO) method has previously been used to obtain this information in a carotid flow...... and stored on the experimental scanner SARUS. The full 3-D velocity profile can be created and examined at peak-systole and end-diastole without ECG gating in two planes. Maximum out-of-plane velocities for the three peak-systoles and end-diastoles were 68.5 5.1 cm/s and 26.3 3.3 cm/s, respectively....... In the longitudinal plane, average maximum peak velocity in flow direction was 65.2 14.0 cm/s at peak-systole and 33.6 4.3 cm/s at end-diastole. A commercial BK Medical ProFocus UltraView scanner using a spectral estimator gave 79.3 cm/s and 14.6 cm/s for the same volunteer. This demonstrates that real-time 3-D...

  14. Comparative studies of D2 receptors and cerebral blood flow in hemi-Parkinsonism rats

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    2000-01-01

    Objective: To study the relationship between dopamine D 2 receptors and cerebral blood flow in hemi-Parkinsonism rats. Methods: Hemi-Parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat to rotate toward the intact side was used to select the rat models, 125 I-IBZM in vivo autoradiography and 99 Tc m -HMPAO regional cerebral biodistribution analysis were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD was used to measure striatum DA and its metabolite content . Results: the lesioned side striatum DA and its metabolites homovanillic acid (HVA) 3,4-dihyroxy-phenylacetic acid (DOPAC) reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-Parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (P 0.05). Conclusions: the 6-OH-DA lesioned side DA content decreased significantly and thus induced a compensative up-regulation of striatum D 2 receptor binding sites in hemi-Parkinsonism rats, which show good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-Parkinsonism

  15. 3D bioprinting and its in vivo applications.

    Science.gov (United States)

    Hong, Nhayoung; Yang, Gi-Hoon; Lee, JaeHwan; Kim, GeunHyung

    2018-01-01

    The purpose of 3D bioprinting technology is to design and create functional 3D tissues or organs in situ for in vivo applications. 3D cell-printing, or additive biomanufacturing, allows the selection of biomaterials and cells (bioink), and the fabrication of cell-laden structures in high resolution. 3D cell-printed structures have also been used for applications such as research models, drug delivery and discovery, and toxicology. Recently, numerous attempts have been made to fabricate tissues and organs by using various 3D printing techniques. However, challenges such as vascularization are yet to be solved. This article reviews the most commonly used 3D cell-printing techniques with their advantages and drawbacks. Furthermore, up-to-date achievements of 3D bioprinting in in vivo applications are introduced, and prospects for the future of 3D cell-printing technology are discussed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 444-459, 2018. © 2017 Wiley Periodicals, Inc.

  16. Label-free in vivo optical micro-angiography imaging of cerebral capillary blood flow within meninges and cortex in mice with the skull left intact

    Science.gov (United States)

    Jia, Yali; Wang, Ruikang K.

    2011-03-01

    Abnormal microcirculation within meninges is common in many neurological diseases. There is a need for an imaging method that is capable of visualizing functional meningeal microcirculations alone, preferably decoupled from the cortical blood flow. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to ~2 mm, with an unprecedented imaging sensitivity to the blood flow at ~4 μm/s. In this study, we demonstrate the utility of ultra-high sensitive OMAG in imaging the detailed blood flow distributions, at a capillary level resolution, within meninges and cortex in mice with the cranium left intact. The results indicate that OMAG can be a valuable tool for the study of meningeal circulations.

  17. Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using 18F/11C-fallypride

    International Nuclear Information System (INIS)

    Kaur, Jasmeet; Khararjian, Armen; Coleman, Robert A.; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

    2014-01-01

    Objectives: The spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18 F-fallypride and 11 C-fallypride. Methods: Male Sprague–Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18 F-fallypride scan or a 11 C-fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results: In vitro studies showed 18 F-fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18 F-fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18 F-fallypride and 11 C-fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18 F-fallypride in spinal cord sections. Conclusions: Our studies showed 18 F-fallypride and 11 C-fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord

  18. SU-F-SPS-06: Implementation of a Back-Projection Algorithm for 2D in Vivo Dosimetry with An EPID System

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez Reyes, B; Rodriguez Perez, E; Sosa Aquino, M [Universidad de Guanajuato, Leon, Guanajuato (Mexico)

    2016-06-15

    Purpose: To implement a back-projection algorithm for 2D dose reconstructions for in vivo dosimetry in radiation therapy using an Electronic Portal Imaging Device (EPID) based on amorphous silicon. Methods: An EPID system was used to calculate dose-response function, pixel sensitivity map, exponential scatter kernels and beam hardenig correction for the back-projection algorithm. All measurements were done with a 6 MV beam. A 2D dose reconstruction for an irradiated water phantom (30×30×30 cm{sup 3}) was done to verify the algorithm implementation. Gamma index evaluation between the 2D reconstructed dose and the calculated with a treatment planning system (TPS) was done. Results: A linear fit was found for the dose-response function. The pixel sensitivity map has a radial symmetry and was calculated with a profile of the pixel sensitivity variation. The parameters for the scatter kernels were determined only for a 6 MV beam. The primary dose was estimated applying the scatter kernel within EPID and scatter kernel within the patient. The beam hardening coefficient is σBH= 3.788×10{sup −4} cm{sup 2} and the effective linear attenuation coefficient is µAC= 0.06084 cm{sup −1}. The 95% of points evaluated had γ values not longer than the unity, with gamma criteria of ΔD = 3% and Δd = 3 mm, and within the 50% isodose surface. Conclusion: The use of EPID systems proved to be a fast tool for in vivo dosimetry, but the implementation is more complex that the elaborated for pre-treatment dose verification, therefore, a simplest method must be investigated. The accuracy of this method should be improved modifying the algorithm in order to compare lower isodose curves.

  19. A simple and sensitive method for determination of vitamins D3 and K1 in rat plasma: application for an in vivo pharmacokinetic study.

    Science.gov (United States)

    Gershkovich, Pavel; Ibrahim, Fady; Sivak, Olena; Darlington, Jerald W; Wasan, Kishor M

    2014-03-01

    To develop and to validate a simple but sensitive method for determination of vitamins D3 and K1 in rat plasma. The sample treatment included protein precipitation by cold acetonitrile, evaporation, reconstitution with methanol and filtration. The chromatography conditions included Xterra RP18 3.5 µm 4.6 × 100 mm column at ambient temperature and mobile phase consisting of methanol/water (93/7, v/v) at 0.5 mL/min flow rate. Vitamin D3 and probucol were detected at 265 nm and vitamin K1 at 239 nm. Rats were administered intravenously by 0.1 mg/kg of vitamin D3 or K1 and the blood samples were withdrawn pre-administration and at pre-determined time points post-administration. The pharmacokinetic analysis was performed using a non-compartmental approach. The calibration curves in rat plasma were linear up to 5000 ng/mL for both vitamins. The limit of quantification (LOQ) was 20 ng/mL for vitamin D3 and 40 ng/mL for K1. Inter- and intra-day precision and accuracy were below 15%. The pharmacokinetic parameters of vitamin D3 following intravenous administration were: AUC0-∞ = 11323 ± 1081 h × ng/mL, Vd = 218 ± 80 mL/kg, CL = 8.9 ± 0.8 mL/h/kg, t1/2 = 16.8 ± 5 h; and of vitamin K1: AUC0-∞ = 2495 ± 297 h × ng/mL, Vd = 60 ±24 mL/kg, CL = 40.5 ± 5.1 mL/h/kg, t1/2 = 1.1 ±0.5 h. The developed HPLC-UV assay is a simple and sensitive method for the determination of vitamins D3 and K1 in rat plasma. A higher dose of vitamin K1 should be used in future studies for accurate estimation of pharmacokinetic parameters. The data show the suitability of the assay for pharmacokinetic studies in rats.

  20. Effects of CD49d-targeted antisense-oligonucleotide on α4 integrin expression and function of acute lymphoblastic leukemia cells: Results of in vitro and in vivo studies.

    Directory of Open Access Journals (Sweden)

    Yann Duchartre

    Full Text Available We recently demonstrated the effectiveness of blocking CD49d with anti-functional antibodies or small molecule inhibitors as a rational targeted approach to the treatment of acute leukemia in combination with chemotherapy. Antisense oligonucleotide promises to be no less specific than antibodies and inhibitors, but more interesting for pharmacokinetics and pharmacodynamics. We addressed this using the published CD49d antisense drug ATL1102. In vitro, we incubated/nucleofected the ALL cell line Kasumi-2 with ATL1102. In vivo, immunodeficient hosts were engrafted with primary ALL cells and treated with ATL1102. Changes in expression of CD49d mRNA and CD49d protein, and of cooperating gene products, including ß1 integrin and CXCR4, as well as survival in the mouse experiments were quantified. We observed dose-dependent down-regulation of CD49d mRNA and protein levels and its partner integrin ß1 cell surface protein level and, up-regulation of CXCR4 surface expression. The suppression was more pronounced after nucleofection than after incubation, where down-regulation was significant only at the higher doses. In vivo effects of ATL1102 were not sufficient to translate into "clinical" benefit in the leukemia model. In summary, antisense oligonucleotides are successful tools for specifically modulating gene expression but sufficient delivery to down-regulate CD49d in vivo may be difficult to achieve.

  1. In vivo biomarker expression patterns are preserved in 3D cultures of Prostate Cancer

    International Nuclear Information System (INIS)

    Windus, Louisa C.E.; Kiss, Debra L.; Glover, Tristan; Avery, Vicky M.

    2012-01-01

    Here we report that Prostate Cancer (PCa) cell-lines DU145, PC3, LNCaP and RWPE-1 grown in 3D matrices in contrast to conventional 2D monolayers, display distinct differences in cell morphology, proliferation and expression of important biomarker proteins associated with cancer progression. Consistent with in vivo growth rates, in 3D cultures, all PCa cell-lines were found to proliferate at significantly lower rates in comparison to their 2D counterparts. Moreover, when grown in a 3D matrix, metastatic PC3 cell-lines were found to mimic more precisely protein expression patterns of metastatic tumour formation as found in vivo. In comparison to the prostate epithelial cell-line RWPE-1, metastatic PC3 cell-lines exhibited a down-regulation of E-cadherin and α6 integrin expression and an up-regulation of N-cadherin, Vimentin and β1 integrin expression and re-expressed non-transcriptionally active AR. In comparison to the non-invasive LNCaP cell-lines, PC3 cells were found to have an up-regulation of chemokine receptor CXCR4, consistent with a metastatic phenotype. In 2D cultures, there was little distinction in protein expression between metastatic, non-invasive and epithelial cells. These results suggest that 3D cultures are more representative of in vivo morphology and may serve as a more biologically relevant model in the drug discovery pipeline. -- Highlights: ► We developed and optimised 3D culturing techniques for Prostate Cancer cell-lines. ► We investigated biomarker expression in 2D versus 3D culture techniques. ► Metastatic PC3 cells re-expressed non-transcriptionally active androgen receptor. ► Metastatic PCa cell lines retain in vivo-like antigenic profiles in 3D cultures

  2. Phospholipase C δ4 regulates cold sensitivity in mice.

    Science.gov (United States)

    Yudin, Yevgen; Lutz, Brianna; Tao, Yuan-Xiang; Rohacs, Tibor

    2016-07-01

    The cold- and menthol-activated transient receptor potential melastatin 8 (TRPM8) channels are thought to be regulated by phospholipase C (PLC), but neither the specific PLC isoform nor the in vivo relevance of this regulation has been established. Here we identify PLCδ4 as the key PLC isoform involved in regulation of TRPM8 channels in vivo. We show that in small PLCδ4(-/-) TRPM8-positive dorsal root ganglion neurons cold, menthol and WS-12, a selective TRPM8 agonist, evoked significantly larger currents than in wild-type neurons, and action potential frequencies induced by menthol or by current injections were also higher in PLCδ4(-/-) neurons. PLCδ4(-/-) mice showed increased behavioural responses to evaporative cooling, and this effect was inhibited by a TRPM8 antagonist; behavioural responses to heat and mechanical stimuli were not altered. We provide evidence for the involvement of a specific PLC isoform in the regulation of cold sensitivity in mice by regulating TRPM8 activity. The transient receptor potential melastatin 8 (TRPM8) ion channel is a major sensor of environmental low temperatures. Ca(2+) -induced activation of phospholipase C (PLC) has been implied in the regulation of TRPM8 channels during menthol- and cold-induced desensitization in vitro. Here we identify PLCδ4 as the key PLC isoform involved in regulation of TRPM8 in sensory dorsal root ganglion (DRG) neurons. We identified two TRPM8-positive neuronal subpopulations, based on their cell body size. Most TRPM8-positive small neurons also responded to capsaicin, and had significantly larger menthol-induced inward current densities than medium-large cells, most of which did not respond to capsaicin. Small, but not medium-large, PLCδ4(-/-) neurons showed significantly larger currents induced by cold, menthol or WS-12, a specific TRPM8 agonist, compared to wild-type (WT) neurons, but TRPM8 protein levels were not different between the two groups. In current-clamp experiments small neurons

  3. Time-resolved blood flow measurement in the in vivo mouse model by optical frequency domain imaging

    Science.gov (United States)

    Walther, Julia; Mueller, Gregor; Meissner, Sven; Cimalla, Peter; Homann, Hanno; Morawietz, Henning; Koch, Edmund

    2009-07-01

    In this study, we demonstrate that phase-resolved Doppler optical frequency domain imaging (OFDI) is very suitable to quantify the pulsatile blood flow within a vasodynamic measurement in the in vivo mouse model. For this, an OFDI-system with a read-out rate of 20 kHz and a center wavelength of 1320 nm has been used to image the time-resolved murine blood flow in 300 μμm vessels. Because OFDI is less sensitive to fringe washout due to axial sample motion, it is applied to analyze the blood flow velocities and the vascular dynamics in six-week-old C57BL/6 mice compared to one of the LDLR knockout strain kept under sedentary conditions or with access to voluntary wheel running. We have shown that the systolic as well as the diastolic phase of the pulsatile arterial blood flow can be well identified at each vasodynamic state. Furthermore, the changes of the flow velocities after vasoconstriction and -dilation were presented and interpreted in the entire physiological context. With this, the combined measurement of time-resolved blood flow and vessel diameter provides the basis to analyze the vascular function and its influence on the blood flow of small arteries of different mouse strains in response to different life styles.

  4. Characterization of Chlamydia MurC-Ddl, a fusion protein exhibiting D-alanyl-D-alanine ligase activity involved in peptidoglycan synthesis and D-cycloserine sensitivity.

    Science.gov (United States)

    McCoy, Andrea J; Maurelli, Anthony T

    2005-07-01

    Recent characterization of chlamydial genes encoding functional peptidoglycan (PG)-synthesis proteins suggests that the Chlamydiaceae possess the ability to synthesize PG yet biochemical evidence for the synthesis of PG has yet to be demonstrated. The presence of D-amino acids in PG is a hallmark of bacteria. Chlamydiaceae do not appear to encode amino acid racemases however, a D-alanyl-D-alanine (D-Ala-D-Ala) ligase homologue (Ddl) is encoded in the genome. Thus, we undertook a genetics-based approach to demonstrate and characterize the D-Ala-D-Ala ligase activity of chlamydial Ddl, a protein encoded as a fusion with MurC. The full-length murC-ddl fusion gene from Chlamydia trachomatis serovar L2 was cloned and placed under the control of the arabinose-inducible ara promoter and transformed into a D-Ala-D-Ala ligase auxotroph of Escherichia coli possessing deletions of both the ddlA and ddlB genes. Viability of the E. coliDeltaddlADeltaddlB mutant in the absence of exogenous D-Ala-D-Ala dipeptide became dependent on the expression of the chlamydial murC-ddl thus demonstrating functional ligase activity. Domain mapping of the full-length fusion protein and site-directed mutagenesis of the MurC domain revealed that the structure of the full fusion protein but not MurC enzymatic activity was required for ligase activity in vivo. Recombinant MurC-Ddl exhibited substrate specificity for D-Ala. Chlamydia growth is inhibited by D-cycloserine (DCS) and in vitro analysis provided evidence for the chlamydial MurC-Ddl as the target for DCS sensitivity. In vivo sensitivity to DCS could be reversed by addition of exogenous D-Ala and D-Ala-D-Ala. Together, these findings further support our hypothesis that PG is synthesized by members of the Chlamydiaceae family and suggest that D-amino acids, specifically D-Ala, are present in chlamydial PG.

  5. Effect of Water Cut on Pressure Drop of Oil (D130) -Water Flow in 4″Horizontal Pipe

    Science.gov (United States)

    Basha, Mehaboob; Shaahid, S. M.; Al-Hems, Luai M.

    2018-03-01

    The oil-water flow in pipes is a challenging subject that is rich in physics and practical applications. It is often encountered in many oil and chemical industries. The pressure gradient of two phase flow is still subject of immense research. The present study reports pressure measurements of oil (D130)-water flow in a horizontal 4″ diameter stainless steel pipe at different flow conditions. Experiments were carried out for different water cuts (WC); 0-100%. Inlet oil-water flow rates were varied from 4000 to 8000 barrels-per-day in steps of 2000. It has been found that the frictional pressure drop decreases for WC = 0 - 40 %. With further increase in WC, friction pressure drop increases, this could be due to phase inversion.

  6. 4D-CT Lung registration using anatomy-based multi-level multi-resolution optical flow analysis and thin-plate splines.

    Science.gov (United States)

    Min, Yugang; Neylon, John; Shah, Amish; Meeks, Sanford; Lee, Percy; Kupelian, Patrick; Santhanam, Anand P

    2014-09-01

    The accuracy of 4D-CT registration is limited by inconsistent Hounsfield unit (HU) values in the 4D-CT data from one respiratory phase to another and lower image contrast for lung substructures. This paper presents an optical flow and thin-plate spline (TPS)-based 4D-CT registration method to account for these limitations. The use of unified HU values on multiple anatomy levels (e.g., the lung contour, blood vessels, and parenchyma) accounts for registration errors by inconsistent landmark HU value. While 3D multi-resolution optical flow analysis registers each anatomical level, TPS is employed for propagating the results from one anatomical level to another ultimately leading to the 4D-CT registration. 4D-CT registration was validated using target registration error (TRE), inverse consistency error (ICE) metrics, and a statistical image comparison using Gamma criteria of 1 % intensity difference in 2 mm(3) window range. Validation results showed that the proposed method was able to register CT lung datasets with TRE and ICE values <3 mm. In addition, the average number of voxel that failed the Gamma criteria was <3 %, which supports the clinical applicability of the propose registration mechanism. The proposed 4D-CT registration computes the volumetric lung deformations within clinically viable accuracy.

  7. Quantification of In Vivo 2D Vector Flow Ultrasound

    DEFF Research Database (Denmark)

    Pedersen, Mads Møller

    2012-01-01

    by the vector technique. With the conventional technique, the manual setting of the angle is operator dependent. With the calculated vector angle, this operator is relieved from the angle setting and the measurement is angle corrected by the identical method every time. With study II the carotid bifurcation...... the clinical parameters: peak systole velocity, end diastole velocity, resistive index, and the flow direction. The results showed significant difference on the velocities and the resistive index. However, no significant difference on the manually defined flow angle and the calculated mean flow angle...... including the carotid bulb and the common carotid artery were scanned on 8 healthy volunteers. The flow patterns of the two structures were outlined and presented to each of 5 experienced radiologists. The complexity of the identical areas were calculated by the vector concentration and compared...

  8. Fluid mechanics of blood flow in human fetal left ventricles based on patient-specific 4D ultrasound scans.

    Science.gov (United States)

    Lai, Chang Quan; Lim, Guat Ling; Jamil, Muhammad; Mattar, Citra Nurfarah Zaini; Biswas, Arijit; Yap, Choon Hwai

    2016-10-01

    The mechanics of intracardiac blood flow and the epigenetic influence it exerts over the heart function have been the subjects of intense research lately. Fetal intracardiac flows are especially useful for gaining insights into the development of congenital heart diseases, but have not received due attention thus far, most likely because of technical difficulties in collecting sufficient intracardiac flow data in a safe manner. Here, we circumvent such obstacles by employing 4D STIC ultrasound scans to quantify the fetal heart motion in three normal 20-week fetuses, subsequently performing 3D computational fluid dynamics simulations on the left ventricles based on these patient-specific heart movements. Analysis of the simulation results shows that there are significant differences between fetal and adult ventricular blood flows which arise because of dissimilar heart morphology, E/A ratio, diastolic-systolic duration ratio, and heart rate. The formations of ventricular vortex rings were observed for both E- and A-wave in the flow simulations. These vortices had sufficient momentum to last until the end of diastole and were responsible for generating significant wall shear stresses on the myocardial endothelium, as well as helicity in systolic outflow. Based on findings from previous studies, we hypothesized that these vortex-induced flow properties play an important role in sustaining the efficiency of diastolic filling, systolic pumping, and cardiovascular flow in normal fetal hearts.

  9. Photocatalytic oxidation of low concentration 2,4-D solution with new TiO2 fiber catalyst in a continuous flow reactor.

    Science.gov (United States)

    Terashima, Y; Ozaki, H; Giri, R R; Tano, T; Nakatsuji, S; Takanami, R; Taniguchi, S

    2006-01-01

    Environmental pollution by low concentrations of 2,4-Dichlorophenoxyacetic acid (2,4-D) is a concern these days due to ever increasingly stringent regulations. Photocatalysis with immobilized TiO2 fiber is a promising oxidation method. Laboratory experiments on photocatalytic degradation of 0.045 mmol l(-1) 2,4-D with the world's first high-strength TiO2 fiber catalyst were carried out in a continuous flow reactor in which the degradations were, in general, similar to those with high 2,4-D concentrations investigated elsewhere. Degradation and mineralization of 2,4-D were significantly enhanced with no initial pH adjustments. The rate constants for total organic carbon (TOC) without pH adjustment were about two-fold bigger than the pH adjustment cases. CO2 gas measurement and carbon mass-balance were carried out for the first time, where about 34% organic carbon converted into CO2 gas during four-hour oxidation. 2,4-Dichlorophenol (2,4-DCP), phenol, benzyl alcohol and two unknowns (RT = 2.65 and 3.78 min.) were detected as aromatic intermediates while Phenol was the new aromatic in HPLC analysis. Dechlorination efficiencies were high (> 70%) in all the cases, and more than 90% efficiencies were observed in chloride mass balance. Bigger flow rates and solution temperature fixed at 20 degrees C without pH adjustment greatly enhanced 2,4-D mineralization. These results can be an important basis in applying the treatment method for dioxin-contaminated water and wastewater.

  10. Biokinetic Analysis and Metabolic Fate of 2,4-D in 2,4-D-Resistant Soybean (Glycine max).

    Science.gov (United States)

    Skelton, Joshua J; Simpson, David M; Peterson, Mark A; Riechers, Dean E

    2017-07-26

    The Enlist weed control system allows the use of 2,4-D in soybean but slight necrosis in treated leaves may be observed in the field. The objectives of this research were to measure and compare uptake, translocation, and metabolism of 2,4-D in Enlist (E, resistant) and non-AAD-12 transformed (NT, sensitive) soybeans. The adjuvant from the Enlist Duo herbicide formulation (ADJ) increased 2,4-D uptake (36%) and displayed the fastest rate of uptake (U 50 = 0.2 h) among treatments. E soybean demonstrated a faster rate of 2,4-D metabolism (M 50 = 0.2 h) compared to NT soybean, but glyphosate did not affect 2,4-D metabolism. Metabolites of 2,4-D in E soybean were qualitatively different than NT. Applying 2,4-D-ethylhexyl ester instead of 2,4-D choline (a quaternary ammonium salt) eliminated visual injury to E soybean, likely due to the time required for initial de-esterification and bioactivation. Excessive 2,4-D acid concentrations in E soybean resulting from ADJ-increased uptake may significantly contribute to foliar injury.

  11. [Standardization of the quantitative flow cytometric test with anti-D antibodies for fetomaternal hemorrhage in RhD negative women].

    Science.gov (United States)

    Spychalska, Justyna; Uhrynowska, Małgorzata; Pyl, Hanna; Klimczak-Jajor, Edyta; Kopeć, Izabella; Peciakowska, Małgorzata; Gutowska, Renata; Gawlak, Maciej; Słomska, Sylwia; Dąbkowska, Syiwia; Szczecina, Roman; Dębska, Marzena; Brojer, Ewa

    2015-07-01

    In order to determine the appropriate dose of anti-D immunoglobulin to be administered as a preventive measure against hemolytic disease of the fetus/newborn in the subsequent pregnancy it is necessary to assess the number of fetal red blood cells that infiltrate/penetrate into the maternal circulation as a result of fetomaternal hemorrhage (FMH). One of the quantitative methods of FMH analysis is based on flow cytometry (FACS) which makes use of monoclonal antibodies to RhD antigen (anti-D test). The aim of the study was to further develop the method, evaluate its sensitivity and reproducibility and to compare it with the test based on the detection of fetal hemoglobin (HbF). The FACS study involved 20 RhD negative pregnant women and 80 RhD negative women after delivery. The following monoclonal antibodies were used: BRAD 3 FITC (anti-RhD antigen), CD45 PerCP (anti leukocyte antigen CD45), and anti-HbF PE. The fluorescence intensity of cells incubated with BRAD 3 FITC was demonstrated to depend on the RhD antigen expression, though the anti-D test also detects the weak D variant. The CD45 PerCP antibodies increased the sensitivity of anti-D test since they eliminated the leukocytes which non-specifically bind anti-D from the analysis. The presence of anti-D antibodies in maternal plasma does not affect the quantitative assessment of the fetal RhD positive fetal cells with BRAD 3 FITC. In case of FMH, the results of the anti-D test were similar to those with anti-HbF antibodies. The flow cytometric test with anti-D and anti-CD45 is useful in the assessment of the fetomaternal hemorrhage in RhD negative women. The sensitivity of the test is estimated at 0.05%.

  12. Sensitivity analysis of time-dependent laminar flows

    International Nuclear Information System (INIS)

    Hristova, H.; Etienne, S.; Pelletier, D.; Borggaard, J.

    2004-01-01

    This paper presents a general sensitivity equation method (SEM) for time dependent incompressible laminar flows. The SEM accounts for complex parameter dependence and is suitable for a wide range of problems. The formulation is verified on a problem with a closed form solution obtained by the method of manufactured solution. Systematic grid convergence studies confirm the theoretical rates of convergence in both space and time. The methodology is then applied to pulsatile flow around a square cylinder. Computations show that the flow starts with symmetrical vortex shedding followed by a transition to the traditional Von Karman street (alternate vortex shedding). Simulations show that the transition phase manifests itself earlier in the sensitivity fields than in the flow field itself. Sensitivities are then demonstrated for fast evaluation of nearby flows and uncertainty analysis. (author)

  13. Studying circulation times of liver cancer cells by in vivo flow cytometry

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G; Li, Y; Fan, Z; Guo, J; Tan, X; Wei, X, E-mail: xwei@fudan.edu.cn [Institutes of Biomedical Sciences, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032 (China)

    2011-02-01

    Hepatocellular carcinoma (HCC) may metastasize to lung kidney and many other organs. The survival rate is almost zero for metastatic HCC patients. Molecular mechanisms of HCC metastasis need to be understood better and new therapies must be developed. A recently developed 'in vivo flow cytometer' combined with real-time confocal fluorescence imaging are used to assess spreading and the circulation kinetics of liver tumor cells. The in vivo flow cytometer has the capability to detect and quantify continuously the number and flow characteristics of fluorescently labeled cells in vivo in real time without extracting blood sample. We have measured the depletion kinetics of two related human HCC cell lines high-metastatic HCCLM3 cells and low-metastatic HepG2 cells which were from the same origin and obtained by repetitive screenings in mice. >60% HCCLM3 cells are depleted within the first hour. Interestingly the low-metastatic HepG2 cells possess noticeably slower depletion kinetics. In comparison <40% HepG2 cells are depleted within the first hour. The differences in depletion kinetics might provide insights into early metastasis processes.

  14. Facilitating tumor functional assessment by spatially relating 3D tumor histology and in vivo MRI: image registration approach.

    Directory of Open Access Journals (Sweden)

    Lejla Alic

    Full Text Available BACKGROUND: Magnetic resonance imaging (MRI, together with histology, is widely used to diagnose and to monitor treatment in oncology. Spatial correspondence between these modalities provides information about the ability of MRI to characterize cancerous tissue. However, registration is complicated by deformations during pathological processing, and differences in scale and information content. METHODOLOGY/PRINCIPAL FINDINGS: This study proposes a methodology for establishing an accurate 3D relation between histological sections and high resolution in vivo MRI tumor data. The key features of the methodology are: 1 standardized acquisition and processing, 2 use of an intermediate ex vivo MRI, 3 use of a reference cutting plane, 4 dense histological sampling, 5 elastic registration, and 6 use of complete 3D data sets. Five rat pancreatic tumors imaged by T2*-w MRI were used to evaluate the proposed methodology. The registration accuracy was assessed by root mean squared (RMS distances between manually annotated landmark points in both modalities. After elastic registration the average RMS distance decreased from 1.4 to 0.7 mm. The intermediate ex vivo MRI and the reference cutting plane shared by all three 3D images (in vivo MRI, ex vivo MRI, and 3D histology data were found to be crucial for the accurate co-registration between the 3D histological data set and in vivo MRI. The MR intensity in necrotic regions, as manually annotated in 3D histology, was significantly different from other histologically confirmed regions (i.e., viable and hemorrhagic. However, the viable and the hemorrhagic regions showed a large overlap in T2(*-w MRI signal intensity. CONCLUSIONS: The established 3D correspondence between tumor histology and in vivo MRI enables extraction of MRI characteristics for histologically confirmed regions. The proposed methodology allows the creation of a tumor database of spatially registered multi-spectral MR images and multi-stained 3D

  15. Preliminary study of in vivo hemodynamic analysis of intracranial aneurysms using time-resolved three-dimensional phase-contrast MRI and in-house software [Presidential award proceedings

    International Nuclear Information System (INIS)

    Isoda, Haruo; Ohkura, Yasuhide; Seo, Taro

    2007-01-01

    We calculated in vivo wall shear stress (WSS) and streamlines of intracranial aneurysms and analyzed the relationships between the hemodynamics and WSS of the aneurysms using time-resolved three-dimensional (3D) phase-contrast magnetic resonance (MR) imaging (4D-Flow) and in-house software. We studied 10 subjects with 11 aneurysms. 4D-flow was performed using a 1.5T GE MR scanner with head coil. 3D time-of-flight (TOF) MR angiography was performed for geometric information. The software calculated the WSS based on interpolated shearing velocity using the data set obtained by 4D-flow near the wall and provided us with 3D streamlines. We acquired 3D streamlines and WSS distribution maps in arbitrary directions during the cardiac phase for all intracranial aneurysms, and each intracranial aneurysm in this study had at least one spiral flow. We noted lower WSS with lower flow velocities at the apex of the spiral flow. (author)

  16. In vivo 1D and 2D correlation MR spectroscopy of the soleus muscle at 7T

    Science.gov (United States)

    Ramadan, Saadallah; Ratai, Eva-Maria; Wald, Lawrence L.; Mountford, Carolyn E.

    2010-05-01

    AimThis study aims to (1) undertake and analyse 1D and 2D MR correlation spectroscopy from human soleus muscle in vivo at 7T, and (2) determine T1 and T2 relaxation time constants at 7T field strength due to their importance in sequence design and spectral quantitation. MethodSix healthy, male volunteers were consented and scanned on a 7T whole-body scanner (Siemens AG, Erlangen, Germany). Experiments were undertaken using a 28 cm diameter detunable birdcage coil for signal excitation and an 8.5 cm diameter surface coil for signal reception. The relaxation time constants, T1 and T2 were recorded using a STEAM sequence, using the 'progressive saturation' method for the T1 and multiple echo times for T2. The 2D L-Correlated SpectroscopY (L-COSY) method was employed with 64 increments (0.4 ms increment size) and eight averages per scan, with a total time of 17 min. ResultsT1 and T2 values for the metabolites of interest were determined. The L-COSY spectra obtained from the soleus muscle provided information on lipid content and chemical structure not available, in vivo, at lower field strengths. All molecular fragments within multiple lipid compartments were chemically shifted by 0.20-0.26 ppm at this field strength. 1D and 2D L-COSY spectra were assigned and proton connectivities were confirmed with the 2D method. ConclusionIn vivo 1D and 2D spectroscopic examination of muscle can be successfully recorded at 7T and is now available to assess lipid alterations as well as other metabolites present with disease. T1 and T2 values were also determined in soleus muscle of male healthy volunteers.

  17. Monitoring the Inhalation Flow Rate of Nebulized Aerosols Using an Ultrasonic Flow Meter: In Vitro Assessment.

    Science.gov (United States)

    Yang, Michael Y; Chan, Hak-Kim

    2017-06-01

    The measurement of aerosol flow rates without obscuration of the flow is of particular concern with in vivo lung deposition studies, where precise knowledge of aerosol particle size distributions is a necessary requirement for the development of predictive correlations. This study examines the utility of an ultrasonic flow meter for such measurements and determines if a valved system can be attached to the flow meter for sampling exhaled aerosols. The flow rate across a D-30 flow meter was compared with and without nebulization of 0.9% saline aerosols from a PARI LC Sprint nebulizer. Particle size distributions of the nebulized aerosol before and after adding the D-30 flow meter and duckbill valve were measured using a Spraytec laser diffraction system. Finally, the ability of the Thor D-30 to capture a realistic breathing profile was assessed. The mean ± standard error flow rates measured by the D-30 flow meter with and without nebulization were 10.4 ± 0.1 versus 10.4 ± 0.1 L/min, 66.4 ± 0.1 versus 67.2 ± 0.1 L/min, and 89.9 ± 0.1 versus 91.4 ± 0.1 L/min. The D-30 flow meter did not considerably affect the volumetric median diameter (VMD) of the aerosols, while the VMD reduced slightly by 0.65 μm at 10 L/min and 0.69 μm at 72 L/min upon the inclusion of a duckbill valve. Time-weighted average inhalation flow rates measured by D-30 flow meters placed upstream and downstream of the one-way valve agreed well, 31.9 versus 32.6 L/min, respectively. The D-30 flow meter can be used to accurately measure inhalation flow rates of nebulized aerosols without significantly impacting particle size distributions, and one-way duckbill valves can be used to isolate the inhalation portion of a breathing pattern to facilitate collection of exhaled doses.

  18. 4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical Remodeling

    Directory of Open Access Journals (Sweden)

    Filippo Piatti

    2017-06-01

    Full Text Available Bicuspid aortic valve (BAV is the most common congenital cardiac disease and is a foremost risk factor for aortopathies. Despite the genetic basis of BAV and of the associated aortopathies, BAV-related alterations in aortic fluid-dynamics, and particularly in wall shear stresses (WSSs, likely play a role in the progression of aortopathy, and may contribute to its pathogenesis. To test whether WSS may trigger aortopathy, in this study we used 4D Flow sequences of phase-contrast cardiac magnetic resonance imaging (CMR to quantitatively compare the in vivo fluid dynamics in the thoracic aorta of two groups of subjects: (i five prospectively enrolled young patients with normo-functional BAV and with no aortic dilation and (ii ten age-matched healthy volunteers. Through the semi-automated processing of 4D Flow data, the aortic bulk flow at peak systole was quantified, and WSSs acting on the endothelium of the ascending aorta were characterized throughout the systolic phase in terms of magnitude and time-dependency through a method recently developed by our group. Variables computed for each BAV patient were compared vs. the corresponding distribution of values obtained for healthy controls. In BAV patients, ascending aorta diameter was measured on cine-CMR images at baseline and at 3-year follow-up. As compared to controls, normo-functional BAV patients were characterized by minor bulk flow disturbances at peak systole. However, they were characterized by evident alterations of WSS distribution and peak values in the ascending aorta. In particular, in four BAV patients, who were characterized by right-left leaflet fusion, WSS peak values exceeded by 27–46% the 90th percentile of the distribution obtained for healthy volunteers. Only in the BAV patient with right-non-coronary leaflet fusion the same threshold was exceeded by 132%. Also, evident alterations in the time-dependency of WSS magnitude and direction were observed. Despite, these fluid

  19. Glycyrrhetinic acid attenuates lipopolysaccharide-induced fulminant hepatic failure in D-galactosamine-sensitized mice by up-regulating expression of interleukin-1 receptor-associated kinase-M

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Xinru [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China); Gong, Xia [Department of Anatomy, Chongqing Medical University, Chongqing 400016 (China); Zhang, Li; Jiang, Rong [Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016 (China); Kuang, Ge [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China); Wang, Bin [Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chen, Xinyu [Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021 (China); Wan, Jingyuan, E-mail: jywan@cqmu.edu.cn [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China)

    2017-04-01

    Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100 mg/kg) 1 h before lipopolysaccharide (LPS)/D-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Toll like receptor 4 (TLR4), interleukin-1 receptor-associated kinases (IRAKs), activation of mitogen-activated protein kinases (MAPKs) and NF-κB, and production of TNF-α were assessed by flow cytometry, western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that pretreatment with GA protected mice against LPS/D-GalN-induced fulminant hepatic failure (FHF), including a dose-dependent alleviation of mortality and ALT/AST elevation, ameliorating hepatic pathological damage, and decreasing TNF-α release. Moreover, GA inhibited LPS-induced activation of MAPKs and NF-κB in response to LPS, but the expression of TLR4 was not affected in vivo and in vitro. Notably, GA pretreatment in vivo suppressed IRAK-1 activity while inducing IRAK-M expression. Silencing of IRAK-M expression with siRNA blocked these beneficial effects of GA on the activation of MAPKs and NF-κB as well as TNF-α production in LPS-primed macrophages. Taken together, we conclude that GA could prevent LPS/D-GalN-induced FHF. The underlying mechanisms may be related to up-regulation of IRAK-M, which in turn caused deactivation of IRAK-1 and subsequent MAPKs and NF-κB, resulting in inhibiting TNF-α production. - Highlights: • Glycyrrhetinic acid protected from LPS/D-GalN-induced liver injury in mice. • Glycyrrhetinic acid inhibited LPS-induced TNF-α production in vivo and in vitro. • Glycyrrhetinic

  20. In vivo and in vitro dermal penetration of 2,4,5,2',4', 5'-hexachlorobiphenyl in young and adult rats

    International Nuclear Information System (INIS)

    Shah, P.V.; Sumler, M.R.; Fisher, H.L.; Hall, L.L.

    1989-01-01

    Penetration of 2,4,5,2',4',5'-[ 14 C]hexachlorobiphenyl (HCB) through skin of young (33 days) and adult (82 days) female Fischer 344 rats was determined in vivo and by two in vitro methods. In vivo dermal penetration at 120 hr was 45% in young and 43% in adults. At 72 hr in vivo dermal penetration was 35% in young and 26% in adults compared to 1.5% for young and 1.0% for adult as measured with a continuous flow in vitro system and 2.9% for young and 1.9% for adults as measured with a static in vitro system. Most of the dermally absorbed HCB remained in the body as only 4.9 and 2.6% of that absorbed was excreted by young and adult rats, respectively, at the end of 120 hr. Significant differences in dermal penetration and kinetics of HCB between young and adult female rats were observed. The elimination of ECB-derived material was approximately six times higher in feces than in urine. A physiological pharmacokinetic model was fitted to the organ and tissue radioactivity distribution data. Parameters in the model determined from dermal dosing of female Fischer 344 rats were in reasonable agreement with those reported in the literature for adult male Sprague-Dawley rats (iv dose). The rate constant for dermal penetration was 0.83 x 10 -4 min -1 for adults and 0.96 x 10 -4 min -1 for young. The delay or lag time parameter for dermal penetration was 4.4 hr in adults and 1.1 hr in young

  1. Identification of contact and respiratory sensitizers using flow cytometry

    International Nuclear Information System (INIS)

    Goutet, Michele; Pepin, Elsa; Langonne, Isabelle; Huguet, Nelly; Ban, Masarin

    2005-01-01

    Identification of the chemicals responsible for respiratory and contact allergies in the industrial area is an important occupational safety issue. This study was conducted in mice to determine whether flow cytometry is an appropriate method to analyze and differentiate the specific immune responses to the respiratory sensitizer trimellitic anhydride (TMA) and to the contact sensitizer dinitrochlorobenzene (DNCB) used at concentrations with comparable immunogenic potential. Mice were exposed twice on the flanks (days 0, 5) to 10% TMA or 1% DNCB and challenged three times on the ears (days 10, 11, 12) with 2.5% TMA or 0.25% DNCB. Flow cytometry analyses were conducted on draining lymph node cells harvested on days 13 and 18. Comparing TMA and DNCB immune responses on day 13, we found obvious differences that persisted for most of them on day 18. An increased proportion of IgE+ cells correlated to total serum IgE level and an enhancement of MHC II molecule expression were observed in the lymph node B lymphocytes from TMA-treated mice. The percentage of IL-4-producing CD4+ lymphocytes and the IL-4 receptor expression were clearly higher following TMA exposure. In contrast, higher proportions of IL-2-producing cells were detected in CD4+ and CD8+ cells from DNCB-treated mice. Both chemicals induced a significant increase in the percentage of IFN-γ-producing cells among CD8+ lymphocytes but to a greater proportion following TMA treatment. In conclusion, this study encourages the use of flow cytometry to discriminate between contact and respiratory sensitizers by identifying divergent expression of immune response parameters

  2. In vivo sensitivity of Phakopsora pachyrhizi to DMI and QoI fungicides

    Directory of Open Access Journals (Sweden)

    Erlei Melo Reis

    2015-03-01

    Full Text Available In in vivo experiments the sensitivity of 18 isolates of Phakopsora pachyrhizi from several regions of Brazil to IDM fungicides (cyproconazole, epoxiconazole and tebuconazole and an IQE (pyraclostrobin were evaluated. The assessments were based on leaflet uredia density. Inhibitory concentration (IC50 and sensitivity reduction factor were determined for all fungicide x strain interactions. Tebuconazole sensitivity reduction was detected for most fungus isolates. In contrast, there was no fungicide shift in sensitivity of the fungus to pyraclostrobin. We conclude that the control failure of soybean rust found in some farms is due to the reduced sensitivity of the fungus to the IDM fungicide and that it remains sensitive to pyraclostrobin.

  3. 4D blood flow mapping using SPIM-microPIV in the developing zebrafish heart

    Science.gov (United States)

    Zickus, Vytautas; Taylor, Jonathan M.

    2018-02-01

    Fluid-structure interaction in the developing heart is an active area of research in developmental biology. However, investigation of heart dynamics is mostly limited to computational uid dynamics simulations using heart wall structure information only, or single plane blood ow information - so there is a need for 3D + time resolved data to fully understand cardiac function. We present an imaging platform combining selective plane illumination microscopy (SPIM) with micro particle image velocimetry (μPIV) to enable 3D-resolved flow mapping in a microscopic environment, free from many of the sources of error and bias present in traditional epi uorescence-based μPIV systems. By using our new system in conjunction with optical heart beat synchronization, we demonstrate the ability obtain non-invasive 3D + time resolved blood flow measurements in the heart of a living zebrafish embryo.

  4. Recanalization and flow regulate venous thrombus resolution and Matrix metalloproteinases expression in vivo

    Science.gov (United States)

    Chabasse, Christine; Siefert, Suzanne A.; Chaudry, Mohammed; Hoofnagle, Mark H.; Lal, Brajesh K.; Sarkar, Rajabrata

    2016-01-01

    Objective We examined the role of thrombus recanalization and ongoing blood flow in the process of thrombus resolution by comparing two murine in vivo models of deep venous thrombosis. Design of study In CD1 mice, we performed surgical inferior vena cava (IVC) ligation (stasis thrombosis), stenosis (thrombosis with recanalization) or sham procedure. We analyzed thrombus weight over time as a measure of thrombus resolution, and quantified the mRNA and protein levels of Membrane-Type Matrix Metalloproteinases (MT-MMPs) as well as effectors of the plasmin complex at day 4, 8 and 12 post-surgery. Results Despite similar initial thrombus size, the presence of ongoing blood flow (stenosis model) was associated with a 45.91% subsequent improvement in thrombus resolution at day 8, and 12.57% at day 12, as compared with stasis thrombosis (ligation model). Immunoblot and real-time PCR demonstrated a difference in MMP-2 and MMP-9 activity at day 8 between the two models (P=.03 and P=.006 respectively), as well as a difference in MT2-MMP gene expression at day 8 (P=.044) and day 12 (P=0.03) and MT1-MMP protein expression at day 4 (P=.021). Histological analyses revealed distinct areas of recanalization in the thrombi of the stenosis model compared to the ligation model, as well as the recruitment of inflammatory cells, especially macrophages, and a focal pattern of localized expression of MT1-MMP and MT3-MMP proteins surrounding the areas of recanalization in the stenosis model. Conclusions Recanalization and ongoing blood flow accelerate deep venous thrombus resolution in vivo, and are associated with distinct patterns of MT1- and MT3-MMP expression and macrophages localization in areas of intra-thrombus recanalization. PMID:26993683

  5. Recanalization and flow regulate venous thrombus resolution and matrix metalloproteinase expression in vivo.

    Science.gov (United States)

    Chabasse, Christine; Siefert, Suzanne A; Chaudry, Mohammed; Hoofnagle, Mark H; Lal, Brajesh K; Sarkar, Rajabrata

    2015-01-01

    We examined the role of thrombus recanalization and ongoing blood flow in the process of thrombus resolution by comparing two murine in vivo models of deep venous thrombosis. In CD1 mice, we performed surgical inferior vena cava ligation (stasis thrombosis), stenosis (thrombosis with recanalization), or sham procedure. We analyzed thrombus weight over time as a measure of thrombus resolution and quantified the messenger RNA and protein levels of membrane-type matrix metalloproteinases (MT-MMPs) as well as effectors of the plasmin complex at days 4, 8, and 12 after surgery. Despite similar initial thrombus size, the presence of ongoing blood flow (stenosis model) was associated with a 45.91% subsequent improvement in thrombus resolution at day 8 and 12.57% at day 12 compared with stasis thrombosis (ligation model). Immunoblot and real-time polymerase chain reaction analysis demonstrated a difference in MMP-2 and MMP-9 activity at day 8 between the two models (P = .03 and P = .006, respectively) as well as a difference in MT2-MMP gene expression at day 8 (P = .044) and day 12 (P = .03) and MT1-MMP protein expression at day 4 (P = .021). Histologic analyses revealed distinct areas of recanalization in the thrombi of the stenosis model compared with the ligation model as well as the recruitment of inflammatory cells, especially macrophages, and a focal pattern of localized expression of MT1-MMP and MT3-MMP proteins surrounding the areas of recanalization in the stenosis model. Recanalization and ongoing blood flow accelerate deep venous thrombus resolution in vivo and are associated with distinct patterns of MT1-MMP and MT3-MMP expression and macrophage localization in areas of intrathrombus recanalization. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  6. Assessment of Reynolds stress components and turbulent pressure loss using 4D flow MRI with extended motion encoding.

    Science.gov (United States)

    Haraldsson, Henrik; Kefayati, Sarah; Ahn, Sinyeob; Dyverfeldt, Petter; Lantz, Jonas; Karlsson, Matts; Laub, Gerhard; Ebbers, Tino; Saloner, David

    2018-04-01

    To measure the Reynolds stress tensor using 4D flow MRI, and to evaluate its contribution to computed pressure maps. A method to assess both velocity and Reynolds stress using 4D flow MRI is presented and evaluated. The Reynolds stress is compared by cross-sectional integrals of the Reynolds stress invariants. Pressure maps are computed using the pressure Poisson equation-both including and neglecting the Reynolds stress. Good agreement is seen for Reynolds stress between computational fluid dynamics, simulated MRI, and MRI experiment. The Reynolds stress can significantly influence the computed pressure loss for simulated (eg, -0.52% vs -15.34% error; P Reynolds stress (P Reynolds stress tensor. The additional information provided by this method improves the assessment of pressure gradients across a stenosis in the presence of turbulence. Unlike conventional methods, which are only valid if the flow is laminar, the proposed method is valid for both laminar and disturbed flow, a common presentation in diseased vessels. Magn Reson Med 79:1962-1971, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  7. Accuracy and Precision of a Plane Wave Vector Flow Imaging Method in the Healthy Carotid Artery

    DEFF Research Database (Denmark)

    Jensen, Jonas; Villagómez Hoyos, Carlos Armando; Traberg, Marie Sand

    2018-01-01

    The objective of the study described here was to investigate the accuracy and precision of a plane wave 2-D vector flow imaging (VFI) method in laminar and complex blood flow conditions in the healthy carotid artery. The approach was to study (i) the accuracy for complex flow by comparing...... of laminar flow in vivo. The precision in vivo was calculated as the mean standard deviation (SD) of estimates aligned to the heart cycle and was highest in the center of the common carotid artery (SD = 3.6% for velocity magnitudes and 4.5° for angles) and lowest in the external branch and for vortices (SD...... the velocity field from a computational fluid dynamics (CFD) simulation to VFI estimates obtained from the scan of an anthropomorphic flow phantom and from an in vivo scan; (ii) the accuracy for laminar unidirectional flow in vivo by comparing peak systolic velocities from VFI with magnetic resonance...

  8. In vivo metabolism of CCl4 by gerbils pretreated with chlordecone, phenobarbital, or mirex

    International Nuclear Information System (INIS)

    Cai, Z.; Mehendale, H.M.

    1990-01-01

    Gerbils are known to be much more sensitive to CCl 4 lethality than rats as indicated by 48 hours LD 50 (0.08 vs 2.8 ml/kg). On the other hand, gerbils are refractory to chlordecone (CD) potentiation of CCl 4 toxicity. To investigate the possible mechanism underlying gerbil's high sensitivity to CCl 4 lethality, the authors studied in vivo metabolism of CCl 4 in gerbils pretreated with dietary CD (10 ppm), phenobarbital (PB, 225 ppm) or mirex (M, 10 ppm). The hepatic content of CCl 4 , the expiration of 14 CCl 4 and 14 CCl 4 -derived Co 2 , and lipid peroxidation were measured and the results were compared with our previous data for rats. After 15-day dietary pretreatment, male gerbils (60-80 g) received 14 CCl 4 (80 ml/kg; sp act: 0.04 mCi/mmol) ip in corn oil and the expired air was collected for 6 hours. More than 80% of the dose administered was expired as parent compound in 6 hours regardless of pretreatments. Expiration of 14 CCl 4 derived 14 CO 2 in control gerbils was 3.5-fold more than in control rats and was increased significantly in pretreated gerbils (M>PB>CD). PB and M pretreatments resulted in significant increase of 14 C label bound to non-lipid fraction of hepatic content as compared with CD or control gerbils. The radiolabel present in hepatic content of control gerbils was 5-fold higher than that of control rats. In vivo liquid peroxidation measured as diene conjugation in lipid extracts from the livers was lower in gerbils than in rats, and there were no significant differences among control and pretreated gerbils. These data indicate that the more extensive metabolism of CCl 4 in gerbils may partially explain their high sensitivity to CCl 4 toxicity. However, the significantly enhanced metabolism of CCl 4 found in CD, PB, or M pretreated gerbils did not lead to amplification of CCl 4 hepatotoxic and lethal effects

  9. In vivo hemodynamic analysis of intracranial aneurysms obtained by magnetic resonance fluid dynamics (MRFD) based on time-resolved three-dimensional phase-contrast MRI

    International Nuclear Information System (INIS)

    Isoda, Haruo; Takeda, Hiroyasu; Yamashita, Shuhei; Takehara, Yasuo; Sakahara, Harumi; Ohkura, Yasuhide; Kosugi, Takashi; Hirano, Masaya; Hiramatsu, Hisaya; Namba, Hiroki; Alley, Marcus T.; Bammer, Roland; Pelc, Norbert J.

    2010-01-01

    Hemodynamics is thought to play a very important role in the initiation, growth, and rupture of intracranial aneurysms. The purpose of our study was to perform in vivo hemodynamic analysis of unruptured intracranial aneurysms of magnetic resonance fluid dynamics using time-resolved three-dimensional phase-contrast MRI (4D-Flow) at 1.5 T and to analyze relationships between hemodynamics and wall shear stress (WSS) and oscillatory shear index (OSI). This study included nine subjects with 14 unruptured aneurysms. 4D-Flow was performed by a 1.5-T magnetic resonance scanner with a head coil. We calculated in vivo streamlines, WSS, and OSI of intracranial aneurysms based on 4D-Flow with our software. We evaluated the number of spiral flows in the aneurysms and compared the differences in WSS or OSI between the vessel and aneurysm and between whole aneurysm and the apex of the spiral flow. 3D streamlines, WSS, and OSI distribution maps in arbitrary direction during the cardiac phase were obtained for all intracranial aneurysms. Twelve aneurysms had one spiral flow each, and two aneurysms had two spiral flows each. The WSS was lower and the OSI was higher in the aneurysm compared to the vessel. The apex of the spiral flow had a lower WSS and higher OSI relative to the whole aneurysm. Each intracranial aneurysm in this study had at least one spiral flow. The WSS was lower and OSI was higher at the apex of the spiral flow than the whole aneurysmal wall. (orig.)

  10. In vivo hemodynamic analysis of intracranial aneurysms obtained by magnetic resonance fluid dynamics (MRFD) based on time-resolved three-dimensional phase-contrast MRI.

    Science.gov (United States)

    Isoda, Haruo; Ohkura, Yasuhide; Kosugi, Takashi; Hirano, Masaya; Takeda, Hiroyasu; Hiramatsu, Hisaya; Yamashita, Shuhei; Takehara, Yasuo; Alley, Marcus T; Bammer, Roland; Pelc, Norbert J; Namba, Hiroki; Sakahara, Harumi

    2010-10-01

    Hemodynamics is thought to play a very important role in the initiation, growth, and rupture of intracranial aneurysms. The purpose of our study was to perform in vivo hemodynamic analysis of unruptured intracranial aneurysms of magnetic resonance fluid dynamics using time-resolved three-dimensional phase-contrast MRI (4D-Flow) at 1.5 T and to analyze relationships between hemodynamics and wall shear stress (WSS) and oscillatory shear index (OSI). This study included nine subjects with 14 unruptured aneurysms. 4D-Flow was performed by a 1.5-T magnetic resonance scanner with a head coil. We calculated in vivo streamlines, WSS, and OSI of intracranial aneurysms based on 4D-Flow with our software. We evaluated the number of spiral flows in the aneurysms and compared the differences in WSS or OSI between the vessel and aneurysm and between whole aneurysm and the apex of the spiral flow. 3D streamlines, WSS, and OSI distribution maps in arbitrary direction during the cardiac phase were obtained for all intracranial aneurysms. Twelve aneurysms had one spiral flow each, and two aneurysms had two spiral flows each. The WSS was lower and the OSI was higher in the aneurysm compared to the vessel. The apex of the spiral flow had a lower WSS and higher OSI relative to the whole aneurysm. Each intracranial aneurysm in this study had at least one spiral flow. The WSS was lower and OSI was higher at the apex of the spiral flow than the whole aneurysmal wall.

  11. Effects of calcitonin gene-related peptide on canine cerebral artery strips and the in-vivo vertebral blood flow in dogs.

    Science.gov (United States)

    Ikegaki, I; Suzuki, Y; Satoh, S; Asano, T; Shibuya, M; Sugita, K

    1989-10-01

    The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F2 alpha (PGF2 alpha). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor(1-29)-NH2 or (D-Pro2, D-Trp7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A2 (STXA2). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF2 alpha-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone.

  12. Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition.

    Directory of Open Access Journals (Sweden)

    Stuart J Smith

    Full Text Available INTRODUCTION: Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS. METHODS: CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS: Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS: Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system.

  13. Integrated light-sheet imaging and flow-based enquiry (iLIFE) system for 3D in-vivo imaging of multicellular organism

    Science.gov (United States)

    Rasmi, Chelur K.; Padmanabhan, Sreedevi; Shirlekar, Kalyanee; Rajan, Kanhirodan; Manjithaya, Ravi; Singh, Varsha; Mondal, Partha Pratim

    2017-12-01

    We propose and demonstrate a light-sheet-based 3D interrogation system on a microfluidic platform for screening biological specimens during flow. To achieve this, a diffraction-limited light-sheet (with a large field-of-view) is employed to optically section the specimens flowing through the microfluidic channel. This necessitates optimization of the parameters for the illumination sub-system (illumination intensity, light-sheet width, and thickness), microfluidic specimen platform (channel-width and flow-rate), and detection sub-system (camera exposure time and frame rate). Once optimized, these parameters facilitate cross-sectional imaging and 3D reconstruction of biological specimens. The proposed integrated light-sheet imaging and flow-based enquiry (iLIFE) imaging technique enables single-shot sectional imaging of a range of specimens of varying dimensions, ranging from a single cell (HeLa cell) to a multicellular organism (C. elegans). 3D reconstruction of the entire C. elegans is achieved in real-time and with an exposure time of few hundred micro-seconds. A maximum likelihood technique is developed and optimized for the iLIFE imaging system. We observed an intracellular resolution for mitochondria-labeled HeLa cells, which demonstrates the dynamic resolution of the iLIFE system. The proposed technique is a step towards achieving flow-based 3D imaging. We expect potential applications in diverse fields such as structural biology and biophysics.

  14. Transgenic expression of microRNA-181d augments the stress-sensitivity of CD4(+CD8(+ thymocytes.

    Directory of Open Access Journals (Sweden)

    Serkan Belkaya

    Full Text Available Physiological stress resulting from infections, trauma, surgery, alcoholism, malnutrition, and/or pregnancy results in a substantial depletion of immature CD4(+CD8(+ thymocytes. We previously identified 18 distinct stress-responsive microRNAs (miRs in the thymus upon systemic stress induced by lipopolysaccharide (LPS or the synthetic glucocorticoid, dexamethasone (Dex. MiRs are short, non-coding RNAs that play critical roles in the immune system by targeting diverse mRNAs, suggesting that their modulation in the thymus in response to stress could impact thymopoiesis. MiR-181d is one such stress-responsive miR, exhibiting a 15-fold down-regulation in expression. We utilized both transgenic and gene-targeting approaches to study the impact of miR-181d on thymopoiesis under normal and stress conditions. The over-expression of miR-181d in developing thymocytes reduced the total number of immature CD4(+CD8(+ thymocytes. LPS or Dex injections caused a 4-fold greater loss of these cells when compared with the wild type controls. A knockout mouse was developed to selectively eliminate miR-181d, leaving the closely spaced and contiguous family member miR-181c intact. The targeted elimination of just miR-181d resulted in a thymus stress-responsiveness similar to wild-type mice. These experiments suggest that one or more of three other miR-181 family members have overlapping or compensatory functions. Gene expression comparisons of thymocytes from the wild type versus transgenic mice indicated that miR-181d targets a number of stress, metabolic, and signaling pathways. These findings demonstrate that selected miRs enhance stress-mediated thymic involution in vivo.

  15. Andrographolide Sensitizes Ras-Transformed Cells to Radiation in vitro and in vivo

    International Nuclear Information System (INIS)

    Hung, Shih-Kai; Hung, Ling-Chien; Kuo, Cheng-Deng

    2010-01-01

    Purpose: Increasing the sensitivity of tumor cells to radiation is a major goal of radiotherapy. The present study investigated the radiosensitizing effects of andrographolide and examined the molecular mechanisms of andrographolide-mediated radiosensitization. Methods and Materials: An H-ras-transformed rat kidney epithelial (RK3E) cell line was used to measure the radiosensitizing effects of andrographolide in clonogenic assays, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assays, and a xenograft tumor growth model. The mechanism of andrographolide-sensitized cell death was analyzed using annexin V staining, caspase 3 activity assays, and terminal transferase uridyl nick end labeling assays. The roles of nuclear factor kappa B (NF-κB) and Akt in andrographolide-mediated sensitization were examined using reporter assays, electrophoretic mobility shift assays, and Western blotting. Results: Concurrent andrographolide treatment (10 μM, 3 h) sensitized Ras-transformed cells to radiation in vitro (sensitizer enhancement ratio, 1.73). Andrographolide plus radiation (one dose of 300 mg/kg peritumor andrographolide and one dose of 6 Gy radiation) resulted in significant tumor growth delay (27 ± 2.5 days) compared with radiation alone (22 ± 1.5 days; p <.05). Radiation induced apoptotic markers (e.g., caspase-3, membrane reversion, DNA fragmentation), and andrographolide treatment did not promote radiation-induced apoptosis. However, the protein level of activated Akt was significantly reduced by andrographolide. NF-κB activity was elevated in irradiated Ras-transformed cells, and andrographolide treatment significantly reduced radiation-induced NF-κB activity. Conclusion: Andrographolide sensitized Ras-transformed cells to radiation both in vitro and in vivo. Andrographolide-mediated radiosensitization was associated with downregulation of Akt and NF-κB activity. These observations indicate that andrographolide is a novel radiosensitizing agent

  16. Experimental quantification of the fluid dynamics in blood-processing devices through 4D-flow imaging: A pilot study on a real oxygenator/heat-exchanger module.

    Science.gov (United States)

    Piatti, Filippo; Palumbo, Maria Chiara; Consolo, Filippo; Pluchinotta, Francesca; Greiser, Andreas; Sturla, Francesco; Votta, Emiliano; Siryk, Sergii V; Vismara, Riccardo; Fiore, Gianfranco Beniamino; Lombardi, Massimo; Redaelli, Alberto

    2018-02-08

    The performance of blood-processing devices largely depends on the associated fluid dynamics, which hence represents a key aspect in their design and optimization. To this aim, two approaches are currently adopted: computational fluid-dynamics, which yields highly resolved three-dimensional data but relies on simplifying assumptions, and in vitro experiments, which typically involve the direct video-acquisition of the flow field and provide 2D data only. We propose a novel method that exploits space- and time-resolved magnetic resonance imaging (4D-flow) to quantify the complex 3D flow field in blood-processing devices and to overcome these limitations. We tested our method on a real device that integrates an oxygenator and a heat exchanger. A dedicated mock loop was implemented, and novel 4D-flow sequences with sub-millimetric spatial resolution and region-dependent velocity encodings were defined. Automated in house software was developed to quantify the complex 3D flow field within the different regions of the device: region-dependent flow rates, pressure drops, paths of the working fluid and wall shear stresses were computed. Our analysis highlighted the effects of fine geometrical features of the device on the local fluid-dynamics, which would be unlikely observed by current in vitro approaches. Also, the effects of non-idealities on the flow field distribution were captured, thanks to the absence of the simplifying assumptions that typically characterize numerical models. To the best of our knowledge, our approach is the first of its kind and could be extended to the analysis of a broad range of clinically relevant devices. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Leptin Reduces the Expression and Increases the Phosphorylation of the Negative Regulators of GLUT4 Traffic TBC1D1 and TBC1D4 in Muscle of ob/ob Mice

    Science.gov (United States)

    Sáinz, Neira; Rodríguez, Amaia; Catalán, Victoria; Becerril, Sara; Ramírez, Beatriz; Lancha, Andoni; Burgos-Ramos, Emma; Gómez-Ambrosi, Javier; Frühbeck, Gema

    2012-01-01

    Leptin improves insulin sensitivity in skeletal muscle. Our goal was to determine whether proteins controlling GLUT4 traffic are altered by leptin deficiency and in vivo leptin administration in skeletal muscle of wild type and ob/ob mice. Leptin-deficient ob/ob mice were divided in three groups: control, leptin-treated (1 mg/kg/d) and leptin pair-fed ob/ob mice. Microarray analysis revealed that 1,546 and 1,127 genes were regulated by leptin deficiency and leptin treatment, respectively. Among these, we identified 24 genes involved in intracellular vesicle-mediated transport in ob/ob mice. TBC1 domain family, member 1 (Tbc1d1), a negative regulator of GLUT4 translocation, was up-regulated (P = 0.001) in ob/ob mice as compared to wild types. Importantly, leptin treatment reduced the transcript levels of Tbc1d1 (P<0.001) and Tbc1d4 (P = 0.004) in the leptin-treated ob/ob as compared to pair-fed ob/ob animals. In addition, phosphorylation levels of TBC1D1 and TBC1D4 were enhanced in leptin-treated ob/ob as compared to control ob/ob (P = 0.015 and P = 0.023, respectively) and pair-fed ob/ob (P = 0.036 and P = 0.034, respectively) mice. Despite similar GLUT4 protein expression in wild type and ob/ob groups a different immunolocalization of this protein was evidenced in muscle sections. Leptin treatment increased GLUT4 immunoreactivity in gastrocnemius and extensor digitorum longus sections of leptin-treated ob/ob mice. Moreover, GLUT4 protein detected in immunoprecipitates from TBC1D4 was reduced by leptin replacement compared to control ob/ob (P = 0.013) and pair-fed ob/ob (P = 0.037) mice. Our findings suggest that leptin enhances the intracellular GLUT4 transport in skeletal muscle of ob/ob animals by reducing the expression and activity of the negative regulators of GLUT4 traffic TBC1D1 and TBC1D4. PMID:22253718

  18. Time-resolved assessment of collateral flow using 4D CT angiography in large-vessel occlusion stroke

    International Nuclear Information System (INIS)

    Froelich, Andreas M.J.; Wolff, Sarah Lena; Psychogios, Marios N.; Schramm, Ramona; Knauth, Michael; Schramm, Peter; Klotz, Ernst; Wasser, Katrin

    2014-01-01

    In acute stroke patients with large vessel occlusion, collateral blood flow affects tissue fate and patient outcome. The visibility of collaterals on computed tomography angiography (CTA) strongly depends on the acquisition phase, but the optimal time point for collateral imaging is unknown. We analysed collaterals in a time-resolved fashion using four-dimensional (4D) CTA in 82 endovascularly treated stroke patients, aiming to determine which acquisition phase best depicts collaterals and predicts outcome. Early, peak and late phases as well as temporally fused maximum intensity projections (tMIP) were graded using a semiquantitative regional leptomeningeal collateral score, compared with conventional single-phase CTA and correlated with functional outcome. The total extent of collateral flow was best visualised on tMIP. Collateral scores were significantly lower on early and peak phase as well as on single-phase CTA. Collateral grade was associated with favourable functional outcome and the strength of this relationship increased from earlier to later phases, with collaterals on tMIP showing the strongest correlation with outcome. Temporally fused tMIP images provide the best depiction of collateral flow. Our findings suggest that the total extent of collateral flow, rather than the velocity of collateral filling, best predicts clinical outcome. (orig.)

  19. Image quality in thoracic 4D cone-beam CT: A sensitivity analysis of respiratory signal, binning method, reconstruction algorithm, and projection angular spacing

    OpenAIRE

    Shieh, Chun-Chien; Kipritidis, John; O’Brien, Ricky T.; Kuncic, Zdenka; Keall, Paul J.

    2014-01-01

    Purpose: Respiratory signal, binning method, and reconstruction algorithm are three major controllable factors affecting image quality in thoracic 4D cone-beam CT (4D-CBCT), which is widely used in image guided radiotherapy (IGRT). Previous studies have investigated each of these factors individually, but no integrated sensitivity analysis has been performed. In addition, projection angular spacing is also a key factor in reconstruction, but how it affects image quality is not obvious. An inv...

  20. In Vivo Chondrogenesis in 3D Bioprinted Human Cell-laden Hydrogel Constructs.

    Science.gov (United States)

    Möller, Thomas; Amoroso, Matteo; Hägg, Daniel; Brantsing, Camilla; Rotter, Nicole; Apelgren, Peter; Lindahl, Anders; Kölby, Lars; Gatenholm, Paul

    2017-02-01

    The three-dimensional (3D) bioprinting technology allows creation of 3D constructs in a layer-by-layer fashion utilizing biologically relevant materials such as biopolymers and cells. The aim of this study is to investigate the use of 3D bioprinting in a clinically relevant setting to evaluate the potential of this technique for in vivo chondrogenesis. Thirty-six nude mice (Balb-C, female) received a 5- × 5- × 1-mm piece of bioprinted cell-laden nanofibrillated cellulose/alginate construct in a subcutaneous pocket. Four groups of printed constructs were used: (1) human (male) nasal chondrocytes (hNCs), (2) human (female) bone marrow-derived mesenchymal stem cells (hBMSCs), (3) coculture of hNCs and hBMSCs in a 20/80 ratio, and (4) Cell-free scaffolds (blank). After 14, 30, and 60 days, the scaffolds were harvested for histological, immunohistochemical, and mechanical analysis. The constructs had good mechanical properties and keep their structural integrity after 60 days of implantation. For both the hNC constructs and the cocultured constructs, a gradual increase of glycosaminoglycan production and hNC proliferation was observed. However, the cocultured group showed a more pronounced cell proliferation and enhanced deposition of human collagen II demonstrated by immunohistochemical analysis. In vivo chondrogenesis in a 3D bioprinted human cell-laden hydrogel construct has been demonstrated. The trophic role of the hBMSCs in stimulating hNC proliferation and matrix deposition in the coculture group suggests the potential of 3D bioprinting of human cartilage for future application in reconstructive surgery.

  1. Alur Kerja Tahap Produksi Karakter Animasi Serial 3D Menggunakan Perangkat Lunak Maxon Cinema 4D

    Directory of Open Access Journals (Sweden)

    Ardiyan Ardiyan

    2011-04-01

    Full Text Available 3D Animation serial for television needs have been showed in the national television program, especially fantasy theme and educational program for children. There are so many and sequential needs which tricked by instant and high quality production so the work flow in creating 3D animation serial are facilitating the producers. The article will explain specifically how the software of Maxon Cinema 4D in process production in 3D animation serial. The article will also clarify and focus on how the work flow of Maxon Cinema 4D software in processing production and post-production stages. The writer does research including audio visual tutorial, end-result comparison and rendering time between some software, self-observation of work flow in creating 3D animation serial using Maxon Cinema 4D software and digital literature study (e-book.  

  2. Experimental Investigation of Two-Phase Oil (D130)-Water Flow in 4″ Pipe for Different Inclination Angles

    Science.gov (United States)

    Shaahid, S. M.; Basha, Mehaboob; Al-Hems, Luai M.

    2018-03-01

    Oil and water are often produced and transported together in pipelines that have various degrees of inclination from the horizontal. The flow of two immiscible liquids oil and water in pipes has been a research topic since several decades. In oil and chemical industries, knowledge of the frictional pressure loss in oil-water flows in pipes is necessary to specify the size of the pump required to pump the emulsions. An experimental investigation has been carried out for measurement of pressure drop of oil (D130)-water two-phase flows in 4 inch diameter inclined stainless steel pipe at different flow conditions. Experiments were conducted for different inclination angles including; 0°, 15°, 30° (for water cuts “WC” 0 - 100%). The flow rates at the inlet were varied from 4000 to 8000 barrels-per-day (BPD). For a given flow rate the frictional pressure drop has been found to increase (for all angles) from WC = 0 - 60%, and thereafter friction pressure drop decreases, this could be due phase inversion. For a given WC 40%, the frictional pressure drop has been found to increase with angle and flow rate. It has been noticed that inclination angle has appreciable effect on frictional pressure drop.

  3. 4-IBP, a σ1 Receptor Agonist, Decreases the Migration of Human Cancer Cells, Including Glioblastoma Cells, In Vitro and Sensitizes Them In Vitro and In Vivo to Cytotoxic Insults of Proapoptotic and Proautophagic Drugs

    Directory of Open Access Journals (Sweden)

    Veronique Mégalizzi

    2007-05-01

    Full Text Available Although the molecular function of cr receptors has not been fully defined and the natural ligand(s is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-(N-tibenzylpiperidin-4-yl-4iodobenzamide (4-IBP, a selective σ1, agonist, has been used to investigate whether this compound is able to modify: 1 in vitro the migration and proliferation of human cancer cells; 2 in vitro the sensitivity of human glioblastoma cells to cytotoxic drugs; and 3 in vivo in orthotopic glioblastoma and non-small cell lung carcinoma (NSCLC models the survival of mice coadministered cytotoxic agents. 4-IBP has revealed weak anti proliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.

  4. ECMOR 4. 4th European conference on the mathematics of oil recovery. Topic D: Simulation of fluid flow. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    1994-01-01

    The report with collected proceedings from a conference, deals with mathematics of oil recovery with the focus on simulation of fluid flow. Topics of proceedings are as follow: Validity of macroscopic viscous fingering models for 2D and 3D-flows; pressure equation for fluid flow in a stochastic medium; predicting multicomponent, multiphase flow in heterogeneous systems using streamtubes; analytic techniques in pressure transient testing; global triangular structure in four-component conservation laws; exact solution of the problem on hydrodynamic interaction between noncommunicating layers under conditions of their joint development; fluid rate in flowing granular medium with moving boundary; complex variable boundary element method for tracking streamlines across fractures; transport equations for miscible displacements in heterogeneous porous media - a streamtube approach; mathematical modelling of condensate film flow by gravity drainage; effect of capillary forces on immiscible two-phase flow in strongly heterogeneous porous media; multidomain direct method and local time steps in reservoir simulation; adaptive methods for chemical flooding; flux continuous for the full tensor equation; discretization on non-orthogonal, curvilinear grids for multi-phase flow; blending finite elements and finite volumes for the solution of miscible incompressible flow. 16 papers are prepared. 240 refs., 122 figs., 6 tabs.

  5. 3-D Vector Flow Estimation With Row-Column-Addressed Arrays.

    Science.gov (United States)

    Holbek, Simon; Christiansen, Thomas Lehrmann; Stuart, Matthias Bo; Beers, Christopher; Thomsen, Erik Vilain; Jensen, Jorgen Arendt

    2016-11-01

    Simulation and experimental results from 3-D vector flow estimations for a 62 + 62 2-D row-column (RC) array with integrated apodization are presented. A method for implementing a 3-D transverse oscillation (TO) velocity estimator on a 3-MHz RC array is developed and validated. First, a parametric simulation study is conducted, where flow direction, ensemble length, number of pulse cycles, steering angles, transmit/receive apodization, and TO apodization profiles and spacing are varied, to find the optimal parameter configuration. The performance of the estimator is evaluated with respect to relative mean bias ~B and mean standard deviation ~σ . Second, the optimal parameter configuration is implemented on the prototype RC probe connected to the experimental ultrasound scanner SARUS. Results from measurements conducted in a flow-rig system containing a constant laminar flow and a straight-vessel phantom with a pulsating flow are presented. Both an M-mode and a steered transmit sequence are applied. The 3-D vector flow is estimated in the flow rig for four representative flow directions. In the setup with 90° beam-to-flow angle, the relative mean bias across the entire velocity profile is (-4.7, -0.9, 0.4)% with a relative standard deviation of (8.7, 5.1, 0.8)% for ( v x , v y , v z ). The estimated peak velocity is 48.5 ± 3 cm/s giving a -3% bias. The out-of-plane velocity component perpendicular to the cross section is used to estimate volumetric flow rates in the flow rig at a 90° beam-to-flow angle. The estimated mean flow rate in this setup is 91.2 ± 3.1 L/h corresponding to a bias of -11.1%. In a pulsating flow setup, flow rate measured during five cycles is 2.3 ± 0.1 mL/stroke giving a negative 9.7% bias. It is concluded that accurate 3-D vector flow estimation can be obtained using a 2-D RC-addressed array.

  6. 3-D Vector Flow Imaging

    DEFF Research Database (Denmark)

    Holbek, Simon

    , if this significant reduction in the element count can still provide precise and robust 3-D vector flow estimates in a plane. The study concludes that the RC array is capable of estimating precise 3-D vector flow both in a plane and in a volume, despite the low channel count. However, some inherent new challenges...... ultrasonic vector flow estimation and bring it a step closer to a clinical application. A method for high frame rate 3-D vector flow estimation in a plane using the transverse oscillation method combined with a 1024 channel 2-D matrix array is presented. The proposed method is validated both through phantom...... hampers the task of real-time processing. In a second study, some of the issue with the 2-D matrix array are solved by introducing a 2-D row-column (RC) addressing array with only 62 + 62 elements. It is investigated both through simulations and via experimental setups in various flow conditions...

  7. Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI.

    Directory of Open Access Journals (Sweden)

    Q Joyce Han

    Full Text Available Right ventricular (RV function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH. The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI to derive RV kinetic energy (KE work density and energy loss in the pulmonary artery (PA to better characterize RV work in PAH patients.4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA.PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007 as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001 throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction.This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.

  8. Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI.

    Science.gov (United States)

    Han, Q Joyce; Witschey, Walter R T; Fang-Yen, Christopher M; Arkles, Jeffrey S; Barker, Alex J; Forfia, Paul R; Han, Yuchi

    2015-01-01

    Right ventricular (RV) function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH). The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI) to derive RV kinetic energy (KE) work density and energy loss in the pulmonary artery (PA) to better characterize RV work in PAH patients. 4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA. PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007) as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001) throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction. This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.

  9. 3D IBFV : Hardware-Accelerated 3D Flow Visualization

    NARCIS (Netherlands)

    Telea, Alexandru; Wijk, Jarke J. van

    2003-01-01

    We present a hardware-accelerated method for visualizing 3D flow fields. The method is based on insertion, advection, and decay of dye. To this aim, we extend the texture-based IBFV technique for 2D flow visualization in two main directions. First, we decompose the 3D flow visualization problem in a

  10. Modulatory effects of L-DOPA on D2 dopamine receptors in rat striatum, measured using in vivo microdialysis and PET

    International Nuclear Information System (INIS)

    Opacka-Juffry, J.; Hume, S. P.; Ashworth, S.; Ahier, R. G.

    1997-01-01

    Putative modulatory effects of L-3,4-dihydroxyphenylalanine (L-DOPA) on D2 dopamine receptor function in the striatum of anaesthetized rats were investigated using both in vivo microdialysis and positron emission tomography (PET) with carbon-11 labelled raclopride as a selective D2 receptor ligand. A single dose of L-DOPA (20 or 100 mg/kg i.p.) resulted in an increase in [ 11 C]raclopride binding potential which was also observed in the presence of the central aromatic decarboxylase inhibitor NSD 1015, confirming that the effect was independent of dopamine. This L-DOPA evoked D2 receptor sensitization was abolished by a prior, long-term administration of L-DOPA in drinking water (5 weeks, 170 mg/kg/day). In the course of acute L-DOPA treatment (20 mg/kg), extracellular GABA levels were reduced by ∼20 % in the globus pallidus. It is likely that L-DOPA sensitising effect on striatal D2 receptors, as confirmed by PET, may implicate striato-pallidal neurones, hence a reduced GABA-ergic output in the projection area. Since the L-DOPA evoked striatal D2 receptor supersensitivity habituates during long-term treatment, the effects reported here may contribute to the fluctuations observed during chronic L-DOPA therapy in Parkinson's disease. (author)

  11. In vivo validation of cardiac output assessment in non-standard 3D echocardiographic images

    Energy Technology Data Exchange (ETDEWEB)

    Nillesen, M M; Lopata, R G P; Gerrits, I H; Thijssen, J M; De Korte, C L [Clinical Physics Laboratory-833, Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); De Boode, W P [Neonatology, Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Huisman, H J [Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Kapusta, L [Pediatric Cardiology, Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)], E-mail: m.m.nillesen@cukz.umcn.nl

    2009-04-07

    Automatic segmentation of the endocardial surface in three-dimensional (3D) echocardiographic images is an important tool to assess left ventricular (LV) geometry and cardiac output (CO). The presence of speckle noise as well as the nonisotropic characteristics of the myocardium impose strong demands on the segmentation algorithm. In the analysis of normal heart geometries of standardized (apical) views, it is advantageous to incorporate a priori knowledge about the shape and appearance of the heart. In contrast, when analyzing abnormal heart geometries, for example in children with congenital malformations, this a priori knowledge about the shape and anatomy of the LV might induce erroneous segmentation results. This study describes a fully automated segmentation method for the analysis of non-standard echocardiographic images, without making strong assumptions on the shape and appearance of the heart. The method was validated in vivo in a piglet model. Real-time 3D echocardiographic image sequences of five piglets were acquired in radiofrequency (rf) format. These ECG-gated full volume images were acquired intra-operatively in a non-standard view. Cardiac blood flow was measured simultaneously by an ultrasound transit time flow probe positioned around the common pulmonary artery. Three-dimensional adaptive filtering using the characteristics of speckle was performed on the demodulated rf data to reduce the influence of speckle noise and to optimize the distinction between blood and myocardium. A gradient-based 3D deformable simplex mesh was then used to segment the endocardial surface. A gradient and a speed force were included as external forces of the model. To balance data fitting and mesh regularity, one fixed set of weighting parameters of internal, gradient and speed forces was used for all data sets. End-diastolic and end-systolic volumes were computed from the segmented endocardial surface. The cardiac output derived from this automatic segmentation was

  12. In vivo validation of cardiac output assessment in non-standard 3D echocardiographic images

    International Nuclear Information System (INIS)

    Nillesen, M M; Lopata, R G P; Gerrits, I H; Thijssen, J M; De Korte, C L; De Boode, W P; Huisman, H J; Kapusta, L

    2009-01-01

    Automatic segmentation of the endocardial surface in three-dimensional (3D) echocardiographic images is an important tool to assess left ventricular (LV) geometry and cardiac output (CO). The presence of speckle noise as well as the nonisotropic characteristics of the myocardium impose strong demands on the segmentation algorithm. In the analysis of normal heart geometries of standardized (apical) views, it is advantageous to incorporate a priori knowledge about the shape and appearance of the heart. In contrast, when analyzing abnormal heart geometries, for example in children with congenital malformations, this a priori knowledge about the shape and anatomy of the LV might induce erroneous segmentation results. This study describes a fully automated segmentation method for the analysis of non-standard echocardiographic images, without making strong assumptions on the shape and appearance of the heart. The method was validated in vivo in a piglet model. Real-time 3D echocardiographic image sequences of five piglets were acquired in radiofrequency (rf) format. These ECG-gated full volume images were acquired intra-operatively in a non-standard view. Cardiac blood flow was measured simultaneously by an ultrasound transit time flow probe positioned around the common pulmonary artery. Three-dimensional adaptive filtering using the characteristics of speckle was performed on the demodulated rf data to reduce the influence of speckle noise and to optimize the distinction between blood and myocardium. A gradient-based 3D deformable simplex mesh was then used to segment the endocardial surface. A gradient and a speed force were included as external forces of the model. To balance data fitting and mesh regularity, one fixed set of weighting parameters of internal, gradient and speed forces was used for all data sets. End-diastolic and end-systolic volumes were computed from the segmented endocardial surface. The cardiac output derived from this automatic segmentation was

  13. In vivo validation of cardiac output assessment in non-standard 3D echocardiographic images

    Science.gov (United States)

    Nillesen, M. M.; Lopata, R. G. P.; de Boode, W. P.; Gerrits, I. H.; Huisman, H. J.; Thijssen, J. M.; Kapusta, L.; de Korte, C. L.

    2009-04-01

    Automatic segmentation of the endocardial surface in three-dimensional (3D) echocardiographic images is an important tool to assess left ventricular (LV) geometry and cardiac output (CO). The presence of speckle noise as well as the nonisotropic characteristics of the myocardium impose strong demands on the segmentation algorithm. In the analysis of normal heart geometries of standardized (apical) views, it is advantageous to incorporate a priori knowledge about the shape and appearance of the heart. In contrast, when analyzing abnormal heart geometries, for example in children with congenital malformations, this a priori knowledge about the shape and anatomy of the LV might induce erroneous segmentation results. This study describes a fully automated segmentation method for the analysis of non-standard echocardiographic images, without making strong assumptions on the shape and appearance of the heart. The method was validated in vivo in a piglet model. Real-time 3D echocardiographic image sequences of five piglets were acquired in radiofrequency (rf) format. These ECG-gated full volume images were acquired intra-operatively in a non-standard view. Cardiac blood flow was measured simultaneously by an ultrasound transit time flow probe positioned around the common pulmonary artery. Three-dimensional adaptive filtering using the characteristics of speckle was performed on the demodulated rf data to reduce the influence of speckle noise and to optimize the distinction between blood and myocardium. A gradient-based 3D deformable simplex mesh was then used to segment the endocardial surface. A gradient and a speed force were included as external forces of the model. To balance data fitting and mesh regularity, one fixed set of weighting parameters of internal, gradient and speed forces was used for all data sets. End-diastolic and end-systolic volumes were computed from the segmented endocardial surface. The cardiac output derived from this automatic segmentation was

  14. Nonenhanced magnetic resonance angiography (MRA) of the calf arteries at 3 Tesla: intraindividual comparison of 3D flow-dependent subtractive MRA and 2D flow-independent non-subtractive MRA.

    Science.gov (United States)

    Knobloch, Gesine; Lauff, Marie-Teres; Hirsch, Sebastian; Schwenke, Carsten; Hamm, Bernd; Wagner, Moritz

    2016-12-01

    To prospectively compare 3D flow-dependent subtractive MRA vs. 2D flow-independent non-subtractive MRA for assessment of the calf arteries at 3 Tesla. Forty-two patients with peripheral arterial occlusive disease underwent nonenhanced MRA of calf arteries at 3 Tesla with 3D flow-dependent subtractive MRA (fast spin echo sequence; 3D-FSE-MRA) and 2D flow-independent non-subtractive MRA (balanced steady-state-free-precession sequence; 2D-bSSFP-MRA). Moreover, all patients underwent contrast-enhanced MRA (CE-MRA) as standard-of-reference. Two readers performed a per-segment evaluation for image quality (4 = excellent to 0 = non-diagnostic) and severity of stenosis. Image quality scores of 2D-bSSFP-MRA were significantly higher compared to 3D-FSE-MRA (medians across readers: 4 vs. 3; p Tesla with significantly higher image quality and diagnostic accuracy compared to 3D flow-dependent subtractive MRA (3D-FSE-MRA). • 2D flow-independent non-subtractive MRA (2D-bSSFP-MRA) is a robust NE-MRA technique at 3T • 2D-bSSFP-MRA outperforms 3D flow-dependent subtractive MRA (3D-FSE-MRA) as NE-MRA of calf arteries • 2D-bSSFP-MRA is a promising alternative to CE-MRA for calf PAOD evaluation.

  15. Quasi-laminar stability and sensitivity analyses for turbulent flows: Prediction of low-frequency unsteadiness and passive control

    Science.gov (United States)

    Mettot, Clément; Sipp, Denis; Bézard, Hervé

    2014-04-01

    This article presents a quasi-laminar stability approach to identify in high-Reynolds number flows the dominant low-frequencies and to design passive control means to shift these frequencies. The approach is based on a global linear stability analysis of mean-flows, which correspond to the time-average of the unsteady flows. Contrary to the previous work by Meliga et al. ["Sensitivity of 2-D turbulent flow past a D-shaped cylinder using global stability," Phys. Fluids 24, 061701 (2012)], we use the linearized Navier-Stokes equations based solely on the molecular viscosity (leaving aside any turbulence model and any eddy viscosity) to extract the least stable direct and adjoint global modes of the flow. Then, we compute the frequency sensitivity maps of these modes, so as to predict before hand where a small control cylinder optimally shifts the frequency of the flow. In the case of the D-shaped cylinder studied by Parezanović and Cadot [J. Fluid Mech. 693, 115 (2012)], we show that the present approach well captures the frequency of the flow and recovers accurately the frequency control maps obtained experimentally. The results are close to those already obtained by Meliga et al., who used a more complex approach in which turbulence models played a central role. The present approach is simpler and may be applied to a broader range of flows since it is tractable as soon as mean-flows — which can be obtained either numerically from simulations (Direct Numerical Simulation (DNS), Large Eddy Simulation (LES), unsteady Reynolds-Averaged-Navier-Stokes (RANS), steady RANS) or from experimental measurements (Particle Image Velocimetry - PIV) — are available. We also discuss how the influence of the control cylinder on the mean-flow may be more accurately predicted by determining an eddy-viscosity from numerical simulations or experimental measurements. From a technical point of view, we finally show how an existing compressible numerical simulation code may be used in

  16. Enhancement in the antitumor immunity contributes to the radio-sensitization of tumors by 2-deoxy-D-glucose

    International Nuclear Information System (INIS)

    Farooque, Abdullah; Dwarakanath, B.S.

    2014-01-01

    The glycolytic inhibitor, 2-deoxy-D-glucose sensitizes tumor cells while protects normal cells to radiation and chemotherapeutics in vitro and in vivo. Further, 2-DG has also been suggested as an adjuvant for low dose radiation therapy. Since immunomodulation plays an important role in tumor responses to anticancer therapies and glycolysis influences the activation of lymphocytes, we investigated the effects of 2-DG on immuno-regulatory networks during radiosensitization of Ehrlich ascites tumor (EAT) in mice. Mice were treated with 10 Gy of focal irradiation to tumor and single dose of 2-DG (2 gm/Kg/b.wt) intravenously. Immuno-phenotyping was done using flow cytometry, while cytokines and antibody classes were analyzed using bead array and ELISA. Further, mRNA and protein levels of transcription factors were assessed in sorted splenic CD4 + cells using real time PCR and Western blot techniques. Immune activation in the form of increase in the expression of NK cells, dendritic cells, macrophages and CD4 + cells, while a decrease was noted in myeloid derived suppressor cells (MDSCs), B cells, tumor tolerant CD4 + PD1 + and CD8 + PD1 + after the combined treatment (2-DG+ Radiation). Interestingly, decrease in the (CD4 + CD62L + ) naive cells with concomitant increase in effector memory cells (CD4 + CD44 + ) indicated the immune activation and memory response. This activation was found to be dependent on the restoration of TCR and CD28 mediated signaling leading to the shift from Th2 and Th17 to Th1 in the form of cytokine and antibody class switching and decrease in inflammation, which was correlated with the modulation of transcriptional factors in splenic CD4 + cells. Interestingly, depletion of T-regulatory cells appears to be partly responsible for the immune activation observed. These studies for the first time revealed the immuno-modulatory potential of 2-DG that should facilitate the optimization of protocols for enhancing the efficacy of radiotherapy, besides

  17. Electromagnetic holographic sensitivity field of two-phase flow in horizontal wells

    Science.gov (United States)

    Zhang, Kuo; Wu, Xi-Ling; Yan, Jing-Fu; Cai, Jia-Tie

    2017-03-01

    Electromagnetic holographic data are characterized by two modes, suggesting that image reconstruction requires a dual-mode sensitivity field as well. We analyze an electromagnetic holographic field based on tomography theory and Radon inverse transform to derive the expression of the electromagnetic holographic sensitivity field (EMHSF). Then, we apply the EMHSF calculated by using finite-element methods to flow simulations and holographic imaging. The results suggest that the EMHSF based on the partial derivative of radius of the complex electric potential φ is closely linked to the Radon inverse transform and encompasses the sensitivities of the amplitude and phase data. The flow images obtained with inversion using EMHSF better agree with the actual flow patterns. The EMHSF overcomes the limitations of traditional single-mode sensitivity fields.

  18. 3D vector flow imaging

    DEFF Research Database (Denmark)

    Pihl, Michael Johannes

    The main purpose of this PhD project is to develop an ultrasonic method for 3D vector flow imaging. The motivation is to advance the field of velocity estimation in ultrasound, which plays an important role in the clinic. The velocity of blood has components in all three spatial dimensions, yet...... are (vx, vy, vz) = (-0.03, 95, 1.0) ± (9, 6, 1) cm/s compared with the expected (0, 96, 0) cm/s. Afterwards, 3D vector flow images from a cross-sectional plane of the vessel are presented. The out of plane velocities exhibit the expected 2D circular-symmetric parabolic shape. The experimental results...... verify that the 3D TO method estimates the complete 3D velocity vectors, and that the method is suitable for 3D vector flow imaging....

  19. Phase-sensitive flow cytometer

    Energy Technology Data Exchange (ETDEWEB)

    Steinkamp, J.A.

    1992-12-31

    This report describes phase-sensitive flow cytometer (FCM) which provides additional FCM capability to use the fluorescence lifetime of one or more fluorochromes bound to single cells to provide additional information regarding the cells. The resulting fluorescence emission can be resolved into individual fluorescence signals if two fluorochromes are present or can be converted directly to a decay lifetime from a single fluorochrome. The excitation light for the fluorochromes is modulated to produce an amplitude modulated fluorescence pulse as the fluorochrome is excited in the FCM. The modulation signal also forms a reference signal that is phase-shifted a selected amount for subsequent mixing with the output modulated fluorescence intensity signal in phase-sensitive detection circuitry. The output from the phase-sensitive circuitry is then an individual resolved fluorochrome signal or a single fluorochrome decay lifetime, depending on the applied phase shifts.

  20. Efficacy of in vitro sensitized cells generated by in vivo priming with OK-432 for adoptive immunotherapy of the poorly immunogenic B16-Bl6 melanoma.

    Science.gov (United States)

    Mukai, S; Kato, H; Kimura, S; Asai, K; Kawahito, Y; Inoue, M; Yamamura, Y; Sano, H; Sugino, S; Shu, S; Kondo, M

    1996-02-01

    We investigated the efficacy of the streptococcal preparation OK-432 as an adjuvant for in vivo priming in induction of sensitized cells for adoptive immunotherapy of the poorly immunogenic B16-BL6 (BL6) melanoma. C57BL/6 (B6) mice were immunized subcutaneously (s.c.) with 3 x 10(6) viable BL6 tumor cells admixed with various doses of OK-432 ranging from 1 to 100 micrograms in the foot-pad. Draining popliteal lymph nodes (LNs) were harvested 7 days after immunization and LN cells were further sensitized with irradiated tumor cells in the presence of 60-300 IU/ml of IL-2 for 11 days. These in vitro sensitized (IVS) cells (2 x 10(6)) were transferred intravenously (i.v.) to B6 mice bearing 4-day pulmonary metastases established by i.v. injection of 2-4 x 10(5) viable BL6 cells. The mice were also received intraperitoneally (i.p.) 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer. Transfer of IVS cells from mice immunized by s.c. injection of tumor cells admixed with 10 micrograms of OK-432 significantly reduced the numbers of BL6 pulmonary metastases compared with that of control IVS' cells without the administration of OK-432 (P = 0.003). These effective IVS cells also significantly prolonged the survival of treated animals (P = 0.003). Functional IVS cells required in vitro stimulation with tumor cells. However, addition of OK-432 in the vaccine resulted in no enhancement of in vitro cytotoxicity and no characteristic change of phenotype of IVS cells. These results suggest that in vivo priming of OK-432 facilitates the sensitization of tumor-reactive T-cells. The procedure of in vivo priming with OK-432 may be beneficial in the adoptive immunotherapy of melanoma.

  1. The Neopuff's PEEP valve is flow sensitive.

    LENUS (Irish Health Repository)

    Hawkes, Colin Patrick

    2011-03-01

    The current recommendation in setting up the Neopuff is to use a gas flow of 5-15 L\\/min. We investigated if the sensitivity of the positive end expiratory pressure (PEEP) valve varies at different flow rates within this range.

  2. Validation of Dynamic optical coherence tomography for non-invasive, in vivo microcirculation imaging of the skin

    DEFF Research Database (Denmark)

    Themstrup, L.; Welzel, Julia; Ciardo, Silvana

    2016-01-01

    Objectives: Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D.......001), and also the redness a measurements were positively correlated with the D-OCT measurements (r = 0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow. Conclusion: This study has...... initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo...

  3. High sensitivity and selectivity in quantitative analysis of drugs in biological samples using 4-column multidimensional micro-UHPLC-MS enabling enhanced sample loading capacity.

    Science.gov (United States)

    de Vries, Ronald; Vereyken, Liesbeth; François, Isabelle; Dillen, Lieve; Vreeken, Rob J; Cuyckens, Filip

    2017-10-09

    Sensitivity is often a critical parameter in quantitative bioanalyses in drug development. For liquid-chromatography-based methods, sensitivity can be improved by reducing the column diameter, but practical sensitivity gains are limited by the reduced sample loading capacity on small internal diameter (I.D.) columns. We developed a set-up that has overcome these limitations in sample loading capacity. The set-up uses 4 columns with gradually decreasing column diameters along the flow-path (2.1 → 1 → 0.5 → 0.15 mm). Samples are pre-concentrated on-line on a 2.1 mm I.D. trapping column and back flushed to a 1 mm I.D. UHPLC analytical column and separated. The peak(s) of interest are transferred using heartcutting to a second trapping column (0.5 mm I.D.), which is back-flushed to a 0.15 mm I.D. micro-UHPLC analytical column for orthogonal separation. The proof of concept of the set-up was demonstrated by the simultaneous analysis of midazolam and 1'-hydroxy midazolam in plasma by injection of 80 μL of protein precipitated plasma. The 4-column funnel set-up proved to be robust and resulted in a 10-50 times better sensitivity compared to a trap-elute approach and 250-500 fold better compared to direct micro-UHPLC analysis. A lower limit of quantification of 100 fg/mL in plasma was obtained for both probe compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Measuring in-vivo and in-situ ex-vivo the 3D deformation of the lamina cribrosa microstructure under elevated intraocular pressure

    Science.gov (United States)

    Wei, Junchao; Yang, Bin; Voorhees, Andrew P.; Tran, Huong; Brazile, Bryn; Wang, Bo; Schuman, Joel; Smith, Matthew A.; Wollstein, Gadi; Sigal, Ian A.

    2018-02-01

    Elevated intraocular pressure (IOP) deforms the lamina cribrosa (LC), a structure within the optic nerve head (ONH) in the back of the eye. Evidence suggests that these deformations trigger events that eventually cause irreversible blindness, and have therefore been studied in-vivo using optical coherence tomography (OCT), and ex-vivo using OCT and a diversity of techniques. To the best of our knowledge, there have been no in-situ ex-vivo studies of LC mechanics. Our goal was two-fold: to introduce a technique for measuring 3D LC deformations from OCT, and to determine whether deformations of the LC induced by elevated IOP differ between in-vivo and in-situ ex-vivo conditions. A healthy adult rhesus macaque monkey was anesthetized and IOP was controlled by inserting a 27- gauge needle into the anterior chamber of the eye. Spectral domain OCT was used to obtain volumetric scans of the ONH at normal and elevated IOPs. To improve the visibility of the LC microstructure the scans were first processed using a novel denoising technique. Zero-normalized cross-correlation was used to find paired corresponding locations between images. For each location pair, the components of the 3D strain tensor were determined using non-rigid image registration. A mild IOP elevation from 10 to 15mmHg caused LC effective strains as large as 3%, and about 50% larger in-vivo than in-situ ex-vivo. The deformations were highly heterogeneous, with substantial 3D components, suggesting that accurate measurement of LC microstructure deformation requires high-resolution volumes. This technique will help improve understanding of LC biomechanics and how IOP contributes to glaucoma.

  5. Vascular effects of leukotriene D4 in human skin

    DEFF Research Database (Denmark)

    Bisgaard, H

    1987-01-01

    Leukotriene D4 (LTD4) increased the blood flow rate in human skin, equipotent to histamine in the dose range of 3.1-200 pmol. The vasodilatation lasted for up to 60 min, and no late reactions occurred. Indomethacin did not affect the LTD4-induced blood flow rate. H1 and H2 antagonists reduced...... as a mediator of the axon reflex, and show that LTD4 causes a direct vasodilatory effect that is not mediated via histamine or cyclooxygenase products. The laser-Doppler flowmeter was applied for dynamic studies of the vasopressor response in the skin during a Valsalva maneuver, and the relative changes...

  6. Atomistic Galois insertions for flow sensitive integrity

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nielson, Hanne Riis

    2017-01-01

    Several program verification techniques assist in showing that software adheres to the required security policies. Such policies may be sensitive to the flow of execution and the verification may be supported by combinations of type systems and Hoare logics. However, this requires user assistance...... and to obtain full automation we shall explore the over-approximating nature of static analysis. We demonstrate that the use of atomistic Galois insertions constitutes a stable framework in which to obtain sound and fully automatic enforcement of flow sensitive integrity. The framework is illustrated...

  7. Ex vivo tracheomalacia model with 3D-printed external tracheal splint.

    Science.gov (United States)

    Kaye, Rachel; Goldstein, Todd; Aronowitz, Danielle; Grande, Daniel A; Zeltsman, David; Smith, Lee P

    2017-04-01

    To design and evaluate an ex vivo model of tracheomalacia with and without a three-dimensional (3D)-printed external tracheal splint. Prospective, ex vivo animal trial. Three groups of ex vivo porcine tracheas were used: 1) control (unmanipulated trachea), 2) tracheomalacia (tracheal rings partially incised and crushed), and 3) splinted tracheomalacia (external custom tracheal splint fitted onto group 2 trachea). Each end of an ex vivo trachea was sealed with a custom-designed and 3D-printed cap; a transducer was placed through one end to measure the pressure inside the trachea. Although the negative pressure was applied to the tracheal lumen, the tracheal wall collapse was measured externally and internally using a bronchoscope. Each group had at least three recorded trials. Tracheal diameter was evaluated using ImageJ software (National Institutes of Health, Bethesda, MD) and was averaged between two raters. Average tracheal occlusion percentage was compared using Student t test. The average occlusion was 31% for group 1, 87.4% for group 2, and 20% for group 3. Significant differences were found between the control and tracheomalacia groups (P tracheomalacia and splinted tracheomalacia groups (P tracheomalacia groups (P = 0.13). Applied pressure was plotted against occlusion and regression line slope differed between the tracheomalacia (0.91) and control (0.12) or splinted tracheomalacia (0.39) groups. We demonstrate the potential for an ex vivo tracheomalacia model to reproduce airway collapse and show that this collapse can be treated successfully with a 3D-printed external splint. These results are promising and justify further studies. N/A. Laryngoscope, 127:950-955, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  8. FLAIR vascular hyperintensities and 4D MR angiograms for the estimation of collateral blood flow in anterior cerebral artery ischemia.

    Directory of Open Access Journals (Sweden)

    Matthias Gawlitza

    Full Text Available To assess FLAIR vascular hyperintensities (FVH and dynamic (4D angiograms derived from perfusion raw data as proposed magnetic resonance (MR imaging markers of leptomeningeal collateral circulation in patients with ischemia in the territory of the anterior cerebral artery (ACA.Forty patients from two tertiary care university hospitals were included. Infarct volumes and perfusion deficits were manually measured on DWI images and TTP maps, respectively. FVH and collateral flow on 4D MR angiograms were assessed and graded as previously specified.Forty-one hemispheres were affected. Mean DWI lesion volume was 8.2 (± 13.9; range 0-76.9 ml, mean TTP lesion volume was 24.5 (± 17.2, range 0-76.7 ml. FVH were observed in 26/41 (63.4% hemispheres. Significant correlations were detected between FVH and TTP lesion volume (ρ = 0.4; P<0.01 absolute (ρ = 0.37; P<0.05 and relative mismatch volume (ρ = 0.35; P<0.05. The modified ASITN/SIR score correlated inversely with DWI lesion volume (ρ = -0.58; P<0.01 and positively with relative mismatch (ρ = 0.29; P< 0.05. ANOVA of the ASITN/SIR score revealed significant inter-group differences for DWI (P<0.001 and TTP lesion volumes (P<0.05. No correlation was observed between FVH scores and modified ASITH/SIR scores (ρ = -0.16; P = 0.32.FVH and flow patterns on 4D MR angiograms are markers of perfusion deficits and tissue at risk. As both methods did not show a correlation between each other, they seem to provide complimentary instead of redundant information. Previously shown evidence for the meaning of these specific MR signs in internal carotid and middle cerebral artery stroke seems to be transferrable to ischemic stroke in the ACA territory.

  9. Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available CD4(+ T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+ cells, and (ii that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+ compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+ T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p and disappearance (d* rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul participated. CCR5-expression defined a CD4(+ subpopulation of predominantly CD45R0(+ memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+ vs CCR5(-; healthy controls; P<0.01. Conversely, CXCR4 expression defined CD4(+ T-cells (predominantly CD45RA(+ naive cells with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+CD45R0(+CD4(+ memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05, naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9 or X4-tropic (n = 4. Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively. Our data are most consistent with models in which CD4(+ T-cell loss is primarily driven by non-specific immune activation.

  10. Sensitivity Analysis for Steady State Groundwater Flow Using Adjoint Operators

    Science.gov (United States)

    Sykes, J. F.; Wilson, J. L.; Andrews, R. W.

    1985-03-01

    Adjoint sensitivity theory is currently being considered as a potential method for calculating the sensitivity of nuclear waste repository performance measures to the parameters of the system. For groundwater flow systems, performance measures of interest include piezometric heads in the vicinity of a waste site, velocities or travel time in aquifers, and mass discharge to biosphere points. The parameters include recharge-discharge rates, prescribed boundary heads or fluxes, formation thicknesses, and hydraulic conductivities. The derivative of a performance measure with respect to the system parameters is usually taken as a measure of sensitivity. To calculate sensitivities, adjoint sensitivity equations are formulated from the equations describing the primary problem. The solution of the primary problem and the adjoint sensitivity problem enables the determination of all of the required derivatives and hence related sensitivity coefficients. In this study, adjoint sensitivity theory is developed for equations of two-dimensional steady state flow in a confined aquifer. Both the primary flow equation and the adjoint sensitivity equation are solved using the Galerkin finite element method. The developed computer code is used to investigate the regional flow parameters of the Leadville Formation of the Paradox Basin in Utah. The results illustrate the sensitivity of calculated local heads to the boundary conditions. Alternatively, local velocity related performance measures are more sensitive to hydraulic conductivities.

  11. Production of interferon-gamma by in vivo tumor-sensitized T cells: Association with active antitumor immunity

    International Nuclear Information System (INIS)

    Bursuker, I.; Pearce, M.T.

    1990-01-01

    The state of active immunity to Meth A fibrosarcoma in mice immunized with an admixture of Meth A cells and Propionibacterium acnes is associated with possession by the host of spleen cells capable of producing interferon-gamma (IFN-gamma) upon in vitro restimulation with irradiated tumor cells. The ability of spleen cells from immunized mice to produce IFN-gamma in response to irradiated Meth A cells decays as active antitumor immunity is replaced by a state of immunological memory. The IFN-producing cells are L3T4+Ly2+, cyclophosphamide-sensitive and radiosensitive T cells, as determined by their sensitivity to corresponding monoclonal antibodies and complement. The induction of IFN-gamma production by in vivo tumor-sensitized T cells is tumor specific, in that spleen cells from mice immunized against Meth A fibrosarcoma can produce IFN in response to irradiated Meth A cells but not in response to another syngeneic tumor M109 lung carcinoma

  12. GRASP [GRound-Water Adjunct Sensitivity Program]: A computer code to perform post-SWENT [simulator for water, energy, and nuclide transport] adjoint sensitivity analysis of steady-state ground-water flow: Technical report

    International Nuclear Information System (INIS)

    Wilson, J.L.; RamaRao, B.S.; McNeish, J.A.

    1986-11-01

    GRASP (GRound-Water Adjunct Senstivity Program) computes measures of the behavior of a ground-water system and the system's performance for waste isolation, and estimates the sensitivities of these measures to system parameters. The computed measures are referred to as ''performance measures'' and include weighted squared deviations of computed and observed pressures or heads, local Darcy velocity components and magnitudes, boundary fluxes, and travel distance and time along travel paths. The sensitivities are computed by the adjoint method and are exact derivatives of the performance measures with respect to the parameters for the modeled system, taken about the assumed parameter values. GRASP presumes steady-state, saturated grondwater flow, and post-processes the results of a multidimensional (1-D, 2-D, 3-D) finite-difference flow code. This document describes the mathematical basis for the model, the algorithms and solution techniques used, and the computer code design. The implementation of GRASP is verified with simple one- and two-dimensional flow problems, for which analytical expressions of performance measures and sensitivities are derived. The linkage between GRASP and multidimensional finite-difference flow codes is described. This document also contains a detailed user's manual. The use of GRASP to evaluate nuclear waste disposal issues has been emphasized throughout the report. The performance measures and their sensitivities can be employed to assist in directing data collection programs, expedite model calibration, and objectively determine the sensitivity of projected system performance to parameters

  13. A novel five-wire micro anemometer with 3D directionality for low speed air flow detection and acoustic particle velocity detecting capability

    Science.gov (United States)

    Li, Zhe; Chang, Wenhan; Gao, Chengchen; Hao, Yilong

    2018-04-01

    In this paper, a novel five-wire micro-fabricated anemometer with 3D directionality based on calorimetric principle is proposed, which is capable of measuring low speed airflow. This structure is realized by vertically bonding two different dies, which can be fabricated on the same wafer resulting in a simple fabrication process. Experiments on speed lower than 200 mm s-1 are conducted, showing good repeatability and directionality. The speed of airflow is controlled by the volumetric flow rate. The measured velocity sensitivity is 9.4 mV · s m-1, with relative direction sensitivity of 37.1 dB. The deviation between the expected and the measured directivity is analyzed by both theories and simulations. A correction procedure is proposed and turns out to be useful to eliminate this deviation. To further explore the potential of our device, we expose it to acoustic plane waves in a standing wave tube, showing consistent planar directivity of figure of eight. The measured velocity sensitivity at 1 kHz and 120 dBC is 4.4 mV · s m-1, with relative direction sensitivity of 27.0 dB. By using the correction method proposed above, the maximum angle error is about  ±2°, showing its good directionality accuracy.

  14. Intratumoral pharmacokinetic analysis by 19F-magnetic resonance spectroscopy and cytostatic in vivo activity of gemcitabine (dFdC) in two small cell lung cancer xenografts

    DEFF Research Database (Denmark)

    Kristjansen, P E; Quistorff, B; Spang-Thomsen, M

    1993-01-01

    BACKGROUND: Gemcitabine, 2'2'difluoro-deoxycytidine (dFdC), has shown activity in several preclinical models, and presently the compound is being clinically evaluated in patients with lung cancer and other solid tumors. DESIGN: The cytostatic in vivo activity of dFdC was tested in the two human.......p. every third day, four times were applied. RESULTS AND CONCLUSION: Significant activity of gemcitabine was demonstrated in both SCLC tumor lines. The tumor line 54A is the most sensitive to radiotherapy, doxorubicin, and nitrosoureas; but in this case the 54B tumors were more sensitive to gemcitabine...

  15. A Comparison of the Capability of Sensitivity Level 3 and Sensitivity Level 4 Fluorescent Penetrants to Detect Fatigue Cracks in Aluminum

    Science.gov (United States)

    Parker, Bradford, H.

    2009-01-01

    Historically both sensitivity level 3 and sensitivity level 4 fluorescent penetrants have been used to perform NASA Standard Level inspections of aerospace hardware. In April 2008, NASA-STD-5009 established a requirement that only sensitivity level 4 penetrants were acceptable for inspections of NASA hardware. Having NASA contractors change existing processes or perform demonstration tests to certify sensitivity level 3 penetrants posed a potentially huge cost to the Agency. This study was conducted to directly compare the probability of detection sensitivity level 3 and level 4 penetrants using both Method A and Method D inspection processes. The study results strongly support the conclusion that sensitivity level 3 penetrants are acceptable for NASA Standard Level inspections

  16. Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects

    Science.gov (United States)

    Gelston, Eloise A; Coller, Janet K; Lopatko, Olga V; James, Heather M; Schmidt, Helmut; White, Jason M; Somogyi, Andrew A

    2012-01-01

    AIMS To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects. METHODS Ten methadone- and eight buprenorphine-maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine-3- and -6-glucuronides and codeine-6-glucuronide. RESULTS The urinary metabolic ratio for O-demethylation was significantly higher (P = 0.0044) in the subjects taking methadone (mean ± SD, 2.8 ± 3.1) compared with those taking buprenorphine (0.60 ± 0.43), likewise for 6-glucuronide formation (0.31 ± 0.24 vs. 0.053 ± 0.027; P D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6. PMID:22092298

  17. Chaotic advection and heat transfer in two similar 2-D periodic flows and in their corresponding 3-D periodic flows

    Science.gov (United States)

    Vinsard, G.; Dufour, S.; Saatdjian, E.; Mota, J. P. B.

    2016-03-01

    Chaotic advection can effectively enhance the heat transfer rate between a boundary and fluids with high Prandtl number. These fluids are usually highly viscous and thus turbulent agitation is not a viable solution since the energy required to mix the fluid would be prohibitive. Here, we analyze previously obtained results on chaotic advection and heat transfer in two similar 2-D periodic flows and on their corresponding 3-D periodic flows when an axial velocity component is superposed. The two flows studied are the flow between eccentric rotating cylinders and the flow between confocal ellipses. For both of these flows the analysis is simplified because the Stokes equations can be solved analytically to obtain a closed form solution. For both 2-D periodic flows, we show that chaotic heat transfer is enhanced by the displacement of the saddle point location during one period. Furthermore, the enhancement by chaotic advection in the elliptical geometry is approximately double that obtained in the cylindrical geometry because there are two saddle points instead of one. We also explain why, for high eccentricity ratios, there is no heat transfer enhancement in the cylindrical geometry. When an axial velocity component is added to both of these flows so that they become 3-D, previous work has shown that there is an optimum modulation frequency for which chaotic advection and heat transfer enhancement is a maximum. Here we show that the optimum modulation frequency can be derived from results without an axial flow. We also explain by physical arguments other previously unanswered questions in the published data.

  18. Synthesis and in vitro evaluation of no-carrier-added 2-(3-(4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole, a potential dopamine D{sub 4} receptor radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gu-Cai; Zhang, Ru [Hunan Institute of Engineering, Hunan Xiangtan (China). College of Chemistry and Chemical Engineering; Xia, Jiao-yun [Changsha Univ. of Science and Technology (China). School of Chemistry and Biology Engineering

    2016-07-01

    The dopamine D{sub 4} receptor has been shown to play important roles in some central nervous system pathologies. Specific radioligands for the D{sub 4} receptor may be useful to understand the function of the D{sub 4} receptor and its correlations with various disorders. 2-(3-(4-(4-[{sup 18}F]Fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole ([{sup 18}F]4) was synthesized through a one-pot two-step procedure with total yield 18.6% (decay corrected). The specific activity of the radioligand was 112 GBq/μmol and its radiochemical purity was >95.0%. Its affinity and selectivity for dopamine D{sub 2}-like receptors were measured through in vitro receptor binding evaluation and the K{sub i} value for the D{sub 4} receptor was determined to be 2.9±0.2 nM, and its selectivity for the dopamine D{sub 4} receptor is 709-fold versus D{sub 2long} receptor, 823-fold versus D{sub 3} receptor. The partition coefficient (Log D) of it was determined to be 2.6±0.1 through octanol-water partition experiment. The ligand presents desirable combination of lipophilicity, affinity and selectivity for the dopamine D{sub 4} receptor. The results suggested that the radioligand shows promises for the in vivo study of the dopamine D{sub 4} receptor.

  19. In vivo validation of a 3D ultrasound system for imaging the lateral ventricles of neonates

    Science.gov (United States)

    Kishimoto, J.; Fenster, A.; Chen, N.; Lee, D.; de Ribaupierre, S.

    2014-03-01

    Dilated lateral ventricles in neonates can be due to many different causes, such as brain loss, or congenital malformation; however, the main cause is hydrocephalus, which is the accumulation of fluid within the ventricular system. Hydrocephalus can raise intracranial pressure resulting in secondary brain damage, and up to 25% of patients with severely enlarged ventricles have epilepsy in later life. Ventricle enlargement is clinically monitored using 2D US through the fontanels. The sensitivity of 2D US to dilation is poor because it cannot provide accurate measurements of irregular volumes such as the ventricles, so most clinical evaluations are of a qualitative nature. We developed a 3D US system to image the cerebral ventricles of neonates within the confines of incubators that can be easily translated to more open environments. Ventricle volumes can be segmented from these images giving a quantitative volumetric measurement of ventricle enlargement without moving the patient into an imaging facility. In this paper, we report on in vivo validation studies: 1) comparing 3D US ventricle volumes before and after clinically necessary interventions removing CSF, and 2) comparing 3D US ventricle volumes to those from MRI. Post-intervention ventricle volumes were less than pre-intervention measurements for all patients and all interventions. We found high correlations (R = 0.97) between the difference in ventricle volume and the reported removed CSF with the slope not significantly different than 1 (p < 0.05). Comparisons between ventricle volumes from 3D US and MR images taken 4 (±3.8) days of each other did not show significant difference (p=0.44) between 3D US and MRI through paired t-test.

  20. In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages.

    Science.gov (United States)

    Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher; Zhang, Qiang; Cobley, Claire M; Gao, Feng; Xia, Younan; Wang, Lihong V

    2010-08-24

    Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bioconjugated with [Nle(4),D-Phe(7)]-alpha-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bioconjugated AuNCs enhanced contrast approximately 300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS).

  1. The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo.

    Science.gov (United States)

    Holme, Ane M; Holm, Maia B; Roland, Marie C P; Horne, Hildegunn; Michelsen, Trond M; Haugen, Guttorm; Henriksen, Tore

    2017-08-02

    The human placenta is highly inaccessible for research while still in utero. The current understanding of human placental physiology in vivo is therefore largely based on animal studies, despite the high diversity among species in placental anatomy, hemodynamics and duration of the pregnancy. The vast majority of human placenta studies are ex vivo perfusion studies or in vitro trophoblast studies. Although in vitro studies and animal models are essential, extrapolation of the results from such studies to the human placenta in vivo is uncertain. We aimed to study human placenta physiology in vivo at term, and present a detailed protocol of the method. Exploiting the intraabdominal access to the uterine vein just before the uterine incision during planned cesarean section, we collect blood samples from the incoming and outgoing vessels on the maternal and fetal sides of the placenta. When combining concentration measurements from blood samples with volume blood flow measurements, we are able to quantify placental and fetal uptake and release of any compound. Furthermore, placental tissue samples from the same mother-fetus pairs can provide measurements of transporter density and activity and other aspects of placental functions in vivo. Through this integrative use of the 4-vessel sampling method we are able to test some of the current concepts of placental nutrient transfer and metabolism in vivo, both in normal and pathological pregnancies. Furthermore, this method enables the identification of substances secreted by the placenta to the maternal circulation, which could be an important contribution to the search for biomarkers of placenta dysfunction.

  2. Radiochemical synthesis and biological evaluation of 3-[4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine as dopamine D{sub 4} receptor radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gu-Cai; Zhang, Ru; Jiang, Kai-Jun; Chen, Bo [Hunan Institute of Engineering, Xiangtan (China). College of Chemistry and Chemical Engineering

    2014-09-01

    A potential dopamine D{sub 4} receptor radioligand, 3-[4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine was synthesized through a one-pot two-step procedure with total yield 18.5% (decay corrected). The molar radioactivity was 115 GBq/μmol and the radiochemical purity was greater than 95.5%. Its affinity and selectivity for dopamine D{sub 2}-like receptors were measured through in vitro receptor binding experiments and the K{sub i} for D{sub 4} receptor was determined to be 17 ± 0.5 nM. The partition coefficient (Log P) of it was determined to be 2.80 ± 0.10 through octanol experiment. The in vivo biodistribution of it in rat brain exposed that the radioligand penetrates through blood-brain- barrier (BBB) and may specifically bind to dopamine D{sub 4} receptor. The results indicated that the radioligand shows promise for the in vivo study of dopamine D{sub 4} receptor. (orig.)

  3. 3D IBFV : hardware-accelerated 3D flow visualization

    NARCIS (Netherlands)

    Telea, A.C.; Wijk, van J.J.

    2003-01-01

    We present a hardware-accelerated method for visualizing 3D flow fields. The method is based on insertion, advection, and decay of dye. To this aim, we extend the texture-based IBFV technique presented by van Wijk (2001) for 2D flow visualization in two main directions. First, we decompose the 3D

  4. X-ray PIV measurement of blood flow in deep vessels of a rat: An in vivo feasibility study.

    Science.gov (United States)

    Park, Hanwook; Yeom, Eunseop; Lee, Sang Joon

    2016-01-18

    X-ray PIV measurement is a noninvasive approach to measure opaque blood flows. However, it is not easy to measure real pulsatile blood flows in the blood vessels located at deep position of the body, because the surrounding tissues significantly attenuate the contrast of X-ray images. This study investigated the effect of surrounding tissues on X-ray beam attenuation by measuring the velocity fields of blood flows in deep vessels of a live rat. The decrease in image contrast was minimized by employing biocompatible CO2 microbubbles as tracer particles. The maximum measurable velocity of blood flows in the abdominal aorta of a rat model was found through comparative examination between the PIV measurement accuracy and the level of image contrast according to the input flow rate. Furthermore, the feasibility of using X-ray PIV to accurately measure in vivo blood flows was demonstrated by determining the velocity field of blood flows in the inferior vena cava of a rat. This study may serve as a reference in conducting in vivo X-ray PIV measurements of pulsatile blood flows in animal disease models and investigating hemodynamic characteristics and circulatory vascular diseases.

  5. Measurement of in vitro and in vivo stent geometry and deformation by means of 3D imaging and stereo-photogrammetry.

    Science.gov (United States)

    Zwierzak, Iwona; Cosentino, Daria; Narracott, Andrew J; Bonhoeffer, Philipp; Diaz, Vanessa; Fenner, John W; Schievano, Silvia

    2014-12-01

    To quantify variability of in vitro and in vivo measurement of 3D device geometry using 3D and biplanar imaging. Comparison of stent reconstruction is reported for in vitro coronary stent deployment (using micro-CT and optical stereo-photogrammetry) and in vivo pulmonary valve stent deformation (using 4DCT and biplanar fluoroscopy). Coronary stent strut length and inter-strut angle were compared in the fully deployed configuration. Local (inter-strut angle) and global (dog-boning ratio) measures of stent deformation were reported during stent deployment. Pulmonary valve stent geometry was assessed throughout the cardiac cycle by reconstruction of stent geometry and measurement of stent diameter. Good agreement was obtained between methods for assessment of coronary stent geometry with maximum disagreement of +/- 0.03 mm (length) and +/- 3 degrees (angle). The stent underwent large, non-uniform, local deformations during balloon inflation, which did not always correlate with changes in stent diameter. Three-dimensional reconstruction of the pulmonary valve stent was feasible for all frames of the fluoroscopy and for 4DCT images, with good correlation between the diameters calculated from the two methods. The largest compression of the stent during the cardiac cycle was 6.98% measured from fluoroscopy and 7.92% from 4DCT, both in the most distal ring. Quantitative assessment of stent geometry reconstructed from biplanar imaging methods in vitro and in vivo has shown good agreement with geometry reconstructed from 3D techniques. As a result of their short image acquisition time, biplanar methods may have significant advantages in the measurement of dynamic 3D stent deformation.

  6. Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

    Science.gov (United States)

    Wang, Mengshu; Zhang, Yong; Feng, Jiao; Gu, Tiejun; Dong, Qingguang; Yang, Xu; Sun, Yanan; Wu, Yongge; Chen, Yan; Kong, Wei

    2013-01-01

    Background Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide) (CS-PLGA) nanoparticles was investigated for intestinal delivery of exendin-4. Methods and results Nanoparticles were prepared using a modified water–oil–water (w/o/w) emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ~30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ~300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis, as evidenced by using endocytic inhibitors. However, under all conditions, CS-PLGA nanoparticles showed a greater potential to be transported into cells, as shown by flow cytometry and confocal microscopy. Transmembrane permeability analysis showed that unmodified and modified PLGA nanoparticles could improve the transport of exendin-4 by up to 8.9- and 16.5-fold, respectively

  7. Syntheses and in vitro evaluation of fluorinated naphthoxazines as dopamine D2/D3 receptor agonists: radiosynthesis, ex vivo biodistribution and autoradiography of [18F]F-PHNO

    International Nuclear Information System (INIS)

    Vasdev, Neil; Seeman, Philip; Garcia, Armando; Stableford, Winston T.; Nobrega, Jose N.; Houle, Sylvain; Wilson, Alan A.

    2007-01-01

    Introduction: Carbon-11-labeled (+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([ 11 C]-(+)-PHNO) is a dopamine D2/D3 agonist radioligand that is currently used to image the high-affinity state of dopamine receptors in humans with positron emission tomography (PET). The present study reports the preparation and evaluation of fluorinated (+)-PHNO derivatives. Methods: Five fluorinated (+)-PHNO derivatives were synthesized and tested in vitro for inhibition of binding of [ 3 H]domperidone in homogenates of rat striatum and inhibition of binding to [ 3 H]-(+)-PHNO in homogenates of human-cloned D2Long receptors in Chinese hamster ovary cells and rat striatum. Radiolabeling with fluorine-18 was carried out for the most promising candidate, N-fluoropropyl-(+)-HNO (F-PHNO), and ex vivo biodistribution and autoradiography studies with this radiopharmaceutical were performed in rodents. Results: (+)-PHNO and the fluorinated analogs inhibited binding of [ 3 H]domperidone and [ 3 H]-(+)-PHNO to the high- and low-affinity states of dopamine D2 receptors, consistent with D2 agonist behavior. The average dissociation constant at the high-affinity state of D2, K i High , was 0.4 nM for F-PHNO and proved to be equipotent with (+)-PHNO (0.7 nM). All other fluorinated derivatives were significantly less potent (K i High =2-102 nM). The most promising candidate, F-PHNO, was labeled with fluorine-18 in 5% uncorrected radiochemical yield, with respect to starting fluoride. Ex vivo biodistribution and autoradiography studies in rodents revealed that [ 18 F]F-PHNO rapidly enters the rodent brain. However, this radiotracer does not reveal specific binding in the brain and is rapidly cleared. Conclusions: Five novel dopamine D2/D3 agonists based on (+)-PHNO were synthesized and evaluated in vitro. F-PHNO was shown to behave as a potent D2 agonist in vitro and was therefore radiolabeled with fluorine-18. Despite the promising in vitro pharmacological profile, [ 18

  8. Synchrotron 4-dimensional imaging of two-phase flow through porous media.

    Science.gov (United States)

    Kim, F H; Penumadu, D; Patel, P; Xiao, X; Garboczi, E J; Moylan, S P; Donmez, M A

    2016-01-01

    Near real-time visualization of complex two-phase flow in a porous medium was demonstrated with dynamic 4-dimensional (4D) (3D + time) imaging at the 2-BM beam line of the Advanced Photon Source (APS) at Argonne National Laboratory. Advancing fluid fronts through tortuous flow paths and their interactions with sand grains were clearly captured, and formations of air bubbles and capillary bridges were visualized. The intense X-ray photon flux of the synchrotron facility made 4D imaging possible, capturing the dynamic evolution of both solid and fluid phases. Computed Tomography (CT) scans were collected every 12 s with a pixel size of 3.25 µm. The experiment was carried out to improve understanding of the physics associated with two-phase flow. The results provide a source of validation data for numerical simulation codes such as Lattice-Boltzmann, which are used to model multi-phase flow through porous media.

  9. Plasma flow in the DIII-D divertor

    International Nuclear Information System (INIS)

    Boedo, J.A.; Porter, G.D.; Schaffer, M.J.

    1998-07-01

    Indications that flows in the divertor can exhibit complex behavior have been obtained from 2-D modeling but so far remain mostly unconfirmed by experiment. An important feature of flow physics is that of flow reversal. Flow reversal has been predicted analytically and it is expected when the ionization source arising from neutral or impurity ionization in the divertor region is large, creating a high pressure zone. Plasma flows arise to equilibrate the pressure. A radiative divertor regime has been proposed in order to reduce the heat and particle fluxes to the divertor target plates. In this regime, the energy and momentum of the plasma are dissipated into neutral gas introduced in the divertor region, cooling the plasma by collisional, radiative and other atomic processes so that the plasma becomes detached from the target plates. These regimes have been the subject of extensive studies in DIII-D to evaluate their energy and particle transport properties, but only recently it has been proposed that the energy transport over large regions of the divertor must be dominated by convection instead of conduction. It is therefore important to understand the role of the plasma conditions and geometry on determining the region of convection-dominated plasma in order to properly control the heat and particle fluxes to the target plates and hence, divertor performance. The authors have observed complex structures in the deuterium ion flows in the DIII-D divertor. Features observed include reverse flow, convective flow over a large volume of the divertor and stagnant flow. They have measured large gradients in the plasma potential across the separatrix in the divertor and determined that these gradients induce poloidal flows that can potentially affect the particle balance in the divertor

  10. Sensitivity to draught in turbulent air flows

    Energy Technology Data Exchange (ETDEWEB)

    Todde, V

    1998-09-01

    Even though the ventilation system is designed to supply air flows at constant low velocity and controlled temperature, the resulting air movement in rooms is strongly characterised by random fluctuations. When an air flow is supplied from an inlet, a shear layer forms between the incoming and the standstill air in the room, and large scale vortices develops by coalescence of the vorticity shed at the inlet of the air supply. After a characteristically downstream distance, large scale vortices loose their identity because of the development of cascading eddies and transition to turbulence. The interaction of these vortical structures will rise a complicated three dimensional air movement affected by fluctuations whose frequencies could vary from fractions of Hz to several KHz. The perception and sensitivity to the cooling effect enhanced by these air movements depend on a number of factors interacting with each other: physical properties of the air flow, part and extension of the skin surface exposed to the air flow, exposure duration, global thermal condition, gender and posture of the person. Earlier studies were concerned with the percentage of dissatisfied subjects as a function of air velocity and temperature. Recently, experimental observations have shown that also the fluctuations, the turbulence intensity and the direction of air velocity have an important impact on draught discomfort. Two experimental investigations have been developed to observe the human reaction to horizontal air movements on bared skin surfaces, hands and neck. Attention was concentrated on the effects of relative turbulence intensity of air velocity and exposure duration on perception and sensitivity to the air movement. The air jet flows, adopted for the draught experiment in the neck, were also the object of an experimental study. This experiment was designed to observe the centre-line velocity of an isothermal circular air jet, as a function of the velocity properties at the outlet

  11. 2D/3D/4D ULTRASOUND IN INFERTILITY MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Uršula Reš-Muravec

    2018-02-01

    Ultrasound in infertility diagnostics: Ultrasound is used for examination of uterus, tubes, ovaries and peritoneal cause of infertility. It can be used in different menstrual phases: proliferative, periovulatory and secretory phase. Examination of uterus: A 2D scan can measure the size of the uterus (length, width and depth and a 2D flow (colour and power doppler. With 3D technology we can measure the whole volume with VOCAL (virtual organ computer-aided analysis and 3D circulation with the index (VI – vascular index, FI – flow index and VFI – vascular flow index in the uterus. A 2D scan can help us define uterine malformations, fibroids and adenomyosis to a certain extent. However, a 3D scan offers more accurate diagnosis of these malformations. Endometrium is examined separately. With 2D the width is measured and morphology and focal lesions (polyp, fibroids, adhesions are examined. With 3D the real sagital plane for the width measurement can be defined . We can measure the volume of endometrium and subendometrium and 3D circulation in endometrium and subendometrium. The FIS (f luid instlation sonography is very useful when examining the endometrium; saline or gel can be used for uterine instalation. We can measure and define the position of the structures in the endometrium more accurately when they are surrouned by saline or gel. We can view these structures with a surface view, similar to the one used for hysteroscopy. With this information we can explain the pathology to the patient and easily plan the surgical procedures. Examination of the tubes: With 2D US we can see the tubes in the pelvis only if there are dilatations, but sometimes it is difficult to distinguish them from the neighbouring forma- tions. With a 3D ultrasound we can define the shape and continuity of the tube and we can view the tube from different angles (inversion mode. Different contrast media are used for determining tubal patency. Tubal patency can be diagnosed with 2D Hy

  12. Volumetric cutaneous microangiography of human skin in vivo by VCSEL swept-source optical coherence tomography

    International Nuclear Information System (INIS)

    Woo June Choi; Wang, R K

    2014-01-01

    We demonstrate volumetric cutaneous microangiography of the human skin in vivo that utilises 1.3-μm high-speed sweptsource optical coherence tomography (SS-OCT). The swept source is based on a micro-electro-mechanical (MEMS)-tunable vertical cavity surface emission laser (VCSEL) that is advantageous in terms of long coherence length over 50 mm and 100 nm spectral bandwidth, which enables the visualisation of microstructures within a few mm from the skin surface. We show that the skin microvasculature can be delineated in 3D SS-OCT images using ultrahigh-sensitive optical microangiography (UHS-OMAG) with a correlation mapping mask, providing a contrast enhanced blood perfusion map with capillary flow sensitivity. 3D microangiograms of a healthy human finger are shown with distinct cutaneous vessel architectures from different dermal layers and even within hypodermis. These findings suggest that the OCT microangiography could be a beneficial biomedical assay to assess cutaneous vascular functions in clinic. (laser biophotonics)

  13. Volumetric cutaneous microangiography of human skin in vivo by VCSEL swept-source optical coherence tomography

    Energy Technology Data Exchange (ETDEWEB)

    Woo June Choi; Wang, R K [University of Washington, Department of Bioengineering, Seattle, Washington 98195 (United States)

    2014-08-31

    We demonstrate volumetric cutaneous microangiography of the human skin in vivo that utilises 1.3-μm high-speed sweptsource optical coherence tomography (SS-OCT). The swept source is based on a micro-electro-mechanical (MEMS)-tunable vertical cavity surface emission laser (VCSEL) that is advantageous in terms of long coherence length over 50 mm and 100 nm spectral bandwidth, which enables the visualisation of microstructures within a few mm from the skin surface. We show that the skin microvasculature can be delineated in 3D SS-OCT images using ultrahigh-sensitive optical microangiography (UHS-OMAG) with a correlation mapping mask, providing a contrast enhanced blood perfusion map with capillary flow sensitivity. 3D microangiograms of a healthy human finger are shown with distinct cutaneous vessel architectures from different dermal layers and even within hypodermis. These findings suggest that the OCT microangiography could be a beneficial biomedical assay to assess cutaneous vascular functions in clinic. (laser biophotonics)

  14. Adjoint sensitivity theory for steady-state ground-water flow

    International Nuclear Information System (INIS)

    1983-11-01

    In this study, adjoint sensitivity theory is developed for equations of two-dimensional steady-state flow in a confined aquifer. Both the primary flow equation and the adjoint sensitivity equation are solved using the Galerkin finite element method. The developed computer code is used to investigate the regional flow parameters of the Leadville Formation of the Paradox Basin in Utah and the Wolcamp carbonate/sandstone aquifer of the Palo Duro Basin in the Texas Panhandle. Two performance measures are evaluated, local heads and velocity in the vicinity of potential high-level nuclear waste repositories. The results illustrate the sensitivity of calculated local heads to the boundary conditions. Local velocity-related performance measures are more sensitive to hydraulic conductivities. The uncertainty in the performance measure is a function of the parameter sensitivity, parameter variance and the correlation between parameters. Given a parameter covariance matrix, the uncertainty of the performance measure can be calculated. Although no results are presented here, the implications of uncertainty calculations for the two studies are discussed. 18 references, 25 figures

  15. ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo.

    Science.gov (United States)

    Yin, Gang; Fan, Jin; Zhou, Wei; Ding, Qingfeng; Zhang, Jun; Wu, Xuan; Tang, Pengyu; Zhou, Hao; Wan, Bowen; Yin, Guoyong

    2017-10-10

    mTOR is a valuable oncotarget for osteosarcoma. The anti-osteosarcoma activity by a novel mTOR kinase inhibitor, CZ415, was evaluated. We demonstrated that CZ415 potently inhibited survival and proliferation of known osteosarcoma cell lines (U2OS, MG-63 and SaOs2), and primary human osteosarcoma cells. Further, CZ415 provoked apoptosis and disrupted cell cycle progression in osteosarcoma cells. CZ415 treatment in osteosarcoma cells concurrently blocked mTORC1 and mTORC2 activation. Intriguingly, ERK-MAPK activation could be a major resistance factor of CZ415. ERK inhibition (by MEK162/U0126) or knockdown (by targeted ERK1/2 shRNAs) dramatically sensitized CZ415-induced osteosarcoma cell apoptosis. In vivo , CZ415 oral administration efficiently inhibited U2OS tumor growth in mice. Its activity was further potentiated with co-administration of MEK162. Collectively, we demonstrate that ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo . CZ415 could be further tested as a promising anti-osteosarcoma agent, alone or in combination of ERK inhibition.

  16. Density-based global sensitivity analysis of sheet-flow travel time: Kinematic wave-based formulations

    Science.gov (United States)

    Hosseini, Seiyed Mossa; Ataie-Ashtiani, Behzad; Simmons, Craig T.

    2018-04-01

    Despite advancements in developing physics-based formulations to estimate the sheet-flow travel time (tSHF), the quantification of the relative impacts of influential parameters on tSHF has not previously been considered. In this study, a brief review of the physics-based formulations to estimate tSHF including kinematic wave (K-W) theory in combination with Manning's roughness (K-M) and with Darcy-Weisbach friction formula (K-D) over single and multiple planes is provided. Then, the relative significance of input parameters to the developed approaches is quantified by a density-based global sensitivity analysis (GSA). The performance of K-M considering zero-upstream and uniform flow depth (so-called K-M1 and K-M2), and K-D formulae to estimate the tSHF over single plane surface were assessed using several sets of experimental data collected from the previous studies. The compatibility of the developed models to estimate tSHF over multiple planes considering temporal rainfall distributions of Natural Resources Conservation Service, NRCS (I, Ia, II, and III) are scrutinized by several real-world examples. The results obtained demonstrated that the main controlling parameters of tSHF through K-D and K-M formulae are the length of surface plane (mean sensitivity index T̂i = 0.72) and flow resistance (mean T̂i = 0.52), respectively. Conversely, the flow temperature and initial abstraction ratio of rainfall have the lowest influence on tSHF (mean T̂i is 0.11 and 0.12, respectively). The significant role of the flow regime on the estimation of tSHF over a single and a cascade of planes are also demonstrated. Results reveal that the K-D formulation provides more precise tSHF over the single plane surface with an average percentage of error, APE equal to 9.23% (the APE for K-M1 and K-M2 formulae were 13.8%, and 36.33%, respectively). The superiority of Manning-jointed formulae in estimation of tSHF is due to the incorporation of effects from different flow regimes as

  17. Preliminary examples of 3D vector flow imaging

    DEFF Research Database (Denmark)

    Pihl, Michael Johannes; Stuart, Matthias Bo; Tomov, Borislav Gueorguiev

    2013-01-01

    This paper presents 3D vector flow images obtained using the 3D Transverse Oscillation (TO) method. The method employs a 2D transducer and estimates the three velocity components simultaneously, which is important for visualizing complex flow patterns. Data are acquired using the experimental ult...... as opposed to magnetic resonance imaging (MRI). The results demonstrate that the 3D TO method is capable of performing 3D vector flow imaging.......This paper presents 3D vector flow images obtained using the 3D Transverse Oscillation (TO) method. The method employs a 2D transducer and estimates the three velocity components simultaneously, which is important for visualizing complex flow patterns. Data are acquired using the experimental...... ultrasound scanner SARUS on a flow rig system with steady flow. The vessel of the flow-rig is centered at a depth of 30 mm, and the flow has an expected 2D circular-symmetric parabolic prole with a peak velocity of 1 m/s. Ten frames of 3D vector flow images are acquired in a cross-sectional plane orthogonal...

  18. Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries: in vivo and in vitro neuroprotective effect of antihypertensive DDPH

    Directory of Open Access Journals (Sweden)

    Li Sun

    2015-01-01

    Full Text Available 1-(2,6-Dimethylphenoxy-2-(3,4-dimethoxyphenylethylamino-propane hydrochloride (DDPH is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemia in vivo, and a rabbit model of isolated basilar arteries in vitro. Our results show that DDPH (10 mg/kg significantly increased hippocampal blood flow in vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in the in vitro rabbit model. DDPH (3 × 10 -5 M also inhibited histamine-stimulated extracellular calcium influx and intracellular calcium release. Our findings suggest that DDPH has a vasodilative effect both in vivo and in vitro, which mediates a neuroprotective effect on ischemic nerve tissue.

  19. 3D Printing of Fluid Flow Structures

    OpenAIRE

    Taira, Kunihiko; Sun, Yiyang; Canuto, Daniel

    2017-01-01

    We discuss the use of 3D printing to physically visualize (materialize) fluid flow structures. Such 3D models can serve as a refreshing hands-on means to gain deeper physical insights into the formation of complex coherent structures in fluid flows. In this short paper, we present a general procedure for taking 3D flow field data and producing a file format that can be supplied to a 3D printer, with two examples of 3D printed flow structures. A sample code to perform this process is also prov...

  20. In Vivo Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study

    Directory of Open Access Journals (Sweden)

    Tiing Yee Siow

    2013-01-01

    Full Text Available 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is a neurotoxin commonly used to produce an animal model of Parkinson’s disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO synthase- (nNOS- derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess in vivo due to its extremely short biological half-life, and so in vivo evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, in vivo localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI, intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first in vivo evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. Although the observed CBF change may be independent of the toxicogenesis of MPTP, this transient hyperperfusion state may serve as an early indicator of neuroinflammation.

  1. A hyperspectral fluorescence system for 3D in vivo optical imaging

    International Nuclear Information System (INIS)

    Zavattini, Guido; Vecchi, Stefania; Mitchell, Gregory; Weisser, Ulli; Leahy, Richard M; Pichler, Bernd J; Smith, Desmond J; Cherry, Simon R

    2006-01-01

    In vivo optical instruments designed for small animal imaging generally measure the integrated light intensity across a broad band of wavelengths, or make measurements at a small number of selected wavelengths, and primarily use any spectral information to characterize and remove autofluorescence. We have developed a flexible hyperspectral imaging instrument to explore the use of spectral information to determine the 3D source location for in vivo fluorescence imaging applications. We hypothesize that the spectral distribution of the emitted fluorescence signal can be used to provide additional information to 3D reconstruction algorithms being developed for optical tomography. To test this hypothesis, we have designed and built an in vivo hyperspectral imaging system, which can acquire data from 400 to 1000 nm with 3 nm spectral resolution and which is flexible enough to allow the testing of a wide range of illumination and detection geometries. It also has the capability to generate a surface contour map of the animal for input into the reconstruction process. In this paper, we present the design of the system, demonstrate the depth dependence of the spectral signal in phantoms and show the ability to reconstruct 3D source locations using the spectral data in a simple phantom. We also characterize the basic performance of the imaging system

  2. In vivo conditions to identify Prkci phosphorylation targets using the analog-sensitive kinase method in zebrafish.

    Directory of Open Access Journals (Sweden)

    Elena Cibrián Uhalte

    Full Text Available Protein kinase C iota is required for various cell biological processes including epithelial tissue polarity and organ morphogenesis. To gain mechanistic insight into different roles of this kinase, it is essential to identify specific substrate proteins in their cellular context. The analog-sensitive kinase method provides a powerful tool for the identification of kinase substrates under in vivo conditions. However, it has remained a major challenge to establish screens based on this method in multicellular model organisms. Here, we report the methodology for in vivo conditions using the analog-sensitive kinase method in a genetically-tractable vertebrate model organism, the zebrafish. With this approach, kinase substrates can uniquely be labeled in the developing zebrafish embryo using bulky ATPγS analogs which results in the thiophosphorylation of substrates. The labeling of kinase substrates with a thiophosphoester epitope differs from phosphoesters that are generated by all other kinases and allows for an enrichment of thiophosphopeptides by immunoaffinity purification. This study provides the foundation for using the analog-sensitive kinase method in the context of complex vertebrate development, physiology, or disease.

  3. Imaging of prostate cancer: a platform for 3D co-registration of in-vivo MRI ex-vivo MRI and pathology

    Science.gov (United States)

    Orczyk, Clément; Mikheev, Artem; Rosenkrantz, Andrew; Melamed, Jonathan; Taneja, Samir S.; Rusinek, Henry

    2012-02-01

    Objectives: Multi-parametric MRI is emerging as a promising method for prostate cancer diagnosis. prognosis and treatment planning. However, the localization of in-vivo detected lesions and pathologic sites of cancer remains a significant challenge. To overcome this limitation we have developed and tested a system for co-registration of in-vivo MRI, ex-vivo MRI and histology. Materials and Methods: Three men diagnosed with localized prostate cancer (ages 54-72, PSA levels 5.1-7.7 ng/ml) were prospectively enrolled in this study. All patients underwent 3T multi-parametric MRI that included T2W, DCEMRI, and DWI prior to robotic-assisted prostatectomy. Ex-vivo multi-parametric MRI was performed on fresh prostate specimen. Excised prostates were then sliced at regular intervals and photographed both before and after fixation. Slices were perpendicular to the main axis of the posterior capsule, i.e., along the direction of the rectal wall. Guided by the location of the urethra, 2D digital images were assembled into 3D models. Cancer foci, extra-capsular extensions and zonal margins were delineated by the pathologist and included in 3D histology data. A locally-developed software was applied to register in-vivo, ex-vivo and histology using an over-determined set of anatomical landmarks placed in anterior fibro-muscular stroma, central. transition and peripheral zones. The mean root square distance across corresponding control points was used to assess co-registration error. Results: Two specimens were pT3a and one pT2b (negative margin) at pathology. The software successfully fused invivo MRI. ex-vivo MRI fresh specimen and histology using appropriate (rigid and affine) transformation models with mean square error of 1.59 mm. Coregistration accuracy was confirmed by multi-modality viewing using operator-guided variable transparency. Conclusion: The method enables successful co-registration of pre-operative MRI, ex-vivo MRI and pathology and it provides initial evidence

  4. Assessment of RELAP5-3D copyright using data from two-dimensional RPI flow tests

    International Nuclear Information System (INIS)

    Davis, C.B.

    1998-01-01

    The capability of the RELAP5-3D copyright computer code to perform multi-dimensional thermal-hydraulic analysis was assessed using data from steady-state flow tests conducted at Rensselaer Polytechnic Institute (RPI). The RPI data were taken in a two-dimensional test section in a low-pressure air/water loop. The test section consisted of a thin vertical channel that simulated a two-dimensional slice through the core of a pressurized water reactor. Single-phase and two-phase flows were supplied to the test section in an asymmetric manner to generate a two-dimensional flow field. A traversing gamma densitometer was used to measure void fraction at many locations in the test section. High speed photographs provided information on the flow patterns and flow regimes. The RPI test section was modeled using the multi-dimensional component in RELAP5-3D Version BF06. Calculations of three RPI experiments were performed. The flow regimes predicted by the base code were in poor agreement with those observed in the tests. The two-phase regions were observed to be in the bubbly and slug flow regimes in the test. However, nearly all of the junctions in the horizontal direction were calculated to be in the stratified flow regime because of the relatively low velocities in that direction. As a result, the void fraction predictions were also in poor agreement with the measured values. Significantly improved results were obtained in sensitivity calculations with a modified version of the code that prevented the horizontal junctions from entering the stratified flow regime. These results indicate that the code's logic in the determination of flow regimes in a multi-dimensional component must be improved. The results of the sensitivity calculations also indicate that RELAP5-3D will provide a significant multi-dimensional hydraulic analysis capability once the flow regime prediction is improved

  5. 3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish Embryogenesis Using Light-Sheet Microscopy

    Directory of Open Access Journals (Sweden)

    Juneyong Eum

    2016-11-01

    Full Text Available Environmental contamination by trinitrotoluene is of global concern due to its widespread use in military ordnance and commercial explosives. Despite known long-term persistence in groundwater and soil, the toxicological profile of trinitrotoluene and other explosive wastes have not been systematically measured using in vivo biological assays. Zebrafish embryos are ideal model vertebrates for high-throughput toxicity screening and live in vivo imaging due to their small size and transparency during embryogenesis. Here, we used Single Plane Illumination Microscopy (SPIM/light sheet microscopy to assess the developmental toxicity of explosive-contaminated water in zebrafish embryos and report 2,4,6-trinitrotoluene-associated developmental abnormalities, including defects in heart formation and circulation, in 3D. Levels of apoptotic cell death were higher in the actively developing tissues of trinitrotoluene-treated embryos than controls. Live 3D imaging of heart tube development at cellular resolution by light-sheet microscopy revealed trinitrotoluene-associated cardiac toxicity, including hypoplastic heart chamber formation and cardiac looping defects, while the real time PCR (polymerase chain reaction quantitatively measured the molecular changes in the heart and blood development supporting the developmental defects at the molecular level. Identification of cellular toxicity in zebrafish using the state-of-the-art 3D imaging system could form the basis of a sensitive biosensor for environmental contaminants and be further valued by combining it with molecular analysis.

  6. In vivo molecular photoacoustic tomography of melanomas targeted by bio-conjugated gold nanocages

    Science.gov (United States)

    Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher; Zhang, Qiang; Cobley, Claire M.; Gao, Feng; Xia, Younan; Wang, Lihong V.

    2010-01-01

    Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bio-conjugated with [Nle4,D-Phe7]-α-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bio-conjugated AuNCs enhanced contrast ~300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS). PMID:20731439

  7. Determination of aerodynamic sensitivity coefficients for wings in transonic flow

    Science.gov (United States)

    Carlson, Leland A.; El-Banna, Hesham M.

    1992-01-01

    The quasianalytical approach is applied to the 3-D full potential equation to compute wing aerodynamic sensitivity coefficients in the transonic regime. Symbolic manipulation is used to reduce the effort associated with obtaining the sensitivity equations, and the large sensitivity system is solved using 'state of the art' routines. The quasianalytical approach is believed to be reasonably accurate and computationally efficient for 3-D problems.

  8. Measurement of blood flow in the left ventricle and aorta using clinical 2D cine phase-contrast magnetic resonance imaging

    International Nuclear Information System (INIS)

    Nakamura, Masanori; Wada, Shigeo; Yokosawa, Suguru; Yamaguchi, Takami; Isoda, Haruo; Takeda, Hiroyasu

    2007-01-01

    A recent development in phase-contrast magnetic resonance imaging (cine PC-MRI) allows the detailed measurement of the blood flow in humans. The objectives of this study are twofold: to discuss the utility of clinical two-dimensional (2D) cine PC-MRI as a practical tool for analyzing hemodynamics in the aorta and left ventricle; to provide flow information at those places as references for computational fluid dynamics studies. Using 2D cine PC-MRI, we mapped velocity profiles at various cross sections of the aorta and left ventricle. The results illustrated the main flow events in the left ventricle during the cardiac cycle, such as ventricular ejection and suction, while the secondary flows were less clear. The velocity profile at the entrance of the ascending aorta appeared to be slightly skewed posteriorly in early systole, but the flow in the central zone of the section was rapid. The estimated stroke volume, peak Reynolds numbers, and Womersley numbers were within the normal physiological range. A sequence of secondary flow images from the plane of the aortic valve to the descending aorta revealed the evolution of a helical flow within the aorta. Flows entering the aortic branches were captured well. Those results demonstrate that clinical 2D cine PC-MRI is a practical adjunct for analyzing blood flow in vivo and would be useful as references to check validity of flow dynamics obtained by computer simulations. (author)

  9. Syntheses and in vitro evaluation of fluorinated naphthoxazines as dopamine D2/D3 receptor agonists: radiosynthesis, ex vivo biodistribution and autoradiography of [{sup 18}F]F-PHNO

    Energy Technology Data Exchange (ETDEWEB)

    Vasdev, Neil [PET Centre for Addiction and Mental Health, Toronto, Ontario, Canada, M5T-1R8 (Canada) and Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada)]. E-mail: neil.vasdev@camhpet.ca; Seeman, Philip [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S-1A8 (Canada); Garcia, Armando [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Stableford, Winston T. [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Nobrega, Jose N. [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S-1A8 (Canada); Houle, Sylvain [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada); Wilson, Alan A. [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada)

    2007-02-15

    Introduction: Carbon-11-labeled (+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([{sup 11}C]-(+)-PHNO) is a dopamine D2/D3 agonist radioligand that is currently used to image the high-affinity state of dopamine receptors in humans with positron emission tomography (PET). The present study reports the preparation and evaluation of fluorinated (+)-PHNO derivatives. Methods: Five fluorinated (+)-PHNO derivatives were synthesized and tested in vitro for inhibition of binding of [{sup 3}H]domperidone in homogenates of rat striatum and inhibition of binding to [{sup 3}H]-(+)-PHNO in homogenates of human-cloned D2Long receptors in Chinese hamster ovary cells and rat striatum. Radiolabeling with fluorine-18 was carried out for the most promising candidate, N-fluoropropyl-(+)-HNO (F-PHNO), and ex vivo biodistribution and autoradiography studies with this radiopharmaceutical were performed in rodents. Results: (+)-PHNO and the fluorinated analogs inhibited binding of [{sup 3}H]domperidone and [{sup 3}H]-(+)-PHNO to the high- and low-affinity states of dopamine D2 receptors, consistent with D2 agonist behavior. The average dissociation constant at the high-affinity state of D2, K {sub i} {sup High}, was 0.4 nM for F-PHNO and proved to be equipotent with (+)-PHNO (0.7 nM). All other fluorinated derivatives were significantly less potent (K {sub i} {sup High}=2-102 nM). The most promising candidate, F-PHNO, was labeled with fluorine-18 in 5% uncorrected radiochemical yield, with respect to starting fluoride. Ex vivo biodistribution and autoradiography studies in rodents revealed that [{sup 18}F]F-PHNO rapidly enters the rodent brain. However, this radiotracer does not reveal specific binding in the brain and is rapidly cleared. Conclusions: Five novel dopamine D2/D3 agonists based on (+)-PHNO were synthesized and evaluated in vitro. F-PHNO was shown to behave as a potent D2 agonist in vitro and was therefore radiolabeled with fluorine-18. Despite the

  10. Multimodal in vivo blood flow sensing combining particle image velocimetry and optical tweezers-based blood steering

    Science.gov (United States)

    Meissner, Robert; Sugden, Wade W.; Siekmann, Arndt F.; Denz, Cornelia

    2018-02-01

    All higher developed organisms contain complex hierarchical networks of arteries, veins and capillaries. These constitute the cardiovascular system responsible for supplying nutrients, gas and waste exchange. Diseases related to the cardiovascular system are among the main causes for death worldwide. In order to understand the processes leading to arteriovenous malformation, we studied hereditary hemorrhagic telangiectasia (HHT), which has a prevalence of 1:5000 worldwide and causes internal bleeding. In zebrafish, HHT is induced by mutation of the endoglin gene involved in HHT and observed to reduce red blood cell (RBC) flow to intersegmental vessels (ISVs) in the tail due to malformations of the dorsal aorta (DA) and posterior cardinal vein (PCV). However, these capillaries are still functional. Changes in the blood flow pattern are observed from in vivo data from zebrafish embryos through particle image velocimetry (PIV). Wall shear rates (WSRs) and blood flow velocities are obtained non-invasively with millisecond resolution. We observe significant increases of blood flow velocity in the DA for endoglin-deficient zebrafish embryos (mutants) at 3 days post fertilization. In the PCV, this increase is even more pronounced. We identified an increased similarity between the DA and the PCV of mutant fish compared to siblings, i.e., unaffected fish. To counteract the reduced RBC flow to ISVs we implement optical tweezers (OT). RBCs are steered into previously unperfused ISVs showing a significant increase of RBC count per minute. We discuss limitations with respect to biocompatibility of optical tweezers in vivo and determination of in vivo wall shear stress (WSS) connected to normal and endoglin-deficicent zebrafish embryos.

  11. Development and utilization of an ex vivo bromodeoxyuridine local lymph node assay protocol for assessing potential chemical sensitizers.

    Science.gov (United States)

    Williams, W C; Copeland, C; Boykin, E; Quell, S J; Lehmann, D M

    2015-01-01

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [(3) H]methyl thymidine. A more recent non-isotopic variation of the assay utilizes bromodeoxyuridine (BrdU) incorporation in vivo. To further improve the utility of this assay, we developed an ex vivo BrdU labeling procedure eliminating the need for in vivo injections. The results of this assay correctly identified a strong sensitizer (i.e., trimellitic anhydride) as well as weak/moderate sensitizers (i.e., eugenol, cinnamaldehyde and hexylcinnaminic aldehyde). As anticipated, neither non-sensitizers isopropanol and lactic acid nor the false negative chemical nickel II sulfate hexahydrate induced a positive threshold response in the assay. The results of this assay are in close agreement with those of the in vivo LLNA:BrdU-enzyme-linked immunosorbent assay labeling procedure. We also used the ex vivo BrdU LLNA procedure to evaluate ammonium hexachloroplatinate, ammonium tetrachloroplatinate and cis-diamminedichloroplatinum(II) and the assay correctly identified them as sensitizers based on the calculation of EC2 values. We conclude that this ex vivo BrdU labeling method offers predictive capacity comparable to previously established LLNA protocols while eliminating animal injections and the use of radioisotope. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  12. Collateral circulation via the circle of Willis in patients with carotid artery steno-occlusive disease: evaluation on 3-T 4D MRA using arterial spin labelling

    International Nuclear Information System (INIS)

    Iryo, Yasuhiko; Hirai, Toshinori; Nakamura, Masanobu; Inoue, Yasuteru; Watanabe, Masaki; Ando, Yukio; Azuma, Minako; Nishimura, Shinichiro; Shigematsu, Yoshinori; Kitajima, Mika; Yamashita, Yasuyuki

    2015-01-01

    Aim: To evaluate whether 3-T four-dimensional (4D) arterial spin-labelling (ASL) -based magnetic resonance angiography (MRA) is useful for assessing the collateral circulation via the circle of Willis in patients with carotid artery steno-occlusive disease. Materials and methods: Institutional review board approval and prior written informed consent from all patients were obtained. The inclusion criteria were fulfilled by 13 patients with carotid artery steno-occlusive disease. All underwent 4D-ASL MRA at 3 T and digital subtraction angiography (DSA). The flow-sensitive alternating inversion recovery (FAIR) preparation scheme with look-locker sampling was used for spin labeling. At 300-ms intervals seven dynamic scans were obtained with a spatial resolution of 0.5×0.5×0.6 mm 3 . The collateral flow via the circle of Willis was read on 4D-ASL MRA and DSA images by two sets of two independent readers each. κ statistics were used to assess interobserver and intermodality agreement. Results: On DSA, collateral flow via the anterior communicating artery (AcomA) was observed in six patients, via the posterior communicating artery (PcomA) in four patients, and via both the AcomA and PcomA in three patients. With respect to the qualitative evaluation of 4D-ASL MRA images, interobserver agreement was excellent for all items (κ=1). 4D-ASL MRA and DSA consensus readings agreed on the type of collateral flow pattern in 10 of the 13 patients (77%). Intermodality agreement was good (κ=0.606; 95% confidence interval (CI): 0.215–0.997). Conclusion: 3 T 4D-ASL MRA may be a useful tool for the evaluation of the collateral circulation in patients with carotid artery steno-occlusive disease. -- Highlights: •3-T 4D-ASL MRA has high spatial and temporal resolution. •There is no need for the use of contrast agents in this technique. •4D-ASL MRA is useful for assessing the collateral flow associated with carotid artery stenosis. •Intermodality agreement between 4D

  13. Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Ouyang; Tao, Yongxin; Qin, Yong [Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou 213164 (China); Chen, Chuanxiang [School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003 (China); Pan, Yan; Deng, Linhong [Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164 (China); Liu, Li [School of pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164 (China); Kong, Yong, E-mail: yzkongyong@126.com [Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou 213164 (China)

    2016-10-01

    Highly fluorescent graphene quantum dots (GQDs)-chitosan (CS) hybrid xerogels (GQDs-CS) were facilely synthesized, and the morphology of GQDs-CS was controllable by varying the content of GQDs in the xerogel. The GQDs-CS exhibited a porous and three-dimensional (3D) network structure when the content of GQDs reached 43% (wt%) in the xerogel, which was beneficial for drug loading and sustained release. The as-prepared GQDs-CS could also be applied for in vivo imaging since it showed strong blue, green and red luminescence under excitation of varying wavelengths. Moreover, the pH-induced protonation/deprotonation of the –NH{sub 2} groups on CS chains can result in a pH-dependent drug delivery behavior of the GQDs-CS hybrid xerogel. - Graphical abstract: Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier. Display Omitted - Highlights: • Highly fluorescent GQDs-CS hybrid xerogels were facilely synthesized. • The as-made xerogels exhibited various morphologies with different GQDs contents. • The GQDs-CS exhibited a porous and 3D network when the content of GQDs reached 43%. • The GQDs-CS could be applied for in vivo imaging since it showed strong luminescence. • The protonation/deprotonation of –NH{sub 2} on CS result in a pH-dependent drug delivery.

  14. Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier

    International Nuclear Information System (INIS)

    Lv, Ouyang; Tao, Yongxin; Qin, Yong; Chen, Chuanxiang; Pan, Yan; Deng, Linhong; Liu, Li; Kong, Yong

    2016-01-01

    Highly fluorescent graphene quantum dots (GQDs)-chitosan (CS) hybrid xerogels (GQDs-CS) were facilely synthesized, and the morphology of GQDs-CS was controllable by varying the content of GQDs in the xerogel. The GQDs-CS exhibited a porous and three-dimensional (3D) network structure when the content of GQDs reached 43% (wt%) in the xerogel, which was beneficial for drug loading and sustained release. The as-prepared GQDs-CS could also be applied for in vivo imaging since it showed strong blue, green and red luminescence under excitation of varying wavelengths. Moreover, the pH-induced protonation/deprotonation of the –NH_2 groups on CS chains can result in a pH-dependent drug delivery behavior of the GQDs-CS hybrid xerogel. - Graphical abstract: Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier. Display Omitted - Highlights: • Highly fluorescent GQDs-CS hybrid xerogels were facilely synthesized. • The as-made xerogels exhibited various morphologies with different GQDs contents. • The GQDs-CS exhibited a porous and 3D network when the content of GQDs reached 43%. • The GQDs-CS could be applied for in vivo imaging since it showed strong luminescence. • The protonation/deprotonation of –NH_2 on CS result in a pH-dependent drug delivery.

  15. In vivo 31P and 1H NMR studies of rat brain tumor pH and blood flow during acute hyperglycemia: Differential effects between subcutaneous and intracerebral locations

    International Nuclear Information System (INIS)

    Ross, B.D.; Mitchell, S.L.; Merkle, H.; Garwood, M.

    1989-01-01

    Surface coil NMR spectroscopy was used to monitor the hyperglycemia-induced alterations in pH and blood flow in vivo in C6 gliomas implanted both subcutaneously and intracerebrally in rats. Tumor pH was calculated from the chemical shift difference between PCr and Pi in the 31 P NMR spectra. Subcutaneous glioma pH decreased 0.8 units by 1 h after intraperitoneal administration of an aqueous 50% glucose solution (6 g glucose per kg body weight). In contrast, hyperglycemia failed to significantly alter the pH of intracerebral gliomas which were monitored for 90 min following administration of glucose. Tumor blood flow (TBF) was determined both pre- and post-glucose administration using deuterium NMR by monitoring the time course of D2O washout following intratumoral injection of saline D2O. Subcutaneous and intracerebral TBF were found to have an average change of -78.1% (range -47.4 to -93.3%, n = 5) and -21.1% (range +6.0 to -37.8%, n = 9), respectively. In addition, laser Doppler blood flow measurements of rat skin and subcutaneous glioma revealed a dramatic reduction in blood flow in both tissues following glucose administration. These results indicate that the effects of acute hyperglycemia are site dependent and that hyperglycemia alone is not beneficial for inducing intracellular acidosis in intracerebral tumors

  16. 3-D Vector Flow Estimation With Row–Column-Addressed Arrays

    DEFF Research Database (Denmark)

    Holbek, Simon; Christiansen, Thomas Lehrmann; Stuart, Matthias Bo

    2016-01-01

    Simulation and experimental results from 3-D vector flow estimations for a 62 + 62 2-D row–column (RC) array with integrated apodization are presented. A method for implementing a 3-D transverse oscillation (TO) velocity estimator on a 3-MHz RC array is developed and validated. First, a parametric...... mean bias B˜ and mean standard deviation σ˜ . Second, the optimal parameter configuration is implemented on the prototype RC probe connected to the experimental ultrasound scanner SARUS. Results from measurements conducted in a flow-rig system containing a constant laminar flow and a straight.......7, −0.9, 0.4)% with a relative standard deviation of (8.7, 5.1, 0.8)% for (vx , vy, vz). The estimated peak velocity is 48.5 ± 3 cm/s giving a −3% bias. The out-of-plane velocity component perpendicular to the cross section is used to estimate volumetric flow rates in the flow rig at a 90° beam...

  17. CASH-FLOW SENSITIVITY TO PAYMENTS FOR MATERIAL RESSOURCES

    Directory of Open Access Journals (Sweden)

    Lavinia Elena BRÎNDESCU OLARIU

    2014-12-01

    Full Text Available The financing decision is taken based on the expectations concerning the future cash-flows generated in the operating activity, which should provide coverage for the debt service and allow for an increase of the shareholders’ wealth. Still, the future cash-flows are affected by risk, which makes the sensitivity analysis a very important part of the decision process. The current research sets to evaluate the sensitivity of the payment capacity to variations of the payments for raw materials and consumables. The study employs 391 forecasted yearly cash-flow statements collected from 50 companies together with detailed information concerning the hypotheses of the forecasts. The results of the study allow for the establishment of benchmarks for the payment capacity’s sensitivity, the determination of the mechanisms through which the variation of payments for raw materials and consumables impacts the payment capacity, as well as the identification of the possible causes of such a variation.

  18. Combined treatment with D-allose, docetaxel and radiation inhibits the tumor growth in an in vivo model of head and neck cancer

    Science.gov (United States)

    Hoshikawa, Hiroshi; Kamitori, Kazuyo; Indo, Kanako; Mori, Terushige; Kamata, Mizuna; Takahashi, Tomoko; Tokuda, Masaaki

    2018-01-01

    The present study was designed to evaluate the effect of one rare sugar, D-allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-allose in an in vivo model of head and neck cancer. Results indicated that D-allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-allose treatment increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D-allose treatment. Combined multiple treatments with docetaxel, radiation and D-allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor-α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D-allose administration. Thus, the present findings suggest that D-allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues. PMID:29456721

  19. D-deprenyl protects nigrostriatal neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity.

    Science.gov (United States)

    Muralikrishnan, Dhanasekharan; Samantaray, Supriti; Mohanakumar, Kochupurackal P

    2003-10-01

    Selegiline (L-deprenyl) is believed to render protection against l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-neurotoxicity to a significant extent via a free radical scavenging mechanism, which is independent of its ability to inhibit monoamine oxidase-B (MAO-B) in the brain. We investigated the hydroxyl radical (.OH) scavenging action and neuroprotective effect of D-deprenyl, its less active isomer, in MPTP-induced dopaminergic neurotoxicity in mice to test whether the chemical structure of the molecule or its biological effects contribute to this property. To achieve this goal we studied the effects of D-deprenyl on: (1).OH production in a Fenton reaction; (2) MPTP-induced.OH generation and dopamine (DA) depletion in vivo, employing a sensitive HPLC-electrochemical procedure; and (3) formation of MPP(+) in vivo in the striatum following systemic administration of MPTP, employing an HPLC-photodiode array detection system. D-deprenyl inhibited ferrous citrate-induced.OH in vitro (0.45 microM) and MPTP-induced.OH in vivo in substantia nigra (SN) and in the striatum (1.0 mg/kg, i.p.). D-deprenyl did not, but L-deprenyl (0.5 mg/kg dose) did significantly inhibit formation of MPP(+) in the striatum 90 min following systemic MPTP injection. It failed to affect MAO-B activity at 0.5 mg/kg in the striatum, but effectively blocked MPTP-induced striatal DA depletion. The potency of D-deprenyl to scavenge MPTP-induced.OH in vivo and to render protection against the dopaminergic neurotoxicity without affecting dopamine turnover, MAO-B activity, or formation of MPP(+) in the brain indicates a direct involvement of.OH in the neurotoxic action of MPTP and antioxidant effect in the neuroprotective action of deprenyl. Copyright 2003 Wiley-Liss, Inc.

  20. 4D flow MRI assessment of right atrial flow patterns in the normal heart - influence of caval vein arrangement and implications for the patent foramen ovale.

    Directory of Open Access Journals (Sweden)

    Jehill D Parikh

    Full Text Available To investigate atrial flow patterns in the normal adult heart, to explore whether caval vein arrangement and patency of the foramen ovale (PFO may be associated with flow pattern.Time-resolved, three-dimensional velocity encoded magnetic resonance imaging (4D flow was employed to assess atrial flow patterns in thirteen healthy subjects (6 male, 40 years, range 25-50 and thirteen subjects (6 male, 40 years, range 21-50 with cryptogenic stroke and patent foramen ovale (CS-PFO. Right atrial flow was defined as vortical, helico-vortical, helical and multiple vortices. Time-averaged and peak systolic and diastolic flows in the caval and pulmonary veins and their anatomical arrangement were compared.A spectrum of right atrial flow was observed across the four defined categories. The right atrial flow patterns were strongly associated with the relative position of the caval veins. Right atrial flow patterns other than vortical were more common (p = 0.015 and the separation between the superior and inferior vena cava greater (10±5mm versus 3±3mm, p = 0.002 in the CS-PFO group. In the left atrium all subjects except one had counter-clockwise vortical flow. Vortex size varied and was associated with left lower pulmonary vein flow (systolic r = 0.61, p = 0.001, diastolic r = 0.63 p = 0.002. A diastolic vortex was less common and time-averaged left atrial velocity was greater in the CS-PFO group (17±2cm/sec versus 15±1, p = 0.048. One CS-PFO subject demonstrated vortical retrograde flow in the descending aortic arch; all other subjects had laminar descending aortic flow.Right atrial flow patterns in the normal heart are heterogeneous and are associated with the relative position of the caval veins. Patterns, other than 'typical' vortical flow, are more prevalent in the right atrium of those with cryptogenic stroke in the context of PFO. Left atrial flow patterns are more homogenous in normal hearts and show a relationship with flow arising from the left

  1. Development and Application of a Low-Volume Flow System for Solution-State in Vivo NMR.

    Science.gov (United States)

    Tabatabaei Anaraki, Maryam; Dutta Majumdar, Rudraksha; Wagner, Nicole; Soong, Ronald; Kovacevic, Vera; Reiner, Eric J; Bhavsar, Satyendra P; Ortiz Almirall, Xavier; Lane, Daniel; Simpson, Myrna J; Heumann, Hermann; Schmidt, Sebastian; Simpson, André J

    2018-06-18

    In vivo nuclear magnetic resonance (NMR) spectroscopy is a particularly powerful technique, since it allows samples to be analyzed in their natural, unaltered state, criteria paramount for living organisms. In this study, a novel continuous low-volume flow system, suitable for in vivo NMR metabolomics studies, is demonstrated. The system allows improved locking, shimming, and water suppression, as well as allowing the use of trace amounts of expensive toxic contaminants or low volumes of precious natural environmental samples as stressors. The use of a double pump design with a sump slurry pump return allows algal food suspensions to be continually supplied without the need for filters, eliminating the possibility of clogging and leaks. Using the flow system, the living organism can be kept alive without stress indefinitely. To evaluate the feasibility and applicability of the flow system, changes in the metabolite profile of 13 C enriched Daphnia magna over a 24-h period are compared when feeding laboratory food vs exposing them to a natural algal bloom sample. Clear metabolic changes are observed over a range of metabolites including carbohydrates, lipids, amino acids, and a nucleotide demonstrating in vivo NMR as a powerful tool to monitor environmental stress. The particular bloom used here was low in microcystins, and the metabolic stress impacts are consistent with the bloom being a poor food source forcing the Daphnia to utilize their own energy reserves.

  2. Chitosan porous 3D scaffolds embedded with resolvin D1 to improve in vivo bone healing.

    Science.gov (United States)

    Vasconcelos, Daniela P; Costa, Madalena; Neves, Nuno; Teixeira, José H; Vasconcelos, Daniel M; Santos, Susana G; Águas, Artur P; Barbosa, Mário A; Barbosa, Judite N

    2018-06-01

    The aim of this study was to investigate the effect chitosan (Ch) porous 3D scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, on bone tissue healing. These scaffolds previous developed by us have demonstrated to have immunomodulatory properties namely in the modulation of the macrophage inflammatory phenotypic profile in an in vivo model of inflammation. Herein, results obtained in an in vivo rat femoral defect model demonstrated that two months after Ch + RvD1 scaffolds implantation, an increase in new bone formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll III ratio were observed. These results suggest that Ch scaffolds embedded with RvD1 were able to lead to the formation of new bone with improvement of trabecular thickness. This study shows that the presence of RvD1 in the acute phase of the inflammatory response to the implanted biomaterial had a positive role in the subsequent bone tissue repair, thus demonstrating the importance of innovative approaches for the control of immune responses to biomedical implants in the design of advanced strategies for regenerative medicine. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1626-1633, 2018. © 2018 Wiley Periodicals, Inc.

  3. Slope instability in complex 3D topography promoted by convergent 3D groundwater flow

    Science.gov (United States)

    Reid, M. E.; Brien, D. L.

    2012-12-01

    Slope instability in complex topography is generally controlled by the interaction between gravitationally induced stresses, 3D strengths, and 3D pore-fluid pressure fields produced by flowing groundwater. As an example of this complexity, coastal bluffs sculpted by landsliding commonly exhibit a progression of undulating headlands and re-entrants. In this landscape, stresses differ between headlands and re-entrants and 3D groundwater flow varies from vertical rainfall infiltration to lateral groundwater flow on lower permeability layers with subsequent discharge at the curved bluff faces. In plan view, groundwater flow converges in the re-entrant regions. To investigate relative slope instability induced by undulating topography, we couple the USGS 3D limit-equilibrium slope-stability model, SCOOPS, with the USGS 3D groundwater flow model, MODFLOW. By rapidly analyzing the stability of millions of potential failures, the SCOOPS model can determine relative slope stability throughout the 3D domain underlying a digital elevation model (DEM), and it can utilize both fully 3D distributions of pore-water pressure and material strength. The two models are linked by first computing a groundwater-flow field in MODFLOW, and then computing stability in SCOOPS using the pore-pressure field derived from groundwater flow. Using these two models, our analyses of 60m high coastal bluffs in Seattle, Washington showed augmented instability in topographic re-entrants given recharge from a rainy season. Here, increased recharge led to elevated perched water tables with enhanced effects in the re-entrants owing to convergence of groundwater flow. Stability in these areas was reduced about 80% compared to equivalent dry conditions. To further isolate these effects, we examined groundwater flow and stability in hypothetical landscapes composed of uniform and equally spaced, oscillating headlands and re-entrants with differing amplitudes. The landscapes had a constant slope for both

  4. Interdependencies of aortic arch secondary flow patterns, geometry, and age analysed by 4-dimensional phase contrast magnetic resonance imaging at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Frydrychowicz, Alex [University Hospital Schleswig-Holstein, Clinic for Radiology and Nuclear Medicine, Luebeck (Germany); Berger, Alexander; Russe, Maximilian F.; Bock, Jelena [University Hospital Freiburg, Department of Radiology, Medical Physics, Freiburg (Germany); Munoz del Rio, Alejandro [University of Wisconsin - Madison, Departments of Radiology and Medical Physics, Madison, WI (United States); Harloff, Andreas [University Hospital Freiburg, Department of Neurology and Clinical Neurophysiology, Freiburg (Germany); Markl, Michael [University Hospital Freiburg, Department of Radiology, Medical Physics, Freiburg (Germany); Northwestern University, Departments of Radiology and Biomedical Engineering, Chicago, IL (United States)

    2012-05-15

    It was the aim to analyse the impact of age, aortic arch geometry, and size on secondary flow patterns such as helix and vortex flow derived from flow-sensitive magnetic resonance imaging (4D PC-MRI). 62 subjects (age range = 20-80 years) without circumscribed pathologies of the thoracic aorta (ascending aortic (AAo) diameter: 3.2 {+-} 0.6 cm [range 2.2-5.1]) were examined by 4D PC-MRI after IRB-approval and written informed consent. Blood flow visualisation based on streamlines and time-resolved 3D particle traces was performed. Aortic diameter, shape (gothic, crook-shaped, cubic), angle, and age were correlated with existence and extent of secondary flow patterns (helicity, vortices); statistical modelling was performed. Helical flow was the typical pattern in standard crook-shaped aortic arches. With altered shapes and increasing age, helicity was less common. AAo diameter and age had the highest correlation (r = 0.69 and 0.68, respectively) with number of detected vortices. None of the other arch geometric or demographic variables (for all, P {>=} 0.177) improved statistical modelling. Substantially different secondary flow patterns can be observed in the normal thoracic aorta. Age and the AAo diameter were the parameters correlating best with presence and amount of vortices. Findings underline the importance of age- and geometry-matched control groups for haemodynamic studies. (orig.)

  5. Interdependencies of aortic arch secondary flow patterns, geometry, and age analysed by 4-dimensional phase contrast magnetic resonance imaging at 3 Tesla

    International Nuclear Information System (INIS)

    Frydrychowicz, Alex; Berger, Alexander; Russe, Maximilian F.; Bock, Jelena; Munoz del Rio, Alejandro; Harloff, Andreas; Markl, Michael

    2012-01-01

    It was the aim to analyse the impact of age, aortic arch geometry, and size on secondary flow patterns such as helix and vortex flow derived from flow-sensitive magnetic resonance imaging (4D PC-MRI). 62 subjects (age range = 20-80 years) without circumscribed pathologies of the thoracic aorta (ascending aortic (AAo) diameter: 3.2 ± 0.6 cm [range 2.2-5.1]) were examined by 4D PC-MRI after IRB-approval and written informed consent. Blood flow visualisation based on streamlines and time-resolved 3D particle traces was performed. Aortic diameter, shape (gothic, crook-shaped, cubic), angle, and age were correlated with existence and extent of secondary flow patterns (helicity, vortices); statistical modelling was performed. Helical flow was the typical pattern in standard crook-shaped aortic arches. With altered shapes and increasing age, helicity was less common. AAo diameter and age had the highest correlation (r = 0.69 and 0.68, respectively) with number of detected vortices. None of the other arch geometric or demographic variables (for all, P ≥ 0.177) improved statistical modelling. Substantially different secondary flow patterns can be observed in the normal thoracic aorta. Age and the AAo diameter were the parameters correlating best with presence and amount of vortices. Findings underline the importance of age- and geometry-matched control groups for haemodynamic studies. (orig.)

  6. Effects of 2-Deoxy-D-Glucose on Metabolic Status, Proliferative Capacity and Growth Rate of FSall Tumor: Observations made by In Vivo 31P-Nuclear Magnetic Resonance Spectroscopy and Flow Cytometry

    International Nuclear Information System (INIS)

    Chang, Hye Sook; Choi, Eun Kyung; Cho, Jeong Gill; Lim, Tae Hwan; Lee, Tae Keun; Yi, Yun; Cho, Young Joo; Kim, Gon Sup

    1991-01-01

    The effect of 2-deoxy-d-glucose (2-DDG) on C 3 H mouse fibrosarcoma (FSall) was studied. Metabolic status, especially for energy metabolism, was studied using in vivo 31 P-MRS, proliferative capacity was observed on flow cytometry (FC) and growth rate was measured after transplantation of 106 viable tumor cells in the dorsum of foot of C 3 Hf/Sed mice. One gram of 2-DDG per kg of body weight was injected intraperitoneally on 12th day of implantation. Average tumor size on 12th day of implantation was 250mm 3 . Growth rate of FSall tumor was measured by tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. The effect of 2-DDG studied in vivo 31 P-MRS suggested that the increase of phosphomonoester (PME) and inorganic phosphate (Pi) by increasing size of tumor, slowed down after 2-DDG injection. Flow cytometry showed significantly increased S-phase and G 2 +M phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG. Authors observed an interesting effect 2-DDG on FSall tumor and attempt to utilize as an adjunct for radiotherapy

  7. Effects of flow rate on crack growth in sensitized type 304 stainless steel in high-temperature aqueous solutions

    International Nuclear Information System (INIS)

    Kwon, H.S.; Wuensche, A.; Macdonald, D.D.

    2000-01-01

    Intergranular stress corrosion cracking (IGSCC) in weld-sensitized, Type 304 (UNS S30400) (1) stainless steel (SS) remains a major threat to the integrity of heat transport circuits (HTC) in boiling water reactors (BWR), in spite of extensive research over the last 30 years. Effects of flow rate on intergranular crack growth in sensitized Type 304 stainless steel (UNS S30400) in distilled water containing 15 ppm or 25 ppm (2.59 x 10 -4 or 4.31 x 10 -4 m) sodium chloride (NaCl) at 250 C were examined using compact tension (CT) specimens under constant loading conditions. On increasing the flow rate, the crack growth rate (CGR) drastically increased, but later decreased to a level that was lower than the initial value. The initial increase in CGR was attributed to an enhanced rate of mass transfer of oxygen to the external surface, where it consumed the current emanating from the crack mouth. However, the subsequent decrease in CGR was attributed to crack flushing, which is a delayed process because of the time required to destroy the aggressive conditions that exist within the crack. Once flushing destroyed the aggressive crack environment, CGR decreased with increasing flow rate. The time over which CGR increased after an increase in the flow rate depended on how fast crack flushing occurred by fluid flow; the higher the flow rate and the greater the crack opening, the faster the crack flushing and the shorter the transition time. Finally, intergranular cracks propagated faster in regions nearer both sides of the Ct specimens, where the oxygen supply to the external surface was enhanced under stirring conditions and where minimal resistance existed to current flow from the crack tip to the external surfaces. This observation provided evidence that the crack's internal and external environments were coupled electrochemically

  8. Dopamine D2 receptor radiotracers [11C](+)-PHNO and [3H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo

    International Nuclear Information System (INIS)

    McCormick, Patrick N.; Kapur, Shitij; Seeman, Philip; Wilson, Alan A.

    2008-01-01

    Introduction: In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [ 11 C](+)-PHNO ([ 11 C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-o l), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [ 3 H]raclopride, which binds to both affinity states. Methods: We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [ 11 C](+)-PHNO and [ 3 H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for 11 C and 3 H. The specific binding ratio {SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum)} was used as the outcome measure. Results: In response to D2 antagonists, partial agonist or full agonist, [ 11 C](+)-PHNO and [ 3 H]raclopride SBRs responded indistinguishably in terms of both ED 50 and Hill slope (e.g., (-)-NPA ED 50 values are 0.027 and 0.023 mg/kg for [ 11 C](+)-PHNO and [ 3 H]raclopride, respectively). In response to AMPH challenge, [ 11 C](+)-PHNO and [ 3 H]raclopride SBRs were inhibited to the same degree. Conclusions: We have shown that the SBRs of [ 11 C](+)-PHNO- and [ 3 H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo applicability of the D2 two-state model, as described by in vitro binding experiments

  9. Effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome patients.

    Science.gov (United States)

    Karadağ, Cihan; Yoldemir, Tevfik; Yavuz, Dilek Gogas

    2018-02-01

    The aim of this study was to identify the effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome (PCOS) patients. Sixty-seven vitamin-D-deficient (25-hydroxyvitamin D [25(OH)D] levels below 20 ng/mL) PCOS patients and 54 vitamin-D-deficient non-PCOS volunteer subjects matched for age and body mass index were enrolled to this prospective study. All participants were given 50 000 IU/week cholecalciferol orally for 8 weeks and 1500 IU/day for 4 weeks. Insulin sensitivity was calculated with the Matsuda insulin sensitivity index (ISI) based on an oral glucose tolerance test. Matsuda ISI, gonadal hormones (estrogen, testosterone, androstenedione), and 25(OH)D levels were studied before and at the end of the 12th week of vitamin D load. After vitamin D supplementation, serum androstenedione levels had decreased significantly (P = 0.007) and Matsuda ISI values had increased significantly (P = 0.001) in the PCOS group but no significant changes were seen in those parameters in controls. We observed positive correlations between 25(OH)D levels and Matsuda ISI (r = 0.307; P < 0.01), and negative correlations between 25(OH)D levels and total testosterone (r = -0.306; P < 0.01) and androstenedione (r = -0.275; P < 0.01) levels in the PCOS group. Vitamin D supplementation increased insulin sensitivity and decreased androgen levels in vitamin-D-deficient women with PCOS but did not have any effect in vitamin-D-deficient non-PCOS women. These results may indicate the possible role of vitamin D in the complex pathogenesis of PCOS. © 2017 Japan Society of Obstetrics and Gynecology.

  10. Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening

    Energy Technology Data Exchange (ETDEWEB)

    Jiguet Jiglaire, Carine, E-mail: carine.jiguet-jiglaire@univ-amu.fr [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Baeza-Kallee, Nathalie; Denicolaï, Emilie; Barets, Doriane [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Metellus, Philippe [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); APHM, Timone Hospital, Department of Neurosurgery, 13005 Marseille (France); Timone Hospital, 264 Rue Saint Pierre, 13385 Marseille Cedex 5 (France); and others

    2014-02-15

    Identification of new drugs and predicting drug response are major challenges in oncology, especially for brain tumors, because total surgical resection is difficult and radiation therapy or chemotherapy is often ineffective. With the aim of developing a culture system close to in vivo conditions for testing new drugs, we characterized an ex vivo three-dimensional culture system based on a hyaluronic acid-rich hydrogel and compared it with classical two-dimensional culture conditions. U87-MG glioblastoma cells and seven primary cell cultures of human glioblastomas were subjected to radiation therapy and chemotherapy drugs. It appears that 3D hydrogel preserves the original cancer growth behavior and enables assessment of the sensitivity of malignant gliomas to radiation and drugs with regard to inter-tumoral heterogeneity of therapeutic response. It could be used for preclinical assessment of new therapies. - Highlights: • We have compared primary glioblastoma cell culture in a 2D versus 3D-matrix system. • In 3D morphology, organization and markers better recapitulate the original tumor. • 3D-matrix culture might represent a relevant system for more accurate drug screening.

  11. Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening

    International Nuclear Information System (INIS)

    Jiguet Jiglaire, Carine; Baeza-Kallee, Nathalie; Denicolaï, Emilie; Barets, Doriane; Metellus, Philippe

    2014-01-01

    Identification of new drugs and predicting drug response are major challenges in oncology, especially for brain tumors, because total surgical resection is difficult and radiation therapy or chemotherapy is often ineffective. With the aim of developing a culture system close to in vivo conditions for testing new drugs, we characterized an ex vivo three-dimensional culture system based on a hyaluronic acid-rich hydrogel and compared it with classical two-dimensional culture conditions. U87-MG glioblastoma cells and seven primary cell cultures of human glioblastomas were subjected to radiation therapy and chemotherapy drugs. It appears that 3D hydrogel preserves the original cancer growth behavior and enables assessment of the sensitivity of malignant gliomas to radiation and drugs with regard to inter-tumoral heterogeneity of therapeutic response. It could be used for preclinical assessment of new therapies. - Highlights: • We have compared primary glioblastoma cell culture in a 2D versus 3D-matrix system. • In 3D morphology, organization and markers better recapitulate the original tumor. • 3D-matrix culture might represent a relevant system for more accurate drug screening

  12. Arterial secondary blood flow patterns visualized with vector flow ultrasound

    DEFF Research Database (Denmark)

    Pedersen, Mads Møller; Pihl, Michael Johannes; Hansen, Jens Munk

    2011-01-01

    This study presents the first quantification and visualisation of secondary flow patterns with vector flow ultrasound. The first commercial implementation of the vector flow method Transverse Oscillation was used to obtain in-vivo, 2D vector fields in real-time. The hypothesis of this study...... was that the rotational direction is constant within each artery. Three data sets of 10 seconds were obtained from three main arteries in healthy volunteers. For each data set the rotational flow patterns were identified during the diastole. Each data set contains a 2D vector field over time and with the vector angles...

  13. 3D and 4D Seismic Technics Today

    Directory of Open Access Journals (Sweden)

    Marcin Marian

    2004-09-01

    Full Text Available Years ago, exploration was done through surface observations and „divining rods“ – now, it is done by satellites, microprocessors, remote sensing, and supercomputers. In the 1970´ s, the exploration success rate was 14 percent, today, it is nearly 29 percent. Not so long ago, three – dimension (3D seismic diagnostic techniques helped recover 25-50 percent of the oil in place – now, 4D seismic helps recover up to 70 percent of the oil in place. 3D and 4D seismic and earth imaging systems also help in understanding the subsurface flow of other fluids, such as groundwater and pollutants.Seismic surveys – a technique in which sound waves are bounced off underground rock struktures to reveal possible oil and gas bearing formation – are now standard fare for the modern petroleum industry. But today’s seismic methods are best at locating „structural traps“ where faults or folds in the underground rock have created zones where oil can become trapped.

  14. 2-Bromo-5-hydroxyphenylporphyrins for photodynamic therapy: photosensitization efficiency, subcellular localization and in vivo studies.

    Science.gov (United States)

    Laranjo, Mafalda; Serra, Arménio C; Abrantes, Margarida; Piñeiro, Marta; Gonçalves, Ana C; Casalta-Lopes, João; Carvalho, Lina; Sarmento-Ribeiro, Ana B; Rocha-Gonsalves, António; Botelho, Filomena

    2013-02-01

    Photodynamic therapy (PDT) is a therapeutic modality capable of inducing cell death by oxidative stress through activation of a sensitizer by light. Aryl-porphyrin with hydroxyl groups are good photosensitizers and presence of bromine atoms can enhance the photodynamic activity through heavy atom effect. These facts and our previous work made pertinent to compare the photodynamic capacity of tetraaryl brominated porphyrin (TBr4) with the corresponding diaryl (BBr2) derivative. Cell cultures were incubated with the sensitizers, ranging from 50nM to 10μM and irradiated until 10J. Cell proliferation was analysed by MTT assay. Flow cytometry studies evaluated cell death pathways, mitochondrial membrane potential and ROS. For in vivo studies Balb/c nu/nu mice were injected with 4×10(6)cells. After PDT, monitoring was carried out for 12 days to establish Kaplan-Meier survival curves. Tumours were excised and histological analysis was performed. Both sensitizers seem to accumulate in the mitochondria. The molecules have no intrinsic cytotoxicity or in non-tumour cells at therapeutic concentrations. Both sensitizers induced a significant decrease of cell proliferation and growth of xenografts of melanoma and colorectal adenocarcinoma. Diaryl BBr2 is more efficient than tetraaryl TBr4, concerning intracellular ROS production, mitochondrial disruption and induction of cell death. The main cell death pathway is necrosis. TBr2 and BBr4 are promising sensitizers with good photodynamic properties and have the ability to induce cell death in human melanoma and colorectal adenocarcinoma in vitro and in vivo. We consider that BBr2 is a molecule that should be the subject of extensive studies towards clinical use. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Haloxyfop mode of action in liquid cultures of proso millet: An analysis of haloxyfop sensitivity changes during growth

    International Nuclear Information System (INIS)

    Irzyk, G.P.

    1989-01-01

    Haloxyfop is a grass-selective herbicide that inhibits acetyl-CoA carboxylase in species that are not tolerant to the herbicide. Liquid cultures of proso millet (Panicum miliaceum) cells treated with haloxyfop at different phases of growth exhibited different levels of sensitivity to the herbicide. Treatment of 1-d cultures with 1 μM haloxyfop completely inhibited growth within 48 h. In contrast, 1 mM haloxyfop was required to elicit a similar response in 4-, 7-, or 10-d cultures. Calculated IC 50 values indicated a 300-fold decrease in haloxyfop sensitivity during the period from 1 to 4 d. This period of growth coincided with the greatest increase in cell number during culture growth and suggested that dividing cells are most sensitive to haloxyfop. Uptake and metabolism of 14 C-haloxyfop in 1-d and 4-d cultures were compared. In both cultures, amounts of radiolabel uptake were similar. Almost all radioactivity extracted from 1- and 4-d cells was present as the parent compound. These results suggested that the sensitivity change was related to other factors. Acetyl-CoA carboxylase activity of proso millet cells, measured in vitro by the acetyl-CoA-dependent incorporation of 14 C-bicarbonate into an acid-stable product, was essentially constant during culture growth. Micromolar concentrations of haloxyfop significantly inhibited acetyl-CoA carboxylase activity from both sensitive and insensitive cultures. Thus, the change in the sensitivity of cultures to haloxyfop was not correlated with changes in acetyl-CoA carboxylase abundance, activity, or sensitivity to haloxyfop during culture growth. In vivo incorporation of 14 C-acetate into lipids was decreased by 1 μM haloxyfop in both 1-d and 4-d cultures at the earliest sampling times but the amount of inhibition was significantly greater in the sensitive cultures

  16. Hydroquinone analog 4-[(Tetrahydro-2H-pyran-2‑yl) oxy] phenol induces C26 colon cancer cell apoptosis and inhibits tumor growth in vivo.

    Science.gov (United States)

    Du, Qigen; Xin, Guang; Niu, Hai; Huang, Wen

    2015-06-01

    The 4[(Tetrahydro‑2H‑pyran‑2‑yl) oxy] phenol (XG‑d) hydroquinone analog, is found in Vaccinium vitis‑idaea  L. Although it is known for its antioxidant properties and high level of safety, its antitumor activity remains to be elucidated. In the present study, the anticancer effect of XG‑d was determined in vitro and in vivo. The cytotoxicity of XG‑d against C26 murine colon carcinoma cells was found to occur in a time‑ and concentration‑dependent manner, whereas little effect was observed in the two normal cell lines (HK‑2 and L02) investigated. Oral administration of XG‑d (100 mg/kg) had effects on the tumor growth of tumor‑bearing mice. Furthermore, marked apoptosis was observed using Hoechst 33258 staining and flow cytometric analysis with annexin V/propidium iodide double staining. XG‑d also downregulated the expression of B‑cell lymphoma 2 (Bcl‑2), increased the expression levels of Bcl‑2‑associated X protein and activated caspase‑9, caspase‑3 and poly(adenosine diphosphate‑ribose) polymerase. The present study demonstrated for the first time, to the best of our knowledge, that XG‑d inhibited cancer cell growth via the induction of apoptosis and was also able to inhibit tumor growth in vivo. These results demonstrated that XG‑d may be used as a potential natural agent for cancer therapy with low toxicity.

  17. Early in vivo experience with the pediatric continuous-flow total artificial heart.

    Science.gov (United States)

    Karimov, Jamshid H; Horvath, David J; Byram, Nicole; Sunagawa, Gengo; Kuban, Barry D; Gao, Shengqiang; Dessoffy, Raymond; Fukamachi, Kiyotaka

    2018-03-30

    Heart transplantation in infants and children is an accepted therapy for end-stage heart failure, but donor organ availability is low and always uncertain. Mechanical circulatory support is another standard option, but there is a lack of intracorporeal devices due to size and functional range. The purpose of this study was to evaluate the in vivo performance of our initial prototype of a pediatric continuous-flow total artificial heart (P-CFTAH), comprising a dual pump with one motor and one rotating assembly, supported by a hydrodynamic bearing. In acute studies, the P-CFTAH was implanted in 4 lambs (average weight: 28.7 ± 2.3 kg) via a median sternotomy under cardiopulmonary bypass. Pulmonary and systemic pump performance parameters were recorded. The experiments showed good anatomical fit and easy implantation, with an average aortic cross-clamp time of 98 ± 18 minutes. Baseline hemodynamics were stable in all 4 animals (pump speed: 3.4 ± 0.2 krpm; pump flow: 2.1 ± 0.9 liters/min; power: 3.0 ± 0.8 W; arterial pressure: 68 ± 10 mm Hg; left and right atrial pressures: 6 ± 1 mm Hg, for both). Any differences between left and right atrial pressures were maintained within the intended limit of ±5 mm Hg over a wide range of ratios of systemic-to-pulmonary vascular resistance (0.7 to 12), with and without pump-speed modulation. Pump-speed modulation was successfully performed to create arterial pulsation. This initial P-CFTAH prototype met the proposed requirements for self-regulation, performance, and pulse modulation. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  18. In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives

    Science.gov (United States)

    Rocha e Silva, Luiz Francisco; Nogueira, Karla Lagos; Pinto, Ana Cristina da Silva; Katzin, Alejandro Miguel; Sussmann, Rodrigo A. C.; Muniz, Magno Perêa; Neto, Valter Ferreira de Andrade; Chaves, Francisco Célio Maia; Coutinho, Julia Penna; Lima, Emerson Silva; Krettli, Antoniana Ursine; Tadei, Wanderli Pedro

    2015-01-01

    4-Nerolidylcatechol (1) is an abundant antiplasmodial metabolite that is isolated from Piper peltatum roots. O-Acylation or O-alkylation of compound 1 provides derivatives exhibiting improved stability and significant in vitro antiplasmodial activity. The aim of this work was to study the in vitro inhibition of hemozoin formation, inhibition of isoprenoid biosynthesis in Plasmodium falciparum cultures, and in vivo antimalarial activity of several 4-nerolidylcatechol derivatives. 1,2-O,O-Diacetyl-4-nerolidylcatechol (2) inhibited in vitro hemozoin formation by up to 50%. In metabolic labeling studies using [1-(n)-3H]geranylgeranyl pyrophosphate, diester 2 significantly inhibited the biosynthesis of isoprenoid metabolites ubiquinone 8, menaquinone 4, and dolichol 12 in cultures of P. falciparum 3D7. Similarly, 2-O-benzyl-4-nerolidylcatechol (3) significantly inhibited the biosynthesis of dolichol 12. P. falciparum in vitro protein synthesis was not affected by compounds 2 or 3. At oral doses of 50 mg per kg of body weight per day, compound 2 suppressed Plasmodium berghei NK65 in infected BALB/c mice by 44%. This in vivo result for derivative 2 represents marked improvement over that obtained previously for natural product 1. Compound 2 was not detected in mouse blood 1 h after oral ingestion or in mixtures with mouse blood/blood plasma in vitro. However, it was detected after in vitro contact with human blood or blood plasma. Derivatives of 4-nerolidylcatechol exhibit parasite-specific modes of action, such as inhibition of isoprenoid biosynthesis and inhibition of hemozoin formation, and they therefore merit further investigation for their antimalarial potential. PMID:25801563

  19. Specific action of T4 endonuclease V on damaged DNA in xeroderma pigmentosum cells in vivo

    International Nuclear Information System (INIS)

    Tanaka, K.; Hayakawa, H.; Sekiguchi, M.; Okada, Y.

    1977-01-01

    The specific action of T4 endonuclease V on damaged DNA in xeroderma pigmentosum cells was examined using an in vivo assay system with hemagglutinating virus of Japan (Sendai virus) inactivated by uv light. A clear dose response was observed between the level of uv-induced unscheduled DNA synthesis of xeroderma pigmentosum cells and the amount of T4 endonuclease V activity added. The T4 enzyme was unstable in human cells, and its half-life was 3 hr. Fractions derived from an extract of Escherichia coli infected with T4v 1 , a mutant defective in the endonuclease V gene, showed no ability to restore the uv-induced unscheduled DNA synthesis of xeroderma pigmentosum cells. However, fractions derived from an extract of T4D-infected E. coli with endonuclease V activity were effective. The T4 enzyme was effective in xeroderma pigmentosum cells on DNA damaged by uv light but not in cells damaged by 4-nitroquinoline 1-oxide. The results of these experiments show that the T4 enzyme has a specific action on human cell DNA in vivo. Treatment with the T4 enzyme increased the survival of group A xeroderma pigmentosum cells after uv irradiation

  20. Bio indices for 2,4-D sensitivity between two plant species: Azolla pinnata R.Br. and Vernonia cinerea L. with their cellular responses.

    Science.gov (United States)

    De, Arnab Kumar; Dey, Narottam; Adak, Malay Kumar

    2016-07-01

    In the present experiment a pteridophytic species Azolla and an angiospermic species Vernonia were evaluated on the basis of cellular reactivity for herbicidal action through ongoing concentrations. Initially, both the species recorded a significant activity of IAA-oxidase as mark of IAA metabolism with herbicidal sensitivity. Still, Vernonia species were more affected on 2,4-D mediated auxin catabolism. The loss of auxin concentrations on the tissues by 2,4-D reaction was also reflected on growth parameters including relative growth rate and chlorophyll biosynthesis. In a dose dependent manner Vernonia plants were more affected with loss of chlorophyll content and decline in relative growth rate. On the other hand, both those parameters were adjusted significantly with 2,4-D accumulation in Azolla . The stability of cellular metabolism was documented by significant down regulation of protein and lipid peroxidation with concomitant moderation to superoxide and hydrogen peroxide accumulation. The later two were more vulnerable to damage in the Vernonia plant with profuse accumulation of protein and lipid peroxidation products. Similarly, tissue specific reaction to superoxide and hydrogen peroxide accumulation were distinctly demarcated in two species significantly. As a whole, the cellular responses and metabolite distribution to 2,4-D sensitization are the features to describe bio-indices for aquatic fern species Azolla with comparison to angiospermic species Vernonia .

  1. Radiosensitization in vitro and in vivo by 3-nitrotriazoles

    International Nuclear Information System (INIS)

    Shibamoto, Y.; Sakano, K.; Kimura, R.; Nishidai, T.; Nishimoto, S.; Ono, K.; Kagiya, T.; Abe, M.

    1986-01-01

    A series of 3-nitro-1,2,4-triazole derivatives bearing various types of side chain (R) at the N1-position (AK-2000 series) were synthesized and their radiosensitizing effect and toxicity in vitro and in vivo were investigated, in comparison with those of Misonidazole (MISO), SR-2508, and RSU-1069. Of the fifteen 3-nitrotriazoles tested, all had sensitizing effects in vitro on hypoxic V79 cells. Also, all but one had definite effects on solid EMT6/KU and SCCVII tumors in vivo. For many of the triazole compounds, the degree of radiosensitization in vitro and in vivo appeared identical. However, they were generally less efficient, both in vitro and in vivo, than the corresponding 2-nitroimidazoles, whereas their aerobic cytotoxicity and toxicity to mice (LD50/7) were comparable to those of the 2-nitroimidazoles. Considering the sensitizing effect and toxicity, AK-2123 (R = CH 2 CONHC 2 H 4 OCH 3 ) may be as useful as MISO, but none of the triazoles have been proved to be superior to SR-2508

  2. Effective sensitivity in 3D PET: The impact of detector dead time on 3D system performance

    International Nuclear Information System (INIS)

    Bailey, D.L.; Jones, T.; Meikle, S.R.

    1996-01-01

    3D PET has higher sensitivity than 2D PET. Sensitivity is determined by two components: the geometric solid angle for detection, and the fractional dead time, i.e., the time for which the detector is unavailable for accepting events. The loss in overall sensitivity as a function of radioactivity concentration due to these factors for 3D PET has been characterized by a parameter, the effective sensitivity, which combines absolute sensitivity and noise equivalent count rates. This parameter includes scatter, system sensitivity, dead time, and random coincidence rates, and permits comparisons between different tomographs as well as the same tomograph under different conditions. Effective sensitivity decreases most rapidly for larger, open 3D tomographs. The loss in effective sensitivity with increasing count rate suggests that new faster scintillation detectors will be needed to realize the sensitivity gain of 3D PET over a wide dynamic range of radioactivity concentrations

  3. Sensitivity studies on the multi-sensor conductivity probe measurement technique for two-phase flows

    Energy Technology Data Exchange (ETDEWEB)

    Worosz, Ted [Department of Mechanical and Nuclear Engineering, The Pennsylvania State University, 230 Reber Building, University Park, PA 16802 (United States); Bernard, Matt [The United States Nuclear Regulatory Commission, 11545 Rockville Pike, Rockville, MD 20852 (United States); Kong, Ran; Toptan, Aysenur [Department of Mechanical and Nuclear Engineering, The Pennsylvania State University, 230 Reber Building, University Park, PA 16802 (United States); Kim, Seungjin, E-mail: skim@psu.edu [Department of Mechanical and Nuclear Engineering, The Pennsylvania State University, 230 Reber Building, University Park, PA 16802 (United States); Hoxie, Chris [The United States Nuclear Regulatory Commission, 11545 Rockville Pike, Rockville, MD 20852 (United States)

    2016-12-15

    Highlights: • Revised conductivity probe circuit to eliminate signal “ghosting” among sensors. • Higher sampling frequencies suggested for bubble number frequency and a{sub i} measurements. • Two-phase parameter sensitivity to measurement duration and bubble number investigated. • Sensors parallel to pipe wall recommended for symmetric bubble velocity measurements. • Sensor separation distance ratio (s/d) greater than four minimizes bubble velocity error. - Abstract: The objective of this study is to advance the local multi-sensor conductivity probe measurement technique through systematic investigation into several practical aspects of a conductivity probe measurement system. Firstly, signal “ghosting” among probe sensors is found to cause artificially high bubble velocity measurements and low interfacial area concentration (a{sub i}) measurements that depend on sampling frequency and sensor impedance. A revised electrical circuit is suggested to eliminate this artificial variability. Secondly, the sensitivity of the probe measurements to sampling frequency is investigated in 13 two-phase flow conditions with superficial liquid and gas velocities ranging from 1.00–5.00 m/s and 0.17–2.0 m/s, respectively. With increasing gas flow rate, higher sampling frequencies, greater than 100 kHz in some cases, are required to adequately capture the bubble number frequency and a{sub i} measurements. This trend is due to the increase in gas velocity and the transition to the slug flow regime. Thirdly, the sensitivity of the probe measurements to the measurement duration as well as the sample number is investigated for the same flow conditions. Measurements of both group-I (spherical/distorted) and group-II (cap/slug/churn-turbulent) bubbles are found to be relatively insensitive to both the measurement duration and the number of bubbles, as long as the measurements are made for a duration long enough to capture a collection of samples characteristic to a

  4. Antimalarial benzoheterocyclic 4-aminoquinolines: Structure-activity relationship, in vivo evaluation, mechanistic and bioactivation studies.

    Science.gov (United States)

    Ongarora, Dennis S B; Strydom, Natasha; Wicht, Kathryn; Njoroge, Mathew; Wiesner, Lubbe; Egan, Timothy J; Wittlin, Sergio; Jurva, Ulrik; Masimirembwa, Collen M; Chibale, Kelly

    2015-09-01

    A novel class of benzoheterocyclic analogues of amodiaquine designed to avoid toxic reactive metabolite formation was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant) and NF54 (sensitive) strains of the malaria parasite Plasmodium falciparum. Structure-activity relationship studies led to the identification of highly promising analogues, the most potent of which had IC50s in the nanomolar range against both strains. The compounds further demonstrated good in vitro microsomal metabolic stability while those subjected to in vivo pharmacokinetic studies had desirable pharmacokinetic profiles. In vivo antimalarial efficacy in Plasmodium berghei infected mice was evaluated for four compounds, all of which showed good activity following oral administration. In particular, compound 19 completely cured treated mice at a low multiple dose of 4×10mg/kg. Mechanistic and bioactivation studies suggest hemozoin formation inhibition and a low likelihood of forming quinone-imine reactive metabolites, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. In vivo SPECT reporter gene imaging of regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Ehsan Sharif-Paghaleh

    Full Text Available Regulatory T cells (Tregs were identified several years ago and are key in controlling autoimmune diseases and limiting immune responses to foreign antigens, including alloantigens. In vivo imaging techniques including intravital microscopy as well as whole body imaging using bioluminescence probes have contributed to the understanding of in vivo Treg function, their mechanisms of action and target cells. Imaging of the human sodium/iodide symporter via Single Photon Emission Computed Tomography (SPECT has been used to image various cell types in vivo. It has several advantages over the aforementioned imaging techniques including high sensitivity, it allows non-invasive whole body studies of viable cell migration and localisation of cells over time and lastly it may offer the possibility to be translated to the clinic. This study addresses whether SPECT/CT imaging can be used to visualise the migratory pattern of Tregs in vivo. Treg lines derived from CD4(+CD25(+FoxP3(+ cells were retrovirally transduced with a construct encoding for the human Sodium Iodide Symporter (NIS and the fluorescent protein mCherry and stimulated with autologous DCs. NIS expressing self-specific Tregs were specifically radiolabelled in vitro with Technetium-99m pertechnetate ((99mTcO(4(- and exposure of these cells to radioactivity did not affect cell viability, phenotype or function. In addition adoptively transferred Treg-NIS cells were imaged in vivo in C57BL/6 (BL/6 mice by SPECT/CT using (99mTcO(4(-. After 24 hours NIS expressing Tregs were observed in the spleen and their localisation was further confirmed by organ biodistribution studies and flow cytometry analysis. The data presented here suggests that SPECT/CT imaging can be utilised in preclinical imaging studies of adoptively transferred Tregs without affecting Treg function and viability thereby allowing longitudinal studies within disease models.

  6. Mapping soil deformation around plant roots using in vivo 4D X-ray Computed Tomography and Digital Volume Correlation.

    Science.gov (United States)

    Keyes, S D; Gillard, F; Soper, N; Mavrogordato, M N; Sinclair, I; Roose, T

    2016-06-14

    The mechanical impedance of soils inhibits the growth of plant roots, often being the most significant physical limitation to root system development. Non-invasive imaging techniques have recently been used to investigate the development of root system architecture over time, but the relationship with soil deformation is usually neglected. Correlative mapping approaches parameterised using 2D and 3D image data have recently gained prominence for quantifying physical deformation in composite materials including fibre-reinforced polymers and trabecular bone. Digital Image Correlation (DIC) and Digital Volume Correlation (DVC) are computational techniques which use the inherent material texture of surfaces and volumes, captured using imaging techniques, to map full-field deformation components in samples during physical loading. Here we develop an experimental assay and methodology for four-dimensional, in vivo X-ray Computed Tomography (XCT) and apply a Digital Volume Correlation (DVC) approach to the data to quantify deformation. The method is validated for a field-derived soil under conditions of uniaxial compression, and a calibration study is used to quantify thresholds of displacement and strain measurement. The validated and calibrated approach is then demonstrated for an in vivo test case in which an extending maize root in field-derived soil was imaged hourly using XCT over a growth period of 19h. This allowed full-field soil deformation data and 3D root tip dynamics to be quantified in parallel for the first time. This fusion of methods paves the way for comparative studies of contrasting soils and plant genotypes, improving our understanding of the fundamental mechanical processes which influence root system development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. In Vivo Chondrogenesis in 3D Bioprinted Human Cell-laden Hydrogel Constructs

    OpenAIRE

    M?ller, Thomas; Amoroso, Matteo; H?gg, Daniel; Brantsing, Camilla; Rotter, Nicole; Apelgren, Peter; Lindahl, Anders; K?lby, Lars; Gatenholm, Paul

    2017-01-01

    Background: The three-dimensional (3D) bioprinting technology allows creation of 3D constructs in a layer-by-layer fashion utilizing biologically relevant materials such as biopolymers and cells. The aim of this study is to investigate the use of 3D bioprinting in a clinically relevant setting to evaluate the potential of this technique for in vivo chondrogenesis. Methods: Thirty-six nude mice (Balb-C, female) received a 5- ? 5- ? 1-mm piece of bioprinted cell-laden nanofibrillated cellulose/...

  8. Visualisation of cerebrospinal fluid flow patterns in albino Xenopus larvae in vivo

    Directory of Open Access Journals (Sweden)

    Mogi Kazue

    2012-04-01

    Full Text Available Abstract Background It has long been known that cerebrospinal fluid (CSF, its composition and flow, play an important part in normal brain development, and ependymal cell ciliary beating as a possible driver of CSF flow has previously been studied in mammalian fetuses in vitro. Lower vertebrate animals are potential models for analysis of CSF flow during development because they are oviparous. Albino Xenopus laevis larvae are nearly transparent and have a straight, translucent brain that facilitates the observation of fluid flow within the ventricles. The aim of these experiments was to study CSF flow and circulation in vivo in the developing brain of living embryos, larvae and tadpoles of Xenopus laevis using a microinjection technique. Methods The development of Xenopus larval brain ventricles and the patterns of CSF flow were visualised after injection of quantum dot nanocrystals and polystyrene beads (3.1 or 5.8 μm in diameter into the fourth cerebral ventricle at embryonic/larval stages 30-53. Results The fluorescent nanocrystals showed the normal development of the cerebral ventricles from embryonic/larval stages 38 to 53. The polystyrene beads injected into stage 47-49 larvae revealed three CSF flow patterns, left-handed, right-handed and non-biased, in movement of the beads into the third ventricle from the cerebral aqueduct (aqueduct of Sylvius. In the lateral ventricles, anterior to the third ventricle, CSF flow moved anteriorly along the outer wall of the ventricle to the inner wall and then posteriorly, creating a semicircle. In the cerebral aqueduct, connecting the third and fourth cerebral ventricles, CSF flow moved rostrally in the dorsal region and caudally in the ventral region. Also in the fourth ventricle, clear dorso-ventral differences in fluid flow pattern were observed. Conclusions This is the first visualisation of the orchestrated CSF flow pattern in developing vertebrates using a live animal imaging approach. CSF flow

  9. In Vivo Real Time Volumetric Synthetic Aperture Ultrasound Imaging

    DEFF Research Database (Denmark)

    Bouzari, Hamed; Rasmussen, Morten Fischer; Brandt, Andreas Hjelm

    2015-01-01

    Synthetic aperture (SA) imaging can be used to achieve real-time volumetric ultrasound imaging using 2-D array transducers. The sensitivity of SA imaging is improved by maximizing the acoustic output, but one must consider the limitations of an ultrasound system, both technical and biological....... This paper investigates the in vivo applicability and sensitivity of volumetric SA imaging. Utilizing the transmit events to generate a set of virtual point sources, a frame rate of 25 Hz for a 90° x 90° field-of-view was achieved. Data were obtained using a 3.5 MHz 32 x 32 elements 2-D phased array...... transducer connected to the experimental scanner (SARUS). Proper scaling is applied to the excitation signal such that intensity levels are in compliance with the U.S. Food and Drug Administration regulations for in vivo ultrasound imaging. The measured Mechanical Index and spatial-peak- temporal...

  10. Scan-rescan reproducibility of segmental aortic wall shear stress as assessed by phase-specific segmentation with 4D flow MRI in healthy volunteers.

    Science.gov (United States)

    van der Palen, Roel L F; Roest, Arno A W; van den Boogaard, Pieter J; de Roos, Albert; Blom, Nico A; Westenberg, Jos J M

    2018-05-26

    The aim was to investigate scan-rescan reproducibility and observer variability of segmental aortic 3D systolic wall shear stress (WSS) by phase-specific segmentation with 4D flow MRI in healthy volunteers. Ten healthy volunteers (age 26.5 ± 2.6 years) underwent aortic 4D flow MRI twice. Maximum 3D systolic WSS (WSSmax) and mean 3D systolic WSS (WSSmean) for five thoracic aortic segments over five systolic cardiac phases by phase-specific segmentations were calculated. Scan-rescan analysis and observer reproducibility analysis were performed. Scan-rescan data showed overall good reproducibility for WSSmean (coefficient of variation, COV 10-15%) with moderate-to-strong intraclass correlation coefficient (ICC 0.63-0.89). The variability in WSSmax was high (COV 16-31%) with moderate-to-good ICC (0.55-0.79) for different aortic segments. Intra- and interobserver reproducibility was good-to-excellent for regional aortic WSSmax (ICC ≥ 0.78; COV ≤ 17%) and strong-to-excellent for WSSmean (ICC ≥ 0.86; COV ≤ 11%). In general, ascending aortic segments showed more WSSmax/WSSmean variability compared to aortic arch or descending aortic segments for scan-rescan, intraobserver and interobserver comparison. Scan-rescan reproducibility was good for WSSmean and moderate for WSSmax for all thoracic aortic segments over multiple systolic phases in healthy volunteers. Intra/interobserver reproducibility for segmental WSS assessment was good-to-excellent. Variability of WSSmax is higher and should be taken into account in case of individual follow-up or in comparative rest-stress studies to avoid misinterpretation.

  11. Expansion of Bone Marrow Mesenchymal Stromal Cells in Perfused 3D Ceramic Scaffolds Enhances In Vivo Bone Formation.

    Science.gov (United States)

    Hoch, Allison I; Duhr, Ralph; Di Maggio, Nunzia; Mehrkens, Arne; Jakob, Marcel; Wendt, David

    2017-12-01

    Bone marrow-derived mesenchymal stromal cells (BMSC), when expanded directly within 3D ceramic scaffolds in perfusion bioreactors, more reproducibly form bone when implanted in vivo as compared to conventional expansion on 2D polystyrene dishes/flasks. Since the bioreactor-based expansion on 3D ceramic scaffolds encompasses multiple aspects that are inherently different from expansion on 2D polystyrene, we aimed to decouple the effects of specific parameters among these two model systems. We assessed the effects of the: 1) 3D scaffold vs. 2D surface; 2) ceramic vs. polystyrene materials; and 3) BMSC niche established within the ceramic pores during in vitro culture, on subsequent in vivo bone formation. While BMSC expanded on 3D polystyrene scaffolds in the bioreactor could maintain their in vivo osteogenic potential, results were similar as BMSC expanded in monolayer on 2D polystyrene, suggesting little influence of the scaffold 3D environment. Bone formation was most reproducible when BMSC are expanded on 3D ceramic, highlighting the influence of the ceramic substrate. The presence of a pre-formed niche within the scaffold pores had negligible effects on the in vivo bone formation. The results of this study allow a greater understanding of the parameters required for perfusion bioreactor-based manufacturing of osteogenic grafts for clinical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Imaging Agonist-Induced D2/D3 Receptor Desensitization and Internalization In Vivo with PET/fMRI.

    Science.gov (United States)

    Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian; Rosen, Bruce R; Mandeville, Joseph B

    2016-04-01

    This study investigated the dynamics of dopamine receptor desensitization and internalization, thereby proposing a new technique for non-invasive, in vivo measurements of receptor adaptations. The D2/D3 agonist quinpirole, which induces receptor internalization in vitro, was administered at graded doses in non-human primates while imaging with simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). A pronounced temporal divergence between receptor occupancy and fMRI signal was observed: occupancy remained elevated while fMRI responded transiently. Analogous experiments with an antagonist (prochlorperazine) and a lower-affinity agonist (ropinirole) exhibited reduced temporal dissociation between occupancy and function, consistent with a mechanism of desensitization and internalization that depends upon drug efficacy and affinity. We postulated a model that incorporates internalization into a neurovascular-coupling relationship. This model yielded in vivo desensitization/internalization rates (0.2/min for quinpirole) consistent with published in vitro measurements. Overall, these results suggest that simultaneous PET/fMRI enables characterization of dynamic neuroreceptor adaptations in vivo, and may offer a first non-invasive method for assessing receptor desensitization and internalization.

  13. Determination of phenols by flow injection and liquid chromatography with on-line quinine-sensitized photo-oxidation and quenched luminol chemiluminescence detection

    International Nuclear Information System (INIS)

    Zhang Wei; Danielson, Neil D.

    2003-01-01

    An on-line quinine-sensitized photo-oxidation with quenched chemiluminescence (CL) detection method is developed for phenols using flow injection (FI) and liquid chromatography (LC). This detection method is based on the decrease of light emission from the luminol CL reaction due to the photo-oxidation of phenols that scavenge the photogenerated reactive oxygen species (e.g. singlet oxygen ( 1 O 2 ) and superoxide (O 2 · - )). On-line photo-oxidation is achieved using a coil photo-reactor made from fluoroethylene-propylene copolymer tubing (3048 mmx0.25 mm i.d.) coiled around a mercury UV lamp. A buffer of pH 7 and a concentration of 350 μM for quinine sulfate are determined optimum for the sensitized photo-oxidation. Using a carrier system flow rate of 60 μl/min, calibration curves taken by FI for 10 phenolic compounds in aqueous solutions showed this decreasing sensitivity order: 4-chlorophenol, phenol, 4-nitrophenol, 3-hydroxy-L-kynurenine, 2-nitrophenol, salicylate, 3-nitrophenol, catechol, 2,4-dinitrophenol, and 2,4-dichlorophenol. This detection method using two tandem coil photo-reactors is also applied for the LC separation of phenol, 4-nitrophenol and 4-chlorophenol on an octadecyl (C18) silica LC column using acetonitrile-H 2 O (40:60, v/v) as a mobile phase. The quenched CL detection limits (about 1 μM or 20 pmol) for phenol and 4-chlorophenol are comparable to those for UV detection at 254 nm. Some selectivity in the quenched CL detection is evident by no interference in the FI phenol response even when benzaldehyde and phenethanol concentrations are 8 and 15 times that of phenol

  14. In vivo imaging of human oral hard and soft tissues by polarization-sensitive optical coherence tomography

    Science.gov (United States)

    Walther, Julia; Golde, Jonas; Kirsten, Lars; Tetschke, Florian; Hempel, Franz; Rosenauer, Tobias; Hannig, Christian; Koch, Edmund

    2017-12-01

    Since optical coherence tomography (OCT) provides three-dimensional high-resolution images of biological tissue, the benefit of polarization contrast in the field of dentistry is highlighted in this study. Polarization-sensitive OCT (PS OCT) with phase-sensitive recording is used for imaging dental and mucosal tissues in the human oral cavity in vivo. An enhanced polarization contrast of oral structures is reached by analyzing the signals of the co- and crosspolarized channels of the swept source PS OCT system quantitatively with respect to reflectivity, retardation, optic axis orientation, and depolarization. The calculation of these polarization parameters enables a high tissue-specific contrast imaging for the detailed physical interpretation of human oral hard and soft tissues. For the proof-of-principle, imaging of composite restorations and mineralization defects at premolars as well as gingival, lingual, and labial oral mucosa was performed in vivo within the anterior oral cavity. The achieved contrast-enhanced results of the investigated human oral tissues by means of polarization-sensitive imaging are evaluated by the comparison with conventional intensity-based OCT.

  15. Critical evaluation of reverse engineering tool Imagix 4D!

    Science.gov (United States)

    Yadav, Rashmi; Patel, Ravindra; Kothari, Abhay

    2016-01-01

    The comprehension of legacy codes is difficult to understand. Various commercial reengineering tools are available that have unique working styles, and are equipped with their inherent capabilities and shortcomings. The focus of the available tools is in visualizing static behavior not the dynamic one. Therefore, it is difficult for people who work in software product maintenance, code understanding reengineering/reverse engineering. Consequently, the need for a comprehensive reengineering/reverse engineering tool arises. We found the usage of Imagix 4D to be good as it generates the maximum pictorial representations in the form of flow charts, flow graphs, class diagrams, metrics and, to a partial extent, dynamic visualizations. We evaluated Imagix 4D with the help of a case study involving a few samples of source code. The behavior of the tool was analyzed on multiple small codes and a large code gcc C parser. Large code evaluation was performed to uncover dead code, unstructured code, and the effect of not including required files at preprocessing level. The utility of Imagix 4D to prepare decision density and complexity metrics for a large code was found to be useful in getting to know how much reengineering is required. At the outset, Imagix 4D offered limitations in dynamic visualizations, flow chart separation (large code) and parsing loops. The outcome of evaluation will eventually help in upgrading Imagix 4D and posed a need of full featured tools in the area of software reengineering/reverse engineering. It will also help the research community, especially those who are interested in the realm of software reengineering tool building.

  16. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    airways in asthmatic patients out of attack. LTD4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate. LTD4 was 1900-7000 times more potent......The aim of the study was to investigate whether inhaled leukotriene (LT) D4 could mimic the characteristics of asthmatic patients after allergen-induced attack, i.e. a prolonged subclinical bronchial obstruction, an increased reactivity of the airways and a late reaction. The effects of LTD4 were...... than histamine. LTD4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial...

  17. The insulin sensitizing effect of topiramate involves KATP channel activation in the central nervous system.

    Science.gov (United States)

    Coomans, C P; Geerling, J J; van den Berg, S A A; van Diepen, H C; Garcia-Tardón, N; Thomas, A; Schröder-van der Elst, J P; Ouwens, D M; Pijl, H; Rensen, P C N; Havekes, L M; Guigas, B; Romijn, J A

    2013-10-01

    Topiramate improves insulin sensitivity, in addition to its antiepileptic action. However, the underlying mechanism is unknown. Therefore, the present study was aimed at investigating the mechanism of the insulin-sensitizing effect of topiramate both in vivo and in vitro. Male C57Bl/6J mice were fed a run-in high-fat diet for 6 weeks, before receiving topiramate or vehicle mixed in high-fat diet for an additional 6 weeks. Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamp. The extent to which the insulin sensitizing effects of topiramate were mediated through the CNS were determined by concomitant i.c.v. infusion of vehicle or tolbutamide, an inhibitor of ATP-sensitive potassium channels in neurons. The direct effects of topiramate on insulin signalling and glucose uptake were assessed in vivo and in cultured muscle cells. In hyperinsulinaemic-euglycaemic clamp conditions, therapeutic plasma concentrations of topiramate (∼4 μg·mL(-1) ) improved insulin sensitivity (glucose infusion rate + 58%). Using 2-deoxy-D-[(3) H]glucose, we established that topiramate improved the insulin-mediated glucose uptake by heart (+92%), muscle (+116%) and adipose tissue (+586%). Upon i.c.v. tolbutamide, the insulin-sensitizing effect of topiramate was completely abrogated. Topiramate did not directly affect glucose uptake or insulin signalling neither in vivo nor in cultured muscle cells. In conclusion, topiramate stimulates insulin-mediated glucose uptake in vivo through the CNS. These observations illustrate the possibility of pharmacological modulation of peripheral insulin resistance through a target in the CNS. © 2013 The British Pharmacological Society.

  18. Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis

    DEFF Research Database (Denmark)

    Kielsgaard Kristensen, Thomas; Vestergaard, Hanne; Bindslev-Jensen, Carsten

    2014-01-01

    The recent progress in sensitive KIT D816V mutation analysis suggests that mutation analysis of peripheral blood (PB) represents a promising diagnostic test in mastocytosis. However, there is a need for systematic assessment of the analytical sensitivity and specificity of the approach in order...... to establish its value in clinical use. We therefore evaluated sensitive KIT D816V mutation analysis of PB as a diagnostic test in an entire case-series of adults with mastocytosis. We demonstrate for the first time that by using a sufficiently sensitive KIT D816V mutation analysis, it is possible to detect...... the mutation in PB in nearly all adult mastocytosis patients. The mutation was detected in PB in 78 of 83 systemic mastocytosis (94%) and 3 of 4 cutaneous mastocytosis patients (75%). The test was 100% specific as determined by analysis of clinically relevant control patients who all tested negative. Mutation...

  19. Computational Study of pH-sensitive Hydrogel-based Microfluidic Flow Controllers

    Science.gov (United States)

    Kurnia, Jundika C.; Birgersson, Erik; Mujumdar, Arun S.

    2011-01-01

    This computational study investigates the sensing and actuating behavior of a pH-sensitive hydrogel-based microfluidic flow controller. This hydrogel-based flow controller has inherent advantage in its unique stimuli-sensitive properties, removing the need for an external power supply. The predicted swelling behavior the hydrogel is validated with steady-state and transient experiments. We then demonstrate how the model is implemented to study the sensing and actuating behavior of hydrogels for different microfluidic flow channel/hydrogel configurations: e.g., for flow in a T-junction with single and multiple hydrogels. In short, the results suggest that the response of the hydrogel-based flow controller is slow. Therefore, two strategies to improve the response rate of the hydrogels are proposed and demonstrated. Finally, we highlight that the model can be extended to include other stimuli-responsive hydrogels such as thermo-, electric-, and glucose-sensitive hydrogels. PMID:24956303

  20. 3D and 4D Bioprinting of the Myocardium: Current Approaches, Challenges, and Future Prospects

    Directory of Open Access Journals (Sweden)

    Chin Siang Ong

    2018-01-01

    Full Text Available 3D and 4D bioprinting of the heart are exciting notions in the modern era. However, myocardial bioprinting has proven to be challenging. This review outlines the methods, materials, cell types, issues, challenges, and future prospects in myocardial bioprinting. Advances in 3D bioprinting technology have significantly improved the manufacturing process. While scaffolds have traditionally been utilized, 3D bioprinters, which do not require scaffolds, are increasingly being employed. Improved understanding of the cardiac cellular composition and multiple strategies to tackle the issues of vascularization and viability had led to progress in this field. In vivo studies utilizing small animal models have been promising. 4D bioprinting is a new concept that has potential to advance the field of 3D bioprinting further by incorporating the fourth dimension of time. Clinical translation will require multidisciplinary collaboration to tackle the pertinent issues facing this field.

  1. Cystoscopic optical coherence tomography for urinary bladder imaging in vivo

    Science.gov (United States)

    Wang, Z. G.; Adler, H.; Chan, D.; Jain, A.; Xie, H. K.; Wu, Z. L.; Pan, Y. T.

    2006-02-01

    This paper summarizes the development of new 2D MEMS mirrors and the pertinent modification to improve OCT endoscopic catheter packaging suitable for in vivo imaging diagnosis of bladder cancers. Comparative study of the newly developed endocopic OCT versus the bench-top OCT is presented. Results of in vivo OCT cystoscopy based on a porcine acute inflammation model are presented to compare time-domain OCT and spectral-domain OCT for in vivo imaging. In addition, results of spectral-domain Doppler OCT are presented to image blood flow in the lamina propria of the bladder. The results of our in vivo animal study using the presented OCT endoscope are discussed for potential problems in the future clinical applications.

  2. In vitro and in vivo tests of PLA/d-HAp nanocomposite

    Science.gov (United States)

    Thom Nguyen, Thi; Hoang, Thai; Mao Can, Van; Son Ho, Anh; Hai Nguyen, Song; Thu Trang Nguyen, Thi; Pham, Thi Nam; Phuong Nguyen, Thu; Le Hien Nguyen, Thi; Thanh Dinh Thi, Mai

    2017-12-01

    The bioactivity of the PLA/d-HAp nanocomposite with 30 wt.% d-HAp was evaluated by in vitro tests and indicated that after 7 immersion days in SBF solution, PLA amorphous part was hydrolyzed and PLA crystal part was remained. The formation of apatite on the surface of the material was observed. The in vivo test results of PLA/d-HAp nanocomposite (70/30 wt/wt) on femur of dogs displayed that 3 months after grafting, the materials did not induce any osteitis, osteomyelitis or structural abnormalities. The histological and x-ray image demonstrated a growth of the bone into the material area, while osteitis and osteomyelitis were not observed.

  3. Sex differences in the pro-inflammatory cytokine response to endotoxin unfold in vivo but not ex vivo in healthy humans.

    Science.gov (United States)

    Wegner, Alexander; Benson, Sven; Rebernik, Laura; Spreitzer, Ingo; Jäger, Marcus; Schedlowski, Manfred; Elsenbruch, Sigrid; Engler, Harald

    2017-07-01

    Clinical data indicate that inflammatory responses differ across sexes, but the mechanisms remain elusive. Herein, we assessed in vivo and ex vivo cytokine responses to bacterial endotoxin in healthy men and women to elucidate the role of systemic and cellular factors underlying sex differences in inflammatory responses. Participants received an i.v. injection of low-dose endotoxin (0.4 ng/kg body mass), and plasma TNF-α and IL-6 responses were analyzed over a period of 6 h. In parallel, ex vivo cytokine production was measured in endotoxin-stimulated blood samples obtained immediately before in vivo endotoxin administration. As glucocorticoids (GCs) play an important role in the negative feedback regulation of the inflammatory response, we additionally analyzed plasma cortisol concentrations and ex vivo GC sensitivity of cytokine production. Results revealed greater in vivo pro-inflammatory responses in women compared with men, with significantly higher increases in plasma TNF-α and IL-6 concentrations. In addition, the endotoxin-induced rise in plasma cortisol was more pronounced in women. In contrast, no sex differences in ex vivo cytokine production and GC sensitivity were observed. Together, these findings demonstrate major differences in in vivo and ex vivo responses to endotoxin and underscore the importance of systemic factors underlying sex differences in the inflammatory response.

  4. Protease-Sensitive Liposomes in Chemotherapy & Chemoradiotherapy: From Material Development to In Vivo Application in Tumor-Bearing Mice

    DEFF Research Database (Denmark)

    Brogaard, Rikke Yding; Melander, Fredrik

    to enhance therapeutic efficacies. In this thesis, the development, characterization, and evaluation of an advanced liposomal DDS and its potential in chemoradiotherapy is presented from material development to in vivo application in tumor*bearing mice. In the first part of the thesis, we report the design...... concept of the liposomal DDS, which leads to rapid cellular uptake. Various lipid compositions are tested in uptake and cytotoxicity experiments in vitro, followed by in vivo experiments where the ability of the liposomal DDS to accumulate in tumors together with its anti*cancer activity is explored...... in tumor*bearing mice. The in vivo data demonstrates superior anti*cancer activity relative to the free drug and to conventional, long circulating liposomes. This indicates that the MMP*sensitive liposomal DDS holds potential in therapeutic applications. In the second part of the thesis, the potential...

  5. Neonatal co-lesion by DSP-4 and 5,7-DHT produces adulthood behavioral sensitization to dopamine D(2) receptor agonists.

    Science.gov (United States)

    Nowak, Przemysław; Nitka, Dariusz; Kwieciński, Adam; Jośko, Jadwiga; Drab, Jacek; Pojda-Wilczek, Dorota; Kasperski, Jacek; Kostrzewa, Richard M; Brus, Ryszard

    2009-01-01

    To assess the possible modulatory effects of noradrenergic and serotoninergic neurons on dopaminergic neuronal activity, the noradrenergic and serotoninergic neurotoxins DSP-4 N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine (50.0 mg/kg, sc) and 5,7-dihydroxytryptamine (5,7-DHT) (37.5 microg icv, half in each lateral ventricle), respectively, were administered toWistar rats on the first and third days of postnatal ontogeny, and dopamine (DA) agonist-induced behaviors were assessed in adulthood. At eight weeks, using an HPLC/ED technique, DSP-4 treatment was associated with a reduction in NE content of the corpus striatum (> 60%), hippocampus (95%), and frontal cortex (> 85%), while 5,7-DHT was associated with an 80-90% serotonin reduction in the same brain regions. DA content was unaltered in the striatum and the cortex. In the group lesioned with both DSP-4 and 5,7-DHT, quinpirole-induced (DA D(2) agonist) yawning, 7-hydroxy-DPAT-induced (DA D(3) agonist) yawning, and apomorphine-induced (non-selective DA agonist) stereotypies were enhanced. However, SKF 38393-induced (DA D(1) agonist) oral activity was reduced in the DSP-4 + 5,7-DHT group. These findings demonstrate that DA D(2)- and D(3)-agonist-induced behaviors are enhanced while DA D(1)-agonist-induced behaviors are suppressed in adult rats in which brain noradrenergic and serotoninergic innervation of the brain has largely been destroyed. This study indicates that noradrenergic and serotoninergic neurons have a great impact on the development of DA receptor reactivity (sensitivity).

  6. Turbulent flow chromatography TFC-tandem mass spectrometry supporting in vitro/vivo studies of NCEs in high throughput fashion.

    Science.gov (United States)

    Verdirame, Maria; Veneziano, Maria; Alfieri, Anna; Di Marco, Annalise; Monteagudo, Edith; Bonelli, Fabio

    2010-03-11

    Turbulent Flow Chromatography (TFC) is a powerful approach for on-line extraction in bioanalytical studies. It improves sensitivity and reduces sample preparation time, two factors that are of primary importance in drug discovery. In this paper the application of the ARIA system to the analytical support of in vivo pharmacokinetics (PK) and in vitro drug metabolism studies is described, with an emphasis in high throughput optimization. For PK studies, a comparison between acetonitrile plasma protein precipitation (APPP) and TFC was carried out. Our optimized TFC methodology gave better S/N ratios and lower limit of quantification (LOQ) than conventional procedures. A robust and high throughput analytical method to support hepatocyte metabolic stability screening of new chemical entities was developed by hyphenation of TFC with mass spectrometry. An in-loop dilution injection procedure was implemented to overcome one of the main issues when using TFC, that is the early elution of hydrophilic compounds that renders low recoveries. A comparison between off-line solid phase extraction (SPE) and TFC was also carried out, and recovery, sensitivity (LOQ), matrix effect and robustness were evaluated. The use of two parallel columns in the configuration of the system provided a further increase of the throughput. Copyright 2009 Elsevier B.V. All rights reserved.

  7. Skeletal muscle blood flow in vivo: detection with rubidium-82 and effects of glucose, insulin, and exercise

    International Nuclear Information System (INIS)

    Mossberg, K.A.; Mullani, N.; Gould, K.L.; Taegtmeyer, H.

    1987-01-01

    In order to assess the effects of glucose, insulin, and exercise on skeletal muscle blood flow in vivo, we measured positron emission from the thigh muscle of anesthetized rabbits after simultaneous aortic bolus injection of 82 Rb and radiolabeled microspheres (15 micron diameter). Estimates of flow with 82 Rb were based on first-pass regional extraction of 82 Rb by skeletal muscle. Flow estimates were made serially as a function of variations in plasma glucose and insulin and changing the muscle contractile state by electrical stimulation. Flow ranged from 3.1 ml/min/100 g at rest to 71 ml/min/100 g during stimulation. There was good agreement between the two methods of flow measurement over the entire range of flows (r = 0.96 at a slope of 0.90). Flow measured by either method did not vary significantly from baseline over a range of plasma glucose from 5 to 30 mM and plasma insulin from 0 to 20 microU/ml. When flow was increased up to 20-fold by electrical stimulation there was a decrease in extraction of 82 Rb proportional to the increase in flow. However, at pharmacologic levels of insulin (greater than 150 microU/ml) flow was increased twofold as measured by radiolabeled microspheres, but not as measured by rubidium. There was no apparent decrease in extraction of 82 Rb with high insulin. The discrepancy between the microsphere measured flow and rubidium measured flow with high plasma insulin levels can be explained by the assumption that the expected decrease in the extraction fraction was counteracted by an increase in Na+/K+-ATPase activity. It is concluded that the first-pass flow model gives valid estimates of skeletal muscle blood flow in vivo with 82 Rb, provided that plasma insulin levels are normal

  8. LHCb base-line level-0 trigger 3D-Flow implementation

    International Nuclear Information System (INIS)

    Crosetto, Dario B.

    1999-01-01

    The LHCb Level-0 trigger implementation with the 3D-Flow system offers full programmability, allowing it to adapt to unexpected operating conditions and enabling new, unpredicted physics. The implementation is described in detail and refers to components and technology available today. The 3D-Flow Processor system is a new, technology-independent concept in very fast, real-time system architectures. Based on the replication of a single type of circuit of 100k gates, which communicates in six directions: bi-directional with North, East, West, and South neighbors, unidirectional from Top to Bottom, the system offers full programmability, modularity, ease of expansion and adaptation to the latest technology. A complete study of its applicability to the LHCb calorimeter triggers is presented. Full description of the input data handling, either in digital or mixed digital-analog form, of the data processing, and the transmission of results to the global level-0 trigger decision unit are provided. Any level-0 trigger algorithm (2x2, 3x3, 4x4, etc.) with up to 20 steps, can be implemented with zero dead-time, while sustaining input data rate (up to 32-bit per input channel, per bunch crossing) at 40 MHz. For each step, each 3D-Flow processor can execute up to 26 operations, inclusive of compare, ranging, finding local maxima, and efficient data exchange with neighboring channels. (One-to-one correspondence between input channel and trigger tower.) Populated with only two main types of components, front-end FPGAs and 3D-Flow processors, a single type of board, it is shown how the whole Level-0 calorimeter trigger can be accommodated into six crates (9U), each containing 16 identical boards. All 3D-Flow inter-chip Bottom to Top ports connection are all contained on the board (data are multiplexed 2 : 1, PCB traces are shorter than 6 cm); all 3D-flow inter-chip North, East, West, and South ports connections, between boards and crates, are multiplexed (8+2) : 1 and are

  9. Stochastic precision analysis of 2D cardiac strain estimation in vivo

    International Nuclear Information System (INIS)

    Bunting, E A; Provost, J; Konofagou, E E

    2014-01-01

    Ultrasonic strain imaging has been applied to echocardiography and carries great potential to be used as a tool in the clinical setting. Two-dimensional (2D) strain estimation may be useful when studying the heart due to the complex, 3D deformation of the cardiac tissue. Increasing the framerate used for motion estimation, i.e. motion estimation rate (MER), has been shown to improve the precision of the strain estimation, although maintaining the spatial resolution necessary to view the entire heart structure in a single heartbeat remains challenging at high MERs. Two previously developed methods, the temporally unequispaced acquisition sequence (TUAS) and the diverging beam sequence (DBS), have been used in the past to successfully estimate in vivo axial strain at high MERs without compromising spatial resolution. In this study, a stochastic assessment of 2D strain estimation precision is performed in vivo for both sequences at varying MERs (65, 272, 544, 815 Hz for TUAS; 250, 500, 1000, 2000 Hz for DBS). 2D incremental strains were estimated during left ventricular contraction in five healthy volunteers using a normalized cross-correlation function and a least-squares strain estimator. Both sequences were shown capable of estimating 2D incremental strains in vivo. The conditional expected value of the elastographic signal-to-noise ratio (E(SNRe|ε)) was used to compare strain estimation precision of both sequences at multiple MERs over a wide range of clinical strain values. The results here indicate that axial strain estimation precision is much more dependent on MER than lateral strain estimation, while lateral estimation is more affected by strain magnitude. MER should be increased at least above 544 Hz to avoid suboptimal axial strain estimation. Radial and circumferential strain estimations were influenced by the axial and lateral strain in different ways. Furthermore, the TUAS and DBS were found to be of comparable precision at similar MERs. (paper)

  10. Accounting for data variability, a key factor in in vivo/in vitro relationships: application to the skin sensitization potency (in vivo LLNA versus in vitro DPRA) example.

    Science.gov (United States)

    Dimitrov, S; Detroyer, A; Piroird, C; Gomes, C; Eilstein, J; Pauloin, T; Kuseva, C; Ivanova, H; Popova, I; Karakolev, Y; Ringeissen, S; Mekenyan, O

    2016-12-01

    When searching for alternative methods to animal testing, confidently rescaling an in vitro result to the corresponding in vivo classification is still a challenging problem. Although one of the most important factors affecting good correlation is sample characteristics, they are very rarely integrated into correlation studies. Usually, in these studies, it is implicitly assumed that both compared values are error-free numbers, which they are not. In this work, we propose a general methodology to analyze and integrate data variability and thus confidence estimation when rescaling from one test to another. The methodology is demonstrated through the case study of rescaling the in vitro Direct Peptide Reactivity Assay (DPRA) reactivity to the in vivo Local Lymph Node Assay (LLNA) skin sensitization potency classifications. In a first step, a comprehensive statistical analysis evaluating the reliability and variability of LLNA and DPRA as such was done. These results allowed us to link the concept of gray zones and confidence probability, which in turn represents a new perspective for a more precise knowledge of the classification of chemicals within their in vivo OR in vitro test. Next, the novelty and practical value of our methodology introducing variability into the threshold optimization between the in vitro AND in vivo test resides in the fact that it attributes a confidence probability to the predicted classification. The methodology, classification and screening approach presented in this study are not restricted to skin sensitization only. They could be helpful also for fate, toxicity and health hazard assessment where plenty of in vitro and in chemico assays and/or QSARs models are available. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Neurotensin analogs [D-TYR11] and [D-PHE11]neurotensin resist degradation by brain peptidases in vitro and in vivo

    International Nuclear Information System (INIS)

    Checler, F.; Vincent, J.P.; Kitabgi, P.

    1983-01-01

    The present study was designed to compare the susceptibility of neurotensin (NT), [ 3 H]NT, [D-Tyr11]NT and [D-Phe11]NT to degradation by 1) rat brain synaptic membranes in vitro and 2) after i.c.v. administration in the rat in vivo. Degradation was assessed by purifying the peptides using reverse phase high-performance liquid chromatography and by measuring the amount of radioactive or absorbing (OD 230) material under each peptide peak. In contrast to NT, [D-Tyr11]NT and [D-Phe11]NT were resistant to degradation by brain synaptic peptidases in vitro. Furthermore, NT was rapidly metabolized in brain tissues after i.c.v. administration, whereas [D-Tyr11]NT was metabolically stable. The present data confirm the central role of NT residue Tyr11 in the mechanisms of NT inactivation by brain synaptic peptidases. They account for the higher in vivo potency of [D-Tyr11]NT as compared with its in vitro potency. Finally, they explain, at least in part, the need to administer large doses of NT in the brain in order to observe neurobehavioral and neuropharmacological effects

  12. Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo.

    Directory of Open Access Journals (Sweden)

    Daniel Brönnimann

    Full Text Available Hemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals. Here we describe a pharmacological approach to modulate cardiac and hemodynamic parameters in adult zebrafish in vivo.Adult zebrafish were paralyzed and orally perfused with salt water. The drugs isoprenaline and sodium nitroprusside were directly applied with the perfusate, thus closely resembling the preferred method for drug delivery in zebrafish, namely within the water. Drug effects on the heart and on blood flow in the submental vein were studied using electrocardiograms, in vivo-microscopy and mathematical flow simulations.Under control conditions, heart rate, blood flow velocity and shear stress varied less than ± 5%. Maximal chronotropic effects of isoprenaline were achieved at a concentration of 50 μmol/L, where it increased the heart rate by 22.6 ± 1.3% (n = 4; p < 0.0001. Blood flow velocity and shear stress in the submental vein were not significantly increased. Sodium nitroprusside at 1 mmol/L did not alter the heart rate but increased blood flow velocity by 110.46 ± 19.64% (p = 0.01 and shear stress by 117.96 ± 23.65% (n = 9; p = 0.03.In this study, we demonstrate that cardiac and hemodynamic parameters in adult zebrafish can be efficiently modulated by isoprenaline and sodium nitroprusside. Together with the suitability of the zebrafish for in vivo-microscopy and genetic modifications, the methodology described permits studying biological processes that are dependent on hemodynamic alterations.

  13. Targeting the AKT/GSK3β/Cyclin D1/Cdk4 Survival Signaling Pathway for Eradication of Tumor Radioresistance Acquired by Fractionated Radiotherapy

    International Nuclear Information System (INIS)

    Shimura, Tsutomu; Kakuda, Satoshi; Ochiai, Yasushi; Kuwahara, Yoshikazu; Takai, Yoshihiro; Fukumoto, Manabu

    2011-01-01

    Purpose: Radioresistance is a major cause of treatment failure of radiotherapy (RT) in human cancer. We have recently revealed that acquired radioresistance of tumor cells induced by fractionated radiation is attributable to cyclin D1 overexpression as a consequence of the downregulation of GSK3β-dependent cyclin D1 proteolysis mediated by a constitutively activated serine-threonine kinase, AKT. This prompted us to hypothesize that targeting the AKT/GSK3β/cyclin D1 pathway may improve fractionated RT by suppressing acquired radioresistance of tumor cells. Methods and Materials: Two human tumor cell lines with acquired radioresistance were exposed to X-rays after incubation with either an AKT inhibitor, AKT/PKB signaling inhibitor-2 (API-2), or a Cdk4 inhibitor (Cdk4-I). Cells were then subjected to immunoblotting, clonogenic survival assay, cell growth analysis, and cell death analysis with TUNEL and annexin V staining. In vivo radiosensitivity was assessed by growth of human tumors xenografted into nude mice. Results: Treatment with API-2 resulted in downregulation of cyclin D1 expression in cells with acquired radioresistance. Cellular radioresistance disappeared completely both in vitro and in vivo with accompanying apoptosis when treated with API-2. Furthermore, inhibition of cyclin D1/Cdk4 by Cdk4-I was sufficient for abolishing radioresistance. Treatment with either API-2 or Cdk4-I was also effective in suppressing resistance to cis-platinum (II)-diamine-dichloride in the cells with acquired radioresistance. Interestingly, the radiosensitizing effect of API-2 was canceled by overexpression of cyclin D1 whereas Cdk4-I was still able to sensitize cells with cyclin D1 overexpression. Conclusion: Cyclin D1/Cdk4 is a critical target of the AKT survival signaling pathway responsible for tumor radioresistance. Targeting the AKT/GSK3β/cyclin D1/Cdk4 pathway would provide a novel approach to improve fractionated RT and would have an impact on tumor eradication in

  14. Improvements on digital inline holographic PTV for 3D wall-bounded turbulent flow measurements

    International Nuclear Information System (INIS)

    Toloui, Mostafa; Mallery, Kevin; Hong, Jiarong

    2017-01-01

    Three-dimensional (3D) particle image velocimetry (PIV) and particle tracking velocimetry (PTV) provide the most comprehensive flow information for unraveling the physical phenomena in a wide range of fluid problems, from microfluidics to wall-bounded turbulent flows. Compared with other 3D PIV techniques, such as tomographic PIV and defocusing PIV, the digital inline holographic PTV (DIH-PTV) provides 3D flow measurement solution with high spatial resolution, low cost optical setup, and easy alignment and calibration. Despite these advantages, DIH-PTV suffers from major limitations including poor longitudinal resolution, human intervention (i.e. requirement for manually determined tuning parameters during tracer field reconstruction and extraction), limited tracer concentration, small sampling volume and expensive computations, limiting its broad use for 3D flow measurements. In this study, we present our latest developments on minimizing these challenges, which enables high-fidelity DIH-PTV implementation to larger sampling volumes with significantly higher particle seeding densities suitable for wall-bounded turbulent flow measurements. The improvements include: (1) adjustable window thresholding; (2) multi-pass 3D tracking; (3) automatic wall localization; and (4) continuity-based out-of-plane velocity component computation. The accuracy of the proposed DIH-PTV method is validated with conventional 2D PIV and double-view holographic PTV measurements in smooth-wall turbulent channel flow experiments. The capability of the technique in characterization of wall-bounded turbulence is further demonstrated through its application to flow measurements for smooth- and rough-wall turbulent channel flows. In these experiments, 3D velocity fields are measured within sampling volumes of 14.7  ×  50.0  ×  14.4 mm 3 (covering the entire depth of the channel) with a velocity resolution of  <1.1 mm/vector. Overall, the presented DIH-PTV method and

  15. Human sensitivity to eye contact in 2D and 3D videoconferencing

    NARCIS (Netherlands)

    Eijk, van R.L.J.; Kuijsters, A.; Dijkstra, K.I.; IJsselsteijn, W.A.

    2010-01-01

    Gaze awareness and eye contact serve important functions in social interaction. In order to maintain those functions in 2D and 3D videoconferencing systems, human sensitivity to eye contact and gaze direction needs to be taken into account in the design of such systems. Here we experimentally

  16. Pressure-sensitive paint on a truncated cone in hypersonic flow at incidences

    International Nuclear Information System (INIS)

    Yang, L.; Erdem, E.; Zare-Behtash, H.; Kontis, K.; Saravanan, S.

    2012-01-01

    Highlights: ► Global pressure map over the truncated cone is obtained at various incidence angles in Mach 5 flow. ► Successful application of AA-PSP in hypersonic flow expands operation area of this technique. ► AA-PSP reveals complex three-dimensional pattern which is difficult for transducer to obtain. ► Quantitative data provides strong correlation with colour Schlieren and oil flow results. ► High spatial resolution pressure mappings identify small scale vortices and flow separation. - Abstract: The flow over a truncated cone is a classical and fundamental problem for aerodynamic research due to its three-dimensional and complicated characteristics. The flow is made more complex when examining high angles of incidence. Recently these types of flows have drawn more attention for the purposes of drag reduction in supersonic/hypersonic flows. In the present study the flow over a truncated cone at various incidences was experimentally investigated in a Mach 5 flow with a unit Reynolds number of 13.5 × 10 6 m −1 . The cone semi-apex angle is 15° and the truncation ratio (truncated length/cone length) is 0.5. The incidence of the model varied from −12° to 12° with 3° intervals relative to the freestream direction. The external flow around the truncated cone was visualised by colour Schlieren photography, while the surface flow pattern was revealed using the oil flow method. The surface pressure distribution was measured using the anodized aluminium pressure-sensitive paint (AA-PSP) technique. Both top and sideviews of the pressure distribution on the model surface were acquired at various incidences. AA-PSP showed high pressure sensitivity and captured the complicated flow structures which correlated well with the colour Schlieren and oil flow visualisation results.

  17. TU-F-12A-05: Sensitivity of Textural Features to 3D Vs. 4D FDG-PET/CT Imaging in NSCLC Patients

    Energy Technology Data Exchange (ETDEWEB)

    Yang, F; Nyflot, M; Bowen, S; Kinahan, P; Sandison, G [University of Washington Medical Center, Seattle, WA (United States)

    2014-06-15

    Purpose: Neighborhood Gray-level difference matrices (NGLDM) based texture parameters extracted from conventional (3D) 18F-FDG PET scans in patients with NSCLC have been previously shown to associate with response to chemoradiation and poorer patient outcome. However, the change in these parameters when utilizing respiratory-correlated (4D) FDG-PET scans has not yet been characterized for NSCLC. The Objectives: of this study was to assess the extent to which NGLDM-based texture parameters on 4D PET images vary with reference to values derived from 3D scans in NSCLC. Methods: Eight patients with newly diagnosed NSCLC treated with concomitant chemoradiotherapy were included in this study. 4D PET scans were reconstructed with OSEM-IR in 5 respiratory phase-binned images and corresponding CT data of each phase were employed for attenuation correction. NGLDM-based texture features, consisting of coarseness, contrast, busyness, complexity and strength, were evaluated for gross tumor volumes defined on 3D/4D PET scans by radiation oncologists. Variation of the obtained texture parameters over the respiratory cycle were examined with respect to values extracted from 3D scans. Results: Differences between texture parameters derived from 4D scans at different respiratory phases and those extracted from 3D scans ranged from −30% to 13% for coarseness, −12% to 40% for contrast, −5% to 50% for busyness, −7% to 38% for complexity, and −43% to 20% for strength. Furthermore, no evident correlations were observed between respiratory phase and 4D scan texture parameters. Conclusion: Results of the current study showed that NGLDM-based texture parameters varied considerably based on choice of 3D PET and 4D PET reconstruction of NSCLC patient images, indicating that standardized image acquisition and analysis protocols need to be established for clinical studies, especially multicenter clinical trials, intending to validate prognostic values of texture features for NSCLC.

  18. 2D NMR studies on muscle and cerebral metabolism in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Gillet, B.; Doan, B.T.; Verre-Sebrie, C.; Fedeli, O.; Beloeil, J.C. (Centre National de la Recherche Scientifique (CNRS), 91 - Gif-sur-Yvette (France). Inst. de Chimie des Substances Naturelles); Peres, M. (CERMA-CEV, 91 - Bretigny-sur-Orge (France)); Barrere, B.; Seylaz, J. (Paris-7 Univ., 75 (France)); Morin, S.; Koenig, J. (Bordeaux-1 Univ., 33 - Talence (France)); Sebille, A. (Faculte de Medecine Saint-Antoine, 75 - Paris (France))

    1994-06-01

    New developments in in vivo 2D[sup 1]H NMR spectroscopy now allow several metabolites, which are not resolved by 1D NMR to be assigned. This report describes the use of this technique to follow the time courses of changes in the concentration of metabolites in the rat brain during physiological and pathophysiological processes (hyperglycemia and hypoxia) and to compare the fatty acid components of normal and dystrophic mouse gastrocnemius muscle. (authors). 15 refs., 5 figs.

  19. In-vivo brain blood flow imaging based on laser speckle contrast imaging and synchrotron radiation microangiography

    International Nuclear Information System (INIS)

    Miao, Peng; Feng, Shihan; Zhang, Qi; Lin, Xiaojie; Xie, Bohua; Liu, Chenwei; Yang, Guo-Yuan

    2014-01-01

    Abstract In-vivo imaging of blood flow in the cortex and sub-cortex is still a challenge in biological and pathological studies of cerebral vascular diseases. Laser speckle contrast imaging (LSCI) only provides cortex blood flow information. Traditional synchrotron radiation micro-angiography (SRA) provides sub-cortical vasculature information with high resolution. In this study, a bolus front-tracking method was developed to extract blood flow information based on SRA. Combining LSCI and SRA, arterial blood flow in the ipsilateral cortex and sub-cortex was monitored after experimental intracerebral hemorrhage of mice. At 72 h after injury, a significant blood flow increase was observed in the lenticulostriate artery along with blood flow decrease in cortical branches of the middle cerebral artery. This combined strategy provides a new approach for the investigation of brain vasculature and blood flow changes in preclinical studies. (paper)

  20. Improved sensitivity and limit-of-detection of lateral flow devices using spatial constrictions of the flow-path.

    Science.gov (United States)

    Katis, Ioannis N; He, Peijun J W; Eason, Robert W; Sones, Collin L

    2018-05-03

    We report on the use of a laser-direct write (LDW) technique that allows the fabrication of lateral flow devices with enhanced sensitivity and limit of detection. This manufacturing technique comprises the dispensing of a liquid photopolymer at specific regions of a nitrocellulose membrane and its subsequent photopolymerisation to create impermeable walls inside the volume of the membrane. These polymerised structures are intentionally designed to create fluidic channels which are constricted over a specific length that spans the test zone within which the sample interacts with pre-deposited reagents. Experiments were conducted to show how these constrictions alter the fluid flow rate and the test zone area within the constricted channel geometries. The slower flow rate and smaller test zone area result in the increased sensitivity and lowered limit of detection for these devices. We have quantified these via the improved performance of a C-Reactive Protein (CRP) sandwich assay on our lateral flow devices with constricted flow paths which demonstrate an improvement in its sensitivity by 62x and in its limit of detection by 30x when compared to a standard lateral flow CRP device. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  1. Comparison between a coupled 1D-2D model and a fully 2D model for supercritical flow simulation in crossroads

    KAUST Repository

    Ghostine, Rabih

    2014-12-01

    In open channel networks, flow is usually approximated by the one-dimensional (1D) Saint-Venant equations coupled with an empirical junction model. In this work, a comparison in terms of accuracy and computational cost between a coupled 1D-2D shallow water model and a fully two-dimensional (2D) model is presented. The paper explores the ability of a coupled model to simulate the flow processes during supercritical flows in crossroads. This combination leads to a significant reduction in the computational time, as a 1D approach is used in branches and a 2D approach is employed in selected areas only where detailed flow information is essential. Overall, the numerical results suggest that the coupled model is able to accurately simulate the main flow processes. In particular, hydraulic jumps, recirculation zones, and discharge distribution are reasonably well reproduced and clearly identified. Overall, the proposed model leads to a 30% reduction in run times. © 2014 International Association for Hydro-Environment Engineering and Research.

  2. Pituitary and brain D2 receptor density measured in vitro and in vivo in EEDQ treated male rats

    International Nuclear Information System (INIS)

    Ekman, A.; Eriksson, E.

    1991-01-01

    The effect of the alkylating compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on dopamine D2 receptor density in rat pituitary and brain was measured using in vitro and in vivo radioligand binding techniques. In the in vitro radioligand binding experiments EEDQ was found to reduce the density (B max ) of [ 3 H]-spiperone binding sites in the striatum by 86% while in the pituitary the corresponding decrease was only 37%. The affinity (K D ) of the remaining striatal and pituitary D2 receptors was not different in EEDQ treated animals as compared to controls. When D2 receptor density was measured in vivo the effect of EEDQ was less pronounced. Thus, in rats given EEDQ the specific binding of either of the two D2 ligands [ 3 H]-raclopride or [ 3 H]-spiperone in striatum and in the limbic forebrain was reduced by 45-62%; moreover, no significant decrease in pituitary D2 receptor density was observed. The data are discussed in relation to the finding that the same dose of EEDQ that failed to influence pituitary D2 receptor density as measured in vivo effectively antagonizes the prolactin decreasing effect of the partial D2 agonist (-)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine [(-)-3-PPP

  3. Use of Cellulases to Predict in vivo Digestible Organic Matter (D value in Pasture Silages Uso de Celulasas para Predecir el Contenido de Materia Orgánica Digestible (Valor D in vivo, en Ensilajes de Praderas

    Directory of Open Access Journals (Sweden)

    Claudia Barchiesi-Ferrari

    2011-06-01

    Full Text Available In pasture-based dairy herds where silage is a widely adopted supplement, optimized feeding requires reliable estimations of nutritional quality of this conserved forage. Metabolizable energy, an important nutritional fraction, can be predicted from digestibility-related traits, such as the digestible organic matter contained in the dry matter (D-value. The aim of the present study was to evaluate the prediction of D-value and dry matter digestibility (DMD of grass silages made from four different pastures and maturity stages, using the pepsin-cellulase method. Fungal cellulase was used, applying different enzyme concentrations, incubation times and types of final wash. The silages were prepared from permanent pasture (Dactylis glomerata L., Lolium perenne L., Bromus catharticus Vahl var. catharticus, Trifolium repens L. and Holcus lanatus L., rotation pasture (Lolium multiflorum Lam. cv. Tama, oats (Avena sativa L., and mixed pasture (L. perenne-T. repens. These were harvested at three different physiological stages (vegetative, ear emergence and dough grain. The treatment using an incubation time of 24 h, a cellulase concentration of 6.25 g L-1 and final wash with water (Treatment 3 presented the best prediction capacity of the in vivo D-value (R² = 0.78 and in vivo DMD (R² = 0.71. In vivo D-value prediction improved (R² = 0.8 when a chemical determination (crude fibre, gross energy, neutral detergent fibre, total ash or acid detergent fibre was included in addition (multiple regression to D-value obtained with cellulases (Treatment 3. Results of DMD obtained with cellulases show good precision, but underestimate in vivo values, and are closer to those obtained with ruminal fluid. Suitable equations could be used to improve accuracy.En sistemas lecheros pastoriles que utilizan ensilaje como suplemento, se requiere conocer el valor nutricional de éste para optimizar la alimentación del ganado. La energía metabolizable, importante fracci

  4. Method of coupling 1-D unsaturated flow with 3-D saturated flow on large scale

    Directory of Open Access Journals (Sweden)

    Yan Zhu

    2011-12-01

    Full Text Available A coupled unsaturated-saturated water flow numerical model was developed. The water flow in the unsaturated zone is considered the one-dimensional vertical flow, which changes in the horizontal direction according to the groundwater table and the atmospheric boundary conditions. The groundwater flow is treated as the three-dimensional water flow. The recharge flux to groundwater from soil water is considered the bottom flux for the numerical simulation in the unsaturated zone, and the upper flux for the groundwater simulation. It connects and unites the two separated water flow systems. The soil water equation is solved based on the assumed groundwater table and the subsequent predicted recharge flux. Then, the groundwater equation is solved with the predicted recharge flux as the upper boundary condition. Iteration continues until the discrepancy between the assumed and calculated groundwater nodal heads have a certain accuracy. Illustrative examples with different water flow scenarios regarding the Dirichlet boundary condition, the Neumann boundary condition, the atmospheric boundary condition, and the source or sink term were calculated by the coupled model. The results are compared with those of other models, including Hydrus-1D, SWMS-2D, and FEFLOW, which demonstrate that the coupled model is effective and accurate and can significantly reduce the computational time for the large number of nodes in saturated-unsaturated water flow simulation.

  5. TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb

    Science.gov (United States)

    Garvin, Jeffrey L.

    2014-01-01

    Nitric oxide (NO) regulates renal function. Luminal flow stimulates NO production in the thick ascending limb (TAL). Transient receptor potential vanilloid 4 (TRPV4) is a mechano-sensitive channel activated by luminal flow in different types of cells. We hypothesized that TRPV4 mediates flow-induced NO production in the rat TAL. We measured NO production in isolated, perfused rat TALs using the fluorescent dye DAF FM. Increasing luminal flow from 0 to 20 nl/min stimulated NO from 8 ± 3 to 45 ± 12 arbitrary units (AU)/min (n = 5; P < 0.05). The TRPV4 antagonists, ruthenium red (15 μmol/l) and RN 1734 (10 μmol/l), blocked flow-induced NO production. Also, luminal flow did not increase NO production in the absence of extracellular calcium. We also studied the effect of luminal flow on NO production in TALs transduced with a TRPV4shRNA. In nontransduced TALs luminal flow increased NO production by 47 ± 17 AU/min (P < 0.05; n = 5). Similar to nontransduced TALs, luminal flow increased NO production by 39 ± 11 AU/min (P < 0.03; n = 5) in TALs transduced with a control negative sequence-shRNA while in TRPV4shRNA-transduced TALs, luminal flow did not increase NO production (Δ10 ± 15 AU/min; n = 5). We then tested the effect of two different TRPV4 agonists on NO production in the absence of luminal flow. 4α-Phorbol 12,13-didecanoate (1 μmol/l) enhanced NO production by 60 ± 11 AU/min (P < 0.002; n = 7) and GSK1016790A (10 ηmol/l) increased NO production by 52 ± 15 AU/min (P < 0.03; n = 5). GSK1016790A (10 ηmol/l) did not stimulate NO production in TRPV4shRNA-transduced TALs. We conclude that activation of TRPV4 channels mediates flow-induced NO production in the rat TAL. PMID:24966090

  6. In vivo formation of beta-oxidized metabolites of leukotriene E4 in the rat

    International Nuclear Information System (INIS)

    Perrin, P.; Zirrolli, J.; Stene, D.O.; Lellouche, J.P.; Beaucourt, J.P.; Murphy, R.C.

    1989-01-01

    Intraperitoneal administration of [ 3 H]-leukotriene E4 in the rat resulted in the appearance of radiolabel in urine and feces. Separation of polar urinary metabolites and chromatographic comparison of synthetic metabolites indicated the in vivo formation of omega-oxidized metabolites of LTE4 with sequential beta-oxidation. Furthermore, the metabolite identified as 16-carboxy-17,18,19,20-tetranor-14,15-dihydro-N-acetyl-LTE4 substantiates the biochemical pathway of beta-oxidation in vivo involving the 2,4-dienoyl CoA reductase as an integral step. These results substantiate beta-oxidation of sulfidopeptide leukotrienes in vivo and these metabolites account for some of the major urinary metabolites of this class of lipid mediator

  7. Sensitivity Analysis of Multidisciplinary Rotorcraft Simulations

    Science.gov (United States)

    Wang, Li; Diskin, Boris; Biedron, Robert T.; Nielsen, Eric J.; Bauchau, Olivier A.

    2017-01-01

    A multidisciplinary sensitivity analysis of rotorcraft simulations involving tightly coupled high-fidelity computational fluid dynamics and comprehensive analysis solvers is presented and evaluated. An unstructured sensitivity-enabled Navier-Stokes solver, FUN3D, and a nonlinear flexible multibody dynamics solver, DYMORE, are coupled to predict the aerodynamic loads and structural responses of helicopter rotor blades. A discretely-consistent adjoint-based sensitivity analysis available in FUN3D provides sensitivities arising from unsteady turbulent flows and unstructured dynamic overset meshes, while a complex-variable approach is used to compute DYMORE structural sensitivities with respect to aerodynamic loads. The multidisciplinary sensitivity analysis is conducted through integrating the sensitivity components from each discipline of the coupled system. Numerical results verify accuracy of the FUN3D/DYMORE system by conducting simulations for a benchmark rotorcraft test model and comparing solutions with established analyses and experimental data. Complex-variable implementation of sensitivity analysis of DYMORE and the coupled FUN3D/DYMORE system is verified by comparing with real-valued analysis and sensitivities. Correctness of adjoint formulations for FUN3D/DYMORE interfaces is verified by comparing adjoint-based and complex-variable sensitivities. Finally, sensitivities of the lift and drag functions obtained by complex-variable FUN3D/DYMORE simulations are compared with sensitivities computed by the multidisciplinary sensitivity analysis, which couples adjoint-based flow and grid sensitivities of FUN3D and FUN3D/DYMORE interfaces with complex-variable sensitivities of DYMORE structural responses.

  8. The use of 4D-CTA in the diagnostic work-up of brain arteriovenous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Willems, Peter W.A. [Toronto Western Hospital, UHN, Division of Neuroradiology, Department of Medical Imaging, Toronto, Ontario (Canada); Leiden University Medical Center, Department of Radiology, Leiden (Netherlands); Taeshineetanakul, Patamintita; Terbrugge, Karel G.; Krings, Timo [Toronto Western Hospital, UHN, Division of Neuroradiology, Department of Medical Imaging, Toronto, Ontario (Canada); Schenk, Barry; Brouwer, Patrick A. [Leiden University Medical Center, Department of Radiology, Leiden (Netherlands)

    2012-02-15

    We aimed to evaluate the use of time-resolved whole-head CT angiography (4D-CTA) in patients with an untreated arteriovenous malformation of the brain (bAVM), as demonstrated by catheter angiography (DSA). Seventeen patients with a DSA-proven bAVM were enrolled. These were subjected to 4D-CTA imaging using a 320 detector row CT scanner. Using a standardized scoring sheet, all studies were analyzed by a panel of three readers. This panel was blind to the DSA results at the time of reading the 4D-CTA. 4D-CTA detected all bAVMs. With regard to the Spetzler-Martin grade, 4D-CTA disagreed with DSA in only one case, where deep venous drainage was missed. Further discrepancies between 4D-CTA and DSA analyses included underestimation of the nidus size in small lesions (four cases), misinterpretation of a feeding vessel (one case), misinterpretation of indirect feeding through pial collaterals (three cases) and oversight of mild arterial enlargement (two cases). 4D-CTA correctly distinguished low-flow from high-flow lesions and detected dural/transosseous feeding (one case), venous narrowing (one case) and venous pouches (nine cases). In this series, 4D-CTA was able to detect all bAVMs. Although some angioarchitectural details were missed or misinterpreted when compared to DSA, 4D-CTA evaluation was sufficiently accurate to diagnose the shunt and classify it. Moreover, 4D-CTA adds cross-sectional imaging and perfusion maps, helpful in treatment planning. 4D-CTA appears to be a valuable new adjunct in the non-invasive diagnostic work-up of bAVMs and their follow-up when managed conservatively. (orig.)

  9. The use of 4D-CTA in the diagnostic work-up of brain arteriovenous malformations

    International Nuclear Information System (INIS)

    Willems, Peter W.A.; Taeshineetanakul, Patamintita; Terbrugge, Karel G.; Krings, Timo; Schenk, Barry; Brouwer, Patrick A.

    2012-01-01

    We aimed to evaluate the use of time-resolved whole-head CT angiography (4D-CTA) in patients with an untreated arteriovenous malformation of the brain (bAVM), as demonstrated by catheter angiography (DSA). Seventeen patients with a DSA-proven bAVM were enrolled. These were subjected to 4D-CTA imaging using a 320 detector row CT scanner. Using a standardized scoring sheet, all studies were analyzed by a panel of three readers. This panel was blind to the DSA results at the time of reading the 4D-CTA. 4D-CTA detected all bAVMs. With regard to the Spetzler-Martin grade, 4D-CTA disagreed with DSA in only one case, where deep venous drainage was missed. Further discrepancies between 4D-CTA and DSA analyses included underestimation of the nidus size in small lesions (four cases), misinterpretation of a feeding vessel (one case), misinterpretation of indirect feeding through pial collaterals (three cases) and oversight of mild arterial enlargement (two cases). 4D-CTA correctly distinguished low-flow from high-flow lesions and detected dural/transosseous feeding (one case), venous narrowing (one case) and venous pouches (nine cases). In this series, 4D-CTA was able to detect all bAVMs. Although some angioarchitectural details were missed or misinterpreted when compared to DSA, 4D-CTA evaluation was sufficiently accurate to diagnose the shunt and classify it. Moreover, 4D-CTA adds cross-sectional imaging and perfusion maps, helpful in treatment planning. 4D-CTA appears to be a valuable new adjunct in the non-invasive diagnostic work-up of bAVMs and their follow-up when managed conservatively. (orig.)

  10. Dopaminergic and cholinergic regulation of Fyn tyrosine kinase phosphorylation in the rat striatum in vivo.

    Science.gov (United States)

    Mao, Li-Min; Wang, John Q

    2015-12-01

    Src and Fyn are two Src family kinase (SFK) members that are expressed in mammalian brains and play important roles in the regulation of a variety of neuronal and synaptic substrates. Here we investigated the responsiveness of these SFKs to changing dopamine receptor signals in dopamine responsive regions of adult rat brains in vivo. Pharmacological activation of dopamine D1 receptors (D1Rs) by a systemic injection of the selective agonist SKF81297 increased phosphorylation of SFKs at a conserved and activation-associated autophosphorylation site (Y416) in the striatum, indicating activation of SFKs following SKF81297 injection. The dopamine D2 receptor (D2R) agonist quinpirole had no effect. Blockade of D1Rs with an antagonist SCH23390 did not alter striatal Y416 phosphorylation, while the D2R antagonist eticlopride elevated it. Between Src and Fyn, SKF81297 seemed to preferentially facilitate Fyn phosphorylation. Activation of muscarinic acetylcholine M4 receptors (M4Rs) with a positive allosteric modulator VU0152100 suppressed SFK Y416 responses to SKF81297. Additionally, SKF81297 induced a correlated increase in phosphorylation of N-methyl-D-aspartate (NMDA) receptor GluN2B subunits at a Fyn site (Y1472), which was attenuated by VU0152100. SKF81297 also enhanced synaptic recruitments of active Fyn and GluN1/GluN2B-containing NMDA receptors. These data demonstrate that D1Rs regulate Fyn and downstream NMDA receptors in striatal neurons in vivo. Acetylcholine through activating M4Rs inhibits Fyn and NMDA receptors in their sensitivity to D1R signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The source of investment cash flow sensitivity in manufacturing firms: Is it asymmetric information or agency costs?

    Directory of Open Access Journals (Sweden)

    Daniel Makina

    2016-09-01

    Full Text Available In the literature, positive investment cash flow sensitivity is attributed to either asymmetric information induced financing constraints or the agency costs of free cash flow. Using data from a sample of 68 manufacturing firms listed on the South African JSE, this paper contributes to the literature by investigating the source of investment cash flow sensitivity. We have found that asymmetric information explains the positive investment cash flow sensitivity better than agency costs. Furthermore, asymmetric information has been observed to be more pronounced in low-dividend-paying firms and small firms. Despite South Africa’s having a developed financial system by international standards, small firms are seen to be financially constrained. We attribute the absence of investment cash flow sensitivity due to agency costs to good corporate governance of South African listed firms. Thus the paper provides further evidence in support of the proposition in the literature that the source of investment cash flow sensitivity may depend on the institutional setting of a country, such as its corporate governance.

  12. Stability and sensitivity analysis of hypersonic flow past a blunt cone

    Science.gov (United States)

    Nichols, Joseph W.; Cook, David; Brock, Joseph M.; Candler, Graham V.

    2017-11-01

    We investigate the effects of nosetip bluntness and low-level distributed roughness on instabilities leading to transition on a 7 degree half-angle blunt cone at Mach 10. To study the sensitivity of boundary layer instabilities to bluntness and roughness, we numerically extract Jacobian matrices directly from the unstructured hypersonic flow solver US3D. These matrices govern the dynamics of small perturbations about otherwise laminar base flows. We consider the frequency response of the resulting linearized dynamical system between different input and output locations along the cone, including close to the nosetip. Using adjoints, our method faithfully captures effects of complex geometry such as strong curvature and roughness that lead to flow acceleration and localized heating in this region. These effects violate the assumption of a slowly-varying base flow that underpins traditional linear stability analyses. We compare our results, which do not rely upon this assumption, to experimental measurements of a Mach 10 blunt cone taken at the AEDC Hypervelocity Ballistic Range G facility. In particular, we assess whether effects of complex geometry can explain discrepancies previously noted between traditional stability analysis and observations. This work is supported by the Office of Naval Research through Grant Number N00014-17-1-2496.

  13. Automatic re-contouring in 4D radiotherapy

    International Nuclear Information System (INIS)

    Lu, Weiguo; Olivera, Gustavo H; Chen, Quan; Chen, Ming-Li; Ruchala, Kenneth J

    2006-01-01

    Delineating regions of interest (ROIs) on each phase of four-dimensional (4D) computed tomography (CT) images is an essential step for 4D radiotherapy. The requirement of manual phase-by-phase contouring prohibits the routine use of 4D radiotherapy. This paper develops an automatic re-contouring algorithm that combines techniques of deformable registration and surface construction. ROIs are manually contoured slice-by-slice in the reference phase image. A reference surface is constructed based on these reference contours using a triangulated surface construction technique. The deformable registration technique provides the voxel-to-voxel mapping between the reference phase and the test phase. The vertices of the reference surface are displaced in accordance with the deformation map, resulting in a deformed surface. The new contours are reconstructed by cutting the deformed surface slice-by-slice along the transversal, sagittal or coronal direction. Since both the inputs and outputs of our automatic re-contouring algorithm are contours, it is relatively easy to cope with any treatment planning system. We tested our automatic re-contouring algorithm using a deformable phantom and 4D CT images of six lung cancer patients. The proposed algorithm is validated by visual inspections and quantitative comparisons of the automatic re-contours with both the gold standard segmentations and the manual contours. Based on the automatic delineated ROIs, changes of tumour and sensitive structures during respiration are quantitatively analysed. This algorithm could also be used to re-contour daily images for treatment evaluation and adaptive radiotherapy

  14. In vivo seasonal assessment of Plasmodium falciparum sensitivity to chloroquine in two different malaria endemic communities in Southern Ghana.

    Science.gov (United States)

    Afari, Edwin A.; Dunyo, Samuel; Appawu, Maxwell; Nkrumah, Francis K.

    1994-08-01

    A two year (1992 to 1993) in vivo assessment of Plasmodium falciparum sensitivity to chloroquine was conducted in two communities at Dodowa (hyperendemic) and Prampram (mesoendemic) in Southern Ghana. A slightly modified World Helath Organization standard field test (7 day test) for response of Plasmodium falciparum asexual parasites to chloroquine was used for the survey. In 1992, 16.2% (12/74) responses were classified as exhibiting chloroquine resistance at RI (14.8% ) and RII (1.4%) in the dry season and 8.2% (10/122) responses at RI in the wet season in the hyperendemic community. Only a single response (1/144; 0.7%) at RI showed resistance in the mesoendemic community. The rest of the responses in both communities were classified as sensitive to chloroquine. In the hyperendemic community, 8.4% (13/154) of responses in the dry season showed resistance at RI and 1.3% (82/150) at RI (0.7%) and RII (0.7%) in the wet season in 1993. In the mesoendemic community 1 (1.0%) response was resistant at RI in the wet season. The rest of the responses were classified as sensitive responses to chloroquine. No RIII response was encountered in any of the communities. The pattern of RI and RII responses did not show any seasonal variations in the mesoendemic community. However, they were generally higher in the dry season than in the wet season in the hyperendemic community.

  15. Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken.

    Science.gov (United States)

    Watanabe, Kensuke P; Kawata, Minami; Ikenaka, Yoshinori; Nakayama, Shouta M M; Ishii, Chihiro; Darwish, Wageh Sobhi; Saengtienchai, Aksorn; Mizukawa, Hazuki; Ishizuka, Mayumi

    2015-10-01

    Coumarin-derivative anticoagulant rodenticides used for rodent control are posing a serious risk to wild bird populations. For warfarin, a classic coumarin derivative, chickens have a high median lethal dose (LD50), whereas mammalian species generally have much lower LD50. Large interspecies differences in sensitivity to warfarin are to be expected. The authors previously reported substantial differences in warfarin metabolism among avian species; however, the actual in vivo pharmacokinetics have yet to be elucidated, even in the chicken. In the present study, the authors sought to provide an in-depth characterization of warfarin metabolism in birds using in vivo and in vitro approaches. A kinetic analysis of warfarin metabolism was performed using liver microsomes of 4 avian species, and the metabolic abilities of the chicken and crow were much higher in comparison with those of the mallard and ostrich. Analysis of in vivo metabolites from chickens showed that excretions predominantly consisted of 4'-hydroxywarfarin, which was consistent with the in vitro results. Pharmacokinetic analysis suggested that chickens have an unexpectedly long half-life despite showing high metabolic ability in vitro. The results suggest that the half-life of warfarin in other bird species could be longer than that in the chicken and that warfarin metabolism may not be a critical determinant of species differences with respect to warfarin sensitivity. © 2015 SETAC.

  16. Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide nanoparticles for intestinal delivery of exendin-4

    Directory of Open Access Journals (Sweden)

    Wang M

    2013-03-01

    Full Text Available Mengshu Wang,1* Yong Zhang,1* Jiao Feng,1 Tiejun Gu,1 Qingguang Dong,1 Xu Yang,2 Yanan Sun,1 Yongge Wu,1 Yan Chen,1 Wei Kong1 1National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, People’s Republic of China; 2BCHT Biopharm Co, Ltd, Changchun, People’s Republic of China*These authors contributed equally to this workBackground: Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide (CS-PLGA nanoparticles was investigated for intestinal delivery of exendin-4.Methods and results: Nanoparticles were prepared using a modified water–oil–water (w/o/w emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ~30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ~300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis

  17. In vivo 3D measurement of moxifloxacin and gatifloxacin distributions in the mouse cornea using multiphoton microscopy

    Science.gov (United States)

    Lee, Seunghun; Lee, Jun Ho; Park, Jin Hyoung; Yoon, Yeoreum; Chung, Wan Kyun; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean

    2016-05-01

    Moxifloxacin and gatifloxacin are fourth-generation fluoroquinolone antibiotics used in the clinic to prevent or treat ocular infections. Their pharmacokinetics in the cornea is usually measured from extracted ocular fluids or tissues, and in vivo direct measurement is difficult. In this study multiphoton microscopy (MPM), which is a 3D optical microscopic technique based on multiphoton fluorescence, was applied to the measurement of moxifloxacin and gatifloxacin distribution in the cornea. Intrinsic multiphoton fluorescence properties of moxifloxacin and gatifloxacin were characterized, and their distributions in mouse cornea in vivo were measured by 3D MPM imaging. Both moxifloxacin and gatifloxacin had similar multiphoton spectra, while moxifloxacin had stronger fluorescence than gatifloxacin. MPM imaging of mouse cornea in vivo showed (1) moxifloxacin had good penetration through the superficial corneal epithelium, while gatifloxacin had relatively poor penetration, (2) both ophthalmic solutions had high intracellular distribution. In vivo MPM results were consistent with previous studies. This study demonstrates the feasibility of MPM as a method for in vivo direct measurement of moxifloxacin and gatifloxacin in the cornea.

  18. Framework for 3D histologic reconstruction and fusion with in vivo MRI: Preliminary results of characterizing pulmonary inflammation in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Rusu, Mirabela, E-mail: mirabela.rusu@gmail.com; Wang, Haibo; Madabhushi, Anant [Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106 (United States); Golden, Thea; Gow, Andrew [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08854 (United States)

    2015-08-15

    Purpose: Pulmonary inflammation is associated with a variety of diseases. Assessing pulmonary inflammation on in vivo imaging may facilitate the early detection and treatment of lung diseases. Although routinely used in thoracic imaging, computed tomography has thus far not been compellingly shown to characterize inflammation in vivo. Alternatively, magnetic resonance imaging (MRI) is a nonionizing radiation technique to better visualize and characterize pulmonary tissue. Prior to routine adoption of MRI for early characterization of inflammation in humans, a rigorous and quantitative characterization of the utility of MRI to identify inflammation is required. Such characterization may be achieved by considering ex vivo histology as the ground truth, since it enables the definitive spatial assessment of inflammation. In this study, the authors introduce a novel framework to integrate 2D histology, ex vivo and in vivo imaging to enable the mapping of the extent of disease from ex vivo histology onto in vivo imaging, with the goal of facilitating computerized feature analysis and interrogation of disease appearance on in vivo imaging. The authors’ framework was evaluated in a preclinical preliminary study aimed to identify computer extracted features on in vivo MRI associated with chronic pulmonary inflammation. Methods: The authors’ image analytics framework first involves reconstructing the histologic volume in 3D from individual histology slices. Second, the authors map the disease ground truth onto in vivo MRI via coregistration with 3D histology using the ex vivo lung MRI as a conduit. Finally, computerized feature analysis of the disease extent is performed to identify candidate in vivo imaging signatures of disease presence and extent. Results: The authors evaluated the framework by assessing the quality of the 3D histology reconstruction and the histology—MRI fusion, in the context of an initial use case involving characterization of chronic

  19. Framework for 3D histologic reconstruction and fusion with in vivo MRI: Preliminary results of characterizing pulmonary inflammation in a mouse model

    International Nuclear Information System (INIS)

    Rusu, Mirabela; Wang, Haibo; Madabhushi, Anant; Golden, Thea; Gow, Andrew

    2015-01-01

    Purpose: Pulmonary inflammation is associated with a variety of diseases. Assessing pulmonary inflammation on in vivo imaging may facilitate the early detection and treatment of lung diseases. Although routinely used in thoracic imaging, computed tomography has thus far not been compellingly shown to characterize inflammation in vivo. Alternatively, magnetic resonance imaging (MRI) is a nonionizing radiation technique to better visualize and characterize pulmonary tissue. Prior to routine adoption of MRI for early characterization of inflammation in humans, a rigorous and quantitative characterization of the utility of MRI to identify inflammation is required. Such characterization may be achieved by considering ex vivo histology as the ground truth, since it enables the definitive spatial assessment of inflammation. In this study, the authors introduce a novel framework to integrate 2D histology, ex vivo and in vivo imaging to enable the mapping of the extent of disease from ex vivo histology onto in vivo imaging, with the goal of facilitating computerized feature analysis and interrogation of disease appearance on in vivo imaging. The authors’ framework was evaluated in a preclinical preliminary study aimed to identify computer extracted features on in vivo MRI associated with chronic pulmonary inflammation. Methods: The authors’ image analytics framework first involves reconstructing the histologic volume in 3D from individual histology slices. Second, the authors map the disease ground truth onto in vivo MRI via coregistration with 3D histology using the ex vivo lung MRI as a conduit. Finally, computerized feature analysis of the disease extent is performed to identify candidate in vivo imaging signatures of disease presence and extent. Results: The authors evaluated the framework by assessing the quality of the 3D histology reconstruction and the histology—MRI fusion, in the context of an initial use case involving characterization of chronic

  20. TM4SF1 Promotes Gemcitabine Resistance of Pancreatic Cancer In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Jia Cao

    Full Text Available TM4SF1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC and affects the development of this cancer. Also, multidrug resistance (MDR is generally associated with tumor chemoresistance in pancreatic cancer. However, the correlation between TM4SF1 and MDR remains unknown. This research aims to investigate the effect of TM4SF1 on gemcitabine resistance in PDAC and explore the possible molecular mechanism between TM4SF1 and MDR.The expression of TM4SF1 was evaluated in pancreatic cancer cell lines and human pancreatic duct epithelial (HPDE cell lines by quantitative RT-PCR. TM4SF1 siRNA transfection was carried out using Hiperfect transfection reagent to knock down TM4SF1. The transcripts were analyzed by quantitative RT-PCR, RT-PCR and western blotting for further study. The cell proliferation and apoptosis were obtained to investigate the sensitivity to gemcitabine of pancreatic cancer cells after silencing TM4SF1 in vitro. We demonstrated that cell signaling of TM4SF1 mediated chemoresistance in cancer cells by assessing the expression of multidrug resistance (MDR genes using quantitative RT-PCR. In vivo, we used orthotopic pancreatic tumor models to investigate the effect of proliferation after silencing TM4SF1 by a lentivirus-mediated shRNA in MIA PaCa-2 cell lines.The mRNA expression of TM4SF1 was higher in seven pancreatic cancer cell lines than in HPDE cell lines. In three gemcitabine-sensitive cell lines (L3.6pl, BxPC-3, SU86.86, the expression of TM4SF1 was lower than that in four gemcitabine-resistant cell lines (MIA PaCa-2, PANC-1, Hs766T, AsPC-1. We evaluated that TM4SF1 was a putative target for gemcitabine resistance in pancreatic cancer cells. Using AsPC-1, MIA PaCa-2 and PANC-1, we investigated that TM4SF1 silencing affected cell proliferation and increased the percentages of cell apoptosis mediated by treatment with gemcitabine compared with cells which were treated with negative control. This resistance was associated

  1. Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial.

    Science.gov (United States)

    Mousa, Aya; Naderpoor, Negar; de Courten, Maximilian Pj; Teede, Helena; Kellow, Nicole; Walker, Karen; Scragg, Robert; de Courten, Barbora

    2017-06-01

    Background: Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of vitamin D, variability in participants' vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion. Objective: To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-standard methods. We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo. Design: Sixty-five overweight or obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous-glucose-tolerance tests (IVGTTs)]. Results: Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m 2 ): 30.9 ± 4.4]. 25(OH)D increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; P = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg -1 · min -1 , respectively; P = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; P = 0.9). Results remained nonsignificant after adjustment for age, sex

  2. Noncontact 3-D Speckle Contrast Diffuse Correlation Tomography of Tissue Blood Flow Distribution.

    Science.gov (United States)

    Huang, Chong; Irwin, Daniel; Zhao, Mingjun; Shang, Yu; Agochukwu, Nneamaka; Wong, Lesley; Yu, Guoqiang

    2017-10-01

    Recent advancements in near-infrared diffuse correlation techniques and instrumentation have opened the path for versatile deep tissue microvasculature blood flow imaging systems. Despite this progress there remains a need for a completely noncontact, noninvasive device with high translatability from small/testing (animal) to large/target (human) subjects with trivial application on both. Accordingly, we discuss our newly developed setup which meets this demand, termed noncontact speckle contrast diffuse correlation tomography (nc_scDCT). The nc_scDCT provides fast, continuous, portable, noninvasive, and inexpensive acquisition of 3-D tomographic deep (up to 10 mm) tissue blood flow distributions with straightforward design and customization. The features presented include a finite-element-method implementation for incorporating complex tissue boundaries, fully noncontact hardware for avoiding tissue compression and interactions, rapid data collection with a diffuse speckle contrast method, reflectance-based design promoting experimental translation, extensibility to related techniques, and robust adjustable source and detector patterns and density for high resolution measurement with flexible regions of interest enabling unique application-specific setups. Validation is shown in the detection and characterization of both high and low contrasts in flow relative to the background using tissue phantoms with a pump-connected tube (high) and phantom spheres (low). Furthermore, in vivo validation of extracting spatiotemporal 3-D blood flow distributions and hyperemic response during forearm cuff occlusion is demonstrated. Finally, the success of instrument feasibility in clinical use is examined through the intraoperative imaging of mastectomy skin flap.

  3. Programmable level-1 trigger with 3D-Flow processor array

    International Nuclear Information System (INIS)

    Crosetto, D.

    1994-01-01

    The 3D-Flow parallel processing system is a new concept in processor architecture, system architecture, and assembly architecture. Compared to the electronics used in present systems, this approach reduces the cost and complexity of the hardware and allows easy assembly, disassembly, incremental upgrading, and maintenance of different interconnection topologies. The 3D-Flow parallel-processing system benefits high energy physics (HEP) by allowing: (1) common less costly hardware to be used in different experiments. (2) new uses of existing installations. (3) tuning of trigger based on the first analyzed data, and (4) selection of desired events directly from raw data. The goal of this parallel-processing architecture is to acquire multiple data in parallel (up to 100 million frames per second) and to process them at high speed, accomplishing digital filtering on the input data, pattern recognition (particle identification), data moving, and data formatting. The main features of the system are its programmability, scalability, high-speed communication, and low cost. The compactness of the 3D-Flow parallel-processing system in concert with the processor architecture allows processor interconnections to be mapped into the geometry of sensors (detectors in HEP) without large interconnection signal delay, enabling real-time pattern recognition. The overall 3D-Flow project has passed a major design review at Fermilab (Reviewers included experts in computers, triggering, system assembly, and electronics)

  4. Sensitivity of in vivo X-ray fluorescence determination of skeletal lead stores

    International Nuclear Information System (INIS)

    Sokas, R.K.; Besarab, A.; McDiarmid, M.A.; Shapiro, I.M.; Bloch, P.

    1990-01-01

    Eighteen patients with known past occupational lead exposure underwent parenteral diagnostic chelation with ethylenediaminetetraacetic acid and x-ray fluorescent determination of in vivo skeletal lead stores at the distal styloid process of the ulna and at the temporal base bone using a cobalt 57 source and measuring lead Ka x-rays. X-ray fluorescent lead measurements in both locations correlated with results of diagnostic chelation. Using a post-chelation urinary excretion of greater than 600 micrograms lead/24 h as the definition of high-lead stores, sensitivity of x-ray fluorescence at the wrist and temple was 56% and 39%, respectively

  5. Sensitive determination of thiols in wine samples by a stable isotope-coded derivatization reagent d0/d4-acridone-10-ethyl-N-maleimide coupled with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis.

    Science.gov (United States)

    Lv, Zhengxian; You, Jinmao; Lu, Shuaimin; Sun, Weidi; Ji, Zhongyin; Sun, Zhiwei; Song, Cuihua; Chen, Guang; Li, Guoliang; Hu, Na; Zhou, Wu; Suo, Yourui

    2017-03-31

    As the key aroma compounds, varietal thiols are the crucial odorants responsible for the flavor of wines. Quantitative analysis of thiols can provide crucial information for the aroma profiles of different wine styles. In this study, a rapid and sensitive method for the simultaneous determination of six thiols in wine using d 0 /d 4 -acridone-10-ethyl-N-maleimide (d 0 /d 4 -AENM) as stable isotope-coded derivatization reagent (SICD) by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) has been developed. Quantification of thiols was performed by using d 4 -AENM labeled thiols as the internal standards (IS), followed by stable isotope dilution HPLC-ESI-MS/MS analysis. The AENM derivatization combined with multiple reactions monitoring (MRM) not only allowed trace analysis of thiols due to the extremely high sensitivity, but also efficiently corrected the matrix effects during HPLC-MS/MS and the fluctuation in MS/MS signal intensity due to instrument. The obtained internal standard calibration curves for six thiols were linear over the range of 25-10,000pmol/L (R 2 ≥0.9961). Detection limits (LODs) for most of analytes were below 6.3pmol/L. The proposed method was successfully applied for the simultaneous determination of six kinds of thiols in wine samples with precisions ≤3.5% and recoveries ≥78.1%. In conclusion, the developed method is expected to be a promising tool for detection of trace thiols in wine and also in other complex matrix. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Dopamine D2 receptor radiotracers [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, Patrick N. [Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada)], E-mail: patrick.mccormick@camhpet.ca; Kapur, Shitij [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); PET Center, Center for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Seeman, Philip [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); PET Center, Center for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada)

    2008-01-15

    Introduction: In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [{sup 11}C](+)-PHNO ([{sup 11}C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-o l), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [{sup 3}H]raclopride, which binds to both affinity states. Methods: We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for {sup 11}C and {sup 3}H. The specific binding ratio {l_brace}SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum){r_brace} was used as the outcome measure. Results: In response to D2 antagonists, partial agonist or full agonist, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs responded indistinguishably in terms of both ED{sub 50} and Hill slope (e.g., (-)-NPA ED{sub 50} values are 0.027 and 0.023 mg/kg for [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride, respectively). In response to AMPH challenge, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs were inhibited to the same degree. Conclusions: We have shown that the SBRs of [{sup 11}C](+)-PHNO- and [{sup 3}H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo

  7. The role of semaphorin 4D as a potential biomarker for antiangiogenic therapy in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ding X

    2016-03-01

    Full Text Available Xiaojie Ding,1,2,* Lijuan Qiu,1,2,* Lijuan Zhang,3 Juemin Xi,1,2 Duo Li,1,2 Xinwei Huang,1,2 Yujiao Zhao,1,2 Xiaodang Wang,1,2 Qiangming Sun1,2 1Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 2Molecular Epidemiology Joint Laboratory, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, 3Department of Pathology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Provincial Tumor Hospital, Kunming, People’s Republic of China*These authors contributed equally to this workBackground: Semaphorin 4D (Sema4D belongs to the class IV semaphorins, and accumulating evidence has indicated that its elevated level may be one strategy by which tumors evade current antiangiogenic therapies. The biological roles of Sema4D in colorectal cancer (CRC, however, remain largely undefined. This study was designed to investigate the effects of Sema4D on tumor angiogenesis and growth in CRC, especially in different vascular endothelial growth factor (VEGF backgrounds.Methods: The expression of Sema4D in human CRC was evaluated by immunohistochemical analysis of tumors and their matching normal control tissues. The expression level of Sema4D and VEGF was investigated in different CRC cell lines. To evaluate the contributions of Sema4D to tumor-induced angiogenesis, two CRC cell lines with opposite VEGF backgrounds were infected with lentiviruses expressing Sema4D or Sema4D short hairpin RNA, followed by in vitro migration and in vivo tumor angiogenic assays.Results: Immunohistochemical analysis of human CRC revealed high levels of Sema4D in a cell surface pattern. In all, 84.85% of CRC samples analyzed exhibited moderate to strong Sema4D expression. The positive ratios of Sema4D staining for well, moderately, and poorly differentiated cancers were 71.43%, 96.67%, and 77.27%, respectively. Sema4D is highly expressed in five different CRC cell lines, while VEGF

  8. Real-time 2-D Phased Array Vector Flow Imaging

    DEFF Research Database (Denmark)

    Holbek, Simon; Hansen, Kristoffer Lindskov; Fogh, Nikolaj

    2018-01-01

    Echocardiography examination of the blood flow is currently either restricted to 1-D techniques in real-time or experimental off-line 2-D methods. This paper presents an implementation of transverse oscillation for real-time 2-D vector flow imaging (VFI) on a commercial BK Ultrasound scanner....... A large field-of-view (FOV) sequence for studying flow dynamics at 11 frames per second (fps) and a sequence for studying peak systolic velocities (PSV) with a narrow FOV at 36 fps were validated. The VFI sequences were validated in a flow-rig with continuous laminar parabolic flow and in a pulsating flow...

  9. Application of Thinned-Skull Cranial Window to Mouse Cerebral Blood Flow Imaging Using Optical Microangiography

    Science.gov (United States)

    Wang, Ruikang K.

    2014-01-01

    In vivo imaging of mouse brain vasculature typically requires applying skull window opening techniques: open-skull cranial window or thinned-skull cranial window. We report non-invasive 3D in vivo cerebral blood flow imaging of C57/BL mouse by the use of ultra-high sensitive optical microangiography (UHS-OMAG) and Doppler optical microangiography (DOMAG) techniques to evaluate two cranial window types based on their procedures and ability to visualize surface pial vessel dynamics. Application of the thinned-skull technique is found to be effective in achieving high quality images for pial vessels for short-term imaging, and has advantages over the open-skull technique in available imaging area, surgical efficiency, and cerebral environment preservation. In summary, thinned-skull cranial window serves as a promising tool in studying hemodynamics in pial microvasculature using OMAG or other OCT blood flow imaging modalities. PMID:25426632

  10. Nonsense mutants in the bacteriophage T4D v gene

    Energy Technology Data Exchange (ETDEWEB)

    Minderhout, L van; Grimbergen, J; Groot, B de [Rijksuniversiteit Leiden (Netherlands). Lab. voor Stralengenetica en Chemische Mutagenese; Cohen (J.A.) Instituut voor Radiopathologie en Stralenbescherming, Leiden (Netherlands))

    1975-09-01

    Ten UV-sensitive mutants of T4D with the v phenotype were isolated. Of these ten mutants, two are amber and two opal. In UV curves and in photoreactivation and multiplicity reactivation experiments the nonsense mutants show the v phenotype in su/sup -/ hosts and almost the T4/sup +/ phenotype in su/sup +/ hosts. The mutations are located between rl and e and are alleles of v/sub 1/. In crosses with irradiated and non-irradiated phages the recombinant frequency is not reduced by uvs5. Amber uvs5 propagated in CR63 su/sup +/ is with B su/sup -/ just as sensitive to UV as uvs5 propagated in B su/sup -/, which permits the conclusion that the capsid of T4 phage particles does not contain the v gene product.

  11. In vivo 3D PIXE-micron-CT imaging of Drosophila melanogaster using a contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Shigeo; Hamada, Naoki; Ishii, Keizo; Nozawa, Yuichiro; Ohkura, Satoru; Terakawa, Atsuki; Hatori, Yoshinobu; Fujiki, Kota; Fujiwara, Mitsuhiro; Toyama, Sho

    2015-04-01

    In this study, we developed a three-dimensional (3D) computed tomography (CT) in vivo imaging system for imaging small insects with micrometer resolution. The 3D CT imaging system, referred to as 3D PIXE-micron-CT (PIXEμCT), uses characteristic X-rays produced by ion microbeam bombardment of a metal target. PIXEμCT was used to observe the body organs and internal structure of a living Drosophila melanogaster. Although the organs of the thorax were clearly imaged, the digestive organs in the abdominal cavity could not be clearly discerned initially, with the exception of the rectum and the Malpighian tubule. To enhance the abdominal images, a barium sulfate powder radiocontrast agent was added. For the first time, 3D images of the ventriculus of a living D. melanogaster were obtained. Our results showed that PIXEμCT can provide in vivo 3D-CT images that reflect correctly the structure of individual living organs, which is expected to be very useful in biological research.

  12. In vitro and in vivo evaluation of a new large animal spirometry device using mainstream CO2 flow sensors.

    Science.gov (United States)

    Ambrisko, T D; Lammer, V; Schramel, J P; Moens, Y P S

    2014-07-01

    A spirometry device equipped with mainstream CO2 flow sensor is not available for large animal anaesthesia. To measure the resistance of a new large animal spirometry device and assess its agreement with reference methods for volume measurements. In vitro experiment and crossover study using anaesthetised horses. A flow partitioning device (FPD) equipped with 4 human CO2 flow sensors was tested. Pressure differences were measured across the whole FPD and across each sensor separately using air flows (range: 90-720 l/min). One sensor was connected to a spirometry monitor for in vitro volume (3, 5 and 7 l) measurements. These measurements were compared with a reference method. Five anaesthetised horses were used for tidal volume (VT) measurements using the FPD and a horse-lite sensor (reference method). Bland-Altman analysis, ANOVA and linear regression analysis were used for data analysis. Pressure differences across each sensor were similar suggesting equal flow partitioning. The resistance of the device increased with flow (range: 0.3-1.5 cmH2 O s/l) and was higher than that of the horse-lite. The limits of agreement for volume measurements were within -1 and 2% in vitro and -12 and 0% in vivo. Nine of 147 VT measurements in horses were outside of the ± 10% limits of acceptance but most of these erroneous measurements occurred with VTs lower than 4 l. The determined correction factor for volume measurements was 3.97 ± 0.03. The limits of agreement for volume measurements by the new device were within ± 10% using clinically relevant range of volumes. The new spirometry device can be recommended for measurement of VT in adult Warmblood horses. © 2013 EVJ Ltd.

  13. Reverse Flow Routing in a Bayesian Framework Using a GPU-accelerated 2D Shallow Water Model

    Science.gov (United States)

    D'Oria, M.; Ferrari, A.; Mignosa, P.; Tanda, M. G.; Vacondio, R.

    2017-12-01

    Knowledge of discharge hydrographs in specific sites of natural rivers is important for water resource management, flood frequency analysis, design of structures, etc. Many times, the flood hydrograph is needed in a river section upstream of a monitoring station; here the flood wave differs from the upstream one because of the effects of resistance, channel storage, lateral inflow, etc. Reverse flow routing is a method that allows obtaining hydrographs in upstream ungauged stations using information available at downstream monitored sites. In this study, we propose an inverse procedure, based on a Bayesian Geostatistical Approach, to solve the reverse problem. The upstream flow values over time (parameters) are considered as random variables and a-priori information about the parameters and observations (downstream discharge or water level values) are combined together in a Bayesian framework. The methodology needs a forward model of the considered open channel that includes the upstream ungauged station and the downstream gauged one and it is able to describe, with sufficient accuracy, the hydraulic routing processes. In many real cases, especially when large floodable areas are involved, a 1D hydraulic model is not able to capture the complex river hydrodynamic and a 2D model must be used. The inverse procedure requires a high number of flow model run to linearize the forward problem through multiple evaluations of a Jacobian matrix (sensitivity of each observation to each parameter) using a finite difference approach. For this reason, the computational efficiency of the forward model is a crucial element to reduce the overall computational costs. Therefore, in this work we used, in combination with the inverse procedure, a GPU-parallel numerical model for the solution of the 2D Shallow Water equations (implemented in CUDA/C++ code) that allows achieving ratio of physical to computational time of about 500-1000 (depending on the test case features). In addition

  14. [68Ga]pentixafor for CXCR4 imaging in a PC-3 prostate cancer xenograft model - comparison with [18F]FDG PET/CT, MRI and ex vivo receptor expression.

    Science.gov (United States)

    Schwarzenböck, Sarah M; Stenzel, Jan; Otto, Thomas; Helldorff, Heike V; Bergner, Carina; Kurth, Jens; Polei, Stefan; Lindner, Tobias; Rauer, Romina; Hohn, Alexander; Hakenberg, Oliver W; Wester, Hans J; Vollmar, Brigitte; Krause, Bernd J

    2017-11-10

    The aim was to characterize the properties of [ 68 Ga]Pentixafor as tracer for prostate cancer imaging in a PC-3 prostate cancer xenograft mouse model and to investigate its correlation with [ 18 F]FDG PET/CT, magnetic resonance imaging (MRI) and ex vivo analyses. Static [ 68 Ga]Pentixafor and [ 18 F]FDG PET as well as morphological/ diffusion weighted MRI and 1 H MR spectroscopy was performed. Imaging data were correlated with ex vivo biodistribution and CXCR4 expression in PC-3 tumors (immunohistochemistry (IHC), mRNA analysis). Flow cytometry was performed for evaluation of localization of CXCR4 receptors ( in vitro PC-3 cell experiments). Tumor uptake of [ 68 Ga]Pentixafor was significantly lower compared to [ 18 F]FDG. Ex vivo CXCR4 mRNA expression of tumors was shown by PCR. Only faint tumor CXCR4 expression was shown by IHC (immuno reactive score of 3). Accordingly, flow cytometry of PC-3 cells revealed only a faint signal, cell membrane permeabilisation showed a slight signal increase. There was no significant correlation of [ 68 Ga]Pentixafor tumor uptake and ex vivo receptor expression. Spectroscopy showed typical spectra of prostate cancer. PC-3 tumor uptake of [ 68 Ga]Pentixafor was existent but lower compared to [ 18 F]FDG. No significant correlation of ex vivo tumor CXCR4 receptor expression and [ 68 Ga]Pentixafor tumor uptake was shown. CXCR4 receptor expression on the surface of PC-3 cells was existent but rather low possibly explaining the limited [ 68 Ga]Pentixafor tumor uptake; receptor localization in the interior of PC-3 cells is presumable as shown by cell membrane permeabilisation. Further studies are necessary to define the role of [ 68 Ga]Pentixafor in prostate cancer imaging.

  15. Predictions of bubbly flows in vertical pipes using two-fluid models in CFDS-FLOW3D code

    International Nuclear Information System (INIS)

    Banas, A.O.; Carver, M.B.; Unrau, D.

    1995-01-01

    This paper reports the results of a preliminary study exploring the performance of two sets of two-fluid closure relationships applied to the simulation of turbulent air-water bubbly upflows through vertical pipes. Predictions obtained with the default CFDS-FLOW3D model for dispersed flows were compared with the predictions of a new model (based on the work of Lee), and with the experimental data of Liu. The new model, implemented in the CFDS-FLOW3D code, included additional source terms in the open-quotes standardclose quotes κ-ε transport equations for the liquid phase, as well as modified model coefficients and wall functions. All simulations were carried out in a 2-D axisymmetric format, collapsing the general multifluid framework of CFDS-FLOW3D to the two-fluid (air-water) case. The newly implemented model consistently improved predictions of radial-velocity profiles of both phases, but failed to accurately reproduce the experimental phase-distribution data. This shortcoming was traced to the neglect of anisotropic effects in the modelling of liquid-phase turbulence. In this sense, the present investigation should be considered as the first step toward the ultimate goal of developing a theoretically sound and universal CFD-type two-fluid model for bubbly flows in channels

  16. Predictions of bubbly flows in vertical pipes using two-fluid models in CFDS-FLOW3D code

    Energy Technology Data Exchange (ETDEWEB)

    Banas, A.O.; Carver, M.B. [Chalk River Laboratories (Canada); Unrau, D. [Univ. of Toronto (Canada)

    1995-09-01

    This paper reports the results of a preliminary study exploring the performance of two sets of two-fluid closure relationships applied to the simulation of turbulent air-water bubbly upflows through vertical pipes. Predictions obtained with the default CFDS-FLOW3D model for dispersed flows were compared with the predictions of a new model (based on the work of Lee), and with the experimental data of Liu. The new model, implemented in the CFDS-FLOW3D code, included additional source terms in the {open_quotes}standard{close_quotes} {kappa}-{epsilon} transport equations for the liquid phase, as well as modified model coefficients and wall functions. All simulations were carried out in a 2-D axisymmetric format, collapsing the general multifluid framework of CFDS-FLOW3D to the two-fluid (air-water) case. The newly implemented model consistently improved predictions of radial-velocity profiles of both phases, but failed to accurately reproduce the experimental phase-distribution data. This shortcoming was traced to the neglect of anisotropic effects in the modelling of liquid-phase turbulence. In this sense, the present investigation should be considered as the first step toward the ultimate goal of developing a theoretically sound and universal CFD-type two-fluid model for bubbly flows in channels.

  17. Regularity of the 3D Navier-Stokes equations with viewpoint of 2D flow

    Science.gov (United States)

    Bae, Hyeong-Ohk

    2018-04-01

    The regularity of 2D Navier-Stokes flow is well known. In this article we study the relationship of 3D and 2D flow, and the regularity of the 3D Naiver-Stokes equations with viewpoint of 2D equations. We consider the problem in the Cartesian and in the cylindrical coordinates.

  18. Shear layer flame stabilization sensitivities in a swirling flow

    Directory of Open Access Journals (Sweden)

    Christopher Foley

    2017-03-01

    Full Text Available A variety of different flame configurations and heat release distributions exist in high swirl, annular flows, due to the existence of inner and outer shear layers as well a vortex breakdown bubble. Each of these different configurations, in turn, has different thermoacoustic sensitivities and influences on combustor emissions, nozzle durability, and liner heating. This paper presents findings on the sensitivities of the outer shear layer- stabilized flames to a range of parameters, including equivalence ratio, bulkhead temperature, flow velocity, and preheat temperature. There is significant hysteresis for flame attachment/detachment from the outer shear layer and this hysteresis is also described. Results are also correlated with extinction stretch rate calculations based on detailed kinetic simulations. In addition, we show that the bulkhead temperature near the flame attachment point has significant impact on outer shear layer detachment. This indicates that understanding the heat transfer between the edge flame stabilized in the shear layer and the nozzle hardware is needed in order to predict shear layer flame stabilization limits. Moreover, it shows that simulations cannot simply assume adiabatic boundary conditions if they are to capture these transitions. We also show that the reference temperature for correlating these transitions is quite different for attachment and local blow off. Finally, these results highlight the deficiencies in current understanding of the influence of fluid mechanic parameters (e.g. velocity, swirl number on shear layer flame attachment. For example, they show that the seemingly simple matter of scaling flame transition points with changes in flow velocities is not understood.

  19. In vivo characterization of the novel CD44v6-targeting Fab fragment AbD15179 for molecular imaging of squamous cell carcinoma: a dual-isotope study

    Science.gov (United States)

    2014-01-01

    Background Patients with squamous cell carcinoma in the head and neck region (HNSCC) offer a diagnostic challenge due to difficulties to detect small tumours and metastases. Imaging methods available are not sufficient, and radio-immunodiagnostics could increase specificity and sensitivity of diagnostics. The objective of this study was to evaluate, for the first time, the in vivo properties of the radiolabelled CD44v6-targeting fragment AbD15179 and to assess its utility as a targeting agent for radio-immunodiagnostics of CD44v6-expressing tumours. Methods The fully human CD44v6-targeting Fab fragment AbD15179 was labelled with 111In or 125I, as models for radionuclides suitable for imaging with SPECT or PET. Species specificity, antigen specificity and internalization properties were first assessed in vitro. In vivo specificity and biodistribution were then evaluated in tumour-bearing mice using a dual-tumour and dual-isotope setup. Results Both species-specific and antigen-specific binding of the conjugates were demonstrated in vitro, with no detectable internalization. The in vivo studies demonstrated specific tumour binding and favourable tumour targeting properties for both conjugates, albeit with higher tumour uptake, slower tumour dissociation, higher tumour-to-blood ratio and higher CD44v6 sensitivity for the 111In-labelled fragment. In contrast, the 125I-Fab demonstrated more favourable tumour-to-organ ratios for liver, spleen and kidneys. Conclusions We conclude that AbD15179 efficiently targets CD44v6-expressing squamous cell carcinoma xenografts, and particularly, the 111In-Fab displayed high and specific tumour uptake. CD44v6 emerges as a suitable target for radio-immunodiagnostics, and a fully human antibody fragment such as AbD15179 can enable further clinical imaging studies. PMID:24598405

  20. Utilization of the ex vivo LLNA: BrdU-ELISA to distinguish the sensitizers from irritants in respect of 3 end points-lymphocyte proliferation, ear swelling, and cytokine profiles.

    Science.gov (United States)

    Arancioglu, Seren; Ulker, Ozge Cemiloglu; Karakaya, Asuman

    2015-01-01

    Dermal exposure to chemicals may result in allergic or irritant contact dermatitis. In this study, we performed ex vivo local lymph node assay: bromodeoxyuridine-enzyme-linked immunosorbent assay (LLNA: BrdU-ELISA) to compare the differences between irritation and sensitization potency of some chemicals in terms of the 3 end points: lymphocyte proliferation, cytokine profiles (interleukin 2 [IL-2], interferon-γ (IFN-γ), IL-4, IL-5, IL-1, and tumor necrosis factor α [TNF-α]), and ear swelling. Different concentrations of the following well-known sensitizers and irritant chemicals were applied to mice: dinitrochlorobenzene, eugenol, isoeugenol, sodium lauryl sulfate (SLS), and croton oil. According to the lymph node results; the auricular lymph node weights and lymph node cell counts increased after application of both sensitizers and irritants in high concentrations. On the other hand, according to lymph node cell proliferation results, there was a 3-fold increase in proliferation of lymph node cells (stimulation index) for sensitizer chemicals and SLS in the applied concentrations; however, there was not a 3-fold increase for croton oil and negative control. The SLS gave a false-positive response. Cytokine analysis demonstrated that 4 cytokines including IL-2, IFN-γ, IL-4, and IL-5 were released in lymph node cell cultures, with a clear dose trend for sensitizers whereas only TNF-α was released in response to irritants. Taken together, our results suggest that the ex vivo LLNA: BrdU-ELISA method can be useful for discriminating irritants and allergens. © The Author(s) 2015.

  1. In vitro and ex vivo effect of hyaluronic acid on erythrocyte flow properties

    Directory of Open Access Journals (Sweden)

    Palatnik S

    2010-02-01

    Full Text Available Abstract Background Hyaluronic acid (HA is present in many tissues; its presence in serum may be related to certain inflammatory conditions, tissue damage, sepsis, liver malfunction and some malignancies. In the present work, our goal was to investigate the significance of hyaluronic acid effect on erythrocyte flow properties. Therefore we performed in vitro experiments incubating red blood cells (RBCs with several HA concentrations. Afterwards, in order to corroborate the pathophysiological significance of the results obtained, we replicated the in vitro experiment with ex vivo RBCs from diagnosed rheumatoid arthritis (RA patients, a serum HA-increasing pathology. Methods Erythrocyte deformability (by filtration through nucleopore membranes and erythrocyte aggregability (EA were tested on blood from healthy donors additioned with purified HA. EA was measured by transmitted light and analyzed with a mathematical model yielding two parameters, the aggregation rate and the size of the aggregates. Conformational changes of cytoskeleton proteins were estimated by electron paramagnetic resonance spectroscopy (EPR. Results In vitro, erythrocytes treated with HA showed increased rigidity index (RI and reduced aggregability, situation strongly related to the rigidization of the membrane cytoskeleton triggered by HA, as shown by EPR results. Also, a significant correlation (r: 0.77, p Conclusions Our results lead us to postulate the hypothesis that HA interacts with the erythrocyte surface leading to modifications in erythrocyte rheological and flow properties, both ex vivo and in vitro.

  2. Chemical-exchange-sensitive MRI of amide, amine and NOE at 9.4 T versus 15.2 T.

    Science.gov (United States)

    Chung, Julius Juhyun; Choi, Wonmin; Jin, Tao; Lee, Jung Hee; Kim, Seong-Gi

    2017-09-01

    Chemical exchange (CE)-sensitive MRI benefits greatly from stronger magnetic fields; however, field effects on CE-sensitive imaging have not yet been studied well in vivo. We have compared CE-sensitive Z-spectra and maps obtained at the fields of 9.4 T and 15.2 T in phantoms and rats with off-resonance chemical-exchange-sensitive spin lock (CESL), which is similar to conventional chemical exchange saturation transfer. At higher fields, the background peak at water resonance has less spread and the exchange rate relative to chemical shift decreases, thus CESL intensity is dependent on B 0 . For the in vivo amide and nuclear Overhauser enhancement (NOE) composite resonances of rat brains, intensities were similar for both magnetic fields, but effective amide proton transfer and NOE values obtained with three-point quantification or a curve fitting method were larger at 15.2 T due to the reduced spread of attenuation at the direct water resonance. When using intermediate exchange-sensitive irradiation parameters, the amine proton signal was 65% higher at 15.2 T than at 9.4 T due to a reduced ratio of exchange rate to chemical shift. In summary, increasing magnetic field provides enhancements to CE-sensitive signals in the intermediate exchange regime and reduces contamination from background signals in the slow exchange regime. Consequently, ultrahigh magnetic field is advantageous for CE-sensitive MRI, especially for amine and hydroxyl protons. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Preoperative 4D CT Localization of Nonlocalizing Parathyroid Adenomas by Ultrasound and SPECT-CT.

    Science.gov (United States)

    Hinson, Andrew M; Lee, David R; Hobbs, Bradley A; Fitzgerald, Ryan T; Bodenner, Donald L; Stack, Brendan C

    2015-11-01

    To evaluate 4-dimensional (4D) computed tomography (CT) for the localization of parathyroid adenomas previously considered nonlocalizing on ultrasound and single-photon emission CT with CT scanning (SPECT-CT). To measure radiation exposure associated with 4D-CT and compared it with SPECT-CT. Case series with chart review. University tertiary hospital. Nineteen adults with primary hyperparathyroidism who underwent preoperative 4D CT from November 2013 through July 2014 after nonlocalizing preoperative ultrasound and technetium-99m SPECT-CT scans. Sensitivity, specificity, predictive values, and accuracy of 4D CT were evaluated. Nineteen patients (16 women and 3 men) were included with a mean age of 66 years (range, 39-80 years). Mean preoperative parathyroid hormone level was 108.5 pg/mL (range, 59.3-220.9 pg/mL), and mean weight of the excised gland was 350 mg (range, 83-797 mg). 4D CT sensitivity and specificity for localization to the patient's correct side of the neck were 84.2% and 81.8%, respectively; accuracy was 82.9%. The sensitivity for localizing adenomas to the correct quadrant was 76.5% and 91.5%, respectively; accuracy was 88.2%. 4D CT radiation exposure was significantly less than the radiation associated with SPECT-CT (13.8 vs 18.4 mSv, P = 0.04). 4D CT localizes parathyroid adenomas with relatively high sensitivity and specificity and allows for the localization of some adenomas not observed on other sestamibi-based scans. 4D CT was also associated with less radiation exposure when compared with SPECT-CT based on our study protocol. 4D CT may be considered as first- or second-line imaging for localizing parathyroid adenomas in the setting of primary hyperparathyroidism. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  4. High resolution anatomical and quantitative MRI of the entire human occipital lobe ex vivo at 9.4T.

    Science.gov (United States)

    Sengupta, S; Fritz, F J; Harms, R L; Hildebrand, S; Tse, D H Y; Poser, B A; Goebel, R; Roebroeck, A

    2018-03-01

    Several magnetic resonance imaging (MRI) contrasts are sensitive to myelin content in gray matter in vivo which has ignited ambitions of MRI-based in vivo cortical histology. Ultra-high field (UHF) MRI, at fields of 7T and beyond, is crucial to provide the resolution and contrast needed to sample contrasts over the depth of the cortex and get closer to layer resolved imaging. Ex vivo MRI of human post mortem samples is an important stepping stone to investigate MRI contrast in the cortex, validate it against histology techniques applied in situ to the same tissue, and investigate the resolutions needed to translate ex vivo findings to in vivo UHF MRI. Here, we investigate key technology to extend such UHF studies to large human brain samples while maintaining high resolution, which allows investigation of the layered architecture of several cortical areas over their entire 3D extent and their complete borders where architecture changes. A 16 channel cylindrical phased array radiofrequency (RF) receive coil was constructed to image a large post mortem occipital lobe sample (~80×80×80mm 3 ) in a wide-bore 9.4T human scanner with the aim of achieving high-resolution anatomical and quantitative MR images. Compared with a human head coil at 9.4T, the maximum Signal-to-Noise ratio (SNR) was increased by a factor of about five in the peripheral cortex. Although the transmit profile with a circularly polarized transmit mode at 9.4T is relatively inhomogeneous over the large sample, this challenge was successfully resolved with parallel transmit using the kT-points method. Using this setup, we achieved 60μm anatomical images for the entire occipital lobe showing increased spatial definition of cortical details compared to lower resolutions. In addition, we were able to achieve sufficient control over SNR, B 0 and B 1 homogeneity and multi-contrast sampling to perform quantitative T 2 * mapping over the same volume at 200μm. Markov Chain Monte Carlo sampling provided

  5. On the relation between 2D:4D and sex-dimorphic personality traits.

    Science.gov (United States)

    Hampson, Elizabeth; Ellis, Connie L; Tenk, Christine M

    2008-02-01

    Several personality traits, including aggressiveness and sensation seeking, have been hypothesized to be influenced by prenatal androgen exposure, though evidence for this proposition is limited. We investigated whether individual differences in aggressiveness, sensation seeking, and several prosocial personality traits can be predicted from differences in the 2D:4D digit ratio, a putative marker of prenatal androgen activity. A total of 164 undergraduates (87 men, 77 women) completed self-report measures of physical and verbal aggression, as well as a standardized measure of sensation seeking, and five scales to assess empathy, nurturance, expressivity/femininity, instrumentality/masculinity, and assertiveness. Two sex-dimorphic tests of spatial ability also were included. Men had a lower 2D:4D ratio than women, confirming the typical sex difference in digit proportions. Significant sex differences were observed on 10 of the 11 personality scales purported to show sex differences and on both tests of spatial ability. The 2D:4D ratio was a significant predictor of scores on three of the four aggression subscales, total aggression, thrill and adventure seeking, and total sensation-seeking, in the sample as a whole and in women. In men, correlations with 2D:4D were significant only for total sensation-seeking and verbal aggression. In both sexes, lower 2D:4D ratios were associated with increased aggressiveness and sensation seeking. For the spatial tests, there was no evidence of any association with 2D:4D in either men or women. The 2D:4D digit ratio may be a valid, though weak, predictor of selective sex-dependent traits that are sensitive to testosterone.

  6. Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

    Science.gov (United States)

    Wu, Bo; Lu, Shu-Ting; Zhang, Liu-Jie; Zhuo, Ren-Xi; Xu, Hai-Bo; Huang, Shi-Wen

    2017-01-01

    Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid–polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), soybean lecithin, and poly(D,L-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment. PMID:28331310

  7. Codelivery of doxorubicin and triptolide with reduction-sensitive lipid-polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment.

    Science.gov (United States)

    Wu, Bo; Lu, Shu-Ting; Zhang, Liu-Jie; Zhuo, Ren-Xi; Xu, Hai-Bo; Huang, Shi-Wen

    2017-01-01

    Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid-polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)- S - S -hexadecyl (mPEG- S - S -C 16 ), soybean lecithin, and poly(D,L-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment.

  8. Deterministic sensitivity analysis of two-phase flow systems: forward and adjoint methods. Final report

    International Nuclear Information System (INIS)

    Cacuci, D.G.

    1984-07-01

    This report presents a self-contained mathematical formalism for deterministic sensitivity analysis of two-phase flow systems, a detailed application to sensitivity analysis of the homogeneous equilibrium model of two-phase flow, and a representative application to sensitivity analysis of a model (simulating pump-trip-type accidents in BWRs) where a transition between single phase and two phase occurs. The rigor and generality of this sensitivity analysis formalism stem from the use of Gateaux (G-) differentials. This report highlights the major aspects of deterministic (forward and adjoint) sensitivity analysis, including derivation of the forward sensitivity equations, derivation of sensitivity expressions in terms of adjoint functions, explicit construction of the adjoint system satisfied by these adjoint functions, determination of the characteristics of this adjoint system, and demonstration that these characteristics are the same as those of the original quasilinear two-phase flow equations. This proves that whenever the original two-phase flow problem is solvable, the adjoint system is also solvable and, in principle, the same numerical methods can be used to solve both the original and adjoint equations

  9. Least Squares Shadowing Sensitivity Analysis of Chaotic Flow Around a Two-Dimensional Airfoil

    Science.gov (United States)

    Blonigan, Patrick J.; Wang, Qiqi; Nielsen, Eric J.; Diskin, Boris

    2016-01-01

    Gradient-based sensitivity analysis has proven to be an enabling technology for many applications, including design of aerospace vehicles. However, conventional sensitivity analysis methods break down when applied to long-time averages of chaotic systems. This breakdown is a serious limitation because many aerospace applications involve physical phenomena that exhibit chaotic dynamics, most notably high-resolution large-eddy and direct numerical simulations of turbulent aerodynamic flows. A recently proposed methodology, Least Squares Shadowing (LSS), avoids this breakdown and advances the state of the art in sensitivity analysis for chaotic flows. The first application of LSS to a chaotic flow simulated with a large-scale computational fluid dynamics solver is presented. The LSS sensitivity computed for this chaotic flow is verified and shown to be accurate, but the computational cost of the current LSS implementation is high.

  10. Acute Cocaine Induces Fast Activation of D1 Receptor and Progressive Deactivation of D2 Receptor Strial Neurons: In Vivo Optical Microprobe [Ca2+]i Imaging

    International Nuclear Information System (INIS)

    Du, C.; Luo, Z.; Volkow, N.D.; Heintz, N.; Pan, Y.; Du, C.

    2011-01-01

    Cocaine induces fast dopamine increases in brain striatal regions, which are recognized to underlie its rewarding effects. Both dopamine D1 and D2 receptors are involved in cocaine's reward but the dynamic downstream consequences of cocaine effects in striatum are not fully understood. Here we used transgenic mice expressing EGFP under the control of either the D1 receptor (D1R) or the D2 receptor (D2R) gene and microprobe optical imaging to assess the dynamic changes in intracellular calcium ([Ca 2+ ] i ) responses (used as marker of neuronal activation) to acute cocaine in vivo separately for D1R- versus D2R-expressing neurons in striatum. Acute cocaine (8 mg/kg, i.p.) rapidly increased [Ca 2+ ] i in D1R-expressing neurons (10.6 ± 3.2%) in striatum within 8.3 ± 2.3 min after cocaine administration after which the increases plateaued; these fast [Ca 2+ ] i increases were blocked by pretreatment with a D1R antagonist (SCH23390). In contrast, cocaine induced progressive decreases in [Ca 2+ ] i in D2R-expressing neurons (10.4 ± 5.8%) continuously throughout the 30 min that followed cocaine administration; these slower [Ca 2+ ] i decreases were blocked by pretreatment with a D2R antagonist (raclopride). Since activation of striatal D1R-expressing neurons (direct-pathway) enhances cocaine reward, whereas activation of D2R expressing neurons suppresses it (indirect-pathway) (Lobo et al., 2010), this suggests that cocaine's rewarding effects entail both its fast stimulation ofD1R (resulting in abrupt activation of direct-pathway neurons) and a slower stimulation of D2R (resulting in longer-lasting deactivation of indirect-pathway neurons). We also provide direct in vivo evidence of D2R and D1R interactions in the striatal responses to acute cocaine administration.

  11. The cryoablation of lung tissue using liquid nitrogen in gel and in the ex vivo pig lung.

    Science.gov (United States)

    Nomori, Hiroaki; Yamazaki, Ikuo; Kondo, Toshiya; Kanno, Masaya

    2017-02-01

    To examine the efficiency of cryoablation using liquid nitrogen in lung tissue, we measured the size and temperature distribution of the frozen area (iceball) in gel and in the ex vivo pig lungs. Cryoprobes with diameters of 2.4 and 3.4 mm (2.4D and 3.4D, respectively) were used. Three temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.5 and 1.5 cm from the cryoprobe. The ex vivo pig lungs were perfused with 37 °C saline and inflated using ventilator to simulate in vivo lung conditions. In gel, the 2.4D and 3.4D probes made iceballs of 3.9 ± 0.1 and 4.8 ± 0.3 cm in diameter, respectively, and the temperature at 1.5 cm from those probes reached -32 ± 8 and -53 ± 5 °C, respectively. In the pig lung, the 2.4D and 3.4D probes made iceballs of 5.2 ± 0.1 and 5.5 ± 0.4 cm in diameter, respectively, and the temperature at 1.5 cm from these probes reached -49 ± 5 and -58 ± 3 °C, respectively. Liquid nitrogen cryoablation using both 2.4D and 3.4D probes made iceballs that were of sufficient size, and effective temperatures were reached in both gel and the ex vivo pig lung.

  12. Increased flow sensitivity from gradient recalled echoes and short TRs

    International Nuclear Information System (INIS)

    Hearshen, D.O.; Froelich, J.W.; Wehrli, F.W.; Haggar, A.M.; Shimakawa, A.

    1986-01-01

    Time-of-flight effects from flow have been characterized in spin-echo images. ''Paradoxical'' enhancement and flow void are observed. Similar enhancement is seen on GRASS images. With no flow void and gradients existing throughout the volume, spins experiencing radio-frequency pulses will give rise to signals even for fast flow, providing a greater velocity sensitivity. GRASS images were obtained from a volunteer with a blood pressure cuff placed over the right thigh. With the cuff inflated, flow in the popliteal vein results in signal saturation. Increasing TR increases intensity in the popliteal vein relative to other vessels. This suggests a clinical role for the technique in assessment of slow flow

  13. 4R-Cembranoid Improves Outcomes after 6-Hydroxydopamine Challenge in Both In vitro and In vivo Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Jing Hu

    2017-05-01

    Full Text Available (1S, 2E, 4R, 6R,-7E, 11E-2, 7, 11-cembratriene-4, 6-diol (4R is one of the cembranoids found in tobacco leaves. Previous studies have found that 4R protected acute rat hippocampal slices against neurotoxicity induced by N-methyl-D-aspartate (NMDA and against the toxic organophosphorus compounds paraoxon and diisopropylfluorophosphate (DFP. Furthermore, in vivo, 4R reduced the infarct size in a rodent ischemic stroke model and neurodegeneration caused by DFP. The present study expanded our previous study by focusing on the effect of 4R in Parkinson's disease (PD and elucidating its underlying mechanisms using 6-hydroxydopamine (6-OHDA-induced injury models. We found that 4R exhibited significant neuroprotective activity in the rat unilateral 6-OHDA-induced PD model in vivo. The therapeutic effect was evident both at morphological and behavioral levels. 4R (6 and 12 mg/kg treatments significantly improved outcomes of 6-OHDA-induced PD in vivo as indicated by reducing forelimb asymmetry scores and corner test scores 4 weeks after injection of 6-OHDA (p < 0.05. The therapeutic effect of 4R was also reflected by decreased depletion of tyrosine hydroxylase (TH in the striatum and substantia nigra (SN on the side injected with 6-OHDA. TH expression was 70.3 and 62.8% of the contralateral side in striatum and SN, respectively, after 6 mg/kg 4R treatment; furthermore, it was 80.1 and 79.3% after treatment with 12 mg/kg of 4R. In the control group, it was 51.9 and 23.6% of the contralateral striatum and SN (p < 0.05. Moreover, 4R also protected differentiated neuro-2a cells from 6-OHDA-induced cytotoxicity in vitro. The activation of p-AKT and HAX-1, and inhibition of caspase-3 and endothelial inflammation, were involved in 4R-mediated protection against 6-OHDA-induced injury. In conclusion, the present study indicates that 4R shows a therapeutic effect in the rat 6-OHDA-induced PD model in vivo and in 6-OHDA-challenged neuro-2a cells in vitro.

  14. Comparison of the Ex Vivo Expansion of UCB-Derived CD34+ in 3D DBM/MBA Scaffolds with USSC as a Feeder Layer.

    Science.gov (United States)

    Sadat Hashemi, Zahra; Forouzandeh Moghadam, Mahdi; Soleimani, Masoud

    2013-10-01

    Ex vivo expansion of hematopoitic stem cells is an alternative way to increase umbilical cord blood (UCB)-CD34+ cells for bone marrow transplantation. For this purpose demineralized bone matrix (DBM) and mineralized bone allograft (MBA) as two scaffolds based on bone matrix and stem cell niche, were simultaneously used to enhance the effect of human mesenchymal progenitor cells (MPCs) - unrestricted somatic stem cells (USSCs) - as a feeder layer. USSCs were isolated and characterized by morphological and immunological analysis then seeded on both scaffolds as a feeder layer. UCB-CD34(+) were isolated by MACS method and were co-culture expanded by USSC in 3D and 2D environments. After 3 weeks expansion, cells were counted and were assessed by karyotype, flow cytometry, clonogenic activity, and long-term culture-initiating cells (LTC-IC). Co-culture expansion in DBM and MBA was 29.22-fold and 27.77-fold, no significant differences in colony and LTC-IC were obtained. Maximum number of colonies belonged to the day 14 with the 73% CFU-GM (Colony Forming Unit- Granulocyte/Macrophage) in contrast to the day 0 which was BFU-E/CFU-E (Burst/Colony Forming Unit-Erythroid). Flow cytometry indicated that the percentage of CD34+ marker was decreased in USSC co-culture and the highest percentage was observed in simple 2D culture. Because of acid extraction in the DBM production process, mineral materials were removed and the protein background that was more flexible was presented. Therefore these results suggest that USSC-DBM can be a suitable ex vivo mimicry niche by intensifying of surface/volume ratio and supporting the stem cell differentiation and expansion.

  15. 3-D numerical modelling of flow around a groin

    DEFF Research Database (Denmark)

    Miller, R.; Roulund, A.; Sumer, B. Mutlu

    2003-01-01

    A 3-D flow code, EllipSys3D, has been implemented to simulate the 3-D flow around a groin in steady current. The k  turbulence model has been used for closure. Two kinds of groins are considered: (1) A vertical-wall groin, and (2) A groin with a side slope. Steady-flow simulations were conducted...

  16. Modulatory action of 2-deoxy-D-glucose on mitomycin C-and 4-nitroquinoline-1-oxide-induced genotoxicity in Swiss albino mice In vivo

    Directory of Open Access Journals (Sweden)

    Mohapatra Rashmi

    2009-09-01

    Full Text Available Background: 2-Deoxy-D-glucose (2-DG, a structural analog of glucose is an effective inhibitor of glucose metabolism and ATP production. It selectively accumulates in cancer cells and interferes with glycolysis leading to cell death. 2-DG is shown to differentially enhance the radiation-induced damage in cancer cells both under euoxic and hypoxic conditions. A combination of 2-DG and ionizing radiation selectively destroys tumors while protecting the normal tissue. 2-DG is being advocated as an adjuvant in the radiotherapy and chemotherapy of cancer. Objective: The present investigation focuses on the modulatory effect of 2-DG on mitomycin C- (MMC and 4-nitroquinoline-1-oxide (4-NQO-induced cytogenetic damage in bone marrow cells of Swiss albino mice in vivo. Materials and Methods: Experimental animals were pretreated with 2-DG (500 mg/kg, i.p. for five consecutive days followed by MMC (2 mg/kg, i.p or 4-NQO (15 mg/kg, i.p., 24h prior to sacrifice. Control animals were given either the mixture of olive oil and acetone (3:1 or distilled water. Bone marrow cells were processed for the micronucleus assay and metaphase analysis for estimating cytogenetic damage. Results: 2-DG significantly (P < 0.001 reduced the frequency of aberrant cells induced by MMC (~90% and 4-NQO (~74%. Incidence of micronucleated polychromatic erythrocytes (MnPCEs induced by the mutagens were reduced up to 68%. Conclusion: 2-DG effectively reduces the MMC-and 4-NQO-induced genotoxicity.

  17. Transfection mediated by pH-sensitive sugar-based gemini surfactants; potential for in vivo gene therapy applications

    NARCIS (Netherlands)

    Wasungu, Luc; Scarzello, Marco; van Dam, Gooitzen; Molema, Grietje; Wagenaar, Anno; Engberts, Jan B. F. N.; Hoekstra, Dick

    In this study, the in vitro and in vivo transfection capacity of novel pH-sensitive sugar-based gemini surfactants was investigated. In an aqueous environment at physiological pH, these compounds form bilayer vesicles, but they undergo a lamellar-to-micellar phase transition in the endosomal pH

  18. A novel dendritic cell-based direct ex vivo assay for detection and enumeration of circulating antigen-specific human T cells.

    Science.gov (United States)

    Carrio, Roberto; Zhang, Ge; Drake, Donald R; Schanen, Brian C

    2018-05-07

    Although a variety of assays have been used to examine T cell responses in vitro, standardized ex vivo detection of antigen-specific CD4 + T cells from human circulatory PBMCs remains constrained by low-dimensional characterization outputs and the need for polyclonal, mitogen-induced expansion methods to generate detectable response signals. To overcome these limitations, we developed a novel methodology utilizing antigen-pulsed autologous human dendritic target cells in a rapid and sensitive assay to accurately enumerate antigen-specific CD4 + T cell precursor frequency by multiparametric flow cytometry. With this approach, we demonstrate the ability to reproducibly quantitate poly-functional T cell responses following both primary and recall antigenic stimulation. Furthermore, this approach enables more comprehensive phenotypic profiling of circulating antigen-specific CD4 + T cells, providing valuable insights into the pre-existing polarization of antigen-specific T cells in humans. Combined, this approach permits sensitive and detailed ex vivo detection of antigen-specific CD4 + T cells delivering an important tool for advancing vaccine, immune-oncology and other therapeutic studies.

  19. CD4(+) NKG2D(+) T cells induce NKG2D down-regulation in natural killer cells in CD86-RAE-1ε transgenic mice.

    Science.gov (United States)

    Lin, Zhijie; Wang, Changrong; Xia, Haizui; Liu, Weiguang; Xiao, Weiming; Qian, Li; Jia, Xiaoqin; Ding, Yanbing; Ji, Mingchun; Gong, Weijuan

    2014-03-01

    The binding of NKG2D to its ligands strengthens the cross-talk between natural killer (NK) cells and dendritic cells, particularly at early stages, before the initiation of the adaptive immune response. We found that retinoic acid early transcript-1ε (RAE-1ε), one of the ligands of NKG2D, was persistently expressed on antigen-presenting cells in a transgenic mouse model (pCD86-RAE-1ε). By contrast, NKG2D expression on NK cells, NKG2D-dependent cytotoxicity and tumour rejection, and dextran sodium sulphate-induced colitis were all down-regulated in this mouse model. The down-regulation of NKG2D on NK cells was reversed by stimulation with poly (I:C). The ectopic expression of RAE-1ε on dendritic cells maintained NKG2D expression levels and stimulated the activity of NK cells ex vivo, but the higher frequency of CD4(+) NKG2D(+) T cells in transgenic mice led to the down-regulation of NKG2D on NK cells in vivo. Hence, high levels of RAE-1ε expression on antigen-presenting cells would be expected to induce the down-regulation of NK cell activation by a regulatory T-cell subset. © 2013 John Wiley & Sons Ltd.

  20. A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing

    Directory of Open Access Journals (Sweden)

    Mohammed-Baker Habhab

    2016-11-01

    Full Text Available Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications.

  1. A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing.

    Science.gov (United States)

    Habhab, Mohammed-Baker; Ismail, Tania; Lo, Joe Fujiou

    2016-11-23

    Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP) based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications.

  2. Integrated Cantilever-Based Flow Sensors with Tunable Sensitivity for In-Line Monitoring of Flow Fluctuations in Microfluidic Systems

    Directory of Open Access Journals (Sweden)

    Nadine Noeth

    2013-12-01

    Full Text Available For devices such as bio-/chemical sensors in microfluidic systems, flow fluctuations result in noise in the sensor output. Here, we demonstrate in-line monitoring of flow fluctuations with a cantilever-like sensor integrated in a microfluidic channel. The cantilevers are fabricated in different materials (SU-8 and SiN and with different thicknesses. The integration of arrays of holes with different hole size and number of holes allows the modification of device sensitivity, theoretical detection limit and measurement range. For an average flow in the microliter range, the cantilever deflection is directly proportional to the flow rate fluctuations in the microfluidic channel. The SiN cantilevers show a detection limit below 1 nL/min and the thinnest SU-8 cantilevers a detection limit below 5 nL/min. Finally, the sensor is applied for in-line monitoring of flow fluctuations generated by external pumps connected to the microfluidic system.

  3. Potencies of vitamin D analogs, 1α-hydroxyvitamin D3 , 1α-hydroxyvitamin D2 and 25-hydroxyvitamin D3 , in lowering cholesterol in hypercholesterolemic mice in vivo.

    Science.gov (United States)

    Quach, Holly P; Dzekic, Tamara; Bukuroshi, Paola; Pang, K Sandy

    2018-04-01

    Vitamin D 3 and the synthetic vitamin D analogs, 1α-hydroxyvitamin D 3 [1α(OH)D 3 ], 1α-hydroxyvitamin D 2 [1α(OH)D 2 ] and 25-hydroxyvitamin D 3 [25(OH)D 3 ] were appraised for their vitamin D receptor (VDR) associated-potencies as cholesterol lowering agents in mice in vivo. These precursors are activated in vivo: 1α(OH)D 3 and 1α(OH)D 2 are transformed by liver CYP2R1 and CYP27A1 to active VDR ligands, 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] and 1α,25-dihydroxyvitamin D 2 [1,25(OH) 2 D 2 ] , respectively. 1α(OH)D 2 may also be activated by CYP24A1 to 1α,24-dihydroxyvitamin D 2 [1,24(OH) 2 D 2 ], another active VDR ligand. 25(OH)D 3 , the metabolite formed via CYP2R1 and or CYP27A1 in liver from vitamin D 3 , is activated by CYP27B1 in the kidney to 1,25(OH) 2 D 3 . In C57BL/6 mice fed the high fat/high cholesterol Western diet for 3 weeks, vitamin D analogs were administered every other day intraperitoneally during the last week of the diet. The rank order for cholesterol lowering, achieved via mouse liver small heterodimer partner (Shp) inhibition and increased cholesterol 7α-hydroxylase (Cyp7a1) expression, was: 1.75 nmol/kg 1α(OH)D 3  > 1248 nmol/kg 25(OH)D 3 (dose ratio of 0.0014) > > 1625 nmol/kg vitamin D 3 . Except for 1.21 nmol/kg 1α(OH)D 2 that failed to lower liver and plasma cholesterol contents, a significant negative correlation was observed between the liver concentration of 1,25(OH) 2 D 3 formed from the precursors and liver cholesterol levels. The composite results show that vitamin D analogs 1α(OH)D 3 and 25(OH)D 3 exhibit cholesterol lowering properties upon activation to 1,25(OH) 2 D 3 : 1α(OH)D 3 is rapidly activated by liver enzymes and 25(OH)D 3 is slowly activated by renal Cyp27b1 in mouse. Copyright © 2018 John Wiley & Sons, Ltd.

  4. Non-Newtonian fluid flow in 2D fracture networks

    Science.gov (United States)

    Zou, L.; Håkansson, U.; Cvetkovic, V.

    2017-12-01

    Modeling of non-Newtonian fluid (e.g., drilling fluids and cement grouts) flow in fractured rocks is of interest in many geophysical and industrial practices, such as drilling operations, enhanced oil recovery and rock grouting. In fractured rock masses, the flow paths are dominated by fractures, which are often represented as discrete fracture networks (DFN). In the literature, many studies have been devoted to Newtonian fluid (e.g., groundwater) flow in fractured rock using the DFN concept, but few works are dedicated to non-Newtonian fluids.In this study, a generalized flow equation for common non-Newtonian fluids (such as Bingham, power-law and Herschel-Bulkley) in a single fracture is obtained from the analytical solutions for non-Newtonian fluid discharge between smooth parallel plates. Using Monte Carlo sampling based on site characterization data for the distribution of geometrical features (e.g., density, length, aperture and orientations) in crystalline fractured rock, a two dimensional (2D) DFN model is constructed for generic flow simulations. Due to complex properties of non-Newtonian fluids, the relationship between fluid discharge and the pressure gradient is nonlinear. A Galerkin finite element method solver is developed to iteratively solve the obtained nonlinear governing equations for the 2D DFN model. Using DFN realizations, simulation results for different geometrical distributions of the fracture network and different non-Newtonian fluid properties are presented to illustrate the spatial discharge distributions. The impact of geometrical structures and the fluid properties on the non-Newtonian fluid flow in 2D DFN is examined statistically. The results generally show that modeling non-Newtonian fluid flow in fractured rock as a DFN is feasible, and that the discharge distribution may be significantly affected by the geometrical structures as well as by the fluid constitutive properties.

  5. In vivo sensitivity estimation and imaging acceleration with rotating RF coil arrays at 7 Tesla

    Science.gov (United States)

    Li, Mingyan; Jin, Jin; Zuo, Zhentao; Liu, Feng; Trakic, Adnan; Weber, Ewald; Zhuo, Yan; Xue, Rong; Crozier, Stuart

    2015-03-01

    Using a new rotating SENSitivity Encoding (rotating-SENSE) algorithm, we have successfully demonstrated that the rotating radiofrequency coil array (RRFCA) was capable of achieving a significant reduction in scan time and a uniform image reconstruction for a homogeneous phantom at 7 Tesla. However, at 7 Tesla the in vivo sensitivity profiles (B1-) become distinct at various angular positions. Therefore, sensitivity maps at other angular positions cannot be obtained by numerically rotating the acquired ones. In this work, a novel sensitivity estimation method for the RRFCA was developed and validated with human brain imaging. This method employed a library database and registration techniques to estimate coil sensitivity at an arbitrary angular position. The estimated sensitivity maps were then compared to the acquired sensitivity maps. The results indicate that the proposed method is capable of accurately estimating both magnitude and phase of sensitivity at an arbitrary angular position, which enables us to employ the rotating-SENSE algorithm to accelerate acquisition and reconstruct image. Compared to a stationary coil array with the same number of coil elements, the RRFCA was able to reconstruct images with better quality at a high reduction factor. It is hoped that the proposed rotation-dependent sensitivity estimation algorithm and the acceleration ability of the RRFCA will be particularly useful for ultra high field MRI.

  6. In vivo sensitivity estimation and imaging acceleration with rotating RF coil arrays at 7 Tesla.

    Science.gov (United States)

    Li, Mingyan; Jin, Jin; Zuo, Zhentao; Liu, Feng; Trakic, Adnan; Weber, Ewald; Zhuo, Yan; Xue, Rong; Crozier, Stuart

    2015-03-01

    Using a new rotating SENSitivity Encoding (rotating-SENSE) algorithm, we have successfully demonstrated that the rotating radiofrequency coil array (RRFCA) was capable of achieving a significant reduction in scan time and a uniform image reconstruction for a homogeneous phantom at 7 Tesla. However, at 7 Tesla the in vivo sensitivity profiles (B1(-)) become distinct at various angular positions. Therefore, sensitivity maps at other angular positions cannot be obtained by numerically rotating the acquired ones. In this work, a novel sensitivity estimation method for the RRFCA was developed and validated with human brain imaging. This method employed a library database and registration techniques to estimate coil sensitivity at an arbitrary angular position. The estimated sensitivity maps were then compared to the acquired sensitivity maps. The results indicate that the proposed method is capable of accurately estimating both magnitude and phase of sensitivity at an arbitrary angular position, which enables us to employ the rotating-SENSE algorithm to accelerate acquisition and reconstruct image. Compared to a stationary coil array with the same number of coil elements, the RRFCA was able to reconstruct images with better quality at a high reduction factor. It is hoped that the proposed rotation-dependent sensitivity estimation algorithm and the acceleration ability of the RRFCA will be particularly useful for ultra high field MRI. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. In vitro and in vivo delivery of siRNA via VIPER polymer system to lung cells.

    Science.gov (United States)

    Feldmann, Daniel P; Cheng, Yilong; Kandil, Rima; Xie, Yuran; Mohammadi, Mariam; Harz, Hartmann; Sharma, Akhil; Peeler, David J; Moszczynska, Anna; Leonhardt, Heinrich; Pun, Suzie H; Merkel, Olivia M

    2018-04-28

    The block copolymer VIPER (virus-inspired polymer for endosomal release) has been reported to be a promising novel delivery system of DNA plasmids both in vitro and in vivo. VIPER is comprised of a polycation segment for condensation of nucleic acids as well as a pH-sensitive segment that exposes the membrane lytic peptide melittin in acidic environments to facilitate endosomal escape. The objective of this study was to investigate VIPER/siRNA polyplex characteristics, and compare their in vitro and in vivo performance with commercially available transfection reagents and a control version of VIPER lacking melittin. VIPER/siRNA polyplexes were formulated and characterized at various charge ratios and shown to be efficiently internalized in cultured cells. Target mRNA knockdown was confirmed by both flow cytometry and qRT-PCR and the kinetics of knockdown was monitored by live cell spinning disk microscopy, revealing knockdown starting by 4 h post-delivery. Intratracheal instillation of VIPER particles formulated with sequence specific siRNA to the lung of mice resulted in a significantly more efficient knockdown of GAPDH compared to treatment with VIPER particles formulated with scrambled sequence siRNA. We also demonstrated using pH-sensitive labels that VIPER particles experience less acidic environments compared to control polyplexes. In summary, VIPER/siRNA polyplexes efficiently deliver siRNA in vivo resulting in robust gene silencing (>75% knockdown) within the lung. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Advanced flow MRI: emerging techniques and applications

    International Nuclear Information System (INIS)

    Markl, M.; Schnell, S.; Wu, C.; Bollache, E.; Jarvis, K.; Barker, A.J.; Robinson, J.D.; Rigsby, C.K.

    2016-01-01

    Magnetic resonance imaging (MRI) techniques provide non-invasive and non-ionising methods for the highly accurate anatomical depiction of the heart and vessels throughout the cardiac cycle. In addition, the intrinsic sensitivity of MRI to motion offers the unique ability to acquire spatially registered blood flow simultaneously with the morphological data, within a single measurement. In clinical routine, flow MRI is typically accomplished using methods that resolve two spatial dimensions in individual planes and encode the time-resolved velocity in one principal direction, typically oriented perpendicular to the two-dimensional (2D) section. This review describes recently developed advanced MRI flow techniques, which allow for more comprehensive evaluation of blood flow characteristics, such as real-time flow imaging, 2D multiple-venc phase contrast MRI, four-dimensional (4D) flow MRI, quantification of complex haemodynamic properties, and highly accelerated flow imaging. Emerging techniques and novel applications are explored. In addition, applications of these new techniques for the improved evaluation of cardiovascular (aorta, pulmonary arteries, congenital heart disease, atrial fibrillation, coronary arteries) as well as cerebrovascular disease (intra-cranial arteries and veins) are presented.

  9. Hypersonic Separated Flows About "Tick" Configurations With Sensitivity to Model Design

    Science.gov (United States)

    Moss, J. N.; O'Byrne, S.; Gai, S. L.

    2014-01-01

    This paper presents computational results obtained by applying the direct simulation Monte Carlo (DSMC) method for hypersonic nonequilibrium flow about "tick-shaped" model configurations. These test models produces a complex flow where the nonequilibrium and rarefied aspects of the flow are initially enhanced as the flow passes over an expansion surface, and then the flow encounters a compression surface that can induce flow separation. The resulting flow is such that meaningful numerical simulations must have the capability to account for a significant range of rarefaction effects; hence the application of the DSMC method in the current study as the flow spans several flow regimes, including transitional, slip, and continuum. The current focus is to examine the sensitivity of both the model surface response (heating, friction and pressure) and flowfield structure to assumptions regarding surface boundary conditions and more extensively the impact of model design as influenced by leading edge configuration as well as the geometrical features of the expansion and compression surfaces. Numerical results indicate a strong sensitivity to both the extent of the leading edge sharpness and the magnitude of the leading edge bevel angle. Also, the length of the expansion surface for a fixed compression surface has a significant impact on the extent of separated flow.

  10. Novel ex vivo culture method for human monocytes uses shear flow to prevent total loss of transendothelial diapedesis function.

    Science.gov (United States)

    Tsubota, Yoshiaki; Frey, Jeremy M; Raines, Elaine W

    2014-01-01

    Monocyte recruitment to inflammatory sites and their transendothelial migration into tissues are critical to homeostasis and pathogenesis of chronic inflammatory diseases. However, even short-term suspension culture of primary human monocytes leads to phenotypic changes. In this study, we characterize the functional effects of ex vivo monocyte culture on the steps involved in monocyte transendothelial migration. Our data demonstrate that monocyte diapedesis is impaired by as little as 4 h culture, and the locomotion step is subsequently compromised. After 16 h in culture, monocyte diapedesis is irreversibly reduced by ∼90%. However, maintenance of monocytes under conditions mimicking physiological flow (5-7.5 dyn/cm²) is sufficient to reduce diapedesis impairment significantly. Thus, through the application of shear during ex vivo culture of monocytes, our study establishes a novel protocol, allowing functional analyses of monocytes not currently possible under static culture conditions. These data further suggest that monocyte-based therapeutic applications may be measurably improved by alteration of ex vivo conditions before their use in patients.

  11. Laminar flow resistance in short microtubes

    Energy Technology Data Exchange (ETDEWEB)

    Phares, D.J. [Texas A and M University, College Station, TX (United States). Dept. of Mechanical Engineering; Smedley, G.T.; Zhou, J. [Glaukos Corp., Laguna Hills, CA (United States). Dept. of Research and Development

    2005-06-01

    We have measured the pressure drop for the flow of liquid through a series of short microtubes ranging from 80 to 150 {mu}m in diameter with aspect ratios between L/D = 2 and L/D = 5. These dimensions were selected to resemble lumens of implantable microstents that are under consideration for the treatment of glaucoma. For physiologically relevant pressure drops and flow rates, we have determined that a fully-developed laminar pipe flow may be assumed throughout the microtube when (L/D) > 0.20Re, where Re is the Reynolds number based on the diameter, D, and L is the length of the tube. We have examined flow rates between 0.1 and 10 {mu}L/s, corresponding to Reynolds numbers between 1 and 150. For smooth microtubes, no difference from macroscopic flow is observed for the tube sizes considered. However, flow resistance is found to be sensitive to the relative surface roughness of the tube walls. (author)

  12. In-vivo studies of new vector velocity and adaptive spectral estimators in medical ultrasound

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Lindskov

    In this PhD project new ultrasound techniques for blood flow measurements have been investigated in-vivo. The focus has mainly been on vector velocity techniques and four different approaches have been examined: Transverse Oscillation, Synthetic Transmit Aperture, Directional Beamforming and Plane...... in conventional Doppler ultrasound. That is angle dependency, reduced temporal resolution and low frame rate. Transverse Oscillation, Synthetic Transmit Aperture and Directional Beamforming can estimate the blood velocity angle independently. The three methods were validated in-vivo against magnetic resonance...... phase contrast angiography when measuring stroke volumes in simple vessel geometry on 11 volunteers. Using linear regression and Bland-Altman analyses good agreements were found, indicating that vector velocity methods can be used for quantitative blood flow measurements. Plane Wave Excitation can...

  13. Syntheses of two potential dopamine D{sub 4} receptor radioligands: {sup 18}F labelled chromeno[3,4-c]pyridin-5-ones

    Energy Technology Data Exchange (ETDEWEB)

    Gu-Cai Li; Duan-Zhi Yin; Ming-Wei Wang; Deng-Feng Cheng; Yong-Xian Wang [Research Center of Radiopharmaceuticals, Shanghai Inst. of Applied Physics, Chinese Academy of Sciences, Shanghai, SH (China)

    2006-07-01

    The dopamine D{sub 4} receptor is hypothesized to relate with the pathophysiology and pharmacotherapy of schizophrenia while its level in brain regions is much lower and to date no suitable tracer is available for the study of D{sub 4} receptor in vivo. Therefore, selective imaging agents for the D{sub 4} subtype are badly needed. Based on the structure-activity analysis of chromeno[3,4-c]pyridin-5-ones as dopamine D{sub 4} receptor ligands, two fluorine-18 labelled chromeno[3,4-c] pyridin-5-one derivatives, 3-(4-[{sup 18}F]fluorobenzyl)-8-hydroxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one and 3-(4-[{sup 18}F]fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one were synthesized through a two-step one-pot method. Their radiochemical yields were around 19.7% (decay-corrected) and radiochemical purities were higher than 95% with specific activities of about 120 GBq/{mu}mol. (orig.)

  14. Sensitivity Analysis of Unsaturated Flow and Contaminant Transport with Correlated Parameters

    Science.gov (United States)

    Relative contributions from uncertainties in input parameters to the predictive uncertainties in unsaturated flow and contaminant transport are investigated in this study. The objectives are to: (1) examine the effects of input parameter correlations on the sensitivity of unsaturated flow and conta...

  15. CD4+ NKG2D+ T cells induce NKG2D down-regulation in natural killer cells in CD86-RAE-1ε transgenic mice

    Science.gov (United States)

    Lin, Zhijie; Wang, Changrong; Xia, Haizui; Liu, Weiguang; Xiao, Weiming; Qian, Li; Jia, Xiaoqin; Ding, Yanbing; Ji, Mingchun; Gong, Weijuan

    2014-01-01

    The binding of NKG2D to its ligands strengthens the cross-talk between natural killer (NK) cells and dendritic cells, particularly at early stages, before the initiation of the adaptive immune response. We found that retinoic acid early transcript-1ε (RAE-1ε), one of the ligands of NKG2D, was persistently expressed on antigen-presenting cells in a transgenic mouse model (pCD86-RAE-1ε). By contrast, NKG2D expression on NK cells, NKG2D-dependent cytotoxicity and tumour rejection, and dextran sodium sulphate-induced colitis were all down-regulated in this mouse model. The down-regulation of NKG2D on NK cells was reversed by stimulation with poly (I:C). The ectopic expression of RAE-1ε on dendritic cells maintained NKG2D expression levels and stimulated the activity of NK cells ex vivo, but the higher frequency of CD4+ NKG2D+ T cells in transgenic mice led to the down-regulation of NKG2D on NK cells in vivo. Hence, high levels of RAE-1ε expression on antigen-presenting cells would be expected to induce the down-regulation of NK cell activation by a regulatory T-cell subset. PMID:24708417

  16. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression.

    Science.gov (United States)

    Scarlatti, G; Tresoldi, E; Björndal, A; Fredriksson, R; Colognesi, C; Deng, H K; Malnati, M S; Plebani, A; Siccardi, A G; Littman, D R; Fenyö, E M; Lusso, P

    1997-11-01

    Following the identification of the C-C chemokines RANTES, MIP-1alpha and MIP-1beta as major human immunodeficiency virus (HIV)-suppressive factors produced by CD8+ T cells, several chemokine receptors were found to serve as membrane co-receptors for primate immunodeficiency lentiretroviruses. The two most widely used co-receptors thus far recognized, CCR5 and CXCR4, are expressed by both activated T lymphocytes and mononuclear phagocytes. CCR5, a specific RANTES, MIP-1alpha and MIP-1 receptor, is used preferentially by non-MT2-tropic HIV-1 and HIV-2 strains and by simian immunodeficiency virus (SIV), whereas CXCR4, a receptor for the C-X-C chemokine SDF-1, is used by MT2-tropic HIV-1 and HIV-2, but not by SIV. Other receptors with a more restricted cellular distribution, such as CCR2b, CCR3 and STRL33, can also function as co-receptors for selected viral isolates. The third variable region (V3) of the gp120 envelope glycoprotein of HIV-1 has been fingered as a critical determinant of the co-receptor choice. Here, we document a consistent pattern of evolution of viral co-receptor usage and sensitivity to chemokine-mediated suppression in a longitudinal follow-up of children with progressive HIV-1 infection. Viral isolates obtained during the asymptomatic stages generally used only CCR5 as a co-receptor and were inhibited by RANTES, MIP-1alpha and MIP-1beta, but not by SDF-1. By contrast, the majority of the isolates derived after the progression of the disease were resistant to C-C chemokines, having acquired the ability to use CXCR4 and, in some cases, CCR3, while gradually losing CCR5 usage. Surprisingly, most of these isolates were also insensitive to SDF-1, even when used in combination with RANTES. An early acquisition of CXCR4 usage predicted a poor prognosis. In children who progressed to AIDS without a shift to CXCR4 usage, all the sequential isolates were CCR5-dependent but showed a reduced sensitivity to C-C chemokines. Discrete changes in the V3 domain

  17. In-vivo quantitative measurement

    International Nuclear Information System (INIS)

    Ito, Takashi

    1992-01-01

    So far by positron CT, the quantitative analyses of oxygen consumption rate, blood flow distribution, glucose metabolic rate and so on have been carried out. The largest merit of using the positron CT is the observation and verification of mankind have become easy. Recently, accompanying the rapid development of the mapping tracers for central nervous receptors, the observation of many central nervous receptors by the positron CT has become feasible, and must expectation has been placed on the elucidation of brain functions. The conditions required for in vitro processes cannot be realized in strict sense in vivo. The quantitative measurement of in vivo tracer method is carried out by measuring the accumulation and movement of a tracer after its administration. The movement model of the mapping tracer for central nervous receptors is discussed. The quantitative analysis using a steady movement model, the measurement of dopamine receptors by reference method, the measurement of D 2 receptors using 11C-Racloprode by direct method, and the possibility of measuring dynamics bio-reaction are reported. (K.I.)

  18. Escherichia coli and Neisseria gonorrhoeae UvrD helicase unwinds G4 DNA structures.

    Science.gov (United States)

    Shukla, Kaustubh; Thakur, Roshan Singh; Ganguli, Debayan; Rao, Desirazu Narasimha; Nagaraju, Ganesh

    2017-10-18

    G-quadruplex (G4) secondary structures have been implicated in various biological processes, including gene expression, DNA replication and telomere maintenance. However, unresolved G4 structures impede replication progression which can lead to the generation of DNA double-strand breaks and genome instability. Helicases have been shown to resolve G4 structures to facilitate faithful duplication of the genome. Escherichia coli UvrD (EcUvrD) helicase plays a crucial role in nucleotide excision repair, mismatch repair and in the regulation of homologous recombination. Here, we demonstrate a novel role of E. coli and Neisseria gonorrhoeae UvrD in resolving G4 tetraplexes. EcUvrD and N gonorrhoeae UvrD were proficient in unwinding previously characterized tetramolecular G4 structures. Notably, EcUvrD was equally efficient in resolving tetramolecular and bimolecular G4 DNA that were derived from the potential G4-forming sequences from the genome of E. coli Interestingly, in addition to resolving intermolecular G4 structures, EcUvrD was robust in unwinding intramolecular G4 structures. These data for the first time provide evidence for the role of UvrD in the resolution of G4 structures, which has implications for the in vivo role of UvrD helicase in G4 DNA resolution and genome maintenance. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  19. [Osteogenesis of human adipose-derived mesenchymal stem cells-biomaterial mixture in vivo after 3D bio-printing].

    Science.gov (United States)

    Song, Yang; Wang, Xiao-fei; Wang, Yu-guang; Sun, Yu-chun; Lv, Pei-jun

    2016-02-18

    To construct human adipose-derived mesenchymal stem cells (hASCs)-biomaterial mixture 3D bio-printing body and detect its osteogenesis in vivo, and to establish a guideline of osteogenesis in vivo by use of 3D bio-printing technology preliminarily. P4 hASCs were used as seed cells, whose osteogenic potential in vitro was tested by alkaline phosphatase (ALP) staining and alizarin red staining after 14 d of osteogenic induction. The cells were added into 20 g/L sodium alginate and 80 g/L gelatin mixture (cell density was 1 × 10(6)/mL), and the cell-sodium alginate-gelatin mixture was printed by Bioplotter 3D bio-printer (Envision company, Germany), in which the cells'survival rate was detected by live- dead cell double fluorescence staining. Next, the printing body was osteogenically induced for 1 week to gain the experimental group; and the sodium alginate-gelatin mixture without cells was also printed to gain the control group. Both the experimental group and the control group were implanted into the back of the nude mice. After 6 weeks of implantation, the samples were collected, HE staining, Masson staining, immunohistochemical staining and Inveon Micro CT test were preformed to analyze their osteogenic capability. The cells'survival rate was 89%± 2% after printing. Six weeks after implantation, the samples of the control group were mostly degraded, whose shape was irregular and gel-like; the samples of the experimental group kept their original size and their texture was tough. HE staining and Masson staining showed that the bone-like tissue and vessel in-growth could be observed in the experimental group 6 weeks after implantation, immunohistochemical staining showed that the result of osteocalcin was positive, and Micro CT results showed that samples of the experimental group had a higher density and the new bone volume was 18% ± 1%. hASCs -biomaterial mixture 3D bio-printing body has capability of ectopic bone formation in nude mice, and it is feasible to

  20. 2D Numerical Simulation and Sensitive Analysis of H-Darrieus Wind Turbine

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad E. Saryazdi

    2018-02-01

    Full Text Available Recently, a lot of attention has been devoted to the use of Darrieus wind turbines in urban areas. The aerodynamics of a Darrieus turbine are very complex due to dynamic stall and changing forces on the turbine triggered by changing horizontal angles. In this study, the aerodynamics of H-rotor vertical axis wind turbine (VAWT has been studied using computational fluid dynamics via two different turbulence models. Shear stress transport (SST k-ω turbulence model was used to simulate a 2D unsteady model of the H-Darrieus turbine. In order to complete this simulation, sensitivity analysis of the effective turbine parameters such as solidity factor, airfoil shape, wind velocity and shaft diameter were done. To simulate the flow through the turbine, a 2D simplified computational domain has been generated. Then fine mesh for each case consisting of different turbulence models and dimensions has been generated. Each mesh in this simulation dependent on effective parameters consisted of domain size, mesh quality, time step and total revolution. The sliding mesh method was applied to evaluate the unsteady interaction between the stationary and rotating components. Previous works just simulated turbine, while in our study sensitivity analysis of effective parameters was done. The simulation results closely match the experimental data, providing an efficient and reliable foundation to study wind turbine aerodynamics. This also demonstrates computing the best value of the effective parameter. The sensitivity analysis revealed best value of the effective parameter that could be used in the process of designing turbine. This work provides the first step in developing an accurate 3D aerodynamic modeling of Darrieus wind turbines. Article History: Received :August 19th 2017; Received: December 15th 2017; Accepted: Januari 14th 2018; Available online How to Cite This Article: Saryazdi, S. M. E. and Boroushaki, M. (2018 2D Numerical Simulation and Sensitive

  1. Vitamin D intake is associated with insulin sensitivity in African American, but not European American, women

    Directory of Open Access Journals (Sweden)

    Oster Robert A

    2010-04-01

    Full Text Available Abstract Background The prevalence of type 2 diabetes is higher among African Americans (AA vs European Americans (EA, independent of obesity and other known confounders. Although the reason for this disparity is not known, it is possible that relatively low levels of vitamin D among AA may contribute, as vitamin D has been positively associated with insulin sensitivity in some studies. The objective of this study was to test the hypothesis that dietary vitamin D would be associated with a robust measure of insulin sensitivity in AA and EA women. Methods Subjects were 115 African American (AA and 137 European American (EA healthy, premenopausal women. Dietary intake was determined with 4-day food records; the insulin sensitivity index (SI with a frequently-sampled intravenous glucose tolerance test and minimal modeling; the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR with fasting insulin and glucose; and body composition with dual-energy X-ray absorptiometry. Results Vitamin D intake was positively associated with SI (standardized β = 0.18, P = 0.05 and inversely associated with HOMA-IR (standardized β = -0.26, P = 0.007 in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/resistance in EA (standardized β = 0.03, P = 0.74 and standardized β = 0.02, P = 0.85 for SI and HOMA-IR, respectively. Similar to vitamin D, dietary calcium was associated with SI and HOMA-IR among AA but not EA. Conclusions This study provides novel findings that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA. Promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.

  2. In vivo flow cytometry for blood cell analysis using differential epi-detection of forward scattered light

    Science.gov (United States)

    Paudel, Hari P.; Jung, Yookyung; Raphael, Anthony; Alt, Clemens; Wu, Juwell; Runnels, Judith; Lin, Charles P.

    2018-02-01

    The present standard of blood cell analysis is an invasive procedure requiring the extraction of patient's blood, followed by ex-vivo analysis using a flow cytometer or a hemocytometer. We are developing a noninvasive optical technique that alleviates the need for blood extraction. For in-vivo blood analysis we need a high speed, high resolution and high contrast label-free imaging technique. In this proceeding report, we reported a label-free method based on differential epi-detection of forward scattered light, a method inspired by Jerome Mertz's oblique back-illumination microscopy (OBM) (Ford et al, Nat. Meth. 9(12) 2012). The differential epi-detection of forward light gives phase contrast image at diffraction-limited resolution. Unlike reflection confocal microscopy (RCM), which detects only sharp refractive index variation and suffers from speckle noise, this technique is suitable for detection of subtle variation of refractive index in biological tissue and it provides the shape and the size of cells. A custom built high speed electronic detection circuit board produces a real-time differential signal which yields image contrast based on phase gradient in the sample. We recorded blood flow in-vivo at 17.2k lines per second in line scan mode, or 30 frames per second (full frame), or 120 frame per second (quarter frame) in frame scan mode. The image contrast and speed of line scan data recording show the potential of the system for noninvasive blood cell analysis.

  3. In vivo measurement of hemodynamic information in stenosed rat blood vessels using X-ray PIV.

    Science.gov (United States)

    Park, Hanwook; Park, Jun Hong; Lee, Sang Joon

    2016-11-28

    Measurements of the hemodynamic information of blood flows, especially wall shear stress (WSS), in animal models with circulatory vascular diseases (CVDs) are important to understand the pathological mechanism of CVDs. In this study, X-ray particle image velocimetry (PIV) with high spatial resolution was applied to obtain velocity field information in stenosed blood vessels with high WSS. 3D clips fabricated with a 3D printer were applied to the abdominal aorta of a rat cadaver to induce artificial stenosis in the real blood vessel of an animal model. The velocity and WSS information of blood flows in the stenosed vessel were obtained and compared at various stenosis severities. In vivo measurement was also conducted by fastening a stenotic clip on a live rat model through surgical intervention to reduce the flow rate to match the limited temporal resolution of the present X-ray PIV system. Further improvement of the temporal resolution of the system might be able to provide in vivo measurements of hemodynamic information from animal disease models under physiological conditions. The present results would be helpful for understanding the relation between hemodynamic characteristics and the pathological mechanism in animal CVD models.

  4. In vivo metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in young whole pumpkin plant.

    Science.gov (United States)

    Sun, Jianteng; Liu, Jiyan; Yu, Miao; Wang, Chang; Sun, Yuzhen; Zhang, Aiqian; Wang, Thanh; Lei, Zhen; Jiang, Guibin

    2013-04-16

    Polybrominated diphenyl ethers (PBDEs) are widely distributed persistent organic pollutants. In vitro and in vivo research using various animal models have shown that PBDEs might be transformed to hydroxylated PBDEs, but there are few studies on in vivo metabolism of PBDEs by intact whole plants. In this research, pumpkin plants (Cucurbita maxima × C. moschata) were hydroponically exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). A debromination product (BDE-28) and four hydroxylated metabolites (5-OH-BDE-47, 6-OH-BDE-47, 4'-OH-BDE-49, and 4-OH-BDE-42) were detected in different parts of the whole plant. In addition, 4-methoxylated-2,2',3,4'-tetraBDE (4-MeO-BDE-42) was observed as a methoxylation product. Root exudates in solution were found to play an important role in metabolizing BDE-47 to a specific OH-PBDE: 4'-OH-BDE-49. BDE-28 was found to translocate more easily and accumulate in shoots than BDE-47 due to the lower hydrophobicity and molecular weight. The concentration ratio between metabolites and parent compound BDE-47 was lower for OH-PBDEs than that for both BDE-28 and 4-MeO-BDE-42. The metabolism pathway of BDE-47 in young whole plants was proposed in this study.

  5. MyD88 mediates in vivo effector functions of alveolar macrophages in acute lung inflammatory responses to carbon nanotube exposure

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Evan A. [Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States); Birch, M. Eileen [National Institute for Occupational Safety and Health, Cincinnati, OH 45213 (United States); Yadav, Jagjit S., E-mail: Jagjit.Yadav@uc.edu [Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States)

    2015-11-01

    Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT-induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wall CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation. We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca{sup 2} {sup +}/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT-induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. - Highlights: • Demonstrated in vivo effector role of alveolar macrophages (AMs) in CNT toxicity • MyD88, MAPKs, and Ca{sup 2} {sup +}/CamKII are required for AM inflammatory responses in vitro. • MyD88 signaling is required for in vivo effector

  6. Sensitizing effects of NOx on CH4 oxidation at high pressure

    DEFF Research Database (Denmark)

    Rasmussen, Christian Lund; Rasmussen, Anja Egede; Glarborg, Peter

    2008-01-01

    The CH4/O2/NOx system is investigated in a laboratory-scale high pressure laminar flow reactor with the purpose of elucidating the sensitizing effects of NOx on CH4 oxidation at high pressures and medium temperatures. Experiments are conducted at 100, 50, and 20 bar, 600-900 K, and stoichiometric...... ratios ranging from highly reducing to oxidizing conditions. The experimental results are interpreted in terms of a detailed kinetic model drawn from previous work of the authors, including an updated reaction subset for the direct interactions of NOx and C1-2 hydrocarbon species relevant...

  7. Significance of flow clustering and sequencing on sediment transport: 1D sediment transport modelling

    Science.gov (United States)

    Hassan, Kazi; Allen, Deonie; Haynes, Heather

    2016-04-01

    This paper considers 1D hydraulic model data on the effect of high flow clusters and sequencing on sediment transport. Using observed flow gauge data from the River Caldew, England, a novel stochastic modelling approach was developed in order to create alternative 50 year flow sequences. Whilst the observed probability density of gauge data was preserved in all sequences, the order in which those flows occurred was varied using the output from a Hidden Markov Model (HMM) with generalised Pareto distribution (GP). In total, one hundred 50 year synthetic flow series were generated and used as the inflow boundary conditions for individual flow series model runs using the 1D sediment transport model HEC-RAS. The model routed graded sediment through the case study river reach to define the long-term morphological changes. Comparison of individual simulations provided a detailed understanding of the sensitivity of channel capacity to flow sequence. Specifically, each 50 year synthetic flow sequence was analysed using a 3-month, 6-month or 12-month rolling window approach and classified for clusters in peak discharge. As a cluster is described as a temporal grouping of flow events above a specified threshold, the threshold condition used herein is considered as a morphologically active channel forming discharge event. Thus, clusters were identified for peak discharges in excess of 10%, 20%, 50%, 100% and 150% of the 1 year Return Period (RP) event. The window of above-peak flows also required cluster definition and was tested for timeframes 1, 2, 10 and 30 days. Subsequently, clusters could be described in terms of the number of events, maximum peak flow discharge, cumulative flow discharge and skewness (i.e. a description of the flow sequence). The model output for each cluster was analysed for the cumulative flow volume and cumulative sediment transport (mass). This was then compared to the total sediment transport of a single flow event of equivalent flow volume

  8. Locoregional deformation pattern of the patellar cartilage after different loading types. High-resolution 3D-MRI volumetry at 3 T in-vivo; Lokoregionaere Deformationsmuster im Patellarknorpel nach unterschiedlichen Belastungsparadigmen. Hochaufloesende 3-D-MR-Volumetrie bei 3 T in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Horng, Annie [University Hospital LMU Munich, Muenchen (Germany). Radiology; Raya, J. [New York Univ. Medical Center, NY (United States). Center of Biomedical Imaging; Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Grosshadern (Germany). Inst. fuer Klinische Radiologie; Zscharn, M. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Grosshadern (DE). Inst. fuer Klinische Radiologie] (and others)

    2011-05-15

    Purpose: To analyze locoregional deformation patterns indicative of contact areas in patellar cartilage after different loading exercises. Materials and Methods: 7 healthy patellae were examined in-vivo before and immediately after standardized loading (kneeling, squatting or knee bends) and after 90 minutes of rest using a sagittal 3D-T1-w FLASH WE sequence (22 msec/ 9.8msec/ 15 / 0.3 x 0.3 x 1.5 mm{sup 3}) at 3 T. After cartilage segmentation and 3D reconstruction, voxel-based and global precision errors (PR) were calculated. The former were used to determine significant differences in local cartilage thickness. Voxel-based 2{sigma}-thickness difference maps were calculated to visualize locoregional deformation patterns. Global changes in volume (Vol), mean thickness (mTh) and cartilage-bone-interface area (CBIA) were calculated. Results: The voxel-based PR depended on cartilage thickness (D) ranging from 0.12 - 0.35 mm. For D {>=} 1 mm the RF was < 0.31 mm (< voxel size), and for D {>=} 2 mm, the RF was < 0.22 mm. The global PR was 83 mm{sup 3} (2.4 %) for Vol, 0.06 mm (2.0 %) for mTh and 16 mm{sup 2} (1.4 %) for CBIA. The focal cartilage deformation equaled 14 % of the local thickness reduction. The deformation areas were oval and located in the peripheral medial (more vertically oriented, all exercises) and caudo-lateral (more horizontally oriented, kneeling and knee bends) aspects of the patella and were least pronounced in knee bends. Significant changes for Vol/mTh ranged from 2.1 to 3.7 %. Conclusion: This MRI-based study is the first to identify in-vivo voxel-based patellar cartilage deformation patterns indicating contact and loading zones after kneeling and squatting. These zones are anatomically and functionally plausible and may represent areas where stress induced degeneration and subsequent OA can originate. The data may facilitate understanding of individual knee loading properties and help to improve and validate biomechanical models for the knee

  9. Tachyon condensation in the D0/D4 system

    International Nuclear Information System (INIS)

    David, Justin R.

    2000-01-01

    The D0/D4 system with a Neveu-Schwarz B-field in the spatial directions of the D4-brane has a tachyon in the spectrum of the (0,4) strings. The tachyon signals the instability of the system to form a bound state of the D0-brane with the D4-brane. We use the Wess-Zumino-Witten like open superstring field theory formulated by Berkovits to study the tachyon potential for this system. The tachyon potential lies outside the universality class of the D-brane anti-D-brane system. It is a function of the B-field. We calculate the tachyon potential at the zeroth level approximation. The minimum of the tachyon potential in this case is expecte