Sample records for brain blood flow

  1. Glial and neuronal control of brain blood flow

    DEFF Research Database (Denmark)

    Attwell, David; Buchan, Alastair M; Charpak, Serge


    Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how these cells control blood flow is crucial for understanding how neural computation is powered, for interpreting functional imaging scans of brains, and for developing treatments for neurological disorders. It is now...... recognized that neurotransmitter-mediated signalling has a key role in regulating cerebral blood flow, that much of this control is mediated by astrocytes, that oxygen modulates blood flow regulation, and that blood flow may be controlled by capillaries as well as by arterioles. These conceptual shifts...... in our understanding of cerebral blood flow control have important implications for the development of new therapeutic approaches....

  2. Functional Imaging of Dolphin Brain Metabolism and Blood Flow

    National Research Council Canada - National Science Library

    Ridgway, Sam; Finneran, James; Carder, Don; Keogh, Mandy; Van Bonn, William; Smith, Cynthia; Scadeng, Miriam; Dubowitz, David; Mattrey, Robert; Hoh, Carl


    .... Diazepam has been shown to induce unihemispheric slow waves (USW), therefore we used functional imaging of dolphins with and without diazepam to observe hemispheric differences in brain metabolism and blood flow...

  3. Cerebral autoregulation control of blood flow in the brain

    CERN Document Server

    Payne, Stephen


    This Brief provides a comprehensive introduction to the control of blood flow in the brain. Beginning with the basic physiology of autoregulation, the author goes on to discuss measurement techniques, mathematical models, methods of analysis, and relevant clinical conditions, all within this single volume. The author draws together this disparate field, and lays the groundwork for future research directions. The text gives an up-to-date review of the state of the art in cerebral autoregulation, which is particularly relevant as cerebral autoregulation moves from the laboratory to the bedside. Cerebral Autoregulation will be useful to researchers in the physical sciences such as mathematical biology, medical physics, and biomedical engineering whose work is concerned with the brain. Researchers in the medical sciences and clinicians dealing with the brain and blood flow, as well as industry professionals developing techniques such as ultrasound, MRI, and CT will also find this Brief of interest.

  4. Brain energy metabolism and blood flow differences in healthy aging

    DEFF Research Database (Denmark)

    Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar


    Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors...... find decreases of both CBF and CMRO(2) but increased OEF, while others find no change, and yet other find divergent changes. In this reanalysis of previously published results from positron emission tomography of healthy volunteers, we determined CMRO(2) and CBF in 66 healthy volunteers aged 21 to 81......, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions...

  5. Multiscale modeling and simulation of brain blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Perdikaris, Paris, E-mail: [Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Grinberg, Leopold, E-mail: [IBM T.J Watson Research Center, 1 Rogers St, Cambridge, Massachusetts 02142 (United States); Karniadakis, George Em, E-mail: [Division of Applied Mathematics, Brown University, Providence, Rhode Island 02912 (United States)


    The aim of this work is to present an overview of recent advances in multi-scale modeling of brain blood flow. In particular, we present some approaches that enable the in silico study of multi-scale and multi-physics phenomena in the cerebral vasculature. We discuss the formulation of continuum and atomistic modeling approaches, present a consistent framework for their concurrent coupling, and list some of the challenges that one needs to overcome in achieving a seamless and scalable integration of heterogeneous numerical solvers. The effectiveness of the proposed framework is demonstrated in a realistic case involving modeling the thrombus formation process taking place on the wall of a patient-specific cerebral aneurysm. This highlights the ability of multi-scale algorithms to resolve important biophysical processes that span several spatial and temporal scales, potentially yielding new insight into the key aspects of brain blood flow in health and disease. Finally, we discuss open questions in multi-scale modeling and emerging topics of future research.

  6. Brain blood-flow changes during motion sickness. [thalamus vascular changes in dogs during swing tests (United States)

    Johnson, W. H.; Hsuen, J.


    The possibility of diminished blood flow in the brain is studied as one of the factors resulting from an increase in skeletal muscle blood volume concomitant with other characteristics of motion sickness. Thermistors are implanted in the thalamus of dogs and blood flow changes are recorded while they are subjected to sinusoidal movement on a two pole swing. Results of these initial steps in a proposed long term exploration of different areas of the brain are presented.

  7. Reflectometric mapping of microregional blood flow and blood volume in the brain cortex. (United States)

    Eke, A


    A reflectometric indicator-dilution method has been developed for mapping the parenchymal minute volume flow and blood content over tiny superficial areas of the brain cortex at 625 or 2500 locations, respectively. About 0.4 ml dextran-saline solution was used as nondiffusible indicator and injected into the feline cerebral circulation for each measurement. The subsequent cerebrocortical transit of the hemodiluted bolus was detected as a temporary change in the tissue optical density [OD(t)] and interpreted as indicator dilution, C(t). This gave the data necessary to calculate the microregional blood volume (mrCBV), mean transit time of the bolus (mrMTT), and the microregional blood flow (mrCBF = mrCBV/mrMTT). A two-dimensional record of the OD(t) function was made on Kodak SO 115 film by 16-mm cinematography, as a reflectometric tool, over an exposed area of the brain cortex during the bolus perfusion. Later, the microregional OD(t) functions were retrieved for analysis in a square array from the developed film by computer-controlled, frame-by-frame scanning densitometry. Maps of mrCBF, mrCBV, and mrMTT were presented as square arrays of gray-scaled pixels. The maximal spatial and temporal resolution of the method was 0.015 mm2 (mrCBF), 0.004 mm2 (mrCBV), 6 maps/min (mrCBF), and 600 maps/min (mrCBV).

  8. A Mixed Approach for Modeling Blood Flow in Brain Microcirculation (United States)

    Lorthois, Sylvie; Peyrounette, Myriam; Davit, Yohan; Quintard, Michel; Groupe d'Etude sur les Milieux Poreux Team


    Consistent with its distribution and exchange functions, the vascular system of the human brain cortex is a superposition of two components. At small-scale, a homogeneous and space-filling mesh-like capillary network. At large scale, quasi-fractal branched veins and arteries. From a modeling perspective, this is the superposition of: (a) a continuum model resulting from the homogenization of slow transport in the small-scale capillary network; and (b) a discrete network approach describing fast transport in the arteries and veins, which cannot be homogenized because of their fractal nature. This problematic is analogous to fast conducting wells embedded in a reservoir rock in petroleum engineering. An efficient method to reduce the computational cost is to use relatively large grid blocks for the continuum model. This makes it difficult to accurately couple both components. We solve this issue by adapting the ``well model'' concept used in petroleum engineering to brain specific 3D situations. We obtain a unique linear system describing the discrete network, the continuum and the well model. Results are presented for realistic arterial and venous geometries. The mixed approach is compared with full network models including various idealized capillary networks of known permeability. ERC BrainMicroFlow GA615102.

  9. Cerebral blood flow and brain atrophy correlated by xenon contrast CT scanning

    Energy Technology Data Exchange (ETDEWEB)

    Kitagawa, Y.; Meyer, J.S.; Tanahashi, N.; Rogers, R.L.; Tachibana, H.; Kandula, P.; Dowell, R.E.; Mortel, K.F.


    Correlations between cerebral blood flow (CBF) measured during stable xenon contrast CT scanning and standard CT indices of brain atrophy were investigated in the patients with senile dementia of Alzheimer type, multi-infarct dementia and idiopathic Parkinson's disease. Compared to age-matched normal volunteers, significant correlations were found in patients with idiopathic Parkinson's disease between cortical and subcortical gray matter blood flow and brain atrophy estimated by the ventricular body ratio, and mild to moderate brain atrophy were correlated with stepwise CBF reductions. However, in patients with senile dementia of Alzheimer type and multi-infarct dementia, brain atrophy was not associated with stepwise CBF reductions. Overall correlations between brain atrophy and reduced CBF were weak. Mild degrees of brain atrophy are not always associated with reduced CBF.

  10. Brain blood flow and cardiovascular responses to hot flashes in postmenopausal women. (United States)

    Lucas, Rebekah A I; Ganio, Matthew S; Pearson, James; Crandall, Craig G


    This study tested two related hypotheses: (1) brain blood flow is reduced during postmenopausal hot flashes, and (2) the magnitude of this reduction in brain blood flow is greater during hot flashes when blood pressure is reduced. Eleven healthy, normotensive postmenopausal women rested in a temperature-controlled laboratory (∼ 25°C) for approximately 120 minutes while waiting for a hot flash to occur. The onset of a hot flash was objectively identified by an abrupt increase in sternal sweat rate (capacitance hygrometry). Middle cerebral artery blood velocity (MCAv; transcranial Doppler) and mean arterial pressure (Finometer) were measured continuously. Each hot flash was divided into eight equal segments, and the segment with the largest reduction in MCAv and mean arterial pressure was identified for each hot flash. During experimental sessions, 25 hot flashes occurred (lasting a mean [SD] of 6.2 [2.8] min, with a mean frequency of 3 [1] hot flashes per participant). Seventy-six percent of hot flashes were accompanied by a clear reduction (>5%) in brain blood flow. For all hot flashes, the mean maximal decrease in MCAv was 12% (9%) (7 [6] cm s). This value did not correlate with corresponding changes in mean arterial pressure (R = 0.36). These findings demonstrate that hot flashes are often accompanied by clear reductions in brain blood flow that do not correspond with short-term reductions in mean arterial blood pressure.

  11. Functional Imaging of Dolphin Brain Metabolism and Blood Flow

    National Research Council Canada - National Science Library

    Ridgway, Sam; Finneran, James; Carder, Don; Keogh, Mandy; Van Bonn, William; Smith, Cynthia; Scadeng, Miriam; Dubowitz, David; Mattrey, Robert; Hoh, Carl


    This report documents the first use of magnetic resonance images (MRls) of living dolphins to register functional brain scans, allowing for the exploration of potential mechanisms of unihemispheric sleep...

  12. Cerebral blood volume and blood flow responses to hyperventilation in brain tumors during isoflurane or propofol anesthesia. (United States)

    Cenic, Aleksa; Craen, Rosemary A; Lee, Ting-Yim; Gelb, Adrian W


    Using computerized tomography, we measured absolute cerebral blood flow (CBF) and cerebral blood volume (CBV) in tumor, peri-tumor, and contralateral normal regions, at normocapnia and hypocapnia, in 16 rabbits with brain tumors (VX2 carcinoma), under isoflurane or propofol anesthesia. In both anesthetic groups, CBV and CBF were highest in the tumor region and lowest in the contralateral normal tissue. For isoflurane, a significant decrease in both CBV and CBF was observed in all tissue regions with hyperventilation (P hyperventilation for all regions (P > 0.10). In addition, there were no differences between CBV values for isoflurane at hypocapnia when compared with CBV values for propofol at normo- or hypocapnia (P > 0.34 and P > 0.35, respectively, in the tumor regions). Our results indicate that propofol increases cerebral vascular tone in both neoplastic and normal tissue vessels compared with isoflurane. CBV and CBF during normocapnia were significantly greater in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol. CBV and CBF remained responsive to hyperventilation only with isoflurane. In rabbits with brain tumors, brain blood flow and volume were significantly larger in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol during normocapnia, and remained responsive to a reduction in PaCO(2). Consequently, during hypocapnia, brain blood flow and volume values with isoflurane were similar to values with propofol.

  13. Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury. (United States)

    Bouzat, Pierre; Sala, Nathalie; Payen, Jean-François; Oddo, Mauro


    Monitoring and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is a standard of care after traumatic brain injury (TBI). However, the pathophysiology of so-called secondary brain injury, i.e., the cascade of potentially deleterious events that occur in the early phase following initial cerebral insult-after TBI, is complex, involving a subtle interplay between cerebral blood flow (CBF), oxygen delivery and utilization, and supply of main cerebral energy substrates (glucose) to the injured brain. Regulation of this interplay depends on the type of injury and may vary individually and over time. In this setting, patient management can be a challenging task, where standard ICP/CPP monitoring may become insufficient to prevent secondary brain injury. Growing clinical evidence demonstrates that so-called multimodal brain monitoring, including brain tissue oxygen (PbtO2), cerebral microdialysis and transcranial Doppler among others, might help to optimize CBF and the delivery of oxygen/energy substrate at the bedside, thereby improving the management of secondary brain injury. Looking beyond ICP and CPP, and applying a multimodal therapeutic approach for the optimization of CBF, oxygen delivery, and brain energy supply may eventually improve overall care of patients with head injury. This review summarizes some of the important pathophysiological determinants of secondary cerebral damage after TBI and discusses novel approaches to optimize CBF and provide adequate oxygen and energy supply to the injured brain using multimodal brain monitoring.

  14. Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant. (United States)

    Iwata, Sachiko; Tachtsidis, Ilias; Takashima, Sachio; Matsuishi, Toyojiro; Robertson, Nicola J; Iwata, Osuke


    Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO₂ index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO₂ index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO₂ index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the

  15. Blood-brain barrier and cerebral blood flow: Age differences in hemorrhagic stroke

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    Semyachkina-Glushkovskaya Oxana


    Full Text Available Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits. There are important differences in the factors, clinical events and outcomes associated with the stroke in infants and adults. However, mechanisms underlying age differences in the stroke development remain largely unknown. Therefore, treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children. The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke. Here, we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats. Using histological methods and magnetic resonance imaging, we found age differences in the type of intracranial hemorrhages. Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum. Using Doppler optical coherent tomography, we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs. adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs. adult brain in rats. However, adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier (BBB permeability. The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB (occludin and claudin-5 in neonatal vs. mature brain in rats.

  16. Increased cerebral blood flow in MELAS shown by Tc-99m HMPAO brain SPECT

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    Peng, N.J.; Tsay, D.G. [Department of Nuclear Medicine, Kaohsiung Veterans General Hospital, Kaohsiung (Taiwan); Liu, R.S. [Department of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei (Taiwan); Li, J.Y.; Kong, K.W. [Division of Neurology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung (Taiwan); Kwok, C.G.; Strauss, H.W. [Division of Nuclear Medicine, Department of Radiology, Stanford University Medical Center, CA (United States)


    We report cerebral SPECT studies on two siblings with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Tc-99m HMPAO brain SPECT was performed 8, 19 and 30 days after a stroke-like episode in one case and 10 days after a stroke-like episode, 6 h after a partial seizure and as a follow-up study in the other. Increased blood flow was seen in both these patients with stroke-like episodes due to MELAS. The cause of the increased blood flow is uncertain, but it may be related to the decreased pH created by local increase in lactic acid. (orig.)

  17. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A


    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several...... meningiomas (4 of 7 cases) in which most of the tumor itself did not receive any isotope. Brain metastases (6) usually had a low flow in the tumor and tumor-near region. The glioblastomas tended to show markedly bending 133Xe wash-out curves pointing to pronounced heterogeneity of blood flow. Most of the flow...... maps, regardless of the tumor types, showed widespread abnormalities of rCBF not only in the tumor region but also in the region remote from the tumor. It is concluded that measurement of rCBF cannot yield accurate differential diagnostic information, but that the widespread derangement of the brain...

  18. Fat intake modulates cerebral blood flow in homeostatic and gustatory brain areas in humans. (United States)

    Frank, Sabine; Linder, Katarzyna; Kullmann, Stephanie; Heni, Martin; Ketterer, Caroline; Cavusoglu, Mustafa; Krzeminski, Alina; Fritsche, Andreas; Häring, Hans-Ulrich; Preissl, Hubert; Hinrichs, Jörg; Veit, Ralf


    The hypothalamus is the central homeostatic control region of the brain and, therefore, highly influenced by nutrients such as glucose and fat. Immediate and prolonged homeostatic effects of glucose ingestion have been well characterized. However, studies that used stimulation with fat have mainly investigated immediate perceptional processes. Besides homeostatic processes, the gustatory cortex, including parts of the insular cortex, is crucial for the processing of food items. The aim of this study was to investigate the effect of high- compared with low-fat meals on the hypothalamus and the insular cortex. Eleven healthy men participated in a single-blinded, functional MRI study of high- and low-fat meals on 2 measurement days. Cerebral blood flow (CBF) was measured before and 30 and 120 min after intake of high- and low-fat yogurts. Hunger was rated and blood samples were taken before each CBF measurement. High-fat yogurt induced a pronounced decrease in CBF in the hypothalamus, and the corresponding CBF change correlated positively with the insulin change. Furthermore, insular activity increased after 120 min in the low-fat condition only. The CBF change in both regions correlated positively in the high-fat condition. The decrease in hypothalamic activity and the interaction with the insular cortex elicited by fat may contribute to an efficient energy homeostasis. Therefore, fat might be a modulator of homeostatic and gustatory brain regions and their interaction. This trial was registered at as NCT01516021.

  19. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A


    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several...

  20. Associations between total cerebral blood flow and age related changes of the brain.

    Directory of Open Access Journals (Sweden)

    Adriaan C G M van Es

    Full Text Available BACKGROUND AND PURPOSE: Although total cerebral blood flow (tCBF is known to be related to age, less is known regarding the associations between tCBF and the morphologic changes of the brain accompanying cerebral aging. The purpose of this study was to investigate whether total cerebral blood flow (tCBF is related to white matter hyperintensity (WMH volume and/or cerebral atrophy. Furthermore, we investigate whether tCBF should be expressed in mL/min, as was done in all previous MR studies, or in mL/100 mL/min, which yielded good results in precious SPECT, PET and perfusion MRI studies investigating regional cerebral blood flow. MATERIALS AND METHODS: Patients were included from the nested MRI sub-study of the PROSPER study. Dual fast spin echo and FLAIR images were obtained in all patients. In addition, single slice phase contrast MR angiography was used for flow measurements in the internal carotids and vertebral arteries. tCBF was expressed in both mL/min and mL/100 mL/min. RESULTS: We found a significant correlation between tCBF in mL/min and both age (r = -.124; p = p

  1. Cerebral Blood Flow and Transcranial Doppler Sonography Measurements of CO(2)-Reactivity in Acute Traumatic Brain Injured Patients

    DEFF Research Database (Denmark)

    Reinstrup, Peter; Ryding, Erik Hilmer; Asgeirsson, Bogi


    BACKGROUND: Cerebral blood flow (CBF) measurements are helpful in managing patients with traumatic brain injury (TBI), and testing the cerebrovascular reactivity to CO(2) provides information about injury severity and outcome. The complexity and potential hazard of performing CBF measurements lim...

  2. Multivariate evaluation of brain function by measuring regional cerebral blood flow and event-related potentials

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    Koga, Yoshihiko; Mochida, Masahiko; Shutara, Yoshikazu; Nakagawa, Kazumi [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine; Nagata, Ken


    To measure the effect of events on human cognitive function, effects of odors by measurement regional cerebral blood flow (rCBF) and P300 were evaluated during the auditory odd-ball exercise. PET showed the increase in rCBF on the right hemisphere of the brain by coffee aroma. rCBF was measured by PET in 9 of right-handed healthy adults men, and P300 was by event-related potential (ERP) in each sex of 20 right-handed healthy adults. ERP showed the difference of the P300 amplitude between men and women, and showed the tendency, by odors except the lavender oil, that women had higher in the P300 amplitude than men. These results suggest the presence of effects on the cognitive function through emotional actions. Next, the relationship between rCBF and ERP were evaluated. The subjects were 9 of the right-handed healthy adults (average: 25.6{+-}3.4 years old). rCBF by PET and P300 amplitude by ERP were simultaneously recorded during the auditory odd-ball exercise using the tone-burst method (2 kHz of the low frequency aimed stimuli and 1 kHz of the high frequency non-aimed stimuli). The rCBF value was the highest at the transverse gyrus of Heschl and the lowest at the piriform cortex among 24 regions of interest (ROI) from both sides. The difference of P300 peak latent time among ROI was almost the same. The brain waves from Cz and Pz were similar and the average amplitude was highest at Pz. We found the high correlation in the right piriform cortex (Fz), and right (Fz, Cz) and left (Cz, Pz) transverse gyrus of Heschl between the P300 amplitude and rCBF. (K.H.)

  3. Discrepancy between blood flow and muscarinic receptor distribution in rat brain after middle cerebral artery occlusion

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    Kuji, Ichiei [Department of Nuclear Medicine, School of Medicine, Kanazawa University, Kanazawa (Japan); Matsuda, Hiroshi [Division of Radiology, National Centre Hospital for Mental, Nervous and Muscular Disorders (NCNP), Tokyo (Japan); Sumiya, Hisashi [Department of Nuclear Medicine, School of Medicine, Kanazawa University, Kanazawa (Japan); Taki, Junichi [Department of Nuclear Medicine, School of Medicine, Kanazawa University, Kanazawa (Japan); Tsuji, Shiro [Department of Nuclear Medicine, School of Medicine, Kanazawa University, Kanazawa (Japan); Kinuya, Keiko [Department of Nuclear Medicine, School of Medicine, Kanazawa University, Kanazawa (Japan); Ichikawa, Akihiro [Department of Nuclear Medicine, School of Medicine, Kanazawa University, Kanazawa (Japan); Shiba, Kazuhiro [Radioisotope Centre, Kanazawa University, Kanazawa (Japan); Mori, Hirofumi [Radioisotope Centre, Kanazawa University, Kanazawa (Japan); Tonami, Norihisa [Department of Nuclear Medicine, School of Medicine, Kanazawa University, Kanazawa (Japan)


    To clarify whether muscarinic acetylcholine receptor (mAChR) binding can be a viable muscarinic neuronal marker which provides therapeutic information different from perfusional information in global brain, we evaluated the discrepancy between the distribution of cerebral blood flow (CBF), mAChR and its five subtypes of messenger ribonucleic acid (mRNA) in the acute (n=9) and chronic (n=8) phases of a middle cerebral artery (MCA) occlusion model and in sham-operated controls (n=6). In the acute phase, regional CBF was markedly reduced in the MCA territory, whereas mAChR was not reduced and the mRNA was reduced only slightly. In the chronic phase, mAChR was reduced markedly in the infarcted lesion and the mRNA was also reduced. The mAChR was slightly reduced in the ipsilateral substantia nigra and pontine nucleus because of remote effects; however, regional CBF in the substantia nigra was slightly increased and did not change in the pontine nucleus. The discrepancy between CBF and mAChR was clarified, and the tendency toward a reduction in mRNA in the acute ischaemic region without a reduction in mAChR suggested the presence of cholinergic neurons which were viable but hypometabolic. It is concluded that mAChR imaging may be of value for the assessment of the viable cholinergic neuron density in vivo. (orig.). With 6 figs.

  4. Multi-modal in vivo imaging of brain blood oxygenation, blood flow and neural calcium dynamics during acute seizures (United States)

    Ringuette, Dene; Jeffrey, Melanie A.; Carlen, Peter L.; Levi, Ofer


    Dysfunction of the vascular endothelium has been implicated in the development of epilepsy. To better understand the relation between vascular function and seizure and provide a foundation for interpreting results from functional imaging in chronic disease models, we investigate the relationship between intracellular calcium dynamics and local cerebral blood flow and blood oxygen saturation during acute seizure-like events and pharmacological seizure rescue. To probe the relation between the aforementioned physiological markers in an acute model of epilepsy in rats, we integrated three different optical modalities together with electrophysiological recordings: Laser speckle contrast imaging (LSCI) was used to study changes in flow speeds, Intrinsic optical signal imaging (IOSI) was used to monitor changes in oxygenated, de-oxygenated, and total hemoglobin concentration, and Calcium-sensitive dye imaging was used to monitor intracellular calcium dynamics. We designed a dedicated cortical flow chamber to remove superficial blood and dye resulting from the injection procedure, which reduced spurious artifacts. The near infrared light used for IOSI and LSCI was delivered via a light pipe integrated with the flow chamber to minimize the effect of fluid surface movement on illumination stability. Calcium-sensitive dye was injected via a glass electrode used for recording the local field potential. Our system allowed us to observe and correlate increases in intracellular calcium, blood flow and blood volume during seizure-like events and provide a quantitative analysis of neurovascular coupling changes associated with seizure rescue via injection of an anti-convulsive agent.

  5. Acute deep brain stimulation changes in regional cerebral blood flow in obsessive-compulsive disorder. (United States)

    Dougherty, Darin D; Chou, Tina; Corse, Andrew K; Arulpragasam, Amanda R; Widge, Alik S; Cusin, Cristina; Evans, Karleyton C; Greenberg, Benjamin D; Haber, Suzanne N; Deckersbach, Thilo


    OBJECTIVE Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conducted to better understand which regions of the cortico-striatal-thalamic-cortical network were acutely affected by VC/VS DBS for OCD. Furthermore, the objective was to identify which brain regions demonstrated changes in perfusion, as stimulation was applied across a dorsoventral lead axis that corresponded to different anatomical locations in the VC/VS. METHODS Six patients receiving VC/VS DBS for OCD underwent oxygen-15 positron emission tomography (15O-PET) scanning. Monopolar DBS was delivered at each of the 4 different electrodes on the stimulating lead in the VC/VS. The data were analyzed using SPM5. Paired t-tests were run in SPSS to identify significant changes in regional cerebral blood flow (rCBF) between stimulation conditions. Pearson's r correlations were run between these significant changes in rCBF and changes in OCD and depressive symptom severity. RESULTS Perfusion in the dorsal anterior cingulate cortex (dACC) significantly increased when monopolar DBS was turned on at the most ventral DBS contact, and this increase in dACC activity was correlated with reductions in depressive symptom severity (r(5) = -0.994, p = 0.001). Perfusion in the thalamus, striatum, and globus pallidus significantly increased when DBS was turned on at the most dorsal contact. CONCLUSIONS DBS of the VC/VS appears to modulate activity in the regions implicated in the pathophysiology of OCD. Different regions in the cortico-striatal-thalamic-cortical circuit showed increased perfusion based on whether the stimulation was more ventral or dorsal along the lead axis in the VC/VS. Evidence was found that DBS at the most ventral site was

  6. Changes in cerebral blood flow and psychometric indicators in veterans with early forms of chronic brain ischemia

    Directory of Open Access Journals (Sweden)

    Vasilenko Т.М.


    Full Text Available The goal is to study the cerebral blood flow and psychometric characteristics in veterans of Afghanistan with early forms of chronic brain ischemia. Material and Methods. The study included 74 veterans of the Afghan war aged from 45 to 55 years: group 1, 28 people with NPNKM; Group 2-28 patients with circulatory encephalopathy stage 1; group 3-18 healthy persons. Doppler examination of cerebral vessels was carried out on the unit «Smart-lite». Reactive and personal anxiety of patients was assessed using the scale of Spielberger, evaluation of the quality of life through the test SAN. Determining the level of neuroticism and psychoticism was conducted by the scale of neuroticism and psy-choticism. Results: The study of cerebral blood flow in the Afghan war veterans showed signs of insolvency of carotid and carotid-basilar anastomoses, hypoperfusion phenomenon with the depletion of autoregulation, violation of the outflow of venous blood at the level of the microvasculature, accompanied by cerebral arteries spasm. More than 40% of patients with early forms of chronic brain ischemia had high personal anxiety, low levels of well-being and activity, with maximum expression of dyscirculatory hypoxia. Conclusion. Readaptation of veterans of Afghanistan is accompanied by the changes in psychometric performance and the formation of the earliest forms of brain chronic ischemia associated with inadequate hemodynamics providing increased functional activity of the brain and the inefficiency of compensatory-adaptive reactions.

  7. Inferring common cognitive mechanisms from brain blood-flow lateralisation data obtained with functional transcranial Doppler ultrasound.

    Directory of Open Access Journals (Sweden)

    Georg eMeyer


    Full Text Available Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV lateralisation data, obtained with functional TransCranial Doppler (fTCD ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralisation Index (LI for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG at two difficulty levels.In the main experiment we demonstrate that the proposed analysis method shows correlated blood-flow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training.CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated.The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques.

  8. Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice. (United States)

    Lin, Ai-Ling; Pulliam, Daniel A; Deepa, Sathyaseelan S; Halloran, Jonathan J; Hussong, Stacy A; Burbank, Raquel R; Bresnen, Andrew; Liu, Yuhong; Podlutskaya, Natalia; Soundararajan, Anuradha; Muir, Eric; Duong, Timothy Q; Bokov, Alex F; Viscomi, Carlo; Zeviani, Massimo; Richardson, Arlan G; Van Remmen, Holly; Fox, Peter T; Galvan, Veronica


    Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders.

  9. Pressure passive cerebral blood flow and breakdown of the blood-brain barrier in experimental fetal asphyxia

    DEFF Research Database (Denmark)

    Lou, H C; Lassen, N A; Tweed, W A


    reaching CBF values up to 6 times normal at normal MABP of about 60 to 70 mmHg, and severe ischemia reaching CBF values close to zero in large cortical areas at MABP of 30 mmHg. CVP remained essentially unchanged at 10--15 mmHg. The severe and prolonged asphyxia rendered the blood-brain barrier leaky...... to the albumin tracer Evans blue. In four other fetuses umbilical cord clamping was omitted. However, only in one of these cases was acidosis completely avoided, and CBF autoregulation maintained. The three other fetuses were acidotic at the end of the surgical procedure and had impaired autoregulation....

  10. Average blood flow and oxygen uptake in the human brain during resting wakefulness

    DEFF Research Database (Denmark)

    Madsen, P L; Holm, S; Herning, M


    The Kety-Schmidt technique can be regarded as the reference method for measurement of global average cerebral blood flow (average CBF) and global average cerebral metabolic rate of oxygen (average CMRO2). However, in the practical application of the method, diffusion equilibrium for inert gas tra...... anatomy. However in the present study, no correlation between CMRO2 and cerebral venous anatomy as imaged by magnetic resonance angiography could be established. Our data show that the interindividual variation of CMRO2 is 11% (coefficient of variation)....

  11. Changes in cerebral blood flow and blood brain barrier in the gerbil hippocampal CA1 region following repeated brief cerebral ischemia. (United States)

    Jingtao, J.; Sato, S.; Yamanaka, N.


    Neuronal damage and changes in cerebral blood flow (CBF) and the permeability of the blood-brain barrier (BBB) following repeated brief periods of ischemia were studied in Mongolian gerbils. The cerebral ischemia was produced by three repeated occlusions of bilateral common carotid arteries for 3 min at 1-h intervals. CBF and permeability of the BBB were examined with tracers (China ink and silver nitrate) at 1, 3, and 7 days post ischemia using light and electron microscopy. Three days after the reperfusion, significant extravasation of tracers, consequential reduction of CBF, extensive neuronal destruction, and intravascular platelet aggregation were observed. Such vascular changes in the CA1 region were more severe than those in the frontal cortex. These findings strongly support the view that microcirculatory disturbance may be a mechanism responsible for delayed neuronal death in the CA1 region of the hippocampus.

  12. Alterations of cerebral blood flow and cerebrovascular reserve in patients with chronic traumatic brain injury accompanying deteriorated intelligence

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun; Bom, Hee Seung [Chonnam National Univ. Hospital, Kwangju (Korea, Republic of)


    The purpose of this study was to evaluate alterations of regional cerbral blood flow (CBF) and cerebrovascular reserve (CVR), and correlation between these alternations and cognitive dysfunctin in patients with chronic traumatic brain injury (TBI) and normal brain MRI findings. Thirty TBI patients and 19 healthy volunteers underwent rest/acetazolaminde brain SPECT using Tc-99m HMPAO. Korean-Wechsler Adult Intelligence scale test was also performed in the patient group. Statistical analysis was performed with statistical parametric mapping software (SPM '97). CBF was diminished in the left hemisphere including Wernicke's area in all patients with lower verbal scale scores. In addition, a reduction in CBF in the right frontal, temporal and parietal cortices was related with depressed scores in information, digital span, arithmetic and similarities. In patients with lower performance scale scores, CBF was mainly diminished in the right hemisphere including superior temporal and supramarginal gyri, premotor, primary somatomotor and a part of prefrontal cortices, left frontal lobe and supramarginal gyrus. CVR was diminished in sixty-four Brodmann's areas compared to control. A reduction in CVR was demonstrated bilaterally in the frontal and temporal lobes in patients with lower scores in both verbal and performance tests, and in addition, both inferior parietal and occipital lobes in information subset. Alterations of CBF and CVR were demonstrated in the symptomatic TBI patients with normal MRI finding. These alterations were correlated with the change of intelligence, of which the complex functions are subserved by multiple interconnected cortical structures.

  13. Reflectance-mode interferometric near-infrared spectroscopy quantifies brain absorption, scattering, and blood flow index in vivo. (United States)

    Borycki, Dawid; Kholiqov, Oybek; Srinivasan, Vivek J


    Interferometric near-infrared spectroscopy (iNIRS) is a new technique that measures time-of-flight- (TOF-) resolved autocorrelations in turbid media, enabling simultaneous estimation of optical and dynamical properties. Here, we demonstrate reflectance-mode iNIRS for noninvasive monitoring of a mouse brain in vivo. A method for more precise quantification with less static interference from superficial layers, based on separating static and dynamic components of the optical field autocorrelation, is presented. Absolute values of absorption, reduced scattering, and blood flow index (BFI) are measured, and changes in BFI and absorption are monitored during a hypercapnic challenge. Absorption changes from TOF-resolved iNIRS agree with absorption changes from continuous wave NIRS analysis, based on TOF-integrated light intensity changes, an effective path length, and the modified Beer-Lambert Law. Thus, iNIRS is a promising approach for quantitative and noninvasive monitoring of perfusion and optical properties in vivo.

  14. The first week after concussion: Blood flow, brain function and white matter microstructure. (United States)

    Churchill, Nathan W; Hutchison, Michael G; Richards, Doug; Leung, General; Graham, Simon J; Schweizer, Tom A


    Concussion is a major health concern, associated with short-term deficits in physical function, emotion and cognition, along with negative long-term health outcomes. However, we remain in the early stages of characterizing MRI markers of concussion, particularly during the first week post-injury when symptoms are most severe. In this study, 52 varsity athletes were scanned using Magnetic Resonance Imaging (MRI), including 26 athletes with acute concussion (scanned 1-7 days post-injury) and 26 matched control athletes. A comprehensive set of functional and structural MRI measures were analyzed, including cerebral blood flow (CBF) and global functional connectivity (Gconn) of grey matter, along with fractional anisotropy (FA) and mean diffusivity (MD) of white matter. An analysis comparing acutely concussed athletes and controls showed limited evidence for reliable mean effects of acute concussion, with only MD showing spatially extensive differences between groups. We subsequently demonstrated that the number of days post-injury explained a significant proportion of inter-subject variability in MRI markers of acutely concussed athletes. Athletes scanned at early acute injury (1-3 days) had elevated CBF and Gconn and reduced FA, but those scanned at late acute injury (5-7 days) had the opposite response. In contrast, MD showed a more complex, spatially-dependent relationship with days post-injury. These novel findings highlight the variability of MRI markers during the acute phase of concussion and the critical importance of considering the acute injury time interval, which has significant implications for studies relating acute MRI data to concussion outcomes.

  15. The first week after concussion: Blood flow, brain function and white matter microstructure

    Directory of Open Access Journals (Sweden)

    Nathan W. Churchill


    Full Text Available Concussion is a major health concern, associated with short-term deficits in physical function, emotion and cognition, along with negative long-term health outcomes. However, we remain in the early stages of characterizing MRI markers of concussion, particularly during the first week post-injury when symptoms are most severe. In this study, 52 varsity athletes were scanned using Magnetic Resonance Imaging (MRI, including 26 athletes with acute concussion (scanned 1–7 days post-injury and 26 matched control athletes. A comprehensive set of functional and structural MRI measures were analyzed, including cerebral blood flow (CBF and global functional connectivity (Gconn of grey matter, along with fractional anisotropy (FA and mean diffusivity (MD of white matter. An analysis comparing acutely concussed athletes and controls showed limited evidence for reliable mean effects of acute concussion, with only MD showing spatially extensive differences between groups. We subsequently demonstrated that the number of days post-injury explained a significant proportion of inter-subject variability in MRI markers of acutely concussed athletes. Athletes scanned at early acute injury (1–3 days had elevated CBF and Gconn and reduced FA, but those scanned at late acute injury (5–7 days had the opposite response. In contrast, MD showed a more complex, spatially-dependent relationship with days post-injury. These novel findings highlight the variability of MRI markers during the acute phase of concussion and the critical importance of considering the acute injury time interval, which has significant implications for studies relating acute MRI data to concussion outcomes.

  16. Regional cerebral blood flow and brain atrophy in senile dementia of Alzheimer type (SDAT). Comparing with multi-infarct dementia (MID), and aged control

    Energy Technology Data Exchange (ETDEWEB)

    Okada, K.; Kobayashi, S.; Yamaguchi, S.; Kitani, M.; Tsunematsu, T.


    To investigate the relationship between the reduction of cerebal blood flow and brain atrophy in SDAT, these were measured in 13 cases of senile dementia of Alzheimer type, and compared to 15 cases of multi-infarct Dementia, 39 cases of lacunar infarction without dementia (non-demented CVD group) and 69 cases of aged normal control. Brain atrophy was evaluated by two-dimensional method on CT film by digitizer and regional cerebral blood flow (rCBF) was measured by /sup 133/Xe inhalation method. The degree of brain atrophy in SDAT was almost similar of that of MID. But it was more severe than that of non-demented group. MID showed the lowest rCBF among these groups. SDAT showed significantly lower rCBF than that of aged control, but rCBF in SDAT was equal to that of lacunar stroke without dementia. Focal reduction of cerebral blood flow in bilateral fronto-parietal and left occipital regions were observed in SDAT. Verbal intelligence score (Hasegawa's score) correlated with rCBF and brain atrophy index in MID, and a tendency of correlation between rCBF and brain atrophy in MID was also observed. However, there was no correlation among those indices in SDAT. These findings suggest that the loss of brain substance dose not correspond to the reduction of rCBF in SDAT and simultaneous measurement of rCBF and brain atrophy was useful to differ SDAT from MID.

  17. Effects of variable blast pressures on blood flow and oxygen saturation in rat brain as evidenced using MRI. (United States)

    Bir, Cynthia; Vandevord, Pamela; Shen, Yimin; Raza, Waqar; Haacke, E Mark


    It has been recognized that primary blast waves may result in neurotrauma in soldiers in theater. A new type of contrast used in magnetic resonance imaging (MRI), susceptibility-weighted imaging (SWI), has been developed that is based on the different susceptibility levels in diverse tissues and can detect decreases in cerebral blood flow (CBF) using inferred oxygen saturation changes in tissue. In addition, a continuous arterial spin-labeled (ASL) MRI sequence was used as a direct measure of regional CBF within the brain tissue. Animals were subjected to whole-body blast exposures of various overpressures within a gas-driven shock tube. When exposed to low levels of overpressure, most rats demonstrated no obvious changes between pre- and postexposure in the conventional MR images. CBF changes measured by SWI and ASL were significantly higher for the overpressure exposed groups as compared to the sham group and tended to increase with pressure increases at the highest two pressures. In the hippocampus, all blast animals had a reduction in the CBF consistently in the range of 0-27%. In summary, low levels of primary blast pressure exposure demonstrated a significant physiologic effect to the brain up to 72 h postexposure. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Effects of acetazolamide on cerebral blood flow and brain tissue oxygenation

    DEFF Research Database (Denmark)

    Lassen, N A; Friberg, L; Kastrup, J


    decreased gradually to 70% of the control value, indicating hyperventilation. At sea level hyperventilation will not increase brain oxygenation significantly in normal man, as the arterial oxygen content only increases minimally, while CBF is unchanged. At high altitude the beneficial effects...... of acetazolamide on the symptoms of acute mountain sickness may well be due to an improved oxygen supply to the brain, as hyperventilation will, at the low ambient PO2, cause a significant increase of the arterial oxygen content, while CBF presumably is unaffected by the drug. During hypoxia at high altitude...

  19. Intermanual transfer of training : blood flow correlates in the human brain

    NARCIS (Netherlands)

    Thut, G; Halsband, U; Roelcke, U; Nienhusmeier, M; Missimer, J; Maguire, RP; Regard, M; Landis, T; Leenders, KL


    In a previous study, we found that relearning of a task with one hand might negatively be influenced by previous, opposite hand training of the analogue task, Thut G., et al., Exp. Brain Res., 108 (1996) 321-327. Drawing of a figure with the right hand, following left hand training, was slower than

  20. Traumatic Brain Injury Creates Biphasic Systemic Hemodynamic and Organ Blood Flow Responses in Rats (United States)


    dura and was secured to the bone and the screws with dental acrylic. The rats were returned to their cages and allowed to recover for 24 h. The...throughout the observation period in our study. Since sympathetic vasoconstrictor fibers are distributed unevenly to all segments of the circulation...There are more sympathetic vasoconstrictor fibers in the kidneys, spleen, and digestive system than in the heart and the brain (Guyton, 1986

  1. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

    DEFF Research Database (Denmark)

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki


    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled...... to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples...... were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined...

  2. Cerebral blood-flow tomography

    DEFF Research Database (Denmark)

    Lassen, N A; Henriksen, L; Holm, S


    . The Xe-133 flow maps are essentially based on the average Xe-133 concentration over the initial 2 min during and after an inhalation of the inert gas lasting 1 min. These maps agreed very well with the early IMP maps obtained over the initial 10 min following an i.v. bolus injection. The subsequent IMP......, and with low radiation exposure to patient and personnel. On the other hand, IMP gives an image of slightly higher resolution. It also introduces a new class of iodinated brain-seeking compounds allowing, perhaps, imaging of other functions more important than mere blood flow....

  3. A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice

    Directory of Open Access Journals (Sweden)

    Maximilian Wiesmann


    Full Text Available APOE ε4 (apoE4 polymorphism is the main genetic determinant of sporadic Alzheimer’s disease (AD. A dietary approach (Fortasyn including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF, functional connectivity (FC, gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10–12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT mice. However, 16–18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging.

  4. Analysis of Regional Cerebral Blood Flow Using {sup 99m}Tc-HMPAO Brain SPECT in Senile Dementia of Alzheimer Type

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myung Hae; Lee, Myung Chul; Koh, Chang Soon; Roh, Jae Kyu; Woo, Chong In [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    {sup 99m}Tc-HMPAO brain SPECT studies were performed in 11 patients with Alzheimer's disease, 7 patients with psychological depression and 12 normal controls. Changes of regional cerebral blood flow was semiquantitatively analyzed and the results were as follows. 1) In 11 patients with Alzheimer's disease, significant reduction of regional cerebral blood flow was found In both temporoparietal areas. 2) Relative perfusion between cerebral hemispheres was rather symmetrical in patient with Alzheimer's disease. 3) All patients with depression showed normal SPECT findings. As for conclusion, {sup 99m}Tc-HMPAO brain SPECT seemed to be a valuable method for clinical assessment and management of patients with Alzheimer's disease.

  5. Blood flow and microgravity (United States)

    Bureau, Lionel; Coupier, Gwennou; Dubois, Frank; Duperray, Alain; Farutin, Alexander; Minetti, Christophe; Misbah, Chaouqi; Podgorski, Thomas; Tsvirkun, Daria; Vysokikh, Mikhail


    The absence of gravity during space flight can alter cardio-vascular functions partially due to reduced physical activity. This affects the overall hemodynamics, and in particular the level of shear stresses to which blood vessels are submitted. Long-term exposure to space environment is thus susceptible to induce vascular remodeling through a mechanotransduction cascade that couples vessel shape and function with the mechanical cues exerted by the circulating cells on the vessel walls. Central to such processes, the glycocalyx - i.e. the micron-thick layer of biomacromolecules that lines the lumen of blood vessels and is directly exposed to blood flow - is a major actor in the regulation of biochemical and mechanical interactions. We discuss in this article several experiments performed under microgravity, such as the determination of lift force and collective motion in blood flow, and some preliminary results obtained in artificial microfluidic circuits functionalized with endothelium that offer interesting perspectives for the study of the interactions between blood and endothelium in healthy condition as well as by mimicking the degradation of glycocalyx caused by long space missions. A direct comparison between experiments and simulations is discussed. xml:lang="fr"

  6. Cerebral Blood Flow Changes in Glioblastoma Patients Undergoing Bevacizumab Treatment Are Seen in Both Tumor and Normal Brain. (United States)

    Andre, Jalal B; Nagpal, Seema; Hippe, Daniel S; Ravanpay, Ali C; Schmiedeskamp, Heiko; Bammer, Roland; Palagallo, Gerald J; Recht, Lawrence; Zaharchuk, Greg


    Bevacizumab (BEV) is increasingly used to treat recurrent glioblastoma (GBM) with some reported improvement in neurocognitive function despite potential neurotoxicities. We examined the effects of BEV on cerebral blood flow (CBF) within recurrent GBM tumor and in the contralateral middle cerebral artery (MCA) territory.Post-chemoradiation patients with histologically confirmed GBM were treated with BEV and underwent routine, serial tumor imaging with additional pseudocontinuous arterial spin labeling (pcASL) following informed consent. Circular regions-of-interest were placed on pcASL images directly over the recurrent tumor and in the contralateral MCA territory. CBF changes before and during BEV treatment were evaluated in tumor and normal tissue. Linear mixed models were used to assess statistical significance.Fifty-three pcASL studies in 18 patients were acquired. Evaluation yielded lower mean tumoral CBF during BEV treatment compared with pre-treatment (45 ± 27 vs. 65 ± 27 ml/100 g/min, p = 0.002), and in the contralateral MCA territory during, compared with pre-BEV treatment (35 ± 8.4 vs. 41 ± 8.4 ml/100 g/min, p = 0.03). The decrease in mean CBF tended to be greater in the tumoral region than in the contralateral MCA, though the difference did not reach statistical significance (31% vs. 13%; p = 0.082). BEV administration results in statistically significant global CBF decrease with a potentially preferential decrease in tumor perfusion compared with normal brain tissue. © The Author(s) 2015 Reprints and permissions:

  7. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism. (United States)

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki; Garcia, Benjamin; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José


    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 . Copyright © 2015 the American Physiological Society.

  8. Simultaneous PET/MR imaging of the brain: feasibility of cerebral blood flow measurements with FAIR-TrueFISP arterial spin labeling MRI

    Energy Technology Data Exchange (ETDEWEB)

    Stegger, Lars [Dept. of Radiology, Diagnostic and Interventional Radiology, Eberhard Karls Univ. Tuebingen, Tuebingen (Germany); Dept. of Nuclear Medicine and European Inst. for Molecular Imaging, Univ. of Munster, Munster (Germany)], E-mail:; Martirosian, Petros; Schick, Fritz [Dept. of Radiology, Section of Experimental Radiology, Eberhard Karls Univ. Tuebingen, Tuebingen (Germany); Schwenzer, Nina; Pfannenberg, Christina; Claussen, Claus D. [Dept. of Radiology, Diagnostic and Interventional Radiology, Eberhard Karls Univ. Tuebingen, Tuebingen (Germany); Bisdas, Sotirios [Dept. of Radiology, Diagnostic and Interventional Neuroradiology, Eberhard Karls Univ. Tuebingen, Tuebingen (Germany); Kolb, Armin; Pichler, Bernd [Dept. of Preclinical Imaging and Radiopharmacy, Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Eberhard Karls Univ. Tuebingen, Tuebingen (Germany); Boss, Andreas [Dept. of Radiology, Diagnostic and Interventional Radiology, Eberhard Karls Univ. Tuebingen, Tuebingen (Germany); Inst. of Diagnostic and Interventional Radiology, Univ. Hospital Zurich, Zurich (Switzerland)


    Background Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) with simultaneous data acquisition promises a comprehensive evaluation of cerebral pathophysiology on a molecular, anatomical, and functional level. Considering the necessary changes to the MR scanner design the feasibility of arterial spin labeling (ASL) is unclear. Purpose To evaluate whether cerebral blood flow imaging with ASL is feasible using a prototype PET/MRI device. Material and Methods ASL imaging of the brain with Flow-sensitive Alternating Inversion Recovery (FAIR) spin preparation and true fast imaging in steady precession (TrueFISP) data readout was performed in eight healthy volunteers sequentially on a prototype PET/MRI and a stand-alone MR scanner with 128 x 128 and 192 x 192 matrix sizes. Cerebral blood flow values for gray matter, signal-to-noise and contrast-to-noise ratios, and relative signal change were compared. Additionally, the feasibility of ASL as part of a clinical hybrid PET/MRI protocol was demonstrated in five patients with intracerebral tumors. Results Blood flow maps showed good delineation of gray and white matter with no discernible artifacts. The mean blood flow values of the eight volunteers on the PET/MR system were 51 {+-} 9 and 51 {+-} 7 mL/100 g/min for the 128 x 128 and 192 x 192 matrices (stand-alone MR, 57 {+-} 2 and 55 {+-} 5, not significant). The value for signal-to-noise (SNR) was significantly higher for the PET/MRI system using the 192 x 192 matrix size (P < 0.01), the relative signal change (dS) was significantly lower for the 192 x 192 matrix size (P = 0.02). ASL imaging as part of a clinical hybrid PET/MRI protocol could successfully be accomplished in all patients in diagnostic image quality. Conclusion ASL brain imaging is feasible with a prototype hybrid PET/MRI scanner, thus adding to the value of this novel imaging technique.

  9. Brain blood flow in the nitroglycerin (GTN) model of migraine: measurement using positron emission tomography and transcranial Doppler. (United States)

    Bednarczyk, E M; Wack, D S; Kassab, M Y; Burch, K; Trinidad, K; Haka, M; Gona, J


    Nitroglycerin has been widely used as a model of experimental migraine. Studies combining measurement of flow velocity using transcranial Doppler (TCD) concurrently with measures of cerebral blood flow (CBF) are uncommon. We report the results of a study combining TCD and positron emission tomography (PET). Healthy volunteers with no personal or family history of migraine underwent measurement of CBF using H215O PET, and velocity using TCD. Measurements were done at baseline, and following i.v. nitroglycerin at 0.125, 0.25 and 0.5 micro g/kg per min. Subcutaneous sumatriptan (6 mg) was injected, with CBF and velocity measured 15, 30, and 60 min later. Nitroglycerin was terminated and measurements obtained 30 min later. Six male and six female subjects were studied. Nitroglycerin increased global CBF while flow velocities decreased. Sumatriptan did not have a significant effect on these values. Regions of increased flow included the anterior cingulate, while regions of decreased flow included the occipital cortex. Our data suggest that nitroglycerin induces regional changes in CBF that are similar to changes reported in spontaneous migraine, but produces distinctly different effects on global CBF and velocity.

  10. Brain docosahexaenoic acid [DHA] incorporation and blood flow are increased in chronic alcoholics: a positron emission tomography study corrected for cerebral atrophy.

    Directory of Open Access Journals (Sweden)

    John C Umhau

    Full Text Available Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22∶6n-3, particularly if liver disease is present. In animal models, excessive alcohol consumption is reported to reduce brain DHA concentration, suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA metabolism also is abnormal in chronic alcoholics.We compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, with 22 non-smoking healthy controls. Using published neuroimaging methods with positron emission tomography (PET, we measured regional coefficients (K* and rates (J(in of DHA incorporation from plasma into the brain of each group using [1-(11C]DHA, and regional cerebral blood flow (rCBF using [(15O]water. Data were partial volume error corrected for brain atrophy. Plasma unesterified DHA concentration also was quantified.Mean K* for DHA was significantly and widely elevated by 10-20%, and rCBF was elevated by 7%-34%, in alcoholics compared with controls. Unesterified plasma DHA did not differ significantly between groups nor did whole brain J(in, the product of K* and unesterified plasma DHA concentration.Significantly higher values of K* for DHA in alcoholics indicate increased brain avidity for DHA, thus a brain DHA metabolic deficit vis-à-vis plasma DHA availability. Higher rCBF in alcoholics suggests increased energy consumption. These changes may reflect a hypermetabolic state related to early alcohol withdrawal, or a general brain metabolic change in chronic alcoholics.

  11. Blood flow distribution in cerebral arteries. (United States)

    Zarrinkoob, Laleh; Ambarki, Khalid; Wåhlin, Anders; Birgander, Richard; Eklund, Anders; Malm, Jan


    High-resolution phase-contrast magnetic resonance imaging can now assess flow in proximal and distal cerebral arteries. The aim of this study was to describe how total cerebral blood flow (tCBF) is distributed into the vascular tree with regard to age, sex and anatomic variations. Forty-nine healthy young (mean 25 years) and 45 elderly (mean 71 years) individuals were included. Blood flow rate (BFR) in 21 intra- and extracerebral arteries was measured. Total cerebral blood flow was defined as BFR in the internal carotid plus vertebral arteries and mean cerebral perfusion as tCBF/brain volume. Carotid/vertebral distribution was 72%/28% and was not related to age, sex, or brain volume. Total cerebral blood flow (717 ± 123 mL/min) was distributed to each side as follows: middle cerebral artery (MCA), 21%; distal MCA, 6%; anterior cerebral artery (ACA), 12%, distal ACA, 4%; ophthalmic artery, 2%; posterior cerebral artery (PCA), 8%; and 20% to basilar artery. Deviating distributions were observed in subjects with 'fetal' PCA. Blood flow rate in cerebral arteries decreased with increasing age (Psystem.

  12. [Nicergoline, an ergot alkaloid, improves ischemic brain damage by ameliorating the decreased cerebral blood flow and metabolism in spontaneously hypertensive rats]. (United States)

    Ueda, T; Ishikawa, T; Kawata, K; Setoyama, K; Maekawa, T; Sakabe, T; Takeshita, H


    Effects of ergot alkaloids, nicergoline (NIC), on survival rate, brain water content, local cerebral blood flow (LCBF: 14C-iodoantipyrine) and glucose utilization (LCGU: 14C-2-deoxyglucose) were examined after bilateral carotid artery occlusion (BCAO) in spontaneously hypertensive rats. Two series of study were performed; the permanent BCAO and 3-hr-BCAO study. After permanent BCAO, the survival rate at 24 hrs of 32% (8 mg/kg, i.p.) or 38% (16mg/kg) in NIC group was higher than that in non-treated group (12%). At the end of 3-hr-BCAO, the increase in water content (dry-wet) in di-mesencephalon was less in NIC (100 micrograms/kg/min, i.v.) group than that in non-treated group. The decrease in LCBF in caudate-putamen (CP), parietal cortex (PC), thalamus (TH), hypothalamus (HT), and substantia nigra (SN) were less in NIC group than those in non-treated group. At the 2-hr-reperfusion after 3-hr-BCAO, the decrease in LCBF in TH and HT were less in NIC group than those in non-treated group. The LCGU in sensory motor cortex, CP, PC, HT, inferior colliculus and pons-reticular were higher in NIC group than those in non-treated group. From these results, it is concluded that nicergoline may have ameliorative effects on survival rate related to the prevention of decreased cerebral blood flow and metabolism following brain ischemia.

  13. Local Control of Blood Flow (United States)

    Clifford, Philip S.


    Organ blood flow is determined by perfusion pressure and vasomotor tone in the resistance vessels of the organ. Local factors that regulate vasomotor tone include myogenic and metabolic autoregulation, flow-mediated and conducted responses, and vasoactive substances released from red blood cells. The relative importance of each of these factors…

  14. Capillary pericytes regulate cerebral blood flow in health and disease

    DEFF Research Database (Denmark)

    Hall, Catherine N; Reynell, Clare; Gesslein, Bodil


    Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD (blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes, is controversial. We demonstrate...... blood flow, capillaries dilate before arterioles and are estimated to produce 84% of the blood flow increase. In pathology, ischaemia evokes capillary constriction by pericytes. We show that this is followed by pericyte death in rigor, which may irreversibly constrict capillaries and damage the blood......-brain barrier. Thus, pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Prevention of pericyte constriction and death may reduce the long-lasting blood flow decrease that damages neurons after stroke....

  15. Cerebral blood flow tomography with xenon-133

    DEFF Research Database (Denmark)

    Lassen, N A


    Cerebral blood flow (CBF) can be measured tomographically by inhalation of Xenon-133. The calculation is based on taking a sequence of tomograms during the wash-in and wash-out phase of the tracer. Due to the dynamic nature of the process, a highly sensitive and fast moving single photon emission...... of other tracers for CBF tomography using SPECT is summarized with emphasis on the 99mTc chelates that freely pass the intact blood-brain barrier. The highly sensitive brain-dedicated SPECT systems described are a prerequisite for achieving high resolution tomograms with such tracers....

  16. Brain SPECT imaging with blood flow markers in epilepsy and balloon occlusion; Hirn-SPECT mit Durchblutungsmarkern in der Epilepsiediagnostik und bei der Ballon-Okklusion

    Energy Technology Data Exchange (ETDEWEB)

    Gruenwald, F. [Bonn Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin


    Brain SPECT imaging is used as a routine technique in presurgical evaluation. In three fields (focus detection, prognosis, stimulation) the value of brain SPECT imaging in cost effective patient management is presented in this paper. Interictal and ictal brain SPECT imaging are used to detect the epileptic focus and are a powerful tool during implantation of subdural or depth electrodes, being able to replace an `invasive` evaluation in some cases. Brain SPECT can be used to estimate the patients` postoperative outcome (memory, seizure frequency). Using activation imaging, the functional activity of brain regions can be estimated prior to resection of larger areas. In balloon occlusion, the blood flow pattern during the occlusion and the risk of ischemia after resection or permanent occlusion of the careotid artery can be estimated by means of brain SPECT. (orig.) [Deutsch] Die Hirn-SPECT-Untersuchung hat inzwischen einen festen Platz in der praechirurgischen Epilepsiediagnostik. Anhand von drei Einsatzgebieten innerhalb dieser Thematik (Fokussuche, Prognose, Stimulationsuntersuchung) wird gezeigt, dass die Indikation zur Hirn-SPECT auch unter Kosten-Nutzen-Aspekten gestellt werden kann. Iktale und interiktale Untersuchungen werden im Rahmen der Fokussuche eingesetzt und koennen bei der Implantation von Subdural- oder Tiefen-Elektroden hilfreich sein und in einzelnen Faellen eine invasive Abklaerung ersetzen. Der Hirn-SPECT-Befund kann zur Abschaetzung des postoperativen `outcome` (Gedaechtnis, Anfallsfrequenz) beitragen. Mittels Aktivierungsuntersuchungen kann vor groesseren resektiven Eingriffen die funktionelle Aktivitaet von Hirnarealen beurteilt werden. Bei der Ballon-Okklusion ist es mit Hilfe der Hirn-SPECT-Untersuchung praeoperativ moeglich, die Durchblutungsverhaeltnisse waehrend der Okklusion und damit das Risiko einer Ischaemie nach Resektion oder permanenter Okklusion zu beurteilen. (orig.)

  17. The effects of neck flexion on cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in related sensory cortices. (United States)

    Fujiwara, Katsuo; Kunita, Kenji; Kiyota, Naoe; Mammadova, Aida; Irei, Mariko


    A flexed neck posture leads to non-specific activation of the brain. Sensory evoked cerebral potentials and focal brain blood flow have been used to evaluate the activation of the sensory cortex. We investigated the effects of a flexed neck posture on the cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in the related sensory cortices. Twelve healthy young adults received right visual hemi-field, binaural auditory and left median nerve stimuli while sitting with the neck in a resting and flexed (20° flexion) position. Sensory evoked potentials were recorded from the right occipital region, Cz in accordance with the international 10-20 system, and 2 cm posterior from C4, during visual, auditory and somatosensory stimulations. The oxidative-hemoglobin concentration was measured in the respective sensory cortex using near-infrared spectroscopy. Latencies of the late component of all sensory evoked potentials significantly shortened, and the amplitude of auditory evoked potentials increased when the neck was in a flexed position. Oxidative-hemoglobin concentrations in the left and right visual cortices were higher during visual stimulation in the flexed neck position. The left visual cortex is responsible for receiving the visual information. In addition, oxidative-hemoglobin concentrations in the bilateral auditory cortex during auditory stimulation, and in the right somatosensory cortex during somatosensory stimulation, were higher in the flexed neck position. Visual, auditory and somatosensory pathways were activated by neck flexion. The sensory cortices were selectively activated, reflecting the modalities in sensory projection to the cerebral cortex and inter-hemispheric connections.

  18. Endovascular blood flow measurement system (United States)

    Khe, A. K.; Cherevko, A. A.; Chupakhin, A. P.; Krivoshapkin, A. L.; Orlov, K. Yu


    In this paper an endovascular measurement system used for intraoperative cerebral blood flow monitoring is described. The system is based on a Volcano ComboMap Pressure and Flow System extended with analogue-to-digital converter and PC laptop. A series of measurements performed in patients with cerebrovascular pathologies allows us to introduce “velocity-pressure” and “flow rate-energy flow rate” diagrams as important characteristics of the blood flow. The measurement system presented here can be used as an additional instrument in neurosurgery for assessment and monitoring of the operation procedure. Clinical data obtained with the system are used for construction of mathematical models and patient-specific simulations. The monitoring of the blood flow parameters during endovascular interventions was approved by the Ethics Committee at the Meshalkin Novosibirsk Research Institute of Circulation Pathology and included in certain surgical protocols for pre-, intra- and postoperative examinations.

  19. The Spatial Associations of Cerebral Blood Flow and Spontaneous Brain Activities with White Matter Hyperintensities—An Exploratory Study Using Multimodal Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Lin Shi


    Full Text Available White matter hyperintensities (WMHs have been reported to be correlated with functional brain changes, but the association of the specific WMHs distribution pattern with regional functional changes remains uncertain. The aim of this study is to explore the possible spatial correlation of WMH with changes in cerebral blood flow (CBF and spontaneous brain activities in elderly using a novel approach. The WMHs, CBF, and spontaneous brain activities measured by intrinsic connectivity contrast (ICC, were quantified using multimodal magnetic resonance imaging for 69 elderly subjects. Such approach enables us to expand our search for newly identified correlated areas by drawing strengths of different modes and provides a means for triangulation as well as complementary insights. The results showed significant positive correlations between WMH volumes in the right superior corona radiata and CBF in the left supplementary motor area, as well as between WMH volumes in left anterior limb internal capsule and CBF in the right putamen. Significant correlations of regional WMH volumes and ICC were also detected between the right anterior corona radiata and the left cuneus, and the right superior occipital cortex, as well as between the right superior corona radiata and the left superior occipital cortex. These findings may suggest a regional compensatory functional enhancement accounting for the maintenance of cognitively normal status, which can be supported by the widely observed phenomenon that mild to moderate WMH load could have little effect on global cognitive performance.

  20. The Spatial Associations of Cerebral Blood Flow and Spontaneous Brain Activities with White Matter Hyperintensities-An Exploratory Study Using Multimodal Magnetic Resonance Imaging. (United States)

    Shi, Lin; Miao, Xinyuan; Lou, Wutao; Liu, Kai; Abrigo, Jill; Wong, Adrian; Chu, Winnie C W; Wang, Defeng; Mok, Vincent C T


    White matter hyperintensities (WMHs) have been reported to be correlated with functional brain changes, but the association of the specific WMHs distribution pattern with regional functional changes remains uncertain. The aim of this study is to explore the possible spatial correlation of WMH with changes in cerebral blood flow (CBF) and spontaneous brain activities in elderly using a novel approach. The WMHs, CBF, and spontaneous brain activities measured by intrinsic connectivity contrast (ICC), were quantified using multimodal magnetic resonance imaging for 69 elderly subjects. Such approach enables us to expand our search for newly identified correlated areas by drawing strengths of different modes and provides a means for triangulation as well as complementary insights. The results showed significant positive correlations between WMH volumes in the right superior corona radiata and CBF in the left supplementary motor area, as well as between WMH volumes in left anterior limb internal capsule and CBF in the right putamen. Significant correlations of regional WMH volumes and ICC were also detected between the right anterior corona radiata and the left cuneus, and the right superior occipital cortex, as well as between the right superior corona radiata and the left superior occipital cortex. These findings may suggest a regional compensatory functional enhancement accounting for the maintenance of cognitively normal status, which can be supported by the widely observed phenomenon that mild to moderate WMH load could have little effect on global cognitive performance.

  1. Pig brain stereotaxic standard space: mapping of cerebral blood flow normative values and effect of MPTP-lesioning

    DEFF Research Database (Denmark)

    Andersen, F; Watanabe, Hideaki; Bjarkam, Carsten


    developed an analogous stereotaxic coordinate system for the brain of the Gottingen miniature pig, based on automatic co-registration of magnetic resonance (MR) images obtained in 22 male pigs. The origin of the pig brain stereotaxic space (0, 0, 0) was arbitrarily placed in the centroid of the pineal gland...

  2. Methods for measurement of cerebral blood flow in man

    DEFF Research Database (Denmark)

    Lassen, N A


    A survey of the currently available methods for the measurement of cerebral blood flow in man is given. Many of the clinically important brain diseases such as tumors, stroke, brain trauma or epilepsy entail focal or regional flow alterations. Therefore a special emphasis is placed on methods all...

  3. Hyperhomocysteinemia decreases bone blood flow

    Directory of Open Access Journals (Sweden)

    Neetu T


    Full Text Available Neetu Tyagi*, Thomas P Vacek*, John T Fleming, Jonathan C Vacek, Suresh C TyagiDepartment of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA *These authors have equal authorshipAbstract: Elevated plasma levels of homocysteine (Hcy, known as hyperhomocysteinemia (HHcy, are associated with osteoporosis. A decrease in bone blood flow is a potential cause of compromised bone mechanical properties. Therefore, we hypothesized that HHcy decreases bone blood flow and biomechanical properties. To test this hypothesis, male Sprague–Dawley rats were treated with Hcy (0.67 g/L in drinking water for 8 weeks. Age-matched rats served as controls. At the end of the treatment period, the rats were anesthetized. Blood samples were collected from experimental or control rats. Biochemical turnover markers (body weight, Hcy, vitamin B12, and folate were measured. Systolic blood pressure was measured from the right carotid artery. Tibia blood flow was measured by laser Doppler flow probe. The results indicated that Hcy levels were significantly higher in the Hcy-treated group than in control rats, whereas vitamin B12 levels were lower in the Hcy-treated group compared with control rats. There was no significant difference in folate concentration and blood pressure in Hcy-treated versus control rats. The tibial blood flow index of the control group was significantly higher (0.78 ± 0.09 flow unit compared with the Hcy-treated group (0.51 ± 0.09. The tibial mass was 1.1 ± 0.1 g in the control group and 0.9 ± 0.1 in the Hcy-treated group. The tibia bone density was unchanged in Hcy-treated rats. These results suggest that Hcy causes a reduction in bone blood flow, which contributes to compromised bone biomechanical properties.Keywords: homocysteine, tibia, bone density

  4. Multi-modal analysis of functional connectivity and cerebral blood flow reveals shared and unique effects of propofol in large-scale brain networks. (United States)

    Qiu, Maolin; Scheinost, Dustin; Ramani, Ramachandran; Constable, R Todd


    Anesthesia-induced changes in functional connectivity and cerebral blow flow (CBF) in large-scale brain networks have emerged as key markers of reduced consciousness. However, studies of functional connectivity disagree on which large-scale networks are altered or preserved during anesthesia, making it difficult to find a consensus amount studies. Additionally, pharmacological alterations in CBF could amplify or occlude changes in connectivity due to the shared variance between CBF and connectivity. Here, we used data-driven connectivity methods and multi-modal imaging to investigate shared and unique neural correlates of reduced consciousness for connectivity in large-scale brain networks. Rs-fMRI and CBF data were collected from the same subjects during an awake and deep sedation condition induced by propofol. We measured whole-brain connectivity using the intrinsic connectivity distribution (ICD), a method not reliant on pre-defined seed regions, networks of interest, or connectivity thresholds. The shared and unique variance between connectivity and CBF were investigated. Finally, to account for shared variance, we present a novel extension to ICD that incorporates cerebral blood flow (CBF) as a scaling factor in the calculation of global connectivity, labeled CBF-adjusted ICD). We observed altered connectivity in multiple large-scale brain networks including the default mode (DMN), salience, visual, and motor networks and reduced CBF in the DMN, frontoparietal network, and thalamus. Regional connectivity and CBF were significantly correlated during both the awake and propofol condition. Nevertheless changes in connectivity and CBF between the awake and deep sedation condition were only significantly correlated in a subsystem of the DMN, suggesting that, while there is significant shared variance between the modalities, changes due to propofol are relatively unique. Similar, but less significant, results were observed in the CBF-adjusted ICD analysis, providing

  5. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A


    maps, regardless of the tumor types, showed widespread abnormalities of rCBF not only in the tumor region but also in the region remote from the tumor. It is concluded that measurement of rCBF cannot yield accurate differential diagnostic information, but that the widespread derangement of the brain...

  6. Low-dose mannitol (0.3 g kg(-1)) improves the pulsatility index and minimum diastolic blood flow velocity in traumatic brain injury. (United States)

    Nincevic, Zeljko; Mestrovic, Julije; Nincevic, Jasna; Sundov, Zeljko; Kuscevic, Dorjan


    The aim of the study was to investigate the effects of using low-dose mannitol (0.3 g kg(-1)) on the pulsatility index (PI) and minimum diastolic blood flow velocity (FV-min) of the middle cerebral artery in a traumatic brain injury (TBI). Low-dose mannitol (0.3 g kg(-1)) was administered to a group of 20 patients with a TBI. Transcranial Doppler (TCD) ultrasonography was used to monitor the PI and FV-min. The study included patients with a diffuse traumatic brain injury and Glasgow coma score  1.4 and FV-min mannitol administration, immediately after administration and 1, 2 and 3 hours after the administration of mannitol. A one-way analysis of variance revealed significant changes in the PI (F = 8.392; p mannitol. Low-dose mannitol administration appears to be efficacious for improving the indicators of disturbed circulation in a TBI (FV-min increase, PI decrease). The maximum decrease in the PI was recorded 1 hour after the administration of mannitol and was 10.9% of the initial value. The maximum increase in the FV-min was recorded 1 hour after administration and was 29.7% of the initial value. These changes were significant ∼ 2 hours later.

  7. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke

    DEFF Research Database (Denmark)

    Olsen, T S; Larsen, B; Herning, M


    In a group of 48 patients with completed stroke, 8 patients had viable collaterally perfused brain tissue which was accessible for rCBF recordings with a two dimensional technique. All 8 had deep subcortical infarcts on CT-scan, and angiographic occlusion of the arteries normally supplying...

  8. Blood Flow and Brain Function: Investigations of neurovascular coupling using BOLD fMRI at 7 tesla

    NARCIS (Netherlands)

    Siero, J.C.W.


    The advent of ultra high field (7 tesla) MRI systems has opened the possibility to probe biological processes of the human body in great detail. Especially for studying brain function using BOLD fMRI there is a large benefit from the increased magnetic field strength. BOLD fMRI is the working horse

  9. Quantitative Erythrocyte Omega-3 EPA Plus DHA Levels are Related to Higher Regional Cerebral Blood Flow on Brain SPECT. (United States)

    Amen, Daniel G; Harris, William S; Kidd, Parris M; Meysami, Somayeh; Raji, Cyrus A


    The interrelationships between omega-3 fatty acids status, brain perfusion, and cognition are not well understood. To evaluate if SPECT brain imaging of cerebral perfusion and cognition varies as a function of omega-3 fatty acid levels. A random sample of 166 study participants was drawn from a psychiatric referral clinical for which erythrocyte quantification of omega-3 eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (the Omega-3 Index) was available. Quantitative brain SPECT was done on 128 regions based on a standard anatomical Atlas. Persons with erythrocyte EPA+DHA concentrations were dichotomized based on membership in top 50th percentile versus bottom 50th percentile categories. Two-sample t-tests were done to identify statistically significant differences in perfusion between the percentile groups. Partial correlations were modeled between EPA+DHA concentration and SPECT regions. Neurocognitive status was assessed using computerized testing (WebNeuro) and was separately correlated to cerebral perfusion on brain SPECT imaging and omega-3 EPA+DHA levels. Partial correlation analyses showed statistically significant relationships between higher omega-3 levels and cerebral perfusion were in the right parahippocampal gyrus (r = 0.20, p = 0.03), right precuneus (r = 0.20, p = 0.03), and vermis subregion 6 (p = 0.21, p = 0.03). Omega-3 Index levels separately correlated to the feeling subsection of the WebNeuro (r = 0.25, p = 0.01). Quantitative omega-3 EPA+DHA erythrocyte concentrations are independently correlated with brain perfusion on SPECT imaging and neurocognitive tests. These results have implications for the role of omega-3 fatty acids toward contributing to cognitive reserve.

  10. Age or ischemia uncouples the blood flow response, tissue acidosis, and direct current potential signature of spreading depolarization in the rat brain. (United States)

    Menyhárt, Ákos; Zölei-Szénási, Dániel; Puskás, Tamás; Makra, Péter; Bari, Ferenc; Farkas, Eszter


    Spreading depolarization (SD) events contribute to lesion maturation in the acutely injured human brain. Neurodegeneration related to SD is thought to be caused by the insufficiency of the cerebral blood flow (CBF) response; yet the mediators of the CBF response, or their deficiency in the aged or ischemic cerebral cortex, remain the target of intensive research. Here, we postulated that tissue pH effectively modulates the magnitude of hyperemia in response to SD, the coupling of which is prone to be dysfunctional in the aged or ischemic cerebral cortex. To test this hypothesis, we conducted systematic correlation analysis between the direct current (DC) potential signature of SD, SD-associated tissue acidosis, and hyperemic element of the CBF response in the isoflurane-anesthetized, young or old, and intact or ischemic rat cerebral cortex. The data demonstrate that the amplitude of the SD-related DC potential shift, tissue acidosis, and hyperemia are tightly coupled in the young intact cortex; ischemia and old age uncouples the amplitude of hyperemia from the amplitude of the DC potential shift and acidosis; the duration of the DC potential shift, hyperemia and acidosis positively correlate under ischemia alone; and old age disproportionally elongates the duration of acidosis with respect to the DC potential shift and hyperemia under ischemia. The coincidence of the variables supports the view that local CBF regulation with SD must have an effective metabolic component, which becomes dysfunctional with age or under ischemia. Finally, the known age-related acceleration of ischemic neurodegeneration may be promoted by exaggerated tissue acidosis.NEW & NOTEWORTHY The hyperemic element of the cerebral blood flow response to spreading depolarization is effectively modulated by tissue pH in the young intact rat cerebral cortex. This coupling becomes dysfunctional with age or under ischemia, and tissue acidosis lasts disproportionally longer in the aged cortex, making

  11. Blood-brain transfer of Pittsburgh compound B in humans. (United States)

    Gjedde, Albert; Aanerud, Joel; Braendgaard, Hans; Rodell, Anders B


    In the labeled form, the Pittsburgh compound B (2-(4'-{N-methyl-[(11)C]}methyl-aminophenyl)-6-hydroxy-benzothiazole, [(11)C]PiB), is used as a biomarker for positron emission tomography (PET) of brain β-amyloid deposition in Alzheimer's disease (AD). The permeability of [(11)C]PiB in the blood-brain barrier is held to be high but the permeability-surface area product and extraction fractions in patients or healthy volunteers are not known. We used PET to determine the clearance associated with the unidrectional blood-brain transfer of [(11)C]PiB and the corresponding cerebral blood flow rates in frontal lobe, whole cerebral cortex, and cerebellum of patients with Alzheimer's disease and healthy volunteers. Regional cerebral blood flow rates differed significantly between the two groups. Thus, regional and whole-brain permeability-surface area products were identical, in agreement with the observation that numerically, but insignificantly, unidirectional blood-brain clearances are lower and extraction fractions higher in the patients. The evidence of unchanged permeability-surface area products in the patients implies that blood flow changes can be deduced from the unidirectional blood-brain clearances of [(11)C]PiB in the patients.

  12. Effect of acupuncture on regional cerebral blood flow at acupoints GV 20, GV. 26, LI, 4. ST. 36, SP. 6 evaluated by Tc-99m ECD brain SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun; Bom, Hee Seung; Kang, Hwa Jeong; Kim, Seong Min; Jeong, Hwan Jeong; Kim, Ji Yeul [College of Medicine, Dongshin Univ., Naju (Korea, Republic of); Ahn, Soo Gi [College of Medicine, Wonkwang Univ., Iksan (Korea, Republic of)


    To evaluate the effect of acupuncture on regional cerebral blood flow (rCBF) at acupoints suggested by oriental medicine to be related to the treatment of cerebrovascular diseases. Rest/acupuncture-stimulation Tc-99m ECD brain SPECT using a same-dose subtraction method was performed on 54 normal volunteers (34 males, 20 females, age range from 18 to 62 years) using six paradigms: acupuncture at acupoints GV. 20, GV. 26, LI. 4, ST. 36 and SP. 6. In the control study, needle location was chosen on a non-meridian focus 1 cm posterior to the right fibular head. All images were spatially normalized, and the differences between rest and acupuncture stimulation were statistically analyzed using SPM for Windows. Acupuncture applied at acupoint GV. 20 increased rCBF in both the anterior frontal lobes, the right frontotemporal lobes, and the left anterior temporal lobe and the left cerebellar hemisphere. Acupuncture at GV. 26 increased rCBF in the left prefrontal cortex. Acupuncture at LI. 4 increased rCBF in the left prefrontal and both the inferior frontal lobes, and the left anterior temporal lobe and the left cerebellar hemisphere. Acupuncture at ST. 36 increased rCBF in the left anterior temporal lobe, the right inferior frontal lobes, and the left cerebellum. Acupuncture at SP 6 increased rCBF in the left inferior frontal and anterior temporal lobes. In the control stimulation, no significant rCBF increase was observed. The results demonstrated a correlation between stimuation at each acupoint with increase in rCBF to the corresponding brain areas.

  13. Anatomy and physiology of the blood-brain barrier. (United States)

    Serlin, Yonatan; Shelef, Ilan; Knyazer, Boris; Friedman, Alon


    Essential requisite for the preservation of normal brain activity is to maintain a narrow and stable homeostatic control in the neuronal environment of the CNS. Blood flow alterations and altered vessel permeability are considered key determinants in the pathophysiology of brain injuries. We will review the present-day literature on the anatomy, development and physiological mechanisms of the blood-brain barrier, a distinctive and tightly regulated interface between the CNS and the peripheral circulation, playing a crucial role in the maintenance of the strict environment required for normal brain function. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Cerebral blood flow tomography with xenon-133

    Energy Technology Data Exchange (ETDEWEB)

    Lassen, N.A.


    Cerebral blood flow (CBF) can be measured tomographically by inhalation of Xenon-/sup 133/. The calculation is based on taking a sequence of tomograms during the wash-in and wash-out phase of the tracer. Due to the dynamic nature of the process, a highly sensitive and fast moving single photon emission computed tomograph (SPECT) is required. Two brain-dedicated SPECT systems designed for this purpose are mentioned, and the method is described with special reference to the limitations inherent in the soft energy of the 133Xe primary photons. CBF tomography can be used for a multitude of clinical and investigative purposes. This article discusses in particular its use for the selection of patients with carotid occlusion for extracranial/intracranial bypass surgery, for detection of severe arterial spasm after aneurysm bleeding, and for detection of low flow areas during severe migraine attacks. The use of other tracers for CBF tomography using SPECT is summarized with emphasis on the /sup 99m/Tc chelates that freely pass the intact blood-brain barrier. The highly sensitive brain-dedicated SPECT systems described are a prerequisite for achieving high resolution tomograms with such tracers.

  15. Ocular Blood Flow Autoregulation Mechanisms and Methods

    Directory of Open Access Journals (Sweden)

    Xue Luo


    Full Text Available The main function of ocular blood flow is to supply sufficient oxygen and nutrients to the eye. Local blood vessels resistance regulates overall blood distribution to the eye and can vary rapidly over time depending on ocular need. Under normal conditions, the relation between blood flow and perfusion pressure in the eye is autoregulated. Basically, autoregulation is a capacity to maintain a relatively constant level of blood flow in the presence of changes in ocular perfusion pressure and varied metabolic demand. In addition, ocular blood flow dysregulation has been demonstrated as an independent risk factor to many ocular diseases. For instance, ocular perfusion pressure plays key role in the progression of retinopathy such as glaucoma and diabetic retinopathy. In this review, different direct and indirect techniques to measure ocular blood flow and the effect of myogenic and neurogenic mechanisms on ocular blood flow are discussed. Moreover, ocular blood flow regulation in ocular disease will be described.

  16. Effects of brain-directed nutrients on cerebral blood flow and neuropsychological testing: a randomized, double-blind, placebo-controlled, crossover trial. (United States)

    Amen, Daniel G; Taylor, Derek V; Ojala, Kristine; Kaur, Jasleen; Willeumier, Kristen


    In a prior open trial of professional football players who displayed the effects of traumatic brain injury, the current reserach team reported significant improvements in clinical symptoms, neuropsychological testing and regional cerebral blood flow (rCBF) following the use of brain-directed nutrients (BDNs) and lifestyle interventions. The current study intended to determine whether supplementation with BDNs improved rCBF and neuropsychological function in healthy individuals. The current study was a randomized, doubleblind, placebo-controlled, crossover trial, which was a more rigorous reseach design than the prior study and did not include lifestyle interventions. Participants underwent evaluation and testing at the Amen Clinics, Inc, a private medical facility in Newport Beach, CA. Thirty healthy adult (15 male and 15 female) participants were recruited from the community though local advertising and met the requirements for eligibility into the study. Twenty-five individuals completed the study, with dropout due to events unrelated to the study itself. The participants were randomly assigned to a treatment order for intervention, either placebo or brain supplements first. The BDNs treatment was comprised of three supplements: fish oil; a high-potency, multiple vitamin/mineral supplement; and a brainenhancement supplement. The placebo treatment was two supplements comprised of rice flour to replace the multiple vitamin/mineral complex and the brain-enhancement supplement and one supplement made of other oils to replace the fish-oil mixture. After 2 mo of this first intervention, a crossover intervention occurred for a final 2 mo, in which participants formerly receiving BDNs received a placebo treatment and participants formerly treated with placebo received the BDNs treatment. Primary outcome measures included (1) an analysis of the changes in rCBF using SPECT and (2) an assessment of the differences in cognitive and emotional function using the Micro

  17. Evaluation of a New Brain Tissue Probe for Intracranial Pressure, Temperature, and Cerebral Blood Flow Monitoring in Patients with Aneurysmal Subarachnoid Hemorrhage. (United States)

    Seule, Martin; Sikorski, Christopher; Sakowitz, Oliver; von Campe, Gord; Santos, Edgar; Orakcioglu, Berk; Unterberg, Andreas; Keller, Emanuela


    To evaluate an intraparenchymal probe for intracranial pressure (ICP) and temperature (TEMP) monitoring as well as determination of cerebral hemodynamics using a near-infrared spectroscopy (NIRS) and indocyanine green (ICG) dye dilution method (NIRS-ICP probe). The NIRS-ICP probe was applied after aneurysmal subarachnoid hemorrhage if multimodal monitoring was established due to poor neurological condition. ICP and TEMP values were obtained from ventricular catheters and systemic temperature sensors. Repeated NIRS-ICG measurements (2 injections within 30 min) were performed daily for determination of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time of ICG (mttICG). Secondary neurologic dysfunction was defined as brain tissue oxygen tension 35 obtained from cerebral probing. A total of 128 NIRS-ICG measurements were performed in ten patients. The correlation coefficients between ICP and TEMP values obtained with the NIRS-ICP probe and values from routine monitoring were r = 0.72 and r = 0.96, respectively. The mean values were 30.3 ± 13.6 ml/100 g/min for CBF, 3.3 ± 1.2 ml/100 g for CBV, and 6.8 ± 1.6 s for mttICG. The coefficients of variation from repeated NIRS-ICG measurements were 10.9 % for CBF, 11.7 % for CBV, and 3.8 % for mttICG. The sensitivity for detection of secondary neurologic dysfunction was 85 % and the specificity 83 % using a CBF-threshold of 25 ml/100 g/min. Multimodal monitoring using the NIRS-ICP probe is feasible with high reproducibility of measurement values and the ability to detect secondary neurologic dysfunction. No safety concerns exist for the routine clinical use of the NIRS-ICP probe.

  18. Support with intra-aortic balloon pump vs. Impella2.5® and blood flow to the heart, brain and kidneys - an experimental porcine model of ischaemic heart failure. (United States)

    Møller-Helgestad, Ole K; Poulsen, Christian B; Christiansen, Evald H; Lassen, Jens F; Ravn, Hanne B


    Cardiogenic shock as a complication to an acute myocardial infarction has an unacceptably high death rate that has not changed for the last 15years. Mortality is partly related to organ hypoperfusion and mechanical assist devices are used for the most severe cases but we do not know which assist device is the best option. Therefore, we have investigated how an IABP and an Impella®-pump influenced blood flow to the brain, heart and kidneys, in a closed-chest porcine model of severe left ventricular failure. 13 pigs were anesthetised and left ventricular failure was induced by occluding the proximal LAD for 45min followed by 30min of reperfusion. Blood flow was measured in the carotid artery, the LAD, and the renal artery. The Impella® and IABP were inserted via the femoral arteries, and the two devices were tested individually and combined after induction of heart failure. Carotid- (p=0.01) and renal blood flow (p=0.045) were higher on Impella®-support, compared to no support. None of the devices altered the blood flow in the LAD. Cardiac power output (p<0.005) and left ventricular work (p<0.00) were also higher on Impella®-support compared to no support. Haemodynamics and blood flow to the brain and kidneys were significantly better on Impella®-support, suggesting that the Impella® is superior to the IABP in a state of ischaemia induced left ventricular failure. These data, however, needs to be confirmed in a proper clinical trial with patients in cardiogenic shock. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Transfer function analysis for the assessment of cerebral autoregulation using spontaneous oscillations in blood pressure and cerebral blood flow

    NARCIS (Netherlands)

    van den Abeelen, Aisha; Beek, Arenda H.E.A.; Slump, Cornelis H.; Panerai, Ronney B.; Claassen, Jurgen A.H.R.


    Cerebral autoregulation (CA) is a key mechanism to protect the brain against excessive fluctuations in blood pressure (BP) and maintain cerebral blood flow. Analyzing the relationship between spontaneous BP and cerebral blood flow velocity (CBFV) using transfer function analysis is a widely used

  20. Cholinesterase inhibition improves blood flow in the ischemic cerebral cortex. (United States)

    Scremin, O U; Li, M G; Scremin, A M; Jenden, D J


    The ability of central cholinesterase inhibition to improve cerebral blood flow in the ischemic brain was tested in Sprague-Dawley rats with tandem occlusion of left middle cerebral and common carotid arteries. Cerebral blood flow was measured with lodo- 14C-antipyrine autoradiography in 170 regions of cerebral cortex. The regional distribution of blood flow was characterized in normal animals by cerebral blood flow maxima in the temporal regions. After 2 h ischemia, minimum cerebral blood flow values were found in the lateral frontal and parietal areas on the left hemisphere, and a new maximum was found in the right hemisphere in an area approximately symmetrical to the ischemic focus. Heptyl-physostigmine (eptastigmine), a carbamate cholinesterase inhibitor with prolonged time of action improved cerebral blood flow in most regions, with the exception of the ischemic core. The drug also enhanced the ischemia-induced rostral shift of cerebral blood flow maxima in the right hemisphere. The effects of eptastigmine were more marked 24 h after ischemia. Discriminant analysis showed that data from only 22 regions was sufficient to achieve 100% accuracy in classifying all cases into the various experimental conditions. The redistribution of cerebral blood flow to the sensorimotor area of the right hemisphere of animals with cerebral ischemia, a phenomenon possibly related to recovery of function, was also enhanced by eptastigmine.

  1. Blood-Brain Transfer of Pittsburgh Compound B in Humans

    Directory of Open Access Journals (Sweden)

    Albert eGjedde


    Full Text Available In the labeled form, the Pittsburgh compound B (2-(4’-{N-methyl-[11C]}methyl-aminophenyl-6-hydroxybenzothiazole,[11C]PiB, is used as a biomarker for positron emission tomography (PET of brain □-amyloiddeposition in Alzheimer’s disease (AD. The permeability of [11C]PiB in the blood-brain barrier is held tobe high but the permeability-surface area product and extraction fractions in patients or healthy volunteersare not known. We used PET to determine the clearance associated with the unidrectional blood-braintransfer of [11C]PiB and the corresponding cerebral blood flow rates in frontal lobe, whole cerebral cortex,and cerebellum of patients with Alzheimer’s disease and healthy volunteers. Regional cerebral blood flowrates differed significantly between the two groups, but regional and whole-brain permeability-surface areaproducts were identical, in agreement with the observation that numerically, but insignificantly, unidirectionalblood-brain clearances are lower and extraction fractions higher in the patients. The evidence of unchangedpermeability-surface area products in the patients implies that blood flow changes can be deduced from theunidirectional blood-brain clearances of [11C]PiB in the patients.

  2. Atlas-based and DTI-guided quantification of human brain cerebral blood flow: feasibility, quality assurance, spatial heterogeneity and age effects. (United States)

    Hasan, Khader M; Ali, Hiba; Shad, Mujeeb U


    Accurate and noninvasive quantification of regional cerebral blood perfusion (CBF) of the human brain tissue would advance the study of the complex interplay between human brain structure and function, in both health and disease. Despite the plethora of works on CBF in gray matter, a detailed quantitative white matter perfusion atlas has not been presented on healthy adults using the International Consortium for Brain Mapping atlases. In this study, we present a host of assurance measures such as temporal stability, spatial heterogeneity and age effects of regional and global CBF in selected deep, cortical gray matter and white matter tracts identified and quantified using diffusion tensor imaging (DTI). We utilized whole brain high-resolution DTI combined with arterial spin labeling to quantify regional CBF on 15 healthy adults aged 23.2-57.1years. We present total brain and regional CBF, corresponding volume, mean diffusivity and fractional anisotropy spatial heterogeneity, and dependence on age as additional quality assurance measures to compare with published trends using both MRI and nuclear medicine methods. Total CBF showed a steady decrease with age in gray matter (r=-0.58; P=.03), whereas total CBF of white matter did not significantly change with age (r=0.11; P=.7). This quantitative report offers a preliminary baseline of CBF, volume and DTI measurements for the design of future multicenter and clinical studies utilizing noninvasive perfusion and DT-MRI. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Regulation of exercise blood flow: Role of free radicals. (United States)

    Trinity, Joel D; Broxterman, Ryan M; Richardson, Russell S


    During exercise, oxygen and nutrient rich blood must be delivered to the active skeletal muscle, heart, skin, and brain through the complex and highly regulated integration of central and peripheral hemodynamic factors. Indeed, even minor alterations in blood flow to these organs have profound consequences on exercise capacity by modifying the development of fatigue. Therefore, the fine-tuning of blood flow is critical for optimal physical performance. At the level of the peripheral circulation, blood flow is regulated by a balance between the mechanisms responsible for vasodilation and vasoconstriction. Once thought of as toxic by-products of in vivo chemistry, free radicals are now recognized as important signaling molecules that exert potent vasoactive responses that are dependent upon the underlying balance between oxidation-reduction reactions or redox balance. Under normal healthy conditions with low levels of oxidative stress, free radicals promote vasodilation, which is attenuated with exogenous antioxidant administration. Conversely, with advancing age and disease where background oxidative stress is elevated, an exercise-induced increase in free radicals can further shift the redox balance to a pro-oxidant state, impairing vasodilation and attenuating blood flow. Under these conditions, exogenous antioxidants improve vasodilatory capacity and augment blood flow by restoring an "optimal" redox balance. Interestingly, while the active skeletal muscle, heart, skin, and brain all have unique functions during exercise, the mechanisms by which free radicals contribute to the regulation of blood flow is remarkably preserved across each of these varied target organs. Published by Elsevier Inc.

  4. Postishemic Cerebral Function and Blood Flow

    Directory of Open Access Journals (Sweden)

    V. V. Aleksandrin


    Full Text Available The impact of massive blood loss on cerebral blood flow-function relationships was studied in rats in the postis-chemic period. Anxiety was examined in the raised cross-shaped labyrinth. Cerebral blood flow was registered by a laser Doppler flowmeter. One-hour massive blood flow substantially increased the level of anxiety in 75% of the rats following 7 and 20 days. There were no significant behavior changes in 25% of the animals. Experimental animals with preserved behavioral parameters showed cerebral blood flow resistance to ischemia and reperfusion while rats with increased anxiety were found to have delayed postischemic hypoperfusion. Thus, a relationship was found between the behavior of the rats and the resistance of cerebral blood flow to ischemia and reperfusion.

  5. Flow distributions and spatial correlations in human brain capillary networks (United States)

    Lorthois, Sylvie; Peyrounette, Myriam; Larue, Anne; Le Borgne, Tanguy


    The vascular system of the human brain cortex is composed of a space filling mesh-like capillary network connected upstream and downstream to branched quasi-fractal arterioles and venules. The distribution of blood flow rates in these networks may affect the efficiency of oxygen transfer processes. Here, we investigate the distribution and correlation properties of blood flow velocities from numerical simulations in large 3D human intra-cortical vascular network (10000 segments) obtained from an anatomical database. In each segment, flow is solved from a 1D non-linear model taking account of the complex rheological properties of blood flow in microcirculation to deduce blood pressure, blood flow and red blood cell volume fraction distributions throughout the network. The network structural complexity is found to impart broad and spatially correlated Lagrangian velocity distributions, leading to power law transit time distributions. The origins of this behavior (existence of velocity correlations in capillary networks, influence of the coupling with the feeding arterioles and draining veins, topological disorder, complex blood rheology) are studied by comparison with results obtained in various model capillary networks of controlled disorder. ERC BrainMicroFlow GA615102, ERC ReactiveFronts GA648377.

  6. Markers for blood-brain barrier integrity

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld


    known when first introduced, but seem to have been forgotten since. Understanding these limitations is important because Evans blue is still the most commonly used marker of brain barrier integrity and those using it seem oblivious to problems arising from its in vivo application. The introduction......In recent years there has been a resurgence of interest in brain barriers and various roles their intrinsic mechanisms may play in neurological disorders. Such studies require suitable models and markers to demonstrate integrity and functional changes at the interfaces between blood, brain......, and cerebrospinal fluid. Studies of brain barrier mechanisms and measurements of plasma volume using dyes have a long-standing history, dating back to the late nineteenth-century. Their use in blood-brain barrier studies continues in spite of their known serious limitations in in vivo applications. These were well...

  7. Blood flow reprograms lymphatic vessels to blood vessels. (United States)

    Chen, Chiu-Yu; Bertozzi, Cara; Zou, Zhiying; Yuan, Lijun; Lee, John S; Lu, MinMin; Stachelek, Stan J; Srinivasan, Sathish; Guo, Lili; Vicente, Andres; Vincente, Andres; Mericko, Patricia; Levy, Robert J; Makinen, Taija; Oliver, Guillermo; Kahn, Mark L


    Human vascular malformations cause disease as a result of changes in blood flow and vascular hemodynamic forces. Although the genetic mutations that underlie the formation of many human vascular malformations are known, the extent to which abnormal blood flow can subsequently influence the vascular genetic program and natural history is not. Loss of the SH2 domain-containing leukocyte protein of 76 kDa (SLP76) resulted in a vascular malformation that directed blood flow through mesenteric lymphatic vessels after birth in mice. Mesenteric vessels in the position of the congenital lymphatic in mature Slp76-null mice lacked lymphatic identity and expressed a marker of blood vessel identity. Genetic lineage tracing demonstrated that this change in vessel identity was the result of lymphatic endothelial cell reprogramming rather than replacement by blood endothelial cells. Exposure of lymphatic vessels to blood in the absence of significant flow did not alter vessel identity in vivo, but lymphatic endothelial cells exposed to similar levels of shear stress ex vivo rapidly lost expression of PROX1, a lymphatic fate-specifying transcription factor. These findings reveal that blood flow can convert lymphatic vessels to blood vessels, demonstrating that hemodynamic forces may reprogram endothelial and vessel identity in cardiovascular diseases associated with abnormal flow.

  8. Bone blood flow and metabolism in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Kemppainen, Jukka; Kaskinoro, Kimmo


    Human bone blood flow and metabolism during physical exercise remains poorly characterised. In the present study we measured femoral bone blood flow and glucose uptake in young healthy subjects by positron emission tomography in three separate protocols. In six women, blood flow was measured...... in femoral bone at rest and during one leg intermittent isometric exercise with increasing exercise intensities. In nine men, blood flow in femur was determined at rest and during dynamic one leg exercise, and two other physiological perturbations: moderate systemic hypoxia (14 O(2) ) at rest and during...... exercise, and during intra-femoral infusion of high-dose adenosine. Bone glucose uptake was measured at rest and during dynamic one leg exercise in five men. The results indicate that isometric exercise increased femoral bone blood flow from rest (1.8 ± 0.6 ml/100g/min) to low intensity exercise (4.1 ± 1...

  9. Ciliary Blood Flow and Aqueous Humor Production (United States)

    Kiel, J.W.; Hollingsworth, M.; Rao, R.; Chen, M.; Reitsamer, H.A.


    Aqueous humor production is a metabolically active process sustained by the delivery of oxygen and nutrients and removal of metabolic waste by the ciliary circulation. This article describes our investigations into the relationship between ciliary blood flow and aqueous humor production. The results presented indicate that there is a dynamic relationship between ciliary blood flow and aqueous humor production, with production being blood flow independent above a critical level of perfusion, and blood flow dependent below it. The results also show that the plateau portion of the relationship shifts up or down depending on the level of secretory stimulation or inhibition, and that oxygen is one critical factor provided by ciliary blood flow. Also presented is a theoretical model of ocular hydrodynamics incorporating these new findings. PMID:20801226

  10. The Physics of Coronary Blood Flow

    CERN Document Server

    Zamir, M


    Coronary blood flow is blood flow to the heart for its own metabolic needs. In the most common form of heart disease there is a disruption in this flow because of obstructive disease in the vessels that carry the flow. The subject of coronary blood flow is therefore associated mostly with the pathophysiology of this disease, rarely with dynamics or physics. Yet, the system responsible for coronary blood flow, namely the "coronary circulation," is a highly sophisticated dynamical system in which the dynamics and physics of the flow are as important as the integrity of the conducting vessels. While an obstruction in the conducting vessels is a fairly obvious and clearly visible cause of disruption in coronary blood flow, any discord in the complex dynamics of the system can cause an equally grave, though less conspicuous, disruption in the flow. This book is devoted specifically to the dynamics and physics of coronary blood flow. While relevance to the clinical and pathophysiological issues is clearly maintaine...

  11. Tomographic cerebral blood flow measurement during carotid surgery

    DEFF Research Database (Denmark)

    Rathenborg, Lisbet Knudsen; Vorstrup, Sidsel; Olsen, K S


    OBJECTIVES: The aim of the study was to depict regional cerebral blood flow (rCBF) during carotid cross clamping using 99mTechnetium-hexamethylpropylene amine oxime (TcHMPAO). This tracer rapidly passes the blood-brain barrier and is retained for hours in the brain tissue. Injecting TcHMPAO during......, Copenhagen, Denmark. MATERIAL: 15 patients who during a period of 4 months underwent carotid endarterectomy. CHIEF OUTCOME MEASURES: Prior to surgery rCBF was determined using 133Xe and SPECT. Intraoperatively stump pressure was measured and a bolus of TcHMPAO was injected for later SPECT measurement. MAIN...

  12. Iodoamphetamine as a new tracer for local cerebral blood flow in the rat

    DEFF Research Database (Denmark)

    Rapin, J R; Le Poncin-Lafitte, M; Duterte, D


    blood flow and a more real estimation of hippocampal flow. It is concluded from the brain uptake of the derivatives of both amphetamines during the first minutes following their injection that these tracers can be used as a chemical microembolus for the measurement of local cerebral blood flow....

  13. Intraoperative multi-exposure speckle imaging of cerebral blood flow. (United States)

    Richards, Lisa M; Kazmi, Sm Shams; Olin, Katherine E; Waldron, James S; Fox, Douglas J; Dunn, Andrew K


    Multiple studies have demonstrated that laser speckle contrast imaging (LSCI) has high potential to be a valuable cerebral blood flow monitoring technique during neurosurgery. However, the quantitative accuracy and sensitivity of LSCI is limited, and highly dependent on the exposure time. An extension to LSCI called multi-exposure speckle imaging (MESI) overcomes these limitations, and was evaluated intraoperatively in patients undergoing brain tumor resection. This clinical study ( n = 8) recorded multiple exposure times from the same cortical tissue area spanning 0.5-20 ms, and evaluated images individually as single-exposure LSCI and jointly using the MESI model. This study demonstrated that the MESI estimates provided the broadest flow sensitivity for sampling the flow magnitude in the human brain, closely followed by the shorter exposure times. Conservation of flow analysis on vascular bifurcations was used to validate physiological accuracy, with highly conserved flow estimates (goodness-of-fit with proper image calibration and acquisition, and was used to monitor blood flow changes after tissue cautery. Results from this study demonstrate that intraoperative MESI can be performed with high quantitative accuracy and sensitivity for cerebral blood flow monitoring.

  14. Blood flow autoregulation in pedicled flaps

    DEFF Research Database (Denmark)

    Bonde, Christian T; Holstein-Rathlou, Niels-Henrik; Elberg, Jens J


    INTRODUCTION: Clinical work on the blood perfusion in skin and muscle flaps has suggested that some degree of blood flow autoregulation exists in such flaps. An autoregulatory mechanism would enable the flap to protect itself from changes in the perfusion pressure. The purpose of the present study...... was to evaluate if, and to what extent, a tissue flap could compensate a reduction in blood flow due to an acute constriction of the feed artery. Further, we wanted to examine the possible role of smooth muscle L-type calcium channels in the autoregulatory mechanism by pharmacological intervention with the L......-type calcium channel blocker nimodipine and the vasodilator papaverine. MATERIAL AND METHODS: Pedicled flaps were raised in pigs. Flow in the pedicle was reduced by constriction of the feed artery (n=34). A transit time flow probe measured the effect on blood flow continuously. Following this, three different...

  15. Analysis of music-brain interaction with simultaneous measurement of regional cerebral blood flow and electroencephalogram beta rhythm in human subjects. (United States)

    Nakamura, S; Sadato, N; Oohashi, T; Nishina, E; Fuwamoto, Y; Yonekura, Y


    To elucidate the neural substrates of the receptive aspect of music, we measured regional cerebral blood flow (rCBF) with positron emission tomography (PET) and simultaneously recorded the electroencephalogram (EEG) in eight normal volunteers. Compared with the rest condition, listening to music caused a significant increase in EEG beta power spectrum (13-30 Hz) averaged over the posterior two third of the scalp. The averaged beta power spectrum was positively correlated with rCBF in the premotor cortex and adjacent prefrontal cortices bilaterally, the anterior portion of the precuneus and the anterior cingulate cortex in both the rest and the music conditions. Listening to music newly recruited the posterior portion of the precuneus bilaterally. This may reflect the interaction of the music with the cognitive processes, such as music-evoked memory recall or visual imagery.

  16. Cortical spreading depression causes a long-lasting decrease in cerebral blood flow and induces tolerance to permanent focal ischemia in rat brain. (United States)

    Otori, Tatsuo; Greenberg, Joel H; Welsh, Frank A


    Cortical spreading depression (CSD) has previously been shown to induce tolerance to a subsequent episode of transient cerebral ischemia. The objective of the present study was to determine whether CSD also induces tolerance to permanent focal ischemia and, if so, whether tolerance may be mediated by alterations in cerebral blood flow (CBF). Sprague-Dawley rats were preconditioned by applying potassium chloride to one hemisphere for 2 hours, evoking 19 +/- 5 episodes of CSD (mean +/- SD, n = 19). Three days later, the middle cerebral artery (MCA) was permanently occluded using an intraluminal suture. In a subset of animals, laser Doppler blood flow (LDF) was monitored over the parietal cortex before and during the first 2 hours of MCA occlusion. Preconditioning with CSD reduced the hemispheric volume of infarction from 248 +/- 115 mm3 (n = 18) in sham-conditioned animals to 161 +/- 81 mm3 (n = 19, P< 0.02). Similarly, CSD reduced the neocortical volume of infarction from 126 +/- 82 mm3 to 60 +/- 61 mm3 (P < 0.01). Moreover, preconditioning with CSD significantly improved LDF during MCA occlusion from 21% +/- 7% (n = 9) of preischemic baseline in sham-conditioned animals to 29% +/- 9% (n = 7, P< 0.02). Preconditioning with CSD therefore preserved relative levels of CBF during focal ischemia and reduced the extent of infarction resulting from permanent MCA occlusion. To determine whether CSD may have altered preischemic baseline CBF, [14 C]iodoantipyrine was used in additional animals to measure CBF 3 days after CSD conditioning or sham conditioning. CSD, but not sham conditioning, significantly reduced baseline CBF in the ipsilateral neocortex to values 67% to 75% of those in the contralateral cortex. Therefore, CSD causes a long-lasting decrease in baseline CBF that is most likely related to a reduction in metabolic rate. A reduction in the rate of metabolism may contribute to the induction of tolerance to ischemia after preconditioning with CSD.

  17. Diagnosis based on nuclear medicine in intensive care as demonstrated by acute and chronic failures of blood flow (brain, lungs, heart, kidneys)

    Energy Technology Data Exchange (ETDEWEB)

    Moser, E.; Buell, U.


    The value of nuclear medicine procedures which are noninvasive and impose little burden on the patient is assessed with respect of intensive care. Firstly, additional data are available to evaluate physiological functions. Secondly, these functions can be monitored under therapy. Thirdly, screening of the contralateral organ or of other organs can be provided. Cerebral procedures yield values of regional cerebral blood flow (ml/100 g/min) in addition to the morphological findings of CT. Cardiovascular procedures are supplementary in describing the regional as well as the global cardiac function. Using myocardium imaging with thallium-201 the extent of infarction can be estimated. In the crucial diagnosis of pulmonary embolism, radionuclide studies provide the necessary information. Renal procedures evaluate single kidney function yielding clearance values (ml/min). Furthermore, radionuclide flow studies are useful to detect early complications of transplanted kidneys. Diagnostic procedures with radionuclides could be even more efficient if all instruments were available in the intensive care unit or could be transported there instead of transferring the patients to the nuclear medicine department.

  18. Geometric analysis and blood flow simulation of basilar artery. (United States)

    Lee, Sang Hyuk; Hur, Nahmkeon; Jeong, Seul-Ki


    The aim of this study was to find a region of low wall shear stress (WSS) in a basilar artery using 3-dimensional (3D) geometric analysis and blood flow simulation. A 61-year-old patient who underwent follow-up time-of-flight magnetic resonance angiography (TOF-MRA) of the brain was recruited as the subject of the present study. In the basilar artery, the angle of the directional vector was calculated for the region of low WSS. The subject's 3D arterial geometry and blood flow velocity from a transcranial Doppler examination were used for a blood flow simulation study. The regions of low WSS identified by both geometric analysis and blood flow simulation were compared, and these methods were repeated for the basilar arteries of various geometries from other patients. Two distinct arterial angulations along the basilar artery were identified: lateral and anterior angulations on the anteroposterior and lateral TOF-MR views, respectively. A low WSS region was observed in the distal portion along the inner curvatures of both angulations in the basilar artery. The directional vectors of the region of low WSS calculated by geometric analysis and blood flow simulation were very similar (correlation coefficient= 0.996, p flow simulation of the basilar artery identified lateral and anterior angulations which determined the low WSS region in the distal portion along the inner curvatures of the angulations.

  19. Brachial blood flow under relative levels of blood flow restriction is decreased in a nonlinear fashion. (United States)

    Mouser, J Grant; Ade, Carl J; Black, Christopher D; Bemben, Debra A; Bemben, Michael G


    Blood flow restriction (BFR), the application of external pressure to occlude venous return and restrict arterial inflow, has been shown to increase muscular size and strength when combined with low-load resistance exercise. BFR in the research setting uses a wide range of pressures, applying a pressure based upon an individual's systolic pressure or a percentage of occlusion pressure; not a directly determined reduction in blood flow. The relationship between relative pressure and blood flow has not been established. To measure blood flow in the arm under relative levels of BFR. Forty-five people (18-40 years old) participated. Arterial occlusion pressure in the right arm was measured using a 5-cm pneumatic cuff. Blood flow in the brachial artery was measured at rest and at pressures between 10% and 90% of occlusion using ultrasound. Blood flow decreased in a nonlinear, stepped fashion. Blood flow decreased at 10% of occlusion and remained constant until decreasing again at 40%, where it remained until 90% of occlusion. The decrease in brachial blood flow is not proportional to the applied relative pressure. The prescription of blood flow restriction should take into account the stimulus provided at each relative level of blood flow. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  20. Frequency encoding in renal blood flow regulation

    DEFF Research Database (Denmark)

    Marsh, Donald J; Sosnovtseva, Olga; Pavlov, Alexey N


    With a model of renal blood flow regulation, we examined consequences of tubuloglomerular feedback (TGF) coupling to the myogenic mechanism via voltage-gated Ca channels. The model reproduces the characteristic oscillations of the two mechanisms and predicts frequency and amplitude modulation...... of the myogenic oscillation by TGF. Analysis by wavelet transforms of single-nephron blood flow confirms that both amplitude and frequency of the myogenic oscillation are modulated by TGF. We developed a double-wavelet transform technique to estimate modulation frequency. Median value of the ratio of modulation...... TGF cycle to the next. We used a blood pressure signal recorded by telemetry from a conscious rat as the input to the model. Blood pressure fluctuations induced variability in the modulation records similar to those found in the nephron blood flow results. Frequency and amplitude modulation can...

  1. The blood-brain barrier in psychoneuroimmunology. (United States)

    Banks, William A


    The term ''psychoneuroimmunology'' connotes separate compartments that interact. The blood-brain barrier (BBB) is both the dividing line, physical and physiologic, between the immune system and the central nervous system (CNS) and the locale for interaction. The BBB restricts unregulated mixing of immune substances in the blood with those in the CNS, directly transports neuroimmune-active substances between the blood and CNS, and itself secretes neuroimmune substances. These normal functions of the BBB can be altered by neuroimmune events. As such, the BBB is an important conduit in the communication between the immune system and the CNS.

  2. Blood, brain and binocular vision. (United States)

    Rostron, Egle; Dickerson, Mary Polly; Heath, Gregory


    A man aged 51 years presented with sudden onset, horizontal, binocular, double vision and right facial weakness. Ocular motility examination demonstrated a right horizontal gaze palsy pattern in keeping with a one-and-a-half syndrome. Since this was associated with a concomitant, ipsilateral, lower motor neuron (LMN) facial (VIIth) cranial nerve palsy, he had acquired an eight-and-a-half syndrome. Diffusion-weighted MRI confirmed a small infarcted area in the pons of the brainstem which correlated with anatomical location of the horizontal gaze centre and VIIth cranial nerve fasciculus. As a result of this presentation, further investigations uncovered a hitherto undiagnosed blood dyscrasia-namely polycythaemia vera. Regular venesection was started which resulted in complete resolution of his ocular motility dysfunction and an improvement of his LMN facial nerve palsy. 2017 BMJ Publishing Group Ltd.

  3. Apparent brain temperature imaging with multi-voxel proton magnetic resonance spectroscopy compared with cerebral blood flow and metabolism imaging on positron emission tomography in patients with unilateral chronic major cerebral artery steno-occlusive disease

    Energy Technology Data Exchange (ETDEWEB)

    Nanba, Takamasa; Nishimoto, Hideaki; Murakami, Toshiyuki; Fujiwara, Shunrou; Ogasawara, Kuniaki [Iwate Medical University, Department of Neurosurgery, Iwate (Japan); Yoshioka, Yoshichika [Osaka University, Open and Transdisciplinary Research Initiatives, Osaka (Japan); Sasaki, Makoto; Uwano, Ikuko [Iwate Medical University, Institute for Biomedical Science, Iwate (Japan); Terasaki, Kazunori [Iwate Medical University, Cyclotron Research Center, Iwate (Japan)


    The purpose of the present study was to determine whether apparent brain temperature imaging using multi-voxel proton magnetic resonance (MR) spectroscopy correlates with cerebral blood flow (CBF) and metabolism imaging in the deep white matter of patients with unilateral chronic major cerebral artery steno-occlusive disease. Apparent brain temperature and CBF and metabolism imaging were measured using proton MR spectroscopy and {sup 15}O-positron emission tomography (PET), respectively, in 35 patients. A set of regions of interest (ROIs) of 5 x 5 voxels was placed on an MR image so that the voxel row at each edge was located in the deep white matter of the centrum semiovale in each cerebral hemisphere. PET images were co-registered with MR images with these ROIs and were re-sliced automatically using image analysis software. In 175 voxel pairs located in the deep white matter, the brain temperature difference (affected hemisphere - contralateral hemisphere: ΔBT) was correlated with cerebral blood volume (CBV) (r = 0.570) and oxygen extraction fraction (OEF) ratios (affected hemisphere/contralateral hemisphere) (r = 0.641). We excluded voxels that contained ischemic lesions or cerebrospinal fluid and calculated the mean values of voxel pairs in each patient. The mean ΔBT was correlated with the mean CBF (r = - 0.376), mean CBV (r = 0.702), and mean OEF ratio (r = 0.774). Apparent brain temperature imaging using multi-voxel proton MR spectroscopy was correlated with CBF and metabolism imaging in the deep white matter of patients with unilateral major cerebral artery steno-occlusive disease. (orig.)

  4. Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain. (United States)

    Liang, Christine L; Ances, Beau M; Perthen, Joanna E; Moradi, Farshad; Liau, Joy; Buracas, Giedrius T; Hopkins, Susan R; Buxton, Richard B


    The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO(2) coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction-independent of details of the model-that if the CBF/CMRO(2) coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/weakest response ratio) of the CMRO(2) response (~1.7-fold) compared to that of the CBF response (~2.4-fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Cerebral blood flow response to functional activation

    DEFF Research Database (Denmark)

    Paulson, Olaf B; Hasselbalch, Steen G; Rostrup, Egill


    Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only...

  6. Neural control of choroidal blood flow. (United States)

    Reiner, Anton; Fitzgerald, Malinda E C; Del Mar, Nobel; Li, Chunyan


    The choroid is richly innervated by parasympathetic, sympathetic and trigeminal sensory nerve fibers that regulate choroidal blood flow in birds and mammals, and presumably other vertebrate classes as well. The parasympathetic innervation has been shown to vasodilate and increase choroidal blood flow, the sympathetic input has been shown to vasoconstrict and decrease choroidal blood flow, and the sensory input has been shown to both convey pain and thermal information centrally and act locally to vasodilate and increase choroidal blood flow. As the choroid lies behind the retina and cannot respond readily to retinal metabolic signals, its innervation is important for adjustments in flow required by either retinal activity, by fluctuations in the systemic blood pressure driving choroidal perfusion, and possibly by retinal temperature. The former two appear to be mediated by the sympathetic and parasympathetic nervous systems, via central circuits responsive to retinal activity and systemic blood pressure, but adjustments for ocular perfusion pressure also appear to be influenced by local autoregulatory myogenic mechanisms. Adaptive choroidal responses to temperature may be mediated by trigeminal sensory fibers. Impairments in the neural control of choroidal blood flow occur with aging, and various ocular or systemic diseases such as glaucoma, age-related macular degeneration (AMD), hypertension, and diabetes, and may contribute to retinal pathology and dysfunction in these conditions, or in the case of AMD be a precondition. The present manuscript reviews findings in birds and mammals that contribute to the above-summarized understanding of the roles of the autonomic and sensory innervation of the choroid in controlling choroidal blood flow, and in the importance of such regulation for maintaining retinal health. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. 21 CFR 870.2120 - Extravascular blood flow probe. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Extravascular blood flow probe. 870.2120 Section... blood flow probe. (a) Identification. An extravascular blood flow probe is an extravascular ultrasonic or electromagnetic probe used in conjunction with a blood flowmeter to measure blood flow in a...

  8. Analyzing Circle of Willis blood flow in ischemic stroke patients through 3D Stroke Arterial Flow Estimation. (United States)

    Chien, Aichi; Viñuela, Fernando


    Background The objective of ischemic stroke (IS) treatment is to achieve revascularization in cerebral arteries to restore blood flow. However, there is no available method to extract arterial flow data from clinical CTA images. We developed 3D Stroke Arterial Flow Estimation (SAFE), which provides blood flow data throughout the Circle of Willis based on 3D CTA and allows comparison of arterial flow distribution in the brain. Methods We implemented a newly developed 3D vascular reconstruction algorithm for clinical stroke CTA images. Based on the patient-specific vascular structure, SAFE calculates time-resolved blood flow information for the entire Circle of Willis and allows quantitative flow study of IS cases. Clinical IS cases are presented to demonstrate the feasibility. Four patients with CTA images and CT perfusion data were studied. To validate the SAFE analysis, correlation analysis comparing blood flow at the MCA, ICA, and BA was performed. Results Different blood flow patterns were found in individual IS patients. Altered flow patterns and high collateral flow rates were found near occlusions in all cases. Quantitative comparison of blood flow data showed that SAFE obtained flow data and CTP were significantly correlated and provide complementary information about cerebral blood flow for individual patients. Conclusions We present SAFE analysis for collecting detailed time-resolved cerebral arterial flow data in the entire Circle of Willis for IS. Further study with more cases may be important to test the clinical utilization of SAFE and helpful to the study of the underlying hemodynamics of stroke.

  9. Quantitative analysis of normal fetal brain volume and flow by three-dimensional power Doppler ultrasound. (United States)

    Hsu, Ju-Chun; Wu, Yi-Cheng; Wang, Peng-Hui; Wang, Hsing-I; Juang, Chi-Mou; Chen, Yi-Jen; Chang, Chia-Ming; Horng, Huann-Cheng; Chen, Chih-Yao; Yang, Ming-Jie; Yen, Ming-Shyen; Chao, Kuan-Chong


    Assessment of the fetal brain volume and blood flow is important in the evaluation of fetal growth. We used three-dimensional (3D) ultrasound and power Doppler to assess the fetal brain volume and the blood flow index during normal gestation. The relationships of these parameters were further analyzed. We assessed the total volume and the blood flow index of the fetal brain in normal pregnancies using 3D ultrasound (Voluson 730). The bilateral parietal diameter (BPD) plane was measured by a 3D transabdominal probe to scan the fetal brain under the power Doppler mode. Then, we quantitatively assessed the total volume of the fetal brain, mean grey area (MG), vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) by applying Kretz VOCAL software. The study included 126 fetuses, ranging from 15 to 38 weeks of gestation. The total volume of the fetal brain was highly positively correlated with the gestational age (GA) (correlation coefficient [r] = 0.976, p flow development quantitatively. Our study indicates that the fetal brain vascularization and blood flow correlates significantly with the advancement of GA. This information may serve as a reference point for further studies of the fetal brain volume and blood flow in abnormal conditions. Copyright © 2013. Published by Elsevier B.V.

  10. Brain network clustering with information flow motifs

    NARCIS (Netherlands)

    Märtens, M.; Meier, J.M.; Hillebrand, Arjan; Tewarie, Prejaas; Van Mieghem, P.F.A.


    Recent work has revealed frequency-dependent global patterns of information flow by a network analysis of magnetoencephalography data of the human brain. However, it is unknown which properties on a small subgraph-scale of those functional brain networks are dominant at different frequencies bands.

  11. Quantifying the influence of oscillatory flow disturbances on blood flow. (United States)

    Gabriel, Sargon A; Ding, Yan; Feng, Yuqing


    Pulsatile blood flow is renowned for inducing localised flow disturbances that are characterised by significant oscillations. These flow disturbances are recognised to have a physiologic significance within the cardiovascular system, particularly with respect to their proatherogenic expression on endothelial cells. Flow disturbances also impart significant influence on the mechanics of cardiovascular flow and are formally shown in the present study to be coupled to the period-average behaviour of a pulsatile flow field, causing it to be misrepresented by its steady-equivalent; which is often used in models of atherogenesis and hence limits their reliability. It is demonstrated that a measure of the localised influence of flow disturbances on the period-average flow can be realised by the relative significance of their kinetic energy, which is quantified by the introduced Oscillatory Kinetic Energy Index (OKEI). A specific measure of direction-reversing oscillations is also developed with the introduction of the Oscillatory Flow Index (OFI), which is an extension of the wall-bound Oscillatory Shear Index (OSI) onto flow and wall spaces. A case study of a human carotid artery is made; wherein pulsatile flow is studied relative to its steady-equivalent state. The introduced indices are demonstrated to collectively identify oscillatory flow disturbances within the flow; quantifying their spatial distribution and influence on the flow field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Effects of Dopamine Infusion on Cerebral Blood Flow, Brain Cell Membrane Function and Energy Metabolism in Experimental Escherichia coli Meningitis in the Newborn Piglet

    National Research Council Canada - National Science Library

    Park, Won Soon; Chang, Yun Sil; Shim, Jae Won; Kim, Mi Jung; Ko, Sun Young; Kim, Sung Shin; Hwang, Jong Hee; Choi, Chang Won; Lee, Munhyang


    .... The decreased cerebral cortical cell membrane Na+, K+ -ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain damage, were significantly attenuated by dopamine infusion...

  13. History of International Society for Cerebral Blood Flow and Metabolism

    DEFF Research Database (Denmark)

    Paulson, Olaf B; Kanno, Iwao; Reivich, Martin


    Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings...... since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has...... grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success...

  14. An implantable blood pressure and flow transmitter. (United States)

    Rader, R. D.; Meehan, J. P.; Henriksen, J. K. C.


    A miniature totally implantable FM/FM telemetry system has been developed to simultaneously measure blood pressure and blood flow, thus providing an appreciation of the hemodynamics of the circulation to the entire body or to a particular organ. Developed for work with animal subjects, the telemetry system's transmission time is controlled by an RF signal that permits an operating life of several months. Pressure is detected by a miniature intravascular transducer and flow is detected by an extravascular interferometric ultrasonic technique. Both pressure and flow are calibrated prior to implanting. The pressure calibration can be checked after the implanting by cannulation; flow calibration can be verified only at the end of the experiment by determining the voltage output from the implanted sensing system as a function of several measured flow rates. The utility of this device has been established by its use in investigating canine renal circulation during exercise, emotional encounters, administration of drugs, and application of accelerative forces.

  15. A preliminary study of brain macrovascular reactivity in impaired glucose tolerance and type-2 diabetes: Quantitative internal carotid artery blood flow using magnetic resonance phase contrast angiography. (United States)

    Selvarajah, Dinesh; Hughes, Timothy; Reeves, Josie; Boland, Elaine; Marques, Jefferson; Gandhi, Rajiv; Griffiths, Paul D; Tesfaye, Solomon; Wilkinson, Iain D


    The aims of this study were (1) to examine cerebrovascular autoregulation in subjects with impaired glucose tolerance and type 2 diabetes and (2) to clarify whether cardiovascular autonomic nerve function is associated with abnormal cerebrovascular autoregulation. Totally, 46 subjects were recruited (12 = impaired glucose tolerance, 17 = type 2 diabetes and 17 = healthy volunteers). Arterial blood flow was assessed within the internal carotid artery at baseline and 20 min after intravenous pharmacological stress (1 g acetazolamide), using quantitative magnetic resonance phase-contrast angiography. Internal carotid artery vascular reactivity and pulsatility index was determined. All subjects underwent baroreceptor reflex sensitivity assessment. Subjects with impaired glucose tolerance and type 2 diabetes had significantly lower internal carotid artery vascular reactivity [40.2%(19.8) and 41.5%(18.7)], respectively, compared with healthy volunteers [57.0%(14.2); analysis of variance, p = 0.02]. There was no significant difference in internal carotid artery vascular reactivity between type 2 diabetes and impaired glucose tolerance groups (p = 0.84). There was a significant positive correlation between baroreceptor reflex sensitivity (low frequency:high frequency) with cardiac rhythm variability (ρ = 0.47, p = 0.04) and PI (ρ = 0.46, p = 0.04). We have demonstrated significant cerebrovascular haemodynamic abnormalities in subjects with type 2 diabetes and impaired glucose tolerance. This was associated with greater sympathovagal imbalance. This may provide an important mechanistic explanation for increased risk of cerebrovascular disease in diabetes. It also highlights that these abnormalities may already be present in prediabetes. © The Author(s) 2016.

  16. The role of cognitive group therapy and happiness training on cerebral blood flow using 99mTc-ECD brain perfusion SPECT: a quasi-experimental study of depressed patients. (United States)

    Azizi, M; Bahrieniain, S A; Baghdasarians, A; Emamipur, S; Azizmohammadi, Z; Qutbi, S M; Javadi, H; Assadi, M; Asli, I N


    The purpose of this study is to investigate the impact of cognitive group therapy and happiness training objectively in the local cerebral blood flow of patients with major depression (MD). The present research is semi-experimental to pre- and post-test with a control group. Three groups were formed, and this number was incorporated in each group: 12 patients were chosen randomly; the first group of depressed patients benefited from the combination of pharmacotherapy and sessions of cognitive group therapy; the second group used a combination of pharmacotherapy and sessions of happiness training; and a third group used only pharmacotherapy. We compared cognitive-behavioural therapy and happiness training efficacy with only pharmacotherapy in MD patients. We performed brain perfusion SPECT in each group, before and after each trial. The study was conducted on 36 patients with MD (32 women and 4 men; mean age: 41.22 ± 9.08; range: 27-65 years). There were significant differences regarding the two trial effects into two experimental groups (p 0.05). In addition, there was significant difference among the regional cerebral blood flow in the frontal and prefrontal regions into two experimental groups before and after trials (p 0.05). This study demonstrated decreased cerebral perfusion in the frontal regions in MD patients, which increased following cognitive group therapy and happiness training. Because of its availability, low costs, easy performance, and the objective semi-quantitative information supplied, brain perfusion SPECT scanning might be useful to assess the diagnosis and therapy efficacy. Further exploration is needed to validate its clinical role.

  17. Hormones and the blood-brain barrier. (United States)

    Hampl, Richard; Bičíková, Marie; Sosvorová, Lucie


    Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

  18. Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype. (United States)

    Phoenix, Timothy N; Patmore, Deanna M; Boop, Scott; Boulos, Nidal; Jacus, Megan O; Patel, Yogesh T; Roussel, Martine F; Finkelstein, David; Goumnerova, Liliana; Perreault, Sebastien; Wadhwa, Elizabeth; Cho, Yoon-Jae; Stewart, Clinton F; Gilbertson, Richard J


    The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The diffusion permeability to water of the rat blood-brain barrier

    DEFF Research Database (Denmark)

    Bolwig, T G; Lassen, N A


    The diffusion permeability to water of the rat blood-brain-barrier (BBB) was studied. Preliminary data obtained with the Oldendorf tissue uptake method (Oldendorf 1970) in seizure experiments suggested that the transfer from blood to brain of labelled water is diffusion-limited. More definite evi...... passage increased from 0.26 to 0.67 when the arterial carbon dioxide tension was changed from 15 to 85 mm Hg, a change increasing the cerebral blood flow about sixfold. This finding suggests that water does not pass the blood-brain barrier as freely as lipophilic gases....

  20. Penile blood flow by xenon-133 washout

    Energy Technology Data Exchange (ETDEWEB)

    Haden, H.T.; Katz, P.G.; Mulligan, T.; Zasler, N.D.


    Penile erectile failure is often attributed to abnormalities of vascular supply or drainage, but few direct measurements of penile blood flow have been made. We describe the xenon washout method for measurement of penile blood flow, and present the results obtained in a group of normal and impotent subjects. The procedure was performed with standard nuclear imaging equipment. Flaccid-state penile blood flow in the impotent patients studied was not significantly different from the normal group, suggesting that flaccid-state measurements may not be helpful in evaluation of erectile failure. However, this method can be used to measure penile venous outflow with stimulated or induced erection, and may provide a method for detecting abnormal venous leakage.

  1. Regulation of blood flow by prostaglandins

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Langberg, H; Risum, N


    Prostaglandins (PGs) belong to the family of prostanoids together with thromboxanes and are produced mainly from arachadonic acid by the enzyme cyclooxygenase. PGs are known to stimulate platelet aggregation, mediate inflammation and edema, play a role in bone metabolism and in biological...... adaptation of connective tissues e.g. tendon. This review covers the role of PG for mediating tissue blood flow at rest and during increases in metabolic demand such as exercise and reactive hyperaemia. There is strong evidence that PGs contribute to elevate blood flow at rest and during reactive hyperaemia...

  2. Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon

    DEFF Research Database (Denmark)

    Strandgaard, S; Jones, J V; MacKenzie, E T


    The effect of arterial hypertension on cerebral blood flow was studied by the intracarotid 133Xe clearance method in baboons. The arterial blood pressure was raised in gradual steps with angiotensin. Baboons with renal hypertension of 8-12 weeks duration were studied along with normotensive baboons....... In initially normotensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had risen to the range of 140 to 154 mm Hg; thereafter cerebral blood flow increased with each rise in mean arterial blood pressure. In the chronically hypertensive baboons, cerebral blood flow...... remained constant until the mean arterial blood pressure had been elevated to the range of 155 to 169 mm Hg. Thus, in chronic hypertension it appears that there are adaptive changes in the cerebral circulation which may help to protect the brain from further increases in arterial blood pressure....

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

    DEFF Research Database (Denmark)

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


    and velocity magnitudes the blood flow patterns were visualised with streamlines in Matlab (Mathworks, Natick, MA, USA). The rotational flow was quantified by the angular frequency for each cardiac cycle, and the mean rotational frequencies and standard deviations were calculated for the abdominal aorta f-1......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...

  4. Using flow feature to extract pulsatile blood flow from 4D flow MRI images (United States)

    Wang, Zhiqiang; Zhao, Ye; Yu, Whitney; Chen, Xi; Lin, Chen; Kralik, Stephen F.; Hutchins, Gary D.


    4D flow MRI images make it possible to measure pulsatile blood flow inside deforming vessel, which is critical in accurate blood flow visualization, simulation, and evaluation. Such data has great potential to overcome problems in existing work, which usually does not reflect the dynamic nature of elastic vessels and blood flows in cardiac cycles. However, the 4D flow MRI data is often low-resolution and with strong noise. Due to these challenges, few efforts have been successfully conducted to extract dynamic blood flow fields and deforming artery over cardiac cycles, especially for small artery like carotid. In this paper, a robust flow feature, particularly the mean flow intensity is used to segment blood flow regions inside vessels from 4D flow MRI images in whole cardiac cycle. To estimate this flow feature more accurately, adaptive weights are added to the raw velocity vectors based on the noise strength of MRI imaging. Then, based on this feature, target arteries are tracked in at different time steps in a cardiac cycle. This method is applied to the clinical 4D flow MRI data in neck area. Dynamic vessel walls and blood flows are effectively generated in a cardiac cycle in the relatively small carotid arteries. Good image segmentation results on 2D slices are presented, together with the visualization of 3D arteries and blood flows. Evaluation of the method was performed by clinical doctors and by checking flow volume rates in the vertebral and carotid arteries.

  5. Information flow dynamics in the brain (United States)

    Rabinovich, Mikhail I.; Afraimovich, Valentin S.; Bick, Christian; Varona, Pablo


    Timing and dynamics of information in the brain is a hot field in modern neuroscience. The analysis of the temporal evolution of brain information is crucially important for the understanding of higher cognitive mechanisms in normal and pathological states. From the perspective of information dynamics, in this review we discuss working memory capacity, language dynamics, goal-dependent behavior programming and other functions of brain activity. In contrast with the classical description of information theory, which is mostly algebraic, brain flow information dynamics deals with problems such as the stability/instability of information flows, their quality, the timing of sequential processing, the top-down cognitive control of perceptual information, and information creation. In this framework, different types of information flow instabilities correspond to different cognitive disorders. On the other hand, the robustness of cognitive activity is related to the control of the information flow stability. We discuss these problems using both experimental and theoretical approaches, and we argue that brain activity is better understood considering information flows in the phase space of the corresponding dynamical model. In particular, we show how theory helps to understand intriguing experimental results in this matter, and how recent knowledge inspires new theoretical formalisms that can be tested with modern experimental techniques.

  6. History of International Society for Cerebral Blood Flow and Metabolism. (United States)

    Paulson, Olaf B; Kanno, Iwao; Reivich, Martin; Sokoloff, Louis


    Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings dealing with CBF and metabolism were arranged, and the fast growing research led to a demand for a specialized journal. In this scientific environment, the International Society for Cerebral Blood Flow and Metabolism (ISCBFM) and its official Journal of Cerebral Metabolism were established in 1981 and has since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success of the society and strengthened the research.

  7. The blood-brain barrier and glutamate. (United States)

    Hawkins, Richard A


    Glutamate concentrations in plasma are 50-100 micromol/L; in whole brain, they are 10,000-12,000 micromol/L but only 0.5-2 micromol/L in extracellular fluids (ECFs). The low ECF concentrations, which are essential for optimal brain function, are maintained by neurons, astrocytes, and the blood-brain barrier (BBB). Cerebral capillary endothelial cells form the BBB that surrounds the entire central nervous system. Tight junctions connect endothelial cells and separate the BBB into luminal and abluminal domains. Molecules entering or leaving the brain thus must pass 2 membranes, and each membrane has distinct properties. Facilitative carriers exist only in luminal membranes, and Na(+)-dependent glutamate cotransporters (excitatory amino acid transporters; EAATs) exist exclusively in abluminal membranes. The EAATs are secondary transporters that couple the Na(+) gradient between the ECF and the endothelial cell to move glutamate against the existing electrochemical gradient. Thus, the EAATs in the abluminal membrane shift glutamate from the ECF to the endothelial cell where glutamate is free to diffuse into blood on facilitative carriers. This organization does not allow net glutamate entry to the brain; rather, it promotes the removal of glutamate and the maintenance of low glutamate concentrations in the ECF. This explains studies that show that the BBB is impermeable to glutamate, even at high concentrations, except in a few small areas that have fenestrated capillaries (circumventricular organs). Recently, the question of whether the BBB becomes permeable in diabetes has arisen. This issue was tested in rats with diet-induced obesity and insulin resistance or with streptozotocin-induced diabetes. Neither condition produced any detectable effect on BBB glutamate transport.

  8. Cerebral blood flow in patients with dementia of Alzheimer's type

    DEFF Research Database (Denmark)

    Postiglione, A; Lassen, N A; Holman, B L


    of the disease. Lateral CBF asymmetry is also very frequent; speech disorders are highly characteristic of left-sided flow reduction, while visuospatial apraxia is dominating in the right-sided cases. In advanced and severe cases of AD, CBF and metabolism tend to be more uniformly reduced throughout the cortex......In the normal brain as well as in Alzheimer's disease (AD), regional cerebral blood flow (CBF) is coupled to metabolic demand and, therefore, changes in CBF reflect variations in neuronal metabolism. The use of radionuclide techniques, such as positron emission tomography (PET) and single photon......-parieto-temporal CBF reduction is highly diagnostic for AD, despite the fact that a similar CBF pattern could also be observed in other types of dementia. Many AD patients with parieto-temporal flow reduction also have a diffuse flow reduction in the frontal cortical areas, particularly in advanced stages...

  9. Cerebral blood flow links insulin resistance and baroreflex sensitivity.

    Directory of Open Access Journals (Sweden)

    John P Ryan

    Full Text Available Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p < .05. Moreover, the relationship between insulin resistance and baroreflex sensitivity was statistically mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01. Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes.

  10. Nonlinear interactions in renal blood flow regulation

    DEFF Research Database (Denmark)

    Marsh, Donald J.; Sosnovtseva, Olga; Chon, Ki H.


    resistance and glomerular capillary pressure. The model couples TGF input to voltage-gated Ca channels. It predicts autoregulation of GFR and renal blood flow, matches experimental measures of tubular pressure and macula densa NaCl concentration, and predicts TGF-induced oscillations and a faster smaller...

  11. Frequency encoding in renal blood flow regulation

    DEFF Research Database (Denmark)

    Marsh, D.J.; Sosnovtseva, Olga; Pavlov, A.N.


    With a model of renal blood flow regulation, we examined consequences of tubuloglomerular feedback (TGF) coupling to the myogenic mechanism via voltage-gated Ca channels. The model reproduces the characteristic oscillations of the two mechanisms and predicts frequency and amplitude modulation...

  12. Cerebral blood flow in acute mountain sickness

    DEFF Research Database (Denmark)

    Jensen, J B; Wright, Anne; Lassen, N A


    Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased...

  13. Blood flow dynamics in the snake spectacle. (United States)

    van Doorn, Kevin; Sivak, Jacob G


    The eyes of snakes are shielded beneath a layer of transparent integument referred to as the 'reptilian spectacle'. Well adapted to vision by virtue of its optical transparency, it nevertheless retains one characteristic of the integument that would otherwise prove detrimental to vision: its vascularity. Given the potential consequence of spectacle blood vessels on visual clarity, one might expect adaptations to have evolved that mitigate their negative impact. Earlier research demonstrated an adaptation to their spatial layout in only one species to reduce the vessels' density in the region serving the foveal and binocular visual fields. Here, we present a study of spectacle blood flow dynamics and provide evidence of a mechanism to mitigate the spectacle blood vessels' deleterious effect on vision by regulation of blood flow through them. It was found that when snakes are at rest and undisturbed, spectacle vessels undergo cycles of dilation and constriction, such that the majority of the time the vessels are fully constricted, effectively removing them from the visual field. When snakes are presented with a visual threat, spectacle vessels constrict and remain constricted for longer periods than occur during the resting cycles, thus guaranteeing the best possible visual capabilities in times of need. Finally, during the snakes' renewal phase when they are generating a new stratum corneum, the resting cycle is abolished, spectacle vessels remain dilated and blood flow remains strong and continuous. The significance of these findings in terms of the visual capabilities and physiology of snakes is discussed.

  14. Stroke and Drug Delivery--In Vitro Models of the Ischemic Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Tornabene, Erica; Brodin, Birger


    and Drug Administration-approved tissue plasminogen activator for treatment of acute ischemic stroke being the most prominent example. A large number of potential drug candidates for treatment of ischemic brain tissue have been developed and subsequently failed in clinical trials. A deeper understanding......Stroke is a major cause of death and disability worldwide. Both cerebral hypoperfusion and focal cerebral infarcts are caused by a reduction of blood flow to the brain, leading to stroke and subsequent brain damage. At present, only few medical treatments of stroke are available, with the Food...... of permeation pathways across the barrier in ischemic and postischemic brain endothelium is important for development of new medical treatments. The blood-brain barrier, that is, the endothelial monolayer lining the brain capillaries, changes properties during an ischemic event. In vitro models of the blood-brain...

  15. Blood-brain barrier damage in vascular dementia. (United States)

    Ueno, Masaki; Chiba, Yoichi; Matsumoto, Koichi; Murakami, Ryuta; Fujihara, Ryuji; Kawauchi, Machi; Miyanaka, Hiroshi; Nakagawa, Toshitaka


    New findings on flow or drainage pathways of brain interstitial fluid and cerebrospinal fluid have been made. The interstitial fluid flow has an effect on the passage of blood-borne substances in the brain parenchyma, especially in areas near blood-brain barrier (BBB)-free regions. Actually, blood-borne substances can be transferred in areas with intact BBB function, such as the hippocampus, the corpus callosum, periventricular areas, and medial portions of the amygdala, presumably through leaky vessels in the subfornical organs or the choroid plexus. Increasing evidence indicates that dysfunction of the BBB function may play a significant role in the pathogenesis of vascular dementia. Accordingly, we have examined which insults seen in patients suffering from vascular dementia have an effect on the BBB using experimental animal models exhibiting some phenotypes of vascular dementia. The BBB in the hippocampus was clearly deteriorated in Mongolian gerbils exposed to acute ischemia followed by reperfusion and also in stroke-prone spontaneously hypertensive rats (SHRSP) showing hypertension. The BBB in the corpus callosum was clearly deteriorated in Wistar rats with permanent ligation of the bilateral common carotid arteries showing chronic hypoperfusion. The BBB in the hippocampus and the olfactory bulb was mildly deteriorated in aged senescence accelerated prone mice (SAMP8) showing cognitive dysfunction. The BBB in the hippocampus was mildly deteriorated in aged animals with hydrocephalus. Mild endothelial damage was seen in hyperglycemic db/db mice. In addition, mRNA expression of osteopontin, matrix metalloproteinase-13 (MMP-13), and CD36 was increased in vessels showing BBB damage in hypertensive SHRSP. As osteopontin, MMP-13 and CD36 are known to be related to brain injury and amyloid β accumulation or clearance, BBB damage followed by increased gene expression of these molecules not only contributes to the pathogenesis of vascular dementia, but also bridges

  16. Influence of Blood Viscosity on Blood Flow and the Effect of Low Molecular Weight Dextran (United States)

    Dormandy, John A.


    Changes in whole blood viscosity are related to changes in the leg blood flow during infusions of low-molecular-weight dextran and Hartmann's solution. A close inverse correlation exists between changes in viscosity and blood flow, the change in blood flow being about three times greater than the change in blood viscosity. The dextran and Hartmann's solution had a similar effect on blood viscosity and blood flow if corrections are made for the difference in haemodilution. PMID:5129616

  17. An Investigation of Head Accelerometry, Cognitive Function, and Brain Blood Flow During Intercollegiate Boxing and its Impact Regarding Head Injury Assessment In Combat (United States)


    Brininger ,Teresa, Kryskow, Elizabeth 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND...ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER HQ USAFA/ADPH 2169 Fieldhouse Drive USAFA, CO 80840 USARIEM Natick, MA 01760 9...Injury, Head Acceleration, MBTI Diagnostics, Cognitive Testing, Brain Acoustic Monitoring, Boxing, Neuropsychology 16. SECURITY CLASSIFICATION OF

  18. Changes in chorioretinal blood flow velocity and cerebral blood flow after carotid endarterectomy. (United States)

    Enaida, Hiroshi; Nagata, Shinji; Takeda, Atsunobu; Nakao, Shintaro; Ikeda, Yasuhiro; Ishibashi, Tatsuro


    To investigate the changes in chorioretinal blood flow velocity and cerebral blood after carotid endarterectomy (CEA). Nine patients with moderate to severe internal carotid artery stenosis underwent CEA. Chorioretinal blood flow velocity was measured by laser speckle flowgraphy (LSFG), while cerebral blood flow (CBF) was measured by single-photon emission computed tomography (SPECT), on the affected side both before and after CEA. LSFG was evaluated in five areas to determine mean blur rate, while CBF was calculated from regional CBF and cerebrovascular reactivity (CVR), at the middle cerebral artery (MCA) region of each patient. Five cases showed an increase (mean 3.49 %, range -29.82 to 35.59 %) of average chorioretinal blood flow velocity using LSFG after CEA. A particularly averaged increase in chorioretinal blood flow was observed in the macular area compared with other areas. Similarly, there was an increase in CBF at rest (mean 11.46 %, range -14.51 to 74.14 %) observed using SPECT after surgery. Improvement of CVR was confirmed in four cases. All general and visual symptoms disappeared after CEA. Severe adverse effects, including hyperperfusion syndrome, were not observed in any cases. LSFG may be useful for the analysis of chorioretinal blood flow changes after CEA.

  19. Regional Cerebral Blood-Flow with 99mTc-ECD Brain Perfusion SPECT in Landau-Kleffner Syndrome: Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Reza Nemati


    Full Text Available Landau-Kleffner syndrome (LKS is a rare childhood disorder characterized by acquired aphasia and epilepsy. 99mTc-ECD SPECT imaging was performed in two right-handed children with LKS. A relative decrease in perfusion was found in the left frontal-temporal cortices of both patients as well as in the left and right parietal cortices of one patient with aphasia, without clinical epilepsy. The degree of regional cerebral perfusion impairment did not correlate with the severity of the clinical and EEG abnormalities, but the area of hypoperfusion was compatible with the speech area of the brain. Overall, although asymmetrical temporoparietal perfusion appears as a common finding in LKS, SPECT findings in LKS alone cannot elucidate the pathogenic features of the disorder in the brain. Here, we present two cases of LKS in which we investigated SPECT perfusion scans.

  20. Diagnostic examination performance by using microvascular leakage, cerebral blood volume, and blood flow derived from 3-T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in the differentiation of glioblastoma multiforme and brain metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres; Nakstad, Per H. [Oslo University Hospital-Ullevaal, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Oslo (Norway); Orheim, Tone E.D. [Oslo University Hospital, Interventional Centre, Oslo (Norway); Graff, Bjoern A. [Oslo University Hospital-Ullevaal, Department of Radiology and Nuclear Medicine, Oslo (Norway); Josefsen, Roger [Oslo University Hospital-Ullevaal, Department of Neurosurgery, Oslo (Norway); Kumar, Theresa [Oslo University Hospital-Ullevaal, Department of Pathology, Oslo (Norway)


    Conventional magnetic resonance (MR) imaging has limited capacity to differentiate between glioblastoma multiforme (GBM) and metastasis. The purposes of this study were: (1) to compare microvascular leakage (MVL), cerebral blood volume (CBV), and blood flow (CBF) in the distinction of metastasis from GBM using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MRI), and (2) to estimate the diagnostic accuracy of perfusion and permeability MR imaging. A prospective study of 61 patients (40 GBMs and 21 metastases) was performed at 3 T using DSC-MRI. Normalized rCBV and rCBF from tumoral (rCBVt, rCBFt), peri-enhancing region (rCBVe, rCBFe), and by dividing the value in the tumor by the value in the peri-enhancing region (rCBVt/e, rCBFt/e), as well as MVL were calculated. Hemodynamic and histopathologic variables were analyzed statistically and Spearman/Pearson correlations. Receiver operating characteristic curve analysis was performed for each of the variables. The rCBVe, rCBFe, and MVL were significantly greater in GBMs compared with those of metastases. The optimal cutoff value for differentiating GBM from metastasis was 0.80 which implies a sensitivity of 95%, a specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 97% for rCBVe ratio. We found a modest correlation between rCBVt and rCBFt ratios. MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region. (orig.)

  1. Narcolepsy: regional cerebral blood flow during sleep and wakefulness

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, F.; Meyer, J.S.; Karacan, I.; Yamaguchi, F.; Yamamoto, M.


    Serial measurements of regional cerebral blood flow were made by the 135Xe inhalation method during the early stages of sleep and wakefulness in eight normal volunteers and 12 patients with narcolepsy. Electroencephalogram, electro-oculogram, and submental electromyogram were recorded simultaneously. In normals, mean hemispheric gray matter blood flow (Fg) during stages I and II sleep was significantly less than waking values. Maximum regional blood flow decreases during sleep occurred in the brainstem-cerebellar, right inferior temporal, and bilateral frontal regions. In patients with narcolepsy, mean hemispheric Fg while awake was 80.5 +- 13 ml per 100 gm brain per minute. During REM sleep, mean hemispheric Fg increased concurrently with large increases in brainstem-cerebellar region flow. During stages I and II sleep without REM, there were significant increases in mean hemispheric Fg and brainstem-cerebellar Fg, just the opposite of changes in normals. In narcolepsy, there appears to be a reversal of normal cerebral deactivation patterns, particularly involving the brainstem, during stages I and II sleep.

  2. Impact of capillary flow hydrodynamics on carrier-mediated transport of opioid derivatives at the blood-brain barrier, based on pH-dependent Michaelis-Menten and Crone-Renkin analyses. (United States)

    Yusof, Siti R; Abbott, N Joan; Avdeef, Alex


    Most studies of blood-brain barrier (BBB) permeability and transport are conducted at a single pH, but more detailed information can be revealed by using multiple pH values. A pH-dependent biophysical model was applied to the mechanistic analysis of published pH-dependent BBB luminal uptake data from three opioid derivatives in rat: pentazocine (Suzuki et al., 2002a, 2002b), naloxone (Suzuki et al., 2010a), and oxycodone (Okura et al., 2008). Two types of data were processed: in situ brain perfusion (ISBP) and brain uptake index (BUI). The published perfusion data were converted to apparent luminal permeability values, Papp, and analyzed by the pCEL-X program (Yusof et al., 2014), using the pH-dependent Crone-Renkin equation (pH-CRE) to determine the impact of cerebrovascular flow on the Michaelis-Menten transport parameters (Avdeef and Sun, 2011). For oxycodone, the ISBP data had been measured at pH7.4 and 8.4. The present analysis indicates a 7-fold lower value of the cerebrovascular flow velocity, Fpf, than that expected in the original study. From the pyrilamine-inhibited data, the flow-corrected passive intrinsic permeability value was determined to be P0=398×10-6cm·s-1. The uptake data indicate that the neutral form of oxycodone is affected by a transporter at pH8.4. The extent of the cation uptake was less certain from the available data. For pentazocine, the brain uptake by the BUI method had been measured at pH5.5, 6.5, and 7.4, in a concentration range 0.1-40mM. Under similar conditions, ISBP data were also available. The pH-CRE determined values of Fpf from both methods were nearly the same, and were smaller than the expected value in the original publication. The transport of the cationic pentazocine was not fully saturated at pH5.5 at 40mM. The transport of the neutral species at pH7.4 appeared to reach saturation at 40mM pentazocine concentration, but not at 12mM. In the case of naloxone, a pH-dependent Michaelis-Menten equation (pH-MME) analysis of

  3. [Cerebral blood flow assessment of preterm infants during respiratory therapy with the expiratory flow increase technique]. (United States)

    Bassani, Mariana Almada; Caldas, Jamil Pedro Siqueira; Netto, Abimael Aranha; Marba, Sérgio Tadeu Martins


    To assess the impact of respiratory therapy with the expiratory flow increase technique on cerebral hemodynamics of premature newborns. This is an intervention study, which included 40 preterm infants (≤34 weeks) aged 8-15 days of life, clinically stable in ambient air or oxygen catheter use. Children with heart defects, diagnosis of brain lesion and/or those using vasoactive drugs were excluded. Ultrasonographic assessments with transcranial Doppler flowmetry were performed before, during and after the increase in expiratory flow session, which lasted 5minutes. Cerebral blood flow velocity and resistance and pulsatility indices in the pericallosal artery were assessed. Respiratory physical therapy did not significantly alter flow velocity at the systolic peak (p=0.50), the end diastolic flow velocity (p=0.17), the mean flow velocity (p=0.07), the resistance index (p=0.41) and the pulsatility index (p=0.67) over time. The expiratory flow increase technique did not affect cerebral blood flow in clinically-stable preterm infants. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  4. Cerebral blood flow assessment of preterm infants during respiratory therapy with the expiratory flow increase technique

    Directory of Open Access Journals (Sweden)

    Mariana Almada Bassani


    Full Text Available Abstract Objective: To assess the impact of respiratory therapy with the expiratory flow increase technique on cerebral hemodynamics of premature newborns. Methods: This is an intervention study, which included 40 preterm infants (≤34 weeks aged 8-15 days of life, clinically stable in ambient air or oxygen catheter use. Children with heart defects, diagnosis of brain lesion and/or those using vasoactive drugs were excluded. Ultrasonographic assessments with transcranial Doppler flowmetry were performed before, during and after the increase in expiratory flow session, which lasted 5min. Cerebral blood flow velocity and resistance and pulsatility indices in the pericallosal artery were assessed. Results: Respiratory physical therapy did not significantly alter flow velocity at the systolic peak (p=0.50, the end diastolic flow velocity (p=0.17, the mean flow velocity (p=0.07, the resistance index (p=0.41 and the pulsatility index (p=0.67 over time. Conclusions: The expiratory flow increase technique did not affect cerebral blood flow in clinically-stable preterm infants.

  5. Tesmilifene modifies brain endothelial functions and opens the blood-brain/blood-glioma barrier. (United States)

    Walter, Fruzsina R; Veszelka, Szilvia; Pásztói, Mária; Péterfi, Zoltán A; Tóth, András; Rákhely, Gábor; Cervenak, László; Ábrahám, Csongor S; Deli, Mária A


    Tesmilifene, a tamoxifen analog with antihistamine action, has chemopotentiating properties in experimental and clinical cancer studies. In our previous works, tesmilifene increased the permeability of the blood-brain barrier (BBB) in animal and culture models. Our aim was to investigate the effects of tesmilifene on brain microvessel permeability in the rat RG2 glioma model and to reveal its mode of action in brain endothelial cells. Tesmilifene significantly increased fluorescein extravasation in the glioma. Short-term treatment with tesmilifene reduced the resistance and increased the permeability for marker molecules in a rat triple co-culture BBB model. Tesmilifene also affected the barrier integrity in brain endothelial cells co-cultured with RG2 glioblastoma cells. Tesmilifene inhibited the activity of P-glycoprotein and multidrug resistance-associated protein-1 efflux pumps and down-regulated the mRNA expression of tight junction proteins, efflux pumps, solute carriers, and metabolic enzymes important for BBB functions. Among the possible signaling pathways that regulate BBB permeability, tesmilifene activated the early nuclear translocation of NFκB. The MAPK/ERK and PI3K/Akt kinase pathways were also involved. We demonstrate for the first time that tesmilifene increases permeability marker molecule extravasation in glioma and inhibits efflux pump activity in brain endothelial cells, which may have therapeutic relevance. Tesmilifene, a chemopotentiator in experimental and clinical cancer studies increases vascular permeability in RG2 glioma in rats and permeability for marker molecules in a culture model of the blood-brain barrier. Tesmilifene inhibits the activity of efflux pumps and down-regulates the mRNA expression of tight junction proteins, transporters, and metabolic enzymes important for the blood-brain barrier functions, which may have therapeutic relevance. © 2015 International Society for Neurochemistry.

  6. Kenyan purple tea anthocyanins ability to cross the blood brain ...

    African Journals Online (AJOL)

    Kenyan purple tea anthocyanins ability to cross the blood brain barrier reinforcing brain antioxidant capacity in mice. K Rashid, FN Wachira, RM Ngure, JN Nyabuga, B Wanyonyi, G Murilla, AO Isaac ...

  7. Red blood cell in simple shear flow (United States)

    Chien, Wei; Hew, Yayu; Chen, Yeng-Long


    The dynamics of red blood cells (RBC) in blood flow is critical for oxygen transport, and it also influences inflammation (white blood cells), thrombosis (platelets), and circulatory tumor migration. The physical properties of a RBC can be captured by modeling RBC as lipid membrane linked to a cytoskeletal spectrin network that encapsulates cytoplasm rich in hemoglobin, with bi-concave equilibrium shape. Depending on the shear force, RBC elasticity, membrane viscosity, and cytoplasm viscosity, RBC can undergo tumbling, tank-treading, or oscillatory motion. We investigate the dynamic state diagram of RBC in shear and pressure-driven flow using a combined immersed boundary-lattice Boltzmann method with a multi-scale RBC model that accurately captures the experimentally established RBC force-deformation relation. It is found that the tumbling (TU) to tank-treading (TT) transition occurs as shear rate increases for cytoplasm/outer fluid viscosity ratio smaller than 0.67. The TU frequency is found to be half of the TT frequency, in agreement with experiment observations. Larger viscosity ratios lead to the disappearance of stable TT phase and unstable complex dynamics, including the oscillation of the symmetry axis of the bi-concave shape perpendicular to the flow direction. The dependence on RBC bending rigidity, shear modulus, the order of membrane spectrin network and fluid field in the unstable region will also be discussed.

  8. Blood-brain barrier permeability imaging using perfusion computed tomography

    Directory of Open Access Journals (Sweden)

    Avsenik Jernej


    Full Text Available Background. The blood-brain barrier represents the selective diffusion barrier at the level of the cerebral microvascular endothelium. Other functions of blood-brain barrier include transport, signaling and osmoregulation. Endothelial cells interact with surrounding astrocytes, pericytes and neurons. These interactions are crucial to the development, structural integrity and function of the cerebral microvascular endothelium. Dysfunctional blood-brain barrier has been associated with pathologies such as acute stroke, tumors, inflammatory and neurodegenerative diseases.

  9. Glutamate Transporters in the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Nielsen, Carsten Uhd; Waagepetersen, Helle Sønderby


    concentration of L-glutamate causes excitotoxicity. A tight control of the brain interstitial fluid L-glutamate levels is therefore imperative, in order to maintain optimal neurotransmission and to avoid such excitotoxicity. The blood-brain barrier, i.e., the endothelial lining of the brain capillaries...... cells. The mechanisms underlying transendothelial L-glutamate transport are however still not well understood. The present chapter summarizes the current knowledge on blood-brain barrier L-glutamate transporters and the suggested pathways for the brain-to-blood L-glutamate efflux....

  10. Mechanisms of microbial traversal of the blood-brain barrier. (United States)

    Kim, Kwang Sik


    Central nervous system (CNS) infections continue to be an important cause of morbidity and mortality. Microbial invasion and traversal of the blood-brain barrier is a prerequisite for CNS infections. Pathogens can cross the blood-brain barrier transcellularly, paracellularly and/or in infected phagocytes (the so-called Trojan-horse mechanism). Consequently, pathogens can cause blood-brain barrier dysfunction, including increased permeability, pleocytosis and encephalopathy. A more complete understanding of the microbial-host interactions that are involved in microbial traversal of the blood-brain barrier and the associated barrier dysfunction should help to develop new strategies to prevent CNS infections.

  11. Low Blood Sugar in Newborns Tied to Brain Problems Later (United States)

    ... TUESDAY, Aug. 8, 2017 (HealthDay News) -- Low blood sugar affects about one in six newborns, and new research suggests it could lead to brain difficulties in childhood. Babies who experience low blood ...

  12. Accurate Blood Flow Measurements : Are Artificial Tracers Necessary?

    NARCIS (Netherlands)

    Poelma, C.; Kloosterman, A.; Hierck, B.P.; Westerweel, J.


    Imaging-based blood flow measurement techniques, such as particle image velocimetry, have become an important tool in cardiovascular research. They provide quantitative information about blood flow, which benefits applications ranging from developmental biology to tumor perfusion studies. Studies

  13. Modified Numerical Simulation Model of Blood Flow in Bend. (United States)

    Liu, X; Zhou, X; Hao, X; Sang, X


    The numerical simulation model of blood flow in bend is studied in this paper. The curvature modification is conducted for the blood flow model in bend to obtain the modified blood flow model in bend. The modified model is verified by U tube. By comparing the simulation results with the experimental results obtained by measuring the flow data in U tube, it was found that the modified blood flow model in bend can effectively improve the prediction accuracy of blood flow data affected by the curvature effect.

  14. Altered cerebral blood flow and cerebrovascular function after voluntary exercise in adult mice. (United States)

    Cahill, Lindsay S; Bishop, Jonathan; Gazdzinski, Lisa M; Dorr, Adrienne; Stefanovic, Bojana; Sled, John G


    The beneficial effects of physical exercise on brain health are well documented, yet how exercise modulates cerebrovascular function is not well understood. This study used continuous arterial spin labeling magnetic resonance imaging with a hypercapnic challenge to examine changes in cerebral blood flow and vascular function after voluntary exercise in healthy, adult mice. Thirty exercise mice and twenty-one control mice were imaged prior to the start of the exercise regime (at 12 weeks of age) and after 4 weeks of voluntary exercise. After the second in vivo imaging session, we performed high-resolution ex vivo anatomical brain imaging to correlate the structural brain changes with functional measures of flow and vascular reserve. We found that exercise resulted in increases in the normocapnic and hypercapnic blood flow in the hippocampus. Moreover, the change in normocapnic blood flow between pre-exercise and post-exercise was positively correlated to the hippocampal structure volume following exercise. There was no overall effect of voluntary exercise on blood flow in the motor cortex. Surprisingly, the hypercapnic hippocampal blood flow when measured prior to the start of exercise was predictive of subsequent exercise activity. Moreover, exercise was found to normalize this pre-existing difference in hypercapnic blood flow between mice.

  15. Regional cerebral blood flow in childhood headache

    Energy Technology Data Exchange (ETDEWEB)

    Roach, E.S.; Stump, D.A.


    Regional cerebral blood flow (rCBF) was measured in 16 cranial regions in 23 children and adolescents with frequent headaches using the non-invasive Xenon-133 inhalation technique. Blood flow response to 5% carbon dioxide (CO2) was also determined in 21 patients, while response to 50% oxygen was measured in the two patients with hemoglobinopathy. Included were 10 patients with a clinical diagnosis of migraine, 4 with musculoskeletal headaches, and 3 with features of both types. Also studied were 2 patients with primary thrombocythemia, 2 patients with hemoglobinopathy and headaches, 1 patient with polycythemia, and 1 with headaches following trauma. With two exceptions, rCBF determinations were done during an asymptomatic period. Baseline rCBF values tended to be higher in these young patients than in young adults done in our laboratory. Localized reduction in the expected blood flow surge after CO2 inhalation, most often noted posteriorly, was seen in 8 of the 13 vascular headaches, but in none of the musculoskeletal headache group. Both patients with primary thrombocythemia had normal baseline flow values and altered responsiveness to CO2 similar to that seen in migraineurs; thus, the frequently reported headache and transient neurologic signs with primary thrombocythemia are probably not due to microvascular obstruction as previously suggested. These data support the concept of pediatric migraine as a disorder of vasomotor function and also add to our knowledge of normal rCBF values in younger patients. Demonstration of altered vasomotor reactivity to CO2 could prove helpful in children whose headache is atypical.

  16. Regulation of coronary blood flow during exercise. (United States)

    Duncker, Dirk J; Bache, Robert J


    Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac output that results in increases in the three main determinants of myocardial oxygen demand: heart rate, myocardial contractility, and ventricular work. The approximately sixfold increase in oxygen demands of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen extraction (which is already 70-80% at rest) increase only modestly in most species. In contrast, in the right ventricle, oxygen extraction is lower at rest and increases substantially during exercise, similar to skeletal muscle, suggesting fundamental differences in blood flow regulation between these two cardiac chambers. The increase in heart rate also increases the relative time spent in systole, thereby increasing the net extravascular compressive forces acting on the microvasculature within the wall of the left ventricle, in particular in its subendocardial layers. Hence, appropriate adjustment of coronary vascular resistance is critical for the cardiac response to exercise. Coronary resistance vessel tone results from the culmination of myriad vasodilator and vasoconstrictors influences, including neurohormones and endothelial and myocardial factors. Unraveling of the integrative mechanisms controlling coronary vasodilation in response to exercise has been difficult, in part due to the redundancies in coronary vasomotor control and differences between animal species. Exercise training is associated with adaptations in the coronary microvasculature including increased arteriolar densities and/or diameters, which provide a morphometric basis for the observed increase in peak coronary blood flow rates in exercise-trained animals. In larger animals trained by treadmill exercise, the formation of new capillaries maintains

  17. Cerebral blood flow and oxygen metabolism in the Rett syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Hideto; Fueki, Noboru; Suzuki, Hisaharu; Sakuragawa, Norio; Iio, Masaaki (National Central Hospital for Mental, Nervous and Muscular Disorders, Tokyo (Japan))


    Positron emission tomography (PET) was performed on six patients with the Rett syndrome and the results were compared with the concurrent clinical status of the patients. The cerebral metabolic rate of oxygen (CMRO{sub 2}) was low in five patients, and oxygen extraction fraction (OEF) was low in four patients; both had a tendency to decline with advancing age. Although the cause is unknown, it is suggested that impaired oxidative metabolism exists in the Rett syndrome. An analysis of the distribution among brain regions showed that the ratios of values for the frontal cortex to those for the temporal cortex for both the cerebral blood flow (CBF) and CMRO{sub 2} were lower than those for the controls, which may indicate the loss of of hyperfrontality in the Rett syndrome. Distribution of brain metabolism may be immature in the Rett syndrome. (author).

  18. Aerobic fitness is associated with greater hippocampal cerebral blood flow in children

    Directory of Open Access Journals (Sweden)

    Laura Chaddock-Heyman


    Full Text Available The present study is the first to investigate whether cerebral blood flow in the hippocampus relates to aerobic fitness in children. In particular, we used arterial spin labeling (ASL perfusion MRI to provide a quantitative measure of blood flow in the hippocampus in 73 7- to 9-year-old preadolescent children. Indeed, aerobic fitness was found to relate to greater perfusion in the hippocampus, independent of age, sex, and hippocampal volume. Such results suggest improved microcirculation and cerebral vasculature in preadolescent children with higher levels of aerobic fitness. Further, aerobic fitness may influence how the brain regulates its metabolic demands via blood flow in a region of the brain important for learning and memory. To add specificity to the relationship of fitness to the hippocampus, we demonstrate no significant association between aerobic fitness and cerebral blood flow in the brainstem. Our results reinforce the importance of aerobic fitness during a critical period of child development.

  19. Estimation of hepatic blood flow by hydrogen gas clearance

    NARCIS (Netherlands)

    Gouma, D. J.; Coelho, J. C.; Schlegel, J.; Fisher, J. D.; Li, Y. F.; Moody, F. G.


    The hydrogen gas clearance technique was evaluated to estimate regional hepatic blood flow. Initially, the H2 gas method was compared to the indocyanine green clearance in mini pigs. The blood flow measured by the H2 gas method (0.49 +/- 0.03 ml/min/gm) was only 39% of the calculated blood flow by

  20. Influence of Gravity on Blood Volume and Flow Distribution (United States)

    Pendergast, D.; Olszowka, A.; Bednarczyk, E.; Shykoff, B.; Farhi, L.


    increased and if there is edema in space. Anecdotal evidence suggests there may be cerebral edema early in flight. Cerebral artery velocity has been shown to be elevated in simulated microgravity. The elevated cerebral artery velocity during simulated microgravity may reflect vasoconstriction of the arteries and not increased cerebral blood flow. The purpose of our investigations was to evaluate the effects of alterations in simulated gravity (+/-), resulting in changes in cardiac output (+/-), and on the blood flow and volume distribution in the lung and brain of human subjects. The first hypothesis of these studies was that blood flow and volume would be affected by gravity, but their distribution in the lung would be independent of gravity and due to vasoactivity changing vascular resistance in lung vessels. The vasodilitation of the lung vasculature (lower resistance) along with increased "compliance" of the heart could account for the absence of increased central venous pressure in microgravity. Secondly, we postulate that cerebral blood velocity is increased in microgravity due to large artery vasoconstriction, but that cerebral blood flow would be reduced due to autoregulation.

  1. Decorrelation-based blood flow velocity estimation: effect of spread of flow velocity, linear flow velocity gradients, and parabolic flow.

    NARCIS (Netherlands)

    Lupotti, F.A.; Steen, A.F.W. van der; Mastik, F.; Korte, C.L. de


    In recent years, a new method to measure transverse blood flow, based on the decorrelation of the radio frequency (RF) signals has been developed. In this paper, we investigated the influence of nonuniform flow on the velocity estimation. The decorrelation characteristics of transverse blood flow

  2. Regulation of regional cerebral blood flow during and between migraine attacks

    DEFF Research Database (Denmark)

    Lauritzen, M; Olsen, T S; Lassen, N A


    Cerebrovascular reactivity to voluntary hyperventilation, moderate hypertension, and physiological activation was studied in nine patients during induced migraine attacks and in four patients between their attacks. Regional cerebral blood flow was measured by the xenon 133 injection technique in ...... abnormalities to the area of the oligemia supports our suggestion that the blood flow changes are caused by a change in local metabolism. Between attacks of migraine, the patients had normal regulation of brain circulation....

  3. Alterations of Regional Cerebral Blood Flow in Major Depressive Disorder

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Hyoung; Chung, Yong An; Seo, Ye Young; Yoo, Ik Dong; Na, Sae Jung; Jung, Hyun Suk; Kim, Ki Jun [College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)


    The authors analyzed how the regional cerebral blood flow (rCBF) findings of patients with major depression differ from the normal control, and our results were compared to previous reports. Twelve patients fulfilling DSM-IV criteria for major depression who were off all psychotropic medications for > 4 weeks (male: 7, female: 5, age range: 19approx52 years, average age: 29.3+-9.9 years) and 14 normal volunteers (male: 8, female: 6, age range: 19approx53 years, average age: 31.4+-9.2 years) were recruited. Images of brain perfusion SPECT were obtained using Tc-99m ECD and patterns of the rCBF were compared between patients with major depression and the healthy control subjects. The patients with major depression showed increase of the r-CBF in right lingual gyrus, right fusiform gyrus, left lingual gyrus, left precuneus, and left superior temporal gyrus, and showed decrease of r-CBF in right pons, left medial frontal gyrus, cingulate gyrus of left limbic lobe, cingulate gyrus of right frontal lobe, and cingulate gyrus of right limbic lobe compared to the normal control. The Tc-99m ECD brain perfusion SPECT findings in our study did not differ from the previously reported regional cerebral blood flow pattern of patients with major depression. Especially, decreased rCBF pattern typical to major depression patients in the right pons, left medial frontal gyrus, and cingulate regions was clearly demonstrated

  4. Skin blood flow changes during apneic spells in preterm infants

    NARCIS (Netherlands)

    Suichies, H.E.; Aarnoudse, J.G.; Okken, A.; Jentink, H.W.; de Mul, F.F.M.; Greve, Jan


    Changes in skin blood flow during apneic spells were determined in 18 preterm infants using a diode laser Doppler flow meter without light conducting fibres. Heart rate, nasal air flow, impedance pneumography, skin and incubator temperature and laser Doppler skin blood flow were recorded

  5. Blood flow in healed and inflamed periodontal tissues of dogs

    Energy Technology Data Exchange (ETDEWEB)

    Hock, J.M.; Kim, S.


    The objectives of this study were to determine if increased blood flow associated with gingivitis would decrease following resolution of gingival inflammation in dogs with periodontitis; if increased blood flow in inflamed gingiva was associated with changes in the blood flow of alveolar bone, and if blood flow in gingiva and alveolar bone increased if periodontitis was reactivated by ligating teeth. Regional blood flow was measured in dogs with pre-existing periodontitis, using radioisotope-labelled, plastic microspheres. In the first experiment on 4 adult Beagle dogs, teeth in the left jaws were treated to resolve the periodontitis, while teeth in the right jaws were not treated. Gingival and bone blood flow were measured after 12 wk. Blood flow was significantly (p<0.05) lower in non-inflamed healed gingiva (32.1 +- 2.7 ml/min/100 g) than in inflamed gingiva (46.1 +- 5.3 ml/min/100 g). No differences in the blood flow of the alveolar bone underlying inflamed or non-inflamed gingiva were present. In the second experiment, the right mandibular teeth of 5 dogs were treated to resolve periodontitis while teeth in the other quadrants were ligated for 4, 10 or 12 wk. The duration of ligation did not alter blood flow. Gingival blood flow around ligated maxillary and mandibular teeth was comparable and approximately 54% higher than around non-ligated teeth (p<0.03). The difference in blood flow between gingiva with G.I.>1 and gingiva with G.I.<2 was significant (p<0.04). Blood flow in bone was not altered by changes in the inflammatory status of the overlying gingiva. The findings suggest that changes in blood flow associated with inflammation are reversible and that blood flow alveolar bone is regulated independently of gingival blood flow.

  6. Topical menthol increases cutaneous blood flow. (United States)

    Craighead, Daniel H; Alexander, Lacy M


    Menthol, the active ingredient in several topically applied analgesics, activates transient receptor potential melastatin 8 (TRPM8) receptors on sensory nerves and on the vasculature inducing a cooling sensation on the skin. Ilex paraguariensis is also a common ingredient in topical analgesics that has potential vasoactive properties and may alter the mechanisms of action of menthol. We sought to characterize the microvascular effects of topical menthol and ilex application and to determine the mechanism(s) through which these compounds may independently and combined alter cutaneous blood flow. We hypothesized that menthol would induce vasoconstriction and that ilex would not alter skin blood flow (SkBF). Three separate protocols were conducted to examine menthol and ilex-mediated changes in SkBF. In protocol 1, placebo, 4% menthol, 0.7% ilex, and combination menthol+ilex gels were applied separately to the skin and red cell flux was continuously measured utilizing laser speckle contrast imaging (LSCI). In protocol 2, seven concentrations of menthol gel (0.04%, 0.4%, 1%, 2%, 4%, 7%, 8%) were applied to the skin to model the dose-response curve. In protocol 3, placebo, menthol, ilex, and menthol+ilex gels were applied to skin under local thermal control (34°C) both with and without sensory nerve blockage (topical lidocaine 4%). Post-occlusive reactive hyperemia (PORH) and local heating (42°C) protocols were conducted to determine the relative contribution of endothelium derived hyperpolarizing factors (EDHFs)/sensory nerves and nitric oxide (NO), respectively. Red cell flux was normalized to mean arterial pressure expressed as cutaneous vascular conductance (CVC: flux·mmHg(-1)) in all protocols. Topical menthol application increased SkBF compared to placebo (3.41±0.33 vs 1.1±0.19CVC: pmenthol (main effect, pmenthol application during PORH (3.62±0.29 vs. 2.50±0.21flux·mmHg(-1); pmenthol-mediated vasodilation at thermoneutral baseline (1.29±0.19flux·mmHg(-1

  7. Simultaneous two-photon imaging of cerebral oxygenation and capillary blood flow in atherosclerotic mice (United States)

    Lu, Xuecong; Li, Baoqiang; Moeini, Mohammad; Lesage, Frédéric


    Gradual changes in brain microvasculature and cerebral capillary blood flow occurring with atherosclerosis may significantly contribute to cognition decline due to their role in brain tissue oxygenation. However, previous stud- ies of the relationship between cerebral capillary blood flow and brain tissue oxygenation are limited. This study aimed to investigate vascular and concomitant changes in brain tissue pO2 with atherosclerosis. Experiments in young healthy C57B1/6 mice (n=6 , WT), young atherosclerotic mice (n=6 , ATX Y) and old atherosclerotic mice (n=6 , ATX O) were performed imaging on the left sensory-motor cortex at resting state under urethane (1.5 g/kg) anesthesia using two-photon fluorescence microscopy. The results showed that pO2 around capillaries, correlated with red blood cell (RBC) flux, increased with atherosclerosis.

  8. Peptide Transport through the Blood-Brain Barrier (United States)


    cause glomerular nephropathies , (c) the potential antigenicity of the vector, i.e., some cationized heterologous proteins are highly immunogenic, (d...I diabetes . N. Enctl. J. Med. 312:1078-1084. 12. Pardridge, W.M. (1988): Recent advances in blood-brain barrier transport. Ann. Rev. Pharmacol...barrier. In: Pathophysiology of the Blood-Brain Barrier: Long Term Consequences of Barrier Dysfunction for the Brain (B.B. Johansson, C. Owman, and H

  9. Intramuscular blood flow quantification with power doppler ultrasonography. (United States)

    Dori, Amir; Abbasi, Hiba; Zaidman, Craig M


    Quantification of blood flow to muscle using ultrasound is limited to large vessels. Small vessel intramuscular blood flow cannot be quantified using ultrasound without specialized methods or intravenous contrast. We describe a technique using power Doppler to quantify postcontraction hyperemia in intramuscular vessels that can be used at the bedside. In 11 healthy subjects, postcontraction intramuscular blood flow in the forearm flexors and tibialis anterior muscles increased with stronger and repeated contractions. Intravascular blood flow measured by pulsed Doppler in the brachial artery similarly increased. Three patients with muscular dystrophies showed a negligible increase of postcontraction intramuscular blood flow. Intramuscular blood flow can be quantified using power Doppler ultrasonography; it increases following contraction and may be reduced in patients with muscular dystrophies. This quantitative, noninvasive technique can be applied at the bedside and may facilitate studies of disease impact on intramuscular blood flow. Muscle Nerve 54: 872-878, 2016. © 2016 Wiley Periodicals, Inc.

  10. The Blood-Brain Barrier: An Engineering Perspective

    Directory of Open Access Journals (Sweden)

    Andrew eWong


    Full Text Available It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich’s first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and it remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore advances in our understanding of the structure and function of the blood-brain barrier are key to advances in treatment of a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases.

  11. The effect of hyperosmotic solutions on the hepatic blood flow

    DEFF Research Database (Denmark)

    Winkler, K; Henriksen, Jens Henrik Sahl; Tygstrup, N


    The present study was undertaken in order to measure the effect of hyperosmotic solutions on portal and hepatic blood flow. In five anaesthetized pigs without arterial blood supply to the liver, portal blood flow rate was measured (electromagnetic flowmeter) during 5 min lasting intravenous...... for these osmotic effects are not known, but they have to be taken into consideration in studies of the portal and hepatic blood flow....

  12. Continuous blood pressure recordings simultaneously with functional brain imaging: studies of the glymphatic system (United States)

    Zienkiewicz, Aleksandra; Huotari, Niko; Raitamaa, Lauri; Raatikainen, Ville; Ferdinando, Hany; Vihriälä, Erkki; Korhonen, Vesa; Myllylä, Teemu; Kiviniemi, Vesa


    The lymph system is responsible for cleaning the tissues of metabolic waste products, soluble proteins and other harmful fluids etc. Lymph flow in the body is driven by body movements and muscle contractions. Moreover, it is indirectly dependent on the cardiovascular system, where the heart beat and blood pressure maintain force of pressure in lymphatic channels. Over the last few years, studies revealed that the brain contains the so-called glymphatic system, which is the counterpart of the systemic lymphatic system in the brain. Similarly, the flow in the glymphatic system is assumed to be mostly driven by physiological pulsations such as cardiovascular pulses. Thus, continuous measurement of blood pressure and heart function simultaneously with functional brain imaging is of great interest, particularly in studies of the glymphatic system. We present our MRI compatible optics based sensing system for continuous blood pressure measurement and show our current results on the effects of blood pressure variations on cerebral brain dynamics, with a focus on the glymphatic system. Blood pressure was measured simultaneously with near-infrared spectroscopy (NIRS) combined with an ultrafast functional brain imaging (fMRI) sequence magnetic resonance encephalography (MREG, 3D brain 10 Hz sampling rate).

  13. Evaluation of regional cerebral blood flow in patient with atypical senile dementia with asymmetrical calcification. (United States)

    Shoyama, Masaru; Ukai, Satoshi; Shinosaki, Kazuhiro


    We report an 83-year-old woman with atypical senile dementia with Fahr-type calcification. Brain computed tomography demonstrated asymmetrical calcification predominant in the basal ganglia on the right side and pronounced diffuse cortical atrophy in the frontotemporal areas. The patient was clinically diagnosed with diffuse neurofibrillary tangles with calcification. Brain single photon emission computed tomography findings revealed that cerebral blood flow was reduced on the right side, as compared with the left side, in widespread areas. Hemispheric asymmetry in both calcification and cerebral blood flow suggests a relationship between calcification and vascular changes. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  14. A quantitative MRI method for imaging blood-brain barrier leakage in experimental traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Blood-brain barrier (BBB disruption is common following traumatic brain injury (TBI. Dynamic contrast enhanced (DCE MRI can longitudinally measure the transport coefficient Ktrans which reflects BBB permeability. Ktrans measurements however are not widely used in TBI research because it is generally considered to be noisy and possesses low spatial resolution. We improved spatiotemporal resolution and signal sensitivity of Ktrans MRI in rats by using a high-sensitivity surface transceiver coil. To overcome the signal drop off profile of the surface coil, a pre-scan module was used to map the flip angle (B1 field and magnetization (M0 distributions. A series of T1-weighted gradient echo images were acquired and fitted to the extended Kety model with reversible or irreversible leakage, and the best model was selected using F-statistics. We applied this method to study the rat brain one hour following controlled cortical impact (mild to moderate TBI, and observed clear depiction of the BBB damage around the impact regions, which matched that outlined by Evans Blue extravasation. Unlike the relatively uniform T2 contrast showing cerebral edema, Ktrans shows a pronounced heterogeneous spatial profile in and around the impact regions, displaying a nonlinear relationship with T2. This improved Ktrans MRI method is also compatible with the use of high-sensitivity surface coil and the high-contrast two-coil arterial spin-labeling method for cerebral blood flow measurement, enabling more comprehensive investigation of the pathophysiology in TBI.

  15. Relationship between cardiac function and resting cerebral blood flow

    DEFF Research Database (Denmark)

    Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja


    a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow...... = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed......) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P...

  16. [Blood-brain barrier transport of opioid analgesics]. (United States)

    Suzuki, Toyofumi


    Opioid analgesics exhibit cationic properties under physiological conditions, and the mechanism underlying permeation of the blood-brain barrier thus cannot be fully explained by simple diffusion alone. Various types of transporters that exhibit substrate specificity are localized on the blood-brain barrier, and play a role in transporting substances from circulating blood and from brain interstitial fluid. Progress is being made in explaining the mechanisms, functions, and physiological roles of polyspecific organic cation transporters, but little evidence has indicated that these previously identified organic cation transporters are involved in the transport of opioid analgesics across the blood-brain barrier. Consequently, clarifying the role of transporters in the distribution of opioid analgesics into the brain and determining their transport molecule will not only provide clues to effective drug delivery to the brain, but will also contribute to optimizing pain relief treatment, and by extension play a role in drug discovery for analgesics. Currently there are enthusiastic discussions in the literature regarding the existence of putative transporters involved in the transport of opioid analgesics across the blood-brain barrier. This review article introduces the results of our research as well as recent findings on the involvement of transporters in the blood-brain barrier transport of opioid analgesics such as morphine, morphine metabolites, oxycodone, fentanyl, codeine, and pentazocine.

  17. Barrier mechanisms in the Drosophila blood-brain barrier

    Directory of Open Access Journals (Sweden)

    Samantha Jane Hindle


    Full Text Available The invertebrate blood-brain barrier field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through GPCR signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate blood-brain barrier has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many blood-brain barrier mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the blood-brain barrier can govern whole animal physiologies. This includes novel functions of blood-brain barrier gap junctions in orchestrating synchronized neuroblast proliferation, and of blood-brain barrier secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate blood-brain barrier anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

  18. Intraoperative cerebral blood flow imaging of rodents (United States)

    Li, Hangdao; Li, Yao; Yuan, Lu; Wu, Caihong; Lu, Hongyang; Tong, Shanbao


    Intraoperative monitoring of cerebral blood flow (CBF) is of interest to neuroscience researchers, which offers the assessment of hemodynamic responses throughout the process of neurosurgery and provides an early biomarker for surgical guidance. However, intraoperative CBF imaging has been challenging due to animal's motion and position change during the surgery. In this paper, we presented a design of an operation bench integrated with laser speckle contrast imager which enables monitoring of the CBF intraoperatively. With a specially designed stereotaxic frame and imager, we were able to monitor the CBF changes in both hemispheres during the rodent surgery. The rotatable design of the operation plate and implementation of online image registration allow the technician to move the animal without disturbing the CBF imaging during surgery. The performance of the system was tested by middle cerebral artery occlusion model of rats.

  19. Cerebral blood flow in normal pressure hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Mamo, H.L.; Meric, P.C.; Ponsin, J.C.; Rey, A.C.; Luft, A.G.; Seylaz, J.A.


    A xenon-133 method was used to measure cerebral blood flow (CBF) before and after cerebrospinal fluid (CSF) removal in patients with normal pressure hydrocephalus (NPH). Preliminary results suggested that shunting should be performed on patients whose CBF increased after CSF removal. There was a significant increase in CBF in patients with NPH, which was confirmed by the favorable outcome of 88% of patients shunted. The majority of patients with senile and presenile dementia showed a decrease or no change in CBF after CSF removal. It is suggested that although changes in CBF and clinical symptoms of NPH may have the same cause, i.e., changes in the cerebral intraparenchymal pressure, there is no simple direct relation between these two events. The mechanism underlying the loss of autoregulation observed in NPH is also discussed.

  20. Cerebral blood flow and metabolism during sleep

    DEFF Research Database (Denmark)

    Madsen, Peter Lund; Vorstrup, S


    A review of the current literature regarding sleep-induced changes in cerebral blood flow (CBF) and cerebral metabolic rate (CMR) is presented. Early investigations have led to the notion that dreamless sleep was characterized by global values of CBF and CMR practically at the level of wakefulness......, while rapid eye movement (REM) sleep (dream sleep) was a state characterized by a dramatically increased level of CBF and possibly also of CMR. However, recent investigations firmly contradict this notion. Investigations on CBF and CMR performed during non-REM sleep, taking the effect of different...... levels of sleep into consideration, show that light sleep (stage II) is characterized by global levels of CBF and CMR only slightly reduced by 3-10% below the level associated with wakefulness, whereas CBF and CMR during deep sleep (stage III-IV) is dramatically reduced by 25-44%. Furthermore, recent...

  1. Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia (United States)

    Gjedde, Albert; Crone, Christian


    Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

  2. Remifentanil decreases oral tissue blood flow while maintaining internal carotid artery blood flow during sevoflurane anesthesia in rabbits. (United States)

    Hirata, Atsushi; Kasahara, Masataka; Matsuura, Nobuyuki; Ichinohe, Tatsuya


    The aim of this study was to investigate the effect of remifentanil infusion on oral tissue blood flow including submandibular gland tissue blood flow (SBF) and internal carotid artery blood flow (ICBF) in rabbits during sevoflurane anesthesia. Twelve male Japan White rabbits were anesthetized with sevoflurane and remifentanil. Remifentanil was infused at 0.2 and 0.4 µg/kg/min. Measurements included circulatory variables, common and external carotid artery blood flow (CCBF, ECBF), ICBF, tongue mucosal blood flow (TMBF), masseter muscle tissue blood flow (MBF), mandibular bone marrow tissue blood flow (BBF), tongue muscle tissue blood flow (TBF), and SBF. Vascular resistances for each tissue, including the tongue mucosa, masseter muscle, mandibular bone marrow, tongue muscle, and submandibular gland, were calculated by dividing the mean arterial pressure by the respective tissue blood flow. Remifentanil infusion decreased oral tissue blood flow and circulatory variables. CCBF, ECBF, and ICBF did not change. The calculated vascular resistance in each oral tissue, except for the tongue mucosa, increased in an infusion-rate-dependent manner. These results showed that remifentanil infusion reduced TMBF, MBF, BBF, TBF, and SBF in an infusion-rate-dependent manner without affecting ICBF under sevoflurane anesthesia.

  3. Heterogeneity of cerebral blood flow: a fractal approach

    Energy Technology Data Exchange (ETDEWEB)

    Kuikka, J.T.; Hartikainen, P. [Department of Clinical Physiology, Kuopioo Univ. Hospital (Finland); Department of Neurology, Kuopio Univ. Hosspital (Finland); Niuvanniemi Hospital, Kuopio (Finland)


    Aim: We demonstrate the heterogeneity of regional cerebral blood flow using a fractal approach and single-photon emission computed tomography (SPECT). Method: Tc-99m-labelled ethylcysteine dimer was injected intravenously in 10 healthy controls and in 10 patients with dementia of frontal lobe type. The head was imaged with a gamma camera and transaxial, sagittal and coronal slices were reconstructed. Two hundred fifty-six symmetrical regions of interest (ROIs) were drawn onto each hemisphere of functioning brain matter. Fractal analysis was used to examine the spatial heterogeneity of blood flow as a function of the number of ROIs. Results: Relative dispersion (=coefficient of variation of the regional flows) was fractal-like in healthy subjects and could be characterized by a fractal dimension of 1.17{+-}0.05 (mean{+-}SD) for the left hemisphere and 1.15{+-}0.04 for the right hemisphere, respectively. The fractal dimension of 1.0 reflects completely homogeneous blood flow and 1.5 indicates a random blood flow distribution. Patients with dementia of frontal lobe type had a significantly lower fractal dimension of 1.04{+-}0.03 than in healthy controls. (orig.) [German] Ziel: Unter Einsatz einer fraktalen Annaeherung und SPECT wird die Heterogenitaet der regionalen Hirndruchblutung demonstriert. Methode: Tc-99m-ECD wurde nach intravenoeser Injektion bei zehn Gesunden sowie bei zehn Patienten mit Demenz vom Frontallappen-Typ eingesetzt. Aus dem SPECT-Umlauf wurden transaxiale, sagittale und koronare Schnitte rekonstruiert. 265 symmetrische Regions of Interest wurden im Gebiet der funktionellen grauen Substanz fuer jede Hemisphaere markiert. Die fraktale Analyse wurde eingesetzt zur Bestimmung der raeumlichen Heterogenitaet der Hirndurchblutung als Funktion der ROI-Anzahl. Ergebnisse: Die relative Streuung (Variationskoeffizient der regionalen Durchblutung) war bei Gesunden fraktalaehnlich geordnet und konnte durch eine Fraktaldimension von 1,17{+-}0,05 (Mittelwert

  4. Local cerebral blood flow and glucose metabolism during seizure in spontaneously epileptic El mice

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, Chisa; Ochi, Hironobu; Yamagami, Sakae; Kawabe, Joji; Kobashi, Toshiko; Okamura, Terue; Yamada, Ryusaku [Osaka City Univ. (Japan). Faculty of Medicine


    Local cerebral blood flow and glucose metabolism were examined in spontaneously epileptic El mice using autoradiography with {sup 125}I-IMP and {sup 14}C-DG in the interictal phase and during seizure. El (+) mice that developed generalized tonic-clonic convulsions and El (-) mice that received no stimulation and had no history of epileptic seizures were examined. The seizure non-susceptible, maternal strain ddY mice were used as control. Uptake ratios for IMP and DG in mouse brain were calculated using the autoradiographic density. In the interictal phase, the pattern of local cerebral blood flow of El (+) mice was similar to that of ddY and El (-) mice, and glucose metabolism in the hippocampus was higher in El (+) mice than in El (-) and ddY mice, but flow and metabolism were nearly matched. During seizure, no significant changed blood flow and increased glucose metabolism in the hippocampus, the epileptic focus, and no markedly changed blood flow and depressed glucose metabolism in other brain regions were observed and considered to be flow-metabolism uncoupling. These observations have never been reported in clinical or experimental studies of epilepsy. Seizures did not cause large regional differences in cerebral blood flow. Therefore, only glucose metabolism is useful for detection of the focus of secondary generalized seizures in El mice, and appeared possibly to be related to the pathophysiology of secondary generalized epilepsy in El mice. (author).

  5. The complementary membranes forming the blood-brain barrier. (United States)

    Hawkins, Richard A; Peterson, Darryl R; Viña, Juan R


    Brain capillary endothelial cells form the blood-brain barrier. They are connected by extensive tight junctions, and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. The polar distribution of transport proteins allows for active regulation of brain extracellular fluid. Experiments on isolated membrane vesicles from capillary endothelial cells of bovine brain demonstrated the polar arrangement of amino acid and glucose transporters, and the utility of such arrangements have been proposed. For instance, passive carriers for glutamine and glutamate have been found only in the luminal membrane of blood-brain barrier cells, while Na-dependent secondary active transporters are at the abluminal membrane. This organization could promote the net removal of nitrogen-rich amino acids from brain, and account for the low level of glutamate penetration into the central nervous system. Furthermore, the presence of a gamma-glutamyl cycle at the luminal membrane and Na-dependent amino acid transporters at the abluminal membrane may serve to modulate movement of amino acids from blood-to-brain. Passive carriers facilitate amino acid transport into brain. However, activation of the gamma-glutamyl cycle by increased plasma amino acids is expected to generate oxoproline within the blood-brain barrier. Oxoproline stimulates secondary active amino acid transporters (Systems A and B(o)+) at the abluminal membrane, thereby reducing net influx of amino acids to brain. Finally, passive glucose transporters are present in both the luminal and abluminal membranes of the blood-brain barrier. Interestingly, a high affinity Na-dependent glucose carrier has been described only in the abluminal membrane. This raises the question whether glucose entry may be regulated to some extent. Immunoblotting studies suggest more than one type of passive glucose transporter exist in the blood-brain barrier, each with an asymmetrical distribution. In conclusion, it

  6. Effect of glomerulopressin on ovarian blood flow in dogs. (United States)

    Uranga, J; Del Castillo, E


    The present study showed that glomerulopressin decreased ovarian blood flow in normal dogs and that this effect could be inhibited by treatment with indomethacin. In addition diabetic dogs had a high plasma level of glomerulopressin and a low ovarian blood flow that was shown to increase after treatment with indomethacin. This suggests that the low ovarian blood flow in diabetis might be due to a prostaglandin synthesizing effect of glomerulopressin.

  7. A Modeling of Cerebral Blood Flow Changes due to Head Motion for fNIRS (United States)

    Takahashi, Kosuke; Tanaka, Takayuki; Nara, Hiroyuki; Kaneko, Shun'ichi; Inoue, Masao; Shimizu, Shunji; Kojima, Satoru


    A method is proposed for measuring brain activity during exercises involving head motion by using functional near-infrared spectroscopy (fNIRS), which investigates cerebral hemodynamics. Obtaining measurements during exercise is difficult because cerebral blood flow changes due to the head motion component (HMC), in addition to neural activity. HMC is an undesirable artifact in the measurement of hemodynamic response caused by neural activity, and as such, it must be estimated and eliminated. In our experiments, cerebral blood flow and head motion were measured during repeated passive forward bending of the subjects. Head motion was measured by 3-D motion capture, and HMC was estimated by deriving a relation between head motion and cerebral blood flow, where the pitch angle was found to be suitable for estimating HMC. In this research, an assumption was made that cerebral blood flow caused by neural activity and that caused by postural change were additive, and thus HMC was eliminated by subtraction.

  8. Cerebral blood flow reduction in Alzheimer's disease: impact of capillary occlusions on mice and humans (United States)

    Berg, Maxime; Merlo, Adlan; Peyrounette, Myriam; Doyeux, Vincent; Smith, Amy; Cruz-Hernandez, Jean; Bracko, Oliver; Haft-Javaherian, Mohammad; Nishimura, Nozomi; Schaffer, Chris B.; Davit, Yohan; Quintard, Michel; Lorthois, Sylvie


    Alzheimer's disease may be the most common form of dementia, yet a satisfactory diagnosis procedure has still to be found. Recent studies suggest that a significant decrease of cerebral blood flow, probably caused by white blood cells stalling small vessels, may be among the earliest biological markers. To assess this hypothesis we derive a blood flow model, validate it against in vitro controlled experiments and in vivo measurements made on mice. We then investigate the influence of capillary occlusions on regional perfusion (sum of all arteriole flowrates feeding the network) of large mice and humans anatomical networks. Consistent with experiments, we observe no threshold effect, so that even a small percentage of occlusions (2-4%) leads to significant blood flow decrease (5-12%). We show that both species share the same linear dependance, suggesting possible translation from mice to human. ERC BrainMicroFlow GA61510, CALMIP HPC (Grant 2017-1541).

  9. Organ hierarchy during low blood flow on-pump: a randomized experimental positron emission tomography study

    DEFF Research Database (Denmark)

    Thomassen, Sisse Anette; Kjærgaard, Benedict; Frøkiær, Jørgen

    knowledge this is the first study investigating organ hierarchy with dynamic PET-CT during profound systemic ischemia due to suboptimal blood flows during normothermic CPB. References 1. Murphy JM, Hessel II EA, Groom RC. Optimal perfusion during cardiopulmonary bypass: an Evidence-based approach. Anesth......].The purpose of this animal study is to investigate the organ hierarchy of brain, liver, kidney and muscle at normal and low blood flows by using dynamic positron tomography (PET-CT) during CPB. Methods CPB at different blood flows will be investigated in an experimental model of six 70 kg pigs...... will be measured with dynamic PET-CT before CPB and during the different blood flows. Systemic oxygen consumption will be estimated by measurement of mixed venous saturation and lactate, and regional muscle oxygen saturation (tSO2) with near infrared spectroscopy at the lower limb. Result: Preliminary data...

  10. Changes in scalp and cortical blood flow during hyperventilation measured with diffusing-wave spectroscopy (United States)

    Li, Jun; Ninck, Markus; Gisler, Thomas


    Changes in scalp and cortical blood flow induced by voluntary hyperventilation are investigated by near-infrared diffusing-wave spectroscopy. The temporal intensity autocorrelation function g(2) (τ) of multiply scattered light is recorded from the forehead of subjects during hyperventilation. Blood flow within the sampled tissue volume is estimated by the mean decay rate of g(2) (τ) . Data measured from six subjects show that the pattern of the hemodynamic response during 50 s hyperventilation is rather complicated: within the first 10 s, in three subjects an initial increase in blood flow is observed; from 10 s to 20 s, the mean blood flow is smaller than its baseline value for all six subjects; for the duration from 20 s to 30 s, the blood flow increases again. However, after 30 s the change is not consistent across subjects. Further study on one of these subjects by using two receivers probing the blood flow in the cortex and in the superficial layers simultaneously, reveals that during hyperventilation, the direction of change in blood flow within the scalp is opposite to the one in the brain. This helps to understand the complicated hemodynamic response observed in our measurements.

  11. Dynamic Effect of Rolling Massage on Blood Flow (United States)

    Chen, Yan-Yan; Yi, Hou-Hui; Li, Hua-Bing; Fang, Hai-Ping


    The Chinese traditional medical massage has been used as a natural therapy to eliminate some diseases. Here, the effect of the rolling massage frequency to the blood flow in the blood vessels under the rolling massage manipulation is studied by the lattice Boltzmann simulation. The simulation results show that when the frequency is smaller than or comparable to the pulsatile frequency of the blood flow, the effect on the blood flux by the rolling massage is small. On the contrast, if the frequency is twice or more times of the pulsatile frequency of the blood flow, the blood flux is greatly enhanced and increases linearly with respect to the frequency. Similar behavior has also been observed on the shear stress on the blood vessel walls. The result is helpful for understanding that the rolling massage has the function of promoting the blood circulation and removing the blood stasis.

  12. Revisiting blood-brain barrier: a chromatographic approach


    Subirats i Vila, Xavier; Muñoz-Pascual, Laura; Abraham, Michael H.; Rosés Pascual, Martí


    Drugs designed to reach a pharmacological CNS target must be effectively transported across the blood-brain barrier (BBB), a thin monolayer of endothelial cells tightly attached together between the blood and the brain parenchyma. Because of the lipidic nature of the BBB, several physicochemical partition models have been studied as surrogates for the passive permeation of potential drug candidates across the BBB (octanol-water, alkane-water, PAMPA...). In the last years, biopartition chromat...

  13. In vivo Mapping of Local Cerebral Blood Flow by Xenon-Enhanced Computed Tomography (United States)

    Gur, David; Good, Walter F.; Wolfson, Sidney K.; Yonas, Howard; Shabason, Leonard


    A noninvasive technique has been developed to measure and display local cerebral blood flow (LCBF) in vivo. In this procedure, nonradioactive xenon gas is inhaled and the temporal changes in radiographic enhancement produced by the inhalation are measured by sequential computerized tomography. The time-dependent xenon concentrations in various anatomical units in the brain are used to derive both the local partition coefficient and the LCBF. Functional mapping of blood flow with excellent anatomical specificity has been obtained in the baboon brain. The response of LCBF to stimuli such as changes in carbon dioxide concentrations as well as the variability in LCBF in normal and diseased tissue can be easily demonstrated. This method is applicable to the study of human physiology and pathologic blood flow alterations.

  14. Regional cerebral and extracranial blood flow measurements in acutely and chronically implanted cats: hydrogen clearance technique. (United States)

    Lamar, J C; Carati, P; Van Delft, A M


    A technique is described for measuring regional blood flow concomitantly in the brain and in extracranial tissues of the cat. Hydrogen clearance using the tissue polarographic electrode appears to be a useful technique for intermittent measurements of cerebral blood flow (CBF) in relatively small areas. H2 was administered by inhalation for 10 min. Both chronic and acutely implanted electrodes were placed at different depths in the cat brain, on the surface of the cortex, and in extracranial tissues. Clearance rates in gray matter of 75 to 119 ml/min/100 g tissue have been obtained and of 11 to 14 ml/min/100 g tissue in white matter. Clearance curves have invariably been monoexponential in character in white matter and biexponential in gray matter. Successful recordings of H2 clearance curves were obtained from both chronically (up to 5 months) and acutely implanted electrodes. A new type of electrode is described. The "paperclip" electrode is placed at the surface of the cortex, has a reactive surface much greater than that of needle electrodes, thus limiting the possible variations due to vascularization differences from one local area to the next, and induces no damage to the brain tissue. To test the reliability of the technique, blood flow was measured during hypercapnia and progressive exsanguination. All electrodes indicated increased rCBF following 5-7% CO2 inhalation. A marked decrease in blood flow was seen with peripheral electrodes during exsanguination, whereas it was necessary to lower arterial blood pressure by more than 60% of the baseline value to record decreased flow in brain tissues. The constancy of response from electrodes and the lack of obvious tissue damage on dissection of the brain renders the method an adequate one. It provides highly focal recording of both CBF and extracranial flow in chronically implanted animals.

  15. Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases. (United States)

    Gabathuler, Reinhard


    The central nervous system is protected by barriers which control the entry of compounds into the brain, thereby regulating brain homeostasis. The blood-brain barrier, formed by the endothelial cells of the brain capillaries, restricts access to brain cells of blood-borne compounds and facilitates nutrients essential for normal metabolism to reach brain cells. This very tight regulation of the brain homeostasis results in the inability of some small and large therapeutic compounds to cross the blood-brain barrier (BBB). Therefore, various strategies are being developed to enhance the amount and concentration of therapeutic compounds in the brain. In this review, we will address the different approaches used to increase the transport of therapeutics from blood into the brain parenchyma. We will mainly concentrate on the physiologic approach which takes advantage of specific receptors already expressed on the capillary endothelial cells forming the BBB and necessary for the survival of brain cells. Among all the approaches used for increasing brain delivery of therapeutics, the most accepted method is the use of the physiological approach which takes advantage of the transcytosis capacity of specific receptors expressed at the BBB. The low density lipoprotein receptor related protein (LRP) is the most adapted for such use with the engineered peptide compound (EPiC) platform incorporating the Angiopep peptide in new therapeutics the most advanced with promising data in the clinic.

  16. Daily rhythm of cerebral blood flow velocity

    Directory of Open Access Journals (Sweden)

    Spielman Arthur J


    Full Text Available Abstract Background CBFV (cerebral blood flow velocity is lower in the morning than in the afternoon and evening. Two hypotheses have been proposed to explain the time of day changes in CBFV: 1 CBFV changes are due to sleep-associated processes or 2 time of day changes in CBFV are due to an endogenous circadian rhythm independent of sleep. The aim of this study was to examine CBFV over 30 hours of sustained wakefulness to determine whether CBFV exhibits fluctuations associated with time of day. Methods Eleven subjects underwent a modified constant routine protocol. CBFV from the middle cerebral artery was monitored by chronic recording of Transcranial Doppler (TCD ultrasonography. Other variables included core body temperature (CBT, end-tidal carbon dioxide (EtCO2, blood pressure, and heart rate. Salivary dim light melatonin onset (DLMO served as a measure of endogenous circadian phase position. Results A non-linear multiple regression, cosine fit analysis revealed that both the CBT and CBFV rhythm fit a 24 hour rhythm (R2 = 0.62 and R2 = 0.68, respectively. Circadian phase position of CBT occurred at 6:05 am while CBFV occurred at 12:02 pm, revealing a six hour, or 90 degree difference between these two rhythms (t = 4.9, df = 10, p Conclusion In conclusion, time of day variations in CBFV have an approximately 24 hour rhythm under constant conditions, suggesting regulation by a circadian oscillator. The 90 degree-phase angle difference between the CBT and CBFV rhythms may help explain previous findings of lower CBFV values in the morning. The phase difference occurs at a time period during which cognitive performance decrements have been observed and when both cardiovascular and cerebrovascular events occur more frequently. The mechanisms underlying this phase angle difference require further exploration.

  17. Retinoic Acid Induces Blood-Brain Barrier Development

    NARCIS (Netherlands)

    Mizee, M.R.; Wooldrik, D.; Lakeman, K.A.M.; van het Hof, B.; Drexhage, J.A.R.; Geerts, D.; Bugiani, M.; Aronica, E.; Mebius, R.E.; Prat, A.; de Vries, H.E.; Reijerkerk, A.


    The blood- brain barrier (BBB) is crucial in the maintenance of a controlled environment within the brain to safeguard optimal neuronal function. The endothelial cells (ECs) of theBBBpossess specific properties that restrict the entry of cells and metabolites into the CNS. The specialized BBB

  18. Retinoic acid induces blood-brain barrier development

    NARCIS (Netherlands)

    Mizee, Mark R.; Wooldrik, Desiree; Lakeman, Kim A. M.; van het Hof, Bert; Drexhage, Joost A. R.; Geerts, Dirk; Bugiani, Marianna; Aronica, Eleonora; Mebius, Reina E.; Prat, Alexandre; de Vries, Helga E.; Reijerkerk, Arie


    The blood-brain barrier (BBB) is crucial in the maintenance of a controlled environment within the brain to safeguard optimal neuronal function. The endothelial cells (ECs) of the BBB possess specific properties that restrict the entry of cells and metabolites into the CNS. The specialized BBB

  19. Regional cerebral blood flow distribution in newly diagnosed schizophrenia and schizophreniform disorder

    DEFF Research Database (Denmark)

    Rubin, P; Holm, S; Madsen, P L


    Regional cerebral blood flow distribution (rCBF) in 24 first admissions with schizophrenia or schizophreniform disorder and in 17 healthy volunteers was examined. Single photon emission computed tomography with a brain-retained tracer, technetium-99m-d,l-hexamethyl-propylene amine oxime, was used...

  20. Regional cerebral blood flow changes associated with clitorally induced orgasm in healthy women

    NARCIS (Netherlands)

    Georgiadis, Janniko R.; Kortekaas, Rudie; Kuipers, Rutger; Nieuwenburg, Arie; Pruim, Jan; Reinders, A. A. T. Simone; Holstege, Gert


    There is a severe lack of knowledge regarding the brain regions involved in human sexual performance in general, and female orgasm in particular. We used [(15)O]-H(2)O positron emission tomography to measure regional cerebral blood flow (rCBF) in 12 healthy women during a nonsexual resting state,

  1. Modeling cerebral blood flow during posture change from sitting to standing

    DEFF Research Database (Denmark)

    Ottesen, Johnny T.; Olufsen, M.; Tran, H.T.


    extremities, the brain, and the heart. We use physiologically based control mechanisms to describe the regulation of cerebral blood flow velocity and arterial pressure in response to orthostatic hypotension resulting from postural change. To justify the fidelity of our mathematical model and control...

  2. Changes in regional cerebral blood flow during the course of classic migraine attacks

    DEFF Research Database (Denmark)

    Lauritzen, M; Skyhøj Olsen, T; Lassen, N A


    and were examined by a series of rCBF studies, spaced by intervals of 5 to 10 minutes. A wave of reduced blood flow originating in the posterior part of the brain and progressing anteriorly was observed in eight of the nine patients. The oligemia advanced at a speed of 2 mm per minute over the hemisphere...

  3. A method for calculating regional cerebral blood flow from emission computed tomography of inert gas concentrations

    DEFF Research Database (Denmark)

    Celsis, P; Goldman, T; Henriksen, L


    Emission tomography of positron or gamma emitting inert gases allows calculation of regional cerebral blood flow (rCBF) in cross-sectional slices of human brain. An algorithm is presented for rCBF calculations from a sequence of time averaged tomograms using inhaled 133Xe. The approach is designed...


    NARCIS (Netherlands)


    In chronic hypoxemia blood flow and oxygen supply to vital organs are maintained, but to nonvital organs they are decreased. We measured organ blood flows (microspheres) and whole blood viscosity in 10 chronically hypoxemic lambs, with an atrial septal defect and pulmonary stenosis, and in 8 control

  5. Regional cerebral blood flow abnormalities in patients with primary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Cermik, Tevfik F. [Hospital of the University of Trakya, Department of Nuclear Medicine, Edirne (Turkey); Trakya Universitesi Hastanesi, Nukleer Tip Anabilim Dali, Gullapoglu Yerleskesi, Edirne (Turkey); Kaya, Meryem; Bedel, Deniz; Berkarda, Sakir; Yigitbasi, Oemer N. [Hospital of the University of Trakya, Department of Nuclear Medicine, Edirne (Turkey); Ugur-Altun, Betuel [Hospital of the University of Trakya, Department of Internal Medicine, Division of Endocrinology, Edirne (Turkey)


    We assessed the alterations in regional cerebral blood flow (rCBF) in patients with primary hyperparathyroidism (PHP) before parathyroidectomy by semiquantitative analysis of brain single photon emission computed tomography (SPECT) images. Included in this prospective study were 14 patients (mean age 47.6 {+-} 10.4 years; 3 male, 11 female) and 10 control subjects (mean age 36.0 {+-} 8.5 years, 6 male, 4 female) were SPECT imaging was performed using a dual-headed gamma camera 60-90 min after intravenous administration of 925 MBq Tc-99m HMPAO. The corticocerebellar rCBF ratios were calculated from 52 brain areas and reference lower values (RLVs) were calculated from the rCBF ratios of control subjects. The regional ratios that were below the corresponding RLV were considered abnormal (hypoperfused). Hypoperfusion was shown in 171 out of 728 regions (23%) and there was a significant correlation between serum calcium, PTH levels and the sum of hypoperfused regions in the patient group (R = 0.75 and P = 0.001, and R = 0.75, P = 0.001, respectively). Significantly reduced rCBF were found in the following cortical regions: bilateral cingulate cortex, superior and inferior frontal cortex, anterior temporal cortex, precentral gyrus, postcentral gyrus and parietal cortex, and right posterior temporal cortex. Our results indicate that alterations in rCBF in patients with PHP can be demonstrated with brain SPECT. The correlation between serum calcium, PTH levels and the sum of hypoperfused regions indicates that there may be a strong relationship between rCBF abnormalities and increased levels of serum calcium and PTH. In addition, the degree of rCBF abnormalities could be determined by brain SPECT in PHP patients with or without psychiatric symptoms. (orig.)

  6. Subcutaneous blood flow during insulin-induced hypoglycaemia

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Sestoft, L


    Subcutaneous blood flow was measured preceding insulin-induced hypoglycaemia, at the onset of hypoglycaemic symptoms and 2 h later in juvenile diabetics with and without autonomic neuropathy and in normal males. In all groups subcutaneous blood flow decreased at the onset of hypoglycaemic symptoms...... compared with pre-hypoglycaemic flow. Two hours after onset of hypoglycaemic symptoms, subcutaneous blood flow was still significantly decreased compared with pre-hypoglycaemic flow. In normal subjects local nerve blockade had no effect on blood flow changes during hypoglycaemia, whereas local alpha......-receptor blockade abolished the vasoconstrictor response. We suggest that circulating catecholamines stimulating vascular alpha-receptors are probably responsible for flow reduction in the subcutaneous tissue during hypoglycaemia....

  7. [Effect of noradrenaline and angiotensin II on the brain and kidney blood supply with changes in systemic arterial pressure]. (United States)

    Beketov, A I; Korneliuk, I K


    Hydrogen clearance was used in experiments on anesthetized cats to demonstrate that intravenous infusions of noradrenaline induced an increase in cerebral blood supply and reduction of renal blood flow both in anesthetized animals and in the presence of hypotension. In these conditions, angiotensin II lowered the cerebral and renal blood flow. Hypotension enhanced the reactions of the cerebral and renal blood flow to the action of vasopressor agents. The intensity of the reactions was consistent with the degree of vascular autocontrol preservation in the brain and kidneys.

  8. Blood flow restricted exercise and vascular function. (United States)

    Horiuchi, Masahiro; Okita, Koichi


    It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR) leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  9. Suboccipital dermatomyotomic stimulation and digital blood flow. (United States)

    Purdy, W R; Frank, J J; Oliver, B


    The effect of gentle, soft tissue manipulation in the suboccipital region on digital blood flow, as a measure of sympathetic nervous system activity, was studied. Digital strain gauge plethysmography was used to measure the changes in pulse contour during (1) a normative test period with the subject in the supine position, (2) after a control interval (placebo) during which the investigator placed his hands under the suboccipital region, and (3) after an interval during which the investigator's fingers applied slow, steady, circular kneading in the suboccipital triangle region. Twenty-five studies were performed in a crossover design with the patient as his or her own control. Total pulse amplitude (Y) and the height from the dicrotic notch to the peak (X) were measured. Examination of the total data of all subjects revealed the occurrence of a significant change in X and Y with simply touching the suboccipital region with the hands. An even more favorable response ensued when suboccipital manipulation was applied. Those subjects reporting comfort or neutral responses had larger significant changes with manipulation when compared with the group reporting the experience as uncomfortable. The response within each group suggests that favorable autonomic changes (sympathetic dampening) occur with specific suboccipital manipulation as well as, indeed, the simple touching of the suboccipital triangle.

  10. Blood Flow Restricted Exercise and Vascular Function

    Directory of Open Access Journals (Sweden)

    Masahiro Horiuchi


    Full Text Available It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  11. Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia. (United States)

    Luo, Chuanming; Liang, Fengyin; Ren, Huixia; Yao, Xiaoli; Liu, Qiang; Li, Mingyue; Qin, Dajiang; Yuan, Ti-Fei; Pei, Zhong; Su, Huanxing


    Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia. © 2016 International Society of

  12. Regional cerebral blood flow in focal cortical epilepsy

    DEFF Research Database (Denmark)

    Hougaard, Kristina Dupont; Oikawa, T; Sveinsdottir, E


    Regional cerebral blood flow (rCBF) was studied in ten patients with focal cortical epilepsy. The blood flow was measured by the intra-arterial injection of xenon 133 (133Xe), and the isotope clearance was recorded by a multidetector scintillation camera with 254 detectors. Three patients were st...

  13. Endothelial progenitor cells physiology and metabolic plasticity in brain angiogenesis and blood-brain barrier modeling

    Directory of Open Access Journals (Sweden)

    Natalia Malinovskaya


    Full Text Available Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons. Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies.

  14. Cerebral blood flow associated with creative performance: a comparative study. (United States)

    Chávez-Eakle, Rosa Aurora; Graff-Guerrero, Ariel; García-Reyna, Juan-Carlos; Vaugier, Víctor; Cruz-Fuentes, Carlos


    Creativity is important for social survival and individual wellbeing; science, art, philosophy and technology have been enriched and expanded by this trait. To our knowledge this is the first study probing differences in brain cerebral blood flow (CBF) between highly creative individuals (scientists and/or artists socially recognized for their contributions to their fields with creativity indexes corresponding to the 99% percentile) and average control subjects while performing a verbal task from the Torrance Tests of Creative Thinking. Additionally, we correlated CBF with creativity dimensions such as fluency, originality and flexibility. Subjects with a high creative performance showed greater CBF activity in right precentral gyrus, right culmen, left and right middle frontal gyrus, right frontal rectal gyrus, left frontal orbital gyrus, and left inferior gyrus (BA 6, 10, 11, 47, 20), and cerebellum; confirming bilateral cerebral contribution. These structures have been involved in cognition, emotion, working memory, and novelty response. The score on the three creativity dimensions--fluency, originality, and flexibility--correlated with CBF activation in right middle frontal gyrus and right rectal gyrus (Brodmann Area 6, 11). Moreover, fluency and flexibility strongly correlated with CBF in left inferior frontal gyrus and originality correlated with CBF in left superior temporal gyrus and cerebellar tonsil. These findings suggest an integration of perceptual, volitional, cognitive and emotional processes in creativity. The higher CBF found in particular brain regions of highly creative individuals during the performance of a creative task provides evidence of a specific neural network related to the creative process.

  15. In vivo cerebral blood flow autoregulation studies using rheoencephalography (United States)

    Bodo, M.; Pearce, F.; Garcia, A.; Van Albert, S.; Settle, T.; Szebeni, J.; Baranyi, L.; Hartings, J.; Armonda, R.


    Acute management of patients with traumatic brain/blast injury is a challenge. To minimize secondary injury and improve outcome, it is critical to detect neurological deterioration early, when it is potentially reversible. One potential monitoring method is cerebral electrical impedance (rheoencephalography-REG) because of its non-invasiveness and good time resolution. Reported here are the results of cerebral blood flow (CBF) manipulations comparing electroencephalogram (EEG) with REG (both intra-cerebral) and measuring with surface and skull REG electrodes. Our hypothesis was that REG would reflect spreading depression and CBF autoregulation. Animal experiments were performed using one rat (four trials with intracerebral electrodes), monkeys (n=8, with surface electrodes) and pigs (n = 24 pigs with skull electrodes; 57 trials, 19 types of liposomes). Challenges included intracranial pressure (ICP) elevation, liposome infusion, and hemorrhage. Data were stored on a PC and evaluated off line. CBF autoregulation was evaluated both by visual inspection and by a Matlab script. These studies confirmed that REG reflects CBF autoregulation and that REG is useful for detecting spreading depression (SD), vasospasm and the lower limit of CBF autoregulation. These findings have clinical relevance for use in noninvasive neuro-monitoring in the neurosurgery intensive care and during transportation of patients with brain injury.

  16. Self-separation of blood plasma from whole blood during the capillary flow in microchannel (United States)

    Nunna, Bharath Babu; Zhuang, Shiqiang; Lee, Eon Soo


    Self-separation of blood plasma from whole blood in microchannels is of great importance due to the enormous range of applications in healthcare and diagnostics. Blood is a multiphase complex fluid, composed of cells suspended in blood plasma. RBCs are the suspended particles whose shape changes during the flow of blood. The primary constituents of blood are erythrocytes or red blood cells (RBCs), leukocytes or white blood cells (WBCs), thrombocytes or platelets and blood plasma. The existence of RBCs in blood makes the blood a non-Newtonian fluid. The current study of separation of blood plasma from whole blood during self-driven flows in a single microchannel without bifurcation, by enhancing the capillary effects. The change in the capillary effect results in a change in contact angle which directly influences the capillary flow. The flow velocity directly influences the net force acting on the RBCs and influence the separation process. The experiments are performed on the PDMS microchannels with different contact angles by altering the surface characteristics using plasma treatment. The change in the separation length is studied during the capillary flow of blood in microchannel. Bharath Babu Nunna is a researcher in mechanical engineering and implementing the novel and innovative technologies in the biomedical devices to enhance the sensitivity of the disease diagnosis.

  17. Blood-brain barrier transport and protein binding of flumazenil and iomazenil in the rat: implications for neuroreceptor studies

    DEFF Research Database (Denmark)

    Videbaek, C; Ott, P; Paulson, O B


    of blood-brain barrier permeability for two benzodiazepine antagonists were performed in 44 rats by the double-indicator technique. Cerebral blood flow was measured by intracarotid Xe-injection. The apparent permeability-surface product (PSapp) was measured while CBF or bolus composition was changed...

  18. Blood-brain barrier transcytosis of insulin in developing rabbits. (United States)

    Duffy, K R; Pardridge, W M


    Previous studies with isolated brain microvessels have suggested that blood insulin is selectively transported through the brain capillary, i.e. the blood-brain barrier (BBB), by receptor-mediated transcytosis. The purpose of the present study is to demonstrate in vivo the uptake of circulating 125I-insulin by brain using thaw-mount autoradiography. However, metabolism of systemic 125I-insulin to 125I-tyrosine would allow for brain uptake of 125I-tyrosine and this would preclude interpretation of the autoradiogram. Therefore, the present studies were performed in developing rabbits, since plasma protein degradation of peptides is greatly reduced in developing animals. 125I-insulin was infused via the carotid artery at a rate of 0.25 ml/min for 1, 5, or 10 min, and the mean brain uptake, relative to a [3H]albumin reference, was 99.3 +/- 5.5%, 110.1 +/- 4.3%, and 143.6 +/- 7.9%, respectively. This uptake was saturable by simultaneously infusing unlabeled insulin. Thaw-mount autoradiography of rabbit brain after a 10-min infusion of 125I-insulin revealed silver grains in the pericapillary space and well within the brain parenchyma. HPLC analysis of acid-ethanol extracts of rabbit blood after a 10-min infusion showed virtually all of the 125I-radioactivity co-migrated with a known insulin standard on a reverse-phase column, indicating minimal degradation of infused 125I-insulin. HPLC analysis of brain radioactivity showed the major peak co-migrated with 125I-insulin and this peak was precipitated by an anti-insulin antiserum. The correlation of the transport data, the autoradiography, and the HPLC analysis support the model that brain insulin originates from blood via receptor-mediated transport of the peptide at the BBB.

  19. Conditions of microvessel occlusion for blood coagulation in flow. (United States)

    Bouchnita, A; Galochkina, T; Kurbatova, P; Nony, P; Volpert, V


    Vessel occlusion is a perturbation of blood flow inside a blood vessel because of the fibrin clot formation. As a result, blood circulation in the vessel can be slowed down or even stopped. This can provoke the risk of cardiovascular events. In order to explore this phenomenon, we used a previously developed mathematical model of blood clotting to describe the concentrations of blood factors with a reaction-diffusion system of equations. The Navier-Stokes equations were used to model blood flow, and we treated the clot as a porous medium. We identify the conditions of partial or complete occlusion in a small vessel depending on various physical and physiological parameters. In particular, we were interested in the conditions on blood flow and diameter of the wounded area. The existence of a critical flow velocity separating the regimes of partial and complete occlusion was demonstrated through the mathematical investigation of a simplified model of thrombin wave propagation in Poiseuille flow. We observed different regimes of vessel occlusion depending on the model parameters both for the numerical simulations and in the theoretical study. Then, we compared the rate of clot growth in flow obtained in the simulations with experimental data. Both of them showed the existence of different regimes of clot growth depending on the velocity of blood flow. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Effect of pulsatile swirling flow on stenosed arterial blood flow. (United States)

    Ha, Hojin; Lee, Sang Joon


    The existence of swirling flow phenomena is frequently observed in arterial vessels, but information on the fluid-dynamic roles of swirling flow is still lacking. In this study, the effects of pulsatile swirling inlet flows with various swirling intensities on the flow field in a stenosis model are experimentally investigated using a particle image velocimetry velocity field measurement technique. A pulsatile pump provides cyclic pulsating inlet flow and spiral inserts with two different helical pitches (10D and 10/3D) induce swirling flow in the stenosed channel. Results show that the pulsatile swirling flow has various beneficial effects by reducing the negative wall shear stress, the oscillatory shear index, and the flow reverse coefficient at the post-stenosis channel. Temporal variations of vorticity fields show that the short propagation length of the jet flow and the early breakout of turbulent flow are initiated as the swirling flow disturbs the symmetric development of the shear layer. In addition, the overall energy dissipation rate of the flow is suppressed by the swirling component of the flow. The results will be helpful for elucidating the hemodynamic characteristics of atherosclerosis and discovering better diagnostic procedures and clinical treatments. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

  1. Translocating the blood-brain barrier using electrostatics

    Directory of Open Access Journals (Sweden)

    Marta eRibeiro


    Full Text Available Mammalian cell membranes regulate homeostasis, protein activity and cell signaling. The charge at the membrane surface has been correlated with these key events.Although mammalian cells are known to be slightly anionic, quantitative information on the membrane charge and the importance of electrostatic interactions in pharmacokinetics and pharmacodynamics remain elusive. Recently, we reported for the first time that brain endothelial cells are more negatively charged than human umbilical cord cells, using zeta-potential dynamic light scattering. Here, we hypothesize that anionicity is a key feature of the blood-brain barrier and contributes to select which compounds cross into the brain. For the sake of comparison, we also studied the membrane surface charge of blood components – red blood cells, platelets and peripheral blood mononuclear cells. To further quantitatively correlate the negative zeta-potential values with membrane charge density, model membranes with different percentages of anionic lipids were also evaluated.From all the cells tested, brain cell membranes are the most anionic and the ones having their lipids mostly exposed, which explains why lipophilic cationic compounds are more prone to cross the blood-brain barrier.

  2. On the flow dependency of the electrical conductivity of blood

    NARCIS (Netherlands)

    Hoetink, AE; Faes, TJC; Visser, KR; Heethaar, RM

    Experiments presented in the literature show that the electrical conductivity of flowing blood depends on flow velocity. The aim of this study is to extend the Maxwell-Fricke theory, developed for a dilute suspension of ellipsoidal particles in an electrolyte, to explain this flow dependency of the

  3. Effects of Pulsatile Blood Flow on Oxygenator Performance. (United States)

    Schraven, Lotte; Kaesler, Andreas; Flege, Christian; Kopp, Rüdger; Schmitz-Rode, Thomas; Steinseifer, Ulrich; Arens, Jutta


    Extracorporeal membrane oxygenation (ECMO) is mainly used for the therapy of acute respiratory distress syndrome and chronic obstructive lung disease. In the last years, the development of these systems underwent huge steps in optimization, but there are still problems with thrombus formation, clogging, and thus insufficient gas exchange. One idea of ECMO optimization is a pulsatile blood flow through the oxygenator, but this is still a controversy discussion. Analyzing available publications, it was not possible to identify a general statement about the effect of pulsatile blood flow on the gas exchange performance. The variety of parameters and circuit components have such a high influence on the outcome that a direct comparison of the studies is difficult. For this reason, we performed a structured study to evaluate the effects of pulsatile blood flow on the gas exchange performance of oxygenator. In in vitro tests according to DIN EN ISO 7199, we tested a small oxygenator (0.25 m 2 exchange surface, polymethylpentene fibers, 33 mL priming volume) with constant and pulsatile blood flow in comparison. Therefore, we varied the mean blood flow from 250 to 1200 mL/min, the amplitude of 0, 20, and 50%, and the frequency of 30, 60, and 90 bpm. The results demonstrate that the gas transfer for pulsatile and constant blood flow was similar (oxygen: 36-64 mL O2 /L Blood ; carbon dioxide 35-80 mL CO2 /L Blood ) for the same mean blood flow ranges. Over all, the results and analyses showed a statistically nonsignificant difference between pulsatile and nonpulsatile flow. Consequently, we conclude that the implementation of pulsatile blood flow has only a small to no effect on the gas exchange performance in an oxygenator. As the results were obtained using an oxygenator with a coiled fiber bundle, the test must be verified for a stacked fiber oxygenator. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  4. Routes for drug translocation across the blood-brain barrier

    DEFF Research Database (Denmark)

    Kristensen, Mie; Brodin, Birger


    A number of potent drugs for the treatment of brain diseases are available. However, in order for them to reach their target site of action, they must pass the blood-brain barrier (BBB). The capillary endothelium comprises the major barrier of the BBB and allows only passive permeation of some...... small lipophilic molecules. Brain delivery of the larger biopharmaceuticals, which today includes an increasing number of novel drug entities, is therefore restricted; both due to their molecular size and their hydrophilic nature. Thus, the development of novel drug entities intended for the treatment...... of brain diseases such as neurodegenerative diseases or brain cancers, require a delivery strategy for overcoming the BBB before reaching its final target within the brain. Peptide-based delivery vectors is an emerging tool as shuttles for drug delivery across the BBB and one may explore receptor...

  5. Iron uptake and transport at the blood-brain barrier

    DEFF Research Database (Denmark)

    Larsen, Annette Burkhart; Thomsen, Louiza Bohn; Moos, Torben

    The mechanism by which iron is transported across the blood-brain barrier (BBB) remains controversial, and in this study we aimed to further clarify mechanisms by which iron is transported into the brain. We analyzed and compared the mRNA and protein expression of a variety of proteins involved...... in the transport of iron (transferrin receptor, divalent metal transporter I (DMT1), steap 2, steap 3, ceruloplasmin, hephaestin and ferroportin) in both primary rat brain capillary endothelial cells (BCEC) and immortalized rat brain capillary endothelial cell line (RBE4) grown in co-culture with defined polarity....... The mRNA expression of the iron-related molecules was also investigated in isolated brain capillaries from iron deficiency, iron reversible and normal rats. We also performed iron transport studies to analyze the routes by which iron is transported through the brain capillary endothelial cells: i) We...

  6. Augmenting regional cerebral blood flow using external-to-internal carotid artery flow diversion method. (United States)

    Divani, Afshin A; Berezina, Tamara L; Vazquez, Gabriela; Zaets, Sergey B; Tummala, Ramachandra; Qureshi, Adnan I


    The objective of this study was to assess the effect of flow diversion by external carotid artery (ECA) occlusion on ipsilateral regional cerebral blood flow (rCBF). Local cerebral hyperperfusion in rats (n = 12) was induced by ligating the right ECA. Ipsilateral rCBF was determined pre- and post-ligation for 120 min using a laser Doppler flow meter. Sham animals (n = 6) were subjected to the craniotomy without ligation of the right ECA. In a separate series of rats (n = 5), brain tissue oxygen levels (pO(2)) in the right and left brain hemispheres were determined before and 90 min after ligation of the right ECA using a tissue oxygenation monitoring unit. We investigated the effect of ECA occlusion hemispheric changes in rCBF in one clinical case as a proof of concept. Ligation of ECA resulted in a statistically significant increase in rCBF on the ipsilateral side compared to the sham-operated rats (p group compared with sham-operated rats. There was no significant variation in MAP for the treated animals. Vascular permeability and cerebral water content in the right hemisphere after ligation of ECA did not significantly differ from the contralateral hemisphere. Ipsilateral hemisphere tissue pO(2) was significantly higher compared to the contralateral area (p ECA resulted in 3.6% and 12.1% increase in peak value and rise-time of the time-density curves. Flow diversion by temporary occlusion of the ECA can result in increased rCBF and cerebral pO(2) on the ipsilateral side. The strategy may represent a viable option to augment rCBF in focal cerebral ischemia.

  7. A microcomputer system for assessment of peripheral blood flow. An example of nasal blood flow. (United States)

    Grönfors, T; Pyykkö, I; Aalto, H; Juhola, M; Ishizaki, H


    We have designed and implemented a microcomputer system for studying the effect of various mediator substances on the nasal blood flow. The system uses an IBM PC/AT microcomputer, which is connected with a Laser Doppler Flowmeter (LDF) and an iontophoretic drug application system. The LDF measures flux from the tissue that in the example is the inferior nasal turbinate. The flux is converted to digital form by an analog-digital converter of 12 bits. The program is implemented in the Pascal language. In the analysis, a flux level, amplitude, rise time and decay time of the pulse wave are determined. The effect of drugs on the flux can be studied by applying them iontophoretically. In the program the length and number of the drug application periods as well as the recording period are user-driven. In the nasal blood flow iontophoretically administered adrenaline reduced significantly the flux parameters and histamine canceled this effect. Tachyphylalaxis was a frequent observation in repeated measurements. The system can be used to evaluate the role of different transmitters in the etiology of chronic rhinitis.

  8. Evaluation of Placental Blood Flow in Patients with Placental Insufficiency

    Directory of Open Access Journals (Sweden)

    Julia E. Dobrokhotova


    Full Text Available Background: Placental insufficiency is a major problem of modern obstetrics due to its link to maternal and perinatal morbidity and mortality. Placental microcirculatory disorders play a decisive role in the pathogenesis of this condition. Thus, an evaluation of placental blood flow is of particular importance and crucial for appropriate diagnosis. The aim of this study was to evaluate placental blood flow in patients with placental insufficiency. SMI (superb microvascular imaging was compared to color Doppler for that purpose. Materials and Methods: Primigravida patients (n=91 at 15 to 16 weeks of gestation were enrolled. Inclusion criteria were spontaneous singleton pregnancy, age from 18 to 45 years. All participants were divided into 2 groups: Group 1 – control group (n=27 and Group 2 – threatened miscarriage group (n=64. Transvaginal ultrasound and color Doppler were performed to assess uteroplacental circulation. Placental blood flow was evaluated using a Toshiba Aplio™ 500 machine equipped with an SMI tool. Results: Placental blood flow assessment in patients with normal pregnancy revealed homogenous placental tissue, normal distribution of vessels, and active blood flow; in patients with pregnancy complications, we found inhomogeneous placenta, decreased blood flow, sporadic vessels, and avascular areas. SMI demonstrated several benefits compared to color Doppler imaging. Color Doppler allows us to assess superficial vessels only, whereas SMI provides more comprehensive data on the overall vascularization of the placenta. Conclusion: SMI by Aplio™ 500 (Toshiba may be an effective tool in the assessment of placental blood flow and the diagnosis and prognosis of placental insufficiency.

  9. Mesenteric, coeliac and splanchnic blood flow in humans during exercise

    DEFF Research Database (Denmark)

    Perko, M J; Nielsen, H B; Skak, C


    1. Exercise reduces splanchnic blood flow, but the mesenteric contribution to this response is uncertain. 2. In nineteen humans, superior mesenteric and coeliac artery flows were determined by duplex ultrasonography during fasting and postprandial submaximal cycling and compared with the splanchnic...... blood flow as assessed by the Indocyanine Green dye-elimination technique. 3. Cycling increased arterial pressure, heart rate and cardiac output, while it reduced total vascular resistance. These responses were not altered in the postprandial state. During fasting, cycling increased mesenteric, coeliac...... the coeliac circulation was not influenced. Postprandial cycling did not influence the mesenteric resistance significantly, but its blood flow decreased by 22 % (0.46 +/- 0.28 l min-1). Coeliac and splanchnic resistance increased by 150 and 63 %, respectively, and the corresponding regional blood flow...

  10. Mesenteric, coeliac and splanchnic blood flow in humans during exercise

    DEFF Research Database (Denmark)

    Perko, M J; Nielsen, H B; Skak, C


    1. Exercise reduces splanchnic blood flow, but the mesenteric contribution to this response is uncertain. 2. In nineteen humans, superior mesenteric and coeliac artery flows were determined by duplex ultrasonography during fasting and postprandial submaximal cycling and compared with the splanchnic...... blood flow as assessed by the Indocyanine Green dye-elimination technique. 3. Cycling increased arterial pressure, heart rate and cardiac output, while it reduced total vascular resistance. These responses were not altered in the postprandial state. During fasting, cycling increased mesenteric, coeliac...... decreased by 51 and 31 % (0.49 +/- 0.07 and 0.96 +/- 0.28 l min-1). Splanchnic blood flow values assessed by duplex ultrasound and by dye-elimination techniques were correlated (r = 0.70; P exercise in humans, splanchnic resistance increases and blood flow is reduced following...

  11. Determinants of coronary blood flow in sandbar sharks, Carcharhinus plumbeus. (United States)

    Cox, Georgina K; Brill, Richard W; Bonaro, Kaitlin A; Farrell, Anthony P


    The coronary circulation first appeared in the chordate lineage in cartilaginous fishes where, as in birds and mammals but unlike most teleost fishes, it supplies arterial blood to the entire myocardium. Despite the pivotal position of elasmobranch fishes in the evolution of the coronary circulation, the determinants of coronary blood flow have never been investigated in this group. Elasmobranch fishes are of special interest because of the morphological arrangement of their cardiomyocytes. Unlike teleosts, the majority of the ventricular myocardium in elasmobranch fishes is distant to the venous blood returning to the heart (i.e., the luminal blood). Also, the majority of the myocardium is in close association with the coronary circulation. To determine the relative contribution of the coronary and luminal blood supplies to cardiovascular function in sandbar sharks, Carcharhinus plumbeus, we measured coronary blood flow while manipulating cardiovascular status using acetylcholine and adrenaline. By exploring inter- and intra-individual variation in cardiovascular variables, we show that coronary blood flow is directly related to heart rate (R 2 = 0.6; P coronary blood flow is inversely related to coronary resistance both in vivo and in vitro, we suggest that in elasmobranch fishes, changes in heart rate mediate changes in coronary vascular resistance, which adjust coronary blood flow appropriately.

  12. Connexin 36 mediates blood cell flow in mouse pancreatic islets. (United States)

    Short, Kurt W; Head, W Steve; Piston, David W


    The insulin-secreting β-cells are contained within islets of Langerhans, which are highly vascularized. Blood cell flow rates through islets are glucose-dependent, even though there are no changes in blood cell flow within in the surrounding exocrine pancreas. This suggests a specific mechanism of glucose-regulated blood flow in the islet. Pancreatic islets respond to elevated glucose with synchronous pulses of electrical activity and insulin secretion across all β-cells in the islet. Connexin 36 (Cx36) gap junctions between islet β-cells mediate this synchronization, which is lost in Cx36 knockout mice (Cx36(-/-)). This leads to glucose intolerance in these mice, despite normal plasma insulin levels and insulin sensitivity. Thus, we sought to investigate whether the glucose-dependent changes in intraislet blood cell flow are also dependent on coordinated pulsatile electrical activity. We visualized and quantified blood cell flow using high-speed in vivo fluorescence imaging of labeled red blood cells and plasma. With the use of a live animal glucose clamp, blood cell flow was measured during either hypoglycemia (∼50 mg/dl) or hyperglycemia (∼300 mg/dl). In contrast to the large glucose-dependent islet blood velocity changes observed in wild-type mice, only minimal differences are observed in both Cx36(+/-) and Cx36(-/-) mice. This observation supports a novel model where intraislet blood cell flow is regulated by the coordinated electrical activity in the islet β-cells. Because Cx36 expression and function is reduced in type 2 diabetes, the resulting defect in intraislet blood cell flow regulation may also play a significant role in diabetic pathology.

  13. What is the blood flow to resting human muscle? (United States)

    Elia, M; Kurpad, A


    1. An investigation was carried out in five healthy lean adults to assess whether forearm and calf plethysmography largely reflect muscle blood flow as measured by 133Xe and whether there is substantial variability in the blood flow to muscles located at different sites in the body. 2. Blood flow to forearm and calf flexors and extensors, biceps, triceps and quadriceps was assessed using the 133Xe clearance technique. Blood flow to forearm skin and subcutaneous adipose tissue was also measured using the 133Xe clearance technique, whereas blood flow to the forearm and calf was measured using strain gauge plethysmography. 3. The mean blood flow to different muscles ranged from 1.4 +/- 0.6 (gastrocnemius) to 1.8 +/- 0.7 (forearm extensor) ml min-1 100 g-1 muscle (1.4 +/- 0.6 and 1.9 +/- 0.8 ml min-1 100 ml-1 muscle, respectively) but there were no significant differences between them. Forearm and calf blood flows (2.7 +/- 0.3 and 3.0 +/- 0.7 ml min-1 100 ml-1 limb tissue, respectively) were about 50% to more than 100% greater (P muscles within them (1.7 +/- 0.5 and 1.4 +/- 0.5 ml min-1 100 g-1 muscle, respectively, or 1.8 +/- 0.6 and 1.5 +/- 0.5 ml min-1 100 ml-1 muscle, respectively). In contrast, the blood flows to 100 g of forearm skin (9.1 +/- 2.6 ml min-1 100 g-1) and adipose tissue (3.8 +/- 1.1 ml min-1 100 g-1) were higher than the blood flow to 100 g of forearm (P < 0.01 and not significant, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Blood-Brain Glucose Transfer in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, Michael; Brock, Birgitte; Egefjord, Lærke


    There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral...... metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease. We randomized 38 patients with AD...... to treatment with liraglutide (n = 18) or placebo (n = 20) for 6 months, and determined the blood-brain glucose transfer capacity (Tmax) in the two groups and a healthy age matched control group (n = 6). In both AD groups at baseline, T max estimates correlated inversely with the duration of AD, as did...

  15. Blood-Brain Glucose Transfer in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, Michael; Brock, Birgitte; Egefjord, Lærke


    to treatment with liraglutide (n = 18) or placebo (n = 20) for 6 months, and determined the blood-brain glucose transfer capacity (T max) in the two groups and a healthy age matched control group (n = 6). In both AD groups at baseline, T max estimates correlated inversely with the duration of AD, as did......There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral...... metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease. We randomized 38 patients with AD...

  16. Rheology of Human Blood, near and at Zero Flow (United States)

    Merrill, E. W.; Gilliland, E. R.; Cokelet, G.; Shin, H.; Britten, A.; Wells, R. E.


    Static normal human blood possesses a distinctive yield stress. When the yield stress is exceeded, the same blood has a stress-shear rate function under creeping flow conditions closely following Casson's model, which implies reversible aggregation of red cells in rouleaux and flow dominated by movement of rouleaux. The yield stress is essentially independent of temperature and its cube root varies linearly with hematocrit value. The dynamic rheological properties in the creeping flow range are such that the relative viscosity of blood to water is almost independent of temperature. Questions raised by these data are discussed, including red cell aggregation promoted by elements in the plasma. PMID:13935042

  17. Postmortem Quetiapine Reference Concentrations in Brain and Blood

    DEFF Research Database (Denmark)

    Skov, Louise; Johansen, Sys Stybe; Linnet, Kristian


    Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations in brain tissue makes interpretation challenging. Here we present a study of 43 cases where the antipsychotic drug quetiapine was quantified in brain tissue...... and related to concentrations in postmortem blood. For cases, where quetiapine was unrelated to the cause of death (N 5 36), the 10–90 percentiles for quetiapine concentrations in brain tissue were 0.030 – 1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding blood 10 –90 percentile values were 0.......007 – 0.39 mg/kg (median 0.15 mg/kg, mean 0.19 mg/kg), giving brainblood ratio 10 –90 percentiles of 2.31 – 6.54 (median 3.87, mean 4.32). Both correspond well to the limited amount of data found in the literature. For cases where quetiapine was a contributing factor to death (N 5 5), the median value...

  18. Early Blood Gas Abnormalities and the Preterm Brain (United States)

    Leviton, Alan; Allred, Elizabeth; Kuban, Karl C. K.; Dammann, Olaf; O'Shea, T. Michael; Hirtz, Deborah; Schreiber, Michael D.; Paneth, Nigel


    The authors explored associations between blood gas abnormalities in more than 1,000 preterm infants during the first postnatal days and indicators of neonatal brain damage. During 2002–2004, women delivering infants before 28 weeks’ gestation at one of 14 participating institutions in 5 US states were asked to enroll in the study. The authors compared infants with blood gas values in the highest or lowest quintile for gestational age and postnatal day (extreme value) on at least 1 of the first 3 postnatal days with the remainder of the subjects, with separate analyses for blood gas abnormalities on multiple days and for partial pressure of oxygen in the alveolar gas of blood gas derangement (hypoxemia, hyperoxemia, hypocapnia, hypercapnia, and acidosis) was associated with multiple indicators of brain damage. However, for some, the associations were seen with only 1 day of exposure; others were evident with 2 or more days’ exposure. Findings suggest that individual blood gas derangements do not increase brain damage risk. Rather, the multiple derangements associated with indicators of brain damage might be indicators of immaturity/vulnerability and illness severity. PMID:20807736

  19. Whole blood viscosity and cerebral blood flow velocities in obese hypertensive or obese normotensive adolescents. (United States)

    Akcaboy, Meltem; Nazliel, Bijen; Goktas, Tayfun; Kula, Serdar; Celik, Bülent; Buyan, Necla


    Obesity affects all major organ systems and leads to increased morbidity and mortality. Whole blood viscosity is an important independent regulator of cerebral blood flow. The aim of the present study was to evaluate the effect of whole blood viscosity on cerebral artery blood flow velocities using transcranial Doppler ultrasound in pediatric patients with obesity compared to healthy controls and analyze the effect of whole blood viscosity and blood pressure status to the cerebral artery blood flow velocities. Sixty patients with obesity diagnosed according to their body mass index (BMI) percentiles aged 13-18 years old were prospectively enrolled. They were grouped as hypertensive or normotensive according to their ambulatory blood pressure monitoring. Whole blood viscosity and middle cerebral artery velocities by transcranial Doppler ultrasound were studied and compared to 20 healthy same aged controls. Whole blood viscosity values in hypertensive (0.0619±0.0077 poise) and normotensive (0.0607±0.0071 poise) groups were higher than controls (0.0616±0.0064 poise), with no significance. Middle cerebral artery blood flow velocities were higher in the obese hypertensive (73.9±15.0 cm/s) and obese normotensive groups (75.2±13.5 cm/s) than controls (66.4±11.5 cm/s), but with no statistical significance. Physiological changes in blood viscosity and changes in blood pressure did not seem to have any direct effect on cerebral blood flow velocities, the reason might be that the cerebral circulation is capable of adaptively modulating itself to changes to maintain a uniform cerebral blood flow.

  20. [Ocular blood flow and retinal electrogenesis in retinitis pigmentosa]. (United States)

    Kiseleva, T N; Zol'nikova, I V; Demenkova, O N; Ramazanova, K A; Egorova, I V; Rogatina, E V; Rogova, S Yu; Kiseleva, T N; Zol'nikova, I V; Demenkova, O N; Ramazanova, K A; Egorova, I V; Rogatina, E V; Rogova, S Yu


    to investigate correlations between changes in ocular hemodynamics revealed by color Doppler flow mapping (CDFM) and pulsed-wave (PW) Doppler imaging, one the one hand, and electrical activity of the retina, on the other, in patients with early, moderate, and severe retinitis pigmentosa (RP). A total of 20 patients (40 eyes) aged from 16 to 40 years (28.4 ± 8.2 years on average) with retinitis pigmentosa were enrolled. The control group consisted of 20 healthy volunteers of the same age range. All participants underwent full-field electroretinography (ERG), flicker ERG, and macular ERG as well as blood flow assessment in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCA) by means of CDFM and PW-Doppler. Ocular blood flow in CRA and SPCA appeared disturbed in patients with early RP. In cases of moderate and severe RP, the peak systolic velocity of CRA and SPCA blood flow was significantly decreased. Systolic and end diastolic blood flow velocities in CRA and SPCA has been shown to be directly related to full-field ERG a-wave and b-wave amplitudes, correspondingly, but negatively correlated with their implicit times. The revealed decrease in CRA and SPCA blood flow indices proves retinal and choroidal circulation deficit in patients with advanced RP. As shown, moderate blood flow changes are already present in early RP and progress as retinal photoreceptors and bipolar cells become suppressed, which may be useful for RP diagnosis and monitoring.

  1. Quantitative myocardial blood flow with Rubidium-82 PET

    DEFF Research Database (Denmark)

    Hagemann, Christoffer E; Ghotbi, Adam A; Kjær, Andreas


    Positron emission tomography (PET) allows assessment of myocardial blood flow in absolute terms (ml/min/g). Quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) extend the scope of conventional semi-quantitative myocardial perfusion imaging (MPI): e.g. in 1......) identification of the extent of a multivessel coronary artery disease (CAD) burden, 2) patients with balanced 3-vessel CAD, 3) patients with subclinical CAD, and 4) patients with regional flow variance, despite of a high global MFR. A more accurate assessment of the ischemic burden in patients with intermediate...

  2. Peripheral blood flow control in diabetes mellitus

    DEFF Research Database (Denmark)

    Hilsted, Jannik


    . Whereas the hemodynamic consequences of vascular denervation are well known (causing blood pressure maladaptation to a number of stimuli such as standing, exercise and agonist infusion) (Hilsted 1985), the consequences of disturbances in autoregulation and distensibility remain to be established....

  3. Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model. (United States)

    Wagner, Sylvia; Zensi, Anja; Wien, Sascha L; Tschickardt, Sabrina E; Maier, Wladislaw; Vogel, Tikva; Worek, Franz; Pietrzik, Claus U; Kreuter, Jörg; von Briesen, Hagen


    The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.

  4. The Coupling of Cerebral Metabolic Rate of Glucose and Cerebral Blood Flow In Vivo

    DEFF Research Database (Denmark)

    Hasselbalch, Steen; Paulson, Olaf Bjarne


    and metabolism was originally performed using the Kety-Schmidt method and this method still represent the gold standard by which subsequent methods have been evaluated. However, in its classical setting, the method overestimates cerebral blood flow. Studies of metabolic changes during activation must take......The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow...... this into account, and subsequent methods for measurement of regional glucose metabolism must be corrected accordingly in order to allow reliable quantitative comparisons of metabolite changes in activation studies. For studies of regional metabolic changes during activation quantification poses further...

  5. Reduced myocardial blood flow in acute and chronic digitalization. (United States)

    Steiness, E; Bille-Brahe, N E; Hansen, J F; Lomholt, N; Ring-Larsen, H


    The myocardial blood flow was measured by the 133Xenon disappearance curve from the left ventricular wall following an injection of 133Xenon in the left coronary artery in 8 dogs without digoxin pretreatment and in 8 chronically digitalized dogs. The myocardial blood flow was significantly less (30%) in the digitalized dogs than in the dogs without pretreatment. In the digitalized dogs as well as in those without pretreatment an intravenous injection of digoxin resulted in a further significant decrease of the myocardial blood flow of about 20% and a significant increase of the coronary vascular resistance. The reduced myocardial blood flow both during acute and chronic digitalization is beleived to be of clinical importance.

  6. MAPK and pro-inflammatory mediators in the walls of brain blood vessels following cerebral ischemia


    Maddahi, Aida


    INTRODUCTION Stroke is a serious neurological disease which may lead to death and severe disability [1, 2]. There are two major types of stroke: ischemic and hemorrhagic stroke. Both are associated with disruption of blood flow to a part of the brain with rapid depletion of cellular energy and oxygen, resulting in ionic disturbances and eventually neuronal cell death [3]. The pathologic process that develops after stroke is divided into acute (within hours), sub-acute (hours to days), ...

  7. Blood flow-vessel interaction in a subclavian aneurysm

    Directory of Open Access Journals (Sweden)

    Alexandru M. MOREGA


    Full Text Available This paper presents a mathematical mode and numerical simulation results of the blood flow-structural interaction, which occurs in a saccular aneurysm emerging out of the left subclavian artery, using computational domains made of by medical images reconstruction. A correlation between the total force per area acting upon the artery walls by the pulsatile blood flow and the rupture probability are also investigated.

  8. Blood flow boosts BMP signaling to keep vessels in shape. (United States)

    Franco, Claudio A; Gerhardt, Holger


    Bone morphogenic proteins (BMPs) and blood flow regulate vascular remodeling and homeostasis. In this issue, Baeyens et al. (2016. J. Cell Biol show that blood flow sensitizes endothelial cells to BMP9 signaling by triggering Alk1/ENG complexing to suppress cell proliferation and to recruit mural cells, thereby establishing endothelial quiescence. © 2016 Franco and Gerhardt.

  9. Blood flow rate measurements with indicator techniques revisited

    DEFF Research Database (Denmark)

    Sejrsen, Per; Bülow, Jens


    In view of the emerging role, disturbances in regional blood flow rate seem to play in the pathogenesis of the metabolic syndrome; we review the concepts of the classical indicator dilution and washout techniques used for determinations of regional blood flow rate. Prerequisites, assumptions......, necessary precautions for the application of these experimental techniques are emphasized. Special attention has been carried out to elucidate the consequence of a choice of indicators having a large distribution volume in the tissues....

  10. Effect of tropicamide on ocular blood flow in the rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, D.; Michel, P.; Jaanus, S.D.


    Intracardiac injection of 15 microspheres labeled with /sup 85/Sr (strontium) and /sup 141/Ce (cerium) were used to determine ocular blood flow in seven rabbits before and 25 min after bilateral application of tropicamide to the cornea. By using two different isotopes distinguishable under gammaspectrometry, each animal served as its own control. After administration of two drops of 1% tropicamide, no significant difference in blood flow between treated and untreated eyes was observed.

  11. Blood flow and arterial endothelial dysfunction: Mechanisms and implications (United States)

    Barakat, Abdul I.


    The arterial endothelium exquisitely regulates vascular function, and endothelial dysfunction plays a critical role in the development of atherosclerosis. Atherosclerotic lesions develop preferentially at arterial branches and bifurcations where the blood flow is disturbed. Understanding the basis for this observation requires elucidating the effects of blood flow on the endothelial cell (EC) function. The goal of this review is: (1) to describe our current understanding of the relationships between arterial blood flow and atherosclerosis, (2) to present the wide array of flow-induced biological responses in ECs, and (3) to discuss the mechanisms by which ECs sense, transmit, and transduce flow-derived mechanical forces. We conclude by presenting some future perspectives in the highly interdisciplinary field of EC mechanotransduction.

  12. Non-invasive pulmonary blood flow analysis and blood pressure mapping derived from 4D flow MRI (United States)

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


    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.

  13. Hepatic and intestinal blood flow following thermal injury

    Energy Technology Data Exchange (ETDEWEB)

    Carter, E.A.; Tompkins, R.G.; Burke, J.F.


    Because cardiac output decreases after burn injuries, investigators have assumed, based upon dye clearance techniques, that hepatic and intestinal blood flow are also decreased following these injuries. Blood flow to the liver, stomach, small intestine, and kidney was determined by the uptake of 201thallium and 125I-labeled fatty acid (para-125I-phenyl-3-methyl pentanoic acid) in a 20% body surface area scald injury that also included plasma volume replacement resuscitation. Uptake of these radioisotopes was determined 15 minutes, 18 hours, and 72 hours after injury. The uptake of the 201thallium and 125I-labeled fatty acid by the gastrointestinal tissues was not statistically different at any of the time periods after comparison of the injured and control (sham-treated) animals. 201Thallium uptake by the kidney was significantly diminished 15 minutes after the burn injury (P less than 0.01). Based on these blood flow measurement techniques, the data suggest that the 20% body surface area scald injury did not alter blood flow to the liver or gastrointestinal tract within the initial 72 hours after the burn injury even though a decrease in renal blood flow was easily detected. These results suggest that the dysfunction of the gastrointestinal system or hepatic system observed after an acute burn injury is not simply the result of hypovolemic shock, which reduces both renal and mesenteric blood flow. These gastrointestinal and hepatic alterations may be related to a factor or factors other than intestinal ischemia.

  14. Tubuloglomerular feedback dynamics and renal blood flow autoregulation in rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Wagner, A J; Marsh, D J


    To decide whether tubuloglomerular feedback (TGF) can account for renal autoregulation, we tested predictions of a TGF simulation. Broad-band and single-frequency perturbations were applied to arterial pressure; arterial blood pressure, renal blood flow and proximal tubule pressure were measured....... blood flow. We conclude that two components can be detected in the dynamic regulation of renal blood flow, i.e., a slow component that represents TGF and a faster component that most likely represents an intrinsic vascular myogenic mechanism.......To decide whether tubuloglomerular feedback (TGF) can account for renal autoregulation, we tested predictions of a TGF simulation. Broad-band and single-frequency perturbations were applied to arterial pressure; arterial blood pressure, renal blood flow and proximal tubule pressure were measured....... Data were analyzed by linear systems analysis. Broad-band forcings of arterial pressure were also applied to the model to compare experimental results with simulations. With arterial pressure as the input and tubular pressure, renal blood flow, or renal vascular resistance as outputs, the model...

  15. Involvement of the Blood-Brain Barrier in Metabolic Regulation. (United States)

    Kastin, Abba J; Pan, Weihong


    Pertinent to pandemic obesity, the discovery of endogenous peptides that affect the ingestion of food has led to the question of how these ingestive peptides exert their actions in the brain. Whereas peripheral sources provide a ready reserve, the availability of ingestive peptides to their central nervous system targets can be regulated by the blood-brain barrier (BBB). Some of the peptides/polypeptides are transported by saturable mechanisms from blood to brain. Examples include leptin, insulin, mahogany, and pancreatic polypeptide. Some enter the brain by passive diffusion, such as neuropeptide Y, orexin A, cocaine- and amphetamine-regulated transcript, cyclo His-Pro, and amylin. Some others may have essentially no penetration of the BBB; this class includes agouti-related protein, melanin-concentrating hormone, and urocortin. The regulatory function of the BBB can be seen in various physiological states. Hyperglycemia may upregulate transport systems for leptin, urocortin, and galanin-like peptide, whereas fasting can down-regulate those for leptin and galanin-like peptide. Thus, the BBB plays a dynamic role in modulating the passage of ingestive peptides from blood to brain.

  16. Vascular Cell Senescence Contributes to Blood-Brain Barrier Breakdown

    NARCIS (Netherlands)

    Yamazaki, Y.; Baker, D.J.; Tachibana, M.; Liu, C.C.; Deursen, J.M.A. van; Brott, T.G.; Bu, G.; Kanekiyo, T.


    BACKGROUND AND PURPOSE: Age-related changes in the cerebrovasculature, including blood-brain barrier (BBB) disruption, are emerging as potential risks for diverse neurological conditions. Because the accumulation of senescent cells in tissues is increasingly recognized as a critical step leading to

  17. Gliomas and the vascular fragility of the blood brain barrier

    Directory of Open Access Journals (Sweden)

    Luiz Gustavo eDubois


    Full Text Available Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB. By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM, characterized by a highly heterogeneous cell population (including tumor stem cells, extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the blood brain barrier and the concerns that arise when this barrier is affected.

  18. Blood-brain transfer of Pittsburgh compound B in humans

    DEFF Research Database (Denmark)

    Gjedde, Albert; Aanerud, Joel; Braendgaard, Hans


    In the labeled form, the Pittsburgh compound B (2-(4'-{N-methyl-[(11)C]}methyl-aminophenyl)-6-hydroxy-benzothiazole, [(11)C]PiB), is used as a biomarker for positron emission tomography (PET) of brain β-amyloid deposition in Alzheimer's disease (AD). The permeability of [(11)C]PiB in the blood...

  19. Blood and Brain Glutamate Levels in Children with Autistic Disorder (United States)

    Hassan, Tamer H.; Abdelrahman, Hadeel M.; Fattah, Nelly R. Abdel; El-Masry, Nagda M.; Hashim, Haitham M.; El-Gerby, Khaled M.; Fattah, Nermin R. Abdel


    Despite of the great efforts that move forward to clarify the pathophysiologic mechanisms in autism, the cause of this disorder, however, remains largely unknown. There is an increasing body of literature concerning neurochemical contributions to the pathophysiology of autism. We aimed to determine blood and brain levels of glutamate in children…

  20. Blood-brain distribution of morphine-6-glucuronide in sheep

    DEFF Research Database (Denmark)

    Villesen, H H; Foster, D J R; Upton, R N


    At present there are few data regarding the rate and extent of brain-blood partitioning of the opioid active metabolite of morphine, morphine-6-glucuronide (M6G). In this study the cerebral kinetics of M6G were determined, after a short-term intravenous infusion, in chronically instrumented consc...... conscious sheep....

  1. The blood flow in the posterior communicant artery. Angiographic study by using magnetic resonance

    CERN Document Server

    Portela, L A P


    did not change the direction of flow present, in the circumstances of this study. The arterial circle of Willis is the most important collateral pathway for the cerebral vessels when one the afferents is occluded. Its normal function, without vascular compromise, has been considered in conflicting ways in the literature. For centuries after its description by Thomas Willis in 1664 it was considered a flow equalizer, with free admixture of blood within it. Since the beginning of this century the dominant view is one of a potential value only, with null effective flow in the communicating arteries. The premise is included in different experimental models. Alternatively, it was considered that the normal direction of flow is antero-posterior, from carotid to posterior cerebral, since carotid flow is greater. Using phase-contrast magnetic resonance angiography, a non-invasive qualitative method, it was found in 40 patients without morphological brain abnormality and in 10 healthy volunteers that flow can be seen ...

  2. Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia. (United States)

    Wiegers, Evita C; Becker, Kirsten M; Rooijackers, Hanne M; von Samson-Himmelstjerna, Federico C; Tack, Cees J; Heerschap, Arend; de Galan, Bastiaan E; van der Graaf, Marinette


    It is unclear whether cerebral blood flow responses to hypoglycemia are altered in people with type 1 diabetes and impaired awareness of hypoglycemia. The aim of this study was to investigate the effect of hypoglycemia on both global and regional cerebral blood flow in type 1 diabetes patients with impaired awareness of hypoglycemia, type 1 diabetes patients with normal awareness of hypoglycemia and healthy controls ( n = 7 per group). The subjects underwent a hyperinsulinemic euglycemic-hypoglycemic glucose clamp in a 3 T MR system. Global and regional changes in cerebral blood flow were determined by arterial spin labeling magnetic resonance imaging, at the end of both glycemic phases. Hypoglycemia generated typical symptoms in patients with type 1 diabetes and normal awareness of hypoglycemia and healthy controls, but not in patients with impaired awareness of hypoglycemia. Conversely, hypoglycemia increased global cerebral blood flow in patients with impaired awareness of hypoglycemia, which was not observed in the other two groups. Regionally, hypoglycemia caused a redistribution of cerebral blood flow towards the thalamus of both patients with normal awareness of hypoglycemia and healthy controls, consistent with activation of brain regions associated with the autonomic response to hypoglycemia. No such redistribution was found in the patients with impaired awareness of hypoglycemia. An increase in global cerebral blood flow may enhance nutrient supply to the brain, hence suppressing symptomatic awareness of hypoglycemia. Altogether these results suggest that changes in cerebral blood flow during hypoglycemia contribute to impaired awareness of hypoglycemia.

  3. Computational model on pulsatile flow of blood through a tapered ...

    Indian Academy of Sciences (India)

    An unsteady two-fluid model of blood flow through a tapered arterial stenosis with variable viscosity in the presence of variable magnetic field has been analysed in the present paper. In this article, blood in the core region is assumed to obey the law of Jeffrey fluid and plasma in the peripheral layer is assumed to be ...

  4. Femoral Blood Flow and Cardiac Output During Blood Flow Restricted Leg Press Exercise (United States)

    Everett, M. E.; Hackney, K.; Ploutz-Snyder, L.


    Low load blood flow restricted resistance exercise (LBFR) causes muscle hypertrophy that may be stimulated by the local ischemic environment created by the cuff pressure. However, local blood flow (BF) during such exercise is not well understood. PURPOSE: To characterize femoral artery BF and cardiac output (CO) during leg press exercise (LP) performed at a high load (HL) and low load (LL) with different levels of cuff pressure. METHODS: Eleven subjects (men/women 4/7, age 31.4+/-12.8 y, weight 68.9+/-13.2 kg, mean+/-SD) performed 3 sets of supine left LP to fatigue with 90 s of rest in 4 conditions: HL (%1-RM/cuff pressure: 80%/0); LL (20%/0); LBFR(sub DBP) (20%/1.3 x diastolic blood pressure, BP); LBFR(sub SBP) (20%/1.3 x supine systolic BP). The cuff remained inflated throughout the LBFR exercise sessions. Artery diameter, velocity time integral (VTI), and stroke volume (SV) were measured using Doppler ultrasound at rest and immediately after each set of exercise. Heart rate (HR) was monitored using a 3-lead ECG. BF was calculated as VTI x vessel cross-sectional area. CO was calculated as HR x SV. The data obtained after each set of exercise were averaged and used for analyses. Multi-level modeling was used to determine the effect of exercise condition on dependent variables. Statistical significance was set a priori at p LL (9.92+/-0.82 cm3) > LBFR(sub dBP)(6.47+/-0.79 cm3) > LBFR(sub SBP) (3.51+/-0.59 cm3). Blunted exercise induced increases occurred in HR, SV, and CO after LBFR compared to HL and LL. HR increased 45% after HL and LL and 28% after LBFR (p<0.05), but SV increased (p<0.05) only after HL. Consequently, the increase (p<0.05) in CO was greater in HL and LL (approximately 3 L/min) than in LBFR (approximately 1 L/min). CONCLUSION: BF during LBFR(sub SBP) was 1/3 of that observed in LL, which supports the hypothesis that local ischemia stimulates the LBFR hypertrophic response. As the cuff did not compress the artery, the ischemia may have occurred

  5. Intra-Arterial Delivery of AAV Vectors to the Mouse Brain After Mannitol Mediated Blood Brain Barrier Disruption (United States)

    Santillan, Alejandro; Sondhi, Dolan; Dyke, Jonathan P.; Crystal, Ronald G.; Gobin, Y. Pierre; Ballon, Douglas J.


    The delivery of therapeutics to neural tissue is greatly hindered by the blood brain barrier (BBB). Direct local delivery via diffusive release from degradable implants or direct intra-cerebral injection can bypass the BBB and obtain high concentrations of the therapeutic in the targeted tissue, however the total volume of tissue that can be treated using these techniques is limited. One treatment modality that can potentially access large volumes of neural tissue in a single treatment is intra-arterial (IA) injection after osmotic blood brain barrier disruption. In this technique, the therapeutic of interest is injected directly into the arteries that feed the target tissue after the blood brain barrier has been disrupted by exposure to a hyperosmolar mannitol solution, permitting the transluminal transport of the therapy. In this work we used contrast enhanced magnetic resonance imaging (MRI) studies of IA injections in mice to establish parameters that allow for extensive and reproducible BBB disruption. We found that the volume but not the flow rate of the mannitol injection has a significant effect on the degree of disruption. To determine whether the degree of disruption we observed with this method was sufficient for delivery of nanoscale therapeutics, we performed IA injections of an adeno-associated viral vector containing the CLN2 gene (AAVrh.10CLN2), which is mutated in the lysosomal storage disorder Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL). We demonstrated that IA injection of AAVrh.10CLN2 after BBB disruption can achieve widespread transgene production in the mouse brain after a single administration. Further, we showed that there exists a minimum threshold of BBB disruption necessary to permit the AAV.rh10 vector to pass into the brain parenchyma from the vascular system. These results suggest that IA administration may be used to obtain widespread delivery of nanoscale therapeutics throughout the murine brain after a single

  6. Altered Regional Cerebral Blood Flow in Chronic Whiplash Associated Disorders

    Directory of Open Access Journals (Sweden)

    David Vállez García


    Full Text Available There is increasing evidence of central hyperexcitability in chronic whiplash-associated disorders (cWAD. However, little is known about how an apparently simple cervical spine injury can induce changes in cerebral processes. The present study was designed (1 to validate previous results showing alterations of regional cerebral blood flow (rCBF in cWAD, (2 to test if central hyperexcitability reflects changes in rCBF upon non-painful stimulation of the neck, and (3 to verify our hypothesis that the missing link in understanding the underlying pathophysiology could be the close interaction between the neck and midbrain structures. For this purpose, alterations of rCBF were explored in a case-control study using H215O positron emission tomography, where each group was exposed to four different conditions, including rest and different levels of non-painful electrical stimulation of the neck. rCBF was found to be elevated in patients with cWAD in the posterior cingulate and precuneus, and decreased in the superior temporal, parahippocampal, and inferior frontal gyri, the thalamus and the insular cortex when compared with rCBF in healthy controls. No differences in rCBF were observed between different levels of electrical stimulation. The alterations in regions directly involved with pain perception and interoceptive processing indicate that cWAD symptoms might be the consequence of a mismatch during the integration of information in brain regions involved in pain processing.

  7. Development and application of a volume penalization immersed boundary method for the computation of blood flow and shear stresses in cerebral vessels and aneurysms

    NARCIS (Netherlands)

    Mikhal, Julia Olegivna; Geurts, Bernardus J.


    A volume-penalizing immersed boundary method is presented for the simulation of laminar incompressible flow inside geometrically complex blood vessels in the human brain. We concentrate on cerebral aneurysms and compute flow in curved brain vessels with and without spherical aneurysm cavities

  8. Effects of Sevoflurane and Propofol on Organ Blood Flow in Left Ventricular Assist Devices in Pigs

    Directory of Open Access Journals (Sweden)

    Paloma Morillas-Sendín


    Full Text Available The aim of this study was to assess the effect of sevoflurane and propofol on organ blood flow in a porcine model with a left ventricular assist device (LVAD. Ten healthy minipigs were divided into 2 groups (5 per group according to the anesthetic received (sevoflurane or propofol. A Biomedicus centrifugal pump was implanted. Organ blood flow (measured using colored microspheres, markers of tissue injury, and hemodynamic parameters were assessed at baseline (pump off and after 30 minutes of partial support. Blood flow was significantly higher in the brain (both frontal lobes, heart (both ventricles, and liver after 30 minutes in the sevoflurane group, although no significant differences were recorded for the lung, kidney, or ileum. Serum levels of alanine aminotransferase and total bilirubin were significantly higher after 30 minutes in the propofol group, although no significant differences were detected between the groups for other parameters of liver function, kidney function, or lactic acid levels. The hemodynamic parameters were similar in both groups. We demonstrated that, compared with propofol, sevoflurane increases blood flow in the brain, liver, and heart after implantation of an LVAD under conditions of partial support.

  9. Blood flow and clearance in tendons. Studies with dogs. (United States)

    Hooper, G; Davies, R; Tothill, P


    Blood flow in intact tendons in dogs was measured using 57Co-labelled microspheres and compared with the simultaneous clearance of a diffusible radionuclide, 85Sr, by the same tendons. Clearance was significantly greater than flow in all tendons, indicating that diffusion from surrounding tissues may be important in the nutrition of normal tendons.

  10. P-glycoprotein function at the blood-brain barrier imaged using 11C-N-desmethyl-loperamide in monkeys. (United States)

    Liow, Jeih-San; Kreisl, William; Zoghbi, Sami S; Lazarova, Neva; Seneca, Nicholas; Gladding, Robert L; Taku, Andrew; Herscovitch, Peter; Pike, Victor W; Innis, Robert B


    11C-Loperamide is an avid substrate for P-glycoprotein (P-gp), but it is rapidly metabolized to 11C-N-desmethyl-loperamide (11C-dLop), which is also a substrate for P-gp and thereby contaminates the radioactive signal in the brain. Should further demethylation of 11C-dLop occur, radiometabolites with low entry into the brain are generated. Therefore, we evaluated the ability of 11C-dLop to quantify the function of P-gp at the blood-brain barrier in monkeys. Six monkeys underwent 12 PET scans of the brain, 5 at baseline and 7 after pharmacologic blockade of P-gp. A subset of monkeys also underwent PET scans with 15O-water to measure cerebral blood flow. To determine whether P-gp blockade affected peripheral distribution of 11C-dLop, we measured whole-body biodistribution in 4 monkeys at baseline and after P-gp blockade. The concentration of 11C-dLop in the brain was low under baseline conditions and increased 5-fold after P-gp blockade. This increase was primarily caused by an increased rate of entry into the brain rather than a decreased rate of removal from the brain. With P-gp blockade, uptake of radioactivity among brain regions correlated linearly with blood flow, suggesting a high single-pass extraction. After correction for cerebral blood flow, the uptake of 11C-dLop was fairly uniform among brain regions, suggesting that the function of P-gp is fairly uniformly distributed in the brain. On whole-body imaging, P-gp blockade significantly affected distribution of radioactivity only to the brain and not to other visually identified source organs. The effective dose estimated for humans was approximately 9 microSv/MBq. PET with 11C-dLop can quantify P-gp function at the blood-brain barrier in monkeys. The single-pass extraction of 11C-dLop is high and requires correction for blood flow to accurately measure the function of this efflux transporter. The low uptake at baseline and markedly increased uptake after P-gp blockade suggest that 11C-dLop will be useful to

  11. Ultrasonic Enrichment of Flowing Blood Cells in Capillars: Influence of the Flow Rate (United States)

    Carreras, Pilar; Gonzalez, Itziar; Ahumada, Oscar

    Red blood cells subjected to standing waves collect at the pressure nodes during their flow motion. Blood is a non-newtonian fluid whose density and other properties are defined by its flow velocity. Their drift motion is governed by the radiation force together with hydrodynamic conditions. This work presents a study of the blood cell enrichment performed in a rectangular capillar at f=1 MHz as a function of their flow motion. The cells collect along the central axis of the capillary in very few seconds, with a clearance in other lateral areas. Optimal flow rates below 100uL/min were found in the experiments.

  12. Peripheral blood brain-derived neurotrophic factor in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, K; Vinberg, M; Kessing, L V


    Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in bipolar disorder, speculated to mirror alterations in brain expression of BDNF. The research area is rapidly evolving; however, recent...... investigations have yielded conflicting results with substantial variation in outcomes, highlighting the need to critically assess the state of current evidence. The aims of the study were to investigate differences in peripheral blood BDNF concentrations between bipolar disorder patients and healthy control......-November 2014) and PsycINFO (1806-November 2014), and 35 studies comprising a total of 3798 participants were included in the meta-analysis. The results indicated that crude peripheral blood BDNF levels may be lower in bipolar disorder patients overall (Hedges' g=-0.28, 95% CI: -0.51 to -0.04, P=0...

  13. Regional cerebral blood flow in schizophrenic patients; In relation to the subtypes of the disease

    Energy Technology Data Exchange (ETDEWEB)

    Sagawa, Katsuo; Sibuya, Isoo; Oiji, Arata; Kawakatsu, Sinobu; Morinobu, Shigeru; Totsuka, Shiro (Yamagata Univ. (Japan). School of Medicine); Kinoshita, Osami; Yazaki, Mitsuyasu


    Seventy-six schizophrenic patients were examined by a Xe-133 inhalation method to determine regional cerebral blood flow. A decreased blood flow was observed in the frontal lobe, especially in the right inferior part. In a study on the relationship between disease subtypes and regional cerebral blood flow, negative symptoms were found more predominantly associated with dissolution type than delusion type. In the group of dissolution type, a decreased blood flow was observed in both the right inferior frontal lobe and the right upper hemisphere, in comparison to the group of delution type. Patients presenting with auditory hallucination had a significantly higher incidence of both negative and positive symptoms, as compared with those not presenting with it. In such patients, a significantly decreased blood flow was also seen in the left upper frontal lobe and the bilateral parietal lobe. Xe-133 inhalation method should assist in evaluating brain function in schizophrenic patients, thus leading to the likelihood of developing a new treatment modality. (N.K.).


    DEFF Research Database (Denmark)

    Pavlov, A.N.; Pavlova, O.N.; Mosekilde, Erik


    The purpose of this study is to demonstrate the possibility of revealing new characteristic features of renal blood flow autoregulation in healthy and pathological states through the application of discrete wavelet transforms to experimental time series for normotensive and hypertensive rats....... A reduction in the variability of the wavelet coefficients in hypertension is observed at both the microscopic level of the blood flow in efferent arterioles of individual nephrons and at the macroscopic level of the blood pressure in the main arteries. The reduction is manifest in both of the main frequency...

  15. Vasodilator interactions in skeletal muscle blood flow regulation

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Nyberg, Michael Permin; Jensen, Lasse Gliemann


    During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by vasodilators formed locally in the muscle tissue, either on the intraluminal or the extraluminal side of the blood vessels. A number...... that this remaining hyperemia may be explained by cAMP and cGMP independent smooth muscle relaxation, such as effects of endothelial derived hyperpolarization factors (EDHFs) or through metabolic modulation of sympathetic effects. The nature and role of EDHF as well as potential novel mechanisms in muscle blood flow...

  16. Mesenteric stenosis, collaterals, and compensatory blood flow

    NARCIS (Netherlands)

    van Petersen, Andre S.; Kolkman, Jeroen J.; Meerwaldt, Robbert; Huisman, Ad B.; van der Palen, Jacobus Adrianus Maria; Zeebregts, Clark J.; Geelkerken, Robert H.


    Background The mesenteric circulation has an extensive collateral network. Therefore, stenosis in one or more mesenteric arteries does not necessarily lead to symptoms. The objective of this study was to determine the effect of collateral flow on celiac artery (CA) and superior mesenteric artery

  17. Mesenteric stenosis, collaterals, and compensatory blood flow

    NARCIS (Netherlands)

    van Petersen, Andre S.; Kolkman, Jeroen J.; Meerwaldt, Robbert; Huisman, Ad B.; van der Palen, Job; Zeebregts, Clark J.; Geelkerken, Robert H.

    Background: The mesenteric circulation has an extensive collateral network. Therefore, stenosis in one or more mesenteric arteries does not necessarily lead to symptoms. The objective of this study was to determine the effect of collateral flow on celiac artery (CA) and superior mesenteric artery

  18. Migration of African trypanosomes across the blood-brain barrier. (United States)

    Masocha, Willias; Rottenberg, Martin E; Kristensson, Krister


    Subspecies of the extracellular parasite, Trypanosoma brucei, which are spread by the tsetse fly in sub-Saharan Africa, cause in humans Sleeping Sickness. In experimental rodent models the parasite can at a certain stage of disease pass through the blood-brain barrier across or between the endothelial cells and the vessel basement membranes. The laminin composition of the basement membranes determines whether they are permissive to parasite penetration. One cytokine, interferon-gamma, plays an important role in regulating the trypanosome trafficking into the brain. Treatment strategies aim at developing drugs that can impede penetration of trypanosomes into the brain and/or that can eliminate trypanosomes once they are inside the brain parenchyma, but have lower toxicity than the ones presently in use.

  19. Estimating blood flow velocity in angiographic image data (United States)

    Hentschke, Clemens M.; Serowy, Steffen; Janiga, Gábor; Rose, Georg; Tönnies, Klaus D.


    We propose a system to estimate blood flow velocity in angiographic image data for patient-specific blood flow simulations. Angiographies are acquired routinely for diagnosis and before treatment of vascular diseases. Projective blood flow is measured in digital subtraction X-ray angiography (2D-DSA) images by tracking contrast agent propagation. Spatial information is added by re-projecting 2D centerline pixels to the reconstructed 3D X-ray rotation angiography (3D-RA) data of the same subject. Ambiguities caused by occluding vessels from the virtual viewpoint of the acquired 2D-DSA image are resolved by a graph-based approach. The blood flow velocity can be used as boundary condition for exact blood flow simulations that can help physicians to understand hemodynamics of the vasculature. Our focus is to analyze cerebral angiographic data. We performed several experiments with phantom and patient data that proved the accuracy and the functionality of our method. We evaluated experimentally the projective flow estimation method and the re-projection method. We measured mean deviations to the ground truth between 11 % and 15.7 % for phantom data. We also showed the ability of our method to produce plausible results with patient-data.

  20. Contributions to the Study of Blood Brain Flux Using Radioactive Tracers. (United States)

    Mureşan, Ioan; Cosma, Ioan


    In this paper, we present an original radiocirculographic method for investigates of cerebral blood flow, which has proven to be very useful, simple, and efficient for studies of brain hemodynamics. Physical considerations on injected radioactive tracer in cardiovascular system, allowed us to state a relationship for the blood flux, F, valued as the amount of fluid-blood that traverses a vascular segment in unit time. All these theoretical facts, along with a host of remarkable clinical results, are presented in a doctoral thesis entitled "The cerebral Hemodynamics in Essential Hypertension and Arteriosclerosis" of the eminent doctor Ioan Mures,an, who died in 1984, at only 50 years old. Using tracers marked with radioactive chrome 51Cr and iodine 131I, it was studied, for patients with various vascular diseases the blood circulation in other territories as an echo of cerebral blood flow. Outstanding results, relating to physiology, diagnosis, and therapy of some diseases, have been obtained. Through intensive collaborations, this method has been operationalized at the University Clinics of Cluj. Here, thousands of patients have been investigated, obtaining quantifiable information which highlighted the patient's condition by emergent and incident blood flows in the global circulatory process and related to other vascular segments.

  1. Viscoelastic capillary flow: the case of whole blood

    Directory of Open Access Journals (Sweden)

    David Rabaud


    Full Text Available The dynamics of spontaneous capillary flow of Newtonian fluids is well-known and can be predicted by the Lucas-Washburn-Rideal (LWR law. However a wide variety of viscoelastic fluids such as alginate, xanthan and blood, does not exhibit the same Newtonian behavior.In this work we consider the Herschel-Bulkley (HB rheological model and Navier-Stokes equation to derive a generic expression that predicts the capillary flow of non-Newtonian fluids. The Herschel-Bulkley rheological model encompasses a wide variety of fluids, including the Power-law fluids (also called Ostwald fluids, the Bingham fluids and the Newtonian fluids. It will be shown that the proposed equation reduces to the Lucas-Washburn-Rideal law for Newtonian fluids and to the Weissenberg-Rabinowitsch-Mooney (WRM law for power-law fluids. Although HB model cannot reduce to Casson’s law, which is often used to model whole blood rheology, HB model can fit the whole blood rheology with the same accuracy.Our generalized expression for the capillary flow of non-Newtonian fluid was used to accurately fit capillary flow of whole blood. The capillary filling of a cylindrical microchannel by whole blood was monitored. The blood first exhibited a Newtonian behavior, then after 7 cm low shear stress and rouleaux formation made LWR fails to fit the data: the blood could not be considered as Newtonian anymore. This non-Newtonian behavior was successfully fit by the proposed equation.

  2. Two methods for calculating regional cerebral blood flow from emission computed tomography of inert gas concentrations

    DEFF Research Database (Denmark)

    Kanno, I; Lassen, N A


    Two methods are described for calculation of regional cerebral blood flow from completed tomographic data of radioactive inert gas distribution in a slice of brain tissue. It is assumed that the tomographic picture gives the average inert gas concentration in each pixel over data collection perio...... are implemented using synthetic data of xenon-133 emission computed tomography and some of the difficulties likely to be encountered in practice are stressed....

  3. Nephron blood flow dynamics measured by laser speckle contrast imaging

    DEFF Research Database (Denmark)

    von Holstein-Rathlou, Niels-Henrik; Sosnovtseva, Olga V; Pavlov, Alexey N


    Tubuloglomerular feedback (TGF) has an important role in autoregulation of renal blood flow and glomerular filtration rate (GFR). Because of the characteristics of signal transmission in the feedback loop, the TGF undergoes self-sustained oscillations in single-nephron blood flow, GFR, and tubular...... pressure and flow. Nephrons interact by exchanging electrical signals conducted electrotonically through cells of the vascular wall, leading to synchronization of the TGF-mediated oscillations. Experimental studies of these interactions have been limited to observations on two or at most three nephrons...... simultaneously. The interacting nephron fields are likely to be more extensive. We have turned to laser speckle contrast imaging to measure the blood flow dynamics of 50-100 nephrons simultaneously on the renal surface of anesthetized rats. We report the application of this method and describe analytic...

  4. Blood flow and stem cells in vascular disease. (United States)

    Zhang, Cheng; Zeng, Lingfang; Emanueli, Costanza; Xu, Qingbo


    It is well known that the altered blood flow is related to vascular diseases, including atherosclerosis, restenosis, and arteriosclerosis, which preferentially located at areas with the disturbed blood flow, suggesting that altered biomechanical stress may exert their effect on the vascular disease. Recent evidence indicated the presence of abundant stem/progenitor cells in the vessel wall, in which laminar shear stress can stimulate these cells to differentiate towards endothelial lineage, while cyclic strain results in smooth muscle differentiation. In line with this, it was evidenced that altered biomechanical stress in stented vessels may lead to 'wrong' direction of vascular stem cell differentiation resulting in restenosis. However, the underlying mechanisms are not well understood. In this article, we will give an overview of the effect of the local flow pattern on stem/progenitor cell differentiation and the possible mechanism on how the blood flow influences stem cell behaviours in the development of vascular diseases.

  5. Intrinsic regulation of blood flow in adipose tissue

    DEFF Research Database (Denmark)

    Henriksen, O; Nielsen, Steen Levin; Paaske, W


    Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called autoregulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated...... subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an autoregulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g-min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue....... Following total ischemia all experiments showed a period with reactive hyperemia, and both duration of hyperemia and excess flow was related to the duration of the ischemia. This response therefore seems more resistant to the experimental procedure, while autoregulation of blood flow to lowered pressure...

  6. Cilia driven flow networks in the brain (United States)

    Wang, Yong; Faubel, Regina; Westendorf, Chrsitian; Eichele, Gregor; Bodenschatz, Eberhard

    Neurons exchange soluble substances via the cerebrospinal fluid (CSF) that fills the ventricular system. The walls of the ventricular cavities are covered with motile cilia that constantly beat and thereby induce a directional flow. We recently discovered that cilia in the third ventricle generate a complex flow pattern leading to partitioning of the ventricular volume and site-directed transport paths along the walls. Transient and daily recurrent alterations in the cilia beating direction lead to changes in the flow pattern. This has consequences for delivery of CSF components along the near wall flow. The contribution of this cilia-induced flow to overall CSF flow remains to be investigated. The state-of-art lattice Boltzmann method is adapted for studying the CFS flow. The 3D geometry of the third ventricle at high resolution was reconstructed. Simulation of CSF flow without cilia in this geometry confirmed that the previous idea about unidirectional flow does not explain how different components of CSF can be delivered to their various target sites. We study the contribution of the cilia-induced flow pattern to overall CSF flow and identify target areas for site-specific delivery of CSF-constituents with respect to the temporal changes.

  7. Pulsatile blood flow, shear force, energy dissipation and Murray's Law

    Directory of Open Access Journals (Sweden)

    Bengtsson Hans-Uno


    Full Text Available Abstract Background Murray's Law states that, when a parent blood vessel branches into daughter vessels, the cube of the radius of the parent vessel is equal to the sum of the cubes of the radii of daughter blood vessels. Murray derived this law by defining a cost function that is the sum of the energy cost of the blood in a vessel and the energy cost of pumping blood through the vessel. The cost is minimized when vessel radii are consistent with Murray's Law. This law has also been derived from the hypothesis that the shear force of moving blood on the inner walls of vessels is constant throughout the vascular system. However, this derivation, like Murray's earlier derivation, is based on the assumption of constant blood flow. Methods To determine the implications of the constant shear force hypothesis and to extend Murray's energy cost minimization to the pulsatile arterial system, a model of pulsatile flow in an elastic tube is analyzed. A new and exact solution for flow velocity, blood flow rate and shear force is derived. Results For medium and small arteries with pulsatile flow, Murray's energy minimization leads to Murray's Law. Furthermore, the hypothesis that the maximum shear force during the cycle of pulsatile flow is constant throughout the arterial system implies that Murray's Law is approximately true. The approximation is good for all but the largest vessels (aorta and its major branches of the arterial system. Conclusion A cellular mechanism that senses shear force at the inner wall of a blood vessel and triggers remodeling that increases the circumference of the wall when a shear force threshold is exceeded would result in the observed scaling of vessel radii described by Murray's Law.

  8. Blood-brain barrier permeability and brain uptake mechanism of kainic Acid and dihydrokainic Acid

    DEFF Research Database (Denmark)

    Gynther, Mikko; Petsalo, Aleksanteri; Hansen, Steen Honoré


    tools in various in vivo central nervous system disease models in rodents, as well as being templates in the design of novel ligands affecting the glutamatergic system. Both molecules are highly polar but yet capable of crossing the blood-brain barrier (BBB). We used an in situ rat brain perfusion...... technique to determine the brain uptake mechanism and permeability across the BBB. To determine KA and DHK concentrations in the rat brain, simple and rapid sample preparation and liquid chromatography mass spectrometer methods were developed. According to our results the BBB permeability of KA and DHK...... is low, 0.25 × 10(-6) and 0.28 × 10(-6) cm/s for KA and DHK, respectively. In addition, the brain uptake is mediated by passive diffusion, and not by active transport. Furthermore, the non-specific plasma and brain protein binding of KA and DHK was determined to be low, which means that the unbound drug...

  9. Monitoring variables affecting positron emission tomography measurements of cerebral blood flow in anaesthetized pigs

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen; Zois, Nora Elisabeth; Simonsen, Mette

    female pigs. Results: We found that low blood pH, high arterial carbon dioxide tension (PaCO2), high heart rate, high body temperature and long anaesthesia time are associated with high CBF in anaesthetized pigs. No associations were noted between CBF and low arterial oxygen tension, haematocrit......, systolic and diastolic blood pressure. Conclusions: Our observations indicate that monitoring of pH, PaCO2, heart rate and body temperature are crucial for maintaining stable levels of CBF and thus optimizing PET imaging of molecular mechanisms in the brain of living pig. Furtermore, anaesthesia length......Background: Positron emission tomography (PET) imaging of anaesthetised pig brains is a useful tool in neuroscience. Stable cerebral blood flow (CBF) is essential for PET, since variations can affect the kinetics of several radiotracers. However, the impact of physiological factors regulating CBF...

  10. Partitioning of red blood cell aggregates in bifurcating microscale flows (United States)

    Kaliviotis, E.; Sherwood, J. M.; Balabani, S.


    Microvascular flows are often considered to be free of red blood cell aggregates, however, recent studies have demonstrated that aggregates are present throughout the microvasculature, affecting cell distribution and blood perfusion. This work reports on the spatial distribution of red blood cell aggregates in a T-shaped bifurcation on the scale of a large microvessel. Non-aggregating and aggregating human red blood cell suspensions were studied for a range of flow splits in the daughter branches of the bifurcation. Aggregate sizes were determined using image processing. The mean aggregate size was marginally increased in the daughter branches for a range of flow rates, mainly due to the lower shear conditions and the close cell and aggregate proximity therein. A counterintuitive decrease in the mean aggregate size was apparent in the lower flow rate branches. This was attributed to the existence of regions depleted by aggregates of certain sizes in the parent branch, and to the change in the exact flow split location in the T-junction with flow ratio. The findings of the present investigation may have significant implications for microvascular flows and may help explain why the effects of physiological RBC aggregation are not deleterious in terms of in vivo vascular resistance.

  11. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. (United States)

    Nau, Roland; Sörgel, Fritz; Eiffert, Helmut


    The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable.

  12. Efflux transporters in blood-brain interfaces of the developing brain

    Directory of Open Access Journals (Sweden)

    Nathalie eStrazielle


    Full Text Available The cerebral microvessel endothelium forming the blood-brain barrier (BBB and the epithelium of the choroid plexuses forming the blood-CSF barrier (BCSFB operate as gatekeepers for the CNS. Exposure of the vulnerable developing brain to chemical insults can have dramatic consequences for brain maturation and lead to life-long neurological diseases. The ability of blood-brain interfaces (BBIs to efficiently protect the immature brain is therefore an important pathophysiological issue. This is also key to our understanding of drug entry into the brain of neonatal and pediatric patients. Nonspecific paracellular diffusion through BBIs is restricted early during development, but other neuroprotective properties of these interfaces differ between the developing and adult brains. This review focuses on the developmental expression and function of multispecific efflux transporters of the ABCB, ABCC, ABCG, SLC21, SLC22, and SLC15 families. These transporters play a key role in preventing brain entry of blood-borne molecules such as drugs, environmental toxicants, and endogenous metabolites, or else in increasing the clearance of potentially harmful organic ions from the brain. The limited data available for laboratory animals and human highlight transporter-specific developmental patterns of expression and function, which differ between BBIs. The BCSFB achieves an adult phenotype earlier than the BBB. Efflux transporters at the BBB appear to be regulated by various factors subsequently secreted by neural progenitors, and astrocytes during development. Their expression is also modulated by oxidative stress, inflammation, and exposure to xenobiotic inducers. A better understanding of these regulatory pathways during development, in particular the signaling pathways triggered by oxidative stress and xenobiotics, may open new opportunities to therapeutic manipulation in view to improve or restore neuroprotective functions of the BBIs in the context of

  13. The blood-brain barrier in systemic lupus erythematosus. (United States)

    Abbott, N J; Mendonça, L L F; Dolman, D E M


    Central nervous system (CNS) involvement may occur in 20-70% of systemic lupus erythematosus (SLE) patients where neurological symptoms are overt; this is termed neuropsychiatric lupus or NPSLE. This review summarizes evidence that damage to the brain endothelium forming the blood-brain barrier (BBB) is a contributory factor in NPSLE. The normal CNS is protected by blood-tissue barriers at three sites, the brain endothelium (BBB), the choroid plexus epithelium (blood-CSF barrier) and the arachnoid epithelium. The tight junctions of the barrier layers severely restrict entry of plasma constituents including proteins, so that the CSF and brain interstitial fluid contain low levels of protein. Methods for diagnosing BBB damage include imaging (CT, MRI) using contrast agents, and analysing protein content and profiles of CSF Changes in the albumin quotient Qalbumin show evidence for barrier damage, while changes in the immunoglobulin (Ig) index can indicate intrathecal antibody production. However, BBB damage may be transient, and hence undetected or underestimated. Few mechanistic studies exist, but the two main candidate mechanisms for BBB damage are microthrombi in cerebral vessels leading to ischaemia, and immune-mediated attack and activation of the endothelium leading to local cytokine production. Both can result in barrier breakdown. Neurological syndromes could then be secondary to damage to the BBB. The implications for treatment of NPSLE are discussed.

  14. Regional cerebral blood flow abnormalities in Alzheimer's Disease

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    Rezai, K.; Damasio, H.; Graff-Radford, N.; Eslinger, P.; Kirchner, P.


    In 37 patients (ages 58-81) with senile dementia of Alzheimer type (SDAT), regional cerebral blood flow (rCBF) was studied utilizing a dedicated SPECT system (Tomomatic-64) that produces rCBF images from 4-minute clearance of Xenon-133 in the brain. The authors have modified the device to acquire 5 continuous tomographic slices simultaneously. A consistent pattern of diminished blood flow was seen in 33 patients in the posterior-temporal and lower-parietal brain regions. Computer programs were developed to quantitate the size of the affected brain tissue in the posterolateral brain areas (confined to the posterior 40% and the lateral 25% of the major and minor brain axes respectively). They have previously reported normal rCBF in 25 volunteers to be greater than 45 ml/min/100g with less than 10% regional variation. Hence, an area was considered abnormal if rCBF measured less than 40 ml/min/100g or was less than 70% of the mean rCBF value in the anterior temporal-frontal regions.

  15. Coded ultrasound for blood flow estimation using subband processing

    DEFF Research Database (Denmark)

    Gran, F.; Udesen, J.; Jensen, J.A.


    This paper investigates the use of coded excitation for blood flow estimation in medical ultrasound. Traditional autocorrelation estimators use narrow-band excitation signals to provide sufficient signal-to-noise-ratio (SNR) and velocity estimation performance. In this paper, broadband coded...... the excitation signal is broadband and has good spatial resolution after pulse compression. This means that time can be saved by using the same data for B-mode imaging and blood flow estimation. Two different coding schemes are used in this paper, Barker codes and Golay codes. The performance of the codes...... for velocity estimation is compared with a conventional approach transmitting a narrow-band pulse. The study was carried out using an experimental ultrasound scanner and a commercial linear array 7 MHz transducer. A circulating flow rig was scanned with a beam-to-flow angle of 60 degrees. The flow in the rig...

  16. Coded Ultrasound for Blood Flow Estimation Using Subband Processing

    DEFF Research Database (Denmark)

    Gran, Fredrik; Udesen, Jesper; Nielsen, Michael Bachamnn


    This paper investigates the use of coded excitation for blood flow estimation in medical ultrasound. Traditional autocorrelation estimators use narrow-band excitation signals to provide sufficient signal-to-noise-ratio (SNR) and velocity estimation performance. In this paper, broadband coded...... the excitation signal is broadband and has good spatial resolution after pulse compression. This means that time can be saved by using the same data for B-mode imaging and blood flow estimation. Two different coding schemes are used in this paper, Barker codes and Golay codes. The performance of the codes...... for velocity estimation is compared with a conventional approach transmitting a narrow-band pulse. The study was carried out using an experimental ultrasound scanner and a commercial linear array 7 MHz transducer. A circulating flow rig was scanned with a beam-to-flow angle of 60°. The flow in the rig...

  17. Impacts of Blood-Brain Barrier in Drug Delivery and Targeting of Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yadollah Omidi


    Full Text Available Introduction: Entry of blood circulating agents into the brain is highly selectively controlled by specific transport machineries at the blood brain barrier (BBB, whose excellent barrier restrictiveness make brain drug delivery and targeting very challenging. Methods: Essential information on BBB cellular microenvironment were reviewed and discussed towards impacts of BBB on brain drug delivery and targeting. Results: Brain capillary endothelial cells (BCECs form unique biological structure and architecture in association with astrocytes and pericytes, in which microenvironment the BCECs express restrictive tight junctional complexes that block the paracellular inward/outward traverse of biomolecules/compounds. These cells selectively/specifically control the transportation process through carrier and/or receptor mediated transport machineries that can also be exploited for the delivery of pharmaceuticals into the brain. Intelligent molecular therapies should be designed using such transport machineries for the efficient delivery of designated drugs into the brain. For better clinical outcomes, these smart pharmaceuticals should be engineered as seamless nanosystems to provide simultaneous imaging and therapy (multimodal theranostics. Conclusion: The exceptional functional presence of BBB selectively controls inward and outward transportation mechanisms, thus advanced smart multifunctional nanomedicines are needed for the effective brain drug delivery and targeting. Fully understanding the biofunctions of BBB appears to be a central step for engineering of intelligent seamless therapeutics consisting of homing device for targeting, imaging moiety for detecting, and stimuli responsive device for on-demand liberation of therapeutic agent.

  18. Intermittent calf and foot compression increases lower extremity blood flow. (United States)

    Eze, A R; Comerota, A J; Cisek, P L; Holland, B S; Kerr, R P; Veeramasuneni, R; Comerota, A J


    Although foot compression increases foot skin perfusion and calf compression increases popliteal artery blood flow, these compression techniques have not been evaluated in combination. The purpose of this study was to evaluate whether calf and foot compression applied separately and simultaneously increase popliteal artery blood flow and/or foot skin perfusion, and to assess the relative merits of compression in patients with superficial femoral artery occlusion. Twenty-two legs from 12 normal volunteers with ankle/brachial indices (ABIs) > 0.96, and 10 legs from 7 claudicator patients with angiographically documented superficial femoral artery (SFA) occlusion and patent popliteal arteries with ABIs pressure pump (Art-Assist-AA 1000; ACI Medical Inc., San Marcos, California) were applied to the subject in the sitting position. Skin blood flow of the great toe was measured with a laser doppler (Laserflo model BPM 403A; TSI Inc., St. Paul, Minnesota), and popliteal artery blood flow was measured using duplex ultrasonography (ATL-Ultramark 9; Advanced Tech Laboratory, Bothell, Washington). Foot and calf compression was applied separately and simultaneously at 120 mm Hg pressure, with a 10-second inflation and 20-second deflation cycle. Popliteal artery blood flow and foot skin perfusion were recorded and the mean of 6 cycles calculated. Precompression popliteal artery blood flow (mL/min) for volunteers was 38.86 +/- 3.94, and for patients was 86.30 +/- 14.55 (P = 0.001). Precompression foot skin perfusion (mL/min/ 100/g tissue) for volunteers was 1.67 +/- 0.29, and for patients was 4.00 +/- 0.92 (P = 0.01). With the application of calf, foot, and simultaneous calf and foot compression, the popliteal artery blood flow increased in volunteers by 124%, 54%, and 173%, respectively, and in patients by 76%, 13%, and 50%. Foot skin perfusion increased in volunteers by 260%, 500%, and 328%, respectively, and in patients by 116%, 246%, and 188%. Relative increases in popliteal

  19. Neuro-inflammation, blood-brain barrier, seizures and autism

    Directory of Open Access Journals (Sweden)

    Theoharides Theoharis C


    Full Text Available Abstract Many children with Autism Spectrum Diseases (ASD present with seizure activity, but the pathogenesis is not understood. Recent evidence indicates that neuro-inflammation could contribute to seizures. We hypothesize that brain mast cell activation due to allergic, environmental and/or stress triggers could lead to focal disruption of the blood-brain barrier and neuro-inflammation, thus contributing to the development of seizures. Treating neuro-inflammation may be useful when anti-seizure medications are ineffective.

  20. Protection of the Blood-Brain Barrier as a Therapeutic Strategy for Brain Damage. (United States)

    Michinaga, Shotaro; Koyama, Yutaka


    Severe brain damage by trauma, ischemia, and hemorrhage lead to fatal conditions including sudden death, subsequent complications of the extremities and cognitive dysfunctions. Despite the urgent need for treatments for these complications, currently available therapeutic drugs are limited. Blood-brain barrier (BBB) disruption is a common pathogenic feature in many types of brain damage. The characteristic pathophysiological conditions caused by BBB disruption are brain edema resulting from an excessive increase of brain water content, inflammatory damage caused by infiltrating immune cells, and hemorrhage caused by the breakdown of microvessel structures. Because these pathogenic features induced by BBB disruption cause fatal conditions, their improvement is a desirable strategy. Many studies using experimental animal models have focused on molecules involved in BBB disruption, including vascular endothelial growth factors (VEGFs), matrix metalloproteinases (MMPs) and endothelins (ETs). The inhibition of these factors in several experimental animals was protective against BBB disruption caused by several types of brain damage, and ameliorated brain edema, inflammatory damage, and hemorrhagic transformation. In patients with brain damage, the up-regulation of these factors was observed and was related to brain damage severity. Thus, BBB protection by targeting VEGFs, MMPs, and ETs might be a novel strategy for the treatment of brain damage.

  1. Direct observation of cerebrospinal fluid bulk flow in the brain (United States)

    Mestre, Humberto; Tithof, Jeffrey; Thomas, John; Kelley, Douglas; Nedergaard, Maiken


    Cerebrospinal fluid (CSF) serves a vital role in normal brain function. Its adequate flow and exchange with interstitial fluid through perivascular spaces (PVS) has been shown to be important in the clearance of toxic metabolites like amyloid- β, and its disturbance can cause severe neurological diseases. It has long been suspected that bulk flow may transport CSF, but limitations in imaging techniques have prevented direct observation of such flows in the PVS. In this talk, we describe a novel approach using high speed two photon laser scanning microscopy which has allowed for the first ever direct observation of CSF flow in the PVS of a mouse brain. By performing particle tracking velocimetry, we quantify the CSF bulk flow speeds and PVS geometry. This technique enables future studies of CSF flow disturbances on a new scale and will pave the way for evaluating the role of these fluxes in neurodegenerative disease. R01NS100366 (to M.N.).

  2. One dimensional blood flow in a planetocentric orbit (United States)

    Haranas, Ioannis; Gkigkitzis, Ioannis


    All life on earth is accustomed to the presence of gravity. When gravity is altered, biological processes can go awry. It is of great importance to ensure safety during a spaceflight. Long term exposure to microgravity can trigger detrimental physiological responses in the human body. Fluid redistribution coupled with fluid loss is one of the effects. In particular, in microgravity blood volume is shifted towards the thorax and head. Sympathetic nervous system-induced vasoconstriction is needed to maintain arterial pressure, while venoconstriction limits venous pooling of blood prevents further reductions in venous return of blood to the heart. In this paper, we modify an existing one dimensional blood flow model with the inclusion of the hydrostatic pressure gradient that further depends on the gravitational field modified by the oblateness and rotation of the Earth. We find that the velocity of the blood flow VB is inversely proportional to the blood specific volume d, also proportional to the oblateness harmonic coefficient J2, the angular velocity of the Earth ωE, and finally proportional to an arbitrary constant c. For c = -0.39073 and ξH = -0.5 mmHg, all orbits result to less blood flow velocities than that calculated on the surface of the Earth. From all considered orbits, elliptical polar orbit of eccentricity e = 0.2 exhibit the largest flow velocity VB = 1.031 m/s, followed by the orbits of inclination i = 45°and 0°. The Earth's oblateness and its rotation contribute a 0.7% difference to the blood flow velocity.

  3. Effects of posture on limb blood flow in late pregnancy. (United States)

    Drummond, G B; Scott, S E; Lees, M M; Scott, D B


    Arm and leg blood flow was measured in 40 patients in late pregnancy in the supine and left lateral positions, and the changes were contrasted with changes found in 15 patients investigated in the early puerperium. A significant reduction in leg flow occurred in the pregnant subjects when the supine position was assumed. A further 30 patients in late pregnancy had leg flow measured in the following positions: left lateral, supine, right lateral, and the two mid-positions. Leg flow significantly increased on moving from the supine to all other positions except the right intermediate position, indicating that a leftward tilt is more effective in preventing caval compression.

  4. Magnetic resonance imaging and measurement of blood flow.


    McDonnell, C H; Herfkens, R J; Norbash, A M; Rubin, G D


    Blood flow can be shown as a negative image with magnetic resonance spin-echo techniques or as a positive image with gradient-echo techniques. Phase contrast refers to techniques where structures can be seen because of flow-induced phase shifts. These techniques can show the presence (slow flow) and also the direction of flow. Gradient-echo techniques--including phase-contrast versions--can be used with cardiac synchronization to obtain multiple images during the cardiac cycle. These images c...

  5. The Effect of Lipemia on Peripheral Blood Flow (United States)

    Zsotér, Thomas; Fam, Wadie M.; McGregor, Maurice


    The effect of lipemia on peripheral blood flow was studied in patients with and without peripheral vascular disease. Blood flow was measured by venous occlusion plethysmography in the calf and/or finger four to six hours after a fatty meal and after intravenous heparin. The abolition of postprandial lipemia by heparin was determined by measuring the plasma lactescence. Heparin resulted in no change in finger flow of either group or in calf flow in the control group. In nine out of 10 patients with occlusive vascular disease of the legs, it resulted in a small but significant increase of calf blood flow. No such alteration was found when heparin was given following a non-fatty meal. In 12 patients with intermittent claudication the clearing of postprandial lipemia by heparin caused prolongation of claudication time, as measured by the appearance of pain on treadmill exercise. It is concluded that, in some cases, postprandial lipemia is associated with a decrease in blood flow in a limb which is already the site of occlusive vascular disease. PMID:14146862

  6. Alterations in Cerebral Blood Flow after Resuscitation from Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Bistra Iordanova


    Full Text Available Greater than 50% of patients successfully resuscitated from cardiac arrest have evidence of neurological disability. Numerous studies in children and adults, as well as in animal models have demonstrated that cerebral blood flow (CBF is impaired after cardiac arrest. Stages of cerebral perfusion post-resuscitation include early hyperemia, followed by hypoperfusion, and finally either resolution of normal blood flow or protracted hyperemia. At the level of the microcirculation the blood flow is heterogeneous, with areas of no flow, low flow, and increased flow. CBF directed therapies in animal models of cardiac arrest improved neurological outcome, and therefore, the alterations in CBF after cardiac arrest likely contribute to the development of hypoxic ischemic encephalopathy. Current intensive care after cardiac arrest is centered upon maintaining systemic oxygenation, normal blood pressure values for age, maintaining general homeostasis, and avoiding hyperthermia. Assessment of CBF and oxygenation is not routinely performed after cardiac arrest. Currently available and underutilized techniques to assess cerebral perfusion include transcranial doppler, near-infrared spectroscopy, and arterial spin labeling magnetic resonance imaging. Limited clinical studies established the role of CBF and oxygenation monitoring in prognostication after cardiac arrest and few studies suggest that guiding critical care post-resuscitation to mean arterial pressures above the minimal autoregulatory range might improve outcome. Important knowledge gaps thus remain in cerebral monitoring and CBF and oxygen goal-directed therapies post-resuscitation from cardiac arrest.

  7. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

    DEFF Research Database (Denmark)

    Lassen, L.H.; Jacobsen, V.B.; Haderslev, P.A.


    Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...... g/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (V-mean) in the middle cerebral artery (MCA), as well as the heart...

  8. Unilateral frontal decortication changes cerebral blood flow distribution during hyperbaric oxygen exposure in rats. (United States)

    Bergö, G W; Engelsen, B; Tyssebotn, I


    Distribution of rCBF was measured with 10.7 +/- 0.5 microns differently radiolabelled microspheres (MS) during control at 1 bar air, and after 5 and 35 min at 5 bar (0.5 MPa) 95% O2 on awake, habituated rats 10 d after right-sided frontal decortication. A decreased tolerance to hyperbaric O2 was found compared to normal rats of the same strain. The systolic arterial pressure increased during O2 exposure (11%, p < 0.05), the mean arterial pressure remained unchanged, but the cardiac output and heart rate fell by 29 and 14% (p < 0.01), respectively. The arterial acid-base balance remained normal during O2 exposure, although a small reduction of CO2 (24%) and HCO3 (11%) was observed (p < 0.01 and p < 0.05), possibly due to increased alveolar ventilation caused by an elevated respiratory rate of 24% (p < 0.05). The arterial O2 content at 5 bar increased by about 30% (p < 0.01). During control, blood flow in 16 regions of each hemisphere was found to be lower, more scattered, and differently distributed on the lesioned side. After 5 min at 5 bar, the blood flow fell in nearly all regions of the brain (up to 40%), similarly in the two brain halves. During the 35 min exposure, the blood flow increased, so that 60% of the examined areas on the lesioned side had blood flow levels of control or above, in contrast to the undisturbed side where blood flow remained below control values. The O2 supply to different regions varied similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Estimation of blood flow rates in large microvascular networks. (United States)

    Fry, Brendan C; Lee, Jack; Smith, Nicolas P; Secomb, Timothy W


    Recent methods for imaging microvascular structures provide geometrical data on networks containing thousands of segments. Prediction of functional properties, such as solute transport, requires information on blood flow rates also, but experimental measurement of many individual flows is difficult. Here, a method is presented for estimating flow rates in a microvascular network based on incomplete information on the flows in the boundary segments that feed and drain the network. With incomplete boundary data, the equations governing blood flow form an underdetermined linear system. An algorithm was developed that uses independent information about the distribution of wall shear stresses and pressures in microvessels to resolve this indeterminacy, by minimizing the deviation of pressures and wall shear stresses from target values. The algorithm was tested using previously obtained experimental flow data from four microvascular networks in the rat mesentery. With two or three prescribed boundary conditions, predicted flows showed relatively small errors in most segments and fewer than 10% incorrect flow directions on average. The proposed method can be used to estimate flow rates in microvascular networks, based on incomplete boundary data, and provides a basis for deducing functional properties of microvessel networks. © 2012 John Wiley & Sons Ltd.

  10. A dynamic model of renal blood flow autoregulation

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Marsh, D J


    To test whether a mathematical model combining dynamic models of the tubuloglomerular feedback (TGF) mechanism and the myogenic mechanism was sufficient to explain dynamic autoregulation of renal blood flow, we compared model simulations with experimental data. To assess the dynamic characteristics...... of renal autoregulation, a broad band perturbation of the arterial pressure was employed in both the simulations and the experiments. Renal blood flow and tubular pressure were used as response variables in the comparison. To better approximate the situation in vivo where a large number of individual...... data, which shows a unimodal curve for the admittance phase. The ability of the model to reproduce the experimental data supports the hypothesis that dynamic autoregulation of renal blood flow is due to the combined action of TGF and the myogenic response....

  11. Mediators of increased blood flow in porcine skin

    Directory of Open Access Journals (Sweden)

    H. D. Moore


    Full Text Available Nicotinates and benzalkonium chloride (B.Cl cause inflammatory changes in human skin, thought to be dependent upon prostaglandin formation. This study has examined the effects of hexyl-nicotinate (HN and B.Cl on blood flow in porcine skin. The role of prostaglandins and interleukin (IL-1 in the blood flow response has been investigated. Blood flow was increased by both HN and B.Cl, the response to B.Cl being more protracted. Cyclooxygenase inhibitor pretreatment reduced these responses. IL-1-like biological activity was identified in normal porcine epidermis and the amounts recovered from inflamed skin were similar. Thus prostaglandin formation in HN or B.Cl-induced inflammation, if IL-1 dependent, is not associated with the loss of significant amounts of the cytokine from the epidermis.

  12. Reduced blood flow to contracting skeletal muscle in ageing humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Hellsten, Ylva


    consequences of ageing and physical inactivity can be challenging; yet, observations from cross-sectional and longitudinal studies on the effects of physical activity have provided some insight. Physical activity has the potential to offset the age-related decline in blood flow to contracting skeletal muscle...... the O2 demand of the active skeletal muscle of aged individuals during conditions where systemic blood flow is not limited by cardiac output seems to a large extent to be related to the level of physical activity. This article is protected by copyright. All rights reserved.......The ability to sustain a given absolute submaximal workload declines with advancing age likely due to a lower level of blood flow and O2 delivery to the exercising muscles. Given that physical inactivity mimics many of the physiological changes associated with ageing, separating the physiological...

  13. Transport across the blood-brain barrier of pluronic leptin. (United States)

    Price, Tulin O; Farr, Susan A; Yi, Xiang; Vinogradov, Serguei; Batrakova, Elena; Banks, William A; Kabanov, Alexander V


    Leptin is a peptide hormone produced primarily by adipose tissue that acts as a major regulator of food intake and energy homeostasis. Impaired transport of leptin across the blood-brain barrier (BBB) contributes to leptin resistance, which is a cause of obesity. Leptin as a candidate for the treatment of this obesity is limited because of the short half-life in circulation and the decreased BBB transport that arises in obesity. Chemical modification of polypeptides with amphiphilic poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) is a promising technology to improve efficiency of delivery of polypeptides to the brain. In the present study, we determined the effects of Pluronic P85 (P85) with intermediate hydrophilic-lipophilic balance conjugated with leptin via a degradable SS bond [leptin(ss)-P85] on food intake, clearance, stability, and BBB uptake. The leptin(ss)-P85 exhibited biological activity when injected intracerebroventricularly after overnight food deprivation and 125I-leptin(ss)-P85 was stable in blood, with a half-time clearance of 32.3 min (versus 5.46 min for leptin). 125I-Leptin(ss)-P85 crossed the BBB [blood-to-brain unidirectional influx rate (K(i)) = 0.272 +/- 0.037 microl/g x min] by a nonsaturable mechanism unrelated to the leptin transporter. Capillary depletion showed that most of the 125I-leptin(ss)-P85 taken up by the brain reached the brain parenchyma. Food intake was reduced when 3 mg of leptin(ss)-P85 was administered via tail vein in normal body weight mice [0-30 min, p penetration by a mechanism-independent BBB leptin transporter.

  14. The blood brain barrier: Insights from development and ageing. (United States)

    Delaney, Conor; Campbell, Matthew


    The blood brain barrier is a necessity for cerebral homeostasis and response to environmental insult, thus loss in functionality with age creates opportunities for disease to arise in the aged brain. Understanding how the barrier is developed and maintained throughout the earlier years of adult life can identify key processes that may have beneficial applications in the restoration of the aged brain. With an unprecedented increasing global aged population, the prevention and treatment of age-associated disorders has become a rising healthcare priority demanding novel approaches for the development of therapeutic strategies. The aging cardiovascular system has long been recognised to be a major factor in age-associated diseases such as stroke, atherosclerosis and cardiac arrest. Changes in the highly specialised cerebral vasculature may similarly drive neurodegenerative and neuropsychiatric disease.

  15. Nanotechnologies: a strategy to overcome blood-brain barrier. (United States)

    De Rosa, Giuseppe; Salzano, Giuseppina; Caraglia, Michele; Abbruzzese, Alberto


    The possibility to treat central nervous system (CNS) disorders is strongly limited by the poor access of many therapeutic agent to the target tissues. This is mainly due to the presence of the blood-brain barrier (BBB), formed by a complex interplay of endothelial cells, astrocyte and pericytes, through which only selected molecules can passively diffuse to reach CNS. Drug pharmacokinetics and biodistribution can be changed by using nanotechnology, in order to improve drug accumulation into the action site and to limit the drug release in the healthy tissues. When the CNS diseases are characterised by BBB altered permeability, an enhanced drug delivery into the brain can be achieved by using nanocarriers. Moreover, modification of nanocarrier surface with specific endogenous or exogenous ligands can promote enhanced BBB crossing, also in case of unaltered endothelium. This review summarizes the most meaningful advances in the field of nanotechnology for brain delivery of therapeutics.

  16. Elucidation of mechanism of blood-brain barrier damage for prevention and treatment of vascular dementia. (United States)

    Ueno, Masaki


    It is well-known that the blood-brain barrier (BBB) plays significant roles in transporting intravascular substances into the brain. The BBB in cerebral capillaries essentially impedes the influx of intravascular compounds from the blood to the brain, while nutritive substances, such as glucose, can be selectively transported through several types of influx transporters in endothelial cells. In the choroid plexus, intravascular substances can invade the parenchyma as fenestrations exist in endothelial cells of capillaries. However, the substances cannot invade the ventricles easily as there are tight junctions between epithelial cells in the choroid plexus. This restricted movement of the substances across the cytoplasm of the epithelial cells constitutes a blood-cerebrospinal fluid barrier (BCSFB). In the brain, there are circumventricular organs, in which the barrier function is imperfect in capillaries. Accordingly, it is reasonable to consider that intravascular substances can move in and around the parenchyma of the organs. Actually, it was reported in mice that intravascular substances moved in the corpus callosum, medial portions of the hippocampus, and periventricular areas via the subfornical organs or the choroid plexus. Regarding pathways of intracerebral interstitial and cerebrospinal fluids to the outside of the brain, two representative drainage pathways, or perivascular drainage and glymphatic pathways, are being established. The first is the pathway in a retrograde direction to the blood flow through the basement membrane in walls of cerebral capillaries, the tunica media of arteries, and the vessels walls of the internal carotid artery. The second is in an anterograde direction to blood flow through the para-arterial routes, aquaporin 4-dependent transport through the astroglial cytoplasm, and para-venous routes, and then the fluids drain into the subarachnoid CSF. These fluids are finally considered to drain into the cervical lymph nodes or veins

  17. Blood flow in ductus venosus in early uncomplicated pregnancy. (United States)

    Sodowski, Krzysztof; Cnota, Wojciech; Czuba, Bartosz; Borowski, Dariusz; Wielgos, Miroslaw; Kaminski, Pawel; Jaczyńska, Renata; Włoch, Agata; Kuka, Dorota; Zwirska-Korczala, Krystyna; Szaflik, Krzysztof


    The ductus venosus is the very important part of fetal venous circulation. It plays a central role in return of venous blood from the placenta. This unique shunt carries well-oxygenated blood from the umbilical vein through the inferior atrial inlet on its way across the foramen ovale. Using Doppler ultrasound, it is possible to assess the blood flow in fetal vessels including ductus venosus. It is observed, in animal and human studies, that the typical waveform for blood flow in ductus venosus in early pregnancy can be different depending on numerous conditions e.g. fetal karyotype. This study is performed to assess the physiologic parameters of blood flow in ductus venosus in uncomplicated early pregnancy. 404 women were examined between 11+0 and 13+6 weeks (+ days) of gestation by ultrasound. Fetal crown-rump length (CRL) was measured to assess the gestational age. The assessment of risk of fetal abnormalities was based on nuchal translucency (NT) measurement. The ductus venosus blood flow with color and spectral Doppler was obtained in all patients. The following features were assessed: pulsatility index (PI), and direction of flow (positive/negative) during atrial contraction (wave A). All cases were followed up to 22 weeks of gestation when the control scan was performed. 30 cases were excluded from the uncomplicated group due to: high risk of fetal abnormalities, fetal loss, confirmed fetal abnormalities and utero-placental pathology. 374 women were considered as uncomplicated pregnancy. In both uncomplicated and complicated groups the mean values for pulsatility index (PI) were established. The mean PI value in uncomplicated pregnancies was: 0.91 (SD +/- 0.32). No significant differences between groups were noticed. In 370 cases of uncomplicated pregnancy the A wave direction was positive but in 1.1% of cases the reverse flow in atrial contraction was observed.

  18. Quantification of regional blood flow to canine flexor tendons

    Energy Technology Data Exchange (ETDEWEB)

    Weidman, K.A.; Simonet, W.T.; Wood, M.B.; Cooney, W.P.; Ilstrup, D.M.


    Although the blood supply and the microcirculation of flexor tendons have been studied and defined extensively using qualitative methods, the quantitative assessment of blood flow has been lacking because of the limitations of the available experimental techniques. The authors studied the regional blood supply to the flexor tendons of dogs by the technique of radionuclide-labeled microspheres. Seven adult mongrel dogs were used. Microsphere injection and tissue-counting techniques previously used for other tissues were applied. Samples of proximal, isthmus, and distal portions of the profundus and superficialis flexor tendons were harvested from each digital unit of available limbs from each dog. Mean (+/- SE) flows (ml/100 g dry tissue/min) were proximal profundus 1.78 +/- 0.60 and superficialis 7.10 +/- 1.50. The differences were significant. The study suggests that regional variation in blood flow to canine digital flexor tendons exists, so that a single value for blood flow to these tendons is not relevant. Furthermore, the study supports the concept of dual (vascular and synovial) nutrition to the digital flexor tendons in dogs. These observations may have implications regarding tendon repair techniques.

  19. Quantification of regional blood flow to canine flexor tendons. (United States)

    Weidman, K A; Simonet, W T; Wood, M B; Cooney, W P; Ilstrup, D M


    Although the blood supply and the microcirculation of flexor tendons have been studied and defined extensively using qualitative methods, the quantitative assessment of blood flow has been lacking because of the limitations of the available experimental techniques. We studied the regional blood supply to the flexor tendons of dogs by the technique of radionuclide-labeled microspheres. Seven adult mongrel dogs were used. Microsphere injection and tissue-counting techniques previously used for other tissues were applied. Samples of proximal, isthmus, and distal portions of the profundus and superficialis flexor tendons were harvested from each digital unit of available limbs from each dog. Mean (+/- SE) flows (ml/100 g dry tissue/min) were proximal profundus 1.78 +/- 0.60 and superficialis 7.10 +/- 1.50. The differences were significant (p less than 0.01). The study suggests that regional variation in blood flow to canine digital flexor tendons exists, so that a single value for blood flow to these tendons is not relevant. Furthermore, the study supports the concept of dual (vascular and synovial) nutrition to the digital flexor tendons in dogs. These observations may have implications regarding tendon repair techniques.

  20. Blood flow and microdialysis in the human femoral head

    DEFF Research Database (Denmark)

    Bøgehøj, Morten; Emmeluth, Claus; Overgaard, Søren


    ischemia and measure changes in blood flow. MATERIAL AND METHODS: In 9 patients undergoing total hip arthroplasty for primary osteoarthrosis, two MD catheters were inserted into the femoral head through two drill holes after the blood flow had been visualized by LD. Then primary samples were collected...... with the femoral head in situ; thereafter, the head was removed and samples were collected over the following 4 hours ex vivo. The variables obtained by MD were concentrations of glucose, lactate, pyruvate, and glycerol in extracellular fluid. RESULTS: The results showed development of ischemia...

  1. Endoscopic retrograde cholangiopancreatography causes reduced myocardial blood flow

    DEFF Research Database (Denmark)

    Christensen, M; Hendel, H W; Rasmussen, V


    BACKGROUND AND STUDY AIMS: Previous studies have shown that up to 50% of healthy patients may develop ST-segment changes during upper gastrointestinal endoscopy. The aim of the study was to evaluate myocardial blood flow in patients during endoscopic retrograde cholangiopancreatography (ERCP...... with either of the two methods, while two patients developed signs of ischemia during ERCP with both the Holter tape recording and on myocardial scintigraphy (P = 0.02). CONCLUSIONS: Patients undergoing ERCP may develop true myocardial ischemia with reduced myocardial blood flow. Although this is a small...

  2. 1-D blood flow modelling in a running human body. (United States)

    Szabó, Viktor; Halász, Gábor


    In this paper an attempt was made to simulate blood flow in a mobile human arterial network, specifically, in a running human subject. In order to simulate the effect of motion, a previously published immobile 1-D model was modified by including an inertial force term into the momentum equation. To calculate inertial force, gait analysis was performed at different levels of speed. Our results show that motion has a significant effect on the amplitudes of the blood pressure and flow rate but the average values are not effected significantly.

  3. Nocturnal foot blood flow in patients with arterial insufficiency

    DEFF Research Database (Denmark)

    Jelnes, Rolf; Tønnesen, K H


    Twenty-four hour continuous recording of xenon (133Xe) wash-out from the forefoot was performed on patients with normal circulations (n = 10) and on patients with different degrees of arterial insufficiency (n = 36). During day hours the calculated subcutaneous blood flow in the forefoot...... was on average the same in patients with normal circulations and in patients with different degrees of arterial insufficiency (mean: 2.0 +/- 0.8 ml min-1 100 g-1). During sleep the blood flow nearly doubled in patients with normal circulations; no systematic change was seen in patients with intermittent...

  4. Disparity in regional cerebral blood flow during electrically induced seizure

    DEFF Research Database (Denmark)

    Sestoft, D; Meden, P; Hemmingsen, R


    This is a presentation of 2 cases in which the intraictal regional cerebral blood flow distribution was measured with the 99mTc-HMPAO single photon emission computerized tomography technique during an electrically induced seizure. Although the seizure was verified as generalized on electroencepha......This is a presentation of 2 cases in which the intraictal regional cerebral blood flow distribution was measured with the 99mTc-HMPAO single photon emission computerized tomography technique during an electrically induced seizure. Although the seizure was verified as generalized...

  5. The effect of hyperosmotic solutions on the hepatic blood flow

    DEFF Research Database (Denmark)

    Winkler, K; Henriksen, Jens Henrik; Tygstrup, N


    infusions of hyperosmotic galactose (50%, 84-100 ml) and mannitol (25%, 100 ml), with physiological saline (100 ml) as control. Portal blood flow increased to a peak value of (39% [P = 0.06] galactose and 37%, [P = 0.06], mannitol) soon after stop of the hyperosmotic infusion. For galactose the change ended...... somewhat earlier than for mannitol. Saline induced a minor increase (15%). Similarly, increments of, on average, 144% of the hepatic blood flow rate was seen in six patients with cirrhosis, following infusion of hyperosmotic galactose, the increase being more pronounced than in the pigs. The causes...

  6. The role of macronutrients in gastrointestinal blood flow. (United States)

    de Aguilar-Nascimento, José Eduardo


    The presence of luminal nutrients after a meal increases gastrointestinal blood flow in a phenomenon called postprandial hyperemia. In many conditions related to splanchnic hypoperfusion, enteral nutrition may play a role in counterbalancing the installed splanchnic low-flow state by producing intestinal hyperemia. However, when the gut is hypoperfused there is a chance of enteral nutrition producing a mismatch of the oxygen demand: supply ratio with subsequence gut ischemia. This article aims to review the effects of macronutrients on gastrointestinal blood flow in both health and critical conditions, especially those related to hepatosplanchnic hypoperfusion. Splanchnic blood flow is related not only to the route (intravenous or enteral) and timing of nutritional support (during the course of the insult) but also to the composition of the formula. Critically ill patients with gut hypoperfusion may tolerate enteral nutrition, but this effect may be restricted to the early post-injury phase. During ischaemia reperfusion injury, immune nutrients may promote different outcomes: glutamine may protect whereas arginine may deteriorate the mucosal barrier and enhance permeability. Understanding the relationship between macronutrients and gastrointestinal blood flow is a major challenge. Ongoing research in nutritional support in hypoperfused, catecholamine-dependent patients will open the door to optimize the recovery of patients in critical care.

  7. Implementing a routine flow cytometry assay for nucleated red blood cell counts in cord blood units. (United States)

    Simard, C; Cloutier, M; Jobin, C; Dion, J; Fournier, D; Néron, S


    As required by standards organizations, Héma-Québec Cord Blood Bank performs enumeration of nucleated red blood cells (NRBCs) in cord blood units (CBUs). This study presents the validation and implementation approaches developed to transfer the routine NRBC enumeration from the manual blood film method to a flow cytometric assay. The flow cytometry method was adapted from Tsuji (Cytometry, 37, 1999, 291). This assay was validated to assess the specificity, detection limit, repeatability, and reproducibility of the method, including interoperator and interlaboratory testing. Finally, postimplementation follow-up and adjustments were performed for CBU over a 7-month period. Blood film and flow cytometry NRBC enumerations showed a strong correlation (n = 40; Pearson's r correlation = 0.90). Validation was successful as exemplified by the correlation in interlaboratory testing (n = 30; r = 0.98). During implementation, our routine laboratory analyses revealed that CBU with low NRBC content (≤2%), representing 26% of all CBU tested, resulted in 15% of repeated reading and/or staining and was the principal source of nonconformity. Small adjustments in the standard operating procedures (SOPs), including a fixed 200-event setting in the NRBC gate for the second reading of the replicates, have completely solved this issue. Flow cytometric NRBC enumerations, now implemented in Héma-Québec Public Cord Blood Bank, is an improvement in the efficiency of our operations by integrating the count for NRBC into our flow cytometry platform. © 2016 John Wiley & Sons Ltd.

  8. Blood Pump Development Using Rocket Engine Flow Simulation Technology (United States)

    Kiris, Cetin C.; Kwak, Dochan


    This viewgraph presentation provides information on the transfer of rocket engine flow simulation technology to work involving the development of blood pumps. Details are offered regarding the design and requirements of mechanical heart assist devices, or VADs (ventricular assist device). There are various computational fluid dynamics issues involved in the visualization of flow in such devices, and these are highlighted and compared to those of rocket turbopumps.

  9. The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling

    DEFF Research Database (Denmark)

    Hess, J.; Jensen, Claus V.; Diemer, Nils Henrik


    Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2......Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2...

  10. A study of the acute effect of smoking on cerebral blood flow using {sup 99m}Tc-ECD SPET

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Yuka; Nishiyama, Yoshihiro; Monden, Toshihide; Satoh, Katashi; Ohkawa, Motoomi [Department of Radiology, Faculty of Medicine, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793 (Japan)


    Cigarette smoking is known to be associated with atherosclerosis, is an important risk factor for stroke and has other serious effects. The aim of this study was to evaluate the acute effect of cigarette smoking on cerebral blood flow using statistical parametric mapping (SPM). Ten healthy volunteers with a smoking habit were studied using technetium-99m-labelled ethylcysteinate dimer single-photon emission tomography (SPET). We evaluated the regional cerebral blood flow under the smoking and resting states. The regional cerebral blood flow on smoking-activated SPET was significantly decreased in the whole brain as compared with that on resting SPET. Our findings therefore suggest that one of the acute effects of cigarette smoking is to induce a diffuse decrease in cerebral blood flow. (orig.)

  11. Perfusion–diffusion compartmental models describe cerebral helium kinetics at high and low cerebral blood flows in sheep (United States)

    Doolette, David J; Upton, Richard N; Grant, Cliff


    This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood:tissue helium exchange in the brain. Helium has different physiochemical properties from previously studied gases, and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Helium kinetics across the cerebrum were determined during and after 15 min of helium inhalation, at separate low and high steady states of cerebral blood flow in seven sheep under isoflurane anaesthesia. Helium concentrations in arterial and sagittal sinus venous blood were determined using gas chromatographic analysis, and sagittal sinus blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion–diffusion compartmental models of the brain were estimated by simultaneous fitting of the models to the sagittal sinus helium concentrations for both blood flow states. Purely perfusion-limited models fitted the data poorly. Models that allowed a diffusion-limited exchange of helium between a perfusion-limited tissue compartment and an unperfused deep compartment provided better overall fit of the data and credible parameter estimates. Fit to the data was also improved by allowing countercurrent diffusion shunt of helium between arterial and venous blood. These results suggest a role of diffusion in blood:tissue helium equilibration in brain. PMID:15649976

  12. Nocturnal variations in peripheral blood flow, systemic blood pressure, and heart rate in humans

    DEFF Research Database (Denmark)

    Sindrup, J H; Kastrup, J; Christensen, H


    Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage uni.......0001). The synchronism of the nocturnal subcutaneous hyperemia and the decrease in systemic mean arterial blood pressure point to a common, possibly central nervous or humoral, eliciting mechanism.......Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage unit...

  13. Could cord blood cell therapy reduce preterm brain injury?

    Directory of Open Access Journals (Sweden)

    Jingang eLi


    Full Text Available Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP. Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia-ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia-ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB derived from preterm and term infants for use in clinical applications.

  14. Permeability of the blood-brain barrier to lead. (United States)

    Bradbury, M W; Deane, R


    This review examines the kinetics and possible mechanisms of lead transport into brain across the microvessel endothelium (the blood-brain barrier). Although severe lead poisoning both in neonatal rats and in young children may cause microvessel damage, there is little evidence that there is either damage or even disturbance of specific transport mechanisms at blood leads linear with time up to 4 hours, reaching spaces in relation to plasma of 6.6 - 8.2 ml/100 g in cerebral tissues at one hour. The concentration of free Pb+ in serum is of the order of 10(-12)M, the majority of lead being bound to protein and to sulfhydryl compounds, such as L-cysteine. Transport into brain has been further studied during short vascular perfusion of one cerebral hemisphere of the rat with oxygenated and buffered physiological saline. This allows total control of the fluid perfusing the cerebral microvessels. In the absence of organic ligands for lead, 203Pb entered brain very fast, with a space of 9.7 ml/100 g in frontal cortex at one min. The presence of albumin, L-cysteine or EDTA abolished measurable uptake. Experiments designed to reveal a role for the anion exchanger or calcium channels gave negative results. However, the effects of potassium depolarization and of varying pH indicated that the lead species passively entering the endothelium might be PbOH+. Experiments with various metabolic inhibitors, including vanadate, suggested that Pb uptake in the endothelium is mitigated by active back transport of lead into blood by the Ca-ATPase pump.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. The role of the blood-brain barrier in hypertension. (United States)

    Setiadi, Anthony; Korim, Willian S; Elsaafien, Khalid; Yao, Song T


    What is the topic of this review? This review highlights the importance of the blood-brain barrier in the context of diseases involving autonomic dysfunction, such as hypertension and heart failure. What advances does it highlight? It highlights the potential role of pro-inflammatory cytokines, leucocytes and angiotensin II in disrupting the blood-brain barrier in cardiovascular diseases. Advances are highlighted in our understanding of neurovascular unit cells, astrocytes and microglia, with a specific emphasis on their pathogenic roles within the brain. The blood-brain barrier (BBB) is a crucial barrier that provides both metabolic and physical protection to an immune-privileged CNS. The BBB has been shown to be disrupted in hypertension. This review addresses the importance of the BBB in maintaining homeostasis in the context of diseases related to autonomic dysfunction, such as hypertension. We highlight the potentially important roles of the immune system and neurovascular unit in the maintenance of the BBB, whereby dysregulation may lead to autonomic dysfunction in diseases such as heart failure and hypertension. Circulating leucocytes and factors such as angiotensin II and pro-inflammatory cytokines are thought ultimately to downregulate endothelial tight junction proteins that are a crucial component of the BBB. The specific mechanisms underlying BBB disruption and their role in contributing to autonomic dysfunction are not yet fully understood but are a growing area of interest. A greater understanding of these systems and advances in our knowledge of the molecular mechanisms causing BBB disruption will allow for the development of future therapeutic interventions in the treatment of autonomic imbalance associated with diseases such as heart failure and hypertension. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  16. Blood flow analysis with considering nanofluid effects in vertical channel (United States)

    Noreen, S.; Rashidi, M. M.; Qasim, M.


    Manipulation of heat convection of copper particles in blood has been considered peristaltically. Two-phase flow model is used in a channel with insulating walls. Flow analysis has been approved by assuming small Reynold number and infinite length of wave. Coupled equations are solved. Numerical solution are computed for the pressure gradient, axial velocity function and temperature. Influence of attention-grabbing parameters on flow entities has been analyzed. This study can be considered as mathematical representation to the vibrance of physiological systems/tissues/organs provided with medicine.

  17. Chaotic Dynamics of Red Blood Cells in a Sinusoidal Flow (United States)

    Dupire, Jules; Abkarian, Manouk; Viallat, Annie


    We show that the motion of individual red blood cells in an oscillating moderate shear flow is described by a nonlinear system of three coupled oscillators. Our experiments reveal that the cell tank treads and tumbles either in a stable way with synchronized cell inclination, membrane rotation and hydrodynamic oscillations, or in an irregular way, very sensitively to initial conditions. By adapting our model described previously, we determine the theoretical diagram for the red cell motion in a sinusoidal flow close to physiological shear stresses and flow variation frequencies and reveal large domains of chaotic motions. Finally, fitting our observations allows a characterization of cell viscosity and membrane elasticity.

  18. Effects of normovolaemic haemodilution on middle cerebral artery blood flow velocity and oxygen delivery. (United States)

    Karadibak, K; Gökmen, N; Erbayraktar, S; Göktay, Y; Taplu, A; Arkan, A; Erkan, N


    Assessment of the effects of normovolaemic haemodilution on middle cerebral artery blood flow velocity with transcranial Doppler ultrasonography, intracranial pressure, cerebral perfusion pressure, arterial oxygen content and cerebral oxygen delivery. Normovolaemic haemodilution was induced in rabbits under general anaesthesia, and the haematocrit was allowed to decrease to 30% in Group 1 (n = 6) and to 20% in Group 2 (n = 6). Peak systolic and diastolic velocities, mean blood flow velocity, and pulsatility and resistance indices of the middle cerebral artery were measured by transcranial Doppler ultrasonography. Changes in intracranial pressure, cerebral perfusion pressure, arterial oxygen content and cerebral oxygen delivery were also assessed. In Group 2, middle cerebral artery blood flow velocity increased from 0.4 +/- 0.01 to 0.51 +/- 0.02 m s(-1) after the induction of normovolaemic haemodilution (P = 0.04), while arterial oxygen content decreased from 16.2 +/- 0.1 to 8.5 +/- 0.1 mLdL(-1) (P = 0.002). The decrease in cerebral oxygen delivery from 6.5 +/- 0.2 to 4.3 +/- 0.2 was also significant (P = 0.02). However, no associated changes in intracranial pressure and cerebral perfusion pressure could be demonstrated. Normovolaemic haemodilution resulted in an increase in the mean blood flow velocity of the middle cerebral artery. However, this increase did not compensate for the consequences of the altered oxygen delivery to the brain when the haematocrit was reduced to 20%.

  19. White Matter Hyperintensity Associations with Cerebral Blood Flow in Elderly Subjects Stratified by Cerebrovascular Risk. (United States)

    Bahrani, Ahmed A; Powell, David K; Yu, Guoquiang; Johnson, Eleanor S; Jicha, Gregory A; Smith, Charles D


    This study aims to add clarity to the relationship between deep and periventricular brain white matter hyperintensities (WMHs), cerebral blood flow (CBF), and cerebrovascular risk in older persons. Deep white matter hyperintensity (dWMH) and periventricular white matter hyperintensity (pWMH) and regional gray matter (GM) and white matter (WM) blood flow from arterial spin labeling were quantified from magnetic resonance imaging scans of 26 cognitively normal elderly subjects stratified by cerebrovascular disease (CVD) risk. Fluid-attenuated inversion recovery images were acquired using a high-resolution 3-dimensional (3-D) sequence that reduced partial volume effects seen with slice-based techniques. dWMHs but not pWMHs were increased in patients at high risk of CVD; pWMHs but not dWMHs were associated with decreased regional cortical (GM) blood flow. We also found that blood flow in WM is decreased in regions of both pWMH and dWMH, with a greater degree of decrease in pWMH areas. WMHs are usefully divided into dWMH and pWMH regions because they demonstrate differential effects. 3-D regional WMH volume is a potentially valuable marker for CVD based on associations with cortical CBF and WM CBF. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Comparison of near-infrared spectroscopy with CT cerebral blood flow measurements in newborn piglets (United States)

    Brown, Derek W.; Picot, Paul A.; Springett, Roger; Delpy, David T.; Lee, Ting-Yim


    Severely premature infants are often at high risk of cerebral hemorrhage or ischemic injury due to their inability to properly regulate blood flow to the brain. If blood flow is too high, the infant is at risk of cerebral hemorrhage, while too little blood flow can result in ischemic injury. The purpose of this research is to design and develop a means of non-invasively measuring cerebral blood flow (CBF) with near infrared spectroscopy (NIRS). Such a device would greatly aid the diagnosis and monitoring of afflicted infants. Previous attempts to measure CBF with NIRS have achieved limited success. In this study we acquired high signal-to-noise NIR spectrum from 600 to 980 nm with a cooled CCD spectrometer. This spectrometer enables the differential path length factor (DPF) to be estimated with accuracy using a second derivative technique described by Matcher et al. The validity of our new approach is determined via direct comparison with a previously validated computed tomography (CT) method. Three newborn piglets were studied. CBF measurements were performed at various partial arterial CO2 tensions (PaCO2) using both the NIRS and CT methods. The results of the two methods correlate well with a relationship of CBFCT equals -4.30 + 1.05 CBFNIRS (r2 equals 0.96).

  1. Blood-brain barrier transport machineries and targeted therapy of brain diseases

    Directory of Open Access Journals (Sweden)

    Jaleh Barar


    Full Text Available Introduction: Desired clinical outcome of pharmacotherapy of brain diseases largely depends upon the safe drug delivery into the brain parenchyma. However, due to the robust blockade function of the blood-brain barrier (BBB, drug transport into the brain is selectively controlled by the BBB formed by brain capillary endothelial cells and supported by astrocytes and pericytes. Methods: In the current study, we have reviewed the most recent literature on the subject to provide an insight upon the role and impacts of BBB on brain drug delivery and targeting. Results: All drugs, either small molecules or macromolecules, designated to treat brain diseases must adequately cross the BBB to provide their therapeutic properties on biological targets within the central nervous system (CNS. However, most of these pharmaceuticals do not sufficiently penetrate into CNS, failing to meet the intended therapeutic outcomes. Most lipophilic drugs capable of penetrating BBB are prone to the efflux functionality of BBB. In contrast, all hydrophilic drugs are facing severe infiltration blockage imposed by the tight cellular junctions of the BBB. Hence, a number of strategies have been devised to improve the efficiency of brain drug delivery and targeted therapy of CNS disorders using multimodal nanosystems (NSs. Conclusion: In order to improve the therapeutic outcomes of CNS drug transfer and targeted delivery, the discriminatory permeability of BBB needs to be taken under control. The carrier-mediated transport machineries of brain capillary endothelial cells (BCECs can be exploited for the discovery, development and delivery of small molecules into the brain. Further, the receptor-mediated transport systems can be recruited for the delivery of macromolecular biologics and multimodal NSs into the brain.

  2. The history of the microsphere method for measuring blood flows with special reference to myocardial blood flow: a personal memoir. (United States)

    Hoffman, Julien I E


    We use many types of equipment and technologies to make our measurements but give little thought to how they developed. Evolution was once described as a series of recoils from blind alleys, and this is exemplified by the gradual development of the microsphere method of measuring blood flows. The microsphere method is one of the most frequently used methods for measuring blood flow to organs and portions of organs. The method can measure myocardial blood flow with reasonable accuracy (within 10%) down to samples weighing >50 mg but probably will not do so for samples weighing 1-10 mg. Microspheres with diameters from 10 to 15 μm provide the best compromise between accurate flow measurement and retention in tissue. Radioactive labels have been almst entirely replaced by fluorescent labels, but colored microspheres and neutron-activated labels are also used.NEW & NOTEWORTHY The contributions of the various individuals who developed the microsphere method of measuring regional blood flows and how these advances took place are brought to light in this paper. Copyright © 2017 the American Physiological Society.

  3. Targeted liposomes for drug delivery across the blood-brain barrier

    NARCIS (Netherlands)

    van Rooy, I.|info:eu-repo/dai/nl/304823074


    Our brain is protected by the blood-brain barrier (BBB). This barrier is formed by specialized endothelial cells of the brain vasculature and prevents toxic substances from entering the brain. The downside of this barrier is that many drugs that have been developed to cure brain diseases cannot

  4. Noninvasive optical measurement of cerebral blood flow in mice using molecular dynamics analysis of indocyanine green.

    Directory of Open Access Journals (Sweden)

    Taeyun Ku

    Full Text Available In preclinical studies of ischemic brain disorders, it is crucial to measure cerebral blood flow (CBF; however, this requires radiological techniques with heavy instrumentation or invasive procedures. Here, we propose a noninvasive and easy-to-use optical imaging technique for measuring CBF in experimental small animals. Mice were injected with indocyanine green (ICG via tail-vein catheterization. Time-series near-infrared fluorescence signals excited by 760 nm light-emitting diodes were imaged overhead by a charge-coupled device coupled with an 830 nm bandpass-filter. We calculated four CBF parameters including arrival time, rising time and mean transit time of a bolus and blood flow index based on time and intensity information of ICG fluorescence dynamics. CBF maps were generated using the parameters to estimate the status of CBF, and they dominantly represented intracerebral blood flows in mice even in the presence of an intact skull and scalp. We demonstrated that this noninvasive optical imaging technique successfully detected reduced local CBF during middle cerebral artery occlusion. We further showed that the proposed method is sufficiently sensitive to detect the differences between CBF status in mice anesthetized with either isoflurane or ketamine-xylazine, and monitor the dynamic changes in CBF after reperfusion during transient middle cerebral artery occlusion. The near-infrared optical imaging of ICG fluorescence combined with a time-series analysis of the molecular dynamics can be a useful noninvasive tool for preclinical studies of brain ischemia.

  5. Cerebral blood flow imaging using time-series analysis of indocyanine green molecular dynamics in mice (United States)

    Ku, Taeyun; Lee, Jungsul; Choi, Chulhee


    Measurement of cerebral perfusion is important for study of various brain disorders such as stroke, epilepsy, and vascular dementia; however, efficient and convenient methods which can provide quantitative information about cerebral blood flow are not developed. Here we propose an optical imaging method using time-series analysis of dynamics of indocyanine green (ICG) fluorescence to generate cerebral blood flow maps. In scalp-removed mice, ICG was injected intravenously, and 740nm LED light was illuminated for fluorescence emission signals around 820nm acquired by cooled-CCD. Time-lapse 2-dimensional images were analyzed by custom-built software, and the maximal time point of fluorescent influx in each pixel was processed as a blood flow-related parameter. The generated map exactly reflected the shape of the brain without any interference of the skull, the dura mater, and other soft tissues. This method may be further applicable for study of other disease models in which the cerebral hemodynamics is changed either acutely or chronically.

  6. Oscillations and chaos in renal blood flow control

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H


    In normotensive, halothane-anesthetized rats, oscillations can be found both in the single-nephron blood flow and in the tubular pressure. Experimental data and computer simulations support the hypothesis that the oscillations are caused by the tubuloglomerular feedback (TGF) mechanism. Model...

  7. Disparity in regional cerebral blood flow during electrically induced seizure

    DEFF Research Database (Denmark)

    Sestoft, D; Meden, P; Hemmingsen, R


    This is a presentation of 2 cases in which the intraictal regional cerebral blood flow distribution was measured with the 99mTc-HMPAO single photon emission computerized tomography technique during an electrically induced seizure. Although the seizure was verified as generalized on electroencepha...

  8. Longitudinal Cerebral Blood Flow Changes during Speech in Hereditary Ataxia (United States)

    Sidtis, John J.; Strother, Stephen C.; Naoum, Ansam; Rottenberg, David A.; Gomez, Christopher


    The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron emission tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a…

  9. Abnormal blood flow in the sublingual microcirculation at high altitude

    NARCIS (Netherlands)

    Martin, Daniel S.; Ince, Can; Goedhart, Peter; Levett, Denny Z. H.; Grocott, Mike P. W.


    We report the first direct observations of deranged microcirculatory blood flow at high altitude, using sidestream dark-field imaging. Images of the sublingual microcirculation were obtained from a group of 12 volunteers during a climbing expedition to Cho Oyu (8,201 m) in the Himalayas.

  10. Whole-body vibration dosage alters leg blood flow

    NARCIS (Netherlands)

    Lythgo, Noel; Eser, Prisca; de Groot, Patricia; Galea, Mary

    The effect of whole-body vibration dosage on leg blood flow was investigated. Nine healthy young adult males completed a set of 14 random vibration and non-vibration exercise bouts whilst squatting on a Galileo 900 plate. Six vibration frequencies ranging from 5 to 30 Hz (5 Hz increments) were used

  11. [Assessing resveratrol effect on ocular blood flow in experiment]. (United States)

    Neroev, V V; Kiseleva, T N; Chudin, A V; Shchipanova, A I; Ramazanova, K A


    To study the effect of resveratrol on ocular blood flow in vivo in healthy rats and those that underwent retinal ischemia/reperfusion. The experimental study was performed on 40 Wistar rats (40 eyes). For ocular blood flow evaluation, color Doppler imaging (CDI), power Doppler (PD), and pulsed-wave spectral Doppler ultrasonography were performed using the Voluson E8 Expert ultrasonic diagnostic system (GE Healthcare). All rats were given resveratrol per os for 2 months of the study. Retinal ischemia/reperfusion injury was induced by a subconjunctival injection of endothelin-1. The control group included 10 intact animals. Signs of ischemic damage of the anterior and posterior eye segments were less pronounced in rats that were given resveratrol during both pre-ischemic (30 days) and post-ischemic (30 days) periods of follow-up. There was also a statistically significant increase in the peak systolic and end diastolic velocity of blood flow as well as a decrease in the resistive index of retrobulbar arteries in those rats that underwent ischemia/reperfusion as compared to the controls. Long-term resveratrol use (2 months) has proved effective in improving ocular blood flow in a rat model of retinal ischemia/reperfusion injury.

  12. Influence of blood flow on the coagulation cascade

    DEFF Research Database (Denmark)

    The influence of diffusion and convetive flows on the blood coagulation cascade is investigated for a controlled perfusion experiment. We present a cartoon model and reaction schemes for parts of the coagulation cascade with sunsequent set up of a mathematical model in two space dimensions plus one...

  13. Patterns of regional cerebral blood flow in acute stroke

    DEFF Research Database (Denmark)

    Olsen, T S; Skriver, E B


    In a consecutive group of 56 stroke patients the regional cerebral blood flow was measured within 84 hours after stroke. A 254 multidetector scintillation camera and the intracarotid Xenon-133 injection method was used to study rCBF. Typical rCBF-patterns are described and compared to the findings...

  14. Determinants of resting cerebral blood flow in sickle cell disease

    NARCIS (Netherlands)

    Bush, Adam M.; Borzage, Matthew T.; Choi, Soyoung; Václavů, Lena; Tamrazi, Benita; Nederveen, Aart J.; Coates, Thomas D.; Wood, John C.


    Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated.

  15. Does isolated myocardial bridge really interfere with coronary blood flow?

    Directory of Open Access Journals (Sweden)

    Eid M. Daoud


    Conclusions: Myocardial bridging must be considered especially in patients at low risk for coronary atherosclerosis but with angina like chest pain or established myocardial ischemia. We suggest that coronary blood flow is decreased in the patients with MB compared with the patients having normal coronary.

  16. Neurophysiological Basis of Cerebral Blood Flow Control: An ...

    African Journals Online (AJOL)

    The book describes the current understanding of cerebral blood flow control. Subjects covered indude the autonomic nervous system, cellular neurophysiology and neurotransmitter systems. There is a good section on ionic channels and ionic pumps, as well as receptors and metaoolism of the central nervous system.

  17. Cerebral blood flow and oxidative metabolism during human endotoxemia

    DEFF Research Database (Denmark)

    Møller, Kirsten; Strauss, Gitte Irene; Qvist, Jesper


    and catecholamines was investigated in eight healthy young volunteers. Cerebral blood flow was measured by the Kety-Schmidt technique at baseline (during normocapnia and voluntary hyperventilation for calculation of subject-specific cerebrovascular CO reactivity), and 90 minutes after an intravenous bolus...

  18. Changes in Peak Expiratory Flow Rate, Blood Pressure and Pulse ...

    African Journals Online (AJOL)

    Changes in Peak Expiratory Flow Rate, Blood Pressure and Pulse Rate Following Ingestion of Increased Coffee Concentrations in Healthy Male Adults. ... It further indicates that, mild doses of coffee confer benefits on airflow in the lungs. While higher doses are also beneficial in improving airflow in the airway, such doses ...

  19. Changes in Peak Expiratory Flow Rate, Blood Pressure and Pulse ...

    African Journals Online (AJOL)

    We studied the effect of different concentrations of coffee on peak expiratory flow rate (PEFR), blood pressure and pulse rate in an attempt to determine some physiological effects of coffee intake. 18 apparently healthy adult males, age range 20 to 30 years, were recruited for the study over a three day period. Varying ...

  20. Increased cerebral blood flow in preeclampsia with magnetic resonance imaging

    NARCIS (Netherlands)

    Zeeman, Gerda G.; Hatab, MR; Twickler, DM


    Objective: The purpose of this study was to compare third trimester and nonpregnant cerebral blood flow of women with preeclampsia to normotensive control subjects with the use of magnetic resonance imaging techniques. Study design: Nine normotensive pregnant women and 12 untreated women with

  1. Velocity estimation using synthetic aperture imaging [blood flow

    DEFF Research Database (Denmark)

    Nikolov, Svetoslav; Jensen, Jørgen Arendt


    Presented an approach for synthetic aperture blood flow ultrasound imaging. Estimates with a low bias and standard deviation can be obtained with as few as eight emissions. The performance of the new estimator is verified using both simulations and measurements. The results demonstrate that a ful...

  2. A New Technology for Detecting Cerebral Blood Flow

    DEFF Research Database (Denmark)

    Schytz, Henrik W; Guo, Song; Jensen, Lars T


    There is a need for real-time non-invasive, continuous monitoring of cerebral blood flow (CBF) during surgery, in intensive care units and clinical research. We investigated a new non-invasive hybrid technology employing ultrasound tagged near infrared spectroscopy (UT-NIRS) that may estimate...

  3. Modeling of internal carotid artery aneurysm and blood flow simulation. (United States)

    Xu, Bingqiang; Zhong, Hua; Duan, Shaoyin


    The rupture of aneurysm is quite common in the clinics, and is hazardous to patients. Its occurrence is considered to be related to the hemodynamic abnormalities. To construct the model of internal carotid artery aneurysm (ICA-A), and have a simulation of blood flow. Based on the CTA data from spiral CT scan, the ICA-A model was constructed, and the types of blood flow, wall shear stress (WSS), Von Mises stress (VMS) and pressure were simulated and calculated. ICA-A model has been built and shape is the same morphology as CT 3D-image. In the whole cardiac cycle, the blood flow of aneurysm body is swirl, its velocity is slower than that of aneurysm neck; the maximum deformation, wall shear stress, pressure and von mises stress of aneurysm wall is at the neck, the minimum is at the top. The highest value appeared at 0.52 s in the cardiac cycle of 0.74 s, the lowest is at 0.21 s. It is effective and practical to construct the model of ICA-A base on CTA data. Blood flow simulation of ICA-A will provide new basis for the study on the occurrence and development of aneurysm.

  4. Physiological activation of the human cerebral cortex during auditory perception and speech revealed by regional increases in cerebral blood flow

    DEFF Research Database (Denmark)

    Lassen, N A; Friberg, L


    Specific types of brain activity as sensory perception auditory, somato-sensory or visual -or the performance of movements are accompanied by increases of blood flow and oxygen consumption in the cortical areas involved with performing the respective tasks. The activation patterns observed by mea...

  5. Middle cerebral artery blood flow velocity in elite power athletes during maximal weight-lifting. (United States)

    Dickerman, R D; McConathy, W J; Smith, G H; East, J W; Rudder, L


    Cerebral blood flow velocity (CBFV) has been shown to significantly increase during dynamic exercise (running) secondary to increases in cardiac output. Static exercise (weight-lifting) induces supraphysiological arterial pressures up to 450/380 mmHg, and thus may alter CBFV. Catastrophic brain injuries such as stroke, cerebral hemorrhage, subarachnoid hemorrhage, retinal hemorrhage and retinal detachment have been associated with weight-lifting. A recent study has shown that intra-ocular pressure (IOP), which is an indirect measure of intracranial pressure, elevates to pathophysiologic levels during weight-lifting. Recent CBFV studies instituting Valsalva have demonstrated decreases in CBFV from 21%-52%. To date, no studies have examined CBFV during maximal weight-lifting to elucidate the cerebrovascular responses to extreme pressure alterations. We recruited nine elite power athletes, including a multi-world record holder in powerlifting, for a transcranial Doppler study of middle cerebral artery blood flow velocity at rest and during maximal weight-lifting. All subjects' resting blood flow velocities were within normal ranges (mean 64.4 +/- 9.5 cm sec2). Blood flow velocities were significantly (p < 0.0001) decreased in all subjects during maximal lifting (mean 48.4 +/- 10.1 cm sec2). Linear regression analysis demonstrated a significant inverse linear relationship in the net change of blood velocities from rest to maximal lift for each subject (r = 0.8585, p < 0.001). This study demonstrates that blood flow velocities are significantly decreased during heavy resistance training. The drop in CBFV during weight-lifting was significantly less than previous Valsalva studies, which likely reveals the cardiovascular, baroreflex, and cerebrovascular system adaptations occurring in these elite power athletes.

  6. Effect of labetalol on cerebral blood flow and middle cerebral arterial flow velocity in healthy volunteers

    DEFF Research Database (Denmark)

    Schroeder, T; Schierbeck, Jens; Howardy, P


    The effect of labetalol, a combined alpha- and beta-adrenoceptor antagonist, on the cerebral circulation was investigated in 7 normotensive subjects. Cerebral blood flow (CBF) was measured with the intravenous 133Xe method and mean flow velocity (Vmean) in the middle cerebral artery was determined...

  7. Ultrasonic Doppler blood flow meter for extracorporeal circulation (United States)

    Dantas, Ricardo G.; Costa, Eduardo T.; Maia, Joaquim M.; Nantes Button, Vera L. d. S.


    In cardiac surgeries it is frequently necessary to carry out interventions in internal heart structures, and where the blood circulation and oxygenation are made by artificial ways, out of the patient's body, in a procedure known as extracorporeal circulation (EC). During this procedure, one of the most important parameters, and that demands constant monitoring, is the blood flow. In this work, an ultrasonic pulsed Doppler blood flowmeter, to be used in an extracorporeal circulation system, was developed. It was used a 2 MHz ultrasonic transducer, measuring flows from 0 to 5 liters/min, coupled externally to the EC arterial line destined to adults perfusion (diameter of 9.53 mm). The experimental results using the developed flowmeter indicated a maximum deviation of 3.5% of full scale, while the blood flow estimator based in the rotation speed of the peristaltic pump presented deviations greater than 20% of full scale. This ultrasonic flowmeter supplies the results in a continuous and trustworthy way, and it does not present the limitations found in those flowmeters based in other transduction methods. Moreover, due to the fact of not being in contact with the blood, it is not disposable and it does not need sterilization, reducing operational costs and facilitating its use.

  8. Coded ultrasound for blood flow estimation using subband processing

    DEFF Research Database (Denmark)

    Gran, Fredrik; Udesen, Jesper; Nielsen, Michael bachmann


    This paper further investigates the use of coded excitation for blood flow estimation in medical ultrasound. Traditional autocorrelation estimators use narrow-band excitation signals to provide sufficient signal-to-noise-ratio (SNR) and velocity estimation performance. In this paper, broadband...... the excitation signal is broadband and has good spatial resolution after pulse compression. Two different codin-schemes are used in this paper, Barker codes and Golay codes. The performance of the codes for velocity estimation is compared to a conventional approach transmitting a narrow-band pulse. The study...... was carried out using an experimental ultrasound scanner and a commercial linear array 7 MHz transducer. A circulating flow rig was scanned with a beam-to-flow angle of 60 degrees. The flow in the rig was laminar and had a parabolic flow-profile with a peak velocity of 0.09 m/s. The mean relative standard...

  9. Ultrasonic character istics and clinical significance of umbilical cord blood flow in acute fetal distress

    Directory of Open Access Journals (Sweden)

    Wei Dai, Yin Xu


    Full Text Available Objective: To study ultrasonic characteristics of umbilical cord blood flow in acute fetal distress and its correlation with umbilical artery blood gas parameters, oxidative stress parameters, neonatal brain injury and myocardial injury. Methods: The pregnant women delivered in Department of Obstetrics of our hospital were chosen during the period from May 2012 to August 2015. The pregnant women with acute fetal distress were included in the distress group, and the healthy pregnant women with no acute fetal distress were included in the control group. The resistance index (RI, pulsatility index (PI and systolic/diastolic (S/D ratio of umbilical artery were measured at 24–30 weeks, 31–36 weeks and 37–41 weeks of pregnancy. After delivery, umbilical artery blood was taken for analysis of blood gas and determination of oxidative stress parameters. The venous blood of newborns was taken to measure the myocardial injury and brain injury parameters. Results: At 24–30 weeks, 31–36 weeks and 37–41 weeks of pregnancy, RI, S/D and PI in pregnant women of distress group were significantly higher than those in control group. The pH, contents of arterial partial pressure of oxygen, vitamin C, vitamin E, superoxide dismutase and glutathione peroxidase in umbilical artery blood in pregnant women of distress group was significantly lower than those in control group and negatively correlated with the umbilical artery RI, PI and S/D. The contents of partial pressure of carbon dioxide in artery, lactic acid and malondialdehyde in pregnant women of distress group were significantly higher than those in control group and positively correlated with the umbilical artery RI, PI and S/D. The contents of lactate dehydrogenase, hydroxybutyrate dehydrogenase, creatine kinase, creatine kinase-MB, S100B, neuron-specific enolase, creatine kinase-BB and Tau in newborns' venous blood in distress group were significantly higher than those in control group and

  10. Vector flow imaging techniques: An innovative ultrasonographic technique for the study of blood flow. (United States)

    Goddi, Alfredo; Fanizza, Marianna; Bortolotto, Chandra; Raciti, Maria Vittoria; Fiorina, Ilaria; He, Xujin; Du, Yigang; Calliada, Fabrizio


    Doppler ultrasonography is routinely used to identify abnormal blood flow. Nevertheless, conventional Doppler can be used to determine only the axial component of blood flow velocity and is angle dependent. A new method of multidimensional angle-independent estimation of flow velocity, called Vector Flow Imaging (VFI), has been proposed. It quantitatively evaluates the true velocity vector's amplitude and direction at any location into a vessel and displays a more intuitive depiction of the flow movements. High frame rate VFI, based on plane wave imaging, allows a detailed dynamic visualization of complex flow by showing even transient events, otherwise undetectable. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:582-588, 2017. © 2017 Wiley Periodicals, Inc.

  11. Regional cerebral blood flow autoregulation in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Strauss, Gitte Irene; Møller, Kirsten


    The absence of cerebral blood flow autoregulation in patients with fulminant hepatic failure (FHF) implies that changes in arterial pressure directly influence cerebral perfusion. It is assumed that dilatation of cerebral arterioles is responsible for the impaired autoregulation. Recently, frontal...... in the anterior cerebral artery would be less affected by an increase in mean arterial pressure compared with the brain area supplied by the middle cerebral artery. Relative changes in cerebral perfusion were determined by transcranial Doppler-measured mean flow velocity (V(mean)), and resistance was determined...... by pulsatility index in the anterior and middle cerebral arteries. Cerebral autoregulation was evaluated by concomitant measurements of mean arterial pressure and V(mean) in the anterior and middle cerebral arteries during norepinephrine infusion. Baseline V(mean) was lower in the brain area supplied...

  12. Uterine artery blood flow velocity waveforms during uterine contractions. (United States)

    Li, H; Gudmundsson, S; Olofsson, P


    No quantitative or qualitative Doppler velocimetry classification of vascular flow resistance covering all stages of forward and reversed flows exists. The objective of this study was to characterize uterine artery (UtA) flow velocity waveforms (FVWs) obtained during an oxytocin challenge test (OCT) and compare them to FVWs in spontaneous normal labor. Uterine artery Doppler velocimetry was performed during and between uterine contractions in 61 high-risk pregnancies subjected to an OCT and in 20 normal pregnancies undergoing spontaneous labor. FVWs were classified relative to the presence of forward/absent/reversed flow during systole and diastole, and the time-averaged flow velocity over the heart cycle. Eleven different FVW classes were identified. No relationship between FVWs recorded during uterine inertia and contractions was found (P >/= 0.2). In both groups, only forward FVWs were recorded between contractions, whereas during contractions flow reversal was more common in the OCT group (P uterine contractions were not predicted by flow patterns recorded during uterine inertia. Reversal of flow direction was more common during oxytocin-induced uterine contractions than during spontaneous contractions. In cases of predominantly reversed flow, domains of the uterus may be supplied by blood from the contralateral UtA. These observations give new insights into the circulatory dynamics of the uterus during labor, and also point to a possible vasoconstrictory effect in the UtAs of oxytocin at high concentrations. Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd.

  13. Blood flow in the cerebral venous system: modeling and simulation. (United States)

    Miraucourt, Olivia; Salmon, Stéphanie; Szopos, Marcela; Thiriet, Marc


    The development of a software platform incorporating all aspects, from medical imaging data, through three-dimensional reconstruction and suitable meshing, up to simulation of blood flow in patient-specific geometries, is a crucial challenge in biomedical engineering. In the present study, a fully three-dimensional blood flow simulation is carried out through a complete rigid macrovascular circuit, namely the intracranial venous network, instead of a reduced order simulation and partial vascular network. The biomechanical modeling step is carefully analyzed and leads to the description of the flow governed by the dimensionless Navier-Stokes equations for an incompressible viscous fluid. The equations are then numerically solved with a free finite element software using five meshes of a realistic geometry obtained from medical images to prove the feasibility of the pipeline. Some features of the intracranial venous circuit in the supine position such as asymmetric behavior in merging regions are discussed.

  14. Brain blood vessel segmentation using line-shaped profiles (United States)

    Babin, Danilo; Pižurica, Aleksandra; De Vylder, Jonas; Vansteenkiste, Ewout; Philips, Wilfried


    Segmentation of cerebral blood vessels is of great importance in diagnostic and clinical applications, especially for embolization of cerebral aneurysms and arteriovenous malformations (AVMs). In order to perform embolization of the AVM, the structural and geometric information of blood vessels from 3D images is of utmost importance. For this reason, the in-depth segmentation of cerebral blood vessels is usually done as a fusion of different segmentation techniques, often requiring extensive user interaction. In this paper we introduce the idea of line-shaped profiling with an application to brain blood vessel and AVM segmentation, efficient both in terms of resolving details and in terms of computation time. Our method takes into account both local proximate and wider neighbourhood of the processed pixel, which makes it efficient for segmenting large blood vessel tree structures, as well as fine structures of the AVMs. Another advantage of our method is that it requires selection of only one parameter to perform segmentation, yielding very little user interaction.

  15. Effects of midazolam on cerebral blood flow in human volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Forster, A.; Juge, O.; Morel, D.


    The effects of intravenously administered midazolam on cerebral blood flow were evaluated in eight healthy volunteers using the /sup 133/Xe inhalation technique. Six minutes after an intravenous dose of 0.15 mg/kg midazolam, the cerebral blood flow decreased significantly (P less than 0.001) from a value of 40.6 +/- 3.3 to a value of 27.0 +/- 5.0 ml . 100 g-1 . min-1. Cerebrovascular resistance (CVR) increased from 2.8 +/- 0.2 to 3.9 to 0.6 mmHg/(ml . 100 g-1 . min-1)(P less than 0.001). Mean arterial blood pressure decreased significantly (P less than 0.05) from 117 +/- 8 to 109 +/- 9 mmHg and arterial carbon dioxide tension increased from 33.9 +/- 2.3 to 38.6 +/- 3.2 mmHg (P less than 0.05). Arterial oxygen tension remained stable throughout the study, 484 +/- 95 mmHg before the administration of midazolam and 453 +/- 76 mmHg after. All the subjects slept after the injection of the drug and had anterograde amnesia of 24.5 +/- 5 min. The decrease in mean arterial blood pressure was probably not important since it remained in the physiologic range for cerebral blood flow autoregulation. The increase in arterial carbon dioxide tension observed after the midazolam injection may have partially counteracted the effect of this new benzodiazepine on cerebral blood flow. Our data suggest that midazolam might be a safe agent to use for the induction of anethesia in neurosurgical patients with intracranial hypertension.

  16. Pharmacological modulation of blood-brain barrier increases permeability of doxorubicin into the rat brain (United States)

    Sardi, Iacopo; la Marca, Giancarlo; Cardellicchio, Stefania; Giunti, Laura; Malvagia, Sabrina; Genitori, Lorenzo; Massimino, Maura; de Martino, Maurizio; Giovannini, Maria G


    Our group recently demonstrated in a rat model that pretreatment with morphine facilitates doxorubicin delivery to the brain in the absence of signs of increased acute systemic toxicity. Morphine and other drugs such as dexamethasone or ondansetron seem to inhibit MDR proteins localized on blood-brain barrier, neurons and glial cells increasing the access of doxorubicin to the brain by efflux transporters competition. We explored the feasibility of active modification of the blood-brain barrier protection, by using morphine dexamethasone or ondansetron pretreatment, to allow doxorubicin accumulation into the brain in a rodent model. Rats were pretreated with morphine (10 mg/kg, i.p.), dexamethasone (2 mg/kg, i.p.) or ondansetron (2 mg/kg, i.p.) before injection of doxorubicin (12 mg/kg, i.p.). Quantitative analysis of doxorubicin was performed by mass spectrometry. Acute hearth and kidney damage was analyzed by measuring doxorubicin accumulation, LDH activity and malondialdehyde plasma levels. The concentration of doxorubicin was significantly higher in all brain areas of rats pretreated with morphine (P < 0.001) or ondansetron (P < 0.05) than in control tissues. The concentration of doxorubicin was significantly higher in cerebral hemispheres and brainstem (P < 0.05) but not in cerebellum of rats pretreated with dexamethasone than in control tissues. Pretreatment with any of these drugs did not increase LDH activity or lipid peroxidation compared to controls. Our data suggest that morphine, dexamethasone or ondansetron pretreatment is able to allow doxorubicin penetration inside the brain by modulating the BBB. This effect is not associated with acute cardiac or renal toxicity. This finding might provide the rationale for clinical applications in the treatment of refractory brain tumors and pave the way to novel applications of active but currently inapplicable chemotherapeutic drugs. PMID:23977451

  17. Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces

    Directory of Open Access Journals (Sweden)

    Strazielle Nathalie


    Full Text Available Abstract Background Prostaglandin E2 (PGE2 is involved in the regulation of synaptic activity and plasticity, and in brain maturation. It is also an important mediator of the central response to inflammatory challenges. The aim of this study was to evaluate the ability of the tissues forming the blood-brain interfaces to act as signal termination sites for PGE2 by metabolic inactivation. Methods The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection. Results The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14-dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma. Conclusion The rat choroidal tissue has a significant ability to metabolize PGE2 during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE2 in the brain, or function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF during the critical early postnatal period of brain development.

  18. MR assessment of absolute myocardial blood flow and vasodilator flow reserve in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kawada, Nanaka; Sakuma, Hajime; Takeda, Kan; Nakagawa, Tsuyoshi; Yamakado, Tetsu; Nakano, Takeshi [Mie Univ., Tsu (Japan). School of Medicine


    Absolute coronary blood flow per myocardial mass and coronary flow reserve for the entire left ventricle were evaluated in normals and in patients with hypertrophic cardiomyopathy (HCM) by using fast cine MR imaging and fast velocity encoded cine (VENC) MR imaging. Nine healthy volunteers and 8 patients with HCM were studied with a 1.5 T imager. Breath-hold cine MR images encompassing the whole left ventricle were acquired on short axis imaging planes in order to evaluate myocardial mass. A fast VENC MR images were obtained to measure blood flow volume in the coronary sinus before and after dipyridamole administration (TR/TE=15/5 ms, FOV=28 x 22 cm, slice thickness=5 mm). Coronary flow reserve was calculated as a ratio of hyperemic to baseline coronary flow volumes. In the baseline state, coronary blood flow per myocardial mass was significantly lower in patients with HCM than in normal myocardium (0.56{+-}0.23 vs. 0.78{+-}0.27 ml/min/g, p<0.05). After dipyridamole administration, coronary blood flow per myocardial mass in patients with HCM increased substantially less than that in healthy subjects (0.99{+-}0.38 vs. 2.22{+-}0.55 ml/min/g, p<0.01), resulting in the significantly decreased coronary flow reserve ratio in HCM in comparison with that in normal myocardium (1.86{+-}0.56 vs. 3.11{+-}1.37, p<0.05). In conclusion, breath-hold velocity encoded cine MR imaging is a noninvasive technique which can provide assessments of altered coronary blood flow volume per myocardial mass and vasodilator flow reserve in patients with HCM. (author)

  19. A novel transgenic zebrafish model for blood-brain and blood-retinal barrier development

    Directory of Open Access Journals (Sweden)

    Sugimoto Masahiko


    Full Text Available Abstract Background Development and maintenance of the blood-brain and blood-retinal barrier is critical for the homeostasis of brain and retinal tissue. Despite decades of research our knowledge of the formation and maintenance of the blood-brain (BBB and blood-retinal (BRB barrier is very limited. We have established an in vivo model to study the development and maintenance of these barriers by generating a transgenic zebrafish line that expresses a vitamin D-binding protein fused with enhanced green fluorescent protein (DBP-EGFP in blood plasma, as an endogenous tracer. Results The temporal establishment of the BBB and BRB was examined using this transgenic line and the results were compared with that obtained by injection of fluorescent dyes into the sinus venosus of embryos at various stages of development. We also examined the expression of claudin-5, a component of tight junctions during the first 4 days of development. We observed that the BBB of zebrafish starts to develop by 3 dpf, with expression of claudin-5 in the central arteries preceding it at 2 dpf. The hyaloid vasculature in the zebrafish retina develops a barrier function at 3 dpf, which endows the zebrafish with unique advantages for studying the BRB. Conclusion Zebrafish embryos develop BBB and BRB function simultaneously by 3 dpf, which is regulated by tight junction proteins. The Tg(l-fabp:DBP-EGFP zebrafish will have great advantages in studying development and maintenance of the blood-neural barrier, which is a new application for the widely used vertebrate model.

  20. A Reconstruction Method of Blood Flow Velocity in Left Ventricle Using Color Flow Ultrasound

    Directory of Open Access Journals (Sweden)

    Jaeseong Jang


    Full Text Available Vortex flow imaging is a relatively new medical imaging method for the dynamic visualization of intracardiac blood flow, a potentially useful index of cardiac dysfunction. A reconstruction method is proposed here to quantify the distribution of blood flow velocity fields inside the left ventricle from color flow images compiled from ultrasound measurements. In this paper, a 2D incompressible Navier-Stokes equation with a mass source term is proposed to utilize the measurable color flow ultrasound data in a plane along with the moving boundary condition. The proposed model reflects out-of-plane blood flows on the imaging plane through the mass source term. The boundary conditions to solve the system of equations are derived from the dimensions of the ventricle extracted from 2D echocardiography data. The performance of the proposed method is evaluated numerically using synthetic flow data acquired from simulating left ventricle flows. The numerical simulations show the feasibility and potential usefulness of the proposed method of reconstructing the intracardiac flow fields. Of particular note is the finding that the mass source term in the proposed model improves the reconstruction performance.

  1. Perlecan and the Blood-Brain Barrier: Beneficial Proteolysis?

    Directory of Open Access Journals (Sweden)

    Jill eRoberts


    Full Text Available The cerebral microvasculature is important for maintaining brain homeostasis. This is achieved via the blood-brain barrier (BBB, composed of endothelial cells with specialized tight junctions, astrocytes and a basement membrane. Prominent components of the basement membrane extracellular matrix (ECM include fibronectin, laminin, collagen IV and perlecan, all of which regulate cellular processes via signal transduction through various cell membrane bound ECM receptors. Expression and proteolysis of these ECM components can be rapidly altered during pathological states of the central nervous system. In particular, proteolysis of perlecan, a heparan sulfate proteoglycan, occurs within hours following ischemia induced by experimental stroke. Proteolysis of ECM components following stroke results in the degradation of the basement membrane and further disruption of the BBB. While it is clear that such proteolysis has negative consequences for the BBB, we propose that it also may lead to generation of ECM protein fragments, including the C-terminal domain V (DV of perlecan, that potentially have a positive influence on other aspects of CNS health. Indeed, perlecan DV has been shown to be persistently generated after stroke and beneficial as a neuroprotective molecule and promoter of post-stroke brain repair. This mini-review will discuss beneficial roles of perlecan protein fragment generation within the brain during stroke.

  2. Sorting Tubules Regulate Blood-Brain Barrier Transcytosis

    Directory of Open Access Journals (Sweden)

    Roberto Villaseñor


    Full Text Available Transcytosis across the blood-brain barrier (BBB regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate intracellular transport in BECs, and we uncovered a pathway for the regulation of receptor-mediated transcytosis. By combining live-cell imaging and mathematical modeling in vitro with super-resolution microscopy of the BBB, we show that intracellular tubules promote transcytosis across the BBB. A monovalent construct (sFab sorted for transcytosis was localized to intracellular tubules, whereas a bivalent construct (dFab sorted for degradation formed clusters with impaired transport along tubules. Manipulating tubule biogenesis by overexpressing the small GTPase Rab17 increased dFab transport into tubules and induced its transcytosis in BECs. We propose that sorting tubules regulate transcytosis in BECs and may be a general mechanism for receptor-mediated transport across the BBB.

  3. Sleep restriction impairs blood-brain barrier function. (United States)

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J; Wang, Yuping; Pan, Weihong


    The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. Copyright © 2014 the authors 0270-6474/14/3414697-10$15.00/0.

  4. How to manage blood pressure after brain injury? (United States)

    Carteron, Laurent; Taccone, Fabio S; Oddo, Mauro


    Manipulation of blood pressure (BP) is a mainstay of therapy in patients with acute brain injury (ABI). In the early emergent phase (first hours from injury), depending on intracranial pathology, BP manipulation aims to: 1) limit the progression of parenchymal hematomas or hemorrhagic transformation (in patients with ischemic/hemorrhagic stroke and aneurysmal subarachnoid hemorrhage [SAH]), and 2) attenuate hypoperfusion and secondary cerebral ischemic insults (in patients with traumatic brain injury [TBI]). During the intensive care unit (ICU) phase, BP management is primarily focused at identifying the so-called "optimal" BP/cerebral perfusion pressure (CPP), i.e. the threshold of mean arterial pressure (MAP)/CPP to prevent secondary cerebral ischemia. BP augmentation is also an essential component of the medical management of delayed cerebral ischemia following SAH. Increasing clinical data support the use of surrogate monitoring modalities of cerebral perfusion (including trans-cranial Doppler and brain tissue oximetry) to indentify BP/CPP targets in ABI patients. We reviewed herein the actual evidence regarding BP control in the early phase after ABI and recent clinical investigations using multimodal monitoring to optimize CPP and BP in severe ABI patients. The main purpose of this review is to provide a pragmatic approach of BP management, taking into account the timing of injury and differences in brain pathologies.

  5. Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells (United States)

    Watkins, Stacey; Robel, Stefanie; Kimbrough, Ian F.; Robert, Stephanie M.; Ellis-Davies, Graham; Sontheimer, Harald


    Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange sites for ions, metabolites, and energy substrates from the blood to the brain. They maintain endothelial tight junctions that form the blood-brain barrier (BBB) and release vasoactive molecules that regulate vascular tone. Malignant gliomas are highly invasive tumors that use the perivascular space for invasion and co-opt existing vessels as satellite tumors form. Here we use a clinically relevant mouse model of glioma and find that glioma cells, as they populate the perivascular space of pre-existing vessels, displace astrocytic endfeet from endothelial or vascular smooth muscle cells. This causes a focal breach in the BBB. Furthermore, astrocyte-mediated gliovascular coupling is lost, and glioma cells seize control over regulation of vascular tone through Ca2+-dependent release of K+. These findings have important clinical implications regarding blood flow in the tumor-associated brain and the ability to locally deliver chemotherapeutic drugs in disease. PMID:24943270

  6. [Assessment of maternal cerebral blood flow in patients with preeclampsia]. (United States)

    Mandić, Vesna; Miković, Zeljko; Dukić, Milan; Vasiljević, Mladenko; Filimonović, Dejan; Bogavac, Mirjana


    Systemic vasoconstriction in preeclamptic patients increases vascular resistance, and is manifested by increased arterial blood flow velocity. The aim of the study is to evaluate if there is a change of Doppler indices in maternal medial cerbral artery (MCA) in severe preeclampsia due to: 1) severity of clinical symptoms, 2) the begining of eclamptic attack and 3) the application of anticonvulsive therapy. A prospective clinical study included 92 pregnant women, gestational age 28-36 weeks. They were divided into three groups: normotensive (n=30), mild preeclampsia (n=33), and severe preeclampsia (n=29). We investigated maternal cerebral circulation by assessing the MCA. We registrated: pulsatility index (Pi), resistance index (Ri), systolic/diastolic ratio (S/D), and the maximum systolic, end diastolic and medium velocity. Patients with severe preeclampsia were divided into two subgroups. subgroup 1 included patients without symptoms of threatening eclampsia (n=18; 62.06%); while subgroup 2 included those with symptoms of preeclampsia (n=11; 37.94%). All patients with severe preeclampsia were treated with magnesium sulfate (MgSO4), and cerebral blood flow was measured before and after the treatment. Statistical analysis was done by oneway ANOVA, Student t-test and t-paired sample test. The difference was considered to be significant if ppreeclamsia we registrated significantly increased values of all velocities (patients with signs of threatening eclampsia). After MgSO4 treatment in patients with severe preeclampsia significantly decreased values of Pi, Ri, S/D ratio and all velocities were registered. In the studied group of patients with severe preclampsia we found increased velocity values, Pi and Ri, especially in patients with signs of threatened eclampsia, suggesting that blood vessels changes are most prominent in severe preeclampsia. Cerebral blood flow meassurements can be used as a clinical test for the prediction of eclampsia. Magnesium-sulfate (MgSO4

  7. Volumetric lattice Boltzmann simulation for blood flow in aorta arteries (United States)

    Deep, Debanjan; Yu, Huidan (Whitney); Teague, Shawn


    Complicated moving boundaries pose a major challenge in computational fluid dynamics for complex flows, especially in the biomechanics of both blood flow in the cardiovascular system and air flow in the respiratory system where the compliant nature of the vessels can have significant effects on the flow rate and wall shear stress. We develop a computation approach to treat arbitrarily moving boundaries using a volumetric representation of lattice Boltzmann method, which distributes fluid particles inside lattice cells. A volumetric bounce-back procedure is applied in the streaming step while momentum exchange between the fluid and moving solid boundary are accounted for in the collision sub-step. Additional boundary-induced migration is introduced to conserve fluid mass as the boundary moves across fluid cells. The volumetric LBM (VLBM) is used to simulate blood flow in both normal and dilated aorta arteries. We first compare flow structure and pressure distribution in steady state with results from Navier-Stokes based solver and good agreements are achieved. Then we focus on wall stress within the aorta for different heart pumping condition and present quantitative measurement of wall shear and normal stress.

  8. Physical insights into the blood-brain barrier translocation mechanisms (United States)

    Theodorakis, Panagiotis E.; Müller, Erich A.; Craster, Richard V.; Matar, Omar K.


    The number of individuals suffering from diseases of the central nervous system (CNS) is growing with an aging population. While candidate drugs for many of these diseases are available, most of these pharmaceutical agents cannot reach the brain rendering most of the drug therapies that target the CNS inefficient. The reason is the blood-brain barrier (BBB), a complex and dynamic interface that controls the influx and efflux of substances through a number of different translocation mechanisms. Here, we present these mechanisms providing, also, the necessary background related to the morphology and various characteristics of the BBB. Moreover, we discuss various numerical and simulation approaches used to study the BBB, and possible future directions based on multi-scale methods. We anticipate that this review will motivate multi-disciplinary research on the BBB aiming at the design of effective drug therapies.

  9. Gut–Brain Axis in Regulation of Blood Pressure

    Directory of Open Access Journals (Sweden)

    Tao Yang


    Full Text Available Hypertension (HTN is an escalating health issue worldwide. It is estimated that 1.56 billion people will suffer from high blood pressure (BP by 2025. Recent studies reported an association between gut dysbiosis and HTN, thus proposing interesting avenues for novel treatments of this condition. The sympathetic nervous system (SNS and the immune system (IS play a recognized role in the onset and progression of HTN, while reciprocal communication between gut microbiota and the brain can regulate BP by modulating the interplay between the IS and SNS. This review presents the current state of the science implicating brain-gut connection in HTN, highlighting potential pathways of their interaction in control of BP.

  10. Gut–Brain Axis in Regulation of Blood Pressure (United States)

    Yang, Tao; Zubcevic, Jasenka


    Hypertension (HTN) is an escalating health issue worldwide. It is estimated that 1.56 billion people will suffer from high blood pressure (BP) by 2025. Recent studies reported an association between gut dysbiosis and HTN, thus proposing interesting avenues for novel treatments of this condition. The sympathetic nervous system (SNS) and the immune system (IS) play a recognized role in the onset and progression of HTN, while reciprocal communication between gut microbiota and the brain can regulate BP by modulating the interplay between the IS and SNS. This review presents the current state of the science implicating brain-gut connection in HTN, highlighting potential pathways of their interaction in control of BP. PMID:29118721

  11. Relationship between haemodynamic impairment and collateral blood flow in carotid artery disease

    DEFF Research Database (Denmark)

    Hartkamp, Nolan S; Petersen, Esben T; Chappell, Michael A


    Collateral blood flow plays a pivotal role in steno-occlusive internal carotid artery (ICA) disease to prevent irreversible ischaemic damage. Our aim was to investigate the effect of carotid artery disease upon cerebral perfusion and cerebrovascular reactivity and whether haemodynamic impairment...... is influenced at brain tissue level by the existence of primary and/or secondary collateral. Eighty-eight patients with steno-occlusive ICA disease and 29 healthy controls underwent MR examination. The presence of collaterals was determined with time-of-flight, two-dimensional phase contrast MRA and territorial...... arterial spin labeling (ASL) imaging. Cerebral blood flow and cerebrovascular reactivity were assessed with ASL before and after acetazolamide. Cerebral haemodynamics were normal in asymptomatic ICA stenosis patients, as opposed to patients with ICA occlusion, in whom the haemodynamics in both hemispheres...

  12. Global brain blood-oxygen level responses to autonomic challenges in obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Paul M Macey

    Full Text Available Obstructive sleep apnea (OSA is accompanied by brain injury, perhaps resulting from apnea-related hypoxia or periods of impaired cerebral perfusion. Perfusion changes can be determined indirectly by evaluation of cerebral blood volume and oxygenation alterations, which can be measured rapidly and non-invasively with the global blood oxygen level dependent (BOLD signal, a magnetic resonance imaging procedure. We assessed acute BOLD responses in OSA subjects to pressor challenges that elicit cerebral blood flow changes, using a two-group comparative design with healthy subjects as a reference. We separately assessed female and male patterns, since OSA characteristics and brain injury differ between sexes. We studied 94 subjects, 37 with newly-diagnosed, untreated OSA (6 female (age mean ± std: 52.1±8.1 yrs; apnea/hypopnea index [AHI]: 27.7±15.6 events/hr and 31 male 54.3±8.4 yrs; AHI: 37.4±19.6 events/hr, and 20 female (age 50.5±8.1 yrs and 37 male (age 45.6±9.2 yrs healthy control subjects. We measured brain BOLD responses every 2 s while subjects underwent cold pressor, hand grip, and Valsalva maneuver challenges. The global BOLD signal rapidly changed after the first 2 s of each challenge, and differed in magnitude between groups to two challenges (cold pressor, hand grip, but not to the Valsalva maneuver (repeated measures ANOVA, p<0.05. OSA females showed greater differences from males in response magnitude and pattern, relative to healthy counterparts. Cold pressor BOLD signal increases (mean ± adjusted standard error at the 8 s peak were: OSA 0.14±0.08% vs. Control 0.31±0.06%, and hand grip at 6 s were: OSA 0.08±0.03% vs. Control at 0.30±0.02%. These findings, indicative of reduced cerebral blood flow changes to autonomic challenges in OSA, complement earlier reports of altered resting blood flow and reduced cerebral artery responsiveness. Females are more affected than males, an outcome which may contribute to the sex

  13. Ozone Therapy on Cerebral Blood Flow: A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Bernardino Clavo


    Full Text Available Ozone therapy is currently being used in the treatment of ischemic disorders, but the underlying mechanisms that result in successful treatment are not well known. This study assesses the effect of ozone therapy on the blood flow in the middle cerebral and common carotid arteries. Seven subjects were recruited for the therapy that was performed by transfusing ozone-enriched autologous blood on 3 alternate days over 1 week. Blood flow quantification in the common carotid artery (n = 14 was performed using color Doppler. Systolic and diastolic velocities in the middle cerebral artery (n = 14 were estimated using transcranial Doppler. Ultrasound assessments were conducted at the following three time points: 1 basal (before ozone therapy, 2 after session #3 and 3 1 week after session #3. The common carotid blood flow had increased by 75% in relation to the baseline after session #3 (P < 0.001 and by 29% 1 week later (P = 0.039. In the middle cerebral artery, the systolic velocity had increased by 22% after session #3 (P = 0.001 and by 15% 1 week later (P = 0.035, whereas the diastolic velocity had increased by 33% after session #3 (P < 0.001 and by 18% 1 week later (P = 0.023. This preliminary Doppler study supports the clinical experience of achieving improvement by using ozone therapy in peripheral ischemic syndromes. Its potential use as a complementary treatment in cerebral low perfusion syndromes merits further clinical evaluation.

  14. Modulation of radial blood flow during Braille character discrimination task. (United States)

    Murata, Jun; Matsukawa, K; Komine, H; Tsuchimochi, H


    Human hands are excellent in performing sensory and motor function. We have hypothesized that blood flow of the hand is dynamically regulated by sympathetic outflow during concentrated finger perception. To identify this hypothesis, we measured radial blood flow (RBF), radial vascular conductance (RVC), heart rate (HR), and arterial blood pressure (AP) during Braille reading performed under the blind condition in nine healthy subjects. The subjects were instructed to read a flat plate with raised letters (Braille reading) for 30 s by the forefinger, and to touch a blank plate as control for the Braille discrimination procedure. HR and AP slightly increased during Braille reading but remained unchanged during the touching of the blank plate. RBF and RVC were reduced during the Braille character discrimination task (decreased by -46% and -49%, respectively). Furthermore, the changes in RBF and RVC were much greater during the Braille character discrimination task than during the touching of the blank plate (decreased by -20% and -20%, respectively). These results have suggested that the distribution of blood flow to the hand is modulated via sympathetic nerve activity during concentrated finger perception.

  15. Ozone Therapy on Cerebral Blood Flow: A Preliminary Report (United States)


    Ozone therapy is currently being used in the treatment of ischemic disorders, but the underlying mechanisms that result in successful treatment are not well known. This study assesses the effect of ozone therapy on the blood flow in the middle cerebral and common carotid arteries. Seven subjects were recruited for the therapy that was performed by transfusing ozone-enriched autologous blood on 3 alternate days over 1 week. Blood flow quantification in the common carotid artery (n = 14) was performed using color Doppler. Systolic and diastolic velocities in the middle cerebral artery (n = 14) were estimated using transcranial Doppler. Ultrasound assessments were conducted at the following three time points: 1) basal (before ozone therapy), 2) after session #3 and 3) 1 week after session #3. The common carotid blood flow had increased by 75% in relation to the baseline after session #3 (P ozone therapy in peripheral ischemic syndromes. Its potential use as a complementary treatment in cerebral low perfusion syndromes merits further clinical evaluation. PMID:15841265

  16. Blood flow and oxygenation in peritendinous tissue and calf muscle during dynamic exercise in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Langberg, H; Green, Sara Marie Ehrenreich


    , and (2) whether blood flow is coupled to oxidative metabolism. 2. Seven individuals performed dynamic plantar flexion from 1 to 9 W. Radial artery and popliteal venous blood were sampled for O2, peritendinous blood flow was determined by 133Xe-washout, calf blood flow by plethysmography, cardiac output...

  17. Retrobulbar ocular blood flow changes after phacoemulsification in patients

    Directory of Open Access Journals (Sweden)

    Yin-Ying Zhao


    Full Text Available AIM:To evaluate retrobulbar ocular blood flow changes after phacoemulsification.METHODS:Prospective consecutive study. Forty-six eyes from 46 cataract patients scheduled for phacoemulsification surgery at Affiliated Eye Hospital, Wenzhou Medical College were recruited, of which 22 patients with normal blood pressure and 24 patients with hypertension. All eyes were examined by a color Doppler imaging at before, 4h, 1d after surgery. Resistance indexes(RIs, peak systolic flow velocity(PSV, end-diastolic flow velocity(EDVwere assessed in the ophthalmic artery(OA, central retinal artery(CRA, and short posterior ciliary arteries(PCA.RESULTS:RIs of a retrobulbar ocular vessels are stable at 4h and 1d in both group postoperatively. A slight decrease in PSV of PCA in hypertension patients, while a slightly increase in normal patients at 4h postoperatively was observed(10.22±4.39 vs 11.73±4.69. There were no significant difference between them(P=0.089. PSV and EDV in CRA are lower in hypertension patients but without statistical significance compared with normal patients. There was a statistically significant decrease in EDV of the PCA in hypertension patients at 4h postoperatively compared with preoperatively(3.23±1.10 vs 3.63±1.15,P=0.036. CONCLUSION:Retinal blood flow was disturbed at super-early after phacoemulsification. Age and hypertension are important risk factors to phacoemusification.

  18. Pressures, flow, and brain oxygenation during plateau waves of intracranial pressure. (United States)

    Dias, Celeste; Maia, Isabel; Cerejo, António; Varsos, Georgios; Smielewski, Peter; Paiva, José-Artur; Czosnyka, Marek


    Plateau waves are common in traumatic brain injury. They constitute abrupt increases of intracranial pressure (ICP) above 40 mmHg associated with a decrease in cerebral perfusion pressure (CPP). The aim of this study was to describe plateau waves characteristics with multimodal brain monitoring in head injured patients admitted in neurocritical care. Prospective observational study in 18 multiple trauma patients with head injury admitted to Neurocritical Care Unit of Hospital Sao Joao in Porto. Multimodal systemic and brain monitoring of primary variables [heart rate, arterial blood pressure, ICP, CPP, pulse amplitude, end tidal CO₂, brain temperature, brain tissue oxygenation pressure, cerebral oximetry (CO) with transcutaneous near-infrared spectroscopy and cerebral blood flow (CBF)] and secondary variables related to cerebral compensatory reserve and cerebrovascular reactivity were supported by dedicated software ICM+ ( . The compiled data were analyzed in patients who developed plateau waves. In this study we identified 59 plateau waves that occurred in 44% of the patients (8/18). During plateau waves CBF, cerebrovascular resistance, CO, and brain tissue oxygenation decreased. The duration and magnitude of plateau waves were greater in patients with working cerebrovascular reactivity. After the end of plateau wave, a hyperemic response was recorded in 64% of cases with increase in CBF and brain oxygenation. The magnitude of hyperemia was associated with better autoregulation status and low oxygenation levels at baseline. Multimodal brain monitoring facilitates identification and understanding of intrinsic vascular brain phenomenon, such as plateau waves, and may help the adequate management of acute head injury at bed side.

  19. Endothelial-dependent vasodilators preferentially increase subendocardial blood flow

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    Pelc, L.R.; Gross, G.J.; Warltier, D.C.


    Interference with arachidonic acid metabolism on the effect of acetylcholine (Ach) or arachidonic acid (AA) to preferentially increase subendocardial perfusion was investigated in anesthetized dogs. Hemodynamics, regional myocardial blood flow (MBF (ml/min/g):radioactive microspheres) and the left ventricular transmural distribution of flow (endo/epi) were measured. Intracoronary infusion of Ach (10 and AA (585 significantly (P < .05*) increased myocardial perfusion and selectively redistributed flow to the subendocardium (increased endo/epi) without changes in systemic hemodynamics. Inhibition of phospholipase A/sub 2/ by quinacrine (Q; 600, ic) attenuated the increase in myocardial perfusion produced by Ach but not by AA and inhibited the redistribution of flow to the subendocardium. The present results suggest that endothelium-dependent vasodilators produce a preferential increase in subendocardial perfusion via a product of AA metabolism.

  20. Blood transfusion in preterm infants improves intestinal tissue oxygenation without alteration in blood flow. (United States)

    Banerjee, J; Leung, T S; Aladangady, N


    The objective of the study was to investigate the splanchnic blood flow velocity and oximetry response to blood transfusion in preterm infants according to postnatal age. Preterm infants receiving blood transfusion were recruited to three groups: 1-7 (group 1; n = 20), 8-28 (group 2; n = 21) and ≥29 days of life (group 3; n = 18). Superior mesenteric artery (SMA) peak systolic (PSV) and diastolic velocities were measured 30-60 min pre- and post-transfusion using Doppler ultrasound scan. Splanchnic tissue haemoglobin index (sTHI), tissue oxygenation index (sTOI) and fractional tissue oxygen extraction (sFTOE) were measured from 15-20 min before to post-transfusion using near-infrared spectroscopy. The mean pretransfusion Hb in group 1, 2 and 3 was 11, 10 and 9 g/dl, respectively. The mean (SD) pretransfusion SMA PSV in group 1, 2 and 3 was 0·63 (0·32), 0·81 (0·33) and 0·97 (0·40) m/s, respectively, and this did not change significantly following transfusion. The mean (SD) pretransfusion sTOI in group 1, 2 and 3 was 36·7 (19·3), 44·6 (10·4) and 41·3 (10·4)%, respectively. The sTHI and sTOI increased (P transfusion in all groups. On multivariate analysis, changes in SMA PSV and sTOI following blood transfusion were not associated with PDA, feeding, pretransfusion Hb and mean blood pressure. Pretransfusion baseline splanchnic tissue oximetry and blood flow velocity varied with postnatal age. Blood transfusion improved intestinal tissue oxygenation without altering mesenteric blood flow velocity irrespective of postnatal ages. © 2016 International Society of Blood Transfusion.

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

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    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)


    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.)

  2. Three-dimensional imaging of absolute blood flow velocity and blood vessel position under low blood flow velocity based on Doppler signal information included in scattered light from red blood cells (United States)

    Kyoden, Tomoaki; Akiguchi, Shunsuke; Tajiri, Tomoki; Andoh, Tsugunobu; Hachiga, Tadashi


    The development of a system for in vivo visualization of occluded distal blood vessels for diabetic patients is the main target of our research. We herein describe two-beam multipoint laser Doppler velocimetry (MLDV), which measures the instantaneous multipoint flow velocity and can be used to observe the blood flow velocity in peripheral blood vessels. By including a motorized stage to shift the measurement points horizontally and in the depth direction while measuring the velocity, the path of the blood vessel in the skin could be observed using blood flow velocity in three-dimensional space. The relationship of the signal power density between the blood vessel and the surrounding tissues was shown and helped us identify the position of the blood vessel. Two-beam MLDV can be used to simultaneously determine the absolute blood flow velocity distribution and identify the blood vessel position in skin.

  3. Outcome of splanchnic blood flow determination in patients with suspected chronic intestinal ischaemia. A retrospective survey

    DEFF Research Database (Denmark)

    Møller, Søren; Madsen, Jan Lysgård


    flow: A, normal response (splanchnic blood flow > or = 200 ml/min); B, possible abnormal response (splanchnic blood flow 51-199 ml/min); and C, definitive abnormal response (splanchnic blood flow 50 ml/min). Where surgery took place, the type of operation was noted. RESULTS: Forty patients had...

  4. The blood-brain barrier as a cause of obesity. (United States)

    Banks, William A


    The dramatic increase in the number of obese and overweight persons has spurred interest in control of appetite, body weight, and adiposity. Leptin is the humoral component of a negative feedback loop between adipose tissue and brain. Leptin is secreted from fat in proportion to the degree of adiposity, is transported across the blood-brain barrier (BBB), and acts in the brain to decrease appetite and increase thermogenesis, actions that ultimately decrease adiposity. However, leptin fails as an adipostat because leptin resistance arises in obesity. The BBB transporter is the first part of the feedback loop to fail, producing the so called "peripheral resistance" to leptin. In this sense, obesity is a disease of the BBB. Failure of leptin as an adipostat raises the question of what its primary role is as does its effects on reproduction, bone, immunity, breathing, cognition, and neurogenesis. Kinetics analysis shows that the BBB transporter performs most efficiently at low serum levels of leptin, suggesting that the feedback loop evolved to operate at lower leptin levels than those seen in ideal body weight. We suggest that low levels of serum leptin inform the brain that adipose reserves are adequate to expend calories on functions other than feeding, such as reproduction and the immune system. This feedback loop is short-circuited when an animal enters starvation. Hallmarks of starvation include decreased secretion of leptin by adipose tissue and hypertriglyceridemia. Triglycerides inhibit the transport of leptin across the BBB, thus attenuating the leptin signal across the BBB and providing a mechanism for peripheral leptin resistance. Triglycerides are elevated in both starvation and obesity. We postulate that hypertriglyceridemia evolved as a starvation signal to the brain that acts in part to inhibit the transport of the leptin across the BBB. The hypertriglyceridemia of obesity invokes this aspect of the starvation response, inducing leptin resistance at the

  5. Sympathetic reflex control of blood flow in human peripheral tissues

    DEFF Research Database (Denmark)

    Henriksen, O


    sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno......Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human...

  6. Cerebral blood flow autoregulation in experimental liver failure

    DEFF Research Database (Denmark)

    Dethloff, T.J.; Larsen, F.S.; Knudsen, Gitte Moos


    Patients with acute liver failure (ALF) display impairment of cerebral blood flow (CBF) autoregulation, which may contribute to the development of fatal intracranial hypertension, but the pathophysiological mechanism remains unclear. In this study, we examined whether loss of liver mass causes...... impairment of CBF autoregulation. Four rat models were chosen, each representing different aspects of ALF: galactosamine (GlN) intoxication represented liver necrosis, 90% hepatectomy (PHx90) represented reduction in liver mass, portacaval anastomosis (PCA) represented shunting of blood...... edema/high ICP. Nor does portacaval shunting or hyperammonemia impair autoregulation. Rather, massive liver necrosis and reduced liver mass are associated with loss of CBF autoregulation Udgivelsesdato: 2008/5...

  7. Quantitative flow and velocity measurements of pulsatile blood flow with 4D-DSA (United States)

    Shaughnessy, Gabe; Hoffman, Carson; Schafer, Sebastian; Mistretta, Charles A.; Strother, Charles M.


    Time resolved 3D angiographic data from 4D DSA provides a unique environment to explore physical properties of blood flow. Utilizing the pulsatility of the contrast waveform, the Fourier components can be used to track the waveform motion through vessels. Areas of strong pulsatility are determined through the FFT power spectrum. Using this method, we find an accuracy from 4D-DSA flow measurements within 7.6% and 6.8% RMSE of ICA PCVIPR and phantom flow probe validation measurements, respectively. The availability of velocity and flow information with fast acquisition could provide a more quantitative approach to treatment planning and evaluation in interventional radiology.

  8. 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...

  9. A mathematical approach for assessing the transport of large neutral amino acids across the blood-brain barrier in man. (United States)

    Dahl, Rasmus Holmboe; Berg, Ronan M G


    Changes in the large neutral amino acid (LNAA) transport across the blood-brain barrier (BBB) is thought to contribute to brain dysfunction in a number of clinical conditions, including phenylketonuria, acute liver failure, and sepsis. Here, we present a novel approach for estimating BBB permeability and the LNAA concentrations in brain extracellular fluid, by demonstrating that they can be mathematically derived on the basis of kinetic constants of the BBB available from the literature, if cerebral blood flow and the arterial and jugular venous LNAA concentrations are known. While it is well known that the permeability surface area product of the BBB to a LNAA from blood to brain (PS1) can be calculated from the arterial LNAA concentrations and kinetic constants of the BBB, we demonstrate that the permeability surface area product from brain to blood (PS2) can be calculated by deriving the substrate activity of the saturable transporter from the kinetic constants and arterial and jugular venous LNAA concentrations, and that the concentration of the LNAA in brain extracellular fluid can then be determined. This approach is methodically simple, and may be useful for assessing the transcerebral exchange kinetics of LNAAs in future human-experimental and clinical studies.

  10. FDM Analysis for Blood Flow through Stenosed Tapered Arteries

    Directory of Open Access Journals (Sweden)

    Sankar DS


    Full Text Available Abstract A computational model is developed to analyze the unsteady flow of blood through stenosed tapered narrow arteries, treating blood as a two-fluid model with the suspension of all the erythrocytes in the core region as Herschel-Bulkley fluid and the plasma in the peripheral layer as Newtonian fluid. The finite difference method is employed to solve the resulting system of nonlinear partial differential equations. The effects of stenosis height, peripheral layer thickness, yield stress, viscosity ratio, angle of tapering and power law index on the velocity, wall shear stress, flow rate and the longitudinal impedance are analyzed. It is found that the velocity and flow rate increase with the increase of the peripheral layer thickness and decrease with the increase of the angle of tapering and depth of the stenosis. It is observed that the flow rate decreases nonlinearly with the increase of the viscosity ratio and yield stress. The estimates of the increase in the longitudinal impedance to flow are considerably lower for the two-fluid Herschel-Bulkley model compared with those of the single-fluid Herschel-Bulkley model. Hence, it is concluded that the presence of the peripheral layer helps in the functioning of the diseased arterial system.

  11. Pulsatile blood flow in elastic artery with model aneurysm (United States)

    Nikolov, N.; Radev, St.; Tabakova, S.


    The mathematical modeling and numerical simulations are expected to play an important role to predict the genesis of different cardiovascular diseases, such as the formation and rupture of aneurysms. In the present work, the numerical solutions of the oscillatory blood flow are constructed for an elastic artery with a model aneurysm by use of the software ANSYS. It is observed that the artery elastic strain behaves in a different way: stably or unstably depending on the different combinations between the flow parameter (outlet pressure) and the elastic modulus of the artery wall.

  12. Rapidly profiling blood-brain barrier penetration with liposome EKC. (United States)

    Wang, Yongjun; Sun, Jin; Liu, Hongzhuo; He, Zhonggui


    This report intended to study the potential of liposome EKC (LEKC) as a convenient and high-throughput screening tool to assess drug penetration across the blood-brain barrier (BBB). The retention factors (k) of 24 structurally diverse compounds were determined with LEKC and vesicle EKC (VEKC), respectively. Principal component analysis of the steady-state concentrations ratio of compounds in the brain and in the blood expressed as log BB, log k(LEKC), log k(VEKC), and other lipophilic descriptors including octanol/water partition coefficient (Clog P), octanol/water distribution coefficients (log D(7.4)), and polar surface area (PSA), showed the maximum similarity of partitioning processes in LEKC to drug penetration across the BBB. Furthermore, the log BB were correlated with the above five lipophilic descriptors, and the results showed that log k(LEKC) gave the better correlation coefficient (r(2) = 0.811, p <0.0001) than those of log D(7.4), Clog P, PSA, and log k(VEKC) (r(2) = 0.730, 0.672, 0.627, and 0.620, p <0.0001). This is the first report of the use of LEKC as a promising rapid tool to profile drug penetration across the BBB.

  13. Spatio-temporal cerebral blood flow perfusion patterns in cortical spreading depression (United States)

    Verisokin, Andrey Yu.; Verveyko, Darya V.; Postnov, Dmitry E.


    Cortical spreading depression (CSD) is an example of one of the most common abnormalities in biophysical brain functioning. Despite the fact that there are many mathematical models describing the cortical spreading depression (CSD), most of them do not take into consideration the role of redistribution of cerebral blood flow (CBF), that results in the formation of spatio-temporal patterns. The paper presents a mathematical model, which successfully explains the CBD role in the CSD process. Numerical study of this model has revealed the formation of stationary dissipative structures, visually analogous to Turing structures. However, the mechanism of their formation is not diffusion. We show these structures occur due to another type of spatial coupling, that is related to tissue perfusion rate. The proposed model predicts that at similar state of neurons the distribution of blood flow and oxygenation may by different. Currently, this effect is not taken into account when the Blood oxygen-level dependent (BOLD) contrast imaging used in functional magnetic resonance imaging (fMRI). Thus, the diagnosis on the BOLD signal can be ambiguous. We believe that our results can be used in the future for a more correct interpretation of the data obtained with fMRI, NIRS and other similar methods for research of the brain activity.

  14. Simulation of branching blood flows on parallel computers. (United States)

    Yue, Xue; Hwang, Feng-Nan; Shandas, Robin; Cai, Xiao-Chuan


    We present a fully parallel nonlinearly implicit algorithm for the numerical simulation of some branching blood flow problems, which require efficient and robust solver technologies in order to handle the high nonlinearity and the complex geometry. Parallel processing is necessary because of the large number of mesh points needed to accurately discretize the system of differential equations. In this paper we introduce a parallel Newton-Krylov-Schwarz based implicit method, and software for distributed memory parallel computers, for solving the nonlinear algebraic systems arising from a Q2-Q1 finite element discretization of the incompressible Navier-Stokes equations that we use to model the blood flow in the left anterior descending coronary artery.

  15. Subcutaneous blood flow in early male pattern baldness

    Energy Technology Data Exchange (ETDEWEB)

    Klemp, P.; Peters, K.; Hansted, B.


    The subcutaneous blood flow (SBF) was measured by the /sup 133/Xe washout method in the scalp of 14 patients with early male pattern baldness. Control experiments were performed in 14 normal haired men matched for age. The SBF in the scalp of the normal individuals was about 10 times higher than previously reported SBF values in other anatomical regions. In patients with early male pattern baldness, SBF was 2.6 times lower than the values found in the normal individuals (13.7 +/- 9.6 vs 35.7 +/- 10.5 ml/100 g/min-1). This difference was statistically significant (p much less than 0.001). A reduced nutritive blood flow to the hair follicles might be a significant event in the pathogenesis of early male pattern baldness.

  16. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt


    hyperaemia whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation......In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... sympathetic vasoconstriction. ATP is released into plasma from erythrocytes and endothelial cells and the plasma concentration increases in both the feeding artery and the vein draining the contracting skeletal muscle. Adenosine also stimulates the formation of NO and prostaglandins, but the plasma adenosine...

  17. Sympathetically-induced changes in microvascular cerebral blood flow and in the morphology of its low-frequency waves. (United States)

    Deriu, F; Roatta, S; Grassi, C; Urciuoli, R; Micieli, G; Passatore, M


    The effect of bilateral cervical sympathetic nerve stimulation on microvascular cerebral blood flow, recorded at various depths in the parietal lobe and in ponto-mesencephalic areas, was investigated by laser-Doppler flowmetry in normotensive rabbits. These areas were chosen as representative of the vascular beds supplied by the carotid and vertebro-basilar systems, which exhibit different degrees of sympathetic innervation, the former being richer than the latter. Sympathetic stimulation at 30 imp/s affects cerebral blood flow in 77% of the parietal lobe and in 43% of the ponto-mesencephalic tested areas. In both cases the predominant effect was a reduction in blood flow (14.7 +/- 5.1% and 4.1 +/- 2.4%, respectively). The extent of the reduction in both areas was less if the stimulation frequency was decreased. Sometimes mean cerebral blood flow showed a small and transient increase, mainly in response to low-frequency stimulation. The morphology was analysed of low-frequency spontaneous oscillations in cerebral blood flow, attributed to vasomotion. Present in 41% of the tested areas (frequency 4-12 cycles/min, peak-to-peak amplitude 10-40% of mean value), these waves decreased in amplitude and increased in frequency during sympathetic stimulation, irrespective of changes in mean flow. The possibility has been proposed that the sympathetic action on low-frequency spontaneous oscillations may contribute to the protective influence that this system is known to exert on the blood-brain barrier in hypertension.

  18. Developmental trajectories of cerebral blood flow and oxidative metabolism at baseline and during working memory tasks. (United States)

    Jog, Mayank A; Yan, Lirong; Kilroy, Emily; Krasileva, Kate; Jann, Kay; LeClair, Holly; Elashoff, David; Wang, Danny J J


    The neurobiological interpretation of developmental BOLD fMRI findings remains difficult due to the confounding issues of potentially varied baseline of brain function and varied strength of neurovascular coupling across age groups. The central theme of the present research is to study the development of brain function and neuronal activity through in vivo assessments of cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) both at baseline and during the performance of a working memory task in a cohort of typically developing children aged 7 to 18years. Using a suite of 4 emerging MRI technologies including MR blood oximetry, phase-contrast MRI, pseudo-continuous arterial spin labeling (pCASL) perfusion MRI and concurrent CBF/BOLD fMRI, we found: 1) At baseline, both global CBF and CMRO2 showed an age related decline while global OEF was stable across the age group; 2) During the working memory task, neither BOLD nor CBF responses showed significant variations with age in the activated fronto-parietal brain regions. Nevertheless, detailed voxel-wise analyses revealed sub-regions within the activated fronto-parietal regions that show significant decline of fractional CMRO2 responses with age. These findings suggest that the brain may become more "energy efficient" with age during development. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Deciphering the Neuronal Circuitry Controlling Local Blood Flow in the Cerebral Cortex with Optogenetics in PV::Cre Transgenic Mice (United States)

    Urban, Alan; Rancillac, Armelle; Martinez, Lucie; Rossier, Jean


    Although it is know since more than a century that neuronal activity is coupled to blood supply regulation, the underlying pathways remains to be identified. In the brain, neuronal activation triggers a local increase of cerebral blood flow (CBF) that is controlled by the neurogliovascular unit composed of terminals of neurons, astrocytes, and blood vessel muscles. It is generally accepted that the regulation of the neurogliovascular unit is adjusted to local metabolic demand by local circuits. Today experimental data led us to realize that the regulatory mechanisms are more complex and that a neuronal system within the brain is devoted to the control of local brain-blood flow. Recent optogenetic experiments combined with functional magnetic resonance imaging have revealed that light stimulation of neurons expressing the calcium binding protein parvalbumin (PV) is associated with positive blood oxygen level-dependent (BOLD) signal in the corresponding barrel field but also with negative BOLD in the surrounding deeper area. Here, we demonstrate that in acute brain slices, channelrhodopsin-2 (ChR2) based photostimulation of PV containing neurons gives rise to an effective contraction of penetrating arterioles. These results support the neurogenic hypothesis of a complex distributed nervous system controlling the CBF. PMID:22715327

  20. Assessment of maternal cerebral blood flow in patients with preeclampsia


    Mandić Vesna; Miković` Željko; Đukić Milan; Vasiljević Mladenko; Filimonović Dejan; Bogavac Mirjana


    Introduction Systemic vasoconstrktion in preeclamptic patients increases vascular resistance, and is manifested by increased arterial blood flow velocity. The aim of the study is to evaluate if there is a change of Doppler indices in maternal medial cerbral artery (MCA) in severe preeclampsia due to: 1) severity of clinical symptoms, 2) the beginning of eclamptic attack and 3) the application of anticonvidsive therapy. Material and methods A prospective clinical study included 92 pregnant wom...

  1. Feasibility of patient specific aortic blood flow CFD simulation. (United States)

    Svensson, Johan; Gårdhagen, Roland; Heiberg, Einar; Ebbers, Tino; Loyd, Dan; Länne, Toste; Karlsson, Matts


    Patient specific modelling of the blood flow through the human aorta is performed using computational fluid dynamics (CFD) and magnetic resonance imaging (MRI). Velocity patterns are compared between computer simulations and measurements. The workflow includes several steps: MRI measurement to obtain both geometry and velocity, an automatic levelset segmentation followed by meshing of the geometrical model and CFD setup to perform the simulations follwed by the actual simulations. The computational results agree well with the measured data.

  2. The Effect of Insulating Blood Warmer Output Tubing on the Temperature of Packed Red Blood Cells at Low Flow Rates (United States)


    blood cells at the point of patient entry at low flow rates . Utilizing a surgical suite, every attempt was made to replicate a true surgical setting...Flow control pumps were used to regulate flow rates of 300, 600, and 900 milliliters per hour (ml/hr) through Fenwall Laboratories blood warming coils

  3. Brain motion and volume transmission: Keeping the interstice flowing. (United States)

    Picard, Nelson A; Zanardi, Carlos A


    Human brain undergoes two different kinds of movements: subtle pulsatile ones associated with the cardiac cycle and others of a greater magnitude related to breathing activity. These motions constitute a pumping force for the circulation of cerebrospinal fluid (CSF). Moreover, brain motion (BM) plays a fundamental role as a driving force for the interstitial and CSF flow of tracers. We hypothesize that BM is more than a mere consequence of cardiac and respiratory activities; that it would be part of a fundamental physiological mechanism by propelling the interstitial flow of messengers, a mechanism also known as 'non-synaptic transmission' or 'volume transmission' (VT). Intracranial hypertension (ICH), a frequent complication of severe head trauma, is related to brain stiffness. Under this circumstance, not only brain perfusion could be at risk, but BM could be engaged as well. Decompressive craniectomy, presently indicated to reduce ICH refractory to medical treatment, could play a role in helping BM and VT. Once brain swelling is overcome, the closure of the cranial bone defect would ensure the recovery of the spatial and temporal patterns of BM. We discuss evidence supportive of the necessary role of a minimal and sequential BM for an adequate VT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Splanchnic blood flow and hepatic glucose production in exercising humans

    DEFF Research Database (Denmark)

    Bergeron, R; Kjaer, M; Simonsen, L


    The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O(2) consumption (VO(2 max)) followed by 30 min at 70% VO(2 max) either with [angiotensin-converti......The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O(2) consumption (VO(2 max)) followed by 30 min at 70% VO(2 max) either with [angiotensin......-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an approximately 20-fold increase (P ... blockade; 0.74 +/- 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 +/- 0.06, ACE blockade; 0.68 +/- 0.10 mmol/min, control) increased during moderate exercise (1.97 +/- 0.29, ACE blockade; 1.91 +/- 0.41 mmol/min, control). Refuting a major role of the RAS for these responses...

  5. Bolus arrival time and cerebral blood flow responses to hypercarbia. (United States)

    Donahue, Manus J; Faraco, Carlos C; Strother, Megan K; Chappell, Michael A; Rane, Swati; Dethrage, Lindsey M; Hendrikse, Jeroen; Siero, Jeroen C W


    The purpose of this study was to evaluate how cerebral blood flow and bolus arrival time (BAT) measures derived from arterial spin labeling (ASL) MRI data change for different hypercarbic gas stimuli. Pseudocontinuous ASL (pCASL) was applied (3.0T; spatial resolution=4 × 4 × 7 mm(3); repetition time/echo time (TR/TE)=3,600/11 ms) sequentially in healthy volunteers (n=12; age=30±4 years) for separate experiments in which (i) normocarbic normoxia (i.e., room air), hypercarbic normoxia (i.e., 5% CO₂/21% O₂/74% N2), and hypercarbic hyperoxia (i.e., carbogen: 5% CO₂/95% O₂) gas was administered (12 L/minute). Cerebral blood flow and BAT changes were quantified using models that account for macrovascular signal and partial volume effects in all gray matter and regionally in cerebellar, temporal, occipital, frontal, and parietal lobes. Regional reductions in BAT of 4.6% to 7.7% and 3.3% to 6.6% were found in response to hypercarbic normoxia and hypercarbic hyperoxia, respectively. Cerebral blood flow increased by 8.2% to 27.8% and 3.5% to 19.8% for hypercarbic normoxia and hypercarbic hyperoxia, respectively. These findings indicate that changes in BAT values may bias functional ASL data and thus should be considered when choosing appropriate experimental parameters in calibrated functional magnetic resonance imaging or ASL cerebrovascular reactivity experiments that use hypercarbic gas stimuli.

  6. Sleep-disordered breathing and arterial blood flow steal represent linked therapeutic targets in cerebral ischaemia. (United States)

    Barlinn, Kristian; Alexandrov, Andrei V


    The pathogenic link between sleep-disordered breathing and early neurological deterioration in acute ischaemic stroke patients is now a subject of clinical investigations. Vasomotor reactivity and intracranial blood flow steal in response to changing vasodilatory stimuli like carbon dioxide play a pivotal role in clinical deterioration with reversed Robin Hood syndrome. A mechanical ventilatory correction in selected acute stroke patients might have a beneficial effect on sleep-disordered breathing and brain perfusion. This is a novel therapeutic target and the missing link in the pathogenesis of early neurological deterioration and stroke recurrence. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.

  7. Cerebral blood flow and oxygenation in infants after birth asphyxia. Clinically useful information?

    DEFF Research Database (Denmark)

    Greisen, Gorm


    of cellular energy charge during the hours following severe birth asphyxia was observed twenty years later by sequential cranial magnetic resonance spectroscopy. This led to the concept of delayed energy failure that is linked to mitochondrial dysfunction and apoptotic cell death. Abnormally increased...... perfusion and lack of normal cerebral blood flow regulation are also typically present, but whether the perfusion abnormalities at this secondary stage are detrimental, beneficial, or a mere epiphenomenon remains elusive. In contrast, incomplete reoxygenation of the brain during and following resuscitation...

  8. Effect of intranasally administered insulin on cerebral blood flow and perfusion

    DEFF Research Database (Denmark)

    Akintola, Abimbola A.; van Opstal, Anna M.; Westendorp, Rudi G.


    (40IU) on cerebral blood flow (CBF) and perfusion in older (60-69 years, n=11) and younger (20-26 years, n=8) adults. Changes in CBF through the major cerebropetal arteries were assessed via phase contrast MR-angiography, and regional cortical tissue perfusion via pseudo-continuous arterial spin.......28±6.75 mL/100g/min versus 63.31±6.84 mL/100g/min, P=0.003). Thus, intranasal insulin improved tissue perfusion of the occipital cortical brain region and the thalamus in older adults....

  9. Measurement of brain perfusion, blood volume, and blood-brain barrier permeability, using dynamic contrast-enhanced T(1)-weighted MRI at 3 tesla

    DEFF Research Database (Denmark)

    Larsson, Henrik B W; Courivaud, Frédéric; Rostrup, Egill


    Assessment of vascular properties is essential to diagnosis and follow-up and basic understanding of pathogenesis in brain tumors. In this study, a procedure is presented that allows concurrent estimation of cerebral perfusion, blood volume, and blood-brain permeability from dynamic T(1)-weighted...... imaging of a bolus of a paramagnetic contrast agent passing through the brain. The methods are applied in patients with brain tumors and in healthy subjects. Perfusion was estimated by model-free deconvolution using Tikhonov's method (gray matter/white matter/tumor: 72 +/- 16/30 +/- 8/56 +/- 45 mL/100 g...... on a pixel-by-pixel basis of cerebral perfusion, cerebral blood volume, and blood-brain barrier permeability....

  10. Pulsed photoacoustic Doppler flow measurements in blood-mimicking phantoms (United States)

    Brunker, J.; Beard, P.


    The feasibility of making spatially resolved measurements of blood flow using pulsed photoacoustic Doppler techniques has been explored. Doppler time shifts were quantified via cross-correlation of pairs of photoacoustic waveforms generated within a blood-simulating phantom using pairs of laser light pulses. The photoacoustic waves were detected using a focussed or planar PZT ultrasound transducer. For each flow measurement, a series of 100 waveform pairs was collected. Previous data processing methods involved rejection of poorly correlated waveform pairs; the modal velocity value and standard deviation were then extracted from the selected distribution of velocity measurements. However, the data selection criteria used in this approach is to some extent arbitrary. A new data analysis protocol, which involves averaging the 100 cross-correlation functions and thus uses all of the measured data, has been designed in order to prevent exclusion of outliers. This more rigorous approach has proved effective for quantifying the linear motion of micron-scale absorbers imprinted on an acetate sheet moving with velocities in the range 0.14 to 1.25 ms-1. Experimental parameters, such as the time separation between the laser pulses and the transducer frequency response, were evaluated in terms of their effect on the accuracy, resolution and range of measurable velocities. The technique was subsequently applied to fluid phantoms flowing at rates less than 5 mms-1 along an optically transparent tube. Preliminary results are described for three different suspensions of phenolic resin microspheres, and also for whole blood. Velocity information was obtained even under non-optimal conditions using a low frequency transducer and a low pulse repetition frequency. The distinguishing advantage of pulsed rather than continuous-wave excitation is that spatially resolved velocity measurements can be made. This offers the prospect of mapping flow within the microcirculation and thus

  11. Sevoflurane effects on retrobulbar arteries blood flow in children. (United States)

    Geeraerts, T; Devys, J-M; Berges, O; Dureau, P; Plaud, B


    Measure of blood flow velocity in retrobulbar vessels is performed to determine the severity of ophthalmic pathologies as glaucoma. In children, this measure is usually performed under general anaesthesia. Sevoflurane is known to not modify cerebral blow flow velocities. However, its effect on retrobulbar circulation is not known. This study was designed to evaluate the effect of sevoflurane on retrobulbar circulation flow velocity in children undergoing examination for ocular disorders under general anaesthesia. Thirteen mechanically ventilated children (Fi(O2))=1) were included. Blood flow velocities of central retinal artery, ophthalmic artery, and middle cerebral artery were measured by Doppler ultrasound during 1 and 2 age-adjusted minimal alveolar concentration (MAC) sevoflurane anaesthesia. Intra-ocular pressure and non-invasive haemodynamic parameters were also measured. End-tidal carbon dioxide tension was controlled during all the study period. Mean arterial pressure decreased from 1 to 2 age-adjusted MAC sevoflurane (58 [12] vs 54 [12] mm Hg, P=0.01). In the ophthalmic artery, end diastolic velocity (EDV) decreased significantly at 2 MAC (1 MAC: 4.4 [4] cm s(-1) vs 2 MAC: 1.4 [2.4] cm s(-1); P=0.04) and resistivity index (RI) increased significantly (1 MAC: 0.83 [0.11] vs 2 MAC: 0.93 [0.09]; P=0.007). Systolic velocity, EDV, and RI remained constant in the central retinal artery and in the middle cerebral artery. High alveolar concentration of sevoflurane decreased blood flow velocity in the ophthalmic artery, but not in the central retinal and the middle cerebral arteries in children ventilated in hyperoxic condition. This effect was related to a decrease in mean arterial pressure. This vessel-dependent effect may be explained by the different autoregulatory mechanisms of these arteries. In the present hyperoxic conditions, the vascular effect of sevoflurane may have been limited in the central retinal artery and not in the ophthalmic artery.

  12. Nitric oxide and prostaglandins influence local skeletal muscle blood flow during exercise in humans: coupling between local substrate uptake and blood flow

    DEFF Research Database (Denmark)

    Kalliokoski, Kari K; Langberg, Henning; Ryberg, Ann Kathrine


    Synergic action of nitric oxide (NO) and prostaglandins (PG) in the regulation of muscle blood flow during exercise has been demonstrated. In the present study, we investigated whether these vasodilators also regulate local blood flow, flow heterogeneity, and glucose uptake within the exercising...

  13. Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone. (United States)

    Prisby, Rhonda D


    Bone tissue is highly vascularized due to the various roles bone blood vessels play in bone and bone marrow function. For example, the vascular system is critical for bone development, maintenance and repair and provides O 2 , nutrients, waste elimination, systemic hormones and precursor cells for bone remodeling. Further, bone blood vessels serve as egress and ingress routes for blood and immune cells to and from the bone marrow. It is becoming increasingly clear that the vascular and skeletal systems are intimately linked in metabolic regulation and physiological and pathological processes. This review examines how agents such as mechanical loading, parathyroid hormone, estrogen, vitamin D and calcitonin, all considered anabolic for bone, have tremendous impacts on the bone vasculature. In fact, these agents influence bone blood vessels prior to influencing bone. Further, data reveal strong associations between vasodilator capacity of bone blood vessels and trabecular bone volume, and poor associations between estrogen status and uterine mass and trabecular bone volume. Additionally, this review highlights the importance of the bone microcirculation, particularly the vascular endothelium and NO-mediated signaling, in the regulation of bone blood flow, bone interstitial fluid flow and pressure and the paracrine signaling of bone cells. Finally, the vascular endothelium as a mediator of bone health and disease is considered. © 2017 Society for Endocrinology.

  14. The effect of blood cell count on coronary flow in patients with coronary slow flow phenomenon. (United States)

    Soylu, Korhan; Gulel, Okan; Yucel, Huriye; Yuksel, Serkan; Aksan, Gokhan; Soylu, Ayşegül İdil; Demircan, Sabri; Yılmaz, Ozcan; Sahin, Mahmut


    The coronary slow flow phenomenon (CSFP) is a coronary artery disease with a benign course, but its pathological mechanisms are not yet fully understood.The purpose of this controlled study was to investigate the cellular content of blood in patients diagnosed with CSFP and the relationship of this with coronary flow rates. Selective coronary angiographies of 3368 patients were analyzed to assess Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) values. Seventy eight of them had CSFP, and their demographic and laboratory findings were compared with 61 patients with normal coronary flow. Patients' demographic characteristics were similar in both groups. Mean corrected TFC (cTFC) values were significantly elevated in CSFP patients (p<0.001). Furthermore, hematocrit and hemoglobin values, and eosinophil and basophil counts of the CSFP patients were significantly elevated compared to the values obtained in the control group (p=0.005, p=0.047, p=0.001 and p=0.002, respectively). The increase observed in hematocrit and eosinophil levels showed significant correlations with increased TFC values (r=0.288 and r=0.217, respectively). Significant changes have been observed in the cellular composition of blood in patients diagnosed with CSFP as compared to the patients with normal coronary blood flow. The increases in hematocrit levels and in the eosinophil and basophil counts may have direct or indirect effects on the rate of coronary blood flow.

  15. Repeatability of Doppler ultrasonographic measurement of equine digital blood flow. (United States)

    Menzies-Gow, Nicola J; Marr, Celia M


    The repeatability and sensitivity of Doppler ultrasonographic measurement of lateral digital arterial and venous blood flow has not been previously determined. Doppler ultrasonography was used to measure blood flow within the forelimb lateral digital vessels in one normal adult Thoroughbred horse on six occasions and in six normal adult Thoroughbred horses on three occasions, each occasion being at least 1 h apart, to determine the within- and between-horse variation. The values obtained from the right and left lateral digital vessels did not differ significantly. The within-horse coefficients of variation (CV) for arterial and venous measurements were all acceptable ( or = 0.71) for all parameters except venous diameter; the between-horse ICC demonstrated good to excellent repeatability (> or = 0.67) for all parameters except TaVb. Doppler ultrasonography can detect differences of 0.005 and 0.01 ml/ min in digital arterial and venous flow, respectively, using measurements from six horses on three occasions (80% power; P < 0.05). Thus, the technique is sufficiently repeatable and sensitive to be able to detect changes in flow during different physiological or pathological states or following pharmacologic intervention.

  16. Correlation of carotid blood flow and corrected carotid flow time with invasive cardiac output measurements. (United States)

    Ma, Irene W Y; Caplin, Joshua D; Azad, Aftab; Wilson, Christina; Fifer, Michael A; Bagchi, Aranya; Liteplo, Andrew S; Noble, Vicki E


    Non-invasive measures that can accurately estimate cardiac output may help identify volume-responsive patients. This study seeks to compare two non-invasive measures (corrected carotid flow time and carotid blood flow) and their correlations with invasive reference measurements of cardiac output. Consenting adult patients (n = 51) at Massachusetts General Hospital cardiac catheterization laboratory undergoing right heart catheterization between February and April 2016 were included. Carotid ultrasound images were obtained concurrently with cardiac output measurements, obtained by the thermodilution method in the absence of severe tricuspid regurgitation and by the Fick oxygen method otherwise. Corrected carotid flow time was calculated as systole time/√cycle time. Carotid blood flow was calculated as π × (carotid diameter)2/4 × velocity time integral × heart rate. Measurements were obtained using a single carotid waveform and an average of three carotid waveforms for both measures. Single waveform measurements of corrected flow time did not correlate with cardiac output (ρ = 0.25, 95% CI -0.03 to 0.49, p = 0.08), but an average of three waveforms correlated significantly, although weakly (ρ = 0.29, 95% CI 0.02-0.53, p = 0.046). Carotid blood flow measurements correlated moderately with cardiac output regardless of if single waveform or an average of three waveforms were used: ρ = 0.44, 95% CI 0.18-0.63, p = 0.004, and ρ = 0.41, 95% CI 0.16-0.62, p = 0.004, respectively. Carotid blood flow may be a better marker of cardiac output and less subject to measurements issues than corrected carotid flow time.

  17. Renal blood flow and metabolism after cold ischaemia

    DEFF Research Database (Denmark)

    Henriksen, J H; Petersen, H K


    .01) immediately after re-established perfusion and 36% (P less than 0.02) 30 min later. In one additional patient, who had a short warm ischaemia (8 min), the flow pattern was the same. As arterial pressure remained constant, the reduced RBF signifies an increased renal vascular resistance. Renal O2-uptake......Peroperative measurements of renal blood flow (RBF), renal O2-uptake, and renal venous lactate/pyruvate (L/P) ratio were performed before and after a period of 30-71 min of hypothermic (10-15 degrees C) renal ischaemia in nine patients, undergoing surgery for renal calculi. Before ischaemia, RBF...... and renal venous L/P ratio were almost constant, indicating no significant anaerobic processes being involved in the flow response. None of the patients showed any signs of reactive hyperaemia. It is concluded that hypothermic renal ischaemia may be followed by an increased renal vascular resistance even...

  18. Probing Brain Oxygenation with Near Infrared spectroscopy, the Role of Carbon Dioxide and Blood Pressure

    CERN Document Server

    Gersten, Alexander


    The fundamentals of near infrared spectroscopy (NIRS) are reviewed. Among the major factors controlling the cerebral blood flow (CBF), the effect of PaCO2 is peculiar in that it violates autoregulatory CBF mechanisms and allows to explore the full range of the CBF. A simple physical model, with a four parameter formula, relating the CBF to PaCO2 is presented. It can be used to transform the fits of one animal to the fits of another one. It enable the use of rats data as monkeys data simply by rescaling the PaCO2 values and the CBF data. Controlled breathing can change the PaCO2. Experiments on human subjects relating the PaCO2 to rSO2, measured with brain oximeters, are presented. A simple model relating the mean blood pressure to CBF is worked out.

  19. Possible involvement of cationic-drug sensitive transport systems in the blood-to-brain influx and brain-to-blood efflux of amantadine across the blood-brain barrier. (United States)

    Suzuki, Toyofumi; Fukami, Toshiro; Tomono, Kazuo


    The purpose of this study was to characterize the brain-to-blood efflux transport of amantadine across the blood-brain barrier (BBB). The apparent in vivo efflux rate constant for [(3) H]amantadine from the rat brain (keff ) was found to be 1.53 × 10(-2) min(-1) after intracerebral microinjection using the brain efflux index method. The efflux of [(3) H]amantadine was inhibited by 1-methyl-4-phenylpyridinium (MPP(+) ), a cationic neurotoxin, suggesting that amantadine transport from the brain to the blood across the BBB potentially involves the rat plasma membrane monoamine transporter (rPMAT). On the other hand, other selected substrates for organic cation transporters (OCTs) and organic anion transporters (OATs), as well as inhibitors of P-glycoprotein (P-gp), did not affect the efflux transport of [(3) H]amantadine. In addition, in vitro studies using an immortalized rat brain endothelial cell line (GPNT) showed that the uptake and retention of [(3) H]amantadine by the cells was not changed by the addition of cyclosporin, which is an inhibitor of P-gp. However, cyclosporin affected the uptake and retention of rhodamine123. Finally, the initial brain uptake of [(3) H]amantadine was determined using an in situ mouse brain perfusion technique. Notably, the brain uptake clearance for [(3) H]amantadine was significantly decreased with the co-perfusion of quinidine or verapamil, which are cationic P-gp inhibitors, while MPP(+) did not have a significant effect. It is thus concluded that while P-gp is not involved, it is possible that rPMAT and the cationic drug-sensitive transport system participate in the brain-to-blood efflux and the blood-to-brain influx of amantadine across the BBB, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Cerebral Blood Flow during Rest Associates with General Intelligence and Creativity (United States)

    Takeuchi, Hikaru; Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Nagase, Tomomi; Nouchi, Rui; Kawashima, Ryuta


    Recently, much scientific attention has been focused on resting brain activity and its investigation through such methods as the analysis of functional connectivity during rest (the temporal correlation of brain activities in different regions). However, investigation of the magnitude of brain activity during rest has focused on the relative decrease of brain activity during a task, rather than on the absolute resting brain activity. It is thus necessary to investigate the association between cognitive factors and measures of absolute resting brain activity, such as cerebral blood flow (CBF), during rest (rest-CBF). In this study, we examined this association using multiple regression analyses. Rest-CBF was the dependent variable and the independent variables included two essential components of cognitive functions, psychometric general intelligence and creativity. CBF was measured using arterial spin labeling and there were three analyses for rest-CBF; namely mean gray matter rest-CBF, mean white matter rest-CBF, and regional rest-CBF. The results showed that mean gray and white matter rest-CBF were significantly and positively correlated with individual psychometric intelligence. Furthermore, mean white matter rest-CBF was significantly and positively correlated with creativity. After correcting the effect of mean gray matter rest-CBF the significant and positive correlation between regional rest-CBF in the perisylvian anatomical cluster that includes the left superior temporal gyrus and insula and individual psychometric intelligence was found. Also, regional rest-CBF in the precuneus was significantly and negatively correlated with individual creativity. Significance of these results of regional rest-CBF did not change when the effect of regional gray matter density was corrected. The findings showed mean and regional rest-CBF in healthy young subjects to be correlated with cognitive functions. The findings also suggest that, even in young cognitively intact

  1. Occlusion cuff for routine measurement of digital blood pressure and blood flow

    DEFF Research Database (Denmark)

    Lassen, N A; Krähenbühl, B; Hirai, M


    A miniaturized blood pressure cuff made of plastic material and applicable to fingers and toes is described. The cuff was compared to rubber cuffs and to bladder-free cuffs. It was found to be more reliable than the former type and much easier to use than the latter type. It is recommended for us...... in conjunction with a mercury-in-Silastic strain gauge for routine measurement of digital blood pressure and blood flow in patients with arterial disease.......A miniaturized blood pressure cuff made of plastic material and applicable to fingers and toes is described. The cuff was compared to rubber cuffs and to bladder-free cuffs. It was found to be more reliable than the former type and much easier to use than the latter type. It is recommended for use...

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

    DEFF Research Database (Denmark)

    Henriksen, O; Ståhlberg, F; Thomsen, C


    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...... 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......., 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...

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

    DEFF Research Database (Denmark)

    Henriksen, O; Ståhlberg, F; Thomsen, C


    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...

  4. Diagnosis of High Blood Pressure

    Medline Plus

    Full Text Available ... blindness. Heart Attack : When the flow of oxygen-rich blood to a section of heart muscle suddenly ... climbing stairs. Stroke : When the flow of oxygen-rich blood to a portion of the brain is ...

  5. Outcome of splanchnic blood flow determination in patients with suspected chronic intestinal ischaemia. A retrospective survey

    DEFF Research Database (Denmark)

    Møller, Søren; Madsen, Jan Lysgård


    flow: A, normal response (splanchnic blood flow > or = 200 ml/min); B, possible abnormal response (splanchnic blood flow 51-199 ml/min); and C, definitive abnormal response (splanchnic blood flow ... a normal meal-induced response, 23 patients had a possible abnormal response and 10 patients had a definitive abnormal response, which gave evidence of chronic intestinal ischaemia. In the total patient population, the increase in splanchnic blood flow was significantly correlated to an increase in hepatic...... oxygen uptake (r = 0.38, P abnormal meal-induced splanchnic blood flow and 30% of these patients...

  6. The effect of glucagon-like peptide-2 on arterial blood flow and cardiac parameters

    DEFF Research Database (Denmark)

    Bremholm, Lasse; Hornum, Mads; Andersen, Ulrik B


    Glucagon-like peptide-2 (GLP-2) is known to increase mesenteric blood flow. The aim of the study was to evaluate the effect of GLP-2 on blood flow in different vascular sites, and dynamic changes in cardiac parameters.......Glucagon-like peptide-2 (GLP-2) is known to increase mesenteric blood flow. The aim of the study was to evaluate the effect of GLP-2 on blood flow in different vascular sites, and dynamic changes in cardiac parameters....

  7. Resuscitation of Hypotensive Traumatic Brain Injured Animals With Spray-Dried Plasma Does Not Adversely Alter Physiology and Improves Blood-Brain Barrier Function. (United States)

    McDaniel, Steven; Golla, Stephanie; Moore, Anthony N; DaCorta, Joe; Bode, Arthur; Pati, Shibani; Dash, Pramod K; Zhao, Jing


    According to the Defense and Veterans Brain Injury Center and the Armed Forces Health Surveillance Center, the number of soldiers who have sustained a traumatic brain injury (TBI) has risen dramatically over the past decade. Studies have shown that brain damage can be exacerbated if blood loss occurs (often occurring in polytrauma). As blood supply is critical for brain function and survival, TBI patients must be properly resuscitated to maintain blood volume, blood pressure, and cerebral perfusion. Recent studies have suggested that blood loss can damage the vascular endothelium and enhance blood-brain barrier (BBB) permeability. Brain endothelial cells and the tight junctions between them are key structural components of the BBB. As the BBB is critical for isolating the brain from potential pathogens and for regulating the influx of molecules into the brain, evaluation of resuscitation fluids for their efficacy to improve BBB function has clinical relevance. Although whole blood and fresh frozen plasma (FFP) contain the essential coagulation factors, ions, and other factors, the transport and storage of these products in remote, austere environments can be challenging. The use of spray-dried plasma (SDP) has several advantages including storage at ambient temperature, can be readily reconstituted before use, and infectious materials can be inactivated during the drying process. In this study, we compared FFP and SDP for their effects on blood pressure, cerebral blood flow, BBB integrity, and markers of endothelial cells and tight junction proteins, in TBI animals with blood loss. All procedures were reviewed and approved by the UTHealth animal welfare committee. Sprague Dawley rats received controlled cortical impact brain injury followed by removal of 25% blood volume. Animals were resuscitated 40 minutes later with either FFP or concentrated SDP (Resusix) Heart rate and blood pressure were monitored continuously using catheters implanted into the femoral artery


    Directory of Open Access Journals (Sweden)

    H. Mazaher


    Full Text Available Vertebrobasilar insufficiency is the cause of cerebrovascular accidents in 20% of cases. There are few reports regarding spectral Doppler indices (SDIs of vertebral arteries (VAs normal blood flow. The objective of this study was to provide basic reference data about SDIs of VAs normal blood flow separately and in comparison with internal carotid arteries (ICAs and common carotid arteries (CCAs normal blood flows SDIs. This cross-sectional study performed on 70 normal patients. Color Doppler sonography (CDS and spectral Doppler sonography (SDS of right and left VAs (RVA and LVA, right and left CCAs (RCCA and LCCA, right and left ICAs (RICA and LICA, were performed. The mean PSV, EDV, and RI values of RVA blood flow were as 41.60 ± 9.6 cm/s, 14.60 ± 3.7 cm/s and 0.65 ± 0.06, and the mean PSV, EDV and RI values of LVA blood flow were as 42.20 ± 10.2 cm/s, 15.20 ± 4.2 cm/s, and 0.64 ± 0.05, respectively. There was not statistically significant difference between the mean PSV, EDV and RI values of RVA and LVA blood flows. The mean PSV and EDV values of VAs blood flows were significantly lower than the values of CCAs and ICCAs blood flows, respectively. The mean RI value of VAs blood flows was significantly lower than the mean RI Value of CCAs blood flows, but there was not statistically significant difference between the mean RI value of VAs blood flows and the mean RI value of ICAs blood flows.

  9. Revisiting blood-brain barrier: A chromatographic approach. (United States)

    Subirats, Xavier; Muñoz-Pascual, Laura; Abraham, Michael H; Rosés, Martí


    Drugs designed to reach a pharmacological CNS target must be effectively transported across the blood-brain barrier (BBB), a thin monolayer of endothelial cells tightly attached together between the blood and the brain parenchyma. Because of the lipidic nature of the BBB, several physicochemical partition models have been studied as surrogates for the passive permeation of potential drug candidates across the BBB (octanol-water, alkane-water, PAMPA...). In the last years, biopartition chromatography is gaining importance as a noncellular system for the estimation of biological properties in early stages of drug development. Microemulsions (ME) are suitable mobile phases, because of their ease of formulation, stability and adjustability to a large number of compositions mimicking biological structures. In the present work, several microemulsion liquid chromatographic (MELC) systems have been characterized by means of the Abraham's solvation parameter model, in order to assess their suitability as BBB distribution or permeability surrogates. In terms of similarity between BBB and MELC systems (dispersion forces arising from solute non-bonded electrons, dipolarity/polarizability, hydrogen-bond acidity and basicity, and molecular volume), the passive permeability surface area product (log PS) for neutral (including zwitterions), fully and partially ionized drugs was found to be well correlated with the ME made of 3.3% SDS (w/v; surfactant) 0.8% heptane (w/v; oil phase) and 6.6% 1-butanol (w/v; co-surfactant) in 50mM aqueous phosphate buffer, pH 7.4. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Resistance exercise with different volumes: blood pressure response and forearm blood flow in the hypertensive elderly

    Directory of Open Access Journals (Sweden)

    Brito AF


    Full Text Available Aline de Freitas Brito,1 Caio Victor Coutinho de Oliveira,2 Maria do Socorro Brasileiro-Santos,1 Amilton da Cruz Santos1 1Physical Education Department, 2Research Laboratory for Physical Training Applied to Performance and Health, Federal University of Paraíba, João Pessoa, Brazil Background: The purpose of this study was to evaluate the effect of two sessions of resistance exercise with different volumes on post-exercise hypotension, forearm blood flow, and forearm vascular resistance in hypertensive elderly subjects.Methods: The study was conducted with ten hypertensive elderly (65±3 years, 28.7±3 kg/m2 subjected to three experimental sessions, ie, a control session, exercise with a set (S1, and exercise with three sets (S3. For each session, the subjects were evaluated before and after intervention. In the pre-intervention period, blood pressure, forearm blood flow, and forearm vascular resistance were measured after 10 minutes of rest in the supine position. Thereafter, the subjects were taken to the gym to perform their exercise sessions or remained at rest during the same time period. Both S1 and S3 comprised a set of ten repetitions of ten exercises, with an interval of 90 seconds between exercises. Subsequently, the measurements were again performed at 10, 30, 50, 70, and 90 minutes of recovery (post-intervention in the supine position.Results: Post-exercise hypotension was greater in S3 than in S1 (systolic blood pressure, −26.5±4.2 mmHg versus −17.9±4.7 mmHg; diastolic blood pressure, −13.8±4.9 mmHg versus −7.7±5 mmHg, P<0.05. Similarly, forearm blood flow and forearm vascular resistance changed significantly in both sessions with an increase and decrease, respectively, that was more evident in S3 than in S1 (P<0.05.Conclusion: Resistance exercises with higher volume were more effective in causing post-exercise hypotension, being accompanied by an increase in forearm blood flow and a reduction of forearm vascular

  11. Impact of extracorporeal blood flow rate on blood pressure, pulse rate and cardiac output during haemodialysis

    DEFF Research Database (Denmark)

    Schytz, Philip Andreas; Mace, Maria Lerche; Soja, Anne Merete Boas


    BACKGROUND: If blood pressure (BP) falls during haemodialysis (HD) [intradialytic hypotension (IDH)] a common clinical practice is to reduce the extracorporeal blood flow rate (EBFR). Consequently the efficacy of the HD (Kt/V) is reduced. However, only very limited knowledge on the effect......L/min diastolic BP, mean arterial pressure, PR and CO remained unchanged. CONCLUSION: Our study does not show any consistent trend in BP changes by a reduction in EBFR. Reduction in EBFR if BP falls during IDH is thus not supported. However, none of the patients experienced IDH. Further studies are required...... to evaluate the impact of changes in EBFR on BP during IDH....

  12. Age and gender related differences in aortic blood flow

    DEFF Research Database (Denmark)

    Traberg, Marie Sand; Pedersen, Mads Møller; Hemmsen, Martin Christian


    is to investigate the blood flow pat- terns within a group of healthy volunteers (4 females, 7 males) aged 23 to 76 years to identify changes and differences related to age and gender. The healthy volunteers were categorized by gender (male/female) and age (below/above 35 years). Subject-specific flow and geometry...... data were acquired using the research interface on a medical ultrasound scanner and segmentation of 3D magnetic resonance angiography respectively. The largest average diameter was among the elderly males (19.7 (± 1.33) mm) and smallest among the young females (12.4 (± 0.605) mm). The highest peak...... systolic velocity was in the young female group (1.02 (± 0.336) m/s) and lowest in the elderly male group (0.836 (± 0.127) m/s). A geometrical change with age was observed as the AA becomes more bended with age. This also affects the blood flow velocity patterns, which are markedly different from young...

  13. Three-dimensional diastolic blood flow in the left ventricle. (United States)

    Khalafvand, Seyed Saeid; Ng, Eddie Yin-Kwee; Zhong, Liang; Hung, Tin-Kan


    Three-dimensional blood flow in a human left ventricle is studied via a computational analysis with magnetic resonance imaging of the cardiac motion. Formation, growth and decay of vortices during the myocardial dilation are analyzed with flow patterns on various diametric planes. They are dominated by momentum transfer during flow acceleration and deceleration through the mitral orifice. The posterior and anterior vortices form an asymmetric annular vortex at the mitral orifice, providing a smooth transition for the rapid inflow to the ventricle. The development of core vortex accommodates momentum for deceleration and for acceleration at end diastolic atrial contraction. The rate of energy dissipation and that of work done by viscous stresses are small; they are approximately balanced with each other. The kinetic energy flux and the rate of work done by pressure delivered to blood from ventricular dilation is well balanced by the total energy influx at the mitral orifice and the rate change of kinetic energy in the ventricle. Published by Elsevier Ltd.

  14. Retinal blood flow measurements and neuroretinal rim damage in glaucoma (United States)

    Logan, J F J; Rankin, S J A; Jackson, A J


    Aim: To assess retinal blood flow characteristics in subjects with normal tension glaucoma (NTG), primary open angle glaucoma (POAG), and a group of controls using the Heidelberg retina flowmeter (HRF). The vascular parameters were correlated against structural damage of the optic nerve head, assessed using the Heidelberg retina tomograph (HRT). Methods: HRF images were obtained in 76 subjects with NTG, 58 with POAG, and 38 controls. Optic nerve head images, acquired using the HRT, were analysed with Moorfields Regression Analysis software. The HRF variables, measured adjacent to a rim segment identified as “abnormal,” were compared with the vascular parameters of the “normal” rim segments. The HRF parameters of the segments identified as normal in glaucoma subjects were compared with matched control segments. Results: The glaucoma subjects had significantly lower retinal haemodynamics than the control subjects. There were no significant differences in the HRF parameters between the NTG and POAG subjects. The discs that had been identified as having abnormal segments had lower HRF values than those with a corresponding normal segment. The glaucoma subjects with normal rim segments had statistically significant lower velocity, flow, and volume measurements than the controls for each location sampled. Conclusion: This study shows a relation between structural damage of the optic nerve head and the level of retinal blood flow. The changes in the circulation could indicate that it may be an early marker of the pathological process. PMID:15258023

  15. Intracoronary ghrelin infusion decreases coronary blood flow in anesthetized pigs. (United States)

    Grossini, Elena; Molinari, Claudio; Mary, David A S G; Ghigo, Ezio; Bona, Gianni; Vacca, Giovanni


    The peptide ghrelin has been linked to the atherosclerotic process and coronary artery disease. We planned to study, for the first time, the primary effects of ghrelin on the intact coronary circulation and determine the mechanisms involved. In 24 sodium pentobarbitone-anesthetized pigs, changes in anterior descending coronary blood flow caused by intracoronary infusion of ghrelin at constant heart rate and arterial pressure were assessed using electromagnetic flowmeters. In 20 pigs, intracoronary infusion of ghrelin decreased coronary blood flow without affecting left ventricular maximum rate of change of left ventricular systolic pressure (dP/dt(max)), filling pressures of the heart or plasma levels of GH. In four pigs, this decrease was graded by step increments of infused dose of the hormone. The mechanisms of the above response were studied in the 20 pigs by repeating the experiment after coronary flow had returned to the control values observed before infusion. The ghrelin-induced coronary vasoconstriction was not affected by iv atropine (five pigs) or phentolamine (five pigs). This response was abolished by iv butoxamine (five pigs) and intracoronary N(omega)-nitro-l-arginine methyl ester (five pigs), even after reversing the increase in arterial pressure and coronary vascular resistance caused by the two blocking agents with iv infusion of papaverine. The present study showed that intracoronary infusion of ghrelin primarily caused coronary vasoconstriction. The mechanisms of this response were shown to involve the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect related to the release of nitric oxide.

  16. Role of the brain melanocortins in blood pressure regulation. (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Fang, Taolin; Aberdein, Nicola; Perez de Lara, Cecilia E; Hall, John E


    Melanocortins play an important role in regulating blood pressure (BP) and sympathetic nervous system (SNS) activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals. In experimental models of hypertension with high SNS activity, blockade of the melanocortin-4 receptor (MC4R) reduces BP despite causing marked hyperphagia and obesity. Activation of the central nervous system (CNS) pro-opiomelanocortin (POMC)-MC4R pathway appears to be an important link between obesity, SNS activation and hypertension. Despite having severe obesity, subjects with MC4R deficiency exhibit reductions in BP, heart rate, and urinary catecholamine excretion, as well as attenuated SNS responses to cold stimuli compared to obese subjects with normal MC4R function. In this review we discuss the importance of the brain POMC-MC4R system in regulating SNS activity and BP in obesity and other forms of hypertension. We also highlight potential mechanisms and brain circuitry by which the melanocortin system regulates cardiovascular function. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Aggressive Antioxidant Reductive Stress Impairs Brain Endothelial Cell Angiogenesis and Blood Brain Barrier Function. (United States)

    Mentor, Shireen; Fisher, David


    Oxidative stress in the brain microvasculature is a common characteristic in models of cerebrovascular disease. Considering the effects of reactive oxygen species activity in vascular-derived insults, it is naturally prudent to hypothesize those interventions inhibiting reactive oxygen species activity, such as antioxidant supplementation, may be beneficial for cerebrovascular disease. Hyper doses of antioxidant supplements, and foods with high antioxidant concentrations, are commonly used as an ongoing remedial and 'over-the-counter' treatments for most seasonal ailments. For the first time, this study reports the adverse effects of excess antioxidants on angiogenic properties of the blood-brain barrier (BBB) which have clinical implications. A medicinal tea, known as Rooibos, commonly used in South Africa and marketed globally, for its prominent antioxidant profile, demonstrated its effects on brain endothelial cellular proliferation, toxicology, mitochondrial activity and permeability. Mouse brain endothelial cells were seeded at cell densities ranging from 103-106 cells/ml and were incubated at pre-determined time intervals of 24 to120 hours. Daily exposure of a selected concentration range of fermented Rooibos tea caused dose-related decreases in cellular proliferation, and unequivocally decreased permeability across our in vitro BBB model. Despite the negative effects on cellular proliferation, no toxicity was observed for all selected fermented Rooibos concentrations. Our data conclusively shows that the use of excess antioxidants perturbs BBB functionality and angiogenic properties, adversely implicating the homeostatic regulation of the brain microenvironment, while suppression in cellular proliferation impacts both the maintenance and repair function of brain capillaries. Our study indicates that excess antioxidants will lead to an impaired response to mechanical-induced injury and pathogenic infection of the BBB, compromising patient recovery. Copyright

  18. Association between blood pressure levels over time and brain atrophy in the elderly

    NARCIS (Netherlands)

    den Heijer, T; Skoog, [No Value; Oudkerk, M; de Leeuw, FE; de Groot, JC; Hofman, A; Breteler, MMB


    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  19. Association between blood pressure levels over time and brain atrophy in the elderly.

    NARCIS (Netherlands)

    Heijer, T.; Skoog, I.; Oudkerk, M.; Leeuw, H.F. de; Groot, J.C. de; Hofman, A.W.I.M.; Breteler, M.H.M.


    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  20. Multimodal measurements of blood plasma and red blood cell volumes during functional brain activation. (United States)

    Herman, Peter; Sanganahalli, Basavaraju G; Hyder, Fahmeed


    As an alternative to functional magnetic resonance imaging (fMRI) with blood oxygenation level dependent (BOLD) contrast, cerebral blood volume (CBV)-weighted fMRI with intravascular contrast agents in animal models have become popular. In this study, dynamic measurements of CBV were performed by magnetic resonance imaging (MRI) and laser-Doppler flowmetry (LDF) in alpha-chloralose anesthetized rats during forepaw stimulation. All recordings were localized to the contralateral primary somatosensory cortex as revealed by BOLD at 11.7 T. Ultra-small superparamagnetic iron oxide (15 mg/kg)--a plasma-borne MRI contrast agent with a half-life of several hours in blood circulation--was used to quantify changes in magnetic field inhomogeneity in blood plasma. The LDF backscattered laser light (805 nm), which reflects the amount of red blood cells, was used to measure alterations in the non-plasma compartment. Dynamic and layer-specific comparisons of the two CBV signals during functional hyperemia revealed excellent correlations (>0.86). These results suggest that CBV measurements from either compartment may be used to reflect dynamic changes in total CBV. Furthermore, by assuming steady-state mass balance and negligible counter flow, these results indicate that volume hematocrit is not appreciably affected during functional activation.

  1. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A


    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

  2. Trigeminal cardiac reflex and cerebral blood flow regulation

    Directory of Open Access Journals (Sweden)

    Dominga Lapi


    Full Text Available The stimulation of some facial regions is known to trigger the trigemino-cardiac reflex: the main stimulus is represented by the contact of the face with water. This phenomenon called diving reflex induces a set of reactions in the cardiovascular and respiratory systems occurring in all mammals, especially marine (whales, seals. During the immersion of the face in the water, the main responses are aimed at reducing the oxygen consumption of the organism. Accordingly reduction in heart rate, peripheral vasoconstriction, blood pooling in certain organs, especially the heart and brain, and an increase in blood pressure have been reported. Moreover, the speed and intensity of the reflex is inversely proportional to the temperature of the water: more cold the water, more reactions as described are strong. In the case of deep diving an additional effect, such as blood deviation, has been reported: the blood is requested within the lungs, to compensate for the increase in the external pressure, preventing them from collapsing.The trigeminal-cardiac reflex is not just confined to the diving reflex; recently it has been shown that a brief proprioceptive stimulation (10 min by jaw extension in rats produces interesting effects both at systemic and cerebral level, reducing the arterial blood pressure and vasodilating the pial arterioles. The arteriolar dilation is associated with rhythmic diameter changes characterized by an increase in the endothelial activity. Fascinating the stimulation of trigeminal nerve is able to activated the nitric oxide release by vascular endothelial. Therefore the aim of this review was to highlight the effects due to trigeminal cardiac reflex induced by a simple mandibular extension, because produced opposite effects compared to those elicited by the diving reflex as it induces hypotension and modulation of cerebral arteriolar tone.

  3. The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease. (United States)

    Deane, R; Sagare, A; Zlokovic, B V


    Low-density lipoprotein receptor related protein-1 (LRP) is a member of the low-density lipoprotein (LDL) receptor family which has been linked to Alzheimer's disease (AD) by biochemical and genetic evidence. Levels of neurotoxic amyloid beta-peptide (Abeta) in the brain are elevated in AD contributing to the disease process and neuropathology. Faulty Abeta clearance from the brain appears to mediate focal Abeta accumulations in AD. Central and peripheral production of Abeta from Abeta-precursor protein (APP), transport of peripheral Abeta into the brain across the blood-brain barrier (BBB) via receptor for advanced glycation end products (RAGE), enzymatic Abeta degradation, Abeta oligomerization and aggregation, neuroinflammatory changes and microglia activation, and Abeta elimination from brain across the BBB by cell surface LRP; all may control brain Abeta levels. Recently, we have shown that a soluble form of LRP (sLRP) binds 70 to 90 % of plasma Abeta, preventing its access to the brain. In AD individuals, the levels of LRP at the BBB are reduced, as are levels of Abeta binding to sLRP in plasma. This, in turn, may increase Abeta brain levels through a decreased efflux of brain Abeta at the BBB and/or reduced sequestration of plasma Abeta associated with re-entry of free Abeta into the brain via RAGE. Thus, therapies which increase LRP expression at the BBB and/or enhance the peripheral Abeta "sink" activity of sLRP, hold potential to control brain Abeta accumulations, neuroinflammation and cerebral blood flow reductions in AD.

  4. Sex, the brain and hypertension: brain oestrogen receptors and high blood pressure risk factors. (United States)

    Hay, Meredith


    Hypertension is a major contributor to worldwide morbidity and mortality rates related to cardiovascular disease. There are important sex differences in the onset and rate of hypertension in humans. Compared with age-matched men, premenopausal women are less likely to develop hypertension. However, after age 60, the incidence of hypertension increases in women and even surpasses that seen in older men. It is thought that changes in levels of circulating ovarian hormones as women age may be involved in the increase in hypertension in older women. One of the key mechanisms involved in the development of hypertension in both men and women is an increase in sympathetic nerve activity (SNA). Brain regions important for the regulation of SNA, such as the subfornical organ, the paraventricular nucleus and the rostral ventral lateral medulla, also express specific subtypes of oestrogen receptors. Each of these brain regions has also been implicated in mechanisms underlying risk factors for hypertension such as obesity, stress and inflammation. The present review brings together evidence that links actions of oestrogen at these receptors to modulate some of the common brain mechanisms involved in the ability of hypertensive risk factors to increase SNA and blood pressure. Understanding the mechanisms by which oestrogen acts at key sites in the brain for the regulation of SNA is important for the development of novel, sex-specific therapies for treating hypertension. © 2016 Authors; published by Portland Press Limited.

  5. Transcutaneous electrical nerve stimulation regulates organ blood flow and apoptosis during controlled hypotension in dogs.

    Directory of Open Access Journals (Sweden)

    Lele Zhang

    Full Text Available Transcutaneous electrical nerve stimulation (TENS is commonly used in clinical practice for alleviating pains and physiological disorders. It has been reported that TENS could counteract the ischemic injury happened in some vital organs. To determine the protective effect of TENS on internal organs during CH in dogs, target hypotension was maintained for 60 min at 50% of the baseline mean arterial pressure (MAP. The perfusion to the brain, liver, stomach, and kidney was recorded and apoptosis within these organs was observed. Results showed that when arriving at the target MAP, and during the maintaining stage for 10 min, perfusion to the stomach and liver in the CH+TENS group was much higher than in the CH group (P<0.05. Perfusion to the cerebral cortex greatly declined in both the controlled pressure groups when compared with the general anesthesia (GA group (P<0.05. After withdrawing CH, the hepatic blood flow in both the CH and CH+TENS groups, and the gastric and cerebral cortical blood flow in the CH+TENS group, were rapidly increased. By the end of MAP restoration, gastric blood flow in the CH group was still low. At 72 h after applying CH, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL-positive cells in stomach and kidney tissue from the CH group were significantly increased compared with those in the GA group (P<0.05. There was no significant difference in TUNEL-positive cells in the liver and hippocampus among the three groups. Our results demonstrated that CH with a 50% MAP level could cause lower perfusion to the liver, stomach, cerebral cortex, and kidney, with apoptosis subsequently occurring in the stomach and kidney. TENS combined GA is able to improve the blood flow to the liver, stomach, and reduce the apoptosis in the stomach and kidney.

  6. Relationship between regional cerebral blood flow and neuropsychiatric symptoms in dementia with Lewy bodies. (United States)

    Yoshida, Taku; Mori, Takaaki; Yamazaki, Kiyohiro; Sonobe, Naomi; Shimizu, Hideaki; Matsumoto, Teruhisa; Kikuchi, Keiichi; Miyagawa, Masao; Mochizuki, Teruhito; Ueno, Shu-ichi


    This aim of this study was to examine the mechanisms underlying the neuropsychiatric symptoms in dementia with Lewy bodies by investigating regional cerebral blood flow. Participants were 27 patients who fulfilled the diagnostic criteria for probable dementia with Lewy bodies. All subjects underwent single-photon emission computed tomography scans using technetium-99 m hexamethylpropyleneamine oxime. Neuropsychiatric symptoms were evaluated by neuropsychiatric inventory. Multiple regression analyses using neuropsychiatric inventory and voxel-based analyses of covariance of the regional cerebral blood flow images between subjects with or without each neuropsychiatric symptom were performed. Additionally, similar voxel-based analyses of covariance between subjects with each neuropsychiatric symptom and normal subjects were performed. There were no significant correlations in any psychiatric symptoms in multiple regression analyses. All subjects had hallucination but none had euphoria. We analyzed eight neuropsychiatric symptom scores with the exception of hallucination and euphoria using voxel-based analyses of covariance. Significant differences of regional cerebral blood flow were shown in groups with agitation, disinhibition, and irritability. Subjects with agitation showed hypoperfusion in the parietal lobule, the precuneus, and the angular gyrus, and hyperperfusion in the fusiform gyrus, the lingual gyrus, and the thalamus. Subjects with disinhibition showed hypoperfusion in the left frontal gyrus. Subjects with irritability showed hyperperfusion in the right frontal gyrus. There were no significant differences in regional cerebral blood flow between subjects with any neuropsychiatric symptoms and normal subjects. This study reveals that dysfunction of specific brain regions is associated with various neuropsychiatric symptoms in dementia with Lewy bodies. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Cerebral blood flow and intracranial pulsatility studied with MRI: measurement, physiological and pathophysiological aspects

    Energy Technology Data Exchange (ETDEWEB)

    Waahlin, Anders


    During each cardiac cycle pulsatile arterial blood inflates the vascular bed of the brain, forcing cerebrospinal fluid (CSF) and venous blood out of the cranium. Excessive arterial pulsatility may be part of a harmful mechanism causing cognitive decline among elderly. Additionally, restricted venous flow from the brain is suggested as the cause of multiple sclerosis. Addressing hypotheses derived from these observations requires accurate and reliable investigational methods. This work focused on assessing the pulsatile waveform of cerebral arterial, venous and CSF flows. The overall aim of this dissertation was to explore cerebral blood flow and intracranial pulsatility using MRI, with respect to measurement, physiological and pathophysiological aspects.Two-dimensional phase contrast magnetic resonance imaging (2D PCMRI) was used to assess the pulsatile waveforms of cerebral arterial, venous and CSF flow. The repeatability was assessed in healthy young subjects. The 2D PCMRI measurements of cerebral arterial, venous and CSF pulsatility were generally repeatable but the pulsatility decreased systematically during the investigation. A method combining 2D PCMRI measurements with invasive CSF infusion tests to determine the magnitude and distribution of compliance within the craniospinal system was developed and applied in a group of healthy elderly. The intracranial space contained approximately two thirds of the total craniospinal compliance. The magnitude of craniospinal compliance was less than suggested in previous studies. The vascular hypothesis for multiple sclerosis was tested. Venous drainage in the internal jugular veins was compared between healthy controls and multiple sclerosis patients using 2D PCMRI. For both groups, a great variability in the internal jugular flow was observed but no pattern specific to multiple sclerosis could be found. Relationships between regional brain volumes and potential biomarkers of intracranial cardiac-related pulsatile

  8. The contribution of astrocytes to the regulation of cerebral blood flow

    Directory of Open Access Journals (Sweden)

    Clare eHowarth


    Full Text Available In order to maintain normal brain function, it is critical that cerebral blood flow (CBF is matched to neuronal metabolic needs. Accordingly, blood flow is increased to areas where neurons are more active (a response termed functional hyperemia. The tight relationships between neuronal activation, glial cell activity, cerebral energy metabolism and the cerebral vasculature, known as neurometabolic and neurovascular coupling, underpin functional MRI (fMRI signals but are incompletely understood. As functional imaging techniques, particularly BOLD fMRI, become more widely used, their utility hinges on our ability to accurately and reliably interpret the findings. A growing body of data demonstrates that astrocytes can serve as a ‘bridge’, relaying information on the level of neural activity to blood vessels in order to coordinate oxygen and glucose delivery with the energy demands of the tissue. It is widely assumed that calcium-dependent release of vasoactive substances by astrocytes results in arteriole dilation and the increased blood flow which accompanies neuronal activity. However, the signaling molecules responsible for this communication between astrocytes and blood vessels are yet to be definitively confirmed. Indeed, there is controversy over whether activity-induced changes in astrocyte calcium are widespread and fast enough to elicit such functional hyperemia responses. In this review, I will summarise the evidence which has convincingly demonstrated that astrocytes are able to modify the diameter of cerebral arterioles. I will discuss the prevalence, presence and timing of stimulus-induced astrocyte calcium transients and describe the evidence for and against the role of calcium-dependent formation and release of vasoactive substances by astrocytes. I will also review alternative mechanisms of astrocyte-evoked changes in arteriole diameter and consider the questions which remain to be answered in this exciting area of research.

  9. Regional cerebral blood flow in various pediatric neurological patients using /sup 123/I-IMP SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Konishi, Tohru; Naganuma, Yoshihiro; Hongou, Kazuhisa; Murakami, Miyako; Yamatani, Miwa; Okada, Toshio


    The recent development of a new radiopharmaceutical /sup 123/I-isopropyl-iodoamphetamine (IMP), which is taken up by the brain from the blood flow, has offered a possibility of constructing scintigraphy maps of regional cerebral blood flow (rCBF) using single photon emission CT. We used this mehtod in various pediatric neurological diseases. Six patients with cerebro-vascular disorders (moya-moya disease 2, infarction 3 and HHE syndrome 1), 6 patients with infectious diseases of CNS (acute encephalitis 4, septic meningitis 1 and SSPE 1) and a miscellaneous group of six patients were studied. The rCBF abnormalities in cerebro-vascular diseases were more extensive and frequent than x-ray CT abnormalities. Repeated studies of IMP-SPECT revealed usefulness for the understanding of changeable hemodynamic pathophysiology and for the judgment of theraptic effectiveness and prognosis. The rCBF decrease in infectious diseases tended to be more diffuse and slight than that in cerebro-vascular diseases. In almost all patients, the area of rCBF decrease coincided with the area of EEG slowing evaluated by EEG topographic analysis. Brain imaging using /sup 123/I-IMP SPECT may reveal functional abnormalities as well as organic lesions. /sup 123/I-IMP SPECT has introduced a new era for the useful application of nuclear medicine to the investigation of pediatric neurological diseases.

  10. Relationships between cerebral flow velocities and neurodevelopmental outcomes in children with moderate to severe traumatic brain injury. (United States)

    O'Brien, Nicole Fortier; Maa, Tensing; Moore-Clingenpeel, Melissa; Rosenberg, Nathan; Yeates, Keith Owen


    This study aimed to determine relationships between cerebral blood flow and neurodevelopmental outcomes in children with moderate to severe traumatic brain injury (TBI). Children with TBI, a Glasgow Coma Score of 8-12, and abnormal brain imaging were enrolled prospectively. Cerebral blood flow velocity (CBFV) was assessed within 24 h of trauma and daily thereafter through death, discharge, or hospital day 8, whichever came first. Twelve months from injury, participants completed neurodevelopmental testing. Sixty-nine patients were enrolled. Low flow velocities (flow velocities (± 2 SD around age/gender normal) were seen in 43% of participants (n = 30). High flow velocities (> 2 SD above age and gender normal with a Lindegaard ratio (LR)  2 SD above age/gender normal with LR ≥ 3) was identified in 28% (n = 19). Children with good outcomes based on GOS-E Peds scoring were more likely to have had normal flow velocity than other flow patterns. No other differences in neurodevelopmental outcomes were noted. Individual patient responses to TBI in terms of CBFV alterations were heterogeneous. Low flow was uniformly associated with a poor outcome. Patients with good outcomes were more likely to have normal flow. This suggests CBFV may serve as a prognostic indicator in children with TBI. Future studies are needed to determine if aberrant CBFVs are also a therapeutic target.

  11. Usefulness of measurement of blood flow by RI plethysmography

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Kenji; Ling, Qing Cheng; Mori, Yutaka; Tanaka, Uzuru; Shimada, Takao [Jikei Univ., Tokyo (Japan). School of Medicine


    We have developed the RI plethysmography, and have applied it to ordinary clinic diagnosis and the evaluation of treatment. The subjects were 58 cases (39 cases of the obstruction of the peripheral blood circulation: ASO 24 cases, TAO 4 cases and arterial sclerotic change 11 cases; the non-abnormal control was 19 cases). The clinical benefit of this method was evaluated. In the cases with 1 and 2 degrees of Fontaine`s classification and ASO and TAO, the blood flow of legs measured by our method significantly decreased in association with symptoms and angiographic findings. This method is suitable to the determination of angiography and evaluation of the effect of treatment. (author)

  12. Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Murrin L Charles


    Full Text Available Abstract Background Methamphetamine (METH, an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial cell activation. Here we hypothesized that METH-induced interference of glucose uptake and transport at the endothelium can disrupt the energy requirement of the blood-brain barrier (BBB function and integrity. We undertake this study because there is no report of METH effects on glucose uptake and transport across the blood-brain barrier (BBB to date. Results In this study, we demonstrate that METH-induced disruption of glucose uptake by endothelium lead to BBB dysfunction. Our data indicate that a low concentration of METH (20 μM increased the expression of glucose transporter protein-1 (GLUT1 in primary human brain endothelial cell (hBEC, main component of BBB without affecting the glucose uptake. A high concentration of 200 μM of METH decreased both the glucose uptake and GLUT1 protein levels in hBEC culture. Transcription process appeared to regulate the changes in METH-induced GLUT1 expression. METH-induced decrease in GLUT1 protein level was associated with reduction in BBB tight junction protein occludin and zonula occludens-1. Functional assessment of the trans-endothelial electrical resistance of the cell monolayers and permeability of dye tracers in animal model validated the pharmacokinetics and molecular findings that inhibition of glucose uptake by GLUT1 inhibitor cytochalasin B (CB aggravated the METH-induced disruption of the BBB integrity. Application of acetyl-L-carnitine suppressed the effects of METH on glucose uptake and BBB function. Conclusion Our findings suggest that impairment of GLUT1 at the brain endothelium by METH may contribute to energy-associated disruption of tight junction assembly and loss of BBB integrity.

  13. Impaired Cerebral Blood Flow Autoregulation During Postraumatic Arterial Hypotension After Fluid Percussion Brain Injury is Prevented by Phenylephrine in Female but Exacerbated in Male Piglets by ERK MAPK Upregulation (United States)

    Armstead, William M.; Kiessling, J. Willis; Kofke, W. Andrew; Vavilala, Monica S.


    Objective Traumatic brain injury (TBI) contributes to morbidity and mortality in children and boys are disproportionately represented. Hypotension is common and worsens outcome after TBI. Extracellular signal-related kinase (ERK) mitogen activated protein kinase (MAPK) is upregulated and reduces CBF after fluid percussion brain injury (FPI) in piglets. We hypothesized that increased CPP via phenylephrine (PHE) sex dependently reduces impairment of cerebral autoregulation during hypotension after FPI through modulation of ERK MAPK. Design Prospective, randomized animal study. Setting University laboratory. Subjects Newborn (1–5 day old) pigs. Interventions CBF, pial artery diameter, ICP and autoregulatory index (ARI) were determined before and after FPI in untreated, pre- and post-injury PHE (1 μg/kg/min iv) treated male and female pigs during normotension and hemorrhagic hypotension. CSF ERK MAPK was determined by ELISA. Measurements and Main Results Reductions in pial artery diameter, CBF, CPP and elevated ICP after FPI were greater in males, which were blunted by PHE pre- or post-FPI. During hypotension and FPI, pial artery dilation was impaired more in males. PHE decreased impairment of hypotensive pial artery dilation after FPI in females, but paradoxically caused vasoconstriction after FPI in males. Papaverine induced pial artery vasodilation was unchanged by FPI and PHE. CBF, CPP, and ARI decreased markedly during hypotension and FPI in males but less in females. PHE prevented reductions in CBF, CPP, and ARI during hypotension in females but increased reductions in males. CSF ERK MAPK was increased more in males than females after FPI. PHE blunted ERK MAPK upregulation in females, but increased ERK MAPK upregulation in males after FPI. Conclusions These data indicate that elevation of CPP with PHE sex dependently prevents impairment of cerebral autoregulation during hypotension after FPI through modulation of ERK MAPK. These data suggest the potential role

  14. Computational fluid dynamics using in vivo ultrasound blood flow measurements

    DEFF Research Database (Denmark)

    Traberg, Marie Sand; Pedersen, Mads Møller; Hemmsen, Martin Christian


    This paper presents a model environment for construction of patient-specific computational fluid dynamic (CFD) models for the abdominal aorta (AA). Realistic pulsatile velocity waveforms are employed by using in vivo ultrasound blood flow measurements. Ultrasound is suitable for acquisition....... The estimated and smoothed velocity profiles were quantitatively compared. The energy contained in the velocity profile after smoothing is 65% larger relative to the noise contaminated estimated profiles. In conclusion, a model environment that produces realistic patient-specific CFD simulation models without...

  15. Elementary wave interactions in blood flow through artery (United States)

    Raja Sekhar, T.; Minhajul


    In this paper, we consider the Riemann problem and interaction of elementary waves for the quasilinear hyperbolic system of conservation laws that arises in blood flow through arteries. We study the properties of solution involving shocks and rarefaction waves and establish the existence and uniqueness conditions. We show that the Riemann problem is solvable for arbitrary initial data under certain condition and construct the condition for no-feasible solution. Finally, we present numerical examples with different initial data and discuss all possible interactions of elementary waves.

  16. Metabolic control of muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher


    to exert control of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarization factor (EDHF) are possible mediators of muscle vasodilation during exercise. In humans, adenosine has been shown to contribute to functional hyperemia as blood flow...... that combined blockade of NOS and PGI2, and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans. Combined vasodilator blockade studies offer the potential to uncover important interactions and compensatory vasodilator responses. The signaling pathways that link metabolic events evoked...

  17. Dynamics of renal blood flow autoregulation in rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Wagner, A J; Marsh, D J


    component most likely represents an intrinsic vascular, myogenic, mechanism. The gain maximum of the admittance in the frequency range corresponding to the autonomous tubular oscillations indicates that the dynamic characteristics responsible for the occurrence of the spontaneous tubular oscillations must......Two separate components could be resolved in tests of the dynamic autoregulation of renal blood flow. The slow component corresponds to the frequency at which spontaneous proximal tubular pressure oscillations are found, and are most likely due to the operation of the TGF. The high frequency...

  18. Validation of Blood Flow Simulations in Intracranial Aneurysms (United States)

    Yu, Yue; Anor, Tomer; Baek, Hyoungsu; Jayaraman, Mahesh; Madsen, Joseph; Karniadakis, George


    Catheter-based digital subtraction angiography (DSA) is the most accurate diagnostic procedure for investigating vascular anomalies and cerebral blood flow. Here we describe utilization of DSA in a patient with an intracranial aneursysm to validate corresponding spectral element simulations. Subsequently, we examine via visualization the structure of flow in internal carotid arteries laden with three different types of aneurysms: (1) a wide-necked saccular aneurysm, (2) a narrower-necked saccular aneurysm, and (3) a case with two adjacent saccular aneurysms. We have found through high resolution simulations that in cases (1) and (3) in physiological conditions a hydrodynamic instability occurs during the decelerating systolic phase resulting in a high frequency oscillation (20-50 Hz). We use the in-silico dye visualization to discriminate among different physical mechanisms causing the instability and contrast their effect with case (2) for which an instability arises only at much higher flowrates.

  19. Skin temperature and subcutaneous adipose blood flow in man

    DEFF Research Database (Denmark)

    Astrup, A; Bülow, J; Madsen, J


    The abdominal subcutaneous adipose tissue blood flow (ATBF) was measured bilaterally by the 133Xe washout method. At one side of the skin (epicutaneous) temperature was varied with a temperature blanket, the other side served as control. There was a significant (P less than 0.001) positive...... correlation between skin temperature and ATBF. In the range from 25 to 37 degrees CATBF increased 9% of the control flow on average per centigrade increase in skin temperature. ATBF at the control side was uninfluenced by the contralateral variations in skin temperature. Although no better correlation could...... be demonstrated between ATBF and subcutaneous temperature than between ATBF and skin temperature, arguments are presented in favour of the hypothesis that ATBF is influenced by the subcutaneous temperature rather than via reflexes from the skin. Infiltration of the 133Xe depots with 20 microgram histamine...

  20. Effects of exercise training with blood flow restriction on blood pressure in medicated hypertensive patients

    Directory of Open Access Journals (Sweden)

    Marcos Antônio Cezar


    Full Text Available Abstract The development of non-pharmacological approaches to hypertension (HA is critical for both prevention and treatment. This study examined the hemodynamic and biochemical responses of medicated hypertensive women to resistance exercise with blood flow restriction (vascular occlusion. Twenty-three women were randomly assigned to one of three groups: High intensity strength training (n = 8; low-intensity resistance exercise with occlusion (n = 8; and control (n = 7. The first two groups underwent eight weeks of training performed twice a week, including three series of wrist flexion exercises with or without vascular occlusion. The exercised with occlusion group showed pre- to post-test reduction in systolic and diastolic blood pressure, mean arterial pressure, and double product, whereas the other groups showed no significant hemodynamic changes. In conclusion, resistance exercise during 8 weeks was effective in lowering blood pressure in medicated hypertensive subjects.

  1. Imaging of Neuronal Activity in Awake Mice by Measurements of Flavoprotein Autofluorescence Corrected for Cerebral Blood Flow

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    Manami Takahashi


    Full Text Available Green fluorescence imaging (e.g., flavoprotein autofluorescence imaging, FAI can be used to measure neuronal activity and oxygen metabolism in living brains without expressing fluorescence proteins. It is useful for understanding the mechanism of various brain functions and their abnormalities in age-related brain diseases. However, hemoglobin in cerebral blood vessels absorbs green fluorescence, hampering accurate assessments of brain function in animal models with cerebral blood vessel dysfunctions and subsequent cerebral blood flow (CBF alterations. In the present study, we developed a new method to correct FAI signals for hemoglobin-dependent green fluorescence reductions by simultaneous measurements of green fluorescence and intrinsic optical signals. Intrinsic optical imaging enabled evaluations of light absorption and scatters by hemoglobin, which could then be applied to corrections of green fluorescence intensities. Using this method, enhanced flavoprotein autofluorescence by sensory stimuli was successfully detected in the brains of awake mice, despite increases of CBF, and hemoglobin interference. Moreover, flavoprotein autofluorescence could be properly quantified in a resting state and during sensory stimulation by a CO2 inhalation challenge, which modified vascular responses without overtly affecting neuronal activities. The flavoprotein autofluorescence signal data obtained here were in good agreement with the previous findings from a condition with drug-induced blockade of cerebral vasodilation, justifying the current assaying methodology. Application of this technology to studies on animal models of brain diseases with possible changes of CBF, including age-related neurological disorders, would provide better understanding of the mechanisms of neurovascular coupling in pathological circumstances.

  2. 3D real-time visualization of blood flow in cerebral aneurysms by light field particle image velocimetry (United States)

    Carlsohn, Matthias F.; Kemmling, André; Petersen, Arne; Wietzke, Lennart


    Cerebral aneurysms require endovascular treatment to eliminate potentially lethal hemorrhagic rupture by hemostasis of blood flow within the aneurysm. Devices (e.g. coils and flow diverters) promote homeostasis, however, measurement of blood flow within an aneurysm or cerebral vessel before and after device placement on a microscopic level has not been possible so far. This would allow better individualized treatment planning and improve manufacture design of devices. For experimental analysis, direct measurement of real-time microscopic cerebrovascular flow in micro-structures may be an alternative to computed flow simulations. An application of microscopic aneurysm flow measurement on a regular basis to empirically assess a high number of different anatomic shapes and the corresponding effect of different devices would require a fast and reliable method at low cost with high throughout assessment. Transparent three dimensional 3D models of brain vessels and aneurysms may be used for microscopic flow measurements by particle image velocimetry (PIV), however, up to now the size of structures has set the limits for conventional 3D-imaging camera set-ups. On line flow assessment requires additional computational power to cope with the processing large amounts of data generated by sequences of multi-view stereo images, e.g. generated by a light field camera capturing the 3D information by plenoptic imaging of complex flow processes. Recently, a fast and low cost workflow for producing patient specific three dimensional models of cerebral arteries has been established by stereo-lithographic (SLA) 3D printing. These 3D arterial models are transparent an exhibit a replication precision within a submillimeter range required for accurate flow measurements under physiological conditions. We therefore test the feasibility of microscopic flow measurements by PIV analysis using a plenoptic camera system capturing light field image sequences. Averaging across a sequence of

  3. Challenges in understanding the impact of blood pressure management on cerebral oxygenation in the preterm brain

    Directory of Open Access Journals (Sweden)

    Aminath eAzhan


    Full Text Available Systemic hypotension in preterm infants has been related to increased mortality, cerebrovascular lesions and neurodevelopmental morbidity. Treatment of hypotension with inotropic medications aims at preservation of end organ perfusion and oxygen delivery, especially the brain. The common inotropic medications in preterm infants include dopamine, dobutamine, adrenalin, with adjunctive use of corticosteroids in cases of refractory hypotension. Whether maintenance of mean arterial blood pressure (MAP by use of inotropic medication is neuroprotective or not remains unclear. This review explores the different inotropic agents and their effects on perfusion and oxygenation in the preterm brain, in clinical studies as well as in animal models. Dopamine and adrenalin, because of their -adrenergic vasoconstrictor actions, have raised concerns of reduction in cerebral blood flow (CBF. Several studies in hypotensive preterm infants have shown that dopamine elevates CBF together with increased MAP, in keeping with limited cerebro-autoregulation. Adrenaline is also effective in raising cerebral perfusion together with MAP in preterm infants. Experimental studies in immature animals show no cerebro-vasoconstrictive effects of dopamine or adrenaline, but demonstrate the consistent findings of increased cerebral perfusion and oxygenation with the use of dopamine, dobutamine and adrenaline, alongside with raised MAP. Both clinical and animal studies report the transitory effects of adrenaline in increasing plasma lactate, and blood glucose, which might render its use as a 2nd line therapy. To investigate the cerebral effects of inotropic agents in long-term outcome in hypotensive preterm infants, carefully designed prospective research possibly including preterm infants with permissive hypotension is required. Preterm animal models would be useful in investigating the relationship between the physiological effects of inotropes and histopathology outcomes in

  4. Lipopolysaccharide impairs amyloid β efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood-brain barrier. (United States)

    Erickson, Michelle A; Hartvigson, Pehr E; Morofuji, Yoichi; Owen, Joshua B; Butterfield, D Allan; Banks, William A


    Defects in the low density lipoprotein receptor-related protein-1 (LRP-1) and p-glycoprotein (Pgp) clearance of amyloid beta (Aβ) from brain are thought to contribute to Alzheimer's disease (AD). We have recently shown that induction of systemic inflammation by lipopolysaccharide (LPS) results in impaired efflux of Aβ from the brain. The same treatment also impairs Pgp function. Here, our aim is to determine which physiological routes of Aβ clearance are affected following systemic inflammation, including those relying on LRP-1 and Pgp function at the blood-brain barrier. CD-1 mice aged between 6 and 8 weeks were treated with 3 intraperitoneal injections of 3 mg/kg LPS at 0, 6, and 24 hours and studied at 28 hours. 125I-Aβ1-42 or 125I-alpha-2-macroglobulin injected into the lateral ventricle of the brain (intracerebroventricular (ICV)) or into the jugular vein (intravenous (IV)) was used to quantify LRP-1-dependent partitioning between the brain vasculature and parenchyma and peripheral clearance, respectively. Disappearance of ICV-injected 14 C-inulin from brain was measured to quantify bulk flow of cerebrospinal fluid (CSF). Brain microvascular protein expression of LRP-1 and Pgp was measured by immunoblotting. Endothelial cell localization of LRP-1 was measured by immunofluorescence microscopy. Oxidative modifications to LRP-1 at the brain microvasculature were measured by immunoprecipitation of LRP-1 followed by immunoblotting for 4-hydroxynonenal and 3-nitrotyrosine. We found that LPS: caused an LRP-1-dependent redistribution of ICV-injected Aβ from brain parenchyma to brain vasculature and decreased entry into blood; impaired peripheral clearance of IV-injected Aβ; inhibited reabsorption of CSF; did not significantly alter brain microvascular protein levels of LRP-1 or Pgp, or oxidative modifications to LRP-1; and downregulated LRP-1 protein levels and caused LRP-1 mislocalization in cultured brain endothelial cells. These results suggest that LRP-1

  5. Targeted liposomes for drug delivery across the blood-brain barrier


    van Rooy, I.


    Our brain is protected by the blood-brain barrier (BBB). This barrier is formed by specialized endothelial cells of the brain vasculature and prevents toxic substances from entering the brain. The downside of this barrier is that many drugs that have been developed to cure brain diseases cannot cross this barrier and do not reach the brain in therapeutic concentrations. An innovative way to help these drugs to reach the brain is by encapsulating them into nanoparticles (e.g. liposomes). A tar...

  6. Multi-exposure speckle imaging of cerebral blood flow: a pilot clinical study (Conference Presentation) (United States)

    Richards, Lisa M.; Kazmi, S. M. S.; Olin, Katherine E.; Waldron, James S.; Fox, Douglas J.; Dunn, Andrew K.


    Monitoring cerebral blood flow (CBF) during neurosurgery is essential for detecting ischemia in a timely manner for a wide range of procedures. Multiple clinical studies have demonstrated that laser speckle contrast imaging (LSCI) has high potential to be a valuable, label-free CBF monitoring technique during neurosurgery. LSCI is an optical imaging method that provides blood flow maps with high spatiotemporal resolution requiring only a coherent light source, a lens system, and a camera. However, the quantitative accuracy and sensitivity of LSCI is limited and highly dependent on the exposure time. An extension to LSCI called multi-exposure speckle imaging (MESI) overcomes these limitations, and was evaluated intraoperatively in patients undergoing brain tumor resection. This clinical study (n = 7) recorded multiple exposure times from the same cortical tissue area, and demonstrates that shorter exposure times (≤1 ms) provide the highest dynamic range and sensitivity for sampling flow rates in human neurovasculature. This study also combined exposure times using the MESI model, demonstrating high correlation with proper image calibration and acquisition. The physiological accuracy of speckle-estimated flow was validated using conservation of flow analysis on vascular bifurcations. Flow estimates were highly conserved in MESI and 1 ms exposure LSCI, with percent errors at 6.4% ± 5.3% and 7.2% ± 7.2%, respectively, while 5 ms exposure LSCI had higher errors at 21% ± 10% (n = 14 bifurcations). Results from this study demonstrate the importance of exposure time selection for LSCI, and that intraoperative MESI can be performed with high quantitative accuracy.

  7. Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis

    DEFF Research Database (Denmark)

    Cramer, Stig P; Modvig, Signe; Simonsen, Helle Juhl


    in the permeability of the blood-brain barrier in normal-appearing white matter of patients with multiple sclerosis and here, for the first time, we present a study on the capability of blood-brain barrier permeability in predicting conversion from optic neuritis to multiple sclerosis and a direct comparison...... with cerebrospinal fluid markers of inflammation, cellular trafficking and blood-brain barrier breakdown. To this end, we applied dynamic contrast-enhanced magnetic resonance imaging at 3 T to measure blood-brain barrier permeability in 39 patients with monosymptomatic optic neuritis, all referred for imaging...... fluid as well as levels of CXCL10 and MMP9 in the cerebrospinal fluid. These findings suggest that blood-brain barrier permeability, as measured by magnetic resonance imaging, may provide novel pathological information as a marker of neuroinflammation related to multiple sclerosis, to some extent...

  8. Effect of low-dose methylprednisolone on peripheral blood endothelial progenitor cells and its significance in rats after brain injury

    Directory of Open Access Journals (Sweden)

    Bin ZHANG


    Full Text Available Objective To explore the effects of low-dose methylprednisolone(MP treatment after traumatic brain injury(TBI in rats on the number of peripheral blood endothelial progenitor cells(EPCs and injury area of the brain.Methods One hundred and fifty-four adult male Wistar rats were involved in the present study,and they were randomly divided into normal control group(n=18,TBI control group(n=38,MP control group(n=30,MP+TBI group(n=30 and TBI+MP group(n=38.The TBI model was reproduced by fluid percussion injury(FPI.MP(5mg/kg was intraperitoneally administered once a day for 4 days.Peripheral venous blood samples were taken on day 1,3,7 and 14,and the counts of EPCs were determined by flow cytometry.The rats were sacrificed on day 1 and 3,brain edema was estimated by dry-wet weight method,and the blood-brain barrier(BBB permeability was determined by Evans-blue extravasation.Results The counts of peripheral blood EPCs were significantly higher in MP control group,MP+TBI group and TBI+MP group on day 1,3 and 7 than that in normal control and TBI control group,and it returned to the level of normal control group on day 14.The BBB permeability was improved and brain edema alleviated in MP+TBI and TBI+MP group on day 3.Conclusion The administration of low-dose MP may increase the count of peripheral blood EPCs in rats,decrease BBB damage,and alleviate brain edema.

  9. [Pulmonary blood flow distribution in acute viral bronchiolitis]. (United States)

    Carvalho, Paulo R A; Cunha, Renato D; Barreto, Sérgio S Menna


    To assess lung perfusion patterns in inpatients with acute viral bronchiolitis using quantitative 99mTc-MAA scintigraphy so as to establish an association with clinical and radiological findings. A comparative, prospective case series study with a focus on diagnosis was carried out in a population of patients with acute viral bronchiolitis admitted to Hospital de Clínicas de Porto Alegre. Inclusion criteria were age between 1 and 24 months and first sudden-onset wheezing episode, suggesting bronchiolitis. The patients in the study were submitted to clinical, radiological and 99mTc-MAA lung perfusion evaluation during the first 24 hours of admission. Statistical analysis employed t test, taking into consideration a significance level of 0.05. The regional distribution of lung blood flow in the 38 patients studied was more pronounced in the upper section of the left lung in relation to the right lung (P1.0 in the upper and middle sections of both lungs. In the lower section it was >1.0 only in the right lung (Pbronchiolitis; only a tendency to redirect lung blood flow towards upper lung sections was observed.

  10. Monitoring blood flow and photobleaching during topical ALA PDT treatment (United States)

    Sands, Theresa L.; Sunar, Ulas; Foster, Thomas H.; Oseroff, Allan R.


    Photodynamic therapy (PDT) using topical aminolevulinic acid (ALA) is currently used as a clinical treatment for nonmelanoma skin cancers. In order to optimize PDT treatment, vascular shutdown early in treatment must be identified and prevented. This is especially important for topical ALA PDT where vascular shutdown is only temporary and is not a primary method of cell death. Shutdown in vasculature would limit the delivery of oxygen which is necessary for effective PDT treatment. Diffuse correlation spectroscopy (DCS) was used to monitor relative blood flow changes in Balb/C mice undergoing PDT at fluence rates of 10mW/cm2 and 75mW/cm2 for colon-26 tumors implanted intradermally. DCS is a preferable method to monitor the blood flow during PDT of lesions due to its ability to be used noninvasively throughout treatment, returning data from differing depths of tissue. Photobleaching of the photosensitizer was also monitored during treatment as an indirect manner of monitoring singlet oxygen production. In this paper, we show the conditions that cause vascular shutdown in our tumor model and its effects on the photobleaching rate.

  11. Adipose tissue and skeletal muscle blood flow during mental stress

    Energy Technology Data Exchange (ETDEWEB)

    Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.


    Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

  12. Thrombospondin 1 and Vasoactive Agents Indirectly Alter Tumor Blood Flow

    Directory of Open Access Journals (Sweden)

    Jeff S. Isenberg


    Full Text Available Nitric oxide (NO plays important physiological roles in the vasculature to regulate angiogenesis, blood flow, and hemostasis. In solid tumors, NO is generally acknowledged to mediate angiogenic responses to several growth factors. This contrasts with conflicting evidence that NO can acutely increase tumor perfusion through local vasodilation or diminish perfusion by preferential relaxation of peripheral vascular beds outside the tumor. Because thrombospondin 1 (TSP1 is an important physiological antagonist of NO in vascular cells, we examined whether, in addition to inhibiting tumor angiogenesis, TSP1 can acutely regulate tumor blood flow. We assessed this activity of TSP1 in the context of perfusion responses to NO as a vasodilator and epinephrine as a vasoconstrictor. Nitric oxide treatment of wild type and TSP1 null mice decreased perfusion of a syngeneic melanoma, whereas epinephrine transiently increased tumor perfusion. Acute vasoactive responses were also independent of the level of tumor-expressed TSP1 in a melanoma xenograft, but recovery of basal perfusion was modulated by TSP1 expression. In contrast, overexpression of truncated TSP1 lacking part of its CD47 binding domain lacked this modulating activity. These data indicate that TSP1 primarily regulates long-term vascular responses in tumors, in part, because the tumor vasculature has a limited capacity to acutely respond to vasoactive agents.

  13. Clustering of microscopic particles in constricted blood flow (United States)

    Bächer, Christian; Schrack, Lukas; Gekle, Stephan


    A mixed suspension of red blood cells (RBCs) and microparticles flows through a cylindrical channel with a constriction mimicking a stenosed blood vessel. Our three-dimensional Lattice-Boltzmann simulations show that the RBCs are depleted right ahead of and after the constriction. Although the RBC mean concentration (hematocrit) is 16.5% or 23.7%, their axial concentration profile is very similar to that of isolated tracer particles flowing along the central axis. Most importantly, however, we find that the stiff microparticles exhibit the opposite behavior. Arriving on a marginated position near the channel wall, they can pass through the constriction only if they find a suitable gap to dip into the dense plug of RBCs occupying the channel center. This leads to a prolonged dwell time and, as a consequence, to a pronounced increase in microparticle concentration right in front of the constriction. For biochemically active particles such as drug delivery agents or activated platelets this clustering may have important physiological consequences, e.g., for the formation of microthrombi.

  14. Screening for ochratoxin A in blood by flow injection analysis. (United States)

    Hult, K; Fuchs, R; Peraica, M; Plestina, R; Ceović, S


    A micromethod for ochratoxin A detection in human sera by flow injection technique is described. The method requires 50 microliter of sera, and it is designed to distinguish samples containing less than 10 ng ochratoxin A per ml. The method is based on fluorescence measurement following a simple extraction procedure for which very small amounts of chemicals are needed. Since the method is not confirmatory, all samples showing fluorescence above a certain intensity have to be reanalysed with some other method where a confirmation step in included. Because of the small amount of serum needed and the rapid procedure (less than 15 min), a large number of samples can be analysed very quickly. The method may therefore be applicable for large screening campaigns conducted to determine the presence of ochratoxin A in blood. This conclusion is based on 1675 samples and 147 standards analysed concurrently by the flow injection technique and an earlier published enzymic method. The method is also suitable for monitoring ochratoxin A levels in the blood of experimental animals.

  15. Integrated Lateral Flow Device for Flow Control with Blood Separation and Biosensing

    Directory of Open Access Journals (Sweden)

    Veronica Betancur


    Full Text Available Lateral flow devices are versatile and serve a wide variety of purposes, including medical, agricultural, environmental, and military applications. Yet, the most promising opportunities of these devices for diagnosis might reside in point-of-care (POC applications. Disposable paper-based lateral flow strips have been of particular interest, because they utilize low-cost materials and do not require expensive fabrication instruments. However, there are constraints on tuning flow rates and immunoassays functionalization in papers, as well as technical challenges in sensors’ integration and concentration units for low-abundant molecular detection. In the present work, we demonstrated an integrated lateral flow device that applied the capillary forces with functionalized polymer-based microfluidics as a strategy to realize a portable, simplified, and self-powered lateral flow device (LFD. The polydimethylsiloxane (PDMS surface was rendered hydrophilic via functionalization with different concentrations of Pluronic F127. Controlled flow is a key variable for immunoassay-based applications for providing enough time for protein binding to antibodies. The flow rate of the integrated LFD was regulated by the combination of multiple factors, including Pluronic F127 functionalized surface properties and surface treatments of microchannels, resistance of the integrated flow resistor, the dimensions of the microstructures and the spacing between them in the capillary pump, the contact angles, and viscosity of the fluids. Various plasma flow rates were regulated and achieved in the whole device. The LFD combined the ability to separate high quality plasma from human whole blood by using a highly asymmetric plasma separation membrane, and created controlled and steady fluid flow using capillary forces produced by the interfacial tensions. Biomarker immunoglobulin G (IgG detection from plasma was demonstrated with a graphene nanoelectronic sensor integrated

  16. Growth inhibition in a brain metastasis model by antibody delivery using focused ultrasound-mediated blood-brain barrier disruption

    NARCIS (Netherlands)

    Kobus, T.; Zervantonakis, I.K.; Zhang, Y; McDannold, N.J.


    HER2-targeting antibodies (i.e. trastuzumab and pertuzumab) prolong survival in HER2-positive breast cancer patients with extracranial metastases. However, the response of brain metastases to these drugs is poor, and it is hypothesized that the blood-brain barrier (BBB) limits drug delivery to the

  17. Do salt cravings in children with autistic disorders reveal low blood sodium depleting brain taurine and glutamine? (United States)

    Good, Peter


    Because boys are four times more likely than girls to develop autism, the role of male hormones (androgens) has received considerable scrutiny. Some researchers implicate arginine vasopressin, an androgen-dependent hormone from the pituitary gland that elicits male behavior. Elevated vasopressin is also the most common cause of low blood sodium (hyponatremia)--most serious in the brains of children. Hyponatremia causes astrocytes to swell, then release the amino acids taurine and glutamine and their water to compensate. Taurin--the brain osmolyte/inhibitory neurotransmitter that suppresses vasopressin--was the amino acid most wasted or depleted in urine of autistic children. Glutamine is a critical metabolic fuel in brain neurons, astrocytes, endothelial cells, and the intestines, especially during hypoglycemia. Because glutamine is not thought to cross the blood-brain barrier significantly, the implications of low blood glutamine in these children are not recognized. Yet children with high brain glutamine from urea cycle disorders are rarely diagnosed with autistic disorders. Other common events in autistic children that release vasopressin are gastrointestinal inflammation, hypoglycemia, and stress. Signs of hyponatremia in these children are salt cravings reported online and anecdotally, deep yellow urine revealing concentration, and relief of autistic behavior by fluid/salt diets. Several interventions offer promise: (a) taurine to suppress vasopressin and replenish astrocytes; (b) glutamine as fuel for intestines and brain; (c) arginine to spare glutamine, detoxify ammonia, and increase brain blood flow; and (d) oral rehydration salts to compensate dilutional hyponatremia. This hypothesis appears eminently testable: Does your child crave salt? Is his urine deep yellow? Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. In vitro models of the blood-brain barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Abbott, N Joan; Burek, Malgorzata


    components of plasma and xenobiotics. This "blood-brain barrier" function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug...

  19. Remodelling of choroidal blood flow in radiation choroidopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Hideo; Muraoka, Kanemitsu; Takahashi, Kyoichi; Sutoh, Noriko [Gunma Univ., Maebashi (Japan). School of Medicine


    Two males, aged 68 and 34 years each, presented with radiation retinopathy. One had received radiation therapy to the whole brain for intracranial metastasis of lung carcinoma 29 months before. The other underwent surgery and radiation for melanoma of the upper eyelid 15 years before. When examined by indocyanine green angiography. both cases showed vasoocclusive changes in the choroid involving the choriocapillaris and major vessels in the affected fundus area. In one eye with severe retinal vascular lesions in the superior temporal quadrant, the vortex vein in the quadrant had obliterated. The venous blood in this quadrant was drained into the inferior temporal vortex vein crossing the presumed watershed zone temporal to the macula. Collaterals had formed between choroidal arteries and between choroidal veins. These cases illustrate that choroidal vascular lesions may be present in radiation retinopathy, that the former may be more pronounced than the latter and that choroidal vessels may undergo extensive remodelling to compensate for the disturbed choroidal circulation. (author)

  20. Massage impairs postexercise muscle blood flow and "lactic acid" removal. (United States)

    Wiltshire, E Victoria; Poitras, Veronica; Pak, Melissa; Hong, Terence; Rayner, Jay; Tschakovsky, Michael E


    This study tested the hypothesis that one of the ways sports massage aids muscle recovery from exercise is by increasing muscle blood flow to improve "lactic acid" removal. Twelve subjects performed 2 min of strenuous isometric handgrip (IHG) exercise at 40% maximum voluntary contraction to elevate forearm muscle lactic acid. Forearm blood flow (FBF; Doppler and Echo ultrasound of the brachial artery) and deep venous forearm blood lactate and H+ concentration ([La-], [H+]) were measured every minute for 10 min post-IHG under three conditions: passive (passive rest), active (rhythmic exercise at 10% maximum voluntary contraction), and massage (effleurage and pétrissage). Arterialized [La-] and [H+] from a superficial heated hand vein was measured at baseline. Data are presented as mean +/- SE. Venoarterial [La-] difference ([La-]v-a) at 30 s of post-IHG was the same across conditions (passive = 6.1 +/- 0.6 mmol x L(-1), active = 5.7 +/- 0.6 mmol x L(-1), massage = 5.5 +/- 0.6 mmol x L(-1), NS), whereas FBF was greater in passive (766 +/- 101 mL x min(-1)) versus active (614 +/- 62 mL x min(-1), P = 0.003) versus massage (540 +/- 60 mL x min(-1), P < 0.0001). Total FBF area under the curve (AUC) for 10 min after handgrip was significantly higher in passive versus massage (4203 +/- 531 vs 3178 +/- 304 mL, P = 0.024) but not versus active (3584 +/- 284 mL, P = 0.217). La(-)- efflux (FBF x [La-]v-a) AUC mirrored FBF AUC (passive = 20.5 +/- 2.8 mmol vs massage = 14.7 +/- 1.6 mmol, P = 0.03, vs active = 15.4 +/- 1.9 mmol, P = 0.064). H+ efflux (FBF x [H+]v-a) was greater in passive versus massage at 30 s (2.2 +/- 0.4e(-5) vs 1.3 +/- 0.2e(-5) mmol, P < 0.001) and 1.5 min (1.0 +/- 0.2e(-5) vs 0.6 +/- 0.09e(-5) mmol, P = 0.003) after IHG. Massage impairs La(-) and H+ removal from muscle after strenuous exercise by mechanically impeding blood flow.