Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients.

The purpose of this study was to determine the prognostic accuracy of perfusion computed tomography (CT), performed at the time of emergency room admission, in acute stroke patients. Accuracy was determined by comparison of perfusion CT with delayed magnetic resonance (MR) and by monitoring the evolution of each patient's clinical condition. Twenty-two acute stroke patients underwent perfusion CT covering four contiguous 10mm slices on admission, as well as delayed MR, performed after a median interval of 3 days after emergency room admission. Eight were treated with thrombolytic agents. Infarct size on the admission perfusion CT was compared with that on the delayed diffusion-weighted (DWI)-MR, chosen as the gold standard. Delayed magnetic resonance angiography and perfusion-weighted MR were used to detect recanalization. A potential recuperation ratio, defined as PRR = penumbra size/(penumbra size + infarct size) on the admission perfusion CT, was compared with the evolution in each patient's clinical condition, defined by the National Institutes of Health Stroke Scale (NIHSS). In the 8 cases with arterial recanalization, the size of the cerebral infarct on the delayed DWI-MR was larger than or equal to that of the infarct on the admission perfusion CT, but smaller than or equal to that of the ischemic lesion on the admission perfusion CT; and the observed improvement in the NIHSS correlated with the PRR (correlation coefficient = 0.833). In the 14 cases with persistent arterial occlusion, infarct size on the delayed DWI-MR correlated with ischemic lesion size on the admission perfusion CT (r = 0.958). In all 22 patients, the admission NIHSS correlated with the size of the ischemic area on the admission perfusion CT (r = 0.627). Based on these findings, we conclude that perfusion CT allows the accurate prediction of the final infarct size and the evaluation of clinical prognosis for acute stroke patients at the time of emergency evaluation. It may also provide information about the extent of the penumbra. Perfusion CT could therefore be a valuable tool in the early management of acute stroke patients.

Blood flow measurements in rats using four color microspheres during blockade of different vasopressor systems

The use of colored microspheres to adequately evaluate blood flow changes under different circumstances in the same rat has been validated with a maximum of three different colors due to methodological limitations. The aim of the present study was to validate the use of four different colors measuring four repeated blood flow changes in the same rat to assess the role of vasopressor systems in controlling arterial pressure (AP). Red (150,000), white (200,000), yellow (150,000), and blue (200,000) colored microspheres were infused into the left ventricle of 6 male Wistar rats 1) at rest and 2) after vasopressin (aAVP, 10 µg/kg, iv), 3) renin-angiotensin (losartan, 10 mg/kg, iv), and 4) sympathetic system blockade (hexamethonium, 20 mg/kg, iv) to determine blood flow changes. AP was recorded and processed with a data acquisition system (1-kHz sampling frequency). Blood flow changes were quantified by spectrophotometry absorption peaks for colored microsphere components in the tissues evaluated. Administration of aAVP and losartan slightly reduced the AP (-5.7 ± 0.5 and -7.8 ± 1.2 mmHg, respectively), while hexamethonium induced a 52 ± 3 mmHg fall in AP. The aAVP injection increased blood flow in lungs (78%), liver (117%) and skeletal muscle (>150%), while losartan administration enhanced blood flow in heart (126%), lungs (100%), kidneys (80%), and gastrocnemius (75%) and soleus (94%) muscles. Hexamethonium administration reduced only kidney blood flow (50%). In conclusion, four types of colored microspheres can be used to perform four repeated blood flow measurements in the same rat detecting small alterations such as changes in tissues with low blood flow.

Investigation of arterial spin labeling MRI for quantitative cerebral blood flow measurement

Arterial spin labeling (ASL) is a technique for noninvasively measuring cerebral perfusion using magnetic resonance imaging. Clinical applications of ASL include functional activation studies, evaluation of the effect of pharmaceuticals on perfusion, and assessment of cerebrovascular disease, stroke, and brain tumor. The use of ASL in the clinic has been limited by poor image quality when large anatomic coverage is required and the time required for data acquisition and processing. This research sought to address these difficulties by optimizing the ASL acquisition and processing schemes. To improve data acquisition, optimal acquisition parameters were determined through simulations, phantom studies and in vivo measurements. The scan time for ASL data acquisition was limited to fifteen minutes to reduce potential subject motion. A processing scheme was implemented that rapidly produced regional cerebral blood flow (rCBF) maps with minimal user input. To provide a measure of the precision of the rCBF values produced by ASL, bootstrap analysis was performed on a representative data set. The bootstrap analysis of single gray and white matter voxels yielded a coefficient of variation of 6.7% and 29% respectively, implying that the calculated rCBF value is far more precise for gray matter than white matter. Additionally, bootstrap analysis was performed to investigate the sensitivity of the rCBF data to the input parameters and provide a quantitative comparison of several existing perfusion models. This study guided the selection of the optimum perfusion quantification model for further experiments. The optimized ASL acquisition and processing schemes were evaluated with two ASL acquisitions on each of five normal subjects. The gray-to-white matter rCBF ratios for nine of the ten acquisitions were within ±10% of 2.6 and none were statistically different from 2.6, the typical ratio produced by a variety of quantitative perfusion techniques. Overall, this work produced an ASL data acquisition and processing technique for quantitative perfusion and functional activation studies, while revealing the limitations of the technique through bootstrap analysis. ^

MEASUREMENT OF TUMOR BLOOD FLOW FOLLOWING NEUTRON IRRADIATION (ACTIVATION)

Clinical oncologists and cancer researchers benefit from information on the vascularization or non-vascularization of solid tumors because of blood flow's influence on three popular treatment types: hyperthermia therapy, radiotherapy, and chemotherapy. The objective of this research is the development of a clinically useful tumor blood flow measurement technique. The designed technique is sensitive, has good spatial resolution, in non-invasive and presents no risk to the patient beyond his usual treatment (measurements will be subsequent only to normal patient treatment).^ Tumor blood flow was determined by measuring the washout of positron emitting isotopes created through neutron therapy treatment. In order to do this, several technical and scientific questions were addressed first. These questions were: (1) What isotopes are created in tumor tissue when it is irradiated in a neutron therapy beam and how much of each isotope is expected? (2) What are the chemical states of the isotopes that are potentially useful for blood flow measurements and will those chemical states allow these or other isotopes to be washed out of the tumor? (3) How should isotope washout by blood flow be modeled in order to most effectively use the data? These questions have been answered through both theoretical calculation and measurement.^ The first question was answered through the measurement of macroscopic cross sections for the predominant nuclear reactions in the body. These results correlate well with an independent mathematical prediction of tissue activation and measurements of mouse spleen neutron activation. The second question was addressed by performing cell suspension and protein precipitation techniques on neutron activated mouse spleens. The third and final question was answered by using first physical principles to develop a model mimicking the blood flow system and measurement technique.^ In a final set of experiments, the above were applied to flow models and animals. The ultimate aim of this project is to apply its methodology to neutron therapy patients. ^

Is intra-operative blood flow predictive for early failure of radiocephalic arteriovenous fistula?

BACKGROUND: For over 50 years, radiocephalic wrist arteriovenous fistulae (RCAVF) have been the primary and best vascular access for haemodialysis. Nevertheless, early failure due to thrombosis or non-maturation is a major complication resulting in their abandonment. This prospective study was designed to investigate the predictive value of intra-operative blood flow on early failure of primary RCAVF before the first effective dialysis. METHODS: We enrolled patients undergoing creation of primary RCAVF for haemodialysis based on the pre-operative ultrasound vascular mapping discussed in a multidisciplinary approach. Intra-operative blood flow measurement was systematically performed once the anastomosis had been completed using a transit-time ultrasonic flowmeter. During the follow-up, blood flow was estimated by colour flow ultrasound at various intervals. Any events related to the RCAVF were recorded. RESULTS: Autogenous RCAVFs (n = 58) in 58 patients were constructed and followed up for an average of 30 days. Thrombosis and non-maturation occurred in eight (14%) and four (7%) patients, respectively. The intra-operative blood flow in functioning RCAVFs was significantly higher compared to non-functioning RCAVFs (230 vs 98 mL/min; P = 0.007), as well as 1 week (753 vs 228 mL/min; P = 0.0008) and 4 weeks (915 vs 245 mL/min, P < 0.0001) later. Blood flow volume measurements with a cut-off value of 120 mL/min had a sensitivity of 67%, specificity of 75% and positive predictive value of 91%. CONCLUSIONS: Blood flow <120 mL has a good predictive value for early failure in RCAVF. During the procedure, this cut-off value may be used to select appropriately which RCAVF should be investigated in the operation theatre in order to correct in real time any abnormality.

Targeting local tissues by transdermal application: Understanding drug physicochemical properties that best exploit protein binding and blood flow effects

The targeting of topically applied drug molecules into tissues below a site of application requires an understanding of the complex interrelationships between the drug, its formulation, the barrier properties of the skin, and the physiological processes occurring below the skin that are responsible for drug clearance from the site, tissue, and/or systemic distribution and eventual elimination. There is still a certain amount of controversy over the ability of topically applied drugs to penetrate into deeper tissues by diffusion or whether this occurs by redistribution in the systemic circulation. The major focus of our work in this area has been in determining how changes in drug structure and physicochemical properties, such as protein binding and lipophilicity, affect drug clearance into the local dermal microcirculation and lymphatics, as well as subsequent distribution into deeper tissues below an application site. The present study outlines our recent thinking on the drug molecule optimal physical attributes, in terms of plasma and tissue partitioning behaviour, that offer the greatest potential for deep tissue targeting. Drug Dev. Res. 46:309-315, 1999. (C) 1999 Wiley-Liss, Inc.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus

La peau est sujette à un vieillissement intrinsèque (processus naturel et chronologique) et extrinsèque (processus induit par l'environnement et notamment les rayons UV). Plusieurs études ont montré que le vieillissement cutané s'accompagne d'une réduction de la densité capillaire au sein du derme et d'une dégradation de plusieurs protéines de la matrice extracellulaire. Cette atteinte morphologique est associée à une diminution de la capacité vasodilatatrice maximale de la microcirculation dermique et en particulier, de la réponse maximale du flux sanguin cutané à un échauffement local de la surface cutanée à des températures avoisinant les 43-44°C. Cette réponse, appelée hyperémie locale induite par la chaleur (local thermal hyperemia), est facilement mesurable par des investigations non invasives, telles que le laser Doppler. Nous avons entrepris cette étude afin d'investiguer les effets de l'âge sur la réactivité de la microcirculation dermique dans des zones cutanées exposées différemment aux rayons UV. Pour ce faire, nous avons étudié, chez des patients jeunes (18 à 30 ans, n=13) et des patients âgés (> 60 ans, n=13), la vasodilatation cutanée induite par réchauffement local de la peau, au niveau de 3 sites anatomiques différents (la cuisse, l'avant- bras et le front). Les mesures ont été effectuées au moyen d'un laser Doppler. Pour chaque sujet et chaque site, la température cutanée fut tout d'abord amenée à 34°C par 2 corps de chauffe (A et B), disposés de manière adjacente sur la peau. La température fut ensuite augmentée à 39°C (corps de chauffe A) et à 41°C (corps de chauffe B) pour une durée de 30 minutes, dans l'optique d'induire une vasodilatation sous- maximale. Ensuite, la température fut augmentée à 43 °C (corps de chauffe A et B) pour 15 minutes supplémentaires. Enfin, la vasodilatation maximale a été induite par un échauffement local à 44°C pour 15 minutes supplémentaires (corps de chauffe A et B). L'enregistrement séquentiel du flux sanguin cutané, effectué chaque minute par laser Doppler imager, donne des images sur lesquelles peut être calculé le flux sanguin cutané (unités de perfusion, PU). Par la suite, nous avons calculé les conductances vasculaires cutanées (CVC), en divisant le flux sanguin (PU) par la tension artérielle moyenne (mmHg), afin de permettre une normalisation entre les différents sujets. Les CVC, évaluées au temps de départ (température 34°C) et après vasodilatation maximale (température 44°C), étaient plus hautes au niveau du front qu'au niveau des 2 autres sites anatomiques. Sur les 3 sites, la CVC maximale (température 44°C) diminuait avec l'âge mais de façon moins importante au niveau du front, en comparaison avec les 2 autres sites. La réponse aux températures sous-maximales (température 39 et 41°C), exprimée en pourcentage de la CVC maximale, ne variait pas avec l'âge ni en fonction du site anatomique étudié. En conclusion, cette étude est la première à étudier simultanément l'hyperémie locale induite par la chaleur sur 3 sites ayant une exposition différente aux rayons UV. Le processus utilisé (laser Doppler imager) est également unique dans la littérature concernant les altérations de la microcirculation cutanée en lien avec l'âge. Cette étude confirme ainsi que le vieillissement cutané intrinsèque et/ou extrinsèque réduit la capacité vasodilatatrice maximale de la microcirculation dermique. Par contre, la réactivité à réchauffement local à des températures moindres ne semble pas être affectée.

Using 80 kVp versus 120 kVp in perfusion CT measurement of regional cerebral blood flow.

Perfusion CT studies of regional cerebral blood flow (rCBF), involving sequential acquisition of cerebral CT sections during IV contrast material administration, have classically been reported to be achieved at 120 kVp. We hypothesized that using 80 kVp should result in the same image quality while significantly lowering the patient's radiation dose, and we evaluated this assumption. In five patients undergoing cerebral CT survey, one section level was imaged at 120 kVp and 80 kVp, before and after IV administration of iodinated contrast material. These four cerebral CT sections obtained in each patient were analyzed with special interest to contrast, noise, and radiation dose. Contrast enhancement at 80 kVp is significantly increased (P < .001), as well as contrast between gray matter and white matter after contrast enhancement (P < .001). Mean noise at 80 kVp is not statistically different (P = .042). Finally, performance of perfusion CT studies at 80 kVp, keeping mAs constant, lowers the radiation dose by a factor of 2.8. We, thus, conclude that 80 kVp acquisition of perfusion CT studies of rCBF will result in increased contrast enhancement and should improve rCBF analysis, with a reduced patient's irradiation.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus.

OBJECTIVE: This study was undertaken to investigate how aging affects dermal microvascular reactivity in skin areas differentially exposed to sunlight, and therefore to different degrees of photoaging. METHODS: We assessed, in young (18-30 years, n = 13) and aged males (≥60 years, n = 13), the thigh, forearm, and forehead's skin vasodilatory response to local heating (LTH) with a LDI. In each subject and at each location, local Tskin was brought from 34°C (baseline) to 39 or 41°C for 30 minutes, to effect submaximal vasodilation, with maximal vasodilation then elicited by further heating to 44°C. RESULTS: The CVCs evaluated at baseline and after maximal vasodilation (CVCmax ) were higher in the forehead than in the two other anatomical locations. On all locations, CVCmax decreased with age but less markedly in the forehead compared to the two other locations. When expressed in % of CVCmax , the plateau increase of CVCs in response to submaximal temperatures (39 and 41°C) did not vary with age, and minimally so with location. CONCLUSION: Skin aging, whether intrinsic or combined with photoaging, reduces the maximal vasodilatory capacity of the dermal microcirculation, but not its reactivity to local heating.

Simultaneous measurement of regional cerebral blood flow by perfusion CT and stable xenon CT: a validation study.

BACKGROUND AND PURPOSE: Knowledge of cerebral blood flow (CBF) alterations in cases of acute stroke could be valuable in the early management of these cases. Among imaging techniques affording evaluation of cerebral perfusion, perfusion CT studies involve sequential acquisition of cerebral CT sections obtained in an axial mode during the IV administration of iodinated contrast material. They are thus very easy to perform in emergency settings. Perfusion CT values of CBF have proved to be accurate in animals, and perfusion CT affords plausible values in humans. The purpose of this study was to validate perfusion CT studies of CBF by comparison with the results provided by stable xenon CT, which have been reported to be accurate, and to evaluate acquisition and processing modalities of CT data, notably the possible deconvolution methods and the selection of the reference artery. METHODS: Twelve stable xenon CT and perfusion CT cerebral examinations were performed within an interval of a few minutes in patients with various cerebrovascular diseases. CBF maps were obtained from perfusion CT data by deconvolution using singular value decomposition and least mean square methods. The CBF were compared with the stable xenon CT results in multiple regions of interest through linear regression analysis and bilateral t tests for matched variables. RESULTS: Linear regression analysis showed good correlation between perfusion CT and stable xenon CT CBF values (singular value decomposition method: R(2) = 0.79, slope = 0.87; least mean square method: R(2) = 0.67, slope = 0.83). Bilateral t tests for matched variables did not identify a significant difference between the two imaging methods (P >.1). Both deconvolution methods were equivalent (P >.1). The choice of the reference artery is a major concern and has a strong influence on the final perfusion CT CBF map. CONCLUSION: Perfusion CT studies of CBF achieved with adequate acquisition parameters and processing lead to accurate and reliable results.

Examining the roles of core and local temperature on forearm skin blood flow

The interaction between local and reflexive control of skin blood flow (SkBF) is unclear. This thesis isolated the roles of rectal (Tre) and local (Tloc) temperature on forearm SkBF regulation at normal and elevated body temperatures, and to investigate the interaction between local and reflexive SkBF control. While either normothermic (Tre ~37.0°C) or hyperthermic (∆Tre +1.1°C), SkBF was assessed on the dorsal aspect of each forearm in 10 participants while Tloc was manipulated in an A-B-A-B fashion between neutral (33.0°C) and hot (38.5°C). Finally, local heating to 44°C was performed to elicit maximal SkBF. Data are presented as a percentage of maximal cutaneous vascular conductance (CVC), calculated as laser-Doppler flux divided by mean arterial pressure. Tloc manipulations performed during normothermia had significantly greater effects on CVC than during hyperthermia. The decreased modification to SkBF from the Tloc changes during hyperthermia suggests that strong reflexive vasodilation attenuates local SkBF control mechanisms.

Outer skull landmark-based coordinates for measurement of cerebral blood flow and intracranial pressure in rabbits

Despite the increased use of intracranial neuromonitoring during experimental subarachnoid hemorrhage (SAH), coordinates for probe placement in rabbits are lacking. This study evaluates the safety and reliability of using outer skull landmarks to identify locations for placement of cerebral blood flow (CBF) and intraparenchymal intracranial pressure (ICP) probes. Experimental SAH was performed in 17 rabbits using an extracranial-intracranial shunt model. ICP probes were placed in the frontal lobe and compared to measurements recorded from the olfactory bulb. CBF probes were placed in various locations in the frontal cortex anterior to the coronary suture. Insertion depth, relation to the ventricular system, and ideal placement location were determined by post-mortem examination. ICP recordings at the time of SAH from the frontal lobe did not differ significantly from those obtained from the right olfactory bulb. Ideal coordinates for intraparenchymal CBF probes in the left and right frontal lobe were found to be located 4.6±0.9 and 4.5±1.2 anterior to the bregma, 4.7±0.7mm and 4.7±0.5mm parasagittal, and at depths of 4±0.5mm and 3.9±0.5mm, respectively. The results demonstrate that the presented coordinates based on skull landmarks allow reliable placement of intraparenchymal ICP and CBF probes in rabbit brains without the use of a stereotactic frame.

Influence of Durotomy on Laser-Doppler Measurement of Spinal Cord Blood Flow in Chondrodystrophic Dogs with Thoracolumbar Disk Extrusion

OBJECTIVES: To assess influence of durotomy on spinal cord blood flow (SCBF) in chondrodystrophic dogs with thoracolumbar disk extrusion. STUDY DESIGN: Prospective cohort study. ANIMALS: Chondrodystrophic dogs with thoracolumbar disk extrusion (n = 11). METHODS: Diagnosis was based on neurologic signs, magnetic resonance imaging (MRI) findings, and surgical confirmation. Regional SCBF was measured 3 times intraoperatively by laser-Doppler flowmetry: (1) before surgical decompression; (2) immediately after decompression by hemilaminectomy-durotomy; and (3) after 15 minutes of lesion lavage. A standardized hemilaminectomy and durotomy performed by the same neurosurgeon, was used to minimize factors that could influence measurement readings. RESULTS: A significant increase in intraoperative SCBF was found immediately after spinal cord decompression and durotomy in dogs but SCBF returned to previous levels or lower after 15 minutes of lavage. Changes in SCBF were not associated with duration of clinical signs; neurologic status, degree of spinal cord compression, or signal intensity changes as assessed by MRI. CONCLUSION: Durotomy does not increase SCBF in dogs with disk extrusion associated spinal cord compression.

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

The role of nitric oxide (NO) in the increase in local cerebral blood flow (LCBF) elicited by focal cortical epileptic seizures was investigated in anesthetized adult rats. Seizures were induced by topical bicuculline methiodide applied through two cranial windows drilled over homotopic sites of the frontal cortex, and LCBF was measured by quantitative autoradiography by using 4-iodo[N-methyl-14C]antipyrine. Superfusion of an inhibitor of NO synthase, N omega-nitro-L-arginine (NA; 1 mM), for 45 min abolished the increase of LCBF induced by topical bicuculline methiodide (10 mM) [164 +/- 18 ml/100 g per min in the artificial cerebrospinal fluid (aCSF)-superfused side and 104 +/- 12 ml/100 g per ml in the NA-superfused side; P < 0.005]. This effect was reversed by coapplication of an excess of L-arginine substrate (10 mM) (218 +/- 22 ml/100 g per min in the aCSF-superfused side and 183 +/- 31 ml/100 g per min in the NA + L-Arg-superfused side) but not by 10 mM D-arginine, a stereoisomer with poor affinity for NO synthase (193 +/- 17 ml/100 g per min in the aCSF-superfused side and 139 +/- 21 ml/100 g per min in the NA + D-Arg-superfused side; P < 0.005). Superfusion of the guanylyl cyclase inhibitor methylene blue attenuated the LCBF increase elicited by topical bicuculline methiodide by 25% +/- 16% (P < 0.05). The present findings suggest that NO is the mediator of the vasodilation in response to focal epileptic seizures.