Simultaneous multimodal optical imaging of cerebral blood flow and oxygenation in focal ischemic core and penumbra in mice

The authors recently developed a primate thromboembolic stroke model. To characterize the primate model, the authors determined serial changes in cerebral blood flow (CBF) and the relation between CBF and cerebral metabolic rate of glucose (CMRglc) using high-resolution positron emission tomography. Thromboembolic stroke was produced in male cynomolgus monkeys (n = 4). Acute obstruction of the left middle cerebral artery was achieved by injecting an autologous blood clot into the left internal carotid artery. Cerebral blood flow was measured with [15O]H2O before and 1, 2, 4, 6, and 24 hours after embolization. CMRglc was measured with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) 24 hours after embolization. Lesion size and location 24 hours after embolization was determined by the 2,3,5-triphenyltetrazolium chloride (TTC) staining method. The results are summarized as follows: (1) 1 hour after embolization, CBF in the temporal cortex and the basal ganglia decreased to < 40% of the contralateral values. In these regions, regarded as an ischemic core, CBF decreased further with time and CMRglc at 24 hours also decreased. Infarcted lesions as indicated by being unstained with TTC were consistently observed in these regions. (2) In the parietal cortex and several regions surrounding the ischemic core, CBF was >40% of the contralateral values 1 hour after embolization and recovered gradually with time (ischemic penumbra). In these regions, CMRglc at 24 hours increased compared with that in the contralateral regions, indicating an uncoupling of CBF and CMRglc. No obvious TTC-unstained lesions were detected in these regions. The authors demonstrated a gradual recovery of reduced CBF, an elevated CMRglc and a CBF-CMRglc uncoupling in the penumbra regions of the primate model. Positron emission tomography investigations using this model will provide better understanding of the pathophysiology of thromboembolic stroke in humans.

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CO2 reactivity and heterogeneity of cerebral blood flow in ischemic, border zone, and normal cortex

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.2.h473 ◽

1989 ◽

Vol 257 (2) ◽

pp. H473-H482 ◽

Cited By ~ 5

Author(s):

S. C. Jones ◽

B. Bose ◽

A. J. Furlan ◽

H. T. Friel ◽

K. A. Easley ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Regional Analysis ◽

Border Zone ◽

Core Area ◽

Border Zones ◽

Short Period ◽

Thioflavine S ◽

Ischemic Core ◽

Normal Cortex

Regional arterial CO2 tension (PaCO2) reactivity of cerebral blood flow (CBF) and the effect of PaCO2 on the spatial and temporal heterogeneity of CBF were investigated by using autoradiographically determined CBF in the rat middle cerebral artery occlusion model after a 2-h period under pentobarbital anesthesia to clarify the relation between PaCO2 reactivity, CBF heterogeneity, and the temporal cycling of CBF. PaCO2 was adjusted to one of four levels. CBF was determined in four cortical areas and white matter using the tissue fractionation of [14C]iodoantipyrine [( 14C]IAP) in combination with vessel mapping using in vivo 4% thioflavine S. Specific PaCO2 reactivity and CBF were normal in the nonischemic cortex, normal, although slightly depressed, in the border zone far from the ischemic core area, and depressed in the border zone adjacent to the ischemic core area (P less than 0.001) and the ischemic core (P less than 0.001). In normocapnic and hypocapnic animals, CBF heterogeneity in the form of regularly spaced CBF columns perpendicular to the cortical surface was observed in the nonischemic hemisphere but was absent in the ischemic core area. In hypercapnic rats, flow columns were present in the ischemic core areas and border zones but were absent on the nonischemic side. There was a highly significant interaction (P less than 0.0001) in observer-determined heterogeneity grades between PaCO2 level and each of three areas, normal, border zone, and ischemic core. In normal cortex, comparison of the thioflavine S-stained vessels with the flow columns provided evidence supporting the concept of capillary recruitment and cycling as a mode of normal cerebral blood flow control. The presence of flow columns in severely ischemic areas in hypercapnic animals indicates that a short period of high PaCO2 transiently augments microregional flow and could enhance the delivery of a therapeutic agent to these microregions of the ischemic core. The regional analysis of PaCO2 reactivity suggests an index of future tissue viability.

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Dissecting the Role of Smooth Muscle Cells versus Pericytes in Regulating Cerebral Blood Flow Using In Vivo Optical Imaging

Neuron ◽

10.1016/j.neuron.2015.06.024 ◽

2015 ◽

Vol 87 (1) ◽

pp. 4-6 ◽

Cited By ~ 10

Author(s):

Jenna Mazzoni ◽

Tyler Cutforth ◽

Dritan Agalliu

Keyword(s):

Blood Flow ◽

Smooth Muscle ◽

Cerebral Blood Flow ◽

Smooth Muscle Cells ◽

Optical Imaging ◽

Muscle Cells ◽

In Vivo Optical Imaging

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Procedure and protocols for optical imaging of cerebral blood flow and hemodynamics in awake mice

Biomedical Optics Express ◽

10.1364/boe.394649 ◽

2020 ◽

Vol 11 (6) ◽

pp. 3288

Author(s):

Yuandong Li ◽

Adiya Rakymzhan ◽

Peijun Tang ◽

Ruikang K. Wang

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Optical Imaging

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Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2021-018239 ◽

2021 ◽

pp. neurintsurg-2021-018239

Author(s):

Gregory A Christoforidis ◽

Niloufar Saadat ◽

Mira Liu ◽

Yong Ik Jeong ◽

Steven Roth ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Infarct Volume ◽

Artery Occlusion ◽

Bolus Administration ◽

Ischemic Core ◽

Cerebral Artery Occlusion

BackgroundSanguinate, a bovine PEGylated carboxyhemoglobin-based oxygen carrier with vasodilatory, oncotic and anti-inflammatory properties designed to release oxygen in hypoxic tissue, was tested to determine if it improves infarct volume, collateral recruitment and blood flow to the ischemic core in hyperacute middle cerebral artery occlusion (MCAO).MethodsUnder an IACUC approved protocol, 14 mongrel dogs underwent endovascular permanent MCAO. Seven received Sanguinate (8 mL/kg) intravenously over 10 min starting 30 min following MCAO and seven received a similar volume of normal saline. Relative cerebral blood flow (rCBF) was assessed using neutron-activated microspheres prior to MCAO, 30 min following MCAO and 30 min following intervention. Pial collateral recruitment was scored and measured by arterial arrival time (AAT) immediately prior to post-MCAO microsphere injection. Diffusion-weighted 3T MRI was used to assess infarct volume approximately 2 hours after MCAO.ResultsMean infarct volumes for control and Sanguinate-treated subjects were 4739 mm3 and 2585 mm3 (p=0.0443; r2=0.687), respectively. Following intervention, rCBF values were 0.340 for controls and 0.715 in the Sanguinate group (r2=0.536; p=0.0064). Pial collateral scores improved only in Sanguinate-treated subjects and AAT decreased by a mean of 0.314 s in treated subjects and increased by a mean of 0.438 s in controls (p<0.0276).ConclusionPreliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration.

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Cerebral Blood Flow Recorded At High Sensitivity in Two Dimensions Using High Resolution Optical Imaging

3rd IEEE International Symposium on Biomedical Imaging: Macro to Nano, 2006. ◽

10.1109/isbi.2006.1625155 ◽

2006 ◽

Cited By ~ 3

Author(s):

I. Vanzetta ◽

T. Deneux ◽

G. Masson ◽

O. Faugeras

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

High Resolution ◽

Optical Imaging ◽

High Sensitivity ◽

Two Dimensions

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Frontiers in Optical Imaging of Cerebral Blood Flow and Metabolism

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.195 ◽

2012 ◽

Vol 32 (7) ◽

pp. 1259-1276 ◽

Cited By ~ 96

Author(s):

Anna Devor ◽

Sava Sakadžić ◽

Vivek J Srinivasan ◽

Mohammad A Yaseen ◽

Krystal Nizar ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Optical Imaging ◽

Three Dimensional ◽

Digital Cameras ◽

Flow Measurements ◽

Optical Fluorescence ◽

Resolution Imaging ◽

Blood Flow Measurements

In vivo optical imaging of cerebral blood flow (CBF) and metabolism did not exist 50 years ago. While point optical fluorescence and absorption measurements of cellular metabolism and hemoglobin concentrations had already been introduced by then, point blood flow measurements appeared only 40 years ago. The advent of digital cameras has significantly advanced two-dimensional optical imaging of neuronal, metabolic, vascular, and hemodynamic signals. More recently, advanced laser sources have enabled a variety of novel three-dimensional high-spatial-resolution imaging approaches. Combined, as we discuss here, these methods are permitting a multifaceted investigation of the local regulation of CBF and metabolism with unprecedented spatial and temporal resolution. Through multimodal combination of these optical techniques with genetic methods of encoding optical reporter and actuator proteins, the future is bright for solving the mysteries of neurometabolic and neurovascular coupling and translating them to clinical utility.

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