The effect of preexisiting hyperglycemia on cerebral blood flow (CBF) and brain penetrating arterioles before and after 2 h of ischemia and 30 min of reperfusion was determined. Male Wistar rats that were either hyperglycemic (50 mg/kg streptozotocin; n=24) or normoglycemic (n=24) were subjected to transient ischemia by filament occlusion or nonischemic. CBF was measured prior to ischemia using microspheres and during transient ischemia using laser Doppler. Edema was compared by wet/dry weights. Constriction to apamin, TRAM-34, and L-NNA, inhibitors of small- and intermediate-conductance calcium-activated potassium channels (SK and IK) and nitric oxide, were compared in penetrating arterioles from the ischemic hemisphere to investigate changes in basal tone and endothelium-dependent vasodilator responses. Preexisiting hyperglycemia did not affect CBF in non-ischemic animals or after transient ischemia; however, edema was significantly greater. Ischemia and reperfusion caused decreased basal tone in penetrating arterioles similarly in normoglycemic and hyperglycemic animals that was restored by apamin, and further increased by TRAM-34 and L-NNA. The restoration of tone in penetrating arterioles by apamin and TRAM-34 suggests that transient ischemia activates SK and IK channels in penetrating arterioles. This effect of ischemia was not different between normoglycemic and hyperglycemic animals, suggesting that it was related to ischemia and reperfusion rather than hyperglycemia.
Hyperglycemia; Ischemic stroke; Lenticulostriate arterioles; Calcium-activated potassium channels; Cerebral edema
A 75-year-old man with a recent history of transient left hemiparesis and dysarthria was referred to our hospital. Angiography showed right internal carotid artery (ICA) occlusion and left ICA 89% stenosis. Positron emission tomography (PET) showed decreased cerebral blood flow (CBF), and increased oxygen extraction fraction (OEF) and cerebral blood volume (CBV) in the right hemisphere.
In the left hemisphere, CBV was increased, but CBF and OEF remained normal. One month after the transient ischemic attack, left carotid artery stenting (CAS) was performed without complications. Diffusion-weighted magnetic resonance imaging (MRI) on the day after CAS showed no fresh ischemic lesion. PET on the second day after CAS showed increased CBF and decreased OEF and CBV in the right hemisphere as compared with those before CAS. In the left hemisphere, decreased CBV was observed and CBF was slightly increased as compared with those before CAS.
The postoperative course was uneventful, but on the fifth day after CAS, the patient suddenly showed a focal seizure and right motor weakness. Emergency computed tomography scanning showed massive intracranial hemorrhage with severe brain edema in the left hemisphere. Although CBF study is useful to predict the hyperperfusion syndrome, we cannot disregard the possibility of intracerebral hemorrhage after CAS for carotid artery stenosis when there is no evidence of hyperperfusion on postoperative CBF study.
hyperperfusion, carotid artery stenting, positron emission tomography
A primary focus of neurointensive care is the prevention of secondary brain injury, mainly caused by ischemia. A noninvasive bedside technique for continuous monitoring of cerebral blood flow (CBF) could improve patient management by detecting ischemia before brain injury occurs. A promising technique for this purpose is diffuse correlation spectroscopy (DCS) since it can continuously monitor relative perfusion changes in deep tissue. In this study, DCS was combined with a time-resolved near-infrared technique (TR-NIR) that can directly measure CBF using indocyanine green as a flow tracer. With this combination, the TR-NIR technique can be used to convert DCS data into absolute CBF measurements. The agreement between the two techniques was assessed by concurrent measurements of CBF changes in piglets. A strong correlation between CBF changes measured by TR-NIR and changes in the scaled diffusion coefficient measured by DCS was observed (R2 = 0.93) with a slope of 1.05 ± 0.06 and an intercept of 6.4 ± 4.3% (mean ± standard error).
(170.1470) Blood or tissue constituent monitoring; (170.3660) Light propagation in tissues; (170.3890) Medical optics instrumentation
Data on the optimal head position for patients with acute ischemic stroke are unavailable. We evaluated the effects of mild head-down tilt (HDT) on cerebral blood flow (CBF) in mice during bilateral common carotid artery occlusion (BCCAO).
Materials and Methods:
We used mice with BCCAO (35 minutes) and divided these into 2 groups ( n=16): BCCAO at 0°-HDT and 5°-HDT. CBF was measured for both hemispheres with a non-invasive laser Doppler blood perfusion imager. Changes in CBF during BCCAO were examined in both groups.
A significantly greater increase in CBF in both hemispheres was observed in 5°-HDT mice than in 0°-HDT mice (126.1% (8.715)% vs. 102.1% (4.718)%; P=0.0294).
HDT enhanced the increase in CBF in both hemispheres in the mouse BCCAO model. The potential mechanism underlying CBF increase enhanced by HDT during BCCAO warrants further investigation.
Bilateral common carotid artery occlusion; brain infarction; cerebral blood flow; head down; mouse
The availability of genetically engineered mice allows unraveling the role of specific proteins in mechanisms of ischemic brain injury. Due to the high variability of their vascular anatomy, mouse models of global cerebral ischemia are rather complex. In the present study, we describe a simple model of mouse forebrain ischemia where the bilateral common carotid artery occlusion (BCCO) is combined with isoflurane-induced hypotension. The forebrain ischemia was induced by BCCO that was preceded by increase of the isoflurane level from 1.5% to 5% in the respiratory gases. This caused a decrease of the mean arterial blood pressure (MABP) to about 30 mmHg and the cerebral blood flow dropped to 5% of the control after the BCCO. During the 10 min ischemic period both MABP and CBF remained stable and the reperfusion was induced by reducing the isoflurane level to 0% followed by removal of the carotid clamps. Mice were allowed 1, 2, 3 or 5 days survival followed by histologic analysis. The number of CA1 uninjured neurons was assessed utilizing a stereological approach.
Neurodegeneration was observed at two days after the onset of reperfusion. At 3 days of recovery, about 40% of neurons survived and the cell death did not further increase at 5 days. Degenerative neurons were also detected in the striatum and sporadically in the cortex. This study demonstrates the feasibility of using the described model in mice that can be utilized to examine the effect of new neuroprotective compounds or use transgenic animals to test new hypothesis.
mouse; global cerebral ischemia; model; hypotension; isoflurane; cell death
This study explored using a novel diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively monitor blood flow and oxygenation changes in head and neck tumors during radiation delivery. A fiber-optic probe connected to the DCS flow-oximeter was placed on the surface of the radiologically/clinically involved cervical lymph node. The DCS flow-oximeter in the treatment room was remotely operated by a computer in the control room. From the early measurements, abnormal signals were observed when the optical device was placed in close proximity to the radiation beams. Through phantom tests, the artifacts were shown to be caused by scattered x rays and consequentially avoided by moving the optical device away from the x-ray beams. Eleven patients with head and neck tumors were continually measured once a week over a treatment period of seven weeks, although there were some missing data due to the patient related events. Large inter-patient variations in tumor hemodynamic responses were observed during radiation delivery. A significant increase in tumor blood flow was observed at the first week of treatment, which may be a physiologic response to hypoxia created by radiation oxygen consumption. Only small and insignificant changes were found in tumor blood oxygenation, suggesting that oxygen utilizations in tumors during the short period of fractional radiation deliveries were either minimal or balanced by other effects such as blood flow regulation. Further investigations in a large patient population are needed to correlate the individual hemodynamic responses with the clinical outcomes for determining the prognostic value of optical measurements.
(170.0170) Medical optics and biotechnology; (170.3660) Light propagation in tissues; (170.3880) Medical and biological imaging; (170.6480) Spectroscopy, speckle
The purpose of this study was to investigate the short-term effects of rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on transient, focal cerebral ischemia in C57BL/6J ob/ob mice with insulin resistance (IR). Male ob/ob, lean, or wild-type (WT) mice were treated with RSV (10 mg/kg per day, i.p.) or vehicle for 3 days. Ischemia was induced by 60 mins of middle cerebral artery occlusion (MCAO) and cortical blood flow (CBF) was monitored by laser-Doppler flowmetry. Infarct volumes were measured 24 h after reperfusion. IR mice exhibited a higher infarct volume compared with Lean or WT mice, and RSV reduced infarct volume only in obese mice (40%±3% versus 32%±3%, P < 0.05). Blood cholesterol and insulin levels were elevated in ob/ob mice but were unaffected by RSV. The CBF reductions during MCAO were similar in all groups and were not affected by RSV. Although RSV did not increase cortical endothelial NO synthase (eNOS) levels in the ob/ob mice, it attenuated the increased cortical expression of intracellular adhesion molecule-1 (ICAM-1) after MCAO from ob/ob mice. Thus, RSV protects against stroke in IR mice by a mechanism independent of effects on the lipid profile, CBF, or eNOS but dependent on suppression of post-MCAO ICAM-1 expression.
middle cerebral artery occlusion; cerebral circulation; endothelial nitric oxide synthase; ICAM-1; statins; strokes
This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation.
Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBFDCS), and changes in oxy-hemoglobin (ΔHbO2), deoxy-hemoglobin (ΔHb), and total hemoglobin concentration (ΔTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBFXeCT) and were then compared to rCBFDCS. Spearman’s rank coefficients were employed to test for associations between rCBFDCS and rCBFXeCT, as well as between rCBF from both modalities and NIRS parameters.
rCBFDCS and rCBFXeCT showed good correlation (rs = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBFDCS and ΔHbO2/ΔTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.
DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.
Near-infrared spectroscopy; Diffuse correlation spectroscopy; Cerebral blood flow; Xenon CT; Neurocritical care
Chronic alcohol consumption impairs cerebral vasoreactivity, and thus may result in an increase in ischemic brain damage. The goal of this study is to examine the influence of chronic alcohol consumption on transient focal ischemia-induced brain damage. Sprague-Dawley rats were divided into two groups, a control group and an alcohol group. Eight weeks after being fed a liquid diet with or without alcohol, responses of parietal pial arterioles to systemic hypoxia and hypercapnia were measured using a cranial window technique. In separate experiments, rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 hours under ketamine/xylazine or isoflurane anesthesia. Regional cerebral blood flow (rCBF) was monitored through a Laser-Doppler flow probe attached to the lateral aspect of the skull. Neurological evaluation and ischemic lesion were assessed 24-hour after reperfusion. Dilation of pial arterioles in response to hypoxia and hypercapnia was significantly reduced in alcohol-fed rats. Alcohol-fed rats had significantly larger infarct volumes and worse neurological outcomes than nonalcoholfed rats under ketamine/xylazine or isoflurane anesthesia. In addition, rCBF measurement indicated that alcohol-fed rats had less regulatory rebound increase in rCBF after the initial drop in rCBF at the onset of MCAO. Our findings suggest that chronic alcohol consumption exacerbates transient focal ischemia-induced brain damage. Increased ischemic brain damage during alcohol consumption may be related to an impaired cerebral vasoreactivity.
To determine the relationship between reductions in the apparent diffusion coefficient of water (ADC) and in cerebral blood flow (CBF) during focal ischemia, we used diffusion-weighted magnetic resonance (D-MR) imaging and autoradiographic CBF analysis to examine rats subjected to 30 or 90 min of permanent middle cerebral artery (MCA) occlusion. In the 30-min occlusion group (n = l0), the area with substantially reduced ADC (15% or more below the contralateral level [ADCJ15]) corresponded best to the area with CBF below 25 ml/lOO g/min and was significantly smaller than the area with CBF below 50 m1/100 g/min (CBF50), a level associated with reduced protein synthesis and delayed necrosis (40 ± 13% versus 74 ± 8% of the ischemic hemisphere; P < 0.OOOl). In the 90-min occlusion group (n = 6), the ADC15 area corresponded best to the CBF30 to CBF35 area and was again significantly smaller than the CBF50 area (54 ± 13% versus 73 ± 20%, P < 0.05). Thus, the area of substantially reduced ADC at 30 and 90 min represents only 53% and 74%, respectively, of the tissue at risk for infarction. These findings indicate a potential limitation in using early D-MR imaging to predict stroke outcome.
diffusion-weighted MRI; focal cerebral ischemia; rat; cerebral blood flow
After recanalization, cerebral blood flow (CBF) can increase above baseline in cerebral ischemia. However, the significance of post-ischemic hyperperfusion for tissue recovery remains unclear. To analyze the course of post-ischemic hyperperfusion and its impact on vascular function, we used magnetic resonance imaging (MRI) with pulsed arterial spin labeling (pASL) and measured CBF quantitatively during and after a 60 minute transient middle cerebral artery occlusion (MCAO) in adult rats. We added a 5% CO2 - challenge to analyze vasoreactivity in the same animals. Results from MRI were compared to histological correlates of angiogenesis. We found that CBF in the ischemic area recovered within one day and reached values significantly above contralateral thereafter. The extent of hyperperfusion changed over time, which was related to final infarct size: early (day 1) maximal hyperperfusion was associated with smaller lesions, whereas a later (day 4) maximum indicated large lesions. Furthermore, after initial vasoparalysis within the ischemic area, vasoreactivity on day 14 was above baseline in a fraction of animals, along with a higher density of blood vessels in the ischemic border zone. These data provide further evidence that late post-ischemic hyperperfusion is a sequel of ischemic damage in regions that are likely to undergo infarction. However, it is transient and its resolution coincides with re-gaining of vascular structure and function.
“Diffuse correlation spectroscopy” (DCS) is a technology for non-invasive transcranial measurement of cerebral blood flow (CBF) that can be hybridized with “near-infrared spectroscopy” (NIRS). Taken together these methods hold potential for monitoring hemodynamics in stroke patients. We explore the utility of DCS and NIRS to measure effects of head-of-bed (HOB) positioning at 30°, 15°, 0°, −5° and 0° angles in patients with acute ischemic stroke affecting frontal cortex and in controls. HOB positioning significantly altered CBF, oxy-hemoglobin (HbO2) and total-hemoglobin (THC) concentrations. Moreover, the presence of an ipsilateral infarct was a significant effect for all parameters. Results are consistent with the notion of impaired CBF autoregulation in the infarcted hemisphere.
Fibrates, one group of peroxisome proliferator-activated receptor (PPAR) activators, are lipid lowering drugs. Fibrates have been shown to attenuate brain tissue injury after focal cerebral ischemia. In this study, we investigated the impact of fenofibrate on cerebral blood flow (CBF) in male wild-type and PPARα-null mice. Animals were treated for 7 days with fenofibrate and subjected to 2 h of filamentous middle cerebral artery occlusion (MCAO) and reperfusion under isoflurane anesthesia. Cortical surface CBF was measured by laser speckle imaging. Regional CBF (rCBF) in non-ischemic animals was measured by 14C-iodoantipyrine autoradiography. Fenofibrate did not affect rCBF and mean arterial blood pressure in non-ischemic animals. In ischemic animals, laser speckle imaging showed delayed expansions of ischemic area, which was attenuated by fenofibrate. Fenofibrate also enhanced CBF recovery after reperfusion. However, such effects of fenofibrate on CBF in the ischemic brain were not observed in PPARα-null mice. These findings show that fenofibrate improves CBF in the ischemic hemisphere. Moreover, fenofibrate requires PPARα expression for the cerebrovascular protective effects in the ischemic brain.
neuroprotection; nuclear receptors; fibrate; PPAR; eNOS; autoradiography; cerebral ischemia
After complete cerebral ischemia, the postischemic blood flow response to functional activation is severely attenuated for several hours. However, little is known about the spatial and temporal extent of the blood flow response in the acute postischemic period after incomplete cerebral ischemia. To investigate the relative cerebral blood flow (rCBF) response in the somatosensory cortex of rat to controlled vibrissae stimulation after transient incomplete ischemia (15-min bilateral common carotid artery occlusion + hypotension), we employed laser speckle imaging combined with statistical parametric mapping. We found that the ischemic insult had a significant impact on the baseline blood flow (P < 0.005) and the activation area in response to functional stimulation was significantly reduced after ischemia (P < 0.005). The maximum rCBF response in the activation area determined from the statistical analysis did not change significantly up to 3 h after ischemia (P > 0.1). However, the time when rCBF response reached its maximum was significantly delayed (P < 0.0001) from 2.4 ± 0.2 secs before ischemia to 3.6 ± 0.1 secs at 20 mins into reperfusion (P < 0.001); the delay was reduced gradually to 2.9 ± 0.2 secs after 3 h, which was still significantly greater than that observed before the insult (P = 0.04).
cerebral blood flow; cerebral ischemia; functional activation; functional recovery; laser speckle imaging; statistical parametric map
Objective: It has been proposed that cerebral blood flow (CBF) response to acetazolamide may be reduced according to the degree of autoregulatory vasodilation in regions with normal oxygen extraction fraction (OEF), whereas the CBF response may be absent in regions with increased OEF where vasodilation may be maximal in response to reduced perfusion pressure. The objective of this study was to test this hypothesis.
Methods: Positron emission tomography (PET) was used to study 30 symptomatic patients with carotid artery steno-occlusive lesions. CBF at baseline and 10 minutes after an intravenous injection of 1 g acetazolamide was measured. The correlation between the change in CBF during acetazolamide administration and the baseline value of OEF in the affected hemisphere was examined.
Results: The baseline OEF value was inversely and non-linearly correlated with the percentage change in CBF during acetazolamide administration (R2 = 0.25, p = 0.02). There was an upward trend of OEF with diminishing acetazolamide response below a critical level around zero response. Acetazolamide response less than 6.65% over baseline (sensitivity 100%, specificity 89%, positive predictive value 50%, negative predictive value 100%) was established as most helpful in predicting abnormally high OEF.
Conclusions: The inverse, non-linear relationship between OEF and CBF response to acetazolamide suggests that these two measurements may not identify haemodynamic impairment in the same patients.
Combined functional, perfusion and diffusion magnetic resonance imaging (MRI) with a temporal resolution of 30 mins was performed on permanent and transient focal ischemic brain injury in rats during the acute phase. The apparent diffusion coefficient (ADC), baseline cerebral blood flow (CBF), and functional MRI (fMRI) blood-oxygen-level-dependent (BOLD), CBF, and CMRO2 responses associated with CO2 challenge and forepaw stimulation were measured. An automated cluster analysis of ADC and CBF data was used to track the spatial and temporal progression of different tissue types (e.g., normal, ‘at risk,’ and ischemic core) on a pixel-by-pixel basis. With permanent ischemia (n = 11), forepaw stimulation fMRI response in the primary somatosensory cortices was lost, although vascular coupling (CO2 response) was intact in some animals. Control experiments in which the right common carotid artery was ligated without causing a stroke (n = 8) showed that the delayed transit time had negligible effect on the fMRI responses in the primary somatosensory cortices. With temporary (15-mins, n = 8) ischemia, transient CBF and/or ADC declines were observed after reperfusion. However, no T2 or TTC lesions were observed at 24 h except in two animals, which showed very small subcortical lesions. Vascular coupling and forepaw fMRI response also remained intact. Finally, comparison of the relative and absolute fMRI signal changes suggest caution when interpreting percent changes in disease states in which the baseline signals are physiologically altered; quantitative CBF fMRI are more appropriate measures. This approach provides valuable information regarding ischemic tissue viability, vascular coupling, and functional integrity associated with ischemic injury and could have potential clinical applications.
BOLD; CBF; CMRO2; DWI; fMRI; ISODATA; penumbra; perfusion–diffusion mismatch; PWI
Epileptic events elicit a large focal increase in cerebral blood flow (CBF) to perfuse metabolically active neurons in the focus. Conflicting data exists, however, on whether hemoglobin saturation increases or decreases in the focus and surrounding cortex, and whether CBF increases globally or is decreased in adjacent areas. How these hemodynamic events correlate with actual changes in tissue oxygenation is also not known. Using laser Doppler flowmetry, oxygen microsensors and intrinsic optical imaging spectroscopy, we demonstrate that the dip in hemoglobin in the focus correlates with a profound but temporary decrease in tissue oxygenation in spite of a large increase in cerebral blood flow (CBF). Furthermore, CBF simultaneously decreases in the cortex immediately adjacent to the focus. These events are then replaced with a longer duration, less focal increase in CBF, CBV and hyperoxygenation, the duration of which correlates with the duration of the seizure. These findings raise the question of whether transient focal hypoxia and vascular steal might contribute to progressive deleterious effects of chronic epilepsy on the adult and developing brain. Possible mechanisms based on recent astrocyte-based models of neurovascular coupling are discussed. Implications for functional magnetic resonance imaging of epileptic events are discussed.
Cerebral blood flow; cerebral cortex; epilepsy; optical imaging; seizure; tissue oxygen
Fibrates, one group of peroxisome proliferator-activated receptor (PPAR) activators, are lipid lowering drugs. Fibrates have been shown to attenuate brain tissue injury after focal cerebral ischemia. In this study, we investigated the impact of fenofibrate on cerebral blood flow (CBF) in male wild type and PPARα-null mice. Animals were treated for 7 days with fenofibrate and subjected to 2 h of filamentous middle cerebral artery occlusion and reperfusion under isoflurane anesthesia. Cortical surface CBF was measured by laser speckle imaging. Regional CBF (rCBF) in nonischemic animals was measured by 14C-iodoantipyrine autoradiography. Fenofibrate did not affect rCBF and mean arterial blood pressure in nonischemic animals. In ischemic animals, laser speckle imaging showed delayed expansions of ischemic area, which was attenuated by fenofibrate. Fenofibrate also enhanced CBF recovery after reperfusion. However, such effects of fenofibrate on CBF in the ischemic brain were not observed in PPARα-null mice. These findings show that fenofibrate improves CBF in the ischemic hemisphere. Moreover, fenofibrate requires PPARα expression for the cerebrovascular protective effects in the ischemic brain.
autoradiography; cerebral ischemia; eNOS; fibrate; nuclear receptors; neuroprotection
Magnetic resonance imaging (MRI) with oxygen challenge (T2∗ OC) uses oxygen as a metabolic biotracer to define penumbral tissue based on CMRO2 and oxygen extraction fraction. Penumbra displays a greater T2∗ signal change during OC than surrounding tissue. Since timely restoration of cerebral blood flow (CBF) should salvage penumbra, T2∗ OC was tested by examining the consequences of reperfusion on T2∗ OC-defined penumbra. Transient ischemia (109±20 minutes) was induced in male Sprague-Dawley rats (n = 8). Penumbra was identified on T2∗-weighted MRI during OC. Ischemia and ischemic injury were identified on CBF and apparent diffusion coefficient maps, respectively. Reperfusion was induced and scans repeated. T2 for final infarct and T2∗ OC were run on day 7. T2∗ signal increase to OC was 3.4% in contralateral cortex and caudate nucleus and was unaffected by reperfusion. In OC-defined penumbra, T2∗ signal increased by 8.4%±4.1% during ischemia and returned to 3.25%±0.8% following reperfusion. Ischemic core T2∗ signal increase was 0.39%±0.47% during ischemia and 0.84%±1.8% on reperfusion. Penumbral CBF increased from 41.94±13 to 116.5±25 mL per 100 g per minute on reperfusion. On day 7, OC-defined penumbra gave a normal OC response and was located outside the infarct. T2∗ OC-defined penumbra recovered when CBF was restored, providing further validation of the utility of T2∗ OC for acute stroke management.
ADC; CBF; imaging; MCAO; T2*
Magnetic resonance imaging (MRI) with oxygen challenge (T2* OC) uses oxygen as a metabolic biotracer to define penumbral tissue based on CMRO2 and oxygen extraction fraction. Penumbra displays a greater T2* signal change during OC than surrounding tissue. Since timely restoration of cerebral blood flow (CBF) should salvage penumbra, T2* OC was tested by examining the consequences of reperfusion on T2* OC-defined penumbra. Transient ischemia (109±20 minutes) was induced in male Sprague-Dawley rats (n=8). Penumbra was identified on T2*-weighted MRI during OC. Ischemia and ischemic injury were identified on CBF and apparent diffusion coefficient maps, respectively. Reperfusion was induced and scans repeated. T2 for final infarct and T2* OC were run on day 7. T2* signal increase to OC was 3.4% in contralateral cortex and caudate nucleus and was unaffected by reperfusion. In OC-defined penumbra, T2* signal increased by 8.4%±4.1% during ischemia and returned to 3.25%±0.8% following reperfusion. Ischemic core T2* signal increase was 0.39%±0.47% during ischemia and 0.84%±1.8% on reperfusion. Penumbral CBF increased from 41.94±13 to 116.5±25 mL per 100 g per minute on reperfusion. On day 7, OC-defined penumbra gave a normal OC response and was located outside the infarct. T2* OC-defined penumbra recovered when CBF was restored, providing further validation of the utility of T2* OC for acute stroke management.
ADC; CBF; imaging; MCAO; T2*
Voltage-dependent anion channel (VDAC) is the main protein in mitochondria-mediated apoptosis, and the modulation of VDAC may be induced by the excessive release of extracellular glutamate. This study examined the role of glutamate release on VDAC-mediated apoptosis in an eleven vessel occlusion model in rats. Male Sprague-Dawley rats (250–350 g) were used for the 11 vessel occlusion ischemic model, which were induced for a 10-min transient occlusion. During the ischemic and initial reperfusion episode, the real-time monitoring of the extracellular glutamate concentration was measured using an amperometric microdialysis biosensor and the cerebral blood flow (CBF) was monitored by laser-Doppler flowmetry. To confirm neuronal apoptosis, the brains were removed 72 h after ischemia to detect the neuron-specific nuclear protein and pro-apoptotic proteins (cleaved caspase-3, VDAC, p53 and BAX). The changes in the mitochondrial morphology were measured by atomic force microscopy. A decrease in the % of CBF was observed, and an increase in glutamate release was detected after the onset of ischemia, which continued to increase during the ischemic period. A significantly higher level of glutamate release was observed in the ischemia group. The increased glutamate levels in the ischemia group resulted in the activation of VDAC and pro-apoptotic proteins in the hippocampus with morphological alterations to the mitochondria. This study suggests that an increase in glutamate release promotes VDAC-mediated apoptosis in an 11 vessel occlusion ischemic model.
Regional cerebral blood flow (CBF), oxygen utilisation, fractional oxygen extraction (OER) and cerebral blood volume (CBV) were measured by positron emission tomography (PET) in 21 patients with occlusive carotid artery disease. In the same patients, measurements of cerebral CO2 reactivity were performed using the intravenous xenon-133 technique. A significant correlation was found in symptomatic hemispheres between the CBF/CBV ratio and CO2 reactivity. Four patients had significant increases in OER and this was associated with a reduction in CBF/CBV ratio implying exhaustion of haemodynamic reserve. CO2 reactivity was reduced below 1.5% mm Hg in all four cases with raised OER but only in two cases with normal OER. In patients with CO2 reactivities above 1.5% mm Hg, OER was normal in all cases. It is concluded that measurements of CO2 reactivity provide a satisfactory method for assessing cerebral haemodynamic reserve.
Acetazolamide (ACZ) was used to stimulate the cerebral vasculature on ten healthy volunteers to assess the cerebral vasomotor reactivity (CVR). We have combined near infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS) and transcranial Doppler (TCD) technologies to non-invasively assess CVR in real-time by measuring oxy- and deoxy-hemoglobin concentrations, using NIRS, local cerebral blood flow (CBF), using DCS, and blood flow velocity (CBFV) in the middle cerebral artery, using TCD. Robust and persistent increases in oxy-hemoglobin concentration, CBF and CBFV were observed. A significant agreement was found between macro-vascular (TCD) and micro-vascular (DCS) hemodynamics, between the NIRS and TCD data, and also within NIRS and DCS results. The relative cerebral metabolic rate of oxygen, rCMRO2, was also determined, and no significant change was observed. Our results showed that the combined diffuse optics-ultrasound technique is viable to follow (CVR) and rCMRO2 changes in adults, continuously, at the bed-side and in real time.
(170.3660) Light propagation in tissues; (170.3890) Medical optics instrumentation; (170.6480) Spectroscopy, speckle; (170.7170) Ultrasound; (290.4210) Multiple scattering
Hemodynamic instability during and after carotid artery stenting (CAS) may reduce cerebral blood flow (CBF), leading to cerebral ischemia. To investigate changes in CBF in the periprocedural period, we continuously recorded the regional cerebral oxygen saturation (rSO2) using near-infrared spectroscopy.
In 46 consecutive patients with carotid artery stenosis, rSO2 was continuously recorded during and after CAS. In addition, the patients underwent SPECT to evaluate a change in CBF on the next day after CAS.
Introprocedural bradycardia (heart rate <50 bpm) occurred in 21 patients (46%) including one transient cardiac arrest. Intraprocedural hypotension (systolic blood pressure <80 mmHg) occurred in 18 patients (39%), and 16 of them showed prolonged hypotension. The rSO2 in patients with bradycardia/hypotension during CAS was significantly less than that in patients without them (p<0.01). Moreover, the SPECT on the next day after CAS demonstrated that the ipsilateral CBF in patients with bradycardia/hypotension during CAS significantly more than that in patients without them (p<0.05).
Intraprocedural hemodynamic instability resulted in a significant decrease in rSO2, leading to a possible severe cerebral ischemia. In addition, intraprocedural bradycardia/hypotension might be related with postprodedural hyperperfusion, causing the morbidity and mortality after CAS.
carotid artery stenting, bradycardia, hypotension, oxygen saturation
The pre-clinical global ischemia model transient bilateral common carotid artery occlusion addresses the unique cascade of events leading to delayed neuronal cell death. However, the inconsistent occurrence of posterior communicating arteries (PcomA) in mice might cause high outcome variability. To determine a means for reducing variability, CD1 mice were subjected to bilateral common carotid artery occlusion for 12 to 40 min. Occlusion duration ≥18 min was applied to mice with bilateral regional cerebral blood flow (rCBF) ≥10% of baseline at 2.5 min of ischemia. However, only groups with ischemic duration ≤18 min were used for statistical analysis because of the high mortality in the other groups. After 7 days, patency of PcomA and hippocampal neuronal loss in the CA1 subfield were evaluated. Outcome variability was reduced when hemispheres containing PcomA were excluded from analysis; ischemic outcome was not affected by the presence of a contralateral PcomA. Extending ischemic duration based on rCBF did not reduce outcome variability because the initial rCBF could not reliably predict PcomA. Therefore, after an optimal ischemic duration, evaluating hippocampal injury in each hemisphere independently according to the existence of PcomA is an effective and reliable method to obtain consistent results in this pre-clinical mouse model.
Cerebral blood flow; Global ischemia; Hippocampus; Posterior communicating artery