Mean Regional Cerebral Blood Flow Research Articles

A longitudinal analysis of cerebral blood flow changes in genetic frontotemporal Dementia: Results from genfi

AbstractBackgroundMutations in the C9orf72, GRN, or MAPT genes are the most prevalent genetic causes of familial frontotemporal dementia (FTD). In a cross‐sectional study of genetic FTD, lower CBF was observed in presymptomatic FTD mutation carriers vs. controls from the same families in 6 regions of interest: the bilateral anterior cingulate cortex, the left medial temporal gyrus, the left and right insulae, and the left and right supramarginal gyri (Mutsaerts et. al. 2019). However, there have been no studies to date that identify longitudinal changes in CBF between FTD genetic subgroups (both presymptomatic and symptomatic) compared to controls.MethodWe compared longitudinal changes in CBF, as measured by ASL‐MRI, in 317 FTD mutation carriers (118 C9orf72, 141 GRN, and 58 MAPT) vs. 261 non‐carrier controls from the Genetic FTD Initiative (GENFI). Linear mixed effects models tested the main effect of carrier status, and its interaction with age, along with covariates of age, sex, site‐of‐scan against each subject’s mean regional cerebral blood flow within the regions of interest from Mutsaerts et al. (2019). Family membership was a random intercept in the model to control for similar genetic and environmental backgrounds.ResultDifferences between genetic subsets of FTD were apparent, with GRN carriers preferentially experiencing decreases within the salience network regions while MAPT carriers expressed differences within the left medial temporal gyrus and bilateral anterior cingulate gyrus. C9orf72 carriers only saw a decrease in CBF within the left insula. Significant interactions between carrier status and age were exclusively evident in MAPT carriers across all regions of interest.ConclusionDifferentiating CBF signatures were found to exist between the genetic FTD subgroups, with the most prominent changes being seen in GRN and MAPT subsets. Evidence continues to mount that CBF may be a viable biomarker in the earlier detection and delineation of genetic FTD variants.

Assessment of regional cerebral blood flow by ct perfusion in patients of Alzheimer’s disease

Background: Alzheimer’s disease is a neurodegenerative disorder and is characterized by progressive cognitive decline which starts with an impairment in the ability to recollect recent memories, but eventually affects all the intellectual functions and finally leads to a total dependence for basic functions of daily life culminating into premature death. Dementia can be defined as a clinical syndrome characterized by a cluster of symptoms and signs manifested by difficulties in memory, disturbances in language and other cognitive functions, changes in behavior, and impairments in activities of daily living. Alzheimer is an age-associated degenerative disorder. The burden of Alzheimer’s disease and that of dementia per se is dependent on age. With increasing life expectancy, the proportion of elderly is increasing and so is the number of patients with Alzheimer’s disease associated dementia. Material and Method: This cross-sectional study was carried out for duration of 18 months at Department of Radiodiagnosis, Era's Lucknow Medical College, Lucknow with an aim to study the parameters viz. cerebral blood flow and cerebral blood volume and to correlate the finding of CT perfusion with the clinical score of dementia. The Patients attending adult psychiatry OPD diagnosed as a case of Alzheimer's as per DSM 4 criteria by fulfilling the inclusion criteria and giving informed consent were taken up for study. They were also evaluated for socio-demographic details and illness related variables. After obtaining an informed consent, demographic information, duration and nature of complaints was noted. All the patients were then subjected to CT Perfusion evaluation. Dementia severity was assessed using Clinical Dementia Rating Scale (CDRS).Result: Age of patients ranged from 60 to 75 years with a mean of 66±4.03 years. Majority of cases were aged between 60 and 69 years (77.5%). There were only 9 patients aged >70 years (22.5%).Forgetfulness (40%), difficulty in thinking (27.5%) and mental confusion (27.5%) were the three most common presenting complaints followed by loneliness (22.5%), agitation (17.5%), depression and mental decline (15% each). Inability to recognize (10%) and hallucinations (7.5%) were among the least common presenting complaints. According to clinical dementia score, a total of 16 (40%) patients were categorized as mild dementia, 20 (50%) as moderate dementia and 4 (10%) as severe dementia respectively. Mean regional cerebral blood flow values for right frontal, left frontal, left temporal, right occipital, right lenticular nucleus and left lenticular nucleus were 39.46±3.82, 39.33±3.87, 45.59±4.66, 45.51±5.02, 45.59±4.76, 45.65±4.49, 42.57±4.23 and 42.87±4.81 ml/100 g/min respectively. Mean global CBF was calculated as 43.32±4.29 ml/100 g/min. Mean regional cerebral blood volume values for right frontal, left frontal, left temporal, right occipital, right lenticular nucleus and left lenticular nucleus were 2.56±0.49, 2.62±0.54, 2.97±0.50, 3.03±0.56, 2.95±0.48, 2.92±0.52, 3.13±0.55 and 3.13±0.55 ml/100 g respectively. Mean global CBF was calculated as 2.91±0.49 ml/100 g/min.Conclusion: A total of 40 patients of Alzheimer’s disease aged 60 to 75 years (Mean age 66±4.03 years; 65% males) were enrolled and subjected to clinical and CT evaluation. According to clinical dementia score, a total of 16 (40%) patients were categorized as mild dementia, 20 (50%) as moderate dementia and 4 (10%) as severe dementia respectively. Mean cerebral blood flow (CBF) ranged from 39.33±3.87 ml/100 g/min (Left frontal region) to 45.65±4.49 ml/100 g/min (Left occipital region) among different brain regions. Mean global CBF was 43.32±4.29 ml/100 g/min.

Efficacy of Early Superficial Temporal Artery–Middle Cerebral Artery Double Anastomoses for Atherosclerotic Occlusion in Patients with Progressing Stroke

We investigated the efficacy of early superficial temporal artery-middle cerebral artery (STA-MCA) double anastomoses for patients with progressing stroke due to atherosclerotic occlusion. Nine consecutive patients who underwent early STA-MCA double anastomoses were enrolled. All patients presented with progressing stroke despite maximal medical treatment. Cerebral blood flow in 7 patients was analyzed by single-photon emission tomography. Clinical outcomes were investigated postoperatively, and we evaluated the utility of early STA-MCA double anastomoses. Nine patients in the present study included those with middle cerebral artery occlusion (n = 6) and internal carotid artery occlusion (n = 3). The mean age was 58.4 years. Subjects comprised 1 female (11.1%) and 8 males (88.9%). The cause was low perfusion ischemia due to atherosclerotic occlusion with a small infarct. The mean regional cerebral blood flow (rCBF) ratio in the middle cerebral artery territory compared to the normal side was 69.6 ± 5.3%. The duration from onset to surgery was 1-8 days (median, 3.11 days). All patients underwent early STA-MCA double anastomoses, and no reperfusion-induced hemorrhage occurred. All of them slowly achieved obvious remission compared to symptoms on admission and achieved a good functional outcome. Early STA-MCA double anastomoses were safe and effective, and early revascularization resulted in rapid neurological improvement. We recommend this procedure for patients with progressive ischemia due to main trunk artery occlusion, when the rCBF flow ratio with the normal side was 70 ± 10%, even at the subacute stage.

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome.

OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

Impaired Global and Regional Cerebral Perfusion in Newborns with Complex Congenital Heart Disease

To compare global and regional cerebral perfusion in newborns with congenital heart disease (CHD) and healthy controls using arterial spin labeling (ASL) magnetic resonance imaging (MRI) prior to open heart surgery. We performed brain MRIs in 101 newborns (58 controls, 43 CHD) using 3-dimensional fast spin echo pseudo-continuous ASL. Cerebral blood flow (CBF) ASL images were linearly coregistered to T2-weighted images for anatomic delineation and selection of regions-of-interest. Anatomic regions included frontal white matter (FWM), occipital white matter (OWM), thalami, and basal ganglia (BG). Newborns with single ventricle CHD demonstrated significantly lower global (P = .044) and regional BG (P = .025) CBF compared with controls. Mean regional CBF in the thalami in cyanotic newborns with CHD was lower compared with controls (P = .004). Mean regional CBF in thalami (P = .02), BG (P = .01), and OWM (P = .03) among newborns with cyanotic CHD was lower than those with acyanotic CHD. Newborns with CHD ventilated prior to MRI had increased global (P = .016) and OWM (P = .013) CBF compared with those not ventilated. Newborns with uncorrected cyanotic or single ventricle CHD show disturbances in cerebral perfusion compared to healthy controls using ASL. Cardiac physiology and preoperative hemodynamic compromise play an important role in preoperative alterations in global and regional cerebral perfusion. Our data suggest that ASL may be useful for studying cerebral perfusion in newborns at high risk for cerebral ischemia, such as those with complex CHD.

Regional reliability of quantitative signal targeting with alternating radiofrequency (STAR) labeling of arterial regions (QUASAR).

BACKGROUND AND PURPOSEQuantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability.METHODSUsing a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution.RESULTSThe mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries.CONCLUSIONSThus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter.

Beneficial synergistic effects of concurrent treatment with theanine and caffeine against cerebral ischemia–reperfusion injury in rats

Theanine and caffeine, 2 naturally occurring components in tea, have repeatedly been shown to deliver unique cognitive benefits when consumed in combination. In this study, we assessed the beneficial synergistic effects of concurrent treatment with theanine and caffeine against cerebral damage in rats. Theanine and caffeine had no effect on physiological variables, including pH, partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2), mean arterial blood pressure, plasma glucose, or regional cerebral blood flow. Treatment with theanine (1 mg/kg body mass, intraperitoneal injection) alone significantly reduced cerebral infarction induced by cerebral ischemia-reperfusion, but caffeine (10 mg/kg, intravenous administration) alone only had a marginal effect. However, the combination of theanine plus caffeine resulted in a significant reduction of cerebral infarction and brain edema compared with theanine monotherapy. Meanwhile, increased malondialdehyde levels as well as decreased superoxide dismutase activity, glutathione peroxidase activity, and glutathione levels observed in the cerebral cortex after cerebral ischemia-reperfusion were significantly ameliorated by the combination therapy. Furthermore, the elevated inflammatory response levels observed in the cortex after cerebral ischemia-reperfusion were markedly attenuated by the combined treatment. Thus, it is suggested that the neuroprotective potential of a combination therapy with theanine and caffeine against cerebral ischemia-reperfusion is partly ascribed to their antioxidant and anti-inflammatory properties.

Arterial spin labeling in patients with chronic cerebral artery steno-occlusive disease: Correlation with 15O-PET

Heterogeneity of arterial transit time due to cerebral artery steno-occlusive lesions hampers accurate regional cerebral blood flow measurement by arterial spin labeling (ASL). To assess the feasibility of regional cerebral blood flow measurement by ASL with multiple-delay time sampling in patients with steno-occlusive diseases by comparing with positron emission tomography (PET), and to determine whether regional arterial transit time measured by this ASL technique is correlated with regional mean transit time, a PET index of perfusion pressure. Sixteen patients with steno-occlusive diseases received both ASL and (15)O-PET. The mean regional cerebral blood flow measured by ASL and PET, regional arterial transit time by ASL, and regional mean transit time by PET were obtained by a region-of-interest analysis. Correlation between regional cerebral blood flow by ASL and that by PET, and correlation between regional arterial transit time by ASL and regional mean transit time by PET were tested using Pearson's correlation coefficient for both absolute and relative values. A multivariate regression analysis was performed to test whether regional arterial transit time by ASL was a significant contributor in modeling regional mean transit time by PET after controlling the effect of regional cerebral blood flow by ASL. A significant positive correlation was found between regional cerebral blood flow by ASL and that by PET for both absolute (r = 0.520, P < 0.0001) and relative (r = 0.691, P < 0.0001) values. A significant positive correlation was found between regional arterial transit time by ASL and regional mean transit time by PET both for absolute (r = 0.369, P = 0.0002) and relative (r = 0.443, P < 0.0001) values. The regression analysis revealed that regional arterial transit time by ASL was a significant contributor in modeling regional mean transit time by PET after controlling regional cerebral blood flow by ASL (P = 0.0011). The feasibility of regional cerebral blood flow measurement using ASL with multiple-delay time sampling was confirmed in patients with cerebral artery steno-occlusive diseases. Moreover, it was suggested that mapping of regional arterial transit time has the potential to detect hemodynamic impairment.

Contribution of nitric oxide synthase (NOS) in blood–brain barrier disruption during acute focal cerebral ischemia in normal rat

Endogenous level of nitric oxide (NO) is increased in the brain following the stroke, and deactivation of NO synthase has been shown to attenuate its destructive actions in animal stroke models using middle cerebral artery occlusion (MCAO) procedures. However, little is known about the effects of NO in cerebral vascular integrity and edema during acute cerebral ischemia. Here we investigated whether NO plays any role in the progression of blood–brain barrier (BBB) disruption and edema formation in ischemia/reperfusion injury. Intraperitoneal administration of NO substrate l-arginine (300mg/kg), or NOS inhibitor (l-NAME, 1mg/kg), was done in normal rats at 20min before a 60-min MCAO. Mean arterial blood pressures (MAP) and regional cerebral blood flow (rCBF) were continuously recorded during experiment. Neurological deficit score (NDS) was evaluated 12h after termination of MCAO followed with evaluations of cerebral infarction volume (CIV), edema formation and cerebral vascular permeability (CVP), as determined by the Evans blue dye extravasations (EBE) technique. No significant changes were observed in the values of MAP and rCBF with l-arginine or l-NAME during ischemia or reperfusion periods. There was a 75–85% reduction in rCBF in during MCAO which returned back to its pre-occlusion level during reperfusion. Acute cerebral ischemia with or without l-arginine augmented NDS (4.00±0.44 and 3.00±0.30), in conjunction with increased CIV (518±57mm3 and 461±65mm3), provoked edema (3.09±0.45% and 3.30±0.49%), and elevated EBE (8.28±2.04μg/g and 5.09±1.41μg/g). Inhibition of NO production by l-NAME significantly improved NDS (1.50±0.22), diminished CIV (248±56mm3), edema (1.18±0.58%) and EBE (1.37±0.12μg/g). This study reconfirms the cerebroprotective properties of reduced tissue NO during acute ischemic stroke, and it also validates the deleterious actions of increased NOS activity on the disruption of cerebral microvascular integrity and edema formation of ischemia/reperfusion injuries in normal rat, without changing arterial blood pressure or blood flows to ischemic regions.

약용식물 추출물이 흰쥐의 뇌혈류학적 변화에 미치는 영향

As an attempt to develop new functional health beverage by using medicinal herb, we investigated the effect of medicinal plant extract (MPE) on mean arterial blood pressure (MABP) and regional cerebral blood flow (rCBF) of rats. The changes of MABP and rCBF were determined by LDF methods. LDF allows for real time, noninvasive, continuous recordings of local CBF. MABP in MPE treated rats showed significant change of MPE 1.0 and 10.0 mg/kg. MPE i.v. administration showed significant increase of rCBF in a dose-dependent manner. Propranolol pretreated MABP showed significant change in the increase of MPE. rCBF of propranolol pretreated rats showed significant change from the i.v. injection concentration of 1.0 and 10.0 mg/kg. The ischemia/ reperfusion induced oxidative stress may have contributed to cerebral damage in rats, and the present study provides clear evidence for the beneficial effect of MPE on ischemia induced brain injury. Also, the action mechanism in elevation effect of MPE on rCBF might be concerned with the role of β-adrenoceptor. The exact component and mechanism remains for the future study.

Assessment of thalamic perfusion in patients with mild traumatic brain injury by true FISP arterial spin labelling MR imaging at 3T

Objective: To assess cerebral blood flow (CBF) changes in patients with mild traumatic brain injury (MTBI) using an arterial spin labelling (ASL) perfusion MRI and to investigate the severity of neuropsychological functional impairment with respect to haemodynamic changes.Materials and methods: Twenty-one patients with MTBI and 20 healthy controls were studied at 3T MR. The median time since the onset of brain injury in patients was 24.6 months. Both patients and controls underwent a traditional consensus battery of neurocognitive tests. ASL was performed using true fast imaging with steady state precession and a flow-sensitive alternating inversion recovery preparation. Regional CBF were measured in both deep and cortical gray matter as well as white matter at the level of basal ganglia.Results: The mean regional CBF was significantly lower in patients with MTBI (45.9 ± 9.8 ml/100 g min−1) as compared to normal controls (57.1 ± 8.1 ml/100 g min−1; p = 0.002) in both sides of thalamus. The decrease of thalamic CBF was significantly correlated with several neurocognitive measures including processing and response speed, memory/learning, verbal fluency and executive function in patients.Conclusions: Haemodynamic impairment can occur and persist in patients with MTBI, the extent of which is more severe in thalamic regions and correlate with neurocognitive dysfunction during the extended course of disease.

Assessment of the Contribution of the External Carotid Artery to Brain Perfusion in Patients With Internal Carotid Artery Occlusion

The purpose of this study was to prospectively investigate the contribution of the ipsilateral external carotid artery (ECA) to cerebral perfusion in patients with internal carotid artery occlusion. Institutional Review Board approval and informed consent were obtained. Thirty functionally independent patients (24 men, 6 women; mean age, 63 years) with an angiographically proven unilateral internal carotid artery occlusion and transient or minor disabling ischemic attacks ipsilateral to the side of the internal carotid artery occlusion were included. Grading of ECA collateral flow was performed with intraarterial digital subtraction angiography. The contribution of the ECA to regional cerebral blood flow was assessed with selective arterial spin labeling MRI. Differences in regional cerebral blood flow were analyzed with Student t test. Twenty percent of the patients had ECA Grade 0 collateral flow (no filling of ophthalmic artery), 20% Grade 1 (filling of carotid siphon), and 60% Grade 2 (filling of anterior and/or middle cerebral artery) as demonstrated on digital subtraction angiography. Although in the Grade 1 group, the ECA supplied a smaller region of the brain compared with the Grade 2 group, the mean regional cerebral blood flow of the perfusion territory supplied by the ECA is similar (P=0.70) in the Grade 1 group (mean+/-SD 57+/-16 mL/min/100 g) and the Grade 2 group (60+/-12 mL/min/100g). In patients with symptomatic internal carotid artery occlusion, focal brain regions may strongly depend on the contribution to cerebral perfusion of the ECA ipsilateral to the side of the internal carotid artery occlusion, even in patients with limited ECA collateral supply as demonstrated on digital subtraction angiography.

Changes in regional cerebral blood flow demonstrated by 99mTc-HMPAO SPECT in euthymic bipolar patients

Single photon emission computed tomography (SPECT) with 99mTc-HMPAO was used to compare regional cerebral blood flow (rCBF) in patients with bipolar disorder and in healthy controls. The sample of this study consisted of 16 euthymic bipolar patients who met the DSM-IV criteria and 10 healthy control subjects. The mean regional cerebral blood flow values of the bipolar euthymic patients were significantly lower than those of the controls in the bilateral medial-basal temporal, occipital; medial frontal; parietal regions and in the cingulate gyrus; the hypoperfusion in the cingulate had the highest significant P value (.001, Bonferroni correction). No significant differences in rCBF emerged between right and left-brain regions. The most important findings of the current study are the presence of regional cerebral perfusion alterations, particularly in the cingulate gyrus in the euthymic bipolar patients. Our results imply that underlying brain dysfunction may be independent from manic or depressive episodes in bipolar disorder. Because of the small number of subjects, however, this finding should be viewed as preliminary.

Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation*

Acute respiratory dysfunction frequently occurs following severe aneurysmal subarachnoid hemorrhage requiring positive end-expiratory pressure (PEEP) ventilation to maintain adequate oxygenation. High PEEP levels, however, may negatively affect cerebral perfusion. The goal of this study was, to examine the influence of various PEEP levels on intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, and systemic hemodynamic variables. Animal research and clinical intervention study. Surgical intensive care unit of a university hospital. Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients suffering subarachnoid hemorrhage. Under continuous monitoring of intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, mean arterial pressure, and cardiac output, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O in the experimental part and from baseline to 20 cm H2O in the clinical part. In animals, high PEEP levels had no adverse effect on intracranial pressure, brain tissue oxygen tension, or regional cerebral blood flow. In patients with severe subarachnoid hemorrhage, stepwise elevation of PEEP resulted in a significant decrease of mean arterial pressure and regional cerebral blood flow. Analyses of covariance revealed that these changes of regional cerebral blood flow depended on mean arterial pressure changes as a result of a disturbed cerebrovascular autoregulation. Consequently, normalization of mean arterial pressure restored regional cerebral blood flow to baseline values. Application of high PEEP does not impair intracranial pressure or regional cerebral blood flow per se but may indirectly affect cerebral perfusion via its negative effect on macrohemodynamic variables in case of a disturbed cerebrovascular autoregulation. Therefore, following severe subarachnoid hemorrhage, a PEEP-induced decrease of mean arterial pressure should be reversed to maintain cerebral perfusion.

Prolonged mild hypothermia therapy protects the brain against permanent focal ischemia.

The efficacy of hypothermic intervention for permanent focal ischemia has yet to be clarified. This study investigated the effect of a prolonged moderate or mild hypothermia on permanent focal ischemia in rats. Two permanent focal ischemia models in male Sprague-Dawley rats were used. Moderate (30 degrees C, in experiment 1) or mild (33 degrees C, in experiment 2) hypothermia was achieved at the time of the induction of focal ischemia and was maintained for 2 hours under general anesthesia. Thereafter, the hypothermic condition was maintained by means of a cold room for a total of 24 hours. The infarct volume and neurological function were analyzed for a maximum of 21 days and compared with that of the normothermia group. Regional cerebral blood flow was monitored for 6 hours in the ischemic core and penumbra region. In experiment 1, the total infarct volume in the normothermic group was 368+/-59 mm(3); in contrast, it was significantly smaller in the hypothermia group: 169+/-33 mm(3) at 48 hours (mean+/-SEM, P:<0.05). In experiment 2, the infarct volume was 211+/-19 mm(3) in the normothermia group and 88+/-15 mm(3) in the hypothermia group at 21 days (P:<0.05). There were significant differences in neurological function from days 2 through 21 between the two groups. Mean regional cerebral blood flow in the penumbra region increased to a level >50% of baseline. Prolonged mild hypothermia suppressed the development of cerebral infarct and neurological deficit chronically after the induction of permanent focal ischemia.

Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57black/6 mice.

We explored susceptibility to injury after global ischemia in SV-129 and C57Black/6 mice, two commonly used-background strains in genetically engineered mice. Mice (n = 84) were subjected to 15, 30, or 75 minutes of bilateral common carotid artery (BCCA) occlusion followed by reperfusion for 72 hours. BCCA occlusion was performed under halothane or chloral hydrate anesthesia, in one experiment, mean arterial blood pressure and regional cerebral blood flow (laser Doppler flowmetry) were matched by controlled exsanguination. Baseline absolute blood flow measurements were obtained in both strains using a tracer, N-isopropyl-[methyl 1,3-14C]-p-iodoamphetamine, indicator fractionation technique (n = 5 per group). Vascular anatomy of the circle of Willis was visualized by intravascular perfusion of carbon black ink (n = 10 per group). Cerebrovascular reactivity was assessed by measuring the diameter of pial vessels (intravital microscopy) to acetylcholine (ACh) superfusion (0.1 to 10 mmol/L) in a closed cranial window preparation (n = 29). Resting blood flow values did not differ between groups in striatum, cerebellum, and brain-stem regions. SV-129 mice were less susceptible than C57Black/6 mice to ischemic injury (0.0 +/- 0.0 versus 1.3 +/- 0.3 damage in hippocampal CA1 region after 30 minutes of ischemia in SV-129 and C57Black/6, respectively; P < .01). Cellular damage (grade 1 to 3 injury) comparable to 30-minute BCCA occlusion was achieved only after 75 minutes of ischemia in SV-129 mice (1.1 +/- 0.3). Ischemic damage was also significantly less in SV-129 mice after blood pressure and flow were matched during ischemia in halothane-anesthetized SV-129 mice (0.5 +/- 0.3 versus 1.4 +/- 0.2, P < .05), or after chloral hydrate anesthesia (0.4 +/- 0.2 versus 1.5 +/- 0.4, P < .05). Hypoplastic posterior communicating arteries were found in all 10 C57Black/6 mice and may explain the greater susceptibility of these mice to injury after BCCA occlusion. More robust vasodilation to ACh in C57Black/6 mice could also indicate genetic differences in responses to vasoactive substances. C57Black/6 mice exhibit enhanced susceptibility to global cerebral ischemic injury, an incompletely formed circle of Willis, and augmented pial vessel dilation to ACh compared with SV-129 mice. Our findings suggest that strain differences may confound results when genetically engineered mice generated from more than a single background strain are used.

Functional anatomy of GO/NO-GO discrimination and response selection – a PET study in man

The purpose of this study was to identify the functional fields activated in relation to the NO-GO decision. Nine healthy subjects participated in the study which consisted of two test positron emission tomography (PET) scans (GO/NO-GO task and response selection task) and one control scan. In the response selection task, subjects were asked to flex their thumb of the right hand when a light emitting diode (LED) placed 60 cm from their eyes turned on red and to flex their index finger of the right hand when LED turned on green. In the GO/NO-GO task, subjects were asked to flex their thumb when the LED turned on red, however, they were asked not to move their fingers when LED turned on green. In the control state, they were asked simply to look at the LED without any movement of finger during the course of the scan. The mean regional cerebral blood flow (rCBF) change images for each task minus control and task minus task were calculated and fields of significant rCBF changes were identified. Several fields in the prefrontal cortex of the right hemisphere were specifically activated in relation to the GO/NO-GO task. The results indicate that the prefrontal cortex of the right hemisphere may be a key structure to make a decision not to move.

Functional anatomy of GO/NO-GO discrimination and response selection — a PET study in man

The purpose of this study was to identify the functional fields activated in relation to the NO-GO decision. Nine healthy subjects participated in the study which consisted of two test positron emission tomography (PET) scans (GO/NO-GO task and response selection task) and one control scan. In the response selection task, subjects were asked to flex their thumb of the right hand when a light emitting diode (LED) placed 60 cm frorn their eyes turned on red and to flex their index finger of the right hand when LED turned on green. In the GO/NO-GO task, subjects were asked to flex their thumb when the LED turned on red, however, they were asked not to move their fingers when LED turned on green. In the control state, they were asked simply to look at the LED without any movement of finger during the course of the scan. The mean regional cerebral blood flow (rCBF) change images for each task minus control and task minus task were calculated and fields of significant rCBF changes were identified. Several fields in the prefrontal cortex of the right hemisphere were specifically activated in relation to the GO/NO-GO task. The results indicate that the prefrontal cortex of the right hemisphere may be a key structure to make a decision not to move.

Assessment of Cerebral Vasomotor Reactivity by Transcranial Doppler Ultrasound and Breath-Holding

Evaluating cerebrovascular vasomotor reactivity seems to be of prognostic relevance for patients with occlusive internal carotid artery disease. To evaluate its clinical usefulness, the recently introduced breath-holding maneuver as a carbon dioxide-dependent vasodilatory stimulus was compared with the acetazolamide challenge by means of transcranial Doppler ultrasound and stable xenon-enhanced computed tomography. In a total of 134 middle cerebral arteries of 74 patients (mean +/- SD age, 62 +/- 9 years) with unilateral or bilateral occlusive carotid artery disease, vasomotor reactivity was estimated by the increase of middle cerebral artery mean blood velocity by transcranial Doppler ultrasound, comparing the breath-holding maneuver and 1 g IV acetazolamide as vasodilatory stimuli. The carotid artery findings were classified as normal, stenosis of 50% to < 70%, 70% to < 90%, 90% to 99%, and occlusion. Eighteen of the 74 patients additionally underwent stable xenon-enhanced computed tomography to calculate the increase of mean cortical regional cerebral blood flow in the middle cerebral artery territory after acetazolamide stimulation. The percentage of mean regional cerebral blood flow changes (n = 36 hemispheres) correlated best with the absolute mean blood velocity changes while breath-holding (P = .007, r = .4332). The absolute mean regional cerebral blood flow changes correlated best with the percentage of mean blood velocity changes after acetazolamide stimulation (P = .004, r = .4580). On all 134 middle cerebral arteries, both vasodilatory stimuli correlated highly significantly (P < .0001) when comparing increases in absolute (r = .5448) or relative (r = .3516) mean blood velocity. Both stimulation techniques similarly indicated significantly reduced vasomotor reactivity with increasing degree of internal carotid artery lesions (P < or = .01). However, the acetazolamide challenge differentiated more accurately between the various groups of internal carotid artery findings. The assessment of vasomotor reactivity by transcranial Doppler ultrasound correlates with cerebral blood flow changes even when different vasodilatory stimuli are used. In cooperative patients the breath-holding maneuver as vasodilatory stimulus seems clinically useful for a first estimation of cerebral vasomotor reactivity.

Estimated cerebral metabolic rate of oxygen in severely brain-injured patients

To evaluate a novel parameter of global cerebral oxygen metabolism, the estimated cerebral metabolic rate of oxygen, for its clinical utility in monitoring acute, severely brain-injured patients. Prospective, observational study. Neuroscience intensive care unit of a university hospital. Sixty-six adults with acute brain trauma undergoing 133Xe regional cerebral blood flow and global cerebral oxygen metabolic studies, in conjunction with other routine monitoring techniques. None. Estimated cerebral metabolic rate of oxygen was calculated as the product of PaCO2 and arterio-jugular oxygen content difference, and compared with the measured cerebral metabolic rate of oxygen (the product of mean regional cerebral blood flow and arterio-jugular oxygen content difference). Good correlations were found between the estimated and the true values (r2 = .56/.67, p < .0001) in 91 studies performed in 66 patients. These findings suggest that the estimated cerebral metabolic rate of oxygen is a useful substitute for the traditional cerebral metabolic rate of oxygen when cerebral blood flow information is not available. In addition, with this parameter, the patient's metabolic status can be assessed more frequently than with cerebral blood flow studies. These measurements do not require special instrumentation and can be done in any intensive care setting.