Reduction Of Regional Cerebral Blood Flow Research Articles

Specifically Decreased Thalamic Blood Flow Following COVID-19 Infection.

Although long COVID refers to numerous COVID-19-related symptoms after infection, including depression, fatigue, anosmia, sleep disturbances, and brain fog, the etiology of long COVID remains largely unknown. A 41-year-old woman presented with a 3-week history of complete insomnia without drowsiness throughout the day after contracting COVID-19. SPECT using N-isopropyl-p-[123I] iodoamphetamine showed a significant regional cerebral blood flow reduction in the bilateral thalamus. We diagnosed her as having insomnia accompanied by thalamic hypoperfusion related to COVID-19 infection. To our knowledge, this is the first case of reduced regional cerebral blood flow specifically confined to the thalamus.

Increase in Matrix Metaloproteinase‐10 is associated with tau, neurodegeneration and reduced brain perfusion in the right temporal lobe

AbstractBackgroundBlood brain barrier dysfunction amplifies neuroinflammation, which may drive Alzheimer’s Dementia (AD) pathology. Regional cerebral blood flow (RCBF), measured by HMPAO SPECT, is an established biomarker for AD diagnosis. Matrix Metalloproteinase‐10 (MMP‐10), an enzyme involved in blood brain barrier function through regulating the breakdown of extracellular matrix, was recently proposed as a biomarker of progression to AD. In this study, we examine the relationship between RCBF and levels of MMP‐10 in the cerebrospinal fluid (CSF).Materials and MethodsDatasets of 91 participants from a heterogenous clinical cohort, investigated for dementia due to cognitive complaints were analysed. CSF levels of MMP‐10 were measured using the OLINK proximity extension array platform. HMPAO SPECT scans were analysed using Statistical Parametric Mapping (SPM). A univariate linear regression model was used in SPM to quantify the impact of MMP‐10 changes on brain perfusion.ResultsSPM results showed that higher levels of MMP‐10 in CSF are associated with significant reduction in RCBF (family‐wise error corrected p<0.05). The neuroimaging signature of changes in RCBF with increasing MMP‐10 is outlined in Figure 1. The main cluster of reduction in perfusion is on the right temporal lobe with an additional cluster on the right medial frontal lobe.ConclusionIncreased levels of MMP‐10 in CSF have been associated with blood brain barrier vulnerability and faster cognitive decline in AD. Here we identified a right sided neuroimaging signature in RCBF with increasing levels MMP‐10. This may indicate that by the time of symptoms onset the right side is the fastest progressing as it is catching up with the left side. Right sided changes have been previously associated with delusions, disinhibition and irritability in AD and linked with increased carer burden. The significant reduction in RCBF of the right temporal lobe identified in our study, further reinforces a role for MMP‐10 as a marker of progression to AD.Acknowledgement: Dr Sofia Michopoulou, is funded through an Integrated Clinical Academic Lectureship by Health Education England (HEE) / NIHR for this research project (NIHR301287). The views expressed in this publication are those of the authors.

Changes in postictal cerebral perfusion are related to the duration of electroconvulsive therapy-induced seizures.

Postictal symptoms may result from cerebral hypoperfusion, which is possibly a consequence of seizure-induced vasoconstriction. Longer seizures have previously been shown to cause more severe postictal hypoperfusion in rats and epilepsy patients. We studied cerebral perfusion after generalized seizures elicited by electroconvulsive therapy (ECT) and its relation to seizure duration. Patients with a major depressive episode who underwent ECT were included. During treatment, 21-channel continuous electroencephalogram (EEG) was recorded. Arterial spin labeling magnetic resonance imaging scans were acquired before the ECT course (baseline) and approximately 1 h after an ECT-induced seizure (postictal) to quantify global and regional gray matter cerebral blood flow (CBF). Seizure duration was assessed from the period of epileptiform discharges on the EEG. Healthy controls were scanned twice to assess test-retest variability. We performed hypothesis-driven Bayesian analyses to study the relation between global and regional perfusion changes and seizure duration. Twenty-four patients and 27 healthy controls were included. Changes in postictal global and regional CBF were correlated with seizure duration. In patients with longer seizure durations, global decrease in CBF reached values up to 28 mL/100 g/min. Regional reductions in CBF were most prominent in the inferior frontal gyrus, cingulate gyrus, and insula (up to 35 mL/100 g/min). In patients with shorter seizures, global and regional perfusion increased (up to 20 mL/100 g/min). These perfusion changes were larger than changes observed in healthy controls, with a maximum median global CBF increase of 12 mL/100 g/min and a maximum median global CBF decrease of 20 mL/100 g/min. Seizure duration is a key factor determining postictal perfusion changes. In future studies, seizure duration needs to be considered as a confounding factor due to its opposite effect on postictal perfusion.

Effects of a multicomponent day-care program on cerebral blood flow in patients with mild cognitive impairment.

Mild cognitive impairment (MCI) is a prodromal phase of dementia and is considered an important period for intervention to prevent conversion to dementia. It has been well established that multicomponent day-care programs including exercise training, cognitive intervention and music therapy have beneficial effects on cognition, but the effects on cerebral blood flow (CBF) in MCI remain unknown. This study examined whether a multicomponent day-care program would have beneficial effects on the longitudinal changes of CBF in MCI patients. Participants were 24 patients with MCI attending a day-care program; they underwent two 99 mTc-ethyl cysteinate dimer single photon emission computed tomography scans during the study period. We evaluated the association between the changes of regional cerebral blood flow and the attendance rate. There was a significant negative correlation between the reduction of regional CBF in the right parietal region and the attendance rate. We found no significant relation between the baseline CBF images and the attendance rate. Our results suggest that continuous participation in a multicomponent day-care program might prevent reduction in brain activity in patients with MCI.

Higher Aortic Stiffness Is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults

Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults. Vanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (n=155; age, 72±7 years; 59% male) or mild cognitive impairment (n=115; age, 73±7 years; 57% male). Aortic pulse wave velocity (PWV; meters per second) was quantified from cardiac magnetic resonance. Resting CBF (milliliters per 100 g per minute) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudocontinuous arterial spin labeling magnetic resonance imaging. Linear regression models related aortic PWV to regional CBF, adjusting for age, race/ethnicity, education, Framingham Stroke Risk Profile (diabetes mellitus, smoking, left ventricular hypertrophy, prevalent cardiovascular disease, atrial fibrillation), hypertension, body mass index, apolipoprotein E4 ( APOE ε4) status, and regional tissue volume. Models were repeated testing PWV× APOE ε4 interactions. Sensitivity analyses excluded participants with prevalent cardiovascular disease and atrial fibrillation. Among participants with normal cognition, higher aortic PWV related to lower frontal lobe CBF (β=-0.43; P=0.04) and higher CVR in the whole brain (β=0.11; P=0.02), frontal lobes (β=0.12; P<0.05), temporal lobes (β=0.11; P=0.02), and occipital lobes (β=0.14; P=0.01). Among APOE ε4 carriers with normal cognition, findings were more pronounced with higher PWV relating to lower whole-brain CBF (β=-1.16; P=0.047), lower temporal lobe CBF (β=-1.81; P=0.004), and higher temporal lobe CVR (β=0.26; P=0.08), although the last result did not meet the a priori significance threshold. Results were similar in sensitivity models. Among participants with mild cognitive impairment, higher aortic PWV related to lower CBF in the occipital lobe (β=-0.70; P=0.02), but this finding was attenuated when participants with prevalent cardiovascular disease and atrial fibrillation were excluded. Among APOE ε4 carriers with mild cognitive impairment, findings were more pronounced with higher PWV relating to lower temporal lobe CBF (β=-1.20; P=0.02). Greater aortic stiffening relates to lower regional CBF and higher CVR in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer's disease. Central arterial stiffening may contribute to reductions in regional CBF despite preserved cerebrovascular reserve capacity.

Characteristic deterioration of ADAS-Jcog subscale scores and correlations with regional cerebral blood flow reductions in Alzheimer's disease.

The Alzheimer Disease Assessment Scale (Japanese version) cognitive subscale (ADAS-Jcog) is composed of a number of subscale tasks. However, it is not clear which subscale tasks are most susceptible to impairment in Alzheimer's disease (AD) or what is the relationship between reduction in regional cerebral blood flow (rCBF) and decreased ADAS-Jcog scores. Subjects were 32 AD patients, aged 52-86years. We examined the relationship between subscale tasks that showed marked score changes and brain regions that showed reduced rCBF over a 2-year period. rCBF was measured by single-photon emission computed tomography (SPECT) with technetium-99m ethyl cysteinate dimer (99mTc-ECD), and the SPECT imaging data were analyzed with the easy Z-score imaging system (eZIS) and voxel-based stereotactic extraction estimation (vbSEE) methods. Total score of ADAS-Jcog deteriorated from 19.5 ± 7.0 to 35.7 ± 15.2 after 2years. Subscale scores were significantly worse in all fields, particularly in orientation, word recall, remembering test instructions, commands, constructional praxis, and ideational praxis, in that order. Significant correlations were found between (1) word recall and commands and rCBF in the left middle temporal lobe, (2) naming objects/fingers and rCBF in the left temporal (middle, inferior) lobe, and (3) constructional and ideational praxis and rCBF in the right parietal (superior, inferior) lobe, temporal (superior, middle) lobe, angular gyrus, and cingulate gyrus. We identified the brain regions associated with specifically impaired subscales of ADAS-Jcog during progressive deterioration of AD over 2years.

Cerebral glucose metabolism changes in Japanese females following human papillomavirus vaccination: A PET study

Background: Human papillomavirus (HPV) vaccine were globally introduced for young females to prevent persistent HPV infection. Few vaccinated individuals exhibit various symptoms following vaccination. To date, there is controversy regarding the pathophysiology and possible association between HPV vaccination and their symptoms. Previous our study reported regional cerebral blood flow reduction mainly in the regions connected to the limbic system.

Unexpected reductions in regional cerebral perfusion during prolonged hypoxia.

Cognitive performance is impaired by hypoxia despite global cerebral oxygen delivery and metabolism being maintained. Using arterial spin labelled (ASL) magnetic resonance imaging, this is the first study to show regional reductions in cerebral blood flow (CBF) in response to decreased oxygen supply (hypoxia) at 2h that increased in area and became more pronounced at 10h. Reductions in CBF were seen in brain regions typically associated with the 'default mode' or 'task negative' network. Regional reductions in CBF, and associated vasoconstriction, within the default mode network in hypoxia is supported by increased vasodilatation in these regions to a subsequent hypercapnic (5% CO2 ) challenge. These results suggest an anatomical mechanism through which hypoxia may cause previously reported deficits in cognitive performance. Hypoxia causes an increase in global cerebral blood flow, which maintains global cerebral oxygen delivery and metabolism. However, neurological deficits are abundant under hypoxic conditions. We investigated regional cerebral microvascular responses to acute (2h) and prolonged (10h) poikilocapnic normobaric hypoxia. We found that 2h of hypoxia caused an expected increase in frontal cortical grey matter perfusion but unexpected perfusion decreases in regions of the brain normally associated with the 'default mode' or 'task negative' network. After 10h in hypoxia, decreased blood flow to the major nodes of the default mode network became more pronounced and widespread. The use of a hypercapnic challenge (5% CO2 ) confirmed that these reductions in cerebral blood flow from hypoxia were related to vasoconstriction. Our findings demonstrate steady-state deactivation of the default network under acute hypoxia, which become more pronounced over time. Moreover, these data provide a unique insight into the nuanced localized cerebrovascular response to hypoxia that is not attainable through traditional methods. The observation of reduced perfusion in the posterior cingulate and cuneal cortex, which are regions assumed to play a role in declarative and procedural memory, provides an anatomical mechanism through which hypoxia may cause deficits in working memory.

Impaired Cerebrovascular Function in Coronary Artery Disease Patients and Recovery Following Cardiac Rehabilitation.

Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to hypercapnia in 34 CAD patients and 21 age-matched controls. Gray matter volume (GMV) images were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate (AC), insular, pre- and post-central gyri, middle temporal, and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the AC, insula, post-central and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in GMV were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-months exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral AC, as well as recovery of CBF in the dorsal aspect of the right AC, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the AC is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control.

Relationship between white matter lesions and regional cerebral blood flow changes during longitudinal follow up in Alzheimer's disease.

The aim of the present study was to evaluate the relationship between baseline white matter lesions (WML) and changes in regional cerebral blood flow during longitudinal follow up of patients with Alzheimer's disease (AD). A total of 38 patients with AD were included in the study (16 men, 22 women; mean age 77.8 years). All patients were evaluated using the Mini-Mental State Examination and brain perfusion single-photon emission computed tomography at baseline with an approximately 2-year follow up. The patients were divided into two subgroups according to the presence of WML on magnetic resonance imaging. Single-photon emission computed tomography data were analyzed using a voxel-by-voxel group analysis with Statistical Parametric Mapping 8 and region of interest analysis using FineSRT. Changes in Mini-Mental State Examination scores and regional cerebral blood flow were analyzed using the Wilcoxon signed-rank test. Mean Mini-Mental State Examination scores in AD patients with WML significantly decreased from 19.4 ± 4.8 to 15.5 ± 6.5 (P = 0.003). Statistical Parametric Mapping 8 and FineSRT analysis showed more severe and widespread regional cerebral blood flow reduction, mainly in the frontal and mesial temporal regions in AD patients with WML compared with those without WML. Baseline WML could predict a rapid progression of cognitive and brain functional impairment during longitudinal follow up in AD. Geriatr Gerontol Int 2016; 16: 836-842.

Brain perfusion and markers of neurodegeneration in rapid eye movement sleep behavior disorder

Potential early markers of neurodegeneration such as subtle motor signs, reduced color discrimination, olfactory impairment, and brain perfusion abnormalities have been reported in idiopathic rapid eye movement sleep behavior disorder, a risk factor for Parkinson's disease and Lewy body dementia. The aim of this study was to reproduce observations of regional cerebral blood flow abnormalities in a larger independent sample of patients and to explore correlations between regional cerebral blood flow and markers of neurodegeneration. Twenty patients with idiopathic rapid eye movement sleep behavior disorder and 20 healthy controls were studied by single-photon emission computerized tomography. Motor examination, color discrimination, and olfactory identification were examined. Patients with rapid eye movement sleep behavior disorder showed decreased regional cerebral blood flow in the frontal cortex and in medial parietal areas and increased regional cerebral blood flow in subcortical regions including the bilateral pons, putamen, and hippocampus. In rapid eye movement sleep behavior disorder, brain perfusion in the frontal cortex and occipital areas was associated with poorer performance in the color discrimination test. Moreover, a relationship between loss of olfactory discrimination and regional cerebral blood flow reduction in the bilateral anterior parahippocampal gyrus, a region known to be involved in olfactory functions, was found. This study provides further evidence of regional cerebral blood flow abnormalities in rapid eye movement sleep behavior disorder that are similar to those seen in Parkinson's disease and Lewy body dementia. Moreover, regional cerebral blood flow anomalies were associated with markers of neurodegeneration.

Physiological and histopathological responses following closed rotational head injury depend on direction of head motion

Rotational inertial forces are thought to be the underlying mechanism for most severe brain injuries. However, little is known about the effect of head rotation direction on injury outcomes, particularly in the pediatric population. Neonatal piglets were subjected to a single non-impact head rotation in the horizontal, coronal, or sagittal direction, and physiological and histopathological responses were observed. Sagittal rotation produced the longest duration of unconsciousness, highest incidence of apnea, and largest intracranial pressure increase, while coronal rotation produced little change, and horizontal rotation produced intermediate and variable derangements. Significant cerebral blood flow reductions were observed following sagittal but not coronal or horizontal injury compared to sham. Subarachnoid hemorrhage, ischemia, and brainstem pathology were observed in the sagittal and horizontal groups but not in a single coronal animal. Significant axonal injury occurred following both horizontal and sagittal rotations. For both groups, the distribution of injury was greater in the frontal and parietotemporal lobes than in the occipital lobes, frequently occurred in the absence of ischemia, and did not correlate with regional cerebral blood flow reductions. We postulate that these direction-dependent differences in injury outcomes are due to differences in tissue mechanical loading produced during head rotation.

Regional Cerebral Blood Flow Patterns Detected by SPECT With Easy Z-score Imaging System Analysis in Early-stage Alzheimer's Disease

The objective of this study is to investigate the characteristic patterns of regional cerebral blood flow reduction in early Alzheimer's disease (AD). Twenty patients were recruited in this study. We performed MRI(Siemens, MAGNETOM Harmony 1.0T,) and single-photon emission computed tomography (SPECT) technetium-99m cysteinate dimmer (99m Tc-ECD) (Toshiba, 7200A−DI), simultaneously, and corrected using voxel-based morphometry as to reduce the atrophic influence. We evaluated regional cerebral blood flow patterns using easy Z-score imaging system (eZIS) analysis, and we calculated the extent of each regions using voxel-based Stereotactic Extraction Estimation (vb SEE)(Level 3 classification). In 8 subjects, MRI and SPECT were reevaluated one or two years after and the comparative study was performed. There was prominent decrease in the bilateral posterior cingulated gyrus, parietal cortex, temporal cortex, and frontal cortex. The eZIS analysis with vb SEE is useful in highlighting the changes in the hypoperfusional regions. These results were in agreement with those of 3D-SSP study with SEE analysis.

Cerebrovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage

We hypothesize that cerebral ischemia leads to enhanced expression of endothelin (ET), 5-hydroxytryptamine (5-HT), and angiotensin II (ANG II) receptors in the vascular smooth muscle cells. Our aim is to correlate the upregulation of cerebrovascular receptors and the underlying molecular mechanisms with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 microl blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular studies. The contractile responses to ET-1, 5-carboxamidotryptamine (5-CT), and ANG II were investigated with myograph. The receptor mRNA and protein levels were analyzed by quantitative real-time PCR and immunohistochemistry, respectively. In addition, regional and global CBFs were measured by an autoradiographic method. As a result, SAH resulted in enhanced contractions to ET-1 and 5-CT. ANG II [via ANG II type 1 (AT(1)) receptors] induced increased contractile responses [in the presence of the ANG II type 2 (AT(2)) receptor antagonist PD-123319]. In parallel the ET(B), 5-HT(1B), and AT(1) receptor, mRNA and protein levels were elevated by time. The regional and global CBF showed a successive reduction with time after SAH. In conclusion, the results demonstrate for the first time that SAH induces the upregulation of ET(B), 5-HT(1B), and AT(1) receptors in a time-dependent manner both at functional, mRNA, and protein levels. These changes occur in parallel with a successive decrease in CBF. Thus there is a temporal correlation between the changes in receptor expression and CBF reduction, suggesting a linkage.

Regional cerebral blood flow reductions, heart failure and Alzheimer's disease

Objectives: To discuss whether there are similarities between the functional brain abnormalities detectable in association with the diagnoses of heart failure (HF) and Alzheimer's disease (AD), focusing particularly on neuroimaging findings in vivo.Methods: Using an electronic database (Medline), we reviewed imaging studies that have evaluated resting cerebral blood flow (CBF), resting glucose metabolism or amyloid deposition in groups of subjects suffering AD or HF compared with healthy controls.Results: Single photon emission computed tomography (SPECT) investigations have reported global CBF reductions in HF groups compared with controls. In one recent SPECT study using modern voxel-based methods for image analysis, regional CBF deficits in the pre-cuneus and posterior cingulate gyrus were detected in a sample of HF sufferers relative to controls. The regional distribution of functional deficits in the latter study was similar to that found in many positron emission tomography (PET) investigations of glucose metabolism at early AD stages, as well as in recent PET investigations of amyloid deposition in AD.Discussion: Imaging studies have rarely investigated whether there are localized functional brain deficits in association with HF. Recent regional CBF SPECT data provide preliminary anatomic support to a view that AD-like brain changes may develop in HF patients, possibly as a consequence of chronic CBF reductions. Additional studies of larger HF samples are needed to confirm this possibility, preferably using PET measures that have afforded greater sensitivity and specificity to identify brain functional abnormalities associated with the diagnosis of AD, such as indices of glucose metabolism and amyloid deposition.

Differentiation of Dementia with Lewy Bodies from Alzheimer’s Disease Using Brain SPECT

We compared regional cerebral blood flow (CBF) patterns in patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) using single photon emission computed tomography (SPECT) and investigated the diagnostic utility of SPECT study in differentiating between DLB and AD. SPECT data on 20 patients with DLB and 75 patients with AD were analyzed using three-dimensional stereotactic surface projections. Regional CBF reduction was determined by quantitative analysis using stereotactic extraction estimation method. The DLB group showed a significant CBF reduction in the temporoparietal, frontal lobe and posterior cingulate, similar to the CBF pattern in the AD group, but regional CBF in the medial and lateral occipital lobes decreased significantly in patients with DLB compared with patients with AD. Receiver operating characteristic analysis revealed that regional CBF measurement of the medial occipital lobe, including the cuneus and lingual gyrus, yielded a sensitivity of 85% and a specificity of 85% in discriminating DLB from AD. Objective and quantitative CBF measurement in the medial occipital lobe may be useful in the clinical differentiation of DLB and AD.

Incidence and mechanisms of cerebral ischemia in early clinical head injury.

Antemortem demonstration of ischemia has proved elusive in head injury because regional CBF reductions may represent hypoperfusion appropriately coupled to hypometabolism. Fifteen patients underwent positron emission tomography within 24 hours of head injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF). We estimated the volume of ischemic brain (IBV) and used the standard deviation of the OEF distribution to estimate the efficiency of coupling between CBF and CMRO2. The IBV in patients was significantly higher than controls (67 +/- 69 vs. 2 +/- 3 mL; P < 0.01). The coexistence of relative ischemia and hyperemia in some patients implies mismatching of perfusion to oxygen use. Whereas the saturation of jugular bulb blood (SjO2) correlated with the IBV (r = 0.8, P < 0.01), SjO2 values of 50% were only achieved at an IBV of 170 +/- 63 mL (mean +/- 95% CI), which equates to 13 +/- 5% of the brain. Increases in IBV correlated with a poor Glasgow Outcome Score 6 months after injury (rho = -0.6, P < 0.05). These results suggest significant ischemia within the first day after head injury. The ischemic burden represented by this "traumatic penumbra" is poorly detected by bedside clinical monitors and has significant associations with outcome.

Cerebral blood volume and blood flow responses to hyperventilation in brain tumors during isoflurane or propofol anesthesia.

Using computerized tomography, we measured absolute cerebral blood flow (CBF) and cerebral blood volume (CBV) in tumor, peri-tumor, and contralateral normal regions, at normocapnia and hypocapnia, in 16 rabbits with brain tumors (VX2 carcinoma), under isoflurane or propofol anesthesia. In both anesthetic groups, CBV and CBF were highest in the tumor region and lowest in the contralateral normal tissue. For isoflurane, a significant decrease in both CBV and CBF was observed in all tissue regions with hyperventilation (P < 0.05), but without accompanying changes in intracranial pressure. However, the percent reduction in regional CBF with hypocapnia was two times larger than that observed in the CBV response (P < 0.01). In contrast, there were no significant changes in CBV and CBF in the Propofol group with hyperventilation for all regions (P > 0.10). In addition, there were no differences between CBV values for isoflurane at hypocapnia when compared with CBV values for propofol at normo- or hypocapnia (P > 0.34 and P > 0.35, respectively, in the tumor regions). Our results indicate that propofol increases cerebral vascular tone in both neoplastic and normal tissue vessels compared with isoflurane. CBV and CBF during normocapnia were significantly greater in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol. CBV and CBF remained responsive to hyperventilation only with isoflurane. In rabbits with brain tumors, brain blood flow and volume were significantly larger in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol during normocapnia, and remained responsive to a reduction in PaCO(2). Consequently, during hypocapnia, brain blood flow and volume values with isoflurane were similar to values with propofol.

Clinical and Radiological Correlates of Reduced Cerebral Blood Flow Measured Using Magnetic Resonance Imaging

Methods for determining cerebral blood flow (CBF) using bolus-tracking magnetic resonance imaging (MRI) have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional CBF in animal stroke models. To determine the clinical and radiological features of patients with severe reductions in CBF on MRI and to analyze the relationship between reduced CBF and ADCs in acute ischemic stroke. Case series. Referral center. We studied 17 patients with nonlacunar acute ischemic stroke in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) were performed within 7 hours of symptom onset. A PWI-DWI mismatch of more than 20% was required. We compared patients with ischemic lesions that had CBF of less than 50% relative to the contralateral hemisphere with patients with lesions that had relative CBF greater than 50%. Characteristics analyzed included age, time to MRI, baseline National Institutes of Health Stroke Scale score, mean ADC, DWI and PWI lesion volumes, and 1-month Barthel Index score. Patients with low CBF (n = 5) had lower ADC values (median, 430 x 10 (-6) mm(2)/s vs. 506 x 10 (-6) mm(2)/s; P =.04), larger DWI volumes (median, 41.8 cm(3) vs. 14.5 cm(3); P =.001) and larger PWI lesions as defined by the mean transit time volume (median, 194.6 cm(3) vs. 69.3 cm(3); P =.01), and more severe baseline National Institutes of Health Stroke Scale scores (median, 15 vs. 9; P =.02). Ischemic lesions with severe CBF reductions, measured using bolus-tracking MRI, are associated with lower mean ADCs, larger DWI and PWI volumes, and higher National Institutes of Health Stroke Scale scores.

Effects of recombinant tissue plasminogen activator after intraluminal thread occlusion in mice: role of hemodynamic alterations.

It has been suggested that recombinant tissue plasminogen activator (rtPA) may cause an aggravation of injury after transient focal ischemia via excitotoxic side effects. Such rtPA toxicity would be of major clinical significance since rtPA is increasingly used in stroke treatment. This study was conducted to evaluate the effects of dose, application time, and hemodynamic changes after intravenous rtPA treatment in focal ischemia. Mice were subjected to a 90-minute episode of middle cerebral artery thread occlusion, and rtPA effects were assessed by laser-Doppler flowmetry, [(14)C]iodoantipyrine autoradiography, and triphenyltetrazolium chloride staining. We provide evidence that rtPA provokes complex hemodynamic alterations in the ischemic brain tissue, which include an initial hyperperfusion and a more delayed hypoperfusion response. Changes are most pronounced in the periphery of the ischemic infarct, where regional blood flow drops below critical thresholds of tissue viability. Our observations suggest that changes of perfusion may at least partly explain the rtPA-induced increase of infarct size, which has previously been reported and which we also confirmed in the present experiments. Notably, both the secondary hypoperfusion and increase of infarct volume were abolished when rtPA-treated animals received additional heparin infusions. This finding suggests that a secondary hypercoagulability may compromise brain perfusion after rtPA delivery. Accordingly, early treatment with heparin might help to prevent the rtPA-induced changes.