Lower Cerebral Blood Flow Values Research Articles

The correlation between changes in gray matter microstructure and cerebral blood flow in Alzheimer's disease.

To investigate the relationship between changes in cerebral blood flow (CBF) and gray matter (GM) microstructure in Alzheimer's disease (AD) and mild cognitive impairment (MCI). A recruited cohort of 23 AD patients, 40 MCI patients, and 37 normal controls (NCs) underwent diffusional kurtosis imaging (DKI) for microstructure evaluation and pseudo-continuous arterial spin labeling (pCASL) for CBF assessment. We investigated the differences in diffusion- and perfusion-related parameters across the three groups, including CBF, mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA). These quantitative parameters were compared using volume-based analyses for the deep GM and surface-based analyses for the cortical GM. The correlation between CBF, diffusion parameters, and cognitive scores was assessed using Spearman coefficients, respectively. The diagnostic performance of different parameters was investigated with k-nearest neighbor (KNN) analysis, using fivefold cross-validation to generate the mean accuracy (mAcc), mean precision (mPre), and mean area under the curve (mAuc). In the cortical GM, CBF reduction primarily occurred in the parietal and temporal lobes. Microstructural abnormalities were predominantly noted in the parietal, temporal, and frontal lobes. In the deep GM, more regions showed DKI and CBF parametric changes at the MCI stage. MD showed most of the significant abnormalities among all the DKI metrics. The MD, FA, MK, and CBF values of many GM regions were significantly correlated with cognitive scores. In the whole sample, the MD, FA, and MK were associated with CBF in most evaluated regions, with lower CBF values associated with higher MD, lower FA, or lower MK values in the left occipital lobe, left frontal lobe, and right parietal lobe. CBF values performed best (mAuc = 0.876) for distinguishing the MCI from the NC group. Last, MD values performed best (mAuc = 0.939) for distinguishing the AD from the NC group. Gray matter microstructure and CBF are closely related in AD. Increased MD, decreased FA, and MK are accompanied by decreased blood perfusion throughout the AD course. Furthermore, CBF values are valuable for the predictive diagnosis of MCI and AD. GM microstructural changes are promising as novel neuroimaging biomarkers of AD.

Association of Cerebral Blood Flow With Longitudinal Changes in Cerebral Microstructural Integrity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Decreased cerebral tissue integrity and cerebral blood flow (CBF) are features of neurodegenerative diseases. Brain tissue maintenance is an energy-demanding process, making it particularly sensitive to hypoperfusion. However, little is known about the association between blood flow and brain microstructural integrity, including in normative aging. To assess associations between CBF and changes in cerebral tissue integrity in white matter and gray matter brain regions. In this longitudinal cohort study, magnetic resonance imaging was performed on 732 healthy adults from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective longitudinal study (baseline age of 18-30 years) that examined participants up to 8 times during 30 years (1985-1986 to 2015-2016). Cerebral blood flow was measured at baseline (year 25 of the CARDIA study), and changes in diffusion tensor indices of fractional anisotropy (FA) and mean diffusivity (MD), measures of microstructural tissue integrity, were measured at both baseline and after approximately 5 years of follow-up (year 30). Analyses were conducted from November 5, 2020, to January 29, 2022. Automated algorithms and linear mixed-effects statistical models were used to evaluate the associations between CBF at baseline and changes in FA or MD. After exclusion of participants with missing or low-quality data, 654 at baseline (342 women; mean [SD] age, 50.3 [3.5] years) and 433 at follow-up (230 women; mean [SD] age, 55.1 [3.5] years) were scanned for CBF or FA and MD imaging. In the baseline cohort, 247 participants were Black (37.8%) and 394 were White (60.2%); in the follow-up cohort, 156 were Black (36.0%) and 277 were White (64.0%). Cross-sectionally, FA and MD were associated with CBF in most regions evaluated, with lower CBF values associated with lower FA or higher MD values, including the frontal white matter lobes (for CBF and MD: mean [SE] β = -1.4 [0.5] × 10-6; for CBF and FA: mean [SE] β = 2.9 [1.0] × 10-4) and the parietal white matter lobes (for CBF and MD: mean [SE] β = -2.4 [0.6] × 10-6; for CBF and FA: mean [SE] β = 4.4 [1.1] × 10-4). Lower CBF values at baseline were also significantly associated with steeper regional decreases in FA or increases in MD in most brain regions investigated, including the frontal (for CBF and MD: mean [SE] β = -1.1 [0.6] × 10-6; for CBF and FA: mean [SE] β = 2.9 [1.0] × 10-4) and parietal lobes (for CBF and MD: mean [SE] β = -1.5 [0.7] × 10-6; for CBF and FA: mean [SE] β = 4.4 [1.1] × 10-4). Results of this longitudinal cohort study of the association between CBF and diffusion tensor imaging metrics suggest that blood flow may be significantly associated with brain tissue microstructure. This work may lay the foundation for investigations to clarify the nature of early brain damage in neurodegeneration. Such studies may lead to new neuroimaging biomarkers of brain microstructure and function for disease progression.

The longitudinal evolution of cerebral blood flow in children with tuberous sclerosis assessed by arterial spin labeling magnetic resonance imaging may be related to cognitive performance.

To study longitudinal changes in tuber and whole-brain perfusion in children with tuberous sclerosis complex (TSC) using arterial spin labeling (ASL) perfusion MRI and correlate them with pathological EEG slow wave activity and neurodevelopmental outcomes. Retrospective longitudinal cohort study of 13 children with TSC, 3 to 6 serial ASL-MRI scans between 2 months and 7 years of age (53 scans in total), and an EEG examination performed within 2 months of the last MRI. Tuber cerebral blood flow (CBF) values were calculated in tuber segmentation masks, and tuber:cortical CBF ratios were used to study tuber perfusion. Logistic regression analysis was performed to identify which initial tuber characteristics (CBF value, volume, location) in the first MRI predicted tubers subsequently associated with EEG slow waves. Whole-brain and lobar CBF values were extracted for all patient scans and age-matched controls. CBF ratios were compared in patients and controls to study longitudinal changes in whole-brain CBF. Perfusion was reduced in tubers associated with EEG slow waves compared with other tubers. Low tuber CBF values around 6 months of age and large tuber volumes were predictive of tubers subsequently associated with EEG slow waves. Patients with severe developmental delay had more severe whole-brain hypoperfusion than those with no/mild delay, which became apparent after 2 years of age and were not associated with a higher tuber load. Dynamic changes in tuber and brain perfusion occur over time. Perfusion is significantly reduced in tubers associated with EEG slow waves. Whole-brain perfusion is significantly reduced in patients with severe delay. • Tubers associated with EEG slow wave activity were significantly more hypoperfused than other tubers, especially after 1 year of age. • Larger and more hypoperfused tubers at 6 months of age were more likely to subsequently be associated with pathological EEG slow wave activity. • Patients with severe developmental delay had more extensive and severe global hypoperfusion than those without developmental delay.

Hypoperfusion in nucleus accumbens in chronic migraine using 3D pseudo-continuous arterial spin labeling imaging MRI

BackgroundNucleus accumbens (NAcc) played an important role in pain mediation, and presents changes of neuronal plasticity and functional connectivity. However, less is known about altered perfusion of NAcc in chronic migraine (CM). The aim of this study is to investigate the altered perfusion of the NAcc in CM using a MR three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) imaging.MethodsThirteen CM patients and 15 normal controls (NC) were enrolled and underwent 3D PCASL and brain structural imaging. The cerebral blood flow (CBF) images were co-registered with the brain structural images, and the volume and CBF value of NAcc were extracted from the raw brain structural images and co-registered CBF images using an individual NAcc mask, which was obtained from the AAL3 template under transformation by the inverse deformation field generated from the segmentation of the brain structural images. The independent sample t test and receiver operating characteristic (ROC) curve was used to investigate the altered volume and perfusion of the NAcc in CM patients.ResultsThere was no significant difference for the volume of bilateral NAccs between CM and NC (p > 0.05). CM presented a lower CBF value (49.34 ± 6.09 ml/100 mg/min) compared with that of NC (55.83 ± 6.55 ml/100 mg/min) in left NAcc (p = 0.01), while right NAcc showed no significant difference between CM and NC (p = 0.11). ROC analysis identified that the area under the curve was 0.73 (95CI% 0.53–0.88) with cut-off value 48.63 ml/100 mg/min with sensitivity 50.00% and specificity 93.33%. The correlation analysis found a negative correlation between the CBF value of the left NAcc and VAS score (r = -0.61, p = 0.04).ConclusionHypoperfusion of the left NAcc was observed in CM, which could be considered as a potential diagnostic imaging biomarker in CM.

Validation of the estimation of the macrovascular contribution in multi-timepoint arterial spin labeling MRI using a 2-component kinetic model.

In this paper, the ability to quantify cerebral blood flow by arterial spin labeling (ASL) was studied by investigating the separation of the macrovascular and tissue component using a 2-component model. Underlying assumptions of this model, especially the inclusion of dispersion in the analysis, were studied, as well as the temporal resolution of the ASL datasets. Four different datasets were acquired: (1) 4D ASL angiography to characterize the macrovascular component and to study dispersion modeling within this component, (2) high temporal resolution ASL data to investigate the separation of the 2 components and the effect of dispersion modelling on this separation, (3) low temporal resolution ASL dataset to study the effect of the temporal resolution on the separation of the 2 components, and (4) low temporal resolution ASL data with vascular crushing. The model that included a gamma dispersion kernel had the best fit to the 4D ASL angiography. For the high temporal resolution ASL dataset, inclusion of the gamma dispersion kernel led to more signal included in the arterial blood volume map, which resulted in decreased cerebral blood flow values. The arterial blood volume and cerebral blood flow maps showed overall higher arterial blood volume values and lower cerebral blood flow values for the high temporal resolution dataset compared to the low temporal resolution dataset. Inclusion of a gamma dispersion kernel resulted in better fitting of the model to the data. The separation of the macrovascular and tissue component is affected by the inclusion of a gamma dispersion kernel and the temporal resolution of the ASL dataset.

Discriminative pattern of reduced cerebral blood flow in Parkinson\u2019s disease and Parkinsonism-Plus syndrome: an ASL-MRI study

BackgroundAccurate identification of Parkinson’s disease (PD) and Parkinsonism-Plus syndrome (PPS), especially in the early stage of the disease, is very important. The purpose of this study was to investigate the discriminative spatial pattern of cerebral blood flow (CBF) between patients with PD and PPS.MethodsArterial spin labeling (ASL) perfusion-weighted imaging was performed in 20 patients with PD (mean age 56.35 ± 7.56 years), 16 patients with PPS (mean age 59.62 ± 6.89 years), and 17 healthy controls (HCs, mean age 54.17 ± 6.58 years). Voxel-wise comparison of the CBF was performed among PD, PPS, and HC groups. The receiver operating characteristic (ROC) curve was used to evaluate the performance of CBF in discriminating between PD and PPS. The relationship between CBF and non-motor neuropsychological scores was assessed by correlation analysis.ResultsPD group showed a significantly decreased CBF in the right cerebelum_crus2, the left middle frontal gyrus (MFG), the triangle inferior frontal gyrus (IFG_Tri), the left frontal medial orbital gyrus (FG_Med_Orb) and the left caudate nucleus (CN) compared with the HC group (P < 0.05). Besides the above regions, the left supplementary motor area (SMA), the right thalamus had decreased CBF in the PPS group compared with the HC group (P < 0.05). PPS group had lower CBF value in the left MFG, the left IFG_Tri, the left CN, the left SMA, and the right thalamus compared with the PD group (P < 0.05). CBFs in left IFG_Tri, the left CN, the left SMA, and the right thalamus had moderate to high capacity in discriminating between PD and PPS patients (AUC 0.719–0.831). The CBF was positively correlated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in PD patients, while positively correlated with the MMSE, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) scores in PPS patients (P < 0.05).ConclusionPD and PPS patients have certain discriminative patterns of reduced CBFs, which can be used as a surrogate marker for differential diagnosis.

Arterial Spin Labeling Perfusion Magnetic Resonance Imaging Reveals Resting Cerebral Blood Flow Alterations Specific to Retinitis Pigmentosa Patients

ABSTRACTPurpose: This study aimed to assess resting cerebral blood flow (CBF) changes in retinitis pigmentosa (RP) patients using a pseudo-continuous arterial spin labeling (pCASL) perfusion method.Methods: Forty-nine RP patients and 51 healthy controls (HCs) underwent T1-weighted structural and pCASL sequence magnetic resonance imaging (MRI) scans at rest. Two-sample t-tests were performed to compare CBF differences between groups. Pearson correlation was used to analyze relationships between CBF values and clinical variables in the RP group.Results: Compared with HCs, RP patients had significantly lower CBF values in the bilateral cuneus/lingual gyrus/precuneus/posterior cingulate/middle occipital gyrus. In the RP group, CBF values in the left middle occipital and inferior occipital gyrus were positively correlated with mean retinal nerve fiber layer thickness; furthermore, CBF values in several regions were correlated with duration of disease and age of onset.Conclusions: Our results highlighted that RP patients exhibited decreased CBF values in the visual cortices and vision-related cortices. The results suggest that altered CBF might contribute to trans-synaptic retrograde degeneration of the visual pathway in RP patients.

Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease.

To investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD). Twenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r. We found a decrease in CBF of 2.2 mL/min/100 g (p < 0.01) and an increase in leakage volume of 0.7% (p < 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (-0.53 < r < -0.40, p < 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03). BBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.

Abstract WP567: The Association Between Decreased Cerebral Blood Flow in Transient Ischemic Attack Patients and Cognition

Patients with transient ischemic attack (TIA) have a 4-fold increase in developing late-life dementia. Cerebral blood flow has shown to be reduced approximately 30% in patients with Alzheimer’s disease (AD). Vascular abnormalities may initiate and aggravate AD pathology prior to the development of clinical symptoms. We hypothesize that middle-aged patients with a history of TIA will have lower cerebral blood flow (CBF) in the hippocampus, thalamus, white matter and grey matter compared to healthy controls. Additionally, we hypothesize that individuals with lower cerebral blood flow in our regions of interest will have lower cognitive scores. Participants between the ages of 45-85 years old without dementia were subject to a clinical brain MRI arterial-spin-labelling CBF sequence accompanied by a cognitive battery. The cognitive battery included the Montreal Cognitive Assessment (MOCA) and a composite memory score created with the Addenbrooke’s Cognitive Examination, the Brief Visuospatial Memory Test Revised, and the Rey Auditory Verbal Learning Test. TIA patients had their assessments within 14-days of ictus. Atlas-based imaging analysis was performed using FSL. Sixty-three (63) healthy controls (63 + 10 years of age) and 51 TIA (69 + 9 years of age) participants were analyzed. In an independent one-tailed t-test, TIA patients had significantly (p&lt;0.05) lower CBF than healthy controls in the left/right hippocampus and thalamus, and right white matter. A multiple regression was performed to predict MOCA and composite memory scores from CBF, while correcting for age, gender and premorbid intelligence. Lower hemispheric CBF in the hippocampus, thalamus, white matter and grey matter each significantly predicted lower MOCA scores (F(4,101), R 2 =[0.1701-0.2013], p&lt;0.05) and lower composite memory scores (F(4,101), R 2 =[0.2429-0.2864], p&lt;0.05) in all participants. In conclusion , TIA patients have significantly lower CBF values in regions of interest compared to healthy control subjects and decreased CBF values in all participants are associated with poorer cognitive scores. By investigating neuroimaging biomarkers associated with cognition in mid-life, we may begin to understand why TIA patients have a higher risk of developing AD in late-life.

3D pseudocontinuous arterial spin-labeling perfusion imaging detected crossed cerebellar diaschisis in acute, subacute and chronic intracerebral hemorrhage

ObjectiveWe aimed to evaluate the value of 3D pseudocontinuous arterial spin-labeling (pCASL) perfusion imaging detected crossed cerebellar diaschisis (CCD) at different stages of intracerebral hemorrhage (ICH). Materials and methodsWe assessed bilateral cerebral blood flow (CBF) values of different brain regions and the relationships between the CCD and clinical status of 16 ICH patients. ResultsThe ICH patients had significantly lower CBF values in the contralateral cerebellum in acute, subacute and chronic stages. The subacute CCD had a significant correlation with clinical status. Conclusions3D pCASL may be an ideal tool to study the phenomenon and clinical consequences of ICH with CCD.

Quantifying the Cerebral Hemodynamic Changes in Hypertensive Patients Using 3D Pseudo-continuous Arterial Spin Labeling.

Objective To investigate the cerebral hemodynamic changes in hypertensive patients using 3D pseudo-continuous arterial spin labeling(3D pCASL).Methods Fifty-eight hypertensive subjects and thirty-four age-matched healthy volunteers were recruited and scanned using the 3D whole-brain pCASL sequence.The regional cerebral blood flow(CBF)values were achieved based on 3D pCASL with SPM8 technique and were manually drawn. Results Compared with healthy volunteers,hypertensive patients had significantly lower CBF values in various regions,with statistical difference at the bilateral centrum semiovale(P=0.000,P=0.000),periventricular white matter(P=0.001,P=0.002),splenium of corpus callosum(P=0.003),frontal lobe(P=0.003),parietal lobe(P=0.014),occipital lobe(P=0.002),temporal lobe(P=0.006),medulla(P=0.012),pons(P=0.016),midbrain(P=0.034),cerebellum(P=0.000),and gray matter(P=0.001).Nevertheless,the CBF values in the thalami,globus pallidus,putamen,and genu of corpus callosum demonstrated no significant inter-group difference(all P>0.05).Conclusions 3D pCASL can be used to detect the subtle hemodynamic abnormalities even at the early stage of hypertension.The observed decrease in CBF in these regions may suggest an increased risk of cerebral small vessel diseases.

Systemic inflammation and alterations to cerebral blood flow in obstructive sleep apnea.

Systemic inflammation and alterations to regional cerebral blood flow (CBF) have been reported previously in obstructive sleep apnea (OSA). This study utilized arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI) to evaluate CBF in OSA patients and determine its relationship with systemic inflammation. Twenty male patients with moderate and severe OSA [apnea-hypopnea index (AHI) >15] and 16 healthy male volunteers (AHI <5) were recruited. Early- or late-phase changes in leucocyte apoptosis and its subsets were determined by flow cytometry. Perfusion MRI data were acquired with a pulsed continuous ASL technique. The CBF maps were compared using voxel-based statistics to determine differences between the OSA and control groups. The differences in CBF, clinical severity and leucocyte apoptosis were correlated. Exploratory groupwise comparison between the two groups revealed that the OSA patients exhibited low CBF values in the vulnerable regions. The lower regional CBF values were correlated with higher clinical disease severity and leucocyte apoptosis. OSA impairs cerebral perfusion in vulnerable regions, and this deficit is associated with increased disease severity. The apparent correlation between systemic inflammation and cerebral perfusion may be indicative of haemodynamic alterations and their consequences in OSA.

Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus.

We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a ‘distributed deviating voxels’ method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total ‘distributed deviating voxels’ demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.

Mean arterial pressure change associated with cerebral blood flow in healthy older adults

We investigate over a 12-year period the association between regional cerebral blood flow (CBF) and cardiovascular risk factors in a prospective cohort of healthy older adults (81.96 ± 3.82 year-old) from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) study. Cardiovascular risk factors were measured over 12 years, and gray matter CBF was measured at the end of the study from high-resolution magnetic resonance imaging using arterial spin labeling. The association between cardiovascular risk factors, their long-term change, and CBF was assessed using multivariate linear regression models. Women were observed to have higher CBF than men (p < 0.05). Increased mean arterial pressure (MAP) over the 12-year period was correlated with a low cerebral blood flow (p < 0.05, R2 = 0.21), whereas no association was detected between CBF and MAP at the time of imaging. High levels of glycemia tended to be associated with low cerebral blood flow values (p < 0.05). Age, alcohol consumption, smoking status, body mass index, history of cardiovascular disease, and hypertension were not associated with CBF. Our main result suggests that change in MAP is the most significant predictor of future CBF in older adults.

Different post label delay cerebral blood flow measurements in patients with Alzheimer's disease using 3D arterial spin labeling

PurposeTo evaluate cerebral blood flow (CBF) in patients with Alzheimer's disease (AD) using a three-dimensional pseudocontinuous arterial spin labeling (PCASL). We aimed to study the effects of different post label delay on the resulting CBF maps and to investigate the characteristics and clinical applications of brain perfusion. Materials and methodsSixteen AD patients and nineteen healthy control subjects were recruited. 3D PCASL was performed using a 3.0T MR scanner. ASL was performed twice with different post label delays (PLD). Comparisons of CBF were made between AD patients and healthy control subjects respectively with PLD of 1.5s and PLD of 2.5s. Relationship between the CBF values and cognition was investigated using correlation analysis. A receiver operating characteristic (ROC) curve was generated for CBF measurements in posterior cingulate region. ResultAD patients with PLD of 1.5s showed lower CBF values primarily in bilateral temporal lobes, precuneus, middle and posterior cingulate gyri, left inferior parietal gyrus, left angular gyrus and left superior frontal gyrus. Lowered cerebral values were also observed in similar regions with PLD of 2.5s, but the clusters of voxel were smaller. CBF values were associated with cognition scores in most of gyri mentioned above. ConclusionHypoperfusion areas were observed in AD patients. PLD of 1.5s was sufficient to display CBF. Considering the complicated AD pathology, multiple PLDs are strongly recommended.

Pseudo-continuous arterial spin labeling quantifies cerebral blood flow in patients with acute ischemic stroke and chronic lacunar stroke

ObjectiveWe employed non-invasive pseudo-continuous arterial spin labeling (pCASL) to quantify cerebral blood flow (CBF) in infarcted and nearby neural regions in patients with acute ischemic stroke (AIS) and chronic lacunar stroke (CLS). The results were compared with CBF in healthy individuals. MethodsAIS and CLS patients were imaged with ASL, diffusion-weighted imaging (DWI) and conventional MRI. CBF maps were created with 3DASL software. Two expert readers identified AIS and CLS lesions on conventional images, DWI images and CBF maps. A senior radiologist calculated CBF values for lesions and nearby regions. Lesion, nearby regions and normal corresponding region values were analyzed using a two-sample t-test. ResultsFifty-six stroke patients (21 with AIS and 35 with CLS) and 30 healthy subjects participated in this study. In the AIS group, AIS lesions appeared in the cortex/white matter, external/internal capsule (EC/IC), and basal ganglia. AIS lesions had lower CBF values than the normal corresponding regions (p<0.05). The mean CBF values in AIS nearby regions were significantly higher than those in normal corresponding regions (p<0.05). In the CLS group, the CBF values in white matter and EC/IC were lower than the CBF values in normal corresponding regions (p=0.063 and 0.052, respectively). The CBF values in CLS nearby regions and normal corresponding regions were not significantly different (p>0.05). ConclusionIn some regions of the brain, CLS lesions, AIS lesions, and their nearby regions have different perfusion statuses. In particular, the AIS nearby regions perfusion in our subjects was significantly higher than that previously reported. pCASL can be a robust imaging technique for diagnosing strokes in clinical practices.

Monitoring of Cerebral Blood Flow and Metabolism Bedside in Patients with Subarachnoid Hemorrhage – A Xenon-CT and Microdialysis Study

Cerebral ischemia is the leading cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Although 70% of the patients show angiographic vasospasm only 30% develop symptomatic vasospasm defined as delayed cerebral ischemia (DCI). Early detection and management of reversible ischemia is of critical importance in patients with SAH. Using a bedside Xenon enhanced computerized tomography (Xenon-CT) scanner makes it possible to measure quantitative regional Cerebral blood flow (CBF) bedside in the neurointensive care setting and intracerebral microdialysis (MD) is a method that offers the possibility to monitor the metabolic state of the brain continuously. Here, we present results from nine SAH patients with both MD monitoring and bedside Xenon-CT measurements. CBF measurements were performed within the first 72 h following bleeding. Six out of nine patients developed DCI at a later stage. Five out of six patients who developed DCI had initial global CBF below 26 ml/100 g/min whereas one had 53 ml/100 g/min. The three patients who did not develop clinical vasospasm all had initial global CBF above 27 ml/100 g/min. High lactate/pyruvate (L/P) ratio was associated with lower CBF values in the area surrounding the catheter. Five out of nine patients had L/P ratio ≥25 and four of these patients had CBF ≤ 22 ml/100 g/min. These preliminary results suggest that patients with initially low global CBF on Xenon-CT may be more likely to develop DCI. Initially low global CBF was accompanied with metabolic disturbances determined by the MD. Most importantly, pathological findings on the Xenon-CT and MD could be observed before any clinical signs of DCI. Combining bedside Xenon-CT and MD was found to be useful and feasible. Further studies are needed to evaluate if DCI can be detected before any other signs of DCI to prevent progress to infarction.

White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome

The dynamic susceptibility contrast magnetic resonance imaging perfusion technique was used to investigate possible hemodynamic changes in normal appearing white matter and deep gray matter (DGM) of 30 patients with clinically isolated syndrome (CIS) and 30 patients with relapsing-remitting multiple sclerosis. Thirty normal volunteers were studied as controls. Cerebral blood volume, cerebral blood flow (CBF), and mean transit time values were estimated. Normalization was achieved for each subject with respect to average values of CBF and mean transit time of the hippocampi's dentate gyrus. Measurements concerned three regions of normal white matter of normal volunteers, normal appearing white matter of CIS and patients with relapsing-remitting multiple sclerosis, and DGM regions, bilaterally. All measured normal appearing white matter and DGM regions of the patients with CIS had significantly higher cerebral blood volume and mean transit time values, while averaged DGM regions had significantly lower CBF values, compared to those of normal volunteers (P < 0.001). Regarding patients with relapsing-remitting multiple sclerosis, all measured normal appearing white matter and DGM regions showed lower CBF values than those of normal volunteers and lower cerebral blood volume and CBF values compared to patients with CIS (P < 0.001). These data provide strong evidence that hemodynamic changes--affecting both white and DGM--may occur even at the earliest stage of multiple sclerosis, with CIS patients being significantly different than relapsing-remitting multiple sclerosis patients.

Variants of the Endothelial Nitric Oxide Gene and Cerebral Blood Flow after Severe Traumatic Brain Injury

Experimental studies suggest that nitric oxide produced by endothelial nitric oxide synthase (NOS3) plays a role in maintaining cerebral blood flow (CBF) after traumatic brain injury (TBI). The purpose of this study was to determine if common variants of the NOS3 gene contribute to hypoperfusion after severe TBI. Fifty-one patients with severe TBI were studied. Cerebral hemodynamics, including global CBF by the stable xenon computed tomography (CT) technique, internal carotid artery flow volume (ICA-FVol), and flow velocity in intracranial vessels, were measured within 12 h of injury, and at 48 h after injury. A blood sample was collected for DNA analysis, and genotyping of the following variants of the NOS3 gene was performed: -786T>C, 894G>T, and 27bp VNTR. Cerebral hemodynamics were most closely related to the-786T>C genotype. CBF averaged 57.7±3.0 mL/100 g/min with the normal T/T genotype, 47.0±2.5 mL/100 g/min with the T/C, and 37.3±8.8 mL/100 g/min with the C/C genotype (p=0.0146). Cerebrovascular resistance followed an inverse pattern with the highest values occurring with the C/C genotype (p=0.0027). The lowest ICA-FVol of 124±43 mL/min was found at 12 h post-injury in the more injured hemisphere of the patients with the C/C genotype (p=0.0085). The mortality rate was 20% in patients with the T/T genotype and 17% with the T/C genotype. In contrast, both of the patients with the C/C genotype were dead at 6 months post-injury (p=0.022). The findings in this study support the importance of NO produced by NOS3 activity in maintaining CBF after TBI, since lower CBF values were found in patients having the -786C allele. The study suggests that a patient's individual genetic makeup may contribute to the brain's response to injury and determine the patient's chances of surviving the injury. The results here will need to be studied in a larger number of patients, but could explain some of the variability in outcome that occurs following severe TBI.

Temporal MRI Assessment of Intracerebral Hemorrhage in Rats

MRI was used to evaluate the effects of experimental intracerebral hemorrhage (ICH) on brain tissue injury and recovery. Primary ICH was induced in rats (n=6) by direct infusion of autologous blood into the striatum. The evolution of ICH damage was assessed by MRI estimates of T(2) and T(1sat) relaxation times, cerebral blood flow, vascular permeability, and susceptibility-weighted imaging before surgery (baseline) and at 2 hours and 1, 7, and 14 days post-ICH. Behavioral testing was done before and at 1, 7, and 14 days post-ICH. Animals were euthanized for histology at 14 days. The MRI appearance of the hemorrhage and surrounding regions changed in a consistent manner over time. Two primary regions of interest were identified based on T(2) values. These included a core, corresponding to the bulk of the hemorrhage, and an adjacent rim; both varied with time. The core was associated with significantly lower cerebral blood flow values at all post-ICH time points, whereas cerebral blood flow varied in the rim. Increases in vascular permeability were noted at 1, 7, and 14 days. Changes in T(1sat) were similar to those of T(2). MRI and histological estimates of tissue loss were well correlated and showed approximately 9% hemispheric tissue loss. Although the cerebral blood flow changes observed with this ICH model may not exactly mimic the clinical situation, our results suggest that the evolution of ICH injury can be accurately characterized with MRI. These methods may be useful to evaluate therapeutic interventions after experimental ICH and eventually in humans.