Lobe Cerebral Blood Flow Research Articles

Cerebral blood flow following successful living kidney transplantation: the VINTAGE study.

Chronic kidney disease (CKD) is a significant risk factor for cerebrovascular disease. However, there is limited research on how successful living donor kidney transplantation (LDKT) affects cerebral blood flow (CBF). This study aims to comprehensively investigate how LDKT influences CBF across various brain levels and regions. Data from 53 recipients between 2016 and 2020 were obtained from the VINTAGE study conducted at our hospital. CBF was measured by level and region using single-photon emission computed tomography (SPECT), according to the Talairach brain atlas. The primary endpoint was the mean difference in CBF before and 1-year post-LDKT. Subgroup analysis using traditional risk factors assessed the heterogeneity of the effect on CBF in the frontal lobe region. LDKT improved blood flow in the anterior cerebral artery and middle cerebral artery but had less impact on the posterior cerebral artery. The most consistent improvements were observed in the frontal lobe region {left frontal lobe: -0.12 [95% confidence interval (CI) -0.18 to -0.05], P<.001; right frontal lobe: -0.13 [95% CI -0.21 to -0.05], P=.001}. Subgroup analysis showed a consistent effect of LDKT on frontal lobe CBF improvement, with no qualitative interaction observed. LDKT contributes to the normalization of CBF, with improvement in anterior circulation and frontal lobe blood flow. To clarify the clinical significance of KT's CBF-improving effect, future studies should investigate the relationship between specific cognitive impairments (e.g. short-term memory, visuospatial ability, executive function) and CBF in each perfusion region.

Hippocampal volume mediates the association of arterial stiffness with cognitive impairment in adult population.

To investigate the association of arterial stiffness with brain perfusion, brain tissue volume and cognitive impairment in the general adult population. This prospective study included 1488 adult participants (age range: 22.8-83.9 years) from the Kailuan study. All participants underwent brachial-ankle pulse wave velocity (PWV) measurement, brain MRI, and Montreal Cognitive Assessment (MoCA). The association of PWV with cerebral blood flow (CBF), brain tissue volume and MoCA score was investigated. Mediation analysis was used to determine whether CBF and brain tissue volume changes mediated the associations between PWV and MoCA score. A 1 standard deviation (SD) increase in PWV was associated with lower total brain CBF [ β (95% CI) -0.67 (-1.2 to -0.14)], total gray matter CBF [β (95% CI) -0.7 [-1.27 to -0.13)], frontal lobe CBF [ β (95% CI) -0.59 (-1.17 to -0.01)], parietal lobe CBF [ β (95% CI) -0.8 (-1.43 to -0.18)], and temporal lobe CBF [ β (95% CI) -0.68 (-1.24 to -0.12)]. Negative associations were found for PWV and total brain volume [ β (95% CI) -4.8 (-7.61 to -1.99)] and hippocampus volume [ β (95% CI) -0.08 (-0.13 to -0.04)]. A 1 SD increase PWV was significantly associated with elevated odds of developing cognitive impairment [odds ratio (95% CI) 1.21 (1.01-1.45)]. Mediation analysis showed that hippocampal volume partially mediated the negative association between PWV and MoCA scores (proportion: 14.173%). High arterial stiffness was associated with decreased total and regional CBF, brain tissue volume, and cognitive impairment. Hippocampal volume partially mediated the effects of arterial stiffness on cognitive impairment.

Higher baseline cerebrospinal fluid platelet‐derived growth factor receptor‐β levels are associated with slower reductions in longitudinal cerebral blood flow among cognitively unimpaired individuals

AbstractBackgroundCerebrospinal fluid (CSF) platelet‐derived growth factor receptor‐β (PDGFR‐β) is an emerging biomarker hypothesized to reflect pericyte damage. CSF PDGFR‐β levels are increased in Alzheimer’s disease (AD), but it is unknown if pericyte injury contributes to cerebrovascular changes common in AD. We examined if PDGFR‐β relates to changes in cerebral blood flow (CBF) and white matter injury in older adults.MethodVanderbilt Memory and Aging Project participants (n = 152, baseline age 73±7 years, 43% mild cognitive impairment [MCI]) underwent baseline lumbar puncture and serial brain MRI over a 7‐year (5.5±2.3) follow‐up period. CSF PDGFR‐β concentrated was measured by immunoassay. MRI included pseudo‐continuous arterial spin‐labeling to quantify CBF, T2‐FLAIR to quantify white matter hyperintensities (WMHs), and diffusion tensor imaging (DTI) to quantify white matter microstructural integrity. Ordinary least squares regression and linear mixed‐effects models related baseline CSF PDGFR‐β to baseline and longitudinal whole brain and regional CBF, WMH, and DTI metrics, adjusting for baseline demographic variables, modified Framingham Stroke Risk Profile, cognitive status, apolipoprotein‐ε4 status, and regional tissue volume. Longitudinal models adjusted for follow‐up time. Follow‐up models tested a CSF PDGFR‐β x cognitive status interaction.ResultIn main models, higher CSF PDGFR‐β levels were cross‐sectionally associated with lower mean diffusivity (indicating better microstructural integrity) in white matter tracts in the frontal, temporal, parietal, and occipital lobes (p‐values&lt;0.03) but were unrelated to WMHs (p‐values&gt;0.18). Models investigating associations with longitudinal white matter variables were null (p‐values&gt;0.35). CSF PDGFR‐β cross‐sectionally interacted with diagnosis on temporal lobe CBF, such that higher CSF PDGFR‐β related to higher CBF in MCI participants (p = 0.01). In longitudinal models, baseline CSF PDGFR‐β interacted with cognitive status on whole brain and occipital lobe CBF (p‐values&lt;0.04). Stratified models showed higher baseline CSF PDGFR‐β related slower reductions in longitudinal CBF in whole brain (p = 0.02), frontal (p = 0.04), temporal (p = 0.02), parietal (p = 0.01), and occipital lobes (p = 0.008) in cognitively unimpaired participants only.ConclusionAmong older adults, higher CSF PDGFR‐β levels are associated with better white matter integrity at study entry and predict slower reductions in longitudinal CBF among cognitively unimpaired individuals. Results suggest that higher PDGFR‐β levels may reflect subclinical vascular remodeling that provides protection to future cerebrovascular compromise.

Visit‐to‐visit blood pressure variability and medial temporal perfusion in APOE e4 homozygotes

AbstractBackgroundBlood pressure variability (BPV), independent of traditionally studied/targeted average blood pressure levels, is an emerging risk factor for cognitive impairment and Alzheimer’s dementia, possibly through links with cerebrovascular disease. Recent studies suggest vulnerability of the medial temporal lobes to tau accumulation and atrophy among individuals with elevated BPV, especially older APOE e4 carriers. Increased BPV has also been linked with lower cerebral blood flow (CBF) and perfusion decline in medial temporal regions, but it remains unclear how BPV and APOE e4 may interact to influence CBF. The aim of the current study was to determine whether the relationship between BPV and medial temporal lobe CBF varies by APOE e4 dose in older adults without dementia.Method105 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative underwent 3‐4 blood pressure measurements between study baseline and 12‐months follow‐up and arterial spin labeling (ASL)‐MRI at 12‐months follow‐up or later (range: 0 – 84 months). Visit‐to‐visit BPV was calculated as variability independent of mean. CBF was determined for medial temporal regions (residualized by precentral [reference region] CBF), including hippocampus, parahippocampal gyrus, and entorhinal cortex. Venipuncture determined APOE e4 allele count (0 alleles: n = 71; 1 allele: n = 28; 2 alleles: n = 6). Multiple linear regression examined the interaction of BPV x APOE e4 dose on medial temporal CBF, controlling for age, sex, race/ethnicity, antihypertensive use, mean blood pressure, and cerebral metabolism (FDG‐PET).ResultElevated BPV was associated with lower CBF in entorhinal cortex (ß = ‐.96 [‐1.62, ‐.31]; p = .005) and parahippocampal gyrus (ß = ‐.63 [‐1.26, ‐.0002]; p = .049) in individuals with 2 APOE e4 alleles, whereas BPV was not significantly associated with CBF in these regions in individuals with 0 or 1 APOE e4 alleles (p’s &gt; = .08). There was no significant interaction of BPV x APOE e4 dose on hippocampal CBF.ConclusionHigher BPV is associated with lower medial temporal CBF in APOE e4/e4 carriers, suggesting BPV may be an understudied vascular risk factor for those at greatest genetic risk for Alzheimer’s disease, with potential therapeutic implications.

Abstract 001: Microvascular reperfusion during endovascular therapy: the balance of supply and demand

Introduction Endovascular therapy (EVT) has revolutionized acute stroke treatment, but large vessel recanalization does not always result in tissue‐level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during EVT. Here we aimed to leverage diffuse correlation spectroscopy (DCS), a novel transcranial optical imaging technique, to assess the relationship between microvascular CBF and post‐EVT outcomes. Methods Frontal lobe CBF was monitored by DCS in 40 patients undergoing EVT. Baseline CBF deficit was calculated as the percentage of CBF impairment on pre‐EVT CT perfusion. Microvascular reperfusion was calculated as the percentage increase in DCS‐derived CBF that occurred with recanalization. The adequacy of reperfusion was defined by persistent CBF deficit, calculated as: baseline CBF deficit ‐ microvascular reperfusion. Good functional outcome was defined as 90‐day modified Rankin Scale ≤2. Results 36 (of 40) patients achieved successful recanalization, in whom microvascular reperfusion in itself was not associated with infarct volume or functional outcome. However, patients with good functional outcomes had a smaller persistent CBF deficit (median: 1%; IQR: ‐11%–16%) than patients with poor outcomes (median: 28%; IQR: 2%–50%), p=0.02. Smaller persistent CBF deficit was also associated with smaller infarct volume (p=0.004). Multivariate models confirmed that persistent CBF deficit was independently associated with infarct volume and functional outcome. Conclusion CBF augmentation alone does not predict post‐EVT outcomes, but when microvascular reperfusion closely matches the baseline CBF deficit, patients experience favorable clinical and radiographic outcomes. By recognizing inadequate reperfusion, bedside CBF monitoring may provide opportunities to personalize post‐EVT care aimed at CBF optimization.

Microvascular reperfusion during endovascular therapy: the balance of supply and demand

BackgroundEndovascular therapy (EVT) has revolutionized the treatment of acute stroke, but large vessel recanalization does not always result in tissue-level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during...

Dobutamine-induced alternations in cerebral blood flow of healthy adults: a 3D pseudocontinuous arterial spin labeling study

BackgroundIt is unclear whether dobutamine, commonly used clinically in echocardiography and short-term congestive heart failure treatment for promoting increased myocardial contractility, affects brain microcirculatory behavior. Cerebral microcirculation plays an important role in ensuring adequate oxygen transport. Therefore, we investigated the effects of dobutamine on cerebral hemodynamics.MethodsForty-eight healthy volunteers without cardiovascular or cerebrovascular disease underwent MRI to obtain cerebral blood flow (CBF) maps using 3D pseudocontinuous arterial spin labeling before and during the dobutamine stress test. Additionally, cerebrovascular morphology was obtained based on 3D-time-off-light (3D-TOF) magnetic resonance angiography (MRA). Electrocardiogram, heart rate (HR), respiration rate (RR), blood pressure, and blood oxygen were simultaneously recorded before and during dobutamine injection and during recovery (not during MRI). The anatomic features of the circle of Willis and the basilar artery (BA) diameter were assessed on MRA images by two radiologists with extensive neuroimaging experience. Binary logistic regression was used to test for the independent determinants of CBF changes.ResultsHR, RR, systolic (SBP), and diastolic blood pressure (DBP) significantly increased after dobutamine infusion. Blood oxygen levels remained similar. Compared to the CBF in the resting state, the CBF values exhibited significantly lower CBF levels in both grey matter and white matter. Furthermore, compared with the CBF in the resting state, that in the stress state was decreased in the anterior circulation, mainly in the frontal lobe (voxel level P < 0.001, pixel level P < 0.05). Logistic regression showed that body mass index (BMI; odds ratio [OR] 5.80, 95% confidence interval [CI] 1.60–21.01, P = 0.008], resting SBP (OR 0.64, 95% CI 0.45–0.92, P = 0.014), and BA diameter (OR 11.04, 95% CI 1.05–116.53, P = 0.046) were significantly associated with frontal lobe CBF changes.ConclusionsDobutamine-induced stress significantly decreased CBF in the frontal lobe anterior circulation. Individuals with a high BMI and low SBP during the dobutamine stress test are more likely to have a stress-induced CBF decrease. Thus, attention should be paid to blood pressure, BMI, and cerebrovascular morphology of patients undergoing dobutamine stress echocardiography or those receiving intensive care or anesthesia.

Reduced temporal lobe cerebral blood flow is associated with regional white matter damage among apolipoprotein E ε4 carriers

AbstractBackgroundReduced cerebral blood flow (CBF) is a risk factor for white matter damage. Apolipoprotein E (APOE) e4, a genetic risk factor for Alzheimer’s disease and vascular health modifier, is associated with lower CBF. However, it remains unknown if lower CBF is associated with more severe white matter damage among APOE‐e4 carriers. We examine whether associations among regional CBF, cerebrovascular reactivity (CVR), and white matter integrity are modified by APOE‐e4 status in older adults.MethodVanderbilt Memory and Aging Project participants (n = 313, 73±7 years) underwent 3T brain MRI. Resting grey matter CBF and CVR (CBF response to hypercapnic stimulus, ΔCBF/100*ΔCO2) were quantified in regions of interest from pseudo‐continuous arterial spin labeling (ASL). Fractional anisotropy (FA) was quantified from diffusion tensor imaging in tracts of interest derived from tractography templates. Linear regressions related regional CBF and CVR to tract‐specific FA, adjusting for demographic and vascular variables, regional tissue volume, cognitive status, and APOE‐e4 status. Follow‐up models tested an APOE‐ε4 status x ASL variable interaction term.ResultIn main models, lower temporal lobe CBF was associated with lower FA in the occipital lobe, suggesting compromised white matter integrity (p = 0.02). Lower CBF and higher CVR in the occipital lobe were associated with compromised lower FA in all lobes (all p‐values&lt;0.04). Temporal lobe CBF and CVR interacted with APOE‐e4 status, such that lower temporal lobe CBF related to lower FA in the frontal lobe (p = 0.01) and higher temporal lobe CVR related to lower FA in the frontal (p = 0.001) and temporal (p = 0.007) lobes among APOE‐e4 carriers only. Frontal lobe CVR interacted with APOE‐e4 status, such that higher CVR related to lower FA in the frontal (p&lt;0.001) and temporal lobes (p = 0.008) in APOE‐e4 carriers only.ConclusionAmong older adults, APOE‐e4 modifies associations between cerebral hemodynamics and white matter integrity, such that reduced CBF and greater CVR in the temporal lobe are associated with greater white matter damage in APOE‐e4 carriers. APOE‐e4 carriers may be more susceptible to changes in temporal lobe hemodynamics, and vascular changes in the temporal lobe may have a stronger impact on brain health outcomes for carriers compared to non‐carriers.

Frontal lobe dysfunction is associated with reduced DAT-SPECT accumulation in Lewy body disease

IntroductionLewy body disease (LBD) causes olfactory or cognitive dysfunction even before motor symptoms emerge. Recent reports indicate that the dopamine transporter (DAT), which can be imaged using single-photon emission computed tomography (123I-ioflupane SPECT), is related to olfactory and cognitive dysfunction in LBD patients. We suspected that decreased cerebral blood flow (CBF) in the frontal lobe might be involved in these relationships. If so, then the results of these examinations may be useful in assessing the pathological progression of Lewy bodies. MethodsWe retrospectively analyzed the data of 139 de novo consecutive patients with LBD. We used the Odor Stick Identification Test for Japanese (OSIT-J) and the Frontal Assessment Battery (FAB) to evaluate olfactory and frontal lobe dysfunction, respectively. Among the 139 patients, ultimately 84 patients were analyzed and underwent 123I-ioflupane SPECT within 3 months (before or after) of the OSIT-J and FAB. We categorized patients on the basis of whether frontal lobe CBF was reduced (n = 28) or normal (n = 56). ResultsThe average OSIT-J and FAB scores were 4.0 and 14.1, respectively, and the scores on the two tests were significantly correlated. Furthermore, OSIT-J scores were significantly correlated with the specific binding ratio (SBR) in both groups. The SBR was correlated with FAB scores in patients with reduced CBF in the frontal lobe, but not in those with normal CBF. ConclusionFrontal lobe dysfunction and striatum dysfunction are correlated in LBD patients only after CBF has declined. Also, there is a time lag in the appearance of olfactory dysfunction and frontal lobe dysfunction in LBD patients. As with pathological development, olfaction is impaired earliest, followed by striatal, and then frontal lobe dysfunction.

Subjective cognitive decline is associated with longitudinal cerebral blood flow reductions and gray matter atrophy in older adults

AbstractBackgroundSubjective cognitive decline (SCD), a potential harbinger of Alzheimer’s disease (AD), has been cross‐sectionally associated with neurodegeneration and cerebrovascular disease markers on brain MRI. However, longitudinal associations are less clear with few existing studies that yield inconsistent findings. Here, we related baseline SCD to longitudinal structural and hemodynamic markers of brain health in older adults free of clinical dementia and stroke.MethodsVanderbilt Memory &amp; Aging Project participants (n=299,72±7 years, 58% male) completed a baseline SCD protocol and multimodal 3T brain MRI, including T 1‐weighted imaging (grey matter volumes) and pseudo‐continuous arterial spin labeling (cerebral blood flow (CBF)) at baseline and multiple follow‐ups (18‐months, 3‐years, 5‐years). Baseline SCD (total and subdomain memory, language, and executive functioning scores) was longitudinally related to global and regional grey matter volumes and CBF (mL/100g/min). Linear mixed effects models, with random intercepts and slopes and a follow‐up time interaction, covaried for baseline age, sex, race/ethnicity, education, diagnosis, mood, and apolipoprotein E (APOE)‐e4 status. Grey matter volume models covaried for intracranial volume. CBF models covaried for associated tissue volume.ResultsMean follow‐up time was 3.8 years. Higher total SCD predicted hippocampal volume reductions (p=0.04), increased inferior lateral ventricular volume (p&lt;0.001; Figure 1A), and global CBF reductions (p&lt;0.001; Figure 1B). Higher scores within each SCD domain predicted hippocampal volume reductions, increased inferior lateral ventricular volume, and global CBF reductions (p‐values&lt;0.04). Higher executive functioning‐SCD related only to frontal and occipital CBF reductions (p‐values&lt;0.003; Figure 1C) but not temporal CBF or lobar atrophy (p‐values&gt;0.07). Language‐SCD predicted reduced frontal CBF (p=0.01; Figure 1D) and temporal lobe volume (p=0.02). Surprisingly, memory‐SCD was not associated with temporal lobe volume or CBF (p‐values&gt;0.05). Sensitivity analyses excluding outliers revealed the same associations.ConclusionsHigher baseline SCD predicted multiple pathways of longitudinal brain changes, including cerebral hemodynamics and volume loss within areas first affected by AD. Executive functioning‐SCD predicted hemodynamic changes and language‐SCD related to alterations within the frontal and temporal lobes. Results suggest the relevance of considering the type of SCD, as specific domains may predict different pathologies over time with important prognostic implications. Future research is needed to understand the clinical consequences of these findings.

Lower Thalamic Blood Flow Is Associated With Slower Stride Velocity in Older Adults.

BackgroundGait deficits are associated with brain atrophy and white matter hyperintensities (WMH) – both markers of underlying cerebral small vessel disease (SVD). Given reduced subcortical cerebral blood flow (CBF) is prevalent in SVD, we tested the hypothesis that regional CBF is positively associated with gait performance among older adults.MethodsThirty-two older adults (55–80 years) with at least one vascular risk factor were recruited. We assessed gait during 2 consecutive walking sequences using a GAITRite system: (1) at a self-selected pace, and (2) while performing a serial subtraction dual-task challenge. We quantified CBF using pseudo-continuous arterial spin labeling MRI within 4 regions of interest: putamen, pallidum, thalamus, and hippocampus. We investigated associations between gait characteristics and overall CBF adjusting for age, sex, and height in an omnibus approach using multivariate analysis of variance, followed by regression analysis with each individual region. We also conducted further regression analyses to investigate associations between gait characteristics and frontal lobe CBF. Sensitivity analyses examined how the observed associations were modified by WMH, executive function, and depressive symptoms. A change of 10% in the model’s adjusted r2 and effect size was considered as a threshold for confounding.ResultsOverall subcortical CBF was not associated with self-paced gait. When examining individual ROI, gait velocity was directly related to thalamic CBF (p = 0.026), and across all gait variables the largest effect sizes were observed in relation to thalamic CBF. In the dual-task condition, gait variables were not related to CBF in either the omnibus approach or individual multiple regressions. Furthermore, no significant associations were observed between frontal CBF and gait variables in either the self-paced or dual-task condition. Sensitivity analyses which were restricted to examine the association of velocity and thalamic CBF identified a cofounding effect of depressive symptoms which increased the effect size of the CBF-gait association by 12%.ConclusionSubcortical hypoperfusion, particularly in regions that comprise central input/output tracts to the cortical tissue, may underlie the association between gait deficits and brain aging.

Microvascular cerebral blood flow fluctuations in association with apneas and hypopneas in acute ischemic stroke.

In a pilot study on acute ischemic stroke (AIS) patients, unexpected periodic fluctuations in microvascular cerebral blood flow (CBF) had been observed. Motivated by the relative lack of information about the impact of the emergence of breathing disorders in association with stroke on cerebral hemodynamics, we hypothesized that these fluctuations are due to apneic and hypopneic events. A total of 28 patients were screened within the first week after stroke with a pulse oximeter. Five (18%) showed fluctuations of arterial blood oxygen saturation ( ) and were included in the study. Near-infrared diffuse correlation spectroscopy (DCS) was utilized bilaterally to measure the frontal lobe CBF alongside respiratory polygraphy. Biphasic CBF fluctuations were observed with a bilateral increase of and for the ipsilesional and contralesional hemispheres, respectively, and a decrease of and for the ipsilesional and contralesional hemispheres, respectively. The polygraph revealed that, in general, the fluctuations were associated with apneic and hypopneic events. This study motivates us to investigate whether the impact of altered respiratory patterns on cerebral hemodynamics can be detrimental in AIS patients.

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.

Anterior-posterior gradient differences in lobar and cingulate cortex cerebral blood flow in late-life depression

Vascular pathology is common in late-life depression, contributing to changes in cerebral function. We examined whether late-life depression was associated with differences in cerebral blood flow (CBF) and whether such differences were related to vascular risk and cerebrovascular pathology, specifically white matter hyperintensity (WMH) volumes. Twenty-three depressed elders and 20 age- and sex-matched elders with no psychiatric history completed cranial 3T MRI. MRI procedures included a pseudo-continuous Arterial Spin Labeling (pcASL) acquisition obtained while on room air and during a hypercapnia challenge allowing for calculation of cerebrovascular reactivity (CVR). Brain segmentation identified frontal, temporal, parietal and cingulate sub-regions in which CBF and CVR were calculated. The depressed group exhibited an anterior-posterior gradient in CBF, with lower CBF throughout the frontal lobe but higher CBF in the parietal lobe, temporal lobe, thalamus and hippocampus. A similar anterior to posterior gradient was observed in the cingulate cortex, with anterior regions exhibiting lower CBF and posterior regions exhibiting higher CBF. We did not observe any group differences in CVR measures. We did not observe significant relationships between CBF and CVR with vascular risk or WMH volumes, aside from an isolated finding associating higher WMH volumes with lower CBF in the rostral anterior cingulate cortex. Decreased anterior CBF in depressed elders might reflect decreased metabolic activity in these regions, while increased posterior CBF may represent either compensatory processes or different activity of posterior intrinsic functional networks. Future work should examine how these findings are related to compensatory changes with aging.

Cerebral blood flow MRI in the nondemented elderly is not predictive of post-operative delirium but is correlated with cognitive performance

Three-dimensional Arterial Spin Labeling (ASL) MRI was performed before surgery in a cohort of 146 prospectively enrolled subjects ≥ 70 years old scheduled to undergo elective surgery. We investigated the prospective association between ASL-derived measures of cerebral blood flow (CBF) before surgery with postoperative delirium incidence and severity using whole-brain and globally normalized voxel-wise analysis. We also investigated the cross-sectional association of CBF with patients’ baseline performance on specific neuropsychological tests, and with a composite general cognitive performance measure (GCP). Out of 146 subjects, 32 (22%) developed delirium. We found no significant association between global and voxel-wise CBF with delirium incidence or severity. We found the most significant positive associations between CBF of the posterior cingulate and precuneus and the Hopkins Verbal Learning Test – Revised total score, Visual Search and Attention Test (VSAT) score and the GCP composite. VSAT score was also strongly associated with right parietal lobe CBF. ASL can be employed in a large, well-characterized older cohort to examine associations between CBF and age-related cognitive performance. Although ASL CBF measures in regions previously associated with preclinical Alzheimer’s Disease were correlated with cognition, they were not found to be indicators of baseline pathology that may increase risk for delirium.

Relationship between neurological complications, cerebrovascular and cerebral perfusion following off-pump coronary artery bypass grafting

Objective:To investigate risk factors for neurological complications after off-pump coronary artery bypass grafting (OPCABG).Methods:We reviewed the cases of 813 patients who underwent OPCABG between August 2010 and September 2013.Data from preoperative 320 dynamic volume computed tomography (CT), CT angiography (CTA), CTA perfusion, and cerebrovascular function examinations were assessed. Neural function was assessed before and 7 days after operation, and patients were assigned to either the neurological complications or non-neurological complications group.Results:Neurological complications were observed in 23.4% (190/813) of patients; cerebral infarction in 1.1% (9/813); hypoxic ischemic encephalopathy in 2.3% (19/813); delirium in 1.5% (12/813); postoperative cognitive dysfunction in 12.9% (105/813); and anxiety/depression in 8.2% (67/813). Patients in the neurological complications group were older, were more likely to have a previous history of cerebrovascular disease and diabetes, had more severe extra-cranial carotid artery stenosis, had more severe stenosis on CTA, and had more perfusion abnormalities compared to patients in the non-neurological- complications group (P < 0.05). Logistic regression analysis identified the following independent risk factors for neurological complications: male gender (odds ratio [OR], 1.816; 95% confidence interval [CI], 1.017–3.244; P = 0.044); cerebrovascular disease history (OR, 1.837; 95% CI, 1.075–3.141; P = 0.026); and perfusion abnormalities (OR, 3.224; 95% CI, 2.073–5.013; P = 0.000). Occipital lobe cerebral blood flow (CBF); differences in temporal lobe, occipital lobe, and basal ganglial time to peak (TTP); and the difference in occipital lobe and basal ganglial mean transit time (MTT) were significantly higher in the neurological complications group (P < 0.05). For the TTP difference, the area under the receiver operating characteristic (ROC) curve was 0.606.Discussion:Neurological complications were observed in 23.4% of patients following OPCABG. Male gender, cerebrovascular disease history, and perfusion abnormalities were independent risk factors for neurological complications. Temporal lobe TTP on CTA perfusion was the best predictor of neurological complications.

CT perfusion-derived mean transit time of cortical brain has a negative correlation with the plasma level of Nitric Oxide after subarachnoid hemorrhage

Vasospasm of both large and small parenchymal arteries may contribute to the occurrence of delayed ischemic neurological deficits, and nitric oxide(NO) is an important mediators in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). We used a rabbit two-hemorrhage model to investigate changes in plasma NO after SAH, and the relationship between NO and brain microcirculation. SAH was induced in rabbits and a control group was sham operated. There were 32 rabbits in each group that survived the second operation, and they were randomly assigned to four groups of eight rabbits each for follow-up assessments on Days 1, 4, 7, or 14, respectively. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated at six regions of interest (ROIs): symmetrical areas of the frontal, parietal-occipital, and temporal lobes. Before the contrast CT scan, blood was drawn from the central artery of the ear for measurement of plasma NO. In the control group, there was no difference in CBV, CBF, and MTT in the six ROIs, and plasma NO was unchanged. Compared to controls, in the SAH group, CBV decreased slightly in the six ROIs (P > 0.05), frontal lobe CBF decreased, MTT increased (P < 0.05, for both), and NO plasma levels were significantly lower (P < 0.01). There was a significant correlation between the increase in MTT and the decrease in plasma NO (P < 0.05), We hypothesized that normalization of NO might have a positive influence on brain microcirculation following SAH.

“Resting” CBF in the epileptic baboon: Correlation with ketamine dose and interictal epileptic discharges

Photosensitive epileptic (SZ) baboons demonstrate different cerebral blood flow (CBF) activation patterns from asymptomatic controls (CTL) during intermittent light stimulation (ILS). This study compares "resting" CBF between PS and CTL animals, and CBF correlations with ketamine dose and interictal epileptic discharges (IEDs) between PS and CTL animals. Continuous intravenous ketamine was administered to eight PS and eight CTL baboons (matched for gender and weight), and maintained at subanesthetic doses (4.8-14.6 mg/kg/hr). Three resting H(2)(15)O-PET studies were attempted in each animal (CTI/Siemens HR+ scanner). Images were acquired in 3D mode (63 contiguous slices, 2.4mm thickness). PET images were co-registered with MRI images (3T Siemens Trio, T1-weighted 3D Turboflash sequence, TE/TR/TI=3.04/2100/785 ms, flip angle=13 degrees ). EEG was used to monitor depth of sedation and for quantification of IED rates. Regional CBF was compared between PS and CTL groups and correlations were analyzed for ketamine dose and IED rates. When subsets of animals of either group, receiving similar doses of ketamine were compared, PS animals demonstrated relative CBF increases in the occipital lobes and decreases in the frontal lobes. Correlation analyses with ketamine dose confirmed the frontal and occipital lobe changes in the PS animals. The negative correlations of CBF with ketamine dose and IED rate overlapped frontally. While frontal lobe CBF was also negatively correlated with IED rate, positive correlations were found in the parietal lobe. "Resting" CBF differs between PS and CTL baboons. Correlation analyses of CBF and ketamine dose reveal that occipital lobe CBF increases and frontal lobe in PS animals are driven by ketamine. While frontal lobe CBF decreases may be related to ketamine's propensity to activate IEDs, positive CBF correlations with IED rate suggest involvement of the parietal lobes in their generation.

Brain volumes and regional cerebral blood flow in carriers of the Swedish Alzheimer amyloid protein mutation.

As a preliminary part of a longitudinal clinical study of carriers of the Swedish amyloid precursor protein (APP) 670/671 mutation, 13 members of a family were investigated with magnetic resonance imaging (MRI) brain volumetry and single photon emission computed tomography (SPECT) cerebral blood flow (CBF) measurements. Five of the family members were mutation carriers; eight were not carriers. Two carriers were younger than 40 years of age and had no evidence of cognitive dysfunction or structural or functional brain changes. One carrier with 4 years to expected disease onset showed poor performance in episodic memory tests and also slightly low temporal lobe CBF, although there were no clearly abnormal findings. One carrier with mild Alzheimer disease (AD) had no clear structural brain changes, although CBF measurements showed clear reduction of temporal lobe CBF. One carrier with severe AD had both temporal lobe atrophy and CBF reduction. This indicates that in carriers of the APP 670/671 mutation, reduction of regional CBF is more severe than regional atrophy. The clearest change related to development of clinical AD was a reduction of CBF in the basal and lateral temporal lobes. Further longitudinal studies of these subjects are needed to confirm these preliminary findings, which might provide important data regarding early brain changes in AD.

Abnormal vasomotor response of human epileptogenic cortex to reversal of hyperventilation A long-term surface cerebral blood flow monitoring study

Abstract Human epileptogenic and nonepileptogenic surface cerebral blood flow (CBF) was studied during hyperventilation (HV) recovery. Bilateral subdural temporal lobe CBF probes were placed for long-term monitoring. Epileptic cortex became ischemic as an inverse linear function of HV duration ( r = 0.923, df=9, P P r = 0.890, df=9, P r = 0.784, df=5, P r = 0.782, df=9, P