Differences In Cerebral Blood Flow Research Articles

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.

S8A-15 SESSION 8A: METOPIC SYNOSTOSIS CEREBRAL BLOOD FLOW OF THE FRONTAL LOBE IN UNTREATED CHILDREN WITH TRIGONOCEPHALY VERSUS HEALTHY CONTROLS: AN ARTERIAL SPIN LABELING STUDY

Introduction: There is an international tendency to be more selective in the indication for surgical correction of trigonocephaly. The choice for surgery is mainly based on the severity of phenotype, with little consensus for the moderate presentation. To date, little is known about cerebral blood flow (CBF) in children with unoperated trigonocephaly. The aim of this study is to determine CBF of the frontal lobe of patients with trigonocephaly to determine whether or not an abnormal CBF can serve as a threshold for surgery. Methods: A prospective cohort study of untreated patients with trigonocephaly using magnetic resonance imaging (MRI) and arterial spin labeling (ASL), determining regional CBF patterns in comparison with a sample of control subjects. These controls showed no cerebral/neurological pathology. Both subjects and controls are at the age of <1 years and sedated using CBF measurements on 3 levels of the frontal lobe bilaterally. Results: Five untreated patients with trigonocephaly and eight control patients with a mean age <1 yearswere included. There was a no difference in CBF between the frontal lobe of untreated patients with trigonocephaly (mean CBF 68.70ml/100g/min; SE 5.42) and the control group (mean CBF 67.34ml/100g/min; SE 4.42; p> 0.10). Conclusion: There is no difference in CBF of the frontal lobe between untreated patients with trigonocephaly and control subjects under the age of 1. As such, a reduced CBF is an unlikely indicator for surgery. Prospectively future studies will be conducted to include more patients with a range of phenotypic severity to further explore the impact of trigonocephaly on CBF.

Cerebrovascular reactivity and its correlation with age in patients with multiple sclerosis.

We assessed cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) within gray matter (GM), normal appearing white matter (NAWM) and white matter (WM) lesions in a group of multiple sclerosis (MS) patients. Furthermore, correlations between CBF, CVR and age were investigated. 31 MS patients and 25 healthy controls (HC) were examined on a 1.5T MRI scanner, using pseudo-continuous arterial spin labeling MRI. MS vs HC CBF and CVR differences were assessed in GM regions of interest (i.e. resting state networks and vascular territories), and within WM. Correlations between CBF/CVR and age were then computed for MS and HC groups. Whereas no significant CBF and CVR differences were observed between MS and HC in any of the considered brain areas, significantly lower CBF was found in WM lesions with respect to NAWM (p < 0.001) in MS patients. Furthermore, CVR was significantly correlated with age in HC, but not in MS patients. The relatively low-grade of inflammation of our MS cohort may be associated with the observed lack of significant CVR differences between MS patients and HC. The loss of correlation between CVR and age in the MS group suggests that CVR may be influenced by MS-related factors.

Combined Assessment of Diffusion Parameters and Cerebral Blood Flow Within Basal Ganglia in Early Parkinson's Disease.

Diffusion tensor imaging (DTI) is a sensitive tool for detecting brain tissue microstructural alterations in Parkinson’s disease (PD). Abnormal cerebral perfusion patterns have also been reported in PD patients using arterial spin labeling (ASL) MRI. In this study we aimed to perform a combined DTI and ASL assessment in PD patients within the basal ganglia, in order to test the relationship between microstructural and perfusion alterations. Fifty-two subjects participated in this study. Specifically, 26 PD patients [mean age (SD) = 66.7 (8.9) years, 21 males, median (IQR) Modified Hoehn and Yahr = 1.5 (1–1.6)] and twenty-six healthy controls [HC, mean age (SD) = 65.2 (7.5), 15 males] were scanned with 1.5T MRI. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) maps were derived from diffusion-weighted images, while cerebral blood flow (CBF) maps were computed from ASL data. After registration to Montreal Neurological Institute standard space, FA, MD, AD, RD and CBF median values were extracted within specific regions of interest: substantia nigra, caudate, putamen, globus pallidus, thalamus, red nucleus and subthalamic nucleus. DTI measures and CBF were compared between the two groups. The relationship between diffusion parameters and CBF was tested with Spearman’s correlations. False discovery rate (FDR)-corrected p-values lower than 0.05 were considered significant, while uncorrected p-values <0.05 were considered a trend. No significant FA, MD and RD differences were observed. AD was significantly increased in PD patients compared with HC in the putamen (p = 0.005, pFDR = 0.035). No significant CBF differences were found between PD patients and HC. Diffusion parameters were not significantly correlated with CBF in the HC group, while a significant correlation emerged for PD patients in the caudate nucleus, for all DTI measures (with FA: r = 0.543, pFDR = 0.028; with MD: r = −0.661, pFDR = 0.002; with AD: r = −0.628, pFDR = 0.007; with RD: r = −0.635, pFDR = 0.003). This study showed that DTI is a more sensitive technique than ASL to detect alterations in the basal ganglia in the early phase of PD. Our results suggest that, although DTI and ASL convey different information, a relationship between microstructural integrity and perfusion changes in the caudate may be present.

Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia

AbstractChronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P < .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P = .025 and P = .034 respectively), but higher compared with the CTT cohort (P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.

Reduced heart rate variability and lower cerebral blood flow associated with poor cognition during recovery following concussion.

Although physiological deficits such as altered cerebral blood flow (CBF), and autonomic nervous system (ANS) dysregulation have been reported following a concussion, the relationship between CBF and ANS with functional outcome post-injury remains unclear. Our present study was designed to examine heart-rate variability (HRV) using percentage of successive NN intervals (pNN50) and CBF on day-3 (T1), day-21 (T2), and day-90 (T3) following a concussion in collegiate athletes (N = 31) in comparison to non-injured controls (N = 31). Continuous RR-interval (3-lead electrocardiogram), middle cerebral artery blood velocity (MCAV; transcranial Doppler ultrasonography), mean arterial pressure (MAP; finger photoplethysmography) were obtained at rest. Cerebrovascular conductance index (CVCi) was estimated as a ratio of MCAV to MAP. Cognition was evaluated with standard assessment of concussion (SAC), and Trails A & B. Compared to the controls, lower HRV (43 ± 15 vs. 27 ± 20%; p < 0.0001) was observed at T1 with normalization at T2 and T3. No difference in MCAV between the control and the concussed groups across the three time points were observed. However, post-hoc analyses indicated a positive relationship between MCAV at T1 phase with HRV and CVCi during T2, and T3 phases. Higher MCAV at T1 was also associated with better cognition scores during the asymptomatic T2 phase in the concussed athletes. Therefore, our results indicate ANS dysregulation during the acute recovery phase after a concussion. Differences in CBF may be one of the underlying causes behind heterogeneity in clinical symptoms and functional outcomes after a concussion and future studies are warranted to validate this finding.

Altered amplitude of low-frequency fluctuation and regional cerebral blood flow in females with primary dysmenorrhea: a resting-state fMRI and arterial spin labeling study.

Purpose: The current study aimed to explore the central mechanism of primary dysmenorrhea (PD) by investigating the alterations in resting state amplitude of low-frequency fluctuation (ALFF) and regional cerebral blood flow (CBF) between PD patients and healthy controls (HCs).Patients and methods: A total of 34 female subjects including 20 PD patients and 14 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling technique (ASL) MRI during menstrual phase. Subsequently, the differences in ALFF and CBF were compared in the two groups. The visual analog scores for pain (VAS-P) and for anxiety (VAS-A) were applied to assess cramping pain and related symptoms in PD patients. Finally, Pearson’s correlation analysis was performed to analyze relationships between the neuroimaging findings and clinical characteristics.Results: Compared to HCs, PD patients had decreased ALFF in the right cerebellum posterior lobe, right middle temporal gyrus, right parahippocampal gyrus, right hippocampus, right brainstem and left parietal lobe. In addition, elevated CBF values were observed in the right inferior frontal gyrus, right precentral gyrus, and right superior temporal gyrus. There was no significant correlation between ALFF, CBF values and clinical characteristics including onset age of dysmenorrhea, VAS-A, and VAS-P in PD patients.Conclusion: The preliminary alterations of ALFF and CBF values in PD patients were observed in different pain-related brain regions, which were involved in multiple dimensions of pain and pain modulation. The combination of rs-fMRI and ASL MRI might provide complementary information for a better understanding of the central mechanism in PD.

The Relationship Between Regional Cerebral Blood Flow Estimates and Alcohol Problems at 5-Year Follow-Up: The Role of Level of Response.

Acute alcohol consumption is associated with temporarily increased regional cerebral blood flow (CBF). The extent of this increase appears to be moderated by individual differences in the level of response (LR) to alcohol's subjective effects. The low LR phenotype is a known risk factor for the development of alcohol problems. This study investigates how the low LR phenotype relates to the relationship between alcohol-related changes in CBF and alcohol problems 5years later. Young adults (ages 18 to 25) were selected based on their LR to alcohol and underwent a neuroimaging protocol including arterial spin labeling and functional scans. These participants were recontacted ~5years later and assessed on alcohol outcomes. A final sample of 107 subjects (54 low and 53 high LR subjects) was included in the analyses. Whole-brain analysis revealed 5 clusters of significant alcohol-induced, versus placebo-induced, CBF changes that were consistent with a previous report. Peak alcohol-placebo CBF response was extracted from these regions and, along with the LR group, submitted to a hierarchical linear regression predicting alcohol problems. Analyses controlled for age, sex, and baseline alcohol problems. In the regression analysis, greater alcohol-placebo CBF difference in the right middle/superior/inferior frontal gyri and bilateral anterior cingulate gyri clusters predicted greater future alcohol problems for the low LR group, whereas this relationship was not found to be significant in the high LR group. This study demonstrates a clinically important relationship between CBF and future alcohol problems, particularly in individuals with a low LR phenotype. These initial results help to elucidate the neurobiological pathways involved in the development of alcohol use disorders for individuals with low LR.

Altered neurovascular coupling and brain arginine metabolism in endothelial nitric oxide synthase deficient mice

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is a key regulator of cerebral blood flow (CBF) dynamics. Mice with eNOS deficiency (eNOS−/-) display age-related increases in amyloid beta in the brain and memory deficits, implicating eNOS dysfunction in the neuropathogenesis and/or development of Alzheimer's disease (AD). The present study systematically investigated behavioural, CBF and brain arginine metabolic profile changes in male and female wildtype (WT) and eNOS−/- mice at 14 months of age. eNOS−/- mice displayed altered behaviour in the Y-maze and open field tests. A real-time microcirculation imager revealed a significant sex difference in the basal CBF and significantly increased perfusion response to whisker stimulations in the Barrel cortex in both male and female eNOS−/- mice relative to their sex-matched WT controls. The treatment of 7-nitroindazole blocked the increased perfusion response to whisker stimulations in eNOS−/- mice. Neurochemically, the most intriguing changes were markedly reduced glutamine levels in both male and female eNOS−/- mice in the frontal cortex, hippocampus, parahippocampal region and cerebellum. These findings demonstrate altered behavioural function, neurovascular coupling and brain arginine metabolism (glutamine in particular) under the condition of eNOS deficiency, which further supports the role of eNOS dysfunction in the AD neuropathogenesis.

Cortical pattern of reduced perfusion in hearing loss revealed by ASL-MRI.

Age-related hearing loss (HL) can be related to brain dysfunction or structural damage and may result in cerebral metabolic/perfusion abnormalities. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) allows investigating noninvasively brain perfusion changes. Pseudocontinuous ASL and T1-weighted MRI (at 3 T) and neuropsychological testing (Montreal Cognitive Assessment) were performed in 31 HL (age range = 47-77 years, mean age ± SD = 63.4 ± 8.4 years, pure-tone average [PTA] HL > 50 dB) and 28 normal hearing (NH; age range = 48-78 years, mean age ± SD = 59.7 ± 7.4 years) subjects. Cerebral blood flow (CBF) and gray matter volume (GMV) were analyzed in the cortical volume to assess perfusion and structural group differences. Two HL subjects showing cognitive impairment were excluded from group comparisons. No significant differences in either global or local atrophy were detected between groups but the HL group exhibited significant regional effects of reduced perfusion within the bilateral primary auditory cortex, with maximal CBF difference (-17.2%) in the right lateral Heschl's gyrus. For the whole sample of HL and NH subjects (n = 59 = 31 HL + 28 NH), the regional CBF was correlated positively to the regional GMV (p = 0.020). In HL subjects (n = 31), the regional CBF was correlated negatively to the audiogram steepness (frequency range: 2-4 kHz, right ear: p = 0.022, left ear: p = 0.015). The observed cortical pattern of perfusion reduction suggests that neuronal metabolism can be related to HL before the recognition of brain structural damage. This also illustrates the potential of ASL-MRI to contribute early functional markers of reduced central processing associated with HL.

Cerebral blood flow in children and adolescents several years after concussion

ABSTRACTObjectives: The long-term effects of concussion in youth remain poorly understood. The objective of this study was to determine the association between history of concussion and cerebral blood flow (CBF) in youth.Methods: A total of 53 children and adolescents with a history of concussion (n = 37) or orthopaedic injury (OI; n = 16) were considered. Measures included pseudo-continuous arterial spin labelling magnetic resonance imaging to quantify CBF, post-concussion symptoms, psychological symptoms, and cognitive testing.Results: Participants (mean age: 14.4 years, 95% CI = 13.8–15.4, range = 8–19) were on average 2.7 years (95% CI = 2.2–3.1) post-injury. Youth with a history of concussion had higher parent-reported physical, cognitive, anxiety, and depression symptoms than children with OI, but the groups did not differ on self-reported symptoms (post-concussive or psychological) or cognitive testing. Global CBF did not differ between groups. Regional CBF analyses suggested that youth with a history of concussion had hypoperfusion in posterior and inferior regions and hyperperfusion in anterior/frontal/temporal regions as compared to those with OI. However, neither global nor regional CBF were significantly associated with demographics, pre-injury functioning, number of concussions, time since injury, post-concussive symptoms, psychological symptoms, or cognitive abilities.Conclusions: Youth with a history of concussion demonstrate differences in regional CBF (not global CBF), but without clear clinical expression.

Resting regional brain activity and connectivity vary with resting blood pressure but not muscle sympathetic nerve activity in normotensive humans: An exploratory study

Blood pressure is tightly controlled by the central nervous system, particularly the brainstem. The aim of this study was to investigate the relationship between mean blood pressure (MBP), muscle sympathetic nerve activity (MSNA) and resting regional brain activity in healthy human subjects. Pseudocontinuous arterial spin labeling and functional magnetic resonance imaging of the brain were performed immediately following a laboratory microneurography recording of MSNA and BP measurement in 31 young, healthy normotensive subjects. Regional cerebral blood flow (CBF) correlated significantly with resting MBP levels in the region encompassing the rostroventrolateral medulla (RVLM), dorsolateral pons, and insular, prefrontal and cingulate cortices. Functional connectivity analysis revealed that the ventrolateral prefrontal cortex displayed greater resting connectivity strength within the RVLM in the lower compared with the higher MBP group. No significant differences in CBF were found when subjects were divided based on their MSNA levels. These results suggest that even subtle differences in resting MBP are associated with significant differences in resting activity in brain regions, which are well known to play a role in cardiovascular function. These data raise the question of the potential long-term consequences of differences in regional brain activity levels and their relationship with systemic blood pressure.

The influence of suturectomy on age-related changes in cerebral blood flow in rabbits with familial bicoronal suture craniosynostosis: A quantitative analysis.

BackgroundCoronal suture synostosis is a condition which can have deleterious physical and cognitive sequelae in humans if not corrected. A well-established animal model has previously demonstrated disruptions in intracranial pressure and developmental abnormalities in rabbits with congenital craniosynostosis compared to wild type rabbits.ObjectiveThe current study aimed to measure the cerebral blood flow (CBF) in developing rabbits with craniosynostosis who underwent suturectomy compared to those with no intervention and compared to wild type rabbits.MethodsRabbits with early onset coronal suture synostosis were assigned to have suturectomy at 10 days of age (EOCS-SU, n = 15) or no intervention (EOCS, n = 18). A subset of each group was randomly selected for measurement at 10 days of age, 25 days of age, and 42 days of age. Wild type rabbits (WT, n = 18) were also randomly assigned to measurement at each time point as controls. Cerebral blood flow at the bilateral hemispheres, cortices, thalami, and superficial cortices was measured in each group using arterial spin-labeling MRI.ResultsAt 25 days of age, CBF at the superficial cortex was significantly higher in EOCS rabbits (192.6 ± 10.1 mL/100 mg/min on the left and 195 ± 9.5 mL/100 mg/min on the right) compared to WT rabbits (99.2 ± 29.1 mL/100 mg/min on the left and 96.2 ± 21.4 mL/100 mg/min on the right), but there was no significant difference in CBF between EOCS-SU (97.6 ± 11.3 mL/100 mg/min on the left and 99 ± 7.4 mL/100 mg/min on the right) and WT rabbits. By 42 days of age the CBF in EOCS rabbits was not significantly different than that of WT rabbits.ConclusionSuturectomy eliminated the abnormally increased CBF at the superficial cortex seen in EOCS rabbits at 25 days of age. This finding contributes to the evidence that suturectomy limits abnormalities of ICP and CBF associated with craniosynostosis.

Cerebral Blood Flow Changes in Multiple Sclerosis and Neuromyelitis Optica and Their Correlations With Clinical Disability.

Distinguishing relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica (NMO) is clinically important because they differ in prognosis and treatment. This study aimed to identify perfusion abnormalities in RRMS and NMO and their correlations with gray matter volume (GMV) atrophy and clinical parameters. Structural and arterial spin labeling MRI scans were performed in 39 RRMS patients, 62 NMO patients, and 73 healthy controls. The gray matter cerebral blood flow (CBF) values were voxel-wisely compared among the three groups with and without GMV correction. The regional CBF changes were correlated with the Expanded Disability Status Scale scores in the corresponding patient groups. Although multiple brain regions showed CBF differences among the three groups without GMV correction, only three of these regions remained significant after GMV correction. Specifically, both the RRMS and NMO groups showed reduced CBF in the occipital cortex and increased CBF in the right putamen compared to the control group. The RRMS group had increased CBF only in the medial prefrontal cortex compared to the other two groups. The occipital CBF was negatively correlated with clinical disability in the NMO group; however, the CBF in the right putamen was positively correlated with clinical disability in both patient groups. These findings suggest that there are perfusion alterations independent of GMV atrophy in RRMS and NMO patients. The regional CBF in the occipital cortex and putamen could be used as imaging features to objectively assess clinical disability in these patients.

O3.7. EFFECT OF N-ACETYLCYSTEINE ON BRAIN GLUTAMATE LEVELS AND RESTING PERFUSION IN SCHIZOPHRENIA

BackgroundSchizophrenia may be associated with elevations in glutamate levels in the anterior cingulate cortex (ACC), and this may be particularly apparent in patients who have not responded well to conventional antipsychotic treatment (Egerton et al., 2012; Mouchliantis et al., 2016). This suggests that compounds that can decrease ACC glutamate levels may have therapeutic potential for this group. N-acetylcysteine (NAC) is one such compound, currently under investigation as an adjunctive therapy for schizophrenia. The effects of NAC on brain glutamate levels and physiology in schizophrenia have not been previously evaluated. The primary aim of this study was to examine whether a single oral dose of NAC can alter brain glutamate levels in schizophrenia. The secondary aim was to characterise the effects of NAC on regional brain perfusion.MethodsIn a double-blind placebo-controlled crossover study, twenty patients with a diagnosis of schizophrenia underwent two 3 Tesla MRI scans, performed one week apart, and following administration of a single oral dose of 2400mg NAC or matching placebo. Proton magnetic resonance spectroscopy (1H-MRS) was used to investigate the effect of NAC on glutamate and Glx (glutamate plus glutamine) levels scaled to creatine (Cr) in the anterior cingulate cortex (ACC) and in the right caudate nucleus. Pulsed continuous arterial spin labelling (pCASL) was used to measure the effects of NAC on resting cerebral blood flow (CBF) in the same regions. 1H-MRS spectra were analysed using LCModel version 6.3-0I using a standard basis set. Individual CBF maps were pre-processed in the Automatic Software for ASL Processing (ASAP) toolbox running in SPM-8 in Matlab 6.5. The effects of NAC on 1H-MRS metabolite levels were determined using paired samples t-tests. Changes in rCBF were determined using within-subjects, second-level analysis implemented in SPM-8.ResultsIn the ACC, Glx/Cr was significantly reduced in the NAC compared to placebo condition (t(17) = 2.40; P = .03, d = 0.64). There was no significant effect of condition on Glu/Cr in the ACC, or on Glx/Cr or Glu/Cr in the right caudate nucleus, or on any of the other metabolites quantifiable from the 1H-MRS spectra. There were no significant differences in CBF in the ACC (mean (SD) placebo = 47.22 (8.81); NAC = 46.83 (7.29); t(18) = .349, P = .73) or in the right caudate nucleus (mean (SD) placebo = 37.51 (7.48); NAC = 37.77 (6.71); t(18) -.310, P = .76) in the NAC compared to placebo condition. There was also no significant difference in global CBF between conditions (mean (SD) placebo = 39.64 (10.02); NAC = 40.03 (9.13); t(18) = -.398, P = .70).DiscussionThese results provide preliminary evidence that NAC may reduce ACC glutamate metabolites in schizophrenia. Future studies will need to determine the extent to which reductions in glutamate metabolites following a single dose of a glutamatergic compound are indicative of longer-term efficacy in improving symptoms.

Cerebral Blood Flow Characteristics Responses Following Acute Aerobic Exercise in Individuals with and without Down Syndrome

Individuals with Down Syndrome (DS) commonly experience low to moderate levels of cognitive impairment and are at a high risk of developing dementia and Alzheimer's diseases (AD). Reduced cerebral blood flow (CBF) and altered CBF characteristics have been observed in the aging population without DS and has shown to have detrimental effects on cerebral microvasculature, which may increase the risk of developing dementia and AD. However, differences in CBF and its characteristics between individuals with and without DS and its response to exercise have not been studied.PurposeTo examine the differences in CBF and its characteristics following a 20‐minute bout of moderate intensity walking in individuals with and without DS.MethodsThirty‐eight young (DS=19, Age=25 yrs) individuals with and without DS participated in this study. Changes in mean middle cerebral artery velocity (mMCAv), mMCAv characteristics (pulsatility index (PI), resistance index (RI)) and hemodynamic variables were measured before, immediately post and 30‐minute post exericse.ResultsBaseline hemodynamics, systolic blood pressure (BP), diastolic BP, mean arterial pressure (MAP), heart rate (HR) and mMCAv were not different between the DS and control group (p&gt;0.05 for all). Neither group showed changes in mMCAv after moderate intensity treadmill walking exercise (p&gt;0.05). However, the DS group exhibited significantly higher PI and RI at all time points when compared to controls (p&lt;0.05 for both).ConclusionsOur results demonstrate that CBF was not altered in individuals with DS at rest and following moderate intensity exercise and was not different from that of controls. However, higher PI and RI in DS group may be associated with reduced distal cerebral perfusion and microvascular damage in individuals with DS. DS (N = 19) Control (N = 19) Baseline Immediate post EX 30‐minute post EX Baseline Immediate post EX 30‐minute post EX SBP (mmHg) 122±14 126±11* 121±13 120±10 130±12* 121±11 DBP (mmHg) 69±9 75±8* 70±9 72±6 81±8* 74±9 MAP (mmHg) 93±10 98±8* 94±9 94±7 103±7* 96±8 mMCAv (cm/s) 64.3±14.9 62.8±13.9 60.8±14.6 69.4±13.1 69.8±14.8 69.6±14.1 PI‡ 0.97±0.14 1.04±0.19 1.02±0.14 0.87±0.12 0.89±0.15 0.86±0.14 RI‡ 0.60±0.05 0.61±0.06 0.61±0.05 0.56±0.05 0.56±0.05 0.55±0.05 Significant group difference, Significant time difference from the baseline. Mean ± SD, Significance level, p &lt; 0.05 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of blood T1 estimation strategy on arterial spin labeled cerebral blood flow quantification in children and young adults with kidney disease

PurposeTo compare blood T1 estimation approaches used for quantifying cerebral blood flow (CBF) with arterial spin labeled (ASL) perfusion MRI in a developmental cohort of chronic kidney disease (CKD) patients with anemia and a control group. Methods61 patients with CKD and 47 age-matched control subjects were studied. Blood T1 approaches included: (1) a fixed value, (2) estimation based on measured hematocrit (Hct), and (3) estimation based on Age+Sex using a published formula. Resulting T1 and CBF values were compared along with group, age and sex effects. ResultsHighly significant group differences in CBF using fixed blood T1 were reduced when Hct-corrected blood T1 was used, and were eliminated entirely when using the Age+Sex estimated approach. In the control cohort, fixed T1 method showed the strongest correlations of CBF with age and sex. Hct-corrected T1 preserved a significant correlation between CBF and age and sex, while Age+Sex estimated T1 produced a poor fit of CBF with age and sex. ConclusionsBlood T1 estimation method can confound the interpretation of CBF changes measured using ASL MRI in patients with CKD. Blood T1 should ideally be corrected for hematocrit effects in clinical populations with anemia.

Abstract P120: Racial Differences in Midlife Brain Health and the Role of Cardiometabolic Risk

Introduction: Blacks are at a higher risk for adverse brain-related outcomes, including stroke and dementia. Due to associations of vascular risk factors with brain health, differences in brain health may result from a greater burden of vascular risk factors in blacks, especially in midlife. However, the role of vascular risk factors in midlife racial disparities in brain health have been underexplored. We thus examined racial differences in midlife brain health and tested whether vascular and metabolic risk factors partly explain cross-sectional racial differences. Hypothesis: A composite cardiometabolic risk (CMR) score statistically mediates cross-sectional relationships between race and brain health measures. Methods: 747 adults (20.6% black) aged 30–54, underwent MRI to assess cerebral blood flow (CBF) and morphology. Components of composite CMR were: body mass index, waist circumference, high-density lipoproteins, triglycerides, glucose, insulin, SBP, and DBP. Mediation was tested using the PROCESS v2.14 macro. All models were adjusted for age, sex, income, education, and intracranial volume. Results: Blacks exhibited lower gray matter volume, smaller hippocampi, less cortical surface area, and a thinner cerebral cortex than whites (all p’s&lt;0.05). We observed no significant differences in CBF by race. CMR partially mediated the association of race with gray matter volume (6.94% mediation) and cortical surface area (9.33% mediation). Independent of CMR, there was a direct effect of race on hippocampal volume, cortical surface area, and cortical thickness. The effect was equivalent to: 6.9, 9.59, 13.06, and 9.98 years of aging, respectively. Conclusions: Race differences in some indicators of brain health are evident in midlife. Cardiovascular and metabolic risk factors may partly explain some of these differences. These results have implications for understanding vascular contributions to disparities in brain health prior to the onset of stroke and other clinical outcomes.

Regional cerebral blood flow in natives at high altitude: An arterial spin labeled MRI study.

It is known that a neurologic sequence occurs at high altitudes (HA); hence, cerebral blood flow (CBF) might vary by altitude. To use arterial spin labeled (ASL) MRI to evaluate absolute CBF differences between subjects who live at HA and lowlands. Cohort prospective trial. In all, 64 HA Tibetans, 19 lowland Tibetans, and 25 lowland Han subjects. CBF was measured with the pulsed ASL sequence at 3T. CBF was correlated with abode altitude in HA Tibetans; CBF differences among HA Tibetans, lowland Tibetans, and lowland Han subjects was assessed. Pearson correlation assessed the correlation. Independent t-tests analyzed group differences. In HA Tibetans, CBF decreased with altitude in the bilateral anterior and posterior cingulate gyri, fusiform gyrus, cerebellar tonsil and cortices, and thalamus as well as left middle and inferior temporal gyri and right insula (P < 0.05); HA Tibetans (vs. lowland Tibetans) had lower CBF in the left hemisphere (precuneus, anterior cingulate gyrus, fusiform gyrus, and lingual gyrus) and right hemisphere (superior parietal lobule, precuneus, posterior cingulate gyrus, and cerebellar tonsil), while they had higher CBF in the left inferior parietal lobule, lentiform nucleus, and inferior frontal gyrus (P < 0.05). The overlapping regions, in which CBF in HA Tibetans correlated with altitude and decreased (vs. lowland Tibetans), were selected for region of interest analysis, and the results showed lower CBF in HA Tibetans than lowland Han subjects (P < 0.05). HA adaptation in Tibetans is associated with a decrease of regional CBF. 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018.

Dysregulation of RNF213 promotes cerebral hypoperfusion

RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF.