Perivascular spaces include a variety of passageways around arterioles, capillaries and venules in the brain, along which a range of substances can move. Although perivascular spaces were first ...identified over 150 years ago, they have come to prominence recently owing to advances in knowledge of their roles in clearance of interstitial fluid and waste from the brain, particularly during sleep, and in the pathogenesis of small vessel disease, Alzheimer disease and other neurodegenerative and inflammatory disorders. Experimental advances have facilitated in vivo studies of perivascular space function in intact rodent models during wakefulness and sleep, and MRI in humans has enabled perivascular space morphology to be related to cognitive function, vascular risk factors, vascular and neurodegenerative brain lesions, sleep patterns and cerebral haemodynamics. Many questions about perivascular spaces remain, but what is now clear is that normal perivascular space function is important for maintaining brain health. Here, we review perivascular space anatomy, physiology and pathology, particularly as seen with MRI in humans, and consider translation from models to humans to highlight knowns, unknowns, controversies and clinical relevance.
•Cerebral blood flow (CBF), measured using a number of neuroimaging phenotypes, is a core metric of brain health, and CBF abnormalities are associated with vascular disease.•Decreased CBF in BD ...depression and differential perfusion patterns in response to tasks were found in studies of CBF in BD across methodologies.•Studies examining CBF in BD prospectively, and as a treatment target are warranted.
Neuroimaging of cerebral blood flow (CBF) can inform our understanding of the pathophysiology of bipolar disorder (BD) as there is increasing support for the concept that BD is in part a vascular disease. Despite numerous studies examining CBF in BD, there has not yet been a review of the literature on the topic of CBF in BD.
A systematic review of the literature on CBF in BD was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Studies included measured CBF by single-photon emission computerized tomography (SPECT), positron emission tomography (PET), arterial spin labelling (ASL) or perfusion weighted imaging (PWI) in a group of BD patients.
Thirty-three studies with a total of 508 subjects with BD and 538 controls were included (n = 15 SPECT; n = 8 PET; n = 7 ASL; n = 1 PWI; n = 2 other). The majority of studies in BD depression and mania reported widespread resting hypoperfusion in cingulate gyrus, frontal, and anterior temporal regions in comparison to healthy controls (HC). Findings in euthymic BD subjects and in symptomatically heterogeneous groups were less consistent. Studies that examined CBF responses to cognitive or emotional stimuli in BD subjects have reported hypoperfusion or different regions involved in comparison to HC.
Important methodological heterogeneity between studies, and small number of subjects per study.
The most consistent findings to date are hypoperfusion in BD mood episodes, and hypoactive CBF responses to emotional or cognitive challenges. Future studies examining CBF are warranted, including prospective studies, studies examining CBF as a treatment target, and multimodal imaging studies.
Determine whether white matter signal fluctuation on T2* weighted BOLD contrast images are associated with aging and cerebral small vessel disease (SVD).
Resting state BOLD data were collected with a ...250 ms repetition time (TR) to achieve unaliased, ungated cardiac sampled BOLD (cs-BOLD) images on 11 young adult controls, 10 healthy older adult controls and 7 adults with extensive white matter hyperintensities (WMH) from SVD. Tissue classes (WM and GM) were segmented on T1 images. WMH were identified on FLAIR images in the SVD group. Raw physiological noise (σphysio) and cardiac pulsatility (i.e. fluctuations at the cardiac frequency) were calculated voxel wise and group differences were tested by ANOVA. It was also possible to calculate σphysio in 2s TR cardiac aliased whole-brain BOLD (wb-BOLD) data (N = 84) obtained from the International Consortium for Brain Mapping.
CS-BOLD metrics showed an aging and SVD effects (p<0.0005). Covariates such as thermal noise, WM volume and partial volume did not influence the significant aging effect seen on the cardiac pulsatility metric (p<0.017) but did influence the σphysio (p = 0.184). As a verification of the cs-BOLD findings, the wb-BOLD also showed a linear aging effect of σphysio in WM. In the SVD adults, cardiac pulsatility and σphysio were lower in WMH regions compared to normal appearing white matter (NAWM) regions (p<0.0013 and p<0.002, respectively). Cardiac pulsatility was better able to distinguish WMH regions from NAWM than σphysio as measured by effect size (Cohen's d 2.2 and 0.88, respectively).
NAWM was found to have graded increases in cardiac pulsations due to age and SVD, independently. Within SVD participants, WMH lesions had reduced physiological noise compared to NAWM. Cardiac pulsatility in resting BOLD data may provide a complementary dynamic measure of WM integrity to add to static FLAIR anatomical images.
An important step in the analysis of magnetic resonance imaging (MRI) data for neuroimaging is the automated segmentation of white matter hyperintensities (WMHs). Fluid Attenuated Inversion Recovery ...(FLAIR-weighted) is an MRI contrast that is particularly useful to visualize and quantify WMHs, a hallmark of cerebral small vessel disease and Alzheimer’s disease (AD). In order to achieve high spatial resolution in each of the three voxel dimensions, clinical MRI protocols are evolving to a three-dimensional (3D) FLAIR-weighted acquisition. The current study details the deployment of deep learning tools to enable automated WMH segmentation and characterization from 3D FLAIR-weighted images acquired as part of a national AD imaging initiative. Based on data from the ongoing Norwegian Disease Dementia Initiation (DDI) multicenter study, two 3D models—one off-the-shelf from the NVIDIA nnU-Net framework and the other internally developed—were trained, validated, and tested. A third cutting-edge Deep Bayesian network model (HyperMapp3r) was implemented without any de-novo tuning to serve as a comparison architecture. The 2.5D in-house developed and 3D nnU-Net models were trained and validated in-house across five national collection sites among 441 participants from the DDI study, of whom 194 were men and whose average age was (64.91 +/- 9.32) years. Both an external dataset with 29 cases from a global collaborator and a held-out subset of the internal data from the 441 participants were used to test all three models. These test sets were evaluated independently. The ground truth human-in-the-loop segmentation was compared against five established WMH performance metrics. The 3D nnU-Net had the highest performance out of the three tested networks, outperforming both the internally developed 2.5D model and the SOTA Deep Bayesian network with an average dice similarity coefficient score of 0.76 +/- 0.16. Our findings demonstrate that WMH segmentation models can achieve high performance when trained exclusively on FLAIR input volumes that are 3D volumetric acquisitions. Single image input models are desirable for ease of deployment, as reflected in the current embedded clinical research project. The 3D nnU-Net had the highest performance, which suggests a way forward for our need to automate WMH segmentation while also evaluating performance metrics during on-going data collection and model retraining.
Despite the generally accepted view that aerobic exercise can have positive effects on brain health, few studies have measured brain responses to exercise over a short time span. The purpose of this ...study was to examine the impact within one hour of a single bout of exercise on brain perfusion and neuronal activation.
Healthy adults (n = 16; age range: 20-35 yrs) were scanned using Magnetic Resonance Imaging (MRI) before and after 20 minutes of exercise at 70% of their age-predicted maximal heart rate. Pseudo-continuous arterial spin labeling (pcASL) was used to measure absolute cerebral blood flow (CBF) prior to exercise (pre) and at 10 min (post-10) and 40 min (post-40) post-exercise. Blood oxygenation level dependent (BOLD) functional MRI (fMRI) was performed pre and post-exercise to characterize activation differences related to a go/no-go reaction time task.
Compared to pre-exercise levels, grey matter CBF was 11% (±9%) lower at post-10 (P<0.0004) and not different at post-40 (P = 0.12), while global WM CBF was increased at both time points post-exercise (P<0.0006). Regionally, the hippocampus and insula showed a decrease in perfusion in ROI-analysis at post-10 (P<0.005, FDR corrected), whereas voxel-wise analysis identified elevated perfusion in the left medial postcentral gyrus at post-40 compared to pre (pcorrected = 0.05). BOLD activations were consistent between sessions, however, the left parietal operculum showed reduced BOLD activation after exercise.
This study provides preliminary evidence of regionalized brain effects associated with a single bout of aerobic exercise. The observed acute cerebrovascular responses may provide some insight into the brain's ability to change in relation to chronic interventions.
Perivascular Spaces (PVS) are a feature of Small Vessel Disease (SVD), and are an important part of the brain's circulation and glymphatic drainage system. Quantitative analysis of PVS on Magnetic ...Resonance Images (MRI) is important for understanding their relationship with neurological diseases. In this work, we propose a segmentation technique based on the 3D Frangi filtering for extraction of PVS from MRI. We used ordered logit models and visual rating scales as alternative ground truth for Frangi filter parameter optimization and evaluation. We optimized and validated our proposed models on two independent cohorts, a dementia sample (N = 20) and patients who previously had mild to moderate stroke (N = 48). Results demonstrate the robustness and generalisability of our segmentation method. Segmentation-based PVS burden estimates correlated well with neuroradiological assessments (Spearman's ρ = 0.74, p < 0.001), supporting the potential of our proposed method.
•CVR is the cerebral hemodynamic response to a vasoactive stressor.•Measuring CVR via MRI during breath hold (BH) is non-invasive and easy to implement.•More than 50 studies have examined this method ...in non-neurological samples.•CVR is generally higher among controls vs. patients with medical conditions.•Ideal methods include ∼20s BH, at end-expiration, and normalized to end-tidal CO2.
Cerebrovascular reactivity (CVR) is the cerebral hemodynamic response to a vasoactive substance. Breath-hold (BH) induced CVR has the advantage of being non-invasive and easy to implement during magnetic resonance imaging (MRI). We systematically reviewed the literature regarding MRI measurement of BH induced CVR. The literature was searched using MEDLINE with the search terms breath-hold; and MRI or cerebrovascular reactivity. The search yielded 2244 results and 54 articles were included. Between-group comparisons have found that CVR was higher among healthy controls than patients with various pathologies (e.g. sleep apnea, diabetes, hypertension etc.). However, counter-intuitive findings have also been reported, including higher CVR among smokers, sedentary individuals, and patients with schizophrenia vs. controls. Methodological studies have highlighted important measurement characteristics (e.g. normalizing signal to end-tidal CO2), and comparisons of BH induced CVR to non-BH methods. Future studies are warranted to address questions about group differences, treatment response, disease progression, and other salient clinical themes. Standardization of CVR and BH designs is needed to fully exploit the potential of this practical non-invasive method.
Background. Ten percent of stroke survivors develop dementia, which increases to more than a third after recurrent stroke. Other survivors develop less severe vascular cognitive impairment. In the ...general population, depression, and diabetes interact in predicting dementia risk, and they are both prevalent in stroke. Objective. To assess the cumulative association of comorbid depressive symptoms and type 2 diabetes with cognitive outcomes among stroke survivors. Methods. Multicenter observational cohort study of people within 6 months of stroke. Depression and cognitive status were screened using the Center for Epidemiological Studies Depression (CES-D) scale and the Montreal Cognitive Assessment (MoCA), respectively. Processing speed, executive function and memory were assessed using the Trail Making Test parts A and B, and the 5 Word Delayed Free Recall task. Results. Among 342 participants (age 67.0 ± 13.5 years, 43.3% female, 46 ± 35 days poststroke), the prevalence of type 2 diabetes was 32.2% and depressive symptoms (CES-D ≥16) were found in 40.6%. Diabetes and depressive symptoms increased the risk of severe cognitive impairment (MoCA <20) with adjusted odds ratio (OR) 2.12 (95% confidence interval CI 1.20-3.74, P = .010) for 1 comorbidity and OR 3.18 (95% CI 1.26-8.02, P = .014) for both comorbidities. Associated cognitive deficits included executive function (F1, 168 = 3.43, P = .035) but not processing speed (F1, 168 = 1.86, P = .16) or memory (F1, 168 = 0.82, P = .44). Conclusions. Diabetes and depressive symptoms were associated cumulatively with poorer cognitive screening outcomes poststroke, particularly deficits in executive function. Having 1 comorbidity doubled the odds of screening for severe cognitive impairment, having both tripled the odds.
The choroid plexus (ChP) of the cerebral ventricles is a source of cerebrospinal fluid (CSF) production and also plays a key role in immune surveillance at the level of blood-to-CSF-barrier (BCSFB). ...In this study, we quantify ChP blood perfusion and BCSFB mediated water exchange from arterial blood into ventricular CSF using non-invasive continuous arterial spin labelling magnetic resonance imaging (CASL-MRI). Systemic administration of anti-diuretic hormone (vasopressin) was used to validate BCSFB water flow as a metric of choroidal CSF secretory function. To further investigate the coupling between ChP blood perfusion and BCSFB water flow, we characterized the effects of two anesthetic regimens known to have large-scale differential effects on cerebral blood flow. For quantification of ChP blood perfusion a multi-compartment perfusion model was employed, and we discovered that partial volume correction improved measurement accuracy. Vasopressin significantly reduced both ChP blood perfusion and BCSFB water flow. ChP blood perfusion was significantly higher with pure isoflurane anesthesia (2-2.5%) when compared to a balanced anesthesia with dexmedetomidine and low-dose isoflurane (1.0 %), and significant correlation between ChP blood perfusion and BCSFB water flow was observed, however there was no significant difference in BCSFB water flow. In summary, here we introduce a non-invasive, robust, and spatially resolved in vivo imaging platform to quantify ChP blood perfusion as well as BCSFB water flow which can be applied to study coupling of these two key parameters in future clinical translational studies.
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