David E. Crane

Impact of a Single Bout of Aerobic Exercise on Regional Brain Perfusion and Activation Responses in Healthy Young Adults

Purpose 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. Methods 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. Results 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. Conclusion 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.

A single session of exercise increases connectivity in sensorimotor-related brain networks: a resting-state fMRI study in young healthy adults

Habitual long term physical activity is known to have beneficial cognitive, structural, and neuro-protective brain effects, but to date there is limited knowledge on whether a single session of exercise can alter the brain’s functional connectivity, as assessed by resting-state functional magnetic resonance imaging (rs-fMRI). The primary objective of this study was to characterize potential session effects in resting-state networks (RSNs). We examined the acute effects of exercise on the functional connectivity of young healthy adults (N = 15) by collecting rs-fMRI before and after 20 min of moderate intensity aerobic exercise and compared this with a no-exercise control group (N = 15). Data were analyzed using independent component analysis, denoising and dual regression procedures. Regions of interest-based group session effect statistics were calculated in RSNs of interest using voxel-wise permutation testing and Cohen’s D effect size. Group analysis in the exercising group data set revealed a session effect in sub-regions of three sensorimotor related areas: the pre and/or postcentral gyri, secondary somatosensory area and thalamus, characterized by increased co-activation after exercise (corrected p < 0.05). Cohen’s D analysis also showed a significant effect of session in these three RSNs (p< 0.05), corroborating the voxel-wise findings. Analyses of the no-exercise dataset produced no significant results, thereby providing support for the exercise findings and establishing the inherent test–retest reliability of the analysis pipeline on the RSNs of interest. This study establishes the feasibility of rs-fMRI to localize brain regions that are associated with acute exercise, as well as an analysis consideration to improve sensitivity to a session effect.

Cardiopulmonary fitness correlates with regional cerebral grey matter perfusion and density in men with coronary artery disease.

Purpose Physical activity is associated with positive effects on the brain but there is a paucity of clinical neuroimaging data in patients with coronary artery disease (CAD), a cardiovascular condition associated with grey matter loss. The purpose of this study was to determine which brain regions are impacted by cardiopulmonary fitness and with the change in fitness after 6 months of exercise-based cardiac rehabilitation. Methods CAD patients underwent magnetic resonance imaging at baseline, and peak volume of oxygen uptake during exercise testing (VO2Peak) was measured at baseline and after 6 months of training. T1-weighted structural images were used to perform grey matter (GM) voxel-based morphometry (VBM). Pseudo-continuous arterial spin labeling (pcASL) was used to produce cerebral blood flow (CBF) images. VBM and CBF data were tested voxel-wise using VO2Peak and age as explanatory variables. Results In 30 men with CAD (mean age 65±7 years), VBM and CBF identified 7 and 5 respective regions positively associated with baseline VO2Peak. These included the pre- and post-central, paracingulate, caudate, hippocampal regions and converging findings in the putamen. VO2Peak increased by 20% at follow-up in 29 patients (t = 9.6, df = 28, p<0.0001). Baseline CBF in the left post-central gyrus and baseline GM density in the right putamen predicted greater change in VO2Peak. Conclusion Perfusion and GM density were associated with fitness at baseline and with greater fitness gains with exercise. This study identifies new neurobiological correlates of fitness and demonstrates the utility of multi-modal MRI to evaluate the effects of exercise in CAD patients.

Gray matter blood flow and volume are reduced in association with white matter hyperintensity lesion burden: a cross-sectional MRI study

Cerebral White Matter Hyperintensities (WMH) are associated with vascular risk factors and age-related cognitive decline. WMH have primarily been associated with global white matter and gray matter (GM) changes and less is known about regional effects in GM. The purpose of this study was to test for an association between WMH and two GM imaging measures: cerebral blood flow (CBF) and voxel-based morphometry (VBM). Twenty-six elderly adults with mild to severe WMH participated in this cross-sectional 3 Tesla magnetic resonance imaging (MRI) study. MRI measures of GM CBF and VBM were derived from arterial spin labeling (ASL) and T1-weighted images, respectively. Fluid-attenuated inversion recovery (FLAIR) images were used to quantify the WMH lesion burden (mL). GM CBF and VBM data were used as dependent variables. WMH lesion burden, age and sex were used in a regression model. Visual rating of WMH with the Fazekas method was used to compare the WMH lesion volume regression approach. WMH volume was normally distributed for this group (mean volume of 22.7 mL, range: 2.2–70.6 mL). CBF analysis revealed negative associations between WMH volume and CBF in the left anterior putamen, subcallosal, accumbens, anterior caudate, orbital frontal, anterior insula, and frontal pole (corrected p < 0.05). VBM analysis revealed negative associations between WMH and GM volume in lingual gyrus, intracalcarine, and bilateral hippocampus (corrected p < 0.05). The visual rating scale corroborated the regression findings (corrected p < 0.05). WMH lesion volume was associated with intra-group GM CBF and structural differences in this cohort of WMH adults with mild to severe lesion burden.

Automated removal of spurious intermediate cerebral blood flow volumes improves image quality among older patients: A clinical arterial spin labeling investigation.

To evaluate the impact of rejecting intermediate cerebral blood flow (CBF) images that are adversely affected by head motion during an arterial spin labeling (ASL) acquisition.

A control point interpolation method for the non-parametric quantification of cerebral haemodynamics from dynamic susceptibility contrast MRI.

DSC-MRI analysis is based on tracer kinetic theory and typically involves the deconvolution of the MRI signal in tissue with an arterial input function (AIF), which is an ill-posed inverse problem. The current standard singular value decomposition (SVD) method typically underestimates perfusion and introduces non-physiological oscillations in the resulting residue function. An alternative vascular model (VM) based approach permits only a restricted family of shapes for the residue function, which might not be appropriate in pathologies like stroke. In this work a novel deconvolution algorithm is presented that can estimate both perfusion and residue function shape accurately without requiring the latter to belong to a specific class of functional shapes. A control point interpolation (CPI) method is proposed that represents the residue function by a number of control points (CPs), each having two degrees of freedom (in amplitude and time). A complete residue function shape is then generated from the CPs using a cubic spline interpolation. The CPI method is shown in simulation to be able to estimate cerebral blood flow (CBF) with greater accuracy giving a regression coefficient between true and estimated CBF of 0.96 compared to 0.83 for VM and 0.71 for the circular SVD (oSVD) method. The CPI method was able to accurately estimate the residue function over a wide range of simulated conditions. The CPI method has also been demonstrated on clinical data where a marked difference was observed between the residue function of normally appearing brain parenchyma and infarcted tissue. The CPI method could serve as a viable means to examine the residue function shape under pathological variations.

Multisite evaluations of a T2‐relaxation‐under‐spin‐tagging (TRUST) MRI technique to measure brain oxygenation

Venous oxygenation (Yv) is an important index of brain physiology and may be indicative of brain diseases. A T2‐relaxation‐under‐spin‐tagging (TRUST) MRI technique was recently developed to measure Yv. A multisite evaluation of this technique would be an important step toward broader availability and potential clinical utilizations of Yv measures.

Temporal Profile of Cerebrovascular Reactivity Impairment, Gray Matter Volumes, and Persistent Symptoms after Mild Traumatic Head Injury

Objective Increased awareness around neurocognitive deficits after mild traumatic brain injury (mTBI) has progressed the search for objective, diagnostic, and monitoring tools, yet imaging biomarkers for mTBI and recovery are not established in clinical use. It has been suggested that mTBI impairs cerebrovascular reactivity (CVR) to CO2, which could be related to post-concussive syndrome (PCS). We investigate CVR evolution after mTBI using blood-oxygen-level dependent (BOLD) magnetic resonance imaging (MRI) and possible correlation with PCS. Methods A prospective cohort of 25 mTBI patients and 18 matched controls underwent BOLD MRI CVR measurements. A subset of 19 mTBI patients underwent follow-up testing. Visits took place at a mean of 63 and 180 days after injury. Symptoms were assessed with the Sport Concussion Assessment Tool 2 (SCAT2). Symptoms, CVR and brain volume [gray matter (GM), white matter (WM), and whole brain (WB)], age, and sex, were examined between groups and longitudinally within traumatic brain injury (TBI) patients. Results Traumatic brain injury participants were 72% males, mean age being 42.7 years. Control participants were 61% with mean age of 38.7 years. SCAT2 scores tended to improve among those mTBI patients with follow-up visits (p = 0.07); however, they did not tend to recover to scores of the healthy controls. Brain volumes were not statistically different between groups at the first visit (WM p = 0.71; GM p = 0.36). In mTBI patients, there was a reduction in GM volume between visits 1 and 2 (p = 0.0046). Although mean CVR indexes were similar (WM p = 0.27; GM p = 0.36; and WB p = 0.35), the correlation between SCAT2 and CVR was negative in controls (WM-r = −0.59; p = 0.010; GM-r = −0.56; p = 0.016; brain-r = −0.58; p = 0.012) and weaker and positive in mTBI (brain-r = 0.4; p = 0.046; GM-r = 0.4; p = 0.048). SCAT2 correlated with GM volume (r = 0.5215, p = 0.0075) in mTBI but not in controls (r = 0.2945, p = 0.2355). Conclusion There is a correlation between lower GM CVR indexes and lower performance on SCAT2 in patients with mTBI, which seems to be associated with more symptoms. This correlation seems to persist well beyond 120 days. mTBI may lead to a decrease in GM volume in these patients.

Modeling and correction of bolus dispersion effects in dynamic susceptibility contrast MRI

Bolus dispersion in DSC‐MRI can lead to errors in cerebral blood flow (CBF) estimation by up to 70% when using singular value decomposition analysis. However, it might be possible to correct for dispersion using two alternative methods: the vascular model (VM) and control point interpolation (CPI). Additionally, these approaches potentially provide a means to quantify the microvascular residue function.

Evaluating quantitative approaches to dynamic susceptibility contrast MRI among carotid endarterectomy patients.

To evaluate two dynamic susceptibility contrast (DSC) quantification methods in symptomatic carotid artery disease patients undergoing carotid endarterectomy (CEA) surgery by comparing methods directly and assessing the reliability of each method in the hemisphere contralateral to surgery.