Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind,... Show moreCerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest including the hippocampus. Fifty-eight patients were randomly assigned (29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medication compliant over 6 months. Mean age was 72.8 +/- 6.2 years, mean mini-mental state examination was 20.4 +/- 3.4. Nilvadipine treatment lowered systolic blood pressure (Delta=-11.5 [95% CI, -19.7 to -3.2] mm Hg; P<0.01), while whole-brain gray-matter CBF remained stable (Delta=5.4 [95% CI, -6.4 to 17.2] mL/100 g per minute; P=0.36). CBF in the hippocampus increased (left: Delta=24.4 [95% CI, 4.3-44.5] mL/100 g per minute; P=0.02; right: Delta=20.1 [95% CI, -0.6 to 40.8] mL/100 g per minute; P=0.06). There was no significant change in CBF in the posterior cingulate cortex (Delta=5.2 [95% CI, -16.5 to 27.0] mL/100 g per minute; P=0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Show less
Bones, I.K.; Harteveld, A.A.; Franklin, S.L.; Osch, M.J.P. van; Hendrikse, J.; Moonen, C.T.W.; ... ; Stralen, M. van 2019
Cerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance.... Show moreCerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance. It is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, is pivotal in the pathophysiology. Recent years have seen increasing use of imaging, primarily dynamic contrast-enhanced magnetic resonance imaging, to assess BBB leakage, but there is considerable variability in the approaches and findings reported in the literature. Although dynamic contrast-enhanced magnetic resonance imaging is well established, challenges emerge in cSVD because of the subtle nature of BBB impairment. The purpose of this work, authored by members of the HARNESS Initiative, is to provide an in-depth review and position statement on magnetic resonance imaging measurement of subtle BBB leakage in clinical research studies, with aspects requiring further research identified. We further aim to provide information and consensus recommendations for new investigators wishing to study BBB failure in cSVD and dementia. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Plas, M.C.E. van der; Teeuwisse, W.M.; Schmid, S.; Chappell, M.; Osch, M.J.P. van 2019
Purpose: The goal of this study was to achieve high temporal resolution, multi-time point pseudo-continuous arterial spin labeling (pCASL) MRI in a time-efficient manner, while maintaining whole... Show morePurpose: The goal of this study was to achieve high temporal resolution, multi-time point pseudo-continuous arterial spin labeling (pCASL) MRI in a time-efficient manner, while maintaining whole-brain coverage.Methods: A Hadamard 8-matrix was used to dynamically encode the pCASL labeling train, thereby providing the first source of temporal information. The second method for obtaining dynamic arterial spin labeling (ASL) signal consisted of a Look-Locker (LL) readout of 4 phases that are acquired with a flip-angle sweep to maintain constant sensitivity over the phases. To obtain whole-brain coverage in the short LL interval, 4 slices were excited simultaneously by multi-banded radiofrequency pulses. After subtraction according to the Hadamard scheme, the ASL signal was corrected for the use of the flip-angle sweep and background suppression pulses. The BASIL toolkit of the Oxford Centre for FMRIB was used to quantify the ASL signal.Results: By combining a time-encoded pCASL labeling scheme with an LL readout and simultaneous multi-slice acquisition, 28 time points of 16 slices with a 75- or 150-ms time resolution were acquired in a total scan time of 10 minutes 20 seconds, from which cerebral blood flow (CBF) maps, arterial transit time maps, and arterial blood volume could be determined.Conclusion: Whole-brain ASL images were acquired with a 75-ms time resolution for the angiography and 150-ms resolution for the perfusion phase by combining the proposed techniques. Reducing the total scan time to 1 minute 18 seconds still resulted in reasonable CBF maps, which demonstrates the feasibility of this approach for practical studies on brain hemodynamics. Show less
Cannabis produces a broad range of acute, dose-dependent psychotropic effects. Only a limited number of neuroimaging studies have mapped these effects by examining the impact of cannabis on resting... Show moreCannabis produces a broad range of acute, dose-dependent psychotropic effects. Only a limited number of neuroimaging studies have mapped these effects by examining the impact of cannabis on resting state brain neurophysiology. Moreover, how genetic variation influences the acute effects of cannabis on resting state brain function is unknown. Here we investigated the acute effects of Delta 9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on resting state brain neurophysiology, and their modulation by catechol-methyl-transferase (COMT) Val158Met genotype. Thirty-nine healthy volunteers participated in a pharmacological MRI study, where we applied Arterial Spin Labelling (ASL) to measure perfusion and functional MRI to assess resting state connectivity. THC increased perfusion in bilateral insula, medial superior frontal cortex, and left middle orbital frontal gyrus. This latter brain area showed significantly decreased connectivity with the precuneus after THC administration. THC effects on perfusion in the left insula were significantly related to subjective changes in perception and relaxation. These findings indicate that THC enhances metabolism and thus neural activity in the salience network. Furthermore, results suggest that recruitment of brain areas within this network is involved in the acute effects of THC. Resting state perfusion was modulated by COMT genotype, indicated by a significant interaction effect between drug and genotype on perfusion in the executive network, with increased perfusion after THC in Val/Met heterozygotes only. This finding suggests that prefrontal dopamine levels are involved in the susceptibility to acute effects of cannabis. (C) 2019 Elsevier B.V. and ECNP. All rights reserved. Show less
Suzuki, Y.; Okell, T.W.; Fujima, N.; Osch, M.J.P. van 2019
Purpose: The recently introduced "Acquisition of ConTRol and labEled imaging in the Same Shot" (ACTRESS) approach was designed to halve the scan time of arterial spin labeling (ASL) -based 4D-MRA... Show morePurpose: The recently introduced "Acquisition of ConTRol and labEled imaging in the Same Shot" (ACTRESS) approach was designed to halve the scan time of arterial spin labeling (ASL) -based 4D-MRA by obtaining both labeled and control images in a single Look-Locker readout. However, application for vessel-selective labeling remains difficult. The aim of this study was to achieve a combination of ACTRESS and vessel-selective labeling to halve the scan time of vessel-selective 4D-MRA.Methods: By Bloch equation simulations, Look-I,ocker pseudocontinuous-ASE, (pCASL) was optimized to achieve constant static tissue signal across the multidelay readout, which is essential for the ACTRESS approach. Additionally, a new subtraction scheme was proposed to achieve visualization of the inflow phase even when labeled blood will have already arrived in the distal arteries during the first phase acquisition due to the long duration of the pCASL labeling module. In vivo studies were performed to investigate the signal variation of the static tissue, as well as to assess image quality of vessel-selective 4D-MRA with ACTRESS.Results: in in vivo studies, the mean signal variation of the static tissue was 8.98% over the Look-Locker phases, thereby minimizing the elevation of background signal. This allowed visualization of peripheral arteries and slowly arriving arterial blood with image quality as good as conventional pCASL, within half the acquisition time. Vesselselective pCASL-ACTRESS enabled the separated visualization of vessels arising from internal and external carotid arteries within this shortened acquisition time.Conclusion: By combining vessel-selective pCASL and ACTRESS approach, 4D-MRA of a single targeted arterial tree was achieved in a few minutes. Show less
Suzuki, Y.; Okell, T.W.; Chappell, M.A.; Osch, M.J.P. van 2019
Purpose: When using simultaneous multi-slice (SMS) EPI for background suppressed (BGS) arterial spin labeling (ASL), correction of through-plane motion could introduce artefacts, because the slices... Show morePurpose: When using simultaneous multi-slice (SMS) EPI for background suppressed (BGS) arterial spin labeling (ASL), correction of through-plane motion could introduce artefacts, because the slices with most effective BGS are adjacent to slices with the least BGS. In this study, a new framework is presented to correct for such artefacts.Methods: The proposed framework consists of 3 steps: (1) homogenization of the static tissue signal over the different slices to eliminate most inter-slice differences because of different levels of BGS, (2) application of motion correction, and (3) extraction of a perfusion-weighted signal using a general linear model. The proposed framework was evaluated by simulations and a functional ASL study with intentional head motion.Results: Simulation studies demonstrated that the strong signal differences between slices with the most and least effective BGS caused sub-optimal estimation of motion parameters when through-plane motion was present. Although use of the M-0 image as the reference for registration allowed 82% improvement of motion estimation for through-plane motion, it still led to residual subtraction errors caused by different static tissue signal between control and label because of different BGS levels. By using our proposed framework, those problems were minimized, and the accuracy of CBF estimation was improved. Moreover, the functional ASL study showed improved detection of visual and motor activation when applying the framework as compared to conventional motion correction, as well as when motion correction was completely omitted.Conclusion: When combining BGS-ASL with SMS-EPI, particular attention is needed to avoid artefacts introduced by motion correction. With the proposed framework, these issues are minimized. Show less
The locus coeruleus is a small brainstem nucleus which contains neuromelanin cells and is involved in a number of cognitive functions such as attention, arousal and stress, as well as several... Show moreThe locus coeruleus is a small brainstem nucleus which contains neuromelanin cells and is involved in a number of cognitive functions such as attention, arousal and stress, as well as several neurological and psychiatric disorders. Locus coeruleus imaging in vivo is generally performed using a T-1-weighted turbo spin echo MRI sequence at 3 Tesla (T). However, imaging at high magnetic field strength can increase the signal-to-noise ratio and offers the possibility of imaging at higher spatial resolution. Therefore, in the present study we explored the possibility of visualizing the locus coeruleus at 7T. To this end, twelve healthy volunteers participated in three scanning sessions: two with 3T MRI and one with 7T MRI. The volumes of the first 3T session were used to segment the locus coeruleus, whereas the volumes of the second 3T and the 7T session were used to quantify the contrast of the locus coeruleus with several reference regions across eight different structural sequences. The results indicate that several of the 7T sequences provide detectable contrast between the locus coeruleus and surrounding tissue. Of the tested sequences, a T1-weighted sequence with spectral presaturation inversion recovery (SPIR) seems the most promising method for visualizing the locus coeruleus at ultra-high field MRI. While there is insufficient evidence to prefer the 7T SPIR sequence over the 3T TSE sequence, the isotropic voxels at 7T are an important advantage when visualizing small structures such as the locus coeruleus. Show less
