Magnetic Resonance Relaxation Anisotropy:Physical Principles and Uses in Microstructure Imaging

Magnetic resonance imaging (MRI) provides an excellent means of studying tissue microstructure noninvasively since the microscopic tissue environment is imprinted on the MRI signal even at macroscopic voxel level. Mesoscopic variations in magnetic field, created by microstructure, influence the transverse relaxation time (T(2)) in an orientation-dependent fashion (T(2) is anisotropic). However, predicting the effects of microstructure upon MRI observables is challenging and requires theoretical insight. We provide a formalism for calculating the effects upon T(2) of tissue microstructure, using a model of cylindrical magnetic field perturbers. In a cohort of clinically healthy adults, we show that the angular information in spin-echo T(2) is consistent with this model. We show that T(2) in brain white matter of nondemented volunteers follows a U-shaped trajectory with age, passing its minimum at an age of ∼30 but that this depends on the particular white matter tract. The anisotropy of T(2) also interacts with age and declines with increasing age. Late-myelinating white matter is more susceptible to age-related change than early-myelinating white matter, consistent with the retrogenesis hypothesis. T(2) mapping may therefore be incorporated into microstructural imaging

Association Between Resting-State Microstates and Ratings on the Amsterdam Resting-State Questionnaire

There is a gap in understanding on how physiologically observed activity is related to the subjective, internally oriented experience during resting state. Microstate analysis is a frequent approach to evaluate resting-state EEG. But the relationship of commonly observed resting-state microstates to psychological domains of resting is not clear. The Amsterdam Resting-State Questionnaire (ARSQ) was recently introduced, offering an effective way to quantify subjective states after a period of resting and associate these quantifiers to psychological and physiological variables. In a sample of 94 healthy volunteers who participated in closed-eyes 5 min resting session with concurrent EEG recording and subsequent filling of the ARSQ we evaluated parameters of microstate Classes A, B, C, D. We showed a moderate negative association between contribution (r = -0.40) of Class C and experienced somatic awareness (SA). The negative correlation between Class C and SA seems reasonable as Class C becomes more dominant when connections to contextual information (and bodily sensations as assessed with SA) are loosened (in reduced attention states, during sleep, hypnosis, or psychosis). We suggest that the use of questionnaires such as the ARSQ is helpful in exploring the variation of resting-state EEG parameters and its relationship to variation in sensory and non-sensory experiences

A beginner's guide to arterial spin labeling (ASL) image processing

Arterial spin labeling (ASL) is a non-invasive and cost-effective MRI technique for brain perfusion measurements. While it has developed into a robust technique for scientific and clinical use, its image processing can still be daunting. The 2019 Ann Arbor ISMRM ASL working group established that education is one of the main areas that can accelerate the use of ASL in research and clinical practice. Specifically, the post-acquisition processing of ASL images and their preparation for region-of-interest or voxel-wise statistical analyses is a topic that has not yet received much educational attention. This educational review is aimed at those with an interest in ASL image processing and analysis. We provide summaries of all typical ASL processing steps on both single-subject and group levels. The readers are assumed to have a basic understanding of cerebral perfusion (patho) physiology; a basic level of programming or image analysis is not required. Starting with an introduction of the physiology and MRI technique behind ASL, and how they interact with the image processing, we present an overview of processing pipelines and explain the specific ASL processing steps. Example video and image illustrations of ASL studies of different cases, as well as model calculations, help the reader develop an understanding of which processing steps to check for their own analyses. Some of the educational content can be extrapolated to the processing of other MRI data. We anticipate that this educational review will help accelerate the application of ASL MRI for clinical brain research

Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer's disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial

BACKGROUND: Drugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease. METHODS: In this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012-003641-15), and is completed. FINDINGS: Between July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or placebo (n=106). Of 197 (93%) participants who completed the study, 171 (81%) had complete primary outcome data. The mean brain volume (BSI) reduction was 19·1 mL (SD 10·3) in the losartan group and 20·0 mL (10·8) in the placebo group. The difference in total volume reduction between groups was -2·29 mL (95% CI -6·46 to 0·89; p=0·14). The number of adverse events was low (22 in the losartan group and 20 in the placebo group) with no differences between treatment groups. There was one treatment-related death per treatment group. INTERPRETATION: 12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. Further research is needed to assess the potential therapeutic benefit from earlier treatment in patients with milder cognitive impairment or from longer treatment periods. FUNDING: Efficacy and Mechanism Evaluation Programme (UK Medical Research Council and National Institute for Health Research)