Quantitative magnetisation transfer imaging in relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.

Myelin-sensitive MRI such as magnetisation transfer imaging has been widely used in the clinical context of multiple sclerosis. The influence of methodology and differences in disease subtype on imaging findings is, however, not well established. Here, we aim to review systematically the use of quantitative magnetisation transfer imaging in the brain in relapsing-remitting multiple sclerosis. We examine how methodological differences, disease effects and their interaction influence magnetisation transfer imaging measures. Articles published before 06/01/2021 were retrieved from online databases (PubMed, EMBASE and Web of Science) with search terms including "magnetisation transfer" and "brain" for systematic review. Only studies which used human in vivo quantitative magnetisation transfer imaging in adults with relapsing-remitting multiple sclerosis (with or without healthy controls) were included. Data including sample size, magnetic field strength, MRI acquisition protocol parameters, treatments and clinical findings were extracted. Where possible, effect sizes were calculated for meta-analyses to determine magnetisation transfer (1) differences between patients and healthy controls; (2) longitudinal change; and, (3) relationships with clinical disability in relapsing-remitting multiple sclerosis. Eighty-six studies met the inclusion/exclusion criteria. MRI acquisition parameters varied widely, and were also underreported. The majority of studies examined MTR (magnetisation transfer ratio) in white matter, but magnetisation transfer metrics, brain regions and results were heterogeneous. Analysis demonstrated a risk of bias due to selective reporting and small sample sizes. A random-effects meta-analysis revealed MTR was 1.1 percent units [95% CI -1.47pu to -0.73pu] lower in relapsing-remitting multiple sclerosis than healthy controls (z-value: -6.04, p<0.001, n=23). Linear mixed-model analysis did not show a significant longitudinal change in MTR across all brain regions (β=-0.14 [-0.9 to 0.61], t-value=-0.38, p=0.71, n=13) or normal-appearing white matter alone (β=-0.082 [-0.13 to -0.29], t-value=0.78, p=0.44, n=7). There was a significant negative association between MTR and clinical disability, as assessed by the Expanded Disability Status Scale (r=-0.30 [95% CI -0.48 to -0.08]; z-value=-2.91, p=0.01, n=8). Evidence suggests that magnetisation transfer imaging is sensitive to pathological changes in relapsing-remitting multiple sclerosis, although the effect of relapsing-remitting multiple sclerosis on magnetisation transfer metrics in different brain tissue types was small in comparison to the inter-study variability. Recommended improvements include: the use of techniques such as MTsat (magnetisation transfer saturation) or ihMTR (inhomogeneous MTR) which provide more robust and specific microstructural measures within clinically feasible acquisition times; detailed methodological reporting standards; and larger, demographically diverse cohorts for comparison, including healthy controls.

Noradrenergic deficits contribute to apathy in Parkinson's disease through the precision of expected outcomes

Apathy is a debilitating feature of many diseases, including Parkinson's disease. We tested the hypothesis that degeneration of the locus coeruleus-noradrenaline system contributes to apathy by modulating the relative weighting of prior beliefs about action outcomes. Participants with mild-to-moderate idiopathic Parkinson's disease (N=17) completed a double-blind, placebo-controlled, crossover study with 40 mg of the noradrenaline reuptake inhibitor atomoxetine. Prior weighting was inferred from psychophysical analysis of performance in an effort-based visuomotor task, and was confirmed as negatively correlated with apathy. Locus coeruleus integrity was assessed in vivo using magnetisation transfer imaging at 7T. The effect of atomoxetine depended on locus coeruleus integrity: participants with a more degenerate locus coeruleus showed a greater increase in prior weighting on atomoxetine versus placebo. The results indicate a contribution of the noradrenergic system to apathy and potential benefit from noradrenergic treatment of people with Parkinson's disease, subject to stratification according to locus coeruleus integrity.

Neural substrate of quality of life in patients with schizophrenia: a magnetisation transfer imaging study

The aim of this study was to investigate the neural substrate underlying quality of life (QoL) and to demonstrate the microstructural abnormalities associated with impaired QoL in a large sample of patients with schizophrenia, using magnetisation transfer imaging. A total of 81 right-handed men with a diagnosis of schizophrenia and 25 age- and sex-similar healthy controls were included and underwent a 3T MRI with magnetization transfer ratio (MTR) to detect microstructural abnormalities. Compared with healthy controls, patients with schizophrenia had grey matter (GM) decreased MTR values in the temporal lobe (BA21, BA37 and BA38), the bilateral insula, the occipital lobe (BA17, BA18 and BA19) and the cerebellum. Patients with impaired QoL had lower GM MTR values relative to patients with preserved QoL in the bilateral temporal pole (BA38), the bilateral insula, the secondary visual cortex (BA18), the vermis and the cerebellum. Significant correlations between MTR values and QoL scores (p < 0.005) were observed in the GM of patients in the right temporal pole (BA38), the bilateral insula, the vermis and the right cerebellum. Our study shows that QoL impairment in patients with schizophrenia is related to the microstructural changes in an extensive network, suggesting that QoL is a bio-psychosocial marker.