Neurometabolic Alterations in Motor Neuron Disease: Insights from Magnetic Resonance Spectroscopy

Abstract

Magnetic resonance spectroscopy (MRS) has contributed important academic insights in motor neuron diseases (MNDs), particularly in amyotrophic lateral sclerosis (ALS). Over the past three decades momentous methodological advances took place, including the emergence of high-field magnetic resonance imaging (MRI) platforms, multi-voxel techniques, whole-brain protocols, novel head-coil designs, and a multitude of open-source imaging suites. Technological advances in MRS are complemented by important conceptual developments in MND, such as the recognition of the importance of extra-motor brain regions, multi-timepoint longitudinal study designs, assessment of asymptomatic mutation carriers, description of genotype-associated signatures, and the gradual characterisation of non-ALS MND phenotypes. We have conducted a systematic review of published MRS studies in MND to identify important emerging research trends, key lessons from pioneering studies, and stereotyped shortcomings. We also sought to highlight notable gaps in the current literature so that research priorities for future studies can be outlined. While MRS remains relatively underutilised in MND compared to other structural, diffusivity and functional imaging modalities, our review suggests that MRS can not only advance our academic understanding of MND biology, but has a multitude of practical benefits for clinical and pharmaceutical trial applications.

Hippocampal Metabolic Alterations in Amyotrophic Lateral Sclerosis: A Magnetic Resonance Spectroscopy Study

“…Since the very first MRS studies on ALS in the early 1990s [ 18 ], less than 100 MRS studies have been published on ALS, which is considerably less than the myriad of structural and functional neuroimaging studies [ 19 ]. With very few exceptions [ 20 ], MRS studies on ALS are primarily cerebral studies.…”

“…Most MRS studies are single voxel initiatives, and whole-brain multi-voxel protocols have only recently been applied to ALS cohorts. Since the publication of pioneering studies on ALS, MRS have been used to ascertain medication effects, evaluate presymptomatic changes in mutation carriers, assess progressive metabolic alterations longitudinally, and explore subcortical changes [ 19 ]. Published MRS studies on ALS overwhelmingly focus on motor regions (i.e., motor cortex, pyramidal tract) and metabolic alterations in frontotemporal areas are poorly characterised.…”

Thalamic pathology in frontotemporal dementia: Predilection for specific nuclei, phenotype‐specific signatures, clinical correlates, and practical relevance

“…Similarly, shape deformation analyses also rely on three‐dimensional T1‐weighted images eliminating the need for additional data acquisition and scanning costs (Patenaude et al., 2011 ). One of the challenges of cortical single‐voxel magentic resonance spectroscopy (MRS) is the consistency in voxel placement (Christidi et al., 2022 ), which is not a problem in thalamus spectroscopy as the structure is readily identified on localizer scans (Sharma et al., 2011 ). As the thalami are paired structures, commenting on symmetry or asymmetry based on retrieved integrity indices is very straightforward.…”

Pre-symptomatic radiological changes in frontotemporal dementia: propagation characteristics, predictive value and implications for clinical trials

“…MR spectroscopy studies have suggested a relatively stereotyped sequence of events, beginning with increased mI/Cr ratio (indicators of glial activity), followed by decreased NAA/mI ratio (markers of loss of neuronal integrity) and subsequent atrophy (Christidi et al, 2022 ). MRS studies of presymptomatic MAPT mutation carriers are predominantly single voxel studies focusing on different regions of interests (ROIs) such as the posterior cingulate gyrus inferior precuneus (Chen et al, 2019a ; Kantarci et al, 2010 ) or medial frontal lobe (Chen et al, 2019c ).…”