Methods for quantitative susceptibility and R2* mapping in whole post-mortem brains at 7T applied to amyotrophic lateral sclerosis.

Susceptibility weighted magnetic resonance imaging (MRI) is sensitive to the local concentration of iron and myelin. Here, we describe a robust image processing pipeline for quantitative susceptibility mapping (QSM) and R2* mapping of fixed post-mortem, whole-brain data. Using this pipeline, we compare the resulting quantitative maps in brains from patients with amyotrophic lateral sclerosis (ALS) and controls, with validation against iron and myelin histology.

Grey matter abnormalities in methcathinone abusers with a Parkinsonian syndrome.

Background: A permanent Parkinsonian syndrome occurs in intravenous abusers of the designer psychostimulant methcathinone (ephedrone). It is attributed to deposition of contaminant manganese, as reflected by characteristic globus pallidus hyperintensity on T1-weighted MRI.

Methods: We have investigated brain structure and function in methcathinone abusers ( = 12) compared to matched control subjects ( = 12) using T1-weighted structural and resting-state functional MRI.

Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative, clinically heterogeneous syndrome pathologically overlapping with frontotemporal dementia. To date, therapeutic trials in animal models have not been able to predict treatment response in humans, and the revised ALS Functional Rating Scale, which is based on coarse disability measures, remains the gold-standard measure of disease progression. Advances in neuroimaging have enabled mapping of functional, structural, and molecular aspects of ALS pathology, and these objective measures may be uniquely sensitive to the detection of propagation of pathology in vivo.

Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease.

SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder.

Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk.

Objective: To discern presymptomatic changes in brain structure or function using advanced MRI in carriers of mutations predisposing to amyotrophic lateral sclerosis (ALS).

Methods: T1-weighted, diffusion weighted and resting state functional MRI data were acquired at 3 T for 12 asymptomatic mutation carriers (psALS), 12 age-matched controls and affected patients with ALS. Cortical thickness analysis, voxel-based morphometry, volumetric and shape analyses of subcortical structures, tract-based spatial statistics of metrics derived from the diffusion tensor, and resting state functional connectivity (FC) analyses were performed.

Challenges in the reproducibility of clinical studies with resting state fMRI: An example in early Parkinson's disease.

Resting state fMRI (rfMRI) is gaining in popularity, being easy to acquire and with promising clinical applications. However, rfMRI studies, especially those involving clinical groups, still lack reproducibility, largely due to the different analysis settings. This is particularly important for the development of imaging biomarkers.

Eye-tracking in amyotrophic lateral sclerosis: A longitudinal study of saccadic and cognitive tasks.

A relative preservation of eye movements is notable in ALS, but saccadic functions have not been studied longitudinally. ALS overlaps with FTD, typically involving executive dysfunction, and eye-tracking offers additional potential for the assessment of extramotor pathology where writing and speaking are both impaired. Eye-tracking measures (including anti-saccade, trail-making and visual search tasks) were assessed at six-monthly intervals for up to two years in a group of ALS (n = 61) and primary lateral sclerosis (n = 7) patients, compared to healthy age-matched controls (n = 39) assessed on a single occasion.

CSF neurofilament light chain reflects corticospinal tract degeneration in ALS.

Objective: Diffusion tensor imaging (DTI) is sensitive to white matter tract pathology. A core signature involving the corticospinal tracts (CSTs) has been identified in amyotrophic lateral sclerosis (ALS). Raised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders.

Aberrant functional connectivity within the basal ganglia of patients with Parkinson's disease.

Resting state functional MRI (rs-fMRI) has been previously shown to be a promising tool for the assessment of early Parkinson's disease (PD). In order to assess whether changes within the basal ganglia network (BGN) are disease specific or relate to neurodegeneration generally, BGN connectivity was assessed in 32 patients with early PD, 19 healthy controls and 31 patients with Alzheimer's disease (AD). Voxel-wise comparisons demonstrated decreased connectivity within the basal ganglia of patients with PD, when compared to patients with AD and healthy controls.

Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage.

Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction.

Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis.

Diagnosis, stratification and monitoring of disease progression in amyotrophic lateral sclerosis currently rely on clinical history and examination. The phenotypic heterogeneity of amyotrophic lateral sclerosis, including extramotor cognitive impairments is now well recognized. Candidate biomarkers have shown variable sensitivity and specificity, and studies have been mainly undertaken only cross-sectionally.

Functional connectivity in the basal ganglia network differentiates PD patients from controls.

Objective: To examine functional connectivity within the basal ganglia network (BGN) in a group of cognitively normal patients with early Parkinson disease (PD) on and off medication compared to age- and sex-matched healthy controls (HC), and to validate the findings in a separate cohort of participants with PD.

Methods: Participants were scanned with resting-state fMRI (RS-fMRI) at 3T field strength. Resting-state networks were isolated using independent component analysis.

Progressive hemiparesis (Mills syndrome) with aphasia in amyotrophic lateral sclerosis.

The onset of motor symptoms in amyotrophic lateral sclerosis (ALS) is strikingly focal. In three-quarters of cases, weakness emerges unilaterally in one limb, typically spreading contiguously over months to become bilateral.(1) An extremely rare clinical syndrome of upper motor neuron-predominant, progressive hemiparesis was first described by American neurologist Charles Karsner Mills (1845-1930).

Comprehensive morphometry of subcortical grey matter structures in early-stage Parkinson's disease.

Previous imaging studies that investigated morphometric group differences of subcortical regions outside the substantia nigra between non-demented Parkinson's patients and controls either did not find any significant differences, or reported contradictory results. Here, we performed a comprehensive morphometric analysis of 20 cognitively normal, early-stage PD patients and 19 matched control subjects. In addition to relatively standard analyses of whole-brain grey matter volume and overall regional volumes, we examined subtle localized surface shape differences in striatal and limbic grey matter structures and tested their utility as a diagnostic marker.

Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease.

Diffusion imaging is a promising marker of microstructural damage in neurodegenerative disorders, but interpretation of its relationship with underlying neuropathology can be complex. Here, we examined both volumetric and brain microstructure abnormalities in 13 amnestic patients with mild cognitive impairment (MCI), who progressed to probable Alzheimer's disease (AD) no earlier than 2 years after baseline scanning, in order to focus on early, and hence more sensitive, imaging markers. We compared them to 22 stable amnestic MCI patients with similar cognitive performance and episodic memory impairment but who did not show progression of symptoms for at least 3 years.

Fractional anisotropy in the posterior limb of the internal capsule and prognosis in amyotrophic lateral sclerosis.

Objective: To explore the value of diffusion tensor imaging applied to those specific cerebral white matter tracts consistently involved pathologically in amyotrophic lateral sclerosis as a source of prognostic biomarkers.

Design: Baseline clinical assessment and 3-T diffusion tensor imaging, repeated after approximately 6 months.Tract-based spatial statistics were used to assess voxel wise correlations of just the baseline diffusion tensor imaging indices with the progression rate (change in disability score/time interval) within the corticospinal tract and corpus callosum.

DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease.

Though mild cognitive impairment is an intermediate clinical state between healthy aging and Alzheimer's disease (AD), there are very few whole-brain voxel-wise diffusion MRI studies directly comparing changes in healthy control, mild cognitive impairment (MCI) and AD subjects. Here we report whole-brain findings from a comprehensive study of diffusion tensor indices and probabilistic tractography obtained in a very large population of healthy controls, MCI and probable AD subjects. As expected from the literature, all diffusion indices converged to show that the cingulum bundle, the uncinate fasciculus, the entire corpus callosum and the superior longitudinal fasciculus are the most affected white matter tracts in AD.

Connectivity-based segmentation of the substantia nigra in human and its implications in Parkinson's disease.

The aims of this study were to i) identify substantia nigra subregions i.e. pars reticulata (SNr) and pars compacta (SNc), in human, and ii) to assess volumetric changes in these subregions in the diagnosis of Parkinson's disease.

MRI characteristics of the substantia nigra in Parkinson's disease: a combined quantitative T1 and DTI study.

The substantia nigra contains dopaminergic cells that project to the striatum and are affected by the neurodegenerative process that appears in Parkinson's disease (PD). For accurate differential diagnosis and for disease monitoring the availability of a sensitive and non-invasive biomarker for Parkinson's disease would be essential. Although there has been notable progress in studying correlates of nigral degeneration by means of magnetic resonance imaging (MRI) in the past decade, MRI and analysis techniques that allow accurate high-resolution mapping of the SN within a clinically acceptable acquisition time are still elusive.

Methods for tractography-driven surface registration of brain structures.

Registration of brain structures should bring anatomically equivalent areas into correspondence which is usually done using information from structural MRI modalities. Correspondence can be improved by using other image modalities that provide complementary data. In this paper we propose and evaluate two novel surface registration algorithms which improve within-surface correspondence in brain structures.