Brain glycogen build-up measured by magnetic resonance spectroscopy in classic infantile Pompe disease.

Classic infantile Pompe disease is caused by abnormal lysosomal glycogen accumulation in multiple tissues, including the brain due to a deficit in acid α-glucosidase. Although treatment with recombinant human acid α-glucosidase has dramatically improved survival, recombinant human acid α-glucosidase does not reach the brain, and surviving classic infantile Pompe patients develop progressive cognitive deficits and white matter lesions. We investigated the feasibility of measuring non-invasively glycogen build-up and other metabolic alterations in the brain of classic infantile Pompe patients.

Probing diffusion of water and metabolites to assess white matter microstructure in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive X-linked neuromuscular disorder caused by the absence of functional dystrophin protein. In addition to muscle, dystrophin is expressed in the brain in both neurons and glial cells. Previous studies have shown altered white matter microstructure in patients with DMD using diffusion tensor imaging (DTI).

Diffusion weighted magnetic resonance spectroscopy revealed neuronal specific microstructural alterations in Alzheimer's disease.

In Alzheimer's disease, reconfiguration and deterioration of tissue microstructure occur before substantial degeneration become evident. We explored the diffusion properties of both water, a ubiquitous marker measured by diffusion MRI, and -acetyl-aspartate, a neuronal metabolite probed by diffusion-weighted magnetic resonance spectroscopy, for investigating cortical microstructural changes downstream of Alzheimer's disease pathology. To this aim, 50 participants from the Swedish BioFINDER-2 study were scanned on both 7 and 3 T MRI systems.

Practical considerations of diffusion-weighted MRS with ultra-strong diffusion gradients.

Introduction: Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) offers improved cellular specificity to microstructure-compared to water-based methods alone-but spatial resolution and SNR is severely reduced and slow-diffusing metabolites necessitate higher -values to accurately characterize their diffusion properties. Ultra-strong gradients allow access to higher -values per-unit time, higher SNR for a given -value, and shorter diffusion times, but introduce additional challenges such as eddy-current artefacts, gradient non-uniformity, and mechanical vibrations.

Methods: In this work, we present initial DW-MRS data acquired on a 3T Siemens Connectom scanner equipped with ultra-strong (300 mT/m) gradients.

Diffusion-weighted MR spectroscopy: Consensus, recommendations, and resources from acquisition to modeling.

Brain cell structure and function reflect neurodevelopment, plasticity, and aging; and changes can help flag pathological processes such as neurodegeneration and neuroinflammation. Accurate and quantitative methods to noninvasively disentangle cellular structural features are needed and are a substantial focus of brain research. Diffusion-weighted MRS (dMRS) gives access to diffusion properties of endogenous intracellular brain metabolites that are preferentially located inside specific brain cell populations.

Implications of Inflammatory Processes on a Developing Central Nervous System in Childhood-Onset Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is increasingly affecting pediatric and adult populations. Neuropsychiatric manifestations (ie, cognitive dysfunction and mood disorders) appear to occur with greater severity and poorer prognosis in childhood-onset SLE (cSLE) versus adult-onset SLE, negatively impacting school function, self-management, and psychosocial health, as well as lifelong health-related quality of life. In this review, we describe pathogenic mechanisms active in cSLE, such as maladaptive inflammatory processes and ischemia, which are hypothesized to underpin central phenotypes in patients with cSLE, and the role of alterations in protective central nervous system (CNS) barriers (ie, the blood-brain barrier) are also discussed.

Lactate: A Theranostic Biomarker for Metabolic Psychiatry?

Alterations in neurometabolism and mitochondria are implicated in the pathophysiology of psychiatric conditions such as mood disorders and schizophrenia. Thus, developing objective biomarkers related to brain mitochondrial function is crucial for the development of interventions, such as central nervous system penetrating agents that target brain health. Lactate, a major circulatory fuel source that can be produced and utilized by the brain and body, is presented as a theranostic biomarker for neurometabolic dysfunction in psychiatric conditions.

Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington's disease.

Introduction: Strong evidence suggests a significant role for iron accumulation in the brain in addition to the well-documented neurodegenerative aspects of Huntington's disease (HD). The putative mechanisms by which iron is linked to the HD pathogenesis are multiple, including oxidative stress, ferroptosis and neuroinflammation. However, no previous study in a neurodegenerative disease has linked the observed increase of brain iron accumulation as measured by MRI with well-established cerebrospinal fluid (CSF) and blood biomarkers for iron accumulation, or with associated processes such as neuroinflammation.

Tract-based white matter hyperintensity patterns in patients with systemic lupus erythematosus using an unsupervised machine learning approach.

Currently, little is known about the spatial distribution of white matter hyperintensities (WMH) in the brain of patients with Systemic Lupus erythematosus (SLE). Previous lesion markers, such as number and volume, ignore the strategic location of WMH. The goal of this work was to develop a fully-automated method to identify predominant patterns of WMH across WM tracts based on cluster analysis.

Longitudinal Monitoring of Microstructural Alterations in Cerebral Ischemia with in Vivo Diffusion-weighted MR Spectroscopy.

Background The time course of cellular damage after acute ischemic stroke (IS) is currently not well known, and specific noninvasive markers of microstructural alterations linked to inflammation are lacking, which hinders the monitoring of anti-inflammatory treatment. Purpose To evaluate the temporal pattern of neuronal and glial microstructural changes after stroke using in vivo single-voxel diffusion-weighted MR spectroscopy. Materials and Methods In this prospective longitudinal study, participants with IS and healthy volunteers (HVs) underwent MRI at 3.

Improved detection limits of J-coupled neurometabolites in the human brain at 7 T with a J-refocused sLASER sequence.

In a standard spin echo, the time evolution due to homonuclear couplings is not reversed, leading to echo time (TE)-dependent modulation of the signal amplitude and signal loss in the case of overlapping multiplet resonances. This has an adverse effect on quantification of several important metabolites such as glutamate and glutamine. Here, we propose a J-refocused variant of the sLASER sequence (J-sLASER) to improve quantification of J-coupled metabolites at ultrahigh field (UHF).

Astrocytic function is associated with both amyloid-β and tau pathology in non-demented carriers.

A growing body of evidence suggests that astrocytes play a major role in the pathophysiology of Alzheimer's disease. Given that is primarily expressed in astrocytes, these cells might be an important link between the ε4 allele and the development of Alzheimer's disease pathology. Here, we investigate this hypothesis by measuring myo-inositol, a metabolite involved in astrocytic functions, with magnetic resonance spectroscopy.

MRI-Based Classification of Neuropsychiatric Systemic Lupus Erythematosus Patients With Self-Supervised Contrastive Learning.

Introduction/purpose: Systemic lupus erythematosus (SLE) is a chronic auto-immune disease with a broad spectrum of clinical presentations, including heterogeneous neuropsychiatric (NP) syndromes. Structural brain abnormalities are commonly found in SLE and NPSLE, but their role in diagnosis is limited, and their usefulness in distinguishing between NPSLE patients and patients in which the NP symptoms are not primarily attributed to SLE (non-NPSLE) is non-existent. Self-supervised contrastive learning algorithms proved to be useful in classification tasks in rare diseases with limited number of datasets.

Cortical glutamate and gamma-aminobutyric acid over the course of a provoked migraine attack, a 7 Tesla magnetic resonance spectroscopy study.

Enhanced activity of the glutamatergic system has been linked to migraine pathophysiology. The present study aimed to assess the involvement of the glutamatergic system in the onset of attacks. We provoked attacks by infusion of glyceryl trinitrate (GTN; 0.

Neuropsychiatric systemic lupus erythematosus is associated with a distinct type and shape of cerebral white matter hyperintensities.

Objectives: Advanced white matter hyperintensity (WMH) markers on brain MRI may help reveal underlying mechanisms and aid in the diagnosis of different phenotypes of SLE patients experiencing neuropsychiatric (NP) manifestations.

Methods: In this prospective cohort study, we included a clinically well-defined cohort of 155 patients consisting of 38 patients with NPSLE (26 inflammatory and 12 ischaemic phenotype) and 117 non-NPSLE patients. Differences in 3 T MRI WMH markers (volume, type and shape) were compared between patients with NPSLE and non-NPSLE and between patients with inflammatory and ischaemic NPSLE by linear and logistic regression analyses corrected for age, sex and intracranial volume.

Diffusion-weighted MR spectroscopy (DW-MRS) is sensitive to LPS-induced changes in human glial morphometry: A preliminary study.

Background: Low-dose lipopolysaccharide (LPS) is a well-established experimental method for inducing systemic inflammation and shown by microscopy to activate microglia in rodents. Currently, techniques for in-vivo imaging of glia in humans are limited to TSPO (Translocator protein) PET, which is expensive, methodologically challenging, and has poor cellular specificity. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) sensitizes MR spectra to diffusion of intracellular metabolites, potentially providing cell-specific information about cellular morphology.

White matter hyperintensities associate with cognitive slowing in patients with systemic lupus erythematosus and neuropsychiatric symptoms.

Objective: To compare cognitive function between patients with different phenotypes of neuropsychiatric systemic lupus erythematosus (NPSLE) and assess its association with brain and white matter hyperintensity (WMH) volumes.

Methods: Patients attending the Leiden University Medical Centre NPSLE clinic between 2007 and 2015 without large brain infarcts were included (n=151; 42±13 years, 91% women). In a multidisciplinary consensus meeting, neuropsychiatric symptoms were attributed to systemic lupus erythematosus (SLE) (NPSLE, inflammatory (n=24) or ischaemic (n=12)) or to minor/non-NPSLE (n=115).

Different phenotypes of neuropsychiatric systemic lupus erythematosus are related to a distinct pattern of structural changes on brain MRI.

Objectives: The underlying structural brain correlates of neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) remain unclear, thus hindering correct diagnosis. We compared brain tissue volumes between a clinically well-defined cohort of patients with NPSLE and SLE patients with neuropsychiatric syndromes not attributed to SLE (non-NPSLE). Within the NPSLE patients, we also examined differences between patients with two distinct disease phenotypes: ischemic and inflammatory.

Quantitative susceptibility mapping in the thalamus and basal ganglia of systemic lupus erythematosus patients with neuropsychiatric complaints.

Systemic lupus erythematosus (SLE) is an auto-immune disease characterized by multi-organ involvement. Although uncommon, central nervous system involvement in SLE, termed neuropsychiatric SLE (NPSLE), is not an exception. Current knowledge on underlying pathogenic mechanisms is incomplete, however, neuroinflammation is thought to play a critical role.

Compartmental diffusion and microstructural properties of human brain gray and white matter studied with double diffusion encoding magnetic resonance spectroscopy of metabolites and water.

Double diffusion encoding (DDE) of the water signal offers a unique ability to separate the effect of microscopic anisotropic diffusion in structural units of tissue from the overall macroscopic orientational distribution of cells. However, the specificity in detected microscopic anisotropy is limited as the signal is averaged over different cell types and across tissue compartments. Performing side-by-side water and metabolite DDE spectroscopic (DDES) experiments provides complementary measures from which intracellular and extracellular microscopic fractional anisotropies (μFA) and diffusivities can be estimated.

Longitudinal changes in cerebral white matter microstructure in newly diagnosed systemic lupus erythematosus patients.

Objectives: To evaluate longitudinal variations in diffusion tensor imaging (DTI) metrics of different white matter (WM) tracts of newly diagnosed SLE patients, and to assess whether DTI changes relate to changes in clinical characteristics over time.

Methods: A total of 17 newly diagnosed SLE patients (19-55 years) were assessed within 24 months from diagnosis with brain MRI (1.5 T Philips Achieva) at baseline, and after at least 12 months.

Pathological characterization of T2*-weighted MRI contrast in the striatum of Huntington's disease patients.

Previous MRI studies consistently reported iron accumulation within the striatum of patients with Huntington's disease (HD). However, the pattern and origin of iron accumulation is poorly understood. This study aimed to characterize the histopathological correlates of iron-sensitive ex vivo MRI contrast change in HD brains.

Proton nuclear magnetic resonance J-spectroscopy of phantoms containing brain metabolites on a portable 0.05 T MRI scanner.

We examined approaches for obtaining H NMR spectra of brain metabolites on a low-field (B = 0.05 T) portable MRI scanner, which was developed in our laboratory with the aim of bringing cost-effective radiological services to populations in underserved, remote regions. The low static magnetic field B dictates low signal to noise ratio for metabolites in the mM concentration range, and results in an overall spectral region for the H resonances of these metabolites narrower than the linewidth obtainable in our scanner.

Functional and structural impairment of transcallosal motor fibres in ALS: a study using transcranial magnetic stimulation, diffusion tensor imaging, and diffusion weighted spectroscopy.

Imaging studies showed that the structure of the corpus callosum (CC) is affected in amyotrophic lateral sclerosis (ALS). Some clinical studies also suggest that interhemispheric connectivity is altered, since mirror movements seem to occur in ALS. Finally, reduced interhemispheric inhibition (IHI), studied by transcranial magnetic stimulation (TMS), has been reported.

Quantitative MRI and laser ablation-inductively coupled plasma-mass spectrometry imaging of iron in the frontal cortex of healthy controls and Alzheimer's disease patients.

Accumulation of iron within the cortex of Alzheimer's disease (AD) patients has been reported by numerous MRI studies using iron-sensitive methods. Validation of iron-sensitive MRI is important for the interpretation of in vivo findings. In this study, the relation between the spatial iron distribution and T∗-weighted MRI in the human brain was investigated using a direct comparison of spatial maps of iron as detected by T∗-weighted MRI, iron histochemistry and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), in postmortem brain tissue of the medial frontal gyrus of three control subjects and six AD patients.