Relationship between MRI brain-age heterogeneity, cognition, genetics and Alzheimer's disease neuropathology.

Background: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).

Five dominant dimensions of brain aging are identified via deep learning: associations with clinical, lifestyle, and genetic measures.

Brain aging is a complex process influenced by various lifestyle, environmental, and genetic factors, as well as by age-related and often co-existing pathologies. MRI and, more recently, AI methods have been instrumental in understanding the neuroanatomical changes that occur during aging in large and diverse populations. However, the multiplicity and mutual overlap of both pathologic processes and affected brain regions make it difficult to precisely characterize the underlying neurodegenerative profile of an individual from an MRI scan.

Gene-SGAN: a method for discovering disease subtypes with imaging and genetic signatures via multi-view weakly-supervised deep clustering.

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors.

Development of an MRI-Compatible Nasal Drug Delivery Method for Probing Nicotine Addiction Dynamics.

Substance abuse is a fundamentally dynamic disease, characterized by repeated oscillation between craving, drug self-administration, reward, and satiety. To model nicotine addiction as a control system, a magnetic resonance imaging (MRI)-compatible nicotine delivery system is needed to elicit cyclical cravings. Using a concentric nebulizer, inserted into one nostril, we delivered each dose equivalent to a single cigarette puff by a syringe pump.

Gray Matter Morphometry Correlates with Attentional Efficiency in Young-Adult Multiple Sclerosis.

Slowed processing on the alerting, orienting and executive control components of attention measured using the Attention Network Test-Interactions (ANT-I) have been widely reported in multiple sclerosis (MS). Despite the assumption that these components correspond to specific neuroanatomical networks in the brain, little is known about gray matter changes that occur in MS and their association with ANT-I performance. We investigated vertex-wise cortical thickness changes and deep gray matter volumetric changes in young MS participants (N = 21, age range: 18-35) with pediatric or young-adult onset and mild disease severity.

White matter correlates of slowed information processing speed in unimpaired multiple sclerosis patients with young age onset.

Slowed information processing speed is among the earliest markers of cognitive impairment in multiple sclerosis (MS) and has been associated with white matter (WM) structural integrity. Localization of WM tracts associated with slowing, but not significant impairment, on specific cognitive tasks in pediatric and young age onset MS can facilitate early and effective therapeutic intervention. Diffusion tensor imaging data were collected on 25 MS patients and 24 controls who also underwent the Symbol Digit Modalities Test (SDMT) and the computer-based Cogstate simple and choice reaction time tests.

Functional, anatomical and diffusion tensor MRI study of radiology expertise.

Background: Repeated practice to acquire expertise could result in the structural and functional changes in relevant brain circuits as a result of long-term potentiation, neurogenesis, glial genesis, and remodeling.

Purpose: The goal of this study is to use task fMRI to study the brain of expert radiologists performing a diagnosis task where a series of medical images were presented during fMRI acquisition for 12s and participants were asked to choose a diagnosis. Structural and diffusion-tensor MRI were also acquired.

Diet modulates brain network stability, a biomarker for brain aging, in young adults.

Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones.

Profiles of cortical inflammation in multiple sclerosis by C-PBR28 MR-PET and 7 Tesla imaging.

Background: Neuroinflammation with microglia activation is thought to be closely related to cortical multiple sclerosis (MS) lesion pathogenesis.

Objective: Using C-PBR28 and 7 Tesla (7T) imaging, we assessed in 9 relapsing-remitting multiple sclerosis (RRMS) and 10 secondary progressive multiple sclerosis (SPMS) patients the following: (1) microglia activation in lesioned and normal-appearing cortex, (2) cortical lesion inflammatory profiles, and (3) the relationship between neuroinflammation and cortical integrity.

Methods: Mean C-PBR28 uptake was measured in focal cortical lesions, cortical areas with 7T quantitative T* (q-T*) abnormalities, and normal-appearing cortex.

Resting-state functional connectivity networks associated with fatigue in multiple sclerosis with early age onset.

Background: Fatigue is one of the most commonly experienced symptoms in multiple sclerosis (MS). The neural correlates of fatigue in MS, in general and specifically in early onset, remain poorly understood. This study employed resting-state fMRI (rsfMRI) to investigate the functional connectivity of fatigue in MS patients with early age onset.

Characterization of gray-matter multiple sclerosis lesions using double inversion recovery, diffusion, contrast-enhanced, and volumetric MRI.

Purpose: To investigate gray-matter (GM) lesions in relapsing-remitting multiple sclerosis (MS) using double-inversion recovery (DIR) MRI, determine GM lesions prevalence, spatial distribution and characterize their contrast-enhancement, diffusion characteristics and compare them to white-matter (WM) lesions. This is the first study, to our knowledge, to investigate GM MS lesions using double-inversion recovery MRI, to determine GM lesion prevalence and location, and characterize contrast-enhancement and diffusion characteristics, compared to WM lesion characteristics in the same patients. We also correlated GM lesion counts, volume and apparent diffusion coefficient (ADC) with total brain, WM, and GM volumes, as well as 25-foot walk test as a clinical disability.

Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging.

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis.

Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF).

Methods: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T* (q-T*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores.

The association between intra- and juxta-cortical pathology and cognitive impairment in multiple sclerosis by quantitative T* mapping at 7 T MRI.

Using quantitative T* at 7 Tesla (T) magnetic resonance imaging, we investigated whether impairment in selective cognitive functions in multiple sclerosis (MS) can be explained by pathology in specific areas and/or layers of the cortex. Thirty-one MS patients underwent neuropsychological evaluation, acquisition of 7 T multi-echo T* gradient-echo sequences, and 3 T anatomical images for cortical surfaces reconstruction. Seventeen age-matched healthy subjects served as controls.

Neuroinflammatory component of gray matter pathology in multiple sclerosis.

Objective: In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation.

Methods: Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent C-PBR28 MR-PET. MS subjects underwent 7T T2*-weighted imaging for cortical lesion segmentation, and neurological and cognitive evaluation.

Beyond focal cortical lesions in MS: An in vivo quantitative and spatial imaging study at 7T.

Objectives: Using quantitative T2* 7-tesla (7T) MRI as a marker of demyelination and iron loss, we investigated, in patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), spatial and tissue intrinsic characteristics of cortical lesion(s) (CL) types, and structural integrity of perilesional normal-appearing cortical gray matter (NACGM) as a function of distance from lesions.

Methods: Patients with MS (18 RRMS, 11 SPMS), showing at least 2 CL, underwent 7T T2* imaging to obtain (1) magnitude images for segmenting focal intracortical lesion(s) (ICL) and leukocortical lesion(s) (LCL), and (2) cortical T2* maps. Anatomical scans were collected at 3T for cortical surface reconstruction using FreeSurfer.

Is the Relationship between Cortical and White Matter Pathologic Changes in Multiple Sclerosis Spatially Specific? A Multimodal 7-T and 3-T MR Imaging Study with Surface and Tract-based Analysis.

Purpose: To investigate in vivo the spatial specificity of the interdependence between intracortical and white matter (WM) pathologic changes as function of cortical depth and distance from the cortex in multiple sclerosis (MS), and their independent contribution to physical and cognitive disability.

Materials And Methods: This study was institutional review board-approved and participants gave written informed consent. In 34 MS patients and 17 age-matched control participants, 7-T quantitative T2* maps, 3-T T1-weighted anatomic images for cortical surface reconstruction, and 3-T diffusion tensor images (DTI) were obtained.

A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging.

We used a surface-based analysis of T2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T2* throughout the cortical width, to map in vivo the spatial distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (≤ 3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (≥ 4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T2* maps were registered to anatomical cortical surfaces for sampling T2* at 25%, 50% and 75% depth from the pial surface.

Reproducibility of T2 * mapping in the human cerebral cortex in vivo at 7 tesla MRI.

Background: To assess the test-retest reproducibility of cortical mapping of T2 * relaxation rates at 7 Tesla (T) MRI. T2 * maps have been used for studying cortical myelo-architecture patterns in vivo and for characterizing conditions associated with changes in iron and/or myelin concentration.

Methods: T2 * maps were calculated from 7T multi-echo T2 *-weighted images acquired during separate scanning sessions on 8 healthy subjects.

Quantitative oxygen extraction fraction from 7-Tesla MRI phase: reproducibility and application in multiple sclerosis.

Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2*-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function.