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

ABSTRACT: 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.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. Seventeen age-matched healthy participants served as controls.ICL were predominantly located in sulci of frontal, parietal, and cingulate cortex; LCL distribution was more random. In MS, T2* was higher in both ICL and LCL, indicating myelin and iron loss, than in NACGM (p < 0.00003) irrespective of CL subtype and MS phenotype. T2* was increased in perilesional cortex, tapering away from CL toward NACGM, the wider changes being for LCL in SPMS. NACGM T2* was higher in SPMS relative to RRMS (p = 0.006) and healthy cortex (p = 0.02).CL had the same degree of demyelination and iron loss regardless of lesion subtype and disease stage. Cortical damage expanded beyond visible CL, close to lesions in RRMS, and more diffusely in SPMS. Evaluation of NACGM integrity, beyond focal CL, could represent a surrogate marker of MS progression.

SUBMITTER: Louapre C

PROVIDER: S-EPMC4653110 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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

Louapre Céline C Govindarajan Sindhuja T ST Giannì Costanza C Langkammer Christian C Sloane Jacob A JA Kinkel Revere P RP Mainero Caterina C

Neurology 20151014 19

<h4>Objectives</h4>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.<h4>Methods</h4>Patients with MS (18 RRMS, 11 SPMS), showin ...[more]

PMID: 26468411

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Project description:Highly specialized cells are fundamental for proper functioning of complex organs. Variations in cell-type specific gene expression and protein composition have been linked to a variety of diseases. Although single cell technologies have emerged as valuable tools to address this cellular heterogeneity, a majority of these workflows lack sufficient in situ resolution for functional classification of cells and are associated with extremely long analysis time, especially when it comes to in situ proteomics. In addition, lack of understanding of single cell dynamics within their native environment limits our ability to explore the altered physiology in disease development. This limitation is particularly relevant in the mammalian brain, where different cell types perform unique functions and exhibit varying sensitivities to insults. The hippocampus, a brain region crucial for learning and memory, is of particular interest due to its obvious involvement in various neurological disorders. Here, we present a combination of experimental and data integration approaches for investigation of cellular heterogeneity and functional disposition within the mouse brain hippocampus using MALDI Imaging mass spectrometry (MALDI-IMS) and shotgun proteomics (LC-MS/MS) coupled with laser-capture microdissection (LCM) along with spatial transcriptomics. Within the dentate gyrus granule cells we identified two proteomically distinct cellular subpopulations that are characterized by a substantial number of discriminative proteins. These cellular clusters contribute to the overall functionality of the dentate gyrus by regulating redox homeostasis, mitochondrial organization, RNA processing, and microtubule organization. Importantly, most of the identified proteins matched their transcripts, verifying the in situ protein identification and supporting their functional analyses. By combining high-throughput spatial proteomics with transcriptomics, our approach enables reliable near-single-cell scale identification of proteins and profiling of inter-cellular heterogeneity within similar cell-types in tissues. This methodology has the potential to be applied to different biological conditions and tissues, providing a deeper understanding of cellular subpopulations in situ.

Dataset Information

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

Publications

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

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