INsIDER cohort
ImagiNg the Interplay between Axonal DamagE and Repair in Multiple Sclerosis
Advanced in-vivo and post-mortem MRI in MS
The INsIDER study is dedicated to advancing our understanding of the pathophysiology of multiple sclerosis (MS), a chronic disease of the central nervous system affecting over 2.3 million people worldwide. By focusing on advanced MRI measures of axonal and myelin damage and repair, INsIDER aims to uncover how these factors influence MS progression and disability. Additionally, the study explores genetic influences on these processes, seeking to identify genetic factors that may impact disease evolution. Using cutting-edge imaging techniques, the study compares pathological changes in individuals with early-stage active relapsing MS—who experience ongoing inflammation and acute axonal damage—with those living with non-active progressive MS, characterized by chronic neurodegeneration. Through innovative imaging analysis and validation with post-mortem data, INsIDER seeks to develop biomarkers for monitoring disease progression and evaluating future neuroprotective and regenerative therapies.
From: GAMER-MRI in Multiple Sclerosis Identifies the Diffusion-Based Microstructural Measures That Are Most Sensitive to Focal Damage: A Deep-Learning-Based Analysis and Clinico-Biological Validation read
MS lesions on FLAIR and diffusion measures. (A) FLAIR: MS lesions are hyperintense and indicated by red dashed boxes. (B) Red: lesions; Green: perilesional white matter tissue. (C) The isotropic compartment from MB. (D) The intra-axonal compartment from MB. (E) The neurite density index from NODDI. (F) The intra-axonal compartment from SMT-NODDI. (G) The intra-axonal compartment from MCMDI. (H) The intra-axonal compartment from NODDIDA. (I) The isotropic compartment from Ball and Stick. (J) The intra-axonal compartment from Ball and Stick.
From: Postmortem quantitative MRI disentangles histological lesion types in multiple sclerosis read
Examples of histopathological lesion types and their correspondent quantitative MRI (qMRI) (MTR, magnetization transfer ratio; MWF, myelin water fraction; QSM, quantitative susceptibility mapping; qT1, quantitative T1; FA, fractional anisotropy; RD, radial diffusivity). (C) Chronic active lesion, showing presence of activated microglia/macrophages at the edge; (D) Remyelinated lesion (shadow plaque), showing uniformly pale myelin stain across the whole lesion area.
- Prof. Dr. Cristina Granziera
- Dr. Alessandro Cagol
- Dr. Lester Melie-Garcia
- Dr. Mario Ocampo-Pineda
- Dr. Po-Jui Lu
- Dr. Matthias Weigel
- Dr. Dimitrios Gkotsoulias
- Dr. Gretel Sanabria-Diaz
- Dr. Xinjie Chen
- Sara Bosticardo
- Antonia Wenger
- Noa Bar Zohar
Advanced MRI Measures of Myelin and Axon Volume Identify Repair in Multiple Sclerosis.
Sanabria-Diaz G, Cagol A, Lu PJ, Barakovic M, Ocampo-Pineda M, Chen X, Weigel M, Ruberte E, Siebenborn NOS, Galbusera R, Schädelin S, Benkert P, Kuhle J, Kappos L, Melie-Garcia L, Granziera C.
Ann Neurol. 2024 Oct 10. doi: 10.1002/ana.27102. Epub ahead of print. PMID: 39390658. read
Quantifying Remyelination Using χ-Separation in White Matter and Cortical Multiple Sclerosis Lesions.
Müller J, Lu PJ, Cagol A, Ruberte E, Shin HG, Ocampo-Pineda M, Chen X, Tsagkas C, Barakovic M, Galbusera R, Weigel M, Schaedelin SA, Wang Y, Nguyen TD, Spincemaille P, Kappos L, Kuhle J, Lee J, Granziera C.
Neurology. 2024 Sep 24;103(6):e209604. doi: 10.1212/WNL.0000000000209604. Epub 2024 Aug 30. PMID: 39213476; PMCID: PMC11362958. read
Advanced Quantitative MRI Unveils Microstructural Thalamic Changes Reflecting Disease Progression in Multiple Sclerosis.
Cagol A, Ocampo-Pineda M, Lu PJ, Weigel M, Barakovic M, Melie-Garcia L, Chen X, Lutti A, Calabrese P, Kuhle J, Kappos L, Sormani MP, Granziera C.
Neurol Neuroimmunol Neuroinflamm. 2024 Nov;11(6):e200299. doi: 10.1212/NXI.0000000000200299. Epub 2024 Sep 13. PMID: 39270143; PMCID: PMC11409727. read
A novel imaging marker of cortical "cellularity" in multiple sclerosis patients.
Barakovic M, Weigel M, Cagol A, Schaedelin S, Galbusera R, Lu PJ, Chen X, Melie-Garcia L, Ocampo-Pineda M, Bahn E, Stadelmann C, Palombo M, Kappos L, Kuhle J, Magon S, Granziera C.
Sci Rep. 2024 Apr 29;14(1):9848. doi: 10.1038/s41598-024-60497-6. PMID: 38684744; PMCID: PMC11059177. read
Characteristics, Prevalence, and Clinical Relevance of Juxtacortical Paramagnetic Rims in Patients With Multiple Sclerosis.
Galbusera R, Bahn E, Weigel M, Cagol A, Lu PJ, Schaedelin SA, Franz J, Barakovic M, Rahmanzadeh R, Dechent P, Nair G, Brück W, Kuhle J, Kappos L, Stadelmann C, Granziera C.
Neurology. 2024 Feb 13;102(3):e207966. doi: 10.1212/WNL.0000000000207966. Epub 2023 Dec 28. Erratum in: Neurology. 2024 Mar 26;102(6):e209252. doi: 10.1212/WNL.0000000000209252. PMID: 38165297; PMCID: PMC11097762. read
Postmortem quantitative MRI disentangles histological lesion types in multiple sclerosis.
Galbusera R, Bahn E, Weigel M, Schaedelin S, Franz J, Lu PJ, Barakovic M, Melie-Garcia L, Dechent P, Lutti A, Sati P, Reich DS, Nair G, Brück W, Kappos L, Stadelmann C, Granziera C.
Brain Pathol. 2023 Nov;33(6):e13136. doi: 10.1111/bpa.13136. Epub 2022 Dec 8. PMID: 36480267; PMCID: PMC10580009. read
An investigation of the association between focal damage and global network properties in cognitively impaired and cognitively preserved patients with multiple sclerosis.
Wenger AL, Barakovic M, Bosticardo S, Schaedelin S, Daducci A, Schiavi S, Weigel M, Rahmanzadeh R, Lu PJ, Cagol A, Kappos L, Kuhle J, Calabrese P, Granziera C.
Front Neurosci. 2023 Feb 7;17:1007580. doi: 10.3389/fnins.2023.1007580. PMID: 36824214; PMCID: PMC9941549. read
Personalized maps of T1 relaxometry abnormalities provide correlates of disability in multiple sclerosis patients.
Chen X, Schädelin S, Lu PJ, Ocampo-Pineda M, Weigel M, Barakovic M, Ruberte E, Cagol A, Marechal B, Kober T, Kuhle J, Kappos L, Melie-Garcia L, Granziera C.
Neuroimage Clin. 2023;37:103349. doi: 10.1016/j.nicl.2023.103349. Epub 2023 Feb 13. PMID: 36801600; PMCID: PMC9958406. read
A New Advanced MRI Biomarker for Remyelinated Lesions in Multiple Sclerosis.
Rahmanzadeh R, Galbusera R, Lu PJ, Bahn E, Weigel M, Barakovic M, Franz J, Nguyen TD, Spincemaille P, Schiavi S, Daducci A, La Rosa F, Absinta M, Sati P, Bach Cuadra M, Radue EW, Leppert D, Kuhle J, Kappos L, Brück W, Reich DS, Stadelmann C, Wang Y, Granziera C.
Ann Neurol. 2022 Sep;92(3):486-502. doi: 10.1002/ana.26441. Epub 2022 Jul 13. PMID: 35713309; PMCID: PMC9527017. read
A comparative assessment of myelin-sensitive measures in multiple sclerosis patients and healthy subjects.
Rahmanzadeh R, Weigel M, Lu PJ, Melie-Garcia L, Nguyen TD, Cagol A, La Rosa F, Barakovic M, Lutti A, Wang Y, Bach Cuadra M, Radue EW, Gaetano L, Kappos L, Kuhle J, Magon S, Granziera C.
Neuroimage Clin. 2022;36:103177. doi: 10.1016/j.nicl.2022.103177. Epub 2022 Aug 30. PMID: 36067611; PMCID: PMC9468574. read
Chronic White Matter Inflammation and Serum Neurofilament Levels in Multiple Sclerosis.
Maggi P, Kuhle J, Schädelin S, van der Meer F, Weigel M, Galbusera R, Mathias A, Lu PJ, Rahmanzadeh R, Benkert P, La Rosa F, Bach Cuadra M, Sati P, Théaudin M, Pot C, van Pesch V, Leppert D, Stadelmann C, Kappos L, Du Pasquier R, Reich DS, Absinta M, Granziera C.
Neurology. 2021 Aug 10;97(6):e543-e553. doi: 10.1212/WNL.0000000000012326. Epub 2021 Jun 4. PMID: 34088875; PMCID: PMC8424501. read
Imaging multiple sclerosis pathology at 160 μm isotropic resolution by human whole-brain ex vivo magnetic resonance imaging at 3 T.
Weigel M, Dechent P, Galbusera R, Bahn E, Nair G, Lu PJ, Kappos L, Brück W, Stadelmann C, Granziera C.
Sci Rep. 2021 Jul 29;11(1):15491. doi: 10.1038/s41598-021-94891-1. PMID: 34326420; PMCID: PMC8322069. read
Myelin and axon pathology in multiple sclerosis assessed by myelin water and multi-shell diffusion imaging.
Rahmanzadeh R, Lu PJ, Barakovic M, Weigel M, Maggi P, Nguyen TD, Schiavi S, Daducci A, La Rosa F, Schaedelin S, Absinta M, Reich DS, Sati P, Wang Y, Bach Cuadra M, Radue EW, Kuhle J, Kappos L, Granziera C.
Brain. 2021 Jul 28;144(6):1684-1696. doi: 10.1093/brain/awab088. PMID: 33693571; PMCID: PMC8374972. read
GAMER-MRI in Multiple Sclerosis Identifies the Diffusion-Based Microstructural Measures That Are Most Sensitive to Focal Damage: A Deep-Learning-Based Analysis and Clinico-Biological Validation.
Lu PJ, Barakovic M, Weigel M, Rahmanzadeh R, Galbusera R, Schiavi S, Daducci A, La Rosa F, Bach Cuadra M, Sandkühler R, Kuhle J, Kappos L, Cattin P, Granziera C.
Front Neurosci. 2021 Apr 6;15:647535. doi: 10.3389/fnins.2021.647535. PMID: 33889069; PMCID: PMC8055933. read
GAMER MRI: Gated-attention mechanism ranking of multi-contrast MRI in brain pathology.
Lu PJ, Yoo Y, Rahmanzadeh R, Galbusera R, Weigel M, Ceccaldi P, Nguyen TD, Spincemaille P, Wang Y, Daducci A, La Rosa F, Bach Cuadra M, Sandkühler R, Nael K, Doshi A, Fayad ZA, Kuhle J, Kappos L, Odry B, Cattin P, Gibson E, Granziera C.
Neuroimage Clin. 2021;29:102522. doi: 10.1016/j.nicl.2020.102522. Epub 2020 Dec 3. PMID: 33360973; PMCID: PMC7773673. read
Automated Detection and Segmentation of Multiple Sclerosis Lesions Using Ultra-High-Field MP2RAGE.
Fartaria MJ, Sati P, Todea A, Radue EW, Rahmanzadeh R, OʼBrien K, Reich DS, Bach Cuadra M, Kober T, Granziera C.
Invest Radiol. 2019 Jun;54(6):356-364. doi: 10.1097/RLI.0000000000000551. PMID: 30829941; PMCID: PMC6499666. read
Advanced MRI in HIV
Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO)
The NAMACO study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up.
- Prof. Dr. Cristina Granziera
Metral, M., Nadin, I., Locatelli, I., Tarr, P. E., Calmy, A., Kovari, H., Brugger, P., Cusini, A., Gutbrod, K., Schmid, P., Schwind, M., Kunze, U., Di Benedetto, C., Pignatti, R., Du Pasquier, R., Darling, K., Cavassini, M., & Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study group, Swiss HIV Cohort Study (2020). How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well-treated HIV-positive population?. HIV medicine, 21(5), 342–348. https://doi.org/10.1111/hiv.12828
Métral, M., Darling, K., Locatelli, I., Nadin, I., Santos, G., Brugger, P., Kovari, H., Cusini, A., Gutbrod, K., Tarr, P. E., Calmy, A., Lecompte, T. D., Assal, F., Monsch, A., Kunze, U., Stoeckle, M., Schwind, M., Schmid, P., Pignatti, R., Di Benedetto, C., … Swiss HIV Cohort Study (2020). The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study: baseline participant profile. HIV medicine, 21(1), 30–42. https://doi.org/10.1111/hiv.12795
Jakeman, B., Scherrer, A. U., Darling, K. E. A., Damas, J., Bieler-Aeschlimann, M., Hasse, B., Schlosser, L., Hachfeld, A., Gutbrod, K., Tarr, P. E., Calmy, A., Assal, F., Kunze, U., Stoeckle, M., Schmid, P., Toller, G., Rossi, S., di Benedetto, C., du Pasquier, R., Cavassini, M., … NAMACO Study Group, a Swiss HIV Cohort Study (2022). Anticholinergic and Sedative Medications Are Associated With Neurocognitive Performance of Well Treated People With Human Immunodeficiency Virus. Open forum infectious diseases, 9(9), ofac457. https://doi.org/10.1093/ofid/ofac457