Dr Alberto Calvi

2019 Entry Clinical Fellowship

Slowly evolving lesions in multiple sclerosis: a new imaging marker for progression

It remains unknown which multiple sclerosis (MS) disease process is the main cause of progressive disability. Brain lesions have been thought to play a relatively minor role in progressive MS, in contrast to the relapsing-remitting forms of MS where lesions are the main cause of symptoms. However, brain biopsies from people with MS have shown substantial chronic activity in lesions, with ongoing inflammation and neurodegeneration.

During my fellowship, I implemented a new way to identify slowly expanding lesions (SELs) on brain magnetic resonance imaging (MRI), as a surrogate marker for the chronic lesion activity.

My project objective was to explore the relationship between SELs and clinical measures, in order to understand their contribution to disability in MS. I analysed 345 scans from a research trial in secondary-progressive MS and 150 scans from an international observational cohort of relapsing-remitting MS patients. SELs constitute up to ~36% of the total lesion volume, with a predominance in SPMS compared to RRMS, in line with findings from pathological studies. SELs demonstrated more structural damage compared to other lesion types, as measured by reductions of the magnetization transfer ratio (MTR, a marker of tissue integrity), and a greater volume of SELs correlated with higher percentage brain volume reduction (a marker of neurodegeneration). SELs were also independently associated with increasing physical and cognitive disability scores. We conclude that SELs are a new and clinically relevant MRI measure that may be of interest in future progressive MS treatment trials. 


Slowly expanding lesions relate to persisting black-holes and clinical outcomes in relapse-onset multiple sclerosis

Calvi A, Tur C, Chard D, Stutters J, Ciccarelli O, Cortese R, Battaglini M, Pietroboni A, De Riz M, Galimberti D, Scarpini E, De Stefano N, Prados F, Barkhof F

NeuroImage: Clinical 2022;35:103048. doi: 10.1016/j.nicl.2022.103048


Association of Slowly Expanding Lesions on MRI With Disability in People With Secondary Progressive Multiple Sclerosis

Calvi A, Carrasco FP, Tur C, Chard DT,et al.

Neurology 2022 Apr 26;98(17):e1783-e1793, DOI: 10.1212/WNL.0000000000200144


In vivo imaging of chronic active lesions in multiple sclerosis

Calvi A, Haider L, Prados F, Tur C, Chard D, Barkhof F

Multiple Sclerosis Journal 2020 Sep 23. doi: 10.1177/1352458520958589


Reduced neurite density in the brain and cervical spinal cord in relapsing-remitting multiple sclerosis: A NODDI study

Collorone S, Cawley N, Grussu F, Prados F, Tona F, Calvi A, Kanber B, Schneider T, Kipp L, Zhang H, Alexander DC, Thompson AJ, Toosy A, Wheeler-Kingshott CAG, Ciccarelli O

Mult Scler.

2019 Nov 4. doi: 10.1177/1352458519885107