Analysis of Advanced MRI Metrics in Radiologically Isolated Syndrome Compared to Multiple Sclerosis Patrick
1Donald
1 Tierney
and Barbara Zucker School of Medicine at Hofstra/Northwell
Background - Radiologically Isolated Syndrome (RIS) is the presentation of central nervous system (CNS) lesions on imaging that are suggestive of MS without the anticipated deficits.1 - Multiple Sclerosis (MS) is a neurological disease characterized by autoimmune demyelination of CNS neurons.5 - A subset of RIS patients develop MS.5 - RIS patients that eventually develop MS cannot yet be distinguished from RIS patients that will not. - The ability to identify that an RIS patient will develop MS enables proactive MS therapy to prevent irreversible disease progression. - RIS and MS patients are currently differentiated via clinical presence (MS) or absence (RIS) of neurologic symptoms.5 - MS can present with a large variety of symptoms based on the location of neuroinflammation, including numbness, paresthesia, weakness, loss of coordination, fatigue, vision issues, and many more. - Advanced MRI metrics, such as brain atrophy and T1/T2 ratio, may be able to categorize demyelinating disease.3 - Brain atrophy is a measure of the total brain volume.2 - T1/T2 ratio is a novel metric hypothesized to indicate the degree of demyelination or dendritic loss and is somewhat correlated with disability metrics.4
and Asaff Harel,
Example MRIs (a)
(b)
- We hypothesize that RIS patients will score better on T1/T2 ratio measurements and have less brain atrophy compared to MS patients due to less severe tissue damage in RIS, which will enable differentiation of the two diseases.
Methods - 9 RIS patients with volumetric T1 and T2 MRIs were identified. - The following inclusion process was completed to identify MS patients (pts.) and match them to RIS patients for MRI analysis. MRI at MRI with current Dr. Harel’s 18-65 Northwell MS protocol MS pts. years old radiology site Volumetric T1 and T2 MRIs available
Figure 1 – Representative volumetric T1-weighted brain MRIs of a patient with RIS (a) and MS (b). The lesions (red arrows) appear similarly across both patients and cannot be discerned by T1-w MRI alone.
(a)
(b)
Analyze MRIs for lesion volume
Match MS pt. sex with RIS pt. sex
Match MS pts. to RIS pts. by lesion volume
MS pt. +/6 years of RIS pt.
Analyze MRIs for T1/T2 ratios & brain atrophy
Match MS pts. to RIS pts. Compare matched T1/T2 ratios & brain atrophy via two-sample t-tests
Discussion - Statistical difference in T1/T2 ratios and brain atrophy of RIS and MS patients will increase validity for this MRI metric for differentiating these demyelinating diseases. - Future direction: Compare T1/T2 ratios and brain atrophy of MRIs in RIS patients that developed MS with those of RIS patients that have not developed MS to differentiate the subtypes of RIS before disease progression to MS.
Resources
Study Aim & Hypothesis - This study aims to determine if RIS patients score differently with regard to T1/T2 ratios and brain atrophy as compared to MS patients, matched for age, sex, and MS lesion volumes.
1 MD
Figure 7: Independent CRISPR knockout of CDK4 or CDK6 does not cause dropout in most breast cancer cell lines studied.
Figure 2 - Example T2-weighted brain MRI with left hemispheric lesions outlined in red (a) and software 3 generated T1/T2 brain MRI (b) in a patient with MS.
(1) Azevedo CJ, Overton E, Khadka S, Buckley J, Liu S, et al. (2015) Early CNS neurodegeneration in radiologically isolated syndrome. Neurol Neuroimmunol Neuroinflamm 2(3). (2) Ghione E, Bergsland N, Dwyer MG, Hagemeier J, Jakimovski D, et al. (2019) Aging and Brain Atrophy in Multiple Sclerosis. J Neuroimaging 29(4): 527-535. (3) Pareto D, Garcia-Vidal A, Alberich M, Auger C, Montalban X, et al. (2020) Ratio of T1Weighted to T2-Weighted Signal Intensity as a Measure of Tissue Integrity… Am J Neuroradiol. https://doi.org/10.3174/ajnr.A6481. (4) Righart R, Biberacher V, Jonkman LE, Klaver R, Schmidt P, et al. (2017) Cortical pathology in multiple sclerosis detected by the T1/T2-weighted ratio from routine magnetic resonance imaging. Ann Neurol 82(4): 519-529. (5) Yamout B, Al Khawajah M. (2017) Radiologically isolated syndrome and multiple sclerosis. Mult Scler Relat Disord 17: 234-237.