Imagine how exciting it must have been. It is 1981 and you are using cutting-edge magnetic resonance imaging (MRI) technology to scan the brain of a person with multiple sclerosis. For the very first time, you are able to peer into their brain and actually SEE the damage firsthand. Game changer.
Some 35 years later, MRI is the primary tool for diagnosing MS and for assessing its progression. However, while MRI is the best tool available, the data we get from scans doesn’t correlate well with a person’s MS symptoms and/or levels of disability. It seems simple: more damage should equal worse symptoms and more disability. In practice, however, there’s a weak correlation between what is seen by MRI and the symptoms and severity of MS. This disconnect limits the use of MRI for assessing how well an individual is responding to disease-modifying therapies (DMTs). This lack of a clinical tool for determining DMT effectiveness motivates one of our core research goals here at Discovery MS: looking for signatures of MS in blood and urine.
Blood- or urine-based tests are preferable to MRI due to increased ease, reduced cost, and shorting testing intervals, but until these tests are developed what CAN clinicians determine from MRI scans?
There are a couple MRI methods that, used in concert, help clinicians monitor their patients. T2-weighted MRI is used to assess the total number of lesions in a patient’s brain and spinal cord; this gives an estimate of the overall disease burden. T1-weighted MRI reveals older, more permanent sites of damage, while addition of the contrast agent gadolinium shows areas of active inflammation.
As discussed above, however, these MRI scans don’t match up well with clinical assessments of MS. These recent papers provide an overview of this so-called clinico-radiological paradox (that is, the lack of clear correlation between what a person with MS experiences and what a clinician sees looking an MRI scan).
Some factors that may contribute to the paradox:
- MRI scans are compared to clinical assessments (such as the Expanded Disability Status Scale (EDSS)), but the clinical assessments themselves might not be doing a good job indicating where an individual is in their disease course.
- Spinal cord lesions haven’t been consistently included in studies, likely skewing assessments of true lesion loads.
- Individuals appear to have different levels of cognitive resilience (that is, how well they compensate for damage). For example, younger brains typically have more adaptability. Relatedly, damage in some brain regions appears to be better compensated for than damage in other regions.
- Brain tissue that appears normal and healthy via MRI may not in fact be completely unaffected by MS, potentially causing an underestimation of true damage.
The promise seen in those early MRI images of MS lesions still exists, however. Researchers are working to overcome these confounders with improved techniques and technologies. Add in new blood- and urine-based tests and the future of clinical management of MS is bright.
Cover image credit: Sayuri Kimbell, watercolor. Part of a series based on open-source neurological images from the Department of Physiology at the University of Wisconsin-Madison, Michigan State University, and the National Museum of Health and Medicine.