Accumulation of hypointense lesions ("black holes") on T ₁ spin-echo MRI correlates with disease progression in multiple sclerosis

Abstract

MRI findings are increasingly used as outcome measures in therapeutic trials in MS. The discrepancy between the extent of the lesions on conventional T2 images and the clinical condition of the patient is one of the problems encountered in such studies. This clinical-radiological paradox prevents the use of MRI data as surrogate markers of disability in MS. A recent pilot study suggested a relationship between hypointense lesions on T1 MRI and disability. To assess in more detail the correlation of changes in hypointense lesion load on T1-weighted spin-echo MR images ("black holes") with changes in disability in MS, we studied 46 patients with clinically definite MS at baseline and after a median follow-up of 40 months. There was a significant correlation between baseline disability and hypointense lesion load (Spearman rank correlation coefficient [SRCC] = 0.46, p = 0.001). In secondary progressive patients, the rate of accumulation of these "black holes" was significantly related to progression rate (SRCC = 0.81, p < 0.0001). We speculate that the appearance of hypointense lesions is the MRI equivalent of a failure of remission. Overall, T1 lesion load measurements correlated better with clinical assessments than T2 lesion load measurements. Quantification of hypointense lesion load on T1-weighted spin-echo MRI helps to resolve the clinical-radiological paradox between disability and MRI and has the potential to be a surrogate marker of disability in MS.

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

“…In contrast to T2 lesions, it has been reported that T1 hypointensities or black holes, particularly chronic black holes, correlate better with physical disability, tissue injury including severe demyelination and axonal injury, and brain atrophy. 42,45,[50][51][52] Recent evidence suggests that the size and duration of enhancing lesions, increased radial diffusion on diffusion tensor imaging (DTI), and lower magnetic transfer ratio (MTR) predispose to chronic black holes, matrix destruction, and brain atrophy. 34,45,46,[53][54][55][56][57][58][59][60] Some controversy remains as to the degree of inflammation found in MS cortical lesions as compared with white matter lesions on histologic examination, but these differences are probably related to stage of MS (early vs. chronic disease).…”

Time-Series Modeling of Multiple Sclerosis Disease Activity: A Promising Window on Disease Progression and Repair Potential?

“…14 T 1 hypointense lesions (considered a hallmark of permanent matrix destruction) were more commonly observed in SPMS than RRMS, 15 and more new lesions remained T 1 hypointense in SPMS. 14,16 One of the few long-term studies involving MRI variables noted that MRI lesions in the first 2 years were associated with clinical outcome 13 years later, but not at the 2-year mark.…”

Recent progress in the diagnosis and treatment of multiple sclerosis

“…Similarly, the presence of cerebellar ataxia in MS is correlated with the presence of cerebellar atrophy on MRI and with a reduction in the concentration of the neuronal marker, Nacetylaspartate, in the cerebellar white matter on MRS. 14 Furthermore, a serial MRI study has revealed that progressive cerebral atrophy correlates with sustained deterioration in the EDSS score. 15 There is also a significant correlation between the progression of disability in secondary progressive MS and the accumulation of hypointense T1 lesions (black holes), 16 which represent regions of substantial axonal loss. 17 It has been hypothesized that the clinical course of MS may vary according to which antigens in the CNS are being targeted by the immune system.…”