Increased diffusivity in acute multiple sclerosis lesions predicts risk of black hole

Abstract

Objective: Diffusion tensor imaging (DTI) quantifies Brownian motion of water within tissue. Inflammation leads to tissue injury, resulting in increased diffusivity and decreased directionality. We hypothesize that DTI can quantify the damage within acute multiple sclerosis (MS) white matter lesions to predict gadolinium (Gd)-enhancing lesions that will persist 12 months later as T1 hypointensities.Methods: A cohort of 22 individuals underwent 7 brain MRI scans over 15 months. DTI parameters were temporally quantified within regions of Gd enhancement. Comparison to the homologous region in the hemisphere contralateral to the Gd-enhancing lesion was also performed to standardize individual lesion DTI parameters. Results:After classifying each Gd-enhancing region as to black hole outcome, radial diffusivity, mean diffusivity, and fractional anisotropy, along with their standardized values, were significantly altered for persistent black holes (PBHs), and remained elevated throughout the study. A Gd-enhancing region with a 40% elevation in radial diffusivity had a 5.4-fold (95% confidence interval [CI]: 2.1, 13.8) increased risk of becoming a PBH, with 70% (95% CI: 51%, 85%) sensitivity and 69% (95% CI: 57%, 80%) specificity. A model of radial diffusivity, with volume and length of Gd enhancement, was associated with a risk of becoming a PBH of 5.0 (95% CI: 2.6, 9.9). Altered DTI parameters displayed a dose relationship to duration of black hole persistence. Conclusions:Elevated radial diffusivity during gadolinium enhancement was associated with increased risk for development of a persistent black hole, a surrogate of severe demyelination and axonal injury. An elevated radial diffusivity within active multiple sclerosis lesions may be indicative of more severe tissue injury. Neurology ® 2010;74:1694 -1701 GLOSSARY ABH ϭ acute black hole; CBH ϭ chronic black hole; DTI ϭ diffusion tensor imaging; FLAIR ϭ fluid-attenuated inversion recovery; Gd ϭ gadolinium; MS ϭ multiple sclerosis; NAWM ϭ normal-appearing white matter; PBH ϭ persistent black hole; RD ϭ radial diffusivity; ROI ϭ region of interest; T1H ϭ chronic T1 hypointensity; TBH ϭ transient black hole.

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

“…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). [61][62][63] Newer MRI techniques, currently experimental in nature, are giving us a glimpse of what these modalities may tell us in the future about MRI brain pathology and clinical relevance.…”

Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema

“…Although decreased DTI-derived fractional anisotropic (FA) has been demonstrated to reflect myelin damage in multiple sclerosis (MS) (Schmierer et al, 2007), it is not a marker specific to myelin damage since other pathological components may also contribute to diffusion anisotropy change (Werring et al, 1999, Assaf et al, 2002). For example, inflammation associated vasogenic edema has been recognized to increase apparent diffusion coefficient (ADC) and underestimate the DTI-derived FA of fiber tracts (Pasternak et al, 2009, Naismith et al, 2010). Increased cellularity has been demonstrated to decrease DTI-derived ADC (Anderson et al, 2000).…”

Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 2—Surveillance for Treatment Complications and Disease Progression

“…92 In one in vivo study of MS, radial diffusivity appeared to provide the closest correlation with tissue integrity. 93 A multicenter validation study indicated that fractional anisotropy was the most comparable DTI measure across centers and endorsed its use in multicenter clinical trials. 94 Werring et al 95 demonstrated that a steady and moderate increase of the apparent diffusion coefficient can precede the development of new plaques by 6 -8 months, and they indicated that structural changes in prelesion normal-appearing white matter occur before inflammation and BBB leakage.…”