Diffusion basis spectrum imaging and diffusion tensor imaging predict persistent black hole formation in multiple sclerosis

Background and objectives: Diffusion basis spectrum imaging (DBSI) extracts multiple anisotropic and isotropic diffusion tensors, providing greater histopathologic specificity than diffusion tensor imaging (DTI). Persistent black holes (PBH) represent areas of severe tissue damage in multiple sclerosis (MS), and a high PBH burden is associated with worse MS disability. This study evaluated the ability of DBSI and DTI to predict which acute contrast-enhancing lesions (CELs) would persist as T₁ hypointensities (i.e. PBHs) 12 months later. We expected that a higher radial diffusivity (RD), representing demyelination, and higher DBSI-derived isotropic non-restricted fraction, representing edema and increased extracellular space, of the acute CEL would increase the likelihood of future PBH development. Methods: In this prospective cohort study, relapsing MS patients with ≥1 CEL(s) underwent monthly MRI scans for 4 to 6 months until gadolinium resolution. DBSI and DTI metrics were quantified when the CEL was most conspicuous during the monthly scans. To determine whether the CEL became a PBH, a follow-up MRI was performed at least 12 months after the final monthly scan. Results: The cohort included 20 MS participants (median age 33 years; 13 women) with 164 CELs. Of these, 59 (36 %) CELs evolved into PBHs. At Gd-max, DTI RD and AD of all CELs increased, and both metrics were significantly elevated for CELs which became PBHs, as compared to non-black holes (NBHs). DTI RD above 0.74 conferred an odds ratio (OR) of 7.76 (CI 3.77–15.98) for a CEL becoming a PBH (AUC 0.80, CI 0.73–0.87); DTI axial diffusivity (AD) above 1.22 conferred an OR of 7.32 (CI 3.38–15.86) for becoming a PBH (AUC 0.75, CI 0.66–0.83). DBSI RD and AD did not predict PBH development in a multivariable model. At Gd-max, DBSI restricted fraction decreased and DBSI non-restricted fraction increased in all CELs, and both metrics were significantly different for CELs which became PBHs, as compared to NBHs. A CEL with a DBSI non-restricted fraction above 0.45 had an OR of 4.77 (CI 2.35–9.66) for becoming a PBH (AUC 0.74, CI 0.66–0.81); a CEL with a DBSI restricted fraction below 0.07 had an OR of 9.58 (CI 4.59–20.02) for becoming a PBH (AUC 0.80, 0.72–0.87). Conclusion: Our findings suggest that greater degree of edema/extracellular space in a CEL is a predictor of tissue destruction, as evidenced by PBH evolution.