Figure 3. Summary of the MRI markers to identify disability progression and SPMS evolution during the disease course.

In both PPMS and SPMS MRI markers are A) increase of number or volume of brain T1-hypointense lesions.⁵⁴ Baseline and 1-year follow-up T1-weighted sequences of a PPMS patient. At follow-up, three new T1-hypointense lesions are visible (orange arrowheads); B) cortical lesion number and volume.⁵⁵ A DIR sequence showing three cortical lesions (orange arrowheads) from a PPMS patient is shown; C) baseline thalamic (blue) and cortical (green) damage and atrophy.⁵¹ Quantification on MT imaging (left) and 3D T1-weighted sequences (right); D) rate of whole brain, brain GM (green) and deep GM (blue) atrophy.⁶⁹ Quantification on a 3D T1-weighted sequence using SIENA and FIRST software. In SPMS also E) brain T2-hyperintense lesion volume (LV) (T2-FLAIR sequence)⁵¹ and F) conversion of DAWM (orange arrowheads and dotted orange areas) into focal WM lesions (T2-FLAIR sequence).⁶⁵ Further promising MRI markers are G) the presence of ≥4 rim positive lesions on susceptibility-based MRI (orange arrowheads)⁸⁵ and H) presence of subpial demyelination (orange arrowheads) on T2* sequence at ultra-high field (i.e., 7 Tesla).¹⁰¹ Figure 3H is adapted from Kilsdonk et al.¹⁰¹ with permission. Relevant OR, HRs or global T2 LV that were suggested to identify disability progression and SPMS evolution during the disease course and that were derived from the literature and discussed in the text are also reported.

Abbreviations: cm=centimeter; DAWM=dirty-appearing white matter; DIR=double inversion recovery; FLAIR=fluid-attenuated inversion recovery; GM=gray matter; LV=lesion volume; MRI=magnetic resonance imaging; MS=multiple sclerosis; MT=magnetization transfer; MTR=magnetization transfer ratio; OR=odds ratio; PP=primary progressive; SP=secondary progressive; y=year; WM=white matter.