After a workshop in 2016 in Toronto on neuroprotection and repair,  a consensus was obtained. Conventional MRI, magnetization transfer ratio, diffusion tensor imaging, susceptibility weighted imaging, imaging of cortical lesions, MR spectroscopy, PET and advanced diffusion imaging were considered.

Jiwon Oh et al. Northamerican Imaging in Multiple Sclerosis (NAIMS). Neurology 2019, 92:519-533

There are no established markers of neuroprotection and repair in MS. Available techniques offer limited measures, and their choice depends on the clinical trial necessity. T1 hypointensity evolution over time is one measure of repair, given the established value of black holes as evidence of axonal damage. Thus the change from acute edema to black hole is one measure. Another is the centripetal pattern of contrast enhancement, denoting repair. MTR recovery over time is similar to contrast enhancement. Radial diffusity of DTI provides measures similar to T1 imaging. Myelin water imaging is useful to follow chronic white matter lesions. It provides one more measure of myelin damage to the evolution of contrast enhancement and T1 imaging. But its long sequence acquisition times may be a drawback in more widespread use for neuroprotection and repair.

Myelin loss is reflected in increased magnetic susceptibility, and may be adjunctive to T2 imaging. Although it also reflects iron deposition, its short acquisition and relative technical feasibility are attractive. Due to expense and technical difficulties, including availability of comercial radioligands, PET or PET/MRI are expected to be of experimental therapeutic utility in the future.

Repair of cortical lesions is na área of great interest as it is closely related to the clinical deficit. There are leukocortical, intracortical and subpial lesions. Double inversion recovery and phase sensitive inversion recovery can detect such lesions in all phases of multiple sclerosis. 7T magnets with T2 imaging may be the most sensitive because of small size and complex architecture of the lesions. Microglial-targeted PET may help this field in the future.

MR spectroscopy may be useful experimentally in the future. DTI assesses axon integrity but is of limited  use in MS presently. Imaging of specific regions is na área of interest. Thalamic volumes correlated with physical and cognitive disability. Hippocampal atrophy is related to memory and depression, and longitudinal evaluations may become a mesure of neuroprotection. Optical coherence tomography i salso useful longitudinally, the caveat being that there are many machines available, and they may measure different things.

There are strong correlations of spinal cord volume to clinical disability. Upper spinal cord trans-sectional area has been used to define a 2% loss per year, faster in progressive multiple sclerosis. DTI, MTI and MWI have shown a robust correlation with disability. Leptomeningeal inflammation has been show non FLAIR MRI 10 minutes after gadolinum injection, not only in MS but also in other neuro-inflammatory diseases. It may reflect primary progressive or more severe disease.

Neuroprotection and repair should be evaluated in separate studies, with different experimental strategies.

Dr Paulo Bittencourt

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