Imaging neuroinflammation in multiple sclerosis using TSPO-PET

Abstract

Conventional MR imaging (MRI) techniques form the cornerstone of multiple sclerosis (MS) diagnostics and clinical follow-up today. MRI is sensitive in demonstrating focal inflammatory lesions and diffuse atrophy. However, especially in progressive MS, there is increasingly widespread diffuse pathology also outside the plaques, often related to microglial activation and neurodegeneration. This cannot be detected using conventional MRI. Positron emission tomography (PET) imaging using 18-kDa translocator protein (TSPO) binding radioligands has recently shown promise as a tool to detect this diffuse pathology in vivo, and for the first time allows one to follow its development longitudinally. It is becoming evident that the more advanced the MS disease is, the more pronounced is microglial activation. PET imaging allows the detection of MS-related pathology at molecular level in vivo. It has potential to enable measurement of effects of new disease-modifying drugs aimed at reducing neurodegeneration and neuroinflammation. PET imaging could thus be included in the design of future clinical trials of progressive MS. There are still technical issues related to the quality of TSPO radioligands and post-processing methodology, and comparison of studies from different PET centres is challenging. In this review, we summarise the main evidence supporting the use of TSPO-PET as a tool to explore the diffuse inflammation in MS.

Keywords: Imaging; Microglia; Multiple sclerosis; Progressive disease.

Fig. 1

In vivo differentiation of chronic T1 lesions using TSPO-PET. Left image a T1-weighted MRI image with two similar-looking (non-gadolinium-enhancing) T1 black holes. TSPO-PET (on the right) shows that in the upper lesion there is microglial activation, confirming this lesion to be a chronic active lesion, whereas in the lower lesion there is no radioligand uptake, confirming this lesion to be a chronic inactive lesion

Fig. 2

PK11195 binding patterns in MS. A schematic drawing of PK11195 binding patterns in T1 lesional (centre of the circle) and perilesional (yellow rim of the circle) WM and NAWM in RRMS compared to SPMS. Red dots PK11195 binding as a sign of microglial activation. RRMS = relapsing–remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis; Gd + = gadolinium positive; Gd− = gadolinium negative; NAWM = normal appearing white matter