Cyclooxygenase-1 and cyclooxygenase-2 densities measured using positron emission tomography are not altered in the brains of individuals with stable multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system that involves immune-mediated demyelination and axonal degeneration. Clinical imaging techniques play a critical role in diagnosing and assessing the prognosis of MS. Magnetic resonance imaging has been most frequently used to visualize demyelination and detect acute and chronic active lesions, which are key indicators of clinical course of illness. Previous research has also highlighted the effectiveness of translocator protein 18-kDa (TSPO) positron emission tomography (PET) imaging for identifying chronic active lesions and progressive pathology. Building on this work, the present study used PET imaging to explore the role of cyclooxygenase-1 and -2 (COX-1 and COX-2)-key enzymes involved in neuroinflammation-in individuals with MS. Five participants with MS were recruited, and lesions were identified using 7 Tesla MRI. No significant differences in COX radioligand binding were observed in the co-registered PET images between lesioned areas and normal-appearing brain tissues, nor between individuals with MS and healthy volunteers. The negative findings underscore the complexity of MS pathology and raise several important considerations for planning future studies using COX PET for imaging in MS.

Keywords: Cyclooxygenase; chronic lesion; multiple sclerosis; novel radiotracer; positron emission tomography.

Figure 1.

Brain images and lesions of the five participants with multiple sclerosis (MS). The lesions are not visible on the [¹¹C]PS13 or [¹¹C]MC1 positron emission tomography (PET) scans. First column: magnetic resonance imaging (MRI) fluid attenuated inversion recovery (FLAIR) images. Second column: the MRI T₁w images. Third column: the MRI T₁w images post-gadoteridol injection. Fourth column: an overlay of [¹¹C]PS13 PET images (averaged from 60 to 90 minutes) on the T₁w image. Fifth column: an overlay of [¹¹C]MC1 PET images (averaged from 60 to 90 minutes) on the T₁w image. Sixth column: the skull-stripped MRI quantitative susceptibility mapping (QSM) images. Paramagnetic rim lesions are noted with yellow arrows; other lesions are noted with red arrows. Each row corresponds to a different participant with MS.

Figure 2.

Comparison of [¹¹C]PS13 and [¹¹C]MC1 standardized uptake value ratio (SUVR) in lesions and contralateral normal-appearing tissue. [¹¹C]PS13 SUVR (a) and [¹¹C]MC1 SUVR (b) at baseline and [¹¹C]PS13 SUVR (c) and [¹¹C]MC1 SUVR (d) changes after blocking were comparable between the ipsilateral lesion area and the contralateral normal-appearing tissue.

Figure 3.

Comparison of [¹¹C]PS13 and [¹¹C]MC1 standardized uptake value ratios (SUVRs) between participants with multiple sclerosis (MS) and healthy volunteers (HVs). [¹¹C]PS13 SUVRs (a) and [¹¹C]MC1 SUVRs (b) in both the whole brain and specific brain regions did not differ significantly between MS participants and HVs. WB: whole brain grey matter; FC: frontal cortex; CIN: cingulate cortex; HP: hippocampus; AMY: amygdala; TC: temporal cortex; PC: parietal cortex; OC: occipital cortex; STR: striatum; THA: thalamus; CC: corpus callosum; INS: insular cortex; WM: cerebrum white matter.