画像バイオマーカーの重要性

抄録

Brain images can provide effective information for the four steps of biomarkers : susceptibility/risk, diagnostic, monitoring, and prognostic. The DAT–SPECT and MRI are particularly useful for capturing structural and functional abnormalities of Parkinson disease (PD) and parkinsonian syndromes.

Although DAT–SPECT is often used primarily as a diagnostic biomarker, it may also be used as a monitoring or prognostic biomarker. Properly performed DAT–SPECT is evaluated visually and using specific binding ratio (SBR). Visually, there are several patterns of decreased uptake, but differentiation is difficult due to low disease characteristics. Therefore, SBR is used for quantification, and even if the entire striatum is used or divided into the caudate nucleus and putamen, the sensitivity and specificity for differentiating degenerative diseases is approximately 90%. As a monitoring biomarker, there have been reports on the correlation between SBR and motor symptoms, the risk of levodopa–induced dyskinesia (LID), cognitive function, depression, and constipation.

Conventional MRI is mainly used as a diagnostic biomarker, but by capturing brain microstructural alterations using diffusion MRI technology (dMRI), it can be used as a biomarker that captures the entire course of PD over several decades, including the prodromal phase.

The dMRI defines a water diffusion model in the smallest unit of voxels and analyzes structural continuity and clusters. There are models such as DTI, NODDI, FWI, and FBA, but the most specific technology for PD has not been established. However, the brain microstructure is the underlying cause of differences in clinical symptoms of PD, such as cognitive dysfunction, psychiatric symptoms, LID, impulse control disorder, use of MAO–B inhibitors, differences between tremor dominant type and akinesia dominant type, and the presence of GBA mutations.

Alterations in brain microstructure are closely related to clinical symptoms, and even in the same degenerative disease, clinical symptoms are thought to change depending on the extent and region of brain degeneration. We also believe that by combining diffusion MRI and DAT–SPECT, we can provide useful information for future personalized medical care as a biomarker for PD from pre–onset to advanced stages.