Advancements in PET Imaging for Diagnostics and Therapeutic Targets in Cerebral Small Vessel Disease

Introduction: 1. Review the current application of positron emission tomography (PET) in the assessment of cerebral small vessel disease (SVD). 2. Evaluate the contribution of PET in improving the diagnosis and treatment of cerebrovascular diseases. 3. Discuss possible directions for future studies to expand the application of PET in cerebrovascular diseases.

Methods: Original studies and reviews involving PET or alternate imaging modalities related to cerebrovascular diseases were acquired via PubMed and Google Scholar search engines. Studies fitting this criterion were evaluated and selected based on quality measures such as study design, sample size, significance of findings, and the rationale behind their statistical procedures. Selected studies were then assessed in order to understand the role of PET imaging in cerebral SVD management.

Results: PET is widely utilized in combination with magnetic resonance imaging (MRI) and computed tomography (CT) for imaging of cerebrovascular diseases. For cerebral small vessel disease, specifically, the mitochondrial 18 kDa translocator protein [¹¹C]PK11195 PET/MRI hybrid imaging was utilized to understand the underlying pathogenesis of the disease. The literature reports that PET has been used to measure microglial activation and neuroinflammation, while dynamic contrast enhanced MRI can detect abnormal permeability of the blood-brain barrier. These imaging results provide evidence that microglial activation and blood-brain barrier permeability are separate pathogenic pathways and, thus, independent therapeutic targets in cerebral SVD. Additional evidence suggests that PET can reveal metabolic information that supplement’s CT/MRI vascular cognitive impairment findings, such as microhemorrhage in cerebral SVD. Because CT and MRI can only determine morphological lesions, the functional consequences of pathological changes must be evaluated through PET. Similarly, PET/CT imaging with FDG and [18F]sodium fluoride (NaF) was necessary in characterizing plaque vulnerability and formation in atherosclerosis; CT detected plaque morphology, while PET revealed metabolic changes and micro-calcification (i.e., macrophage activities, inflammation, and molecular calcification). The PET/MRI combination is reportedly used for the assessment of atherosclerosis. Research indicates that it elucidates links between atherosclerosis and neurological diseases, which furthers our understanding of atherogenesis and the evaluation of potential drug targets. Recent PET studies have focused on the development of less invasive methods, such as phase-contrast PET for noninvasive quantification of cerebral blood flow. Given the sizable clinical application of PET, these new developments could greatly aid in the assessment of cerebrovascular diseases.

Conclusions: Using PET imaging to assess cerebral SVD provides valuable information about disease pathogenesis, progression, and potential therapeutic targets with focus on molecular aspects of these disorders. Existing literature regarding cerebrovascular diseases, such as cerebral SVD and vasculitis, has demonstrated the value of PET imaging in disease management. Future studies should consider exploring the integration of PET imaging in other cerebrovascular diseases, especially with the development of noninvasive PET procedures, which could add greater value to the application of PET within clinical settings.