Neuroimaging with PET/CT in chronic traumatic encephalopathy: what nuclear medicine can do to move the field forward

ABSTRACT

Introduction

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative syndrome, caused by single or repeated traumatic brain injuries. Since a few years ago, post mortem examination represented the only effective method to diagnose CTE through the detection of its peculiar neuropathological features (i.e. tau protein aggregates) at a macroscopic and microscopic level. Several efforts have been made to develop radiopharmaceuticals characterized by high affinity for tau aggregates, suitable for imaging through positron emission computed tomography (Tau-PET).

Areas covered

The various radiopharmaceuticals utilized for the molecular imaging of CTE through Tau-PET are covered, with specific reference to their applications in clinical practice. Furthermore, PET probes binding to the translocator protein (TSPO), a marker of brain injury and repair, are reviewed as potential tools for the imaging of neuroinflammatory cascade associated with CTE.

Expert opinion

Molecular neuroimaging of CTE with Tau-PET is an intriguing, although still not completely explored, tool for the in vivo detection and monitoring of neuropathological hallmarks associated with CTE. Furthermore, some novel tracers, such as TSPO-ligands, hold the promise to get an insight into the complex physiopathological mechanisms leading from brain injury to symptomatic CTE.

KEYWORDS:

• Molecular imaging
• Tau PET
• chronic traumatic encephalopathy
• neuroinflammation
• translocator protein
• precision medicine

Article highlights

• Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative syndrome, related to repeated brain injuries (TBI), commonly diagnosed in retired contact sports athletes.

• CTE has been categorized as a primary tauopathy. Therefore, according to current criteria, diagnosis is possible only through brain post mortem examination.

• Neuroinflammation, and particularly microglia activation, has been detected in brain specimen of subjects affected by CTE at post mortem examination.

• Molecular imaging through PET/CT with radiopharmaceuticals targeting tau-aggregates (Tau-PET) or neuroinflammation biomarkers have been applied for the in vivo identification of neuropathological hallmarks associated with CTE.

• Tau-PET showed significantly increased tracer incorporation in subcortical and some cortical areas of subjects with TBI history respect to healthy controls and a meaningfully different pattern of distribution in comparison with patients affected by Alzheimer’s Disease.

• PET with tracers binding to translocator protein (TSPO) has been successfully applied for the detection of neuroinflammatory changes in subjects with CTE, although the sensitivity of TSPO-ligand is strictly dependent by a single genetic polymorphism.

Acknowledgments

The authors thank Prof. Martin G. Pomper for having kindly contributed to the paper with a courtesy image.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.