Supervised clustering for TSPO PET imaging

Abstract

Purpose This technical note seeks to act as a practical guide for implementing a supervised clustering algorithm (SVCA) reference region approach and to explain the main strengths and limitations of the technique in the context of 18-kilodalton translocator protein (TSPO) positron emission tomography (PET) studies in experimental medicine. Background TSPO PET is the most widely used imaging technique for studying neuroinflammation in vivo in humans. Quantifying neuroinflammation with PET can be a challenging and invasive procedure, especially in frail patients, because it often requires blood sampling from an arterial catheter. A widely used alternative to arterial sampling is SVCA, which identifies the voxels with minimal specific binding in the PET images, thus extracting a pseudo-reference region for non-invasive quantification. Unlike other reference region approaches, SVCA does not require specification of an anatomical reference region a priori, which alleviates the limitation of TSPO contamination in anatomically-defined reference regions in individuals with underlying inflammatory processes. Furthermore, SVCA can be applied to any TSPO PET tracer across different neurological and neuropsychiatric conditions, providing noninvasivequantification of TSPO expression. Methods We provide an overview of the development of SVCA as well as step-by-step instructions for implementing SVCA with suggestions for specific settings. We review the literature on SVCAapplications using first- and second- generation TSPO PET tracers and discuss potential clinically relevant limitations and applications. Conclusions The correct implementation of SVCA can provide robust and reproducible estimates of brain TSPO expression. This review encourages the standardisation of SVCA methodology in TSPO PET analysis, ultimately aiming to improve replicability and comparability across study sites.

Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression

“…Additional corrections (including scatter, random, normalisation, and deadtime correction), were performed using the standard console software that applied PET/MR reconstruction algorithm correction. Additional information on the PET and MRI protocols can be found in the original report on these data (Schubert et al, 2021a).…”

“…The [ 11 C]PK11195 DVR in CP was estimated from the parametric maps after performing partial volume correction using the Richardson-Lucy deconvolution method with 6mm point spread function provided by the PETPVC toolbox (Thomas et al, 2016). For both methods, the same reference region derived from a supervised clustering of dynamic PET images was applied (Schubert et al, 2021a). Additional details about the PET image processing and quantification are found in our previous studies (Turkheimer et al, 2020, Schubert et al, 2021b)…”

Neuroinflammation PET imaging of the translocator protein (TSPO) in Alzheimer's disease: An update

“…There have been significant advances in the methodological understanding of TSPO PET imaging in recent years (Schubert et al, 2021; Wimberley et al, 2021). The reader may refer to previous reviews for aspects regarding TSPO tracers (Cumming et al, 2018) and a critical assessment of the advantages and drawbacks of each quantification method (Wimberley et al, 2021).…”

“…This has implications for the choice of quantification model and reference region. The reader may refer to recent articles for an overview of TSPO cellular expression (Nutma et al, 2021), the methodological implications of TSPO biology on quantification (Turkheimer et al, 2015), and the appropriate choice of quantification method (Schubert et al, 2021; Wimberley et al, 2021).…”

Imaging translocator protein expression with positron emission tomography

“…The advantages and limitations of the methods in the current literature are outlined to aid researchers to choose methods that will allow them to generate the most relevant parameters and pharmacological/biological indices for their studies. A further article on the topic of quantification outlines the requirements for implementation of the supervised cluster analysis method [8] for the identification of an appropriate pseudo-reference region [9]. We have also included reviews of the use of TSPO PET imaging in several neurological diseases (apart from Alzheimer's disease, for which there are a number of reviews already [10,11]) such as glioma [12], epilepsy [13], psychiatric conditions [14], and substance abuse [15].…”