In Vivo Imaging of Human Neuroinflammation

Abstract

Neuroinflammation is implicated in the pathophysiology of a growing number of human disorders, including multiple sclerosis, chronic pain, traumatic brain injury, and amyotrophic lateral sclerosis. As a result, interest in the development of novel methods to investigate neuroinflammatory processes, for the purpose of diagnosis, development of new therapies, and treatment monitoring, has surged over the past 15 years. Neuroimaging offers a wide array of non- or minimally invasive techniques to characterize neuroinflammatory processes. The intent of this Review is to provide brief descriptions of currently available neuroimaging methods to image neuroinflammation in the human central nervous system (CNS) in vivo. Specifically, because of the relatively widespread accessibility of equipment for nuclear imaging (positron emission tomography [PET]; single photon emission computed tomography [SPECT]) and magnetic resonance imaging (MRI), we will focus on strategies utilizing these technologies. We first provide a working definition of “neuroinflammation” and then discuss available neuroimaging methods to study human neuroinflammatory processes. Specifically, we will focus on neuroimaging methods that target (1) the activation of CNS immunocompetent cells (e.g. imaging of glial activation with TSPO tracer [11C]­PBR28), (2) compromised BBB (e.g. identification of MS lesions with gadolinium-enhanced MRI), (3) CNS-infiltration of circulating immune cells (e.g. tracking monocyte infiltration into brain parenchyma with iron oxide nanoparticles and MRI), and (4) pathological consequences of neuroinflammation (e.g. imaging apoptosis with [99mTc]­Annexin V or iron accumulation with T2* relaxometry). This Review provides an overview of state-of-the-art techniques for imaging human neuroinflammation which have potential to impact patient care in the foreseeable future.

Hyperpolarized 13C magnetic resonance spectroscopy detects toxin‐induced neuroinflammation in mice

“…However, to date 1 H MRS is only used in a narrow set of clinical pathologies, at those centers with the appropriate expertise to interpret the data. Although optimization of 1 H MRS for the assessment of neuroinflammation is ongoing, 21 this methodology is not yet standard clinical procedure, and alternative strategies are needed. 13 C MRS holds great promise for assessing in vivo metabolism.…”

A Facile Radiolabeling of [18F]FDPA via Spirocyclic Iodonium Ylides: Preliminary PET Imaging Studies in Preclinical Models of Neuroinflammation

“…10 Intensive efforts therefore have been made to improve PET imaging quality and quantitative process with the development of a rich library of TSPO PET ligands. 11–13 Particularly a PET ligand [ 18 F]1 ([ 18 F]DPA-714; Figure 1), developed by James and Kassiou et al , has shown improved bioavailability, lower nonspecific binding, and higher non-displaceable binding potential ( BP ND ). 14, 15 Initial evaluation of this radiopharmaceutical in healthy human volunteers validated its biodistribution profile towards TSPO.…”

Exploring the heterogeneity of MS lesions using positron emission tomography: a reappraisal of their contribution to disability

“…However, additional biases may still influence the quantification process for this family of tracers. First, the affinity to platelets, monocytes and plasma proteins alters the free plasma concentration of the tracers across subjects, with a possible impact on input function calculation, when input function is used for signal modelling (2). This evidence supports the application of quantification methods based on the extraction of reference regions directly from brain images in order to avoid fluctuation in the measure of input function, a strategy that was applied for PBR28 (21,22,41) and [ 18 F]DPA-714 (36).…”