Abstract

Neuroinflammation plays a central role in a variety of neurological diseases, including stroke, multiple sclerosis, Alzheimer’s disease, and malignant CNS neoplasms, among many other. Different cell types and molecular mediators participate in a cascade of events in the brain that is ultimately aimed at control, regeneration and repair, but leads to damage of brain tissue under pathological conditions. Non-invasive molecular imaging of key players in the inflammation cascade holds promise for identification and quantification of the disease process before it is too late for effective therapeutic intervention. In this review, we focus on molecular imaging techniques that target inflammatory cells and molecules that are of interest in neuroinflammation, especially those with high translational potential. Over the past decade, a plethora of molecular imaging agents have been developed and tested in animal models of (neuro)inflammation, and a few have been translated from bench to bedside. The most promising imaging techniques to visualize neuroinflammation include MRI, positron emission tomography (PET), single photon emission computed tomography (SPECT), and optical imaging methods. These techniques enable us to image adhesion molecules to visualize endothelial cell activation, assess leukocyte functions such as oxidative stress, granule release, and phagocytosis, and label a variety of inflammatory cells for cell tracking experiments. In addition, several cell types and their activation can be specifically targeted in vivo, and consequences of neuroinflammation such as neuronal death and demyelination can be quantified. As we continue to make progress in utilizing molecular imaging technology to study and understand neuroinflammation, increasing efforts and investment should be made to bring more of these novel imaging agents from the “bench to bedside.”

Highlights

  • Neuroinflammation plays a central role in a variety of neurological diseases, including cerebrovascular disease, demyelinating diseases, Pulli and Chen neurodegeneration (e.g., Alzheimer’s disease), and malignant CNS neoplasms, among many others [1,2,3,4,5,6]

  • We focus on molecular imaging techniques that target inflammatory cells and molecules that are of interest in neuroinflammation, especially those with high translational potential

  • In a study on 10 ischemic stroke patients injected with ultra-small paramagnetic iron oxide (USPIO) 7 days after symptoms onset, USPIO uptake was seen in ischemic brain area and differed from DTPA-Gd indicated blood-brain barrier (BBB) breakdown, showing that phagocyte imaging is feasible in stroke patients (Figure 8D) [173]

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Summary

Introduction

Neuroinflammation plays a central role in a variety of neurological diseases, including cerebrovascular disease (e.g., stroke), demyelinating diseases (e.g., multiple sclerosis, MS), Pulli and Chen neurodegeneration (e.g., Alzheimer’s disease), and malignant CNS neoplasms (e.g., glioblastoma multiforme), among many others [1,2,3,4,5,6]. In EAE, MPOGd detected more and smaller active inflammatory brain lesions than DTPA-Gd (Figure 4A), and MPO-expressing cells and demyelinated areas correlated well with MPO-Gd enhanced MR imaging findings [45]. In the MCAO mouse model of stroke, MPO-Gd enhanced MR imaging detected widespread secretion of MPO into the ischemic areas, and MPO-Gd positive lesion volume correlated well with infarct size (Figure 4C) [47].

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