Metabolic and molecular imaging in inflammatory arthritis

Abstract

It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases such as the inflammatory arthritides. As such, visualising and measuring metabolic tissue activity could be useful to identify biomarkers of disease activity already in a very early phase. Recent advances in imaging have led to the development of so-called 'metabolic imaging' tools that can detect these changes in metabolism in an increasingly accurate manner and non-invasively.Nuclear imaging techniques such as ¹⁸F-D-glucose and fibroblast activation protein inhibitor-labelled positron emission tomography are increasingly used and have yielded impressing results in the visualisation (including whole-body staging) of inflammatory changes in both early and established arthritis. Furthermore, optical imaging-based bedside techniques such as multispectral optoacoustic tomography and fluorescence optical imaging are advancing our understanding of arthritis by identifying intra-articular metabolic changes that correlate with the onset of inflammation with high precision and without the need of ionising radiation.Metabolic imaging holds great potential for improving the management of patients with inflammatory arthritis by contributing to early disease interception and improving diagnostic accuracy, thereby paving the way for a more personalised approach to therapy strategies including preventive strategies. In this narrative review, we discuss state-of-the-art metabolic imaging methods used in the assessment of arthritis and inflammation, and we advocate for more extensive research endeavours to elucidate their full field of application in rheumatology.

Keywords: Arthritis; Arthritis, Rheumatoid; Inflammation; Lipids; Ultrasonography.

Figure 1

Overview of the functioning principles of the metabolic and molecular imaging of arthritis with PET/CT, MSOT and FOI. In PET/CT (left panel), fibroblast-targeted and macrophage-targeted radionuclide are administered intravenously to trace the activity of the mesenchymal and monocyte cell compartments in the joints throughout the whole body. In FOI (middle panel), joints are exposed to light at specific wavelengths after the intravenous administration of indocyanine green contrast agent, allowing the visualisation of microvascular changes with high resolution through the use of a near-infrared thermal camera and a computer system. In MSOT (right panel), target tissues are exposed to near-infrared laser light, which exploits the photoacoustic effect by inducing chromophore substances inside the joint to emit low-energy sound waves. These optoacoustic profiles are specific for each molecule and can be captured and quantified by a specific receiver. FOI, fluorescence optical imaging; MSOT, multispectral optoacoustic tomography; PET, positron emission tomography.

Figure 2

Schematic representation of the molecules and structures that can be assessed by molecular and molecular imaging. The cellular metabolism of synovial fibroblast and macrophages can be detected by FAPI-targeted and macrophage-targeted PET/CT, respectively; fluorescent optical imaging (FOI) visualises neovascularisation and microcirculation; multispectral optoacoustic tomography can be used to measure the relative concentration of metabolites related to inflammation such as haemoglobin, collagen fibres and lipids. FAPI, fibroblast activation protein inhibitor; ; MSOT, multispectral optoacoustic tomography; PET, positron emission tomography.

Figure 3

Examples of applied metabolic imaging to joints and entheses. Panel (A)Ga-FAPI-04-positron emission tomography/CT scans showing avid intra-articularGa-FAPI uptake in the wrist, metacarpophalangeal and ankle joints (left and upper quadrant) and in the shoulder joints of patients with rheumatoid arthritis. Panel (B) fluorescence optical imaging acquisitions showing changes in micro vascularisation and increased blood flow in the finger joints of a patient with rheumatoid arthritis (left) and early psoriatic arthritis (right). Panel (C) multispectral optoacoustic tomography scans of the Achilles tendon enthesis (left) and of the lateral humeral epicondyle enthesis of a patient with psoriatic arthritis showing the distribution of lipid and collagen (left) and haemoglobin (right) superimposed to ultrasound. Ga-FAPI, ⁶⁸Ga-fibroblast activation protein inhibitor.