Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease

Abstract

Early detection of musculoskeletal disease leads to improved therapies and patient outcomes, and would benefit greatly from imaging at the cellular and molecular level. As it becomes clear that assessment of multiple tissues and functional processes are often necessary to study the complex pathogenesis of musculoskeletal disorders, the role of multi-modality molecular imaging becomes increasingly important. New positron emission tomography-magnetic resonance imaging (PET-MRI) systems offer to combine high-resolution MRI with simultaneous molecular information from PET to study the multifaceted processes involved in numerous musculoskeletal disorders. In this article, we aim to outline the potential clinical utility of hybrid PET-MRI to these non-oncologic musculoskeletal diseases. We summarize current applications of PET molecular imaging in osteoarthritis (OA), rheumatoid arthritis (RA), metabolic bone diseases and neuropathic peripheral pain. Advanced MRI approaches that reveal biochemical and functional information offer complementary assessment in soft tissues. Additionally, we discuss technical considerations for hybrid PET-MR imaging including MR attenuation correction, workflow, radiation dose, and quantification.

Keywords: Positron emission tomography-magnetic resonance imaging (PET-MRI); arthritis; musculoskeletal imaging; nuclear medicine; osteoporosis.

Figure 1

Schematic of integrated PET-MRI systems. (A) Concept for integration of PET and MRI: PET insert placed inside the MRI scanner, matching the centers of both fields of view. This is made possible by an (B) MRI-compatible PET insert based on APD detectors which can be positioned inside the magnet. Each (C) detector module consists of a scintillator block, APD array and preamplifier surrounded by MRI-compatible copper shielding. This model has been expanded using silicon photomultipliers (SiPMs) into 3T whole-body systems which are now commercially available from several venders. Reprinted by permission from Macmillan Publishers Ltd: Nature Medicine (5) 2008. PET, positron emission tomography; MRI, magnetic resonance; APD, avalanche photodiode.

Figure 2

Concordance between bone abnormalities on MRI and increased ¹⁸F-NaF uptake on PET. (A) Fused ¹⁸F-NaF PET/CT and (B) MRI image of the patellofemoral joint a subject with patellofemoral pain. Bone marrow edema identified on MRI in the apex of the patella corresponded to increased ¹⁸F-NaF PET uptake. Simultaneous PET/MRI systems present an opportunity to study the role metabolic activity in structural MRI findings widely used to assess OA progression. From reference (69), with permission. ¹⁸F-NaF, ¹⁸F-sodium fluoride; PET, positron emission tomography; CT, computed tomography; MRI, magnetic resonance; OA, osteoarthritis.

Figure 3

PET and MRI imaging of rheumatoid arthritis in the hand. (A,B) 3D projection image of ¹⁸F-FDG uptake in a (A) healthy subject and (B) a subject with rheumatoid arthritis of the hand and wrist (78) [This research was originally published in JNM. Beckers C, Ribbens C, André B, Marcelis S, Kaye O, Mathy L, Kaiser MJ, Hustinx R, Foidart J, Malaise MG. Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET. J Nucl Med 2004;45:956-64. © by the Society of Nuclear Medicine and Molecular Imaging, Inc.]. ¹⁸F-FDG PET can assess the metabolic activity of synovitis and has been correlated with underlying disease activity. (C,D) MRI. (C) Coronal STIR and (D) axial fat-suppressed T2-weighted images of a subject with early rheumatoid arthritis of the wrist and normal radiographic findings. Synovitis can be observed as high signal intensity (arrows) as can bone marrow edema (asterisks) [Narváez JA, Narváez J, De Lama E, De Albert M. MR imaging of early rheumatoid arthritis. Radiographics 2010;30:143-63. (79) with permission]. MRI provides high-resolution anatomical images to assess structural changes for diagnosis and staging of RA disease. Hybrid PET-MRI systems offer to combine high-resolution morphologic images with early molecular markers to enhance the study of RA. ¹⁸F-FDG, ¹⁸F-fluorodeoxyglucose; PET, positron emission tomography; MRI, magnetic resonance; RA, rheumatoid arthritis.

Figure 4

FDG uptake in rat model of neuropathic limb pain. (A) Representative spared-nerve injury (SNI) (top row) and control (bottom row) animals on transaxial MRI, PET, and PET/MRI with labelled sciatic nerves (arrows). Significantly increased ¹⁸F-FDG uptake is seen on the side with spared-nerve injury (left) compared with the control side (right). No significant differences between sides are observed in control animal sciatic nerves. (B) Autoradiography of sciatic nerve specimens from spared-nerve injury animals showed that normalized radiotracer uptake is higher in the injured sciatic nerve (left) than in the control sciatic nerve (right). PET/MRI offers to combine molecular information to localize neuropathic pain with MRI which is able to provide high-resolution visualization of anatomical abnormalities (107). [This research was originally published in JNM. Behera D, Jacobs KE, Behera S, Rosenberg J, Biswal S. (18)F-FDG PET/MRI can be used to identify injured peripheral nerves in a model of neuropathic pain. J Nucl Med 2011;52:1308-12. © by the Society of Nuclear Medicine and Molecular Imaging, Inc.]. MRI, magnetic resonance; PET, positron emission tomography; ¹⁸F-FDG, ¹⁸F-fluorodeoxyglucose.