Non-Oncologic MSK PET-MR
Feliks Kogan1

1Stanford University, United States

Synopsis

New PET-MRI systems promise to combine high-resolution morphologic MR imaging with simultaneous functional information from PET to potentially provide a complete imaging modality for studying musculoskeletal disease. This educational talk will discuss emerging applications of PET-MRI in non-oncologic musculoskeletal disease and comparative advantages of PET-MRI over hybrid PET-computed tomography (PET/CT) systems or MRI alone. Technical considerations and challenges as they specifically relate to PET-MRI of musculoskeletal disease will also be discussed.

Introduction

New PET-MRI systems promise to combine high-resolution morphologic MR imaging with simultaneous functional information from PET1-7 to study the complex processes involved in numerous musculoskeletal disorders. While PET is widely clinically utilized in detection, characterization, and assessment of treatment response in malignant musculoskeletal disease, it has had limited application to non-oncologic musculoskeletal disease. PET offers incomparable abilities to provide quantitative information about molecular and physiologic changes that often precede structural and biochemical changes8,9. In combination, hybrid PET-MRI can offer early detection of disease as well as improved diagnostic sensitivity and specificity and offers a power combination to study important non-oncologic musculoskeletal diseases such as osteoarthritis, rheumatoid arthritis, metabolic bone disease and pain.

Osteoarthritis (OA)

Osteoarthritis a chronic degenerative disease affecting all tissues in the joint which is a leading cause of pain and disability10. MRI is able to provide excellent high-resolution, multi-contrast morphologic information of joint tissues as well as important information about tissue microstructure which is thought to degrade before structural changes are seen with conventional imaging methods11-13. While MRI is unmatched in its ability to evaluate soft tissue, it has some limitation for imaging osseous abnormalities and functional imaging of bone with MRI remains a challenge. PET imaging with 18F-Sodium Fluoride(18F-NaF) is able to assess osteoblast activity in subchondral bone. Functional imaging of subchondral bone is vital, as this is the only highly vascularized tissue in the joint and has the ability to reflect rapid changes. Initial results with simultaneous 18F-NaF PET-MRI showed that the 18F-NaF PET uptake in subchondral bone marrow lesions(BML), osteophytes, and sclerosis identified on MRI was significantly higher than that of normal appearing bone on MRI. Furthermore, a correlation was observed between BML and osteophyte grades based on semi-quantitative scoring systems. Additionally, 18F-NaF PET was able to detect areas of increase uptake that appeared normal on MRI suggesting that increased bone activity detected with 18F-NaF PET may serve as a marker for early OA in this population. This is further supported by data in a unilateral ACL-tear early model of OA where significantly increased 18F-NaF PET uptake was observed in the subchondral bone of ACL-injured knee joints, compared with their uninjured contralateral knees14. Hybrid PET-MR imaging of OA is also able to study spatial relationships between early mechanisms of disease across tissues. Multiple studies have shown correlations between increases in cartilage T2/T1ρ relaxation times, which are associated with early cartilage matrix changes, increased 18F-NaF uptake measures of bone remodeling in adjacent subchondral bone14,15. This supports an interdependent relationship between bone and cartilage with early degenerative changes in one tissue having an effect on the neighboring tissue. Additionally, fluorodeoxyglucose (18F-FDG), a PET-labeled analog of glucose, has been applied to study synovitis and the inflammatory component of BMLs in OA16-18. This allows PET/MR to simultaneously assess several early metabolic and biochemical marker of knee OA progression across all tissues in the joint.

Rheumatoid arthritis (RA)

Rheumatoid arthritis is a painful inflammatory autoimmune disease characterized by systemic inflammation, and destruction of articular and periarticular tissues. Patient outcomes in RA are tied to early initiation of new targeted disease modifying anti-rheumatic drugs (DMARDs)19. PET-MRI offers the ability to change clinical management of these patients through early detection and treatment monitoring of early inflammatory and cellular changes in RA. PET imaging with 18F-FDG or a more specific marker of inflammation (11C-(R)-PK11195) may provide the most sensitive method for detection and quantitative characterization of inflammation in RA20,21. Additionally, MRI provides an optimal technique for musculoskeletal imaging and evaluation of morphologic changes. Early PET-MRI studies have shown feasibility for imaging of inflammation in early RA of the hand, showing sites of synovitis and tenosynovitis on contrast-enhanced MRI that corresponded to increased uptake on FDG PET22.

Pain

Neuropathic pain is a debilitating pain symptom secondary to neural damage in the somatosensory nervous system23. One of the primary challenges to treatment of neuropathic pain is diagnosing its source and location. FDG PET-MRI results has shown sensitivity for FDG imaging of neuroinflammation at the site of the impinged spinal nerve24. Further, multi-modality analysis with FDG PET and morphologic MRI demonstrated potential for detecting non-spinal sources of sciatica and ruling out nerve root impingements irrelevant to the patient’s symptoms. Additionally, 18F-FTC-146, new radioligand which specifically binds to sigma-1 receptors, offers improved specificity to pain and has its application in complex regional pain syndrome was shown to alter pain management in 7-of-8 patient studied25.

Other Non-Ocologic Musculoskeletal Disease

PET-MRI has also been applied for diagnosis of bone infection and stress fractures as well as studies of muscle activation. 18F-FDG PET-MRI significantly increased diagnostic certainty for detection of spondylodiscitis, improving sensitivity from 54% to 100% and specificity from 71% to 88% compared to MRI alone in patients with inconclusive clinical or MRI findings26. Additionally, 18F-NaF PET-MRI performed better than PET/CT in detection of stress fractures. This was due to earlier depiction of T1-weighted MRI changes than changes on CT, which provided radiologists higher diagnostic confidence27. Further, the diagnostically relevant findings from soft-tissue and bone marrow pathology on MRI provided more diagnostic information and higher diagnostic confidence for evaluation of foot pain of unclear cause on 18F-NaF PET-MRI compared with PET/CT. A high correlation was also shown between SUV measurements of PET-MRI and PET/CT, demonstrating that PET-MRI is technically feasible and robust. Lastly, simultaneous acquisition of PET and MRI data has allowed for analysis of the relationship between 18F-FDG measures of glucose metabolism and T2 relaxation time changes in skeletal muscle following the same exercise paradigm on the same time course, which would not have been possible with sequential scanning28.

Technical Considerations and Challenges

Technical advancements have made integrated PET-MRI systems possible3,29. Current technical considerations and challenges in PET-MRI include correction of attenuation of PET photons using MR images, PET-MRI workflow, and quantification and interpretation of data1,3,5,7 will be discussed.

Conclusion

Integrated PET-MRI systems potentially provide a complete imaging modality for studying musculoskeletal disease. The addition of molecular PET information to established MRI applications may offer earlier detection, improved sensitivity, and greater specificity in many non-oncologic musculoskeletal diseases as well as new markers for studying disease pathophysiology and treatment response.

Acknowledgements

I receive research support from National Institute of Health (NIH) grants R01EB002524 and K99EB022634.

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Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)