Hybrid MRI Techniques
Feliks Kogan1
1Stanford University, Stanford, CA, United States

Synopsis

Hybrid MRI methods promise to combine the high-resolution multi-contrast imaging benefits of MRI with new approaches aimed at early disease detection and clinical interventions. PET-MRI systems add metabolic and functional information from PET to potentially provide a complete imaging modality for studying musculoskeletal disease while high-intensity focused-ultrasound offers therapeutic interventions for bone tumors. This educational talk will discuss emerging applications of these technologies and their comparative advantages. Technical considerations and challenges as they specifically relate to musculoskeletal disease will also be discussed.

PET-MRI Hybrid Imaging

New PET-MRI systems promise to combine high-resolution morphologic MR imaging with simultaneous functional information from PET to study the complex processes involved in numerous musculoskeletal disorders. PET offers incomparable abilities to provide quantitative information about molecular and physiologic changes that often precede structural and biochemical changes (1,2). 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.

PET-MRI of Oncologic MSK Disease

MRI is the gold standard modality for assessing T-stage in Bone sarcomas (BS) and soft tissue sarcomas (STS) given its excellent soft tissue contrast, high spatial resolution, and multiplanar capability. It is critical in preoperative and radiation planning, depicting tumor relationship to neurovascular structures, fascial planes, muscular compartments, and adjacent joints (3,4). Combining MRI with PET measures such as standardized uptake values (SUV), total lesion glycoslysis (TLG), and metabolic tumor volume (MTV) provides powerful multiparametric evaluation(5). Additional benefits of adding localized PET evaluation to MRI for primary BS and STS assessment include prognostication and guiding biopsy. Baseline BS and STS FDG activity has been shown to independently predict survival in several studies (6-8). Lastly, there are clear advantages to combined PET and MRI for therapy response assessment and disease monitoring (9,10). Similar advantages are seen in applications for imaging of multiple myeloma. A study comparing whole body MRI and PET/CT in assessment of active disease in MM found better sensitivity and specificity for MRI, but noted that when used in combination, PET and WBMRI were found to have a specificity and positive predictive value of 100%, heralding a role integrated PET/MRI(11).

PET-MRI of Degenerative Joint Changes

Osteoarthritis(OA) a chronic degenerative disease affecting all tissues in the joint which is a leading cause of pain and disability(12.) There is increasing evidence that OA is a disease with numerous phenotypes suggesting that reliable biomarkers are necessary for better understanding, prevention, diagnosis, and treatment of OA across all joint tissues. MRI is able to provide excellent high-resolution, multi-contrast morphologic information of joint tissues as well as important information about tissue microstructure such as collagen matrix organization, glycosaminoglycan (GAG) content, and hydration, which is thought to degrade before structural changes are seen with conventional imaging methods(13-15). 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. [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(16,17). Even more striking, significantly increased subchondral bone metabolic activity was seen in structurally regions of normal-appearing bone and adjacent cartilage in an OA-group compared to a healthy cohort(16). 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 knees(18). In addition to the knee, increased [18F]NaF bone activity has also been observed in hip OA(19). 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 and T1ρ relaxation times, which are associated with early cartilage matrix changes, increased [18F]NaF uptake measures of bone remodeling in adjacent subchondral bone(18,20,21). This supports an interdependent relationship between bone and cartilage with early degenerative changes in one tissue having an effect on the neighboring tissue. Dynamic contrast enhanced MRI (DCE-MRI) has also been shown increased synovial inflammation adjacent to increased [18F]NaF subchondral metabolic bone activity in order to study important inflammatory factors in the development of osteophytes(22). Additionally, fluorodeoxyglucose ([18F]FDG), a PET-labeled analog of glucose, has been applied to study synovitis and the inflammatory component of BMLs in OA(17,23-25) as well as looking at graft revascularization after surgery(26). This allows PET/MR to simultaneously assess several early metabolic and biochemical marker of knee OA progression across all tissues in the joint

PET-MRI of Bone Physiology

The acute effect of loading on bone tissue and physiology can offer important information with regard to joint function. It has been shown that acute loading alters the bone physiology affecting [18F]NaF kinetics(27). A step-up, jump down exercise protocol induced a significant increase in [18F]NaF uptake in healthy volunteers(27). Further, changes in [18F]NaF uptake induced by exercise in this study suggest a localized response in bone tissue that may be load-dependent. This has also been observed in OA subjects following a single-legged squat exercise(28). Of particular interest, focal regions of considerably increased PET uptake (“hot spots”) were observed in both bone that appeared unremarkable at baseline and in bone that already had adjacent structural findings on MRI (BMLs, Osteophytes, Cartilage Lesions) at baseline(29). In particular, regions with BMLs had a significantly greater increase in uptake measures compared to structurally normal bone. This suggests that [18F]NaF PET can identify regions on MRI where there is an improper response of the joint unit to loading.

PET-MRI of Pain

Neuropathic pain is a debilitating pain symptom secondary to neural damage in the somatosensory nervous system(30). 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 nerve(31). 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, a 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 studied(32). This methodology, using PET to determine regions of pain generators and high-resolution MR neurography has been applied to knee pain, foot pain, sciatica and others(33-35).

PET-MRI Technical Considerations and Challenges

Technical Considerations and Challenges Technical advancements have made integrated PET-MRI systems possible(36,37). Current technical considerations and challenges in PET-MRI include correction of attenuation of PET photons using MR images, PET-MRI workflow, imaging around metal and quantification and interpretation of data(36,38-41) will be discussed.

MR-Guided Focused Ultrasound (MRgFUS)

MRI–guided high-intensity focused ultrasound (HIFU) ablation is emerging technology that is showing potential to shift how we treat bone tumors; offering noninvasive energy deposition in bone with minimal damage to the surrounding tissues(42). MR guidance allows a more reliable target delineation thanks to a higher contrast resolution, and provides an accurate quantitative feedback from the treated region, offering key advantages over ultrasound guidance. In particular, MRI methods for temperature mapping offer a key advantage to image treatment delivery while high-resolution imaging can inform treatment margins and success. MRgFUS has already received FDA approval for treatment of bone metastases(43-45). In addition, MRgFUS has been applied to desmoid tumors, showing potential improvement over surgical interventions in tumor resection and limiting tumor spread(46). It has also been applied in treatment facet joint osteoarthritis, demonstrating improved pain scores and functional disability, with results that are comparable to radiofrequency denervation in a preliminary study(47). Other applictions may include vascular malformations, soft tissue tumors and benign bone tumors.

Acknowledgements

No acknowledgement found.

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