Synopsis

Keywords: Skeletal, PET/MR, Multiple Myeloma

In this study we evaluated the diagnostic performance of whole-body T2-weighted imaging with uniform 2-point Dixon fat-suppression for the detection of multiple myeloma. Furthermore, we evaluated the added sensitivity, change in disease stage, and change in treatment plan with the sequential addition of DWI and FDG PET. T2-Dixon demonstrated higher sensitivity than both DWI and PET. Adding DWI did not change stage or treatment plan. However, the addition of PET did change the treatment plan in one patient with extra-osseous disease. Whole-body PET-MRI with T2-Dixon is a promising and efficient tool for assessment of multiple myeloma.

Introduction

Whole-body MRI is the most sensitive test for detection of multiple myeloma (MM) lesions^1–5. Early detection of focal lesions is important to identify patients who should receive early treatment to prevent morbidity from symptomatic bone disease⁶. 18F‐fluorodeoxyglucose (FDG) PET is widely considered the reference imaging standard to assess treatment response in MM⁷. Therefore, a combined whole-body PET/MRI may be the most comprehensive imaging approach for MM.

Whole-body (WB) diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) are often used to assess MM. However, DWI (especially wide field of view WB imaging) suffers from limitations, such as prolonged scan times, image distortion, incomplete bone marrow and subcutaneous fat suppression, and poor anatomic delineation, often leading to incomplete exams, non-diagnostic images, and inaccurate/imprecise ADC^8–17. WB T2-weighted fast-spin-echo imaging with uniform Dixon-based fat-suppression (T2-Dixon) has shown promise to outperform DWI in detection of metastatic bone lesions¹⁸. Moreover, Dixon-based approach provides a more uniform fat-suppression than the spectral-fat-suppression techniques and also generates in- and opposed-phase (IP and OP) images that assist with lesion characterization based on fat content^19,20. Hence, we evaluated the diagnostic performance of WB T2-Dixon for detection of MM lesions, and the incremental performance of DWI and PET to detect additional lesions, and the overall impact on patient management.

Methods

This IRB-approved retrospective study reviewed WB PET/MRI exams for MM between August 2019 and April 2022.

Exams were performed on a PET/MRI scanner (Signa PET/MR, GE Healthcare), 60 minutes after FDG intravenous injection. Simultaneously, in each PET bed, the following MRI sequences were acquired (Table 1): T1-weighted two-point Dixon for MR-based attenuation correction, 3D T1-weighted gradient-echo with Dixon, and T2-weighed fast spin-echo with Dixon. Once all PET beds were completed from skull to feet, axial whole-body DWI was acquired.

Two readers (one fellowship trained radiologist/nuclear medicine physician and one musculoskeletal radiologist with PET/MRI experience) interpreted the studies in consensus per following: blinded to PET and DWI, T2-Dixon (water-only) images were reviewed alongside T1-Dixon (water-only) images. IP, OP, and fat-only images were also available to help with lesion characterization as needed, simulating real-life practice.
Disease extent was recorded for each of the following 8 body compartments: calvarium, scapulae/sternum, ribs, cervicothoracic spine, lumbosacral spine, pelvis, lower extremities, upper extremities, and extraosseous. For each compartment up to 3 focal lesions were recorded and evaluated on a 5-point Likert scale (Table 2). Lesions rated ≥3 were considered suspicious. Number of lesions per compartment (up to 5) were noted. Diffuse disease was also recorded, and any superimposed focal lesions were also recorded.
Exams were subsequently re-evaluated with the addition of DWI. The number and level of suspicion for lesions seen on DWI were recorded in a similar manner and subsequently on PET. Reference standard for lesion detection and characterization was consensus assessment utilizing all available PET/MRI images, prior/follow up imaging, clinical history, and histology.

In order to determine the impact of each sequence on patient management, a hematologist oncologist with subspecialty expertise in treatment of multiple myeloma reviewed the imaging results and all available clinical/imaging/histologic information to determine if a change in management would result based on adding information from DWI, PET, or both, compared to using only the information obtained by T1- and T2-weighted Dixon images. Sensitivity for T2, DWI, and PET were compared by McNemar test. P <0.05 was considered significant.

Results

34 MM patients were reviewed (average age 67 years (range 34-83), 38% female). DWI was not obtained in 3 patients who requested exam termination due to discomfort and were excluded. In the remaining 31 patients, 139 focal lesions were identified per the reference standard. T2-Dixon had a significantly higher sensitivity than DWI and PET, respectively 93%, 66% and 47%, P<0.001 (Table 3). Adding DWI to T2-Dixon resulted in detection of 3 additional lesions, but this did not change disease stage or treatment strategy. Adding PET to T2-Dixon and DWI resulted in detection of 7 additional lesions and changed management by detecting an otherwise normal-appearing lymph node. There were 5 false positive lesions for T2-Dixon, 9 for DWI, and 2 for PET. Among 11 patients with diffuse bone marrow disease, T2-Dixon identified all cases, DWI identified 10/11 (91%) and PET only detected 6/11 (55%) (P=0.06).

Discussion

Whole-body T2 with Dixon fat-suppression detected more lesions than DWI in the setting of MM; adding DWI did not impact disease stage or patient management. However, while PET demonstrated lower sensitivity than T2-Dixon in detection of focal and diffuse disease, it remains the best modality for follow-up and can identify extra-osseous disease. Hence, whole-body PET/MRI with T2-Dixon demonstrates promise as a rapid imaging modality in assessment of MM.

Limitations of this study include its retrospective nature and small sample size. Another limitation was absence of independent evaluation of DWI and PET. However, our approach aimed to simulate real-life clinical practice to assess the incremental value in adding DWI and PET to detect lesions in addition to WB T2.

Conclusion

Whole-body PET-MRI with T2-Dixon is a promising and efficient tool for the assessment of multiple myeloma; the addition of DWI did not impact disease detection or staging and did not impact patient management.

Acknowledgements

We wish to acknowledge support from GE Healthcare and Bracco Diagnostics who provide research support to the University of Wisconsin. Dr. Reeder is the Fred Lee Sr. Endowed Chair of Radiology.

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