Correlation of Bone Pathology on MRI with 18F-fluoride PET Uptake in Subchondral Bone
Feliks Kogan1, Audrey Fan1, Emily McWalter1, Edwin Oei2, Andrew Quon1, and Garry Gold1

1Radiology, Stanford University, Stanford, CA, United States, 2Radiology, Erasmus Medical Center, Rotterdam, Netherlands

Synopsis

Osteoarthritis (OA) is a debilitating disease that affects 27 million
Americans, causing pain, stiffness and loss of mobility. Simultaneous PET-MR imaging provides an opportunity to combine metabolic information regarding bone remodeling with high resolution images on MR. This work demonstrates that simultaneous 18F-fluoride PET/MR may provide additional metabolic information regarding bone pathology seen on conventional MR. This will allow for a better understanding of the role of bone degeneration in OA disease processes. Additionally, 18F-fluoride PET/MR may detect knee abnormalities unseen on MRI alone and is a promising tool for detection of early metabolic changes in OA.

Purpose

Osteoarthritis (OA) is a debilitating disease that affects 27 million
 Americans, causing pain, stiffness and loss of mobility1. Magnetic resonance imaging (MRI) provides an excellent opportunity to non-invasively study and understand complex disease processes involved in OA2. However, characterization of bone pathology on MRI is limited to qualitative assessment of osteophytes and marrow signal changes3 and is poorly understood. 18F-fluoride is a long recognized bone-seeking agent that is able to probe bony remodeling4. This study aims to correlate and characterize bone pathology observed on MRI with 18F-fluoride uptake on PET.

Methods

Both knees of nine subjects with idiopathic or traumatic radiographic knee OA (Kelgren-Lawrence grade 1-3) were imaged on a 3T whole-body PET-MR hybrid system (GE Healthcare, Milwaukee, WI) following injection of between 2.5 and 5 mCi of 18F-fluoride under an approved IRB protocol. Two experienced radiologists identified bone pathology on MR images. This included areas of high T2 signal referred to as “bone marrow lesions” (BMLs)5, osteophytes identified on ultra-short echo time (uTE) MR images and subchondral sclerosis (areas of low signal intensity of subchondral bone on both fat-saturated T2-weighted FSE images and Dixon fat images). Additionally, BMLs and osteophytes were scored according to MRI Osteoarthritis Knee Score (MOAKS)3. The maximum pixel standardized uptake values (SUVmax) from volumes of interest (VOI) on PET images corresponding to bone pathology identified on MRI were compared between different bone pathologies as well as between individual pathology lesion grade. VOIs with SUV greater than 4 times the natural bone background (mean SUV of background bone) were identified (VOIHigh) on PET SUV maps. A Wilcoxon signed-rank test was used to compare SUVmax from different bone pathology to each other as well as within BML and osteophyte grade. Additionally, SUVmax from VOIHigh that didn’t correlate with MRI findings were identified and were compared to MR findings of bone pathology.

Results

Figure 1 displays example PET (SUV) and MRI images of two patients with traumatic OA showing correlation between BML (blue arrow), osteophytes (red arrows), and sclerosis (green arrows) on MRI with high 18F-fluoride uptake on PET. High 18F-fluoride uptake in subchondral bone did not always correspond to structural damage detected on MRI (purple arrows) (23 of the 103 areas of VOIHigh) (Figure 2a). Additionally, many of the small osteophytes used to identify early signs of OA on radiographs did not show focal uptake of 18F-fluoride (orange arrows) (Figure 2b). Bone marrow lesions (BMLs) observed on T2-weighted FSE images acquired with fat saturation consistently correlated with 18F-fluoride PET VOIHigh (25 of 26 lesions) (Figure 3b). Furthermore, SUVmax associated with BMLs was significantly higher than that of osteophytes or subchondral sclerosis (p<0.001) (Figure 3). Additionally, significant correlations were observed between SUVmax and BML grade based off MOAKS scoring (p<0.05) (Figure 4a). Association between 18F-fluoride VOIHigh and MRI findings of osteophytes (49 of 70) and subchondral sclerosis (6 of 10) was less consistent. However, similar to BMLs, there were significant correlations between SUVmax and osteophyte grade (p<0.05) (Figure 4b).

Discussion

The sensitivity of 18F-fluoride PET to bone remodeling make it an optimal tool to better understand subchondral bone pathology on MRI. Subchondral bone is a region that is associated with the development of pain as well as cartilage degeneration. Early results suggest that BMLs are significantly more metabolically active than osteophytes and sclerosis. Furthermore, significant differences were observed in 18F-fluoride PET uptake between osteophyte and BML grade identified with MR. However, there were large standard deviations observed within each type of bone pathology and within lesion grade. The sensitivity of 18F-fluoride PET/MR to bone remodeling may help us to better understand and characterize these lesions in subchondral bone. Additionally, a lack of metabolic activity may signal that certain pathology play a reduced role in OA progression. Lastly, high 18F-fluoride uptake that does not correlate with MR findings suggests that metabolic abnormalities in the bone may occur prior to when structural changes are seen on MRI.

Conclusion

This work demonstrates that simultaneous 18F-fluoride PET/MR may provide additional metabolic information regarding bone pathology compared with conventional MR. This will allow for a better understanding of the role of bone degeneration in OA disease processes. Additionally, 18F-fluoride PET/MR may detect knee abnormalities unseen on MRI alone and is a promising tool for detection of early metabolic changes in OA.

Acknowledgements

This work was supported by NIH Grants R01-EB002524, R01-AR063643, K24-AR062068 and GE Healthcare

References

1. Arden N, Nevitt MC. Osteoarthritis: epidemiology. Best Practice & Research Clinical Rheumatology 2006;20(1):3-25.

2. Li X, Majumdar S. Quantitative MRI of articular cartilage and its clinical applications. J Magn Reson Imaging 2013;38(5):991-1008.

3. Hunter D, Guermazi A, Lo G, Grainger A, Conaghan P, Boudreau R, Roemer F. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthritis and Cartilage 2011;19(8):990-1002.

4. Czernin J, Satyamurthy N, Schiepers C. Molecular mechanisms of bone 18F-NaF deposition. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2010;51(12):1826-1829.

5. Roemer FW, Frobell R, Hunter DJ, Crema MD, Fischer W, Bohndorf K, Guermazi A. MRI-detected subchondral bone marrow signal alterations of the knee joint: terminology, imaging appearance, relevance and radiological differential diagnosis. Osteoarthritis Cartilage 2009;17(9):1115-1131.

Figures

Figure 1: PET (SUV) and MRI images of 2 patients with traumatic OA showing correlation between BML (blue arrow), osteophytes (red arrows), sclerosis (green arrows) on MRI with high 18F-fluoride uptake on PET.

Figure 2: PET (SUV) and MRI images of 2 patients with traumatic OA. [a] Several regions of high uptake on PET (purple arrows) do not correlate with MR findings. Additionally, [b] several small osteophytes identified on MR do not correlate with high 18F-fluoride PET uptake (orange uptake).

Figure 3: [a] Plot of average SUVmax associated with each type of bone pathology. BMLs showed significantly (p<0.001) higher 18F-fluoride uptake compared to other pathology. [b] Chart of mean and standard deviation of SUVmax between bone pathology as well as concordance between MRI findings and high uptake on PET (VOIHigh).

Figure 4: Mean SUVmax associated with MRI findings as a function of [a] BML grade and [b] osteophyte grade. Significant differences were observed between lesion grade on MRI, and PET uptake. The sensitivity of 18F-fluoride may be able to improve understanding and characterizations of these lesions.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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