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 mobility
1. Magnetic resonance imaging
(MRI) provides an excellent opportunity to non-invasively study and understand
complex disease processes involved in OA
2. However,
characterization of bone pathology on MRI is limited to qualitative assessment
of osteophytes and marrow signal changes
3 and is poorly understood.
18F-fluoride is a long recognized bone-seeking agent that is able to probe bony
remodeling
4. 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 T
2 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 (SUV
max) 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 (VOI
High) on PET SUV maps. A Wilcoxon
signed-rank test was used to compare SUV
max from different bone
pathology to each other as well as within BML and osteophyte grade. Additionally,
SUV
max from VOI
High 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 VOI
High)
(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 VOI
High (25 of 26 lesions) (Figure 3b). Furthermore, SUV
max
associated with BMLs was significantly higher than that of osteophytes or
subchondral sclerosis (p<0.001) (Figure 3). Additionally, significant correlations
were observed between SUV
max and BML grade based off MOAKS scoring (p<0.05) (Figure 4a). Association
between
18F-fluoride VOI
High 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 SUV
max
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 HealthcareReferences
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