Min Chen1,2, Chuanli Cheng1, Chao Zou1, and Guanxun Cheng2
1Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China, 2Radiology Department, Peking University Shenzhen Hospital, Shenzhen, China
Synopsis
Keywords: Joints, Quantitative Imaging, axial spondyloarthritis; bone marrow; fatty acids
Changes
of bone marrow fatty acids (FAs) composition have been detected in several
inflammatory and metabolic diseases by MRI. However, the alteration of
sacroiliac FAs composition in axial spondyloarthritis (axSpA) remains unknown.
We observed changes of bone marrow FAs composition of the sacroiliac joint in
patients with axSpA compared to controls using chemical shift-encoded MRI
(CSE-MRI). The changes differed between areas with fat metaplasia and areas
without fat metaplasia in axSpA. Our results indicated bone marrow FAs
including saturated FA, mono-unsaturated FA and poly-unsaturated FA may play
different roles in the pathogenesis of axSpA.
Introduction
Axial spondyloarthritis (axSpA) is a group of inflammatory
diseases that can cause chronic low back pain, stiffness and bone fusion of the
axial skeleton1. Immunological alterations in axSpA lead to abnormal
activity of osteoblasts, osteoclasts, fibroclasts and macrophages, and cause
inflammation, bone erosion and abnormal bone proliferation2. MRI
studies have shown that subchondral fat metaplasia in the sacroiliac joint is
useful in diagnosis of axSpA and may play a key role in the development of
joint ankylosis3, indicating bone marrow fat alteration may have a
place in the disease pathogenesis. Triglycerides that contribute to MR signal
of human lipids can be categorized as saturated (SFA), monounsatrurated (MUFA)
and poly unsaturated (PUFA) fatty acids4. Changes of bone marrow
fatty acids composition in osteoporosis, diabetes, osteoarthritis and systemic
lupus erythematous has been detected in vivo using MRI5,6. The
alteration of bone marrow fat saturation have not been investigated in axSpA.
In this study, we aimed to bone marrow fatty acids composition of the
sacroiliac joint in patients with axSpA compared to controls using chemical
shift-encoded MRI (CSE-MRI).Methods
Patients with axSpA and non-SpA controls (age and body mass
index matched) were prospectively included. All patients underwent an MRI scan
of the sacroiliac joint on a clinical 3.0T MRI scanner (uMR780, United Imaging,
Shanghai, China) with a 12-channel body flexed array coil. An additional multiple
gradient-echo CSE-MRI protocol was added for fatty acids analysis, including
two consecutively scanned 20-echo sequences. For sequence 1, the 20 TEs gave an
echo train length of n= (1:20) × 1.58 ms. For sequence 2, the 20 TEs gave an
echo train length of n= 0.78 + (1:20) × 1.58 ms. The other parameters were
identical for the two sequences as following: repetition time (TR) = 35 ms,
flip angle (FA) =5 °, receiver bandwidth = 900 Hz, number of averages (NA) = 1,
field of view = 400 × 305 mm, acquisition matrix = 208 × 118, the reconstructed
pixel resolution = 0.96 × 0.96 mm2, slice thickness = 2 mm, 48 axial
slices, scan time = 1:04 minutes. Fatty acids maps were generated by previously
described postprocessing methods7 using MATLAB (MathWorks, Natick,
Massachusetts). Regions of interest (ROIs) for FAs measurements were manually
placed in the subchondral area of sacrum and ilium. In axSpA patients, ROIs
were placed in areas with and without fat metaplasia.
Regions with obvious bone
marrow edema and sclerosis were avoided. The following intergroup comparison of
proton-density fat fraction (PDFF), SFA, UFA, MUFA and PUFA was performed using
independent t test: (1) areas with fat metaplasia in axSpA vs non-SpA, and (2)
areas without fat metaplasia in axSpA vs non-SpA. Examples of FA maps are shown in Figure 1.Results
In total, 48 patients with axSpA (mean age, 32.5 ± 6.2 years,
25 male, 23 female,) and 37 non-SpA controls (mean age, 32.1 ± 6.1 years, 18
male, 19 female) were included. Results of FA composition analysis and
comparison between axSpA vs. controls are summarized in Table 1 and Figure 2.
In male, axSpA patients showed significant increase in MUFA
(+12%, p<0.001), decrease in PUFA (-10%, p=0.001) in areas with fat
metaplasia, and decrease in SFA (-6%, p=0.001), increase in MUFA (+10%,
p=0.002) in areas without fat metaplasia in the sacrum; and significant
increase in MUFA (+9%, p<0.001), decrease in PUFA (-11%, p<0.001) in
areas with fat metaplasia of the ilium in comparison to controls.
In female, significant change was found only in SFA in areas
with fat metaplasia of the ilium (+7%, p=0.036) in patients with axSpA.Discussion
Previous studies indicated that SFA, MUFA, PUFA may have
different roles on bone metabolism and inflammation process8. In general, our study showed a decrease of PUFA and increase of MUFA in
axSpA, and the changes were more significant in male and in areas with fat
metaplasia. PUFA was suggested to be protective for bone health through promoting
osteoblastgenesis and enhancing osteoblastic activity8, and showed
anti-inflammatory effects by reducing inflammatory cytokines production
production9. Our finding indicated that PUFA may also play a role in
the pathogenesis of axSpA. The
role of MUFA on bone metabolism and inflammation was not consistent in
literature. In our study, we found a significant increase of MUFA in the sacrum
and ilium in male patients with axSpA, and a tendency of MUFA increase in the
sacrum in female patients. In contrast, there was a tendency of decrease of
MUFA in the ilium of female with axSpA. Most human in vitro studies suggested that SFA can induce inflammation and
showed pro-inflammatory actions9. In our study, SFA decreased in
areas without fat metaplasia and increased in areas with fat metaplasia in
axSpA, and the changes were significant in the sacrum of male, and in the ilium
of female, respectively. We hypothesized that the decrease of SFA in the areas
without fat metaplasia in axSpA may represent a compensation in the disease
procedure.Conclusion
In conclusion, our results indicated that bone marrow FAs
composition of the sacroiliac joint alter in patients with axSpA and can be
detected using CSE-MRI. Bone marrow FAs may play a role in the pathogenesis of
the disease.Acknowledgements
This work was supported by the General Program for Clinical
Research at Peking University Shenzhen Hospital (No. LCYJ2021007) and Shenzhen
High-level Hospital Fund.References
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