Nico Sollmann1,2,3, Noah B. Bonnheim4, Gabby B. Joseph1, Ravi Chachad1, Jiamin Zhou1, Jeannie F. Bailey4, Xiaojie Guo4, Ann A. Lazar5, Thomas M. Link1, Aaron J. Fields4, and Roland Krug1
1Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 2Department of Diagnostic and Interventional Radiology, University Hospital Ulm, Ulm, Germany, 3Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, Munich, Germany, 4Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, United States, 5Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States
Synopsis
Low back pain (LBP) is a global health burden, and up to 90% of affected
patients are diagnosed with non-specific LBP. A structure increasingly
recognized as a potential contributor to LBP is paraspinal musculature (PSM). In
this study we revealed that the fat fraction (FF) of PSM derived from chemical
shift encoding-based water-fat MRI (CSE-MRI) is associated with the Goutallier
classification (GC) at each lumbar level as well as with self-reported pain. In contrast, other
parameters (muscle volume, lumbar indentation value [LIV], muscle-fat index
[MFI]) do not significantly correlate to the FF, despite being frequently used to
evaluate PSM quality.
Introduction
Globally, LBP is the most
common and costly musculoskeletal condition1. However, the clinical
management of LBP is challenged by the fact that structural causes can be
identified in just a minority of affected patients, while large numbers of
patients are diagnosed with non-specific LBP2,3.
A structure that is increasingly recognized as a
potential contributor to LBP is PSM, but findings from imaging are inconclusive
and the distinct role of PSM in LBP has not been well explored to date4,5. One potential reason is that conventional T1-
and T2-weighted sequences limit analysis to mostly qualitative morphologic
assessment and do not provide quantitative or objective information on PSM
composition. A more robust characterization of PSM using advanced quantitative
MRI could potentially help elucidate the role of PSM in LBP.
One promising technique to quantitatively and
objectively assess tissue composition is CSE-MRI6,7. However, associations between the FF of PSM
and parameters derived from conventional MRI remain unclear in patients with
chronic LBP, obscuring our understanding of how alterations in PSM composition
relate to LBP. The purpose of this study was to investigate the associations
between parameters derived from conventional MRI and the FF of PSM from CSE-MRI,
and to investigate which PSM parameters are associated with self-reported pain
in patients with chronic LBP.Methods
Eighty-four patients with chief complaint of chronic LBP (mean age±SD: 44.6±13.4 years, 36 females) were prospectively enrolled
in this study, which was part of the Back Pain Consortium (BACPAC) Research
Program, a translational effort to address the need for effective and
personalized therapies for chronic LBP. Patients with disc herniation and pain on the Visual Analogue Scale (VAS)
for leg pain ≥4 or ≥50% on the VAS for LBP, or a diagnosis of clinically
relevant lumbar vertebral abnormalities (e.g., spondylolisthesis,
spondylolysis, lumbar scoliosis) were not enrolled. Patients underwent 3-Tesla
MRI of the lumbar spine, including T1-weighted FSE and iterative decomposition
of water and fat with echo asymmetry and least-squares estimation (IDEAL)
sequences (Table 1)7,8. IDEAL processing included phase error
correction and a complex-based water-fat decomposition considering a pre-calibrated six-peak fat spectrum and a single T2*9. Axial FF
maps were computed as the ratio of the fat signal over the sum of fat and water
signals10.
The axial
T1-weighted FSE images were used to assess the GC (Figure 1)11,12 and LIV (Figure
2)11 per each spinal level (L1-S1). In addition, the
co-lateral multifidus and erector spinae muscles were manually segmented13 (two consecutive slices per disc level spanning
the L1-S1 levels; Figure 3) to calculate
the muscle volume, FF (from IDEAL), and MFI (mean muscle signal intensity
divided by mean subcutaneous fat signal intensity from T1-weighted FSE)14,15. Four
randomly selected cases were segmented by four readers, and one reader
performed two separate measurements in these selected patients. Mixed effects
and linear regression models (adjusted for age, sex, and body mass index) were calculated
to assess relationships between the different PSM parameters and with VAS
scores.Results
The FF of PSM was highest at levels L4/L5 and L5/S1 and showed excellent
inter-rater (intra-class correlation coefficient [ICC]=0.92) and intra-rater
agreement (ICC=0.98). The FF was statistically significantly associated with GC
at all investigated levels (p<0.001
per level), but not with muscle volume, LIV, or MFI (Table 2). A subgroup analysis suggested that early and subtle
changes in PSM composition are detectable with CSE-MRI but not with GC.
Furthermore, averaged over all spinal levels, the FF (β coefficient: 0.09,
95%-confidence interval [95%-CI]: 0.003–0.17, p=0.042) and GC (β coefficient: 0.98, 95%-CI: 0.27–1.68, p=0.006) were statistically significantly
associated with VAS scores for pain. Discussion
The FF provides a non-invasive, quantitative,
and objective marker of a tissue’s relative fat content6,7,10. Recently, CSE-MRI has been applied to study
the FF of PSM8,16,17, and, importantly, validated against tissue
histopathology and magnetic resonance spectroscopy18,19. Yet, in chronic LBP, CSE-MRI has only been
used in one small recent study to explore the FF related to pain, revealing
that cartilage endplate damage at level L4/L5 was predictive of pain when
adjacent to PSM that showed a high FF as a potential indicator of decreased
muscle quality8. Our results indicate that in the absence of
CSE-MRI (as a non-standard technique in LBP), the GC may be the most accurate
method of assessing fatty infiltration of PSM, as the GC score significantly
associated with the FF as well as VAS scores. Notably, subgroup analysis revealed that GC grades 0&1 were not
statistically significantly associated with FF, suggesting that the GC may,
however, fail to detect subtle changes at early stages of PSM degeneration. Yet,
detection of such early degenerative changes in patients with chronic LBP may
have important treatment implications, given that therapies targeting the PSM
may provide clinical benefit and also affect other spinal pathologies8.Conclusion
In absence of CSE-MRI, GC grading may be the best and easy-to-apply measure
for PSM quality. Given high sensitivity of CSE-MRI to fatty changes in the PSM
and its ability to detect muscle alterations at early stages of degeneration, it
may harbor great potential for further investigations of the role of PSM in
chronic LBP.Acknowledgements
This
research was supported by the National Institutes of Health through the NIH
HEAL Initiative under award numbers U19-AR076737 and UH2-AR076719 as well as by
the German Academic Exchange Service (Deutscher Akademischer Austauschdienst,
DAAD: N.S.), the Joachim Herz Foundation (N.S.), and the Rolf W. Günther
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