Nico Sollmann1,2,3, Noah B. Bonnheim4, Gabby B. Joseph1, Ann A. Lazar5, Ravi Chachad1, Jiamin Zhou1, Jeannie F. Bailey4, Xiaojie Guo4, 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, but patient phenotyping
based on imaging that would facilitate timely and effective treatment regimens
lacks behind. One issue is that associations between different structures at
the degenerative lumbar spine are not yet well characterized. In this study we revealed
that facet joint arthropathy (FJA) at level L4/L5 is associated with the fat
fraction (FF) of adjacent paraspinal musculature (PSM) as derived from chemical
shift encoding-based water-fat MRI (CSE-MRI), as well as with Modic-type endplate
changes, endplate defects, and intervertebral degenerative disk disease (DDD)
in patients with chronic LBP.
Introduction
Globally, LBP shows a point
prevalence of activity-limiting pain of about 7%, with >500 million people
affected1,2. Notably, only in about 10% of patients can LBP be attributed to a specific
pathology, while the great majority of patients is
assigned a diagnosis of non-specific LBP3,4. This exerts negative impact on timely and
efficient treatment initiation.
One obstacle
for better understanding of contributors to LBP is that many lumbar MRI findings are common in patients
with and without LBP, thus hampering definition of causal relationships in
individual patients5,6. Further, biomechanical properties of the
lumbar spine and their alterations in response to improper load and
degeneration seem key to advanced understanding of contributors to LBP, which
would require not only focusing on one component, but investigating
associations between different structures to elucidate pain mechanisms and
patient phenotyping.
The lumbar
facet joints (FJs) can be common generators of LBP7,8. They play important
roles in load transmission, load-bearing, and restricting excessive axial
rotation7,8. Concomitant DDD
has been suggested a risk factor for FJA, but data are inconclusive and potential
additional associations of FJA with other components that may relate to altered
load sharing are scarce. A structure that is increasingly recognized as a relevant mediator in LBP is
PSM9,10, which is adjacent to FJs and has recently been
investigated by advanced quantitative imaging using CSE-MRI11,12. Against this background, this study’s
hypothesis was that FJA is associated with the FF of PSM as well as with degenerative
endplate, intervertebral disk, and vertebral body changes.Methods
Eighty-four patients suffering from chronic LBP (36 females, mean age±SD: 44.6±13.4 years) were
prospectively enrolled as 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 evidence of distinct patho-anatomical causes for LBP (e.g., disc
herniation, spondylolisthesis, lumbar scoliosis, or spondylolysis) were excluded.
All patients underwent 3-Tesla imaging of the lumbar spine, including sagittal
and axial T1- and T2-weighted FSE and iterative decomposition of water and fat
with echo asymmetry and least-squares estimation (IDEAL) sequences (Table 1)12,13. IDEAL processing considered phase error
correction, a complex-based water-fat decomposition (pre-calibrated six-peak
fat spectrum), and a single T2*14. The axial FF
maps were computed as the ratio of the fat signal over the sum of fat and water
signals15.
A musculoskeletal radiologist (>30 years of
experience) evaluated FJ changes using the grading by Pathria et al.
(Figure 1)16, bone marrow lesions at the vertebral endplates
(Modic-type endplate changes I-III)17, endplate defects (e.g., erosive intervertebral osteochondrosis or Scheuermann
variant)18,19, and DDD using the Pfirrmann classification (Figure 2)20. The bilateral multifidus and erector spinae muscles
were manually segmented21 (two consecutive slices per disc level spanning
the L1-S1 levels; Figure 3),
followed by extraction of the FF of PSM (from IDEAL; inter-rater agreement: intra-class
correlation coefficient [ICC]=0.92; intra-rater agreement: ICC=0.98). Mixed
effects models (adjusted for age, sex, and body mass index) were calculated to
assess relationships between the different scorings, FF of PSM, and the Oswestry
Disability Index (ODI)22.Results
The FF of PSM was statistically significantly associated with the
grading for FJA at level L4/L5 (β-coefficient: 1.77, 95%-confidence interval
[95%-CI]: 0.57-2.96, p=0.004), but
not at the other lumbar levels (p>0.05).
Similarly, FJA was significantly associated with Modic-type endplate changes (β-coefficient:
0.13, 95%-CI: 0.04-0.22, p=0.006),
endplate defects (β-coefficient: 0.11, 95%-CI: 0.03-0.19, p=0.011), and DDD (β-coefficient: 0.25, 95%-CI: 0.04-0.46, p=0.022) for level L4/L5, respectively.
At level L4/L5, the mean FF±SD of PSM amounted to 17.8±9.1%. Table 2 provides an overview of the
prevalence and grading of degenerative findings. Regarding self-reported pain
and disability, FJA was statistically significantly associated with the ODI at
levels L2/L3 (p=0.040), L4/L5 (p=0.005), and L5/S1 (p=0.008). Discussion
The results of
this study point towards an integrative model of degenerative spine pathology
on the basis of FJA. By showing associations between FJA and Modic-type
endplate changes, endplate defects, DDD, and, notably, FF of PSM, the interplay
between different components at the degenerative spine is emphasized. Previous
work using density measures from computed tomography (CT) or a muscle-fat index
from conventional T1-weighted imaging suggested that fatty infiltration of PSM
may relate to FJA23; yet, by
means of CSE-MRI that provides valid quantitative measures of muscle
composition24,25, this has not
been demonstrated. Further, the herein revealed relationships amongst various
spinal pathologies warrants future longitudinal studies to identify causal
mechanisms and patient phenotypes most likely to benefit from
pathology-specific treatments. Associations almost exclusively for the L4/L5
level seem to correspond to recent findings, demonstrating that cartilage endplate damage was predictive
of symptoms when adjacent to PSM with high FF12. Yet, follow-up work–ideally combining imaging
with finite element analysis to further explore the role of load sharing and
FJA26–may reveal causes for the observed
relationships at this specific level.Conclusion
In patients
with chronic LBP, FJA is associated with a range of other degenerative changes
at level L4/L5, supporting simultaneous investigation of multiple level-wise
components to better explain pain and disability. Specifically, associations
between various spinal pathologies motivates future longitudinal studies to elucidate
causal mechanisms and to identify patient phenotypes that would most likely benefit
from pathology-specific treatment strategies. 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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