Proteomic analysis of serum in a population-based cohort did not reveal a biomarker for Modic changes.

Introduction: Modic changes (MC) are bone marrow lesions of vertebral bones, which can be detected with magnetic resonance imaging (MRI) adjacent to degenerated intervertebral discs. Defined by their appearance on T1 and T2 weighted images, there are three interconvertible types: MC1, MC2, and MC3. The inter-observer variability of the MRI diagnosis is high, therefore a diagnostic serum biomarker complementing the MRI to facilitate diagnosis and follow-up would be of great value. Methods: We used a highly sensitive and reproducible proteomics approach: DIA/SWATH-MS to find serum biomarkers in a subset of the Northern Finland Birth Cohort 1966. Separately, we measured a panel of factors involved in inflammation and angiogenesis to confirm some potential biomarkers published before with an ELISA-based method called V-Plex. Results: We found neither an association between the serum concentrations of the proteins detected with DIA/SWATH-MS with the presence of MC, nor a correlation with the size of the MC lesions. We did not find any association between the factors measured with the V-Plex and the presence of MC or their size. Conclusion: Altogether, our study suggests that a robust and generally usable biomarker to facilitate the diagnosis of MC cannot readily be found in serum.

Design of the COMEBACK and BACKHOME Studies, Longitudinal Cohorts for Comprehensive Deep Phenotyping of Adults with Chronic Low-Back Pain (cLBP): a part of the BACPAC Research Program.

Objective: The University of California, San Francisco (UCSF) Core Center for Patient-centric, Mechanistic Phenotyping in Chronic Low Back Pain (REACH) is one of the three NIH Back Pain Consortium (BACPAC) Research Programs Mechanistic Research Centers (MRCs). The goal of UCSF REACH is to define cLBP phenotypes and pain mechanisms that can lead to effective, personalized treatments for patients across the population. The primary objective of this research project is to address the critical need for new diagnostic and prognostic markers, and associated patient classification protocols for chronic low back pain (cLBP) treatment. Design: To meet this objective, REACH is conducting two large investigator-initiated translational research cohort studies called: The Longitudinal Clinical Cohort for Comprehensive Deep Phenotyping of Chronic Low-Back Pain (cLBP) Adults Study (comeBACK) and the Chronic Low-Back Pain (cLBP) in Adults Study (BACKHOME). Setting: comeBACK is a longitudinal multicenter in-person observational study of 450 adults with chronic low back pain designed to perform comprehensive deep phenotyping. While, the BACKHOME study is a site-less longitudinal observational e-cohort of approximately 3000 U.S. adults with cLBP. To our knowledge, BACKHOME is the largest prospective remote registry of nationwide adults with cLBP. Methods: Both the comeBACK and BACKHOME studies are collecting a robust and comprehensive set of risk factors, outcomes, and covariates in order to perform deep phenotyping of cLBP patients based on combined biopsychosocial variables to: define cLBP subtypes, establish phenotyping tools for routine clinical evaluation, and lead to improved cLBP outcomes in the future. The data from both studies will be used to establish techniques to develop a patient-centric definition of treatment success and to analyze cLBP patient traits to define clinically useful cLBP phenotypes, using a combination of traditional data analyses and deep learning methods. Conclusions: These 2 pivotal studies, in conjunction with the ancillary studies being performed in both comeBACK and BACKHOME, and the other BACPAC-consortium research projects, we will be able to address a number of diagnostic and therapeutic issues in this complex and diverse patient population with cLBP. These studies will help clarify biopsychosocial mechanisms of cLBP with the aim to provide a foundation to improve the evaluation of treatment effectiveness and to spur new avenues of therapeutic research, including personalized outcome measures that constitute a clinically meaningful treatment effect for individual cLBP patients.

Predictors of response in PROMIS-global in a chronic low back pain specialty clinic: STarTBack and chronic overlapping pain conditions.

BACKGROUND: Tools, such as the STarTBack Screening Tool (SBT), have been developed to identify risks of progressing to chronic disability in low back pain (LBP) patients in the primary care population. However, less is known about predictors of change in function after treatment in the specialty care population. OBJECTIVE: We pursued a retrospective observational cohort study involving LBP patients seen in a multidisciplinary specialty clinic to assess which features can predict change in function at follow-up. METHODS: The SBT was administered at initial visit, and a variety of patient characteristics were available in the chart including the presence of chronic overlapping pain conditions (COPCs). Patient Reported Outcomes Measurement Information System-10 (PROMIS-10) global physical health (PH) and global mental health (MH) were measured at baseline and at pragmatic time points during follow-up. Linear regression was used to estimate adjusted associations between available features and changes in PROMIS scores. RESULTS: 241 patients were followed for a mean of 17.0 ± 7.5 months. Mean baseline pain was 6.7 (SD 2.1), PROMIS-10 global MH score was 44.8 (SD 9.3), and PH score was 39.4 (SD 8.6). 29.7% were low-risk on the SBT, 41.8% were medium-risk, and 28.5% were high-risk. Mean change in MH and PH scores from baseline to the follow-up questionnaire were 0.86 (SD 8.11) and 2.39 (SD 7.52), respectively. Compared to low-risk patients, high-risk patients had a mean 4.35 points greater improvement in their MH score (p= 0.004) and a mean 3.54 points greater improvement in PH score (p= 0.006). Fewer COPCs also predicted greater improvement in MH and PH. CONCLUSIONS: SBT and the presence of COPC, which can be assessed at initial presentation to a specialty clinic, can predict change in PROMIS following treatment. Effort is needed to identify other factors that can help predict change in function after treatment in the specialty care setting.

Establishing a Gold Standard for Noninvasive Identification of Painful Lumbar Discs: Prospective Comparison of Magnetic Resonance Spectroscopy vs Low-Pressure Provocation Discography.

PURPOSE: Verifying lumbar disc pain can present a clinical challenge. Low-pressure provocative discography (PD) has served as the gold standard, although it is invasive and often a challenge to interpret. We reported that magnetic resonance spectroscopy (MRS) biomarkers accurately predict PD results in lumbar discs and improved outcomes for patients with surgery at positive MRS levels versus nonsurgery. To further substantiate MRS for diagnosing painful discs, we report a prospective comparison of 2 MRS-derived measures: NOCISCORE (pain) and SI-SCORE (degeneration severity). METHODS: Lumbar MRS and software-based postprocessing (NOCISCAN-LS, Aclarion Inc.) was performed in 44 discs in 14 patients (prospective cohort [PC]). PC data were compared to prior data used to establish the NOCISCORE (training cohort [TC]). The NOCISCORE was converted to an ordinal value (high/intermediate/low; NOCI+/mild/-) and compared against painful (P) versus nonpainful (NP) control diagnosis (PD) for 19 discs where PD was performed in the PC (12 NP; 7 P). Sensitivity, specificity, and positive and negative predictive values were calculated. The SI-SCORE was compared against MRI Pfirrmann Grades for 465 discs in 126 patients (PC plus TC). RESULTS: For the PC, MRS (NOCI+/-) compared to PD (P/NP) with an accuracy of 87% and sensitivity and specificity of 100%. The positive and negative predictive values of MRS were 100%. NOCISCOREs were significantly higher for PD+ versus PD- discs for PC and TC (P < 0.05), and the NOCISCORE distributions for PD+/- group were not statistically different between the PC and TC (P > 0.05). SI-SCORES differed between Pfirrmann Grades 1 and 2 (less degenerated) versus Grades 3 and 4 (more degenerated; P < 0.05), with a progressively decreasing trend with Pfirrmann Grades 1-5. CONCLUSION: These current data provide prospective confirmation of the predictive value of disc MRS for distinguishing painful discs and for assessing the disc structural integrity. CLINICAL RELEVANCE: NOCISCAN is an adoptable, noninvasive, and objectively quantitative test to improve management of low back pain patients.

Preferences for risks and benefits of treatment outcomes for chronic low back pain: Choice-based conjoint measure development and discrete choice experiment.

INTRODUCTION: Understanding individual patient preferences for chronic low back pain (cLBP) outcomes is essential for targeting available therapeutic options; yet tools to elicit patient outcome preferences are limited. OBJECTIVE: To develop and test a choice-based conjoint (CBC) measure, commonly used in behavioral economics research, to elicit what outcomes patients with cLBP want to achieve and avoid. DESIGN: We developed a survey-based CBC measure to allow patients to make risk/benefit trade-off choices between possible treatment outcomes. After extensive literature, clinician, and patient input, our measure included seven attributes: fatigue, anxiety/depression, difficulty thinking/making decisions, pain intensity, physical abilities, change in pain, and ability to enjoy life despite pain. Random-parameters logit models were used to estimate strength of preferences, and latent class analysis was used to identify patient characteristics associated with distinct preference. SETTING: Online study using the Sawtooth web-based platform. PARTICIPANTS: Two hundred eleven individuals with cLBP recruited from online advertising as well as at clinical sites across multiple academic and private institutions. INTERVENTIONS: Not applicable. RESULTS: The most valued outcome was the highest level of physical activity (ß = 1.6-1.98; p < .001), followed by avoiding cognitive difficulties (ß = -1.48; p < .001). Avoidance of severe pain was comparable to avoiding constant fatigue and near-constant depression/anxiety (ß = -0.99, -1.02); p < .001). There was an association between preferences and current pain/disability status; patients with higher pain had a stronger preference to avoid severe pain, whereas those with higher disability have stronger preferences for achieving physical activity. The latent class analysis identified two distinct groups: (1) more risk-seeking and willing to accept worse outcomes (56%); and (2) more risk-averse with a stronger preference for achieving maximum benefits (44%). CONCLUSIONS: Our study illuminated cLBP patient preferences for treatment outcomes and heterogeneity in these preferences. Patients stressed the importance of reaching high physical activity and avoiding cognitive declines, even over a desire to avoid pain. More work is needed to understand patient preferences to aid informed, shared decisions.

Type 2 diabetes impairs annulus fibrosus fiber deformation and rotation under disc compression in the University of California Davis type 2 diabetes mellitus (UCD-T2DM) rat model.

Understanding the biomechanical behavior of the intervertebral disc is crucial for studying disease mechanisms and developing tissue engineering strategies for managing disc degeneration. We used synchrotron small-angle X-ray scattering to investigate how changes to collagen behavior contribute to alterations in the disc's ability to resist compression. Coccygeal motion segments from 6-month-old lean Sprague-Dawley rats ( n=7) and diabetic obese University of California Davis type 2 diabetes mellitus (UCD-T2DM) rats ( n=6, diabetic for 68±7 days) were compressed during simultaneous synchrotron scanning to measure collagen strain at the nanoscale (beamline 7.3.3 of the Advanced Light Source). After compression, the annulus fibrosus was assayed for nonenzymatic cross-links. In discs from lean rats, resistance to compression involved two main energy-dissipation mechanisms at the nanoscale: (1) rotation of the two groups of collagen fibrils forming the annulus fibrosus and (2) straightening (uncrimping) and stretching of the collagen fibrils. In discs from diabetic rats, both mechanisms were significantly impaired. Specifically, diabetes reduced fibril rotation by 31% and reduced collagen fibril strain by 30% (compared to lean discs). The stiffening of collagen fibrils in the discs from diabetic rats was consistent with a 31% higher concentration of nonenzymatic cross-links and with evidence of earlier onset plastic deformations such as fibril sliding and fibril-matrix delamination. These findings suggest that fibril reorientation, stretching, and straightening are key deformation mechanisms that facilitate whole-disc compression, and that type 2 diabetes impairs these efficient and low-energy elastic deformation mechanisms, thereby altering whole-disc behavior and inducing the earlier onset of plastic deformation.

An exploration of knowledge-organizing technologies to advance transdisciplinary back pain research.

Chronic low back pain (LBP) is influenced by a broad spectrum of patient-specific factors as codified in domains of the biopsychosocial model (BSM). Operationalizing the BSM into research and clinical care is challenging because most investigators work in silos that concentrate on only one or two BSM domains. Furthermore, the expanding, multidisciplinary nature of BSM research creates practical limitations as to how individual investigators integrate current data into their processes of generating impactful hypotheses. The rapidly advancing field of artificial intelligence (AI) is providing new tools for organizing knowledge, but the practical aspects for how AI may advance LBP research and clinical are beginning to be explored. The goals of the work presented here are to: (1) explore the current capabilities of knowledge integration technologies (large language models (LLM), similarity graphs (SGs), and knowledge graphs (KGs)) to synthesize biomedical literature and depict multimodal relationships reflected in the BSM, and; (2) highlight limitations, implementation details, and future areas of research to improve performance. We demonstrate preliminary evidence that LLMs, like GPT-3, may be useful in helping scientists analyze and distinguish cLBP publications across multiple BSM domains and determine the degree to which the literature supports or contradicts emergent hypotheses. We show that SG representations and KGs enable exploring LBP's literature in novel ways, possibly providing, trans-disciplinary perspectives or insights that are currently difficult, if not infeasible to achieve. The SG approach is automated, simple, and inexpensive to execute, and thereby may be useful for early-phase literature and narrative explorations beyond one's areas of expertise. Likewise, we show that KGs can be constructed using automated pipelines, queried to provide semantic information, and analyzed to explore trans-domain linkages. The examples presented support the feasibility for LBP-tailored AI protocols to organize knowledge and support developing and refining trans-domain hypotheses.

Magnetic resonance spectroscopy (MRS) identification of chemically painful lumbar discs leads to improved 6-, 12-, and 24-month outcomes for discogenic low back pain surgeries.

PURPOSE: MRS was shown to reliably quantify relative levels of degenerative pain biomarkers, differentiating painful versus non-painful discs in patients with chronic discogenic low back pain (DLBP), and this correlates with surgical success rates. We now report results based on more patients and longer follow-up. METHODS: Disc MRS was performed in DLBP patients who subsequently received lumbar surgery. Custom post-processing (NOCISCAN-LS®; Aclarion Inc.) calculated disc-specific NOCISCORES® that reflect relative differences in degenerative pain biomarkers for diagnosing chemically painful discs. Outcomes in 78 patients were evaluated using Oswestry Disability Index (ODI) scores. Surgical success (≥ 15-point ODI improvement) was compared between surgeries that were "Concordant" (Group C) versus "Discordant" (Group D) with NOCISCORE-based diagnosis for painful discs. RESULTS: Success rates were higher for Group C versus Group D: 6 months (88% vs. 62%; p = 0.01), 12 months (91% vs. 56%; p < 0.001), and 24 months (85% vs. 63%; p = 0.07). Success rates for Group C surgeries were also higher than Group D surgeries in a variety of sub-group comparisons. Group C had a greater reduction in ODI from pre-operative to follow-up than Group D [absolute change (% change), (p)]: 6 months: - 35 (- 61%) versus - 23 (- 39%), (p < 0.05); 12 months: - 39 (- 69%) versus - 22 (- 39%), (p < 0.01); and 24 months: - 38 (- 66%) versus - 26 (- 48%), (p < 0.05). CONCLUSION: More successful, sustained outcomes were obtained when surgically treating chemically painful discs identified by NOCISCAN-LS post-processed disc MRS exams. Results suggest that NOCISCAN-LS provides a valuable new diagnostic tool to help clinicians better select treatment levels.

Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition.

Poor nutrient transport through the cartilage endplate (CEP) is a key factor in the etiology of intervertebral disc degeneration and may hinder the efficacy of biologic strategies for disc regeneration. Yet, there are currently no treatments for improving nutrient transport through the CEP. In this study we tested whether intradiscal delivery of a matrix-modifying enzyme to the CEP improves solute transport into whole human and bovine discs. Ten human lumbar motion segments harvested from five fresh cadaveric spines (38-66 years old) and nine bovine coccygeal motion segments harvested from three adult steers were treated intradiscally either with collagenase enzyme or control buffer that was loaded in alginate carrier. Motion segments were then incubated for 18 h at 37 °C, the bony endplates removed, and the isolated discs were compressed under static (0.2 MPa) and cyclic (0.4-0.8 MPa, 0.2 Hz) loads while submerged in fluorescein tracer solution (376 Da; 0.1 mg/ml). Fluorescein concentrations from site-matched nucleus pulposus (NP) samples were compared between discs. CEP samples from each disc were digested and assayed for sulfated glycosaminoglycan (sGAG) and collagen contents. Results showed that enzymatic treatment of the CEP dramatically enhanced small solute transport into the disc. Discs with enzyme-treated CEPs had up to 10.8-fold (human) and 14.0-fold (bovine) higher fluorescein concentration in the NP compared to site-matched locations in discs with buffer-treated CEPs (p < 0.0001). Increases in solute transport were consistent with the effects of enzymatic treatment on CEP composition, which included reductions in sGAG content of 33.5% (human) and 40% (bovine). Whole disc biomechanical behavior-namely, creep strain and disc modulus-was similar between discs with enzyme- and buffer-treated CEPs. Taken together, these findings demonstrate the potential for matrix modification of the CEP to improve the transport of small solutes into whole intact discs.

Multi-domain biopsychosocial postoperative recovery trajectories associate with patient outcomes following lumbar fusion.

PURPOSE: The purpose of this study is to describe and assess the impact of multi-domain biopsychosocial (BPS) recovery on outcomes following lumbar spine fusion. We hypothesized that discrete patterns of BPS recovery (e.g., clusters) would be identified, and then associated with postoperative outcomes and preoperative patient data. METHODS: Patient-reported outcomes for pain, disability, depression, anxiety, fatigue, and social roles were collected at multiple timepoints for patients undergoing lumbar fusion between baseline and one year. Multivariable latent class mixed models assessed composite recovery as a function of (1) pain, (2) pain and disability, and (3) pain, disability, and additional BPS factors. Patients were assigned to clusters based on their composite recovery trajectories over time. RESULTS: Using all BPS outcomes from 510 patients undergoing lumbar fusion, three multi-domain postoperative recovery clusters were identified: Gradual BPS Responders (11%), Rapid BPS Responders (36%), and Rebound Responders (53%). Modeling recovery from pain alone or pain and disability alone failed to generate meaningful or distinct recovery clusters. BPS recovery clusters were associated with number of levels fused and preoperative opioid use. Postoperative opioid use (p < 0.01) and hospital length of stay (p < 0.01) were associated with BPS recovery clusters even after adjusting for confounding factors. CONCLUSION: This study describes distinct clusters of recovery following lumbar spine fusion derived from multiple BPS factors, which are related to patient-specific preoperative factors and postoperative outcomes. Understanding postoperative recovery trajectories across multiple health domains will advance our understanding of how BPS factors interact with surgical outcomes and could inform personalized care plans.

CAPER: patient preferences to inform nonsurgical treatment of chronic low back pain: a discrete-choice experiment.

OBJECTIVE: We developed and used a discrete-choice measure to study patient preferences with regard to the risks and benefits of nonsurgical treatments when they are making treatment selections for chronic low back pain. METHODS: "CAPER TREATMENT" (Leslie Wilson) was developed with standard choice-based conjoint procedures (discrete-choice methodology that mimics an individual's decision-making process). After expert input and pilot testing, our final measure had 7 attributes (chance of pain relief, duration of relief, physical activity changes, treatment method, treatment type, treatment time burden, and risks of treatment) with 3-4 levels each. Using Sawtooth software (Sawtooth Software, Inc., Provo, UT, USA), we created a random, full-profile, balanced-overlap experimental design. Respondents (n = 211) were recruited via an emailed online link and completed 14 choice-based conjoint choice pairs; 2 fixed questions; and demographic, clinical, and quality-of-life questions. Analysis was performed with random-parameters multinomial logit with 1000 Halton draws. RESULTS: Patients cared most about the chance of pain relief, followed closely by improving physical activity, even more than duration of pain relief. There was comparatively less concern about time commitment and risks. Gender and socioeconomic status influenced preferences, especially with relation to strength of expectations for outcomes. Patients experiencing a low level of pain (Pain, Enjoyment, and General Activity Scale [PEG], question 1, numeric rating scale score<4) had a stronger desire for maximally improved physical activity, whereas those in a high level of pain (PEG, question 1, numeric rating scale score>6) preferred both maximum and more limited activity. Highly disabled patients (Oswestry Disability Index score>40) demonstrated distinctly different preferences, placing more weight on achieving pain control and less on improving physical activity. CONCLUSIONS: Individuals with chronic low back pain were willing to trade risks and inconveniences for better pain control and physical activity. Additionally, different preference phenotypes exist, which suggests a need for clinicians to target treatments to particular patients.

ISSLS Prize in Bioengineering Science 2023: Age- and sex-related differences in lumbar intervertebral disc degeneration between patients with chronic low back pain and asymptomatic controls.

PURPOSE: Clinical management of disc degeneration in patients with chronic low back pain (cLBP) is hampered by the challenge of distinguishing pathologic changes relating to pain from physiologic changes related to aging. The goal of this study was to use imaging biomarkers of disc biochemical composition to distinguish degenerative changes associated with cLBP from normal aging. METHODS: T1ρ MRI data were acquired from 133 prospectively enrolled subjects for this observational study (80 cLBP, 53 controls; mean ± SD age = 43.9 ± 13.4 years; 61 females, 72 males). The mean T1ρ relaxation time in the nucleus pulposus (NP-T1ρ; n = 650 discs) was used as a quantitative biomarker of disc biochemical composition. Linear regression was used to assess associations between NP-T1ρ and age, sex, spinal level, and study group, and their interactions. RESULTS: NP-T1ρ values were lower in cLBP patients than controls (70.8 ± 22.8 vs. 76.4 ± 22.2 ms, p = 0.009). Group differences were largest at L5-S1 (ΔT1ρcLBP-control = -11.3 ms, p < 0.0001), representing biochemical deterioration typically observed over a 9-12 year period (NP-T1ρ declined by 0.8-1.1 ms per year [95% CI]). Group differences were large in younger patients and diminished with age. Finally, the age-dependence of disc degeneration was stronger in controls than cLBP patients. CONCLUSION: Aging effects on the biochemical composition of the L5-S1 disc may involve a relatively uniform set of factors from which many cLBP patients deviate. NP-T1ρ values at L5-S1 may be highly relevant to clinical phenotyping, particularly in younger individuals.

The Back Pain Consortium (BACPAC) Research Program: Structure, Research Priorities, and Methods.

In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it is often attributed to complex, multifaceted issues involving biological, psychological, and social components. Due to the difficulty in treating the true cause of chronic low back pain (cLBP), an over-reliance on opioid pain medications among cLBP patients has developed, which is associated with increased prevalence of opioid use disorder and increased risk of death. To combat the rise of opioid-related deaths, the National Institutes of Health (NIH) initiated the Helping to End Addiction Long-TermSM (HEAL) initiative, whose goal is to address the causes and treatment of opioid use disorder while also seeking to better understand, diagnose, and treat chronic pain. The NIH Back Pain Consortium (BACPAC) Research Program, a network of 14 funded entities, was launched as a part of the HEAL initiative to help address limitations surrounding the diagnosis and treatment of cLBP. This paper provides an overview of the BACPAC research program's goals and overall structure, and describes the harmonization efforts across the consortium, define its research agenda, and develop a collaborative project which utilizes the strengths of the network. The purpose of this paper is to serve as a blueprint for other consortia tasked with the advancement of pain related science.

Theoretical Schemas to Guide Back Pain Consortium (BACPAC) Chronic Low Back Pain Clinical Research.

BACKGROUND: Chronic low back pain (cLBP) is a complex with a heterogenous clinical presentation. A better understanding of the factors that contribute to cLBP is needed for accurate diagnosis, optimal treatment, and identification of mechanistic targets for new therapies. The Back Pain Consortium (BACPAC) Research Program provides a unique opportunity in this regard, as it will generate large clinical datasets, including a diverse set of harmonized measurements. The Theoretical Model Working Group was established to guide BACPAC research and to organize new knowledge within a mechanistic framework. This article summarizes the initial work of the Theoretical Model Working Group. It includes a three-stage integration of expert opinion and an umbrella literature review of factors that affect cLBP severity and chronicity. METHODS: During Stage 1, experts from across BACPAC established a taxonomy for risk and prognostic factors (RPFs) and preliminary graphical depictions. During Stage 2, a separate team conducted a literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to establish working definitions, associated data elements, and overall strength of evidence for identified RPFs. These were subsequently integrated with expert opinion during Stage 3. RESULTS: The majority (∼80%) of RPFs had little strength-of-evidence confidence, whereas seven factors had substantial confidence for either a positive association with cLBP (pain-related anxiety, serum C-reactive protein, diabetes, and anticipatory/compensatory postural adjustments) or no association with cLBP (serum interleukin 1-beta / interleukin 6, transversus muscle morphology/activity, and quantitative sensory testing). CONCLUSION: This theoretical perspective will evolve over time as BACPAC investigators link empirical results to theory, challenge current ideas of the biopsychosocial model, and use a systems approach to develop tools and algorithms that disentangle the dynamic interactions among cLBP factors.

Magnetic Resonance Imaging of the Lumbar Spine: Recommendations for Acquisition and Image Evaluation from the BACPAC Spine Imaging Working Group.

Management of patients suffering from low back pain (LBP) is challenging and requires development of diagnostic techniques to identify specific patient subgroups and phenotypes in order to customize treatment and predict clinical outcome. The Back Pain Consortium (BACPAC) Research Program Spine Imaging Working Group has developed standard operating procedures (SOPs) for spinal imaging protocols to be used in all BACPAC studies. These SOPs include procedures to conduct spinal imaging assessments with guidelines for standardizing the collection, reading/grading (using structured reporting with semi-quantitative evaluation using ordinal rating scales), and storage of images. This article presents the approach to image acquisition and evaluation recommended by the BACPAC Spine Imaging Working Group. While the approach is specific to BACPAC studies, it is general enough to be applied at other centers performing magnetic resonance imaging (MRI) acquisitions in patients with LBP. The herein presented SOPs are meant to improve understanding of pain mechanisms and facilitate patient phenotyping by codifying MRI-based methods that provide standardized, non-invasive assessments of spinal pathologies. Finally, these recommended procedures may facilitate the integration of better harmonized MRI data of the lumbar spine across studies and sites within and outside of BACPAC studies.

The relative influence of model parameters on finite element analysis simulations of intervertebral body fusion device static compression performance.

Non-clinical mechanical performance testing is a critical aspect of intervertebral body fusion device (IBFD) development and regulatory evaluation. Recently, stakeholders have begun leveraging computational modeling and simulations such as finite element analysis (FEA) in addition to traditional bench testing. FEA offers advantages such as reduced experiment time, lower costs associated with elimination of bench testing (e.g. specimen manufacture and test execution), and elucidating quantities of interest that traditional testing cannot provide (e.g. stress and strain distributions). However, best practices for FEA of IBFDs are not well defined, and modeler decision making can significantly influence simulation setup and results. Therefore, the goal of this study was to determine the relative influence of modeling parameters when using FEA to assess non-clinical mechanical performance of IBFDs. FEA was used to conduct a series of IBFD static uniaxial compression simulations. Several parameters relating to implant geometry, loading/boundary conditions, and material properties were carefully controlled to assess their relative influence on two output variables (IBFD stiffness and yield load). Results were most influenced by device geometry, while the effects of boundary conditions and material properties were more significant within IBFDs of identical or similar geometries. These results will aid stakeholders in the development of standardized best practices for using FEA to assess non-clinical mechanical performance of IBFDs.

Magnetic Resonance Imaging Characteristics Associated with Treatment Success from Basivertebral Nerve Ablation: An Aggregated Cohort Study of Multicenter Prospective Clinical Trials Data.

OBJECTIVE: Investigate associations between endplate and motion segment magnetic resonance imaging (MRI) characteristics and treatment outcomes following basivertebral nerve radiofrequency ablation (BVN RFA) in patients with clinically suspected vertebral endplate pain (VEP). DESIGN: Aggregated cohort study of 296 participants treated with BVN RFA from three prospective clinical trials. METHODS: Baseline MRI characteristics were analyzed using stepwise logistic regression to identify factors associated with treatment success. Predictive models used three definitions of treatment success: (1) ≥50% low back pain (LBP) visual analog scale (VAS), (2) ≥15-point Oswestry Disability Index (ODI), and (3) ≥50% VAS or ≥15-point ODI improvements at 3-months post-BVN RFA. RESULTS: The presence of lumbar facet joint fluid (odds ratio [OR] 0.586) reduced the odds of BVN RFA treatment success in individuals with clinically suspected VEP. In patients with a less advanced degenerative disc disease (DDD) profile, a > 50% area of the endplate with bone marrow intensity changes (BMIC) was predictive of treatment success (OR 4.689). Both regressions areas under the curve (AUCs) were under 70%, indicating low predictive value. All other vertebral endplate, intervertebral disc, nerve roots facet joint, spinal segmental alignment, neuroforamina, lateral recesses, and central canal MRI characteristics were not associated with BVN RFA success. CONCLUSIONS: In patients with vertebrogenic low back pain with Modic changes, the presence of degenerative findings of the anterior and posterior column was not associated with a clinically important impact on BVN RFA treatment success. None of the models demonstrated strong predictive value, indicating that the use of objective imaging biomarkers (Type 1 and/or 2 Modic changes) and a correlating presentation of pain remain the most useful patient selection factors for BVN RFA.

Pain Location and Exacerbating Activities Associated with Treatment Success Following Basivertebral Nerve Ablation: An Aggregated Cohort Study of Multicenter Prospective Clinical Trial Data.

OBJECTIVE: Develop pain location "maps" and investigate the relationship between low back pain (LBP)-exacerbating activities and treatment response to basivertebral nerve radiofrequency ablation (BVN RFA) in patients with clinically suspected vertebral endplate pain (VEP). DESIGN: Aggregated cohort study of 296 patients treated with BVN RFA at 33 centers in three prospective trials. METHODS: Participant demographics, pain diagrams, and LBP-exacerbating activities were analyzed for predictors using stepwise logistic regression. Treatment success definitions were: (1) ≥50% LBP visual analog scale (VAS), (2) ≥15-point Oswestry Disability Index (ODI), and (3) ≥50% VAS or ≥15-point ODI improvements at 3 months post-BVN RFA. RESULTS: Midline LBP correlated with BVN RFA treatment success in individuals with clinically-suspected VEP. Duration of pain ≥5 years (OR 2.366), lack of epidural steroid injection within 6 months before BVN RFA (OR 1.800), lack of baseline opioid use (OR 1.965), LBP exacerbation with activity (OR 2.099), and a lack of LBP with spinal extension (OR 1.845) were factors associated with increased odds of treatment success. Regressions areas under the curve (AUCs) were under 70%, indicative of low predictive value. CONCLUSIONS: This study demonstrates that midline LBP correlates with BVN RFA treatment success in individuals with VEP. While none of the regression models demonstrated strong predictive value, the pain location and exacerbating factors identified in this analysis may aid clinicians in identifying patients where VEP should be more strongly suspected. The use of objective imaging biomarkers (Type 1 and/or 2 Modic changes) and a correlating presentation of anterior spinal element pain remain the most useful patient selection factors for BVN RFA.

Spatial distribution of fat infiltration within the paraspinal muscles: implications for chronic low back pain.

PURPOSE: Fat infiltration (FI) of the paraspinal muscles (PSMs) measured using MRI is an aspect of muscle quality and is considered to be worse in chronic low back pain (cLBP) patients. However, there is not a clear association between paraspinal muscle FI and cLBP, leaving the clinical importance of paraspinal muscle composition unestablished. The spatial distribution of FI in the PSMs may inform mechanistic understanding of non-specific cLBP as it relates to degenerative intervertebral disc (IVD) pathology. We hypothesized that paraspinal muscle fat-mapping would reveal distinct FI distribution patterns in relation to cLBP symptoms and proximity to symptomatic IVD degeneration. METHODS: From advanced-sequence water-fat MRI of 40 axial cLBP patients and 21 controls, we examined the spatial distribution of paraspinal muscle FI in relation to the center of rotation at the L4L5 disc. Using statistical parametric mapping, we compared FI patterns for multifidus (MF), erector spinae (ES), and psoas between patients and controls, and to the presence and severity of adjacent degenerative IVD pathology. RESULTS: The spatial distribution of PSMs FI differs between PSMs and according to symptoms and the adjacent degenerative IVD pathology. Furthermore, the region of MF closest to the disc center of rotation appears most susceptible to FI in the presence of symptomatic IVD degeneration. CONCLUSION: Our study identified spatial distribution patterns of FI in the PSMs as a potential diagnostic biomarker that may also provide granular mechanistic insights into spine biomechanics related to cLBP, as well as advancing the use of prior summary measures limited to overall muscle FI.