Haiyan Sun, Mingwei He, Jinlei Pang, Xiangfei Guo, Yansong Huo, Jun Ma
Background
Intervertebral disc degeneration (IDD) is a widespread issue associated with chronic lumbar pain and disability. This study aimed to identify lactate metabolism-related genes in IDD and elucidate their mechanistic roles in disease progression.
Methods
IDD datasets were analyzed using R packages GEOquery, sva, and limma for data retrieval, batch correction, and normalization. Differential gene expression analysis identified significant genes between IDD and control groups, from which lactate metabolism-related differentially expressed genes (LMRDEGs) were derived. Relationships among the LMRDEGs were assessed using Spearman's correlation analysis, and functional enrichment was conducted using ClusterProfiler. Gene set enrichment analysis identified biological processes associated with IDD. Diagnostic models were assessed using receiver operating characteristic (ROC) curve. Immune cell infiltration and correlations with core genes were analyzed via the CIBERSORT algorithm. Regulatory networks were constructed, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to validate the expression of hub LMRDEGs in IDD.
Results
A total of 1325 differentially expressed genes were identified, yielding seven LMRDEGs: TGFβ2, GSR, MB, MMP2, SLC16A7, PER2, and STAT3, which are enriched in blood circulation regulation and hypoxic response, as well as pathways like AGE–RAGE signaling in diabetic complications. ROC analysis indicated potential hub genes (MMP2, MB, TGFβ2, and PER2), while immune infiltration analysis uncovered significant variations in immune cell distribution. RT-qPCR confirmed MMP2, MB, and SLC16A7 as molecular indicators reflecting lactate metabolism abnormalities in IDD.
Conclusion
This study clarifies how lactate metabolism contributes to IDD through molecular mechanisms and its interplay with immunological features, providing a theoretical basis for understanding the early pathogenesis of IDD.
{"title":"Lactate Metabolism in Intervertebral Disc Degeneration: Unveiling Novel Mechanisms Through Bioinformatics","authors":"Haiyan Sun, Mingwei He, Jinlei Pang, Xiangfei Guo, Yansong Huo, Jun Ma","doi":"10.1002/jsp2.70126","DOIUrl":"https://doi.org/10.1002/jsp2.70126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a widespread issue associated with chronic lumbar pain and disability. This study aimed to identify lactate metabolism-related genes in IDD and elucidate their mechanistic roles in disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>IDD datasets were analyzed using R packages GEOquery, sva, and limma for data retrieval, batch correction, and normalization. Differential gene expression analysis identified significant genes between IDD and control groups, from which lactate metabolism-related differentially expressed genes (LMRDEGs) were derived. Relationships among the LMRDEGs were assessed using Spearman's correlation analysis, and functional enrichment was conducted using ClusterProfiler. Gene set enrichment analysis identified biological processes associated with IDD. Diagnostic models were assessed using receiver operating characteristic (ROC) curve. Immune cell infiltration and correlations with core genes were analyzed via the CIBERSORT algorithm. Regulatory networks were constructed, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to validate the expression of hub LMRDEGs in IDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1325 differentially expressed genes were identified, yielding seven LMRDEGs: <i>TGFβ2</i>, <i>GSR</i>, <i>MB</i>, <i>MMP2</i>, <i>SLC16A7</i>, <i>PER2</i>, and <i>STAT3</i>, which are enriched in blood circulation regulation and hypoxic response, as well as pathways like AGE–RAGE signaling in diabetic complications. ROC analysis indicated potential hub genes (<i>MMP2, MB, TGFβ2</i>, and <i>PER2</i>), while immune infiltration analysis uncovered significant variations in immune cell distribution. RT-qPCR confirmed <i>MMP2</i>, <i>MB</i>, and <i>SLC16A7</i> as molecular indicators reflecting lactate metabolism abnormalities in IDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study clarifies how lactate metabolism contributes to IDD through molecular mechanisms and its interplay with immunological features, providing a theoretical basis for understanding the early pathogenesis of IDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neharika Bhadouria, Justin Tiao, Angelica Baburova, Charu Jain, Bowen Wang, Antonia Demopoulos, Philip Nasser, Andrew P. Hallmark, Veeraj Shah, Jennifer R. Weiser, Deepak Vashishth, Chitra L. Dahia, Yunsoo Lee, Andrew C. Hecht, James C. Iatridis
Background
Intervertebral disc degeneration (IVDD) is a major cause of global disability that increases with age. IVD age may affect its injury susceptibility, yet few studies examine spine biomechanical changes with age, fewer address multiple injury types, and none investigate the interplay between age and injury.
Methods
An ex vivo mouse lumbar spine biomechanical study to determine the effects of age, injury, and their interaction. IVDs of 4, 12, and 24 months' mice were subjected to two injury types: Full disc puncture (DP) mimicking advanced IVDD and annulus fibrosus and endplate (AF + EP) injury simulating herniation with endplate junction failure. Spines were tested biomechanically, analyzed radiologically for IVD dimensions, and with FTIR and histology for biochemical content.
Results
Both age and injury significantly altered biomechanical properties of IVDs. Injury had a greater effect than age, and DP caused larger changes than AF + EP injury. Injury and age exhibited an interactive effect, resulting in more pronounced biomechanical dysfunction in middle-aged (12 months) and geriatric IVDs (24 months), likely due to age-related loss of proteoglycans and collagen denaturation shown with FTIR and histology.
Conclusions
We conclude that both age and injury independently and synergistically affect ex vivo biomechanical properties of mouse lumbar spine. The more severe biomechanical change in middle-aged and geriatric mouse lumbar spines suggests similar injuries may cause greater spinal dysfunction in individuals of comparable ages. These findings provide context for future in vivo studies investigating long-term effects of acute spine injuries.
{"title":"Injury Induces More Severe Biomechanical Changes in Middle-Aged and Geriatric Lumbar Spines in a Mouse Ex Vivo Model","authors":"Neharika Bhadouria, Justin Tiao, Angelica Baburova, Charu Jain, Bowen Wang, Antonia Demopoulos, Philip Nasser, Andrew P. Hallmark, Veeraj Shah, Jennifer R. Weiser, Deepak Vashishth, Chitra L. Dahia, Yunsoo Lee, Andrew C. Hecht, James C. Iatridis","doi":"10.1002/jsp2.70127","DOIUrl":"https://doi.org/10.1002/jsp2.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is a major cause of global disability that increases with age. IVD age may affect its injury susceptibility, yet few studies examine spine biomechanical changes with age, fewer address multiple injury types, and none investigate the interplay between age and injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An ex vivo mouse lumbar spine biomechanical study to determine the effects of age, injury, and their interaction. IVDs of 4, 12, and 24 months' mice were subjected to two injury types: Full disc puncture (DP) mimicking advanced IVDD and annulus fibrosus and endplate (AF + EP) injury simulating herniation with endplate junction failure. Spines were tested biomechanically, analyzed radiologically for IVD dimensions, and with FTIR and histology for biochemical content.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both age and injury significantly altered biomechanical properties of IVDs. Injury had a greater effect than age, and DP caused larger changes than AF + EP injury. Injury and age exhibited an interactive effect, resulting in more pronounced biomechanical dysfunction in middle-aged (12 months) and geriatric IVDs (24 months), likely due to age-related loss of proteoglycans and collagen denaturation shown with FTIR and histology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We conclude that both age and injury independently and synergistically affect ex vivo biomechanical properties of mouse lumbar spine. The more severe biomechanical change in middle-aged and geriatric mouse lumbar spines suggests similar injuries may cause greater spinal dysfunction in individuals of comparable ages. These findings provide context for future in vivo studies investigating long-term effects of acute spine injuries.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Condoliase is a treatment for lumbar disc herniation. This enzyme exerts its medicinal effects by digesting chondroitin sulfate (CS), which is abundant in the nucleus pulposus. However, the behavior of administered condoliase in the nucleus pulposus is not clear. Because the purpose of this study is to understand the mechanism of enzyme action, we evaluated the properties of condoliase in the nucleus pulposus.
Methods
The following were evaluated: (1) The diffusibility of fluorescein labeled condoliase injected into isolated porcine nucleus pulposus. (2) The time dependence of condoliase activity in porcine nucleus pulposus or CS solution. (3) The morphology of the enzyme-treated nucleus pulposus tissue was characterized using scanning electron microscopy.
Results
After injection into the nucleus pulposus, condoliase was difficult to diffuse spontaneously, and the rate of CS-disaccharides production was significantly increased up to a peak at 24 h and decreased thereafter. Not all of the CS in the nucleus pulposus was digested by condoliase. These results suggested that condoliase digested CS locally without causing its spontaneous diffusion within the nucleus pulposus. Moreover, condoliase did not digest the collagen fibers that form the supportive architecture of the nucleus pulposus.
Conclusions
We demonstrated that condoliase is retained in the nucleus pulposus and exerts its pharmacological effects by locally degrading CS without degrading collagen fibers. The results obtained in this study can be useful in predicting the mechanism of the pharmacological action of condoliase in clinical practice.
{"title":"Enzymatic Behavior of Condoliase in Porcine Nucleus Pulposus: Ex Vivo and In Vitro Assessment","authors":"Ippei Watanabe, Ko Takeda, Taiichi Shirogane","doi":"10.1002/jsp2.70131","DOIUrl":"https://doi.org/10.1002/jsp2.70131","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Condoliase is a treatment for lumbar disc herniation. This enzyme exerts its medicinal effects by digesting chondroitin sulfate (CS), which is abundant in the nucleus pulposus. However, the behavior of administered condoliase in the nucleus pulposus is not clear. Because the purpose of this study is to understand the mechanism of enzyme action, we evaluated the properties of condoliase in the nucleus pulposus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The following were evaluated: (1) The diffusibility of fluorescein labeled condoliase injected into isolated porcine nucleus pulposus. (2) The time dependence of condoliase activity in porcine nucleus pulposus or CS solution. (3) The morphology of the enzyme-treated nucleus pulposus tissue was characterized using scanning electron microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After injection into the nucleus pulposus, condoliase was difficult to diffuse spontaneously, and the rate of CS-disaccharides production was significantly increased up to a peak at 24 h and decreased thereafter. Not all of the CS in the nucleus pulposus was digested by condoliase. These results suggested that condoliase digested CS locally without causing its spontaneous diffusion within the nucleus pulposus. Moreover, condoliase did not digest the collagen fibers that form the supportive architecture of the nucleus pulposus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We demonstrated that condoliase is retained in the nucleus pulposus and exerts its pharmacological effects by locally degrading CS without degrading collagen fibers. The results obtained in this study can be useful in predicting the mechanism of the pharmacological action of condoliase in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Cina, Miklovana Tuci, Ferran Pellisé, Caglar Yilgor, Ahmet Alanay, Javier Pizones, Frank Kleinstück, Ibrahim Obeid, Yann Philippe Charles, Sarah Richner-Wunderlin, Fabio Galbusera, Catherine R. Jutzeler, European Spine Study Group
Background
Accurate computation of radiological parameters related to spinal alignment is clinically crucial for diagnosing and managing conditions, such as adolescent idiopathic scoliosis and adult spinal deformities. Key parameters, including sacral slope, pelvic tilt, pelvic incidence, and lumbar lordosis, are required to assess lumbosacral alignment. Artificial Intelligence (AI) has demonstrated strong potential in automating these assessments, reducing clinician workload and improving consistency. However, AI models require large, diverse, high-quality datasets to perform reliably across different clinical settings. Privacy concerns and data ownership issues often hinder data sharing, limiting the creation of centralized datasets.
Methods
In this study, we demonstrate that federated learning (FL) enables the training of deep learning models across four hospitals without compromising patient privacy. In particular, we compared FL against a centralized approach, where data from all the hospitals are pooled together and a model is trained on them, and a local approach consisting of training individual models exclusively on data from each respective hospital, resulting in distinct hospital-specific models.
Results
FL achieved performance comparable to centralized training (errors ~5°), where data is pooled, and consistently outperformed models trained on data from individual hospitals, both in internal (~8°) and external (~10°) testing.
Conclusion
This work highlights FL as a viable solution for collaborative AI development in spinal imaging, facilitating the use of diverse, multi-institutional data while circumventing privacy barriers and complex data-sharing agreements. Additionally, FL demonstrates particular benefits for smaller hospitals, enabling them to achieve superior model performance by effectively leveraging data from hospitals with larger datasets.
{"title":"Simulating Federated Learning to Enable Multi-Hospital Collaboration for Lumbopelvic Alignment Estimation","authors":"Andrea Cina, Miklovana Tuci, Ferran Pellisé, Caglar Yilgor, Ahmet Alanay, Javier Pizones, Frank Kleinstück, Ibrahim Obeid, Yann Philippe Charles, Sarah Richner-Wunderlin, Fabio Galbusera, Catherine R. Jutzeler, European Spine Study Group","doi":"10.1002/jsp2.70120","DOIUrl":"https://doi.org/10.1002/jsp2.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Accurate computation of radiological parameters related to spinal alignment is clinically crucial for diagnosing and managing conditions, such as adolescent idiopathic scoliosis and adult spinal deformities. Key parameters, including sacral slope, pelvic tilt, pelvic incidence, and lumbar lordosis, are required to assess lumbosacral alignment. Artificial Intelligence (AI) has demonstrated strong potential in automating these assessments, reducing clinician workload and improving consistency. However, AI models require large, diverse, high-quality datasets to perform reliably across different clinical settings. Privacy concerns and data ownership issues often hinder data sharing, limiting the creation of centralized datasets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we demonstrate that federated learning (FL) enables the training of deep learning models across four hospitals without compromising patient privacy. In particular, we compared FL against a centralized approach, where data from all the hospitals are pooled together and a model is trained on them, and a local approach consisting of training individual models exclusively on data from each respective hospital, resulting in distinct hospital-specific models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FL achieved performance comparable to centralized training (errors ~5°), where data is pooled, and consistently outperformed models trained on data from individual hospitals, both in internal (~8°) and external (~10°) testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work highlights FL as a viable solution for collaborative AI development in spinal imaging, facilitating the use of diverse, multi-institutional data while circumventing privacy barriers and complex data-sharing agreements. Additionally, FL demonstrates particular benefits for smaller hospitals, enabling them to achieve superior model performance by effectively leveraging data from hospitals with larger datasets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anja Stirnimann, Leon Schlagenhof, Benjamin Gantenbein, Fabian Ille
Background
Intervertebral disc (IVD) degeneration (IDD) contributes to global disability and involves incompletely understood molecular processes. Recent advances in omics technologies help to unravel the complex biology of IDD and develop novel therapies.
Methods
This narrative review explores how omics approaches—particularly RNA sequencing—have advanced our understanding of IVD biology and how these findings contribute to leveraging the intrinsic regenerative potential of the IVD, with a specific focus on nucleus pulposus progenitor cells (NPPCs). Relevant literature addressing transcriptomic, genomic, proteomic, metabolomic, and epigenetic data, as well as emerging mult-iomics approaches, was summarized.
Results
Single-omics studies have provided insight into cellular heterogeneity, gene expression changes, genetic susceptibility loci, proteomic changes, metabolic alterations, and epigenetic regulation. Further, they have highlighted key pathways associated with extracellular matrix remodeling, inflammation, and progenitor cell depletion in IDD. Inconsistencies between TEK (the gene encoding TIE2) mRNA levels and TIE2 (Angiopoietin-1 receptor) protein expression, discussed in this review, emphasize the limitations of single-omics analyses and underscore the need for multi-omics studies, which are currently underrepresented in the field. By enabling a system-level understanding, multi-omics offers a comprehensive framework to decode the networks driving IDD and identify biomarkers and therapeutic targets to restore disc function and reduce pain.
Conclusions
Although NPPCs hold promise for IVD regeneration, translational challenges such as cell survival and efficacy persist. Omics-informed insights into the IVD microenvironment may support the development of combinatorial strategies, including co-delivery of modulators to enhance NPPC survival and the effectiveness of therapies.
{"title":"Advancing Intervertebral Disc Biology via Omics: Implications for Nucleus Pulposus Progenitor Cell-Based Regeneration","authors":"Anja Stirnimann, Leon Schlagenhof, Benjamin Gantenbein, Fabian Ille","doi":"10.1002/jsp2.70130","DOIUrl":"https://doi.org/10.1002/jsp2.70130","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration (IDD) contributes to global disability and involves incompletely understood molecular processes. Recent advances in omics technologies help to unravel the complex biology of IDD and develop novel therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review explores how omics approaches—particularly RNA sequencing—have advanced our understanding of IVD biology and how these findings contribute to leveraging the intrinsic regenerative potential of the IVD, with a specific focus on nucleus pulposus progenitor cells (NPPCs). Relevant literature addressing transcriptomic, genomic, proteomic, metabolomic, and epigenetic data, as well as emerging mult-iomics approaches, was summarized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Single-omics studies have provided insight into cellular heterogeneity, gene expression changes, genetic susceptibility loci, proteomic changes, metabolic alterations, and epigenetic regulation. Further, they have highlighted key pathways associated with extracellular matrix remodeling, inflammation, and progenitor cell depletion in IDD. Inconsistencies between <i>TEK</i> (the gene encoding TIE2) mRNA levels and TIE2 (Angiopoietin-1 receptor) protein expression, discussed in this review, emphasize the limitations of single-omics analyses and underscore the need for multi-omics studies, which are currently underrepresented in the field. By enabling a system-level understanding, multi-omics offers a comprehensive framework to decode the networks driving IDD and identify biomarkers and therapeutic targets to restore disc function and reduce pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although NPPCs hold promise for IVD regeneration, translational challenges such as cell survival and efficacy persist. Omics-informed insights into the IVD microenvironment may support the development of combinatorial strategies, including co-delivery of modulators to enhance NPPC survival and the effectiveness of therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taylor J. Bader, Manmeet Dhiman, Lucas Lo Vercio, Jacques Bouchard, Fred Nicholls, Nathan Evaniew, Bradley Jacobs, Kenneth C. Thomas, Paul Salo, David A. Hart, Neil A. Duncan, Ganesh Swamy
Background
Stability of the spine and intervertebral disc (IVD) integrity is enabled by the highly organized fibrocartilaginous annulus fibrosus (AF). The shear properties of the AF are important in maintaining IVD integrity. AF shear mechanics in degenerative disc (DD) remain underexplored, especially in comparing minimally degenerative (non-DD) and symptomatic DD individuals. This study measured tissue mechanical properties (AF simple shear modulus and dynamic shear properties) and examined structure (with optical coherence tomography (OCT)) in surgical DD and non-DD control individuals.
Methods
Whole AF tissue samples were collected from non-DD donors (N = 13) and DD surgical individuals (N = 30). Two anterior outer AF (OAF) 5 mm cubes were sectioned from each sample and subjected to shear in two orientations, radial (coronal plane, G1) and circumferential (sagittal plane, G2). Tissues underwent static shear and dynamic shear protocols to a maximum of 10% shear strain. Following mechanical tests, average lamellar thickness was assessed using OCT.
Results
Static shear moduli were significantly reduced for DD tissue compared to non-DD in both the radial (G1) (non-DD: 83.0 ± 41.3 kPa, DD: 24.1 ± 23.7 kPa) and the circumferential (G2) (non-DD: 226.2 ± 81.9 kPa, DD: 54.0 ± 40.2 kPa) orientations (p < 0.05). Further dynamic mechanical alterations were detected in hysteresis, phase shift, and dynamic modulus. Shear moduli correlated negatively with lamellar thickness (G1: rs = −0.63, G2: rs = −0.71).
Conclusions
There were significant alterations in AF shear moduli and dynamic properties in DD individuals when compared to non-DD controls. Structural correlations highlight the role of the highly organized AF lamellar structure on shear modulus values. These findings suggest that altered AF mechanics may contribute to DD pathology and associated low back pain, warranting further investigation into structural and functional AF changes in symptomatic individuals.
{"title":"Reduced Shear Modulus and Altered Lamellar Morphology of the Outer Annulus Fibrosus in Painful Intervertebral Disc Degeneration Compared With Tissue From Non-Surgical Controls","authors":"Taylor J. Bader, Manmeet Dhiman, Lucas Lo Vercio, Jacques Bouchard, Fred Nicholls, Nathan Evaniew, Bradley Jacobs, Kenneth C. Thomas, Paul Salo, David A. Hart, Neil A. Duncan, Ganesh Swamy","doi":"10.1002/jsp2.70123","DOIUrl":"10.1002/jsp2.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Stability of the spine and intervertebral disc (IVD) integrity is enabled by the highly organized fibrocartilaginous annulus fibrosus (AF). The shear properties of the AF are important in maintaining IVD integrity. AF shear mechanics in degenerative disc (DD) remain underexplored, especially in comparing minimally degenerative (non-DD) and symptomatic DD individuals. This study measured tissue mechanical properties (AF simple shear modulus and dynamic shear properties) and examined structure (with optical coherence tomography (OCT)) in surgical DD and non-DD control individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole AF tissue samples were collected from non-DD donors (<i>N</i> = 13) and DD surgical individuals (<i>N</i> = 30). Two anterior outer AF (OAF) 5 mm cubes were sectioned from each sample and subjected to shear in two orientations, radial (coronal plane, G1) and circumferential (sagittal plane, G2). Tissues underwent static shear and dynamic shear protocols to a maximum of 10% shear strain. Following mechanical tests, average lamellar thickness was assessed using OCT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Static shear moduli were significantly reduced for DD tissue compared to non-DD in both the radial (G1) (non-DD: 83.0 ± 41.3 kPa, DD: 24.1 ± 23.7 kPa) and the circumferential (G2) (non-DD: 226.2 ± 81.9 kPa, DD: 54.0 ± 40.2 kPa) orientations (<i>p</i> < 0.05). Further dynamic mechanical alterations were detected in hysteresis, phase shift, and dynamic modulus. Shear moduli correlated negatively with lamellar thickness (G1: r<sub>s</sub> = −0.63, G2: r<sub>s</sub> = −0.71).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There were significant alterations in AF shear moduli and dynamic properties in DD individuals when compared to non-DD controls. Structural correlations highlight the role of the highly organized AF lamellar structure on shear modulus values. These findings suggest that altered AF mechanics may contribute to DD pathology and associated low back pain, warranting further investigation into structural and functional AF changes in symptomatic individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madison M. Buckles, Abdulkadir Nur, Nada H. Warda, Jacob C. Moncher, Mohammad Yunus Ansari
Background
The nucleus pulposus (NP) in the intervertebral disc (IVD) is the first structure to exhibit degenerative changes during IVD degeneration (IDD). Currently, micro-computed tomography (micro-CT) imaging of the NP is a limiting factor in detecting IDD at an early stage. While contrast-enhanced micro-CT has been investigated, an effective contrast agent for IVD has not been identified. This study investigates potassium iodide (KI) as an effective contrast agent for micro-CT-based IVD visualization across multiple animal models to study IDD.
Methods
We collected tails and spines from mice, rats, rabbits, sheep, and stained them with KI followed by micro-CT imaging. For IDD, we performed caudal annular needle puncture surgery (NPS) in age and sex-matched mice (n = 10) and stained with KI for imaging with micro-CT. For the aging model, we compared IVDs from old to young mice.
Results
Compared to unstained IVDs, KI effectively stained and visualized the 3D structure of the NP, exhibiting X-ray attenuation properties comparable to bone. KI contrast staining enabled accurate and reproducible quantification of IVD height and NP volume. The cross-sectional micro-CT images of NPS IVDs were indistinguishable from the histological findings of the same sample and showed similar degenerative changes in the NP. We also found that KI staining is reversible, and the tissue remains compatible with downstream histological processing and immunostaining. Notably, KI successfully stained the NP in decalcified tissue, offering an advantage for NP analysis by removing bone background in micro-CT scans. Additionally, we estimated that up to 15 sagittal sections, each 5 μm thick with 75 μm spacing, would be needed to fully assess IVD degeneration in mice.
Conclusions
This study demonstrated that KI can be used to positively stain NP in the intact tail or spine and provide qualitative and quantitative data without any adverse effects on the immune/histological processing of the samples.
{"title":"High-Resolution 3-Dimensional Micro-CT Imaging of Intervertebral Discs Using a Novel Contrast Agent","authors":"Madison M. Buckles, Abdulkadir Nur, Nada H. Warda, Jacob C. Moncher, Mohammad Yunus Ansari","doi":"10.1002/jsp2.70125","DOIUrl":"10.1002/jsp2.70125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The nucleus pulposus (NP) in the intervertebral disc (IVD) is the first structure to exhibit degenerative changes during IVD degeneration (IDD). Currently, micro-computed tomography (micro-CT) imaging of the NP is a limiting factor in detecting IDD at an early stage. While contrast-enhanced micro-CT has been investigated, an effective contrast agent for IVD has not been identified. This study investigates potassium iodide (KI) as an effective contrast agent for micro-CT-based IVD visualization across multiple animal models to study IDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected tails and spines from mice, rats, rabbits, sheep, and stained them with KI followed by micro-CT imaging. For IDD, we performed caudal annular needle puncture surgery (NPS) in age and sex-matched mice (<i>n</i> = 10) and stained with KI for imaging with micro-CT. For the aging model, we compared IVDs from old to young mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to unstained IVDs, KI effectively stained and visualized the 3D structure of the NP, exhibiting X-ray attenuation properties comparable to bone. KI contrast staining enabled accurate and reproducible quantification of IVD height and NP volume. The cross-sectional micro-CT images of NPS IVDs were indistinguishable from the histological findings of the same sample and showed similar degenerative changes in the NP. We also found that KI staining is reversible, and the tissue remains compatible with downstream histological processing and immunostaining. Notably, KI successfully stained the NP in decalcified tissue, offering an advantage for NP analysis by removing bone background in micro-CT scans. Additionally, we estimated that up to 15 sagittal sections, each 5 μm thick with 75 μm spacing, would be needed to fully assess IVD degeneration in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrated that KI can be used to positively stain NP in the intact tail or spine and provide qualitative and quantitative data without any adverse effects on the immune/histological processing of the samples.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ravij Mehta, Sarthak Mohanty, Andrew Parker Hallmark, Veeraj Shah, Tom Ross, Eric A. Bogner, Tejbir S. Pannu, Mathieu Bannwarth, Sohrab Virk, Sravisht Iyer, James C. Farmer, Russel C. Huang, Darren R. Lebl, Bernard A. Rawlins, Harvinder S. Sandhu, Han Jo Kim, Matthew E. Cunningham, Sheeraz Qureshi, Todd J. Albert, Chitra L. Dahia
Background
Aging is a major risk factor for IVD degeneration and chronic lower back pain. Comparing degenerative patterns in human and mice, a commonly used pre-clinical model, is crucial for validating it in preclinical mechanistic research. The goal of the study was to compare the effect of age and spine level on degeneration in human and mouse lumbar IVDs.
Methods
T2-weighted MRI images of human lumbar spine were graded using the Pfirrmann system. H&E-stained mid-coronal sections of mouse lumbar IVDs were scored using the Melgoza and Chenna system. Age, gender, IVD level, and lumbar IVD degeneration scores, respectively, were used for statistical analysis in each species. Linear regression and one-way ANOVA with post hoc Tukey analysis were used to compare regression slopes and intercepts. Age conversion from mouse to human was performed according to the Jackson Laboratory's outline of mouse age and its human equivalents. Generalized estimating equations (GEE) were used to model continuous degeneration scores, accounting for intra-subject correlation due to multiple IVD levels per subject. Main effects included sex, IVD level (L1–S1), and age, with an interaction term assessing the impact of age across levels. An autoregressive correlation structure was specified.
Results
Age significantly correlated with IVD degeneration in humans (p < 0.0001) and mice (p < 0.0002). And the IVD level predicted degeneration in both species (L5–S1 in human, and L6–S1 in mice). Normalizing age and pathology revealed an earlier onset of degeneration in humans than in mice.
Conclusions
Age and spinal IVD level influence lumbar IVD degeneration in both human and mice with a higher rate of degeneration at the lumbosacral junction in both species. These findings suggest that mice are a suitable model for studying the cellular and molecular basis of IVD degeneration and associated neurological symptoms, with the L6–S1 level being the most relevant.
{"title":"Age and Spinal Level as Predictors of Lumbar Disc Degeneration in Humans and Mice: A Comparative Analysis","authors":"Ravij Mehta, Sarthak Mohanty, Andrew Parker Hallmark, Veeraj Shah, Tom Ross, Eric A. Bogner, Tejbir S. Pannu, Mathieu Bannwarth, Sohrab Virk, Sravisht Iyer, James C. Farmer, Russel C. Huang, Darren R. Lebl, Bernard A. Rawlins, Harvinder S. Sandhu, Han Jo Kim, Matthew E. Cunningham, Sheeraz Qureshi, Todd J. Albert, Chitra L. Dahia","doi":"10.1002/jsp2.70122","DOIUrl":"10.1002/jsp2.70122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Aging is a major risk factor for IVD degeneration and chronic lower back pain. Comparing degenerative patterns in human and mice, a commonly used pre-clinical model, is crucial for validating it in preclinical mechanistic research. The goal of the study was to compare the effect of age and spine level on degeneration in human and mouse lumbar IVDs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>T2-weighted MRI images of human lumbar spine were graded using the Pfirrmann system. H&E-stained mid-coronal sections of mouse lumbar IVDs were scored using the Melgoza and Chenna system. Age, gender, IVD level, and lumbar IVD degeneration scores, respectively, were used for statistical analysis in each species. Linear regression and one-way ANOVA with post hoc Tukey analysis were used to compare regression slopes and intercepts. Age conversion from mouse to human was performed according to the Jackson Laboratory's outline of mouse age and its human equivalents. Generalized estimating equations (GEE) were used to model continuous degeneration scores, accounting for intra-subject correlation due to multiple IVD levels per subject. Main effects included sex, IVD level (L1–S1), and age, with an interaction term assessing the impact of age across levels. An autoregressive correlation structure was specified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Age significantly correlated with IVD degeneration in humans (<i>p</i> < 0.0001) and mice (<i>p</i> < 0.0002). And the IVD level predicted degeneration in both species (L5–S1 in human, and L6–S1 in mice). Normalizing age and pathology revealed an earlier onset of degeneration in humans than in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Age and spinal IVD level influence lumbar IVD degeneration in both human and mice with a higher rate of degeneration at the lumbosacral junction in both species. These findings suggest that mice are a suitable model for studying the cellular and molecular basis of IVD degeneration and associated neurological symptoms, with the L6–S1 level being the most relevant.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kevin M. Bell, Rachel E. Roos, Zakiy Alfikri, William Anderst, Anna Bailes, William W. Clark, Harold A. Cook, Jessa Darwin, Marit Johnson, Gina P. McKernan, Sebastian Murati, Bambang Parmanto, Nam V. Vo, Leming Zhou, Gwendolyn A. Sowa
<div> <section> <h3> Background</h3> <p>The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB<sup>3</sup>P conducted a prospective, observational cohort study to identify phenotypes from over 1000 participants with chronic low back pain (cLBP). This article reports findings from multi-level inertial measurement unit (IMU) kinematic data collected during performance-based tests obtained at the in-person LB<sup>3</sup>P enrollment visit.</p> </section> <section> <h3> Methods</h3> <p>Participants with cLBP were recruited and performed self-paced and fast-paced movements while wearing inertial measurement units (IMUs) placed over T1/T2, T12/L1, L5/S1, and along the right femur. For self-paced tests: axial rotation (AR), lateral bending (LB), and flexion and extension (F/E), participants performed to their maximum range of motion (ROM), and for fast-paced tests: combined rotation/flexion (CRF), AR, LB, flexion, five times sit to stand (5STS), and postural lifting strategy (PLS), participants performed at their maximum speed. ROM, velocity, acceleration, and lumbopelvic rhythm (LPR) were calculated for tests using IMU data. LPR was calculated as the ratio of absolute lumbar to hip movement and was extracted for each motion quartile (0%–25%, 25%–50%, 50%–75%, and 75%–100%) during neutral-to-flexion and neutral-to-extension.</p> </section> <section> <h3> Results</h3> <p>Analysis of sensor data of 954 participants (58.6 ± 16.4 years old; 40% male and 60% female) revealed variable kinematic patterns across spinal and hip regions during isolated and functional movements. Noticeable variations were observed based on movement type, with the trunk region demonstrating predominant mobility during self-paced movements like AR and LB, while the hip region played a critical role in functional tasks (CRF, 5STS, PLS). LPR evaluation indicated that individuals with cLBP typically adopt a hip-dominant movement pattern, with slightly greater lumbar contributions during the initial phase of flexion. Sex and age analyses unveiled females generally exhibit greater ROM and higher velocities compared to males. Younger participants (< 60 years old) show more dynamic movement patterns, except in the hip region during F/E, where older (≥ 60) participants exhibited greater excursion.</p> </section> <section> <h3> Conclusions</h3> <p>This study characterized spinal and hip movement in
{"title":"Lumbopelvic Kinematics During Functional Tasks in a Chronic Low Back Pain Observational Cohort","authors":"Kevin M. Bell, Rachel E. Roos, Zakiy Alfikri, William Anderst, Anna Bailes, William W. Clark, Harold A. Cook, Jessa Darwin, Marit Johnson, Gina P. McKernan, Sebastian Murati, Bambang Parmanto, Nam V. Vo, Leming Zhou, Gwendolyn A. Sowa","doi":"10.1002/jsp2.70117","DOIUrl":"https://doi.org/10.1002/jsp2.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB<sup>3</sup>P conducted a prospective, observational cohort study to identify phenotypes from over 1000 participants with chronic low back pain (cLBP). This article reports findings from multi-level inertial measurement unit (IMU) kinematic data collected during performance-based tests obtained at the in-person LB<sup>3</sup>P enrollment visit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants with cLBP were recruited and performed self-paced and fast-paced movements while wearing inertial measurement units (IMUs) placed over T1/T2, T12/L1, L5/S1, and along the right femur. For self-paced tests: axial rotation (AR), lateral bending (LB), and flexion and extension (F/E), participants performed to their maximum range of motion (ROM), and for fast-paced tests: combined rotation/flexion (CRF), AR, LB, flexion, five times sit to stand (5STS), and postural lifting strategy (PLS), participants performed at their maximum speed. ROM, velocity, acceleration, and lumbopelvic rhythm (LPR) were calculated for tests using IMU data. LPR was calculated as the ratio of absolute lumbar to hip movement and was extracted for each motion quartile (0%–25%, 25%–50%, 50%–75%, and 75%–100%) during neutral-to-flexion and neutral-to-extension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analysis of sensor data of 954 participants (58.6 ± 16.4 years old; 40% male and 60% female) revealed variable kinematic patterns across spinal and hip regions during isolated and functional movements. Noticeable variations were observed based on movement type, with the trunk region demonstrating predominant mobility during self-paced movements like AR and LB, while the hip region played a critical role in functional tasks (CRF, 5STS, PLS). LPR evaluation indicated that individuals with cLBP typically adopt a hip-dominant movement pattern, with slightly greater lumbar contributions during the initial phase of flexion. Sex and age analyses unveiled females generally exhibit greater ROM and higher velocities compared to males. Younger participants (< 60 years old) show more dynamic movement patterns, except in the hip region during F/E, where older (≥ 60) participants exhibited greater excursion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study characterized spinal and hip movement in ","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145196320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Richard D. Bell, Evie C. Reddick, David J. Lillyman, Fei San Lee, Rebecca A. Wachs
Background
Preclinical models of disc degeneration are important tools to discover disease pathology. Histopathology is often used to understand these changes, but analyses remain reliant on pathologists or graders using time-consuming scoring systems. The integration of computational pathology can improve this process by leveraging machine learning (ML) algorithms. Thus, this work aimed to develop a segmentation model to identify seven distinct disc tissues and utilize the segmented tissue areas generated from the model, along with other derived measures, to estimate pathological changes that align with traditional histological scoring.
Methods
Hematoxylin and eosin-stained motion segment sections were collected from four independent studies. Each study included a disc injury puncture in Sprague Dawley rats. An active learning technique and a trained deep convolutional neural network were used to infer tissue segmentation. The model was then applied to untrained images to infer tissue segmentation, extract geometric and cell count features, and correlate these measurements with histologic scores from a standard scoring system.
Results
The segmentation model was highly performant with an Intersection over Union (mIOU) and frequency weighted Intersection over Union (fwIOU) of 0.83 ± 0.04 and 0.94 ± 0.02 in the Test set, respectively. The ML-derived measures correlated well with histologic scores, with absolute ranges from rho = 0.65 to 0.87. Further, these ML-derived measures were altered with disc degeneration with significant differences in NP cell number, NP area ratio, NP/AF border, NP roundness, and AF perimeter. Lastly, our model could measure additional tissue changes not captured through a standard histological scoring system.
Conclusions
Herein, we developed the first computational pathology model to phenotype disc degeneration tissue. Our model significantly correlates with traditional histopathology scoring methods, detects subtle differences between groups by directly measuring pathologic features in the images, and increases efficiency by automating the majority of the process.
背景椎间盘退变的临床前模型是发现疾病病理的重要工具。组织病理学通常用于了解这些变化，但分析仍然依赖于病理学家或使用耗时评分系统的评分员。计算病理学的整合可以通过利用机器学习（ML）算法来改善这一过程。因此，本研究旨在建立一个分割模型，以识别七种不同的椎间盘组织，并利用该模型产生的分割组织区域，以及其他衍生测量，来估计与传统组织学评分一致的病理变化。方法收集4个独立研究的苏木精和伊红染色的运动切片。每项研究都包括在Sprague Dawley大鼠中穿刺椎间盘损伤。采用主动学习技术和训练好的深度卷积神经网络进行组织分割。然后将该模型应用于未经训练的图像，以推断组织分割，提取几何和细胞计数特征，并将这些测量结果与标准评分系统中的组织学评分相关联。结果该分割模型具有良好的分割性能，在测试集中，mIOU （Intersection over Union）和fwIOU （frequency weighted Intersection over Union）分别为0.83±0.04和0.94±0.02。ml衍生的测量结果与组织学评分有很好的相关性，其绝对范围为rho = 0.65至0.87。此外，这些ml衍生的测量随椎间盘退变而改变，在NP细胞数量、NP面积比、NP/AF边界、NP圆度和AF周长方面存在显著差异。最后，我们的模型可以测量通过标准组织学评分系统无法捕获的额外组织变化。在此，我们建立了第一个计算病理模型来表型椎间盘退变组织。我们的模型与传统的组织病理学评分方法显著相关，通过直接测量图像中的病理特征来检测组间的细微差异，并通过自动化大部分过程来提高效率。
{"title":"Automated Computational Pathology to Assess Degenerative Disc Histology","authors":"Richard D. Bell, Evie C. Reddick, David J. Lillyman, Fei San Lee, Rebecca A. Wachs","doi":"10.1002/jsp2.70119","DOIUrl":"https://doi.org/10.1002/jsp2.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preclinical models of disc degeneration are important tools to discover disease pathology. Histopathology is often used to understand these changes, but analyses remain reliant on pathologists or graders using time-consuming scoring systems. The integration of computational pathology can improve this process by leveraging machine learning (ML) algorithms. Thus, this work aimed to develop a segmentation model to identify seven distinct disc tissues and utilize the segmented tissue areas generated from the model, along with other derived measures, to estimate pathological changes that align with traditional histological scoring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Hematoxylin and eosin-stained motion segment sections were collected from four independent studies. Each study included a disc injury puncture in Sprague Dawley rats. An active learning technique and a trained deep convolutional neural network were used to infer tissue segmentation. The model was then applied to untrained images to infer tissue segmentation, extract geometric and cell count features, and correlate these measurements with histologic scores from a standard scoring system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The segmentation model was highly performant with an Intersection over Union (mIOU) and frequency weighted Intersection over Union (fwIOU) of 0.83 ± 0.04 and 0.94 ± 0.02 in the Test set, respectively. The ML-derived measures correlated well with histologic scores, with absolute ranges from rho = 0.65 to 0.87. Further, these ML-derived measures were altered with disc degeneration with significant differences in NP cell number, NP area ratio, NP/AF border, NP roundness, and AF perimeter. Lastly, our model could measure additional tissue changes not captured through a standard histological scoring system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Herein, we developed the first computational pathology model to phenotype disc degeneration tissue. Our model significantly correlates with traditional histopathology scoring methods, detects subtle differences between groups by directly measuring pathologic features in the images, and increases efficiency by automating the majority of the process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145196259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号