Pub Date : 2026-03-07eCollection Date: 2026-03-01DOI: 10.1002/jsp2.70167
Chunshuai Wu, Chaochen Li, Guanhua Xu, Jiajia Chen, Liangliang Wang, Haiyan Gu, Jinlong Zhang, Hongxiang Hong, Chunyan Ji, Zhiming Cui
Background: Traumatic cervical spinal cord injury (TCSCI) often leads to significant patient paralysis. Current clinical diagnosis relies heavily on empirical interpretation of magnetic resonance imaging (MRI) and the American Spinal Injury Association Impairment Scale (AIS) grade, lacking robust quantitative markers to precisely reflect injury severity. This study aimed to build an artificial intelligence (AI) pipeline for AIS grade prediction based on radiomic features extracted from manually defined regions.
Methods: We included 189 patients with TCSCI who underwent MRI within 48 h post-injury. MRI images from 130 patients were used for developing an AI model encompassing image segmentation. Radiomic features were extracted from manually delineated volumes of interest (VOIs). T2-weighted imaging (T2WI) sagittal images were randomly divided into training (n = 104), validation (n = 13), and test (n = 13) sets for segmentation. A total of 183 patients (excluding AIS E) were included in the AIS grade prediction task. Model performance was evaluated using mean dice similarity coefficient (mDICE), mean intersection over union (mIOU), mean specificity, and mean sensitivity.
Results: An optimized UCTransnet network, leveraging a Transformer architecture for formal training, combined with a U-Net++ network for pretraining, achieved promising results in segmenting the spinal cord injury site on T2WI sagittal images (mDICE: 0.777 ± 0.021, mIOU: 0.646 ± 0.025, mean specificity: 0.998 ± 0.001, mean sensitivity: 0.895 ± 0.015). Subsequently, an ensemble model (we named Em-En) constructed using selected radiomic features from the manual VOIs demonstrated superior performance for predicting AIS grades in terms of sensitivity, specificity, accuracy, and clinical decision-making benefit compared to other tested models.
Conclusions: This study presents an AI-assisted pipeline for predicting the severity of TCSCI. The developed resources provide a theoretical foundation for the clinical application of AI-assisted diagnostic methods, potentially lowering the interpretation barrier for MRI and offering clinicians preliminary quantitative indicators of injury severity. The source code is publicly available.
{"title":"Severity Prediction of Traumatic Cervical Spinal Cord Injury With an AI Model Based on MRI Radiomics.","authors":"Chunshuai Wu, Chaochen Li, Guanhua Xu, Jiajia Chen, Liangliang Wang, Haiyan Gu, Jinlong Zhang, Hongxiang Hong, Chunyan Ji, Zhiming Cui","doi":"10.1002/jsp2.70167","DOIUrl":"10.1002/jsp2.70167","url":null,"abstract":"<p><strong>Background: </strong>Traumatic cervical spinal cord injury (TCSCI) often leads to significant patient paralysis. Current clinical diagnosis relies heavily on empirical interpretation of magnetic resonance imaging (MRI) and the American Spinal Injury Association Impairment Scale (AIS) grade, lacking robust quantitative markers to precisely reflect injury severity. This study aimed to build an artificial intelligence (AI) pipeline for AIS grade prediction based on radiomic features extracted from manually defined regions.</p><p><strong>Methods: </strong>We included 189 patients with TCSCI who underwent MRI within 48 h post-injury. MRI images from 130 patients were used for developing an AI model encompassing image segmentation. Radiomic features were extracted from manually delineated volumes of interest (VOIs). T2-weighted imaging (T2WI) sagittal images were randomly divided into training (<i>n</i> = 104), validation (<i>n</i> = 13), and test (<i>n</i> = 13) sets for segmentation. A total of 183 patients (excluding AIS E) were included in the AIS grade prediction task. Model performance was evaluated using mean dice similarity coefficient (mDICE), mean intersection over union (mIOU), mean specificity, and mean sensitivity.</p><p><strong>Results: </strong>An optimized UCTransnet network, leveraging a Transformer architecture for formal training, combined with a U-Net++ network for pretraining, achieved promising results in segmenting the spinal cord injury site on T2WI sagittal images (mDICE: 0.777 ± 0.021, mIOU: 0.646 ± 0.025, mean specificity: 0.998 ± 0.001, mean sensitivity: 0.895 ± 0.015). Subsequently, an ensemble model (we named Em-En) constructed using selected radiomic features from the manual VOIs demonstrated superior performance for predicting AIS grades in terms of sensitivity, specificity, accuracy, and clinical decision-making benefit compared to other tested models.</p><p><strong>Conclusions: </strong>This study presents an AI-assisted pipeline for predicting the severity of TCSCI. The developed resources provide a theoretical foundation for the clinical application of AI-assisted diagnostic methods, potentially lowering the interpretation barrier for MRI and offering clinicians preliminary quantitative indicators of injury severity. The source code is publicly available.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 1","pages":"e70167"},"PeriodicalIF":3.9,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12966994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377744","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}
Pub Date : 2026-03-03eCollection Date: 2026-03-01DOI: 10.1002/jsp2.70168
Hisakazu Shitozawa, Ryo Nakamichi, Aki Yoshida, Masataka Ueda, Taichi Saito, Koji Uotani, Yoshiaki Oda, Ryo Takatori, Kazutaka Yamashita, Toshifumi Ozaki
Objective: Major cause of low-back pain is intervertebral disc degeneration (IVDD), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel, PIEZO1, is involved in various musculoskeletal tissues, but its role in the annulus fibrosus (AF) remains unclear. This study aimed to elucidate the function of PIEZO1 in AF cells under mechanical stimulation.
Methods: Primary rat AF cells were subjected to cyclic tensile strain (CTS) at low (2%) and high (12%) strain levels to investigate strain-dependent effects on osteogenic gene expression. We evaluated the effects of Piezo1, Piezo2, and Trpv4 knockdown by RNA interference to identify the upstream mechanotransducer. Furthermore, PIEZO1 was activated using the agonist Yoda1, followed by RNA-sequencing analysis and evaluation of its effects on BMP2-induced osteogenesis in rat AF cells. We also examined the effects of Yoda1 in primary human AF cells.
Results: Low-strain CTS significantly suppressed osteogenic marker expression, which was not observed with high strain. Piezo1 knockdown reversed this suppression, whereas Piezo2 and Trpv4 had no effect. Piezo1 activation by Yoda1 produced similar anti-osteogenic effects in both rat and human AF cells. RNA sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited BMP2-induced osteogenesis and nuclear translocation of p-Smad1/5/9.
Conclusions: Piezo1 maintains AF cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin-mediated inhibition of BMP signaling, which may represent a novel therapeutic target for IVDD.
{"title":"Mechanosensitive Ion Channel PIEZO1 Suppresses BMP2-Induced Ossification of the Annulus Fibrosus Cells.","authors":"Hisakazu Shitozawa, Ryo Nakamichi, Aki Yoshida, Masataka Ueda, Taichi Saito, Koji Uotani, Yoshiaki Oda, Ryo Takatori, Kazutaka Yamashita, Toshifumi Ozaki","doi":"10.1002/jsp2.70168","DOIUrl":"https://doi.org/10.1002/jsp2.70168","url":null,"abstract":"<p><strong>Objective: </strong>Major cause of low-back pain is intervertebral disc degeneration (IVDD), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel, PIEZO1, is involved in various musculoskeletal tissues, but its role in the annulus fibrosus (AF) remains unclear. This study aimed to elucidate the function of PIEZO1 in AF cells under mechanical stimulation.</p><p><strong>Methods: </strong>Primary rat AF cells were subjected to cyclic tensile strain (CTS) at low (2%) and high (12%) strain levels to investigate strain-dependent effects on osteogenic gene expression. We evaluated the effects of <i>Piezo1</i>, <i>Piezo2</i>, and <i>Trpv4</i> knockdown by RNA interference to identify the upstream mechanotransducer. Furthermore, PIEZO1 was activated using the agonist Yoda1, followed by RNA-sequencing analysis and evaluation of its effects on BMP2-induced osteogenesis in rat AF cells. We also examined the effects of Yoda1 in primary human AF cells.</p><p><strong>Results: </strong>Low-strain CTS significantly suppressed osteogenic marker expression, which was not observed with high strain. <i>Piezo1</i> knockdown reversed this suppression, whereas <i>Piezo2</i> and <i>Trpv4</i> had no effect. Piezo1 activation by Yoda1 produced similar anti-osteogenic effects in both rat and human AF cells. RNA sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited BMP2-induced osteogenesis and nuclear translocation of p-Smad1/5/9.</p><p><strong>Conclusions: </strong>Piezo1 maintains AF cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin-mediated inhibition of BMP signaling, which may represent a novel therapeutic target for IVDD.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 1","pages":"e70168"},"PeriodicalIF":3.9,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355113","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}
Erin Archibeck, Nicholas Harris, Patricia Zheng, Aaron Scheffler, Wolf Mehling, Conor O'Neill, Jeffrey Lotz, Grace O'Connell, Jeannie F Bailey
Background: Individuals with chronic low back pain (LBP) often present with significant physical dysfunction. The underlying cause is difficult to diagnose due to the heterogeneous nature of LBP categories.
Methods: Two hundred and fifty-six patients were assessed as having either nociceptive (NC) or nociplastic (NP) chronic low back pain using validated surveys, including the PainDETECT Questionnaire and a chronic overlapping pain condition screener. Additional covariates of anxiety, depression, and fear avoidance were evaluated using standard surveys. Physical function was judged objectively using a sit-to-stand test (STS; quantified using marker-less motion capture calculated kinematic scores and movement metrics) and subjectively (PROMIS-physical function survey). Demographics (age, sex, BMI), psychological factors, and biomechanical outcomes were compared across pain categories using nonparametric statistics and regression modeling.
Results: Compared to the NC group, the NP group was significantly older (NP: 61.0 ± 21.0, NC: 53.5 ± 29.3, p = 0.03) and reported higher levels of anxiety (NP: 51.2 ± 17.4, NC: 48.0 ± 13.4, p = 0.002) and depression (NP: 49.0 ± 14.7, NC: 41.0 ± 10.8, p = 0.009). NP also had worse perceived physical function (PROMIS-PF) (NP: 39.3 ± 6.9, NC: 42.1 ± 7.3, p < 0.001) and slower STS times (NP: 12.5 ± 6.1 s, NC: 12.0 ± 5.8, p = 0.03). Despite these differences, the NP group exhibited biomechanical function closer to the healthy control average motion trajectory (K-score; NP: 77.6 ± 8.1, NC: 75.6 ± 8.1, p = 0.03) during the STS task. Regression models evaluating the association between biomechanical variables and pain categories, while adjusting for age, sex, and BMI, identified significant differences between pain categories only for PROMIS-physical function.
Conclusion: While individuals with nociplastic pain reported lower perceived physical function and exhibited differences in demographic and psychological factors, pain categories were not significant predictors of objective biomechanical measures after adjusting for age, sex, and BMI. However, pain category was a significant predictor of PROMIS-PF, suggesting that it is more closely associated with perceived functional limitations than with quantitative biomechanical performance.
{"title":"Comparing Movement Patterns and Physical Function Between Chronic Low Back Pain Patients With Nociplastic and Nociceptive Pain Categories.","authors":"Erin Archibeck, Nicholas Harris, Patricia Zheng, Aaron Scheffler, Wolf Mehling, Conor O'Neill, Jeffrey Lotz, Grace O'Connell, Jeannie F Bailey","doi":"10.1002/jsp2.70166","DOIUrl":"https://doi.org/10.1002/jsp2.70166","url":null,"abstract":"<p><strong>Background: </strong>Individuals with chronic low back pain (LBP) often present with significant physical dysfunction. The underlying cause is difficult to diagnose due to the heterogeneous nature of LBP categories.</p><p><strong>Methods: </strong>Two hundred and fifty-six patients were assessed as having either nociceptive (NC) or nociplastic (NP) chronic low back pain using validated surveys, including the PainDETECT Questionnaire and a chronic overlapping pain condition screener. Additional covariates of anxiety, depression, and fear avoidance were evaluated using standard surveys. Physical function was judged objectively using a sit-to-stand test (STS; quantified using marker-less motion capture calculated kinematic scores and movement metrics) and subjectively (PROMIS-physical function survey). Demographics (age, sex, BMI), psychological factors, and biomechanical outcomes were compared across pain categories using nonparametric statistics and regression modeling.</p><p><strong>Results: </strong>Compared to the NC group, the NP group was significantly older (NP: 61.0 ± 21.0, NC: 53.5 ± 29.3, <i>p</i> = 0.03) and reported higher levels of anxiety (NP: 51.2 ± 17.4, NC: 48.0 ± 13.4, <i>p</i> = 0.002) and depression (NP: 49.0 ± 14.7, NC: 41.0 ± 10.8, <i>p</i> = 0.009). NP also had worse perceived physical function (PROMIS-PF) (NP: 39.3 ± 6.9, NC: 42.1 ± 7.3, <i>p</i> < 0.001) and slower STS times (NP: 12.5 ± 6.1 s, NC: 12.0 ± 5.8, <i>p</i> = 0.03). Despite these differences, the NP group exhibited biomechanical function closer to the healthy control average motion trajectory (K-score; NP: 77.6 ± 8.1, NC: 75.6 ± 8.1, <i>p</i> = 0.03) during the STS task. Regression models evaluating the association between biomechanical variables and pain categories, while adjusting for age, sex, and BMI, identified significant differences between pain categories only for PROMIS-physical function.</p><p><strong>Conclusion: </strong>While individuals with nociplastic pain reported lower perceived physical function and exhibited differences in demographic and psychological factors, pain categories were not significant predictors of objective biomechanical measures after adjusting for age, sex, and BMI. However, pain category was a significant predictor of PROMIS-PF, suggesting that it is more closely associated with perceived functional limitations than with quantitative biomechanical performance.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 1","pages":"e70166"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12950820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348353","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}
Jan Ulrich Jansen, Graciosa Quelhas Teixeira, Elias Salzer, Andrea Vernengo, Sibylle Grad, Keita Ito, Cornelia Neidlinger-Wilke, Hans-Joachim Wilke
Background: Biomaterials play an increasing role in intervertebral disc regeneration and require preclinical testing, typically performed using organ culture and in vitro models. Native human discs are limited, and animal models often fail to mimic human disc degeneration. Thus, enzymes like chondroitinase ABC (chABC) and papain are used to simulate degenerative tissue changes and enable biomaterial injection. In previous work, we characterized the biomechanical and morphological effects of papain, which forms cavities in the disc. In contrast, chABC does not form cavities, but its biomechanical effects remain insufficiently characterized. This study aims to evaluate the macroscopic and biomechanical effects of chABC-specifically, range of motion (ROM), neutral zone (NZ), and disc height-in a bovine organ culture model, and assess the distribution of an injected hydrogel, comparing the results to published papain data.
Methods: Four groups of fresh bovine tail segments were prepared (n ≥ 10) and three received injections of chABC, papain, or PBS, followed by 7 days of culture. For papain and PBS, published data were supplemented with new specimens. Complex simulated physiological loading was applied to diminish disc swelling. The maximum volume of a serum-albumin-hydrogel was injected into all four groups. ROM, NZ, and disc height were measured before and after enzyme treatment, loading, and injection. Post-injection, microCT scans visualized material distribution within the discs.
Results: ChABC increased ROM by up to 92.1%, NZ by up to 79.4%, and decreased disc height by 2.1 mm. Hydrogel injection decreased ROM and NZ but increased disc height in all groups while enzyme treatments allowed more hydrogel injection (0.6 mL for chABC). Exemplary scans showed cloud-like hydrogel spread for chABC and a round-shaped degradation defect for papain.
Conclusions: The findings indicate that chABC better simulates disc degeneration, whereas papain better models nucleotomies, and both enzymes preserve annulus integrity-providing valuable models for biomechanical testing.
{"title":"Chondroitinase Versus Papain Digestion Leads to Different Outcome for In Vitro Simulation of Degenerated Discs.","authors":"Jan Ulrich Jansen, Graciosa Quelhas Teixeira, Elias Salzer, Andrea Vernengo, Sibylle Grad, Keita Ito, Cornelia Neidlinger-Wilke, Hans-Joachim Wilke","doi":"10.1002/jsp2.70164","DOIUrl":"10.1002/jsp2.70164","url":null,"abstract":"<p><strong>Background: </strong>Biomaterials play an increasing role in intervertebral disc regeneration and require preclinical testing, typically performed using organ culture and in vitro models. Native human discs are limited, and animal models often fail to mimic human disc degeneration. Thus, enzymes like chondroitinase ABC (chABC) and papain are used to simulate degenerative tissue changes and enable biomaterial injection. In previous work, we characterized the biomechanical and morphological effects of papain, which forms cavities in the disc. In contrast, chABC does not form cavities, but its biomechanical effects remain insufficiently characterized. This study aims to evaluate the macroscopic and biomechanical effects of chABC-specifically, range of motion (ROM), neutral zone (NZ), and disc height-in a bovine organ culture model, and assess the distribution of an injected hydrogel, comparing the results to published papain data.</p><p><strong>Methods: </strong>Four groups of fresh bovine tail segments were prepared (<i>n</i> ≥ 10) and three received injections of chABC, papain, or PBS, followed by 7 days of culture. For papain and PBS, published data were supplemented with new specimens. Complex simulated physiological loading was applied to diminish disc swelling. The maximum volume of a serum-albumin-hydrogel was injected into all four groups. ROM, NZ, and disc height were measured before and after enzyme treatment, loading, and injection. Post-injection, microCT scans visualized material distribution within the discs.</p><p><strong>Results: </strong>ChABC increased ROM by up to 92.1%, NZ by up to 79.4%, and decreased disc height by 2.1 mm. Hydrogel injection decreased ROM and NZ but increased disc height in all groups while enzyme treatments allowed more hydrogel injection (0.6 mL for chABC). Exemplary scans showed cloud-like hydrogel spread for chABC and a round-shaped degradation defect for papain.</p><p><strong>Conclusions: </strong>The findings indicate that chABC better simulates disc degeneration, whereas papain better models nucleotomies, and both enzymes preserve annulus integrity-providing valuable models for biomechanical testing.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 1","pages":"e70164"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12950828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348333","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}
Chitra L. Dahia, Lachlan J. Smith, Makarand V. Risbud, Benjamin Gantenbein
The seventh biennial ORS-PSRS International Spine Research Symposium was held from November 10-14, 2024, at Skytop Lodge in Pennsylvania, USA. Jointly organized by the PSRS and ORS, the meeting brought together over 195 participants from 13 countries. Selected contributors were invited to submit full-length manuscripts for this JOR Spine Special Issue.