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Two neural shape models (NSMs)\u2014B-NSM (bone-only) and BC-NSM (bone+cartilage), trained on the Osteoarthritis Initiative (OAI), encoded femoral bone and cartilage shapes. The study endpoints were shape scores (B-Score, BC-Score), regional bone surface area, and cartilage thickness. Cross-sectional and longitudinal changes were assessed with linear mixed-effects models; \u03b7p\n                    <jats:sup>2<\/jats:sup>\n                    evaluated sensitivity to change. Cosine similarity compared trajectories of progressive bone and cartilage shape changes in PTOA (this data) and idiopathic-OA (OAI data).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    At 3-weeks, ACLR knee B-Scores were significantly lower (p=0.010) than contralateral knees from surgical notchplasty. Over 30-months, ACLR knee B- and BC-Scores significantly increased (p&lt;0.001, p&lt;0.001) compared to baseline, with no significant change in scores of other knees. Bone surface area (\u03b7\n                    <jats:sub>p<\/jats:sub>\n                    <jats:sup>2<\/jats:sup>\n                    =0.01) increased from periarticular osteophyte lipping rather than subchondral plate enlargement, with concomitant region-specific femoral cartilage thinning and thickening (\u03b7\n                    <jats:sub>p<\/jats:sub>\n                    <jats:sup>2<\/jats:sup>\n                    =0.02). B-Score (\u03b7\n                    <jats:sub>p<\/jats:sub>\n                    <jats:sup>2<\/jats:sup>\n                    =0.45) was more sensitive to longitudinal change than BC-Score (\u03b7\n                    <jats:sub>p<\/jats:sub>\n                    <jats:sup>2<\/jats:sup>\n                    =0.30). ACLR knee bone shape changes aligned with idiopathic-OA progression (cosine similarity=0.25); cartilage thickness changes did not (cosine similarity=0.09).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Early and progressive bone remodeling and spatiotemporal cartilage thickness changes were observed post-ACLR. Both B- and B+C-Scores outperformed bone surface area and cartilage thickness measures in quantifying longitudinal changes in ACLR knees. ACLR bone shape features exhibited a linear progressive pattern similar to idiopathic-OA, while the cartilage thickness changes were nonlinear. NSM-derived, reader-independent, shape metrics of the bone and cartilage may serve as early biomarkers to study PTOA in ACLRs, or as quantitative endpoints for prevention and early-intervention trials.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.16.25340352","type":"posted-content","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T08:10:17Z","timestamp":1763453417000},"source":"Crossref","is-referenced-by-count":0,"title":["Neural Shape Modeling Reveals Early and Progressive Femoral Bone Shape and Cartilage Thickness Changes After Anterior Cruciate Ligament Reconstruction"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-9660","authenticated-orcid":false,"given":"Anoosha","family":"Pai S","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6864-138X","authenticated-orcid":false,"given":"McKenzie S.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2564-9071","authenticated-orcid":false,"given":"Marianne S.","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth L.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4998-5846","authenticated-orcid":false,"given":"Constance R.","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3207-822X","authenticated-orcid":false,"given":"Garry E.","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0580-7308","authenticated-orcid":false,"given":"Feliks","family":"Kogan","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-3508","authenticated-orcid":false,"given":"Brian A.","family":"Hargreaves","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3667-6796","authenticated-orcid":false,"given":"Akshay S.","family":"Chaudhari","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University, Stanford, USA"},{"name":"Department of Biomedical Data Science, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6717-8979","authenticated-orcid":false,"given":"Anthony A.","family":"Gatti","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University, Stanford, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061319150508000_2025.11.16.25340352v2.1","doi-asserted-by":"crossref","unstructured":"Li, E. , Tan, J. , Xu, K. , Pan, Y. & Xu, P . 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