Background: We introduce a quantitative measure of epiphyseal cartilage vascularity and examine vessel networks during human skeletal maturation. Understanding early morphological changes in the distal femoral condyle is expected to provide information on the pathogenesis of developmental diseases such as juvenile osteochondritis dissecans. Methods: Twenty-two cadaveric knees from donors ranging from 1 month to 10 years of age were included in the study. Images of bone, cartilage, and vascularity were acquired simultaneously with a 3-dimensional gradient-recalled-echo magnetic resonance imaging (MRI) sequence. The secondary ossification center volume and total epiphysis cartilage volume ratio and articular-epiphyseal cartilage complex and epiphyseal cartilage widths were measured. Epiphyseal cartilage vascularity was visualized for 9 data sets with quantitative susceptibility mapping and vessel filtering, resulting in 3-dimensional data to inform vessel network segmentation and to calculate vascular density. Results: Three distinct, non-anastomosing vascular networks (2 peripheral and 1 central) supply the distal femoral epiphyseal cartilage. The central network begins regression as early as 3 months and is absent by 4 years. From 1 month to 3 years, the ratio of central to peripheral vascular area density decreased from 1.0 to 0.5, and the ratio of central to peripheral vascular skeletal density decreased from 0.9 to 0.6. A narrow, peripheral vascular rim was present at 8 years but had disappeared by 10 years. The secondary ossification center progressively acquires the shape of the articular-epiphyseal cartilage complex by 8 years of age, and the central areas of the medial and lateral femoral condyles are the last to ossify. Conclusions: Using cadaveric pediatric knees, we provide quantitative, 3-dimensional measures of epiphyseal cartilage vascular regression during skeletal development using vessel image features. Central areas with both early vascular regression and delayed ossification correspond to predilection sites of juvenile osteochondritis dissecans in this limited case series. Our findings highlight specific vascular vulnerabilities that may lead to improved understanding of the pathogenesis and better-informed clinical management decisions in developmental skeletal diseases. Clinical Relevance: This paradigm shift in understanding of juvenile osteochondritis dissecans etiology and disease progression may critically impact future patient management. Our findings highlight specific vascular vulnerabilities during skeletal maturation in a group of active young patients seen primarily by orthopaedic surgeons and sports medicine professionals.
Bibliographical noteFunding Information:
Disclosure: One author (M.J.N.) received a grant (no. 285909) from the Academy of Finland. One author (S.Z.) received a grant (no. P41 EB015894) from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) of the National Institutes of Health (NIH). One author (F.T.) received a grant (no. K01 OD021293) from the NIH; one author (C.S.C.) served as a mentor on this grant. One author (C.P.J.) received a grant (no. K01 AR070894) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the NIH; two authors (J.M.E. and C.S.C.) served as mentors on this grant. Three authors (C.S.C., F.T., and J.M.E.) received a grant (no. R01 AR070020) from the NIAMS of the NIH. AlloSource generously provided the specimens. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A130).
NOTE: The authors thank Melissa Roy (Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota) for her contributions to the segmentation of the MRI data.
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