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Juvenile osteochondritis dissecans (JOCD) is a developmental disease characterized by formation of intra-articular (osteo)chondral flaps or fragments. Evidence-based treatment guidelines for JOCD are currently lacking. An animal model would facilitate study of JOCD and evaluation of diagnostic and treatment approaches. The purpose of this study was to assess the suitability of miniature pigs as a model of JOCD at the distal femur. First, stifle (knee) joints harvested from three juvenile miniature pigs underwent magnetic resonance imaging (MRI) to establish the vascular architecture of the distal femoral epiphyseal cartilage. Second, vessels supplying the axial or abaxial aspects of the medial femoral condyle were surgically interrupted in four additional juvenile miniature pigs, and the developing epiphyseal cartilage lesions were monitored using three consecutive MRI examinations over nine weeks. The miniature pigs were then euthanized, and their distal femora were harvested for histological evaluation. Vascular architecture of the distal femoral epiphyseal cartilage in the miniature pigs was found to be nearly identical to that of juvenile human subjects, characterized by separate vascular beds supplying the axial and abaxial aspects of the condyles. Surgical interruption of the vascular supply to the abaxial aspect of the medial femoral condyle resulted in ischemic cartilage necrosis (a precursor lesion of JOCD) in 75% (3/4) of the miniature pigs. Cartilage lesions were identified during the first MRI performed 3 weeks post-operatively. No clinically apparent JOCD-like lesions developed. In conclusion, miniature pigs are suitable for modeling JOCD precursor lesions. Further investigation of the model is warranted to assess induction of clinically apparent JOCD lesions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2130-2137, 2019., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Purpose To retrospectively determine if a modified clinical magnetic resonance (MR) imaging protocol provides information on the origin of juvenile osteochondritis dissecans (JOCD) lesions and allows for staging on the basis of the proposed natural history of JOCD to better guide clinical management of the disease. Materials and Methods This institutional review board-approved, HIPAA-compliant, retrospective study was performed in 13 consecutive patients (mean age, 14.9 years; age range, 10-22 years; nine male and four female patients) and one additional comparative patient (a 44-year-old man), in which 19 knees with 20 JOCD lesions were imaged. Seventeen lesions occurred in the medial femoral condyle, two occurred in the lateral femoral condyle, and one occurred in the medial trochlea. The clinical 3-T MR imaging protocol was supplemented with a routinely available multiecho gradient-recalled-echo sequence with the shortest attainable echo time of approximately 4 msec (T2* mapping). Results At the earliest manifestation, the lesion was entirely cartilaginous (n = 1). Subsequently, primary cartilaginous lesions within the epiphyseal cartilage developed a rim calcification that originated from normal subjacent bone, which defined a clear cleft between the lesion progeny and the parent bone (n = 9). Secondarily, progeny lesions became ossified (n = 7) while at the same time forming varying degrees of osseous bridging and/or clefting with the parent bone. Two healed lesions with a linear bony scar and one detached lesion were identified. Conclusion The modified MR imaging protocol allowed for identification of the epiphyseal cartilage origin and subsequent stages of ossification in JOCD. The approach allows further elucidation of the natural history of the disease and may better guide clinical management. © RSNA, 2016.

Purpose: To evaluate multiple MRI parameters in a surgical model of osteochondrosis (OC) in goats., Methods: Focal ischemic lesions of two different sizes were induced in the epiphyseal cartilage of the medial femoral condyles of goats at 4 days of age by surgical transection of cartilage canal blood vessels. Goats were euthanized and specimens harvested 3, 4, 5, 6, 9 and 10 weeks post-op. Ex vivo MRI scans were conducted at 9.4 Tesla for mapping the T1, T2, T1ρ, adiabatic T1ρ and TRAFF relaxation times of articular cartilage, unaffected epiphyseal cartilage, and epiphyseal cartilage within the area of the induced lesion. After MRI scans, safranin O staining was conducted to validate areas of ischemic necrosis induced in the medial femoral condyles of six goats, and to allow comparison of MRI findings with the semi-quantitative proteoglycan assessment in corresponding safranin O-stained histological sections., Results: All relaxation time constants differentiated normal epiphyseal cartilage from lesions of ischemic cartilage necrosis, and the histological staining results confirmed the proteoglycan (PG) loss in the areas of ischemia. In the scanned specimens, all of the measured relaxation time constants were higher in the articular than in the normal epiphyseal cartilage, consistently allowing differentiation between these two tissues., Conclusions: Multiparametric MRI provided a sensitive approach to discriminate between necrotic and viable epiphyseal cartilage and between articular and epiphyseal cartilage, which may be useful for diagnosing and monitoring OC lesions and, potentially, for assessing effectiveness of treatment interventions.

Ostechondritis dissecans (OCD) is an orthopaedic disease characterized by formation of osteochondral defects in developing joints. Epiphyseal cartilage necrosis (osteochondrosis [OC]) caused by focal failure of vascular supply is the known precursor lesion of OCD, but it remains to be established how the severity of vascular failure drives lesion healing or progression. In the current study we have implemented a novel piglet model of induced osteochondrosis of the lateral trochlear ridge of the femur to determine the role that the extent of ischemia plays in the development and progression of OC/OCD lesions. Ten 4-week-old Yorkshire piglets underwent surgical interruption of the vascular supply to the entirety (n = 4 pigs) or the distal half (n = 6 pigs) of the lateral trochlear ridge of the femur. At 2, 6, and 12 weeks postoperatively, distal femora were evaluated by magnetic resonance imaging (MRI) to determine the fate of induced OC lesions. At 12 weeks, piglets were euthanized, and the surgical sites were examined histologically. After complete devascularization, lesion size increased between the 6- and 12-week MRI by an average of 24.8 mm2 (95% CI: [-2.2, 51.7]; p = 0.071). During the same period, lesion size decreased by an average of 7.6 mm2 (95% CI: [-24.5, 19.4]; p = 0.83) in piglets receiving partial devascularization. At 12 weeks, average ± SD lesion size was larger (p<0.001) in piglets undergoing complete (73.5 ± 17.6 mm2) vs. partial (16.5 ± 9.8 mm2) devascularization. Our study demonstrates how the degree of vascular interruption determines lesion size and likelihood of healing in a large animal model of trochlear OC. [ABSTRACT FROM AUTHOR]

Failure of endochondral ossification due to interruption of the vascular supply to the epiphyseal cartilage is a critical step in the development of osteochondritis dissecans (OCD). Herein we describe the vascular architecture of the distal humeral epiphyseal cartilage in pigs and identify characteristic features that have been associated with sites predisposed to OCD development across species. Distal humeral specimens were harvested from pigs (n = 5, ages = 1, 10, 18, 30, and, 42 days old) and imaged at 9.4T magnetic resonance imaging (MRI) using a 3D gradient recalled echo sequence. The MRI data were processed using a quantitative susceptibility mapping (QSM) pipeline to visualize the vascular architecture. Specimens were also evaluated histologically to identify the presence of ischemic epiphyseal cartilage necrosis (osteochondrosis [OC]‐latens) and associated failure of endochondral ossification (OC‐manifesta). The QSM data enabled visualization of two distinct vascular beds arising from the perichondrium at the lateral and medial aspects of the distal humeral epiphysis. Elongated vessels originating from these beds coursed axially to supply the lateral and medial thirds of epiphyseal cartilage. At 18 days of age and older, a shift from perichondrial to transosseous blood supply was noted axially, which appeared more pronounced on the lateral side. This shift coincided with histologic identification of OC‐latens (30‐ and 42‐day‐old specimens) and OC‐manifesta (18‐ and 42‐day‐old specimens) lesions in the corresponding regions. The vascular anatomy and its evolution at the distal humeral epiphysis closely resembles that previously reported at predilection sites of knee OCD, suggesting a shared pathophysiology between the knee and elbow joints. [ABSTRACT FROM AUTHOR]

This study investigated the sensitivity of T1ρ and T2 relaxation time mapping to detect acute ischemic injury to the secondary ossification center (SOC) and epiphyseal cartilage of the femoral head in a piglet model of Legg–Calvé–Perthes disease. Six piglets underwent surgery to induce global right femoral head ischemia and were euthanized 48 h later. Fresh operated and contralateral‐control femoral heads were imaged ex vivo with T1, T2, and T1ρ mapping using a 9.4T magnetic resonance imaging scanner. The specimens were imaged a second time after a freeze/thaw cycle and then processed for histology. T1, T2, and T1ρ measurements in the SOC, epiphyseal cartilage, articular cartilage, and metaphysis were compared between operated and control femoral heads using paired t tests. The effects of freeze/thaw, T1ρ spin‐lock frequency, and fat saturation were also investigated. Five piglets with histologically confirmed ischemic injury were quantitatively analyzed. T1ρ was increased in the SOC (101 ± 15 vs. 73 ± 16 ms; p = 0.0026) and epiphyseal cartilage (84.9 ± 9.2 vs. 74.3 ± 3.6 ms; p = 0.031) of the operated versus control femoral heads. T2 was also increased in the SOC (28.7 ± 2.0 vs. 22.7 ± 1.7; p = 0.0037) and epiphyseal cartilage (57.4 ± 4.7 vs. 49.0 ± 2.7; p = 0.0041). No changes in T1 were detected. The sensitivities of T1ρ and T2 mapping in detecting ischemic injury were maintained after a freeze/thaw cycle, and T1ρ sensitivity was maintained after varying spin‐lock frequency and applying fat saturation. In conclusion, T1ρ and T2 mapping are sensitive in detecting ischemic injury to the SOC and epiphyseal cartilage of the femoral head as early as 48 h after ischemia induction. [ABSTRACT FROM AUTHOR]

Purpose: Mucopolysaccharidosis (MPS) VII is a genetic, lysosomal storage disease characterized by abnormal accumulation of glycosaminoglycans in cells and tissues. MPS VII patients exhibit multiple failures of endochondral ossification during postnatal growth, including markedly delayed cartilage-to-bone conversion in the vertebrae and long bones. Cartilage canals provide the template for vascularization at the onset of secondary ossification. The objective of this study was to investigate whether abnormal cartilage canal architecture and enzyme-mediated extracellular matrix (ECM) remodeling contribute to delayed cartilage-to-bone conversion in MPS VII. Materials and Methods: The epiphyseal cartilage canal networks of 9-day-old healthy control and MPS VII-affected dog vertebrae were characterized using high-resolution, contrast-free quantitative susceptibility mapping magnetic resonance imaging. Relative expression levels of matrix metalloproteinases (MMPs) 9, 13 and 14 were examined using immunohistochemistry, while tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) were examined using in situ enzyme staining. Results: Interestingly, the density, number, connectivity and thickness of cartilage canals was not significantly different between MPS VII and control vertebrae. Immunohistochemistry revealed diminished MMP-9, but normal MMP-13 and 14 expression by epiphyseal cartilage chondrocytes, while ALP and TRAP enzyme expression by chondrocytes and chondroclasts, respectively, were both diminished in MPS VII. Conclusions: Our findings suggest that while the epiphyseal cartilage canal network in MPS VII is normal at the onset of secondary ossification, expression of enzymes required for cartilage resorption and replacement with mineralized ECM, and initiation of angiogenesis, is impaired. [ABSTRACT FROM AUTHOR]

Background: Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder thought to be caused by disruption of blood supply to the developing femoral head. There is potential for imaging to help assess revascularization of the femoral head.Purpose: To investigate whether quantitative susceptibility mapping (QSM) can detect neovascularization in the epiphyseal cartilage following ischemic injury to the developing femoral head.Study Type: Prospective.Animal Model: Right femoral head ischemia was surgically induced in 6-week-old male piglets. The animals were sacrificed 48 hours (n = 3) or 4 weeks (n = 7) following surgery, and the operated and contralateral control femoral heads were harvested for ex vivo MRI.Field Strength/sequence: Preclinical 9.4T MRI to acquire susceptibility-weighted 3D gradient echo (GRE) images with 0.1 mm isotropic spatial resolution.Assessment: The 3D GRE images were used to manually segment the cartilage overlying the femoral head and were subsequently postprocessed using QSM. Vessel volume, cartilage volume, and vessel density were measured and compared between operated and control femoral heads at each timepoint. Maximum intensity projections of the QSM images were subjectively assessed to identity differences in cartilage canal appearance, location, and density.Statistical Tests: Paired t-tests with Bonferroni correction were used (P < 0.008 considered significant).Results: Increased vascularity of the epiphyseal cartilage following ischemic injury was clearly identified using QSM. No changes were detected 48 hours after surgery. Vessel volume, cartilage volume, and vessel density were all increased in the operated vs. control femoral heads 4 weeks after surgery (P = 0.001, 0.002, and 0.001, respectively). Qualitatively, the increase in vessel density at 4 weeks was due to the formation of new vessels that were organized in a brush-like orientation in the epiphyseal cartilage, consistent with the histological appearance of neovascularization.Data Conclusion: QSM can detect neovascularization in the epiphyseal cartilage following ischemic injury to the femoral head.Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:106-113. [ABSTRACT FROM AUTHOR]