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Purpose: To evaluate the influence of skeletal maturation on sodium (23Na) MRI relaxation parameters and the accuracy of tissue sodium concentration (TSC) quantification in human knee cartilage. Methods: Twelve pediatric knee specimens were imaged with whole‐body 10.5 T MRI using a density‐adapted 3D radial projection sequence to evaluate 23Na parameters: B1+, T1, biexponential T2*$$ {\mathrm{T}}_2^{\ast } $$, and TSC. Water, collagen, and sulfated glycosaminoglycan (sGAG) content were calculated from osteochondral biopsies. The TSC was corrected for B1+, relaxation, and water content. The literature‐based TSC (TSCLB) used previously published values for corrections, whereas the specimen‐specific TSC (TSCSP) used measurements from individual specimens. 23Na parameters were evaluated in eight cartilage compartments segmented on proton images. Associations between 23Na parameters, TSCLB − TSCSP difference, biochemical content, and age were determined. Results: From birth to 12 years, cartilage water content decreased by 18%; collagen increased by 59%; and sGAG decreased by 36% (all R2 ≥ 0.557). The short T2*$$ {\mathrm{T}}_2^{\ast } $$ (T2*S$$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$) decreased by 72%, and the signal fraction relaxing with T2*S$$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ (fT2*S$$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$) increased by 55% during the first 5 years but remained relatively stable after that. TSCSP was significantly correlated with sGAG content from biopsies (R2 = 0.739). Depending on age, TSCLB showed higher or lower values than TSCSP. The TSCLB − TSCSP difference was significantly correlated with T2*S$$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.850), fT2*S$$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.651), and water content (R2 = 0.738). Conclusion: TSC and relaxation parameters measured with 23Na MRI provide noninvasive information about changes in sGAG content and collagen matrix during cartilage maturation. Cartilage TSC quantification assuming fixed relaxation may be feasible in children older than 5 years. [ABSTRACT FROM AUTHOR]

Current clinical MRI of patients with juvenile osteochondritis dissecans (JOCD) is limited by the low reproducibility of lesion instability evaluation and inability to predict which lesions will heal after nonoperative treatment and which will later require surgery. The aim of this study is to verify the ability of apparent diffusion coefficient (ADC) to detect differences in lesion microstructure between different JOCD stages, treatment groups, and healthy, unaffected contralateral knees. Pediatric patients with JOCD received quantitative diffusion MRI between January 2016 and September 2020 in this prospective research study. A disease stage (I‐IV) and stability of each JOCD lesion was evaluated. ADCs were calculated in progeny lesion, interface, parent bone, cartilage overlying lesion, control bone, and control cartilage regions. ADC differences were evaluated using linear mixed models with Bonferroni correction. Evaluated were 30 patients (mean age, 13 years; 21 males), with 40 JOCD‐affected and 12 healthy knees. Nine patients received surgical treatment after MRI. Negative Spearman rank correlations were found between ADCs and JOCD stage in the progeny lesion (ρ = −0.572; p < 0.001), interface (ρ = −0.324; p = 0.041), and parent bone (ρ = −0.610; p < 0.001), demonstrating the sensitivity of ADC to microstructural differences in lesions at different JOCD stages. We observed a significant increase in the interface ADCs (p = 0.007) between operative (mean [95% CI] = 1.79 [1.56–2.01] × 10−3 mm2/s) and nonoperative group (1.27 [0.98–1.57] × 10−3 mm2/s). Quantitative diffusion MRI detects microstructural differences in lesions at different stages of JOCD progression towards healing and reveals differences between patients assigned for operative versus nonoperative treatment. [ABSTRACT FROM AUTHOR]

Juvenile osteochondritis dissecans (JOCD) is a pediatric orthopedic disorder that involves the articular–epiphyseal cartilage complex and underlying bone. Clinical disease is often characterized by the presence of radiographically apparent osteochondral flaps and fragments. The existence of early JOCD lesions (osteochondrosis latens [OCL] and osteochondrosis manifesta [OCM]) that precede the development of osteochondral flaps and fragments is also well recognized. However, identification of naturally occurring OCL lesions (confined to cartilage) using noninvasive imaging techniques has not yet been accomplished. We hypothesized that 10.5 T magnetic resonance imaging (MRI) can identify naturally occurring OCL lesions at predilection sites in intact joints of juvenile pigs. Unilateral elbows and knees (stifles) were harvested from three pigs aged 4, 8, and 12 weeks, and scanned in a 10.5 T MRI to obtain morphological 3D DESS images, and quantitative T2 and T1ρ relaxation time maps. Areas with increased T2 and T1ρ relaxation times in the articular–epiphyseal cartilage complex were identified in 1/3 distal femora and 3/3 distal humeri and were considered suspicious for OCL or OCM lesions. Histological assessment confirmed the presence of OCL or OCM lesions at each of these sites and failed to identify additional lesions. Histological findings included necrotic vascular profiles associated with areas of chondronecrosis either confined to the epiphyseal cartilage (OCL, 4‐ and 8‐week‐old specimens) or resulting in a delay in endochondral ossification (OCM, 12‐week‐old specimen). Future studies with clinical MR systems (≤7 T) are needed to determine whether these MRI methods are suitable for the in vivo diagnosis of early JOCD lesions in humans. Statement of Clinical Significance: Having identified quantitative and morphological markers useful for the early identification and characterization of juvenile osteochondritis dissecans lesions in ex vivo pig specimens on the highly sensitive 10.5 T magnetic resonance imaging platform, the methods are poised for future translation to human studies at clinical field strengths. [ABSTRACT FROM AUTHOR]

Juvenile osteochondritis dissecans (JOCD) is an orthopedic joint disorder of children and adolescents that can lead to premature osteoarthritis. Thirteen patients (mean age: 12.3 years, 4 females), 15 JOCD‐affected and five contralateral healthy knees, that had a baseline and a follow‐up magnetic resonance imaging (MRI) (mean interval of 8.9 months) and were treated nonoperatively during this interval were included. Retrospectively, patients were assigned to operative or nonoperative groups based on their electronic medical records. Volumetric mean T2* values were calculated within regions of interest (progeny lesion, interface, parent bone) and region matched control bone in healthy contralateral knees and condyles. The normalized percentage difference of T2* between baseline and follow up MRI in nonoperative patients significantly increased in progeny lesion (−47.8%, p < 0.001), parent bone (−13.9%, p < 0.001), and interface (−32.3%, p = 0.011), whereas the differences in operative patients were nonsignificant and below 11%. In nonoperative patients, the progeny lesion (p < 0.001) and interface T2* values (p = 0.012) were significantly higher than control bone T2* at baseline, but not at follow‐up (p = 0.219, p = 1.000, respectively). In operative patients, the progeny lesion and interface T2* values remained significantly elevated compared to the control bone both at baseline (p < 0.001, p < 0.001) and follow‐up (p < 0.001, p < 0.001), respectively. Clinical Significance: Longitudinal T2* mapping differentiated nonhealing from healing JOCD lesions following initial nonoperative treatment, which may assist in prognosis and improve the ability of surgeons to make recommendations regarding operative versus nonoperative treatment. [ABSTRACT FROM AUTHOR]

Juvenile osteochondritis dissecans (JOCD) lesions contain cartilaginous, fibrous and osseous tissues which are difficult to distinguish with clinical, morphological magnetic resonance imaging (MRI). Quantitative T2* mapping has earlier been used to evaluate microstructure and composition of all aforementioned tissues as well as bone mineral density. However, the ability of T2* mapping to detect changes in tissue composition between different JOCD lesion regions, different disease stages, and between stable and unstable lesions has not been demonstrated. This study analyzed morphological and T2* MRI data from 25 patients (median age, 12.1 years) with 34 JOCD‐affected and 13 healthy knees. Each lesion was assigned a stage reflecting the natural history of JOCD, with stages I and IV representing early and healed lesion, respectively. T2* values were evaluated within the progeny lesion, interface and parent bone of each lesion and in the control bone region. T2* was negatively correlated with JOCD stage in progeny lesion (ρ = −0.871; p < 0.001) and interface regions (ρ = −0.649; p < 0.001). Stage IV progeny showed significantly lower T2* than control bone (p = 0.028). T2* was significantly lower in parent bone than in control bone of patients with stable lesions (p = 0.009), but not in patients with unstable lesions (p = 0.14). Clinical significance: T2* mapping enables differentiation between different stages of JOCD and quantitative measurement of the ossification degree in progeny lesion and interface. The observed T2* decrease in healed and stable lesions may indicate increased bone density as a result of the active repair process. T2* mapping provides quantitative information about JOCD lesion composition. [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]

Background: Osteochondritis dissecans (OCD) occurs most commonly in the knees of young individuals. This condition is known to cause pain and discomfort in the knee and can lead to disability and early knee osteoarthritis. The cause is not well understood, and treatment plans are not well delineated. The Research in Osteochondritis Dissecans of the Knee (ROCK) group established a multicenter, prospective cohort to better understand this disease. Purpose: To provide a baseline report of the ROCK multicenter prospective cohort and present a descriptive analysis of baseline data for patient characteristics, lesion characteristics, and clinical findings of the first 1000 cases enrolled into the prospective cohort. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients were recruited from centers throughout the United States. Baseline data were obtained for patient characteristics, sports participation, patient-reported measures of functional capabilities and limitations, physical examination, diagnostic imaging results, and initial treatment plan. Descriptive statistics were completed for all outcomes of interest. Results: As of November 2020, a total of 27 orthopaedic surgeons from 17 institutions had enrolled 1004 knees with OCD, representing 903 patients (68.9% males; median age, 13.1 years; range, 6.3-25.4 years), into the prospective cohort. Lesions were located on the medial femoral condyle (66.2%), lateral femoral condyle (18.1%), trochlea (9.5%), patella (6.0%), and tibial plateau (0.2%). Most cases involved multisport athletes (68.1%), with the most common primary sport being basketball for males (27.3% of cases) and soccer for females (27.6% of cases). The median Pediatric International Knee Documentation Committee (Pedi-IKCD) score was 59.9 (IQR, 45.6-73.9), and the median Pediatric Functional Activity Brief Scale (Pedi-FABS) score was 21.0 (IQR, 5.0-28.0). Initial treatments were surgical intervention (55.4%) and activity restriction (44.0%). When surgery was performed, surgeons deemed the lesion to be stable at intraoperative assessment in 48.1% of cases. Conclusion: The multicenter ROCK group has been able to enroll the largest knee OCD cohort to date. This information is being used to further understand the pathology of OCD, including its cause, associated comorbidities, and initial presentation and symptoms. The cohort having been established is now being followed longitudinally to better define and elucidate the best treatment algorithms based on these presenting signs and symptoms. [ABSTRACT FROM AUTHOR]

➤: Osteochondritis dissecans occurs most frequently in the active pediatric and young adult populations, commonly affecting the knee, elbow, or ankle, and may lead to premature osteoarthritis.➤: While generally considered an idiopathic phenomenon, various etiopathogenetic theories are being investigated, including local ischemia, aberrant endochondral ossification of the secondary subarticular physis, repetitive microtrauma, and genetic predisposition.➤: Diagnosis is based on the history, physical examination, radiography, and advanced imaging, with elbow ultrasonography and novel magnetic resonance imaging protocols potentially enabling early detection and in-depth staging.➤: Treatment largely depends on skeletal maturity and lesion stability, defined by the presence or absence of articular cartilage fracture and subchondral bone separation, as determined by imaging and arthroscopy, and is typically nonoperative for stable lesions in skeletally immature patients and operative for those who have had failure of conservative management or have unstable lesions.➤: Clinical practice guidelines have been limited by a paucity of high-level evidence, but a multicenter effort is ongoing to develop accurate and reliable classification systems and multimodal decision-making algorithms with prognostic value. [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]

ABSTRACT In vivo visualization of subclinical osteochondrosis (OC) lesions, characterized by necrosis of epiphyseal growth cartilage, is necessary to clarify the pathogenesis of this disease. Hence, our objectives were to demonstrate induced necrosis of the epiphyseal cartilage in vivo using MRI and to monitor progression or resolution of resulting lesions. We also aimed to improve the goat model of OC by introducing controlled exercise. Vascular supply to the epiphyseal cartilage was surgically interrupted in four 5-day-old goats to induce ischemic cartilage necrosis in a medial femoral condyle. Starting 3 weeks postoperatively, goats underwent daily controlled exercise until euthanasia at 6, 10, 11 ( n = 2) weeks postoperatively. T2 maps of operated and control femora were obtained in vivo at 3 ( n = 4), 6 ( n = 4), 9 ( n = 3), and 11 ( n = 2) weeks postoperatively using a 3 T MR scanner. In vivo MRI findings were validated against MRI results obtained ex vivo at 9.4 T in three goats and compared to histological results in all goats. Surgical interruption of the vascular supply caused ischemic cartilage necrosis in three out of four goats. T2 maps obtained in vivo at 3 T identified regions of increased relaxation time consistent with discrete areas of cartilage necrosis 3-11 weeks postoperatively and demonstrated delayed progression of the ossification front at 9 ( n = 1) and 11 ( n = 2) weeks postoperatively. In vivo MRI findings were confirmed by ex vivo MRI at 9.4 T and by histology. Identification of cartilage necrosis in clinical patients in the early stages of OC using T2 maps may provide valuable insight into the pathogenesis of this condition. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:868-875, 2017. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the feasibility of SWIFT with variable flip angle (VFA) for measurement of T1 relaxation time in Gd-agarose-phantoms and osteochondral specimens, including regions of very short T2*, and compare with T1 measured using standard methods Methods T1s of agarose phantoms with variable concentration of Gd-DTPA2− and nine pairs of native and trypsin-treated bovine cartilage-bone specimens were measured. For specimens, VFA-SWIFT, inversion recovery (IR) fast spin echo (FSE) and saturation recovery FSE were used. For phantoms, additionally spectroscopic IR was used. Differences and agreement between the methods were assessed using nonparametric Wilcoxon and Kruskal-Wallis tests and intraclass correlation. Results The different T1 mapping methods agreed well in the phantoms. VFA-SWIFT allowed reliable measurement of T1 in the osteochondral specimens, including regions where FSE-based methods failed. The T1s measured by VFA-SWIFT were shifted toward shorter values in specimens. However, the measurements correlated significantly (highest correlation VFA-SWIFT versus FSE was r = 0.966). SNR efficiency was generally highest for SWIFT, especially in the subchondral bone. Conclusion Feasibility of measuring T1 relaxation time using VFA-SWIFT in osteochondral specimens and phantoms was demonstrated. A shift toward shorter T1s was observed for VFA-SWIFT in specimens, reflecting the higher sensitivity of SWIFT to short T2* spins. Magn Reson Med 74:175-184, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Level of Evidence: 5 Technical Efficacy Stage: 3 [ABSTRACT FROM AUTHOR]

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., (Copyright © 2019 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Purpose: To evaluate the feasibility of SWIFT with variable flip angle (VFA) for measurement of T 1 relaxation time in Gd-agarose-phantoms and osteochondral specimens, including regions of very short T 2 *, and compare with T 1 measured using standard methods METHODS: T 1 s of agarose phantoms with variable concentration of Gd-DTPA 2- and nine pairs of native and trypsin-treated bovine cartilage-bone specimens were measured. For specimens, VFA-SWIFT, inversion recovery (IR) fast spin echo (FSE) and saturation recovery FSE were used. For phantoms, additionally spectroscopic IR was used. Differences and agreement between the methods were assessed using nonparametric Wilcoxon and Kruskal-Wallis tests and intraclass correlation., Results: The different T 1 mapping methods agreed well in the phantoms. VFA-SWIFT allowed reliable measurement of T 1 in the osteochondral specimens, including regions where FSE-based methods failed. The T 1 s measured by VFA-SWIFT were shifted toward shorter values in specimens. However, the measurements correlated significantly (highest correlation VFA-SWIFT versus FSE was r = 0.966). SNR efficiency was generally highest for SWIFT, especially in the subchondral bone., Conclusion: Feasibility of measuring T 1 relaxation time using VFA-SWIFT in osteochondral specimens and phantoms was demonstrated. A shift toward shorter T 1 s was observed for VFA-SWIFT in specimens, reflecting the higher sensitivity of SWIFT to short T 2 * spins. Magn Reson Med 74:175-184, 2015. © 2014 Wiley Periodicals, Inc., (© 2014 Wiley Periodicals, Inc.)