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Rotating frame spin-lattice relaxation, with the characteristic time constant T1ρ, provides a means to access motion-restricted (slow) spin dynamics in MRI. As a result of their restricted motion, these spins are sometimes characterized by a short transverse relaxation time constant T2 and thus can be difficult to detect directly with conventional image acquisition techniques. Here, we introduce an approach for three-dimensional adiabatic T1ρ mapping based on a magnetization-prepared sweep imaging with Fourier transformation (MP-SWIFT) sequence, which captures signal from almost all water spin populations, including the extremely fast relaxing pool. A semi-analytical procedure for T1ρ mapping is described. Experiments on phantoms and musculoskeletal tissue specimens (tendon, articular and epiphyseal cartilages) were performed at 9.4 T for both the MP-SWIFT and fast spin echo (FSE) read outs. In the phantom with liquids having fast molecular tumbling and a single-valued T1ρ time constant, the measured T1ρ values obtained with MP-SWIFT and FSE were similar. Conversely, in normal musculoskeletal tissues, T1ρ values measured with MP-SWIFT were much shorter than the values obtained with FSE. Studies of biological tissue specimens demonstrated that T1ρ-weighted SWIFT provides higher contrast between normal and diseased tissues relative to conventional acquisitions. Adiabatic T1ρ mapping with SWIFT readout captures contributions from the otherwise undetected fast relaxing spins, allowing more informative T1ρ measurements of normal and diseased states. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Osteochondritis dissecans (OCD) of the knee is a focal idiopathic alteration of subchondral bone and/or its precursor with risk for instability and disruption of adjacent cartilage. Treatment options focused on preventing premature osteoarthritis vary depending on multiple patient and lesion characteristics, including lesion mobility., Purpose: To differentiate lesion mobility before arthroscopy using a multivariable model that includes patient demographic characteristics and physical examination findings., Study Design: Cohort study (Diagnosis); Level of evidence, 2., Methods: Demographic, preoperative physical examination, and radiographic data were collected from a multicenter national prospective cohort of patients with OCD of the knee. Inclusion criteria included patients <19 years of age and patients with arthroscopically confirmed mobility status based on the Research on Osteochondritis Dissecans of the Knee arthroscopy classification. Multivariable logistic regression analysis using stepwise model selection was used to determine factors associated with the likelihood of a mobile versus an immobile lesion. A 75% partition of the data was used for model training, and 25% was used as a validation cohort. Quantitative model fit statistics were computed using the holdout data, including sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), along with the corresponding 95% CI., Results: A total of 407 patients in the prospective cohort met inclusion criteria, and 62% were male. The mean ± SD age was 13.7 ± 2.2 years, height 161.8 ± 5.3 cm, and weight 59.2 ± 42.2 kg. Arthroscopic evaluation yielded 235 immobile and 172 mobile lesions. Multivariable analysis determined that the best model to predict lesion mobility included chronologic age ≥14 years ( P < .001), effusion on physical examination ( P < .001), and any loss of range of motion on physical examination ( P = .07), while controlling for male sex ( P = .38) and weight >54.4 kg ( P = .12). In the 25% holdout validation sample (n = 102), a sensitivity of 83%, a specificity of 82%, and an AUC of 0.89 (95% CI, 0.82-0.95) were achieved with these predictive factors., Conclusion: Age, effusion, and loss of motion can predict knee OCD lesion mobility at the time of arthroscopy. Education about lesion mobility can help with surgical planning and patient and family counseling., Competing Interests: One or more of the authors has declared potential conflict of interest or source of funding (see the Appendix, available in the online version of this article). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Self-supervised learning has shown great promise because of its ability to train deep learning (DL) magnetic resonance imaging (MRI) reconstruction methods without fully sampled data. Current self-supervised learning methods for physics-guided reconstruction networks split acquired undersampled data into two disjoint sets, where one is used for data consistency (DC) in the unrolled network, while the other is used to define the training loss. In this study, we propose an improved self-supervised learning strategy that more efficiently uses the acquired data to train a physics-guided reconstruction network without a database of fully sampled data. The proposed multi-mask self-supervised learning via data undersampling (SSDU) applies a holdout masking operation on the acquired measurements to split them into multiple pairs of disjoint sets for each training sample, while using one of these pairs for DC units and the other for defining loss, thereby more efficiently using the undersampled data. Multi-mask SSDU is applied on fully sampled 3D knee and prospectively undersampled 3D brain MRI datasets, for various acceleration rates and patterns, and compared with the parallel imaging method, CG-SENSE, and single-mask SSDU DL-MRI, as well as supervised DL-MRI when fully sampled data are available. The results on knee MRI show that the proposed multi-mask SSDU outperforms SSDU and performs as well as supervised DL-MRI. A clinical reader study further ranks the multi-mask SSDU higher than supervised DL-MRI in terms of signal-to-noise ratio and aliasing artifacts. Results on brain MRI show that multi-mask SSDU achieves better reconstruction quality compared with SSDU. The reader study demonstrates that multi-mask SSDU at R = 8 significantly improves reconstruction compared with single-mask SSDU at R = 8, as well as CG-SENSE at R = 2., (© 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Objective: To determine if the quantitative MRI techniques T2 and T1ρ mapping are sensitive to ischemic injury to epiphyseal cartilage in vivo in a piglet model of Legg-Calvé-Perthes disease using a clinical 3T MRI scanner. We hypothesized that T2 and T1ρ relaxation times would be increased in the epiphyseal cartilage of operated vs contralateral-control femoral heads 1 week following onset of ischemia., Design: Unilateral femoral head ischemia was surgically induced in eight piglets. Piglets were imaged 1 week post-operatively in vivo at 3T MRI using a magnetization-prepared 3D fast spin echo sequence for T2 and T1ρ mapping and a 3D gradient echo sequence for cartilage segmentation. Ischemia was confirmed in all piglets using gadolinium contrast-enhanced MRI. Median T2 and T1ρ relaxation times were measured in the epiphyseal cartilage of the ischemic and control femoral heads and compared using paired t-tests. Histological assessment was performed on a subset of five piglets., Results: T2 and T1ρ relaxation times were significantly increased in the epiphyseal cartilage of the operated vs control femoral heads (ΔT2 = 11.9 ± 3.7 ms, 95% CI = [8.8, 15.0] ms, P < 0.0001; ΔT1ρ = 12.8 ± 4.1 ms, 95% CI = [9.4, 16.2] ms, P < 0.0001). Histological assessment identified chondronecrosis in the hypertrophic and deep proliferative zones within ischemic epiphyseal cartilage., Conclusions: T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in vivo at clinical 3T MRI. These techniques may be clinically useful to assess injury and repair to the epiphyseal cartilage to better stage the extent of ischemic damage in Legg-Calvé-Perthes disease., (Copyright © 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Following their success in numerous imaging and computer vision applications, deep-learning (DL) techniques have emerged as one of the most prominent strategies for accelerated MRI reconstruction. These methods have been shown to outperform conventional regularized methods based on compressed sensing (CS). However, in most comparisons, CS is implemented with two or three hand-tuned parameters, while DL methods enjoy a plethora of advanced data science tools. In this work, we revisit [Formula: see text]-wavelet CS reconstruction using these modern tools. Using ideas such as algorithm unrolling and advanced optimization methods over large databases that DL algorithms utilize, along with conventional insights from wavelet representations and CS theory, we show that [Formula: see text]-wavelet CS can be fine-tuned to a level close to DL reconstruction for accelerated MRI. The optimized [Formula: see text]-wavelet CS method uses only 128 parameters compared to >500,000 for DL, employs a convex reconstruction at inference time, and performs within <1% of a DL approach that has been used in multiple studies in terms of quantitative quality metrics.

Meniscal tears are a common orthopedic injury, yet their healing is difficult to assess post-operatively. This impedes clinical decisions as the healing status of the meniscus cannot be accurately determined non-invasively. Thus, the objectives of this study were to explore the utility of a goat model and to use quantitative magnetic resonance imaging (MRI) techniques, histology, and biomechanical testing to assess the healing status of surgically induced meniscal tears. Adiabatic T1ρ, T2, and T2* relaxation times were quantified for both operated and control menisci ex vivo. Histology was used to assign healing status, assess compositional elements, and associate healing status with compositional elements. Biomechanical testing determined the failure load of healing lesions. Adiabatic T1ρ, T2, and T2* were able to quantitatively identify different healing states. Histology showed evidence of diminished proteoglycans and increased vascularity in both healed and non-healed menisci with surgically induced tears. Biomechanical results revealed that increased healing (as assessed histologically and on MRI) was associated with greater failure load. Our findings indicate increased healing is associated with greater meniscal strength and decreased signal differences (relative to contralateral controls) on MRI. This indicates that quantitative MRI may be a viable method to assess meniscal tears post-operatively., (© 2021. The Author(s).)

The identification of gene fusions from RNA sequencing data is a routine task in cancer research and precision oncology. However, despite the availability of many computational tools, fusion detection remains challenging. Existing methods suffer from poor prediction accuracy and are computationally demanding. We developed Arriba, a novel fusion detection algorithm with high sensitivity and short runtime. When applied to a large collection of published pancreatic cancer samples ( n = 803), Arriba identified a variety of driver fusions, many of which affected druggable proteins, including ALK, BRAF, FGFR2, NRG1, NTRK1, NTRK3, RET, and ROS1. The fusions were significantly associated with KRAS wild-type tumors and involved proteins stimulating the MAPK signaling pathway, suggesting that they substitute for activating mutations in KRAS In addition, we confirmed the transforming potential of two novel fusions, RRBP1 - RAF1 and RASGRP1 - ATP1A1 , in cellular assays. These results show Arriba's utility in both basic cancer research and clinical translation., (© 2021 Uhrig et al.; Published by Cold Spring Harbor Laboratory Press.)

Purpose: To develop a strategy for training a physics-guided MRI reconstruction neural network without a database of fully sampled data sets., Methods: Self-supervised learning via data undersampling (SSDU) for physics-guided deep learning reconstruction partitions available measurements into two disjoint sets, one of which is used in the data consistency (DC) units in the unrolled network and the other is used to define the loss for training. The proposed training without fully sampled data is compared with fully supervised training with ground-truth data, as well as conventional compressed-sensing and parallel imaging methods using the publicly available fastMRI knee database. The same physics-guided neural network is used for both proposed SSDU and supervised training. The SSDU training is also applied to prospectively two-fold accelerated high-resolution brain data sets at different acceleration rates, and compared with parallel imaging., Results: Results on five different knee sequences at an acceleration rate of 4 shows that the proposed self-supervised approach performs closely with supervised learning, while significantly outperforming conventional compressed-sensing and parallel imaging, as characterized by quantitative metrics and a clinical reader study. The results on prospectively subsampled brain data sets, in which supervised learning cannot be used due to lack of ground-truth reference, show that the proposed self-supervised approach successfully performs reconstruction at high acceleration rates (4, 6, and 8). Image readings indicate improved visual reconstruction quality with the proposed approach compared with parallel imaging at acquisition acceleration., Conclusion: The proposed SSDU approach allows training of physics-guided deep learning MRI reconstruction without fully sampled data, while achieving comparable results with supervised deep learning MRI trained on fully sampled data., (© 2020 International Society for Magnetic Resonance in Medicine.)

Study Design: Ex vivo porcine imaging study., Objectives: Quantitatively evaluate change in MRI signal at the discs caudal to spinal fusion instrumentation. Individuals who receive posterior spinal instrumentation are at risk of developing accelerated disc degeneration at adjacent levels. Degeneration is associated with a loss of biochemical composition and mechanical integrity of the disc, which can be noninvasively assessed through quantitative T2* (qT2*) MRI techniques. However, qT2* is sensitive to magnetic susceptibility introduced by metal., Methods: Nine ex vivo porcine lumbar specimens were imaged with 3 T MRI. Fast spin-echo T2-weighted (T2w) images and gradient-echo qT2* maps were acquired, both without and with posterior spinal fusion instrumentation. Average T2* relaxation times of the nuclei pulposi (NP) were measured at the adjacent and sub-adjacent discs and measurements were compared using t tests before and after instrumentation. The size of the signal void and metal artifact were determined (modified ASTM F2119-07) within the vertebral body and spinal cord for both MRI sequences. The relationship between T2* signal loss and distance from the instrumentation was evaluated using Pearson's correlation., Results: There was no significant difference between adjacent and sub-adjacent NP T2* relaxation time prior to instrumentation (p = 0.86). Following instrumentation, there was a significant decrease in the T2* relaxation time at the adjacent NP (average = 20%, p = 0.02), and no significant difference at the sub-adjacent NP (average = - 3%, p = 0.30). Furthermore, there was a significant negative correlation between signal loss and distance to disc (r = - 0.61, p < 0.01)., Conclusions: Spinal fusion instrumentation interferes with T2* relaxation time measurements at the adjacent disc but not at the sub-adjacent discs. However, there is sufficient signal at the adjacent disc to quantify changes in the T2* relaxation time following spinal fusion. Hence, baseline MRI scan following spinal fusion surgery are required to interpret and track changes in disc health at the caudal discs., Level of Evidence: N/A.

Objective: Evaluate articular cartilage by magnetic resonance imaging (MRI) T2∗ mapping within the distal femur and proximal tibia in adolescents with juvenile osteochondritis dissecans (JOCD)., Design: JOCD imaging studies acquired between August 2011 and February 2019 with clinical and T2∗ mapping MRI knee images were retrospectively collected and analyzed for 31 participants (9F/22M, 15.0 ± 3.8 years old) with JOCD lesions in the medial femoral condyle (MFC). In total, N = 32 knees with JOCD lesions and N = 14 control knees were assessed. Mean T2∗ values in four articular cartilage regions-of-interest (MFC, lateral femoral condyle (LFC), medial tibia (MT), and lateral tibia (LT)) and lesion volume were measured and analyzed using Wilcoxon-rank-sum tests and Spearman correlation coefficients (R)., Results: Mean ± standard error T2∗ differences observed between the lesion-sided MFC and the LFC in JOCD-affected knees (28.5 ± 0.9 95% confidence interval [26.8, 30.3] vs 26.3 ± 0.7 [24.8, 27.7] ms, P = 0.088) and between the affected- and control-knee MFC (28.5 ± 0.9 [26.8, 30.3] vs 28.5 ± 0.6 [27.1, 29.9] ms, P = 0.719) were nonsignificant. T2∗ was significantly increased in the lesion-sided MT vs the LT for the JOCD-affected knees (21.5 ± 0.7 [20.1, 22.9] vs 18.0 ± 0.7 [16.5, 19.5] ms, P = 0.002), but this same difference was also observed between the MT and LT in control knees (21.0 ± 0.6 [19.7, 22.3] vs 18.1 ± 1.1 [15.8, 20.4] ms, P = 0.037). There was no significant T2∗ difference between the affected- and control-knee MT (21.5 ± 0.7 [20.1, 22.9] vs 21.0 ± 0.6 [19.7, 22.3] ms, P = 0.905). T2∗ within the lesion-sided MFC was not correlated with patient age (R = 0.20, P = 0.28) or lesion volume (R = 0.06, P = 0.75). T2∗ values were slightly increased near lesions in later-stage JOCD subjects but without statistical significance., Conclusions: T2∗ relaxations times were not significantly different from control sites in the articular cartilage overlying JOCD lesions in the MFC or adjacent MT cartilage in early-stage JOCD., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: To evaluate the feasibility of arterial spin labeling (ASL) imaging of epiphyseal bone marrow in the distal femoral condyle of the knee at 7T MRI., Methods: The knees of 7 healthy volunteers were imaged with ASL using a 7T whole body MRI scanner and a 28-channel knee coil. ASL imaging used a flow-sensitive alternating inversion recovery method for labeling and a single-shot fast spin echo sequence for image readout. ASL imaging with a single oblique transverse slice was performed at 2 slice positions in the distal femoral condyle. Blood flow was measured in 2 regions of interest: the epiphyseal bone marrow and the overlying patellofemoral cartilage. To analyze perfusion SNR, 200 noise images were also acquired using the same ASL imaging protocol with RF pulses turned off., Results: Knee bone marrow perfusion imaging was successfully performed with all volunteers. The overall mean of blood flow in the knee bone marrow was 32.90 ± 2.41 mL/100 g/min, and the blood flow was higher at the more distal slice position. We observed significant B 0 and B 1 + inhomogeneities, which need to be addressed in the future to improve the quality of ASL imaging and increase the reliability of knee bone marrow perfusion measurements., Conclusion: Bone marrow perfusion imaging of the distal femoral condyle is feasible using ASL at 7T. Further technical development is needed to improve the ASL method to overcome existing challenges., (© 2019 International Society for Magnetic Resonance in Medicine.)

Bone perfusion is an essential physiological measure reflecting vasculature status and tissue viability of the skeletal system. Arterial spin labeling (ASL), as a non-invasive and non-contrast enhanced perfusion imaging method, is an attractive approach for human research studies. To evaluate the feasibility of ASL perfusion imaging of knee bone marrow in the distal femoral condyle at a 3 T MRI scanner, a study was performed with eight healthy volunteers (three males and five females, 26 ± 2 years old) and two patients (male, 15 and 11 years old) with diagnosed stage II juvenile osteochondritis dissecans (JOCD). ASL imaging utilized a flow-sensitive alternating inversion recovery method for labeling and a single-shot fast spin echo sequence for image readout. In addition to quantitative knee bone marrow ASL imaging, studies were also performed to evaluate the effects of prolonged post-bolus delay and varied labeling size. ASL imaging was successfully performed with all volunteers. Despite the benefits of hyper-intensive signal suppression within bone marrow, the use of a prolonged post-bolus delay caused excessive perfusion signal decay, resulting in low perfusion signal-to-noise ratio (SNR) and poor image quality. Bone marrow perfusion signal changed with the labeling size, suggesting that the measured bone marrow perfusion signal is flow-associated. The means and standard deviations of bone marrow blood flow, spatial SNR, and temporal SNR from the quantitative perfusion study were 38.3 ± 5.2 mL/100 g/min, 3.31 ± 0.48, and 1.33 ± 0.31, respectively. The imaging results from JOCD patients demonstrated the potential of ASL imaging to detect disease-associated bone marrow perfusion changes. This study demonstrates that it is feasible to perform ASL imaging of knee bone marrow in the distal femoral condyle at 3 T.

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.)

Objectives The purpose of this study was to validate T2* mapping as an objective, noninvasive method for the prediction of acetabular cartilage damage. Methods This is the second step in the validation of T2*. In a previous study, we established a quantitative predictive model for identifying and grading acetabular cartilage damage. In this study, the model was applied to a second cohort of 27 consecutive hips to validate the model. A clinical 3.0-T imaging protocol with T2* mapping was used. Acetabular regions of interest (ROI) were identified on magnetic resonance and graded using the previously established model. Each ROI was then graded in a blinded fashion by arthroscopy. Accurate surgical location of ROIs was facilitated with a 2-dimensional map projection of the acetabulum. A total of 459 ROIs were studied. Results When T2* mapping and arthroscopic assessment were compared, 82% of ROIs were within 1 Beck group (of a total 6 possible) and 32% of ROIs were classified identically. Disease prediction based on receiver operating characteristic curve analysis demonstrated a sensitivity of 0.713 and a specificity of 0.804. Model stability evaluation required no significant changes to the predictive model produced in the initial study. Conclusions These results validate that T2* mapping provides statistically comparable information regarding acetabular cartilage when compared to arthroscopy. In contrast to arthroscopy, T2* mapping is quantitative, noninvasive, and can be used in follow-up. Unlike research quantitative magnetic resonance protocols, T2* takes little time and does not require a contrast agent. This may facilitate its use in the clinical sphere.

MR measurements can be accurately performed during 4486 km of running, opening a window into in vivo assessment of hindfoot articular cartilage under extreme ultra-endurance loading. This observational cross-sectional study included 22 randomized participants of TransEurope FootRace between Italy and the North Cape, which was accompanied by a trailer-mounted 1.5T MRI scanner over 9 weeks. Four follow up MR examinations of subtalar and midtarsal joints were performed. Statistics of cartilage T2*  and thickness were obtained. Nearly all observed joints showed an initial significant mean T2*  increase of 20.9% and 26.3% for the left and right side, followed by a relative decrease of 28.5% and 16.0% during the second half, respectively. It could be demonstrated that mobile MRI field studies allow in vivo functional tissue observations under extreme loading. Elevated T2*  values recovered during the second half of the ultramarathon supported the evidence that this response is a physiological adaptive mechanism of chondrocyte function via upregulation of de novo synthesis of proteoglycans and collagen. These changes occurred in a distinct asymmetric pattern leaving a "biochemical signature" of articular cartilage that allows in vivo insight into joint loading. In conclusion, the normal articular cartilage of the hindfoot is resilient and adaptive, leaving extreme endurance activities up to limitless human ambition., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (© Georg Thieme Verlag KG Stuttgart · New York.)

Femoroacetabular impingement (FAI) is a condition in which subtle deformities of the femoral head and acetabulum (hip socket) result in pathological abutment during hip motion. FAI is a common cause of hip pain and can lead to acetabular cartilage damage and osteoarthritis. For some patients with FAI, surgical intervention is indicated, and it can improve quality of life and potentially delay the onset of osteoarthritis. For other patients, however, surgery is contraindicated because significant cartilage damage has already occurred. Unfortunately, current imaging modalities (X-rays and conventional MRI) are subjective and lack the sensitivity to distinguish these two groups reliably. In this paper, we describe the pairing of T2* mapping data (an investigational, objective MRI sequence) and a spatial proportional odds model for surgically obtained ordinal outcomes (Beck's scale of cartilage damage). Each hip in the study is assigned its own spatial dependence parameter, and a Dirichlet process prior distribution permits clustering of said parameters. Using the fitted model, we produce a six-color, patient-specific predictive map of the entire acetabular cartilage. Such maps will facilitate patient education and clinical decision making. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Purpose: The aim of the present work was to validate and optimize adiabatic T 1ρ and T 2ρ mapping for in vivo measurements of articular cartilage at 3 Tesla (T)., Methods: Phantom and in vivo experiments were systematically performed on a 3T clinical system to evaluate the sequences using hyperbolic secant HS1 and HS4 pulses. R 1ρ and R 2ρ relaxation rates were studied as a function of agarose and chondroitin sulfate concentration and pulse duration. Optimal in vivo protocol was determined by imaging the articular cartilage of two volunteers and varying the sequence parameters, and successively applied in eight additional subjects. Reproducibility was assessed in phantoms and in vivo., Results: Relaxation rates depended on agarose and chondroitin sulfate concentration. The sequences were able to generate relaxation time maps with pulse lengths of 8 and 6 ms for HS1 and HS4, respectively. In vivo findings were in good agreement with the phantoms. The implemented adiabatic T 1ρ and T 2ρ sequences demonstrated regional variation in relaxation time maps of femorotibial cartilage. Reproducibility in phantoms and in vivo was good to excellent for both adiabatic T 1ρ and T 2ρ ., Conclusions: The findings indicate that sequences are suitable for quantitative in vivo assessment of articular cartilage at 3 T. Magn Reson Med 77:1265-1275, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

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 use quantitative susceptibility mapping (QSM) to investigate changes in cartilage canals in the distal femur of juvenile goats after their surgical transection., Methods: Chondronecrosis was surgically induced in the right medial femoral condyles of four 4-day-old goats. Both the operated and control knees were harvested at 2, 3, 5, and 10 weeks after the surgeries. Ex vivo MRI scans were conducted at 9.4 Tesla using T RAFF (relaxation time along a fictitious field)-weighted fast spin echo imaging and QSM to detect areas of chondronecrosis and investigate cartilage canal abnormalities. Histological sections from these same areas stained with hematoxylin and eosin and safranin O were evaluated to assess the affected tissues., Results: Both the histological sections and the T RAFF -weighted images of the femoral condyles demonstrated focal areas of chondronecrosis, evidenced by pyknotic chondrocyte nuclei, loss of matrix staining, and altered MR image contrast. At increasing time points after surgery, progressive changes and eventual disappearance of abnormal cartilage canals were observed in areas of chondronecrosis by using QSM., Conclusion: Abnormal cartilage canals were directly visualized in areas of surgically induced chondronecrosis. Quantitative susceptibility mapping enabled investigation of the vascular changes accompanying chondronecrosis in juvenile goats. Magn Reson Med 77:1276-1283, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Several laboratory and rotating frame quantitative MRI parameters were evaluated and compared for detection of changes in articular cartilage following selective enzymatic digestion. Bovine osteochondral specimens were subjected to 44 h incubation in control medium or in collagenase or chondroitinase ABC to induce superficial collagen or proteoglycan (glycosaminoglycan) alterations. The samples were scanned at 9.4 T for T1 , T1 Gd (dGEMRIC), T2 , adiabatic T1 ρ , adiabatic T2 ρ , continuous-wave T1 ρ , TRAFF2 , and T1 sat relaxation times and for magnetization transfer ratio (MTR). For reference, glycosaminoglycan content, collagen fibril orientation and biomechanical properties were determined. Changes primarily in the superficial cartilage were noted after enzymatic degradation. Most of the studied parameters were sensitive to the destruction of collagen network, whereas glycosaminoglycan depletion was detected only by native T1 and T1 Gd relaxation time constants throughout the tissue and by MTR superficially. T1 , adiabatic T1 ρ , adiabatic T2 ρ , continuous-wave T1 ρ , and T1 sat correlated significantly with the biomechanical properties while T1 Gd correlated with glycosaminoglycan staining. The findings indicated that most of the studied MRI parameters were sensitive to both glycosaminoglycan content and collagen network integrity, with changes due to enzymatic treatment detected primarily in the superficial tissue. Strong correlation of T1 , adiabatic T1ρ , adiabatic T2 ρ , continuous-wave T1 ρ , and T1 sat with the altered biomechanical properties, reflects that these parameters were sensitive to critical functional properties of cartilage. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1111-1120, 2016., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Chronic myeloid leukemia (CML) is driven by the fusion kinase Bcr-Abl. Bcr-Abl tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), revolutionized CML therapy. Nevertheless, about 20 % of CMLs display primary or acquired TKI resistance. TKI resistance can be either caused by mutations within the Bcr-Abl kinase domain or by aberrant signaling by its effectors, e.g. Lyn or Gab2. Bcr-Abl mutations are frequently observed in TKI resistance and can only in some cases be overcome by second line TKIs. In addition, we have previously shown that the formation of Gab2 complexes can be regulated by Bcr-Abl and that Gab2 signaling counteracts the efficacy of four distinct Bcr-Abl inhibitors. Therefore, TKI resistance still represents a challenge for disease management and alternative therapies are urgently needed., Findings: Using different CML cell lines and models, we identified the clinically approved TKIs sorafenib (SF) and axitinib (AX) as drugs overcoming the resistance mediated by the Bcr Abl(T315I) mutant as well as the one mediated by Gab2 and Lyn(Y508F). In addition, we demonstrated that AX mainly affects the Bcr-Abl/Grb2/Gab2 axis, whereas SF seems to act independently of the fusion kinase and most likely by blocking signaling pathways up- and downstream of Gab2., Conclusion: We demonstrate that SF and AX show potency in various and mechanistically distinct scenarios of TKI resistance, including Bcr-Abl(T315I) as well as Lyn- and Gab2-mediated resistances. Our data invites for further evaluation und consideration of these inhibitors in the treatment of TKI resistant CML.

26-year-old female with prior anterior cruciate ligament reconstruction developed an enlarging lytic bone lesion around the tibial screw with sequential imaging over the course of one year demonstrating progression of this finding, which was confirmed histologically to be a giant cell tumor of bone. The lesion originated around the postoperative bed, making the diagnosis challenging during the early course of the presentation. The case demonstrates giant cell tumor which originated in the metaphysis and subsequently grew to involve the epiphysis; therefore, early course of the disease not involving the epiphysis should not exclude this diagnosis.

Image blurring due to off-resonance and fast T 2 * signal decay is a common issue in radial ultrashort echo time MRI sequences. One solution is to use a higher readout bandwidth, but this may be impractical for some techniques like pointwise encoding time reduction with radial acquisition (PETRA), which is a hybrid method of zero echo time and single point imaging techniques. Specifically, PETRA has severe specific absorption rate (SAR) and radiofrequency (RF) pulse peak power limitations when using higher bandwidths in human measurements. In this study, we introduce gradient modulation (GM) to PETRA to reduce image blurring artifacts while keeping SAR and RF peak power low. Tolerance of GM-PETRA to image blurring was evaluated in simulations and experiments by comparing with the conventional PETRA technique. We performed inner ear imaging of a healthy subject at 7T. GM-PETRA showed significantly less image blurring due to off-resonance and fast T 2 * signal decay compared to PETRA. In in vivo imaging, GM-PETRA nicely captured complex structures of the inner ear such as the cochlea and semicircular canals. Gradient modulation can improve the PETRA image quality and mitigate SAR and RF peak power limitations without special hardware modification in clinical scanners.

Purpose: To evaluate the sensitivity of quantitative MRI techniques (T 1 , T 1,Gd , T 2 , continous wave (CW) T 1ρ dispersion, adiabatic T 1ρ , adiabatic T 2ρ , RAFF and inversion-prepared magnetization transfer (MT)) for assessment of human articular cartilage with varying degrees of natural degeneration., Methods: Osteochondral samples (n = 14) were obtained from the tibial plateaus of patients undergoing total knee replacement. MRI of the specimens was performed at 9.4T and the relaxation time maps were evaluated in the cartilage zones. For reference, quantitative histology, OARSI grading and biomechanical measurements were performed and correlated with MRI findings., Results: All MRI parameters, except T 1,Gd , showed statistically significant differences in tangential and full-thickness regions of interest (ROIs) between early and advanced osteoarthritis (OA) groups, as classified by OARSI grading. CW-T 1ρ showed significant dispersion in all ROIs and featured classical laminar structure of cartilage with spin-lock powers below 1000 Hz. Adiabatic T 1ρ , T 2ρ , CW-T 1ρ, MT, and RAFF correlated strongly with OARSI grade and biomechanical parameters., Conclusion: MRI parameters were able to differentiate between early and advanced OA. Furthermore, rotating frame methods, namely adiabatic T 1ρ , adiabatic T 2ρ , CW-T 1ρ , and RAFF, as well as MT experiment correlated strongly with biomechanical parameters and OARSI grade, suggesting high sensitivity of the parameters for cartilage degeneration. Magn Reson Med 74:249-259, 2015. © 2014 Wiley Periodicals, Inc., (© 2014 Wiley Periodicals, Inc.)

Objective: The purpose of this study was to assess whether the presence of intraarticular gadopentetate dimeglumine during clinical MR arthrography significantly alters the T2* relaxation time of hip articular cartilage in patients with femoroacetabular impingement., Subjects and Methods: T2* mapping of 10 patient volunteers (seven female patients, three male patients; age range, 14-49 years; mean, 33.0 ± 12.2 [SD] years) with symptomatic femoroacetabular impingement was performed before and after intraarticular administration of gadopentetate dimeglumine. Overall 323 ROIs were defined in each acetabular and femoral cartilage before and after gadolinium injection. Agreement of the T2* relaxation times before and after gadolinium injection was assessed with the Krippendorff alpha coefficient and linear regression through the origin., Results: T2* relaxation times before and after gadolinium injection in both acetabular and femoral cartilage were found to agree strongly. Specifically, estimated Krippendorff alpha values were greater than 0.8 for both acetabular and femoral cartilage, linear regressions through the origin yielded estimated slopes very close to 1, and R(2) values were greater than 0.98., Conclusion: The results indicate that intraarticular injection of gadopentetate dimeglumine according to the protocol described in this study has little effect on the T2* of femoral and acetabular cartilage. The results suggest that T2* mapping can be safely performed as an addition to a standard clinical hip imaging protocol that includes gadopentetate dimeglumine administration.

Objective: Identify and interrupt the vascular supply to portions of the distal femoral articular-epiphyseal cartilage complex (AECC) in goat kids to induce cartilage necrosis, characteristic of early lesions of osteochondrosis (OC); then utilize magnetic resonance imaging (MRI) to identify necrotic areas of cartilage., Design: Distal femora were perfused and cleared in goat kids of various ages to visualize the vascular supply to the distal femoral AECC. Vessels located on the axial aspect of the medial femoral condyle (MFC) and on the abaxial side of the lateral trochlear ridge were transected in eight 4- to 5-day-old goats to induce cartilage necrosis. Goats were euthanized 1, 2, 3, 4, 5, 6, 9, and 10 weeks post operatively and operated stifles were harvested. Adiabatic T1ρ relaxation time maps of the harvested distal femora were generated using a 9.4 T MR scanner, after which samples were evaluated histologically., Results: Interruption of the vascular supply to the MFC caused lesions of cartilage necrosis in 6/8 goat kids that were demonstrated histologically. Adiabatic T1ρ relaxation time mapping identified these areas of cartilage necrosis in 5/6 cases. No significant findings were detected after transection of perichondrial vessels supplying the lateral trochlear ridge., Conclusions: Cartilage necrosis, characteristic of early OC, can be induced by interrupting the vascular supply to the distal femoral AECC in goat kids. The ability of high field MRI to identify these areas of cartilage necrosis in the AECC using the adiabatic T1ρ sequence suggests that this technique may be useful in the future for the early diagnosis of OC., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)