Teaming up to overcome challenges toward translation of new therapeutics for osteoarthritis.

As a leading global cause of musculoskeletal-related disability, osteoarthritis (OA) represents a public health urgency. Understanding of disease pathogenesis has advanced substantially in the past decade, yet no disease-modifying therapeutics have advanced to the clinic. To address this challenge, the CARE-AP (Cartilage Repair strategies to alleviate Arthritis Pain) collaborative research team was convened to bring together relevant multidisciplinary expertise and perspectives from across the VA research community nationwide. The first CARE-AP Annual Research Symposium took place (virtually) in February 2022 with roughly 90 participants. A number of innovative and therapeutic strategies were discussed, including siRNA approaches coupled with novel nanoparticle-based delivery systems, cellular engineering approaches to develop reparative cells that can probe the joint environment and respond to disease-specific cues, and novel biofabrication techniques to improve tissue engineering and effect "biological joint replacement." In addition, challenges and advances in rehabilitation approaches, imaging outcomes, and clinical studies were presented, which were integrated into a framework of recommendations for running "preclinical trials" to improve successful clinical translation.

High-Field MRI Advantages and Applications in Rheumatology.

Imaging of rheumatologic diseases has historically been performed using conventional radiography. MRI offers an opportunity for detection of altered marrow signal in early disease that is not visible on other imaging modalities such as radiography, computed tomography, or sonography. This review describes the advantages of current MRI techniques in the diagnosis and treatment monitoring of rheumatologic diseases. In addition, this review discusses novel MRI techniques at high-field magnetic strength which may be deployed in the future to allow for improved imaging resolution and quantitative assessment of both axial and peripheral joints.

Neurovascular crossing patterns between leash of Henry and deep branch of radial nerve: implications for neurointervention and diagnostic imaging.

OBJECTIVE: To detail the neurovascular crossing patterns between the leash of Henry (LoH) and the deep branch of the radial nerve (DBRN) in supination and pronation of the forearm, using imaging methods with anatomic correlation. MATERIALS AND METHODS: This cross-sectional study was performed ex vivo with HRUS and MRI with anatomic correlation on 6 samples and in vivo with HRUS with Doppler on 55 participants scanned bilaterally. The in vivo participants were enrolled over a 6-month period. The crossing patterns between the LoH and DBRN were assessed ex vivo and in vivo. Additional morphological features of the DBRN, LoH, and fat plane were assessed in vivo only. Biometric features of the participants were recorded. Statistical analyses were performed using Shapiro-Wilk, parametric and non-parametric tests. RESULTS: The most common neurovascular crossing pattern was the ascending branch of the radial recurrent artery (RRAab) crossing below (ex vivo: 83.3%, in vivo: 85.3%) and the muscular branch crossing above (ex vivo: 100%, in vivo: 63.2% %) the DBRN. Both the deep and superficial surfaces of the DBRN exhibited an intimate relationship with the vessels of the LoH. A positive correlation between vessel diameter and anthropometric factors was observed. In addition, the muscular branch exhibited a significantly smaller diameter than the RRAab. CONCLUSION: Our study detailed the relationship between the LoH and the DBRN and highlighted the high incidence of vessel crossing above the DBRN at the level of the muscular branch. Knowledge of neurovascular crossings is crucial for understanding neurovascular entrapment syndromes and planning interventional procedures to reduce vascular complications.

Evaluation of spine disorders using high contrast imaging of the cartilaginous endplate.

Introduction: Many spine disorders are caused by disc degeneration or endplate defects. Because nutrients entering the avascular disc are channeled through the cartilaginous endplate (CEP), structural and compositional changes in the CEP may block this solute channel, thereby hindering disc cell function. Therefore, imaging the CEP region is important to improve the diagnostic accuracy of spine disorders. Methods: A clinically available T1-weighted and fat-suppressed spoiled gradient recalled-echo (FS-SPGR) sequence was optimized for high-contrast CEP imaging, which utilizes the short T1 property of the CEP. The FS-SPGR scans with and without breath-hold were performed for comparison on healthy subjects. Then, the FS-SPGR sequence which produced optimal image quality was employed for patient scans. In this study, seven asymptomatic volunteers and eight patients with lower back pain were recruited and scanned on a 3T whole-body MRI scanner. Clinical T2-weighted fast spin-echo (T2w-FSE) and T1-weighted FSE (T1w-FSE) sequences were also scanned for comparison. Results: For the asymptomatic volunteers, the FS-SPGR scans under free breathing conditions with NEX = 4 showed much higher contrast-to-noise ratio values between the CEP and bone marrow fat (BMF) (CNRCEP-BMF) (i.e., 7.8 ± 1.6) and between the CEP and nucleus pulposus (NP) (CNRCEP-NP) (i.e., 6.1 ± 1.2) compared to free breathing with NEX = 1 (CNRCEP-BMF: 4.0 ± 1.1 and CNRCEP-NP: 2.5 ± 0.9) and breath-hold condition with NEX = 1 (CNRCEP-BMF: 4.2 ± 1.3 and CNRCEP-NP: 2.8 ± 1.3). The CEP regions showed bright linear signals with high contrast in the T1-weighted FS-SPGR images in the controls, while irregularities of the CEP were found in the patients. Discussion: We have developed a T1-weighted 3D FS-SPGR sequence to image the CEP that is readily translatable to clinical settings. The proposed sequence can be used to highlight the CEP region and shows promise for the detection of intervertebral disc abnormalities.

Imaging of Rheumatic Diseases Affecting the Lower Limb.

Imaging methods capable of detecting inflammation, such as MR imaging and ultrasound, are of paramount importance in rheumatic disease management, not only for diagnostic purposes but also for monitoring disease activity and treatment response. However, more advanced stages of arthritis, characterized by findings of cumulative structural damage, have traditionally been accomplished by radiographs and computed tomography. The purpose of this review is to provide an overview of imaging of some of the most prevalent inflammatory rheumatic diseases affecting the lower limb (osteoarthritis, rheumatoid arthritis, and gout) and up-to-date recommendations regarding imaging diagnostic workup.

Fast dual-echo estimation of apparent long T2 fraction using ultrashort echo time magnetic resonance imaging in tibialis tendons and its osteoporosis-related differences in women.

Background: Tendon and bone comprise a critical interrelating unit. Bone loss, including that seen with osteopenia (OPe) or osteoporosis (OPo), may be associated with a reduction in tendon quality, though this remains incompletely investigated. Clinical magnetic resonance imaging (MRI) sequences cannot directly detect signals from tendons because of the very short T2. Clinical MRI may detect high-graded abnormalities by changes in the adjacent structures like bone. However, ultrashort echo time MRI (UTE-MRI) can capture high signals from all tendons. To determine if the long T2 fraction, as measured by a dual-echo UTE-MRI sequence, is a sensitive quantitative technique to the age- and bone-loss-related changes of the lower leg tendons. Methods: This is a cross-sectional study conducted between January 2018 to February 2020 in the lower legs of 14 female patients with OPe [72±6 years old, body mass index (BMI) =25.8±6.2 kg/m2] and 31 female patients with OPo (73±6 years old, BMI=22.0±3.8 kg/m2), as well as 30 female subjects with normal bone (Normal, 35±18 years old, BMI =23.2±4.3 kg/m2), were imaged on a 3T clinical scanner using a dual-echo 3D Cones UTE sequence. We defined the apparent long T2 signal fraction (aFrac-LongT2) of tendons as the ratio between the signal at the second echo time (TE =2.2 ms) to the UTE signal. The average aFrac-LongT2 and the cross-sectional area were calculated for the anterior tibialis tendons (ATTs) and the posterior tibialis tendons (PTTs). The Kruskal-Wallis rank test was used to compare the differences in aFrac-LongT2 and the cross-sectional area of the tendons between the groups. Results: The aFrac-LongT2 of the ATTs and PTTs were significantly higher in the OPo group compared with the Normal group (22.2% and 34.8% in the ATT and PTT, respectively, P<0.01). The cross-sectional area in the ATTs was significantly higher for the OPo group than in the Normal group (Normal/OPo difference was 28.7, P<0.01). Such a difference for PTTs did not reach the significance level. Mean aFrac-LongT2 and cross-sectional area in the OPe group were higher than the Normal group and lower than the OPo group. However, the differences did not show statistical significance, likely due to the higher BMI in the OPe group. Conclusions: Dual-echo UTE-MRI is a rapid quantification technique, and aFrac-LongT2 values showed significant differences in tendons between Normal and OPo patients.

Ultrashort echo time MRI detects significantly lower collagen but higher pore water in the tibial cortex of female patients with osteopenia and osteoporosis.

Ultrashort echo time (UTE) MRI can quantify the major proton pool densities in cortical bone, including total (TWPD), bound (BWPD), and pore water (PWPD) proton densities, as well as the macromolecular proton density (MMPD), associated with the collagen content, which is calculated using macromolecular fraction (MMF) from UTE magnetization transfer (UTE-MT) modeling. This study aimed to investigate the differences in water and collagen contents in tibial cortical bone, between female osteopenia (OPe) patients, osteoporosis (OPo) patients, and young participants (Young). Being postmenopausal and above 55 yr old were the inclusion criteria for OPe and OPo groups. The tibial shaft of 14 OPe (72.5 ± 6.8 yr old), 31 OPo (72.0 ± 6.4 yr old), and 31 young subjects (28.0 ± 6.1 yr old) were scanned using a knee coil on a clinical 3T scanner. Basic UTE, inversion recovery UTE, and UTE-MT sequences were performed. Investigated biomarkers were compared between groups using Kruskal-Wallis test. Spearman's correlation coefficients were calculated between the TH DXA T-score and UTE-MRI results. MMF, BWPD, and MMPD were significantly lower in OPo patients than in the young group, whereas T1, TWPD, and PWPD were significantly higher in OPo patients. The largest OPo/Young average percentage differences were found in MMF (41.9%), PWPD (103.5%), and MMPD (64.0%). PWPD was significantly higher (50.7%), while BWPD was significantly lower (16.4%) in OPe than the Young group on average. MMF was found to be significantly lower (27%) in OPo patients compared with OPe group. T1, MMF, TWPD, PWPD, and MMPD values significantly correlated with the TH DXA T-scores (provided by the patients and only available for OPe and OPo patients). DXA T-score showed the highest correlations with PWPD (R = 0.55) and MMF (R = 0.56) values. TWPD, PWPD, and MMF estimated using the UTE-MRI sequences were recommended to evaluate individuals with OPe and OPo.

Ultrashort echo time (UTE) is an MRI technique that can quantify the water and collagen content of cortical bone. Water in the bone can be found residing in pores (pore water) or bound to the bone matrix (bound water). We investigated the differences in water and collagen contents of tibial cortical bone between female osteopenia patients, osteoporosis patients, and young participants. Bound water and collagen contents were significantly lower in osteoporosis patients than in the young group, whereas total water and pore water contents were significantly higher in osteoporosis patients. Pore water was significantly higher, while bound water was significantly lower in osteopenia than in the Young group. Collagen content was found to be significantly lower in osteoporosis patients compared with the osteopenia group. The estimated water and collagen contents were significantly correlated with the TH bone densitometry measures in the patients.

More accurate trabecular bone imaging using UTE MRI at the resonance frequency of fat.

High-resolution magnetic resonance imaging (HR-MRI) has been increasingly used to assess the trabecular bone structure. High susceptibility at the marrow/bone interface may significantly reduce the marrow's apparent transverse relaxation time (T2*), overestimating trabecular bone thickness. Ultrashort echo time MRI (UTE-MRI) can minimize the signal loss caused by susceptibility-induced T2* shortening. However, UTE-MRI is sensitive to chemical shift artifacts, which manifest as spatial blurring and ringing artifacts partially due to non-Cartesian sampling. In this study, we proposed UTE-MRI at the resonance frequency of fat to minimize marrow-related chemical shift artifacts and the overestimation of trabecular thickness. Cubes of trabecular bone from six donors (75 ± 4 years old) were scanned using a 3 T clinical scanner at the resonance frequencies of fat and water, respectively, using 3D UTE sequences with five TEs (0.032, 1.1, 2.2, 3.3, and 4.4 ms) and a clinical 3D gradient echo (GRE) sequence at 0.2 × 0.2 × 0.4 mm3 voxel size. Trabecular bone thickness was measured in 30 regions of interest (ROIs) per sample. MRI results were compared with thicknesses obtained from micro-computed tomography (µCT) at 50 µm3 voxel size. Linear regression models were used to calculate the coefficient of determination between MRI- and µCT-based trabecular thickness. All MRI-based trabecular thicknesses showed significant correlations with µCT measurements. The correlations were higher (examined with paired Student's t-test, P < 0.01) for 3D UTE images performed at the fat frequency (R2 = 0.59-0.74, P < 0.01) than those at the water frequency (R2 = 0.18-0.52, P < 0.01) and clinical GRE images (R2 = 0.39-0.47, P < 0.01). Significantly reduced correlations were observed with longer TEs. This study highlighted the feasibility of UTE-MRI at the fat frequency for a more accurate assessment of trabecular bone thickness.

Deep Convolutional Neural Network for Dedicated Regions-of-Interest Based Multi-Parameter Quantitative Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of the Knee Joint.

We proposed an end-to-end deep learning convolutional neural network (DCNN) for region-of-interest based multi-parameter quantification (RMQ-Net) to accelerate quantitative ultrashort echo time (UTE) MRI of the knee joint with automatic multi-tissue segmentation and relaxometry mapping. The study involved UTE-based T1 (UTE-T1) and Adiabatic T1ρ (UTE-AdiabT1ρ) mapping of the knee joint of 65 human subjects, including 20 normal controls, 29 with doubtful-minimal osteoarthritis (OA), and 16 with moderate-severe OA. Comparison studies were performed on UTE-T1 and UTE-AdiabT1ρ measurements using 100%, 43%, 26%, and 18% UTE MRI data as the inputs and the effects on the prediction quality of the RMQ-Net. The RMQ-net was modified and retrained accordingly with different combinations of inputs. Both ROI-based and voxel-based Pearson correlation analyses were performed. High Pearson correlation coefficients were achieved between the RMQ-Net predicted UTE-T1 and UTE-AdiabT1ρ results and the ground truth for segmented cartilage with acceleration factors ranging from 2.3 to 5.7. With an acceleration factor of 5.7, the Pearson r-value achieved 0.908 (ROI-based) and 0.945 (voxel-based) for UTE-T1, and 0.733 (ROI-based) and 0.895 (voxel-based) for UTE-AdiabT1ρ, correspondingly. The results demonstrated that RMQ-net can significantly accelerate quantitative UTE imaging with automated segmentation of articular cartilage in the knee joint.

Bone Biomarkers Based on Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is increasingly used to evaluate the microstructural and compositional properties of bone. MRI-based biomarkers can characterize all major compartments of bone: organic, water, fat, and mineral components. However, with a short apparent spin-spin relaxation time (T2*), bone is invisible to conventional MRI sequences that use long echo times. To address this shortcoming, ultrashort echo time MRI sequences have been developed to provide direct imaging of bone and establish a set of MRI-based biomarkers sensitive to the structural and compositional changes of bone. This review article describes the MRI-based bone biomarkers representing total water, pore water, bound water, fat fraction, macromolecular fraction in the organic matrix, and surrogates for mineral density. MRI-based morphological bone imaging techniques are also briefly described.

Ultrasound attenuation of cortical bone correlates with biomechanical, microstructural, and compositional properties.

BACKGROUND: We investigated the relationship of two commonly used quantitative ultrasound (QUS) parameters, speed of sound (SoS) and attenuation coefficient (α), with water and macromolecular contents of bovine cortical bone strips as measured with ultrashort echo time (UTE) magnetic resonance imaging (MRI). METHODS: SoS and α were measured in 36 bovine cortical bone strips utilizing a single-element transducer with nominal 5 MHz center frequency based on the time of flight principles after accommodating for reflection losses. Specimens were then scanned using UTE MRI to measure total, bound, and pore water proton density (TWPD, BWPD, and PWPD) as well as macromolecular proton fraction and macromolecular transverse relaxation time (T2-MM). Specimens were also scanned using microcomputed tomography (µCT) at 9-µm isometric voxel size to measure bone mineral density (BMD), porosity, and pore size. The elastic modulus (E) of each specimen was measured using a 4-point bending test. RESULTS: α demonstrated significant positive Spearman correlations with E (R = 0.69) and BMD (R = 0.44) while showing significant negative correlations with porosity (R = -0.41), T2-MM (R = -0.47), TWPD (R = -0.68), BWPD (R = -0.67), and PWPD (R = -0.45). CONCLUSIONS: The negative correlation between α and T2-MM is likely indicating the relationship between QUS and collagen matrix organization. The higher correlations of α with BWPD than with PWPD may indicate that water organized in finer structure (bound to matrix) provides lower acoustic impedance than water in larger pores, which is yet to be investigated thoroughly. RELEVANCE STATEMENT: This study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone, including the collagenous matrix and water. Investigating the full potential of QUS and its validation facilitates a more affordable and accessible tool for bone health monitoring in clinics. KEY POINTS: • Ultrasound attenuation demonstrated significant positive correlations with bone mechanics and mineral density. • Ultrasound attenuation demonstrated significant negative correlations with porosity and bone water contents. • This study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone.

Whole knee joint mapping using a phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence.

PURPOSE: To develop a 3D phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence for whole knee joint mapping on a clinical 3 T scanner. METHODS: This new sequence includes six major features: (1) a magnetization reset module, (2) a train of adiabatic full passage pulses for spin locking, (3) a phase modulation scheme (i.e., RF cycling pair), (4) a fat saturation module, (5) a variable flip angle scheme, and (6) a 3D UTE Cones sequence for data acquisition. A simple exponential fitting was used for T1ρ quantification. Phantom studies were performed to investigate PM-UTE-AdiabT1ρ 's sensitivity to compositional changes and reproducibility as well as its correlation with continuous wave-T1ρ measurement. The PM-UTE-AdiabT1ρ technique was then applied to five ex vivo and five in vivo normal knees to measure T1ρ values of femoral cartilage, meniscus, posterior cruciate ligament, anterior cruciate ligament, patellar tendon, and muscle. RESULTS: The phantom study demonstrated PM-UTE-AdiabT1ρ 's high sensitivity to compositional changes, its high reproducibility, and its strong linear correlation with continuous wave-T1ρ measurement. The ex vivo and in vivo knee studies demonstrated average T1ρ values of 105.6 ± 8.4 and 77.9 ± 3.9 ms for the femoral cartilage, 39.2 ± 5.1 and 30.1 ± 2.2 ms for the meniscus, 51.6 ± 5.3 and 29.2 ± 2.4 ms for the posterior cruciate ligament, 79.0 ± 9.3 and 52.0 ± 3.1 ms for the anterior cruciate ligament, 19.8 ± 4.5 and 17.0 ± 1.8 ms for the patellar tendon, and 91.1 ± 8.8 and 57.6 ± 2.8 ms for the muscle, respectively. CONCLUSION: The 3D PM-UTE-AdiabT1ρ sequence allows volumetric T1ρ assessment for both short and long T2 tissues in the knee joint on a clinical 3 T scanner.

T1rho MR properties of human patellar cartilage: correlation with indentation stiffness and biochemical contents.

OBJECTIVE: Cartilage degeneration involves structural, compositional, and biomechanical alterations that may be detected non-invasively using quantitative MRI. The goal of this study was to determine if topographical variation in T1rho values correlates with indentation stiffness and biochemical contents of human patellar cartilage. DESIGN: Cadaveric patellae from unilateral knees of 5 donors with moderate degeneration were imaged at 3-Telsa with spiral chopped magnetization preparation T1rho sequence. Indentation testing was performed, followed by biochemical analyses to determine water and sulfated glycosaminoglycan contents. T1rho values were compared to indentation stiffness, using semi-circular regions of interest (ROIs) of varying sizes at each indentation site. ROIs matching the resected tissues were analyzed, and univariate and multivariate regression analyses were performed to compare T1rho values to biochemical contents. RESULTS: Grossly, superficial degenerative change of the cartilage (i.e., roughened texture and erosion) corresponded with regions of high T1rho values. High T1rho values correlated with low indentation stiffness, and the strength of correlation varied slightly with the ROI size. Spatial variations in T1rho values correlated positively with that of the water content (R2 = 0.10, p < 0.05) and negatively with the variations in the GAG content (R2 = 0.13, p < 0.01). Multivariate correlation (R2 = 0.23, p < 0.01) was stronger than either of the univariate correlations. CONCLUSION: These results demonstrate the sensitivity of T1rho values to spatially varying function and composition of cartilage and that the strength of correlation depends on the method of data analysis and consideration of multiple variables.

Achilles tendon and enthesis assessment using ultrashort echo time magnetic resonance imaging (UTE-MRI) T1 and magnetization transfer (MT) modeling in psoriatic arthritis.

The purpose of this study is to investigate the use of ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques (T1 and magnetization transfer [MT] modeling) for imaging of the Achilles tendons and entheses in patients with psoriatic arthritis (PsA) compared with asymptomatic volunteers. The heels of twenty-six PsA patients (age 59 ± 15 years, 41% female) and twenty-seven asymptomatic volunteers (age 33 ± 11 years, 47% female) were scanned in the sagittal plane with UTE-T1 and UTE-MT modeling sequences on a 3-T clinical scanner. UTE-T1 and macromolecular proton fraction (MMF; the main outcome of MT modeling) were calculated in the tensile portions of the Achilles tendon and at the enthesis (close to the calcaneus bone). Mann-Whitney-U tests were used to examine statistically significant differences between the two cohorts. UTE-T1 in the entheses was significantly higher for the PsA group compared with the asymptomatic group (967 ± 145 vs. 872 ± 133 ms, p < 0.01). UTE-T1 in the tendons was also significantly higher for the PsA group (950 ± 145 vs. 850 ± 138 ms, p < 0.01). MMF in the entheses was significantly lower in the PsA group compared with the asymptomatic group (15% ± 3% vs. 18% ± 3%, p < 0.01). MMF in the tendons was also significantly lower in the PsA group compared with the asymptomatic group (17% ± 4% vs. 20% ± 5%, p < 0.01). Percentage differences in MMF between the asymptomatic and PsA groups (-16.6% and -15.0% for the enthesis and tendon, respectively) were higher than the T1 differences (10.8% and 11.7% for the enthesis and tendon, respectively). The results suggest higher T1 and lower MMF in the Achilles tendons and entheses in PsA patients compared with the asymptomatic group. This study highlights the potential of UTE-T1 and UTE-MT modeling for quantitative evaluation of entheses and tendons in PsA patients.

Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial.

Various types of cellular injection have become a popular and costly treatment option for patients with knee osteoarthritis despite a paucity of literature establishing relative efficacy to each other or corticosteroid injections. Here we aimed to identify the safety and efficacy of cell injections from autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic human umbilical cord tissue-derived mesenchymal stromal cells, in comparison to corticosteroid injection (CSI). The study was a phase 2/3, four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients with a diagnosis of knee osteoarthritis (Kellgren-Lawrence II-IV). Participants were randomized to the three different arms with a 3:1 distribution. Arm 1: autologous bone marrow aspirate concentrate (n = 120), CSI (n = 40); arm 2: umbilical cord tissue-derived mesenchymal stromal cells (n = 120), CSI (n = 40); arm 3: stromal vascular fraction (n = 120), CSI (n = 40). The co-primary endpoints were the visual analog scale pain score and Knee injury and Osteoarthritis Outcome Score pain score at 12 months versus baseline. Analyses of our primary endpoints, with 440 patients, revealed that at 1 year post injection, none of the three orthobiologic injections was superior to another, or to the CSI control. In addition, none of the four groups showed a significant change in magnetic resonance imaging osteoarthritis score compared to baseline. No procedure-related serious adverse events were reported during the study period. In summary, this study shows that at 1 year post injection, there was no superior orthobiologic as compared to CSI for knee osteoarthritis. ClinicalTrials.gov Identifier: NCT03818737.

Correlations between elastic modulus and ultrashort echo time (UTE) adiabatic T1ρ relaxation time (UTE-Adiab-T1ρ) in Achilles tendons and entheses.

Patients with psoriatic arthritis commonly have abnormalities of their entheses, which are the connections between tendons and bone. There are shortcomings with the use of conventional magnetic resonance imaging (MRI) sequences for the evaluation of entheses and tendons, whereas ultrashort echo time (UTE) sequences are superior for the detection of high signals, and can also be used for non-invasive quantitative assessments of these structures. The combination of UTE-MRI with an adiabatic-T1ρ preparation (UTE-Adiab-T1ρ) allows for reliable assessment of entheses and tendons with decreased susceptibility to detrimental magic angle effects. This study aimed to investigate the relationship between quantitative UTE-MRI measures and the biomechanical properties of Achilles tendons and entheses. In total, 28 tendon-enthesis sections were harvested from 11 fresh-frozen human cadaveric foot-ankle specimens (52 ± years old). Tendon-enthesis sections were scanned using the UTE-Adiab-T1ρ and UTE-T1 sequences on a clinical 3 T scanner. MRI-based measures and indentation tests were performed on the enthesis, transitional, and tensile tendon zones of the specimens. Hayes' elastic modulus showed significant inverse correlations (Spearman's) with UTE-Adiab-T1ρ in all zones (R= - 0.46, - 0.54, and - 0.61 in enthesis, transition, and tensile tendon zones, respectively). Oliver-Pharr's elastic modulus showed significant inverse correlations with UTE-Adiab-T1ρ in transition (R= - 0.52) and tensile tendon zone (R=- 0.60). UTE-T1 did not show significant correlations with the elastic modulus. UTE-MRI and elastic modulus were significantly lower in the tensile tendon compared with the enthesis regions This study highlights the potential of the UTE-Adiab-T1ρ technique for the non-invasive evaluation of tendons and enthuses.

MRI Advancements in Musculoskeletal Clinical and Research Practice.

Over the past decades, MRI has become increasingly important for diagnosing and longitudinally monitoring musculoskeletal disorders, with ongoing hardware and software improvements aiming to optimize image quality and speed. However, surging demand for musculoskeletal MRI and increased interest to provide more personalized care will necessitate a stronger emphasis on efficiency and specificity. Ongoing hardware developments include more powerful gradients, improvements in wide-bore magnet designs to maintain field homogeneity, and high-channel phased-array coils. There is also interest in low-field-strength magnets with inherently lower magnetic footprints and operational costs to accommodate global demand in middle- and low-income countries. Previous approaches to decrease acquisition times by means of conventional acceleration techniques (eg, parallel imaging or compressed sensing) are now largely overshadowed by deep learning reconstruction algorithms. It is expected that greater emphasis will be placed on improving synthetic MRI and MR fingerprinting approaches to shorten overall acquisition times while also addressing the demand of personalized care by simultaneously capturing microstructural information to provide greater detail of disease severity. Authors also anticipate increased research emphasis on metal artifact reduction techniques, bone imaging, and MR neurography to meet clinical needs.

MRI-based porosity index (PI) and suppression ratio (SR) in the tibial cortex show significant differences between normal, osteopenic, and osteoporotic female subjects.

Introduction: Ultrashort echo time (UTE) MRI enables quantitative assessment of cortical bone. The signal ratio in dual-echo UTE imaging, known as porosity index (PI), as well as the signal ratio between UTE and inversion recovery UTE (IR-UTE) imaging, known as the suppression ratio (SR), are two rapid UTE-based bone evaluation techniques developed to reduce the time demand and cost in future clinical studies. The goal of this study was to investigate the performance of PI and SR in detecting bone quality differences between subjects with osteoporosis (OPo), osteopenia (OPe), and normal bone (Normal). Methods: Tibial midshaft of fourteen OPe (72 ± 6 years old), thirty-one OPo (72 ± 6 years old), and thirty-seven Normal (36 ± 19 years old) subjects were scanned using dual-echo UTE and IR-UTE sequences on a clinical 3T scanner. Measured PI, SR, and bone thickness were compared between OPo, OPe, and normal bone (Normal) subjects using the Kruskal-Wallis test by ranks. Spearman's rank correlation coefficients were calculated between dual-energy x-ray absorptiometry (DEXA) T-score and UTE-MRI results. Results: PI was significantly higher in the OPo group compared with the Normal (24.1%) and OPe (16.3%) groups. SR was significantly higher in the OPo group compared with the Normal (41.5%) and OPe (21.8%) groups. SR differences between the OPe and Normal groups were also statistically significant (16.2%). Cortical bone was significantly thinner in the OPo group compared with the Normal (22.0%) and OPe (13.0%) groups. DEXA T-scores in subjects were significantly correlated with PI (R=-0.32), SR (R=-0.50), and bone thickness (R=0.51). Discussion: PI and SR, as rapid UTE-MRI-based techniques, may be useful tools to detect and monitor bone quality changes, in addition to bone morphology, in individuals affected by osteoporosis.