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PurposeThis cross-sectional study investigates the utility of the quantitative ultrashort echo time (UTE) adiabatic T1ρ (UTE-Adiab-T1ρ) magnetic resonance imaging (MRI) in detecting potential differences in Achilles tendons and entheses of patients with psoriatic arthritis disease (PsA) compared with asymptomatic volunteers.Material and methodThe Achilles tendons of forty-four PsA patients (59 ± 15 years old, 38 % female) and thirty-seven asymptomatic volunteers (32 ± 10 years old, 51 % female) were scanned on a 3 T clinical scanner in the sagittal plane using a 3-inch surface coil. The 3D UTE-Adiab-T1ρ sequences with fat saturation (FS) were used to measure UTE-Adiab-T1ρ. Tenderness of the tendons, the SF-12 health survey, and visual analog scale (VAS) were recorded for the patients. The Kruskal Wallis test was used to examine the differences in UTE-Adiab-T1ρ values between asymptomatic volunteers and patients, as well as subgroups of patients with pain in the Achilles tendon region and those treated with Biologics. Spearman's correlation coefficients were calculated between UTE-Adiab-T1ρ and patient evaluations. P values

Magnetization transfer (MT) magnetic resonance imaging (MRI) can be used to estimate the fraction of water and macromolecular proton pools in tissues. MT modeling paired with ultrashort echo time acquisition (UTE-MT modeling) has been proposed to improve the evaluation of the myotendinous junction and fibrosis in muscle tissues, which the latter increases with aging. This study aimed to determine if the UTE-MT modeling technique is sensitive to age-related changes in the skeletal muscles of the lower leg. Institutional review board approval was obtained, and all recruited subjects provided written informed consent. The legs of 31 healthy younger (28.1 ± 6.1 years old, BMI = 22.3 ± 3.5) and 20 older (74.7 ± 5.5 years old, BMI = 26.7 ± 5.9) female subjects were imaged using UTE sequences on a 3 T MRI scanner. MT ratio (MTR), macromolecular fraction (MMF), macromolecular T2 (T2-MM), and water T2 (T2-W) were calculated using UTE-MT modeling for the anterior tibialis (ATM), posterior tibialis (PTM), soleus (SM), and combined lateral muscles. Results were compared between groups using the Wilcoxon rank sum test. Three independent observers selected regions of interest (ROIs) and processed UTE-MRI images separately, and the intraclass correlation coefficient (ICC) was calculated for a reproducibility study. Significantly lower mean MTR and MMF values were present in the older compared with the younger group in all studied lower leg muscles. T2-MM showed significantly lower values in the older group only for PTM and SM muscles. In contrast, T2-W showed significantly higher values in the older group. The age-related differences were more pronounced for MMF (-17 to -19%) and T2-W (+20 to 47%) measurements in all muscle groups compared with other investigated MR measures. ICCs were higher than 0.93, indicating excellent consistency between the ROI selection and MRI measurements of independent readers. As demonstrated by significant differences between younger and older groups, this research emphasizes the potential of UTE-MT MRI techniques in evaluating age-related skeletal muscle changes.

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.

The cartilaginous endplate (CEP) plays a pivotal role in facilitating the supply of nutrients and, transport of metabolic waste, as well as providing mechanical support for the intervertebral disc (IVD). Recent technological advances have led to a surge in MR imaging studies focused on the CEP. This article describes the anatomy and functions of the CEP as well as MRI techniques for both qualitative and quantitative assessment of the CEP. Effective CEP MR imaging sequences require two key features: high spatial resolution and relatively short echo time. High spatial resolution spoiled gradient echo (SPGR) and ultrashort echo time (UTE) sequences, fulfilling these requirements, are the basis for most of the sequences employed in CEP imaging. This article reviews existing sequences for qualitative CEP imaging, such as the fat-suppressed SPGR and UTE, dual-echo subtraction UTE, inversion recovery prepared and fat-suppressed UTE, and dual inversion recovery prepared UTE sequences. These sequences are employed together with other techniques for quantitative CEP imaging, including measurements of T2*, T2, T1, T1ρ, magnetization transfer, perfusion, and diffusion tensor parameters. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Introduction: Eye emergencies make up nearly 3% of US emergency department (ED) visits. While emergency physicians (EP) should diagnose and treat these ophthalmologic emergencies, many trainees report limited ocular exposure and insufficient training throughout their residency to confidently conduct a thorough slit-lamp exam.Methods: We created an interdisciplinary, simulation-based mastery learning (SBML) curriculum to teach emergency attending physicians how to operate the slit lamp with multimodal learning methodology at a tertiary academic center. The EPs first demonstrate their initial slit-lamp competency with a 20-item checklist, and they then review the necessary curricular content to pass their independent readiness test before completing their in-person teaching and demonstration session with an ophthalmology attending to demonstrate procedural mastery (minimal passing score >90%).Results: Fifteen EPs were enrolled; all completed the final exam of the curriculum. The pre- and post-curriculum checklist scores increased by an average of seven points (P = .002); 86.7% of EPs felt confident in completing a slit-lamp exam after the curriculum, compared to 20% at the beginning. Five of 15 reported teaching learners within the two-month post-curricular period, ranging from 5–30 students. The hands-on teaching was the most positively reviewed element of the curriculum.Conclusion: The SBML program successfully trained EPs on performing a comprehensive slit-lamp exam with promising results of downstream education to junior learners. We encourage other institutions to leverage SBML as a teaching modality for procedural-based training and advocate cross-discipline education initiatives.

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.

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

Evaluation of 3D bone morphology of the glenohumeral joint is necessary for pre-surgical planning. Zero echo time (ZTE) magnetic resonance imaging (MRI) provides excellent bone contrast and can potentially be used in place of computed tomography. Segmentation of shoulder anatomy, particularly humeral head and acetabulum, is needed for detailed assessment of each anatomy and for pre-surgical preparation. In this study we compared performance of two popular deep learning models based on Google's DeepLab and U-Net to perform automated segmentation on ZTE MRI of human shoulders. Axial ZTE images of normal shoulders (n=31) acquired at 3-Tesla were annotated for training with a DeepLab and 2D U-Net, and the trained model was validated with testing data (n=13). While both models showed visually satisfactory results for segmenting the humeral bone, U-Net slightly over-estimated while DeepLab under-estimated the segmented area compared to the ground truth. Testing accuracy quantified by Dice score was significantly higher (p

Motivation: Increased risk of fractures in patients with type-2 diabetes mellitus (T2DM) despite higher average bone mineral density is unexplained with routine diagnostic tools like DEXA and CT. Goal(s): This study aimed to examine the feasibility of using ultrashort echo time (UTE) magnetization transfer (MT) modeling to detect the potential differences between T2DM and normal rats. Approach: The macromolecular fraction (MMF) and proton exchange rate (kab) from UTE-MT modeling on the tibial bone of Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats were compared. Results: There was a significant difference in MMF and kab measures between the two groups. Impact: The MMF and kab measures can detect potential bone alternations related to T2DM which may help to better understand the pathogenesis of T2DM bone fractures.

ObjectiveCartilage 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.DesignCadaveric 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.ResultsGrossly, 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

BackgroundTendon 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.MethodsThis 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.ResultsThe 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

PurposeTo develop a 3D phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence for whole knee joint mapping on a clinical 3 T scanner.MethodsThis 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.ResultsThe 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.ConclusionThe 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.

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.

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

BackgroundThe calcaneal enthesis, an osseous footprint where the Achilles tendon seamlessly integrates with the bone, represents a complex interface crucial for effective force transmission. Bone adapts to mechanical stress and remodels based on the applied internal and external forces. This study explores the relationship between the elasticity of the Achilles tendon enthesis and the bone microstructure in the calcaneal crescent.MethodsIn total, 19 calcaneal-enthesis sections, harvested from 10 fresh-frozen human cadaveric foot-ankle specimens (73.8 ± 6.0 years old, seven female), were used in this study. Indentation tests were performed at the enthesis region, and Hayes' elastic modulus was calculated for each specimen. Micro-CT scanning was performed at 50-micron voxel size to assess trabecular bone microstructure within six regions of interest (ROIs) and the cortical bone thickness along the calcaneal crescent.ResultsSignificant Spearman correlations were observed between the enthesis elastic modulus and trabecular bone thickness in the distal entheseal (ROI 3) and proximal plantar (ROI 4) regions (R = 0.786 and 0.518, respectively).ConclusionThis study highlights the potential impacts of Achilles tendon enthesis on calcaneal bone microstructure, which was pronounced in the distal calcaneal enthesis, suggesting regional differences in load transfer mechanism that require further investigation.

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.

Novel compositional magnetic resonance (MR) imaging techniques have allowed for both the qualitative and quantitative assessments of tissue changes in osteoarthritis, many of which are difficult to characterize on conventional MR imaging. Ultrashort echo time (UTE) and zero echo time (ZTE) MR imaging have not been broadly implemented clinically but have several applications that leverage contrast mechanisms for morphologic evaluation of bone and soft tissue, as well as biochemical assessment in various stages of osteoarthritis progression. Many of the musculoskeletal tissues implicated in the initiation and progression of osteoarthritis are short T2 in nature, appearing dark as signal has already decayed to its minimum when image sampling starts. UTE and ZTE MR imaging allow for the qualitative and quantitative assessments of these short T2 tissues (bone, tendon, calcified cartilage, meniscus, and ligament) with both structural and functional reference standards described in the literature [1-3]. This review will describe applications of UTE and ZTE MR imaging in musculoskeletal tissues focusing on its role in knee osteoarthritis. While the review will address tissue-specific applications of these sequences, it is understood that osteoarthritis is a whole joint process with involvement and interdependence of all tissues. KEY POINTS: • UTE MR imaging allows for the qualitative and quantitative evaluation of short T2 tissues (bone, calcified cartilage, and meniscus), enabling identification of both early degenerative changes and subclinical injuries that may predispose to osteoarthritis. • ZTE MR imaging allows for the detection of signal from bone, which has some of the shortest T2 values, and generates tissue contrast similar to CT, potentially obviating the need for CT in the assessment of osseous features of osteoarthritis.

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.

The purpose of the current study was to investigate the effects of B0 and linear eddy currents on ultrashort echo time double echo steady state (UTE-DESS) imaging and to determine whether eddy current correction (ECC) effectively resolves imaging artifacts caused by eddy currents. 3D UTE-DESS sequences based on either projection radial or spiral cones trajectories were implemented on a 3-T clinical MR scanner. An off-isocentered thin-slice excitation approach was used to measure eddy currents. The measurements were repeated four times using two sets of tested gradient waveforms with opposite polarities and two different slice locations to measure B0 and linear eddy currents simultaneously. Computer simulation was performed to investigate the eddy current effect. Finally, a phantom experiment, an ex vivo experiment with human synovium and ankle samples, and an in vivo experiment with human knee joints, were performed to demonstrate the effects of eddy currents and ECC in UTE-DESS imaging. In a computer simulation, the two echoes (S+ and S-) in UTE-DESS imaging exhibited strong distortion at different orientations in the presence of B0 and linear eddy currents, resulting in both image degradation as well as misalignment of pixel location between the two echoes. The same phenomenon was observed in the phantom, ex vivo, and in vivo experiments, where the presence of eddy currents degraded S+, S-, echo subtraction images, and T2 maps. The implementation of ECC dramatically improved both the image quality and image registration between the S+ and S- echoes. It was concluded that ECC is crucial for reliable morphological and quantitative UTE-DESS imaging.

The cortical bone porous microstructure can be evaluated using ultrashort echo time (UTE) MRI. UTE-MRI-based evaluation of bone has been underutilized partly due to the high cost and time demands of MRI in general. The porosity index (PI) and the suppression ratio (SR) are two rapid UTE-based bone evaluation techniques (~ 5 mins scan time each), which can potentially reduce the time demand and cost in future clinical studies. We have investigated the relationship of PI and SR measures with human cortical bone microstructural and mechanical properties. PI and SR showed significant correlations with microstructural and mechanical properties.

Evaluation of 3D bone morphology of the glenohumeral joint is necessary for pre-surgical planning. Zero echo time (ZTE) MRI provides excellent bone contrast, and we developed a deep learning model to perform automated segmentation of major bones (i.e., humerus and others) from ZTE to aid evaluation. Axial ZTE images of normal shoulders (n=31) acquired at 3T were annotated for training with a 2D U-Net, and the trained model was validated with testing data (n=10 normal shoulder, n=6 symptomatic). Testing accuracy was around 80 to 90% (Dice score) for either cohort, except for a few failed cases with very low scores.

Ultrashort echo time (UTE) MRI can image and consequently enable quantitative assessment of cortical bone. UTE-MRI-based evaluation of bone is largely underutilized due to the high cost and time demands of MRI in general. 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 (∼ 5 mins scan time each), which can potentially reduce the time demand and cost in future clinical studies. This study aimed to investigate the correlations of PI and SR measures with cortical bone microstructural and mechanical properties. Cortical bone strips (n = 135) from tibial and femoral midshafts of 37 donors (61 ± 24 years old) were scanned using a dual-echo 3D Cones UTE sequence and a 3D Cones IR-UTE sequence for PI and SR calculations, respectively. Average bone mineral density, porosity, and pore size were measured using microcomputed tomography (μCT). Bone mechanical properties were measured using 4-point bending tests. The μCT measures showed significant correlations with PI (moderate to strong, R = 0.68-0.71) and SR (moderate, R = 0.58-0.68). Young's modulus, yield stress, and ultimate stress demonstrated significant moderate correlations with PI and SR (R = 0.52-0.62) while significant strong correlations with μCT measures (R > 0.7). PI and SR can potentially serve as fast and noninvasive (non-ionizing radiation) biomarkers for evaluating cortical bone in various bone diseases.

The purpose of this study was to determine the negative predictive value (NPV) of a 12- to 14-wk posttreatment PET/CT for 2-y progression-free survival (PFS) and locoregional control (LRC) in patients with p16-positive locoregionally advanced oropharyngeal cancer (LA-OPC). Study was a secondary endpoint in NRG-HN002, a noncomparative phase II trial in p16-positive LA-OPC, stage T1-T2, N1-N2b or T3, N0-N2b, and ≤10 pack-year smoking. Patients were randomized in a 1:1 ratio to reduced-dose intensity-modulated radiotherapy (IMRT) with or without cisplatin. Methods: PET/CT scans were reviewed centrally. Tumor response evaluations for the primary site, right neck, and left neck were performed using a 5-point ordinal scale (Hopkins criteria). Overall scores were then assigned as negative, positive, or indeterminate. Patients with a negative score for all 3 evaluation sites were given an overall score of negative. The hypotheses were NPV for PFS and LRC at 2-y posttreatment ≤ 90% versus >90% (1-sided P value, 0.10). Results: A total of 316 patients were enrolled, of whom 306 were randomized and eligible. Of these, 131 (42.8%) patients consented to a posttherapy PET/CT, and 117 (89.3%) patients were eligible for PET/CT analysis. The median time from the end of treatment to PET/CT scan was 94 d (range, 52-139 d). Estimated 2-y PFS and LRC rates in the analysis subgroup were 91.3% (95% CI, 84.6, 95.8%) and 93.8% (95% CI, 87.6, 97.5%), respectively. Posttreatment scans were negative for residual tumor for 115 patients (98.3%) and positive for 2 patients (1.7%). NPV for 2-y PFS was 92.0% (90% lower confidence bound [LCB] 87.7%; P = 0.30) and for LRC was 94.5% (90% LCB 90.6%; P = 0.07). Conclusion: In the context of deintensification with reduced-dose radiation, the NPV of a 12- to 14-wk posttherapy PET/CT for 2-y LRC is estimated to be >90%, similar to that reported for patients receiving standard chemoradiation. However, there is insufficient evidence to conclude that the NPV is >90% for PFS.

Osteoarthritis is a common chronic degenerative disease that causes pain and disability with increasing incidence worldwide. The osteochondral junction is a dynamic region of the joint that is associated with the early development and progression of osteoarthritis. Despite the substantial advances achieved in the imaging of cartilage and application to osteoarthritis in recent years, the osteochondral junction has received limited attention. This is primarily related to technical limitations encountered with conventional MR sequences that are relatively insensitive to short T2 tissues and the rapid signal decay that characterizes these tissues. MR sequences with ultrashort echo time (UTE) are of great interest because they can provide images of high resolution and contrast in this region. Here, we briefly review the anatomy and function of cartilage, focusing on the osteochondral junction. We also review basic concepts and recent applications of UTE MR sequences focusing on the osteochondral junction.

BACKGROUND: Anaplastic thyroid cancer is a rare and aggressive cancer with no standard radiotherapy-based local treatment. Based on data suggesting synergy between pazopanib and paclitaxel in anaplastic thyroid cancer, NRG Oncology did a double-blind, placebo-controlled, randomised phase 2 clinical trial comparing concurrent paclitaxel and intensity-modulated radiotherapy (IMRT) with the addition of pazopanib or placebo with the aim of improving overall survival in this patient population. METHODS: Eligible patients were aged 18 years or older with a pathological diagnosis of anaplastic thyroid cancer, any TNM stage, Zubrod performance status of 0-2, no recent haemoptysis or bleeding, and no brain metastases. Patients were enrolled from 34 centres in the USA. Initially, a run-in was done to establish safety. In the randomised phase 2 trial, patients in the experimental group (pazopanib) received 2-3 weeks of weekly paclitaxel (80 mg/m2) intravenously and daily pazopanib suspension 400 mg orally followed by concurrent weekly paclitaxel (50 mg/m2), daily pazopanib (300 mg), and IMRT 66 Gy given in 33 daily fractions (2 Gy fractions). In the control group (placebo), pazopanib was replaced by matching placebo. Patients were randomly assigned (1:1) to the two treatment groups by permuted block randomisation by NRG Oncology with stratification by metastatic disease. All investigators, patients, and funders of the study were masked to group allocation. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with Clinicaltrials.gov, NCT01236547, and is complete. FINDINGS: The safety run-showed the final dosing regimen to be safe based on two out of nine participants having adverse events of predefined concern. Between June 23, 2014, and Dec 30, 2016, 89 patients were enrolled to the phase 2 trial, of whom 71 were eligible (36 in the pazopanib group and 35 in the placebo group; 34 [48%] males and 37 [52%] females). At the final analysis (data cutoff March 9, 2020), with a median follow-up of 2·9 years (IQR 0·002-4·0), 61 patients had died. Overall survival was not significantly improved with pazopanib versus placebo, with a median overall survival of 5·7 months (95% CI 4·0-12·8) in the pazopanib group versus 7·3 months (4·3-10·6) in the placebo group (hazard ratio 0·86, 95% CI 0·52-1·43; one-sided log-rank p=0·28). 1-year overall survival was 37·1% (95% CI 21·1-53·2) in the pazopanib group and 29·0% (13·2-44·8) in the placebo group. The incidence of grade 3-5 adverse events did not differ significantly between the treatment groups (pazopanib 88·9% [32 of 36 patients] and placebo 85·3% [29 of 34 patients]; p=0·73). The most common clinically significant grade 3-4 adverse events in the 70 eligible treated patients (36 in the pazopanib group and 34 in the placebo group) were dysphagia (13 [36%] vs 10 [29%]), radiation dermatitis (8 [22%] vs 13 [38%]), increased alanine aminotransferase (12 [33%] vs none), increased aspartate aminotransferase (eight [22%] vs none), and oral mucositis (five [14%] vs eight [24%]). Treatment-related serious adverse events were reported for 16 (44%) patients on pazopanib and 12 (35%) patients on placebo. The most common serious adverse events were dehydration and thromboembolic event (three [8%] each) in patients on pazopanib and oral mucositis (three [8%]) in those on placebo. There was one treatment-related death in each group (sepsis in the pazopanib group and pneumonitis in the placebo group). INTERPRETATION: To our knowledge, this study is the largest randomised anaplastic thyroid cancer study that has completed accrual showing feasibility in a multicenter NCI National Clinical Trials Network setting. Although no significant improvement in overall survival was recorded in the pazopanib group, the treatment combination was shown to be feasible and safe, and hypothesis-generating data that might warrant further investigation were generated. FUNDING: National Cancer Institute and Novartis.

AbstractRepeated computed tomography (CT) examinations increase patients' ionizing radiation exposure and health costs, making an alternative method desirable. Cortical and trabecular bone, however, have short T2 relaxation times, causing low signal intensity on conventional magnetic resonance (MR) sequences. Different techniques are available to create a "CT-like" contrast of bone, such as ultrashort echo time, zero echo time, gradient-echo, and susceptibility-weighted image MR sequences, and artificial intelligence. This systematic review summarizes the essential technical background and developments of ultrashort echo time, zero echo time, gradient-echo, susceptibility-weighted image MR imaging sequences and artificial intelligence; presents studies on research and clinical applications of "CT-like" MR imaging; and describes their main advantages and limitations. We also discuss future opportunities in research, which patients would benefit the most, the most appropriate situations for using the technique, and the potential to replace CT in the clinical workflow.

Magnetic resonance imaging (MRI) is widely regarded as the most comprehensive imaging modality to assess skeletal muscle quality and quantity. Magnetization transfer (MT) imaging can be used to estimate the fraction of water and macromolecular proton pools, with the latter including the myofibrillar proteins and collagen, which are related to the muscle quality and its ability to generate force. MT modeling combined with ultrashort echo time (UTE-MT modeling) may improve the evaluation of the myotendinous junction and regions with fibrotic tissues in the skeletal muscles, which possess short T2 values and higher bound-water concentration. The fat present in muscle has always been a source of concern in macromolecular fraction (MMF) calculation. This study aimed to investigate the impact of fat fraction (FF) on the estimated MMF in bovine skeletal muscle phantoms embedded in pure fat. MMF was calculated for several regions of interest (ROIs) with differing FFs using UTE-MT modeling with and without T1 measurement and B1 correction. Calculated MMF using measured T1 showed a robust trend, particularly with a negligible error ( 30%. However, MMF estimation using a constant T1 was robust only for regions with FF < 10%. The MTR and T1 values were also robust for only FF < 10%. This study highlights the potential of the UTE-MT modeling with accurate T1 measurement for robust muscle assessment while remaining insensitive to fat infiltration up to moderate levels.

IntroductionUltrashort 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).MethodsTibial 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.ResultsPI 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).DiscussionPI 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.

TP53 mutation is the most frequent genetic event in head and neck squamous cell carcinoma (HNSCC), found in more than 80% of patients with human papillomavirus-negative disease. As mutations in the TP53 gene are associated with worse outcomes in HNSCC, novel therapeutic approaches are needed for patients with TP53-mutated tumors. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issues of identifying and developing clinical trials for patients with TP53 mutations. Subcommittees, or breakout groups, were tasked with developing clinical studies in both the locally advanced and recurrent and/or metastatic (R/M) disease settings as well as considering signal-seeking trial designs. A fourth breakout group was focused on identifying and standardizing biomarker integration into trial design; this information was provided to the other breakout groups prior to the meeting to aid in study development. A total of 4 concepts were prioritized to move forward for further development and implementation. This article summarizes the proceedings of the Clinical Trials Planning Meeting with the goal of developing clinical trials for patients with TP53-mutant HNSCC that can be conducted within the National Clinical Trials Network.

Magnetic resonance imaging (MRI) uses a large magnetic field and radio waves to generate images of tissues in the body. Conventional MRI techniques have been developed to image and quantify tissues and fluids with long transverse relaxation times (T2s), such as muscle, cartilage, liver, white matter, gray matter, spinal cord, and cerebrospinal fluid. However, the body also contains many tissues and tissue components such as the osteochondral junction, menisci, ligaments, tendons, bone, lung parenchyma, and myelin, which have short or ultrashort T2s. After radio frequency excitation, their transverse magnetizations typically decay to zero or near zero before the receiving mode is enabled for spatial encoding with conventional MR imaging. As a result, these tissues appear dark, and their MR properties are inaccessible. However, when ultrashort echo times (UTEs) are used, signals can be detected from these tissues before they decay to zero. This review summarizes recent technical developments in UTE MRI of tissues with short and ultrashort T2 relaxation times. A series of UTE MRI techniques for high-resolution morphological and quantitative imaging of these short-T2 tissues are discussed. Applications of UTE imaging in the musculoskeletal, nervous, respiratory, gastrointestinal, and cardiovascular systems of the body are included.