Performance of MR learned pulse sequences for 3D bi-exponential, stretched-exponential, and mono-exponential T2 and T1ρ mapping of knee cartilage.

PURPOSE: To compare the performance of a learned magnetization-prepared gradient echo (L-MPGRE) sequence against a commonly used sequence for 3D T2 and T1ρ mapping of the knee joint, the magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS), on bi-exponential (BE), stretched-exponential (SE), and mono-exponential (ME) relaxation models. METHODS: We used a combined differentiable and non-differentiable optimization to learn pulse sequence structure and its parameters for 3D T2 and T1ρ mapping of the knee joint using ME, SE, and BE models. The learned pulse sequence framework was used to improve quantitative accuracy and SNR and to reduce filtering effects. We compare the measured multi-compartment values between the two sequences (n = 8), and their repeatability (n = 4) in healthy volunteers (n = 12 total). RESULTS: The voxel-wise median absolute percentage difference (MAPD) between the T2 and T1ρ maps obtained with each sequence was 18.6% and 19.9%, respectively. The T2 and T1ρ repeatability tests showed a MAPD of 18.5% and 19.1% for MAPSS, and 16.8% and 15.5% for L-MPGRE. Bland-Altman region of interest (ROI)-wise analysis shows that bias is small, close to -1.5%, and the coefficient of variation is around 5.5% when comparing ROIs from both sequences. CONCLUSION: The L-MPGRE sequences can be used as a replacement for MAPSS for T2 and T1ρ mapping in the knee cartilage with advantages, achieving similar accuracy and 15% better repeatability in only half of its scan time.

Feasibility of 3D MRI fingerprinting for rapid knee cartilage T1, T2, and T1ρ mapping at 0.55T: Comparison with 3T.

Low-field strength scanners present an opportunity for more inclusive imaging exams and bring several challenges including lower signal-to-noise ratio (SNR) and longer scan times. Magnetic resonance fingerprinting (MRF) is a rapid quantitative multiparametric method that can enable multiple quantitative maps simultaneously. To demonstrate the feasibility of an MRF sequence for knee cartilage evaluation in a 0.55T system we performed repeatability and accuracy experiments with agar-gel phantoms. Additionally, five healthy volunteers (age 32 ± 4 years old, 2 females) were scanned at 3T and 0.55T. The MRI acquisition protocols include a stack-of-stars T1ρ-enabled MRF sequence, a VIBE sequence with variable flip angles (VFA) for T1 mapping, and fat-suppressed turbo flash (TFL) sequences for T2 and T1ρ mappings. Double-Echo steady-state (DESS) sequence was also used for cartilage segmentation. Acquisitions were performed at two different field strengths, 0.55T and 3T, with the same sequences but protocols were slightly different to accommodate differences in signal-to-noise ratio and relaxation times. Cartilage segmentation was done using five compartments. T1, T2, and T1ρ values were measured in the knee cartilage using both MRF and conventional relaxometry sequences. The MRF sequence demonstrated excellent repeatability in a test-retest experiment with model agar-gel phantoms, as demonstrated with correlation and Bland-Altman plots. Underestimation of T1 values was observed on both field strengths, with the average global difference between reference values and the MRF being 151 ms at 0.55T and 337 ms at 3T. At 0.55T, MRF measurements presented significant biases but strong correlations with the reference measurements. Although a larger error was present in T1 measurements, MRF measurements trended similarly to the conventional measurements for human subjects and model agar-gel phantoms.

Assessment of cardiac and skeletal muscle metabolites using 1H-MRS and chemical-shift encoded magnetic resonance imaging: Impact of diabetes, RAGE, and DIAPH1.

Diabetes affects metabolism and metabolite concentrations in multiple organs. Previous preclinical studies have shown that receptor for advanced glycation end products (RAGE, gene symbol Ager) and its cytoplasmic domain binding partner, Diaphanous-1 (DIAPH1), are key mediators of diabetic micro- and macro-vascular complications. In this study, we used 1H-Magnetic Resonance Spectroscopy (MRS) and chemical shift encoded (CSE) Magnetic Resonance Imaging (MRI) to investigate the metabolite and water-fat fraction in the heart and hind limb muscle in a murine model of type 1 diabetes (T1D) and to determine if the metabolite changes in the heart and hind limb are influenced by (a) deletion of Ager or Diaph1 and (b) pharmacological blockade of RAGE-DIAPH1 interaction in mice. Nine cohorts of male mice, with six mice per cohort, were used: wild type non-diabetic control mice (WT-NDM), WT-diabetic (WT-DM) mice, Ager knockout non-diabetic (RKO-NDM) and diabetic mice (RKO-DM), Diaph1 knockout non-diabetic (DKO-NDM), and diabetic mice (DKO-DM), WT-NDM mice treated with vehicle, WT-DM mice treated with vehicle, and WT-DM mice treated with RAGE229 (antagonist of RAGE-DIAPH1 interaction). A Point Resolved Spectroscopy (PRESS) sequence for 1H-MRS, and multi-echo gradient recalled echo (GRE) for CSE were employed. Triglycerides, and free fatty acids in the heart and hind limb obtained from MRS and MRI were compared to those measured using biochemical assays. Two-sided t-test, non-parametric Kruskal-Wallis Test, and one-way ANOVA were employed for statistical analysis. We report that the results were well-correlated with significant differences using MRI and biochemical assays between WT-NDM and WT-DM, as well as within the non-diabetic groups, and within the diabetic groups. Deletion of Ager or Diaph1, or treatment with RAGE229 attenuated diabetes-associated increases in triglycerides in the heart and hind limb in mice. These results suggest that the employment of 1H-MRS/MRI is a feasible non-invasive modality to monitor metabolic dysfunction in T1D and the metabolic consequences of interventions that block RAGE and DIAPH1.

Characterization of Age-Related and Sex-Related Differences of Relaxation Parameters in the Intervertebral Disc Using MR-Fingerprinting.

BACKGROUND: Multiparameter characterization using MR fingerprinting (MRF) can quantify multiple relaxation parameters of intervertebral disc (IVD) simultaneously. These parameters may vary by age and sex. PURPOSE: To investigate age- and sex-related differences in the relaxation parameters of the IVD of the lumbar spine using a multiparameter MRF technique. STUDY TYPE: Prospective. SUBJECTS: 17 healthy subjects (8 male; mean age = 34 ± 10 years, range 20-60 years). FIELD STRENGTH/SEQUENCE: 3D-MRF sequence for simultaneous acquisition of proton density, T1 , T2 , and T1ρ maps at 3.0T. ASSESSMENT: Global mean T1 , T2 , and T1ρ of all lumbar IVDs and mean T1 , T2 , and T1ρ of each individual IVD (L1-L5) were measured. Gray level co-occurrence matrix was used to quantify textural features (median, contrast, correlation, energy, and homogeneity) from T1 , T2 , and T1ρ maps. STATISTICAL TESTS: Spearman rank correlations (R) evaluated the association between age and T1 , T2 , and T1ρ of IVD. Mann-Whitney U-tests evaluated differences between males and females in T1 , T2 , and T1ρ of IVD. Statistical significance was defined as P-value <0.05. RESULTS: There was a significant negative correlation between age and global mean values of all IVDs for T1 (R = -0.637), T2 (R = -0.509), and T1ρ (R = -0.726). For individual IVDs, there was a significant negative correlation between age and mean T1 at all IVD segments (R range = -0.530 to -0.708), between age and mean T2 at L2-L3, L3-L4, and L4-L5 (R range = -0.493 to 0.640), and between age and mean T1ρ at all segments except L1-L2 (R range = -0.632 to -0.763). There were no significant differences between sexes in global mean T1 , T2, and T1ρ (P-value = 0.23-0.76) The texture features with the highest significant correlations with age for all IVDs were global T1ρ mean (R = -0.726), T1 energy (R = -0.681), and T1 contrast (R = 0.709). CONCLUSION: This study showed that the 3D-MRF technique has potential to characterize age-related differences in T1 , T2, or T1ρ of IVD in healthy subjects. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Data-driven optimization of sampling patterns for MR brain T1ρ mapping.

PURPOSE: The goal of this study was to apply a fast data-driven optimization algorithm, called bias-accelerated subset selection, for MR brain T1ρ mapping to generate optimized sampling patterns (SPs) for compressed sensing reconstruction of brain 3D-T1ρ MRI. METHODS: Five healthy volunteers were recruited, and fully sampled Cartesian 3D-T1ρ MRIs were obtained. Variable density (VD) and Poisson disc (PD) undersampling was used as the input to SP optimization process. The reconstruction used 3 compressed sensing methods: spatiotemporal finite differences, low-rank plus sparse with spatial finite differences, and low rank. The performance of images and T1ρ maps using PD-SP and VD-SP and their optimized sampling patterns (PD-OSP and VD-OSP) were compared to the fully sampled reference using normalized root mean square error (NRMSE). RESULTS: The VD-OSP with spatiotemporal finite differences reconstruction (NRMSE = 0.078) and the PD-OSP with spatiotemporal finite differences reconstruction (NRMSE = 0.079) at the highest acceleration factors (AF = 30) showed the largest improvement compared to the respective nonoptimized SPs (VD NRMSE = 0.087 and PD NRMSE = 0.149). Prospective undersampling was tested at AF = 4, with VD-OSP NRMSE = 0.057 versus PD-OSP NRMSE = 0.060, with optimized sampling performing better that input PD or VD sampling. For brain T1ρ mapping, the VD-OSP with low rank reconstruction for AFs <10 and VD-OSP with spatiotemporal finite differences for AFs >10 perform better. CONCLUSIONS: The study demonstrated that the appropriate use of data-driven optimized sampling and suitable compressed sensing reconstruction technique can be employed to potentially accelerate 3D T1ρ mapping for brain imaging applications.

Optimizing variable flip angles in magnetization-prepared gradient-echo sequences for efficient 3D-T1ρ mapping.

PURPOSE: To optimize the choice of the flip angles of magnetization-prepared gradient-echo sequences for improved accuracy, precision, and speed of 3D-T1ρ mapping. METHODS: We propose a new optimization approach for finding variable flip-angle values that improve magnetization-prepared gradient-echo sequences used for 3D-T1ρ mapping. This new approach can improve the accuracy and SNR, while reducing filtering effects. We demonstrate the concept in the three different versions of the magnetization-prepared gradient-echo sequences that are typically used for 3D-T1ρ mapping and evaluate their performance in model agarose phantoms (n = 4) and healthy volunteers (n = 5) for knee joint imaging. We also tested the optimization with sequence parameters targeting faster acquisitions. RESULTS: Our results show that optimized variable flip angle can improve the accuracy and the precision of the sequences, seen as a reduction of the mean of normalized absolute difference from about 5%-6% to 3%-4% in model phantoms and from 15%-16% to 11%-13% in the knee joint, and improving SNR from about 12-28 to 22-32 in agarose phantoms and about 7-14 to 13-17 in healthy volunteers. The optimization can also compensate for the loss in quality caused by making the sequence faster. This results in sequence configurations that acquire more data per unit of time with SNR and mean of normalized absolute difference measurements close to its slower versions. CONCLUSION: The optimization of the variable flip angle can be used to increase accuracy and precision, and to improve the speed of the typical imaging sequences used for quantitative 3D-T1ρ mapping of the knee joint.

Age and gender differences in lumbar intervertebral disk strain using mechanical loading magnetic resonance imaging.

The objective of the current study was to investigate age- and gender-related differences in lumbar intervertebral disk (IVD) strain with the use of static mechanical loading and continuous three-dimensional (3D) golden-angle radial sparse parallel (GRASP) MRI. A continuous 3D-GRASP stack-of-stars trajectory of the lumbar spine was performed on a 3-T scanner with static mechanical loading. Compressed sensing reconstruction, motion deformation maps, and Lagrangian strain maps during loading and recovery in the X-, Y-, and Z-directions were calculated for segmented IVD segments from L1/L2 to L5/S1. Mean IVD height was measured at rest. Spearman coefficients were used to evaluate the associations between age and global IVD height and global IVD strain. Mann-Whitney tests were used to compare global IVD height and global IVD strain in males and females. The prospective study enrolled 20 healthy human volunteers (10 males, 10 females; age 34.6 ± 11.4 [mean ± SD], range 22-56 years). Significant increases in compressive strain were observed with age, as evidenced by negative correlations between age and global IVD strain during loading (ρ = -0.76, p = 0.0046) and recovery (ρ = -0.68, p = 0.0251) in the loading X-direction. There was no significant correlation between age and global IVD height, global IVD strain during loading and recovery in the Y-direction, and global IVD strain during loading and recovery in the Z-direction. There were no significant differences between males and females in global IVD height and global IVD strain during loading and recovery in the X-, Y-, and Z-directions. It was concluded that our study demonstrated the significant role aging plays in internal dynamic strains in the lumbar IVD during loading and recovery. Older healthy individuals have reduced IVD stiffness and greater IVD compression during static mechanical loading of the lumbar spine. The GRASP-MRI technique demonstrates the feasibility to identify changes in IVD mechanical properties with early IVD degeneration due to aging.

Repeatability of Quantitative Knee Cartilage T1 , T2 , and T1ρ Mapping With 3D-MRI Fingerprinting.

BACKGROUND: Three-dimensional MR fingerprinting (3D-MRF) techniques have been recently described for simultaneous multiparametric mapping of knee cartilage. However, investigation of repeatability remains limited. PURPOSE: To assess the intra-day and inter-day repeatabilities of knee cartilage T1 , T2 , and T1ρ maps using a 3D-MRF sequence for simultaneous measurement. STUDY TYPE: Prospective. SUBJECTS: Fourteen healthy subjects (35.4 ± 9.3 years, eight males), scanned on Day 1 and Day 7. FIELD STRENGTH/SEQUENCE: 3 T/3D-MRF, T1 , T2 , and T1ρ maps. ASSESSMENT: The acquisition of 3D-MRF cartilage (simultaneous acquisition of T1 , T2 , and T1ρ maps) were acquired using a dictionary pattern-matching approach. Conventional cartilage T1 , T2 , and T1ρ maps were acquired using variable flip angles and a modified 3D-Turbo-Flash sequence with different echo and spin-lock times, respectively, and were fitted using mono-exponential models. Each sequence was acquired on Day 1 and Day 7 with two scans on each day. STATISTICAL TESTS: The mean and SD for cartilage T1 , T2 , and T1ρ were calculated in five manually segmented regions of interest (ROIs), including lateral femur, lateral tibia, medial femur, medial tibia, and patella cartilages. Intra-subject and inter-subject repeatabilities were assessed using coefficient of variation (CV) and intra-class correlation coefficient (ICC), respectively, on the same day and among different days. Regression and Bland-Altman analysis were performed to compare maps between the conventional and 3D-MRF sequences. RESULTS: The CV in all ROIs was lower than 7.4%, 8.4%, and 7.5% and the ICC was higher than 0.56, 0.51, and 0.52 for cartilage T1 , T2 , and T1ρ , respectively. The MRF results had a good agreement with the conventional methods with a linear regression slope >0.61 and R2 > 0.59. CONCLUSION: The 3D-MRF sequence had high intra-subject and inter-subject repeatabilities for simultaneously measuring knee cartilage T1 , T2 , and T1ρ with good agreement with conventional sequences. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Age-Dependent Changes in Knee Cartilage T1 , T2 , and T1p Simultaneously Measured Using MRI Fingerprinting.

BACKGROUND: Magnetic resonance fingerprinting (MRF) techniques have been recently described for simultaneous multiparameter cartilage mapping of the knee although investigation of their ability to detect early cartilage degeneration remains limited. PURPOSE: To investigate age-dependent changes in knee cartilage T1 , T2 , and T1p relaxation times measured using a three-dimensional (3D) MRF sequence in healthy volunteers. STUDY TYPE: Prospective. SUBJECTS: The study group consisted of 24 healthy asymptomatic human volunteers (15 males with mean age 34.9 ± 14.4 years and 9 females with mean age 44.5 ± 13.1 years). FIELD STRENGTH/SEQUENCE: A 3.0 T gradient-echo-based 3D-MRF sequence was used to simultaneously create proton density-weighted images and T1 , T2 , and T1p maps of knee cartilage. ASSESSMENT: Mean global cartilage and regional cartilage (lateral femur, lateral tibia, medial femur, medial tibia, and patella) T1 , T2 , and T1ρ relaxation times of the knee were measured. STATISTICAL TESTS: Kruskal-Wallis tests were used to compared cartilage T1 , T2 , and T1ρ relaxation times between different age groups, while Spearman correlation coefficients was used to determine the association between age and cartilage T1 , T2 , and T1ρ relaxation times. The value of P < 0.05 was considered statistically significant. RESULTS: Higher age groups showed higher global and regional cartilage T1 , T2 , and T1ρ . There was a significant difference between age groups in global cartilage T2 and T1ρ but no significant difference (P = 0.13) in global cartilage T1. Significant difference was also present between age groups in cartilage T2 and T1ρ for medial femur cartilage and medial tibia cartilage. There were significant moderate correlations between age and T2 and T1ρ for global cartilage (R2  = 0.63-0.64), medial femur cartilage (R2  = 0.50-0.56), and medial tibia cartilage (R2  = 0.54-0.66). CONCLUSION: Cartilage T2 and T1p relaxation times simultaneously measured using a 3D-MRF sequence in healthy volunteers showed age-dependent changes in knee cartilage, primarily within the medial compartment.

Updates on Compositional MRI Mapping of the Cartilage: Emerging Techniques and Applications.

Osteoarthritis (OA) is a widely occurring degenerative joint disease that is severely debilitating and causes significant socioeconomic burdens to society. Magnetic resonance imaging (MRI) is the preferred imaging modality for the morphological evaluation of cartilage due to its excellent soft tissue contrast and high spatial resolution. However, its utilization typically involves subjective qualitative assessment of cartilage. Compositional MRI, which refers to the quantitative characterization of cartilage using a variety of MRI methods, can provide important information regarding underlying compositional and ultrastructural changes that occur during early OA. Cartilage compositional MRI could serve as early imaging biomarkers for the objective evaluation of cartilage and help drive diagnostics, disease characterization, and response to novel therapies. This review will summarize current and ongoing state-of-the-art cartilage compositional MRI techniques and highlight emerging methods for cartilage compositional MRI including MR fingerprinting, compressed sensing, multiexponential relaxometry, improved and robust radio-frequency pulse sequences, and deep learning-based acquisition, reconstruction, and segmentation. The review will also briefly discuss the current challenges and future directions for adopting these emerging cartilage compositional MRI techniques for use in clinical practice and translational OA research studies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis.

Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effective treatment. Here we establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, we identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis. Oral treatment with the pyrazolopyridine KDU731 results in a potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhoea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclinical evaluation as a drug candidate for the treatment of cryptosporidiosis.

Optimization of spin-lock times in T1ρ mapping of knee cartilage: Cramér-Rao bounds versus matched sampling-fitting.

PURPOSE: To compare different optimization approaches for choosing the spin-lock times (TSLs), in spin-lattice relaxation time in the rotating frame (T1ρ ) mapping. METHODS: Optimization criteria for TSLs based on Cramér-Rao lower bounds (CRLB) are compared with matched sampling-fitting (MSF) approaches for T1ρ mapping on synthetic data, model phantoms, and knee cartilage. The MSF approaches are optimized using robust methods for noisy cost functions. The MSF approaches assume that optimal TSLs depend on the chosen fitting method. An iterative non-linear least squares (NLS) and artificial neural networks (ANN) are tested as two possible T1ρ fitting methods for MSF approaches. RESULTS: All optimized criteria were better than non-optimized ones. However, we observe that a modified CRLB and an MSF based on the mean of the normalized absolute error (MNAE) were more robust optimization approaches, performing well in all tested cases. The optimized TSLs obtained the best performance with synthetic data (3.5-8.0% error), model phantoms (1.5-2.8% error), and healthy volunteers (7.7-21.1% error), showing stable and improved quality results, comparing to non-optimized approaches (4.2-13.3% error on synthetic data, 2.1-6.2% error on model phantoms, 9.8-27.8% error on healthy volunteers). CONCLUSION: A modified CRLB and the MSF based on MNAE are robust optimization approaches for choosing TSLs in T1ρ mapping. All optimized criteria allowed good results even using rapid scans with two TSLs when a complex-valued fitting is done with iterative NLS or ANN.

3D magnetic resonance fingerprinting for rapid simultaneous T1, T2, and T1ρ volumetric mapping of human articular cartilage at 3 T.

Quantitative MRI can detect early biochemical changes in cartilage; however, the conventional techniques only measure one parameter (e.g., T1 , T2 , and T1ρ ) at a time while also being comparatively slow. We implemented a 3D magnetic resonance fingerprinting (3D-MRF) technique for simultaneous, volumetric mapping of T1 , T2 , and T1ρ in knee articular cartilage in under 9 min. It is evaluated on 11 healthy volunteers (mean age: 53 ± 9 years), five mild knee osteoarthritis (OA) patients (Kellgren-Lawrence (KL) score: 2, mean age: 60 ± 4 years), and the National Institute of Standards and Technology (NIST)/International Society for Magnetic Resonance in Medicine (ISMRM) system phantom. Proton density image, and T1 , T2, T1ρ relaxation times, and B1 + were estimated in the NIST/ISMRM system phantom as well as in the human knee medial and lateral femur, medial and lateral tibia, and patellar cartilage. The repeatability and reproducibility of the proposed technique were assessed in the phantom using analysis of the Bland-Altman plots. The intrasubject repeatability was assessed with the coefficient of variation (CV) and root mean square CV (rmsCV). The Mann-Whitney U test was used to assess the difference between healthy subjects and mild knee OA patients. The Bland-Altman plots in the NIST/ISMRM phantom demonstrated an average difference of 0.001% ± 015%, 1.2% ± 7.1%, and 0.47% ± 3% between two scans from the same 3-T scanner (repeatability), and 0.002% ± 015%, 0.62% ± 10.5%, and 0.97% ± 14% between the scans acquired on two different 3-T scanners (reproducibility) for T1 , T2 , and T1ρ , respectively. The in vivo knee study showed excellent repeatability with rmsCV less than 1%, 2%, and 1% for T1 , T2 , and T1ρ , respectively. T1ρ relaxation time in the mild knee OA patients was significantly higher (p < 0.05) than in healthy subjects. The proposed 3D-MRF sequence is fast, reproducible, robust to B1 + inhomogeneity, and can simultaneously measure the T1 , T2 , T1ρ , and B1 + volumetric maps of the knee joint in a single scan within a clinically feasible scan time.

Simultaneous bilateral T1 , T2 , and T1ρ relaxation mapping of the hip joint with magnetic resonance fingerprinting.

Quantitative MRI can detect early biochemical changes in cartilage, but its bilateral use in clinical routines is challenging. The aim of this prospective study was to demonstrate the feasibility of magnetic resonance fingerprinting for bilateral simultaneous T1 , T2 , and T1ρ mapping of the hip joint. The study population consisted of six healthy volunteers with no known trauma or pain in the hip. Monoexponential T1 , T2 , and T1ρ relaxation components were assessed in femoral lateral, superolateral, and superomedial, and inferior, as well as acetabular, superolateral, and superomedial subregions in left and right hip cartilage. Aligned ranked nonparametric factorial analysis was used to assess the side's impact on the subregions. Kruskal-Wallis and Wilcoxon tests were used to compare subregions, and coefficient of variation to assess repeatability. Global averages of T1 (676.0 ± 45.4 and 687.6 ± 44.5 ms), T2 (22.5 ± 2.6 and 22.1 ± 2.5 ms), and T1ρ (38.2 ± 5.5 and 38.2 ± 5.5 ms) were measured in the left and right hip, and articular cartilage, respectively. The Kruskal-Wallis test showed a significant difference between different subregions' relaxation times regardless of the hip side (p < 0.001 for T1 , p = 0.012 for T2 , and p < 0.001 for T1ρ ). The Wilcoxon test showed that T1 of femoral layers was significantly (p < 0.003) higher than that for acetabular cartilage. The experiments showed excellent repeatability with CVrms of 1%, 2%, and 4% for T1 , T2 , and T1ρ, respectively. It was concluded that bilateral T1 , T2 , and T1ρ relaxation times, as well as B1+ maps, can be acquired simultaneously from hip joints using the proposed MRF sequence.

Unbound vitamin D concentrations are not decreased in critically ill patients.

BACKGROUND: Free concentrations of highly protein bound hormones, such as cortisol and thyroxine, are unchanged in critical illness despite substantial decreases in total concentration. Total 25-hydroxyvitamin D (25(OH)D) concentration is decreased in critical illness, but the free concentration of 25(OH)D has had less attention. AIM: To compare total and calculated free 25(OH)D concentrations in critically ill patients with healthy controls. METHODS: In this case-control study, 38 patients with critical illness were compared with 68 healthy controls; 25(OH)D was measured by liquid chromatography tandem mass spectrometry (LCMS/MS) and vitamin D binding protein (VDBP) by direct sandwich enzyme-linked immunosorbent assay. Total and calculated free 25(OH)D concentrations were compared using unpaired t-tests. RESULTS: Total 25(OH)D concentrations were significantly lower in critically ill patients than controls (37 (95% confidence interval 31-43) vs 57 (53-60) nmol/L). Calculated free concentrations of 25(OH)D were not lower in critically ill patients than healthy controls (26 (22-29) vs 19 (18-20) pmol/L). CONCLUSIONS: Calculated free 25(OH)D concentrations are not decreased in critical illness. Measuring total 25(OH)D concentrations in patients with critical illness potentially underestimates vitamin D and overestimates the number of patients who are deficient in vitamin D.

Simultaneous T1 , T2 , and T1ρ relaxation mapping of the lower leg muscle with MR fingerprinting.

PURPOSE: To develop a novel MR-fingerprinting (MRF) pulse sequence that is insensitive to B1+ and B0 imperfections for simultaneous T1 , T2 , and T1ρ relaxation mapping. METHODS: We implemented a totally balanced spin-lock (TB-SL) module to encode T1ρ relaxation into an existing MRF framework that encoded T1 and T2 . The spin-lock module used two 180° pulses with compensatory phases to reduce T1ρ sensitivity to B1 and B0 inhomogeneities. We compared T1ρ measured using TB-SL MRF in Bloch simulations, model agar phantoms, and in vivo experiments to those with a self-compensated spin-lock preparation module (SC-SL). The TB-SL MRF repeatability was evaluated in maps acquired in the lower leg skeletal muscle of 12 diabetic peripheral neuropathy patients, scanned two times each during visits separated by about 30 days. RESULTS: The phantom relaxation times measured with TB-SL and SC-SL MRF were in good agreement with reference values in regions with low B1 inhomogeneities. Compared with SC-SL, TB-SL MRF showed in experiments greater robustness against severe B1 inhomogeneities and in Bloch simulations greater robustness against B1 and B0 . We measured with TB-SL MRF an average T1 = 950.1 ± 28.7 ms, T2 = 26.0 ± 1.2 ms, and T1ρ = 31.7 ± 3.2 ms in skeletal muscle across patients. Bland-Altman analysis demonstrated low bias between TB-SL and SC-SL MRF and between TB-SL MRF maps acquired in two visits. The coefficient of variation was less than 3% for all measurements. CONCLUSION: The proposed TB-SL MRF sequence is fast and insensitive to B1+ and B0 imperfections. It can simultaneously map T1 , T2 , T1ρ , and B1+ in a single scan and can potentially be used to study muscle composition.

Measurement of Three-Dimensional Internal Dynamic Strains in the Intervertebral Disc of the Lumbar Spine With Mechanical Loading and Golden-Angle Radial Sparse Parallel-Magnetic Resonance Imaging.

BACKGROUND: Noninvasive measurement of internal dynamic strain can be potentially useful to characterize spine intervertebral disc (IVD) in the setting of injury or degenerative disease. PURPOSE: To develop and demonstrate a noninvasive technique to quantify three-dimensional (3D) internal dynamic strains in the IVD using a combination of static mechanical loading of the IVD using a magnetic resonance imaging (MRI)-compatible ergometer. STUDY TYPE: Prospective. SUBJECTS: Silicone gel phantom studies were conducted to assess strain variation with load and repeatability. Mechanical testing was done on the phantoms to confirm MR results. Eight healthy human volunteers (four men and four woman, age = 29 ± 5 years) underwent MRI using a rest, static loading, and recovery paradigm. Repeatability tests were conducted in three subjects. FIELD STRENGTH/SEQUENCE: MRI (3 T) with 3D continuous golden-angle radial sparse parallel (GRASP) and compressed sensing (CS) reconstruction. ASSESSMENT: CS reconstruction of the images, motion deformation, and Lagrangian strain maps were calculated for five IVD segments from L1/L2 to L5/S1. STATISTICAL TESTS: Ranges of displacement and strain in each subject and the resulting mean and standard deviation were calculated. Student t-tests were used to calculate changes in strain from loading to recovery. The correlation coefficient (CC) in the repeatability study was calculated. RESULTS: The most compressive strain experienced by the IVD segments under loaded conditions was in the L4/L5 segment (-7.5 ± 2.9%). The change in minimum strain from load to recovery was the most for the L4/L5 segment (-7.5% to -5.0%, P = 0.026) and the least for the L1/L2 segment (-4.4% to -3.9%, P = 0.51). In vivo repeatability in three subjects shows strong correlation between scans in subjects done 6 months apart, with CCs equal to 0.86, 0.94, and 0.94 along principal directions. DATA CONCLUSION: This study shows the feasibility of using static mechanical loading with continuous GRASP-MRI acquisition with CS reconstruction to measure 3D internal dynamic strains in the spine IVD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Performance Comparison of Compressed Sensing Algorithms for Accelerating T1ρ Mapping of Human Brain.

BACKGROUND: 3D-T1ρ mapping is useful to quantify various neurologic disorders, but data are currently time-consuming to acquire. PURPOSE: To compare the performance of five compressed sensing (CS) algorithms-spatiotemporal finite differences (STFD), exponential dictionary (EXP), 3D-wavelet transform (WAV), low-rank (LOW) and low-rank plus sparse model with spatial finite differences (L + S SFD)-for 3D-T1ρ mapping of the human brain with acceleration factors (AFs) of 2, 5, and 10. STUDY TYPE: Retrospective. SUBJECTS: Eight healthy volunteers underwent T1ρ imaging of the whole brain. FIELD STRENGTH/SEQUENCE: The sequence was fully sampled 3D Cartesian ultrafast gradient echo sequence with a customized T1ρ preparation module on a clinical 3T scanner. ASSESSMENT: The fully sampled data was undersampled by factors of 2, 5, and 10 and reconstructed with the five CS algorithms. Image reconstruction quality was evaluated and compared to the SENSE reconstruction of the fully sampled data (reference) and T1ρ estimation errors were assessed as a function of AF. STATISTICAL TESTS: Normalized root mean squared errors (nRMSE) and median normalized absolute deviation (MNAD) errors were calculated to compare image reconstruction errors and T1ρ estimation errors, respectively. Linear regression plots, Bland-Altman plots, and Pearson correlation coefficients (CC) are shown. RESULTS: For image reconstruction quality, at AF = 2, EXP transforms had the lowest mRMSE (1.56%). At higher AF values, STFD performed better, with the smallest errors (3.16% at AF = 5, 4.32% at AF = 10). For whole-brain quantitative T1ρ mapping, at AF = 2, EXP performed best (MNAD error = 1.62%). At higher AF values (AF = 5, 10), the STFD technique had the least errors (2.96% at AF = 5, 4.24% at AF = 10) and the smallest variance from the reference T1ρ estimates. DATA CONCLUSION: This study demonstrates the use of different CS algorithms that may be useful in reducing the scan time required to perform volumetric T1ρ mapping of the brain. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 1.

Current status of functional MRI of osteoarthritis for diagnosis and prognosis.

PURPOSE OF REVIEW: Osteoarthritis is a major source of disability, pain and socioeconomic cost worldwide. The epidemiology of the disorder is multifactorial including genetic, biological and biomechanical components, some of them detectable by MRI. This review provides the most recent update on MRI biomarkers which can provide functional information of the joint structures for diagnosis, prognosis and treatment response monitoring in osteoarthritis trials. RECENT FINDINGS: Compositional or functional MRI can provide clinicians with valuable information on glycosaminoglycan content (chemical exchange saturation transfer, sodium MRI, T1ρ) and collagen organization (T2, T2, apparent diffusion coefficient, magnetization transfer) in joint structures. Other parameters may also provide useful information, such as volumetric measurements of joint structures or advanced image data postprocessing and analysis. Automated tools seem to have a great potential to be included in these efforts providing standardization and acceleration of the image data analysis process. SUMMARY: Functional or compositional MRI has great potential to provide noninvasive imaging biomarkers for osteoarthritis. Osteoarthritis as a whole joint condition needs to be diagnosed in early stages to facilitate selection of patients into clinical trials and/or to measure treatment effectiveness. Advanced evaluation including machine learning, neural networks and multidimensional data analysis allow for wall-to-wall understanding of parameter interactions and their role in clinical evaluation of osteoarthritis.

Accelerated mono- and biexponential 3D-T1ρ relaxation mapping of knee cartilage using golden angle radial acquisitions and compressed sensing.

PURPOSE: To use golden-angle radial sampling and compressed sensing (CS) for accelerating mono- and biexponential 3D spin-lattice relaxation time in the rotating frame (T1ρ ) mapping of knee cartilage. METHODS: Golden-angle radial stack-of-stars and Cartesian 3D-T1ρ -weighted knee cartilage datasets (n = 12) were retrospectively undersampled by acceleration factors (AFs) 2-10. CS-based reconstruction using 8 different sparsifying transforms were compared for mono- and biexponential T1ρ -mapping of knee cartilage, including spatio-temporal finite differences, wavelets, dictionary from principal component analysis, and exponential decay models, and also low rank and low rank plus sparse models (L+S). Complex-valued fitting was used and Marchenko-Pastur principal component analysis filtering also tested. RESULTS: Most CS methods performed well for an AF of 2, with relative median normalized absolute deviation below 10% for monoexponential and biexponential mapping. For monoexponential mapping, radial sampling obtained a median normalized absolute deviation below 10% up to AF of 10, while Cartesian obtained this level of error only up to AF of 4. Radial sampling was also better with biexponential T1ρ mapping, with median normalized absolute deviation below 10% up to AF of 6. CONCLUSION: Golden-angle radial acquisitions combined with CS outperformed Cartesian acquisitions for 3D-T1ρ mapping of knee cartilage, being it is a good alternative to Cartesian sampling for reducing scan time and/or improving image and mapping quality. The methods exponential decay models, spatio-temporal finite differences, and low rank obtained the best results for radial sampling patterns.