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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]