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The dynamic contrast-enhanced (DCE)-MRI parameter K trans can quantify the intensity of synovial inflammation (synovitis) in knees with osteoarthritis (OA), but requires the use of gadolinium-based contrast agent (GBCA). Diffusion tensor imaging (DTI) measures the diffusion of water molecules with parameters mean diffusivity (MD) and fractional anisotropy (FA), and has been proposed as a method to detect synovial inflammation without the use of GBCA. The purpose of this study is to (1) determine the ability of DTI to quantify the intensity of synovitis in OA by comparing MD and FA with our imaging gold standard K trans within the synovium and (2) compare DTI and DCE-MRI measures with the semi-quantitative grading of OA severity with the Kellgren-Lawrence (KL) and MRI Osteoarthritis Knee Score (MOAKS) systems, in order to assess the relationship between synovitis intensity and OA severity. Within the synovium, MD showed a significant positive correlation with K trans (r = 0.79, p < 0.001), while FA showed a significant negative correlation with K trans (r = -0.72, p = 0.0026). These results show that DTI is able to quantify the intensity of synovitis within the whole synovium without the use of exogenous contrast agent. Additionally, MD, FA, and K trans values did not vary significantly when knees were separated by KL grade (p = 0.15, p = 0.32, p = 0.41, respectively), while MD (r = 0.60, p = 0.018) and K trans (r = 0.62, p = 0.013) had a significant positive correlation and FA (r = -0.53, p = 0.043) had a negative correlation with MOAKS. These comparisons indicate that quantitative measures of the intensity of synovitis may provide information in addition to morphological assessment to evaluate OA severity. Using DTI to quantify the intensity of synovitis without GBCA may be helpful to facilitate a broader clinical assessment of the severity of OA., (© 2021 John Wiley & Sons, Ltd.)

Cartilage transmits and redistributes biomechanical loads in the knee joint during exercise. Exercise-induced loading alters cartilage hydration and is detectable using quantitative magnetic resonance imaging (MRI), where T 2 relaxation time (T 2 ) is influenced by cartilage collagen composition, fiber orientation, and changes in the extracellular matrix. This study characterized short-term transient responses of healthy knee cartilage to running-induced loading using bilateral scans and image registration. Eleven healthy female recreational runners (33.73 ± 4.22 years) and four healthy female controls (27.25 ± 1.38 years) were scanned on a 3T GE MRI scanner with quantitative 3D double-echo in steady-state before running over-ground (runner group) or resting (control group) for 40 min. Subjects were scanned immediately post-activity at 5-min intervals for 60 min. T 2 times were calculated for femoral, tibial, and patellar cartilage at each time point and analyzed using a mixed-effects model and Bonferroni post hoc. There were immediate decreases in T 2 (mean ± SEM) post-run in superficial femoral cartilage of at least 3.3% ± 0.3% (p = .002) between baseline and Time 0 that remained for 25 min, a decrease in superficial tibial cartilage T 2 of 2.9% ± 0.4% (p = .041) between baseline and Time 0, and a decrease in superficial patellar cartilage T 2 of 3.6% ± 0.3% (p = .020) 15 min post-run. There were decreases in the medial posterior region of superficial femoral cartilage T 2 of at least 5.3 ± 0.2% (p = .022) within 5 min post-run that remained at 60 min post-run. These results increase understanding of transient responses of healthy cartilage to repetitive, exercise-induced loading and establish preliminary recommendations for future definitive studies of cartilage response to running., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Magnetic resonance imaging (MRI) is commonly used to evaluate the morphology of the knee in athletes with high-knee impact; however, complex repeated loading of the joint can lead to biochemical and structural degeneration that occurs before visible morphological changes. In this study, we utilized multiparametric quantitative MRI to compare morphology and composition of articular cartilage and subchondral bone shape between young athletes with high-knee impact (basketball players; n = 40) and non-knee impact (swimmers; n = 25). We implemented voxel-based relaxometry to register all cases to a single reference space and performed a localized compositional analysis of T 1ρ - and T 2 -relaxation times on a voxel-by-voxel basis. Additionally, statistical shape modeling was employed to extract differences in subchondral bone shape between the two groups. Evaluation of cartilage composition demonstrated a significant prolongation of relaxation times in the medial femoral and tibial compartments and in the posterolateral femur of basketball players in comparison to relaxation times in the same cartilage compartments of swimmers. The compositional analysis also showed depth-dependent differences with prolongation of the superficial layer in basketball players. For subchondral bone shape, three total modes were found to be significantly different between groups and related to the relative sizes of the tibial plateaus, intercondylar eminences, and the curvature and concavity of the patellar lateral facet. In summary, this study identified several characteristics associated with a high-knee impact which may expand our understanding of local degenerative patterns in this population., (© 2020 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Chemical exchange saturation transfer of glycosaminoglycans, gagCEST, is a quantitative MR technique that has potential for assessing cartilage proteoglycan content at field strengths of 7 T and higher. However, its utility at 3 T remains unclear. The objective of this work was to implement a rapid volumetric gagCEST sequence with higher gagCEST asymmetry at 3 T to evaluate its sensitivity to osteoarthritic changes in knee articular cartilage and in comparison with T 2 and T 1ρ measures. We hypothesize that gagCEST asymmetry at 3 T decreases with increasing severity of osteoarthritis (OA). Forty-two human volunteers, including 10 healthy subjects and 32 subjects with medial OA, were included in the study. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were assessed for all subjects, and Kellgren-Lawrence grading was performed for OA volunteers. Healthy subjects were scanned consecutively at 3 T to assess the repeatability of the volumetric gagCEST sequence at 3 T. For healthy and OA subjects, gagCEST asymmetry and T 2 and T 1ρ relaxation times were calculated for the femoral articular cartilage to assess sensitivity to OA severity. Volumetric gagCEST imaging had higher gagCEST asymmetry than single-slice acquisitions (p = 0.015). The average scan-rescan coefficient of variation was 6.8%. There were no significant differences in average gagCEST asymmetry between younger and older healthy controls (p = 0.655) or between healthy controls and OA subjects (p = 0.310). T 2 and T 1ρ relaxation times were elevated in OA subjects (p < 0.001 for both) compared with healthy controls and both were moderately correlated with total KOOS scores (rho = -0.181 and rho = -0.332 respectively). The gagCEST technique developed here, with volumetric scan times under 10 min and high gagCEST asymmetry at 3 T, did not vary significantly between healthy subjects and those with mild-moderate OA. This further supports a limited utility for gagCEST imaging at 3 T for assessment of early changes in cartilage composition in OA., (© 2020 John Wiley & Sons, Ltd.)

Purpose: To develop a super-resolution technique using convolutional neural networks for generating thin-slice knee MR images from thicker input slices, and compare this method with alternative through-plane interpolation methods., Methods: We implemented a 3D convolutional neural network entitled DeepResolve to learn residual-based transformations between high-resolution thin-slice images and lower-resolution thick-slice images at the same center locations. DeepResolve was trained using 124 double echo in steady-state (DESS) data sets with 0.7-mm slice thickness and tested on 17 patients. Ground-truth images were compared with DeepResolve, clinically used tricubic interpolation, and Fourier interpolation methods, along with state-of-the-art single-image sparse-coding super-resolution. Comparisons were performed using structural similarity, peak SNR, and RMS error image quality metrics for a multitude of thin-slice downsampling factors. Two musculoskeletal radiologists ranked the 3 data sets and reviewed the diagnostic quality of the DeepResolve, tricubic interpolation, and ground-truth images for sharpness, contrast, artifacts, SNR, and overall diagnostic quality. Mann-Whitney U tests evaluated differences among the quantitative image metrics, reader scores, and rankings. Cohen's Kappa (κ) evaluated interreader reliability., Results: DeepResolve had significantly better structural similarity, peak SNR, and RMS error than tricubic interpolation, Fourier interpolation, and sparse-coding super-resolution for all downsampling factors (p < .05, except 4 × and 8 × sparse-coding super-resolution downsampling factors). In the reader study, DeepResolve significantly outperformed (p < .01) tricubic interpolation in all image quality categories and overall image ranking. Both readers had substantial scoring agreement (κ = 0.73)., Conclusion: DeepResolve was capable of resolving high-resolution thin-slice knee MRI from lower-resolution thicker slices, achieving superior quantitative and qualitative diagnostic performance to both conventionally used and state-of-the-art methods., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: To demonstrate and evaluate the scan time and quantitative accuracy of simultaneous bilateral-knee imaging compared with single-knee acquisitions., Methods: Hardware modifications and safety testing was performed to enable MR imaging with two 16-channel flexible coil arrays. Noise covariance and sensitivity-encoding g-factor maps for the dual-coil-array configuration were computed to evaluate coil cross-talk and noise amplification. Ten healthy volunteers were imaged on a 3T MRI scanner with both dual-coil-array bilateral-knee and single-coil-array single-knee configurations. Two experienced musculoskeletal radiologists compared the relative image quality between blinded image pairs acquired with each configuration. Differences in T 2 relaxation time measurements between dual-coil-array and single-coil-array acquisitions were compared with the standard repeatability of single-coil-array measurements using a Bland-Altman analysis., Results: The mean g-factors for the dual-coil-array configuration were low for accelerations up to 6 in the right-left direction, and minimal cross-talk was observed between the two coil arrays. Image quality ratings of various joint tissues showed no difference in 89% (95% confidence interval: 85-93%) of rated image pairs, with only small differences ("slightly better" or "slightly worse") in image quality observed. The T 2 relaxation time measurements between the dual-coil-array configuration and the single-coil configuration showed similar limits of agreement and concordance correlation coefficients (limits of agreement: -0.93 to 1.99 ms; CCC: 0.97 (95% confidence interval: 0.96-0.98)), to the repeatability of single-coil-array measurements (limits of agreement: -2.07 to 1.96 ms; CCC: 0.97 (95% confidence interval: 0.95-0.98))., Conclusion: A bilateral coil-array setup can image both knees simultaneously in similar scan times as conventional unilateral knee scans, with comparable image quality and quantitative accuracy. This has the potential to improve the value of MRI knee evaluations. Magn Reson Med 80:529-537, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop and optimize a multislice glycosaminoglycan (GAG) chemical exchange saturation transfer (GagCEST) sequence for volumetric imaging of articular cartilage, and to validate the sequence against T 1ρ relaxation times in whole joint imaging of tibiotalar cartilage., Methods: Ex vivo experiments were used to observe the effect of the number of partitions and shot TR on signal-to-noise ratio and measured GagCEST asym . GagCEST imaging of the entire tibiotalar joint was also performed on 10 healthy subjects. The measured GagCEST asym was compared and correlated with T 1ρ relaxation times., Results: Ex vivo studies showed a higher average GagCEST asym from articular cartilage on multislice acquisitions acquired with two or more partitions than observed with a single-slice acquisition. In healthy human subjects, an average GagCEST asym of 8.8 ± 0.7% was observed. A coefficient of variation of GagCEST asym across slices of less than 15% was seen for all subjects. Across subjects, a Pearson correlation coefficient of -0.58 was observed between the measured gagCEST asym and T 1ρ relaxation times., Conclusions: We demonstrated the feasibility and optimization of multislice GagCEST mapping of articular cartilage. Volumetric analysis and decreased scan times will help to advance the clinical utility of GagCEST imaging of articular cartilage. Magn Reson Med 77:1134-1141, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Creatine, a key component of muscle energy metabolism, exhibits a chemical exchange saturation transfer (CEST) effect between its amine group and bulk water, which has been exploited to spatially and temporally map creatine changes in skeletal muscle before and after exercise. In addition, exercise leads to an increase in muscle perfusion. In this work, we determined the effects of perfused blood on the CEST effects from creatine in skeletal muscle. Experiments were performed on healthy human subjects (n = 5) on a whole-body Siemens 7T magnetic resonance imaging (MRI) scanner with a 28-channel radiofrequency (RF) coil. Reactive hyperemia, induced by inflation and subsequent deflation of a pressure cuff secured around the thigh, was used to increase tissue perfusion whilst maintaining the levels of creatine kinase metabolites. CEST, arterial spin labeling (ASL) and 31 P MRS data were acquired at baseline and for 6 min after cuff deflation. Reactive hyperemia resulted in substantial increases in perfusion in human skeletal muscle of the lower leg as measured by the ASL mean percentage difference. However, no significant changes in CrCEST asymmetry (CrCEST asym ) or 31 P MRS-derived PCr levels of skeletal muscle were observed following cuff deflation. This work demonstrates that perfusion changes do not have a major confounding effect on CrCEST measurements., (Copyright © 2016 John Wiley & Sons, Ltd.)

Purpose: To develop a chemical exchange saturation transfer (CEST)-based technique to measure free creatine (Cr) and to validate the technique by measuring the distribution of Cr in muscle with high spatial resolution before and after exercise., Methods: Phantom studies were performed to determine contributions from other Cr kinase metabolites to the CEST effect from Cr (CrCEST). CEST, T2 , magnetization transfer ratio and (31) P magnetic resonance spectroscopy acquisitions of the lower leg were performed before and after plantar flexion exercise on a 7T whole-body magnetic resonance scanner on healthy volunteers., Results: Phantom studies demonstrated that while Cr exhibited significant CEST effect there were no appreciable contributions from other metabolites. In healthy human subjects, following mild plantar flexion exercise, increases in the CEST effect from Cr were observed, which recovered exponentially back to baseline. This technique exhibited good spatial resolution and was able to differentiate differences in muscle utilization among subjects. The CEST effect from Cr results were compared with (31) P magnetic resonance spectroscopy results showing good agreement in the Cr and phosphocreatine recovery kinetics., Conclusion: Demonstrated a CEST-based technique to measure free Cr changes in in vivo muscle. The CEST effect from Cr imaging can spatially map changes in Cr concentration in muscle following mild exercise. This may serve as a tool for the diagnosis and treatment of various disorders affecting muscle., (Copyright © 2013 Wiley Periodicals, Inc.)

Glutamate (Glu) is a major excitatory neurotransmitter in the brain and has been shown to decrease in the early stages of Alzheimer's disease (AD). Using a glutamate chemical (amine) exchange saturation transfer (GluCEST) method, we imaged the change in [Glu] in the APP-PS1 transgenic mouse model of AD at high spatial resolution. Compared with wild-type controls, AD mice exhibited a notable reduction in GluCEST contrast (~30%) in all areas of the brain. The change in [Glu] was further validated through (1) H MRS. A positive correlation was observed between GluCEST contrast and (1) H MRS-measured Glu/total creatine ratio. This method potentially provides a novel noninvasive biomarker for the diagnosis of the disease in preclinical stages and enables the development of disease-modifying therapies for AD., (Copyright © 2012 John Wiley & Sons, Ltd.)

Creatine (Cr), phosphocreatine (PCr) and adenosine-5-triphosphate (ATP) are major metabolites of the enzyme creatine kinase (CK). The exchange rate of amine protons of CK metabolites at physiological conditions has been limited. In the current study, the exchange rate and logarithmic dissociation constant (pKa) of amine protons of CK metabolites were calculated. Further, the chemical exchange saturation transfer effect (CEST) of amine protons of CK metabolites with bulk water was explored. At physiological temperature and pH, the exchange rate of amine protons in Cr was found to be 7-8 times higher than PCr and ATP. A higher exchange rate in Cr was associated with lower pKa value, suggesting faster dissociation of its amine protons compared to PCr and ATP. CEST MR imaging of these metabolites in vitro in phantoms displayed predominant CEST contrast from Cr and negligible contribution from PCr and ATP with the saturation pulse parameters used in the current study. These results provide a new method to perform high-resolution proton imaging of Cr without contamination from PCr. Potential applications of these finding are discussed., (Copyright © 2012 John Wiley & Sons, Ltd.)

The sensitivity of chemical exchange saturation transfer (CEST) on glycosaminoglycans (GAGs) in human knee cartilage (gagCEST) in vivo was evaluated at 3 and 7 T field strengths. Calculated gagCEST values without accounting for B(0) inhomogeneity (~0.6 ppm) were >20%. After B(0) inhomogeneity correction, calculated gagCEST values were negligible at 3 T and ~6% at 7 T. These results suggest that accurate B(0) correction is a prerequisite for observing reliable gagCEST. Results obtained with varying saturation pulse durations and amplitudes as well as the consistency between numerical simulations and our experimental results indicate that the negligible gagCEST observed at 3 T is due to direct saturation effects and fast exchange rate. As GAG loss from cartilage is expected to result in a further reduction in gagCEST, gagCEST method is not expected to be clinically useful at 3 T. At high fields such as 7 T, this method holds promise as a viable clinical technique., (Copyright © 2011 Wiley Periodicals, Inc.)

Proton exchange imaging is important as it allows for visualization and quantification of the distribution of specific metabolites with conventional MRI. Current exchange mediated MRI methods suffer from poor contrast as well as confounding factors that influence exchange rates. In this study we developed a new method to measure proton exchange which combines chemical exchange saturation transfer and T(1)(ρ) magnetization preparation methods (CESTrho). We demonstrated that this new CESTrho sequence can detect proton exchange in the slow to intermediate exchange regimes. It has a linear dependence on proton concentration which allows it to be used to quantitatively measure changes in metabolite concentration. Additionally, the magnetization scheme of this new method can be customized to make it insensitive to changes in exchange rate while retaining its dependency on solute concentration. Finally, we showed the feasibility of using CESTrho in vivo. This sequence is able to detect proton exchange at intermediate exchange rates and is unaffected by the confounding factors that influence proton exchange rates thus making it ideal for the measurement of metabolites with exchangeable protons in this exchange regime., (Copyright © 2011 Wiley Periodicals, Inc.)

Cimetidine disposition was determined in six patients undergoing continuous ambulatory peritoneal dialysis to ascertain the need for modification of conventional dosing regimens. Blood, dialysis fluid, and urine were collected for 48 hours after administration of a single intravenous dose of cimetidine. The following values were obtained: elimination half-life, 4.3 hours; systemic or total body clearance, 191 +/- 55 ml/min; and dialysis clearance, 4.2 +/- 3.1 ml/min. Approximately 2% of a cimetidine dose is removed by dialysis, indicating that there is no need to adjust the conventional renal failure dosing regimen in patients undergoing continuous ambulatory peritoneal dialysis.

The distribution of synchronous neoplasms was retrospectively analyzed in 220 patients undergoing initial colonoscopic evaluation for colorectal neoplasms. In 159 of the 220 patients, an index neoplasm was present in the rectosigmoid region. Of these 159 patients, 32 had an index rectosigmoid adenoma less than 5 mm in diameter (diminutive), 105 had an index rectosigmoid adenoma greater than or equal to 5 mm in diameter and 22 had an index rectosigmoid adenocarcinoma. Among these patients with different index neoplasms the frequency of synchronous neoplasms was 34%, 53%, and 73%, respectively. The synchronous neoplasm was an adenoma greater than or equal to 5 mm in diameter in 13%, 40%, and 64%, respectively. The synchronous neoplasm was a carcinoma in 0%, 7%, and 5%, respectively. Two or more synchronous neoplasms occurred in 9%, 34%, and 41% of the index neoplasm groups, respectively. Finally, symptoms providing an indication for colonoscopy were present in 31%, 75%, and 86%, respectively. It is concluded that patients with diminutive index adenomas had fewer and smaller synchronous neoplasms (P less than 0.025) than patients with larger adenomas or invasive carcinoma as the index lesion. Thus, total colonoscopy does not appear to be necessary in asymptomatic patients with only diminutive adenomas found at flexible sigmoidoscopy.