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Background: Patients with type‐2 diabetes (T2DM) are at increased risk of developing diabetic foot ulcers (DFU) and experiencing impaired wound healing related to underlying microvascular disease. Purpose: To evaluate the sensitivity of intra‐voxel incoherent motion (IVIM) and blood oxygen level dependent (BOLD) MRI to microvascular changes in patients with DFUs. Study Type: Case–control. Population: 20 volunteers who were age and body mass index matched, including T2DM patients with DFUs (N = 10, mean age = 57.5 years), T2DM patients with controlled glycemia and without DFUs (DC, N = 5, mean age = 57.4 years) and healthy controls (HC, N = 5, mean age = 52.8 years). Field strength/Sequence: 3T/multi‐b‐value IVIM and dynamic BOLD. Assessment: Resting IVIM parameters were obtained using a multi‐b‐value diffusion‐weighted imaging sequence and two IVIM models were fit to obtain diffusion coefficient (D), pseudo‐diffusion coefficient (D*), perfusion fraction (f) and microvascular volume fraction (MVF) parameters. Microvascular reactivity was evaluated by inducing an ischemic state in the foot with a blood pressure cuff during dynamic BOLD imaging. Perfusion indices were assessed in two regions of the foot: the medial plantar (MP) and lateral plantar (LP) regions. Statistical Tests: Effect sizes of group mean differences were assessed using Hedge's g adjusted for small sample sizes. Results: DFU participants exhibited elevated D*, f, and MVF values in both regions (g ≥ 1.10) and increased D (g = 1.07) in the MP region compared to DC participants. DC participants showed reduced f and MVF compared to HC participants in the MP region (g ≥ 1.06). Finally, the DFU group showed reduced tolerance for ischemia in the LP region (g = −1.51) and blunted reperfusion response in both regions (g < −2.32) compared to the DC group during the cuff‐occlusion challenge. Data Conclusion: The combined use of IVIM and BOLD MRI shows promise in differentiating perfusion abnormalities in the feet of diabetic patients and suggests hyperperfusion in DFU patients. Level of Evidence: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Purpose: Knee cartilage experiences repetitive loading during physical activities, which is altered during the pathogenesis of diseases like osteoarthritis. Analyzing the biomechanics during motion provides a clear understanding of the dynamics of cartilage deformation and may establish essential imaging biomarkers of early‐stage disease. However, in vivo biomechanical analysis of cartilage during rapid motion is not well established. Methods: We used spiral displacement encoding with stimulated echoes (DENSE) MRI on in vivo human tibiofemoral cartilage during cyclic varus loading (0.5 Hz) and used compressed sensing on the k‐space data. The applied compressive load was set for each participant at 0.5 times body weight on the medial condyle. Relaxometry methods were measured on the cartilage before (T1ρ, T2) and after (T1ρ) varus load. Results: Displacement and strain maps showed a gradual shift of displacement and strain in time. Compressive strain was observed in the medial condyle cartilage and shear strain was roughly half of the compressive strain. Male participants had more displacement in the loading direction compared to females, and T1ρ values did not change after cyclic varus load. Compressed sensing reduced the scanning time up to 25% to 40% when comparing the displacement maps and substantially lowered the noise levels. Conclusion: These results demonstrated the ease of which spiral DENSE MRI could be applied to clinical studies because of the shortened imaging time, while quantifying realistic cartilage deformations that occur through daily activities and that could serve as biomarkers of early osteoarthritis. [ABSTRACT FROM AUTHOR]

Diffusion‐tensor magnetic resonance imaging (DT‐MRI) offers objective measures of muscle characteristics, providing insights into age‐related changes. We used DT‐MRI to probe skeletal muscle microstructure and architecture in a large healthy‐aging cohort, with the aim of characterizing age‐related differences and comparing these to muscle strength. We recruited 94 participants (43 female; median age = 56, range = 22–89 years) and measured microstructure parameters—fractional anisotropy (FA) and mean diffusivity (MD)—in 12 thigh muscles, and architecture parameters—pennation angle, fascicle length, fiber curvature, and physiological cross‐sectional area (PCSA)—in the rectus femoris (RF) and biceps femoris longus (BFL). Knee extension and flexion torques were also measured for comparison to architecture measures. FA and MD were associated with age (β = 0.33, p = 0.001, R2 = 0.10; and β = −0.36, p < 0.001, R2 = 0.12), and FA was negatively associated with Type I fiber proportions from the literature (β = −0.70, p = 0.024, and R2 = 0.43). Pennation angle, fiber curvature, fascicle length, and PCSA were associated with age in the RF (β = −0.22, 0.26, −0.23, and −0.31, respectively; p < 0.05), while in the BFL only curvature and fascicle length were associated with age (β = 0.36, and −0.40, respectively; p < 0.001). In the RF, pennation angle and PCSA were associated with strength (β = 0.29, and 0.46, respectively; p < 0.01); in the BFL, only PCSA was associated with strength (β = 0.43; p < 0.001). Our results show skeletal muscle architectural changes with aging and intermuscular differences in the microstructure. DT‐MRI may prove useful for elucidating muscle changes in the early stages of sarcopenia and monitoring interventions aimed at preventing age‐associated microstructural changes in muscle that lead to functional impairment. [ABSTRACT FROM AUTHOR]

Throughout the body, muscle structure and function can be interrogated using a variety of noninvasive magnetic resonance imaging (MRI) methods. Recently, intravoxel incoherent motion (IVIM) MRI has gained momentum as a method to evaluate components of blood flow and tissue diffusion simultaneously. Much of the prior research has focused on highly vascularized organs, including the brain, kidney, and liver. Unique aspects of skeletal muscle, including the relatively low perfusion at rest and large dynamic range of perfusion between resting and maximal hyperemic states, may influence the acquisition, postprocessing, and interpretation of IVIM data. Here, we introduce several of those unique features of skeletal muscle; review existing studies of IVIM in skeletal muscle at rest, in response to exercise, and in disease states; and consider possible confounds that should be addressed for muscle‐specific evaluations. Most studies used segmented nonlinear least squares fitting with a b‐value threshold of 200 sec/mm2 to obtain IVIM parameters of perfusion fraction (f), pseudo‐diffusion coefficient (D*), and diffusion coefficient (D). In healthy individuals, across all muscles, the average ± standard deviation of D was 1.46 ± 0.30 × 10−3 mm2/sec, D* was 29.7 ± 38.1 × 10−3 mm2/sec, and f was 11.1 ± 6.7%. Comparisons of reported IVIM parameters in muscles of the back, thigh, and leg of healthy individuals showed no significant difference between anatomic locations. Throughout the body, exercise elicited a positive change of all IVIM parameters. Future directions including advanced postprocessing models and potential sequence modifications are discussed. Level of Evidence: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Purpose: To develop an anomalous (non‐Gaussian) diffusion model for characterizing skeletal muscle perfusion using multi‐b‐value DWI. Theory and methods: Fick's first law was extended for describing tissue perfusion as anomalous superdiffusion, which is non‐Gaussian diffusion exhibiting greater particle spread than that of the Gaussian case. This was accomplished using a space‐fractional derivative that gives rise to a power‐law relationship between mean squared displacement and time, and produces a stretched exponential signal decay as a function of b‐value. Numerical simulations were used to estimate parameter errors under in vivo conditions, and examine the effect of limited SNR and residual fat signal. Stretched exponential DWI parameters, α and D, were measured in thigh muscles of 4 healthy volunteers at rest and following in‐magnet exercise. These parameters were related to a stable distribution of jump‐length probabilities and used to estimate microvascular volume fractions. Results: Numerical simulations showed low dispersion in parameter estimates within 1.5% and 1%, and bias errors within 3% and 10%, for α and D, respectively. Superdiffusion was observed in resting muscle, and to a greater degree following exercise. Resting microvascular volume fraction was between 0.0067 and 0.0139 and increased between 2.2‐fold and 4.7‐fold following exercise. Conclusions: This model captures superdiffusive molecular motions consistent with perfusion, using a parsimonious representation of the DWI signal, providing approximations of microvascular volume fraction comparable with histological estimates. This signal model demonstrates low parameter‐estimation errors, and therefore holds potential for a wide range of applications in skeletal muscle and elsewhere in the body. [ABSTRACT FROM AUTHOR]

Purpose: To examine multi-component relaxation modelling for quantification of on-and off-resonance relaxation signals in multi-echo ultra-short echo time (UTE) data of human Achilles tendon (AT) and compare bias and dispersion errors of model parameters to that of the bi-component model. Theory and Methods: Multi-component modelling is demonstrated for quantitative multi-echo UTE analysis of AT and supported using a novel method for determining number of MR-visible off-resonance components, UTE data from six healthy volunteers, and analysis of proton NMR measurements from ex vivo bovine AT. Cramer-Rao lower bound expressions are presented for multi-and bi-component models and parameter estimate variances are compared. Bias error in bi-component estimates is characterized numerically. Results: Two off-resonance components were consistently detected in all six volunteers and in bovine AT data. Multi-component model exhibited superior quality of fit, with a marginal increase in estimate variance, when compared to the bi-component model. Bi-component estimates exhibited notable bias particularly in R2.1* in the presence of off-resonance components. Conclusion: Multi-component modelling more reliably quantifies tendon matrix water components while also providing quantitation of additional non-water matrix constituents. Further work is needed to interpret the origin of the observed offresonance signals with preliminary assignments made to chemical groups in lipids and proteoglycans. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance imaging of ex vivo cartilage measures parameters such as T2 and magnetization transfer ratio (MTR), which reflect structural changes associated with osteoarthritis. Samples are often immersed in aqueous solutions to prevent dehydration and to to improve susceptibility matching. This study sought to determine the extent to which T2 and MTR changes are attributable to immersion alone and to identify immersion conditions to minimize this confounding factor. Methods: T2 and MTR were measured before and after immersion for up to 24 hours at 4°C. Bovine nasal and articular cartilage and human articular cartilage were studied. Experimental groups included undisturbed immersion in Fluorinert FC‐770, a susceptibility‐matched, hydrophobic liquid with minimal tissue penetration, and immersion in Fluorinert, Dulbecco's phosphate‐buffered saline (DPBS), or saline, with removal from the magnet between scans. 19F and 1H‐MRI were used to detect cartilage penetration by Fluorinert and swelling, respectively. Results: Saline and DPBS immersion rapidly increased T2, wet weight and cartilage volume and decreased MTR, suggesting increased water content for all cartilage types. Fluorinert‐immersed samples exhibited minimal changes in T2 or MTR. No ingress of Fluorinert was detected after 2 weeks of continuous immersion at 4°C. Conclusion: Ex vivo quantitative MR studies of cartilage may be confounded by the effects of immersion in aqueous solution, which may be comparable to or larger than effects attributed to pathology. These effects may be mitigated by immersion in perfluorocarbon liquids such as Fluorinert FC‐770. [ABSTRACT FROM AUTHOR]

Background and Purpose: Myelin water fraction (MWF) mapping permits direct visualization of myelination patterns in the developing brain and in pathology. MWF is conventionally measured through multiexponential T2 analysis which is very sensitive to noise, leading to inaccuracies in derived MWF estimates. Although noise reduction filters may be applied during postprocessing, conventional filtering can introduce bias and obscure small structures and edges. Advanced nonblurring filters, while effective, exhibit a high level of complexity and the requirement for supervised implementation for optimal performance. The purpose of this paper is to demonstrate the ability of the recently introduced nonlocal estimation of multispectral magnitudes (NESMA) filter to greatly improve the determination of MWF parameter estimates from gradient and spin echo (GRASE) imaging data.Methods: We evaluated the performance of the NESMA filter for MWF mapping from clinical GRASE imaging data of the human brain, and compared the results to those calculated from unfiltered images. Numerical and in vivo analyses of the brains of three subjects, representing different ages, were conducted.Results: Our results demonstrated the potential of the NESMA filter to permit high-quality in vivo MWF mapping. Indeed, NESMA permits substantial reduction of random variation in derived MWF estimates while preserving accuracy and detail.Conclusions: In vivo estimation of MWF in the human brain from GRASE imaging data was markedly improved through use of the NESMA filter. The use of NESMA may contribute to the goal of high-quality MWF mapping in clinically feasible imaging times. [ABSTRACT FROM AUTHOR]

Introduction: We investigated brain demyelination in aging, mild cognitive impairment (MCI), and dementia using a direct magnetic resonance imaging marker of myelin. Methods: Brains of young and old controls, and old subjects with MCI, Alzheimer's disease, or vascular dementia were scanned using our recently developed myelin water fraction (MWF) mapping technique, which provides greatly improved accuracy over previous comparable methods. Maps of MWF, a direct and specific myelin measure, and relaxation times and magnetization transfer ratio, indirect and nonspecific measures, were constructed. Results: MCI subjects showed decreased MWF compared with old controls. Demyelination was greater in Alzheimer's disease or vascular dementia. As expected, decreased MWF was accompanied by decreased magnetization transfer ratio and increased relaxation times. The young subjects showed greater myelin content than the old subjects. Discussion: We believe this to be the first demonstration of myelin loss in MCI, Alzheimer's disease, and vascular dementia using a method that provides a quantitative magnetic resonance imaging–based measure of myelin. Our findings add to the emerging evidence that myelination may represent an important biomarker for the pathology of MCI and dementia. This study supports the investigation of the role of myelination in MCI and dementia through use of this quantitative magnetic resonance imaging approach in clinical studies of disease progression, and relationship of functional status to myelination status. Furthermore, mapping MWF may permit myelin to serve as a therapeutic target in clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Brain glucose hypometabolism is a prominent feature of Alzheimer's disease (AD), and in this case–control study we used Magnetic Resonance Spectroscopy (MRS) to assess AD‐related differences in the posterior cingulate/precuneal ratio of glucose, lactate, and other metabolites. Methods: J‐modulated Point‐Resolved Spectroscopy (J‐PRESS) and Prior‐Knowledge Fitting (ProFit) software was used to measure glucose and other metabolites in the posterior cingulate/precuneus of 25 AD, 27 older controls, and 27 younger control participants. Clinical assessments for AD participants included cognitive performance measures, insulin resistance metrics and CSF biomarkers. Results: AD participants showed substantially elevated glucose, lactate, and ascorbate levels compared to older (and younger) controls. In addition, the precuneal glucose elevation discriminated well between AD participants and older controls. Myo‐inositol correlated with CSF p‐Tau181P, total Tau, and the Clinical Dementia Rating (CDR) sum‐of‐boxes score within the AD group. Interpretation: Higher glucose to creatine ratios in the AD brain likely reflect lower glucose utilization. Our findings reveal pronounced metabolic abnormalities in the AD brain and strongly suggest that brain glucose merits further investigation as a candidate AD biomarker. [ABSTRACT FROM AUTHOR]

This work characterizes the effect of lipid and noise signals on muscle diffusion parameter estimation in several conventional and non-Gaussian models, the ultimate objectives being to characterize popular fat suppression approaches for human muscle diffusion studies, to provide simulations to inform experimental work and to report normative non-Gaussian parameter values. The models investigated in this work were the Gaussian monoexponential and intravoxel incoherent motion (IVIM) models, and the non-Gaussian kurtosis and stretched exponential models. These were evaluated via simulations, and in vitro and in vivo experiments. Simulations were performed using literature input values, modeling fat contamination as an additive baseline to data, whereas phantom studies used a phantom containing aliphatic and olefinic fats and muscle-like gel. Human imaging was performed in the hamstring muscles of 10 volunteers. Diffusion-weighted imaging was applied with spectral attenuated inversion recovery (SPAIR), slice-select gradient reversal and water-specific excitation fat suppression, alone and in combination. Measurement bias (accuracy) and dispersion (precision) were evaluated, together with intra- and inter-scan repeatability. Simulations indicated that noise in magnitude images resulted in <6% bias in diffusion coefficients and non-Gaussian parameters (α, K), whereas baseline fitting minimized fat bias for all models, except IVIM. In vivo, popular SPAIR fat suppression proved inadequate for accurate parameter estimation, producing non-physiological parameter estimates without baseline fitting and large biases when it was used. Combining all three fat suppression techniques and fitting data with a baseline offset gave the best results of all the methods studied for both Gaussian diffusion and, overall, for non-Gaussian diffusion. It produced consistent parameter estimates for all models, except IVIM, and highlighted non-Gaussian behavior perpendicular to muscle fibers (α ~ 0.95, K ~ 3.1). These results show that effective fat suppression is crucial for accurate measurement of non-Gaussian diffusion parameters, and will be an essential component of quantitative studies of human muscle quality. [ABSTRACT FROM AUTHOR]

Skeletal muscle mitochondrial oxidative capacity declines with age and negatively affects walking performance, but the mechanism for this association is not fully clear. We tested the hypothesis that impaired oxidative capacity affects muscle performance and, through this mechanism, has a negative effect on walking speed. Muscle mitochondrial oxidative capacity was measured by in vivo phosphorus magnetic resonance spectroscopy as the postexercise phosphocreatine resynthesis rate, kPCr, in 326 participants (154 men), aged 24-97 years (mean 71), in the Baltimore Longitudinal Study of Aging. Muscle strength and quality were determined by knee extension isokinetic strength, and the ratio of knee extension strength to thigh muscle cross-sectional area derived from computed topography, respectively. Four walking tasks were evaluated: a usual pace over 6 m and for 150 s, and a rapid pace over 6 m and 400 m. In multivariate linear regression analyses, kPCr was associated with muscle strength (β = 0.140, P = 0.007) and muscle quality (β = 0.127, P = 0.022), independent of age, sex, height, and weight; muscle strength was also a significant independent correlate of walking speed ( P < 0.02 for all tasks) and in a formal mediation analysis significantly attenuated the association between kPCr and three of four walking tasks (18-29% reduction in β for kPCr). This is the first demonstration in human adults that mitochondrial function affects muscle strength and that inefficiency in muscle bioenergetics partially accounts for differences in mobility through this mechanism. [ABSTRACT FROM AUTHOR]

Purpose To compare the ordinary monoexponential model with three anomalous relaxation models-the stretched Mittag-Leffler, stretched exponential, and biexponential functions-using both simulated and experimental cartilage relaxation data. Methods Monte Carlo simulations were used to examine both the ability of identifying a given model under high signal-to-noise ratio (SNR) conditions and the accuracy and precision of parameter estimates under more modest SNR as would be encountered clinically. Experimental transverse relaxation data were analyzed from normal and enzymatically degraded cartilage samples under high SNR and rapid echo sampling to compare each model. Results Both simulation and experimental results showed improvement in signal representation with the anomalous relaxation models. The stretched exponential model consistently showed the lowest mean squared error in experimental data and closely represents the signal decay over multiple decades of the decay time (e.g., 1-10 ms, 10-100 ms, and >100 ms). The stretched exponential parameter αse showed an inverse correlation with biochemically derived cartilage proteoglycan content. Conclusion Experimental results obtained at high field suggest potential application of αse as a measure of matrix integrity. Simulation reflecting more clinical imaging conditions, indicate the ability to robustly estimate αse and distinguish between normal and degraded tissue, highlighting its potential as a biomarker for human studies. Magn Reson Med 76:953-962, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose To compare the reliability and stability of the multicomponent-driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and Carl-Purcell-Meiboom-Gill (CPMG) approaches to parameter estimation. Methods The stability and reliability of mcDESPOT and CPMG-derived parameter estimates were compared through examination of energy surfaces, evaluation of model sloppiness, and Monte Carlo simulations. Comparisons were performed on an equal time basis and assuming a two-component system. Parameter estimation bias, reflecting accuracy, and dispersion, reflecting precision, were derived for a range of signal-to-noise ratios (SNRs) and relaxation parameters. Results The energy surfaces for parameters incorporated into the mcDESPOT signal model exhibit flatness, a complex structure of local minima, and instability to noise to a much greater extent than the corresponding surfaces for CPMG. Although both mcDESPOT and CPMG performed well at high SNR, the CPMG approach yielded parameter estimates of considerably greater accuracy and precision at lower SNR. Conclusion mcDESPOT and CPMG both permit high-quality parameter estimates under SNR that are clinically achievable under many circumstances, depending upon available hardware and resolution and acquisition time constraints. At moderate to high SNR, the mcDESPOT approach incorporating two-step phase increments can yield accurate parameter estimates while providing values for longitudinal relaxation times that are not available through CPMG. However, at low SNR, the CPMG approach is more stable and provides superior parameter estimates. Magn Reson Med 75:2406-2420, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose Transverse relaxation analysis with several signal models has been used extensively to determine tissue and material properties. However, the derivation of corresponding parameter values is notoriously unreliable. We evaluate improvements in the quality of parameter estimation using Bayesian analysis and incorporating the Rician noise model, as appropriate for magnitude MR images. Theory and Methods Monoexponential, stretched exponential, and biexponential signal models were analyzed using nonlinear least squares (NLLS) and Bayesian approaches. Simulations and phantom and human brain data were analyzed using three different approaches to account for noise. Parameter estimation bias (reflecting accuracy) and dispersion (reflecting precision) were derived for a range of signal-to-noise ratios (SNR) and relaxation parameters. Results All methods performed well at high SNR. At lower SNR, the Bayesian approach yielded parameter estimates of considerably greater precision, as well as greater accuracy, than did NLLS. Incorporation of the Rician noise model greatly improved accuracy and, to a somewhat lesser extent, precision, in derived transverse relaxation parameters. Analyses of data obtained from solution phantoms and from brain were consistent with simulations. Conclusion Overall, estimation of parameters characterizing several different transverse relaxation models was markedly improved through use of Bayesian analysis and through incorporation of the Rician noise model. Magn Reson Med 74:785-802, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background To evaluate the sensitivity and specificity of classification of pathomimetically degraded bovine nasal cartilage at 3 Tesla and 37°C using univariate MRI measurements of both pure parameter values and intensities of parameter-weighted images. Methods Pre- and posttrypsin degradation values of T1, T2, T2*, magnetization transfer ratio (MTR), and apparent diffusion coefficient (ADC), and corresponding weighted images, were analyzed. Classification based on the Euclidean distance was performed and the quality of classification was assessed through sensitivity, specificity and accuracy (ACC). Results The classifiers with the highest accuracy values were ADC (ACC = 0.82 ± 0.06), MTR (ACC = 0.78 ± 0.06), T1 (ACC = 0.99 ± 0.01), T2 derived from a three-dimensional (3D) spin-echo sequence (ACC = 0.74 ± 0.05), and T2 derived from a 2D spin-echo sequence (ACC = 0.77 ± 0.06), along with two of the diffusion-weighted signal intensities (b = 333 s/mm2: ACC = 0.80 ± 0.05; b = 666 s/mm2: ACC = 0.85 ± 0.04). In particular, T1 values differed substantially between the groups, resulting in atypically high classification accuracy. The second-best classifier, diffusion weighting with b = 666 s/mm2, as well as all other parameters evaluated, exhibited substantial overlap between pre- and postdegradation groups, resulting in decreased accuracies. Conclusion Classification according to T1 values showed excellent test characteristics (ACC = 0.99), with several other parameters also showing reasonable performance (ACC > 0.70). Of these, diffusion weighting is particularly promising as a potentially practical clinical modality. As in previous work, we again find that highly statistically significant group mean differences do not necessarily translate into accurate clinical classification rules. J. Magn. Reson. Imaging 2015;42:136-144. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT This work evaluates the ability of quantitative MRI to discriminate between normal and pathological human osteochondral plugs characterized by the Osteoarthritis Research Society International (OARSI) histological system. Normal and osteoarthritic human osteochondral plugs were scored using the OARSI histological system and imaged at 3 T using MRI sequences producing T1 and T2 contrast and measuring T1, T2, and T2* relaxation times, magnetization transfer, and diffusion. The classification accuracies of quantitative MRI parameters and corresponding weighted image intensities were evaluated. Classification models based on the Mahalanobis distance metric for each MRI measurement were trained and validated using leave-one-out cross-validation with plugs grouped according to OARSI histological grade and score. MRI measurements used for classification were performed using a region-of-interest analysis which included superficial, deep, and full-thickness cartilage. The best classifiers based on OARSI grade and score were T1- and T2-weighted image intensities, which yielded accuracies of 0.68 and 0.75, respectively. Classification accuracies using OARSI score-based group membership were generally higher when compared with grade-based group membership. MRI-based classification-either using quantitative MRI parameters or weighted image intensities-is able to detect early osteoarthritic tissue changes as classified by the OARSI histological system. These findings suggest the benefit of incorporating quantitative MRI acquisitions in a comprehensive clinical evaluation of OA. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:640-650, 2015. [ABSTRACT FROM AUTHOR]

Purpose Previous work has evaluated the quality of different analytic methods for extracting relaxation times from magnitude imaging data exhibiting Rician noise. However, biexponential analysis of relaxation in tissue, including cartilage, and materials is of increasing interest. We, therefore, analyzed biexponential transverse relaxation decay in the presence of Rician noise and assessed the accuracy and precision of several approaches to determining component fractions and apparent transverse relaxation times. Theory and Methods Comparisons of four different voxel-by-voxel fitting methods were performed using Monte Carlo simulations, and phantom and ex vivo bovine nasal cartilage (BNC) experiments. In each case, preclinical and clinical imaging field strengths of 7 Tesla (T) and 3T, respectively, and parameters, were investigated across a range of signal-to-noise ratios (SNR). Results were compared with Cramér-Rao lower bound calculations. Results As expected, at high SNR, all methods performed well. At lower SNR, fits explicitly incorporating the analytic form of the Rician noise maintained performance. The much more efficient correction scheme of Gudbjartsson and Patz performed almost as well in many cases. Ex vivo experiments on phantoms and BNC were consistent with simulation results. Conclusion Explicit incorporation of Rician noise greatly improves accuracy and precision in the analysis of biexponential transverse decay data. Magn Reson Med 73:352-366, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Evaluation of mechanical characteristics of cartilage by magnetic resonance imaging would provide a noninvasive measure of tissue quality both for tissue engineering and when monitoring clinical response to therapeutic interventions for cartilage degradation. We use results from multiexponential transverse relaxation analysis to predict equilibrium and dynamic stiffness of control and degraded bovine nasal cartilage, a biochemical model for articular cartilage. Sulfated glycosaminoglycan concentration/wet weight (ww) and equilibrium and dynamic stiffness decreased with degradation from 103.6 ± 37.0 µg/mg ww, 1.71 ± 1.10 MPa and 15.3 ± 6.7 MPa in controls to 8.25 ± 2.4 µg/mg ww, 0.015 ± 0.006 MPa and 0.89 ± 0.25MPa, respectively, in severely degraded explants. Magnetic resonance measurements were performed on cartilage explants at 4 °C in a 9.4 T wide-bore NMR spectrometer using a Carr-Purcell-Meiboom-Gill sequence. Multiexponential T2 analysis revealed four water compartments with T2 values of approximately 0.14, 3, 40 and 150 ms, with corresponding weight fractions of approximately 3, 2, 4 and 91%. Correlations between weight fractions and stiffness based on conventional univariate and multiple linear regressions exhibited a maximum r2 of 0.65, while those based on support vector regression (SVR) had a maximum r2 value of 0.90. These results indicate that (i) compartment weight fractions derived from multiexponential analysis reflect cartilage stiffness and (ii) SVR-based multivariate regression exhibits greatly improved accuracy in predicting mechanical properties as compared with conventional regression. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Noninvasive monitoring of tissue quality would be of substantial use in the development of cartilage tissue engineering strategies. Conventional MR parameters provide noninvasive measures of biophysical tissue properties and are sensitive to changes in matrix development, but do not clearly distinguish between groups with different levels of matrix development. Furthermore, MR outcomes are nonspecific, with particular changes in matrix components resulting in changes in multiple MR parameters. To address these limitations, we present two new approaches for the evaluation of tissue engineered constructs using MR, and apply them to immature and mature engineered cartilage after 1 and 5 weeks of development, respectively. First, we applied multiexponential T2 analysis for the quantification of matrix macromolecule-associated water compartments. Second, we applied multivariate support vector machine analysis using multiple MR parameters to improve detection of degree of matrix development. Monoexponential T2 values decreased with maturation, but without further specificity. Much more specific information was provided by multiexponential analysis. The T2 distribution in both immature and mature constructs was qualitatively comparable to that of native cartilage. The analysis showed that proteoglycan-bound water increased significantly during maturation, from a fraction of 0.05 ± 0.01 to 0.07 ± 0.01. Classification of samples based on individual MR parameters, T1, T2, km or apparent diffusion coefficient, showed that the best classifiers were T1 and km, with classification accuracies of 85% and 84%, respectively. Support vector machine analysis improved the accuracy to 98% using the combination ( km, apparent diffusion coefficient). These approaches were validated using biochemical and Fourier transform infrared imaging spectroscopic analyses, which showed increased proteoglycan and collagen with maturation. In summary, multiexponential T2 and multivariate support vector machine analyses provide improved sensitivity to changes in matrix development and specificity to matrix composition in tissue engineered cartilage. These approaches show substantial potential for the evaluation of engineered cartilage tissue and for extension to other tissue engineering constructs. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The noninvasive early detection of specific matrix alterations in degenerative cartilage disease would be of substantial use in basic science studies and clinically, but remains an elusive goal. Recently developed MRI methods exhibit some specificity, but require contrast agents or nonstandard pulse sequences and hardware. We present a multiexponential approach which does not require contrast agents or specialized hardware, and uses a standard multiple-echo spin-echo sequence. Experiments were performed on tissue models of degenerative cartilage using enzymes with distinct actions. MR results were validated using histologic, biochemical and infrared spectroscopic analyses. The sulfated glycosaminoglycan per dry weight (dw) in bovine nasal cartilage was 0.72 ± 0.06 mg/mg dw and was reduced through chondroitinase AC and collagenase digestion to 0.56 ± 0.12 and 0.58 ± 0.13 mg/mg dw, respectively. Multiexponential analysis of data obtained at 9.4 T permitted the identification of tissue compartments assigned to the proteoglycan component of the matrix and to bulk water. Enzymatic treatment resulted in a significant reduction in the ratio of proteoglycan-bound to free water from 0.13 ± 0.02 in control cartilage to 0.03 ± 0.02 and 0.05 ± 0.06 under chondroitinase AC and collagenase treatment, respectively. As expected, monoexponential T2 increased with both degradation protocols, but without further specificity to the nature of the degradation. An important eventual extension of this approach may be to map articular cartilage degeneration in the clinical setting. As an initial step towards this, localized multiexponential T2 analysis was performed on control and trypsin treated excised bovine patella. The results obtained on this articular cartilage sample were readily interpretable in terms of proteoglycan-associated and relatively free water compartments. In potential clinical applications, signal-to-noise ratio constraints will define the threshold for the detection of macromolecular compartment changes at a given spatial scale. The multiexponential approach has potential application to the early detection of cartilage degradation with the use of appropriate pulse parameters under high signal-to-noise ratio conditions. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article discusses a study that determines the effectiveness of using multiexponential transverse relaxation analysis to improve specificity of matrix assessment in mapping proteoglycan (PG)-bound water in cartilage. The researchers use mature and young bovine nasal cartilage model systems in mapping the PG-bound water fraction in cartilage. Study reveals a feasibility of performing imaging-based multiexponential analysis of transverse relaxation data in mapping PG in cartilage.

MRI is increasingly used to evaluate cartilage in tissue constructs, explants, and animal and patient studies. However, while mean values of MR parameters, including T1, T2, magnetization transfer rate km, apparent diffusion coefficient (ADC), and the dGEMRIC-derived fixed charge density, correlate with tissue status, the ability to classify tissue according to these parameters has not been explored. Therefore, the sensitivity and specificity with which each of these parameters was able to distinguish between normal and trypsin-degraded, and between normal and collagenase-degraded, cartilage explants were determined. Initial analysis was performed using a training set to determine simple group means to which parameters obtained from a validation set were compared. T1 and apparent diffusion coefficient showed the greatest ability to discriminate between normal and degraded cartilage. Further analysis with k-means clustering, which eliminates the need for a priori identification of sample status, generally performed comparably. Use of fuzzy c-means (FCM) clustering to define centroids likewise did not result in improvement in discrimination. Finally, an FCM clustering approach in which validation samples were assigned in a probabilistic fashion to control and degraded groups was implemented, reflecting the range of tissue characteristics seen with cartilage degradation. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

MR techniques are sensitive to the early stages of osteoarthritis, characterized by disruption of collagen and loss of proteoglycan (PG), but are of limited specificity. Here, water compartments in normal and trypsin-degraded bovine nasal cartilage were identified using a nonnegative least squares multiexponential analysis of T2 relaxation. Three components were detected: T2,1 = 2.3 ms, T2,2 = 25.2 ms, and T2,3 = 96.3 ms, with fractions w1 = 6.2%, w2 = 14.5%, and w3 = 79.3%, respectively. Trypsinization resulted in increased ( P < 0.01) values of T2,2 = 64.2 ms and T2,3 = 149.4 ms, supporting their assignment to water compartments that are bound and loosely associated with PG, respectively. The T2 of the rapidly relaxing component was not altered by digestion, supporting assignment to relatively immobile collagen-bound water. Relaxation data were simulated for a range of TE, number of echoes, and SNR to guide selection of acquisition parameters and assess the accuracy and precision of experimental results. Based on this, the expected experimental accuracy of measured T2s and associated weights was within 2% and 4% respectively, with precision within 1% and 3%. These results demonstrate the potential of multiexponential T2 analysis to increase the specificity of MR characterization of cartilage. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objective: To introduce otolaryngologists to outcomes-linked reimbursement (“pay-for-performance”), identify clinical practice implications, and recommend changes for successful transition from the traditional “pay-for-effort” reimbursement model. Study design: Policy review. Results: Payers are actively linking reimbursement to quality. Since the Institute of Medicine issued its report on medical errors in 1999, there has been much public and private concern over patient safety. In an effort to base health care payment on quality, “pay-for-performance” programs reward or penalize hospitals and physicians for their ability to maintain standards of care established by payers and regulatory groups. More than 100 such programs are operational in the United States today. This reimbursement model relies on detailed documentation in specific patient care areas to facilitate evaluation of outcomes for purposes of determining reimbursement. Because performance criteria for reimbursement have not yet been proposed within otolaryngology–head and neck surgery, otolaryngologists must be involved to ensure the adoption of reasonable goals and development of reasonable systems for documentation. Conclusion: “Pay-for-performance” reimbursement is increasingly common in the current era of outcomes-based medicine. It will assume an even greater role over the next 3 years and will directly affect most otolaryngologists. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to begin investigating the relationship between nodal yield in neck dissection and the likelihood of finding cervical metastases in T1 and T2 head and neck squamous cell carcinoma (HNSCC). No clinical implications are drawn from this preliminary work.Study Design and Setting: This study was a retrospective analysis of 564 patients with T1 and T2 HNSCC of the oral cavity, oropharynx, or hypopharynx from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program registry. A multivariate analysis was performed to evaluate the relationship between nodal yield in neck dissection and the discovery of cervical metastases. Other independent factors included in the analysis were gender, age, race, and primary site of tumor.Results: Compared with nodal yield < 13, cervical metastases were more likely to be found for nodal yield 21-28 (P < 0.001, odds ratio [OR] = 3.68), 29-40 (P = 0.021, OR = 1.98), and >40 (P < 0.001, OR = 3.52). Increased age, male sex, and oropharynx and hypopharynx primaries were also associated with a significantly increased likelihood of finding cervical metastases.Conclusion: In T1 and T2 cases of HNSCC, nodal yield >20, increased age, male sex, and primary site correspond with an increased likelihood of finding cervical metastases. (Otolaryngol Head Neck Surg 2003;128:185-90.) [Copyright &y& Elsevier]

Tuning forks have been used as clinical pure tone generators since the middle of the nineteenth century. The development of electronic signal sources has fostered innumerable advances in audiologic diagnosis, yet the tuning fork remains in daily use by thousands of physicians, for rapid and reliable screening of auditory acuity. This study examines tuning forks as oscillators, determining harmonic distortion with real-time spectral analysis. Various methods of striking the instrument are compared, with regard to harmonic distortion and sound pressure level generated. Tuning forks are, thus, compared to their electronic counterparts for the first time in the literature. Gentle striking of a steel, 256 Hz. fork on the thenar eminence produces tones comparable in purity to those generated by ANSI-calibrated audiometers. Similar results were obtained with forks of higher frequency; however, careful use of light aluminum alloy forks may produce equally satisfactory results. [ABSTRACT FROM AUTHOR]

The auditory system responds to pulsatile energy flow from the environment. Compression and rarefaction of gaseous molecular mass is transduced into electromechanical forms, in order to produce an effect at the cortical level. For energy input to have consistent meaning, transduction must preserve information coded within the pattern of energy flow. Distortion, or alteration of the original form, occurs in many ways throughout the chain of generation/transmission/reception/interpretation. Parameters of energy flow are discussed, and distortion of each parameter is presented in a context which permits the development of a distortion-based analysis of common clinical problems in otolaryngology. [ABSTRACT FROM AUTHOR]

Aging is associated with impaired endothelium‐dependent vasodilation that leads to muscle perfusion impairment and contributes to organ dysfunction. Impaired muscle perfusion may result in inadequate delivery of oxygen and nutrients during and after muscle contraction, leading to muscle damage. The ability to study the relationship between perfusion and muscle damage has been limited using traditional muscle perfusion measures, which are invasive and risky. To overcome this limitation, we optimized a diffusion‐weighted MRI sequence and validated an intravoxel incoherent motion (IVIM) analysis based on Monte Carlo simulation to study muscle perfusion impairment with aging during post‐exercise hyperemia. Simulation results demonstrated that the bias of IVIM‐derived perfusion fraction (fp) and diffusion of water molecules in extra‐vascular tissue (D) ranged from −3.3% to 14% and from −16.5% to 0.002%, respectively, in the optimized experimental condition. The dispersion in fp and D ranged from 3.2% to 9.5% and from 0.9% to 1.1%, respectively. The mid‐thigh of the left leg of four younger (21–30 year old) and four older (60–90 year old) healthy females was studied using the optimized protocol at baseline and at seven time increments occurring every 3.25 min following in‐magnet dynamic knee extension exercise performed using a MR‐compatible ergometer with a workload of 0.4 bar for 2.5 min. After exercise, both fp and D significantly increased in the rectus femoris (active muscle during exercise) but not in adductor magnus (inactive muscle), reflecting the fact that the local increase in perfusion with both groups showed a maximum value in the second post‐exercise time‐point. A significantly greater increase in perfusion from the baseline (p < 0.05) was observed in the younger group (37 ± 12.05%) compared with the older group (17.57 ± 15.92%) at the first post‐exercise measurement. This work establishes a reliable non‐invasive method that can be used to study the effects of aging on dynamic changes in muscle perfusion as they relate to important measures of physical function. [ABSTRACT FROM AUTHOR]