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Skeletal muscle energy production is influenced by both lean body mass and adipose tissue but the effect of their distribution on energy metabolism is unclear. This study examined variations in quadriceps muscle energy metabolism in healthy adults with varied relative amounts of lean and adipose tissue. Results suggest increased adiposity is associated with reduced muscle energetic efficiency with more reliance on glycolysis, and when accompanied with reduced lean mass, is associated with reduced maximum oxidative capacity.

Osteoarthritis (OA) is globally the most prevalent joint disease and causes patients great pain, limited joint mobility, and psychological distress. Short- and long-term therapies like steroid injections and arthroplasty exist, respectively. Joint arthroplasty can effectively treat symptomatic end-stage OA, but most patients do not go through with surgery because they are not qualified, have comorbidities, or do not wish to undergo surgery. As a result, patients can turn to opioid agonists for pain relief, which contributes to the growing opioid epidemic that mars our communities. Cooled radiofrequency ablation (C-RFA) is an effective treatment modality that can alleviate the pain associated with moderate to severe OA, especially in patients who have tried and failed conservative therapy. This review article elucidates the benefits of C-RFA, while also walking through the technical steps to performing the procedure. For patients suffering from debilitating joint OA, especially of the knee, C-RFA is a minimally invasive procedure that ensures pain relief.

PurposeKnee 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.MethodsWe used spiral DENSE MRI on in vivo human tibiofemoral cartilage during cyclic varus loading (0.5 Hz) and employed compressed sensing on the k-space data. The applied compressive load was set for each participant at 0.5× body weight on the medial condyle. Relaxometry methods were measured on the cartilage before (T1ρ, T2) and after (T1ρ) varus load.ResultsDisplacement 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 T1ρvalues did not change after cyclic varus load. Compressed sensing reduced the scanning time up to 25-40% when comparing the displacement maps and substantially lowered the noise levels.ConclusionThese results demonstrated the ease of which spiral DENSE MRI could be applied to clinical studies due to the shortened imaging time, while quantifying realistic cartilage deformations that occur through daily activities, and that could serve as biomarkers of early osteoarthritis.

This was a multicenter retrospective cohort study.The purpose of this study was to compare the surgical and radiographic outcomes of patients undergoing posterior cervical fusion (PCF) with constructs extending from C2 to T2 to patients with constructs extending from C3 to T1.Limited evidence exists regarding the appropriate level of proximal and distal extension of PCF constructs.A multicenter retrospective cohort study of patients who underwent PCF between 2012 and 2020 was performed. Surgical and radiographic outcomes were compared between those who had C3-T1 or C2-T2 constructs.A total of 155 patients were included in the study (C2-T2: 106 patients, C3-T1: 49 patients). There were no significant differences in demographics or preoperative symptoms between cohorts. Fusion rates were significantly higher in the C2-T2 (93%) than the C3-T1 (80%, P=0.040) cohort. When comparing the C2-T2 to the C3-T1 cohort, the C3-T1 cohort had a significantly greater rate of proximal junctional failure (2% vs. 10%, P=0.006), distal junctional failure (1% vs. 20%, P0.001) and distal screw loosening (4% vs. 15%, P=0.02). Although ∆C2-C7 sagittal vertical axis increased significantly in both cohorts (C2-T2: 6.2 mm, P=0.04; C3-T1: 8.4 mm, P0.001), correction did not significantly differ between groups (P=0.32). The C3-T1 cohort had a significantly greater increase in ∆C2 slope (8.0 vs. 3.1 degrees, P=0.03) and ∆C0-C2 Cobb angle (6.4 vs. 1.2 degrees, P=0.04).In patients undergoing PCF, a C2-T2 construct demonstrated lower rates of pseudarthrosis, distal junctional failure, proximal junctional failure, and compensatory upper cervical hyperextension compared with a C3-T1 construct.

To establish the effectiveness of cooled radiofrequency ablation in managing hip pain from osteoarthritis at 6 months after receiving treatment in patients who failed conservative treatments and are not surgical candidates due to comorbidities or unwillingness to undergo arthroplasty surgery by targeting the femoral and obturator branches and assessing the degree of hip pain relief and change of function. This prospective pilot study includes a total of 11 consecutive patients experiencing persistent chronic hip pain in the setting of advanced osteoarthritis. Patients initially underwent anesthetic blocks of the obturator and femoral nerve branches to determine cooled radiofrequency ablation candidacy. After adequate response to the anesthetic blocks (> 50% immediate pain relief), patients were subjected to the procedures 2–3 weeks later. Treatment response was evaluated utilizing clinically validated questionnaires and visual analog score in order to assess impact on pain severity, stiffness, and functional activities of daily living. Follow-up outcome scores were collected up to 6 months after cooled radiofrequency ablation procedure. A total of 11 hips were treated consecutively between August 2019 and March 2020 (mean patient age 61.4 years; 8 M:3F). The mean total HOOS score improved significantly from baseline at 17.0 ± 6.0 to 52.9 ± 5.4 at a mean of 6.2 months after treatment (p

To assess the functional parameters of the Achilles tendons among asymptomatic college level athletes using shear wave elastography (SWE) and to describe the relationship to athlete demographics and anthropometric lower extremity measurements. Sixty-five athletes were included in this IRB-approved study. SWE measurements were made on two tendon positions (neutral state and active maximum dorsiflexion) with two different probe orientations (longitudinal and transverse). Associations were assessed with BMI, tibial/foot length, type of sports, and resting/maximal dorsiflexion-plantar flexion angles. Thirty-five (53.8%) males and 30 (46.2%) females with an overall mean age of 20.9 years (± 2.8), mean height of 176 cm (± 0.11), and mean weight of 74.1 kg (± 12) were studied. In the neutral state, the mean wave velocity of 7.5 m sec−1 and the mean elastic modulus of 176.8 kPa were recorded. In active maximum dorsiflexion, the mean velocity was 8.3 m sec−1 and mean elastic modulus was 199 kPa. On the transverse view, the mean velocity and elastic measurements were significantly lower (p = 0.0001). No significant differences in SWE parameters were seen between male and female athletes regardless of probe orientation (p

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 off-resonance signals with preliminary assignments made to chemical groups in lipids and proteoglycans.

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.

This study aims to describe the normative Achilles tendon properties in a collegiate subject cohort. Achilles tendon evaluations in 65 asymptomatic college-level athletes by ultrasound B mode on two tendon positions (neutral state and active maximum dorsiflexion). Correlation was made to BMI, tibial/foot length, maximal calf circumference, type of sports, resting/maximal dorsiflexion-plantar flexion angles among other factors. The mean Achilles tendon length was found to be 14.9 cm, mean transverse dimension of 1.38 cm, thickness of 0.49 cm and cross-sectional area of 0.61 cm2 in the relaxed state. Males had greater tendon length than the female athletes (15.5 (M) vs 14.3cm (F) in the relaxed position and 16.1 (M) vs 15.2cm (F) in the stretched position), tendon width (1.4 vs 1.3 cm), tendon thickness (0.51 vs 0.46 cm), tendon cross-sectional area (0.65 vs 0.57 cm2) and foot length (27.6 cm vs 26.6 cm). The Achilles tendon parameters such as length in the relaxed state had a statistically significant correlation with the height, weight, and foot length, while the tendon length in the dorsiflexed-stretched position had a statistically significant relationship to foot length, tibia length, calf circumference and range of motion (both in maximum dorsiflexion and plantar flexion positions; p

This study aims to determine the accuracy of a novel ultrasonography (US) scanning and reporting protocol to detect recurrences. The secondary aim is to compare US and MRI accuracy and agreement. In this IRB-approved prospective study, consecutive patients presenting for MRI surveillance after resection were enrolled and underwent same-day US. Blinded to clinical information and the MRI, the US scanner characterized lesions using a proposed novel lexicon. Outcome was defined either by histology or a subsequent MRI scan confirming the presence or absence of recurrence. Fisher’s exact test and Kappa test were performed to assess of the significance and agreement between US, MRI, and outcome. A total of 68 US scans were performed on 55 patients. The overall accuracy to diagnose recurrence was the same for US and MRI (92.6%) while US was less sensitive (75.0% vs. 91.7%) but more specific (97.6% vs. 92.9%) than MRI. The two lesions missed by US but not MRI were an entirely intraosseous metastasis and a subcentimeter skin nodule. There was strong agreement between US and MRI with outcome (k = 0.787 and 0.801, respectively). These pilot data suggest the accuracy of this novel US local recurrence surveillance method is comparable to MRI. A multi-institutional prospective trial would increase power and determine reproducibility.

To introduce cooled radiofrequency nerve ablation (C-RFA) as an alternative to managing symptomatically moderate to severe glenohumeral osteoarthritis (OA) in patients who have failed other conservative treatments and who are not surgical candidates or refuse surgery.This prospective pilot study includes a total of 12 patients experiencing chronic shoulder pain from moderate to severe glenohumeral OA. Patients underwent anesthetic blocks of the axillary, lateral pectoral, and suprascapular nerves to determine candidacy for C-RFA treatment. Adequate response after anesthetic block was over 50% immediate pain relief. Once patients were deemed candidates, they underwent C-RFA of the three nerves 2-3 weeks later. Treatment response was evaluated using the clinically validated American Shoulder and Elbow Surgeons (ASES) score and visual analog scale (VAS) to assess pain, stiffness, and functional activities of daily living. Follow-up outcome scores were collected up to 6 months after C-RFA procedure.Twelve patients underwent C-RFA procedure for shoulder OA. VAS scores significantly improved from 8.8 ± 0.6 to 2.2 ± 0.4 6 months after the C-RFA treatment (p 0.001). Patient's ASES score results significantly improved in total ASES from 17.2 ± 6.6 to 65.7 ± 5.9 (p 0.0005). No major complications arose. No patients received re-treatment or underwent shoulder arthroplasty.Image-guided axillary, lateral pectoral, and suprascapular nerve C-RFA has minimal complications and is a promising alternative to treat chronic shoulder pain and stiffness from glenohumeral arthritis.

Retrospective cohort study.The aim was to compare the outcomes of patients with incompletely corrected cervical deformity against those without deformity following short-segment anterior cervical decompression and fusion for clinically significant radiculopathy or myelopathy.Cervical deformity has increasingly been recognized as a driver of disability and has been linked to worse patient-reported outcomes measures (PROMs) after surgery.Patients 18 years or above who underwent 1-3 level anterior cervical decompression and fusion to address radiculopathy and/or myelopathy at a single institution between 2014 and 2018 with at least 1 year of PROMs were reviewed. Patients were categorized based on cervical deformity into 2 groups: sagittal vertebral axis (cSVA) ≥40 mm as the deformity group, and cSVA40 mm as the nondeformity group. Patient demographics, surgical parameters, preoperative and postoperative radiographs, and minimum 1-year PROMs were compared.Of the 230 patients, 191 (83%) were in the nondeformity group and 39 (17%) in the deformity group. Patients with deformity were more likely to be male (69.2% vs. 40.3%, P0.001) and have a greater body mass index (32.8 vs. 29.7, P=0.028). The deformity group had significantly greater postoperative cSVA (44.2 vs. 25.1 mm, P0.001) but also had significantly greater ∆cSVA (-4.87 vs. 0.25 mm, P=0.007) than the nondeformity group. Both groups had significant improvements in visual analog scale arm, visual analog scale neck, Short-Form 12 Physical Component Score, and neck disability index (NDI) (P0.001). However, the deformity group experienced significantly greater ∆NDI and ∆mental component score (MCS)-12 scores (-19.45 vs. -11.11, P=0.027 and 7.68 vs. 1.32, P=0.009).Patients with preoperative cervical sagittal deformity experienced relatively greater improvements in NDI and MCS-12 scores than those without preoperative deformity. These results suggest that complete correction of sagittal alignment is not required for patients to achieve significant clinical improvement.III.

Skeletal muscle density, as determined by computed tomography (CT), has been shown to decline with age, resulting in increased frailty and morbidity. However, the mechanism underlying this decrease in muscle density remains elusive. We sought to investigate the role of intramyocellular lipid (IMCL) accumulation in the age-related decline in muscle density. Muscle density was measured using computerized tomography (CT), and IMCL content was quantified using in vivo proton magnetic resonance spectroscopy (1H-MRS). The study population consisted of 314 healthy participants (142 men, 32–98 years) of the Baltimore Longitudinal Study of Aging (BLSA). In addition to IMCL quantification, obesity-related covariates were measured, including body mass index (BMI), waist circumference, and circulating triglyceride concentration. Higher IMCL concentrations were significantly correlated with lower muscle density in older individuals, independent of age, sex, race, and the obesity-associated covariates (p < 0.01). Lower muscle density was also significantly associated with greater age-adjusted IMCL, a variable we constructed using LOESS regression (p < 0.05). Our results suggest that the accumulation of IMCL may be associated with a decrease in muscle density. This may serve to define a potential therapeutic target for treatment of age-associated decreased muscle function.

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. 19 F and 1 H-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.

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 [Formula: see text] , 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 [Formula: see text] , 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.

This was a retrospective cohort study.The goal of this study is to evaluate the outcomes of patients with cervical degenerative spondylolisthesis (DS) undergoing anterior cervical discectomy and fusion (ACDF), specifically comparing surgeries that include versus exclude the DS level.DS has been extensively studied in the lumbar spine associated with both back and leg pain leading to worse patient quality of life measures. Conversely, there is a relative dearth of literature regarding surgical and clinical outcomes in the setting of cervical DS.A total of 315 patients undergoing ACDF between 2014 and 2018 with minimum of 1-year postoperative patient-reported outcome measures (PROMs) were retrospectively reviewed. Forty-six patients were found to have DS and were categorized based on whether an ACDF was performed at the same level (SL) or at a different level (DL) than the spondylolisthesis. Patient demographics, surgical parameters, preoperative and postoperative radiographs, and PROMs were compared between groups.Of the 315 patients, a total of 46 met the inclusion criteria including 21 SL and 25 DL patients. There were no significant differences in patient demographics between the groups. The SL cohort had a significantly worse preoperative sagittal vertical axis (SL: 34.4 vs. 26.1, P=0.025) but no difference in postoperative or delta sagittal vertical axis. Both patient cohorts reported significant postoperative improvement in all PROMs, except Short-Form 12 Mental Component Score in the SL group. There were no differences between the groups regarding Visual Analog Scale Neck, Visual Analog Scale Arm, Neck Disability Index, or Short-Form 12 Physical Component Score. Regression analysis demonstrated SL to be a significant negative predictor for improvement in Short-Form 12 Mental Component Score (β: -11.27, P=0.10).Patients treated only at their neurologically symptomatic levels, excluding asymptomatic listhesis in their construct, can expect equivalent radiographic as well as physical function, disability, and pain outcomes 1 year after ACDF compared with patients whose listhetic level was included in their construct.Level III.

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.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.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 inMulti-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 off-resonance signals with preliminary assignments made to chemical groups in lipids and proteoglycans.

To assess the functional parameters of the Achilles tendons among asymptomatic college level athletes using shear wave elastography (SWE) and to describe the relationship to athlete demographics and anthropometric lower extremity measurements.Sixty-five athletes were included in this IRB-approved study. SWE measurements were made on two tendon positions (neutral state and active maximum dorsiflexion) with two different probe orientations (longitudinal and transverse). Associations were assessed with BMI, tibial/foot length, type of sports, and resting/maximal dorsiflexion-plantar flexion angles.Thirty-five (53.8%) males and 30 (46.2%) females with an overall mean age of 20.9 years (± 2.8), mean height of 176 cm (± 0.11), and mean weight of 74.1 kg (± 12) were studied. In the neutral state, the mean wave velocity of 7.5 m secSWE can distinguish functional differences in Achilles tendon stiffness between athletes engaged in running-intensive sports compared with other athletes.

Background A common feature of hip arthritis is the presence of labra tears. Recent literature suggests against the use of magnetic resonance imaging (MRI) in patients aged >45 years for the assessment of hip pain related to arthritis. Purpose To determine if radiographic features of osteoarthritis detectable on routine hip radiographs are accurate and reliable surrogate markers of degenerative acetabular labral tears identified on MR arthrography (MRA) and corroborated during arthroscopy. Material and Methods A retrospective study involving 86 symptomatic patients (hip pain) with radiologic work-up included MRA and pelvic or hip radiographs that underwent hip arthroscopy within three months. Imaging characteristics assessed on hip radiographs include measurements of superior acetabular, femoral head osteophyte, cortical thickness of the femoral shaft, and minimum joint space as well as presence of subchondral sclerosis of the femoral head and acetabulum, femoral shaft buttressing, and grade of arthritis. Presence of a labral tear was determined by consensus between three readers as well as by surgical correlation. The Pearson’s chi-squared and Fisher’s exact tests were used to compare presence of labral tears with each radiographic feature. Results Seventy-one patients (82.6%) had labral tears: 49 (69%) women and 22 (31%) men. Receiver operating characteristic analysis showed statistical significance ( PConclusions Radiographic markers such as the acetabular and femoral head osteophyte sizes demonstrated statistical significance with the presence of labral tears.

PurposeIntervertebral disc degeneration (IVDD), resulting in the depletion of hydrophilic glycosaminoglycans (GAGs) located in the nucleus pulposus (NP), can lead to debilitating neck and back pain. Magnetic Resonance Imaging (MRI) is a promising means of IVD assessment due to the sensitivity of MRI tissue relaxation properties to matrix composition. Furthermore, anomalous (i.e. non-monoexponential) relaxation models have shown higher sensitivity to specific matrix components compared to conventional monoexponential models. Here, we extend the use of the stretched exponential model, an anomalous relaxation model, to IVD relaxometry data.Theory and MethodsT1ρ and T2 relaxation data were measured in the cervical IVDs of healthy volunteers and IVDs adjacent to cervical fusion, and analyzed using both conventional and stretched-exponential (SE) models. Model differences were evaluated via goodness of fit in the healthy data. Normalized histograms of the resultant quantitative MRI (qMRI) maps were described using stable distributions, and data were compared across adjacent disc segments.ResultsIn the healthy IVDs, we found lower mean squared error in the SE relaxation model fitting behavior compared to monoexponential models, supporting anomalous relaxation behavior in healthy IVDs. SE model parameter αT1ρ increased level-wise in the caudal direction, especially in the nucleus pulposus, while conventional T1ρ and T2 monoexponential measures did not vary. For IVDs adjacent to cervical fusion, SE parameters deviated near the fusion site compared with those in the healthy population.ConclusionSE modeling of T1ρ relaxation provides greater sensitivity to level-wise variation in IVD matrix properties compared with conventional relaxation modeling, and could provide improved sensitivity to early stages of IVD degeneration. The improved model fit and correlation between the SE αT1ρ parameter with IVD level suggests SE modeling may be a more sensitive method for detection of GAG content variation.

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.

Purpose We applied our recently introduced Bayesian analytic method to achieve clinically-feasible in-vivo mapping of the proteoglycan water fraction (PgWF) of human knee cartilage with improved spatial resolution and stability as compared to existing methods. Materials and methods Multicomponent driven equilibrium single-pulse observation of T 1 and T 2 (mcDESPOT) datasets were acquired from the knees of two healthy young subjects and one older subject with previous knee injury. Each dataset was processed using Bayesian Monte Carlo (BMC) analysis incorporating a two-component tissue model. We assessed the performance and reproducibility of BMC and of the conventional analysis of stochastic region contraction (SRC) in the estimation of PgWF. Stability of the BMC analysis of PgWF was tested by comparing independent high-resolution (HR) datasets from each of the two young subjects. Results Unlike SRC, the BMC-derived maps from the two HR datasets were essentially identical. Furthermore, SRC maps showed substantial random variation in estimated PgWF, and mean values that differed from those obtained using BMC. In addition, PgWF maps derived from conventional low-resolution (LR) datasets exhibited partial volume and magnetic susceptibility effects. These artifacts were absent in HR PgWF images. Finally, our analysis showed regional variation in PgWF estimates, and substantially higher values in the younger subjects as compared to the older subject. Conclusions BMC-mcDESPOT permits HR in-vivo mapping of PgWF in human knee cartilage in a clinically-feasible acquisition time. HR mapping reduces the impact of partial volume and magnetic susceptibility artifacts compared to LR mapping. Finally, BMC-mcDESPOT demonstrated excellent reproducibility in the determination of PgWF.

Summary 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, kPC r, 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, kPC r 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

OBJECTIVES: Obesity, body composition, and mitochondrial dysfunction play important roles in the development of metabolic diseases, but it is unknown if increased visceral fat (VF) specifically alters mitochondrial bioenergetic capacity. We determined whether in vivo and ex vivo bioenergetic indexes are associated with total body composition, visceral fat (VF), and body composition subtypes. METHODS: This pilot study included 34 healthy adults (56% female, median age 27.9 y). Body composition and fat distribution were assessed by dual energy x-ray absorptiometry. Subjects were categorized as lean (BMI 30% body fat in women or >23% body fat in men, n = 8), or overweight/obese (O/O, BMI > 25 kg/m(2), n = 12). Ex vivo mitochondrial function was assessed using a Seahorse extracellular flux analyzer in peripheral blood mononuclear cells (PBMC) and isolated monocytes. In a subset (n = 21), maximum in vivo ATP synthesis was assessed in the quadriceps using 31P-Magnetic resonance spectroscopy based on the phosphocreatine recovery time constant (τPCr) following a standardized leg exercise. Statistical analyses included Spearman correlations and Kruskal-Wallis tests. RESULTS: In monocytes, but not PBMCs, % spare respiratory capacity was inversely associated with % body fat (r = −0.42, P = 0.02) and positively associated with lean body mass (r = 0.36, P = 0.04) but was not significantly associated with VF. Skeletal muscle τPCr was positively associated with % body fat (r = 0.58, P

Sarcopenia is associated with poor outcomes in a variety of conditions, including malignancy. Abdominal skeletal muscle area (SMA) segmentation using computed tomography (CT) has been shown to be an accurate surrogate for identifying sarcopenia. While magnetic resonance imaging (MRI) segmentation of SMA has been validated in cadaver limbs, few studies have validated abdominal SMA segmentation using MRI at lumbar level mid-L3. Our objective was to assess the reproducibility and concordance of CT and MRI segmentation analyses of SMA at mid-L3. This retrospective analysis included a random sample of 10 patients with renal cell carcinoma (RCC) and CT abdomen/pelvis, used to assess intra-observer variability of SMA measurements using CT. An additional sample of 9 patients with RCC and both CT and T2-weighted (T2w) MRI abdomen/pelvis was used to assess intra-observer variability of SMA using MRI and concordance of SMA between MRI and CT. SMA was segmented using Slice-O-Matic. SMA reproducibility was assessed using intraclass correlation coefficient (ICC). SMA concordance was analyzed using Bland–Altman plot and Pearson correlation coefficient. The intra-observer variability of CT and MRI SMA at mid-L3 was low, with ICC of 0.998 and 0.985, respectively. Bland–Altman analysis revealed bias of 0.74% for T2w MRI over CT. The Pearson correlation coefficient was 0.997 (p < 0.0001), demonstrating strong correlation between CT and T2w MRI. Abdominal SMA at mid-L3 is reproducibly segmented for both CT and T2w MRI, with strong correlation between the 2 modalities. T2w MRI can be used interchangeably with CT for assessment of SMA and sarcopenia. This finding has important clinical implications.

Whether individuals with insulin resistance (IR) but without criteria for diabetes exhibit reduced mitochondrial oxidative capacity is unclear; addressing this question could guide research for new therapeutics. We investigated 248 participants without diabetes from the Baltimore Longitudinal Study of Aging (BLSA) to determine whether impaired mitochondrial capacity is associated with prediabetes, IR, and duration and severity of hyperglycemia exposure. Mitochondrial capacity was assessed as the postexercise phosphocreatine recovery time constant (τPCr) by 31P-magnetic resonance spectroscopy, with higher τPCr values reflecting reduced capacity. Prediabetes was defined using the American Diabetes Association criteria from fasting and 2-h glucose measurements. IR and sensitivity were calculated using HOMA-IR and Matsuda indices. The duration and severity of hyperglycemia exposure were estimated as the number of years from prediabetes onset and the average oral glucose tolerance test (OGTT) 2-h glucose measurement over previous BLSA visits. Covariates included age, sex, body composition, physical activity, and other confounders. Higher likelihood of prediabetes, higher HOMA-IR, and lower Matsuda index were associated with longer τPCr. Among 205 participants with previous OGTT data, greater severity and longer duration of hyperglycemia were independently associated with longer τPC. In conclusion, in individuals without diabetes a more impaired mitochondrial capacity is associated with greater IR and a higher likelihood of prediabetes.

Maximum in vivo oxidative capacity of skeletal muscle declines with age, and this negatively affects both muscle strength and walking speed. However, it remains unclear whether the loss of oxidative capacity is caused by reduced volume and function of mitochondria or limited substrate availability secondary to impaired perfusion. We sought to elucidate the role of impaired perfusion on the age-related decline of oxidative capacity in 71 participants (44 men, 22–87 years) from an Intramural National Institute on Aging population study. This study enrolls healthy subjects across a wide age range who are subjected to a large panel of functional and biochemical tests. Maximum oxidative capacity was assessed by phosphorus magnetic resonance spectroscopy (31P-MRS) in the mid-thigh (vastus lateralis) of the left leg as post-exercise phosphocreatine (PCr) recovery time (τPCr), with longer τPCr reflecting lower oxidative capacity. Resting muscle perfusion was characterized using a customized diffusion-weighted MRI method based on a formalism that describes superdiffusive transport of blood through tissue. We found both oxidative capacity and perfusion were significantly lower at older age (p

Aging is associated with impaired endothelium-dependent vasodilation that contributes to organ dysfunction and progression of cardiovascular disease. Impaired muscle perfusion results in inadequate adaptation to oxygen and nutrient demands during and after muscle contraction, limiting performance. Accurately measuring muscle perfusion is essential for understanding mechanisms by which aging contributes to declining physical function. Therefore, we developed and validated a non-invasive diffusion-weighted MRI (DW-MRI) technique to characterize perfusion and diffusivity of water molecules in skeletal muscle in response to exercise. The mid-thigh of the left leg of four younger (21–30 year-old) and four older (60–90 year-old) healthy female volunteers was studied using DW-MRI at rest (baseline) and at 7 time points following in-magnet knee extension exercise with a temporal resolution of 3.25min. Exercise was performed using a MR-compatible ergometer with a workload of 0.4bar for 2.5min. After exercise, both perfusion and diffusivity significantly increased from baseline with a peak at the second dynamic in rectus femoris (active during exercise) compared to medial adductor (inactive) in both age groups, reflecting the local increase in blood flow. However, different time-courses of perfusion were observed in younger versus older groups following exercise. A significantly steeper (p

PURPOSE: Magnetic resonance imaging of ex-vivo cartilage measures parameters such as T(2) and magnetization transfer ratio (MTR), which reflect structural changes associated with osteoarthritis. Samples are often immersed in aqueous solutions to prevent dehydration and to improve susceptibility matching. This study sought to determine the extent to which T(2) and MTR changes are attributable to immersion alone and to identify immersion conditions to minimize this confounding factor. METHODS: T(2) 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, DPBS or saline, with removal from the magnet between scans. (19)F and (1)H MRI were used to detect cartilage penetration by Fluorinert and swelling, respectively. RESULTS: Saline and DPBS immersion rapidly increased T(2), wet weight and cartilage volume and decreased MTR, suggesting increased water content for all cartilage types. Fluorinert-immersed samples exhibited minimal changes in T(2) or MTR. No ingress of Fluorinert was detected after two 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.

Summary Objective The purpose of this study is to evaluate the ability of machine learning to discriminate between magnetic resonance images (MRI) of normal and pathological human articular cartilage obtained under standard clinical conditions. Method An approach to MRI classification of cartilage degradation is proposed using pattern recognition and multivariable regression in which image features from MRIs of histologically scored human articular cartilage plugs were computed using weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHRM). The WND-CHRM method was first applied to several clinically available MRI scan types to perform binary classification of normal and osteoarthritic osteochondral plugs based on the Osteoarthritis Research Society International (OARSI) histological system. In addition, the image features computed from WND-CHRM were used to develop a multiple linear least-squares regression model for classification and prediction of an OARSI score for each cartilage plug. Results The binary classification of normal and osteoarthritic plugs yielded results of limited quality with accuracies between 36% and 70%. However, multiple linear least-squares regression successfully predicted OARSI scores and classified plugs with accuracies as high as 86%. The present results improve upon the previously-reported accuracy of classification using average MRI signal intensities and parameter values. Conclusion MRI features detected by WND-CHRM reflect cartilage degradation status as assessed by OARSI histologic grading. WND-CHRM is therefore of potential use in the clinical detection and grading of osteoarthritis.

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, 2015. © 2015 Wiley Periodicals, Inc.

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, 2015. © 2015 Wiley Periodicals, Inc.

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.

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.

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.

Skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, which is critically important in health and disease, can be measured in vivo and noninvasively in humans via phosphorus-31 magnetic resonance spectroscopy (31PMRS). However, the approach has not been widely adopted in translational and clinical research, with variations in methodology and limited guidance from the literature. Increased optimization, standardization, and dissemination of methods for in vivo 31PMRS would facilitate the development of targeted therapies to improve OXPHOS capacity and could ultimately favorably impact cardiovascular health. 31PMRS produces a noninvasive, in vivo measure of OXPHOS capacity in human skeletal muscle, as opposed to alternative measures obtained from explanted and potentially altered mitochondria via muscle biopsy. It relies upon only modest additional instrumentation beyond what is already in place on magnetic resonance scanners available for clinical and translational research at most institutions. In this work, we outline a method to measure in vivo skeletal muscle OXPHOS. The technique is demonstrated using a 1.5 Tesla whole-body MR scanner equipped with the suitable hardware and software for 31PMRS, and we explain a simple and robust protocol for in-magnet resistive exercise to rapidly fatigue the quadriceps muscle. Reproducibility and feasibility are demonstrated in volunteers as well as subjects over a wide range of functional capacities.

In this paper, we investigate the automatic detection of white and brown adipose tissues using Positron Emission Tomography/Computed Tomography (PET/CT) scans, and develop methods for the quantification of these tissues at the whole-body and body-region levels. We propose a patient-specific automatic adiposity analysis system with two modules. In the first module , we detect white adipose tissue (WAT) and its two sub-types from CT scans: Visceral Adipose Tissue (VAT) and Subcutaneous Adipose Tissue (SAT). This process relies conventionally on manual or semi-automated segmentation, leading to inefficient solutions. Our novel framework addresses this challenge by proposing an unsupervised learning method to separate VAT from SAT in the abdominal region for the clinical quantification of central obesity. This step is followed by a context driven label fusion algorithm through sparse 3D Conditional Random Fields (CRF) for volumetric adiposity analysis. In the second module , we automatically detect, segment, and quantify brown adipose tissue (BAT) using PET scans because unlike WAT, BAT is metabolically active. After identifying BAT regions using PET, we perform a co-segmentation procedure utilizing asymmetric complementary information from PET and CT. Finally, we present a new probabilistic distance metric for differentiating BAT from non-BAT regions. Both modules are integrated via an automatic body-region detection unit based on one-shot learning. Experimental evaluations conducted on 151 PET/CT scans achieve state-of-the-art performances in both central obesity as well as brown adiposity quantification.

Skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, which is critically important in health and disease, can be measured in vivo and noninvasively in humans via phosphorus-31 magnetic resonance spectroscopy (31PMRS). However, the approach has not been widely adopted in translational and clinical research, with variations in methodology and limited guidance from the literature. Increased optimization, standardization, and dissemination of methods for in vivo 31PMRS would facilitate the development of targeted therapies to improve OXPHOS capacity and could ultimately favorably impact cardiovascular health. 31PMRS produces a noninvasive, in vivo measure of OXPHOS capacity in human skeletal muscle, as opposed to alternative measures obtained from explanted and potentially altered mitochondria via muscle biopsy. It relies upon only modest additional instrumentation beyond what is already in place on magnetic resonance scanners available for clinical and translational research at most institutions. In this work, we outline a method to measure in vivo skeletal muscle OXPHOS. The technique is demonstrated using a 1.5 Tesla whole-body MR scanner equipped with the suitable hardware and software for 31PMRS, and we explain a simple and robust protocol for in-magnet resistive exercise to rapidly fatigue the quadriceps muscle. Reproducibility and feasibility are demonstrated in volunteers as well as subjects over a wide range of functional capacities.