Differences in peripheral microcirculatory blood flow regulation in chronic kidney disease based on wavelet analysis of resting near-infrared spectroscopy.

Vascular impairment is closely related to increased mortality in chronic kidney disease (CKD). The objective of this study was to assess impairments in the regulation of peripheral microvascular perfusion in patients with CKD based on time-frequency spectral analysis of resting near-infrared spectroscopy (NIRS) signals. Total hemoglobin (tHb) concentration and tissue saturation index (TSI) signals were collected using NIRS for a continuous 5 mins at 10 Hz from the forearm of 55 participants (34 CKD including 5 with end-stage renal disease, and 21 age-matched control). Continuous wavelet transform-based spectral analysis was used to quantify the spectral amplitude within five pre-defined frequency intervals (I, 0.0095-0.021 Hz; II, 0.021-0.052 Hz; III, 0.052-0.145 Hz; IV, 0.145-0.6 Hz and V, 0.6-2.0 Hz), representing endothelial, neurogenic, myogenic, respiratory and heartbeat activity, respectively. CKD patients showed lower tHb average spectral amplitude within the neurogenic frequency interval compared with controls (p = 0.014), consistent with an increased sympathetic outflow observed in CKD. CKD patients also showed lower TSI average spectral amplitude within the endothelial frequency interval compared with controls (p = 0.046), consistent with a reduced endothelial function in CKD. These findings demonstrate the potential of wavelet analysis of NIRS to provide complementary information on peripheral microvascular regulation in CKD.

Feasibility of Multiparametric Perfusion Assessment in Diabetic Foot Ulcer Using Intravoxel Incoherent Motion and Blood Oxygenation-Level Dependent MRI.

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.

Differences in Achilles tendon mechanical properties between professional ballet dancers and collegiate athletes utilizing shear wave elastography.

PURPOSE: To report normative stiffness parameters obtained using shear wave elastography in dorsiflexion from the Achilles tendons in asymptomatic professional ballet dancers and compare them with college-level athletes. METHODS: An Institutional Review Board (IRB)-approved study consists of 28 professional ballet dancers and 64 asymptomatic collegiate athletes. The athletes were further subdivided into runner and non-runner disciplines. Shear wave elastography (SWE) measurements were made in maximum ankle dorsiflexion position. RESULTS AND DISCUSSION: Forty-eight (52%) males and 44 (48%) females were examined with an overall mean age of 22.2 (± 3.8 years). There were no significant SWE differences between dominant and non-dominant legs in both groups and comparing spin vs. non-spin leg of ballet dancers (p > 0.05). Ballet dancers had significantly higher short-axis velocity values than runners and non-runners (2.34 m/s increase and 2.79 m/s increase, respectively, p < 0.001). Long-axis velocity was significantly higher in ballet dancers compared to non-runners (by 0.80 m/s, p < 0.001), but was not different between ballet dancers and runners (p > 0.05). Short-axis modulus was significantly higher in dancers compared to runners and non-runners (by 135.2 kPa and 159.2 kPa, respectively, p < 0.001). Long-axis modulus (LAM) was not significantly different in ballet dancers when compared to runners. CONCLUSION: Asymptomatic professional ballet dancers exhibit greater short-axis tendon stiffness compared to athletes and greater long-axis tendon stiffness compared to non-runners but similar to runners. The functional benefit from elevated short-axis stiffness in dancers is not clear but may be related to greater axial loading and adaptations of the tendon matrix.

Multi-frame biomechanical and relaxometry analysis during in vivo loading of the human knee by spiral dualMRI and compressed sensing.

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.

Intravoxel Incoherent Motion Magnetic Resonance Imaging in Skeletal Muscle: Review and Future Directions.

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.

Pilot study for treatment of symptomatic shoulder arthritis utilizing cooled radiofrequency ablation: a novel technique.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Brain Activity During Experimental Knee Pain and Its Relationship With Kinesiophobia in Patients With Patellofemoral Pain: A Preliminary Functional Magnetic Resonance Imaging Investigation.

CONTEXT: The etiology of patellofemoral pain has remained elusive, potentially due to an incomplete understanding of how pain, motor control, and kinesiophobia disrupt central nervous system functioning. OBJECTIVE: To directly evaluate brain activity during experimental knee pain and its relationship to kinesiophobia in patients with patellofemoral pain. DESIGN: Cross-sectional. METHODS: Young females clinically diagnosed with patellofemoral pain (n = 14; 14.4 [3.3] y; body mass index = 22.4 [3.8]; height = 1.61 [0.1] m; body mass = 58.4 [12.7] kg). A modified Clarke test (experimental pain condition with noxious induction via patella pressure and quadriceps contraction) was administered to the nondominant knee (to minimize limb dominance confounds) of patients during brain functional magnetic resonance imaging (fMRI) acquisition. Patients also completed a quadriceps contraction without application of external pressure (control contraction). Kinesiophobia was measured using the Tampa Scale of Kinesiophobia. The fMRI analyses assessed brain activation during the modified Clarke test and control contraction and assessed relationships between task-induced brain activity and kinesiophobia. Standard processing for neuroimaging and appropriate cluster-wise statistical thresholds to determine significance were applied to the fMRI data (z > 3.1, P < .05). RESULTS: The fMRI revealed widespread neural activation in the frontal, parietal, and occipital lobes, and cerebellum during the modified Clarke test (all zs > 4.4, all Ps < .04), whereas neural activation was localized primarily to frontal and cerebellar regions during the control contraction test (all zs > 4.4, all Ps < .01). Greater kinesiophobia was positively associated with greater activity in the cerebello-frontal network for the modified Clarke test (all zs > 5.0, all Ps < .01), but no relationships between kinesiophobia and brain activity were observed for the control contraction test (all zs < 3.1, all Ps > .05). CONCLUSIONS: Our novel experimental knee pain condition was associated with alterations in central nociceptive processing. These findings may provide novel complementary pathways for targeted restoration of patient function.

Parsimonious modeling of skeletal muscle perfusion: Connecting the stretched exponential and fractional Fickian diffusion.

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.

Multi-component T2∗ relaxation modelling in human Achilles tendon: Quantifying chemical shift information in ultra-short echo time imaging.

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.

Review of Extraosseous Applications of Thermal Ablation in the Treatment of Moderate to Severe Large Joint Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease worldwide, leading to significant pain, restricted range of motion, and disability. A gap exists between short- and long-term symptom-relieving therapies. Although arthroplasty is an effective treatment for symptomatic end-stage disease, most patients ultimately do not receive a joint replacement due to suboptimal surgical qualifications, comorbidities, or an aversion to surgery. The lack of additional treatment options in this setting makes opioid agonists a commonly used pharmacologic agent, contributing to the addiction epidemic that greatly afflicts our communities. Cooled radiofrequency ablation (CRFA) has arisen as a treatment modality in the setting of moderate to severe OA among patients refractory to conservative management, generally showing greater efficacy compared with other existing strategies. This review focuses on the benefits of CRFA and its technical feasibility as a management option among patients experiencing debilitating large joint OA with limited clinical options.

Shear wave elastography assessment and comparison study of the Achilles tendons in optimally conditioned asymptomatic young collegiate athletes.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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 < 0.05) with SWE values being higher in the running group vs non-running group (p < 0.05). In neutral state, longitudinal SWE measurements correlated with the tibia-foot length whereas transverse measurements correlated with the tendon diameter and ankle resting angle (ARA) (p < 0.005). CONCLUSION: SWE can distinguish functional differences in Achilles tendon stiffness between athletes engaged in running-intensive sports compared with other athletes.

In vivo Sonographic Characterization of The Achilles Tendons in Healthy Young Collegiate Athletes as a Function of Ankle Position.

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 < .05 for all comparison). Differences in the correlation between the Achilles tendon parameters and body habitus was recorded as a function of ankle position. Tendon dimensions and cross-sectional areas were larger in male vs female athletes. Calf circumferences and Achilles tendon resting angle were outlined. No significant difference was found in the Achilles tendon dimensions regardless of the leg dominance with similar range of motion regardless of athlete gender.

Stabilization of T2 relaxation and magnetization transfer in cartilage explants by immersion in perfluorocarbon liquid.

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.

Diffusion-weighted MRI with intravoxel incoherent motion modeling for assessment of muscle perfusion in the thigh during post-exercise hyperemia in younger and older adults.

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.

Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content.

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.

The effect of noise and lipid signals on determination of Gaussian and non-Gaussian diffusion parameters in skeletal muscle.

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.

Anomalous T2 relaxation in normal and degraded cartilage.

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.

Analysis of mcDESPOT- and CPMG-derived parameter estimates for two-component nonexchanging systems.

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.

Region of interest correction factors improve reliability of diffusion imaging measures within and across scanners and field strengths.

Diffusion tensor imaging (DTI) measures are commonly used as imaging markers to investigate individual differences in relation to behavioral and health-related characteristics. However, the ability to detect reliable associations in cross-sectional or longitudinal studies is limited by the reliability of the diffusion measures. Several studies have examined the reliability of diffusion measures within (i.e. intra-site) and across (i.e. inter-site) scanners with mixed results. Our study compares the test-retest reliability of diffusion measures within and across scanners and field strengths in cognitively normal older adults with a follow-up interval less than 2.25 years. Intra-class correlation (ICC) and coefficient of variation (CoV) of fractional anisotropy (FA) and mean diffusivity (MD) were evaluated in sixteen white matter and twenty-six gray matter bilateral regions. The ICC for intra-site reliability (0.32 to 0.96 for FA and 0.18 to 0.95 for MD in white matter regions; 0.27 to 0.89 for MD and 0.03 to 0.79 for FA in gray matter regions) and inter-site reliability (0.28 to 0.95 for FA in white matter regions, 0.02 to 0.86 for MD in gray matter regions) with longer follow-up intervals were similar to earlier studies using shorter follow-up intervals. The reliability of across field strengths comparisons was lower than intra- and inter-site reliabilities. Within and across scanner comparisons showed that diffusion measures were more stable in larger white matter regions (>1500 mm(3)). For gray matter regions, the MD measure showed stability in specific regions and was not dependent on region size. Linear correction factor estimated from cross-sectional or longitudinal data improved the reliability across field strengths. Our findings indicate that investigations relating diffusion measures to external variables must consider variable reliability across the distinct regions of interest and that correction factors can be used to improve consistency of measurement across field strengths. An important result of this work is that inter-scanner and field strength effects can be partially mitigated with linear correction factors specific to regions of interest. These data-driven linear correction techniques can be applied in cross-sectional or longitudinal studies.