Publications by authors named "David A Reiter"

41 Publications

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

Skeletal Radiol 2021 May 20. Epub 2021 May 20.

Department of Radiology and Imaging Sciences, Emory School of Medicine, 59 Executive Park South, 4th Floor Suite 4009, Atlanta, GA, 30329, USA.

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http://dx.doi.org/10.1007/s00256-021-03818-4DOI Listing
May 2021

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

Skeletal Radiol 2021 May 8. Epub 2021 May 8.

Department of Radiology and Imaging Sciences, Emory School of Medicine, 59 Executive Park South, 4th Floor Suite 4009, Atlanta, GA, 30329, USA.

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 and the mean elastic modulus of 176.8 kPa were recorded. In active maximum dorsiflexion, the mean velocity was 8.3 m sec 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.
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http://dx.doi.org/10.1007/s00256-021-03798-5DOI Listing
May 2021

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

Magn Reson Med 2021 08 16;86(2):1045-1057. Epub 2021 Mar 16.

National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.

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 , 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 , 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.
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http://dx.doi.org/10.1002/mrm.28766DOI Listing
August 2021

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

Magn Reson Med 2021 07 15;86(1):415-428. Epub 2021 Feb 15.

Department of Radiology & Imaging Sciences, School of Medicine, Emory University, Atlanta, Georgia, USA.

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 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.
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http://dx.doi.org/10.1002/mrm.28686DOI Listing
July 2021

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

J Foot Ankle Surg 2020 Sep - Oct;59(5):898-902. Epub 2020 Jul 3.

Associate Professor of Orthopedics, Department of Orthopaedic Surgery, Emory School of Medicine, Atlanta, GA.

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 cm 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 cm) 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.
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http://dx.doi.org/10.1053/j.jfas.2020.01.009DOI Listing
July 2020

Age and Muscle Function Are More Closely Associated With Intracellular Magnesium, as Assessed by P Magnetic Resonance Spectroscopy, Than With Serum Magnesium.

Front Physiol 2019 27;10:1454. Epub 2019 Nov 27.

Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.

Total serum magnesium is a common clinical measurement for assessing magnesium status; however, magnesium in blood represents less than 1% of the body's total magnesium content. We measured intramuscular ionized magnesium by phosphorus magnetic resonance spectroscopy (P-MRS) and tested the hypothesis that this measure better correlates with skeletal muscle function and captures more closely the effect of aging than the traditional measure of total serum magnesium. Data were collected from 441 participants (age 24-98 years) in the Baltimore Longitudinal Study of Aging (BLSA), a study of normative aging that encompasses a broad age range. Results showed that intramuscular ionized magnesium was negatively associated with age (β = -0.29, < 0.001, = 0.08) and positively associated with knee-extension strength (β = 0.31, < 0.001, and = 0.1 in women; and β = 0.2, = 0.003, and = 0.04 in men), while total serum magnesium showed no association with age or strength ( = 0.27 and 0.1, respectively). Intramuscular ionized magnesium was significantly lower in women that in men ( < 0.001), perhaps due to chronic latent Mg deficiency in women that is not otherwise detected by serum magnesium levels. Based on these findings, we suggest that intramuscular ionized magnesium from P-MRS is a better clinical measure of magnesium status than total serum magnesium, and could be measured when muscle weakness of unidentified etiology is detected. It may also be used to monitor the effectiveness of oral magnesium interventions, including supplementation.
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http://dx.doi.org/10.3389/fphys.2019.01454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892402PMC
November 2019

The Role of Muscle Perfusion in the Age-Associated Decline of Mitochondrial Function in Healthy Individuals.

Front Physiol 2019 12;10:427. Epub 2019 Apr 12.

Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.

Maximum oxidative capacity of skeletal muscle measured by phosphorus magnetic resonance spectroscopy (P-MRS) declines with age, and negatively affects whole-body aerobic capacity. 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 muscle perfusion. Therefore, we sought to elucidate the role of muscle perfusion on the age-related decline of muscle oxidative capacity and ultimately whole-body aerobic capacity. Muscle oxidative capacity was assessed by P-MRS post-exercise phosphocreatine recovery time (τ), with higher τ reflecting lower oxidative capacity, in 75 healthy participants (48 men, 22-89 years) of the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing study. Muscle perfusion was characterized as an index of blood volume at rest using a customized diffusion-weighted MRI technique and analysis method developed in our laboratory. Aerobic capacity (peak-VO) was also measured during a graded treadmill exercise test in the same visit. Muscle oxidative capacity, peak-VO, and resting muscle perfusion were significantly lower at older ages independent of sex, race, and body mass index (BMI). τ was significantly associated with resting muscle perfusion independent of age, sex, race, and BMI (-value = 0.004, β = -0.34). τ was also a significant independent predictor of peak-VO and, in a mediation analysis, significantly attenuated the association between muscle perfusion and peak-VO (34% reduction for β in perfusion). These findings suggest that the age-associated decline in muscle oxidative capacity is partly due to impaired muscle perfusion and not mitochondrial dysfunction alone. Furthermore, our findings show that part of the decline in whole-body aerobic capacity observed with aging is also due to reduced microvascular blood volume at rest, representing a basal capacity of the microvascular system, which is mediated by muscle oxidative capacity. This finding suggests potential benefit of interventions that target an overall increase in muscle perfusion for the restoration of energetic capacity and mitochondrial function with aging.
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http://dx.doi.org/10.3389/fphys.2019.00427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473080PMC
April 2019

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.

NMR Biomed 2019 05 12;32(5):e4072. Epub 2019 Mar 12.

Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

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 (f ) 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 f 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 f 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.
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http://dx.doi.org/10.1002/nbm.4072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530599PMC
May 2019

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

Magn Reson Med 2019 05 22;81(5):3209-3217. Epub 2019 Jan 22.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.

Purpose: Magnetic resonance imaging of ex vivo cartilage measures parameters such as T 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 T and MTR changes are attributable to immersion alone and to identify immersion conditions to minimize this confounding factor.

Methods: T 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. F and H-MRI were used to detect cartilage penetration by Fluorinert and swelling, respectively.

Results: Saline and DPBS immersion rapidly increased T , wet weight and cartilage volume and decreased MTR, suggesting increased water content for all cartilage types. Fluorinert-immersed samples exhibited minimal changes in T 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.
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http://dx.doi.org/10.1002/mrm.27650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687396PMC
May 2019

MRI quantitation of abdominal skeletal muscle correlates with CT-based analysis: implications for sarcopenia measurement.

Appl Physiol Nutr Metab 2019 Aug 7;44(8):814-819. Epub 2019 Jan 7.

c Department of Urology, Emory University School of Medicine, Atlanta, GA 30322, USA.

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 ( < 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.
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http://dx.doi.org/10.1139/apnm-2018-0473DOI Listing
August 2019

Use of the NESMA Filter to Improve Myelin Water Fraction Mapping with Brain MRI.

J Neuroimaging 2018 11 12;28(6):640-649. Epub 2018 Jul 12.

Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD.

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 T 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.
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http://dx.doi.org/10.1111/jon.12537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212320PMC
November 2018

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

Alzheimers Dement 2018 08 19;14(8):998-1004. Epub 2018 Apr 19.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

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.
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http://dx.doi.org/10.1016/j.jalz.2018.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097903PMC
August 2018

Clinical high-resolution mapping of the proteoglycan-bound water fraction in articular cartilage of the human knee joint.

Magn Reson Imaging 2017 11 20;43:1-5. Epub 2017 Jun 20.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address:

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 and T (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.
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http://dx.doi.org/10.1016/j.mri.2017.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632579PMC
November 2017

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

NMR Biomed 2017 Jul 6;30(7). Epub 2017 Apr 6.

National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

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.
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http://dx.doi.org/10.1002/nbm.3718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876728PMC
July 2017

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle.

J Vis Exp 2017 01 19(119). Epub 2017 Jan 19.

Davis Heart and Lung Research Institute, The Ohio State University;

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 (PMRS). 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 PMRS would facilitate the development of targeted therapies to improve OXPHOS capacity and could ultimately favorably impact cardiovascular health. PMRS 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 PMRS, 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.
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http://dx.doi.org/10.3791/54977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352276PMC
January 2017

Muscle strength mediates the relationship between mitochondrial energetics and walking performance.

Aging Cell 2017 06 9;16(3):461-468. Epub 2017 Feb 9.

Translational Gerontology Branch, National Institutes of Health, Baltimore, MD, USA.

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, k , 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, k was associated with muscle strength (β = 0.140, P = 0.007) and muscle quality (β = 0.127, P = 0.022), independent of age, sex, height, and weight; muscle strength was also a significant independent correlate of walking speed (P < 0.02 for all tasks) and in a formal mediation analysis significantly attenuated the association between k and three of four walking tasks (18-29% reduction in β for k ). This is the first demonstration in human adults that mitochondrial function affects muscle strength and that inefficiency in muscle bioenergetics partially accounts for differences in mobility through this mechanism.
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http://dx.doi.org/10.1111/acel.12568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418194PMC
June 2017

Insulin Resistance Is Associated With Reduced Mitochondrial Oxidative Capacity Measured by 31P-Magnetic Resonance Spectroscopy in Participants Without Diabetes From the Baltimore Longitudinal Study of Aging.

Diabetes 2017 Jan 13;66(1):170-176. Epub 2016 Oct 13.

Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD

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 (τ) by P-magnetic resonance spectroscopy, with higher τ 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 τ Among 205 participants with previous OGTT data, greater severity and longer duration of hyperglycemia were independently associated with longer τ In conclusion, in individuals without diabetes a more impaired mitochondrial capacity is associated with greater IR and a higher likelihood of prediabetes.
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http://dx.doi.org/10.2337/db16-0754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204309PMC
January 2017

31P Magnetic Resonance Spectroscopy Assessment of Muscle Bioenergetics as a Predictor of Gait Speed in the Baltimore Longitudinal Study of Aging.

J Gerontol A Biol Sci Med Sci 2016 12 13;71(12):1638-1645. Epub 2016 Apr 13.

Translational Gerontology Branch and

Background: Aerobic fitness and muscle bioenergetic capacity decline with age; whether such declines explain age-related slowing of walking speed is unclear. We hypothesized that muscle energetics and aerobic capacity are independent correlates of walking speed in simple and challenging performance tests and that they account for the observed age-related decline in walking speed in these same tests.

Methods: Muscle bioenergetics was assessed as postexercise recovery rate of phosphocreatine (PCr), k , using phosphorus magnetic resonance spectroscopy (P-MRS) in 126 participants (53 men) of the Baltimore Longitudinal Study of Aging aged 26-91 years (mean = 72 years). Four walking tasks were administered-usual pace over 6 m and 150 seconds and fast pace over 6 m and 400 m. Separately, aerobic fitness was assessed as peak oxygen consumption (peak VO) using a graded treadmill test.

Results: All gait speeds, k , and peak VO were lower with older age. Independent of age, sex, height, and weight, both k and peak VO were positively and significantly associated with fast pace and long distance walking but only peak VO and not k was significantly associated with usual gait speed over 6 m. Both k and peak VO substantially attenuated the association between age and gait speed for all but the least stressful walking task of 6 m at usual pace.

Conclusion: Muscle bioenergetics assessed using P-MRS is highly correlated with walking speed and partially explains age-related poorer performance in fast and long walking tasks.
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http://dx.doi.org/10.1093/gerona/glw059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106855PMC
December 2016

Anomalous T2 relaxation in normal and degraded cartilage.

Magn Reson Med 2016 09 4;76(3):953-62. Epub 2015 Sep 4.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.

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.
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http://dx.doi.org/10.1002/mrm.25913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779070PMC
September 2016

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

Neuroimage 2015 Oct 2;119:406-16. Epub 2015 Jul 2.

Intramural Research Program, National Institute on Aging, National Institute of Health, Baltimore, MD 21224, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neuroimage.2015.06.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519407PMC
October 2015

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

Magn Reson Med 2016 06 3;75(6):2406-20. Epub 2015 Jul 3.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.

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.
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http://dx.doi.org/10.1002/mrm.25801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958911PMC
June 2016

Classification of histologically scored human knee osteochondral plugs by quantitative analysis of magnetic resonance images at 3T.

J Orthop Res 2015 May 5;33(5):640-50. Epub 2015 Mar 5.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, 3001 S. Hanover Street, Baltimore, Maryland.

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.
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http://dx.doi.org/10.1002/jor.22810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875433PMC
May 2015

Sensitivity and specificity of univariate MRI analysis of experimentally degraded cartilage under clinical imaging conditions.

J Magn Reson Imaging 2015 Jul 18;42(1):136-44. Epub 2014 Oct 18.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.

Background: To evaluate the sensitivity and specificity of classification of pathomimetically degraded bovine nasal cartilage at 3 Tesla and 37°C using univariate MRI measurements of both pure parameter values and intensities of parameter-weighted images.

Methods: Pre- and posttrypsin degradation values of T1 , T2 , T2 *, magnetization transfer ratio (MTR), and apparent diffusion coefficient (ADC), and corresponding weighted images, were analyzed. Classification based on the Euclidean distance was performed and the quality of classification was assessed through sensitivity, specificity and accuracy (ACC).

Results: The classifiers with the highest accuracy values were ADC (ACC = 0.82 ± 0.06), MTR (ACC = 0.78 ± 0.06), T1 (ACC = 0.99 ± 0.01), T2 derived from a three-dimensional (3D) spin-echo sequence (ACC = 0.74 ± 0.05), and T2 derived from a 2D spin-echo sequence (ACC = 0.77 ± 0.06), along with two of the diffusion-weighted signal intensities (b = 333 s/mm(2) : ACC = 0.80 ± 0.05; b = 666 s/mm(2) : ACC = 0.85 ± 0.04). In particular, T1 values differed substantially between the groups, resulting in atypically high classification accuracy. The second-best classifier, diffusion weighting with b = 666 s/mm(2) , as well as all other parameters evaluated, exhibited substantial overlap between pre- and postdegradation groups, resulting in decreased accuracies.

Conclusion: Classification according to T1 values showed excellent test characteristics (ACC = 0.99), with several other parameters also showing reasonable performance (ACC > 0.70). Of these, diffusion weighting is particularly promising as a potentially practical clinical modality. As in previous work, we again find that highly statistically significant group mean differences do not necessarily translate into accurate clinical classification rules.
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http://dx.doi.org/10.1002/jmri.24773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402115PMC
July 2015

Bayesian analysis of transverse signal decay with application to human brain.

Magn Reson Med 2015 Sep 19;74(3):785-802. Epub 2014 Sep 19.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.

Purpose: Transverse relaxation analysis with several signal models has been used extensively to determine tissue and material properties. However, the derivation of corresponding parameter values is notoriously unreliable. We evaluate improvements in the quality of parameter estimation using Bayesian analysis and incorporating the Rician noise model, as appropriate for magnitude MR images.

Theory And Methods: Monoexponential, stretched exponential, and biexponential signal models were analyzed using nonlinear least squares (NLLS) and Bayesian approaches. Simulations and phantom and human brain data were analyzed using three different approaches to account for noise. Parameter estimation bias (reflecting accuracy) and dispersion (reflecting precision) were derived for a range of signal-to-noise ratios (SNR) and relaxation parameters.

Results: All methods performed well at high SNR. At lower SNR, the Bayesian approach yielded parameter estimates of considerably greater precision, as well as greater accuracy, than did NLLS. Incorporation of the Rician noise model greatly improved accuracy and, to a somewhat lesser extent, precision, in derived transverse relaxation parameters. Analyses of data obtained from solution phantoms and from brain were consistent with simulations.

Conclusion: Overall, estimation of parameters characterizing several different transverse relaxation models was markedly improved through use of Bayesian analysis and through incorporation of the Rician noise model.
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http://dx.doi.org/10.1002/mrm.25457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366365PMC
September 2015

Incorporation of Rician noise in the analysis of biexponential transverse relaxation in cartilage using a multiple gradient echo sequence at 3 and 7 Tesla.

Magn Reson Med 2015 Jan 28;73(1):352-66. Epub 2014 Feb 28.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.

Purpose: Previous work has evaluated the quality of different analytic methods for extracting relaxation times from magnitude imaging data exhibiting Rician noise. However, biexponential analysis of relaxation in tissue, including cartilage, and materials is of increasing interest. We, therefore, analyzed biexponential transverse relaxation decay in the presence of Rician noise and assessed the accuracy and precision of several approaches to determining component fractions and apparent transverse relaxation times.

Theory And Methods: Comparisons of four different voxel-by-voxel fitting methods were performed using Monte Carlo simulations, and phantom and ex vivo bovine nasal cartilage (BNC) experiments. In each case, preclinical and clinical imaging field strengths of 7 Tesla (T) and 3T, respectively, and parameters, were investigated across a range of signal-to-noise ratios (SNR). Results were compared with Cramér-Rao lower bound calculations.

Results: As expected, at high SNR, all methods performed well. At lower SNR, fits explicitly incorporating the analytic form of the Rician noise maintained performance. The much more efficient correction scheme of Gudbjartsson and Patz performed almost as well in many cases. Ex vivo experiments on phantoms and BNC were consistent with simulation results.

Conclusion: Explicit incorporation of Rician noise greatly improves accuracy and precision in the analysis of biexponential transverse decay data.
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http://dx.doi.org/10.1002/mrm.25111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171354PMC
January 2015

Prediction of cartilage compressive modulus using multiexponential analysis of T(2) relaxation data and support vector regression.

NMR Biomed 2014 Apr 12;27(4):468-77. Epub 2014 Feb 12.

National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Evaluation of mechanical characteristics of cartilage by magnetic resonance imaging would provide a noninvasive measure of tissue quality both for tissue engineering and when monitoring clinical response to therapeutic interventions for cartilage degradation. We use results from multiexponential transverse relaxation analysis to predict equilibrium and dynamic stiffness of control and degraded bovine nasal cartilage, a biochemical model for articular cartilage. Sulfated glycosaminoglycan concentration/wet weight (ww) and equilibrium and dynamic stiffness decreased with degradation from 103.6 ± 37.0 µg/mg ww, 1.71 ± 1.10 MPa and 15.3 ± 6.7 MPa in controls to 8.25 ± 2.4 µg/mg ww, 0.015 ± 0.006 MPa and 0.89 ± 0.25MPa, respectively, in severely degraded explants. Magnetic resonance measurements were performed on cartilage explants at 4 °C in a 9.4 T wide-bore NMR spectrometer using a Carr-Purcell-Meiboom-Gill sequence. Multiexponential T2 analysis revealed four water compartments with T2 values of approximately 0.14, 3, 40 and 150 ms, with corresponding weight fractions of approximately 3, 2, 4 and 91%. Correlations between weight fractions and stiffness based on conventional univariate and multiple linear regressions exhibited a maximum r(2) of 0.65, while those based on support vector regression (SVR) had a maximum r(2) value of 0.90. These results indicate that (i) compartment weight fractions derived from multiexponential analysis reflect cartilage stiffness and (ii) SVR-based multivariate regression exhibits greatly improved accuracy in predicting mechanical properties as compared with conventional regression.
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http://dx.doi.org/10.1002/nbm.3083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608539PMC
April 2014

Stabilization of the inverse Laplace transform of multiexponential decay through introduction of a second dimension.

J Magn Reson 2013 Nov 24;236:134-9. Epub 2013 Jul 24.

Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

We propose a new approach to stabilizing the inverse Laplace transform of a multiexponential decay signal, a classically ill-posed problem, in the context of nuclear magnetic resonance relaxometry. The method is based on extension to a second, indirectly detected, dimension, that is, use of the established framework of two-dimensional relaxometry, followed by projection onto the desired axis. Numerical results for signals comprised of discrete T1 and T2 relaxation components and experiments performed on agarose gel phantoms are presented. We find markedly improved accuracy, and stability with respect to noise, as well as insensitivity to regularization in quantifying underlying relaxation components through use of the two-dimensional as compared to the one-dimensional inverse Laplace transform. This improvement is demonstrated separately for two different inversion algorithms, non-negative least squares and non-linear least squares, to indicate the generalizability of this approach. These results may have wide applicability in approaches to the Fredholm integral equation of the first kind.
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http://dx.doi.org/10.1016/j.jmr.2013.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818505PMC
November 2013

Single cell spectroscopy: noninvasive measures of small-scale structure and function.

Methods 2013 Dec 22;64(2):119-28. Epub 2013 Jul 22.

Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, United States.

The advancement of spectroscopy methods attained through increases in sensitivity, and often with the coupling of complementary techniques, has enabled real-time structure and function measurements of single cells. The purpose of this review is to illustrate, in light of advances, the strengths and the weaknesses of these methods. Included also is an assessment of the impact of the experimental setup and conditions of each method on cellular function and integrity. A particular emphasis is placed on noninvasive and nondestructive techniques for achieving single cell detection, including nuclear magnetic resonance, in addition to physical, optical, and vibrational methods.
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http://dx.doi.org/10.1016/j.ymeth.2013.07.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833896PMC
December 2013

Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity of the default mode network.

Neuroimage 2013 Jan 18;64:112-9. Epub 2012 Sep 18.

Clinical Research Branch, National Institute on Aging Intramural Research Program, 3001 S. Hanover St., Baltimore, MD 21225, USA.

The balance between excitatory glutamatergic projection neurons and inhibitory GABAergic interneurons determines the function of cortical microcircuits. How these neurotransmitters relate to the functional status of an entire macro-scale network remains unknown. The posteromedial cortex (PMC) is the default mode network (DMN) node with the greatest functional connectivity; therefore, we hypothesized that PMC glutamate and GABA predict intrinsic functional connectivity (iFC) across the entire DMN. In 20 healthy men, we combined J-resolved magnetic resonance spectroscopy to measure glutamate and GABA in the PMC and resting fMRI followed by group Independent Components Analysis to extract the entire DMN. We showed that, controlling for age and partial GM volume in the MRS voxel, PMC glutamate and GABA explained about half of the variance of DMN iFC (represented by the network's beta coefficient for rest). Glutamate correlated positively and GABA correlated negatively with DMN iFC; in an alternative statistical model which included the glutamate/GABA ratio, the ratio correlated positively with DMN iFC. Age had no independent association with DMN iFC. No other network was associated with PMC glutamate or GABA. We conclude that regional neurotransmitter concentrations in a network node strongly predict network but not global brain iFC.
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http://dx.doi.org/10.1016/j.neuroimage.2012.09.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3801193PMC
January 2013

Noninvasive high resolution mechanical strain maps of the spine intervertebral disc using nonrigid registration of magnetic resonance images.

J Biomech 2012 May 13;45(8):1534-9. Epub 2012 Apr 13.

Department of Mechanical and Aerospace Engineering, University of California Davis, CA, USA.

High resolution strain measurements are of particular interest in load bearing tissues such as the intervertebral disc (IVD), permitting characterization of biomechanical conditions which could lead to injury and degenerative outcomes. Magnetic resonance (MR) imaging produces excellent image contrast in cartilaginous tissues, allowing for image-based strain determination. Nonrigid registration (NRR) of MR images has previously demonstrated sub-voxel registration accuracy although its accuracy and precision in determining strain has not been evaluated. Accuracy and precision of NRR-derived strain measurements were evaluated using computer generated deformations applied to both computer generated images and MR images. Two different measures of registration similarity--the cost function which drives the registration algorithm--were compared: Mutual Information (MI) and Least Squares (LS). Strain error was evaluated with respect to signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and strain heterogeneity. Additionally, the creep strain response from an in vitro loaded porcine IVD is shown and comparisons between similarity measures are presented. MI showed a decrease in strain precision with increasing CNR and decreasing SNR while LS was insensitive to both. Both similarity measures showed a decrease in strain precision with increasing strain heterogeneity. When computer generated heterogeneous strains were applied to MR images of the IVD, LS showed substantially lower strain error in comparison to MI. Results suggest that LS-driven NRR provides a more accurate image-based method for mapping large and heterogeneous strain fields and this method can be applied to studies of the IVD and, potentially, other soft tissues which present sufficient image texture.
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http://dx.doi.org/10.1016/j.jbiomech.2012.03.005DOI Listing
May 2012