In JoVE (2)

Other Publications (16)

Articles by Theodore F. Towse in JoVE

 JoVE Medicine

Human Brown Adipose Tissue Depots Automatically Segmented by Positron Emission Tomography/Computed Tomography and Registered Magnetic Resonance Images

1Chemical and Physical Biology Program, Vanderbilt University, 2Department of Physical Medicine and Rehabilitation, Vanderbilt University School of Medicine, 3Radiology & Radiological Sciences, Vanderbilt University Medical Center, 4Department of Pharmacology, Vanderbilt University


JoVE 52415

 JoVE Medicine

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

1Institute of Imaging Science, Vanderbilt University, 2Department of Radiology and Radiological Sciences, Vanderbilt University, 3Department of Biomedical Engineering, Vanderbilt University, 4Department of Molecular Physiology and Biophysics, Vanderbilt University, 5Department of Physical Medicine and Rehabilitation, Vanderbilt University, 6Department of Physics and Astronomy, Vanderbilt University


JoVE 52352

Other articles by Theodore F. Towse on PubMed

BOLD MRI Mapping of Transient Hyperemia in Skeletal Muscle After Single Contractions

NMR in Biomedicine. Oct, 2004  |  Pubmed ID: 15468084

Transient increases in signal intensity (DeltaSI, peak 2.6 +/- 0.6 %, mean +/- SE, n = 14) were observed in axial, gradient-echo, echo-planar magnetic resonance images acquired at 1.5 T from human anterior tibialis muscle following single, 1 s duration, isometric ankle dorsiflexion contractions. The magnitude of the MRI-measured DeltaSI was not significantly different using TR of 2000 vs 500 ms, or using spin-echo vs gradient-echo echo-planar pulse sequences. However, DeltaSI measured by gradient-echo sequences was significantly greater at 3 vs 1.5 T (3.8 +/- 0.8 vs 1.6 +/- 0.2 %, n = 5). The time course of the transient DeltaSI (peak at 7.9 +/- 0.4 s after each contraction, decay with half-time of 4.6 +/- 0.6 s) was comparable to the time course of the transient increase in relative heme saturation (13 +/- 2 %, n = 5) measured after single contractions in another group of subjects by near-infrared spectroscopy (peak at 9.3 +/- 0.5 s, decay with half-time 6.2 +/- 0.8 s, n = 8). Simulations of intravascular and extravascular blood-oxygenation level-dependent (BOLD) effects in muscle suggested that intravascular BOLD makes a major contribution to the transient changes, although other factors such as increased vascular volume or increased muscle cell T2 may also contribute. The transients can be exploited for muscle functional imaging analogous to BOLD-based brain functional imaging, and might provide an index of peripheral vascular function.

Effect of Physical Activity on MRI-measured Blood Oxygen Level-dependent Transients in Skeletal Muscle After Brief Contractions

Journal of Applied Physiology (Bethesda, Md. : 1985). Aug, 2005  |  Pubmed ID: 15802369

The signal intensity (SI) in gradient-echo, echo-planar magnetic resonance images (repetition time/echo time = 1,000/40) of anterior tibialis muscle in active [estimated energy expenditure 42.4 +/- 3.7 (SD), n = 8] vs. sedentary (32.3 +/- 0.6 kcal.kg(-1).day(-1), n = 8) young adult (18-34 yr old) human subjects was measured after single, 1-s-duration maximum voluntary ankle dorsiflexion contractions. There was no difference between groups in anterior tibial muscle cross-sectional area or peak force. In both groups there was a transient increase in anterior tibialis muscle SI, which peaked 5-7 s after the end of each contraction. The magnitude of the SI transient was over threefold greater [5.5 +/- 1.0 (SE) vs. 1.5 +/- 0.4%] and persisted twice as long (half-recovery time 5.4 +/- 0.4 vs. 2.7 +/- 0.3 s) in the active subjects. In the same subjects, blood flow in popliteal, anterior tibial, and posterior tibial arteries was measured by cardiac-gated CINE magnetic resonance angiography before and after 2 min of dynamic, repetitive ankle dorsiflexion exercise. There was no difference between groups in resting or postexercise flow in anterior tibial artery, although popliteal and posterior tibial artery flow after exercise tended to be greater in the active group. The results indicate that transient hyperemia and oxygenation in muscle after single contractions are enhanced by chronic physical activity to a greater extent than peak muscle blood flow.

A Gated 31P NMR Method for the Estimation of Phosphocreatine Recovery Time and Contractile ATP Cost in Human Muscle

NMR in Biomedicine. Aug, 2006  |  Pubmed ID: 16642462

Muscle phosphocreatine (PCr) recovery time constant (an index of muscle aerobic capacity) and contractile ATP cost were estimated from a gated (31)P NMR protocol which does not require intense, repetitive exercise. Subjects performed 2-s duration, maximum voluntary isometric ankle dorsiflexion contractions at 30-s intervals for 8 min (total 15 contractions), while single-shot (31)P spectra (51.7 MHz, TR 3 s) were acquired from the anterior compartment muscle. Spectra from the sixth through 15th contractions were retrospectively sorted, yielding 10 spectra (each 10 averages) gated to times before and after contraction. There was no significant decrease in muscle pH, allowing the calculation of contractile ATP cost directly from the percentage change in PCr during contraction cycles [8.86 +/- 0.82% (SE, n = 11) of PCr at rest], corresponding to an ATP cost of 1.69 +/- 0.16 mM/s (range 0.99-2.49 mM/s), assuming an 8.2 mM ATP concentration. The time constant for PCr recovery (tau 41.8 +/- 4.2 s, range 22.0-60.8 s) was calculated from tau = -Deltat/ln[D/(D + Q)], where Q is the percentage change in PCr due to contraction, D is the additional steady-state percentage drop in PCr from rest and Deltat is the interval between contractions. In the same subjects, the monoexponential PCr recovery time constant after more intense, repetitive isometric ankle dorsiflexion exercise (30 s at 0.5 Hz, 50% duty cycle) was similar to (36.2 +/- 3.5 s, range 16.5-58.8 s) and well correlated with (r = 0.82) the gated result. In contrast to the gated protocol, muscle pH decreased from 7.01 +/- 0.01 to 6.78 +/- 0.04 during recovery after the repetitive protocol. Hence the gated protocol allows the estimation of muscle ATP cost and PCr recovery without intense exercise or muscle acidification.

Parallel Increases in Phosphocreatine and Total Creatine in Human Vastus Lateralis Muscle During Creatine Supplementation

International Journal of Sport Nutrition and Exercise Metabolism. Dec, 2007  |  Pubmed ID: 18156666

Short-term creatine supplementation is reported to result in a decreased ratio of phosphocreatine (PCr) to total creatine (TCr) in human skeletal muscle at rest. Assuming equilibrium of the creatine kinase reaction, this decrease in PCr:TCr implies increased cytoplasmic ADP and decreased Gibbs free energy of ATP hydrolysis in muscle, which seems contrary to the reported ergogenic benefits of creatine supplementation. This study measured changes in PCr and TCr in vastus lateralis muscle of adult men (N = 6, 21-35 y old) during and 1 day after 5 d of creatine monohydrate supplementation (0.43 g.kg body weight(-1).d(-1)) using noninvasive 31P and 1H magnetic-resonance spectroscopy (MRS). Plasma and red-blood-cell creatine increased by 10-fold and 2-fold, respectively, by the third day of supplementation. MRS-measured skeletal muscle PCr and TCr increased linearly and in parallel throughout the 5 d, and there was no significant difference in the percentage increase in muscle PCr (11.7% +/- 2.3% after 5 d) vs. TCr (14.9% +/- 4.1%) at any time point. The results indicate that creatine supplementation does not alter the PCr:TCr ratio, and hence the cytoplasmic Gibbs free energy of ATP hydrolysis, in human skeletal muscle at rest.

Contrasting Influences of Age and Sex on Muscle Fatigue

Medicine and Science in Sports and Exercise. Feb, 2008  |  Pubmed ID: 18202580

Greater resistance to muscle fatigue has been observed in women versus men and in older versus young individuals. As suggested mechanisms for these differences include task intensity and duty cycle, the purpose of this study was to evaluate fatigue in healthy young and older men and women during maximum-effort isometric contractions with a 70% duty cycle (7 s of contraction, 3 s of rest). We hypothesized that no differences in fatigue would be observed across age or sex, in contrast to studies incorporating lower duty cycles.

Phosphocreatine Recovery Kinetics Following Low- and High-intensity Exercise in Human Triceps Surae and Rat Posterior Hindlimb Muscles

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. Jan, 2009  |  Pubmed ID: 18945946

Previous studies have suggested the recovery of phosphocreatine (PCr) after exercise is at least second-order in some conditions. Possible explanations for higher-order PCr recovery kinetics include heterogeneity of oxidative capacity among skeletal muscle fibers and ATP production via glycolysis contributing to PCr resynthesis. Ten human subjects (28 +/- 3 yr; mean +/- SE) performed gated plantar flexion exercise bouts consisting of one contraction every 3 s for 90 s (low-intensity) and three contractions every 3 s for 30 s (high-intensity). In a parallel gated study, the sciatic nerve of 15 adult male Sprague-Dawley rats was electrically stimulated at 0.75 Hz for 5.7 min (low intensity) or 5 Hz for 2.1 min (high intensity) to produce isometric contractions of the posterior hindlimb muscles. [(31)P]-MRS was used to measure relative [PCr] changes, and nonnegative least-squares analysis was utilized to resolve the number and magnitude of exponential components of PCr recovery. Following low-intensity exercise, PCr recovered in a monoexponential pattern in humans, but a higher-order pattern was typically observed in rats. Following high-intensity exercise, higher-order PCr recovery kinetics were observed in both humans and rats with an initial fast component (tau < 15 s) resolved in the majority of humans (6/10) and rats (5/8). These findings suggest that heterogeneity of oxidative capacity among skeletal muscle fibers contributes to a higher-order pattern of PCr recovery in rat hindlimb muscles but not in human triceps surae muscles. In addition, the observation of a fast component following high-intensity exercise is consistent with the notion that glycolytic ATP production contributes to PCr resynthesis during the initial stage of recovery.

Quantitative Analysis of the Postcontractile Blood-oxygenation-level-dependent (BOLD) Effect in Skeletal Muscle

Journal of Applied Physiology (Bethesda, Md. : 1985). Jul, 2011  |  Pubmed ID: 21330621

Previous studies show that transient increases in both blood flow and magnetic resonance image signal intensity (SI) occur in human muscle after brief, single contractions, and that the SI increases are threefold larger in physically active compared with sedentary subjects. This study examined the relationship between these transient changes by measuring anterior tibial artery flow (Doppler ultrasound), anterior muscle SI (3T, one-shot echo-planar images, TR/TE = 1,000/35), and muscle blood volume and hemoglobin saturation [near-infrared spectroscopy (NIRS)] in the same subjects after 1-s-duration maximum isometric ankle dorsiflexion contractions. Arterial flow increased to a peak 5.9 ± 0.7-fold above rest (SE, n = 11, range 2.6-10.2) within 7 s and muscle SI increased to a peak 2.7 ± 0.6% (range 0.0-6.0%) above rest within 12 s after the contractions. The peak postcontractile SI change was significantly correlated with both peak postcontractile flow (r = 0.61, n = 11) and with subject activity level (r = 0.63, n = 10) estimated from 7-day accelerometer recordings. In a subset of 7 subjects in which NIRS data acquisition was successful, the peak magnitude of the postcontractile SI change agreed well with SI calculated from the NIRS blood volume and saturation changes (r = 0.80, slope = 1.02, intercept = 0.16), confirming the blood-oxygenation-level-dependent (BOLD) mechanism underlying the SI change. The magnitudes of postcontractile changes in blood saturation and SI were reproduced by a simple one-compartment muscle vascular model that incorporated the observed pattern of postcontractile flow, and which assumed muscle O(2) consumption peaks within 2 s after a brief contraction. The results show that muscle postcontractile BOLD SI changes depend critically on the balance between O(2) delivery and O(2) consumption, both of which can be altered by chronic physical activity.

Postmaximal Contraction Blood Volume Responses Are Blunted in Obese and Type 2 Diabetic Subjects in a Muscle-specific Manner

American Journal of Physiology. Heart and Circulatory Physiology. Aug, 2011  |  Pubmed ID: 21572006

The purpose of this study was to determine whether there are differences in postisometric contraction blood volume and oxygenation responses among groups of type 2 diabetes mellitus (T2DM), obese, and lean individuals detectable using MRI. Eight T2DM patients were individually matched by age, sex, and race to non-T2DM individuals with similar body mass index (obese) and lean subjects. Functional MRI was performed using a dual-gradient-recalled echo, echo-planar imaging sequence with a repetition time of 1 s and at two echo times (TE = 6 and 46 ms). Data were acquired before, during, and after 10-s isometric dorsiflexion contractions performed at 50 and 100% of maximal voluntary contraction (MVC) force. MRI signal intensity (SI) changes from the tibialis anterior and extensor digitorum longus muscles were plotted as functions of time for each TE. From each time course, the difference between the minimum and the maximum postcontraction SI (ΔSI) were determined for TE = 6 ms (ΔSI(6)) and TE = 46 ms (ΔSI(46)), reflecting variations in blood volume and oxyhemoglobin saturation, respectively. Following 50% MVC contractions, the mean postcontraction ΔSI(6) values were similar in the three groups. Following MVC only, and in the EDL muscle only, T2DM and obese participants had ∼56% lower ΔSI(6) than the lean individuals. Also following MVC only, the ΔSI(46) response in the EDL was lower in T2DM subjects than in lean individuals. These data suggest that skeletal muscle small vessel impairment occurs in T2DM and body mass index-matched subjects, in muscle-specific and contraction intensity-dependent manners.

Peripheral Microvascular Response to Muscle Contraction is Unaltered by Early Diabetes but Decreases with Age

Journal of Applied Physiology (Bethesda, Md. : 1985). Nov, 2011  |  Pubmed ID: 21799123

Long-term or untreated diabetes leads to micro- and macrovascular complications. However, there are few tests to evaluate microvascular function. A postcontraction blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) technique was exploited to measure peripheral microvascular function in diabetics and healthy controls matched with respect to age, body mass index, and physical activity. Postcontraction BOLD microvascular response was measured following 1-s maximal isometric ankle dorsiflexion in individuals with diabetes mellitus type I [DMI, n = 15, age 33 ± 3 yr (means ± SE), median diabetes duration = 5.5 yr] and type II (DMII, n = 16, age 45 ± 2 yr, median duration = 2.4 yr); responses were compared with controls (CONI and CONII). Peripheral macrovascular function of the popliteal and tibial arteries was assessed during exercise hyperemia with phase contrast magnetic resonance angiography following repetitive exercise. There were no group differences as a result of diabetes in peripheral microvascular function (peak BOLD response: DMI = 2.04 ± 0.38% vs. CONI = 2.08 ± 0.48%; DMII = 0.93 ± 0.24% vs. CONII = 1.13 ± 0.24%; mean ± SE), but the BOLD response was significantly influenced by age (partial r = -0.384, P = 0.003), supporting its sensitivity as a measure of microvascular function. Eleven individuals had no microvascular BOLD response, including three diabetics with neuropathy and four controls with a family history of diabetes. There were no differences in peripheral macrovascular function between groups when assessing exercise hyperemia or the pulsitility and resistive indexes. Although the BOLD microvascular response was not impaired in early diabetes, these results encourage further investigation of muscle BOLD as it relates to peripheral microvascular health.

Multi-parametric MRI Characterization of Healthy Human Thigh Muscles at 3.0 T - Relaxation, Magnetization Transfer, Fat/water, and Diffusion Tensor Imaging

NMR in Biomedicine. Sep, 2014  |  Pubmed ID: 25066274

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo-pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin-echo T2 imaging (with and without fat signal suppression, FS), selective inversion recovery for T1 and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re-imaged an average of 35 days later. Pre-testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between-day intra-class correlations were observed in all quantitative indices except for the macromolecular-to-free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two-way analysis of variance revealed no significant between-day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland-Altman plots, and low repeatability coefficients were obtained for all parameters. Among-muscle differences in the quantitative MRI indices and inter-class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T1 , T2 , fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters.

Anisotropic Smoothing Improves DT-MRI-Based Muscle Fiber Tractography

PloS One. 2015  |  Pubmed ID: 26010830

To assess the effect of anisotropic smoothing on fiber tracking measures, including pennation angle, fiber tract length, and fiber tract number in the medial gastrocnemius (MG) muscle in healthy subjects using diffusion-weighted magnetic resonance imaging (DW-MRI).

Correlations Between Quantitative Fat-water Magnetic Resonance Imaging and Computed Tomography in Human Subcutaneous White Adipose Tissue

Journal of Medical Imaging (Bellingham, Wash.). Oct, 2015  |  Pubmed ID: 26702407

Beyond estimation of depot volumes, quantitative analysis of adipose tissue properties could improve understanding of how adipose tissue correlates with metabolic risk factors. We investigated whether the fat signal fraction (FSF) derived from quantitative fat-water magnetic resonance imaging (MRI) scans at 3.0 T correlates to CT Hounsfield units (HU) of the same tissue. These measures were acquired in the subcutaneous white adipose tissue (WAT) at the umbilical level of 21 healthy adult subjects. A moderate correlation exists between MRI- and CT-derived WAT values for all subjects, [Formula: see text], [Formula: see text], with a slope of [Formula: see text], (95% CI [Formula: see text]), indicating that a decrease of 1 HU equals a mean increase of 0.38% FSF. We demonstrate that FSF estimates obtained using quantitative fat-water MRI techniques correlate with CT HU values in subcutaneous WAT, and therefore, MRI-based FSF could be used as an alternative to CT HU for assessing metabolic risk factors.

Comparison of Muscle BOLD Responses to Arterial Occlusion at 3 and 7 Tesla

Magnetic Resonance in Medicine. Mar, 2016  |  Pubmed ID: 25884888

The purpose of this study was to determine the feasibility of muscle BOLD (mBOLD) imaging at 7 Tesla (T) by comparing the changes in R2* of muscle at 3 and 7T in response to a brief period of tourniquet-induced ischemia.

Characterizing Active and Inactive Brown Adipose Tissue in Adult Humans Using PET-CT and MR Imaging

American Journal of Physiology. Endocrinology and Metabolism. Jul, 2016  |  Pubmed ID: 27166284

Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means ± SD; 60.2 ± 7.6 vs. 62.4 ± 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 ± 11.5 vs. -74.5 ± 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.

FloWave.US: Validated, Open-source, and Flexible Software for Ultrasound Blood Flow Analysis

Journal of Applied Physiology (Bethesda, Md. : 1985). Oct, 2016  |  Pubmed ID: 27516540

Automated software improves the accuracy and reliability of blood velocity, vessel diameter, blood flow, and shear rate ultrasound measurements, but existing software offers limited flexibility to customize and validate analyses. We developed FloWave.US-open-source software to automate ultrasound blood flow analysis-and demonstrated the validity of its blood velocity (aggregate relative error, 4.32%) and vessel diameter (0.31%) measures with a skeletal muscle ultrasound flow phantom. Compared with a commercial, manual analysis software program, FloWave.US produced equivalent in vivo cardiac cycle time-averaged mean (TAMean) velocities at rest and following a 10-s muscle contraction (mean bias <1 pixel for both conditions). Automated analysis of ultrasound blood flow data was 9.8 times faster than the manual method. Finally, a case study of a lower extremity muscle contraction experiment highlighted the ability of FloWave.US to measure small fluctuations in TAMean velocity, vessel diameter, and mean blood flow at specific time points in the cardiac cycle. In summary, the collective features of our newly designed software-accuracy, reliability, reduced processing time, cost-effectiveness, and flexibility-offer advantages over existing proprietary options. Further, public distribution of FloWave.US allows researchers to easily access and customize code to adapt ultrasound blood flow analysis to a variety of vascular physiology applications.

Post-contractile BOLD Contrast in Skeletal Muscle at 7 T Reveals Inter-individual Heterogeneity in the Physiological Responses to Muscle Contraction

NMR in Biomedicine. Dec, 2016  |  Pubmed ID: 27753155

Muscle blood oxygenation-level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre-contraction signal intensity were observed in the soleus muscle. We observed considerable inter-subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (TR : 1000 and 2500 ms) to determine the potential of T1 -related inflow effects on the magnitude of the post-contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two TR values (3.8 ± 0.9 versus 4.0 ± 0.6% for TR  = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post-contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction.

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