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Vanderbilt, United States

Elder C.P.,Institute of Imaging Science | Wilkens K.L.,Institute of Imaging Science | Chance M.A.,Institute of Imaging Science | Sanchez O.A.,Institute of Imaging Science | And 2 more authors.
Journal of Applied Physiology

Surface electromyography (EMG) can assess muscle recruitment patterns during cycling, but has limited applicability to studies of deep muscle recruitment and electrically stimulated contractions. We determined whether muscle recruitment timing could be inferred from MRI-measured transverse relaxation time constant (T2) changes and a cycle ergometer modified to vary power as a function of pedal angle. Six subjects performed 6 min of single-leg cycling under two conditions (E0°-230° and E90°-230°), which increased the power from 0°-230° and 90-230° of the pedal cycle, respectively. The difference condition produced a virtual power output from 0-180° (V0°-180°). Recruitment was assessed by integrating EMG over the pedal cycle (IEMG) and as the (post-pre) exercise T2 change (ΔT2). For E0°-230°, the mean IEMG for vastus medialis and lateralis (VM/VL; 49.3 ± 3.9 mV.s; mean ± SE) was greater (P < 0.05) than that for E90°-230° (17.9 ± 1.9 mV.s); the corresponding ΔT2 values were 8.7 ± 1.0 and 1.4 ± 0.5 ms (P < 0.05). For E0°-230° and E90°-230°, the IEMG values for biceps femoris/long head (BFL) were 37.7 ± 5.4 and 27.1 ± 5.6 mV.s (P > 0.05); the corresponding ΔT2 values were 0.9 ± 0.9 and 1.5 ± 0.9 ms (P > 0.05). MRI data indicated activation of the semitendinosus and BF/short head for E0°-230° and E90°-230°. For V0°-180°, ΔT2 was 7.2 ± 0.9 ms for VM/VL and -0.6 ± 0.6 ms for BFL; IEMG was 31.5 ± 3.7 mV.s for VM/VL and 10.6 ± 7.0 mV.s for BFL. MRI and EMG data indicate VM/VL activity from 0 to 180° and selected hamstring activity from 90 to 230°. Combining ΔT2 measurements with variable loading allows the spatial and temporal patterns of recruitment during cycling to be inferred from MRI data. Copyright © 2011 the American Physiological Society. Source

Kovtunov K.V.,Novosibirsk State University | Truong M.L.,Institute of Imaging Science | Barskiy D.A.,Novosibirsk State University | Salnikov O.G.,Novosibirsk State University | And 8 more authors.
Journal of Physical Chemistry C

Long-lived spin states of hyperpolarized propane-d6 gas were demonstrated following pairwise addition of parahydrogen gas to propene-d6 using heterogeneous parahydrogen-induced polarization (HET-PHIP). Hyperpolarized molecules were synthesized using Rh/TiO2 solid catalyst with 1.6 nm Rh nanoparticles. Hyperpolarized (PH ∼ 1%) propane-d6 was detected at high magnetic field (9.4 T) spectroscopically and by high-resolution 3D gradient-echo MRI (4.7 T) as the gas flowed through the radiofrequency coil with a spatial and temporal resolution of 0.5 × 0.5 × 0.5 mm3 and 17.7 s, respectively. Stopped-flow hyperpolarized propane-d6 gas was also detected at 0.0475 T with an observed nuclear spin polarization of PH ∼ 0.1% and a relatively long lifetime with T1,eff = 6.0 ± 0.3 s. Importantly, it was shown that the hyperpolarized protons of the deuterated product obtained via pairwise parahydrogen addition could be detected directly at low magnetic field. Importantly, the relatively long low-field T1,eff of HP propane-d6 gas is not susceptible to paramagnetic impurities as tested by exposure to ∼0.2 atm oxygen. This long lifetime and nontoxic nature of propane gas could be useful for bioimaging applications including potentially pulmonary low-field MRI. The feasibility of high-resolution low-field 2D gradient-echo MRI was demonstrated with 0.88 × 0.88 mm2 spatial and ∼0.7 s temporal resolution, respectively, at 0.0475 T. © 2014 American Chemical Society. Source

Sanchez O.A.,Institute of Imaging Science | Copenhaver E.A.,Institute of Imaging Science | Chance M.A.,Institute of Imaging Science | Fowler M.J.,Vanderbilt University | And 4 more authors.
American Journal of Physiology - Heart and Circulatory Physiology

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 (ΔSI6) and TE = 46 ms (ΔSI46), reflecting variations in blood volume and oxyhemoglobin saturation, respectively. Following 50% MVC contractions, the mean postcontraction ΔSI6 values were similar in the three groups. Following MVC only, and in the EDL muscle only, T2DM and obese participants had ~56% lower ΔSI6 than the lean individuals. Also following MVC only, the ΔSI46 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. © 2011 by the American Physiological Society. Source

Englund E.K.,Institute of Imaging Science | Elder C.P.,Institute of Imaging Science | Xu Q.,Institute of Imaging Science | Ding Z.,Institute of Imaging Science | And 3 more authors.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology

The purposes of this study were to create a three-dimensional representation of strain during isometric contraction in vivo and to interpret it with respect to the muscle fiber direction. Diffusion tensor MRI was used to measure the muscle fiber direction of the tibialis anterior (TA) muscle of seven healthy volunteers. Spatial-tagging MRI was used to measure linear strains in six directions during separate 50% maximal isometric contractions of the TA. The strain tensor (E) was computed in the TA's deep and superficial compartments and compared with the respective diffusion tensors. Diagonalization of E revealed a planar strain pattern, with one nonzero negative strain (j{cyrillic, ukrainian}N) and one nonzero positive strain (j{cyrillic, ukrainian}P); both strains were larger in magnitude (P < 0.05) in the deep compartment [j{cyrillic, ukrainian}N = -40.4 ± 4.3%, j{cyrillic, ukrainian}P = 35.1 ± 3.5% (means ± SE)] than in the superficial compartment (j{cyrillic, ukrainian}N = -24.3 ± 3.9%, j{cyrillic, ukrainian}P = 6.3 ± 4.9%). The principal shortening direction deviated from the fiber direction by 24.0 ± 1.3° and 39.8 ± 6.1° in the deep and superficial compartments, respectively (P < 0.05, deep vs. superficial). The deviation of the shortening direction from the fiber direction was due primarily to the lower angle of elevation of the shortening direction over the axial plane than that of the fiber direction. It is concluded that three-dimensional analyses of strain interpreted with respect to the fiber architecture are necessary to characterize skeletal muscle contraction in vivo. The deviation of the principal shortening direction from the fiber direction may relate to intramuscle variations in fiber length and pennation angle. © 2011 the American Physiological Society. Source

Walsh A.J.,Vanderbilt University | Cook R.S.,Institute of Imaging Science | Cook R.S.,Vanderbilt University | Manning H.C.,Vanderbilt University | And 5 more authors.
Cancer Research

Abnormal cellular metabolism is a hallmark of cancer, yet there is an absence of quantitative methods to dynamically image this powerful cellular function. Optical metabolic imaging (OMI) is a noninvasive, highresolution, quantitative tool for monitoring cellular metabolism. OMI probes the fluorescence intensities and lifetimes of the autofluorescent metabolic coenzymes reduced NADH and flavin adenine dinucleotide. We confirm that OMI correlates with cellular glycolytic levels across a panel of human breast cell lines using standard assays of cellular rates of glucose uptake and lactate secretion (P < 0.05, r = 0.89). In addition, OMI resolves differences in the basal metabolic activity of untransformed from malignant breast cells (P < 0.05) and between breast cancer subtypes (P< 0.05), defined by estrogen receptor and/or HER2 expression or absence. In vivo OMI is sensitive to metabolic changes induced by inhibition of HER2 with the antibody trastuzumab (herceptin) in HER2-overexpressing human breast cancer xenografts in mice. This response was confirmed with tumor growth curves and stains for Ki67 and cleaved caspase-3. OMI resolved trastuzumab-induced changes in cellular metabolism in vivo as early as 48 hours posttreatment (P < 0.05), whereas fluorodeoxyglucose-positron emission tomography did not resolve any changes with trastuzumab up to 12 days posttreatment (P > 0.05). In addition, OMI resolved cellular subpopulations of differing response in vivo that are critical for investigating drug resistance mechanisms. Importantly, OMI endpoints remained unchanged with trastuzumab treatment in trastuzumabresistant xenografts (P > 0.05). OMI has significant implications for rapid cellular-level assessment of metabolic response to molecular expression and drug action, which would greatly accelerate drug development studies. © 2013 AACR. Source

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