Ultrahigh-b diffusion-weighted imaging for quantitative evaluation of myelination in shiverer mouse spinal cord.

PURPOSE: To perform a quantitative evaluation of myelination on WT and myelin-deficient (shiverer) mouse spinal cords using ultrahigh-b diffusion-weighted imaging (UHb-DWI). METHODS: UHb-DWI of ex vivo on spinal cord specimens of two shiverer (C3HeB/FeJ-shiverer, homozygous genotype for MbPshi ) and six WT (Black Six, C3HeB/FeJ) mice were acquired using 3D multishot diffusion-weighted stimulated-echo EPI, a homemade RF coil, and a small-bore 7T MRI system. Imaging was performed in transaxial plane with 75 × 75 µm2 in-plane resolution, 1-mm-slice thickness, and radial DWI using bmax = 42,890 s/mm2 . Histological evaluation was performed on upper thoracic sections using optical and transmission electron microscopy. Numerical Monte Carlo simulations (MCSs) of water diffusion were performed to facilitate interpretation of UHb-DWI signal-b curves. RESULTS: The white matter ultrahigh-b radial DWI (UHb-rDWI) signal-b curves of WT mouse cords behaved biexponentially with high-b diffusion coefficient DH < 0.020 × 10-3 mm2 /s. However, as expected with less myelination, the signal-b of shiverer mouse cords behaved monoexponentially with significantly greater DH = 0.162 × 10-3 , 0.142 × 10-3 , and 0.164 × 10-3 mm2 /s at anterodorsal, posterodorsal, and lateral columns, respectively. The axial DWI signals of all mouse cords behaved monoexponentially with D = (0.718-1.124) × 10-3 mm2 /s. MCS suggests that these elevated DH are mainly induced by increased water exchange at the myelin sheath. Microscopic results were consistent with the UHb-rDWI findings. CONCLUSION: UHb-DWI provides quantitative differences in myelination of spinal cords from myelin-deficit shiverer and WT mice. UHb-DWI may become a powerful tool to evaluate myelination in demyelinating disease models that may translate to human diseases, including multiple sclerosis.

Skeletal Muscle Mitochondrial Adaptations to Maximal Strength Training in Older Adults.

Maximal strength training (MST) results in robust improvements in skeletal muscle force production, efficiency, and mass. However, the effects of MST on muscle mitochondria are still unknown. Accordingly, the purpose of this study was to examine, from the molecular level to whole-muscle, mitochondrial adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older adults using immunoblotting, spectrophotometry, high-resolution respirometry in permeabilized muscle fibers, in vivo 31P magnetic resonance spectroscopy (31P-MRS), and gas exchange. As anticipated, MST resulted in an increased isometric knee-extensor force from 133 ± 36 to 147 ± 49 Nm (p < .05) and quadriceps muscle volume from 1,410 ± 103 to 1,555 ± 455 cm3 (p < .05). Mitochondrial complex (I-V) protein abundance and citrate synthase activity were not significantly altered by MST. Assessed ex vivo, maximal ADP-stimulated respiration (state 3CI+CII, PRE: 23 ± 6 and POST: 14 ± 5 ρM·mg-1·s-1, p < .05), was decreased by MST, predominantly, as a result of a decline in complex I-linked respiration (p < .05). Additionally, state 3 free-fatty acid linked respiration was decreased following MST (PRE: 19 ± 5 and POST: 14 ± 3 ρM·mg-1·s-1, p < .05). Assessed in vivo, MST slowed the PCr recovery time constant (PRE: 49 ± 13 and POST: 57 ± 16 seconds, p < .05) and lowered, by ~20% (p = .055), the quadriceps peak rate of oxidative ATP synthesis, but did not significantly alter the oxidation of lipid. Although these, likely qualitative, mitochondrial adaptations are potentially negative in terms of skeletal muscle energetic capacity, they need to be considered in light of the many improvements in muscle function that MST affords older adults.

Diffusion MRI using two-dimensional single-shot radial imaging (2D ss-rDWI) with variable flip angle and random view ordering.

PURPOSE: The main objective of this study is to develop a 2D single-shot radial-DWI (2D ss-rDWI) technique to reduce motion artifacts and geometric distortion in DW images. METHOD: A diffusion-preparation module is developed and applied prior to the data acquisition. Because the diffusion-prepared longitudinal magnetization is measured over multiple RF excitations in each shot, 2D ss-rDWI is subject to low signal-to-noise ratio (SNR). We used variable-flip angle (VFA), random view ordering (RVO), and sliding spokes, and compared the performances to constant flip angle (CFA), smooth view ordering (SVO), and identical spoke averaging, respectively. For each technique, we performed numerical simulation and MRI experiments on a fluid phantom as well as in-vivo human brain studies with a 3 T MRI system. RESULTS: Using VFA, optimal SNR was acquired for 2D ss-rDWI. Using SVO, the high signal is clustered at specific quadrant in 2D k-space: the first quadrant using high initial flip angle or the last quadrant using the low flip angle. This clustered signal in k-space led to geometric distortion in image space. 2D ss-rDWI using RVO spreads the high signaled spokes over all angular directions and removes the view-order-related distortion. The in-vivo images using 2D ss-rDWI with VFA and RVO show no geometric distortion at the skull base brain, but greatly reduced SNR compared with those using 2D ss-DWEPI. CONCLUSION: 2D ss-rDWI is optimized by using VFA with RVO. The resultant DWI using 2D ss-rDWI is insensitive to motion-induced artifacts and geometric distortion. Even with low SNR, it may be useful for DWI of organs limited by severe susceptibility-induced geometric distortion.

Continuous prospectively navigated multi-echo GRE for improved BOLD imaging of the kidneys.

The objective of this study is to develop improved methods for renal blood oxygenation level dependent (BOLD) imaging. T2* mapping of the kidneys, or renal BOLD imaging, may depict renal oxygen levels and may be valuable as a noninvasive means of following the progression of renal disease. Current renal BOLD data is limited by imaging in a single breath hold, which results in low resolution and low signal-to-noise ratio (SNR). We compare a new free-breathing renal BOLD method with conventional breath-hold BOLD (BH-BOLD). A multi-echo GRE sequence with continuous prospective respiratory navigation and real-time feedback was developed that allows high resolution and high SNR renal BOLD imaging with constant sequence repetition time (TR) during free-breathing BOLD (FB-BOLD). The sequence was evaluated in 10 normal volunteers and compared with conventional BH-BOLD. Scan time for the FB-BOLD sequence was approximately three minutes, compared with 15 seconds for the BH-BOLD sequence. SNR of source images and residual error of T2* fitting were compared between the two methods. The FB-BOLD sequence produced motion-free T2* maps of the kidneys with SNR 1.9 times higher than BH-BOLD images. Residual error of T2* fitting was consistently lower in the right kidney with FB-BOLD (30% less than BH-BOLD) but higher in the left kidney (80% more than BH-BOLD), likely related to placement of the navigator on the right hemidiaphragm. A free-breathing prospectively navigated renal BOLD sequence allows flexible tradeoff between scan time, resolution, and SNR.

Ultra-high-b radial diffusion-weighted imaging (UHb-rDWI) of human cervical spinal cord.

BACKGROUND: Injury in the cervical spinal cord (CSC) can lead to varying degrees of neurologic deficit and persistent disability. Diffusion tensor imaging (DTI) is a promising method to evaluate white matter integrity and pathology. However, the conventional DTI results are limited with respect to the specific details of neuropathology and microstructural architecture. In this study we used ultrahigh-b radial-DWI (UHb-rDWI) with b-values ranging from 0 to ∼7500 s/mm2 and calculated decay constant (DH ) at the high b-values, which gives much deeper insight about the microscopic environment of CSC white matter. PURPOSE: To evaluate a novel diffusion MRI, UHb-rDWI technique for imaging of the CSC. STUDY TYPE: Longitudinal. SUBJECTS: Four healthy controls, each scanned twice. FIELD STRENGTH/SEQUENCE: 3T/2D single shot diffusion-weighted stimulated echo planar imaging with reduced field of view. ASSESSMENT: The signal from each pixel of b0 (b = 0) and b-value (b ≠ 0) images were fitted to a biexponential function and normalized. The signal-b curve is obtained by dividing the latter curve by the former. DH was obtained from the curve at b >4000 s/mm2 . A Monte-Carlo Simulation (MCS) was performed to investigate how DH changes upon the increased water-exchange at the CSC. RESULTS: The signal-b curves plotted at multiple levels of healthy CSC are almost identical on two successive scans and show a biexponential decay behavior: fast exponential decay at lower b-values and much slower decay at UHb-values. The mean values of DH were measured as (0.0607 ± 0.02531) ×10-3 and (0.0357 ± 0.02072) ×10-3 s/mm2 at the lateral funiculus and posterior column, respectively. MCS of diffusion MRI shows that the DH is elevated by increased water exchange between the intra- and extraaxonal spaces. DATA CONCLUSION: UHb-rDWI signal-b plots of the normal CSC were highly reproducible on successive scans and their biexponential decay behavior can be used to characterize normal spinal white matter. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:204-211.

Study of kinetics of 19F-MRI using a fluorinated imaging agent (19FIT) on a 3T clinical MRI system.

PURPOSE: To use 19F imaging tracer (19FIT-27) to evaluate kinetics in major organs. INTRODUCTION: Kinetics studies using proton MRI are difficult because of low concentration of 19FIT-27 protons relative to background water protons. Because there is no background source of 19F NMR in a biological body, 19F may be an ideal nucleus to directly trace 19FIT-27. However, there are several challenges for reliable 19F MR imaging and spectroscopy, particularly with clinical whole-body MRI systems, which include low concentrations and long 19F T1. METHODS AND MATERIALS: We performed a dynamic 19F MRI study on mice at a 3T whole-body MRI system using a homemade transmit/receive (Tx/Rx) switch and a Tx/Rx volume RF coil. We used a newly developed fluorine imaging agent, which has 27 identical fluorine atoms with identical chemical shift, a relatively short T1, and high hydrophilicity. Basic kinetics parameters were estimated from the 19F signal-time curve. RESULTS AND DISCUSSIONS: Resultant fluorine images show fairly high spatial (3 × 3 × 3 mm3) and temporal resolutions. Biodistribution and kinetics of 19FIT-27 are obtained via 19F images for major uptake organs. CONCLUSIONS: Whole-body dynamic 19F MRI of newly developed 19FIT-27 in mice was obtained with fairly high spatial and temporal resolutions on a 3T clinical MRI system. The present study demonstrates the feasibility of 19F MRI using our newly developed compound to investigate major organ kinetics.

Maximal strength training increases muscle force generating capacity and the anaerobic ATP synthesis flux without altering the cost of contraction in elderly.

Aging is associated with a progressive decline in skeletal muscle function, then leading to impaired exercise tolerance. Maximal strength training (MST) appears to be a practical and effective intervention to increase both exercise capacity and efficiency. However, the underlying physiological mechanisms responsible for these functional improvements are still unclear. Accordingly, the purpose of this study was to examine the intramuscular and metabolic adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older individuals (75 ±â€¯9 yrs) by employing a combination of molecular, magnetic resonance 1H-imaging and 31P-spectroscopy, muscle biopsies, motor nerve stimulation, and indirect calorimetry techniques. Dynamic and isometric muscle strength were both significantly increased by MST. The greater torque-time integral during sustained isometric maximal contraction post-MST (P = 0.002) was associated with increased rates of ATP synthesis from anaerobic glycolysis (PRE: 10 ±â€¯7 mM·min-1; POST: 14 ±â€¯7 mM·min-1, P = 0.02) and creatine kinase reaction (PRE: 31 ±â€¯10 mM·min-1; POST: 41 ±â€¯10 mM·min-1, P = 0.006) such that the ATP cost of contraction was not significantly altered. Expression of fast myosin heavy chain, quadriceps muscle volume, and submaximal cycling net efficiency were also increased with MST (P = 0.005; P = 0.03 and P = 0.03, respectively). Overall, MST induced a shift toward a more glycolytic muscle phenotype allowing for greater muscle force production during sustained maximal contraction. Consequently, some of the MST-induced improvements in exercise tolerance might stem from a greater anaerobic capacity to generate ATP, while the improvement in exercise efficiency appears to be independent from an alteration in the ATP cost of contraction.

Impaired Muscle Efficiency but Preserved Peripheral Hemodynamics and Mitochondrial Function With Advancing Age: Evidence From Exercise in the Young, Old, and Oldest-Old.

Muscle weakness in the elderly has been linked to recurrent falls and morbidity; therefore, elucidating the mechanisms contributing to the loss of muscle function and mobility with advancing age is critical. To this aim, we comprehensively examined skeletal muscle metabolic function and hemodynamics in 11 young (23 ± 2 years), 11 old (68 ± 2 years), and 10 oldest-old (84 ± 2 years) physical activity-matched participants. Specifically, oxidative stress markers, mitochondrial function, and the ATP cost of contraction as well as peripheral hemodynamics were assessed during dynamic plantar flexion exercise at 40 per cent of maximal work rate (WRmax). Both the PCr recovery time constant and the peak rate of mitochondrial ATP synthesis were not significantly different between groups. In contrast, the ATP cost of dynamic contractions (young: 1.5 ± 1.0, old: 3.4 ± 2.1, oldest-old: 6.1 ± 3.6 mM min-1 W-1) and systemic markers of oxidative stress were signficantly increased with age, with the ATP cost of contraction being negatively correlated with WRmax (r = .59, p < .05). End-of-exercise blood flow per Watt rose significantly with increasing age (young: 37 ± 20, old: 82 ± 68, oldest-old: 154 ± 93 mL min-1 W-1). These findings suggest that the progressive deterioration of muscle contractile efficiency with advancing age may play an important role in the decline in skeletal muscle functional capacity in the elderly.

Characterizing Intraorbital Optic Nerve Changes on Diffusion Tensor Imaging in Thyroid Eye Disease Before Dysthyroid Optic Neuropathy.

OBJECTIVE: The aim of this study was to determine whether the optic nerve is affected by thyroid eye disease (TED) before the development of dysthyroid optic neuropathy with diffusion-tensor imaging (DTI). METHODS: Twenty TED patients and 20 controls were included. The mean, axial, and radial diffusivities and fractional anisotropy (FA) value were measured at the optic nerves in DTI. Extraocular muscle diameters were measured on computed tomography. The diffusivities and FA of the optic nerves were compared between TED and controls and between active and inactive stages of TED. The correlations between these DTI parameters and the clinical features were determined. RESULTS: The mean, axial, and radial diffusivities were lower in TED compared with the controls (P < 0.05). In contrast, FA was higher in TED (P = 0.001). Radial diffusivity was lower in the active stage of TED than the inactive stage (P = 0.035). The FA was higher in the TED group than in the control group (P = 0.021) and was positively correlated with clinical activity score (r = 0.364, P = 0.021), modified NOSPECS score (r = 0.469, P = 0.002), and extraocular muscle thickness (r = 0.325, P = 0.041) in the TED group. Radial diffusivity was negatively correlated with modified NOSPECS score (r = -0.384, P = 0.014), and axial diffusivity was positively correlated with exophthalmos degree (r = 0.363, P = 0.025). CONCLUSIONS: The diffusivities and FA reflected changes in the optic nerve before dysthyroid optic neuropathy in TED. The FA, in particular, reflected TED activity and severity.

Oxygen delivery and the restoration of the muscle energetic balance following exercise: implications for delayed muscle recovery in patients with COPD.

Patients with chronic obstructive pulmonary disease (COPD) experience a delayed recovery from skeletal muscle fatigue following exhaustive exercise that likely contributes to their progressive loss of mobility. As this phenomenon is not well understood, this study sought to examine postexercise peripheral oxygen (O2) transport and muscle metabolism dynamics in patients with COPD, two important determinants of muscle recovery. Twenty-four subjects, 12 nonhypoxemic patients with COPD and 12 healthy subjects with a sedentary lifestyle, performed dynamic plantar flexion exercise at 40% of the maximal work rate (WRmax) with phosphorus magnetic resonance spectroscopy (31P-MRS), near-infrared spectroscopy (NIRS), and vascular Doppler ultrasound assessments. The mean response time of limb blood flow at the offset of exercise was significantly prolonged in patients with COPD (controls: 56 ± 27 s; COPD: 120 ± 87 s; P < 0.05). In contrast, the postexercise time constant for capillary blood flow was not significantly different between groups (controls: 49 ± 23 s; COPD: 51 ± 21 s; P > 0.05). The initial postexercise convective O2 delivery (controls: 0.15 ± 0.06 l/min; COPD: 0.15 ± 0.06 l/min) and the corresponding oxidative adenosine triphosphate (ATP) demand (controls: 14 ± 6 mM/min; COPD: 14 ± 6 mM/min) in the calf were not significantly different between controls and patients with COPD (P > 0.05). The phosphocreatine resynthesis time constant (controls: 46 ± 20 s; COPD: 49 ± 21 s), peak mitochondrial phosphorylation rate, and initial proton efflux were also not significantly different between groups (P > 0.05). Therefore, despite perturbed peripheral hemodynamics, intracellular O2 availability, proton efflux, and aerobic metabolism recovery in the skeletal muscle of nonhypoxemic patients with COPD are preserved following plantar flexion exercise and thus are unlikely to contribute to the delayed recovery from exercise in this population.

Two-dimensional single-shot diffusion-weighted stimulated EPI with reduced FOV for ultrahigh-b radial diffusion-weighted imaging of spinal cord.

PURPOSE: High-resolution diffusion-weighted imaging (DWI) of the spinal cord (SC) is problematic because of the small cross-section of the SC and the large field inhomogeneity. Obtaining the ultrahigh-b DWI poses a further challenge. The purpose of the study was to design and validate two-dimensional (2D) single-shot diffusion-weighted stimulated echo planar imaging with reduced field of view (2D ss-DWSTEPI-rFOV) for ultrahigh-b radial DWI (UHB-rDWI) of the SC. METHODS: A novel time-efficient 2D ss-DWSTEPI-rFOV sequence was developed based on the stimulated echo sequence. Reduced-phase field of view was obtained by using two slice-selective 90 ° radiofrequency pulses in the presence of the orthogonal slice selection gradients. The sequence was validated on a cylindrical phantom and demonstrated on SC imaging. RESULTS: Ultrahigh-b radial diffusion-weighted ( bmax = 7300 s/mm2) images of the SC with greatly reduced distortion were obtained. The exponential plus constant fitting of the diffusion-decay curve estimated the constant fraction (restricted water fraction) as 0.36 ± 0.05 in the SC white matter. CONCLUSION: A novel 2D ss-DWSTEPI-rFOV sequence has been designed and demonstrated for high-resolution UHB-rDWI of localized anatomic structures with significantly reduced distortion induced by nonlinear static field inhomogeneity. Magn Reson Med 77:2167-2173, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Fractional anisotropy and diffusivity changes in thyroid-associated orbitopathy.

INTRODUCTION: To investigate the extraocular muscle (EOM) changes in thyroid-associated orbitopathy (TAO) on DTI and the correlations between DTI parameters and clinical features. METHODS: Twenty TAO patients and 20 age- and sex-matched controls provided informed consent and were enrolled. Ten-directional DTI was acquired in orbit. Fractional anisotropy (FA), mean, axial, and radial diffusivities were obtained at medial and lateral EOMs in both orbits. EOM thickness was measured in patients using axial CT images. FA and diffusivities were compared between patients and controls. The relationships between DTI values and muscle thickness and exophthalmos were evaluated. DTI values compared between patients in active and inactive phases by clinical activity score of TAO. DTI values were also compared between acute and chronic stages by the duration of disease. RESULTS: In medial EOM, FA was significantly lower in patients (p < 0.001) and negatively correlated with muscle thickness (r = -0.604, p < 0.001). Radial diffusivity was significantly higher in patients (p = 0.010) and correlated with muscle thickness (r = 0.349, p = 0.027). In lateral EOM, DTI values did not differ between patients and controls. In the acute stage, the diffusivities of the medial rectus EOM were increased compared with the chronic stage. DTI values of the medial and lateral rectus EOM did not differ significantly between active and inactive phases. CONCLUSION: DTI can be used to diagnose TAO with FA and radial diffusivity change in EOM. Diffusivities can be used to differentiate acute and chronic stage of TAO. However, DTI values showed limitation in reflecting TAO activity according to the CAS.

Evidence of a metabolic reserve in the skeletal muscle of elderly people.

The purpose of the present study was to determine whether mitochondrial function is limited by O2 availability or the intrinsic capacity of mitochondria to synthesize ATP in elderly individuals. To this aim, we examined, in comparison to free-flow conditions (FF), the effect of superimposing reactive hyperemia (RH), induced by a period of brief ischemia during the last min of exercise, on O2 availability and mitochondrial function in the calf muscle. 12 healthy, untrained, elderly subjects performed dynamic plantar flexion exercise and phosphorus magnetic resonance spectroscopy (31P-MRS), near-infrared spectroscopy (NIRS), and Doppler ultrasound were used to assess muscle metabolism and peripheral hemodynamics. Limb blood flow [area under the curve (AUC), FF: 1.5±0.5L; RH: 3.2±1.1L, P<0.01] and convective O2 delivery (AUC, FF: 0.30±0.13L; RH: 0.64±0.29L, P<0.01) were significantly increased in RH in comparison to FF. RH was also associated with significantly higher capillary blood flow (P<0.05) and this resulted in a 33% increase in estimated peak mitochondrial ATP synthesis rate (FF: 24±11 mM.min-1; RH: 31±7 mM.min-1, P<0.05). These results document a hemodynamic reserve in the contracting calf muscle of the elderly accessible by superimposing reactive hyperemia. Furthermore, this increase in O2 availability enhanced mitochondrial function thus indicating a skeletal muscle metabolic reserve despite advancing age and low level of physical activity.

Characterization of spinal cord white matter by suppressing signal from hindered space. A Monte Carlo simulation and an ex vivo ultrahigh-b diffusion-weighted imaging study.

Signal measured from white matter in diffusion-weighted imaging is difficult to interpret because of the heterogeneous structure of white matter. Characterization of the white matter will be straightforward if the signal contributed from the hindered space is suppressed and purely restricted signal is analyzed. In this study, a Monte Carlo simulation (MCS) of water diffusion in white matter was performed to understand the behavior of the diffusion-weighted signal in white matter. The signal originating from the hindered space of an excised pig cervical spinal cord white matter was suppressed using the ultrahigh-b radial diffusion-weighted imaging. A light microscopy image of a section of white matter was obtained from the excised pig cervical spinal cord for the MCS. The radial diffusion-weighted signals originating from each of the intra-axonal, extra-axonal, and total spaces were studied using the MCS. The MCS predicted that the radial diffusion-weighted signal remains almost constant in the intra-axonal space and decreases gradually to about 2% of its initial value in the extra-axonal space when the b-value is increased to 30,000s/mm2. The MCS also revealed that the diffusion-weighted signal for a b-value greater than 20,000s/mm2 is mostly from the intra-axonal space. The decaying behavior of the signal-b curve obtained from ultrahigh-b diffusion-weighted imaging (bmax∼30,000s/mm2) of the excised pig cord was very similar to the decaying behavior of the total signal-b curve synthesized in the MCS. A mono-exponential plus constant fitting of the signal-b curve obtained from a white matter pixel estimated the values of constant fraction and apparent diffusion coefficient of decaying fraction as 0.32±0.05 and (0.16±0.01)×10-3mm2/s, respectively, which agreed well with the results of the MCS. The signal measured in the ultrahigh-b region (b>20,000s/mm2) is mostly from the restricted (intra-axonal) space. Integrity and intactness of the axons can be evaluated by assessing the remaining signal in the ultrahigh-b region.

Accuracy and precision of quantitative 31P-MRS measurements of human skeletal muscle mitochondrial function.

Although theoretically sound, the accuracy and precision of (31)P-magnetic resonance spectroscopy ((31)P-MRS) approaches to quantitatively estimate mitochondrial capacity are not well documented. Therefore, employing four differing models of respiratory control [linear, kinetic, and multipoint adenosine diphosphate (ADP) and phosphorylation potential], this study sought to determine the accuracy and precision of (31)P-MRS assessments of peak mitochondrial adenosine-triphosphate (ATP) synthesis rate utilizing directly measured peak respiration (State 3) in permeabilized skeletal muscle fibers. In 23 subjects of different fitness levels, (31)P-MRS during a 24-s maximal isometric knee extension and high-resolution respirometry in muscle fibers from the vastus lateralis was performed. Although significantly correlated with State 3 respiration (r = 0.72), both the linear (45 ± 13 mM/min) and phosphorylation potential (47 ± 16 mM/min) models grossly overestimated the calculated in vitro peak ATP synthesis rate (P < 0.05). Of the ADP models, the kinetic model was well correlated with State 3 respiration (r = 0.72, P < 0.05), but moderately overestimated ATP synthesis rate (P < 0.05), while the multipoint model, although being somewhat less well correlated with State 3 respiration (r = 0.55, P < 0.05), most accurately reflected peak ATP synthesis rate. Of note, the PCr recovery time constant (τ), a qualitative index of mitochondrial capacity, exhibited the strongest correlation with State 3 respiration (r = 0.80, P < 0.05). Therefore, this study reveals that each of the (31)P-MRS data analyses, including PCr τ, exhibit precision in terms of mitochondrial capacity. As only the multipoint ADP model did not overstimate the peak skeletal muscle mitochondrial ATP synthesis, the multipoint ADP model is the only quantitative approach to exhibit both accuracy and precision.

Synchronous Radial 1H and 23Na Dual-Nuclear MRI on a Clinical MRI System, Equipped With a Broadband Transmit Channel.

The purpose of this work was to synchronously acquire proton (1H) and sodium (23Na) image data on a 3T clinical MRI system within the same sequence, without internal modification of the clinical hardware, and to demonstrate synchronous acquisition with 1H/23Na-GRE imaging with Cartesian and radial k-space sampling. Synchronous dual-nuclear imaging was implemented by: mixing down the 1H signal so that both the 23Na and 1H signal were acquired at 23Na frequency by the conventional MRI system; interleaving 1H/23Na transmit pulses in both Cartesian and radial sequences; and using phase stabilization on the 1H signal to remove mixing effects. The synchronous 1H/23Na setup obtained images in half the time necessary to sequentially acquire the same 1H and 23Na images with the given setup and parameters. Dual-nuclear hardware and sequence modifications were used to acquire 23Na images within the same sequence as 1H images, without increases to the 1H acquisition time. This work demonstrates a viable technique to acquire 23Na image data without increasing 1H acquisition time using minor additional custom hardware, without requiring modification of a commercial scanner with multinuclear capability.

Accuracy of Diffusion Tensor Imaging for Diagnosing Cervical Spondylotic Myelopathy in Patients Showing Spinal Cord Compression.

OBJECTIVE: To assess the performance of diffusion tensor imaging (DTI) for the diagnosis of cervical spondylotic myelopathy (CSM) in patients with deformed spinal cord but otherwise unremarkable conventional magnetic resonance imaging (MRI) findings. MATERIALS AND METHODS: A total of 33 patients who underwent MRI of the cervical spine including DTI using two-dimensional single-shot interleaved multi-section inner volume diffusion-weighted echo-planar imaging and whose spinal cords were deformed but showed no signal changes on conventional MRI were the subjects of this study. Mean diffusivity (MD), longitudinal diffusivity (LD), radial diffusivity (RD), and fractional anisotropy (FA) were measured at the most stenotic level. The calculated performance of MD, FA, MD∩FA (considered positive when both the MD and FA results were positive), LD∩FA (considered positive when both the LD and FA results were positive), and RD∩FA (considered positive when both the RD and FA results were positive) in diagnosing CSM were compared with each other based on the estimated cut-off values of MD, LD, RD, and FA from receiver operating characteristic curve analysis with the clinical diagnosis of CSM from medical records as the reference standard. RESULTS: The MD, LD, and RD cut-off values were 1.079 × 10(-3), 1.719 × 10(-3), and 0.749 × 10(-3) mm(2)/sec, respectively, and that of FA was 0.475. Sensitivity, specificity, positive predictive value and negative predictive value were: 100 (4/4), 44.8 (13/29), 20 (4/20), and 100 (13/13) for MD; 100 (4/4), 27.6 (8/29), 16 (4/25), and 100 (8/8) for FA; 100 (4/4), 58.6 (17/29), 25 (4/16), and 100 (17/17) for MD∩FA; 100 (4/4), 68.9 (20/29), 30.8 (4/13), and 100 (20/20) for LD∩FA; and 75 (3/4), 68.9 (20/29), 25 (3/12), and 95.2 (20/21) for RD∩FA in percentage value. Diagnostic performance comparisons revealed significant differences only in specificity between FA and MD∩FA (p = 0.003), FA and LD∩FA (p < 0.001), FA and RD∩FA (p < 0.001), MD and LD∩FA (p = 0.024) and MD and RD∩FA (p = 0.024). CONCLUSION: Fractional anisotropy combined with MD, RD, or LD is expected to be more useful than FA and MD for diagnosing CSM in patients who show deformed spinal cords without signal changes on MRI.

Decreased brain PME/PDE ratio in bipolar disorder: a preliminary (31) P magnetic resonance spectroscopy study.

OBJECTIVES: The aim of the present study was to measure brain phosphorus-31 magnetic resonance spectroscopy ((31) P MRS) metabolite levels and the creatine kinase reaction forward rate constant (kf ) in subjects with bipolar disorder (BD). METHODS: Subjects with bipolar euthymia (n = 14) or depression (n = 11) were recruited. Healthy comparison subjects (HC) (n = 23) were recruited and matched to subjects with BD on age, gender, and educational level. All studies were performed on a 3-Tesla clinical magnetic resonance imaging system using a (31) P/(1) H double-tuned volume head coil. (31) P spectra were acquired without (1) H-decoupling using magnetization-transfer image-selected in vivo spectroscopy. Metabolite ratios from a brain region that includes the frontal lobe, corpus callosum, thalamus, and occipital lobe are expressed as a percentage of the total phosphorus (TP) signal. Brain pH was also investigated. RESULTS: Beta-nucleoside-triphosphate (ß-NTP/TP) in subjects with bipolar depression was positively correlated with kf (p = 0.039, r(2) = 0.39); similar correlations were not observed in bipolar euthymia or HC. In addition, no differences in kf and brain pH were observed among the three diagnostic groups. A decrease in the ratio of phosphomonoesters to phosphodiesters (PME/PDE) was observed in subjects with bipolar depression relative to HC (p = 0.032). We also observed a trend toward an inverse correlation in bipolar depression characterized by decreased phosphocreatine and increased depression severity. CONCLUSIONS: In our sample, kf was not altered in the euthymic or depressed mood state in BD. However, decreased PME/PDE in subjects with bipolar depression was consistent with differences in membrane turnover. These data provide preliminary support for alterations in phospholipid metabolism and mitochondrial function in bipolar depression.

Impact of age on exercise-induced ATP supply during supramaximal plantar flexion in humans.

Currently, the physiological factors responsible for exercise intolerance and bioenergetic alterations with age are poorly understood due, at least in art, to the confounding effect of reduced physical activity in the elderly. Thus, in 40 healthy young (22 ± 2 yr) and old (74 ± 8 yr) activity-matched subjects, we assessed the impact of age on: 1) the relative contribution of the three major pathways of ATP synthesis (oxidative ATP synthesis, glycolysis, and the creatine kinase reaction) and 2) the ATP cost of contraction during high-intensity exercise. Specifically, during supramaximal plantar flexion (120% of maximal aerobic power), to stress the functional limits of the skeletal muscle energy systems, we used (31)P-labeled magnetic resonance spectroscopy to assess metabolism. Although glycolytic activation was delayed in the old, ATP synthesis from the main energy pathways was not significantly different between groups. Similarly, the inferred peak rate of mitochondrial ATP synthesis was not significantly different between the young (25 ± 8 mM/min) and old (24 ± 6 mM/min). In contrast, the ATP cost of contraction was significantly elevated in the old compared with the young (5.1 ± 2.0 and 3.7 ± 1.7 mM·min(-1)·W(-1), respectively; P < 0.05). Overall, these findings suggest that, when young and old subjects are activity matched, there is no evidence of age-related mitochondrial and glycolytic dysfunction. However, this study does confirm an abnormal elevation in exercise-induced skeletal muscle metabolic demand in the old that may contribute to the decline in exercise capacity with advancing age.

Wideband arrhythmia-Insensitive-rapid (AIR) pulse sequence for cardiac T1 mapping without image artifacts induced by an implantable-cardioverter-defibrillator.

PURPOSE: To develop and evaluate a wideband arrhythmia-insensitive-rapid (AIR) pulse sequence for cardiac T1 mapping without image artifacts induced by implantable-cardioverter-defibrillator (ICD). METHODS: We developed a wideband AIR pulse sequence by incorporating a saturation pulse with wide frequency bandwidth (8.9 kHz) to achieve uniform T1 weighting in the heart with ICD. We tested the performance of original and "wideband" AIR cardiac T1 mapping pulse sequences in phantom and human experiments at 1.5 Tesla. RESULTS: In five phantoms representing native myocardium and blood and postcontrast blood/tissue T1 values, compared with the control T1 values measured with an inversion-recovery pulse sequence without ICD, T1 values measured with original AIR with ICD were considerably lower (absolute percent error > 29%), whereas T1 values measured with wideband AIR with ICD were similar (absolute percent error < 5%). Similarly, in 11 human subjects, compared with the control T1 values measured with original AIR without ICD, T1 measured with original AIR with ICD was significantly lower (absolute percent error > 10.1%), whereas T1 measured with wideband AIR with ICD was similar (absolute percent error < 2.0%). CONCLUSION: This study demonstrates the feasibility of a wideband pulse sequence for cardiac T1 mapping without significant image artifacts induced by ICD.