Predicted effects of image acquisition and analysis conditions on DTMRI tractography-based muscle architecture estimates.

PURPOSE: To quantify the effects of the intrinsic signal pattern, image acquisition conditions, and data analysis conditions on diffusion-tensor MRI (DTMRI) tractography-based muscle architecture estimates using a sampling-reconstruction assessment framework. METHODS: Numerical models of muscles were constructed with realistic architectural properties. DTMRI signals were computed at signal-to-noise ratio (SNR) of 24-96 and common voxel sizes. Fiber tracking was performed, and the results were compared with the known architectural properties. RESULTS: SNR exerted the most significant impact on the outcome. The outcome variables approached asymptotes at SNR ≈ 54. Large in-plane voxel dimensions reduced the similarity between reconstructed fibers and the known architectural properties. Higher order polynomials helped reconstruct fibers with more complicated geometry but overfit noise for less complex geometries. The intrinsic fiber curvature also affected the robustness of polynomial smoothing to SNR. Other conditions, such as the fiber dimensionality, voxel aspect ratio, and slice thickness, did not affect the outcomes. CONCLUSION: SNR ≥ 54 is recommended for accurate muscle architecture characterization using DTMRI. Averaged across all simulated conditions, the greatest percent errors under SNR = 54 were -5.6% and -4.0% for the pennation angle and fiber-tract length estimates, respectively. For fiber tracts with intermediate intrinsic curvature, the greatest percent error for the curvature estimate was 9.8% for SNR = 54. Smaller in-plane voxel size (≤1.5 mm) is preferred to minimize the estimation error in architectural properties. If necessary, slice thickness may be adjusted within typical ranges to achieve sufficient SNR when slices are aligned near the fiber direction. Third-order polynomial fitting is appropriate for smoothing fiber tracts.

The impact of diffusion tensor imaging tractography settings on muscle fascicle architecture and diffusion parameter estimates: Tract length, completion, and curvature are most sensitive to tractography settings.

Diffusion-tensor (DT)-MRI tractography provides information about properties relevant to muscle health and function, including estimates of architectural properties such as fascicle length, pennation angle, and curvature and diffusion properties such as mean diffusivity (MD) and fractional anisotropy (FA). Tractography settings, including integration algorithms, thresholds for early tract termination, and tract smoothing approaches, impact the accuracy of the muscle property estimates. However, muscle DT-MRI tractography is performed using a variety of these settings, complicating comparisons between different studies. The effects of different tractography settings on muscle architecture estimates have not been fully explored, and optimized settings for muscle tractography have not yet been determined. We examined the influence of integration algorithm and termination check settings combined with a range of step sizes, termination criteria, and smoothing polynomial orders on tract characteristics, completion/reason for termination, and goodness of fit between fiber tracts and smoothing polynomials using 3-T DT-MR images of the lower leg muscles of seven healthy adults. We found that tract length and completion were highly sensitive to strict FA and intersegment angle thresholds (25%-69% reduction in complete fiber tracts from lowest to highest minimum FA threshold and 11%-36% reduction from highest to lowest intersegment angle threshold). Higher order polynomials (third and fourth order vs. second order) better fit the muscle fiber trajectories, but curvature estimates were highly sensitive to smoothing polynomial order (3.9-6.6 m-1 increase for second- vs. fourth-order fitting polynomials). Step size impacted curvature estimates, albeit to a lesser degree. Integration algorithm had little impact, and mean pennation angle, and tract-based FA and MD, were relatively insensitive to all parameters. The results demonstrate which muscle diffusion measures and architectural estimates are most sensitive to varying tractography settings and support the need for consistent reporting of tractography details to aid interpretation and comparison of results between studies.

Neurosurgical Implant Safety in 7 T MRI: A Scoping Review.

The use of 7 Tesla (T) magnetic resonance imaging (MRI) is expanding across neurosurgical and neurologic specialties. However, few neurosurgical-related implants have been tested for safety at 7 T, limiting its use in patients with cranial fixation, shunt placements, and other implants. Implant safety can be determined via the American Society for Testing Materials International (ASTM) guidelines. To assess the current state of neurosurgical implant safety at 7 T, a systematic search was performed using PubMed, MEDLINE, Web of Knowledge, and citation matching. Studies written in English that included at least one neurosurgical implant and at least one safety outcome were included. Data were extracted for implant studied, implant composition, deflection angle, torque, temperature change, and ASTM guidelines followed. PRISMA reporting guidelines for scoping reviews were followed. Overall, 18 studies consisting of 45 unique implants were included. Implants included cranial fixation devices, aneurysm clips, spinal rods, pedicle screws, ventriculoperitoneal (VP) shunts, deep brain stimulation devices, and electroencephalogram (EEG) caps and electrodes. Cranial fixation devices, deep brain stimulation devices, spinal rods, and pedicle screws are likely 7 T MRI compatible based on outcomes reported. Aneurysm clips and EEG devices had variable safety outcomes. The VP shunts studied lost functionality after 7 T MRI exposure. We identified several implants that are likely compatible with 7 T MRI. Given the growth in 7 T imaging and expansion of the technology, neurosurgical implants should be constructed with the aforementioned considerations. Caution must be taken with all implants, especially aneurysm clips, programmable VP shunts, and EEG recording devices. It is also noteworthy that several implant testing reports did not report following ASTM standards. This scoping review seeks to concisely summarize all neurosurgical-related implants that have been tested for safety in 7 T MRI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Quantitative Muscle Fascicle Tractography Using Brightness-Mode Ultrasound.

A muscle's architecture, defined as the geometric arrangement of its fibers with respect to its mechanical line of action, impacts its abilities to produce force and shorten or lengthen under load. Ultrasound and other noninvasive imaging methods have contributed significantly to our understanding of these structure-function relationships. The goal of this work was to develop a MATLAB toolbox for tracking and mathematically representing muscle architecture at the fascicle scale, based on brightness-mode ultrasound imaging data. The MuscleUS_Toolbox allows user-performed segmentation of a region of interest and automated modeling of local fascicle orientation; calculation of streamlines between aponeuroses of origin and insertion; and quantification of fascicle length, pennation angle, and curvature. A method is described for optimizing the fascicle orientation modeling process, and the capabilities of the toolbox for quantifying and visualizing fascicle architecture are illustrated in the human tibialis anterior muscle. The toolbox is freely available.

Chemical exchange rotation transfer imaging of phosphocreatine in muscle.

In chemical exchange saturation transfer (CEST) imaging, the signal at 2.6 ppm from the water resonance in muscle has been assigned to phosphocreatine (PCr). However, this signal has limited specificity for PCr since the signal is also sensitive to exchange with protein and macromolecular protons when using some conventional quantification methods, and will vary with changes in the water longitudinal relaxation rate. Correcting for these effects while maintaining reasonable acquisition times is challenging. As an alternative approach to overcome these problems, here we evaluate chemical exchange rotation transfer (CERT) imaging of PCr in muscle at 9.4 T. Specifically, the CERT metric, AREXdouble,cpw at 2.6 ppm, was measured in solutions containing the main muscle metabolites, in tissue homogenates with controlled PCr content, and in vivo in rat leg muscles. PCr dominates CERT metrics around 2.6 ppm (although with nontrivial confounding baseline contributions), indicating that CERT is well-suited to PCr specific imaging, and has the added benefit of requiring a relatively small number of acquisitions.

Slice-selective extended phase graphs in gradient-crushed, transient-state free precession sequences: An application to MR fingerprinting.

PURPOSE: Slice-selective, gradient-crushed, transient-state sequences such as those used in MR fingerprinting (MRF) relaxometry are sensitive to slice profile effects. Whereas balanced steady-state free precession MRF profile effects have been studied, less attention has been given to gradient-crushed MRF forms. Extensions of the extended phase graph (EPG) formalism, called slice-selective EPG (ssEPG), are proposed that model slice profile effects. THEORY AND METHODS: The hard-pulse approximation to slice-selective excitation in the spatial domain is reformulated in k-space. Excitation is modeled by standard EPG shift and transition operators. This ssEPG modeling is validated against Bloch simulations and phantom slice profile measurements. ssEPG relaxometry accuracy and variability are compared with other EPG methods in phantoms and human leg in vivo. The role of ∆B0 interactions with slice profile and gradient crushers is investigated. RESULTS: Simulations and slice profile measurements show that ssEPG can model highly dynamic slice profile effects of gradient-crushed sequences. The MRF ssEPG T2 estimates over 0 < T2 < 100 ms improve accuracy by > 10 ms at some values relative to other modeling approaches. Small deviations in B0 can produce substantial bias in T2 estimations from a range of MRF sequence types, and these effects can be modeled and understood by ssEPG. CONCLUSION: Transient-state, gradient-crushed sequences such as those used in MRF are sensitive to slice profile effects, and these effects depend on RF pulse choice, gradient crusher strength, and ∆B0 . It was found ssEPG was the most accurate EPG-based means to model these effects.

Skeletal muscle diffusion tensor-MRI fiber tracking: rationale, data acquisition and analysis methods, applications and future directions.

The mechanical functions of muscles involve the generation of force and the actuation of movement by shortening or lengthening under load. These functions are influenced, in part, by the internal arrangement of muscle fibers with respect to the muscle's mechanical line of action. This property is known as muscle architecture. In this review, we describe the use of diffusion tensor (DT)-MRI muscle fiber tracking for the study of muscle architecture. In the first section, the importance of skeletal muscle architecture to function is discussed. In addition, traditional and complementary methods for the assessment of muscle architecture (brightness-mode ultrasound imaging and cadaver analysis) are presented. Next, DT-MRI is introduced and the structural basis for the reduced and anisotropic diffusion of water in muscle is discussed. The third section discusses issues related to the acquisition of skeletal muscle DT-MRI data and presents recommendations for optimal strategies. The fourth section discusses methods for the pre-processing of DT-MRI data, the available approaches for the calculation of the diffusion tensor and the seeding and propagating of fiber tracts, and the analysis of the tracking results to measure structural properties pertinent to muscle biomechanics. Lastly, examples are presented of how DT-MRI fiber tracking has been used to provide new insights into how muscles function, and important future research directions are highlighted. Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of muscle BOLD responses to arterial occlusion at 3 and 7 Tesla.

PURPOSE: 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. METHODS: Eight subjects (three male), aged 29.5 ± 6.1 years (mean ± standard deviation, SD), 167.0 ± 10.6 cm tall with a body mass of 62.0 ± 18.0 kg, participated in the study. Subjects reported to the lab on four separate occasions including a habituation session, two MRI scans, and in a subset of subjects, a session during which changes in blood flow and blood oxygenation were quantified using Doppler ultrasound (U/S) and near-infrared spectroscopy (NIRS) respectively. For statistical comparisons between 3 and 7T, R2* rate constants were calculated as R2* = 1/T2*. RESULTS: The mean preocclusion R2* value was greater at 7T than at 3T (60.16 ± 2.95 vs. 35.17 ± 0.35 s(-1), respectively, P < 0.001). Also, the mean ΔR2 *END and ΔR2*POST values were greater for 7T than for 3T (-2.36 ± 0.25 vs. -1.24 ± 0.39 s(-1), respectively, Table 1). CONCLUSION: Muscle BOLD contrast at 7T is as much as six-fold greater than at 3T. In addition to providing greater SNR and CNR, 7T mBOLD studies may offer further advantages in the form of greater sensitivity to pathological changes in the muscle microcirculation.

Post-contractile BOLD contrast in skeletal muscle at 7 T reveals inter-individual heterogeneity in the physiological responses to muscle contraction.

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.

Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which there is no cure. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found. The hypothesis of this study is that T1 and extracellular volume fraction (ECV) mapping using cardiovascular magnetic resonance (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without myocardial late gadolinium enhancement (LGE). METHODS: Thirty-one DMD and 11 healthy control participants were prospectively enrolled. CMR using a modified Look-Locker (MOLLI) sequence was performed in all participants before and after contrast administration. T1 and ECV maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6-segment AHA model. Global and segmental values were compared between DMD and controls using a Wilcoxon rank-sum test. RESULTS: The DMD participants had significantly higher mean native T1 compared with controls (1045 ms vs. 988 ms, p = 0.001). DMD participants with normal LVEF and without evidence of LGE also demonstrated elevated mean native T1 (1039 ms vs. 988 ms, p = 0.002, and 1038 ms vs. 988 ms, p = 0.011). DMD participants had a significantly greater mean ECV than controls (0.31 vs. 0.24, p < 0.001), even in the settings of normal LVEF (0.28 vs. 0.24, p < 0.001) and negative LGE (0.29 vs. 0.24, p = 0.001). CONCLUSIONS: DMD participants have elevated LV myocardial native T1 and ECV, even in the setting of normal LVEF and in the absence of LGE. T1 and ECV mapping in DMD have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials.

Noninvasive measurements of glycogen in perfused mouse livers using chemical exchange saturation transfer NMR and comparison to (13)C NMR spectroscopy.

Liver glycogen represents an important physiological form of energy storage. It plays a key role in the regulation of blood glucose concentrations, and dysregulations in hepatic glycogen metabolism are linked to many diseases including diabetes and insulin resistance. In this work, we develop, optimize, and validate a noninvasive protocol to measure glycogen levels in isolated perfused mouse livers using chemical exchange saturation transfer (CEST) NMR spectroscopy. Model glycogen solutions were used to determine optimal saturation pulse parameters which were then applied to intact perfused mouse livers of varying glycogen content. Glycogen measurements from serially acquired CEST Z-spectra of livers were compared with measurements from interleaved natural abundance (13)C NMR spectra. Experimental data revealed that CEST-based glycogen measurements were highly correlated with (13)C NMR glycogen spectra. Monte Carlo simulations were then used to investigate the inherent (i.e., signal-to-noise-based) errors in the quantification of glycogen with each technique. This revealed that CEST was intrinsically more precise than (13)C NMR, although in practice may be prone to other errors induced by variations in experimental conditions. We also observed that the CEST signal from glycogen in liver was significantly less than that observed from identical amounts in solution. Our results demonstrate that CEST provides an accurate, precise, and readily accessible method to noninvasively measure liver glycogen levels and their changes. Furthermore, this technique can be used to map glycogen distributions via conventional proton magnetic resonance imaging, a capability universally available on clinical and preclinical magnetic resonance imaging (MRI) scanners vs (13)C detection, which is limited to a small fraction of clinical-scale MRI scanners.

Comparison of twice refocused spin echo versus stimulated echo diffusion tensor imaging for tracking muscle fibers.

PURPOSE: To compare the precision of measuring the pennation angle and fiber length in the vastus lateralis (VL) using two distinctly different diffusion tensor imaging (DTI) sequences. MATERIALS AND METHODS: We imaged the thigh of 10 normal subjects on a 3T magnetic resonance (MR) imager with twice refocused spin echo (TRSE) and stimulated echo (STEAM) DTI-MRI techniques. Both techniques took the same total acquisition time and employed the same diffusion weighting and gradient directions. Using the diffusion tensor images produced by each sequence, muscle fiber bundles were tracked from the aponeurosis by following the first eigenvector of the diffusion tensor. From these tracks we calculated the pennation angle and fiber length. RESULTS: The STEAM acquisition resulted in significantly higher signal-to-noise ratio (SNR), lower apparent diffusion coefficient (ADC), higher fractional anisotropy (FA) values, and longer fibers than TRSE. Although no difference in the pennation angle between the two acquisitions was found, the TRSE sequence had a significantly greater within-subject dispersion in the pennation angle of tracked fibers, which may indicate a reduction in the coherence of fiber bundles. CONCLUSION: DTI of muscle using a STEAM acquisition resulted in significant improvements in the SNR and FA, resulting in tracking a larger number of muscle fiber bundles over longer distances and with less within-subject dispersion.

Evaluation of post-contrast myocardial t1 in duchenne muscular dystrophy using cardiac magnetic resonance imaging.

The objective of the study was to perform a retrospective pilot study to evaluate the potential of myocardial T1 in assessment of Duchenne muscular dystrophy (DMD) cardiomyopathy. Early identification of DMD cardiac disease, particularly myocardial fibrosis, would allow earlier therapy, potentially improving outcomes. Shortened myocardial T1 measured by cardiac MRI (CMR) is a measure of cardiac fibrosis that may be detected before late gadolinium enhancement (LGE). We hypothesized that the post-contrast T1 obtained from the Look-Locker sequences (T1LL), an easily obtainable surrogate of myocardial T1, would be abnormally shortened in DMD compared with controls. T1LL measurement was performed on 21 DMD subjects and 11 controls; to account for individual variations in gadolinium distribution, myocardial T1LL was divided by blood pool T1LL, deriving T1LL ratios. DMD subjects had shorter mean T1LL ratio than controls (1.42 vs 1.72, p < 0.001). Subset analyses in DMD subjects with normal LVEF and without LGE also demonstrated significantly shorter T1LL ratio (-0.28, p < 0.001 and -0.25, p = 0.028). Post-contrast T1LL ratio is abnormally shortened in DMD compared with controls, even in DMD patients with otherwise normal CMRs. The application of more aggressive therapy for those with shorter T1LL may favorably alter morbidity and improve mortality associated with DMD cardiomyopathy. These data suggest that further prospective evaluation of myocardial T1 will be of benefit to patients with DMD.

Multi-parametric MRI characterization of inflammation in murine skeletal muscle.

Myopathies often display a common set of complex pathologies that include muscle weakness, inflammation, compromised membrane integrity, fat deposition, and fibrosis. Multi-parametric, quantitative, non-invasive imaging approaches may be able to resolve these individual pathological components. The goal of this study was to use multi-parametric MRI to investigate inflammation as an isolated pathological feature. Proton relaxation, diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT-MRI), and dynamic contrast enhanced (DCE-MRI) parameters were calculated from data acquired in a single imaging session conducted 6-8 hours following the injection of λ-carrageenan, a local inflammatory agent. T2 increased in the inflamed muscle and transitioned to bi-exponential behavior. In diffusion measurements, all three eigenvalues and the apparent diffusion coefficient increased, but λ3 had the largest relative change. Analysis of the qMT data revealed that the T1 of the free pool and the observed T1 both increased in the inflamed tissue, while the ratio of exchanging spins in the solid pool to those in the free water pool (the pool size ratio) significantly decreased. DCE-MRI data also supported observations of an increase in extracellular volume. These findings enriched the understanding of the relation between multiple quantitative MRI parameters and an isolated inflammatory pathology, and may potentially be employed for other single or complex myopathy models.

Multi-parametric MRI characterization of healthy human thigh muscles at 3.0 T - relaxation, magnetization transfer, fat/water, and diffusion tensor imaging.

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.

A Comparison of Skeletal Muscle Diffusion Tensor Imaging Tractography Seeding Methods.

The internal arrangement of a muscle's fibers with respect to its mechanical line of action (muscle architecture) is a major determinant of muscle function. Muscle architecture can be quantified using diffusion tensor magnetic resonance imaging-based tractography, which propagates streamlines from a set of seed points by integrating vectors that represent the direction of greatest water diffusion (and by inference, the local fiber orientation). Previous work has demonstrated that tractography outcomes are sensitive to the method for defining seed points, but this sensitivity has not been fully examined. To do so, we developed a realistic simulated muscle architecture and implemented four novel methods for tract seeding: seeding along the muscle-aponeurosis boundary with an updated procedure for rounding seed points prior to lookup in the muscle boundary mask and diffusion tensor matrix (APO-3); voxel-based seeding throughout the muscle volume at a user-specified spatial frequency (VXL-1); voxel-based seeding throughout the muscle volume at a variable spatial frequency (VXL-2), and seeding near external and internal muscle boundaries (VXL-3). We then implemented these methods in an example human dataset. The updated aponeurosis seeding procedures allow more accurate and robust tract propagation from seed points. The voxel-based seeding methods had quantification outcomes that closely matched the updated aponeurosis seeding method. Further, the voxel-based methods can accelerate the overall workflow and may be beneficial in high throughput analysis of multi-muscle datasets. Continued evaluation of these methods in a wider range of muscle architectures is warranted.

Assessment of Mechanically Induced Changes in Helical Fiber Microstructure Using Diffusion Tensor Imaging.

Noninvasive methods to detect microstructural changes in collagen-based fibrous tissues are necessary to differentiate healthy from damaged tissues in vivo but are sparse. Diffusion Tensor Imaging (DTI) is a noninvasive imaging technique used to quantitatively infer tissue microstructure with previous work primarily focused in neuroimaging applications. Yet, it is still unclear how DTI metrics relate to fiber microstructure and function in musculoskeletal tissues such as ligament and tendon, in part because of the high heterogeneity inherent to such tissues. To address this limitation, we assessed the ability of DTI to detect microstructural changes caused by mechanical loading in tissue-mimicking helical fiber constructs of known structure. Using high-resolution optical and micro-computed tomography imaging, we found that static and fatigue loading resulted in decreased sample diameter and a re-alignment of the macro-scale fiber twist angle similar with the direction of loading. However, DTI and micro-computed tomography measurements suggest microstructural differences in the effect of static versus fatigue loading that were not apparent at the bulk level. Specifically, static load resulted in an increase in diffusion anisotropy and a decrease in radial diffusivity suggesting radially uniform fiber compaction. In contrast, fatigue loads resulted in increased diffusivity in all directions and a change in the alignment of the principal diffusion direction away from the constructs' main axis suggesting fiber compaction and microstructural disruptions in fiber architecture. These results provide quantitative evidence of the ability of DTI to detect mechanically induced changes in tissue microstructure that are not apparent at the bulk level, thus confirming its potential as a noninvasive measure of microstructure in helically architected collagen-based tissues, such as ligaments and tendons.

A registration strategy to characterize DTI-observed changes in skeletal muscle architecture due to passive shortening.

Skeletal muscle architecture is a key determinant of muscle function. Architectural properties such as fascicle length, pennation angle, and curvature can be characterized using Diffusion Tensor Imaging (DTI), but acquiring these data during a contraction is not currently feasible. However, an image registration-based strategy may be able to convert muscle architectural properties observed at rest to their contracted state. As an initial step toward this long-term objective, the aim of this study was to determine if an image registration strategy could be used to convert the whole-muscle average architectural properties observed in the extended joint position to those of a flexed position, following passive rotation. DTI and high-resolution fat/water scans were acquired in the lower leg of seven healthy participants on a 3T MR system in +20° (plantarflexion) and -10° (dorsiflexion) foot positions. The diffusion and anatomical images from the two positions were used to propagate DTI fiber-tracts from seed points along a mesh representation of the aponeurosis of fiber insertion. The -10° and +20° anatomical images were registered and the displacement fields were used to transform the mesh and fiber-tracts from the +20° to the -10° position. Student's paired t-tests were used to compare the mean architectural parameters between the original and transformed fiber-tracts. The whole-muscle average fiber-tract length, pennation angle, curvature, and physiological cross-sectional areas estimates did not differ significantly. DTI fiber-tracts in plantarflexion can be transformed to dorsiflexion position without significantly affecting the average architectural characteristics of the fiber-tracts. In the future, a similar approach could be used to evaluate muscle architecture in a contracted state.

Cardiac magnetic resonance assessment of acute rejection and cardiac allograft vasculopathy in pediatric heart transplant.

BACKGROUND: In pediatric heart transplant (PHT), cardiac catheterization with endomyocardial biopsy (EMB) is standard for diagnosing acute rejection (AR) and cardiac allograft vasculopathy (CAV) but is costly and invasive. OBJECTIVES: To evaluate the ability of cardiac magnetic resonance (CMR) to noninvasively identify differences in PHT patients with AR and CAV. METHODS: Patients were enrolled at three children's hospitals. Data were collected from surveillance EMB or EMB for-cause AR. Patients were excluded if they had concurrent diagnoses of AR and CAV, CMR obtained >7days from AR diagnosis, they had EMB negative AR, or could not undergo contrasted, unsedated CMR. Kruskal-Wallis test was used to compare groups: (1) No AR or CAV (Healthy), (2) AR, (3) CAV. Wilcoxon rank-sum test was used for pairwise comparisons. RESULTS: Fifty-nine patients met inclusion criteria (median age 17years [IQR 15-19]) 10 (17%) with AR, and 11 (19%) with CAV. AR subjects had worse left ventricular ejection fraction compared to Healthy patients (p = 0.001). Global circumferential strain (GCS) was worse in AR (p = 0.054) and CAV (p = 0.019), compared to Healthy patients. ECV, native T1, and T2 z-scores were elevated in patients with AR. CONCLUSIONS: CMR was able to identify differences between CAV and AR. CAV subjects had normal global function but abnormal GCS which may suggest subclinical dysfunction. AR patients have abnormal function and tissue characteristics consistent with edema (elevated ECV, native T1 and T2 z-scores). Characterization of CMR patterns is critical for the development of noninvasive biomarkers for PHT and may decrease dependence on EMB.

Quantitative effects of inclusion of fat on muscle diffusion tensor MRI measurements.

PURPOSE: To determine the minimum water percentage in a muscle region of interest that would allow diffusion tensor (DT-) MRI data to reflect the diffusion properties of pure muscle accurately. MATERIALS AND METHODS: Proton density-weighted images with and without fat saturation were obtained at the mid-thigh in four subjects. Co-registered DT-MR images were used to calculate the diffusion tensor's eigenvalues and fractional anisotropy. RESULTS: The eigenvalues transitioned monotonically as a function of water signal percentage from values near to those expected for pure fat to those for pure muscle. Also, the fractional anisotropy transitioned monotonically from 0.50 (fat) to 0.20 (muscle). For water signal percentages >55%, none of the diffusion indices differed significantly from those for regions of >90% muscle. CONCLUSION: Accounting for the T1 and T2 values of muscle and fat and the pulse sequence properties, it is concluded that, as a conservative estimate, regions must contain at least 76% muscle tissue to reflect the diffusion properties of pure muscle accurately.