William Triplett

T₂ mapping provides multiple approaches for the characterization of muscle involvement in neuromuscular diseases: a cross-sectional study of lower leg muscles in 5-15-year-old boys with Duchenne muscular dystrophy.

Skeletal muscles of children with Duchenne muscular dystrophy (DMD) show enhanced susceptibility to damage and progressive lipid infiltration, which contribute to an increase in the MR proton transverse relaxation time (T2). Therefore, the examination of T2 changes in individual muscles may be useful for the monitoring of disease progression in DMD. In this study, we used the mean T2, percentage of elevated pixels and T2 heterogeneity to assess changes in the composition of dystrophic muscles. In addition, we used fat saturation to distinguish T2 changes caused by edema and inflammation from fat infiltration in muscles. Thirty subjects with DMD and 15 age‐matched controls underwent T2‐weighted imaging of their lower leg using a 3‐T MR system. T2 maps were developed and four lower leg muscles were manually traced (soleus, medial gastrocnemius, peroneal and tibialis anterior). The mean T2 of the traced regions of interest, width of the T2 histograms and percentage of elevated pixels were calculated. We found that, even in young children with DMD, lower leg muscles showed elevated mean T2, were more heterogeneous and had a greater percentage of elevated pixels than in controls. T2 measures decreased with fat saturation, but were still higher (P < 0.05) in dystrophic muscles than in controls. Further, T2 measures showed positive correlations with timed functional tests (r = 0.23–0.79). The elevated T2 measures with and without fat saturation at all ages of DMD examined (5–15 years) compared with unaffected controls indicate that the dystrophic muscles have increased regions of damage, edema and fat infiltration. This study shows that T2 mapping provides multiple approaches that can be used effectively to characterize muscle tissue in children with DMD, even in the early stages of the disease. Therefore, T2 mapping may prove to be clinically useful in the monitoring of muscle changes caused by the disease process or by therapeutic interventions in DMD. Copyright

Longitudinal measurements of MRI-T2 in boys with Duchenne muscular dystrophy: effects of age and disease progression.

Duchenne muscular dystrophy (DMD) is characterized by an increased muscle damage and progressive replacement of muscle by noncontractile tissue. Both of these pathological changes can lengthen the MRI transverse proton relaxation time (T2). The current study measured longitudinal changes in T2 and its distribution in the lower leg of 16 boys with DMD (5-13years, 15 ambulatory) and 15 healthy controls (5-13years). These muscles were chosen to allow extended longitudinal monitoring, due to their slow progression compared with proximal muscles in DMD. In the soleus muscle of boys with DMD, T2 and the percentage of pixels with an elevated T2 (⩾2SD above control mean T2) increased significantly over 1year and 2years, while the width of the T2 histogram increased over 2years. Changes in soleus T2 variables were significantly greater in 9-13years old compared with 5-8years old boys with DMD. Significant correlations between the change in all soleus T2 variables over 2years and the change in functional measures over 2years were found. MRI measurement of muscle T2 in boys with DMD is sensitive to disease progression and shows promise as a clinical outcome measure.

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Objective: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with Duchenne muscular dystrophy (DMD) using MRI and magnetic resonance spectroscopy (MRS). Methods: Transverse relaxation time (T2) and fat fraction were measured by MRI/MRS in lower extremity muscles of 15 boys with DMD (age 5.0–6.9 years) taking corticosteroids and 15 corticosteroid-naive boys. Subsequently, fat fraction was measured in a subset of these boys at 1 year. Finally, MRI/MRS data were collected from 16 corticosteroid-naive boys with DMD (age 5–8.9 years) at baseline, 3 months, and 6 months. Five boys were treated with corticosteroids after baseline and the remaining 11 served as corticosteroid-naive controls. Results: Cross-sectional comparisons demonstrated lower muscle T2 and less intramuscular (IM) fat deposition in boys with DMD on corticosteroids, suggesting reduced inflammation/damage and fat infiltration with treatment. Boys on corticosteroids demonstrated less increase in IM fat infiltration at 1 year. Finally, T2 by MRI/MRS detected effects of corticosteroids on leg muscles as early as 3 months after drug initiation. Conclusions: These results demonstrate the ability of MRI/MRS to detect therapeutic effects of corticosteroids in reducing inflammatory processes in skeletal muscles of boys with DMD. Our work highlights the potential of MRI/MRS as a biomarker in evaluating therapeutic interventions in DMD.

On random walks and entropy in diffusion-weighted magnetic resonance imaging studies of neural tissue.

In diffusion‐weighted MRI studies of neural tissue, the classical model assumes the statistical mechanics of Brownian motion and predicts a monoexponential signal decay. However, there have been numerous reports of signal decays that are not monoexponential, particularly in the white matter.

Magnetic Resonance Imaging and Spectroscopy Assessment of Lower Extremity Skeletal Muscles in Boys with Duchenne Muscular Dystrophy: A Multicenter Cross Sectional Study

Introduction Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in functional deficits. However, these functional declines are often not able to be quantified in clinical trials for DMD until after age 7. In this study, we hypothesized that 1H2O T2 derived using 1H-MRS and MRI-T2 will be sensitive to muscle involvement at a young age (5–7 years) consistent with increased inflammation and muscle damage in a large cohort of DMD subjects compared to controls. Methods MR data were acquired from 123 boys with DMD (ages 5–14 years; mean 8.6 SD 2.2 years) and 31 healthy controls (age 9.7 SD 2.3 years) using 3-Tesla MRI instruments at three institutions (University of Florida, Oregon Health & Science University, and Children’s Hospital of Philadelphia). T2-weighted multi-slice spin echo (SE) axial images and single voxel 1H-MRS were acquired from the lower leg and thigh to measure lipid fraction and 1H2O T2. Results MRI-T2, 1H2O T2, and lipid fraction were greater (p<0.05) in DMD compared to controls. In the youngest age group, DMD values were different (p<0.05) than controls for the soleus MRI-T2, 1H2O T2 and lipid fraction and vastus lateralis MRI-T2 and 1H2O T2. In the boys with DMD, MRI-T2 and lipid fraction were greater (p<0.05) in the oldest age group (11–14 years) than the youngest age group (5–6.9 years), while 1H2O T2 was lower in the oldest age group compared to the young age group. Discussion Overall, MR measures of T2 and lipid fraction revealed differences between DMD and Controls. Furthermore, MRI-T2 was greater in the older age group compared to the young age group, which was associated with higher lipid fractions. Overall, MR measures of T2 and lipid fraction show excellent sensitivity to DMD disease pathologies and potential therapeutic interventions in DMD, even in the younger boys.

Chemical shift-based MRI to measure fat fractions in dystrophic skeletal muscle.

The relationship between fat fractions (FFs) determined based on multiple TE, unipolar gradient echo images and 1H magnetic resonance spectroscopy (MRS) was evaluated using different models for fat‐water decomposition, signal‐to‐noise ratios, and excitation flip angles.

Broca's area and its striatal and thalamic connections: a diffusion-MRI tractography study.

In the recent decades structural connectivity between Brocas area and the basal ganglia has been postulated in the literature, though no direct evidence of this connectivity has yet been presented. The current study investigates this connectivity using a novel diffusion-weighted imaging (DWI) fiber tracking method in humans in vivo. Our findings suggest direct connections between sub-regions of Brocas area and the anterior one-third of the putamen, as well as the ventral anterior nucleus of the thalamus. Thus, we are the first to provide a detailed account of inferred circuitry involving basal ganglia, thalamus, and Brocas area, which would be a prerequisite to substantiate their support of language processing.

Skeletal Muscles of Ambulant Children with Duchenne Muscular Dystrophy: Validation of Multicenter Study of Evaluation with MR Imaging and MR Spectroscopy

PURPOSE To validate a multicenter protocol that examines lower extremity skeletal muscles of children with Duchenne muscular dystrophy (DMD) by using magnetic resonance (MR) imaging and MR spectroscopy in terms of reproducibility of these measurements within and across centers. MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review boards of all participating centers, and informed consent was obtained from each participant or a guardian. Standardized procedures with MR operator training and quality assurance assessments were implemented, and data were acquired at three centers by using different 3-T MR imaging instruments. Measures of maximal cross-sectional area (CSAmax), transverse relaxation time constant (T2), and lipid fraction were compared among centers in two-compartment coaxial phantoms and in two unaffected adult subjects who visited each center. Also, repeat MR measures were acquired twice on separate days in 30 boys with DMD (10 per center) and 10 unaffected boys. Coefficients of variation (CVs) were computed to examine the repeated-measure variabilities within and across centers. RESULTS CSAmax, T2 from MR imaging and MR spectroscopy, and lipid fraction were consistent across centers in the phantom (CV, <3%) and in the adult subjects who traveled to each site (CV, 2%-7%). High day-to-day reproducibility in MR measures was observed in boys with DMD (CSAmax, CV = 3.7% [25th percentile, 1.3%; 75th percentile, 5.1%]; contractile area, CV = 4.2% [25th percentile, 0.8%; 75th percentile, 4.9%]; MR imaging T2, CV = 3.1% [25th percentile, 1.2%; 75th percentile, 4.7%]; MR spectroscopy T2, CV = 3.9% [25th percentile, 1.5%; 75th percentile, 5.1%]; and lipid fraction, CV = 4.7% [25th percentile, 1.0%; 75th percentile, 5.3%]). CONCLUSION The MR protocol implemented in this multicenter study achieved highly reproducible measures of lower extremity muscles across centers and from day to day in ambulatory boys with DMD.

Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort

The aim of this study was to describe Duchenne muscular dystrophy (DMD) disease progression in the lower extremity muscles over 12 months using quantitative magnetic resonance (MR) biomarkers, collected across three sites in a large cohort.

Imaging white matter in human brainstem

The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo.