High spatial and angular resolution diffusion weighted imaging (DWI) with network analysis provid... more High spatial and angular resolution diffusion weighted imaging (DWI) with network analysis provides a unique framework for the study of brain structure in vivo. DWI-derived brain connectivity patterns are best characterized with graph theory using an edge weight to quantify the strength of white matter connections between gray matter nodes. Here a dimensionless, scale-invariant edge weight is introduced to measure node connectivity. This edge weight metric provides reasonable and consistent values over any size scale (e.g. rodents to humans) used to quantify the strength of connection. Firstly, simulations were used to assess the effects of tractography seed point density and random errors in the estimated fiber orientations; with sufficient signal-to-noise ratio (SNR), edge weight estimates improve as the seed density increases. Secondly to evaluate the application of the edge weight in the human brain, ten repeated measures of DWI in the same healthy human subject were analyzed. M...
Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in... more 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 (H2OT2)-H-1 derived using H-1-MRS and MRI-T-2 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). T-2-weighted multi-slice spin echo (SE) axial images and single voxel H-1-MRS were acquired from the lower leg and thigh to measure lipid fraction and (H2OT2)-H-1. Results: MRI-T-2, (H2OT2)-H-1, and ...
The Imaging DMD project is a natural history study to follow a cohort of 100+ DMD boys for five y... more The Imaging DMD project is a natural history study to follow a cohort of 100+ DMD boys for five years with periodic MRI, MRS, and functional outcomes evaluations. Based on our studies to date, what are emerging as the most useful MR parameters in terms of sensitivity to disease progress and predictive value are:
In this study, we applied continuous random walk theory (CTRW) to develop a new model that charac... more In this study, we applied continuous random walk theory (CTRW) to develop a new model that characterizes anomalous diffusion in magnetic resonance imaging experiments. Furthermore, we applied a classification scheme based on information theoretic a techniques to characterize the degree of heterogeneity and complexity in biological tissues. From a CTRW approach, the Fourier transform of the generalized solution to the diffusion equation comes in the form of the Mittag-Leffler function. In this solution form, the relative stochastic uncertainty in the diffusion process can be computed with spectral entropy. We interrogated both white and gray matter regions of a fixed rat brain with diffusion - weighted magnetic resonance imaging experiments up to 26,000 s/mm² by independently weighting q and Δ. to investigate the effects on the diffusion phenomena. Our model fractional order parameters, α and β, and entropy measure, H(q, Δ), differentiated between tissue types and extracted differing...
Objective: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with... more 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).
Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in... more 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 1 H 2 O T 2 derived using 1 H-MRS and MRI-T 2 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.
Broca&amp... more Broca's area is crucially involved in language processing. The sub-regions of Broca's area (pars triangularis, pars opercularis) presumably are connected via corticocortical pathways. However, growing evidence suggests that the thalamus may also be involved in language and share some of the linguistic functions supported by Broca's area. Functional connectivity is thought to be achieved via corticothalamic/thalamocortical white matter pathways. Our study investigates structural connectivity between Broca's area and the thalamus, specifically ventral anterior nucleus and pulvinar. We demonstrate that Broca's area shares direct connections with these thalamic nuclei and suggest a local Broca's area-thalamus network potentially involved in linguistic processing. Thalamic connectivity with Broca's area may serve to selectively recruit cortical regions storing multimodal features of lexical items and to bind them together during lexical-semantic processing. In addition, Broca's area-thalamic circuitry may enable cortico-thalamo-cortical information transfer and modulation between BA 44 and 45 during language comprehension and production.
The human brainstem is critical for the control of many life-sustaining functions, such as consci... more 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 11.1T 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.
To validate a multicenter protocol that examines lower extremity skeletal muscles of children wit... more 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. 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. 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%]). 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.
Skeletal muscles of children with Duchenne muscular dystrophy (DMD) show enhanced susceptibility ... more 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.
In this high-resolution magnetic resonance imaging (MRI) study at 17.6 Tesla of a fixed rat brain... more In this high-resolution magnetic resonance imaging (MRI) study at 17.6 Tesla of a fixed rat brain, we used the continuous time random walk theory (CTRW) for Brownian motion to characterize anomalous diffusion. The complex mesoporus structure of biological tissues (membranes, organelles, and cells) perturbs the motion of the random walker (water molecules in proton MRI) introducing halts between steps (waiting times) and restrictions on step sizes (jump lengths). When such waiting times and jump lengths are scaled with probability distributions that follow simple inverse power laws (t (-(1+α)), |x|(-(1+β))) non-Gaussian motion gives rise to sub- and super- diffusion. In the CTRW approach, the Fourier transform yields a solution to the generalized diffusion equation that can be expressed by the Mittag-Leffler function (MLF), E α (- D α, β|q|(β)Δ(α)). We interrogated both white and gray matter regions in a 1 mm slice of a fixed rat brain (190 μm in plane resolution) with diffusion weighted MRI experiments using b-values up to 25,000 s/mm (2), by independently varying q and Δ. When fitting these data to our model, the fractional order parameters, α and β, and the entropy measure, [Formula: see text], were found to provide excellent contrast between white and gray matter and to give results that were sensitive to the type of diffusion experiment performed.
Purpose: The relationship between fat fractions (FFs) determined based on multiple TE, unipolar g... more Purpose: The relationship between fat fractions (FFs) determined based on multiple TE, unipolar gradient echo images and 1 H magnetic resonance spectroscopy (MRS) was evaluated using different models for fat-water decomposition, signal-to-noise ratios, and excitation flip angles. Methods: A combination of single-voxel proton spectroscopy ( 1 H-MRS) and gradient echo imaging was used to determine muscle FFs in both normal and dystrophic muscles. In order to cover a large range of FFs, the soleus and vastus lateralis muscles of 22 unaffected control subjects, 16 subjects with collagen VI deficiency (COL6), and 71 subjects with Duchenne muscular dystrophy (DMD) were studied. 1 H-MRS-based FF were corrected for the increased muscle 1 H 2 O T 1 and T 2 values observed in dystrophic muscles. Results: Excellent agreement was found between coregistered FFs derived from gradient echo images fit to a multipeak model with noise bias correction and the relaxation-corrected 1 H-MRS FFs (y ¼ 0.93x þ 0.003; R 2 ¼ 0.96) across the full range of FFs. Relaxation-corrected 1 H-MRS FFs and imagingbased FFs were significantly elevated (P < 0.01) in the muscles of COL6 and DMD subjects. Conclusion: FFs, T 2 , and T 1 were all sensitive to muscle involvement in dystrophic muscle. MRI offered an additional advantage over single-voxel spectroscopy in that the tissue heterogeneity in FFs could be readily determined. Magn Reson Med 72:8-19,
In the recent decades structural connectivity between Broca's area and the basal ganglia has been... more In the recent decades structural connectivity between Broca's 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 Broca's 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 Broca's area, which would be a prerequisite to substantiate their support of language processing.
High spatial and angular resolution diffusion weighted imaging (DWI) with network analysis provid... more High spatial and angular resolution diffusion weighted imaging (DWI) with network analysis provides a unique framework for the study of brain structure in vivo. DWI-derived brain connectivity patterns are best characterized with graph theory using an edge weight to quantify the strength of white matter connections between gray matter nodes. Here a dimensionless, scale-invariant edge weight is introduced to measure node connectivity. This edge weight metric provides reasonable and consistent values over any size scale (e.g. rodents to humans) used to quantify the strength of connection. Firstly, simulations were used to assess the effects of tractography seed point density and random errors in the estimated fiber orientations; with sufficient signal-to-noise ratio (SNR), edge weight estimates improve as the seed density increases. Secondly to evaluate the application of the edge weight in the human brain, ten repeated measures of DWI in the same healthy human subject were analyzed. M...
Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in... more 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 (H2OT2)-H-1 derived using H-1-MRS and MRI-T-2 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). T-2-weighted multi-slice spin echo (SE) axial images and single voxel H-1-MRS were acquired from the lower leg and thigh to measure lipid fraction and (H2OT2)-H-1. Results: MRI-T-2, (H2OT2)-H-1, and ...
The Imaging DMD project is a natural history study to follow a cohort of 100+ DMD boys for five y... more The Imaging DMD project is a natural history study to follow a cohort of 100+ DMD boys for five years with periodic MRI, MRS, and functional outcomes evaluations. Based on our studies to date, what are emerging as the most useful MR parameters in terms of sensitivity to disease progress and predictive value are:
In this study, we applied continuous random walk theory (CTRW) to develop a new model that charac... more In this study, we applied continuous random walk theory (CTRW) to develop a new model that characterizes anomalous diffusion in magnetic resonance imaging experiments. Furthermore, we applied a classification scheme based on information theoretic a techniques to characterize the degree of heterogeneity and complexity in biological tissues. From a CTRW approach, the Fourier transform of the generalized solution to the diffusion equation comes in the form of the Mittag-Leffler function. In this solution form, the relative stochastic uncertainty in the diffusion process can be computed with spectral entropy. We interrogated both white and gray matter regions of a fixed rat brain with diffusion - weighted magnetic resonance imaging experiments up to 26,000 s/mm² by independently weighting q and Δ. to investigate the effects on the diffusion phenomena. Our model fractional order parameters, α and β, and entropy measure, H(q, Δ), differentiated between tissue types and extracted differing...
Objective: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with... more 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).
Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in... more 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 1 H 2 O T 2 derived using 1 H-MRS and MRI-T 2 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.
Broca&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Broca&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s area is crucially involved in language processing. The sub-regions of Broca&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s area (pars triangularis, pars opercularis) presumably are connected via corticocortical pathways. However, growing evidence suggests that the thalamus may also be involved in language and share some of the linguistic functions supported by Broca&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s area. Functional connectivity is thought to be achieved via corticothalamic/thalamocortical white matter pathways. Our study investigates structural connectivity between Broca&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s area and the thalamus, specifically ventral anterior nucleus and pulvinar. We demonstrate that Broca&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s area shares direct connections with these thalamic nuclei and suggest a local Broca&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s area-thalamus network potentially involved in linguistic processing. Thalamic connectivity with Broca&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s area may serve to selectively recruit cortical regions storing multimodal features of lexical items and to bind them together during lexical-semantic processing. In addition, Broca&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s area-thalamic circuitry may enable cortico-thalamo-cortical information transfer and modulation between BA 44 and 45 during language comprehension and production.
The human brainstem is critical for the control of many life-sustaining functions, such as consci... more 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 11.1T 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.
To validate a multicenter protocol that examines lower extremity skeletal muscles of children wit... more 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. 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. CSAmax, T2 from MR imaging and MR spectroscopy, and lipid fraction were consistent across centers in the phantom (CV, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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%]). 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.
Skeletal muscles of children with Duchenne muscular dystrophy (DMD) show enhanced susceptibility ... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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.
In this high-resolution magnetic resonance imaging (MRI) study at 17.6 Tesla of a fixed rat brain... more In this high-resolution magnetic resonance imaging (MRI) study at 17.6 Tesla of a fixed rat brain, we used the continuous time random walk theory (CTRW) for Brownian motion to characterize anomalous diffusion. The complex mesoporus structure of biological tissues (membranes, organelles, and cells) perturbs the motion of the random walker (water molecules in proton MRI) introducing halts between steps (waiting times) and restrictions on step sizes (jump lengths). When such waiting times and jump lengths are scaled with probability distributions that follow simple inverse power laws (t (-(1+α)), |x|(-(1+β))) non-Gaussian motion gives rise to sub- and super- diffusion. In the CTRW approach, the Fourier transform yields a solution to the generalized diffusion equation that can be expressed by the Mittag-Leffler function (MLF), E α (- D α, β|q|(β)Δ(α)). We interrogated both white and gray matter regions in a 1 mm slice of a fixed rat brain (190 μm in plane resolution) with diffusion weighted MRI experiments using b-values up to 25,000 s/mm (2), by independently varying q and Δ. When fitting these data to our model, the fractional order parameters, α and β, and the entropy measure, [Formula: see text], were found to provide excellent contrast between white and gray matter and to give results that were sensitive to the type of diffusion experiment performed.
Purpose: The relationship between fat fractions (FFs) determined based on multiple TE, unipolar g... more Purpose: The relationship between fat fractions (FFs) determined based on multiple TE, unipolar gradient echo images and 1 H magnetic resonance spectroscopy (MRS) was evaluated using different models for fat-water decomposition, signal-to-noise ratios, and excitation flip angles. Methods: A combination of single-voxel proton spectroscopy ( 1 H-MRS) and gradient echo imaging was used to determine muscle FFs in both normal and dystrophic muscles. In order to cover a large range of FFs, the soleus and vastus lateralis muscles of 22 unaffected control subjects, 16 subjects with collagen VI deficiency (COL6), and 71 subjects with Duchenne muscular dystrophy (DMD) were studied. 1 H-MRS-based FF were corrected for the increased muscle 1 H 2 O T 1 and T 2 values observed in dystrophic muscles. Results: Excellent agreement was found between coregistered FFs derived from gradient echo images fit to a multipeak model with noise bias correction and the relaxation-corrected 1 H-MRS FFs (y ¼ 0.93x þ 0.003; R 2 ¼ 0.96) across the full range of FFs. Relaxation-corrected 1 H-MRS FFs and imagingbased FFs were significantly elevated (P < 0.01) in the muscles of COL6 and DMD subjects. Conclusion: FFs, T 2 , and T 1 were all sensitive to muscle involvement in dystrophic muscle. MRI offered an additional advantage over single-voxel spectroscopy in that the tissue heterogeneity in FFs could be readily determined. Magn Reson Med 72:8-19,
In the recent decades structural connectivity between Broca's area and the basal ganglia has been... more In the recent decades structural connectivity between Broca's 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 Broca's 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 Broca's area, which would be a prerequisite to substantiate their support of language processing.
Uploads
Papers by William Triplett