Spin-echo Diffusion Tensor Imaging Research Articles

3D MRI of explanted sheep hearts with submillimeter isotropic spatial resolution: comparison between diffusion tensor and structure tensor imaging

ObjectiveThe aim of the study is to compare structure tensor imaging (STI) with diffusion tensor imaging (DTI) of the sheep heart (approximately the same size as the human heart).Materials and methodsMRI acquisition on three sheep ex vivo hearts was performed at 9.4 T/30 cm with a seven-element RF coil. 3D FLASH with an isotropic resolution of 150 µm and 3D spin-echo DTI at 600 µm were performed. Tensor analysis, angles extraction and segments divisions were performed on both volumes.ResultsA 3D FLASH allows for visualization of the detailed structure of the left and right ventricles. The helix angle determined using DTI and STI exhibited a smooth transmural change from the endocardium to the epicardium. Both the helix and transverse angles were similar between techniques. Sheetlet organization exhibited the same pattern in both acquisitions, but local angle differences were seen and identified in 17 segments representation.DiscussionThis study demonstrated the feasibility of high-resolution MRI for studying the myocyte and myolaminar architecture of sheep hearts. We presented the results of STI on three whole sheep ex vivo hearts and demonstrated a good correspondence between DTI and STI.

Diffusion time dependency along the human corpus callosum and exploration of age and sex differences as assessed by oscillating gradient spin-echo diffusion tensor imaging

Conventional diffusion imaging uses pulsed gradient spin echo (PGSE) waveforms with diffusion times of tens of milliseconds (ms) to infer differences of white matter microstructure. The combined use of these long diffusion times with short diffusion times (<10 ​ms) enabled by oscillating gradient spin echo (OGSE) waveforms can enable more sensitivity to changes of restrictive boundaries on the scale of white matter microstructure (e.g. membranes reflecting the axon diameters). Here, PGSE and OGSE images were acquired at 4.7 ​T from 20 healthy volunteers aged 20–73 years (10 males). Mean, radial, and axial diffusivity, as well as fractional anisotropy were calculated in the genu, body and splenium of the corpus callosum (CC). Monte Carlo simulations were also conducted to examine the relationship of intra- and extra-axonal radial diffusivity with diffusion time over a range of axon diameters and distributions.The results showed elevated diffusivities with OGSE relative to PGSE in the genu and splenium (but not the body) in both males and females, but the OGSE-PGSE difference was greater in the genu for males. Females showed positive correlations of OGSE-PGSE diffusivity difference with age across the CC, whereas there were no such age correlations in males. Simulations of radial diffusion demonstrated that for axon sizes in human brain both OGSE and PGSE diffusivities were dominated by extra-axonal water, but the OGSE-PGSE difference nonetheless increased with area-weighted outer-axon diameter. Therefore, the lack of OGSE-PGSE difference in the body is not entirely consistent with literature that suggests it is composed predominantly of axons with large diameter. The greater OGSE-PGSE difference in the genu of males could reflect larger axon diameters than females. The OGSE-PGSE difference correlation with age in females could reflect loss of smaller axons at older ages. The use of OGSE with short diffusion times to sample the microstructural scale of restriction implies regional differences of axon diameters along the corpus callosum with preliminary results suggesting a dependence on age and sex.

Deletion of the WNK3-SPAK kinase complex in mice improves radiographic and clinical outcomes in malignant cerebral edema after ischemic stroke

The WNK-SPAK kinase signaling pathway controls renal NaCl reabsorption and systemic blood pressure by regulating ion transporters and channels. A WNK3-SPAK complex is highly expressed in brain, but its function in this organ remains unclear. Here, we investigated the role of this kinase complex in brain edema and white matter injury after ischemic stroke. Wild-type, WNK3 knockout, and SPAK heterozygous or knockout mice underwent transient middle cerebral artery occlusion. One cohort of mice underwent magnetic resonance imaging. Ex-vivo brains three days post-ischemia were imaged by slice-selective spin-echo diffusion tensor imaging magnetic resonance imaging, after which the same brain tissues were subjected to immunofluorescence staining. A second cohort of mice underwent neurological deficit analysis up to 14 days post-transient middle cerebral artery occlusion. Relative to wild-type mice, WNK3 knockout, SPAK heterozygous, and SPAK knockout mice each exhibited a >50% reduction in infarct size and associated cerebral edema, significantly less demyelination, and improved neurological outcomes. We conclude that WNK3-SPAK signaling regulates brain swelling, gray matter injury, and demyelination after ischemic stroke, and that WNK3-SPAK inhibition has therapeutic potential for treating malignant cerebral edema in the setting of middle cerebral artery stroke.

Second-order motion-compensated spin echo diffusion tensor imaging of the human heart.

Myocardial microstructure has been challenging to probe in vivo. Spin echo-based diffusion-weighted sequences allow for single-shot acquisitions but are highly sensitive to cardiac motion. In this study, the use of second-order motion-compensated diffusion encoding was compared with first-order motion-compensated diffusion-weighted imaging during systolic contraction of the heart. First- and second-order motion-compensated diffusion encoding gradients were incorporated into a triggered single-shot spin echo sequence. The effect of contractile motion on the apparent diffusion coefficients and tensor orientations was investigated in vivo from basal to apical level of the heart. Second-order motion compensation was found to increase the range of systolic trigger delays from 30%-55% to 15%-77% peak systole at the apex and from 25%-50% to 15%-79% peak systole at the base. Diffusion tensor analysis yielded more physiological transmural distributions when using second-order motion-compensated diffusion tensor imaging. Higher-order motion-compensated diffusion encoding decreases the sensitivity to cardiac motion, thereby enabling cardiac DTI over a wider range of time points during systolic contraction of the heart.

Direct comparison of in-vivo and post-mortem spin-echo based diffusion tensor imaging in the porcine heart

Background Spin-echo based cardiac diffusion tensor imaging (DTI) is highly sensitive to myocardial strain [1]. Imaging during systolic contraction requires precise planning of the sequence timing [2]. Second order motion compensated diffusion encoding has recently been proposed for small animal imaging [3] to reduce the impact of myocardial strain on the diffusion tensor. It is the objective of the present work to compare second order motion compensated spin-echo DTI of the in-vivo and post-mortem porcine heart on a clinical MR system.

Assessment of diffusion tensor MR imaging (DTI) in liver fibrosis with minimal confounding effect of hepatic steatosis.

Given the potential confounding effect of fat on apparent diffusion coefficient (ADC) in the liver, we have assessed diffusion tensor imaging in liver fibrosis with minimal effect of fat on ADC and fractional anisotropy (FA). Thirty-six mice were used, among which 20 mice were CCl4 treated for fibrosis induction. Diffusion tensor imaging was performed at 9.4T using a spin-echo diffusion tensor imaging sequence with six gradient directions. Hepatic fat fraction obtained by MR spectroscopy was used as hepatic fat content. Fibrosis scores were obtained from histopathology. The hepatic fat fractions of the two animal groups were below 5.5% and not different (5.3 ± 1.5 vs. 4.6 ± 1.1%; P = 0.115). Fibrosis scores were higher in CCl4 -treated mice (0.0 ± 0.0 vs. 2.1 ± 0.7; P < 0.001). Nonetheless, there was no difference in ADC between the two groups (0.711 ± 0.068 × 10(-3) vs. 0.718 ± 0.095 × 10(-3) mm(2) s(-1) ; P = 0.911). The treated group had a lower FA than control (0.552 ± 0.050 vs. 0.586 ± 0.013; P = 0.023). ADC was not correlated with hepatic fat fraction and fibrosis. FA was correlated with hepatic fat fraction (r = 0.418, P = 0.011) and fibrosis (r = -0.411, P = 0.012). FA may be more sensitive to mild-to-moderate liver fibrosis than ADC. In addition to ADC, FA may also be sensitive to hepatic fat content, and therefore need careful interpretation in liver fibrosis with concomitant fatty liver.

In vivo DTI longitudinal measurements of acute sciatic nerve traction injury and the association with pathological and functional changes

ObjectiveTo explore the feasibility of longitudinally measuring acute traction injury to the sciatic nerve using 1.5T clinical MRI scanner of diffusion tensor imaging (DTI) and to analyze the associations of the measurements [regarding fractional anisotropy (FA), apparent diffusion coefficient (ADC), eigenvalue (λ|| and λ⊥)] with limb function and pathology. Materials and methodsAcute traction injuries to the sciatic nerve were created in the right hind limbs of 32 New Zealand white rabbits, the left hind limbs were chosen as sham operation nerves. MRI scans were performed at intervals from pre-operation through 8 weeks post-operation follow up. Scanning sequences included T2WI, STIR, and single shot spin echo DTI with single shot EPI acquisition (SE-DTI-SSEPI). Parameters of FA, ADC, axial diffusivity (λ||) and radial diffusivity (λ⊥) were then calculated from the DTI. The limb functions and pathologic changes were evaluated and compared. ResultsDiffusion Tensor Tractography (DTT) only revealed the proximal portion of the injured nerves 1–3 days after traction injury but did not reveal the nerve of the distal and traction portions at all. Nerve fibers of the distal and traction portions were not revealed by DTT until after the 1st week. They were elongated gradually and recovered almost to the normal at 8th week. The value of FA and λ⊥of the injured nerves, which varied in different portions, were significantly different between the traction injury nerves and the sham operation nerves, whereas the value of ADC and λ|| were not significantly different. The curve lines of FA value-time for the proximal, traction and distal portions of the injured nerve correlated well to the functional and pathological changes of the limb affected, while the DTI parameters did not change that much in the sham-operated nerves. ConclusionsDTI obtained on a 1.5T clinical MRI scanner can demonstrate early abnormal changes following traction injury to the sciatic nerve in rabbits. The curve lines of FA-time and λ⊥-time for nerve traction injury are consistent with the pathological and functional changes of the limb affected. DTI may thus be a sensitive and reliable method to evaluate degeneration and regeneration of the nerve after traction injury.

Diffusion Tensor MRI to Assess Damage in Healthy and Dystrophic Skeletal Muscle after Lengthening Contractions

The purpose of this study was to determine if variables calculated from diffusion tensor imaging (DTI) would serve as a reliable marker of damage after a muscle strain injury in dystrophic (mdx) and wild type (WT) mice. Unilateral injury to the tibialis anterior muscle (TA) was induced in vivo by 10 maximal lengthening contractions. High resolution T1- and T2-weighted structural MRI, including T2 mapping and spin echo DTI was acquired on a 7T small animal MRI system. Injury was confirmed by a significant loss of isometric torque (85% in mdx versus 42% in WT). Greater increases in apparent diffusion coefficient (ADC), axial, and radial diffusivity (AD and RD) of the injured muscle were present in the mdx mice versus controls. These changes were paralleled by decreases in fractional anisotropy (FA). Additionally, T2 was increased in the mdx mice, but the spatial extent of the changes was less than those in the DTI parameters. The data suggest that DTI is an accurate indicator of muscle injury, even at early time points where the MR signal changes are dominated by local edema.

Assessment of Skeletal Muscle Damage in Mice using Diffusion Tensor MRI

Diagnosis of acute muscle strains is still typically made based on physical exam and patient history, but muscle injuries can be detected with magnetic resonance imaging (MRI). Conventionally, muscle strains are revealed best by T2-weighted MRI, which optimizes contrast between edema and muscular tissue. PURPOSE: To determine if variables calculated from diffusion tensor imaging (DTI) would serve as an earlier and more sensitive marker of damage after a muscle strain injury in dystrophic (mdx) and control mice. We hypothesize that DTI biomarkers will provide a more informative assessment of muscle injury, and these measures will further elucidate the increased susceptibility to injury of the mdx model. METHODS: Unilateral injury to the tibialis anterior muscle (TA) was induced by 15 maximal lengthening contractions in mdx mice (n=3) and control mice (n=3). High resolution T1 and T2-weighted structural MRI (100μm × 100μm × 750 μm) including T2 mapping and spin echo DTI (150μm × 150μm × 750 μm × 12 directions) were acquired on a 7T MRI system. T2 and diffusion tensor parameters (ie apparent diffusion coefficient [ADC], fractional anisotropy [FA], axial and radial diffusivity [AD and RD]) were calculated at each pixel location. TA imaging was compared to functional changes and HE staining and immunofluorescent labeling of TA cross-sections. RESULTS: Injury was confirmed by a significant loss of isometric torque (85% in mdx vs. 42% in controls). Parameter values were calculated as the percent increase in relation to the contralateral, uninjured TA of each animal. Greater increase in ADC, AD, and RD of the injured muscle was present in the mdx mice vs. controls when compared at proximal, medial, and distal locations of the muscle. These changes were paralleled by decreases in FA. On average, changes in DTI parameters were 1.8× greater in the mdx mice vs. controls. In comparison, changes in T2 did not indicate clear differences between mdx and controls. CONCLUSIONS: These data suggest that DTI may be a better indicator of muscle injury, even at early time points where the MR signal changes are dominated by local edema. Supported by grants from the Muscular Dystrophy association (MDA, grant 4278) and NIH-NIAMS (K01AR053235) to RML

Cerebellar Development in the Preterm Neonate: Effect of Supratentorial Brain Injury

Cerebellar injury has been increasingly recognized as a complication of preterm birth, with decreased cerebellar volumes seen on follow-up neuroimaging. A cohort of 38 preterm newborns, including 14 with two scans, was studied with MRI, including single-shot fast spin-echo diffusion tensor imaging (DTI) sequence specifically to assess the posterior fossa. Early changes in the cerebellum [apparent diffusion coefficient (ADC) and fractional anisotropy (FA)] were assessed and correlated with supratentorial manifestations of injury [intraventricular hemorrhage (IVH) or white matter injury (WMI)]. ADC decreased and FA increased with increasing gestational age in both cerebellar gray and white matter. Severe IVH was associated with increased ADC in the middle cerebellar peduncles and hila of the cerebellar nuclei, decreased ADC in the cerebellar cortex, and decreased FA in all three regions. Changes with WMI were not consistent. Significant developmental changes in water diffusion were seen in cerebellar gray and white matter that were altered in patients with supratentorial IVH. DTI studies may provide an early indicator for cerebellar injury and abnormal cerebellar development in preterm neonates.

Three dimensional myoarchitecture of the human tongue determined in vivo by diffusion tensor imaging with tractography

To study the anatomical relationships involving the intrinsic and extrinsic myofiber populations of the human tongue employing diffusion tensor imaging (DTI) with tractography. Images of the human tongue in vivo were obtained using a twice-refocused spin echo DTI pulse sequence at 1.5 T, isotropic 3 x 3 x 3 mm(3) voxels, b-value 500 seconds/mm(2), and 90 different diffusion sensitizing gradient directions. Multivoxel tracts were generated along the vectors, corresponding to the directions of maximal diffusion in each voxel. The data was visualized using custom fiber tracking software and images compared with known anatomy. DTI tractography depicts the complete three-dimensional (3D) myoarchitecture of the human tongue, specifically demonstrating the geometric relationships between the intrinsic and extrinsic myofiber populations. These results define the manner in which key extrinsic fiber populations merge with the longitudinally-, transversely-, and vertically-aligned intrinsic fibers. The current results display for the first time the use of DTI tractography in vivo to visualize the complete structural anatomy of the human tongue and allow us to consider fundamental structure-function relationships.

Single-shot fast spin-echo diffusion tensor imaging of the lumbar spine at 1.5 and 3 T

Diffusion tensor imaging (DTI) of the lumbar spine could improve diagnostic specificity. The purpose of this work was to determine the feasibility of and to validate DTI with single-shot fast spin-echo (SSFSE) for lumbar intervertebral discs at 1.5 and 3 T. Six normal volunteers were scanned with DTI-SSFSE using an eight- and a three-b-value protocol at 1.5 and 3 T, respectively. Apparent diffusion coefficient (ADC) values were computed and validated based on those obtained at 1.5 T from corresponding diffusion tensor scans using line scan diffusion imaging (LSDI), a technique that has been previously validated for use in the spine. Pearson correlation coefficients for LSDI and DTI-SSFSE ADC values were .88 and .89 for 1.5 and 3 T, respectively, with good quantitative agreement according to the Bland-Altman method. Results indicate that DTI-SSFSE is a candidate as a clinical sequence for obtaining diffusion tensor images of the lumbar intervertebral discs with scan times shorter than 4 min.

Single-shot fast spin-echo diffusion tensor imaging of the brain and spine with head and phased array coils at 1.5 T and 3.0 T.

In this study, we investigated the use of a single-shot fast spin-echo-based sequence to perform diffusion tensor imaging (DTI) with improved anatomic fidelity through the entire brain and the cervical spine. Traditionally, diffusion tensor images have been acquired by single-shot echo-planar imaging (EPI) methods in which large distortions result from magnetic susceptibility effects, especially near air-tissue interfaces. These distortions can be problematic, especially in anterior and inferior portions of the brain, and they also can severely limit applications in the spine. At higher magnetic fields these magnetic susceptibility artifacts are increased. The single-shot fast spin-echo (SSFSE) method used in this study utilizes radiofrequency rephasing in the transverse plane and thus provides diffusion images with negligible distortion even at 3 Tesla. In addition, the SSFSE sequence does not require multiple fast-receivers, which are not available on many magnetic resonance (MR) systems. Phased array coils were used to increase the signal-to-noise ratio of the images, offering a major inherent advantage in diffusion tensor imaging of the spine and brain. The mean diffusion measurements obtained with the SSFSE acquisition were not statistically different (p > 0.05) from EPI-based acquisitions. Compared to routine T(2)-weighted MR images, the DTI-EPI sequence showed up to 20% in elongation of the brain in the anterior-posterior direction on a sagittal image due to magnetic susceptibility distortions, whereas in the DTI-SSFSE, the image distortions were negligible. The diffusion tensor SSFSE method was also able to assess diffusion abnormalities in a brain stem hemorrhage, unaffected by the spatial distortions that limited conventional EPI acquisition.

Study of the effect of CSF suppression on white matter diffusion anisotropy mapping of healthy human brain.

Healthy human brain diffusion anisotropy maps derived from standard spin echo diffusion tensor imaging (DTI) were compared with those using fluid-attenuated inversion recovery (FLAIR) preparation prior to DTI to null the signal from cerebrospinal fluid (CSF). Consistent comparisons entailed development of DTI postprocessing methods, image masking based on fitting quality, and an objective region-of-interest-based method for assessment of white matter extent. FLAIR DTI achieved an extended delineation of major white-matter tracts (genu, splenium, and body of the corpus callosum) close to large CSF-filled spaces (lateral ventricles), but did not affect representation of tracts remote from CSF (internal and external capsules and coronal radiation). This result, which was detectable qualitatively (visual inspection), was verified quantitatively by analyses of the relative anisotropy (RA) distribution over white matter structures for 11 subjects. FLAIR DTI thus suppresses the CSF signal that otherwise masks underlying anisotropic parenchymal tissue through partial volume averaging.