Diffusion imaging of post-mortem brains could provide valuable data for validation of diffusion tractography of white matter pathways. Long scans (e.g., overnight) may also enable high-resolution diffusion images for visualization of fine structures. However, alterations to post-mortem tissue (T2 and diffusion coefficient) present significant challenges to diffusion imaging with conventional diffusion-weighted spin echo (DW-SE) acquisitions, particularly for imaging human brains on clinical scanners. Diffusion-weighted steady-state free precession (DW-SSFP) has been proposed as an alternative acquisition technique to ameliorate this tradeoff in large-bore clinical scanners. In this study, both DWSE and DW-SSFP are optimized for use in fixed white matter on a clinical 3-Tesla scanner. Signal calculations predict superior performance from DW-SSFP across a broad range of protocols and conditions. DW-SE and DW-SSFP data in a whole, post-mortem human brain are compared for 6- and 12-hour scan durations. Tractography is performed in major projection, commissural and association tracts (corticospinal tract, corpus callosum, superior longitudinal fasciculus and cingulum bundle). The results demonstrate superior tract-tracing from DW-SSFP data, with 6-hour DW-SSFP data performing as well as or better than 12-hour DW-SE scans. These results suggest that DW-SSFP may be a preferred method for diffusion imaging of post-mortem human brains. The ability to estimate multiple fibers in imaging voxels is also demonstrated, again with greater success in DW-SSFP data.
► Comparison of DW-SE and DW-SSFP for post-mortem imaging on clinical scanners. ► Optimization of protocols predicts 50-130% higher SNR efficiency in DW-SSFP. ► Comparison of tractography 6- and 12-hour DW-SE and DW-SSFP scans. ► Lower uncertainty on fibre direction in DW-SSFP produces superior tractography. ► Crossing fibres can be estimated from 12-hour DW-SSFP data.
Diffusion; Tractography; Post mortem; Steady-state free precession; DTI
The choice of imaging parameters for functional MRI can have an impact on the accuracy of functional localization by affecting the image quality and the degree of blood oxygenation-dependent (BOLD) contrast achieved. By improving sampling efficiency, parallel acquisition techniques such as sensitivity encoding (SENSE) have been used to shorten readout trains in single-shot (SS) echo planar imaging (EPI). This has been applied to susceptibility artifact reduction and improving spatial resolution. SENSE together with single-shot spin-echo (SS-SE) imaging may also reduce off-resonance artifacts. The goal of this work was to investigate the BOLD response of a SENSE-adapted SE-EPI on a three Tesla scanner. Whole-brain fMRI studies of seven healthy right hand-dominant volunteers were carried out in a three Tesla scanner. fMRI was performed using an SS-SE EPI sequence with SENSE. The data was processed using statistical parametric mapping. Both, group and individual subject data analyses were performed. Individual average percentage and maximal percentage signal changes attributed to the BOLD effect in M1 were calculated for all the subjects as a function of echo time. Corresponding activation maps and the sizes of the activated clusters were also calculated. Our results show that susceptibility artifacts were reduced with the use of SENSE; and the acquired BOLD images were free of the typical quadrature artifacts of SS-EPI. Such measures are crucial at high field strengths. SS SE-EPI with SENSE offers further benefits in this regard and is more specific for oxygenation changes in the microvasculature bed. Functional brain activity can be investigated with the help of single-shot spin echo EPI using SENSE at high magnetic fields.
Bold-fMRI; parallel imaging; sense; spin-echo echo planar imaging; Tesla
Diffusion tensor imaging (DTI) is widely used to non-invasively study neural tissue micro-structure. While DTI tractography of large nerve fibers is well accepted, visualization of smaller fibers and resolution of branching fibers is challenging. Sensitivity of DTI to diffusion anisotropy can be further enhanced using long diffusion time that can provide a more accurate representation of the tissue micro-structure. We previously reported that ex vivo fixed brain DTI at long tdiff (192 ms) showed improved sensitivity to fiber tracking compared to short tdiff (48 ms) in 4% formalin-fixed non-human primate (NHP) brains. This study further tested the hypothesis that DTI at longer diffusion time improves DTI fiber tracking in the in vivo NHP brains on a clinical 3 Tesla MRI scanner. Compared to fixed brains, the in vivo ADC was larger by a factor of 5. Also, the white-matter FA was 28% higher in the in vivo study as compared to our ex vivo experiments. Compared to short tdiff, long tdiff increased white-matter FA by 6.0±0.5%, diffusion was more anisotropic, tensor orientations along major fiber tracts were more coherent, and tracked fibers were about 10.1±2.9% longer in the corpus callosum and 7.3±2.8% longer along the cortico-spinal tract. The overall improvements in tractography were, however, less pronounced in the in vivo brain than in fixed brains. Nonetheless, these in vivo findings reinforce that DTI tractography at long diffusion time improves tracking of smaller fibers in regions of low fractional anisotropy.
DTI; Fiber tracking; MRI; Fractional anisotropy; Non-human primate; Fixed brain.
Echo planar imaging (EPI) is an MRI technique of particular value to neuroscience, with its use for virtually all functional MRI (fMRI) and diffusion imaging of fiber connections in the human brain. EPI generates a single 2D image in a fraction of a second; however, it requires 2–3 seconds to acquire multi-slice whole brain coverage for fMRI and even longer for diffusion imaging. Here we report on a large reduction in EPI whole brain scan time at 3 and 7 Tesla, without significantly sacrificing spatial resolution, and while gaining functional sensitivity. The multiplexed-EPI (M-EPI) pulse sequence combines two forms of multiplexing: temporal multiplexing (m) utilizing simultaneous echo refocused (SIR) EPI and spatial multiplexing (n) with multibanded RF pulses (MB) to achieve m×n images in an EPI echo train instead of the normal single image. This resulted in an unprecedented reduction in EPI scan time for whole brain fMRI performed at 3 Tesla, permitting TRs of 400 ms and 800 ms compared to a more conventional 2.5 sec TR, and 2–4 times reductions in scan time for HARDI imaging of neuronal fibertracks. The simultaneous SE refocusing of SIR imaging at 7 Tesla advantageously reduced SAR by using fewer RF refocusing pulses and by shifting fat signal out of the image plane so that fat suppression pulses were not required. In preliminary studies of resting state functional networks identified through independent component analysis, the 6-fold higher sampling rate increased the peak functional sensitivity by 60%. The novel M-EPI pulse sequence resulted in a significantly increased temporal resolution for whole brain fMRI, and as such, this new methodology can be used for studying non-stationarity in networks and generally for expanding and enriching the functional information.
Diffusion MRI is a useful imaging technique with many clinical applications. Many diffusion MRI studies have utilized Echo-Planar Imaging (EPI) acquisition techniques. In this study, we have developed a rapid Diffusion Prepared - Fast Imaging with Steady-State Free Precession (DP-FISP) MRI acquisition for a preclinical 7T scanner providing diffusion-weighted images in less than 500 ms and DTI assessments in approximately 1 minute with minimal image artifacts in comparison to EPI. Phantom Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA) assessments obtained from the DP-FISP acquisition resulted in good agreement with EPI and spin echo diffusion methods. The mean ADC was 2.0×10−3 mm2/s, 1.90 ×10−3 mm2/s and 1.97×10−3 mm2/s for DP-FISP, DW-SE and DW-EPI, respectively. The mean FA was 0.073, 0.072, and 0.070 for DP-FISP, DW-SE and DW-EPI, respectively. Initial in vivo studies show reasonable ADC values in a normal mouse brain and polycystic rat kidneys.
diffusion; MRI; FISP; 7T
Diffusion is an important mechanism for molecular transport in living biological tissues. Diffusion magnetic resonance imaging (dMRI) provides a unique probe to examine microscopic structures of the tissues in vivo, but current dMRI techniques usually ignore the spatio-temporal evolution process of the diffusive medium. In the present study, we demonstrate the feasibility to reveal the spatio-temporal diffusion process inside the human brain based on a numerical solution of the diffusion equation. Normal human subjects were scanned with a diffusion tensor imaging (DTI) technique on a 3-Tesla MRI scanner, and the diffusion tensor in each voxel was calculated from the DTI data. The diffusion equation, a partial-derivative description of Fick’s Law for the diffusion process, was discretized into equivalent algebraic equations. A finite-difference method was employed to obtain the numerical solution of the diffusion equation with a Crank-Nicholson iteration scheme to enhance the numerical stability. By specifying boundary and initial conditions, the spatio-temporal evolution of the diffusion process inside the brain can be virtually reconstructed. Our results exhibit similar medium profiles and diffusion coefficients as those of light fluorescence dextrans measured in integrative optical imaging experiments. The proposed method highlights the feasibility to non-invasively estimate the macroscopic diffusive transport time for a molecule in a given region of the brain.
diffusion equation; diffusion tensor imaging (DTI); numerical solution; spatio-temporal process
Magnetic resonance imaging (MRI) is being used to probe the central nervous system (CNS) of patients with multiple sclerosis (MS), a chronic demyelinating disease. Conventional T2-weighted MRI (cMRI) largely fails to predict the degree of patients' disability. This shortcoming may be due to poor specificity of cMRI for clinically relevant pathology. Diffusion tensor imaging (DTI) has shown promise to be more specific for MS pathology. In this study we investigated the association between histological indices of myelin content, axonal count and gliosis, and two measures of DTI (mean diffusivity [MD] and fractional anisotropy [FA]), in unfixed post mortem MS brain using a 1.5-T MR system. Both MD and FA were significantly lower in post mortem MS brain compared to published data acquired in vivo. However, the differences of MD and FA described in vivo between white matter lesions (WMLs) and normal-appearing white matter (NAWM) were retained in this study of post mortem brain: average MD in WMLs was 0.35×10−3 mm2/s (SD, 0.09) versus 0.22 (0.04) in NAWM; FA was 0.22 (0.06) in WMLs versus 0.38 (0.13) in NAWM. Correlations were detected between myelin content (Trmyelin) and (i) FA (r=−0.79, p<0.001), (ii) MD (r=0.68, p<0.001), and (iii) axonal count (r=−0.81, p<0.001). Multiple regression suggested that these correlations largely explain the apparent association of axonal count with (i) FA (r=0.70, p<0.001) and (ii) MD (r=−0.66, p<0.001). In conclusion, this study suggests that FA and MD are affected by myelin content and – to a lesser degree – axonal count in post mortem MS brain.
Magnetic resonance imaging (MRI) is being used to probe the central nervous system (CNS) of patients with multiple sclerosis (MS), a chronic demyelinating disease. Conventional T2-weighted MRI (cMRI) largely fails to predict the degree of patients' disability. This shortcoming may be due to poor specificity of cMRI for clinically relevant pathology. Diffusion tensor imaging (DTI) has shown promise to be more specific for MS pathology. In this study we investigated the association between histological indices of myelin content, axonal count and gliosis, and two measures of DTI (mean diffusivity [MD] and fractional anisotropy [FA]), in unfixed post mortem MS brain using a 1.5-T MR system. Both MD and FA were significantly lower in post mortem MS brain compared to published data acquired in vivo. However, the differences of MD and FA described in vivo between white matter lesions (WMLs) and normal-appearing white matter (NAWM) were retained in this study of post mortem brain: average MD in WMLs was 0.35 × 10− 3 mm2/s (SD, 0.09) versus 0.22 (0.04) in NAWM; FA was 0.22 (0.06) in WMLs versus 0.38 (0.13) in NAWM. Correlations were detected between myelin content (Trmyelin) and (i) FA (r = − 0.79, p < 0.001), (ii) MD (r = 0.68, p < 0.001), and (iii) axonal count (r = − 0.81, p < 0.001). Multiple regression suggested that these correlations largely explain the apparent association of axonal count with (i) FA (r = 0.70, p < 0.001) and (ii) MD (r = − 0.66, p < 0.001). In conclusion, this study suggests that FA and MD are affected by myelin content and – to a lesser degree – axonal count in post mortem MS brain.
The goal of this study was to characterize the effects of pressure-driven brain infusions using high field intra-operative MRI. Understanding these effects is critical for upcoming neurodegeneration and oncology trials using convection-enhanced delivery (CED) to achieve large drug distributions with minimal off-target exposure.
MATERIALS AND METHODS
High-resolution T2-weighted and diffusion-tensor images were acquired serially on a 7 Tesla MRI scanner during six CED infusions in non-human primates. The images were used to evaluate the size, distribution, diffusivity and temporal dynamics of the infusions.
The infusion distribution had high contrast in the T2-weighted images. Diffusion tensor images showed the infusion increased diffusivity, reduced tortuosity and reduced anisotropy. These results suggested CED caused an increase in the extracellular space.
High-field intra-operative MRI can be used to monitor the distribution of infusate and changes in the geometry of the brain’s porous matrix. These techniques could be used to optimize the effectiveness of pressure-driven drug delivery to the brain.
7T MRI; convection-enhanced drug delivery; diffusion; extracellular space; non-human primate
In this work we investigate the effects of echo planar imaging (EPI) distortions on diffusion tensor imaging (DTI) based fiber tractography results. We propose a simple experimental framework that would enable assessing the effects of EPI distortions on the accuracy and reproducibility of fiber tractography from a pilot study on a few subjects. We compare trajectories computed from two diffusion datasets collected on each subject that are identical except for the orientation of phase encode direction, either right–left (RL) or anterior–posterior (AP). We define metrics to assess potential discrepancies between RL and AP trajectories in association, commissural, and projection pathways. Results from measurements on a 3 Tesla clinical scanner indicated that the effects of EPI distortions on computed fiber trajectories are statistically significant and large in magnitude, potentially leading to erroneous inferences about brain connectivity. The correction of EPI distortion using an image-based registration approach showed a significant improvement in tract consistency and accuracy. Although obtained in the context of a DTI experiment, our findings are generally applicable to all EPI-based diffusion MRI tractography investigations, including high angular resolution (HARDI) methods. On the basis of our findings, we recommend adding an EPI distortion correction step to the diffusion MRI processing pipeline if the output is to be used for fiber tractography.
Echo planar imaging; Diffusion tensor imaging; Fiber tractography; Image distortions; Susceptibility
Quantification of non-Gaussianity for water diffusion in brain by means of diffusional kurtosis imaging (DKI) is reviewed. Diffusional non-Gaussianity is a consequence of tissue structure that creates diffusion barriers and compartments. The degree of non-Gaussianity is conveniently quantified by the diffusional kurtosis and derivative metrics, such as the mean, axial, and radial kurtoses. DKI is a diffusion-weighted MRI technique that allows the diffusional kurtosis to be estimated with clinical scanners using standard diffusion-weighted pulse sequences and relatively modest acquisition times. DKI is an extension of the widely used diffusion tensor imaging method, but requires the use of at least 3 b-values and 15 diffusion directions. This review discusses the underlying theory of DKI as well as practical considerations related to data acquisition and post-processing. It is argued that the diffusional kurtosis is sensitive to diffusional heterogeneity and suggested that DKI may be useful for investigating ischemic stroke and neuropathologies, such as Alzheimer’s disease and schizophrenia.
diffusion; non-Gaussian; brain; MRI; kurtosis; DKI; DTI
In this study, a new approach to high-speed fMRI using multi-slab echo-volumar imaging (EVI) is developed that minimizes geometrical image distortion and spatial blurring, and enables nonaliased sampling of physiological signal fluctuation to increase BOLD sensitivity compared to conventional echo-planar imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286 ms temporal resolution (4 mm isotropic voxel size) and partial brain 2-slab EVI with 136 ms temporal resolution (4×4×6 mm3 voxel size) was performed on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain moving average filtering (2 s width) to suppress physiological noise from cardiac and respiratory fluctuations further improved mean (visual: 196%, motor: 140%) and maximum (visual: 384%, motor: 200%) t-scores and increased extents of activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity enhancement, which is attributed to high sampling rate at only moderately reduced temporal signal-to-noise ratio (mean: − 52%) and longer sampling of the BOLD effect in the echo-time domain compared to EPI, was measured in auditory cortex. Two-slab EVI further improved temporal resolution for measuring task-related activation and enabled mapping of five major resting state networks (RSNs) in individual subjects in 5 min scans. The bilateral sensorimotor, the default mode and the occipital RSNs were detectable in time frames as short as 75 s. In conclusion, the high sampling rate of real-time multi-slab EVI significantly improves sensitivity for studying the temporal dynamics of hemodynamic responses and for characterizing functional networks at high field strength in short measurement times.
fMRI; echo-volumar imaging; real-time; temporal resolution; BOLD sensitivity; physiological noise; event related; resting state networks
Diffusion tensor imaging (DTI) is gaining increasing importance for anatomical imaging of the developing mouse brain. However, the application of DTI to mouse brain imaging at microscopic levels is hindered by the limitation on achievable spatial resolution. In this study, fast diffusion tensor microimaging (DTMI) of the mouse brain based on a diffusion-weighted gradient and spin echo (DW-GRASE) technique with twin-navigator echo phase correction is presented. Compared to echo planar and spin echo acquisition, the DW-GRASE acquisition resulted in significant reduction in scan time and had minimal image distortion, thereby allowing acquisition at higher spatial resolution. In this study, three dimensional DTMI of the mouse brains at spatial resolutions of 50 – 60 µm revealed unprecedented anatomical details. Thin fiber bundles in the adult striatum and white matter tracts in the embryonic day 12 mouse brains were visualized for the first time. The study demonstrated that data acquired using the DTMI technique allow three dimensional mapping of gene expression data and can serve as a platform to study gene expression patterns in the context of neuroanatomy in the developing mouse brain.
diffusion tensor imaging; mouse; brain; gene expression mapping
Background and objective
Diffusion tensor (DT) magnetic resonance imaging (MRI) has the potential to disclose subtle abnormalities in the brain of migraine patients. This ability may be increased by the use of high field magnets. A DT MRI on a 3.0 tesla scanner was used to measure the extent of tissue damage of the brain normal appearing white (NAWM) and grey matter in migraine patients with T2 visible abnormalities.
Dual echo, T1 weighted and DT MRI with diffusion gradients applied in 32 non‐collinear directions were acquired from 16 patients with migraine and 15 sex and age matched controls. Lesion load on T2 weighted images was measured using a local thresholding segmentation technique, and brain atrophy assessed on T1 weighted images using SIENAx. Mean diffusivity and fractional anisotropy histograms of the NAWM and mean diffusivity histograms of the grey matter were also derived.
Brain atrophy did not differ between controls and patients. Compared with healthy subjects, migraine patients had significantly reduced mean diffusivity histogram peak height of the grey matter (p = 0.04). No diffusion changes were detected in patients' NAWM. In migraine patients, no correlation was found between T2 weighted lesion load and brain DT histogram derived metrics, whereas age was significantly correlated with grey matter mean diffusivity histogram peak height (p = 0.05, r = −0.52).
DT MRI at high field strength discloses subtle grey matter damage in migraine patients, which might be associated with cognitive changes in these patients.
migraine; grey matter; magnetic resonance imaging; diffusion tensor imaging
An avidly pursued new dimension in magnetic resonance imaging (MRI) research is the acquisition of physiological and biochemical information non-invasively using the nuclear spins of the water molecules in the human body. In this trial, a recent and unique accomplishment was the introduction of the ability to map human brain function non-invasively. Today, functional images with subcentimetre resolution of the entire human brain can be generated in single subjects and in data acquisition times of several minutes using 1.5 tesla (T) MRI scanners that are often used in hospitals for clinical purposes. However, there have been accomplishments beyond this type of imaging using significantly higher magnetic fields such as 4 T. Efforts for developing high magnetic field human brain imaging and functional mapping using MRI (fMRI) were undertaken at about the same time. It has been demonstrated that high magnetic fields result in improved contrast and, more importantly, in elevated sensitivity to capillary level changes coupled to neuronal activity in the blood oxygenation level dependent (BOLD) contrast mechanism used in fMRI. These advantages have been used to generate, for example, high resolution functional maps of ocular dominance columns, retinotopy within the small lateral geniculate nucleus, true single-trial fMRI and early negative signal changes in the temporal evolution of the BOLD signal. So far these have not been duplicated or have been observed as significantly weaker effects at much lower field strengths. Some of these high-field advantages and accomplishments are reviewed in this paper.
High resolution diffusion tensor images of the mouse brain were acquired using the pulsed gradient spin echo (PGSE) sequence and the oscillating gradient spin echo (OGSE) sequence. The OGSE tensor images demonstrated frequency-dependent changes in diffusion measurements, including apparent diffusion coefficient (ADC) and fractional anisotropy (FA), in major brain structures. Maps of the rate of change in ADC with oscillating gradient frequency revealed novel tissue contrast in the mouse hippocampus, cerebellum, and cerebral cortex. The observed frequency-dependent contrasts resembled neuronal soma-specific Nissl staining and nuclei-specific DAPI staining in the mouse brain, which suggests that the contrasts might be related to key features of cytoarchitecture in the brain. In the mouse cuprizone model, OGSE-based diffusion MRI revealed significantly higher frequency-dependence of perpendicular diffusivity (λ┴) in the demyelinated caudal corpus callosum at 4 weeks after cuprizone treatment, compared to control mice and mice at 6 weeks after cuprizone treatment. The elevated frequency-dependence of λ┴ coincided with the infiltration of activated microglia/macrophages and disruption of axons during acute demyelination in the caudal corpus callosum. The results demonstrate the potential of OGSE-based diffusion MRI for providing tissue contrasts complimentary to conventional PGSE-based diffusion MRI.
oscillating gradient; diffusion tensor imaging; mouse brain; cerebellum; hippocampus; microstructure
The developing human brain shows rapid myelination and axonal changes during childhood, adolescence and early adulthood, requiring successive evaluations to determine normative values for potential pathological assessment. Fiber characteristics can be examined by axial and radial diffusivity procedures, which measure water diffusion parallel and perpendicular to axons, and primarily show axonal status and myelin changes, respectively. Such measures are lacking from wide-spread sites for the developing brain. Diffusion tensor imaging data were acquired from 30 healthy subjects (age, 17.7±4.6, range 8–24 years; body-mass-index, 21.5±4.5 kg/m2; 18 male) using a 3.0-Tesla MRI scanner. Diffusion tensors were calculated, principal eigenvalues determined, and axial and radial diffusivity maps calculated and normalized to a common space. A set of regions-of-interest were outlined from wide-spread brain areas within rostral, thalamic, hypothalamic, cerebellar, and pontine regions, and average diffusivity values were calculated using normalized diffusivity maps and these regions-of-interest masks. Age-related changes were assessed with Pearson’s correlations, and gender differences evaluated with Student’s t-tests. Axial and radial diffusivity values declined with age in the majority of brain areas, except for mid hippocampus, where axial diffusivity values correlated positively with age. Gender differences emerged within putamen, thalamic, hypothalamic, cerebellar, limbic, temporal, and other cortical sites. Documentation of normal axial and radial diffusivity values will help assess disease-related tissue changes. Axial and radial diffusivity change with age, with fiber structure and organization differing between sexes in several brain areas. The findings may underlie gender-based functional characteristics, and mandate partitioning age- and gender-related changes during developmental brain pathology evaluation.
Diffusion tensor imaging; Axons; Myelin; Brain maturation; Water diffusion
Both post-mortem and neuroimaging studies have contributed significantly to what we know about the brain and schizophrenia. MRI studies of volumetric reduction in several brain regions in schizophrenia have confirmed early speculations that the brain is disordered in schizophrenia. There is also a growing body of evidence suggesting that a disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, are responsible for the clinical symptoms and cognitive dysfunctions observed in this disorder. Thus an interest in white matter fiber tracts, subserving anatomical connections between distant, as well as proximal, brain regions, is emerging. This interest coincides with the recent advent of diffusion tensor imaging (DTI), which makes it possible to evaluate the organization and coherence of white matter fiber tracts. This is an important advance as conventional MRI techniques are insensitive to fiber tract direction and organization, and have not consistently demonstrated white matter abnormalities. DTI may, therefore, provide important new information about neural circuitry, and it is increasingly being used in neuroimaging studies of psychopathological disorders. Of note, in the past five years 18 DTI studies in schizophrenia have been published, most describing white matter abnormalities. Questions still remain, however, regarding what we are measuring that is abnormal in this disease, and how measures obtained using one method correspond to those obtained using other methods? Below we review the basic principles involved in MR-DTI, followed by a review of the different methods used to evaluate diffusion. Finally, we review MR-DTI findings in schizophrenia.
Diffusion tensor imaging; Schizophrenia; White matter; Fiber tracts
Single-shot EPI is the most common acquisition technique for whole-brain diffusion tensor imaging (DTI) studies in vivo. Higher field MRI systems are readily available and advantageous for acquiring DTI due to increased signal. One of the practical issues for DTI with single-shot EPI at high field is incomplete fat suppression resulting in a chemically-shifted fat artifact within the brain image. Unsuppressed fat is especially detrimental in DTI because the diffusion coefficient of fat is two orders of magnitude lower than that of parenchyma, producing brighter appearing fat artifacts with greater diffusion weighting. In this work, several fat suppression techniques were tested alone and in combination with the goal of finding a method that provides robust fat suppression and can be utilized in high-resolution single-shot EPI DTI studies. Combination of chemical shift saturation with slice-select gradient reversal within a dual-spin-echo diffusion preparation period was found to provide robust fat suppression at 3T.
In vivo neuroimaging methods permit longitudinal quantitative examination of the dynamic course of neurodegenerative conditions in humans and animal models and enable assessment of therapeutic efforts in mitigating disease effects on brain systems. The study of conditions affecting white matter, such as multiple sclerosis, demyelinating conditions, and drug and alcohol dependence, can be accomplished with diffusion tensor imaging (DTI), a technique uniquely capable of probing the microstructural integrity of white matter fibers in the living brain. We used a 3T clinical MR scanner equipped with an insert gradient coil that yields an order of magnitude increase in performance over the whole-body hardware to acquire in vivo DTI images of rat brain. The resolution allowed for fiber tracking evaluation of fractional anisotropy (FA) and apparent diffusion coefficients in the genu and splenium of the corpus callosum. A comparison of short (46 min) and long (92 min) acquisition time DTI protocols indicated low but adequate signal-to-noise ratio (SNR=6.2) of the shorter protocol to conduct quantitative fiber tracking enhanced by multiple acquisitions. As observed in human studies, FA in the rat splenium was higher than in the genu. Advantages of this technology include the use of similar user interface, pulse sequences, and field strength for preclinical animal and clinical human research, enhancing translational capabilities. An additional benefit of scanning at lower field strength, such as 3T, is the reduction of artifacts due to main field inhomogeneity relative to higher field animal systems.
Rationale and Objectives
Both single-shot diffusion-weighted echo-planar imaging (EPI) and line scan diffusion imaging (LSDI) can be used to obtain magnetic resonance diffusion tensor data and to calculate directionally invariant diffusion anisotropy indices, ie, indirect measures of the organization and coherence of white matter fibers in the brain. To date, there has been no comparison of EPI and LSDI. Because EPI is the most commonly used technique for acquiring diffusion tensor data, it is important to understand the limitations and advantages of LSDI relative to EPI.
Materials and Methods
Five healthy volunteers underwent EPI and LSDI diffusion on a 1.5 Tesla magnet (General Electric Medical Systems, Milwaukee, WI). Four-mm thick coronal sections, covering the entire brain, were obtained. In addition, one subject was tested with both sequences over four sessions. For each image voxel, eigenvectors and eigenvalues of the diffusion tensor were calculated, and fractional anisotropy (FA) was derived. Several regions of interest were delineated, and for each, mean FA and estimated mean standard deviation were calculated and compared.
Results showed no significant differences between EPI and LSDI for mean FA for the five subjects. When inter-session reproducibility for one subject was evaluated, there was a significant difference between EPI and LSDI in FA for the corpus callosum and the right uncinate fasciculus. Moreover, errors associated with each FA measure were larger for EPI than for LSDI.
Results indicate that both EPI- and LSDI-derived FA measures are sufficiently robust. However, when higher accuracy is needed, LSDI provides smaller error and smaller inter-subject and inter-session variability than EPI.
Diffusion; single-shot EPI; LSDI; anisotropy
Although animal studies have demonstrated frontal white matter and behavioral changes resulting from prenatal cocaine exposure, no human studies have associated neuropsychological deficits in attention and inhibition with brain structure. We used diffusion tensor imaging to investigate frontal white matter integrity and executive functioning in cocaine-exposed children.
Six direction diffusion tensor images were acquired using a Siemens 3T scanner with a spin-echo echo-planar imaging pulse sequence on right-handed cocaine-exposed (n = 28) and sociodemographically similar non-exposed children (n = 25; mean age: 10.6 years) drawn from a prospective, longitudinal study. Average diffusion and fractional anisotropy were measured in the left and right frontal callosal and frontal projection fibers. Executive functioning was assessed using two well-validated neuropsychological tests (Stroop color-word test and Trail Making Test).
Cocaine-exposed children showed significantly higher average diffusion in the left frontal callosal and right frontal projection fibers. Cocaine-exposed children were also significantly slower on a visual-motor set-shifting task with a trend toward lower scores on a verbal inhibition task. Controlling for gender and intelligence, average diffusion in the left frontal callosal fibers was related to prenatal exposure to alcohol and marijuana and an interaction between cocaine and marijuana exposure. Performance on the visual-motor set-shifting task was related to prenatal cocaine exposure and an interaction between cocaine and tobacco exposure. Significant correlations were found between test performance and fractional anisotropy in areas of the frontal white matter.
Prenatal cocaine exposure, alone and in combination with exposure to other drugs, is associated with slightly poorer executive functioning and subtle microstructural changes suggesting less mature development of frontal white matter pathways. The relative contribution of postnatal environmental factors, including characteristics of the caregiving environment and stressors associated with poverty and out-of-home placement, on brain development and behavioral functioning in polydrug-exposed children awaits further research.
prenatal exposure; cocaine infants; neuroimaging; cognitive function; neuropsychology
Sensitive and specific in vivo measures of axonal damage, an important determinant of clinical status in multiple sclerosis (MS), might greatly benefit prognostication and therapy assessment. Diffusion tensor spectroscopy (DTS) combines features of diffusion tensor imaging and magnetic resonance spectroscopy, allowing measurement of the diffusion properties of intracellular, cell-type-specific metabolites. As such, it may be sensitive to disruption of tissue microstructure within neurons. In this cross-sectional pilot study, diffusion of the neuronal metabolite N-acetylaspartate (NAA) was measured in the human normal appearing corpus callosum on a 7 tesla MRI scanner, comparing 15 MS patients and 14 healthy controls. We found that NAA parallel diffusivity is lower in MS (p=0.030) and inversely correlated with both water parallel diffusivity (p=0.020) and clinical severity (p=0.015). Interpreted in the context of previous experiments, our findings provide preliminary evidence that DTS can distinguish axonopathy from other processes such as inflammation, edema, demyelination, and gliosis. By detecting reduced diffusion of NAA parallel to axons in white matter, DTS may thus be capable of distinguishing axonal disruption in MS in the setting of increased parallel diffusion of water, which is commonly observed in MS but pathologically nonspecific.
Dynamic diffusion MRI was used to visualize hyperacute stroke formation in the brain of a cynomolgus macaque. Under fluoroscopic guidance, a microcatheter was placed into the middle cerebral artery (MCA). The animal was immediately transferred to a 1.5T clinical scanner. Dynamic T2-weighted imaging during bolus injection of Oxygen-17 enriched water through the microcatheter mapped out the territory perfused by the MCA segment. Serial diffusion measurements were made using diffusion-weighted echo-planar imaging, with a temporal resolution of 15 seconds, during injection of a glue embolus into the microcatheter. The apparent diffusion coefficient declined within the lesion core. A wave of transient diffusion decline spread through peripheral uninvolved brain immediately following stroke induction. The propagation speed and pattern is consistent with spreading peri-infarct depolarizations (PID). The detection of PIDs following embolic stroke in a higher nonhuman primate brain supports the hypothesis that spreading depressions may occur following occlusive stroke in humans.
Non-human primates; MCAo; Stroke; Oxygen-17; Cortical spreading depression (CSD); Diffusion MRI.
We present and validate a novel diffusion tensor imaging (DTI) approach for segmenting the human whole-brain into partitions representing grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF). The approach utilizes the contrast among tissue types in the DTI anisotropy vs. diffusivity rotational invariant space. The DTI-based whole-brain GM and WM fractions (GMf and WMf) are contrasted with the fractions obtained from conventional magnetic resonance imaging (cMRI) tissue segmentation (or clustering) methods that utilized dual echo (proton density-weighted (PDw), and spin-spin relaxation-weighted (T2w) contrast, in addition to spin-lattice relaxation weighted (T1w) contrasts acquired in the same imaging session and covering the same volume. In addition to good correspondence with cMRI estimates of brain volume, the DTI-based accurately depicts expected age vs. WM and GM volume-to-total intracranial brain volume percentage trends on the rapidly developing brains of a cohort of 29 children (6–18 years). This approach promises to extend DTI utility to both micro and macrostructural aspects of tissue organization.
DTI; Segmentation; Icosa21; Child Brain Development; Meta Analysis