Current Diffusion Tensor Imaging Research Articles

Diffusion Tensor Imaging of Skeletal Muscle Contraction Using Oscillating Gradient Spin Echo.

Diffusion tensor imaging (DTI) measures water diffusion in skeletal muscle tissue and allows for muscle assessment in a broad range of neuromuscular diseases. However, current DTI measurements, typically performed using pulsed gradient spin echo (PGSE) diffusion encoding, are limited to the assessment of non-contracted musculature, therefore providing limited insight into muscle contraction mechanisms and contraction abnormalities. In this study, we propose the use of an oscillating gradient spin echo (OGSE) diffusion encoding strategy for DTI measurements to mitigate the effect of signal voids in contracted muscle and to obtain reliable diffusivity values. Two OGSE sequences with encoding frequencies of 25 and 50 Hz were tested in the lower leg of five healthy volunteers with relaxed musculature and during active dorsiflexion and plantarflexion, and compared with a conventional PGSE approach. A significant reduction of areas of signal voids using OGSE compared with PGSE was observed in the tibialis anterior for the scans obtained in active dorsiflexion and in the soleus during active plantarflexion. The use of PGSE sequences led to unrealistically elevated axial diffusivity values in the tibialis anterior during dorsiflexion and in the soleus during plantarflexion, while the corresponding values obtained using the OGSE sequences were significantly reduced. Similar findings were seen for radial diffusivity, with significantly higher diffusivity measured in plantarflexion in the soleus muscle using the PGSE sequence. Our preliminary results indicate that DTI with OGSE diffusion encoding is feasible in human musculature and allows to quantitatively assess diffusion properties in actively contracting skeletal muscle. OGSE holds great potential to assess microstructural changes occurring in the skeletal muscle during contraction, and for non-invasive assessment of contraction abnormalities in patients with muscle diseases.

Brain Diffusion Tensor Imaging Findings in Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is a type of autoimmune thyroid disease. Diffusion tensor imaging (DTI) can evaluate microstructural brain involvement in various diseases. We aimed to investigate whether there were any DTI differences in patients with HT, and the relationship between DTI values and disease duration time and thyroid peroxidase antibodies (TPOAb) levels. We prospectively included 36 patients with HT (mean age 41.6 ± 13.8 years, range 18-64 years) and 18 age and sex-matched healthy control subjects (mean age 41.6 ± 13.1 years, range 18-63 years). All patients were euthyroid at the time of imaging. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values of 15 distinct neuroanatomical locations were measured and compared. FA values of the patients with HT were lower in cingulum, globus pallidus (GP), cerebellar white matter (CWM) than the control (P = .019, .002, and <.001, respectively). MD values of the CWM in patients were higher than the control (P = .008). AD values of patients with HT were lower in the cingulum, posterior limbs of the internal capsule, GP, and putamen (P = .038, .038, .030, and .045, respectively). RD values of cingulum and CWM in HT were higher than controls (P <.001 and P = .011, respectively). There was a negative relationship between the FA values of PLIC and a positive relationship between the MD values of the corona radiata and TPOAb levels were detected. The current DTI study presented microstructural changes in the neurocognitive-related areas that may be related to accompanying neurological findings in HT.

General psychopathology factor and unresolved-disorganized attachment uniquely correlated to white matter integrity using diffusion tensor imaging

BackgroundA dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a general psychopathology factor (GPF) associated with risk for multiple psychiatric disorders. It is, however, unknown how GPF relates to white matter integrity (WMI). In the current diffusion tensor imaging (DTI) study, we examined how GPF relates to abnormalities in a skeleton representation of white matter tracts, taking into account a trans-diagnostic risk factor: unresolved-disorganized attachment (Ud) resulting from loss or trauma. MethodsUnique associations between GPF, Ud, and WMI were examined in a combined sample of adolescents (N = 63) with childhood sexual abuse-related posttraumatic stress disorder (N = 18), anxiety and depressive disorders (N = 26) and without psychiatric disorder (N = 19). WMI was measured using DTI. Ud was measured using the Adult Attachment Interview. We controlled for puberty stage, gender, age, and IQ. ResultsControlling for GPF, Ud was associated with reduced fractional anisotropy (FA) in the splenium and inferior fronto-occipital fasciculus (IFOF). Controlling for Ud, GPF was associated with reduced FA in the genu and body of the corpus callosum. ConclusionsDecreasing WMI in the genu and body with increasing psychopathology across diagnoses suggests demyelinization in these areas and may underlie comorbidity and presence of symptoms that transcend psychopathological diagnoses. In contrast, trauma-related WMI reductions in the splenium and IFOF may account for heterogeneity within diagnostic categories as a function of childhood trauma. These findings support the importance of a dimensional approach in addition to traditional diagnostic classifications in clinical research and practice.

A meta-analysis of diffusion tensor imaging of substantia nigra in patients with Parkinson\u2019s disease

Parkinson’s disease (PD) is a common neurodegenerative disease characterized by severe, selective loss of pigmented neurons in the substantial nigra (SN). Previous studies have indicated that such loss could be detected by diffusion tensor imaging (DTI). Here, we try to consolidate current DTI data to both quantitatively determine the imaging changes in SN, as well as explore the potential use of DTI for PD diagnosis. Fourteen research articles are included in this meta-analysis, each obtained by searching PubMed, EMBASE, or Cochrane library database dated until July 2017. The articles contain 14 trials with 298 total PD patients and 283 healthy controls (HCs). The results show not only significantly lower FA values of SN in PD compared to that of HCs (WMD = −0.02, 95% CI = [−0.03, −0.02], p < 0.00001), but also a significantly higher MD in PD compared to HCs (WMD = 0.05, 95% CI = [0.03, 0.07], P < 0.0001). This indicates that the sharp difference detected between PD patients and HCs can be detected by DTI. By further analyzing the heterogeneity, we found that FA measurement of SN could be potentially used as a surrogate, noninvasive diagnostic marker toward PD diagnosis.

WHITE MATTER MICROSTRUCTURAL AND EXTRACELLULAR FREE-WATER CHANGES ASSOCIATED WITH COGNITION IN AMNESTIC MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE

Alzheimer's Disease (AD) and amnestic Mild Cognitive Impairment (aMCI) are associated with white matter (WM) microstructure abnormalities revealed by diffusion tensor imaging (DTI) methods (Acosta-Cabronero et al., 2010). However, the current DTI model suffers from partial volume effects, therefore preventing accurate quantification of WM abnormalities and their roles in cognitive deficits in the prodromal and clinical stages of AD (Metzler-Baddeley et al., 2012). Free-water (FW) imaging method can resolve this problem by differentiating the water compartment in the extracellular space from tissue in a voxel-based manner (Pasternak et al., 2009). We hypothesized that aMCI would have widespread FW increase and temporal WM microstructural damage whereas AD would have further deterioration. Moreover, we sought to investigate the association of FW increases and WM microstructural changes with memory impairment. 39 healthy controls (HC), 41 aMCI, and 36 AD patients underwent MR imaging (Siemens Tim Trio, 3T). The FW method was applied to derive individual FW and tissue compartment fractional anisotropy (FAT) maps. To assess group differences, we carried out voxel-wise statistical analyses on the FW and FAT images using two-sample t-tests. To assess region-specific WM changes underlying cognitive decline across aMCI and AD subjects, we built voxel-wise general linear models (GLM) with the skeletonized FW/DTI indices as the dependent variable, visual/verbal memory performance z-scores as the independent variables. All analyses were controlled for age, gender, handedness, and ethnicity. aMCI had widespread FW increases compared to HC. FW was further increased in AD compared with aMCI (Fig. 1A & C). Moreover, aMCI only had focal FAT reductions in frontal, hippocampal-temporal regions. FAT was further reduced in frontal, parietal, and occipital regions in AD (Fig. 1B & D). More importantly, visual/verbal memory impairment in aMCI and AD patients were associated with FW increases in several WM regions, but not in the body of the fornix. In contrast, visual/verbal memory decline was associated with FAT reductions in the body of the fornix (Fig. 2). Our findings suggest that FW correction isolates vascular damage from WM microstructural alterations and characterize their differential contributions to cognitive impairment in AD. Increased free-water (FW) and reduced tissue compartment fractional anisotropy (FAT) alone AD progression. (A) aMCI had widespread FW increase than HC. The FW level further increased when they reached the AD stage. White matter skeleton is highlighted in green color. (B) FAT reduced in frontal, mid-temporal and parietal regions in aMCI. Then, it further reduced in frontal and occipital parts in AD stage. All results are reported at the threshold of p < 0.05, TFCE and FWE corrected. (C) Mean FW (derived from group difference mask) increase in AD progression (D) Mean FAT (derived from group difference mask) reduce in AD progression. ‘**’ indicates p<0.05. Free-water (FW) increase and tissue compartment fractional anisotropy (FAT) deterioration correlated with verbal memory deficits. (A) Whole-brain voxel-wise linear regression indicated that increased FW values in widespread brain regions were associated with worse verbal memory. (B) Region-specific FAT reduce was associated with verbal memory deficits only in the body of fornix. White matter skeleton is highlighted in green color. All results are reported at the threshold of p < 0.05, TFCE and FWE corrected.

MO-FG-CAMPUS-IeP3-04: Evaluation of Reproducibility of Diffusion Tensor Imaging Metrics Using Automatically Generated Regions of Interest

Purpose: To establish diffusion tensor imaging (DTI) as a valid diagnostic tool, it is essential to first establish the reproducibility of DTI metrics, such as fractional anisotropy (FA) and mean diffusivity (MD). In this study, we developed two fully automated pipelines for obtaining FA and MD in multiple ROIs, and used them to evaluate intra- and inter-session reproducibility. Methods: Twenty subjects were scanned at 3.0T in two identical sessions separated by 1 week. During each session, the subjects were scanned twice with identical protocols, which comprised a 3D T1 anatomical scan and a DTI scan of 7 minutes. Two pipelines were developed for image analysis. In the first approach, DTI images were linearly registered to anatomical images, which were then non-linearly registered to the MNI152 brain template. And DTI tensor fitting was performed in the MNI152 space. In the second pipeline, the tensor fitting was performed in the native space and the resulting FA maps were non-linearly registered to the FMRIB58 FA template. The reproducibility of FA and MD were evaluated for 48 white matter ROIs using coefficients of variation (CV) and intraclass correlation coefficients (ICC). Results: The second pipeline was found to have higher reproducibility, with 85% of ROIs having inter-session CV =0.82 for FA and >=0.79 for MD. Large variations were only found in small or narrow ROIs which are more prone to partial volume effect and misalignment. Most ROIs had higher inter-session CV than intra-session CV, though the difference was not statistically significant. Conclusion: Our results indicate that current DTI technology can achieve high enough reproducibility for many clinical applications, and that a fully automated image registration pipeline can be a valid and efficient approach for extracting FA and MD information from a large number of ROIs.

The influence of comorbid oppositional defiant disorder on white matter microstructure in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are highly comorbid disorders. ADHD has been associated with altered white matter (WM) microstructure, though the literature is inconsistent, which may be due to differences in the in- or exclusion of participants with comorbid ODD. WM abnormalities in ODD are still poorly understood, and it is unclear whether comorbid ODD in ADHD may have confounded the current ADHD literature. Diffusion Tensor Imaging (DTI) was used to compare fractional anisotropy (FA) and mean diffusivity (MD) between ADHD patients with (n = 42) and without (n = 117) comorbid ODD. All participants were between 8–25 years and groups did not differ in mean age or gender. Follow-up analyses were conducted to examine the role of antisocial behaviour (conduct problems) on FA and MD values in both groups. Comorbid ODD in ADHD was associated with lower FA in left frontotemporal WM, which appeared independent of ADHD symptoms. FA was negatively associated with antisocial behaviour in ADHD + ODD, but not in ADHD-only. Comorbid ODD is associated with WM abnormalities in individuals with ADHD, which appears to be independent of ADHD symptoms. Altered WM microstructure in comorbid ODD may play a role in inconsistencies in the current DTI literature in ADHD. Altered development of these tracts may contribute to social-emotional and cognitive problems in children with oppositional and antisocial behaviour.

Statistically-driven 3D fiber reconstruction and denoising from multi-slice cardiac DTI using a Markov random field model.

The construction of subject-specific dense and realistic 3D meshes of the myocardial fibers is an important pre-requisite for the simulation of cardiac electrophysiology and mechanics. Current diffusion tensor imaging (DTI) techniques, however, provide only a sparse sampling of the 3D cardiac anatomy based on a limited number of 2D image slices. Moreover, heart motion affects the diffusion measurements, thus resulting in a significant amount of noisy fibers. This paper presents a Markov random field (MRF) approach for dense reconstruction of 3D cardiac fiber orientations from sparse DTI 2D slices. In the proposed MRF model, statistical constraints are used to relate the missing and the known fibers, while a consistency term is encoded to ensure that the obtained 3D meshes are locally continuous. The validation of the method using both synthetic and real DTI datasets demonstrates robust fiber reconstruction and denoising, as well as physiologically meaningful estimations of cardiac electrical activation.

Contralateral interictal spikes are related to tapetum damage in left temporal lobe epilepsy.

In temporal lobe epilepsy (TLE), the epileptogenic focus is focal and unilateral in the majority of patients. A key characteristic of focal TLE is the presence of subclinical epileptiform activity in both the ictal and contralateral "healthy" hemisphere. Such interictal activity is clinically important, as it may reflect the spread of pathology, potentially leading to secondary epileptogenesis. The role played by white matter pathways in this process is unknown. We compared three interhemispheric white matter tracts (anterior commissure, fornix, and tapetum) to determine the pathway most associated with the presence of contralateral interictal spikes. Forty patients with unilateral left or right TLE were categorized based on the presence or absence of contralateral interictal spikes. Analyses of variance (ANOVAs) were run on diffusion properties from each tract. The analyses revealed that patients with left TLE and with bilateral interictal spikes had lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the tapetum. Patients with right TLE did not show this effect. No significant associations with bilateral activity were observed for the other tracts. Blood oxygen level-dependent (BOLD) functional connectivity data revealed that homotopic lateral, not mesial, temporal areas were reliably correlated in bilateral patients, independent of ictal side. Our results indicate that, among the tracts investigated, only the tapetum was associated with contralateral epileptiform activity, implicating this structure in seizures and possible secondary epileptogenesis. We describe two mechanisms that might explain this association (the interruption of inhibitory signals or the toxic effect of carrying epileptiform signals toward the healthy hemisphere), but also acknowledge other rival factors that may be at work. We also report that patients with TLE with bilateral spikes had increased lateral bitemporal lobe connectivity. Our current results can be seen as bringing together important functional and structural data to elucidate the basis of contralateral interictal activity in focal, unilateral epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Fronto-limbic microstructure and structural connectivity in remission from major depression

Previous research has suggested that abnormalities within the amygdala and prefrontal cortex (PFC) may underlie major depressive disorder (MDD). The contribution of microstructural alterations within these regions in adult MDD is still equivocal. Therefore, seventeen middle-aged medication-free remitted MDD patients and 21 matched never-depressed control subjects underwent structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Despite comparable amygdala volumes, remitted MDD patients revealed decreased mean diffusivity (MD) and increased fractional anisotropy (FA) within the left amygdala, which may be interpreted as greater cell density and increased number of fibers, respectively. This last notion was supported by probabilistic tractography results, which revealed increased connectivity from the left amygdala to the hippocampus, the cerebellum and the brain stem. Further, altered microstructure as indicated by increased MD possibly reflecting decreased cell density within the medial PFC (mPFC) was found. Taken together, the current DTI study shows that abnormal microstructure and connectivity of the amygdala and mPFC might be key factors in the pathophysiology of MDD that may account for functional changes.

Transmural heterogeneity of left ventricular myocardium remodeling in postinfarct porcine model revealed by MR diffusion tensor imaging

To investigate the transmural heterogeneity of left ventricular myocardium structural remodeling. Ex vivo diffusion tensor imaging (DTI) was performed in six adult porcine heart samples with apical septum infarction collected 13 weeks after permanent left anterior descending coronary artery ligation and six age-matched intact controls. Alterations in diffusion indices and myocardial fiber orientation, including fractional anisotropy (FA), mean apparent diffusion coefficient (mean ADC), axial diffusivity (λ(∥) ), radial diffusivity (λ(⟂) ), and fiber helix angle were investigated at five transmural zones across myocardium wall in regions adjacent and remote to the infarct. In both adjacent and remote regions of infarcted hearts, FA showed no significant alteration across transmural zones compared to controls. However, mean ADC, λ(∥) , and λ(⟂) exhibited significant decreases at endocardium zones but not epicardium zones. Moreover, myocardial fiber helix angle shifted towards left-handed orientation at all transmural zones, especially in regions adjacent to the infarct, becoming more aligned with the epicardium fiber orientation. These experimental DTI findings indicate that the endocardium was more vulnerable to infarction, leading to more pronounced microstructural changes during remodeling. The current DTI approach reveals additional information in delineating postinfarct remodeling process, which may provide insights into cardiac mechanics and clinical assessment of cardiac diseases.

Structural disruption of the dorsal cingulum bundle is associated with impaired Stroop performance in patients with schizophrenia

Previous diffusion tensor imaging (DTI) studies have shown structural abnormalities of the cingulum bundle (CB) in patients with schizophrenia. However, regional specificity and functional relevance of the pregenual and dorsal CB subdivisions has not been fully studied. In the current study, 31 patients with schizophrenia and 65 age- and gender-matched healthy subjects underwent DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) in cross sections of dorsal and pregenual CB tractography. To test the hypothesis of region-specific association with neurocognition, all of the patients and 31 controls performed the Stroop task, which is assumed to mainly involve dorsal cingulate function. The verbal memory subscale of Wechsler Memory Scale-Revised and premorbid IQs estimated from the Japanese version of the National Adult Reading Test, which were non-specific to dorsal cingulate function, were also employed as control neurocognitive indices. Significant bilateral FA reductions in the pregenual and dorsal CB, and bilateral MD increases in the dorsal CB were observed in the patients compared with the controls. As predicted, significant associations between DTI measures and neurocognition were found in the schizophrenia group only: double-dissociable correlation between higher MD in the dorsal, not in the pregenual CB, and a longer reaction time in the Stroop task, not verbal memory or premorbid IQs. The current DTI study suggests that structural disruption of the dorsal CB has region-specific functional relevance to selective attention deficits, although structural disruption also exists in the pregenual CB in patients with schizophrenia.

Deterministic and Probabilistic Tractography Based on Complex Fibre Orientation Distributions

We propose an integral concept for tractography to describe crossing and splitting fibre bundles based on the fibre orientation distribution function (ODF) estimated from high angular resolution diffusion imaging (HARDI). We show that in order to perform accurate probabilistic tractography, one needs to use a fibre ODF estimation and not the diffusion ODF. We use a new fibre ODF estimation obtained from a sharpening deconvolution transform (SDT) of the diffusion ODF reconstructed from q-ball imaging (QBI). This SDT provides new insight into the relationship between the HARDI signal, the diffusion ODF, and the fibre ODF. We demonstrate that the SDT agrees with classical spherical deconvolution and improves the angular resolution of QBI. Another important contribution of this paper is the development of new deterministic and new probabilistic tractography algorithms using the full multidirectional information obtained through use of the fibre ODF. An extensive comparison study is performed on human brain datasets comparing our new deterministic and probabilistic tracking algorithms in complex fibre crossing regions. Finally, as an application of our new probabilistic tracking, we quantify the reconstruction of transcallosal fibres intersecting with the corona radiata and the superior longitudinal fasciculus in a group of eight subjects. Most current diffusion tensor imaging (DTI)-based methods neglect these fibres, which might lead to incorrect interpretations of brain functions.

In vivo diffusion tensor imaging of the human calf muscle

To demonstrate the feasibility of in vivo calf muscle fiber tracking in human subjects. An EPI-based diffusion tensor imaging (DTI) sequence with six-direction diffusion gradient sensitization was implemented, and DT images were acquired at 3 Tesla on five subjects using an extremity coil. The mean diffusivity, fractional anisotropy (FA), and fiber angle (with respect to the magnet z-axis) were measured in different muscles, and fibers were tracked from several regions of interest (ROIs). The fiber orientations in the current DTI studies agree well with those determined in previous spectroscopic studies. The orientation angles ranged from 13.4 degrees in the lateral gastrocnemius to 48.5 degrees in the medial soleus. The diffusion ellipsoid in muscle tissue is anisotropic and approximates a prolate model, as shown by color maps of the anisotropy. Fibers were tracked from the different muscle regions, and the unipennate and bipennate structure of muscle fibers was visualized. The study clearly shows that in vivo fiber tracking of muscle fibers is feasible and could potentially be applied to study muscle structure function relationships.