Publications

This work describes a new diffusion MR framework for imaging and modeling of microstructure that we call q-space trajectory imaging (QTI). The QTI framework consists of two parts: encoding and modeling. First we propose q-space trajectory encoding, which uses time-varying gradients to probe a trajectory in q-space, in contrast to traditional pulsed field gradient sequences that attempt to probe a point in q-space. Then we propose a microstructure model, the diffusion tensor distribution (DTD) model, which takes advantage of additional information provided by QTI to estimate a distributional model over diffusion tensors. We show that the QTI framework enables microstructure modeling that is not possible with the traditional pulsed gradient encoding as introduced by Stejskal and Tanner. In our analysis of QTI, we find that the well-known scalar b-value naturally extends to a tensor-valued entity, i.e., a diffusion measurement tensor, which we call the b-tensor. We show that b-tensors of rank 2 or 3 enable estimation of the mean and covariance of the DTD model in terms of a second order tensor (the diffusion tensor) and a fourth order tensor. The QTI framework has been designed to improve discrimination of the sizes, shapes, and orientations of diffusion microenvironments within tissue. We derive rotationally invariant scalar quantities describing intuitive microstructural features including size, shape, and orientation coherence measures. To demonstrate the feasibility of QTI on a clinical scanner, we performed a small pilot study comparing a group of five healthy controls with five patients with schizophrenia. The parameter maps derived from QTI were compared between the groups, and 9 out of the 14 parameters investigated showed differences between groups. The ability to measure and model the distribution of diffusion tensors, rather than a quantity that has already been averaged within a voxel, has the potential to provide a powerful paradigm for the study of complex tissue architecture.

Stejskal and Tanner’s ingenious pulsed field gradient design from 1965 has made diffusion NMR and MRI the mainstay of most studies seeking to resolve microstructural information in porous systems in general and biological systems in particular. Methods extending beyond Stejskal and Tanner’s design, such as double diffusion encoding (DDE) NMR and MRI, may provide novel quantifiable metrics that are less easily inferred from conventional diffusion acquisitions. Despite the growing interest on the topic, the terminology for the pulse sequences, their parameters, and the metrics that can be derived from them remains inconsistent and disparate among groups active in DDE. Here, we present a consensus of those groups on terminology for DDE sequences and associated concepts. Furthermore, the regimes in which DDE metrics appear to provide microstructural information that cannot be achieved using more conventional counterparts (in a model-free fashion) are elucidated. We highlight in particular DDE’s potential for determining microscopic diffusion anisotropy and microscopic fractional anisotropy, which offer metrics of microscopic features independent of orientation dispersion and thus provide information complementary to the standard, macroscopic, fractional anisotropy conventionally obtained by diffusion MR. Finally, we discuss future vistas and perspectives for DDE.

The technique of stray field diffusion NMR is adapted to study the diffusion properties of water in monodisperse wet foams. We show for the first time, that the technique is capable of observing q-space diffusion diffraction peaks in monodisperse aqueous foams with initial bubble sizes in the range of 50-85μm. The position of the peak maximum can be correlated simply to the bubble size in the foam leading to a technique that can investigate the stability of the foam over time. The diffusion technique, together with supplementary spin-spin relaxation analysis of the diffusion data is used to follow the stability and coarsening behaviour of monodisperse foams with a water fraction range between 0.24 and 0.33. The monodisperse foams remain stable for a period of hours in terms of the initial bubble size. The duration of this stable period correlates to the initial size of the bubbles. Eventually the bubbles begin to coarsen and this is observed in changes in the position of the diffusion diffraction maxima.

BACKGROUND: Structural alterations of the lateral temporal cortex (LTC) in association with memory impairments have been reported in schizophrenia. This study investigated whether alterations of LTC structure were linked with impaired facial and/or verbal memory in young first-degree relatives of people with schizophrenia and, thus, may be indicators of vulnerability to the illness. METHODS: Subjects included 27 non-psychotic, first-degree relatives of schizophrenia patients, and 48 healthy controls, between the ages of 13 and 28. Participants underwent high-resolution magnetic resonance imaging (MRI) at 1.5Tesla. The LTC was parcellated into superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, and temporal pole. Total cerebral and LTC volumes were measured using semi-automated morphometry. The Wechsler Memory Scale - Third Edition and the Children’s Memory Scale - Third Edition assessed facial and verbal memory. General linear models tested for associations among LTC subregion volumes, familial risk and memory. RESULTS: Compared with controls, relatives had significantly smaller bilateral middle temporal gyri. Moreover, right middle temporal gyral volume showed a significant positive association with delayed facial memory in relatives. CONCLUSION: These results support the hypothesis that smaller middle temporal gyri are related to the genetic liability to schizophrenia and may be linked with reduced facial memory in persons at genetic risk for the illness. The findings add to the growing evidence that children at risk for schizophrenia on the basis of positive family history have cortical and subcortical structural brain abnormalities well before psychotic illness occurs.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5-3.0] vs. 3.2 [3.0-3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30-0.41] vs. 0.23 [0.21-0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%-5.21%] vs. 4.63% [4.39%-4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.

BACKGROUND: Dystonia, a debilitating movement disorder characterized by abnormal fixed positions and/or twisting postures, is associated with dysfunction of motor control networks. While gross brain lesions can produce secondary dystonias, advanced neuroimaging techniques have been required to identify network abnormalities in primary dystonias. Prior neuroimaging studies have provided valuable insights into the pathophysiology of dystonia, but few directly assessed the gross volume of motor control regions, and to our knowledge, none identified abnormalities common to multiple types of idiopathic focal dystonia.

Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.

Tracing white matter fiber bundles is an integral part of analyzing brain connectivity. An accurate estimate of the underlying tissue parameters is also paramount in several neuroscience applications. In this work, we propose to use a joint fiber model estimation and tractography algorithm that uses the NODDI (neurite orientation dispersion diffusion imaging) model to estimate fiber orientation dispersion consistently and smoothly along the fiber tracts along with estimating the intracellular and extracellular volume fractions from the diffusion signal. While the NODDI model has been used in earlier works to estimate the microstructural parameters at each voxel independently, for the first time, we propose to integrate it into a tractography framework. We extend this framework to estimate the NODDI parameters for two crossing fibers, which is imperative to trace fiber bundles through crossings as well as to estimate the microstructural parameters for each fiber bundle separately. We propose to use the unscented information filter (UIF) to accurately estimate the model parameters and perform tractography. The proposed approach has significant computational performance improvements as well as numerical robustness over the unscented Kalman filter (UKF). Our method not only estimates the confidence in the estimated parameters via the covariance matrix, but also provides the Fisher-information matrix of the state variables (model parameters), which can be quite useful to measure model complexity. Results from in-vivo human brain data sets demonstrate the ability of our algorithm to trace through crossing fiber regions, while estimating orientation dispersion and other biophysical model parameters in a consistent manner along the tracts.

OBJECTIVE: We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity.

Rasagiline is a monoamine oxidase type B inhibitor that possesses no amphetamine-like properties, and provides symptomatic relief in early and late stages of Parkinson’s disease (PD). Data in animal models of PD suggest that chronic administration of rasagiline is associated with structural changes in the substantia nigra, and raise the question whether the structure and function of the basal ganglia could be different in PD patients treated chronically with rasagiline as compared with PD patients not treated with rasagiline. Here, we performed a retrospective cross-sectional magnetic resonance imaging (MRI) study at 3 T that investigated nigrostriatal function and structure in PD patients who had taken rasagiline before testing (\~8 months), PD who had not taken rasagiline before testing, and age-matched controls. The two PD groups were selected a priori to not differ significantly in age, sex, disease duration, severity of symptoms, cognitive status, and total levodopa equivalent daily dose of medication. We evaluated percent signal change in the posterior putamen during force production using functional MRI, free-water in the posterior substantia nigra using diffusion MRI, and performance on a bimanual coordination task using a pegboard test. All patients were tested after overnight withdrawal from antiparkinsonian medication. The rasagiline group had greater percent signal change in the posterior putamen, less free-water in the posterior substantia nigra, and better performance on the coordination task than the group not taking rasagiline. These findings point to a possible chronic effect of rasagiline on the structure and function of the basal ganglia in PD. Hum Brain Mapp 37:2894-2903, 2016. © 2016 Wiley Periodicals, Inc.