Faculty Bibliography

A variety of regression schemes have been proposed on images or shapes, although available methods do not handle them jointly. In this paper, we present a framework for joint image and shape regression which incorporates images as well as anatomical shape information in a consistent manner. Evolution is described by a generative model that is the analog of linear regression, which is fully characterized by baseline images and shapes (intercept) and initial momenta vectors (slope). Further, our framework adopts a control point parameterization of deformations, where the dimensionality of the deformation is determined by the complexity of anatomical changes in time rather than the sampling of the image and/or the geometric data. We derive a gradient descent algorithm which simultaneously estimates baseline images and shapes, location of control points, and momenta. Experiments on real medical data demonstrate that our framework effectively combines image and shape information, resulting in improved modeling of 4D (3D space + time) trajectories.

4D pathological anatomy modeling is key to understanding complex pathological brain images. It is a challenging problem due to the difficulties in detecting multiple appearing and disappearing lesions across time points and estimating dynamic changes and deformations between them. We propose a novel semi-supervised method, called 4D active cut, for lesion recognition and deformation estimation. Existing interactive segmentation methods passively wait for user to refine the segmentations which is a difficult task in 3D images that change over time. 4D active cut instead actively selects candidate regions for querying the user, and obtains the most informative user feedback. A user simply answers 'yes' or 'no' to a candidate object without having to refine the segmentation slice by slice. Compared to single-object detection of the existing methods, our method also detects multiple lesions with spatial coherence using Markov random fields constraints. Results show improvement on the lesion detection, which subsequently improves deformation estimation.

Temporal modeling frameworks often operate on scalar variables by summarizing data at initial stages as statistical summaries of the underlying distributions. For instance, DTI analysis often employs summary statistics, like mean, for regions of interest and properties along fiber tracts for population studies and hypothesis testing. This reduction via discarding of variability information may introduce significant errors which propagate through the procedures. We propose a novel framework which uses distribution-valued variables to retain and utilize the local variability information. Classic linear regression is adapted to employ these variables for model estimation. The increased stability and reliability of our proposed method when compared with regression using single-valued statistical summaries, is demonstrated in a validation experiment with synthetic data. Our driving application is the modeling of age-related changes along DTI white matter tracts. Results are shown for the spatiotemporal population trajectory of genu tract estimated from 45 healthy infants and compared with a Krabbe's patient.

Post-acquisition motion correction is widely performed in diffusion-weighted imaging (DWI) to guarantee voxel-wise correspondence between DWIs. Whereas this is primarily motivated to save as many scans as possible if corrupted by motion, users do not fully understand the consequences of different types of interpolation schemes on the final analysis. Nonetheless, interpolation might increase the partial volume effect while not preserving the volume of the diffusion profile, whereas excluding poor DWIs may affect the ability to resolve crossing fibers especially with small separation angles. In this paper, we investigate the effect of interpolating diffusion measurements as well as the elimination of bad directions on the reconstructed fiber orientation diffusion functions and on the estimated fiber orientations. We demonstrate such an effect on synthetic and real HARDI datasets. Our experiments demonstrate that the effect of interpolation is more significant with small fibers separation angles where the exclusion of motion-corrupted directions decreases the ability to resolve such crossing fibers.

Medical imaging studies increasingly use longitudinal images of individual subjects in order to follow-up changes due to development, degeneration, disease progression or efficacy of therapeutic intervention. Repeated image data of individuals are highly correlated, and the strong causality of information over time lead to the development of procedures for joint segmentation of the series of scans, called 4D segmentation. A main aim was improved consistency of quantitative analysis, most often solved via patient-specific atlases. Challenging open problems are contrast changes and occurance of subclasses within tissue as observed in multimodal MRI of infant development, neurodegeneration and disease. This paper proposes a new 4D segmentation framework that enforces continuous dynamic changes of tissue contrast patterns over time as observed in such data. Moreover, our model includes the capability to segment different contrast patterns within a specific tissue class, for example as seen in myelinated and unmyelinated white matter regions in early brain development. Proof of concept is shown with validation on synthetic image data and with 4D segmentation of longitudinal, multimodal pediatric MRI taken at 6, 12 and 24 months of age, but the methodology is generic w.r.t. different application domains using serial imaging.

Understanding the growth patterns of the early brain is crucial to the study of neuro-development. In the early stages of brain growth, a rapid sequence of biophysical and chemical processes take place. A crucial component of these processes, known as myelination, consists of the formation of a myelin sheath around a nerve fiber, enabling the effective transmission of neural impulses. As the brain undergoes myelination, there is a subsequent change in the contrast between gray matter and white matter as observed in MR scans. In this work, gray-white matter contrast is proposed as an effective measure of appearance which is relatively invariant to location, scanner type, and scanning conditions. To validate this, contrast is computed over various cortical regions for an adult human phantom. MR (Magnetic Resonance) images of the phantom were repeatedly generated using different scanners, and at different locations. Contrast displays less variability over changing conditions of scan compared to intensity-based measures, demonstrating that it is less dependent than intensity on external factors. Additionally, contrast is used to analyze longitudinal MR scans of the early brain, belonging to healthy controls and Down's Syndrome (DS) patients. Kernel regression is used to model subject-specific trajectories of contrast changing with time. Trajectories of contrast changing with time, as well as time-based biomarkers extracted from contrast modeling, show large differences between groups. The preliminary applications of contrast based analysis indicate its future potential to reveal new information not covered by conventional volumetric or deformation-based analysis, particularly for distinguishing between normal and abnormal growth patterns.

Diffusion-weighted imaging (DWI) is known to be prone to artifacts related to motion originating from subject movement, cardiac pulsation, and breathing, but also to mechanical issues such as table vibrations. Given the necessity for rigorous quality control and motion correction, users are often left to use simple heuristics to select correction schemes, which involves simple qualitative viewing of the set of DWI data, or the selection of transformation parameter thresholds for detection of motion outliers. The scientific community offers strong theoretical and experimental work on noise reduction and orientation distribution function (ODF) reconstruction techniques for HARDI data, where post-acquisition motion correction is widely performed, e.g., using the open-source DTIprep software (1), FSL (the FMRIB Software Library) (2), or TORTOISE (3). Nonetheless, effects and consequences of the selection of motion correction schemes on the final analysis, and the eventual risk of introducing confounding factors when comparing populations, are much less known and far beyond simple intuitive guessing. Hence, standard users lack clear guidelines and recommendations in practical settings. This paper reports a comprehensive evaluation framework to systematically assess the outcome of different motion correction choices commonly used by the scientific community on different DWI-derived measures. We make use of human brain HARDI data from a well-controlled motion experiment to simulate various degrees of motion corruption and noise contamination. Choices for correction include exclusion/scrubbing or registration of motion corrupted directions with different choices of interpolation, as well as the option of interpolation of all directions. The comparative evaluation is based on a study of the impact of motion correction using four metrics that quantify (1) similarity of fiber orientation distribution functions (fODFs), (2) deviation of local fiber orientations, (3) global brain connectivity via graph diffusion distance (GDD), and (4) the reproducibility of prominent and anatomically defined fiber tracts. Effects of various motion correction choices are systematically explored and illustrated, leading to a general conclusion of discouraging users from setting ad hoc thresholds on the estimated motion parameters beyond which volumes are claimed to be corrupted.

Longitudinal imaging studies involve tracking changes in individuals by repeated image acquisition over time. The goal of these studies is to quantify biological shape variability within and across individuals, and also to distinguish between normal and disease populations. However, data variability is influenced by outside sources such as image acquisition, image calibration, human expert judgment, and limited robustness of segmentation and registration algorithms. In this paper, we propose a two-stage method for the statistical analysis of longitudinal shape. In the first stage, we estimate diffeomorphic shape trajectories for each individual that minimize inconsistencies in segmented shapes across time. This is followed by a longitudinal mixed-effects statistical model in the second stage for testing differences in shape trajectories between groups. We apply our method to a longitudinal database from PREDICT-HD and demonstrate our approach reduces unwanted variability for both shape and derived measures, such as volume. This leads to greater statistical power to distinguish differences in shape trajectory between healthy subjects and subjects with a genetic biomarker for Huntington's disease (HD).

Diffusion tensor imaging has become an important modality in the field of neuroimaging to capture changes in micro-organization and to assess white matter integrity or development. While there exists a number of tractography toolsets, these usually lack tools for preprocessing or to analyze diffusion properties along the fiber tracts. Currently, the field is in critical need of a coherent end-to-end toolset for performing an along-fiber tract analysis, accessible to non-technical neuroimaging researchers. The UNC-Utah NA-MIC DTI framework represents a coherent, open source, end-to-end toolset for atlas fiber tract based DTI analysis encompassing DICOM data conversion, quality control, atlas building, fiber tractography, fiber parameterization, and statistical analysis of diffusion properties. Most steps utilize graphical user interfaces (GUI) to simplify interaction and provide an extensive DTI analysis framework for non-technical researchers/investigators. We illustrate the use of our framework on a small sample, cross sectional neuroimaging study of eight healthy 1-year-old children from the Infant Brain Imaging Study (IBIS) Network. In this limited test study, we illustrate the power of our method by quantifying the diffusion properties at 1 year of age on the genu and splenium fiber tracts.

In the last decade, diffusion MRI (dMRI) studies of the human and animal brain have been used to investigate a multitude of pathologies and drug-related effects in neuroscience research. Study after study identifies white matter (WM) degeneration as a crucial biomarker for all these diseases. The tool of choice for studying WM is dMRI. However, dMRI has inherently low signal-to-noise ratio and its acquisition requires a relatively long scan time; in fact, the high loads required occasionally stress scanner hardware past the point of physical failure. As a result, many types of artifacts implicate the quality of diffusion imagery. Using these complex scans containing artifacts without quality control (QC) can result in considerable error and bias in the subsequent analysis, negatively affecting the results of research studies using them. However, dMRI QC remains an under-recognized issue in the dMRI community as there are no user-friendly tools commonly available to comprehensively address the issue of dMRI QC. As a result, current dMRI studies often perform a poor job at dMRI QC. Thorough QC of dMRI will reduce measurement noise and improve reproducibility, and sensitivity in neuroimaging studies; this will allow researchers to more fully exploit the power of the dMRI technique and will ultimately advance neuroscience. Therefore, in this manuscript, we present our open-source software, DTIPrep, as a unified, user friendly platform for thorough QC of dMRI data. These include artifacts caused by eddy-currents, head motion, bed vibration and pulsation, venetian blind artifacts, as well as slice-wise and gradient-wise intensity inconsistencies. This paper summarizes a basic set of features of DTIPrep described earlier and focuses on newly added capabilities related to directional artifacts and bias analysis.