Publications

2016

Wang C, Ji F, Hong Z, Poh JS, Krishnan R, Lee J, Rekhi G, Keefe RSE, Adcock RA, Wood SJ, Fornito A, Pasternak O, Chee MW, Zhou J. Disrupted Salience Network Functional Connectivity and White-Matter Microstructure in Persons at Risk For Psychosis: Findings from the LYRIKS Study. Psychol Med. 2016;46(13):2771–83.
BACKGROUND: Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression. METHOD: We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis. RESULTS: ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years. CONCLUSIONS: Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.
Bartling S, Jakab M, Kikinis R. CT-based Atlas of the Ear. 2016.
The Surgical Planning Laboratory at Brigham and Women’s Hospital, Harvard Medical School, developed the SPL Ear Atlas. The atlas was derived from a high-resolution flat-panel computed tomography (CT) scan (aprox 140 µm high contrast resultion), using semi-automated image segmentation and three-dimensional reconstruction techniques [Gupta, Bartling, et al. AJNR Am J Neuroradiol. 2004.]. The current version consists of: 1. the original CT scan; 2. a set of detailed label maps; 3. a set of three-dimensional models of the labeled anatomical structures; 4. mrb (Medical Reality Bundle) file archive that contains the mrml scene file and all data for loading into Slicer 4 for displaying the volumes in 3D Slicer version 4.0 or greater; 5. several pre-defined 3D-views (“anatomy teaching files”). The SPL Ear Atlas provides important reference information for surgical planning, anatomy teaching, and template driven segmentation. Visualization of the data requires 3D Slicer. This software package can be downloaded from here. We are pleased to make this atlas available to our colleagues for free download. Please note that the data is being distributed under the Slicer license. By downloading these data, you agree to acknowledge our contribution in any of your publications that result form the use of this atlas. This work is funded as part of the Neuroimaging Analysis Center, grant number P41 RR013218, by the NIH’s National Center for Research Resources (NCRR) and grant number P41 EB015902, by the NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the Google Faculty Research Award.
Peters TM, Linte CA. Image-guided Interventions and Computer-integrated Therapy: Quo Vadis?. Med Image Anal. 2016;33:56–63.
Significant efforts have been dedicated to minimizing invasiveness associated with surgical interventions, most of which have been possible thanks to the developments in medical imaging, surgical navigation, visualization and display technologies. Image-guided interventions have promised to dramatically change the way therapies are delivered to many organs. However, in spite of the development of many sophisticated technologies over the past two decades, other than some isolated examples of successful implementations, minimally invasive therapy is far from enjoying the wide acceptance once envisioned. This paper provides a large-scale overview of the state-of-the-art developments, identifies several barriers thought to have hampered the wider adoption of image-guided navigation, and suggests areas of research that may potentially advance the field.

2015

Dalca A V, Sridharan R, Sabuncu MR, Golland P. Predictive Modeling of Anatomy with Genetic and Clinical Data. Med Image Comput Comput Assist Interv. 2015;9351:519–26.

We present a semi-parametric generative model for predicting anatomy of a patient in subsequent scans following a single baseline image. Such predictive modeling promises to facilitate novel analyses in both voxel-level studies and longitudinal biomarker evaluation. We capture anatomical change through a combination of population-wide regression and a non-parametric model of the subject’s health based on individual genetic and clinical indicators. In contrast to classical correlation and longitudinal analysis, we focus on predicting new observations from a single subject observation. We demonstrate prediction of follow-up anatomical scans in the ADNI cohort, and illustrate a novel analysis approach that compares a patient’s scans to the predicted subject-specific healthy anatomical trajectory.

Maier-Hein KH, Westin CF, Shenton ME, Weiner MW, Raj A, Thomann P, Kikinis R, Stieltjes B, Pasternak O. Widespread White Matter Degeneration Preceding the Onset of Dementia. Alzheimers Dement. 2015;11(5):485–93.

BACKGROUND: Brain atrophy in subjects with mild cognitive impairment (MCI) introduces partial volume effects, limiting the sensitivity of diffusion tensor imaging to white matter microstructural degeneration. Appropriate correction isolates microstructural effects in MCI that might be precursors of Alzheimer s disease (AD). METHODS: Forty-eight participants (18 MCI, 15 AD, and 15 healthy controls) had magnetic resonance imaging scans and clinical evaluations at baseline and follow-up after 36 months. Ten MCI subjects were diagnosed with AD at follow-up and eight remained MCI. Free-water (FW) corrected measures on the white matter skeleton were compared between groups. RESULTS: FW corrected radial diffusivity, but not uncorrected radial diffusivity, was increased across the brain of the converted group compared with the nonconverted group (P < .05). The extent of increases was similar to that found comparing AD with controls. CONCLUSION: Partial volume elimination reveals microstructural alterations preceding dementia. These alterations may prove to be an effective and feasible early biomarker of AD.

Sjölund J, Szczepankiewicz F, Nilsson M, Topgaard D, Westin CF, Knutsson H. Constrained Optimization of Gradient Waveforms for Generalized Diffusion Encoding. J Magn Reson. 2015;261:157–68.

Diffusion MRI is a useful probe of tissue microstructure. The conventional diffusion encoding sequence, the single pulsed field gradient, has recently been challenged as more general gradient waveforms have been introduced. Out of these, we focus on q-space trajectory imaging, which generalizes the scalar b-value to a tensor valued entity. To take full advantage of its capabilities, it is imperative to respect the constraints imposed by the hardware, while at the same time maximizing the diffusion encoding strength. We provide a tool that achieves this by solving a constrained optimization problem that accommodates constraints on maximum gradient amplitude, slew rate, coil heating and positioning of radio frequency pulses. The method’s efficacy and flexibility is demonstrated both experimentally and by comparison with previous work on optimization of isotropic diffusion sequences.

Wachinger C, Toews M, Langs G, Wells WM III, Golland P. Keypoint Transfer Segmentation. Inf Process Med Imaging. 2015;24:233–45.

We present an image segmentation method that transfers label maps of entire organs from the training images to the novel image to be segmented. The transfer is based on sparse correspondences between keypoints that represent automatically identified distinctive image locations. Our segmentation algorithm consists of three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and (iii) keypoint-based probabilistic transfer of organ label maps. We introduce generative models for the inference of keypoint labels and for image segmentation, where keypoint matches are treated as a latent random variable and are marginalized out as part of the algorithm. We report segmentation results for abdominal organs in whole-body CT and in contrast-enhanced CT images. The accuracy of our method compares favorably to common multi-atlas segmentation while offering a speed-up of about three orders of magnitude. Furthermore, keypoint transfer requires no training phase or registration to an atlas. The algorithm’s robustness enables the segmentation of scans with highly variable field-of-view.

Menze BH, Jakab A, Bauer S, Kalpathy-Cramer J, Farahani K, al. et. The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS). IEEE Trans Med Imaging. 2015;34(10):1993–2024.

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

Langs G, Golland P, Ghosh SS. Predicting Activation Across Individuals with Resting-State Functional Connectivity Based Multi-Atlas Label Fusion. Med Image Comput Comput Assist Interv. 2015;9350:313–20.

The alignment of brain imaging data for functional neuroimaging studies is challenging due to the discrepancy between correspondence of morphology, and equivalence of functional role. In this paper we map functional activation areas across individuals by a multi-atlas label fusion algorithm in a functional space. We learn the manifold of resting-state fMRI signals in each individual, and perform manifold alignment in an embedding space. We then transfer activation predictions from a source population to a target subject via multi-atlas label fusion. The cost function is derived from the aligned manifolds, so that the resulting correspondences are derived based on the similarity of intrinsic connectivity architecture. Experiments show that the resulting label fusion predicts activation evoked by various experiment conditions with higher accuracy than relying on morphological alignment. Interestingly, the distribution of this gain is distributed heterogeneously across the cortex, and across tasks. This offers insights into the relationship between intrinsic connectivity, morphology and task activation. Practically, the mechanism can serve as prior, and provides an avenue to infer task-related activation in individuals for whom only resting data is available.