Publications

2018

Sydnor VJ, Rivas-Grajales AM \ia, Lyall AE, Zhang F, Bouix S, Karmacharya S, Shenton ME, Westin C-F, Makris N, Wassermann D, et al. A comparison of three fiber tract delineation methods and their impact on white matter analysis. Neuroimage. 2018;178:318–331. doi:10.1016/j.neuroimage.2018.05.044
Diffusion magnetic resonance imaging (dMRI) is an important method for studying white matter connectivity in the brain in vivo in both healthy and clinical populations. Improvements in dMRI tractography algorithms, which reconstruct macroscopic three-dimensional white matter fiber pathways, have allowed for methodological advances in the study of white matter; however, insufficient attention has been paid to comparing post-tractography methods that extract white matter fiber tracts of interest from whole-brain tractography. Here we conduct a comparison of three representative and conceptually distinct approaches to fiber tract delineation: 1) a manual multiple region of interest-based approach, 2) an atlas-based approach, and 3) a groupwise fiber clustering approach, by employing methods that exemplify these approaches to delineate the arcuate fasciculus, the middle longitudinal fasciculus, and the uncinate fasciculus in 10 healthy male subjects. We enable qualitative comparisons across methods, conduct quantitative evaluations of tract volume, tract length, mean fractional anisotropy, and true positive and true negative rates, and report measures of intra-method and inter-method agreement. We discuss methodological similarities and differences between the three approaches and the major advantages and drawbacks of each, and review research and clinical contexts for which each method may be most apposite. Emphasis is given to the means by which different white matter fiber tract delineation approaches may systematically produce variable results, despite utilizing the same input tractography and reliance on similar anatomical knowledge.
Merino-Caviedes S, Cordero-Grande L, Perez MT, Casaseca-de-la-Higuera P, Martin-Fernandez M, Deriche R, Alberola-López C. A Second Order Multi-Stencil Fast Marching Method with a Non-Constant Local Cost Model. IEEE Trans Image Process. 2018. doi:10.1109/TIP.2018.2880507
The Fast Marching method is widely employed in several fields of image processing. Some years ago a Multi-Stencil version (MSFM) was introduced to improve its accuracy by solving the equation for a set of stencils and choosing the best solution at each considered node. The following work proposes a modified numerical scheme for MSFM to take into account the variation of the local cost, which has proven to be second order. The influence of the stencil set choice on the algorithm outcome with respect to stencil orthogonality and axis swapping is also explored, where stencils are taken from neighborhoods of varying radius. The experimental results show that the proposed schemes improve the accuracy of their original counterparts, and that the use of permutation-invariant stencil sets provides robustness against shifted vector coordinates in the stencil set.
Yun JH, Lamb A, Chase R, Singh D, Parker MM, Saferali A, Vestbo J, Tal-Singer R, Castaldi PJ, Silverman EK, et al. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141(6):2037–2047. doi:10.1016/j.jaci.2018.04.010
BACKGROUND: Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE: We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD.
Chad JA, Pasternak O, Salat DH, Chen J. Re-examining age-related differences in white matter microstructure with free-water corrected diffusion tensor imaging. Neurobiol Aging. 2018;71:161–170. doi:10.1016/j.neurobiolaging.2018.07.018
Diffusion tensor imaging (DTI) has been used extensively to investigate white matter (WM) microstructural changes during healthy adult aging. However, WM fibers are known to shrink throughout the lifespan, leading to larger interstitial spaces with age. This could allow more extracellular free water molecules to bias DTI metrics, which are relied upon to provide WM microstructural information. Using a cohort of 212 participants, we demonstrate that WM microstructural changes in aging are potentially less pronounced than previously reported once the free water compartment is eliminated. After free water elimination, DTI parameters show age-related differences that match histological evidence of myelin degradation and debris accumulation. The fraction of free water is further shown to associate better with age than any of the conventional DTI parameters. Our findings suggest that DTI analyses involving free water are likely to yield novel insight into retrospective re-analysis of data and to answer new questions in ongoing DTI studies of brain aging.
Jakabek D, Power BD, Macfarlane MD, Walterfang M, Velakoulis D, van Westen D, Lätt J, Nilsson M, Looi JCL, Santillo AF. Regional structural hypo- and hyperconnectivity of frontal-striatal and frontal-thalamic pathways in behavioral variant frontotemporal dementia. Hum Brain Mapp. 2018;39(10):4083–4093. doi:10.1002/hbm.24233
Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal-subcortical connections. We aim to characterize the grey and white matter components of frontal-thalamic and frontal-striatal circuits in bvFTD. Twenty-four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal-striatal-thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p = .032, and 217% in the thalamus, p = .004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p = .002, and 65% in the thalamus, p = .020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal-subcortical networks; however, longitudinal studies are necessary to test this hypothesis.
Ramos-Llordén G, Vegas-Sánchez-Ferrero G, Bjork M, Vanhevel F, Parizel PM, Estepar RSJ, Dekker AJ den, Sijbers J. NOVIFAST: A Fast Algorithm for Accurate and Precise VFA MRI Mapping. IEEE Trans Med Imaging. 2018;37(11):2414–2427. doi:10.1109/TMI.2018.2833288
In quantitative magnetic resonance mapping, the variable flip angle (VFA) steady state spoiled gradient recalled echo (SPGR) imaging technique is popular as it provides a series of high resolution weighted images in a clinically feasible time. Fast, linear methods that estimate maps from these weighted images have been proposed, such as DESPOT1 and iterative re-weighted linear least squares. More accurate, non-linear least squares (NLLS) estimators are in play, but these are generally much slower and require careful initialization. In this paper, we present NOVIFAST, a novel NLLS-based algorithm specifically tailored to VFA SPGR mapping. By exploiting the particular structure of the SPGR model, a computationally efficient, yet accurate and precise map estimator is derived. Simulation and in vivo human brain experiments demonstrate a twenty-fold speed gain of NOVIFAST compared with conventional gradient-based NLLS estimators while maintaining a high precision and accuracy. Moreover, NOVIFAST is eight times faster than the efficient implementations of the variable projection (VARPRO) method. Furthermore, NOVIFAST is shown to be robust against initialization.
Nardelli P, Jimenez-Carretero D, Bermejo-Pelaez D, Washko GR, Rahaghi FN, Ledesma-Carbayo MJ, Estepar RSJ. Pulmonary Artery-Vein Classification in CT Images Using Deep Learning. IEEE Trans Med Imaging. 2018;37(11):2428–2440. doi:10.1109/TMI.2018.2833385
Recent studies show that pulmonary vascular diseases may specifically affect arteries or veins through different physiologic mechanisms. To detect changes in the two vascular trees, physicians manually analyze the chest computed tomography (CT) image of the patients in search of abnormalities. This process is time consuming, difficult to standardize, and thus not feasible for large clinical studies or useful in real-world clinical decision making. Therefore, automatic separation of arteries and veins in CT images is becoming of great interest, as it may help physicians to accurately diagnose pathological conditions. In this paper, we present a novel, fully automatic approach to classify vessels from chest CT images into arteries and veins. The algorithm follows three main steps: first, a scale-space particles segmentation to isolate vessels; then a 3-D convolutional neural network (CNN) to obtain a first classification of vessels; finally, graph-cuts’ optimization to refine the results. To justify the usage of the proposed CNN architecture, we compared different 2-D and 3-D CNNs that may use local information from bronchus- and vessel-enhanced images provided to the network with different strategies. We also compared the proposed CNN approach with a random forests (RFs) classifier. The methodology was trained and evaluated on the superior and inferior lobes of the right lung of 18 clinical cases with noncontrast chest CT scans, in comparison with manual classification. The proposed algorithm achieves an overall accuracy of 94%, which is higher than the accuracy obtained using other CNN architectures and RF. Our method was also validated with contrast-enhanced CT scans of patients with chronic thromboembolic pulmonary hypertension to demonstrate that our model generalizes well to contrast-enhanced modalities. The proposed method outperforms state-of-the-art methods, paving the way for future use of 3-D CNN for artery/vein classification in CT images.
Koppelmans V, Scott JM, Downs ME, Cassady KE, Yuan P, Pasternak O, Wood SJ, De Dios YE, Gadd NE, Kofman I, et al. Exercise effects on bed rest-induced brain changes. PLoS One. 2018;13(10):e0205515. doi:10.1371/journal.pone.0205515
PURPOSE: Spaceflight negatively affects sensorimotor behavior; exercise mitigates some of these effects. Head down tilt bed rest (HDBR) induces body unloading and fluid shifts, and is often used to investigate spaceflight effects. Here, we examined whether exercise mitigates effects of 70 days HDBR on the brain and if fitness and brain changes with HDBR are related.
Nilsson M, Englund E, Szczepankiewicz F, van Westen D, Sundgren PC. Imaging brain tumour microstructure. Neuroimage. 2018;182:232–250. doi:10.1016/j.neuroimage.2018.04.075
Imaging is an indispensable tool for brain tumour diagnosis, surgical planning, and follow-up. Definite diagnosis, however, often demands histopathological analysis of microscopic features of tissue samples, which have to be obtained by invasive means. A non-invasive alternative may be to probe corresponding microscopic tissue characteristics by MRI, or so called ’microstructure imaging’. The promise of microstructure imaging is one of ’virtual biopsy’ with the goal to offset the need for invasive procedures in favour of imaging that can guide pre-surgical planning and can be repeated longitudinally to monitor and predict treatment response. The exploration of such methods is motivated by the striking link between parameters from MRI and tumour histology, for example the correlation between the apparent diffusion coefficient and cellularity. Recent microstructure imaging techniques probe even more subtle and specific features, providing parameters associated to cell shape, size, permeability, and volume distributions. However, the range of scenarios in which these techniques provide reliable imaging biomarkers that can be used to test medical hypotheses or support clinical decisions is yet unknown. Accurate microstructure imaging may moreover require acquisitions that go beyond conventional data acquisition strategies. This review covers a wide range of candidate microstructure imaging methods based on diffusion MRI and relaxometry, and explores advantages, challenges, and potential pitfalls in brain tumour microstructure imaging.
Moutal N, Nilsson M, Topgaard D, Grebenkov D. The Kärger vs bi-exponential model: Theoretical insights and experimental validations. J Magn Reson. 2018;296:72–78. doi:10.1016/j.jmr.2018.08.015
We revise three common models accounting for water exchange in pulsed-gradient spin-echo measurements: a bi-exponential model with time-dependent water fractions, the Kärger model, and a modified Kärger model designed for restricted diffusion, e.g. inside cells. The three models are compared and applied to experimental data from yeast cell suspensions. The Kärger model and the modified Kärger model yield very close results and accurately fit the data. The bi-exponential model, although less rigorous, has a natural physical interpretation and suggests a new experimental modality to estimate the water exchange time.