Publications

2014
Helmer KG, Pasternak O, Fredman E, Preciado RI, Koerte IK, Sasaki T, Mayinger M, Johnson AM, Holmes JD, Forwell LA, et al. Hockey Concussion Education Project, Part 1. Susceptibility-weighted imaging study in male and female ice hockey players over a single season. J Neurosurg. 2014;120 (4) :864-72.Abstract
OBJECT: Concussion, or mild traumatic brain injury (mTBI), is a commonly occurring sports-related injury, especially in contact sports such as hockey. Cerebral microbleeds (CMBs), which appear as small, hypointense lesions on T₂*-weighted images, can result from TBI. The authors use susceptibility-weighted imaging (SWI) to automatically detect small hypointensities that may be subtle signs of chronic and acute damage due to both subconcussive and concussive injury. The goal was to investigate how the burden of these hypointensities changes over time, over a playing season, and postconcussion, in comparison with subjects who did not suffer a medically observed and diagnosed concussion. METHODS: Images were obtained in 45 university-level adult male and female ice hockey players before and after a single Canadian Interuniversity Sports season. In addition, 11 subjects (5 men and 6 women) underwent imaging at 72 hours, 2 weeks, and 2 months after concussion. To identify subtle changes in brain tissue and potential CMBs, nonvessel clusters of hypointensities on SWI were automatically identified, and a hypointensity burden index was calculated for all subjects at the beginning of the season (BOS), the end of the season (EOS), and at postconcussion time points (where applicable). RESULTS: A statistically significant increase in the hypointensity burden, relative to the BOS, was observed for male subjects with concussions at the 2-week postconcussion time point. A smaller, nonsignificant rise in the burden for female subjects with concussions was also observed within the same time period. There were no significant changes in burden for nonconcussed subjects of either sex between the BOS and EOS time points. However, there was a statistically significant difference in the burden between male and female subjects in the nonconcussed group at both the BOS and EOS time points, with males having a higher burden. CONCLUSIONS: This method extends the utility of SWI from the enhancement and detection of larger (> 5 mm) CMBs, which are often observed in more severe cases of TBI, to cases involving smaller lesions in which visual detection of injury is difficult. The hypointensity burden metric proposed here shows statistically significant changes over time in the male subjects. A smaller, nonsignificant increase in the burden metric was observed in the female subjects.
Pasternak O, Koerte IK, Bouix S, Fredman E, Sasaki T, Mayinger M, Helmer KG, Johnson AM, Holmes JD, Forwell LA, et al. Hockey Concussion Education Project, Part 2. Microstructural white matter alterations in acutely concussed ice hockey players: a longitudinal free-water MRI study. J Neurosurg. 2014;120 (4) :873-81.Abstract
OBJECT: Concussion is a common injury in ice hockey and a health problem for the general population. Traumatic axonal injury has been associated with concussions (also referred to as mild traumatic brain injuries), yet the pathological course that leads from injury to recovery or to long-term sequelae is still not known. This study investigated the longitudinal course of concussion by comparing diffusion MRI (dMRI) scans of the brains of ice hockey players before and after a concussion. METHODS: The 2011-2012 Hockey Concussion Education Project followed 45 university-level ice hockey players (both male and female) during a single Canadian Interuniversity Sports season. Of these, 38 players had usable dMRI scans obtained in the preseason. During the season, 11 players suffered a concussion, and 7 of these 11 players had usable dMRI scans that were taken within 72 hours of injury. To analyze the data, the authors performed free-water imaging, which reflects an increase in specificity over other dMRI analysis methods by identifying alterations that occur in the extracellular space compared with those that occur in proximity to cellular tissue in the white matter. They used an individualized approach to identify alterations that are spatially heterogeneous, as is expected in concussions. RESULTS: Paired comparison of the concussed players before and after injury revealed a statistically significant (p < 0.05) common pattern of reduced free-water volume and reduced axial and radial diffusivities following elimination of free-water. These free-water-corrected measures are less affected by partial volumes containing extracellular water and are therefore more specific to processes that occur within the brain tissue. Fractional anisotropy was significantly increased, but this change was no longer significant following the free-water elimination. CONCLUSIONS: Concussion during ice hockey games results in microstructural alterations that are detectable using dMRI. The alterations that the authors found suggest decreased extracellular space and decreased diffusivities in white matter tissue. This finding might be explained by swelling and/or by increased cellularity of glia cells. Even though these findings in and of themselves cannot determine whether the observed microstructural alterations are related to long-term pathology or persistent symptoms, they are important nonetheless because they establish a clearer picture of how the brain responds to concussion.
Sasaki T, Pasternak O, Mayinger M, Muehlmann M, Savadjiev P, Bouix S, Kubicki M, Fredman E, Dahlben B, Helmer KG, et al. Hockey Concussion Education Project, Part 3. White matter microstructure in ice hockey players with a history of concussion: a diffusion tensor imaging study. J Neurosurg. 2014;120 (4) :882-90.Abstract
OBJECT: The aim of this study was to examine the brain's white matter microstructure by using MR diffusion tensor imaging (DTI) in ice hockey players with a history of clinically symptomatic concussion compared with players without a history of concussion. METHODS: Sixteen players with a history of concussion (concussed group; mean age 21.7 ± 1.5 years; 6 female) and 18 players without a history of concussion (nonconcussed group; mean age 21.3 ± 1.8 years, 10 female) underwent 3-T DTI at the end of the 2011-2012 Canadian Interuniversity Sports ice hockey season. Tract-based spatial statistics (TBSS) was used to test for group differences in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and the measure "trace," or mean diffusivity. Cognitive evaluation was performed using the Immediate Postconcussion Assessment and Cognitive Test (ImPACT) and the Sport Concussion Assessment Tool-2 (SCAT2). RESULTS: TBSS revealed a significant increase in FA and AD, and a significant decrease in RD and trace in several brain regions in the concussed group, compared with the nonconcussed group (p < 0.05). The regions with increased FA and decreased RD and trace included the right posterior limb of the internal capsule, the right corona radiata, and the right temporal lobe. Increased AD was observed in a small area in the left corona radiata. The DTI measures correlated with neither the ImPACT nor the SCAT2 scores. CONCLUSIONS: The results of the current study indicate that a history of concussion may result in alterations of the brain's white matter microstructure in ice hockey players. Increased FA based on decreased RD may reflect neuroinflammatory or neuroplastic processes of the brain responding to brain trauma. Future studies are needed that include a longitudinal analysis of the brain's structure and function following a concussion to elucidate further the complex time course of DTI changes and their clinical meaning.
Garlapati RR, Roy A, Joldes GR, Wittek A, Mostayed A, Doyle B, Warfield SK, Kikinis R, Knuckey N, Bunt S, et al. More accurate neuronavigation data provided by biomechanical modeling instead of rigid registration. J Neurosurg. 2014;120 (6) :1477-83.Abstract
It is possible to improve neuronavigation during image-guided surgery by warping the high-quality preoperative brain images so that they correspond with the current intraoperative configuration of the brain. In this paper, the accuracy of registration results obtained using comprehensive biomechanical models is compared with the accuracy of rigid registration, the technology currently available to patients. This comparison allows investigation into whether biomechanical modeling provides good-quality image data for neuronavigation for a larger proportion of patients than rigid registration. Preoperative images for 33 neurosurgery cases were warped onto their respective intraoperative configurations using both the biomechanics-based method and rigid registration. The Hausdorff distance-based evaluation process, which measures the difference between images, was used to quantify the performance of both registration methods. A statistical test for difference in proportions was conducted to evaluate the null hypothesis that the proportion of patients for whom improved neuronavigation can be achieved is the same for rigid and biomechanics-based registration. The null hypothesis was confidently rejected (p < 10(-4)). Even the modified hypothesis that fewer than 25% of patients would benefit from the use of biomechanics-based registration was rejected at a significance level of 5% (p = 0.02). The biomechanics-based method proved particularly effective in cases demonstrating large craniotomy-induced brain deformations. The outcome of this analysis suggests that nonlinear biomechanics-based methods are beneficial to a large proportion of patients and can be considered for use in the operating theater as a possible means of improving neuronavigation and surgical outcomes.
Asami T, Hyuk Lee S, Bouix S, Rathi Y, Whitford TJ, Niznikiewicz M, Nestor P, McCarley RW, Shenton ME, Kubicki M. Cerebral white matter abnormalities and their associations with negative but not positive symptoms of schizophrenia. Psychiatry Res. 2014;222 (1-2) :52-9.Abstract
Although diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) abnormalities in multiple white matter (WM) regions in schizophrenia, relationship between abnormal FA and negative symptoms has not been fully explored. DTI data were acquired from twenty-four patients with chronic schizophrenia and twenty-five healthy controls. Regional brain abnormalities were evaluated by conducting FA comparisons in the cerebral and each lobar WMs between groups. Focal abnormalities were also evaluated with a voxel-wise tract specific method. Associations between structural WM changes and negative symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS). The patient group showed decreased FA in the cerebrum, especially in the frontal lobe, compared with controls. A voxel-wise analysis showed FA decreases in almost all WM tracts in schizophrenia. Correlation analyses demonstrated negative relationships between FA in the cerebrum, particularly in the left hemisphere, and SANS global and global rating scores (Anhedonia-Asociality, Attention, and Affective-Flattening), and also associations between FA of left frontal lobe and SANS global score, Anhedonia-Asociality, and Attention. This study demonstrates that patients with chronic schizophrenia evince widespread cerebral FA abnormalities and that these abnormalities, especially in the left hemisphere, are associated with negative symptoms.
Appia V, Yezzi A, Arepalli C, Faber T, Stillman A, Tannenbaum A. A complete system for automatic extraction of left ventricular myocardium from CT images using shape segmentation and contour evolution. IEEE Trans Image Process. 2014;23 (3) :1340-51.Abstract
The left ventricular myocardium plays a key role in the entire circulation system and an automatic delineation of the myocardium is a prerequisite for most of the subsequent functional analysis. In this paper, we present a complete system for an automatic segmentation of the left ventricular myocardium from cardiac computed tomography (CT) images using the shape information from images to be segmented. The system follows a coarse-to-fine strategy by first localizing the left ventricle and then deforming the myocardial surfaces of the left ventricle to refine the segmentation. In particular, the blood pool of a CT image is extracted and represented as a triangulated surface. Then, the left ventricle is localized as a salient component on this surface using geometric and anatomical characteristics. After that, the myocardial surfaces are initialized from the localization result and evolved by applying forces from the image intensities with a constraint based on the initial myocardial surface locations. The proposed framework has been validated on 34-human and 12-pig CT images, and the robustness and accuracy are demonstrated.
Naaz F, Chariker JH, Pani JR. Computer-Based Learning: Graphical Integration of Whole and Sectional Neuroanatomy Improves Long-Term Retention. Cogn Instr. 2014;32 (1) :44-64.Abstract
A study was conducted to test the hypothesis that instruction with graphically integrated representations of whole and sectional neuroanatomy is especially effective for learning to recognize neural structures in sectional imagery (such as MRI images). Neuroanatomy was taught to two groups of participants using computer graphical models of the human brain. Both groups learned whole anatomy first with a three-dimensional model of the brain. One group then learned sectional anatomy using two-dimensional sectional representations, with the expectation that there would be transfer of learning from whole to sectional anatomy. The second group learned sectional anatomy by moving a virtual cutting plane through the three-dimensional model. In tests of long-term retention of sectional neuroanatomy, the group with graphically integrated representation recognized more neural structures that were known to be challenging to learn. This study demonstrates the use of graphical representation to facilitate a more elaborated (deeper) understanding of complex spatial relations.
Crabb MG, Davidson JL, Little R, Wright P, Morgan AR, Miller CA, Naish JH, Parker GJM, Kikinis R, McCann H, et al. Mutual Information as a Measure of Image Quality for 3-D Dynamic Lung Imaging with EIT. Physiol Meas. 2014;35 (5) :863-79.Abstract
We report on a pilot study of dynamic lung electrical impedance tomography (EIT) at the University of Manchester. Low-noise EIT data at 100 frames per second were obtained from healthy male subjects during controlled breathing, followed by magnetic resonance imaging (MRI) subsequently used for spatial validation of the EIT reconstruction. The torso surface in the MR image and electrode positions obtained using MRI fiducial markers informed the construction of a 3D finite element model extruded along the caudal-distal axis of the subject. Small changes in the boundary that occur during respiration were accounted for by incorporating the sensitivity with respect to boundary shape into a robust temporal difference reconstruction algorithm. EIT and MRI images were co-registered using the open source medical imaging software, 3D Slicer. A quantitative comparison of quality of different EIT reconstructions was achieved through calculation of the mutual information with a lung-segmented MR image. EIT reconstructions using a linear shape correction algorithm reduced boundary image artefacts, yielding better contrast of the lungs, and had 10% greater mutual information compared with a standard linear EIT reconstruction.
Preti MG, Makris N, Papadimitriou G, Laganà MM, Griffanti L, Clerici M, Nemni R, Westin C-F, Baselli G, Baglio F. A Novel Approach of Groupwise fMRI-Guided Tractography Allowing to Characterize the Clinical Evolution of Alzheimer's Disease. PLoS One. 2014;9 (3) :e92026.Abstract
Guiding diffusion tract-based anatomy by functional magnetic resonance imaging (fMRI), we aim to investigate the relationship between structural connectivity and functional activity in the human brain. To this purpose, we introduced a novel groupwise fMRI-guided tractographic approach, that was applied on a population ranging between prodromic and moderate stages of Alzheimer's disease (AD). The study comprised of 15 subjects affected by amnestic mild cognitive impairment (aMCI), 14 diagnosed with AD and 14 elderly healthy adults who were used as controls. By creating representative (ensemble) functionally guided tracts within each group of participants, our methodology highlighted the white matter fiber connections involved in verbal fluency functions for a specific population, and hypothesized on brain compensation mechanisms that potentially counteract or reduce cognitive impairment symptoms in prodromic AD. Our hope is that this fMRI-guided tractographic approach could have potential impact in various clinical studies, while investigating white/gray matter connectivity, in both health and disease.
Lee JW, Norden AD, Ligon KL, Golby AJ, Beroukhim R, Quackenbush J, Wells III WM, Oelschlager K, Maetzold D, Wen PY. Tumor Associated Seizures in Glioblastomas are Influenced by Survival Gene Expression in a Region-specific Manner: A Gene Expression Imaging Study. Epilepsy Res. 2014;108 (5) :843-52.Abstract

Tumor associated seizures (TAS) are common and cause significant morbidity. Both imaging and gene expression features play significant roles in determining TAS, with strong interactions between them. We describe gene expression imaging tools which allow mapping of brain regions where gene expression has significant influence on TAS, and apply these methods to study 77 patients who underwent surgical evaluation for supratentorial glioblastomas. Tumor size and location were measured from MRI scans. A 9-set gene expression profile predicting long-term survivors was obtained from RNA derived from formalin-fixed paraffin embedded tissue. A total of 32 patients (42%) experienced preoperative TAS. Tumor volume was smaller (31.1 vs. 58.8 cubic cm, p<0.001) and there was a trend toward median survival being higher (48.4 vs. 32.7 months, p=0.055) in patients with TAS. Although the expression of only OLIG2 was significantly lower in patients with TAS in a groupwise analysis, gene expression imaging analysis revealed regions with significantly lower expression of OLIG2 and RTN1 in patients with TAS. Gene expression imaging is a powerful technique that demonstrates that the influence of gene expression on TAS is highly region specific. Regional variability should be evaluated with any genomic or molecular markers of solid brain lesions.

Fedorov A, Wells III WM, Kikinis R, Tempany CM, Vangel MG. Application of Tolerance Limits to the Characterization of Image Registration Performance. IEEE Trans Med Imaging. 2014;33 (7) :1541-50.Abstract

Deformable image registration is used increasingly in image-guided interventions and other applications. However, validation and characterization of registration performance remain areas that require further study. We propose an analysis methodology for deriving tolerance limits on the initial conditions for deformable registration that reliably lead to a successful registration. This approach results in a concise summary of the probability of registration failure, while accounting for the variability in the test data. The (β, γ) tolerance limit can be interpreted as a value of the input parameter that leads to successful registration outcome in at least 100β% of cases with the 100γ% confidence. The utility of the methodology is illustrated by summarizing the performance of a deformable registration algorithm evaluated in three different experimental setups of increasing complexity. Our examples are based on clinical data collected during MRI-guided prostate biopsy registered using publicly available deformable registration tool. The results indicate that the proposed methodology can be used to generate concise graphical summaries of the experiments, as well as a probabilistic estimate of the registration outcome for a future sample. Its use may facilitate improved objective assessment, comparison and retrospective stress-testing of deformable.

Woolgar A, Golland P, Bode S. Coping With Confounds in Multivoxel Pattern Analysis: What Should We Do About Reaction Time Differences? A Comment On Todd, Nystrom & Cohen 2013. Neuroimage. 2014;98 :506-12.Abstract
Multivoxel pattern analysis (MVPA) is a sensitive and increasingly popular method for examining differences between neural activation patterns that cannot be detected using classical mass-univariate analysis. Recently, Todd et al. ("Confounds in multivariate pattern analysis: Theory and rule representation case study", 2013, NeuroImage 77: 157-165) highlighted a potential problem for these methods: high sensitivity to confounds at the level of individual participants due to the use of directionless summary statistics. Unlike traditional mass-univariate analyses where confounding activation differences in opposite directions tend to approximately average out at group level, group level MVPA results may be driven by any activation differences that can be discriminated in individual participants. In Todd et al.'s empirical data, factoring out differences in reaction time (RT) reduced a classifier's ability to distinguish patterns of activation pertaining to two task rules. This raises two significant questions for the field: to what extent have previous multivoxel discriminations in the literature been driven by RT differences, and by what methods should future studies take RT and other confounds into account? We build on the work of Todd et al. and compare two different approaches to remove the effect of RT in MVPA. We show that in our empirical data, in contrast to that of Todd et al., the effect of RT on rule decoding is negligible, and results were not affected by the specific details of RT modelling. We discuss the meaning of and sensitivity for confounds in traditional and multivoxel approaches to fMRI analysis. We observe that the increased sensitivity of MVPA comes at a price of reduced specificity, meaning that these methods in particular call for careful consideration of what differs between our conditions of interest. We conclude that the additional complexity of the experimental design, analysis and interpretation needed for MVPA is still not a reason to favour a less sensitive approach.
Fitzsimmons J, Hamoda HM, Swisher T, Terry D, Rosenberger G, Seidman LJ, Goldstein J, Mesholam-Gately R, Petryshen T, Wojcik J, et al. Diffusion tensor imaging study of the fornix in first episode schizophrenia and in healthy controls. Schizophr Res. 2014;156 (2-3) :157-60.Abstract
BACKGROUND: The fornix is a compact bundle of white matter fibers that project from the hippocampus to the mamillary bodies and septal nuclei. Its association with memory, as well as with symptoms in schizophrenia, has been reported in chronic schizophrenia. The purpose of this study is to determine whether or not fornix abnormalities are evident at the onset of schizophrenia. METHODS: Diffusion tensor imaging (DTI) and DT tractography were used to evaluate the fornix in 21 patients with first episode schizophrenia (16 males/5 females) and 22 healthy controls (13 males/9 females). Groups were matched on age, gender, parental socioeconomic status, education and handedness. Fractional anisotropy (FA), a measure of white matter integrity, radial diffusivity (RD), thought to reflect myelin integrity, trace, a possible marker of atrophy or cell loss, and axial diffusivity (AD), thought to reflect axonal integrity, were averaged over the entire tract extracted by means of DT tractography, and used to investigate fornix abnormalities in first episode schizophrenia compared with healthy controls. RESULTS: Significant group differences were found between first episode patients and controls for FA (p=0.0001), RD (p=0.001) and trace (p=0.006). CONCLUSION: These findings suggest abnormalities in the fornix in the early stages of schizophrenia, and further suggest that white matter abnormalities, which are apparent in the early course of the disease, may reflect myelin disturbances.
Liu S, Cai W, Wen L, Feng DD, Pujol S, Kikinis R, Fulham MJ, Eberl S. Multi-Channel neurodegenerative pattern analysis and its application in Alzheimer's disease characterization. Comput Med Imaging Graph. 2014;38 (6) :436-44.Abstract
Neuroimaging has played an important role in non-invasive diagnosis and differentiation of neurodegenerative disorders, such as Alzheimer's disease and Mild Cognitive Impairment. Various features have been extracted from the neuroimaging data to characterize the disorders, and these features can be roughly divided into global and local features. Recent studies show a tendency of using local features in disease characterization, since they are capable of identifying the subtle disease-specific patterns associated with the effects of the disease on human brain. However, problems arise if the neuroimaging database involved multiple disorders or progressive disorders, as disorders of different types or at different progressive stages might exhibit different degenerative patterns. It is difficult for the researchers to reach consensus on what brain regions could effectively distinguish multiple disorders or multiple progression stages. In this study we proposed a Multi-Channel pattern analysis approach to identify the most discriminative local brain metabolism features for neurodegenerative disorder characterization. We compared our method to global methods and other pattern analysis methods based on clinical expertise or statistics tests. The preliminary results suggested that the proposed Multi-Channel pattern analysis method outperformed other approaches in Alzheimer's disease characterization, and meanwhile provided important insights into the underlying pathology of Alzheimer's disease and Mild Cognitive Impairment.
Rathi Y, Michailovich O, Laun F, Setsompop K, Grant PE, Westin C-F. Multi-shell Diffusion Signal Recovery from Sparse Measurements. Med Image Anal. 2014;18 (7) :1143-56.Abstract
For accurate estimation of the ensemble average diffusion propagator (EAP), traditional multi-shell diffusion imaging (MSDI) approaches require acquisition of diffusion signals for a range of b-values. However, this makes the acquisition time too long for several types of patients, making it difficult to use in a clinical setting. In this work, we propose a new method for the reconstruction of diffusion signals in the entire q-space from highly undersampled sets of MSDI data, thus reducing the scan time significantly. In particular, to sparsely represent the diffusion signal over multiple q-shells, we propose a novel extension to the framework of spherical ridgelets by accurately modeling the monotonically decreasing radial component of the diffusion signal. Further, we enforce the reconstructed signal to have smooth spatial regularity in the brain, by minimizing the total variation (TV) norm. We combine these requirements into a novel cost function and derive an optimal solution using the Alternating Directions Method of Multipliers (ADMM) algorithm. We use a physical phantom data set with known fiber crossing angle of 45° to determine the optimal number of measurements (gradient directions and b-values) needed for accurate signal recovery. We compare our technique with a state-of-the-art sparse reconstruction method (i.e., the SHORE method of Cheng et al. (2010)) in terms of angular error in estimating the crossing angle, incorrect number of peaks detected, normalized mean squared error in signal recovery as well as error in estimating the return-to-origin probability (RTOP). Finally, we also demonstrate the behavior of the proposed technique on human in vivo data sets. Based on these experiments, we conclude that using the proposed algorithm, at least 60 measurements (spread over three b-value shells) are needed for proper recovery of MSDI data in the entire q-space.
Ng TS, Lin AP, Koerte IK, Pasternak O, Liao HJ, Merugumala S, Bouix S, Shenton ME. Neuroimaging in repetitive brain trauma. Alzheimers Res Ther. 2014;6 (1) :10.Abstract
Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report.
Parmar C, Rios Velazquez E, Leijenaar R, Jermoumi M, Carvalho S, Mak RH, Mitra S, Shankar UB, Kikinis R, Haibe-Kains B, et al. Robust Radiomics feature quantification using semiautomatic volumetric segmentation. PLoS One. 2014;9 (7) :e102107.Abstract
Due to advances in the acquisition and analysis of medical imaging, it is currently possible to quantify the tumor phenotype. The emerging field of Radiomics addresses this issue by converting medical images into minable data by extracting a large number of quantitative imaging features. One of the main challenges of Radiomics is tumor segmentation. Where manual delineation is time consuming and prone to inter-observer variability, it has been shown that semi-automated approaches are fast and reduce inter-observer variability. In this study, a semiautomatic region growing volumetric segmentation algorithm, implemented in the free and publicly available 3D-Slicer platform, was investigated in terms of its robustness for quantitative imaging feature extraction. Fifty-six 3D-radiomic features, quantifying phenotypic differences based on tumor intensity, shape and texture, were extracted from the computed tomography images of twenty lung cancer patients. These radiomic features were derived from the 3D-tumor volumes defined by three independent observers twice using 3D-Slicer, and compared to manual slice-by-slice delineations of five independent physicians in terms of intra-class correlation coefficient (ICC) and feature range. Radiomic features extracted from 3D-Slicer segmentations had significantly higher reproducibility (ICC = 0.85±0.15, p = 0.0009) compared to the features extracted from the manual segmentations (ICC = 0.77±0.17). Furthermore, we found that features extracted from 3D-Slicer segmentations were more robust, as the range was significantly smaller across observers (p = 3.819e-07), and overlapping with the feature ranges extracted from manual contouring (boundary lower: p = 0.007, higher: p = 5.863e-06). Our results show that 3D-Slicer segmented tumor volumes provide a better alternative to the manual delineation for feature quantification, as they yield more reproducible imaging descriptors. Therefore, 3D-Slicer can be employed for quantitative image feature extraction and image data mining research in large patient cohorts.
Cavallari M, Moscufo N, Meier D, Skudlarski P, Pearlson GD, White WB, Wolfson L, Guttmann CRG. Thalamic fractional anisotropy predicts accrual of cerebral white matter damage in older subjects with small-vessel disease. J Cereb Blood Flow Metab. 2014;34 (8) :1321-7.Abstract
White matter hyperintensities (WMHs) and lacunes are magnetic resonance imaging hallmarks of cerebral small-vessel disease, which increase the risk of stroke, cognitive, and mobility impairment. Although most studies of cerebral small-vessel disease have focused on white matter abnormalities, the gray matter (GM) is also affected, as evidenced by frequently observed lacunes in subcortical GM. Diffusion tensor imaging (DTI) is sensitive to subtle neurodegenerative changes in deep GM structures. We explored the relationship between baseline DTI characteristics of the thalamus, caudate, and putamen, and the volume and subsequent accrual of WMHs over a 4-year period in 56 community-dwelling older (⩾75 years) individuals. Baseline thalamic fractional anisotropy (FA) was an independent predictor of WMH accrual. WMH accrual also correlated with baseline lacune count and baseline WMH volume, the latter showing the strongest predictive power, explaining 27.3% of the variance. The addition of baseline thalamic FA in multivariate modeling increased this value by 70%, which explains 46.5% of the variance in WMH accrual rate. Thalamic FA might serve as a novel predictor of cerebral small-vessel disease progression in clinical settings and trials. Furthermore, our findings point to the possibility of a causal relationship between thalamic damage and the accrual of WMHs.
Huang W, Li X, Chen Y, Li X, Chang M-C, Oborski MJ, Malyarenko DI, Muzi M, Jajamovich GH, Fedorov A, et al. Variations of dynamic contrast-enhanced magnetic resonance imaging in evaluation of breast cancer therapy response: a multicenter data analysis challenge. Transl Oncol. 2014;7 (1) :153-66.Abstract
Pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) time-course data allows estimation of quantitative parameters such as K (trans) (rate constant for plasma/interstitium contrast agent transfer), v e (extravascular extracellular volume fraction), and v p (plasma volume fraction). A plethora of factors in DCE-MRI data acquisition and analysis can affect accuracy and precision of these parameters and, consequently, the utility of quantitative DCE-MRI for assessing therapy response. In this multicenter data analysis challenge, DCE-MRI data acquired at one center from 10 patients with breast cancer before and after the first cycle of neoadjuvant chemotherapy were shared and processed with 12 software tools based on the Tofts model (TM), extended TM, and Shutter-Speed model. Inputs of tumor region of interest definition, pre-contrast T1, and arterial input function were controlled to focus on the variations in parameter value and response prediction capability caused by differences in models and associated algorithms. Considerable parameter variations were observed with the within-subject coefficient of variation (wCV) values for K (trans) and v p being as high as 0.59 and 0.82, respectively. Parameter agreement improved when only algorithms based on the same model were compared, e.g., the K (trans) intraclass correlation coefficient increased to as high as 0.84. Agreement in parameter percentage change was much better than that in absolute parameter value, e.g., the pairwise concordance correlation coefficient improved from 0.047 (for K (trans)) to 0.92 (for K (trans) percentage change) in comparing two TM algorithms. Nearly all algorithms provided good to excellent (univariate logistic regression c-statistic value ranging from 0.8 to 1.0) early prediction of therapy response using the metrics of mean tumor K (trans) and k ep (=K (trans)/v e, intravasation rate constant) after the first therapy cycle and the corresponding percentage changes. The results suggest that the interalgorithm parameter variations are largely systematic, which are not likely to significantly affect the utility of DCE-MRI for assessment of therapy response.
Langs G, Sweet A, Lashkari D, Tie Y, Rigolo L, Golby AJ, Golland P. Decoupling Function and Anatomy in Atlases of Functional Connectivity Patterns: Language Mapping in Tumor Patients. Neuroimage. 2014;103 :462-75.Abstract
In this paper we construct an atlas that summarizes functional connectivity characteristics of a cognitive process from a population of individuals. The atlas encodes functional connectivity structure in a low-dimensional embedding space that is derived from a diffusion process on a graph that represents correlations of fMRI time courses. The functional atlas is decoupled from the anatomical space, and thus can represent functional networks with variable spatial distribution in a population. In practice the atlas is represented by a common prior distribution for the embedded fMRI signals of all subjects. We derive an algorithm for fitting this generative model to the observed data in a population. Our results in a language fMRI study demonstrate that the method identifies coherent and functionally equivalent regions across subjects. The method also successfully maps functional networks from a healthy population used as a training set to individuals whose language networks are affected by tumors.

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