Publications

Diffusion MRI is a useful tool to investigate the microstructure of brain tumors. However, the presence of fast diffusing isotropic signals originating from non-restricted edematous fluids, within and surrounding tumors, may obscure estimation of the underlying tissue characteristics, complicating the radiological interpretation and quantitative evaluation of diffusion MRI. A multi-shell regularized free water (FW) elimination model was therefore applied to separate free water from tissue-related diffusion components from the diffusion MRI of 26 treatment-na ıve glioma patients. We then investigated the diagnostic value of the derived measures of FW maps as well as FW-corrected tensor-derived maps of fractional anisotropy (FA). Presumed necrotic tumor regions display greater mean and variance of FW content than other parts of the tumor. On average, the area under the receiver operating characteristic (ROC) for the classification of necrotic and enhancing tumor volumes increased by 5% in corrected data compared to non-corrected data. FW elimination shifts the FA distribution in non-enhancing tumor parts toward higher values and significantly increases its entropy (p = 0.003), whereas skewness is decreased (p = 0.004). Kurtosis is significantly decreased (p < 0.001) in high-grade tumors. In conclusion, eliminating FW contributions improved quantitative estimations of FA, which helps to disentangle the cancer heterogeneity.

Conventionally, as a preprocessing step, functional MRI (fMRI) data are spatially smoothed before further analysis, be it for activation mapping on task-based fMRI or functional connectivity analysis on resting-state fMRI data. When images are smoothed volumetrically, however, isotropic Gaussian kernels are generally used, which do not adapt to the underlying brain structure. Alternatively, cortical surface smoothing procedures provide the benefit of adapting the smoothing process to the underlying morphology, but require projecting volumetric data on to the surface. In this paper, leveraging principles from graph signal processing, we propose a volumetric spatial smoothing method that takes advantage of the gray-white and pial cortical surfaces, and as such, adapts the filtering process to the underlying morphological details at each point in the cortex.

Pulmonary hypertension is characterized histologically by intimal and medial thickening in the small pulmonary arteries, eventually resulting in vascular "pruning." Computed tomography (CT)-based quantification of pruning is associated with clinical measures of pulmonary hypertension, but it is not established whether CT-based pruning correlates with histologic arterial remodeling. Our sample consisted of 138 patients who underwent resection for early-stage lung adenocarcinoma. From histologic sections, we identified small pulmonary arteries and measured the relative area comprising the intima and media (VWA%), with higher VWA% representing greater histologic remodeling. From pre-operative CTs, we used image analysis algorithms to calculate the small vessel volume fraction (BV5/TBV) as a CT-based indicator of pruning (lower BV5/TBV represents greater pruning). We investigated relationships of CT pruning and histologic remodeling using Pearson correlation, simple linear regression, and multivariable regression with adjustment for age, sex, height, weight, smoking status, and total pack-years. We also tested for effect modification by sex and smoking status. In primary models, more severe CT pruning was associated with greater histologic remodeling. The Pearson correlation coefficient between BV5/TBV and VWA% was -0.41, and in linear regression models, VWA% was 3.13% higher (95% CI: 1.95-4.31%, p < 0.0001) per standard deviation lower BV5/TBV. This association persisted after multivariable adjustment. We found no evidence that these relationships differed by sex or smoking status. Among individuals who underwent resection for lung adenocarcinoma, more severe CT-based vascular pruning was associated with greater histologic arterial remodeling. These findings suggest CT imaging may be a non-invasive indicator of pulmonary vascular pathology.

Spaceflight induces lasting enlargement of the brain’s ventricles as well as intracranial fluid shifts. These intracranial fluid shifts have been attributed to prolonged microgravity exposure, however, the potential effects of hypergravity exposure during launch and landing have yet to be elucidated. Here we describe a case report of a Crewmember who experienced an Aborted Launch ("CAL"). CAL’s launch and landing experience was dissociated from prolonged microgravity exposure. Using MRI, we show that hypergravity exposure during the aborted launch did not induce lasting ventricular enlargement or intracranial fluid shifts resembling those previously reported with spaceflight. This case study therefore rules out hypergravity during launch and landing as a contributing factor to previously reported long-lasting intracranial fluid changes following spaceflight.

BACKGROUND: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia, but they can also appear in otherwise healthy individuals. Imaging studies implicate language networks in the generation of AVH; however, it remains unclear if alterations reflect biologic substrates of AVH, irrespective of diagnostic status, age, or illness-related factors. We applied multimodal imaging to identify AVH-specific pathology, evidenced by overlapping gray or white matter deficits between schizophrenia patients and healthy voice-hearers. METHODS: Diffusion-weighted and T1-weighted magnetic resonance images were acquired in 35 schizophrenia patients with AVH (SCZ-AVH), 32 healthy voice-hearers (H-AVH), and 40 age- and sex-matched controls without AVH. White matter fractional anisotropy (FA) and gray matter thickness (GMT) were computed for each region comprising ICBM-DTI and Desikan-Killiany atlases, respectively. Regions were tested for significant alterations affecting both SCZ-AVH and H-AVH groups, relative to controls. RESULTS: Compared with controls, the SCZ-AVH showed widespread FA and GMT reductions; but no significant differences emerged between H-AVH and control groups. While no overlapping pathology appeared in the overall study groups, younger (

The fate of subcortical diffusion-weighted imaging (DWI) lesions in stroke patients is highly variable, ranging from complete tissue loss to no visible lesion on follow-up. Little is known about within-lesion heterogeneity and its relevance for stroke outcome. Patients with subcortical stroke and recruited through the prospective DEDEMAS study (NCT01334749) were examined at baseline ( = 45), six months ( = 45), and three years ( = 28) post-stroke. We performed high-resolution structural MRI including DWI. Tissue fate was determined voxel-wise using fully automated tissue segmentation. Within-lesion heterogeneity at baseline was assessed by free water diffusion imaging measures. The majority of DWI lesions (66%) showed cavitation on six months follow-up but the proportion of tissue turning into a cavity was small (9 ± 13.5% of the DWI lesion). On average, 69 ± 25% of the initial lesion resolved without any visually apparent signal abnormality. The extent of cavitation at six months post-stroke was independently associated with clinical outcome, i.e. modified Rankin scale score at six months (OR = 4.71, = 0.005). DWI lesion size and the free water-corrected tissue mean diffusivity at baseline independently predicted cavitation. In conclusion, the proportion of cavitating tissue is typically small, but relevant for clinical outcome. Within-lesion heterogeneity at baseline on advanced diffusion imaging is predictive of tissue fate.

Studies using diffusion tensor imaging (DTI) have documented alterations in the attention and executive system in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). While abnormalities in the frontal lobe have also been reported, the associated white matter fiber bundles have not been investigated comprehensively due to the complexity in tracing them through fiber crossings. Furthermore, most studies have used a non-specific DTI model to understand white matter abnormalities. We present results from a first study that uses a multi-shell diffusion MRI (dMRI) data set coupled with an advanced multi-fiber tractography algorithm to probe microstructural measures related to axonal/cellular density and volume of fronto-striato-thalamic pathways in children with ADHD (N = 30) and healthy controls (N = 28). Head motion was firstly examined as a priority in order to assure that no group difference existed. We investigated 45 different white matter fiber bundles in the brain. After correcting for multiple comparisons, we found lower axonal/cellular packing density and volume in ADHD children in 8 of the 45 fiber bundles, primarily in the right hemisphere as follows: 1) Superior longitudinal fasciculus-II (SLF-II) (right), 2) Thalamus to precentral gyrus (right), 3) Thalamus to superior-frontal gyrus (right), 4) Caudate to medial orbitofrontal gyrus (right), 5) Caudate to precentral gyrus (right), 6) Thalamus to paracentral gyrus (left), 7) Caudate to caudal middlefrontal gyrus (left), and 8) Cingulum (bilateral). Our results demonstrate reduced axonal/cellular density and volume in certain frontal lobe white matter fiber tracts, which sub-serve the attention function and executive control systems. Further, our work shows specific microstructural abnormalities in the striato-thalamo-cortical connections, which have not been previously reported in children with ADHD.

The corticospinal tract (CST) is one of the most well studied tracts in human neuroanatomy. Its clinical significance can be demonstrated in many notable traumatic conditions and diseases such as stroke, spinal cord injury (SCI) or amyotrophic lateral sclerosis (ALS). With the advent of diffusion MRI and tractography the computational representation of the human CST in a 3D model became available. However, the representation of the entire CST and, specifically, the hand motor area has remained elusive. In this paper we propose a novel method, using manually drawn ROIs based on robustly identifiable neuroanatomic structures to delineate the entire CST and isolate its hand motor representation as well as to estimate their variability and generate a database of their volume, length and biophysical parameters. Using 37 healthy human subjects we performed a qualitative and quantitative analysis of the CST and the hand-related motor fiber tracts (HMFTs). Finally, we have created variability heat maps from 37 subjects for both the aforementioned tracts, which could be utilized as a reference for future studies with clinical focus to explore neuropathology in both trauma and disease states.

The long-term neurologic consequences of exposure to repetitive head impacts (RHI) are not well understood. This study used magnetic resonance spectroscopy (MRS) to examine later-life neurochemistry and its association with RHI and clinical function in former National Football League (NFL) players. The sample included 77 symptomatic former NFL players and 23 asymptomatic individuals without a head trauma history. Participants completed cognitive, behavior, and mood measures. N-acetyl aspartate, glutamate/glutamine, choline, myo-inositol, creatine, and glutathione were measured in the posterior (PCG) and anterior (ACG) cingulate gyrus, and parietal white matter (PWM). A cumulative head impact index (CHII) estimated RHI. In former NFL players, a higher CHII correlated with lower PWM creatine (r = -0.23, p = 0.02). Multivariate mixed-effect models examined neurochemical differences between the former NFL players and asymptomatic individuals without a history of head trauma. PWM N-acetyl aspartate was lower among the former NFL players (mean diff. = 1.02, p = 0.03). Between-group analyses are preliminary as groups were recruited based on symptomatic status. The ACG was the only region associated with clinical function, including positive correlations between glutamate (r = 0.32, p = 0.004), glutathione (r = 0.29, p = 0.02), and myo-inositol (r = 0.26, p = 0.01) with behavioral/mood symptoms. Other positive correlations between ACG neurochemistry and clinical function emerged (i.e., behavioral/mood symptoms, cognition), but the positive directionality was unexpected. All analyses controlled for age, body mass index, and education (for analyses examining clinical function). In this sample of symptomatic former NFL players, there was a direct effect between RHI and reduced cellular energy metabolism (i.e., lower creatine). MRS neurochemicals associated with neuroinflammation also correlated with behavioral/mood symptoms.