[Show abstract][Hide abstract] ABSTRACT: Post-mortem studies reveal a high rate of cavum septi pellucidi (CSP) in chronic traumatic encephalopathy (CTE). It remains, however, to be determined whether or not the presence of CSP may be a potential in vivo imaging marker in populations at high risk to develop CTE. The aim of this study was to evaluate CSP in former professional American football players presenting with cognitive and behavioral symptoms compared to non-contact sport athletes. 72 symptomatic former professional football players (mean age 54.53 years, SD 7.97) as well as 14 former professional non-contact sports athletes (mean age 57.14 years, SD 7.35) underwent high-resolution structural 3T magnetic resonance imaging. Two raters independently evaluated the CSP, and interrater reliability was calculated. Within NFL players an association of CSP measures with cognitive and behavioral functioning was evaluated using a multivariate mixed effects model. The measurements of the two raters were highly correlated (CSP length: rho = 0.98; ICC 0.99; p<0.0001; septum length: rho = 0.93; ICC 0.96; p<0.0001). For presence versus absence of CSP, there was high agreement (Cohen's kappa=0.83, p-value<0.0001). A higher rate of CSP, a greater length of CSP as well as a greater ratio of CSP length to septum length was found in symptomatic former professional football players compared to athlete controls. Additionally, a greater length of CSP was associated with decreased performance on a list learning task (NAB List A Immediate Recall, p=0.04) and decreased test scores on a measure of estimate verbal intelligence (WRAT-4 Reading test, p=0.02). Given the high prevalence of CSP in neuropathologically confirmed CTE in addition to the results of this study, CSP may serve as a potential early in vivo imaging marker to identify those at high risk for CTE. Future research is needed to investigate the pathomechanism underlying the development of CSP following repetitive head impacts, and its potential association with neuropathologically confirmed CTE.
Journal of neurotrauma 09/2015; DOI:10.1089/neu.2015.3880 · 3.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Youth football players may incur hundreds of repetitive head impacts (RHI) in one season. Our recent research suggests that exposure to RHI during a critical neurodevelopmental period prior to age 12 may lead to greater later-life mood, behavioral, and cognitive impairments. Here we examine the relationship between age of first exposure (AFE) to RHI through tackle football and later-life corpus callosum (CC) microstructure using magnetic resonance diffusion tensor imaging (DTI). Forty retired National Football League (NFL) players, ages 40-65, were matched by age and divided into two groups based on their AFE to tackle football: before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and seeded using deterministic tractography. Dependent measures were fractional anisotropy (FA), trace, axial diffusivity and radial diffusivity. Results showed that former NFL players in the AFE <12 group had significantly lower FA in anterior three CC regions and higher radial diffusivity in the most anterior CC region than those in the AFE ≥12 group. This is the first study to find a relationship between AFE to RHI and later-life CC microstructure. These results suggest that incurring RHI during critical periods of CC development may disrupt neurodevelopmental processes, including myelination, resulting in altered CC microstructure and greater vulnerability to aging processes.
Journal of neurotrauma 07/2015; DOI:10.1089/neu.2014.3822 · 3.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diffusion imaging tractography is increasingly used to trace critical fiber tracts in brain tumor patients to reduce the risk of post-operative neurological deficit. However, the effects of peritumoral edema pose a challenge to conventional tractography using the standard diffusion tensor model. The aim of this study was to present a novel technique using a two-tensor unscented Kalman filter (UKF) algorithm to track the arcuate fasciculus (AF) in brain tumor patients with peritumoral edema.
Ten right-handed patients with left-sided brain tumors in the vicinity of language-related cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-Tesla magnetic resonance imaging (MRI) including a diffusion-weighted dataset with 31 directions. Fiber tractography was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform the delineation of the AF. Results from the two different tractography algorithms were compared visually and quantitatively.
Using single-tensor streamline tractography, the AF appeared disrupted in four patients and contained few fibers in the remaining six patients. Two-tensor UKF tractography delineated an AF that traversed edematous brain areas in all patients. The volume of the AF was significantly larger on two-tensor UKF than on single-tensor streamline tractography (p < 0.01).
Two-tensor UKF tractography provides the ability to trace a larger volume AF than single-tensor streamline tractography in the setting of peritumoral edema in brain tumor patients.
[Show abstract][Hide abstract] ABSTRACT: In a previous study we have demonstrated, using a novel diffusion MRI analysis called free-water imaging, that the early stages of schizophrenia are more likely associated with a neuroinflammatory response and less so with a white matter deterioration or a demyelination process. What is not known is how neuroinflammation and white matter deterioration change along the progression of the disorder. In this study we apply the free-water measures on a population of 29 chronic schizophrenia subjects and compare them with 25 matching controls. Our aim was to compare the extent of free-water imaging abnormalities in chronic subjects with the ones previously obtained for subjects at their first psychotic episode. We find that chronic subjects showed a limited extent of abnormal increase in the volume of the extracellular space, suggesting a less extensive neuroinflammatory response relative to patients at the onset of schizophrenia. At the same time, the chronic schizophrenia subjects had greater extent of reduced fractional anisotropy compared to the previous study, suggesting increased white matter deterioration along the progression of the disease. Our findings substantiate the role of neuroinflammation in the earlier stages of the disorder, and the effect of neurodegeneration that is worsening in the chronic phase.
Schizophrenia Research 12/2014; 161(1). DOI:10.1016/j.schres.2014.07.031 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diffusion tensor imaging (DTI) tractography enables the graphical reconstruction of the white matter pathways in vivo. The use of this technique to display the key fiber tracts in brain tumor patients for reducing the risk of post-operative neurologic deficit has increased in recent years. However, the effects of peritumoral edema pose a major challenge to the conventional single-tensor streamline fiber tracking method.
To present a novel technique using the two-tensor unscented Kalman filter (UKF) algorithm for the tracking of arcuate fasciculus (AF) in brain tumor patients by resolving the effects of peritumoral edema.
Ten patients with malignant brain tumors in the vicinity of language-related areas underwent 3-T magnetic resonance imaging including a diffusion-weighted data set with 31 gradient directions. DTI data was preprocessed using an automatic quality control pipeline method. Fiber tracking was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform delineation of the AF. Results from two different algorithms were compared side-by-side.
Single-tensor streamline and two-tensor UKF tractography showed fundamental differences in mapping the fiber tracts in the edema area surrounding the malignant brain tumor. Using single-tensor streamline tractography, 4 of 10 patients showed disrupted and incomplete AF and the remaining six patients demonstrated only a slender fiber bundle. In contrast, the two-tensor UKF tractography could fully delineate the AF within such edematous brain areas in all ten patients.
The findings suggest that two-tensor UKF tractography provides the ability to trace the AF more accurately than single-tensor streamline tractography particularly in the setting of peritumoral edema in brain tumor patients. UKF tractography may be helpful in the quest to preserve the language function in brain surgery.
19th Annual Scientific Meeting of the Society for Neuro-Oncology, Miami, Florida USA; 11/2014
[Show abstract][Hide abstract] ABSTRACT: Diffusion weighted imaging (DWI) has been extensively used to study the microarchitecture of white matter in schizophrenia. However, popular DWI-derived measures such as fractional anisotropy (FA) may be sensitive to many types of pathologies, and thus the interpretation of reported differences in these measures remains difficult. Combining DWI with magnetization transfer ratio (MTR) – a putative measure of white matter myelination – can help us reveal the underlying mechanisms. Previous findings hypothesized that MTR differences in schizophrenia are associated with free water concentrations, which also affect the DWIs. In this study we use a recently proposed DWI-derived method called free-water imaging to assess this hypothesis. We have reanalyzed data from a previous study by using a fiber-based analysis of free-water imaging, providing a free-water fraction, as well as mean diffusivity and FA corrected for free-water, in addition to MTR along twelve major white matter fiber bundles in 40 schizophrenia patients and 40 healthy controls. We tested for group differences in each fiber bundle and for each measure separately and computed correlations between the MTR and the DWI-derived measures separately for both groups. Significant higher average MTR values in patients were found for the right uncinate fasciculus, the right arcuate fasciculus and the right inferior-frontal occipital fasciculus. No significant results were found for the other measures. No significant differences in correlations were found between MTR and the DWI-derived measures. The results suggest that MTR and free-water imaging measures can be considered complementary, promoting the acquisition of MTR in addition to DWI to identify group differences, as well as to better understand the underlying mechanisms in schizophrenia.
Schizophrenia Research 10/2014; 161(1). DOI:10.1016/j.schres.2014.09.046 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Current research on concussion is primarily focused on injury identification and treatment. Prevention initiatives are, however, important for reducing the incidence of brain injury. This report examines the development and implementation of an interactive electronic teaching program (an e-module) that is designed specifically for concussion education within an adolescent population. This learning tool and the accompanying consolidation rubric demonstrate that significant engagement occurs in addition to the knowledge gained among participants when it is used in a school curriculum setting.
Journal of Neurosurgery 10/2014; 121(6):1-6. DOI:10.3171/2014.8.JNS132804 · 3.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: One key pitfall in diffusion magnetic resonance imaging (dMRI) clinical neuroimaging research is the challenge of understanding and interpreting the results of a complex analysis pipeline. The sophisticated algorithms employed by the analysis software, combined with the relatively non-specific nature of many diffusion measurements, lead to challenges in interpretation of the results. This paper is aimed at an intended audience of clinical researchers who are learning about dMRI or trying to interpret dMRI results, and who may be wondering "Does dMRI tell us anything about the white matter?" We present a critical review of dMRI methods and measures used in clinical neuroimaging research, focusing on the most commonly used analysis methods and the most commonly reported measures. We describe important pitfalls in every section, and provide extensive references for the reader interested in more detail.
Schizophrenia Research 09/2014; 161(1). DOI:10.1016/j.schres.2014.09.007 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Both peritumoral edema and crossing fibers pose a major challenge to the corticospinal tract (CST) modeling in malignant brain tumor patients when using the conventional single-tensor streamline fiber tracking method. The aim of this study is to present a novel technique using a two-tensor unscented Kalman filter (UKF) that resolves the effects of peritumoral edema and crossing fibers in tracing the CST.
Four patients with malignant brain tumors in the vicinity of motor cortex underwent pre-surgical 3-Tesla magnetic resonance imaging including a diffusion-weighted sequence with 31 gradient direction. Fiber tracking was performed to delineate the CST using both single tensor streamline and two-tensor UKF tractography techniques[1,2], based on a two-regions-of interest approach. The two-tensor UKF tractography was designed using a mixture of two Gaussian tensors. The model parameters were estimated using UKF and subsequently propagated in the most consistent direction. Results from the two techniques were compared side-by-side.
The two-tensor UKF tractography could fully delineate the CST, whereas the CST displayed by single-tensor streamline tractography were incomplete or disrupted.
These findings suggest that two-tensor UKF tractography is able to trace the CST more accurately than single-tensor streamline tractography in the settings of peritumoral edema and crossing fibers. Two-tensor UKF tractography may be helpful in the quest to preserve motor function in brain surgery.
7th National Image-Guided Therapy Workshop, Boston MA, USA.; 09/2014
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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.
Partial volume elimination reveals microstructural alterations preceding dementia. These alterations may prove to be an effective and feasible early biomarker of AD.
Alzheimer's and Dementia 07/2014; 11(5). DOI:10.1016/j.jalz.2014.04.518 · 12.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a cohort of community-recruited elderly subjects with normal cognition at initial evaluation, we found that baseline fornix white matter (WM) microstructure was significantly correlated with early volumetric longitudinal tissue change across a region of interest (called fornix significant ROI, fSROI), which overlaps circuits known to be selectively vulnerable to Alzheimer's dementia pathology. Other WM and gray matter regions had much weaker or non-existent associations with longitudinal tissue change. Tissue loss in fSROI was in turn a significant factor in a survival model of cognitive decline, as was baseline fornix microstructure. These findings suggest that WM deterioration in the fornix and tissue loss in fSROI may be the early beginnings of posterior limbic circuit and default mode network degeneration. We also found that gray matter baseline volumes in the entorhinal cortex and hippocampus predicted cognitive decline in survival models. But since GM regions did not also significantly predict brain-tissue loss, our results may imply a view in which early, prodromal deterioration appears as two quasi independent processes in white and gray matter regions of the limbic circuit crucial to memory.
[Show abstract][Hide abstract] 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.
Alzheimer's Research and Therapy 02/2014; 6(1):10. DOI:10.1186/alzrt239 · 3.98 Impact Factor
[Show abstract][Hide abstract] 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.
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.
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.
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.
Journal of Neurosurgery 02/2014; 120(4). DOI:10.3171/2013.12.JNS132090 · 3.74 Impact Factor