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1.  A fully automated tool to identify the aorta and compute flow using Phase-contrast MRI: validation and application in a large population based study 
To assess if fully automated localization of the aorta can be achieved using phase contrast (PC) magnetic resonance (MR) images.
Materials and Methods
PC cardiac gated MR images were obtained as part of a large population-based study. A fully automated process using the Hough transform was developed to localize the ascending aorta (AAo) and descending aorta (DAo). The study was designed to validate this technique by determining: 1) its performance in localizing the AAo and DAo; 2) its accuracy in generating AAo flow volume and DAo flow volume; and 3) its robustness on studies with pathological abnormalities or imaging artifacts.
The algorithm was applied successfully on 1,884 participants. In the randomly selected 50-study validation set, linear regression shows an excellent correlation between the automated (A) and manual (M) methods for AAo flow (r = 0.99) and DAo flow (r = 0.99). Bland-Altman difference analysis demonstrates strong agreement with minimal bias for: AAo flow (mean difference (A-M) = 0.47 ± 2.53 ml), and DAo flow (mean difference (A-M) = 1.74 ± 2.47 ml).
A robust fully automated tool to localize the aorta and provide flow volume measurements on phase contrast MRI was validated on a large population-based study.
PMCID: PMC3969872  PMID: 24115597
automatic; localization; phase contrast; aorta; segmentation
2.  Cognitive Impact of Lacunar Infarcts and White Matter Hyperintensity Volume 
Subcortical lacunar infarcts and white matter hyperintensities (WMH) are common neuroradiological findings, but few studies associate between these insults and cognition in a community-dwelling population.
The Dallas Heart Study is a population-based initiative whose assessments included demographic and clinical findings including brain MRI and the Montreal Cognitive Assessment (MoCA). The presence and number of lacunes in subjects aged over 55 years were assessed by study physicians. The WMH volume was measured by an automated method. The association between the presence and number of lacunar infarcts and of WMH volume with the total MoCA score and subdomains was assessed using linear regression with adjustment for age, gender and self-reported ethnicity.
In 609 subjects with valid data, both the presence and the increasing number of lacunes were associated with lower MoCA scores, even after adjusting for demographic variables. The presence of lacunes was also associated with lower scores in the memory, executive and attention subdomains. The WMH volume was not significantly associated with the MoCA score.
The presence and increasing number of lacunes in midlife is associated with a lower performance in multiple domains of a cognitive screening measure after adjusting for demographic factors.
PMCID: PMC4448068  PMID: 26034488
Cognition; Memory; Montreal Cognitive Assessment; Lacune; White matter hyperintensity; Magnetic resonance imaging
3.  Impact of Normal Aging versus Hypertension, Abnormal BMI and Diabetes on White Matter Hyperintensity Volume 
Background and Purpose
The natural history of WMH progression due to normal aging versus comorbid vascular insults remains unclear. We therefore investigated age related differences in WMH volumes among a group with comorbid hypertension, abnormal BMI and/or diabetes to a normal aging group drawn from the same population lacking any of these comorbidities.
WMH volumes were acquired using 3T MRI for 2011 Dallas Heart Study participants. The slope of the WMH vs. age regression was compared between normal and comorbidities groups before and after age 50 where a change in slope was demonstrated.
Aging was linearly associated with greater log WMH volume for both normal (p=0.02) and comorbidity (p < 0.0001) groups. Above 50 years more rapid increases in WMH volumes for age were seen in the group with comorbidities (p <.0001) but not the normal group (p-value=0.173). The between-group difference in slope of expected WMH for age was significantly greater in the comorbidities group beyond age 50 (p=0.0008) but not before (p=0.752).
After age 50, but not before, comorbid hypertension, obesity and diabetes was associated with significantly larger WMH volumes for age compared to a normal aging group lacking these conditions. These results support the assertion that age related differences in WMH volumes are significantly increased in the presence of comorbidities, but the effect is only detectable after age 50.
PMCID: PMC3928033  PMID: 24203844
White Matter Hyperintensity; Aging
4.  Oxygenation in Cervical Cancer and Normal Uterine Cervix assessed using BOLD MRI at 3 T1 
NMR in biomedicine  2012;25(12):1321-1330.
Hypoxia is reported to be a biomarker for poor prognosis in cervical cancer. However, a practical non-invasive method is needed for routine clinical evaluation of tumor hypoxia. This study examined the potential use of BOLD (Blood Oxygenation Level Dependent) contrast MRI as a non-invasive technique to assess tumor vascular oxygenation at 3 T. Following IRB-approved informed consent and in compliance with HIPAA, successful results were achieved in nine patients with locally advanced cervical cancer (FIGO stage IIA to IVA) and three normal volunteers. In the first four patients, dynamic T2*-weighted MRI was performed in the transaxial plane using a multi-shot EPI sequence while patients breathed room air followed by oxygen (15 dm3/min). Later, a multi-echo gradient echo examination was added to provide quantitative R2* measurements. Baseline T2*-weighted signal intensity was quite stable, but increased to various extents in tumors upon initiation of oxygen breathing. Signal in normal uterus increased significantly, while iliacus muscle did not change. R2* responded significantly in healthy uterus, cervix, and eight cervical tumors. This preliminary study demonstrates that BOLD MRI of cervical cancer at 3 T is feasible. However, more patients must be evaluated and followed clinically before any prognostic value can be determined.
PMCID: PMC3445718  PMID: 22619091
hypoxia; MRI; cervical cancer; BOLD; oxygen
5.  Donepezil effects on hippocampal and prefrontal functional connectivity in Alzheimer’s disease: Preliminary report 
Journal of Alzheimer's disease : JAD  2012;31(0 3):S221-S226.
We used functional connectivity magnetic resonance imaging (fcMRI) to investigate changes in interhemispheric brain connectivity in 11 patients with mild Alzheimer’s disease (AD) following eight weeks of treatment with the cholinesterase inhibitor donepezil. We examined functional connectivity between four homologous temporal, frontal, and occipital regions. These regions were selected to represent sites of AD neuropathology, sites of donepezil-related brain activation change in prior studies, and sites that are minimally affected by the pathologic changes of AD. Based on previous findings of selective, localized frontal responses to donepezil, we predicted that frontal connectivity would be most strongly impacted by treatment. Of the areas we examined, we found that treatment had a significant effect only on functional connectivity between right and left dorsolateral prefrontal cortices. Implications for understanding the impact of donepezil treatment on brain functioning and behavior in patients with AD are discussed. This preliminary report suggests that fcMRI may provide a useful index of treatment outcome in diseases affecting brain connectivity. Future research should investigate these treatment-related changes in larger samples of patients and age-matched controls.
PMCID: PMC3749074  PMID: 22886013
Alzheimer’s disease; donepezil; functional connectivity; dorsolateral prefrontal cortex; hippocampus
6.  Regionally Selective Atrophy after Traumatic Axonal Injury 
Archives of neurology  2010;67(11):1336-1344.
To determine the spatial distribution of cortical and subcortical volume loss in patients with diffuse traumatic axonal injury and to assess the relationship between regional atrophy and functional outcome.
Prospective imaging study. Longitudinal changes in global and regional brain volumes were assessed using high-resolution magnetic resonance imaging (MRI)-based morphometric analysis.
Inpatient traumatic brain injury unit
Patients or Other Participants
Twenty-five patients with diffuse traumatic axonal injury and 22 age- and sex-matched controls.
Main Outcome Measure
Changes in global and regional brain volumes between initial and follow-up MRI were used to assess the spatial distribution of post-traumatic volume loss. The Glasgow Outcome Scale – Extended was the primary measure of functional outcome.
Patients underwent substantial global atrophy with mean brain parenchymal volume loss of 4.5% (95% Confidence Interval: 2.7 – 6.3%). Decreases in volume (at a false discovery rate of 0.05) were seen in several brain regions including the amygdala, hippocampus, thalamus, corpus callosum, putamen, precuneus, postcentral gyrus, paracentral lobule, and parietal and frontal cortices, while other regions such as the caudate and inferior temporal cortex were relatively resistant to atrophy. Loss of whole brain parenchymal volume was predictive of long-term disability, as was atrophy of particular brain regions including the inferior parietal cortex, pars orbitalis, pericalcarine cortex, and supramarginal gyrus.
Traumatic axonal injury leads to substantial post-traumatic atrophy that is regionally selective rather than diffuse, and volume loss in certain regions may have prognostic value for functional recovery.
PMCID: PMC3465162  PMID: 20625067
7.  Effects of Lamotrigine on Hippocampal Activation in Corticosteroid-Treated Patients 
Journal of affective disorders  2010;126(3):415-419.
An extensive animal literature suggests that stress or excessive corticosteroid exposure is associated with changes in hippocampal function and memory. These findings are pertinent to psychiatric disorders with elevated cortisol, Cushing’s disease and the millions of patients receiving prescription corticosteroids. In animals, agents that decrease glutamate release attenuate the effects of corticosteroids on the hippocampus. Minimal data are available on preventing or reversing the effects of corticosteroids on the human hippocampus. We previously reported improvement in memory in corticosteroid-treated patients given lamotrigine. In this report, we examined the impact of lamotrigine on task-related hippocampal activation in patients taking prescription corticosteroids.
A total of 28 outpatients taking long-term oral prednisone for medical conditions, such as renal transplant rejection, were randomized to lamotrigine or placebo for 24 weeks. Hippocampal activation in response to a visual memory task was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI).
Consistent with a reduction in glutamate release, the right posterior hippocampus showed a significant decrease in task-related activation in the lamotrigine group as compared to the placebo group.
The modest sample size and an assessment period of only 24 weeks are study limitations.
Between-group differences in hippocampal activation were observed. The results suggest that an agent that modulates glutamate may modify the effects of long-term corticosteroid exposure on the human hippocampus.
PMCID: PMC2947572  PMID: 20580827
functional magnetic resonance imaging; lamotrigine; prednisone; hippocampus
8.  Diffusion Tensor Imaging Biomarkers for Traumatic Axonal Injury: Analysis of Three Analytic Methods 
Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3T magnet. Patients were scanned approximately eight months post-injury, and underwent an outcomes assessment at that time. Histogram analysis of FA and MD showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury.
PMCID: PMC3097093  PMID: 21070694
DTI; DAI; Traumatic Brain Injury; memory; Tractography; cognitive outcomes
9.  Cerebral Atrophy after Traumatic White Matter Injury: Correlation with Acute Neuroimaging and Outcome 
Journal of Neurotrauma  2008;25(12):1433-1440.
Traumatic brain injury (TBI) is a pathologically heterogeneous disease, including injury to both neuronal cell bodies and axonal processes. Global atrophy of both gray and white matter is common after TBI. This study was designed to determine the relationship between neuroimaging markers of acute diffuse axonal injury (DAI) and cerebral atrophy months later. We performed high-resolution magnetic resonance imaging (MRI) at 3 Tesla (T) in 20 patients who suffered non-penetrating TBI, during the acute (within 1 month after the injury) and chronic stage (at least 6 months after the injury). Volume of abnormal fluid-attenuated inversion-recovery (FLAIR) signal seen in white matter in both acute and follow-up scans was quantified. White and gray matter volumes were also quantified. Functional outcome was measured using the Functional Status Examination (FSE) at the time of the chronic scan. Change in brain volumes, including whole brain volume (WBV), white matter volume (WMV), and gray matter volume (GMV), correlates significantly with acute DAI volume (r = −0.69, −0.59, −0.58, respectively; p < 0.01 for all). Volume of acute FLAIR hyperintensities correlates with volume of decreased FLAIR signal in the follow-up scans (r = −0.86, p < 0.001). FSE performance correlates with acute hyperintensity volume and chronic cerebral atrophy (r = 0.53, p = 0.02; r = −0.45, p = 0.03, respectively). Acute axonal lesions measured by FLAIR imaging are strongly predictive of post-traumatic cerebral atrophy. Our findings suggest that axonal pathology measured as white matter lesions following TBI can be identified using MRI, and may be a useful measure for DAI-directed therapies.
PMCID: PMC2858299  PMID: 19072588
MR imaging; post-traumatic atrophy; TBI

Results 1-9 (9)