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1.  Migraine with Aura Is Associated with an Incomplete Circle of Willis: Results of a Prospective Observational Study 
PLoS ONE  2013;8(7):e71007.
To compare the prevalence of an incomplete circle of Willis in patients with migraine with aura, migraine without aura, and control subjects, and correlate circle of Willis variations with alterations in cerebral perfusion.
Migraine with aura, migraine without aura, and control subjects were prospectively enrolled in a 1∶1∶1 ratio. Magnetic resonance angiography was performed to examine circle of Willis anatomy and arterial spin labeled perfusion magnetic resonance imaging to measure cerebral blood flow. A standardized template rating system was used to categorize circle of Willis variants. The primary pre-specified outcome measure was the frequency of an incomplete circle of Willis. The association between circle of Willis variations and cerebral blood flow was also analyzed.
170 subjects were enrolled (56 migraine with aura, 61 migraine without aura, 53 controls). An incomplete circle of Willis was significantly more common in the migraine with aura compared to control group (73% vs. 51%, p = 0.02), with a similar trend for the migraine without aura group (67% vs. 51%, p = 0.08). Using a quantitative score of the burden of circle of Willis variants, migraine with aura subjects had a higher burden of variants than controls (p = 0.02). Compared to those with a complete circle, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow (p = 0.05). Specific posterior cerebral artery variants were associated with greater asymmetries of blood flow in the posterior cerebral artery territory.
An incomplete circle of Willis is more common in migraine with aura subjects than controls, and is associated with alterations in cerebral blood flow.
PMCID: PMC3724801  PMID: 23923042
2.  Clinical Neuroimaging Using Arterial Spin-Labeled Perfusion MRI 
The two most common methods for measuring perfusion with MRI are based on dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL). Although clinical experience to date is much more extensive with DSC perfusion MRI, ASL methods offer several advantages. The primary advantages are that completely noninvasive absolute cerebral blood flow (CBF) measurements are possible with relative insensitivity to permeability, and that multiple repeated measurements can be obtained to evaluate one or more interventions or to perform perfusion-based functional MRI. ASL perfusion and perfusion-based fMRI methods have been applied in many clinical settings, including acute and chronic cerebrovascular disease, CNS neoplasms, epilepsy, aging and development, neurodegenerative disorders, and neuropsychiatric diseases. Recent technical advances have improved the sensitivity of ASL perfusion MRI, and increasing use is expected in the coming years. This review focuses on ASL perfusion MRI and applications in clinical neuroimaging.
PMCID: PMC2031222  PMID: 17599701
Magnetic resonance imaging; Arterial spin labeling; Arterial spin tagging; Perfusion; Functional MRI
3.  Atheroprotective lipoprotein effects of a niacin-simvastatin combination compared to low- and high-dose simvastatin monotherapy 
American heart journal  2009;157(4):687.e1-687.e8.
Niacin has multiple lipoprotein effects that may provide cardiovascular benefit when added to statin monotherapy.
In this randomized, placebo-controlled trial (n = 75) of magnetic resonance imaging of carotid atherosclerosis, we performed a secondary comparison of combination niacin-statin (simvastatin 20 mg/Niacin-ER 2G [S20/N]) to monotherapy with moderate (20 mg [S20]) and high-dose (80 mg [S80]) simvastatin on lipids, apolipoproteins (apo), low density lipoprotein (LDL) and high density lipoprotein (HDL) particle subclasses, and inflammatory markers.
At baseline, average age was 71, 72% were male, 62.5% used statins, and average LDL-cholesterol was 111 mg/dL. At 12 months, S20/N, compared to S80, significantly reduced apoB (−36.6% vs −11.9%; P = .05) and lipoprotein(a) (−18% vs +3.5%; P = .001) and had at least an equivalent effect on LDL-cholesterol (−39.3% vs −24.3%; P = .24). The combination reduced the proportion of subjects with atherogenic LDL pattern-B (50% to 11.5%) compared to S80 (56% to 56%) (P = .01). Despite increases in plasma free fatty acids (+62.4%; F = 5.65, P = .005 vs S20 and S80), plasma triglycerides (−29.4%; F = 6.88, P = .002 vs S20 and S80), and very-low-density lipoprotein (−44.2%; F = 7.94, P < .001 vs S20 and S80), levels were reduced by S20/N. S20/N increased HDL-cholesterol levels (+18.1%) as compared to S20 (0%) and S80 (+5.9%) (P < .001 vs both statin arms), largely due to an increase in HDL particle size (+4.6%; P = .01 vs both statin arms).
We demonstrate that full-dose niacin/moderate-dose simvastatin combination has sustained benefits on atherogenic apoB lipoproteins, at least comparable to high-dose simvastatin, while also raising HDL-cholesterol. Results of large clinical trials will inform whether niacin-statin combinations reduce cardiovascular disease events.
PMCID: PMC3088112  PMID: 19332196
4.  Hippocampal Volumetry and Memory fMRI in Temporal Lobe Epilepsy 
Epilepsy & behavior : E&B  2009;16(1):128-138.
This study examined the utility of structural and functional MRI at 1.5 and 3 Tesla (T) in the pre-surgical evaluation and prediction of post-surgical cognitive outcome in temporal lobe epilepsy (TLE). Forty-nine patients undergoing presurgical evaluation for temporal lobe (TL) resection and twenty-five control subjects were studied. Patients completed standard pre-surgical evaluations including, intracarotid amobarbital test (IAT) and neuropsychological testing. During functional imaging, subjects performed a complex visual scene-encoding task. High-resolution structural MRI scans were used to quantify hippocampal volumes. Both structural and functional imaging successfully lateralized the seizure focus and correlated with IAT memory lateralization, with improvement for functional imaging at 3T as compared to 1.5T. Ipsilateral structural and functional MRI data was related to cognitive outcome and greater functional asymmetry was related to earlier age of onset. These findings support continued investigation of the utility of MRI and fMRI in the presurgical evaluation of TLE.
PMCID: PMC2749903  PMID: 19674939
Temporal Lobe Epilepsy; Epilepsy Surgery; fMRI; Neuropsychological Outcome; Wada; IAT
5.  Combination antiretroviral therapy modulates the blood oxygen level–dependent amplitude in human immunodeficiency virus–seropositive patients 
Journal of neurovirology  2008;14(5):418.
Combination antiretroviral therapy (cART) limits human immunodeficiency virus (HIV) replication in the central nervous system (CNS) and prevents progressive neurological dysfunction. We examined if the degree of CNS penetration by cART, as estimated by the CNS penetration effectiveness (CPE) score, affects brain activity as measured by the amplitude of the blood oxygen level–dependent functional magnetic resonance imaging (BOLD fMRI) response. HIV+ patients on low-CPE cART (n = 12) had a significantly greater BOLD fMRI response amplitude than HIV+ patients on high-CPE cART (n = 12) or seronegative controls (n = 10). An increase in the BOLD fMRI response in HIV patients on low-CPE cART may reflect continued HIV replication in the CNS leading to increased oxidative stress and associated metabolic demands.
PMCID: PMC2819068  PMID: 19040188
combination antiretroviral therapy (cART); functional magnetic resonance imaging; HIV-associated neurocognitive disorders
6.  Differentiation between Glioblastomas and Solitary Brain Metastases Using Diffusion Tensor Imaging 
NeuroImage  2008;44(3):653-660.
The purpose of this study is to determine whether diffusion tensor imaging (DTI) metrics including tensor shape measures such as linear and planar anisotropy coefficients (CL and CP) can help differentiate glioblastomas from solitary brain metastases. Sixty-three patients with histopathologic diagnosis of glioblastomas (22 men, 16 women, mean age 58.4 years) and brain metastases (13 men, 12 women, mean age 56.3 years) were included in this study. Contrast-enhanced T1-weighted, fluid attenuated inversion recovery (FLAIR) images, fractional anisotropy (FA), apparent diffusion coefficient (ADC), CL and CP maps were co-registered and each lesion was semi-automatically subdivided into four regions: central, enhancing, immediate peritumoral and distant peritumoral. DTI metrics as well as the normalized signal intensity from the contrast-enhanced T1-weighted images were measured from each region. Univariate and multivariate logistic regression analyses were employed to determine the best model for classification. The results demonstrated that FA, CL and CP from glioblastomas were significantly higher than those of brain metastases from all segmented regions (p < 0.05), and the differences from the enhancing regions were most significant (p < 0.001). FA and CL from the enhancing region had the highest prediction accuracy when used alone with an area under the curve of 0.90. The best logistic regression model included three parameters (ADC, FA and CP) from the enhancing part, resulting in 92% sensitivity, 100% specificity and area under the curve of 0.98. We conclude that DTI metrics, used individually or combined, have a potential as a noninvasive measure to differentiate glioblastomas from metastases.
PMCID: PMC2655208  PMID: 18951985
7.  Mineral Volume and Morphology in Carotid Plaque Specimens Using High-Resolution MRI and CT 
High-resolution MRI methods have been used to evaluate carotid artery atherosclerotic plaque content. The purpose of this study was to assess the performance of high-resolution MRI in evaluation of the quantity and pattern of mineral deposition in carotid endarterectomy (CEA) specimens, with quantitative micro-CT as the gold standard.
Methods and Results
High-resolution MRI and CT were compared in 20 CEA specimens. Linear regression comparing mineral volumes generated from CT (VCT) and MRI (VMRI) data demonstrated good correlation using simple thresholding (VMRI=-0.01+0.98VCT; R2=0.90; threshold=4×noise) and k-means clustering methods (VMRI=-0.005+1.38VCT; R2=0.93). Bone mineral density (BMD) and bone mineral content (BMC [mineral mass]) were calculated for CT data and BMC verified with ash weight. Patterns of mineralization like particles, granules, and sheets were more clearly depicted on CT.
Mineral volumes generated from MRI or CT data were highly correlated. CT provided a more detailed depiction of mineralization patterns and provided BMD and BMC in addition to mineral volume. The extent of mineralization as well as the morphology may ultimately be useful in assessing plaque stability.
PMCID: PMC1959411  PMID: 15947239
magnetic resonance imaging; computed tomography; carotid arteries; calcium
8.  Noninvasive Measurement of Cerebral Blood Flow and Blood Oxygenation Using Near-Infrared and Diffuse Correlation Spectroscopies in Critically Brain-Injured Adults 
Neurocritical care  2010;12(2):173-180.
This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation.
Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBFDCS), and changes in oxy-hemoglobin (ΔHbO2), deoxy-hemoglobin (ΔHb), and total hemoglobin concentration (ΔTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBFXeCT) and were then compared to rCBFDCS. Spearman’s rank coefficients were employed to test for associations between rCBFDCS and rCBFXeCT, as well as between rCBF from both modalities and NIRS parameters.
rCBFDCS and rCBFXeCT showed good correlation (rs = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBFDCS and ΔHbO2/ΔTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.
DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.
PMCID: PMC2844468  PMID: 19908166
Near-infrared spectroscopy; Diffuse correlation spectroscopy; Cerebral blood flow; Xenon CT; Neurocritical care

Results 1-8 (8)