Faculty Bibliography

The brain is a spatially heterogeneous and temporally dynamic organ, with different regions requiring different amount of blood supply at different time. Therefore, the ability of the blood vessels to dilate or constrict, known as Cerebral-Vascular-Reactivity (CVR), represents an important domain of vascular function. An imaging marker representing this dynamic property will provide new information of cerebral vessels under normal and diseased conditions such as stroke, dementia, atherosclerosis, small vessel diseases, brain tumor, traumatic brain injury, and multiple sclerosis. In order to perform this type of measurement in humans, it is necessary to deliver a vasoactive stimulus such as CO2 and/or O2 gas mixture while quantitative brain magnetic resonance images (MRI) are being collected. In this work, we presented a MR compatible gas-delivery system and the associated protocol that allow the delivery of special gas mixtures (e.g., O2, CO2, N2, and their combinations) while the subject is lying inside the MRI scanner. This system is relatively simple, economical, and easy to use, and the experimental protocol allows accurate mapping of CVR in both healthy volunteers and patients with neurological disorders. This approach has the potential to be used in broad clinical applications and in better understanding of brain vascular pathophysiology. In the video, we demonstrate how to set up the system inside an MRI suite and how to perform a complete experiment on a human participant.

OBJECTIVE: The purpose of this study was to develop an algorithm incorporating MRI metrics to classify patients with mild traumatic brain injury (mTBI) and controls. METHODS: This was an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant prospective study. We recruited patients with mTBI and healthy controls through the emergency department and general population. We acquired data on a 3.0T Siemens Trio magnet including conventional brain imaging, resting-state fMRI, diffusion-weighted imaging, and magnetic field correlation (MFC), and performed multifeature analysis using the following MRI metrics: mean kurtosis (MK) of thalamus, MFC of thalamus and frontal white matter, thalamocortical resting-state networks, and 5 regional gray matter and white matter volumes including the anterior cingulum and left frontal and temporal poles. Feature selection was performed using minimal-redundancy maximal-relevance. We used classifiers including support vector machine, naive Bayesian, Bayesian network, radial basis network, and multilayer perceptron to test maximal accuracy. RESULTS: We studied 24 patients with mTBI and 26 controls. Best single-feature classification uses thalamic MK yielding 74% accuracy. Multifeature analysis yields 80% accuracy using the full feature set, and up to 86% accuracy using minimal-redundancy maximal-relevance feature selection (MK thalamus, right anterior cingulate volume, thalamic thickness, thalamocortical resting-state network, thalamic microscopic MFC, and sex). CONCLUSION: Multifeature analysis using diffusion-weighted imaging, MFC, fMRI, and volumetrics may aid in the classification of patients with mTBI compared with controls based on optimal feature selection and classification methods. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that classification algorithms using multiple MRI features accurately identifies patients with mTBI as defined by American Congress of Rehabilitation Medicine criteria compared with healthy controls.

Importance: Cerebrovascular reactivity (CVR) is an inherent indicator of the dilatory capacity of cerebral arterioles for a vasomotor stimulus for maintaining a spontaneous and instant increase of cerebral blood flow (CBF) in response to neural activation. The integrity of this mechanism is essential to preserving healthy neurovascular coupling; however, to our knowledge, no studies have investigated whether there are CVR abnormalities in multiple sclerosis (MS). Objective: To use hypercapnic perfusion magnetic resonance imaging to assess CVR impairment in patients with MS. Design, Setting, and Participants: A total of 19 healthy volunteers and 19 patients with MS underwent perfusion magnetic resonance imaging based on pseudocontinuous arterial spin labeling to measure CBF at normocapnia (ie, breathing room air) and hypercapnia. The hypercapnia condition is achieved by breathing 5% carbon dioxide gas mixture, which is a potent vasodilator causing an increase of CBF. Main Outcomes and Measures: Cerebrovascular reactivity was calculated as the percent increase of normocapnic to hypercapnic CBF normalized by the change in end-tidal carbon dioxide, which was recorded during both conditions. Group analysis was performed for regional and global CVR comparison between patients and controls. Regression analysis was also performed between CVR values, lesion load, and brain atrophy measures in patients with MS. Results: A significant decrease of mean (SD) global gray matter CVR was found in patients with MS (3.56 [0.81]) compared with healthy controls (5.08 [1.56]; P = .001). Voxel-by-voxel analysis showed diffuse reduction of CVR in multiple regions of patients with MS. There was a significant negative correlation between gray matter CVR and lesion volume (R = 0.6, P = .004) and a significant positive correlation between global gray matter CVR and gray matter atrophy index (R = 0.5, P = .03). Conclusions and Relevance: Our quantitative imaging findings suggest impairment in functional cerebrovascular pathophysiology, by measuring a diffuse decrease in CVR, which may be the underlying cause of neurodegeneration in MS.

BACKGROUND AND PURPOSE: Cerebrovascular oxygenation changes during respiratory challenges have clinically important implications for brain function, including cerebral autoregulation and the rate of brain metabolism. SWI is sensitive to venous oxygenation level by exploitation of the magnetic susceptibility of deoxygenated blood. We assessed cerebral venous blood oxygenation changes during simple voluntary breath-holding (apnea) and hyperventilation by use of SWI at 3T. MATERIALS AND METHODS: We performed SWI scans (3T; acquisition time of 1 minute, 28 seconds; centered on the anterior commissure and the posterior commissure) on 10 healthy male volunteers during baseline breathing as well as during simple voluntary hyperventilation and apnea challenges. The hyperventilation and apnea tasks were separated by a 5-minute resting period. SWI venograms were generated, and the signal changes on SWI before and after the respiratory stress tasks were compared by means of a paired Student t test. RESULTS: Changes in venous vasculature visibility caused by the respiratory challenges were directly visualized on the SWI venograms. The venogram segmentation results showed that voluntary apnea decreased the mean venous blood voxel number by 1.6% (P < .0001), and hyperventilation increased the mean venous blood voxel number by 2.7% (P < .0001). These results can be explained by blood CO2 changes secondary to the respiratory challenges, which can alter cerebrovascular tone and cerebral blood flow and ultimately affect venous oxygen levels. CONCLUSIONS: These results highlight the sensitivity of SWI to simple and noninvasive respiratory challenges and its potential utility in assessing cerebral hemodynamics and vasomotor responses.

The development of chemical exchange saturation transfer (CEST) and magnetization transfer (MT) contrast in MRI has enabled the enhanced detection of metabolites and biomarkers in vivo. In brain MRI, the separation between CEST and MT contrast has been particularly difficult due to overlaps in the frequency responses of the contrast mechanisms. We demonstrate here that MT and CEST contrast can be separated in the brain by the so-called uniform-MT (uMT) technique, thus opening the door to addressing long-standing ambiguities in this field. These methods could be useful for keeping track of important endogenous metabolites and for providing an improved understanding of neurological and neurodegenerative disorders. Examples are shown from white and gray matter regions in healthy volunteers and patients with multiple sclerosis, which demonstrated that the MT effects in the brain were asymmetric and that the uMT method could make them uniform.

PURPOSE: To examine thalamic and cortical injuries using fractional amplitude of low-frequency fluctuations (fALFFs) and functional connectivity MRI (fcMRI) based on resting state (RS) and task-related fMRI in patients with mild traumatic brain injury (MTBI). MATERIALS AND METHODS: Twenty-seven patients and 27 age-matched controls were recruited. The 3 Tesla fMRI at RS and finger tapping task were used to assess fALFF and fcMRI patterns. fALFFs were computed with filtering (0.01-0.08 Hz) and scaling after preprocessing. fcMRI was performed using a standard seed-based correlation method, and delayed fcMRI (coherence) in frequency domain were also performed between thalamus and cortex. RESULTS: In comparison with controls, MTBI patients exhibited significantly decreased fALFFs in the thalamus (and frontal/temporal subsegments) and cortical frontal and temporal lobes; as well as decreased thalamo-thalamo and thalamo-frontal/ thalamo-temporal fcMRI at rest based on RS-fMRI (corrected P < 0.05). This thalamic and cortical disruption also existed at task-related condition in patients. CONCLUSION: The decreased fALFFs (i.e., lower neuronal activity) in the thalamus and its segments provide additional evidence of thalamic injury in patients with MTBI. Our findings of fALFFs and fcMRI changes during motor task and resting state may offer insights into the underlying cause and primary location of disrupted thalamo-cortical networks after MTBI. J. Magn. Reson. Imaging 2013. (c) 2013 Wiley Periodicals, Inc.

PURPOSE: Measurement of venous oxygenation (Yv ) is a critical step toward quantitative assessment of brain oxygen metabolism, a key index in many brain disorders. The present study aims to develop a noninvasive, rapid, and reproducible method to measure Yv in a vessel-specific manner. THEORY: The method, T2 -Relaxation-Under-Phase-Contrast MRI, utilizes complex subtraction of phase-contrast to isolate pure blood signal, applies nonslice-selective T2 -preparation to measure T2 , and converts T2 to oxygenation using a calibration plot. METHODS: Following feasibility demonstration, several technical aspects were examined, including validation with an established global Yv technique, test-retest reproducibility, sensitivity to detect oxygenation changes due to hypoxia and caffeine challenges, applicability of echo-planar-imaging (EPI) acquisition to shorten scan duration, and ability to study veins with a caliber of 1-2 mm. RESULTS: T2 -Relaxation-Under-Phase-Contrast was able to simultaneously measure Yv in all major veins in the brain, including sagittal sinus, straight sinus, great vein, and internal cerebral vein. T2 -Relaxation-Under-Phase-Contrast results showed an excellent agreement with the reference technique, high sensitivity to oxygenation changes, and test-retest variability of 3.5 +/- 1.0%. The use of segmented-EPI was able to reduce the scan duration to 1.5 minutes. It was also feasible to study pial veins and deep veins. CONCLUSION: T2 -Relaxation-Under-Phase-Contrast MRI is a promising technique for vessel-specific oxygenation measurement. Magn Reson Med, 2013. (c) 2013 Wiley Periodicals, Inc.

Background: Atrophy of the hippocampus is a key pathological hallmark of Alzheimer's disease (AD). An interest of subfields of hippocampal imaging has emerged in recent years due to the advent of ultra-high field MR. This work was to evaluate the imaging parameters on human postmortem brain at 7T MR using 3D susceptibility-sensitivity imaging (SWI) with enhanced tissue susceptibility contrast to better identify these layers and hippocampal subfields that are not available on conventional MR in order to better understand the transition of the hippocampus in AD as disease progresses. Methods: Imaging was performed on a 7.0T Siemens MAGNETOM using a 24-element phased array head coil. Post-mortem brain specimens of the hippocampus were obtained from 3 patients (mean: 72.2+4.3 years) with clinically diagnosed AD and 4 age-matched healthy controls (71.4+5.2 years). Coronal brain slices were preserved and fixed in 2% agar for this study. High resolution 3D SWI was obtained with isotropic voxel size 150~320mum. For imaging optimization to better visualize amyloid plaques, we varied TR, TE, BWand flip angle from 30-100ms, 12-36ms, 60-140Hz/ pixel and 10-40degree; respectively. The SWI filtered phase images were used (multiplication factor of 4 ~ 8) to enhance susceptibility contrast in the SWI images. Results: With optimal SWI parameters TR/TE/FA of 80ms/ 20ms/30IS at 7T, Figure 1 exemplifies the excellent image contrast for visualization of hippocampal layers (Fig A) and subfields (Fig B) in an elderly post-mortem brain without AD, specifically for cell types/layers: (1) Alveus; (2) Stratum Oriens; (3) Stratum Pyramidale; (4) Stratum Radiatum; (5) Stratum Lacunosum; (6) Stratum Moleculare; and for Hippocampal Formation subfields: (1) Hippocampal Head; (2, 2') Dentate Gyrus, (3, 3') Cornu Ammonis (CA1), (4) CA2, (5) CA3, (6) Pre-Subiculum/ Subiculum, (7) Para-Subiculum, (8) Entorhinal Cortex. There was significant atrophy of the whole hippocampal formation and subfields inADsamples with lessening of the!

BACKGROUND AND PURPOSE: CC is extensively involved in MS with interhemispheric dysfunction. The purpose of this study was to determine whether interhemispheric correlation is altered in MS by use of a recently developed RS-fMRI homotopy technique and whether these homotopic changes correlate with CC pathology. MATERIALS AND METHODS: Twenty-four patients with relapsing-remitting MS and 24 age-matched healthy volunteers were studied with RS-fMRI and DTI acquired at 3T. The Pearson correlation of each pair of symmetric interhemispheric voxels of RS-fMRI time-series data was performed to compute VMHC, and z-transformed for subsequent group-level analysis. In addition, 5 CC segments in the midsagittal area and DTI-derived FA were measured to quantify interhemispheric microstructural changes and correlate with global and regional VMHC in MS. RESULTS: Relative to control participants, patients with MS exhibited an abnormal homotopic pattern with decreased VMHC in the primary visual, somatosensory, and motor cortices and increased VMHC in several regions associated with sensory processing and motor control including the insula, thalamus, pallidum, and cerebellum. The global VMHC correlates moderately with the average FA of the entire CC for all participants in both groups (r = 0.3; P = .03). CONCLUSIONS: Our data provide preliminary evidence of the potential usefulness of VMHC analyses for the detection of abnormalities of interhemispheric coordination in MS. We demonstrated that the whole-brain homotopic RS-fMRI pattern was altered in patients with MS, which was partially associated with the underlying structural degenerative changes of CC measured with FA.