Jianhui Zhong

Factors influencing contrast in fast spin-echo MR imaging.

Multi-echo pulse sequences for producing T2-weighted images in much reduced imaging times have recently been developed for routine clinical use. A number of recent articles have described the contrast obtained with fast spin-echo (FSE) sequences and have generally indicated that they depict tissues very similarly to conventional spin-echo (SE) imaging. There are, however, some important differences in contrast between some tissues in FSE images. This work presents a detailed study of the contrast obtained with FSE imaging sequences and examines the image sequence and tissue parameters which influence contrast. The use of multiple refocusing pulses produces several subtle effects not seen in conventional SE imaging sequences, and in this study the precise nature and extent of such effects are described. The relative contributions to image contrast of magnetization transfer, the decoupling of J-modulation effects, the production of stimulated echoes and direct saturation effects, of diffusion and of the effects of the differential attenuation of different spatial frequencies, are each quantified. The mechanisms responsible for the brighter fat signal seen in FSE images, as well as the loss of signal from some other tissues, are explained. Computer simulations, phantom experiments, and clinical images are all used to support the conclusions.

Change in boron coordination in alkali borate glasses, and mixed alkali effects, as elucidated by NMR

NMR with substantial enhancement in signal-to-noise ratio (primarily from gisnal averaging and fast passage techniques) and thermal analysis are utilized to reinvestigate binary alkali borate glasses. The experimental results for the Li, Na, K, Rb and Cs borate glasses at various alkali contents show a strong dependence of the fraction, N4, of 4-coordinated borons on the particular alkali ion. NMR and thermal analysis experimental results for half-and-half mixed LiNa, LiK, LiRb and LiCs borate glasses at different total alkali content are also presented in this paper. It was found that the measured N4 for the mixed alkali glass is less than the value expected from a simple superposition of the values of the constituent alkalis, and in some cases is even less than either of the N4 values for the relevant single alkali glasses. 11B and 133Cs nuclear magnetic resonance results and Tg measurements are used to strengthen the evidence supporting the pairing model suggested by several workers for the mixed alkali effect.

Modeling liver motion and deformation during the respiratory cycle using intensity‐based nonrigid registration of gated MR images

We present a technique for modeling liver motion during the respiratory cycle using intensity-based nonrigid registration of gated magnetic resonance (MR) images. Three-dimensional MR images of the abdomens of four volunteers were acquired at end-inspiration, end-expiration, and eight time points in between using respiratory gating. The deformation fields between the images were computed using intensity-based rigid and nonrigid registration algorithms. Global motion is modeled by a rigid transformation while local motion is modeled by a free-form deformation based on B-splines. Much of the liver motion was cranial-caudal translation, which was captured by the rigid transformation. However, there was still substantial residual deformation (approximately 10 mm averaged over the entire liver in four volunteers, and 34 mm at one place in the liver of one volunteer). The computed organ motion model can potentially be used to determine an appropriate respiratory-gated radiotherapy window during which the position of the target is known within a specified excursion.

Persistence of HIV− Associated Cognitive Impairment, Inflammation and Neuronal Injury in era of Highly Active Antiretroviral Treatment

Objective:To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of HAART. Design:This study is an observational cohort study. Methods:MRS was performed in 268 patients: HIV-negative controls (N = 28), HIV-positive neuroasymptomatic individuals (N = 124), and individuals with AIDS dementia complex (ADC; N = 50) on stable antiretroviral therapy (ART) with a mean duration of infection of 12 years and CD4 cell count of 309 cells/μl. Four metabolites were measured over creatine: N-acetyl aspartate (NAA), marker of neuronal integrity; choline (Cho), myoinositol, markers of inflammation, and glutamate and glutamine (Glx) in the basal ganglia, frontal white matter (FWM), and mid-frontal cortex. Analyses included analysis of variance, analysis of covariance, linear, and nonparametric regression models. Results:Cognitive impairment was found in 48% of HIV-infected individuals. Both HIV-positive groups showed significant increases in myoinositol/creatine or Cho/creatine in all brain regions when compared to controls; a significant decrease in Glx/creatine in the FWM was observed in the neuroasymptomatic group; and only individuals with ADC showed a significant reduction in NAA/creatine, although a significant trend for decreasing NAA/creatine in the basal ganglia was found across the groups. Effects related to aging and duration of infection, but not central nervous system penetration effectiveness were observed. Conclusion:Brain inflammatory changes remain ubiquitous among HIV-infected individuals, whereas neuronal injury occurs predominantly in those with cognitive impairment. Together these findings indicate that despite the widespread use of HAART, HIV-associated cognitive impairment and brain injury persist in the setting of chronic and stable disease.

Subject-specific changes in brain white matter on diffusion tensor imaging after sports-related concussion

BACKGROUND AND PURPOSE Current approaches to diffusion tensor imaging (DTI) analysis do not permit identification of individual-level changes in DTI indices. We investigated the ability of wild bootstrapping analysis to detect subject-specific changes in brain white matter (WM) before and after sports-related concussion. MATERIALS AND METHODS A prospective cohort study was performed in nine high school athletes engaged in hockey or football and six controls. Subjects underwent DTI pre- and postseason within a 3-month interval. One athlete was diagnosed with concussion (scanned within 72 h), and eight suffered between 26 and 399 subconcussive head blows. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in each WM voxel. Bootstrap samples were generated, and a permuted t test was used to compare voxel-wise FA/MD changes in each subject pre- vs. postseason. RESULTS The percentage of WM voxels with significant (p<.05) pre-post FA changes was highest for the concussion subject (3.2%), intermediary for those with subconcussive head blows (mean 1.05%±.15%) and lowest for controls (mean 0.28%±.01%). Similarly, the percentage of WM voxels with significant MD changes was highest for the concussion subject (3.44%), intermediary for those with subconcussive head blows (mean 1.48%±.17%) and lowest for controls (mean 0.48%±.05%). Significantly changed FA and MD voxels colocalized in the concussion subject to the right corona radiata and right inferior longitudinal fasciculus. CONCLUSIONS Wild bootstrap analysis detected significantly changed WM in a single concussed athlete. Athletes with multiple subconcussive head blows had significant changes in a percentage of their WM that was over three times higher than controls. Efforts to understand the significance of these WM changes and their relationship to head impact forces appear warranted.

Consequences of repeated blood-brain barrier disruption in football players

The acknowledgement of risks for traumatic brain injury in American football players has prompted studies for sideline concussion diagnosis and testing for neurological deficits. While concussions are recognized etiological factors for a spectrum of neurological sequelae, the consequences of sub-concussive events are unclear. We tested the hypothesis that blood-brain barrier disruption (BBBD) and the accompanying surge of the astrocytic protein S100B in blood may cause an immune response associated with production of auto-antibodies. We also wished to determine whether these events result in disrupted white matter on diffusion tensor imaging (DT) scans. Players from three college football teams were enrolled (total of 67 volunteers). None of the players experienced a concussion. Blood samples were collected before and after games (n = 57); the number of head hits in all players was monitored by movie review and post-game interviews. S100B serum levels and auto-antibodies against S100B were measured and correlated by direct and reverse immunoassays (n = 15 players; 5 games). A subset of players underwent DTI scans pre- and post-season and after a 6-month interval (n = 10). Cognitive and functional assessments were also performed. After a game, transient BBB damage measured by serum S100B was detected only in players experiencing the greatest number of sub-concussive head hits. Elevated levels of auto-antibodies against S100B were elevated only after repeated sub-concussive events characterized by BBBD. Serum levels of S100B auto-antibodies also predicted persistence of MRI-DTI abnormalities which in turn correlated with cognitive changes. Even in the absence of concussion, football players may experience repeated BBBD and serum surges of the potential auto-antigen S100B. The correlation of serum S100B, auto-antibodies and DTI changes support a link between repeated BBBD and future risk for cognitive changes.

Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era

Cerebral atrophy is a well-described, but poorly understood complication of human immunodeficiency virus (HIV) infection. Despite reduced prevalence of HIV-associated dementia in the highly active antiretroviral therapy (HAART) era, HIV continues to affect the brains of patients with chronic infection. In this study we examine patterns of brain volume loss in HIV-infected patients on HAART, and demographic and clinical factors contributing to brain volume loss. We hypothesized that nadir CD4+ lymphocyte count, duration of HIV infection, and age would be associated with reduced cortical volumes. Volumes of cortical and subcortical regions in 69 HIV-infected neuroasymptomatic (NA) individuals and 13 with at least mild acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) were measured using voxel-based morphometry. Demographic and clinical factors (age, plasma HIV RNA level, current and nadir CD4 counts, duration of infection, central nervous system [CNS] penetration of antiretroviral regimen) along with their interactions were entered into a regression model selection algorithm to determine the final models that best described regional brain volumes. Relative to NA, individuals with ADC exhibited decreased total gray matter and parietal cortex volumes and increased total ventricular volumes. Final regression models showed overall cerebral volume, including gray and white matter volume and volumes of the parietal, temporal, and frontal lobes and the hippocampus, were most strongly associated with disease history factors (nadir CD4 and duration of infection). In contrast, basal ganglia volumes were related most strongly to current disease factors, most notably plasma HIV RNA. These findings indicate that individuals with a history of chronic HIV infection with previous episodes of severely impaired immune function, as reflected by reduced nadir CD4+ lymphocyte count, may be at greatest risk for cerebral atrophy. The pattern of HIV-associated brain loss may be changing from a subcortical to a cortical disease among patients who are largely asymptomatic on HAART.

Changes in Relative Cerebral Blood Volume 1 Month after Radiation-Temozolomide Therapy Can Help Predict Overall Survival in Patients with Glioblastoma

PURPOSE To evaluate perfusion parameter changes in patients with glioblastoma multiforme by comparing the perfusion magnetic resonance (MR) imaging measurements obtained before combined radiation and temozolomide therapy (RT-TMZ) with the follow-up MR imaging measurements obtained 1 month after completion of this treatment. MATERIALS AND METHODS Institutional review board approval was obtained, and HIPAA guidelines were followed. The data of 36 patients (24 male [median age, 63 years]; 12 female [median age, 59 years]) with glioblastoma multiforme who were treated with RT-TMZ were retrospectively reviewed. The hypothesis was that a change in relative cerebral blood volume (rCBV) 1 month after RT-TMZ is predictive of overall survival. Linear regression analysis was performed to correlate changes in tumor size and perfusion parameters with overall survival. Receiver operating characteristic (ROC) curves were evaluated for 1-year survival. Overall survival was assessed with Kaplan-Meir survival curves and log-rank testing. RESULTS Percentage change in rCBV at 1 month after RT-TMZ correlated with overall survival. Increased rCBV after treatment was a strong predictor of poor survival (median survival, 235 days versus 529 days with decreased rCBV) (P < .008, log-rank test). The ROC curves for 1-year survival showed a greater area under the curve (0.806; 95% confidence interval [CI]: 0.698, 0.970) (P = .005) with rCBV than with tumor size (0.556; 95% CI: 0.342, 0.729) (P = .382). The overall survival for patients with increased tumor size, based on Macdonald criteria, was shorter than that for patients who showed no progression (stable or partial response), but the difference was not significant (median survival, 442 days versus 598 days) (P = .761, log-rank test). CONCLUSION Change in rCBV after RT-TMZ appears to correlate with overall survival.

Effects of susceptibility variations on NMR measurements of diffusion

Abstract A pulsed-gradient spin-echo method has been used to measure the water self-diffusion coefficient in various media containing susceptibility variations arising from the presence of superparamagnetic iron oxide particles. These include aqueous suspensions, polyacrylamide gels, and rat livers. The results for each medium indicate that, contrary to intuition, the apparent diffusion coefficient decreases as the iron particle concentration increases. A simple theoretical model has been developed to interpret the data. This model relates the changes in apparent diffusion to the variance of the internal gradient distribution generated by the iron particles. A computer simulation of nuclei undergoing a random walk in an inhomogeneous medium was performed and the results provide qualitative confirmation of the experimental observations. The relevance of these phenomena to measurements of molecular diffusion in heterogeneous systems and their use to estimate internal gradient strengths are discussed.

Functional MRI study of auditory and visual oddball tasks

To seek neural sources of endogenous event-related potentials, brain activations related to rare target stimuli detection in auditory and visual oddball tasks were imaged using a high temporal resolution functional MRI technique. There were multiple modality specific and modality non-specific activations. Auditory specific activations were seen in the bilateral transverse temporal gyri and posterior superior temporal planes while visual specific activations were seen in the bilateral occipital lobes and their junctions with the temporal lobes. Modality non-specific activations were seen in multiple areas including the bilateral parietal and temporal association areas, bilateral prefrontal cortex, bilateral premotor areas, bilateral supplementary motor areas and anterior cingulate gyrus. Results were consistent with previous intracranial evoked potential recording studies, and supported the multiple generator theory of the endogenous event-related potentials.