Chun S. Zuo

Proton Echo-Planar Spectroscopic Imaging of J-Coupled Resonances in Human Brain at 3 and 4 Tesla

In this multicenter study, 2D spatial mapping of J‐coupled resonances at 3T and 4T was performed using short‐TE (15 ms) proton echo‐planar spectroscopic imaging (PEPSI). Water‐suppressed (WS) data were acquired in 8.5 min with 1‐cm3 spatial resolution from a supraventricular axial slice. Optimized outer volume suppression (OVS) enabled mapping in close proximity to peripheral scalp regions. Constrained spectral fitting in reference to a non‐WS (NWS) scan was performed with LCModel using correction for relaxation attenuation and partial‐volume effects. The concentrations of total choline (tCho), creatine + phosphocreatine (Cr+PCr), glutamate (Glu), glutamate + glutamine (Glu+Gln), myo‐inositol (Ins), NAA, NAA+NAAG, and two macromolecular resonances at 0.9 and 2.0 ppm were mapped with mean Cramer‐Rao lower bounds (CRLBs) between 6% and 18% and ∼150‐cm3 sensitive volumes. Aspartate, GABA, glutamine (Gln), glutathione (GSH), phosphoethanolamine (PE), and macromolecules (MMs) at 1.2 ppm were also mapped, although with larger mean CRLBs between 30% and 44%. The CRLBs at 4T were 19% lower on average as compared to 3T, consistent with a higher signal‐to‐noise ratio (SNR) and increased spectral resolution. Metabolite concentrations were in the ranges reported in previous studies. Glu concentration was significantly higher in gray matter (GM) compared to white matter (WM), as anticipated. The short acquisition time makes this methodology suitable for clinical studies. Magn Reson Med, 2007.

Potential heating effect in the gravid uterus during MR HASTE imaging.

Our purpose was to evaluate if temperature changes occur in maternal or fetal tissues during HASTE imaging. Methods: Pregnant pigs were scanned with the HASTE technique, and temperatures were measured with phase maps and temperature probes inserted into the amniotic fluid and fetal brain. Results: Fiberoptic probes showed that no heating occurred in fetal tissues or amniotic fluid during HASTE imaging. Conclusion: Our current HASTE protocols do not deposit a significant amount of heat in the gravid uterus. J. Magn. Reson. Imaging 2001;13:856–861.

Effects of Low-Intensity Pulsed Ultrasound, Dexamethasone/TGF-β1 and/or BMP-2 on the Transcriptional Expression of Genes in Human Mesenchymal Stem Cells: Chondrogenic vs. Osteogenic Differentiation

The effects of low-intensity pulsed ultrasound (LIPUS) on the differentiation of human mesenchymal stem cells (hMSCs) were investigated in this study. hMSCs were subjected to LIPUS with or without dexamethasone/transforming growth factor-beta1 (TD) or bone morphogenetic protein-2 (BMP-2) and the effects of this treatment were assessed. TD-treated hMSCs exhibited characteristic chondrogenic morphology and increased messenger RNA (mRNA) expression of chondrogenic markers and LIPUS enhanced the chondrogenic differentiation of hMSCs treated with TD. The expression of Runx2, an osteogenic transcription factor was not altered in either TD treatment group; however, a significant increase was detected in the LIPUS only group. The osteogenic appearance exhibited 3 days after LIPUS and/or BMP-2 treatment. Increases in the mRNA expression levels of osteogenic markers, Runx2 and ALP were also detected. There was no additive or altered effect with combined LIPUS and BMP-2 treatment. LIPUS alone can increase osteogenic differentiation of hMSCs and LIPUS enhances TD-mediated chondrogenic differentiation of hMSCs. Clinically, LIPUS may differentially influence bone vs. cartilage repair.

Proton nuclear magnetic resonance measurement of p‐boronophenylalanine (BPA): A therapeutic agent for boron neutron capture therapy

Noninvasive in vivo quantitation of boron is necessary for obtaining pharmacokinetic data on candidate boronated delivery agents developed for boron neutron capture therapy (BNCT). Such data, in turn, would facilitate the optimization of the temporal sequence of boronated drug infusion and neutron irradiation. Current approaches to obtaining such pharmacokinetic data include: positron emission tomography employing F-18 labeled boronated delivery agents (e.g., p-boronophenylalanine), ex vivo neutron activation analysis of blood (and very occasionally tissue) samples, and nuclear magnetic resonance (NMR) techniques. In general, NMR approaches have been hindered by very poor signal to noise achieved due to the large quadrupole moments of B-10 and B-11 and (in the case of B-10) very low gyromagnetic ratio, combined with low physiological concentrations of these isotopes under clinical conditions. This preliminary study examines the feasibility of proton NMR spectroscopy for such applications. We have utilized proton NMR spectroscopy to investigate the detectability of p-boronophenylalanine fructose (BPA-f) at typical physiological concentrations encountered in BNCT. BPA-f is one of the two boron delivery agents currently undergoing clinical phase-I/II trials in the U.S., Japan, and Europe. This study includes high-resolution 1H spectroscopic characterization of BPA-f to identify useful spectral features for purposes of detection and quantification. The study examines potential interferences, demonstrates a linear NMR signal response with concentration, and presents BPA NMR spectra in ex vivo blood samples and in vivo brain tissues.

Coenzyme Q10 Effects on Creatine Kinase Activity and Mood in Geriatric Bipolar Depression

Introduction: Despite the prevalence, associated comorbidities, and functional consequences of bipolar depression (BPD), underlying disease mechanisms remain unclear. Published studies of individuals with bipolar disorder implicate abnormalities in cellular energy metabolism. This study tests the hypotheses that the forward rate constant (kfor) of creatine kinase (CK) is altered in older adults with BPD and that CoEnzyme Q10 (CoQ10), known to have properties that enhance mitochondrial function, increases kfor in elderly individuals with BPD treated with CoQ10 compared with untreated age- and sex-matched controls. Methods: Ten older adults (ages 55 and above) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition [DSM IV]) bipolar disorder, current episode depressed and 8 older controls underwent two 4 Tesla 31Phosphorus magnetic resonance spectroscopy (31PMRS) scans 8 weeks apart using a magnetization transfer (MT) acquisition scheme to calculate kfor. The BPD group was treated with open-label CoEnzyme Q10 400 mg/d titrated up by 400 mg/d every 2 weeks to a maximum of 1200 mg/d. The Montgomery Asberg Depression Rating Scale (MADRS) was used to measure depression symptom severity. Baseline kfor and changes in kfor were compared between individuals with BPD and controls, not receiving CoQ. Clinical ratings were compared across time and associated with kfor changes using repeated measures linear regression. Results: The kfor of CK was nonsignificantly lower for BPD than healthy controls at baseline (BPD mean (standard deviation [SD]) = 0.19 (0.02), control mean (SD) = 0.20 (0.02), Wilcoxon rank sum exact P = .40). The kfor for both CoQ10-treated BPD and controls increased after 8 weeks (mean increase (SD) = 0.03 (0.04), Wilcoxon signed rank exact P = .01), with no significant difference in 8-week changes between groups (BPD mean change (SD) = 0.03 (0.03), control mean change (SD) = 0.03 (0.05), Wilcoxon rank sum exact P = .91). In an exploratory analysis, depression severity decreased with CoQ10 treatment in the group with BPD (F 3,7 = 4.87, P = .04) with significant reductions in the MADRS at weeks 2 (t 9 = −2.40, P = .04) and 4 (t 9 = −3.80, P = .004). Conclusions: This study employing the novel MRS technique of MT did not demonstrate significance between group differences in the kfor of CK but did observe a trend that would require confirmation in a larger study. An exploratory analysis suggested a reduction in depression symptom severity during treatment with high-dose CoEnzyme Q10 for older adults with BPD. Further studies exploring alterations of high-energy phosphate metabolites in geriatric BPD and efficacy studies of CoQ10 in a randomized controlled trial are both warranted.

Static and dynamic posterior cingulate cortex nodal topology of default mode network predicts attention task performance

Characterization of the default mode network (DMN) as a complex network of functionally interacting dynamic systems has received great interest for the study of DMN neural mechanisms. In particular, understanding the relationship of intrinsic resting-state DMN brain network with cognitive behaviors is an important issue in healthy cognition and mental disorders. However, it is still unclear how DMN functional connectivity links to cognitive behaviors during resting-state. In this study, we hypothesize that static and dynamic DMN nodal topology is associated with upcoming cognitive task performance. We used graph theory analysis in order to understand better the relationship between the DMN functional connectivity and cognitive behavior during resting-state and task performance. Nodal degree of the DMN was calculated as a metric of network topology. We found that the static and dynamic posterior cingulate cortex (PCC) nodal degree within the DMN was associated with task performance (Reaction Time). Our results show that the core node PCC nodal degree within the DMN was significantly correlated with reaction time, which suggests that the PCC plays a key role in supporting cognitive function.

Visualization and quantification of renal R2* changes during water diuresis

To refine and evaluate methods for analysis of renal blood oxygenation level dependent (BOLD) MRI data.

In vivo bone marrow lipid characterization with line scan Carr-Purcell-Meiboom-Gill proton spectroscopic imaging

Line scan Carr-Purcell-Meiboom-Gill spectroscopic imaging sequences have been used to extract lipid chemical composition indices in healthy adult bone marrow in the knee at 1.5 T. Since several spectroscopic echo readouts follow each excitation, the information acquired reflects a balance between spectral T2 decay processes and spectral resolution. To examine this balance in detail, data sets with two different echo spacings and spectral resolutions have been acquired to compare the information available from each in studies of bone marrow. Oils for which high field (7 T) proton spectra were recorded were used to evaluate the accuracy of lipid chemical composition indices extracted from the line scan Carr-Purcell-Meiboom-Gill spectroscopic imaging methods at 1.5 T. The extension of the method to fast spectroscopic imaging of bone marrow with multiple echoes is demonstrated.

Super-paramagnetic iron oxide nanoparticles for use in extrapulmonary tuberculosis diagnosis

The limited sensitivity of serological tests for mycobacterial antigens has encouraged the development of a nanoparticle probe specific for the extrapulmonary form of Mycobacterium tuberculosis (Mtb). We developed an innovative probe comprised of super-paramagnetic iron oxide (SPIO) nanoparticles conjugated with Mtb surface antibody (MtbsAb-nanoparticles) to provide ultrasensitive imaging of biomarkers involved in extrapulmonary Mtb infection. MtbsAb-nanoparticles were significantly conjugated with Mtb bacilli. The extent of contrast enhancement reduction on magnetic resonance imaging (MRI) for Mtb and human monocytic THP1 cells was proportional to the concentration of MtbsAb-nanoparticles. When MtbsAb-nanoparticles were intravenously injected into mice bearing Mtb granulomas, the granulomatous site showed a 14-fold greater reduction in signal intensity enhancement on T(2) -weighted MR images compared with an opposing site that received PBS injection. Mtb sAb-nanoparticles represent a new non-invasive technology for the diagnosis of extrapulmonary Mtb.

Measurement of creatine kinase reaction rate in human brain using magnetization transfer image-selected in vivo spectroscopy (MT-ISIS) and a volume 31P/1H radiofrequency coil in a clinical 3-T MRI system

High‐energy phosphate metabolism, which allows the synthesis and regeneration of adenosine triphosphate (ATP), is a vital process for neuronal survival and activity. In particular, creatine kinase (CK) serves as an energy reservoir for the rapid buffering of ATP levels. Altered CK enzyme activity, reflecting compromised high‐energy phosphate metabolism or mitochondrial dysfunction in the brain, can be assessed using magnetization transfer (MT) MRS. MT 31P MRS has been used to measure the forward CK reaction rate in animal and human brain, employing a surface radiofrequency coil. However, long acquisition times and excessive radiofrequency irradiation prevent these methods from being used routinely for clinical evaluations. In this article, a new MT 31P MRS method is presented, which can be practically used to measure the CK forward reaction rate constant in a clinical MRI system employing a volume head 31P coil for spatial localization, without contamination from the scalp muscle, and an acquisition time of 30 min. Other advantages associated with the method include radiofrequency homogeneity within the regions of interest of the brain using a volume coil with image‐selected in vivo spectroscopy localization, and reduction of the specific absorption rate using nonadiabatic radiofrequency pulses for MT saturation. The mean value of kf was measured as 0.320 ± 0.075 s−1 from 10 healthy volunteers with an age range of 18–40 years. These values are consistent with those obtained using earlier methods, and the technique may be used routinely to evaluate energetic processes in the brain on a clinical MRI system. Copyright