Xiao-Yong Zhang

A new NOE-mediated MT signal at around −1.6 ppm for detecting ischemic stroke in rat brain

In the present work, we reported a new nuclear Overhauser enhancement (NOE)-mediated magnetization transfer (MT) signal at around -1.6ppm (NOE(-1.6)) in rat brain and investigated its application in the detection of acute ischemic stroke in rodent model. Using continuous wave (CW) MT sequence, the NOE(-1.6) is reliably detected in rat brain. The amplitude of this new NOE signal in rat brain was quantified using a 5-pool Lorentzian Z-spectral fitting method. Amplitudes of amide, amine, NOE at -3.5ppm (NOE(-3.5)), as well as NOE(-1.6) were mapped using this fitting method in rat brain. Several other conventional imaging parameters (R1, R2, apparent diffusion coefficient (ADC), and semi-solid pool size ratio (PSR)) were also measured. Our results show that NOE(-1.6), R1, R2, ADC, and APT signals from stroke lesion have significant changes at 0.5-1h after stroke. Compared with several other imaging parameters, NOE(-1.6) shows the strongest contrast differences between stroke and contralateral normal tissues and stays consistent over time until 2h after onset of stroke. Our results demonstrate that this new NOE(-1.6) signal in rat brain is a new potential contrast for assessment of acute stroke in vivo and might provide broad applications in the detection of other abnormal tissues.

MR imaging of a novel NOE-mediated magnetization transfer with water in rat brain at 9.4 T.

To detect, map, and quantify a novel nuclear Overhauser enhancement (NOE)‐mediated magnetization transfer (MT) with water at approximately −1.6 ppm [NOE(−1.6)] in rat brain using MRI.

Accuracy in the quantification of chemical exchange saturation transfer (CEST) and relayed nuclear Overhauser enhancement (rNOE) saturation transfer effects

Accurate quantification of chemical exchange saturation transfer (CEST) effects, including dipole–dipole mediated relayed nuclear Overhauser enhancement (rNOE) saturation transfer, is important for applications and studies of molecular concentration and transfer rate (and thereby pH or temperature). Although several quantification methods, such as Lorentzian difference (LD) analysis, multiple‐pool Lorentzian fits, and the three‐point method, have been extensively used in several preclinical and clinical applications, the accuracy of these methods has not been evaluated. Here we simulated multiple‐pool Z spectra containing the pools that contribute to the main CEST and rNOE saturation transfer signals in the brain, numerically fit them using the different methods, and then compared their derived CEST metrics with the known solute concentrations and exchange rates. Our results show that the LD analysis overestimates contributions from amide proton transfer (APT) and intermediate exchanging amine protons; the three‐point method significantly underestimates both APT and rNOE saturation transfer at −3.5 ppm (NOE(−3.5)). The multiple‐pool Lorentzian fit is more accurate than the other two methods, but only at lower irradiation powers (≤1 μT at 9.4 T) within the range of our simulations. At higher irradiation powers, this method is also inaccurate because of the presence of a fast exchanging CEST signal that has a non‐Lorentzian lineshape. Quantitative parameters derived from in vivo images of rodent brain tumor obtained using an irradiation power of 1 μT were also compared. Our results demonstrate that all three quantification methods show similar contrasts between tumor and contralateral normal tissue for both APT and the NOE(−3.5). However, the quantified values of the three methods are significantly different. Our work provides insight into the fitting accuracy obtainable in a complex tissue model and provides guidelines for evaluating other newly developed quantification methods.

CEST imaging of fast exchanging amine pools with corrections for competing effects at 9.4 T

Chemical exchange saturation transfer (CEST) imaging of fast exchanging amine protons at 3 ppm offset from the water resonant frequency is of practical interest, but quantification of fast exchanging pools by CEST is challenging. To effectively saturate fast exchanging protons, high irradiation powers need to be applied, but these may cause significant direct water saturation as well as non‐specific semi‐solid magnetization transfer (MT) effects, and thus decrease the specificity of the measured signal. In addition, the CEST signal may depend on the water longitudinal relaxation time (T1w), which likely varies between tissues and with pathology, further reducing specificity. Previously, an analysis of the asymmetry of saturation effects (MTRasym) has been commonly used to quantify fast exchanging amine CEST signals. However, our results show that MTRasym is greatly affected by the above factors, as well as asymmetric MT and nuclear Overhauser enhancement (NOE) effects. Here, we instead applied a relatively more specific inverse analysis method, named AREX (apparent exchange‐dependent relaxation), that has previously been applied only to slow and intermediate exchanging solutes. Numerical simulations and controlled phantom experiments show that, although MTRasym depends on T1w and semi‐solid content, AREX acquired in steady state does not, which suggests that AREX is more specific than MTRasym. By combining with a fitting approach instead of using the asymmetric analysis to obtain reference signals, AREX can also avoid contaminations from asymmetric MT and NOE effects. Animal experiments show that these two quantification methods produce differing contrasts between tumors and contralateral normal tissues in rat brain tumor models, suggesting that conventional MTRasym applied in vivo may be influenced by variations in T1w, semi‐solid content, or NOE effect. Thus, the use of MTRasym may lead to misinterpretation, while AREX with corrections for competing effects likely enhances the specificity and accuracy of quantification to fast exchanging pools.

Assignment of the molecular origins of CEST signals at 2 ppm in rat brain

Chemical exchange saturation transfer effects at 2 ppm (CEST@2ppm) in brain have previously been interpreted as originating from creatine. However, protein guanidino amine protons may also contribute to CEST@2ppm. This study aims to investigate the molecular origins and specificity of CEST@2ppm in brain.

R1 correction in amide proton transfer imaging: indication of the influence of transcytolemmal water exchange on CEST measurements.

Amide proton transfer (APT) imaging may potentially detect mobile proteins/peptides non‐invasively in vivo, but its specificity may be reduced by contamination from other confounding effects such as asymmetry of non‐specific magnetization transfer (MT) effects and spin–lattice relaxation with rate R1 (=1/T1). Previously reported spillover, MT and R1 correction methods were based on a two‐pool model, in which the existence of multiple water compartments with heterogeneous relaxation properties in real tissues was ignored. Such simple models may not adequately represent real tissues, and thus such corrections may be unreliable. The current study investigated the effectiveness and accuracy of correcting for R1 in APT imaging via simulations and in vivo experiments using tumor‐bearing rats subjected to serial injections of Gd‐DTPA that produced different tissue R1 values in regions of blood–brain‐barrier breakdown. The results suggest that conventional measurements of APT contrast (such as APT* and MTRasym) may be significantly contaminated by R1 variations, while the R1‐corrected metric AREX* was found to be relatively unaffected by R1 changes over a broad range (0.4–1 Hz). Our results confirm the importance of correcting for spin–lattice relaxation effects in quantitative APT imaging, and demonstrate the reliability of using the observed tissue R1 for corrections to obtain more specific and accurate measurements of APT contrast in vivo. The results also indicate that, due to relatively fast transcytolemmal water exchange, the influence of intra‐ and extracellular water compartments on CEST measurements with seconds long saturation time may be ignored in tumors. Copyright

Double-chambered left ventricle in echocardiography.

In this article, we describe a double‐chambered left ventricle (LV) in a 37‐year‐old man. Its accessory chamber attached to the inferior and posterior wall of LV, and had normal systolic contraction without any regional wall motion abnormality. A double‐chambered LV was suspected on echocardiography and confirmed by cardiac computed tomography scanning and cardiac magnet resonance imaging. Our aim is to accentuate the value of echocardiography in this rare anomaly. (Echocardiography 2012;29:E67‐E68)

Influence of water compartmentation and heterogeneous relaxation on quantitative magnetization transfer imaging in rodent brain tumors.

The goal of this study was to investigate the influence of water compartmentation and heterogeneous relaxation properties on quantitative magnetization transfer (qMT) imaging in tissues, and in particular whether a two‐pool model is sufficient to describe qMT data in brain tumors.

Sphincter of Oddi dysfunction in hypercholesterolemic rabbits

Background and objectives The mechanisms that trigger gallbladder evacuation dysfunction, the key risk factor for gallstone formation, have not yet been fully elucidated. The sphincter of Oddi (SO) plays important roles in the regulation of gallbladder evacuation and maintenance of normal hydraulic pressure of the biliary tract. The aim of our study was to investigate the effects of hypercholesterolemia on the motility function of SO and the underlying mechanisms of SO dysfunction (SOD). Methods Forty New Zealand white rabbits were divided randomly into the control group fed with standard chow and the experimental (Ch) group fed with a high-cholesterol diet for 8 weeks. Changes in the maximal gallbladder emptying rate, gallbladder evacuation with cholecystokinin-octapeptide (CCK-8) stimulation and SO functions of both groups were measured in vivo; B ultrasound examination was used for dynamic observation of peristaltic movements in vivo; SO pressure was measured using manometry; morphological characteristics were observed by electronic microscope; laser scanning confocal fluorescence microscopy was used to identify changes in [Ca2+]i and Ca2+ oscillation in primary SO smooth muscle cells (SMCs). Results Gallbladder cholestasis was observed during early stages of gallstone formation in Ch rabbits. CCK-8 could not improve the gallbladder cholestatic state in Ch group. Passive dilation of SO significantly improved the cholestatic state in Ch rabbits (P<0.05), although the maximal gallbladder emptying rate was still lower than that of the control group. Manometry data indicted a significant increase in the base pressure of the SO low-pressure ampulla segment and high-pressure segment (P<0.05) in Ch group. laser scanning confocal fluorescence microscopy assay data indicated that [Ca2+]i in SO cells of Ch group significantly increased and were in a state of overload (P<0.05); Ca2+ oscillation signals in SO cells of Ch group were also abnormal. Conclusion Hypercholesterolemia initially induced SOD, leading to increased gallbladder evacuation resistance and cholestasis. We suggested that [Ca2+]i overload and/or Ca2+ oscillation abnormality potentially play important roles in the pathogenesis of SOD.

Measurement of APT using a combined CERT-AREX approach with varying duty cycles

The goal is to develop an imaging method where contrast reflects amide-water magnetization exchange, with minimal signal contributions from other sources. Conventional chemical exchange saturation transfer (CEST) imaging of amides (often called amide proton transfer, or APT, and quantified by the metric MTRasym) is confounded by several factors unrelated to amides, such as aliphatic protons, water relaxation, and macromolecular magnetization transfer. In this work, we examined the effects of combining our previous chemical exchange rotation (CERT) approach with the non-linear AREX method while using different duty cycles (DC) for the label and reference scans. The dependencies of this approach, named AREXdouble,vdc, on tissue parameters, including T1, T2, semi-solid component concentration (fm), relayed nuclear Overhauser enhancement (rNOE), and nearby amines, were studied through numerical simulations and control sample experiments at 9.4T and 1μT irradiation. Simulations and experiments show that AREXdouble,vdc is sensitive to amide-water exchange effects, but is relatively insensitive to T1, T2, fm, nearby amine, and distant aliphatic protons, while the conventional metric MTRasym, as well as several other APT imaging methods, are significantly affected by at least some of these confounding factors.