Investigation of optimizing and translating pH‐sensitive pulsed‐chemical exchange saturation transfer (CEST) imaging to a 3T clinical scanner

Chemical exchange saturation transfer (CEST) MRI provides a sensitive detection mechanism that allows characterization of dilute labile protons usually undetectable by conventional MRI. Particularly, amide proton transfer (APT) imaging, a variant of CEST MRI, has been shown capable of detecting ischemic acidosis, and may serve as a surrogate metabolic imaging marker. For preclinical CEST imaging, continuous‐wave (CW) radiofrequency (RF) irradiation is often applied so that the steady state CEST contrast can be reached. On clinical scanners, however, specific absorption rate (SAR) limit and hardware preclude the use of CW irradiation, and instead require an irradiation scheme of repetitive RF pulses (pulsed‐CEST imaging). In this work, CW‐ and pulsed‐CEST MRI were systematically compared using a tissue‐like pH phantom on an imager capable of both CW and pulsed RF irradiation schemes. The results showed that the maximally obtainable pulsed‐CEST contrast is approximately 95% of CW‐CEST contrast, and their optimal RF irradiation powers are equal. Moreover, the pulsed‐CEST sequence was translated to a 3 Tesla clinical scanner and detected pH contrast from the labile creatine amine groups (1.9 ppm). Furthermore, pilot endogenous APT imaging of normal human volunteers was demonstrated, warranting future APT MRI of stroke patients to elucidate its diagnostic value. Magn Reson Med 60:834–841, 2008. © 2008 Wiley‐Liss, Inc.     

Correction for artifacts induced by B(0) and B(1) field inhomogeneities in pH-sensitive chemical exchange saturation transfer (CEST) imaging.

Chemical exchange saturation transfer (CEST) imaging provides an indirect detection mechanism that allows quantification of certain labile groups unobservable using conventional MRI. Recently, amide proton transfer (APT) imaging, a variant form of CEST imaging, has been shown capable of detecting lactic acidosis during acute ischemia, providing information complementary to that of perfusion and diffusion MRI. However, CEST contrast is usually small, and therefore, it is important to optimize experimental conditions for reliable and quantitative CEST imaging. In particular, CEST imaging is sensitive to B(0) and B(1) field, while on the other hand; field inhomogeneities persist despite recent advances in magnet technologies, especially for in vivo imaging at high fields. Consequently, correction algorithms that can compensate for field inhomogeneity-induced measurement errors in CEST imaging might be very useful. In this study, the dependence of CEST contrast on field distribution was solved and a correction algorithm was developed to compensate for field inhomogeneity-induced CEST imaging artifacts. In addition, the proposed algorithm was verified with both numerical simulation and experimental measurements, and showed nearly complete correction of CEST imaging measurement errors caused by moderate field inhomogeneity.     

Fast multislice pH‐weighted chemical exchange saturation transfer (CEST) MRI with Unevenly segmented RF irradiation

Chemical exchange saturation transfer (CEST) MRI is a versatile imaging technique for measuring microenvironment properties via dilute CEST labile groups. Conventionally, CEST MRI is implemented with a long radiofrequency irradiation module, followed by fast image acquisition to obtain the steady state CEST contrast. Nevertheless, the sensitivity, scan time, and spatial coverage of the conventional CEST MRI method may not be optimal. Our study proposed a segmented radiofrequency labeling scheme that includes a long primary radiofrequency irradiation module to generate the steady state CEST contrast and repetitive short secondary radiofrequency irradiation module immediately after the image acquisition so as to maintain the steady state CEST contrast for multislice acquisition and signal averaging. The proposed CEST MRI method was validated experimentally with a tissue‐like pH phantom and optimized for the maximal contrast‐to‐noise ratio. In addition, the proposed sequence was evaluated for imaging ischemic acidosis via pH‐weighted endogenous amide proton transfer MRI, which showed similar contrast as conventional amide proton transfer MRI. In sum, a fast multislice relaxation self‐compensated CEST MRI sequence was developed, with significantly improved sensitivity and suitable for in vivo applications. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

NOrmalized MAgnetization Ratio (NOMAR) filtering for creation of tissue selective contrast maps

An MRI segmentation technique based on collecting two additional saturation transfer images is proposed as an aid for improved detection of chemical exchange saturation transfer agents. In this approach, the additional images are acquired at saturation frequencies of ?12.5 and ?50 ppm. Use of the ratio of these images allows differentiation of voxels with low magnetization transfer contrast (such as fat, cerebrospinal fluid, edema, or blood) from target tissue voxels using a global threshold determined by histogram analysis. We demonstrate that this technique can reduce artifacts, in vitro, in a phantom containing tubes with chemical exchange saturation transfer contrast agent embedded in either crosslinked bovine serum albumin or buffer, and in vivo for detecting diamagnetic CEST (DIACEST) liposomes injected into mice. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Development of chemical exchange saturation transfer at 7T

Chemical exchange saturation transfer (CEST) MRI is a molecular imaging method that has previously been successful at reporting variations in tissue protein and glycogen contents and pH. We have implemented amide proton transfer (APT), a specific form of chemical exchange saturation transfer imaging, at high field (7T) and used it to study healthy human subjects and patients with multiple sclerosis. The effects of static field inhomogeneities were mitigated using a water saturation shift referencing method to center each z‐spectrum on a voxel‐by‐voxel basis. Contrary to results obtained at lower fields, APT imaging at 7T revealed significant contrast between white and gray matters, with a higher APT signal apparent within the white matter. Preliminary studies of multiple sclerosis showed that the APT asymmetry varied with the type of lesion examined. An increase in APT asymmetry relative to healthy tissue was found in some lesions. These results indicate the potential utility of APT at high field as a noninvasive biomarker of white matter pathology, providing complementary information to other MRI methods in current clinical use. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Relaxation-compensated fast multislice amide proton transfer (APT) imaging of acute ischemic stroke.

Amide proton transfer (APT) imaging is a variant form of chemical exchange saturation transfer (CEST) imaging that is based on the magnetization exchange between bulk water and labile endogenous amide protons. Given that chemical exchange is pH-dependent, APT imaging has been shown capable of imaging ischemic tissue acidosis, and as such, may serve as a surrogate metabolic imaging marker complementary to perfusion and diffusion MRI. In order for APT imaging to properly diagnose heterogeneous pathologies such as stroke and cancer, fast volumetric APT imaging has to be developed. In this study the evolution of CEST contrast after RF irradiation was solved showing that although the CEST steady state is reached by the apparent longitudinal relaxation rate, the decreases of CEST contrast after irradiation is governed by the intrinsic relaxation constant. A volumetric APT imaging sequence is proposed that acquires multislice images immediately after a single long continuous wave (CW) RF irradiation, wherein the relaxation-induced loss of CEST contrast is compensated for during postprocessing. The proposed technique was verified by numerical simulation, a tissue-like dual-pH phantom, and demonstrated on an embolic stroke animal model. In summary, our study has established a fast volumetric pH-weighted APT imaging technique, allowing further investigation to fully evaluate its diagnostic power.     

羊驼胚胎移植研究动态

羊驼作为中国首次引进的动物新品种,其繁殖时间较长,作为一项普遍饲养的畜牧业,存在许多不利因素。运用家畜胚胎移植技术,可以提高羊驼的繁殖速度及品质。因此,掌握胚胎移植技术,加速发展羊驼养殖业,应是目前一项重要任务。