化学交换饱和转移在心脏磁共振中的研究进展

化学交换饱和转移（chemical exchange saturation transfer，CEST）MRI成像是一种新兴的基于饱和质子与周围水中质子化学交换的体内分子成像技术，将传统的解剖成像扩展到组织酸碱度成像及体内多种生化代谢成像，且具有无辐射、非侵入性等显著优势，成为时下研究一大热点。目前CEST在心血管磁共振成像的应用研究刚刚起步，本文主要对其原理及其在心脏磁共振的临床应用价值研究进展予以详细阐述。     

化学交换饱和转移成像在胶质瘤的应用研究进展

胶质瘤是最常见的原发性中枢神经系统肿瘤,侵袭性强,预后极差。其生长过程中伴随着肿瘤组织内蛋白质、谷氨酸、胺等物质含量的改变。化学交换饱和转移成像(Chemical exchange saturation transfer,CEST)是一种依赖于酰胺(-NH)、胺(-NH2)和羟基(-OH)基团中可移动质子和自由水进行化学交换的新型无创性MRI技术,从分子水平反映组织内蛋白质或多肽中可移动质子含量及pH值的变化。该技术可发现并量化胶质瘤内部分子水平的改变。本文就CEST技术原理及在胶质瘤术前诊断及鉴别诊断、分级、分子分型预测、疗效评估的研究进展及CEST技术存在的不足进行综述。     

化学交换饱和转移成像技术在肌肉骨骼系统的研究进展

化学交换饱和转移成像(chemical exchange saturation transfer,CEST)技术是一种新型磁共振成像技术,它可利用磁化传输比不对称(magnetization transfer ratio asymmetry,MTRasym)分析产生半定量的结果,对肌骨系统相关疾病的早期诊断和手术决策具有重要意义.传统MRI只能反映病变的形态学差异,很难为疾病的早期诊断提供帮助.CEST技术具有无侵入性和定量检测的优势,已应用于骨关节炎的早期诊断、椎间盘变性及软骨修复手术术后评估等.作者重点总结了CEST的原理、信号测定及其在肌肉骨骼系统的临床应用.     

脑部化学交换饱和转移成像研究

化学交换饱和转移(chemical exchange saturation transfer,CEST)成像是在磁化传递及化学交换理论基础上发展起来的一种磁共振成像新方法,其扩展了磁共振分子影像新领域,但还处于研究阶段。其以细胞内物质为内源性对比剂,通过水信号间接检测代谢物信息,进行组织的酸碱度成像及其各种代谢物成像。本文主要探讨MRI领域中与水相关的化学交换饱和转移现象,阐述其原理、研究现状及其在不同场强磁共振仪上脑部疾病的应用。     

酰胺质子转移成像在泌尿生殖系统疾病中的研究进展

酰胺质子转移成像是一种新型磁共振分子成像技术.它是化学交换饱和转移成像的一个分支,通过检测组织内源性蛋白质或多肽中的酰胺质子-水质子交换速率反映细胞内蛋白质浓度及pH值变化.本文拟对酰胺质子转移成像在泌尿生殖系统疾病中的应用进展做一综述.     

化学交换饱和转移效应量化方法的应用进展

化学交换饱和转移(chemical exchange saturation transfer,CEST)是一种新兴的分子成像技术,通过分子间化学交换现象间接获得代谢物浓度信息,进行疾病诊断、预后评估等.然而得到的CEST信号并不是单纯来自化学交换,而混杂了诸如传统磁化转移效应(magnetization transfer,MT)、直接饱和效应(direct water saturation,DS)、核奥氏效应(nuclear overhauser enhancement,NOE)等效应.去除或利用这些效应以提高量化的准确度和成像质量是向临床转化的关键.     

氨基质子转移成像用于缺血性脑卒中进展

缺血性脑卒中是致残率及致死率均较高的脑血管疾病。影像学检查对于精准诊疗缺血性脑卒中具有重要作用。氨基质子转移(APT)成像是一种新型化学交换饱和转移(CEST)成像技术,可反映组织pH值变化,在评估缺血性脑卒中组织代谢微环境、指导治疗及评估预后等方面展现出巨大潜能。本文对APT成像技术的基本原理及其在缺血性脑卒中的研究及应用进展进行综述。     

化学交换饱和转移MRI中B0场不均匀性校正的研究进展

化学交换饱和转移（CEST）MRI数据采集过程中主磁场B0的不均匀部分会导致空间编码错误,扭曲CEST成像,产生伪影并严重影响定量分析的准确性,因此需要对MRI进行匀场校正。近年来,研究者对B0场不均匀性的校正问题进行了一系列研究,通过优化线性拟合算法、改进采集序列等手段,可以在一定程度上降低B0场不均匀性带来的伪影,减少扫描时间并且提高对比噪声比。本文旨在对B0场不均匀性校正的研究进行综述。     

磁共振氨基质子转移成像的临床应用

磁共振氨基质子转移(amide proton transfer,APT)成像是一种基于化学交换饱和转移技术且可反映生物组织中内源性游离蛋白和肽类含量以及氨基质子交换速率的无创性分子磁共振成像方法。APT加权图像是通过对Z谱中水频率两侧±3.5 ppm处的非对称性磁化转移率进行计算得到的。近年来,APT磁共振成像(magnetic resonance imaging,MRI)已被越来越多地应用于疾病诊断中。本文针对目前APT MRI在临床应用和科学研究方面的进展予以综述。     

深度学习在化学交换饱和转移磁共振成像中的研究进展

化学交换饱和转移(chemical exchange saturation transfer, CEST)是一种新型的MRI技术,其基本原理是通过水信号的减少来间接实现对特定低浓度溶质分子的检测。采集速度慢、量化速度慢、量化评估不准确等问题影响着CEST MRI在临床中的应用推广,如何改善这些问题也成为研究的重点。深度学习作为人工智能的一种新的研究方向,近几年才应用于CEST MRI技术。本文在广泛调研国内外文献的基础上,对深度学习在临床CEST MRI上应用进行了深入分析与梳理。其中,在量化方面,一方面介绍了通过给深度神经网络(deep neural network, DNN)中输入临床中采集3 T的Z谱数据,预测出高场的CEST参数,进而得到比较明显的CEST信号;另一方面介绍了DNN结合磁化转移指纹识别(magnetization transfer fingerprinting, MTF)技术的方法改善传统量化方法中拟合参数精度低和拟合效率低的问题;在加速方面,一方面介绍深度学习用于CEST MRI加速采集;另一方面介绍了深度学习用于改善传统多池洛伦兹拟合量化速度慢的问题。供对本...     

A review of optimization and quantification techniques for chemical exchange saturation transfer MRI toward sensitive in vivo imaging

Chemical exchange saturation transfer (CEST) MRI is a versatile imaging method that probes the chemical exchange between bulk water and exchangeable protons. CEST imaging indirectly detects dilute labile protons via bulk water signal changes following selective saturation of exchangeable protons, which offers substantial sensitivity enhancement and has sparked numerous biomedical applications. Over the past decade, CEST imaging techniques have rapidly evolved owing to contributions from multiple domains, including the development of CEST mathematical models, innovative contrast agent designs, sensitive data acquisition schemes, efficient field inhomogeneity correction algorithms, and quantitative CEST (qCEST) analysis. The CEST system that underlies the apparent CEST‐weighted effect, however, is complex. The experimentally measurable CEST effect depends not only on parameters such as CEST agent concentration, pH and temperature, but also on relaxation rate, magnetic field strength and more importantly, experimental parameters including repetition time, RF irradiation amplitude and scheme, and image readout. Thorough understanding of the underlying CEST system using qCEST analysis may augment the diagnostic capability of conventional imaging. In this review, we provide a concise explanation of CEST acquisition methods and processing algorithms, including their advantages and limitations, for optimization and quantification of CEST MRI experiments. Copyright © 2015 John Wiley & Sons, Ltd.     

A theoretical analysis of chemical exchange saturation transfer echo planar imaging (CEST‐EPI) steady state solution and the CEST sensitivity efficiency‐based optimization approach

Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute labile protons and microenvironmental properties, augmenting routine relaxation‐based MRI. Recent developments of quantitative CEST (qCEST) analysis such as omega plots and RF‐power based ratiometric calculation have extended our ability to elucidate the underlying CEST system beyond the simplistic apparent CEST measurement. CEST MRI strongly varies with experimental factors, including the RF irradiation level and duration as well as repetition time and flip angle. In addition, the CEST MRI effect is typically small, and experimental optimization strategies have to be carefully evaluated in order to enhance the CEST imaging sensitivity. Although routine CEST MRI has been optimized largely based on maximizing the magnitude of the CEST effect, the CEST signal‐to‐noise (SNR) efficiency provides a more suitable optimization index, particularly when the scan time is constrained. Herein, we derive an analytical solution of the CEST effect that takes into account key experimental parameters including repetition time, imaging flip angle and RF irradiation level, and solve its SNR efficiency. The solution expedites CEST imaging sensitivity calculation, substantially faster than the Bloch–McConnell equation‐based numerical simulation approach. In addition, the analytical solution‐based SNR formula enables the exhaustive optimization of CEST MRI, which simultaneously predicts multiple optimal parameters such as repetition time, flip angle and RF saturation level based on the chemical shift and exchange rate. The sensitivity efficiency‐based optimization approach could simplify and guide imaging of CEST agents, including glycogen, glucose, creatine, gamma‐aminobutyric acid and glutamate. Copyright © 2016 John Wiley & Sons, Ltd.     

In vitro study of endogenous CEST agents at 3 T and 7 T

Chemical exchange saturation transfer (CEST) has been an intensive research area in MRI, providing contrast mechanisms for the amplified detection and monitoring of biomarkers and physiologically active molecules. In biological tissues and organs, many endogenous CEST agents coexist, and their CEST effects may overlap. The interpretation of such overlapped CEST effects can be addressed when the individual CEST effects originating from various metabolites are characterized. In this work, we present the in vitro measurements of the CEST effects from endogenous CEST agents that are commonly found in biological tissues and organs, at the external magnetic fields of 3 T and 7 T and under various pH conditions. Together with the proton NMR spectra measured at 11.7 T, these CEST effects have been evaluated in consideration of the chemical exchange rates, chemical shifts, and acidities of the labile protons. Amine protons of small metabolites might not be visible at 3 T, but some of them can be probed at 7 T, wherein their CEST effects may overlap with those from coexisting amide and hydroxyl protons.     

Sensitivity‐enhanced chemical exchange saturation transfer (CEST) MRI with least squares optimization of Carr Purcell Meiboom Gill multi‐echo echo planar imaging

Chemical exchange saturation transfer (CEST) imaging is a novel MRI technique that is sensitive to biomolecules, local pH and temperature, and offers considerable advantages for in vivo applications. However, the magnitude of CEST effect for dilute CEST agents undergoing slow or intermediate chemical exchange is typically small, requiring the use of signal averaging to enhance its sensitivity. Given that T₂‐induced signal loss can be normalized by asymmetry analysis, the magnitude of CEST effect is independent of echo time. Therefore, CEST MRI with multi‐echo echo planar imaging (EPI) readout should yield the same CEST effect as conventional single echo acquisition. Importantly, CEST multi‐echo (CESTme) EPI images can be averaged to enhance CEST MRI sensitivity. The goal of this study was to validate CESTme EPI using a creatine–agarose gel CEST phantom with similar T₂ as biological tissue. Using least‐squares optimization, we found that the sensitivity of CESTme sequence was significantly higher than that obtained by conventional single echo CEST‐EPI acquisition. Specifically, signal‐to‐noise ratio and contrast‐to‐noise ratio from the proposed CESTme EPI were approximately equivalent to that obtained by doubling the number of signal averages of the standard single echo CEST MRI sequence. In summary, our results demonstrated CESTme EPI for sensitivity‐enhanced CEST imaging. Copyright © 2014 John Wiley & Sons, Ltd.     

Dendritic PARACEST contrast agents for magnetic resonance imaging

MRI contrast agents based on chemical exchange‐dependent saturation transfer (CEST), such as Yb(III)DOTAM complexes, are highly suitable for pH mapping. In this paper, the synthesis of Yb(III)DOTAM‐functionalized poly(propylene imine) dendrimers is described. The applicability of these dendritic PARACEST MRI agents for pH mapping has been evaluated on a 7 T NMR spectrometer and on a 3 T clinical MRI scanner. As expected, based on the different numbers of exchangeable amide protons, the lowest detectable concentration of the first and third generation dendritic PARACEST agents is by a respective factor of about 4 and 16 lower than that of a mononuclear reference complex. The pH dependence of the CEST effect observed for these compounds depends on the generation of the poly(propylene imine) dendrimer. Upon going to higher generations of the Yb(III)DOTAM‐terminated dendrimer, a shift of the maximum CEST effect towards lower pH values was observed. This allows for a fine‐tuning of the responsive pH region by varying the dendritic framework. Copyright © 2007 John Wiley & Sons, Ltd.     

Developing imidazoles as CEST MRI pH sensors

A series of intra‐molecular hydrogen bonded imidazoles and related heterocyclic compounds were screened for their N–H chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) contrast properties. Of the compounds, imidazole‐4,5‐dicarboxamides (I45DCs) were found to provide the strongest contrast, with the contrast produced at a large chemical shift from water (7.8 ppm) and strongly dependent on pH. We have tested several probes based on this scaffold, and demonstrated that these probes could be applied for in vivo detection of kidney pH after intravenous administration. Copyright © 2016 John Wiley & Sons, Ltd.     

磁共振氨基质子转移成像技术原理和应用

本文概述了氨基质子转移(amide proton transfer,APT)技术与化学交换饱和转移(chemical exchange saturation transfer,CEST)技术的关系、APT技术的原理、影响APT技术的诸多因素,特别是在体APT成像需研究核奥氏效应(nuclear Overhauser effect,NOE)的重要性。阐述了APT技术的应用,主要有p H成像、温度成像、APT加权像在各器官组织的临床应用。     

A method for accurate pH mapping with chemical exchange saturation transfer (CEST) MRI

Chemical exchange saturation transfer (CEST) MRI holds enormous promise for imaging pH. Whereas the routine CEST‐weighted MRI contrast is complex and susceptible to confounding factors such as labile proton ratio, chemical shift, bulk water relaxation and RF saturation, ratiometric CEST imaging simplifies pH determination. However, the conventional ratiometric CEST (RCEST) MRI approach is limited to CEST agents with multiple exchangeable groups. To address this limitation, RF power‐based ratiometric CEST (PRCEST) imaging has been proposed that ratios CEST effects obtained under different RF power levels. Nevertheless, due to concomitant RF saturation (spillover) effect, the recently proposed PRCEST imaging is somewhat dependent on parameters including bulk water relaxation time and chemical shift. Herein we hypothesized that RF power‐based ratiometric analysis of RF spillover effect‐corrected inverse CEST asymmetry (PRICEST) provides enhanced pH measurement. The postulation was verified numerically, and validated experimentally using an in vitro phantom. Briefly, our study showed that the difference between MRI‐determined pH (pH_MRI) and electrode‐measured pH being 0.12 ± 0.13 and 0.04 ± 0.03 for PRCEST and PRICEST imaging, respectively, and the newly proposed PRICEST imaging provides significantly more accurate pH determination than PRCEST imaging (P < 0.01, Wilcoxon signed‐rank test). Notably, the exchange rate shows dominantly base‐catalysed relationship with pH, independent of creatine concentration (P > 0.10, Analysis of Covariance). In addition, the derived labile proton ratio linearly scales with creatine concentration (P < 0.01, Pearson Regression). To summarize, PRICEST MRI provides concentration‐independent pH imaging, augmenting prior quantitative CEST methods for accurate pH mapping. Copyright © 2015 John Wiley & Sons, Ltd.     

Entrapment of a neutral Tm(III)‐based complex with two inner‐sphere coordinated water molecules into PEG‐stabilized vesicles: towards an alternative strategy to develop high‐performance LipoCEST contrast agents for MR imaging

Chemical exchange saturation transfer (CEST) probes issued from the encapsulation of a water proton paramagnetic shift reagent into the inner aqueous volume of lipid vesicles provide an emerging class of frequency‐selective contrast agents with huge potential in the field of molecular magnetic resonance imaging (MRI). This work deals with the generation of such LipoCEST agents properly designed to optimize, under isotonic conditions, the chemical shift offset of the intra‐liposomal water protons as well as the number of exchangeable protons under reasonably low radiofrequency (RF) fields of saturation. The strategy lies in the loading of poly(ethylene glycol)‐stabilized nanosized liposomes with uncharged lanthanide chelates, binding more than one water molecule in the first hydration sphere, exemplified here by [Tm(III)–DO3A (H₂O)₂] complex. The key properties of the probes are demonstrated by complementary NMR investigations. The residence lifetime of the water molecules coordinated to the lanthanide center was outstandingly short (9.5 ± 0.2 ns from ¹⁷O NMR), and indeed relevant for effective LipoCEST responsiveness. The ¹H NMR CEST spectra (7.01 T magnetic field) prove that the theoretically expected optimal sensitivity can be approximated in the nanomolar concentration range, at reasonably low RF presaturation pulses (6.7–12 μT) and saturation frequency offsets of the intra‐liposomal water protons beyond 10 ppm, making possible selective irradiation in biological environment. CEST‐MRI images (7.01 T magnetic field and 10–12 μT RF pulse) explicitly confirm the interest of these newly conceived LipoCEST agents, indeed among the most efficient ones developed so far under isosmotic conditions. Copyright © 2014 John Wiley & Sons, Ltd.     

磁共振新技术在肺结节诊断中的研究进展

MRI具有无辐射、软组织分辨率高、多参数、多序列成像的优势,广泛应用于全身各系统。以往由于肺内氢质子含量低、呼吸运动伪影以及磁化率伪影等原因,MRI被认为不能用于肺部扫描。随着MRI技术的飞速发展,如并行采集技术、呼吸门控技术、新序列的研发以及人工智能的发展,肺部MRI成像逐渐完善。随着人们对辐射剂量和肺结节关注度的增加,肺部MRI的临床需求也逐渐增加。本文将从MRI新技术在结节检出和良恶性鉴别两方面展开综述,包括放射状容积内插式屏气序列、超短回波时间、零回波时间、压缩感知容积内插式屏气序列、纵向弛豫时间定量成像和化学交换饱和转移等MRI新技术。