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高分辨分子间多量子相干磁共振谱:为活体应用所做的技术改进

High-Resolution Intermolecular Multiple Quantum Coherence Magnetic Resonance Spectroscopy: Technical Improvements for in Vivo Applications

【作者】 陈希

【导师】 陈忠;

【作者基本信息】 厦门大学 , 凝聚态物理, 2008, 博士

【摘要】 活体定域磁共振谱(in vivo localized Magnetic Resonance Spectroscopy,MRS)提供了一种非侵入性的获得生物组织分子信息的手段。然而,由于组织结构间的磁化率变化导致了局部不均匀磁场,由此引起的谱线增宽大大降低了质子MRS谱的质量。由于磁化率差异引起的局部静磁场梯度在目前的磁共振成像系统上难以通过高阶匀场线圈进行校正。因此,人们提出了不少高分辨技术,这些技术利用如分子内多量子相干(intramolecularMultiple-Quantum Coherences,MQCs)和分子间核Overhauser效应(NuclearOverhauser Effects,NOEs)等各种自旋-自旋相互作用来获得对内在磁场不均匀性不敏感的高分辨谱图。分子间多量子相干(intermolecularMultiple-Quantum Coherence,iMQC)信号源于自旋间的偶极耦合相互作用。当磁场变化的空间尺度大于发生相互耦合的自旋的相干距离时,分子间多量子相干能够提高谱图的分辨率。本论文的研究重点在于iMQC高分辨谱学在应用方面的技术改进及其在不均匀场下MRS应用的可行性和性能研究。本论文的主要结果概述如下:一、系统研究探讨了基于各类回波的高分辨方法特别是iMQC方法的高分辨性质和机理,揭示了回波类高分辨谱学的原理是被观测自旋核的化学位移不能在回波波峰处重聚。比较和总结各个高分辨方法的优缺点,阐述了iMQC高分辨方法的优越性。这些工作对以后核磁共振高分辨谱学提供了重要的理论基础和实验依据。二、先前提出的分子间零量子相干(intermolecular Zero-QuantumCoherence,iZQC)高分辨方法均存在残留的强溶剂传统单量子信号的问题,该信号会引起很强的t1脊噪声。本论文提出了带有分子间二量子滤波(intermolecular Double-Quantum Filter,iDQF)的改进型HOMOGENIZED序列,命名为iDQF-HOMOGENIZED。该序列不仅能够有效抑制残留传统单量子信号,而且能够使溶剂iZQC信号最小化。文中分析了iDQF-HOMOGENIZED溶剂抑制效率,深入分析比较了新序列和已有的主要几种iMQC高分辨序列的性能。在葡萄果肉的实验中,新序列能够获得明显的分辨率提高和有效的水峰压制,初步表明了它在活体定域谱中的潜在应用前景。三、先前的iMQC高分辨技术均需要同时在F1和F2维进行包含全部溶质化学位移频率的采样,其结果是采样时间大大延长。在本章中,t1维的稀疏采样和折叠校正被用于提高分子间零量子相干谱的采样速率。在高场系统上,加速因子能够达到50倍。而且,在该序列中,能够通过t1期的编排获得三种表观J耦合常数的比例缩放:同核去偶(无J裂峰,即零倍的J常数)、不变的J常数和二倍放大的J常数。水峰抑制方面,分子间二量子滤波和双水门回波的联合使用也进一步改进了水峰压制效率。我们在气泡模型、离体猪脑组织和完整跳跳鱼上检验了该细新序列的可行性和性能。

【Abstract】 In vivo magnetic resonance spectroscopy(MRS) offers a noninvasive method to obtain molecular information in biological tissues.However,broadened spectral lines due to magnetic field inhomogeneities induced by variations in magnetic susceptibilities among various tissues and cellular structures can degrade substantially the quality of proton MRS.The field gradients caused by magnetic susceptibility differences at air-tissue boundaries can hardly be homogenized by high-order shims available on current magnetic resonance(MR) systems.Several high-resolution methods have been proposed,utilizing spin-spin interactions such as intramolecular multiple quantum coherences(MQCs) and intermolecular nuclear Overhauser effects(NOEs) to obtain spectra independent of intrinsic field inhomogeneities.The signals based on intermolecular multiple-quantum coherences(iMQCs) come from distant dipolar coupling between spins.It is capable of improving spectral resolution when magnetic susceptibilities vary over distances much larger than the correlation distance between coupled spins.The work of this thesis focuses on technical improvements of high-resolution iMQC spectroscopy under inhomogeneous fields and its feasibility for single-voxel MRS study of inhomogeneous tissues.The main results of this thesis are summarized as follows:1.The characters and mechanisms of echo-based high-resolution methods were analyzed.The principle of echo-based high-resolution spectroscopy was revealed here:the key point of echo-based high-resolution nuclear magnetic resonance methods is the chemical shift information of observed spins should not be lost at the echo peaks in time-domain.Comparisons between high-resolution methods were made,and the preponderance of iMQC method over other high-resolution methods was revealed.This part of work provides the theoretical bases and experimental guides for the researches of high-resolution spectroscopy.2.With the intermolecular zero-quantum coherence(iZQC) high-resolution methods proposed previously,strong residual conventional single-quantum coherence(SQC) signal originating mainly from solvent resonance result in strong t1 ridge noises.A modified HOMOGENIZED with an intermolecular double-quantum filter(iDQF),named iDQF-HOMOGENIZED,is presented to suppress the residual conventional SQC signals as well as solvent iZQC signals. The solvent-suppression efficiency of the iDQF-HOMOGENIZED is analyzed and a thorough comparison of the new sequence with several relevant pulse sequences is made.Dramatic resolution enhancement and solvent suppression in the measurements of a piece of grape sarcocarp suggest potential applications of the method in in vivo spectroscopy.3.Previous iMQC high-resolution methods all require 2D spectra sampling of the full ranges of chemical shifts of solute evolutions in both F1 and F2 dimensions, resulting in a prolonged scanning time for data acquisition.In this work,sparse sampling in the t1 dimension and subsequent fold-over correction are utilized to speed up the iZQC spectroscopy by up to 50 times on high-field MR systems. Furthermore,three types of spectra with homo-decoupling,original J-coupling constants,and doubled J-coupling constants respectively are obtained with manipulation of the t1 period.The water suppression is also improved by the combined use of iDQF and excitation sculpting.The feasibilities of this group of new sequences are demonstrated by experiments using an agar gel phantom with an air bubble,in vitro pig brain tissues and an intact post mortem mudskipper.

  • 【网络出版投稿人】 厦门大学
  • 【网络出版年期】2010年 02期
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