New Reference Signal Injection Method for In Vivo Quantification

用于体内定量的新参考信号注入方法

• 批准号: 7845697
• 负责人: Donghoon Lee
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7845697
• 关键词: Affect; Algorithms; Amplifiers; Animals; Area; Biochemical; Biological Assay; Calibration; Cell Nucleus; Characteristics; Clinical; Coiled Bodies; Computer software; Coupled; Couples; Coupling; Data; Development; Diagnostic Procedure; Disease; Exercise; Freezing; Frequencies; Gastrocnemius Muscle; Goals; High Pressure Liquid Chromatography; Human; Image; Immune; In Vitro; Injection of therapeutic agent; Knowledge; Leg; Limb structure; Magnetic Resonance Spectroscopy; Measurement; Measures; Methods; Modification; Organ; Physiologic pulse; Physiological; Procedures; Process; Protocols documentation; Publishing; RF coil; Radiation; Rattus; Relaxation; Research; Research Personnel; Rest; Sampling; Signal Transduction; Skeletal Muscle; Surface; Techniques; Time; Tissue Harvesting; Validation; Water; Width; computerized data processing; data acquisition; design; improved; in vitro testing; in vivo; magnetic field; prototype; public health relevance; research study; tool

DESCRIPTION (provided by applicant): Magnetic resonance spectroscopy (MRS) has evolved from a strictly in vitro research tool for chemists to a powerful, non-invasive, diagnostic technique. However, the full potential of MRS-its ability to quantitatively assess metabolite content in vivo-is rarely achieved in practice. Assessment of metabolite content, commonly referred to as absolute quantification, requires accurate determination of the proportionality factor between the local magnetic field (B1m) generated by excited nuclei within the measurement volume and the integrated area of the corresponding spectral peak in the processed data. An impractical level of diligence is required to quantify or control all of the parameters that affect this proportionality factor. As a result, nearly all MRS results are presented in terms of arbitrary units or as ratios, which are difficult to interpret and of limited clinical value. We have developed a new technique, SPIRIT (Synthetic Peak Injection using a Radiation Immune Tickler coil), that could allow more practical and accurate quantification of MRS. We use a small, inductively coupled RF coil to inject an artificial signal, the pseudo-signal, in the main RF coil used to acquire the in vivo signal. The amplitude, frequency and line-width of the pseudo-signal are easily varied and are first set in proportion to a real peak corresponding to a known in vitro metabolite concentration. The same pseudo-signal is then injected during the data acquisition period of an in vivo measurement and used as a calibration factor to convert the real signals into units of metabolite concentration. The salient feature of the SPIRIT method is the use of inductive coupling to inject the pseudo-signal. Since inductive coupling is also the mechanism by which B1m couples to the main RF coil, any subsequent manipulations of the data that affect the proportionality factor- including coil loading conditions, gain of the receiver amplifiers, and data processing algorithms-have an equal effect on the real and pseudo-signals. This makes the proportionality factor immune to these data manipulations and substantially decreases the burden of the metabolite quantification process. We have built a prototype SPIRIT probe that uses a surface coil to excite and receive the in vivo signals. This simple coil was useful for demonstrating feasibility but, like all surface coils, it creates a nonuniform B1 field, which complicates the quantification process. In this project we will build two additional SPIRIT probes that create uniform B1 fields to excite and receive the metabolite signals, validate the method by comparison against biochemical assays of metabolite content in rat hind limb, and demonstrate the ability to accurately quantify changes in metabolite content in human skeletal muscle during physiological perturbations. Our project focuses on measurements in skeletal muscle but the methods could easily be transferred to other organs. Our goal is to validate a powerful new tool for noninvasive quantification of metabolite content that will allow researchers and clinicians access to the full potential of MRS. PUBLIC HEALTH RELEVANCE: We have developed a new method of converting magnetic resonance spectroscopy (MRS) data into units of metabolite concentration. We propose to validate the method in animal studies and demonstrate its value in humans. Successful completion of the project could have widespread impact on a variety of diseases by providing researchers and clinicians with a more practical noninvasive tool for measuring metabolite concentration.

描述(申请人提供)：磁共振波谱(MRS)已经从化学家严格意义上的体外研究工具发展成为一种强大的、非侵入性的诊断技术。然而，MRS的全部潜力--其定量评估体内代谢物含量的能力--在实践中很少实现。代谢物含量的评估，通常被称为绝对量化，需要准确地确定测量体积内激发核产生的局部磁场(B1m)与处理数据中相应光谱峰的积分面积之间的比例因子。需要不切实际的勤奋程度来量化或控制影响这一比例系数的所有参数。因此，几乎所有的MRS结果都是以任意的单位或比率呈现的，这很难解释，临床价值有限。我们开发了一种新技术SPIRIT(使用辐射免疫Tickler线圈的合成峰值注入)，可以更实用和准确地定量MRS。我们使用一个小型的电感耦合RF线圈在用于获取体内信号的主RF线圈中注入人工信号-伪信号。伪信号的幅度、频率和线宽很容易改变，并且首先与与已知的体外代谢物浓度相对应的真实峰值成比例地设置。然后，在活体测量的数据采集期间注入相同的伪信号，并将其用作校准因子，以将真实信号转换为代谢物浓度单位。SPIRIT方法的显著特点是使用电感耦合注入伪信号。由于电感耦合也是B1M耦合到主射频线圈的机制，因此对影响比例系数的任何后续数据操作--包括线圈加载条件、接收放大器的增益和数据处理算法--对实信号和伪信号都有相同的影响。这使得比例因子不受这些数据操作的影响，并大大减少了代谢物量化过程的负担。我们已经建造了一个原型精神探测器，它使用表面线圈来激发和接收体内信号。这个简单的线圈对于演示可行性很有用，但像所有的表面线圈一样，它产生了一个不均匀的B1场，这使得量化过程变得复杂。在这个项目中，我们将另外建造两个SPIRIT探头，它们创建统一的B1场来激发和接收代谢物信号，通过与大鼠后肢代谢物含量的生化分析进行比较来验证该方法，并展示在生理扰动期间准确量化人类骨骼肌代谢物含量变化的能力。我们的项目专注于骨骼肌的测量，但这种方法很容易移植到其他器官。我们的目标是验证一种强大的新工具，用于非侵入性量化代谢物含量，使研究人员和临床医生能够充分发挥夫人的公共卫生相关性：我们开发了一种将磁共振波谱(MRS)数据转换为代谢物浓度单位的新方法。我们建议在动物研究中验证该方法，并在人类身上证明其价值。该项目的成功完成可能会为研究人员和临床医生提供一种更实用的非侵入性代谢物浓度测量工具，从而对各种疾病产生广泛的影响。

项目成果

Quantitative 19F imaging using inductively coupled reference signal injection.

使用电感耦合参考信号注入进行定量 19F 成像。

• DOI: 10.1002/mrm.22298
• 发表时间: 2010
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Lee,Donghoon;Marro,Kenneth;Shankland,Eric;Mathis,Mark
• 通讯作者: Mathis,Mark

Elimination of contaminating cap genes in AAV vector virions reduces immune responses and improves transgene expression in a canine gene therapy model.

• DOI: 10.1038/gt.2014.4
• 发表时间: 2014-04
• 期刊: GENE THERAPY
• 影响因子: 5.1
• 作者: Wang, Z.;Halbert, C. L.;Lee, D.;Butts, T.;Tapscott, S. J.;Storb, R.;Miller, A. D.
• 通讯作者: Miller, A. D.

Quantitative in vivo magnetic resonance spectroscopy using synthetic signal injection.

使用合成信号注射的定量体内磁共振波谱。

• DOI: 10.1371/journal.pone.0015166
• 发表时间: 2010
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Marro,KennethI;Lee,Donghoon;Shankland,EricG;Mathis,CMark;Hayes,CecilE;Friedman,SethD;Kushmerick,MartinJ
• 通讯作者: Kushmerick,MartinJ