New Reference Signal Injection Method for In Vivo Quantification

描述（由申请人提供）：磁共振波谱（MRS）已从化学家的严格体外研究工具发展为强大的非侵入性诊断技术。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（通常称为绝对定量）需要准确确定测量体积内激发核产生的局部磁场（B1 m）与处理数据中相应光谱峰的积分面积之间的比例因子。要量化或控制影响这一比例系数的所有参数，需要付出不切实际的努力。因此，几乎所有的MRS结果都是以任意单位或比率表示的，这很难解释，临床价值有限。我们已经开发了一种新的技术，SPIRIT（合成峰值注入使用辐射免疫线圈），可以允许更实际和准确的量化MRS。我们使用一个小的，电感耦合RF线圈注入人工信号，伪信号，在主RF线圈用于获取体内信号。伪信号的振幅、频率和线宽容易变化，并且首先与对应于已知体外代谢物浓度的真实的峰成比例地设置。然后在体内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的信号转换成代谢物浓度的单位。SPIRIT方法的显著特征是使用电感耦合来注入伪信号。由于电感耦合也是B1 m耦合到主RF线圈的机制，因此影响比例因子的任何后续数据操作（包括线圈负载条件、接收器放大器的增益和数据处理算法）对真实的和伪信号具有相同的影响。这使得比例因子不受这些数据操作的影响，并大大降低了代谢物定量过程的负担。我们已经建立了一个原型SPIRIT探头，使用表面线圈激发和接收体内信号。这个简单的线圈对于证明可行性很有用，但是，像所有表面线圈一样，它会产生不均匀的B1场，这使量化过程变得复杂。在这个项目中，我们将建立两个额外的SPIRIT探针，创建均匀的B1场，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测定比较来验证该方法，并证明在生理扰动期间准确量化人体骨骼肌代谢物含量变化的能力。我们的项目侧重于骨骼肌的测量，但这些方法可以很容易地转移到其他器官。我们的目标是验证一种强大的新工具，用于无创定量代谢物含量，使研究人员和临床医生能够充分发挥MRS的潜力。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，并证明其在人类中的价值。该项目的成功完成可能会对各种疾病产生广泛的影响，为研究人员和临床医生提供更实用的非侵入性工具来测量代谢物浓度。

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.