Admittance to measure cardiac mechanics in mice

描述（由申请人提供）：转基因小鼠提供了一种机制来定义单个基因的体内表型。这与产生导致充血性心力衰竭的心肌疾病的基因尤其相关。评估大型动物血流动力学表型的经典方法是通过左心室（LV）压力-容积（PV）分析。然而，小鼠左室体积小、心率快，一直困扰着其绝对容积和瞬时容积的测定。电导测量通过产生与任何心肌大小或心率兼容的瞬时左室容积信号，为这个问题提供了一个有吸引力的解决方案。不幸的是，第一代电导仪即使在一个较低的频率下也会产生由血液和心肌组成的瞬时电导（体积）信号。PV分析只需要血液成分。通过测量导纳（复电导），提出了克服这一限制的机制。导纳由左室血和心肌电导的幅度以及心肌电导的相角组成。传统的单频电导仅测量电导信号的幅度，其中包括血液和心肌成分。由于可测量的相位角是肌肉所特有的，导纳提供了一种更好的方法来确定和消除心肌对组合左室电导（体积）信号的瞬时贡献。本拨款申请的目标是开发、校准和验证一台仪器，以实时测量导纳信号的幅度和相位角。为了实现这一目标，我们将- 1)开发模拟硬件和数字数据采集导纳仪器，2)开发一种更准确的方法，使用FEM从导纳测量中获得左室体积，以及3)证明导纳仪器优于传统的单频MRI。

DESCRIPTION (provided by applicant): Genetically altered mice provide a mechanism to define the in vivo phenotype of individual genes. This is especially relevant to genes implicated in producing myocardial diseases leading to congestive heart failure. The classic method to assess the hemodynamic phenotype in larger animals is through left ventricular (LV) pressure-volume (PV) analysis. However, determining absolute and instantaneous volume in the murine LV has been plagued by its small size and rapid heart rate. Conductance measurements offer an attractive solution to this problem by generating an instantaneous LV volume signal compatible with any myocardial size or heart rate. Unfortunately, the first generation conductance instrument generates an instantaneous conductance (volume) signal composed of blood and myocardium even at a single lower frequency. Only the blood component is desired for PV analysis. A mechanism to overcome this limitation is proposed by measuring admittance (complex conductance). Admittance is composed of both the magnitude of LV blood and myocardial conductance, and the phase angle of myocardial conductance. Traditional single frequency conductance measures only the magnitude of the conductance signal, which includes both the blood and myocardial components. Because measurable phase angle is unique to muscle, admittance offers a better method to determine and remove the instantaneous myocardial contribution to the combined LV conductance (volume) signal. The GOAL of this grant application is to develop, calibrate, and validate an INSTRUMENT to measure both the magnitude and the phase angle of the admittance signal in real time. To accomplish this goal, we will - 1) Develop both analog hardware and digital data acquisition Admittance Instruments, 2) Develop a more accurate method to derive LV volume from admittance measurements using FEM, and 3) Demonstrate that an Admittance Instrument is superior to traditional single frequency with MRI.