在体棕色脂肪磁共振温度测量及其活性评估研究

Brown adipose tissue (BAT) is a specific tissue whose main function is consuming energy. Therefore BAT is considered as the new therapeutic target for obesity and the related metabolic diseases. The most key indicator for evaluating the ability of consuming energy and generating heat is BAT activity. The current main method for activity evaluation is invasive biological method, such as biopsy. Therefore, the development of method for evaluating BAT activity in vivo is of scientific significance for in-depth studying of the relationship between BAT and obesity and the related diseases. The temperature change of BAT after activated is the most direct appearance of BAT activity. As a result, thermometry in BAT is considered to be the best method to evaluate BAT activity. However, there is no such a method to measure the temperature of BAT precisely at present. On the strength of my previous study in ex-vivo BAT, the current project aims to establish an in-vivo magnetic resonance thermometric method for BAT. To solve the challenge of low precision in BAT thermometry, the project will solve the following scientific issue: the relationship of the BAT’s physical parameters, signal acquisition parameters and signal models with the precision of measured temperatures. The project will adopt theoretical calculation and analog simulation methods to explore and find the optimal parameters who are related to the noise performance of measured temperatures, and then establish the in-vivo magnetic resonance thermometric method. Finally, the quantitative relation between BAT activity by biological method and the temperature profiles established by thermometric method are evaluated using in vivo experiments. The established thermometric method based on magnetic resonance imaging in this project is thought to provide a new method to promote the in-depth study of the relationship between BAT and obesity and other related diseases.

棕色脂肪组织是一种以消耗能量为主要功能的特殊脂肪组织，是治疗肥胖和相关代谢疾病的新靶点。棕色脂肪的活性是衡量其耗能产热能力的关键指标，当前其评估主要是活检等有创的生物学方法，因此，发展无创在体棕色脂肪活性评估方法对于深入探究棕色脂肪与相关疾病的关系具有重要科学价值。棕色脂肪激活时的温度变化是其活性的最直观表现，因此，温度测量被认为是在体活性评估的最有效方法，但是，目前尚缺乏精准在体测温方法。本项目在前期离体组织研究基础之上，提出在体棕色脂肪磁共振温度成像方法，针对测温精度低的挑战，围绕物理参数、成像参数及估算模型对测温精度的影响机制这一关键科学问题，利用理论计算和模拟仿真研究影响测温精度的参数，确立最优参数并建立在体温度成像算法；基于在体激活实验，以生物学方法为对照，研究棕色脂肪活性与温度变化的定量关系，建立在体评估方法。本项目研究将为促进棕色脂肪活性与肥胖及相关疾病关系的研究提供新方法。

棕色脂肪组织（BAT）是一种“好脂肪”，被激活后能够消耗体内能量，是抵抗肥胖及相关代谢疾病的新靶点，评估其活性对于研究棕色脂肪与相关代谢疾病相互关系具有重要临床意义。磁共振成像具有多参数成像、无电离辐射等优点，成为研究在体棕色脂肪的有力影像手段。.棕色脂肪组织激活后的磁共振无创温度测量可对其活性进行评估。由于脂肪中氢质子的共振频率对温度不敏感，使得传统的质子共振频率漂移(Proton resonance frequency shift，PRFS)温度成像算法不适用于BAT。本项目提出了一种新的脂肪参考PRFS的磁共振温度成像算法，该算法考虑了影响现有算法的各种不利影响因素，如脂肪共振多峰信号模型，表观横向弛豫时间T2*的温度依赖性等。该算法采用双步迭代温度估计(Dual-step iterative temperature estimation，DITE)的方法来提高温度精确度。本论文利用蒙特卡洛模型、水脂混合仿体实验和离体、在体BAT实验对所提出算法的温度成像效果进行了评估，并和现有的同类算法进行了比较。结果显示本论文算法的温度估计值和荧光光纤温度计的测量结果具有较高的一致性，比同类算法具有更好的准确度和精确度。在离体BAT加热实验中，本项目算法在120次温度测量中的平均估计偏差、偏差的标准差和均方值误差分别是-0.08/0.46/0.56℃。大鼠在体棕色脂肪组织激活实验中，测温精度也达到0.88℃。综上，本项目提出的在体棕色脂肪温度成像算法能够在棕色脂肪组织中实现精确的温度测量。.本项目基于磁共振成像成功开发了适用于在体棕色脂肪活性评估的方法，为棕色脂肪与肥胖及相关代谢疾病关系研究提供了有力的影像手段，对于促进相关疾病的诊治具有重要的临床意义。