目的 制作脂肪管模型模拟人体骨骼肌脂肪的分布状态，解释骨骼肌¹H-MRS中脂峰的形态特征、基本原理及影响因素。测定3T场强下，骨骼肌代谢物的驰豫时间值，以水为内部参照，实现骨骼肌代谢物的¹H-MRS的定量分析。评估骨骼肌代谢物的¹H-MRS的定量分析的有效性、可行性和可重复性，论证骨骼肌¹H-MRS的临床应用价值。最后，通过¹H-MRS定量分析一组初发Ⅱ型糖尿病患者的IMCL，初步判断中国人Ⅱ型糖尿病患者IMCL的范围及其与IR的关系。 材料与方法 1、模型研究：利用分布于毛细玻璃管中的大豆油和脂肪乳注射液分别模拟肌纤维细胞外、细胞内脂肪制成模型。观察模型¹H-MRS特征及改变模型与B₀角度后波峰位置的改变。比较模型中脂峰特征与在体小腿胫骨前肌及比目鱼肌¹H-MRS中0.8～1.8ppm脂峰的相似性。 2、测定代谢物驰豫时间值，进行绝对定量分析：24名健康志愿者，男16例，女8例，年龄22～33岁(平均年龄26.6±3.3岁，中位年龄25.5岁)，BMI值(22.1±2.5)㎏/m2。随机分为2组，分别行比目鱼肌和胫骨前肌的系列¹HMRS检查，进行代谢物驰豫时间的测定。T1时间测量采用渐近饱和法，固定TE=20ms，依次改变TR值的大小，共选取8个不同TR值，为770，900，1100，1200，1500， 2000，3000和5000ms。T2时间测量时固定TR=3000ms，依次改变TE值的大小，共选取8个不同TE值，为20，30，45，60，90，135，200和270ms。采用jMRUI v3.0AMARE对谱线数据进行定量分析，将所获得的各代谢物波峰下面积与TR、 TE的变化关系进行曲线拟合，计算T1、T2值。利用所测定的3T场强下骨骼肌代谢物的T1、T2值做驰豫校正，计算骨骼肌各代谢物的绝对浓度值。 3、骨骼肌¹H-MRS绝对定量的可重复性研究：20名健康志愿者，男11例，女9例，年龄22～37岁(平均年龄(28±3.6)岁，中位年龄27岁)，BMI值(21.34±2.5) ㎏/m2。接受右小腿比目鱼肌和胫骨前肌相同部位的多次¹H-MRS检查，评价¹H-MRS作为定量分析骨骼肌代谢物含量的方法的可行性和可靠性。检查程序包括：①即刻重复检查 受检者置入磁场后常规定位完成第一次比目鱼肌和胫骨前肌的检查，之后间隔5分钟，受检者不离开磁场，在第一次检查相同VOI部位行第二次检查：②短期重复检查 即刻重复检查结束后，离开磁场自由活动休息20～30分钟后进行；③长期重复检查 在短期重复检查结束后4～7天再进行一次相同部位的检查。所有检查的扫描参数保持不变，比目鱼肌和胫骨前肌检查的先后顺序采用随机原则进行。采用SSPS 16.0统计软件进行分析处理，计算各组数据间的平均值差别、变异系数及相关性，p<0.05认为有统计学意义。 4、糖尿病病人IMCL的研究：24例初发Ⅱ型糖尿病病人接受小腿胫骨前肌和比目鱼肌¹H-MRS检查测定IMCL，评价IMCL与BMI、腰臀比、空腹血糖、空腹胰岛素、糖化血红蛋白、糖化血清蛋白、血浆甘油三酯、游离脂肪酸、 HOMA-IR值的相关性。 结果 1、脂肪管模型很好的模拟了在体骨骼肌¹H-MRS脂峰形态，即0.8～1.8ppm部位出现两组甘油三酸酯的亚甲基峰和甲基峰，其中心频率相差0.2～0.3ppm，分别代表IMCL和EMCL。由于骨骼肌组织肌纤维走行的高度有序性及IMCL和EMCL分子分布状态不同，分子相同部位氢的电子云屏蔽效应出现差异，感应的化学位移不同而造成波谱中波峰的分离。这种IMCL与EMCL波峰的分离在肌束与B₀一致时最佳，两者夹角接近魔角(54.7°)时，IMCL和EMCL相互融合无法分离。 2、比目鱼肌中T1值水(1384ms)>>Cr3(1064ms)>TMA(964ms)>>Lip (373～375ms)， T2值水(26.47ms)<
PURPOSE To elucidate the characteristics of lipid peaks in ¹H-MR spectroscopy of skeletal muscle by phantoms making from tubes filling with different kinds of lipid, discuss the underlining principles and the influencing factors. To measure the relaxation times of metabolites of m. tibialis anterior (TA) and m. soleus muscle(SOL) in vivo at 3T, and quantify muscle metabolites correcting by the measured relaxation times using water as reference. To evaluate the utility, reliability and reproducibility of metabolites measuring by ¹H-MRS. At last, to preliminary decide the relationship between IMCL and IR in Chinese type Ⅱ diabetes mellitus patients. MATERIALS AND METHOD 1.Phantom study: Fat phantoms imitating the distribution of lipids in skeletal muscle were constructed using capillaritubers filled with soybean oil and fat emulsion injection which were representing EMCL (extramyocellular lipid) and IMCL respectively. ¹H-MR spectroscopy was obtained while phantoms were paralleled and angled different degrees with B₀. Observe the features of the spectra especially the peak at 0.8～1.8ppm. 2.Measure relaxation times, make absolute quantification: 24 healthy volunteers (16 men, 8 women; mean age, 26.6years) were recruited in the study。 Relaxation times of metabolites of m. tibialis anterior(TA) and m. soleus muscle(S) were calculated by series of ¹H-MRS taken on the volunteers divided randomly into TA group and SOL group. A progressive saturation experiment was performed to determine the T1 relaxation times. Spectra with eight different TRs (770, 900, 1100, 1200, 1500, 2000, 3000 and 5000ms) were acquired at 3 T keeping TE fixed to 20ms, TM fixed to 10ms. For measurement of T2 relaxation times, spectra were obtained with eight TEs (20, 30, 45, 60, 90, 135, 200 and 270ms) with TR=3000ms. After data were phase corrected by water peak, spectra were processed using the AMARES time-domain fitting algorithm. T1 and T2 relaxation times of SOL and TA were calculated by curve fitting using SSPS 16.0. Absolute concentrations of different metabolites were determined using ¹H-MRS corrected by the calculated T1 and T2 relaxation times at 3.0T. 3.Reliability and reproducibility study: altogether 20 healthy volunteer(11men, 9 women; mean age, 28 years; mean BMI, 21.34 ㎏/m2.) were enrolled into this study. ¹H-MRS were taken in SOL and TA several times in one subject in order to evaluate the reliability and reproducibility of measuring metabolites using ¹H-MRS. The 1HMRS measurement include: ①intersession examination, which means shortly after first exam, the subject accepted a second exam without leaving the magnet. ② short-term repeat examination, which means the subject accept a third exam after having resting for about 30 minutes outside of the magnet. ③long-term examination, which means the subject accept a fourth exam after 4 to 7days.All the measurement were taken on the same position of the calf and with same exam parameters. SSPS 16.0 were used to analyze the difference of means, variance coefficient and correlation coefficient between different exams. P values ＜0.05 were considered significant. 4.IMCL of Chinese type Ⅱ diabetes mellitus patients: ¹H-MRS were undertaken in 24 newly diagnosed type Ⅱ diabetes mellitus patients prospectively to get the concentration of IMCL. The relationship between IMCL and BMI, waist hip ratio, fasting plasma glucose; fasting plasma insulin , Hemoglobin A1c , glycolsyl-protein, fasting plasma glyceride, HOMA-IR were evaluated. Results 1.The spectra of fat phantoms are very similar with that of muscles, that is, two groups of methylene and methyl with a resonance frequency shift of 0.2～0.3ppm representing IMCL and EMCL respectively. IMCL and EMCL experience different chemical shifts because their molecule are distributed in different states and muscle tissue has highly ordered structure, that results in the separation of IMCL and EMCL. The separation of IMCL and EMCL is maximized when the orientation of the muscle fibre bundles are paralleled to B₀, IMCL and EMCL can't be separated when the angle between fibre bundles and B₀ is equal to the magic angle(54.7°). 2.The calculated T1 relaxation times of SOL metabolites were: water ( 1384ms) >>Cr3 (1064ms) ＞TMA (964ms) >>Lip (373～375ms), T2relaxation times were water(26.47ms)<