Nonlinear Reconstruction for MR Spectroscopic Imaging of Human Calf in Diabetes

 描述（由申请方提供）：人们非常关注定义导致肌细胞内和肌细胞外脂质（IMCL和EMCL）蓄积增加和脂质不饱和比增加的过程，并确定这些变化与胰岛素抵抗（IR）发生和进展为2型糖尿病（T2 D）的关系。因此，需要开发用于脂质和代谢物表征的新型成像技术，以允许在体内对这些过程进行重复的非侵入性评估。为了实现这一目标，当前提案将开发和试点测试使用沿着一个频谱和一个空间维度的非均匀欠采样（NUS）的基于五维（5D）MR光谱成像（MRSI）数据的新型加速多梯度/自旋回波的非线性重建。最近，在回波平面光谱成像（EPSI）中增加了第二维光谱，称为回波平面相关光谱成像（EP-COSI）。将在使用15通道膝关节线圈的3 T MRI扫描仪上实现5D EP-COSI的多回波（ME）版本（名为ME-EPCOSI），其能够比EP-COSI更快地采集数据。该序列将被进一步优化，以使用绝热全通道1800射频（RF）脉冲实现更好的切片重聚焦，因为绝热RF脉冲将改善切片选择轮廓并比常用的Mao RF脉冲更好地减少化学位移伪影。这种新的序列将能够更好地区分骨骼肌中的不饱和和饱和脂质组比传统的MRS技术，并将允许代谢物成像的多个肌肉群同时更好地了解IMCL和胰岛素敏感性之间的具体关系。提出了两个具体目标：1）完成NUS 5D ME-EP-COSI技术的开发，以允许在20名年轻健康人类志愿者中同时测定具有不同1型/2型纤维和IMCL含量的三个小腿肌肉群中的IMCL和EMCL水平以及脂质不饱和指数，并使用常规3D MRSI比较其性能;和2）利用该新技术研究20名患有T2 D的患者和20名匹配的非糖尿病健康受试者。拟议的研究将测试以下两个假设：1）基于NUS的5D MEEP-COSI技术将比完全编码的5D EPCOSI和MRSI序列更稳健，能够在小牛骨骼肌的多个切片中同时记录2D COSY光谱，2）相对于健康对照，T2 D患者将表现出：a）增加骨骼肌IMCL和EMCL，和B）降低胆碱、IMCL和EMCL脂质不饱和指数。所提出的多维MR光谱成像有望促进一种重要的新研究工具的开发和验证，该工具将显著推进IR和T2 D发展机制的研究，并最终可作为一种方便的方法，快速、无创地评估对旨在改善IR和通过使肌肉脂质代谢正常化治疗T2 D的新治疗干预措施的反应。

 DESCRIPTION (provided by applicant): There is considerable interest in defining the processes that lead to the increased accumulation of intramyocellular and extramyocellular lipids (IMCL and EMCL) and lipid unsaturation ratios, and determining the relationships of these changes to the development of insulin resistance (IR) and progression to type 2 diabetes (T2D). Thus, development of novel imaging techniques for lipid and metabolite characterization is needed to allow repeated, non-invasive assessment of these processes in vivo. To achieve this goal, the current proposal will develop and pilot test non-linear reconstruction of a novel accelerated multi- gradient/spin-echo based five-dimensional (5D) MR Spectroscopic Imaging (MRSI) data using non-uniform undersampling (NUS) along one spectral and one spatial dimensions. Recently, a 2nd spectral dimension was added to echo-planar-spectroscopic imaging (EPSI) and named echo-planar correlated spectroscopic imaging (EP-COSI). A multi-echo (ME) version of 5D EP-COSI, named ME-EPCOSI, which is capable of acquiring the data faster than EP-COSI will be implemented on a 3T MRI scanner using a 15- channel knee coil. The sequence will be further optimized for achieving better slice refocusing using the adiabatic full passage 1800 radio-frequency (RF) pulses as the adiabatic RF pulses will improve slice selection profile and reduce chemical shift artifacts better than the commonly used Mao RF pulse. This new sequence will enable better discrimination between the unsaturated and saturated lipid groups in skeletal muscle than the conventional MRS techniques and will allow metabolite imaging of multiple muscle groups simultaneously to better understand the specific relationship between IMCL and insulin sensitivity. Two specific goals are proposed: 1) complete the development of the NUS 5D ME-EP-COSI technology to allow simultaneous determination of IMCL and EMCL levels and lipid unsaturation indices in three calf muscle groups with differing type1/type 2 fiber and IMCL content in 20 young healthy human volunteers and to compare its performance using conventional 3D MRSI; and 2) utilize this new technology to study 20 patients with T2D and 20 matched non-diabetic, healthy subjects. The proposed studies will test the following two hypotheses: 1) a NUS-based 5D MEEP-COSI technique will be more robust than the fully encoding 5D EPCOSI and MRSI sequences, enabling simultaneous recording of 2D COSY spectra in multiple slices of calf skeletal muscle, 2) relative to healthy controls, patients with T2D will exhibit: a) increased skeletal muscle IMCL and EMCL, and b) reduced choline, IMCL and EMCL lipid unsaturation indices. The proposed multi-dimensional MR spectroscopic imaging is expected to facilitate the development and validation of an important new research tool that will significantly advance research in the mechanisms of the development of IR and T2D and may ultimately serve as a convenient methodology to rapidly and non-invasively assess responses to new therapeutic interventions designed to ameliorate IR and treat T2D by normalizing muscle lipid metabolism.