Advanced NMR/MRI Methods for Liver Cancer

肝癌的先进 NMR/MRI 方法

• 批准号: 7475380
• 负责人: Yasvir Avindra Tesiram
• 金额: $ 7.75万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7475380
• 关键词: Age; Animal Model; Animals; Behavior; Biochemical Markers; Cancer Model; Cell Nucleus; Chloroform; Choline; Clinic; Clinical; Data; Detection; Development; Diagnosis; Diet; Disease; Early Diagnosis; Equation; Fatty Acids; Frequencies; Glycerol; Hepatocarcinogenesis; Human; Image; Imagery; Imaging Techniques; In Vitro; Individual; Invasive; Investigation; Laboratories; Lead; Lipids; Liver; Liver Extract; Liver diseases; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetism; Malignant neoplasm of liver; Mechanics; Methanol; Methods; Modeling; Mus; Nodule; Nuclear Magnetic Resonance; Numbers; Object Attachment; Pathology; Pathway interactions; Patients; Performance; Phase; Phospholipids; Physiologic pulse; Pulse taking; Purpose; Radio; Rattus; Research; Sampling; Signal Transduction; Spectrum Analysis; Staging; Standards of Weights and Measures; System; Testing; Thinking; Time; Tissue Extracts; Today; Transforming Growth Factor alpha; Transgenic Mice; Transgenic Organisms; Unsaturated Fatty Acids; Vertebral column; Week; Weight; Work; adenoma; base; c-myc Genes; carcinogenesis; choline deficient diet; concept; design; improved; in vivo; instrument; magnetic field; methyl group; mouse model; novel; programs; quantum; research study; theories; tool; tumor; visual information

DESCRIPTION (provided by applicant): The early diagnosis of liver cancer is critical in determining relevant treatment methods. Imaging techniques, including magnetic resonance imaging (MRI) techniques continue to be developed and while standard imaging techniques such as T2 and T1 weighted MRI lead to visualization of nodules, adenomas and tumors, it is generally too late for the patient to be successfully treated due to the limitation of detection with standard MRI. In our laboratory we have pursued the diagnosis of liver disease by observing the profiles of biochemical markers using nuclear magnetic resonance (NMR) spectra. Using a customized radio-frequency pulse program based on single quantum coherence spectroscopy, our preliminary year long study of hepatocarcinogenesis in the rat, induced by a choline deficient (CD) diet, showed marked differences in fatty acid species when compared to controls. Such a pulse sequence, wherein tailored and selective radio-frequency pulses were incorporated within the 2D heteronuclear correlation (HSQC) framework, allowed for the unequivocal determination of the number of double bonds contained in an unsaturated fatty acid containing compound. Previously, the signal from NMR spectra of these compounds were thought to be chemically equivalent and thus could not be resolved to implicate the presence of an individual fatty acid moiety. However, by using this pulse sequence, we have found that in CD animals, the fatty acid profile within weeks of being on the diet, is dominated by compounds containing two to four double bonds and with age is dominated by compounds containing one double bond at a concentration that is approximately four times greater than the CS (choline sufficient) controls. We propose here that the method of selectively observing chosen signals in an in vivo spectrum, will be a valuable method for characterizing the state of the liver at a very early stage. Improvements to the concepts, methods and pulse sequence programs leading to the tailored HSQC sequence mentioned above will lead to development of novel pulse sequences specifically designed to detect individual metabolites, and will lead to improved clinical MR methods suitable for accurate and early diagnosis of disease. This forms the basis for one of two specific aims of the proposed course of study. In the second part of our study we propose to implement the methods on a small animal magnetic resonance imaging spectrometer and test the validity and accuracy of the methods on a transgenic mouse model of liver cancer at chosen time-points over a period of 8 months. The results from this study will be compared with normal controls. At the end of each time point, the liver from each group of mice will be excised and fatty acid speciation determined by our modified HSQC method and cross-validated with the results obtained by the customized pulse sequence methods deployed on the small MRI spectrometer. While the application here stops at the animal model level, the long-term objective is to validate a non-invasive, method for the diagnosis of liver cancer by MRI/S in the clinic and one that augments current staging methods.

描述（由申请人提供）： 肝癌的早期诊断对于确定相关治疗方法至关重要。成像技术（包括磁共振成像（MRI）技术）继续开发，而标准成像技术（例如T2和T1加权MRI）会导致结节，腺瘤和肿瘤的可视化，但由于对标准MRI进行检测的限制，患者通常无法成功治疗患者，这通常为时已晚。在我们的实验室中，我们通过使用核磁共振（NMR）光谱观察生化标记的特征来追求肝病的诊断。使用基于单个量子相干性光谱的定制射频脉冲程序，与对照组相比，我们对大鼠肝癌发生的初步研究很长。这样的脉冲序列，其中量身定制和选择性的射频脉冲被纳入2D异核相关性（HSQC）框架中，可以明确测定含有不饱和脂肪酸含量的混合物中包含的双键的数量。以前，这些化合物的NMR光谱的信号被认为是化学等效物的，因此无法解决以暗示存在单个脂肪酸部分的存在。但是，通过使用此脉冲序列，我们发现在CD动物中，饮食中的几周内的脂肪酸剖面由包含两到四个双键的化合物主导，并且随着年龄的增长，在含有一个双键的化合物中，该化合物的浓度大约是CS（胆碱足够的）控制。我们在这里建议，在体内谱中有选择性观察所选信号的方法将是在很早就表征肝脏状态的一种有价值的方法。改进概念，方法和脉搏序列程序，导致上述量身定制的HSQC序列将导致专门设计用于检测单个代谢物的新型脉冲序列的发展，并将导致改进的临床MR方法，适合于准确和早期诊断疾病。这构成了拟议研究过程的两个具体目标之一的基础。在研究的第二部分中，我们建议在小动物磁共振成像光谱仪上实施这些方法，并在8个月的时间内在所选时间点上测试肝癌转基因小鼠模型的方法的有效性和准确性。这项研究的结果将与正常对照组进行比较。在每个时间点结束时，将切除每组小鼠的肝脏，并通​​过我们修改的HSQC方法确定的脂肪酸形成，并通过在小MRI光谱仪上部署的定制脉冲序列方法获得的结果进行了交叉验证。虽然这里的应用停止在动物模型水平上，但长期目标是验证一种非侵入性的方法，用于通过MRI/S诊断诊断诊断诊断诊断诊断诊所的肝癌，并在诊所中验证一种增强当前分期方法的方法。