Narrow linewidth MRS to detect breast cancer

描述(申请人提供)：这项研究和培训计划将使我能够应用一种新的磁共振(MR)信号来获得关于肿瘤的非侵入性化学信息，最终有助于诊断和治疗决策。这项研究的目的是概述两种方法进入临床有用的诊断的进展。 A)一种经过验证的非侵入性测量脂肪化学成分的方法将被应用于提高乳腺癌诊断的特异性。 B)我们还将开发一种相关的磁共振方法，以非侵入性地测量与癌症有关的代谢物，这种方法将适用于比现有技术更多的器官 由于脂质特异性方法已经在小鼠身上得到证实，我们对该序列的目标集中在确定该数据的意义上。在初始化和优化序列之后，我们的研究将验证我们的数据，即光谱中的峰，与肥胖小鼠脂肪组织的化学成分之间的联系。下一步，人类研究将测量乳房组织中的脂肪，以确定MR识别的病变周围的脂肪是否与恶性肿瘤相关，或描述疾病的程度。该提案还提出了一种新的方法，可以非侵入性地测量身体中除脂肪以外的化学成分，包括已知的癌症重要标志代谢物。这种测量对于诊断脑癌和前列腺癌至关重要，但标准技术在应用于其他器官时产生的数据质量很差。我们将展示我们的方法适用于其他器官，如乳房。由于我的训练是作为一名MR物理学家，完成这项工作还需要大量的生物医学培训，这将通过课堂作业、指导和实践经验相结合来完成。这份提案有四个主要的培训目标。1)分子生物学和癌症生物学的培训将从分子生物学课程开始，然后是癌症生物学课程。课程的补充将是与我的合作导师、癌症生物学和肿瘤微环境方面的知名专家的讨论，以及出席关于癌症研究的全国性会议。 2)先进的活体磁共振技术培训将包括正式课程和动手培训，培训将由该主题主要教科书的作者罗宾·德·格拉夫博士指导。 3)人类研究研究和生物统计学方面的培训将包括为期一学期的生物统计学和临床研究伦理课程，以及为研究人员举办的临床技能强化讲习班。实践培训将在我的临床合作者的指导下进行，他们是一名乳房放射科医生和一名癌症病理学家，他们都是杰出的临床医生，都拥有广泛的研究成就。4)建议中明确概述了发展我独立职业道路的科学和职业指导，包括结构化的指导计划和与更广泛的科学界的互动。

DESCRIPTION (provided by applicant): This research and training program will enable me to apply a new kind of magnetic resonance (MR) signal to get noninvasive chemical information about tumors, which could ultimately aid diagnosis and treatment decisions. The research aims outline the progression of two methods into clinically useful diagnostics. A) A proven method that noninvasively measures the chemical composition of fat will be applied to improve the specificity of breast cancer diagnoses. B) We will also develop a related MR method to noninvasively measure metabolites related to cancer, which will be applicable to a larger number of organs than current techniques Because the lipid-specific method has been demonstrated in mice, our aims for that sequence focus on establishing the significance of that data. After initializing and optimizing the sequence our studies will validate the connection between our data, i.e., peaks in a spectrum, and the chemical composition of adipose tissue in obese mice. Next, human studies will measure the fat in breast tissue to determine whether fat surrounding MR-identified lesions correlates to malignancy or delineates the extent of disease. The proposal also presents a new method that can noninvasively measure chemical components in the body besides fat, including metabolites known to be important markers of cancer. Such measurements have become crucial for diagnosing brain and prostate cancer, but standard techniques yield poor quality data when applied to other organs. We will show that our method works in other organs, such as breast. Since my training is as an MR physicist, completing this work will also require significant amounts of biomedical training, which will be accomplished through a combination of class work, mentorship, and hands- on experience. There are four major training goals in this proposal. 1) Training in molecular biology and cancer biology will begin with a course in molecular biology followed by one in cancer biology. Courses will be supplemented by discussions with my co-mentors, renowned experts in cancer biology and tumor microenvironments, and attendance at national meetings on cancer research. 2) Training in advanced in vivo magnetic resonance techniques will include both formal coursework as well as hands-on training, which will be guided by Dr. Robin De Graaf, author of the leading textbook on the subject. 3) Training in human research studies and biostatistics will include semester long courses in biostatistics and in the ethics of clinical investigations, as well as an intensive workshop on clinical skills for researchers. Hands-on training will be under the guidance of my clinical collaborators, a breast radiologist and a cancer pathologist, both distinguished clinicians who boast extensive research accomplishments. 4) Scientific and career guidance to develop my independent career path are explicitly outlined in the proposal, including a structured mentoring plan and interaction with the broader scientific community.