Narrow linewidth MRS to detect breast cancer

描述（由申请人提供）：这项研究和培训计划将使我能够应用一种新的磁共振（MR）信号来获得有关肿瘤的非侵入性化学信息，这最终可以帮助诊断和治疗决策。研究目的概述了两种方法在临床上有用的诊断的进展。 一种经证实的非侵入性测量脂肪化学成分的方法将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MR方法，以非侵入性地测量与癌症相关的代谢物，这将适用于比现有技术更多的器官 由于脂质特异性方法已在小鼠中得到证实，因此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后，我们的研究将验证我们的数据之间的联系，即，光谱中的峰值，以及肥胖小鼠脂肪组织的化学组成。接下来，人类研究将测量乳腺组织中的脂肪，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方法，可以无创地测量体内除脂肪外的化学成分，包括已知是癌症重要标志物的代谢物。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。我们将证明我们的方法在其他器官，如乳房。由于我的培训是作为一名磁共振物理学家，完成这项工作还需要大量的生物医学培训，这将通过课堂工作，导师和实践经验的结合来完成。本建议有四个主要培训目标。1)分子生物学和癌症生物学的培训将开始，首先是分子生物学课程，然后是癌症生物学课程。课程将通过与我的共同导师，著名的癌症生物学和肿瘤微环境专家的讨论，以及参加国家癌症研究会议来补充。 2)先进的体内磁共振技术的培训将包括正式的课程和实践培训，这将由该主题的主要教科书作者Robin De Graaf博士指导。 3)人类研究和生物统计学培训将包括生物统计学和临床研究伦理学的学期课程，以及研究人员临床技能的密集研讨会。实践培训将在我的临床合作者的指导下进行，他们是乳腺放射科医生和癌症病理学家，两位杰出的临床医生都拥有广泛的研究成果。4)提案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.