Hyperpolarized C-13 MR Pulse Sequence Developments for Novel Contrast

描述（由申请人提供）：本项目概述了新兴领域超极化碳-13 MRI中新型图像对比度的生物工程技术发展。这一领域的初步研究非常有希望，特别是在癌症应用方面，第一批前列腺癌患者的人体试验预计将在6个月内在加州大学旧金山分校进行。该“独立之路”奖申请包括候选人Peder Larson博士向独立研究者过渡的指导职业发展计划，以及描述超极化碳-13 mr的拟议技术发展的随附研究计划。候选人Peder Larson博士目前是加州大学旧金山分校的博士后学者，致力于超极化碳-13 MRI的技术发展。他的研究生工作是在斯坦福大学的电子工程专业，专注于改进半固体组织的MRI，这在传统的MRI中是看不见的。指导和职业发展计划将补充他的工程背景，有价值的接触超极化物理和化学，生物系统和生物化学，临床前研究和跨学科合作，以促进过渡到一个独立的生物工程研究者。他的目标是成为生物工程或放射学的一名教员，在那里他可以研究具有潜在临床应用的技术生物医学成像发展。超极化碳-13核磁共振成像需要专门的方法，因为与传统核磁共振成像不同，信号衰减迅速且不可恢复。本项目提出了快速有效的动态代谢成像方法，以提供当前技术无法获得的局部灌注、摄取和速率信息。与超极化碳-13对比的新来源也被提出，包括一种区分流动代谢物与组织内代谢物的方法，以及开发多种碳-13试剂的专门技术。在正常动物的临床前研究将用于研究新的成像方法。这将促进方法从开发到未来临床应用的转化。

DESCRIPTION (provided by applicant): This project outlines technical bioengineering developments for new types of image contrast in the emerging field of hyperpolarized carbon-13 MRI. Preliminary research in this field is extremely promising, particularly for cancer applications, and the first human trials in prostate cancer patients are slated to occur at UCSF within 6 months. This "Pathway to Independence" award application includes a mentored career development plan for transition of the candidate, Dr. Peder Larson, into an independent investigator, as well an accompanying research plan describing the proposed technical developments for hyperpolarized carbon-13 MR. The candidate, Dr. Peder Larson, is currently a Postdoctoral Scholar at UCSF working on technical developments for hyperpolarized carbon-13 MRI. His graduate work was in Electrical Engineering at Stanford and focused on improving MRI of semi-solid tissues, which are invisible in conventional MRI. The mentoring and career development plan will supplement his engineering background with valuable exposure to hyperpolarization physics and chemistry, biological systems and biochemistry, pre-clinical research, and inter-disciplinary collaboration to facilitate the transition to an independent bioengineering investigator. His goals are to become a faculty member in bioengineering or radiology where he can research technical biomedical imaging developments with potential clinical applications. Hyperpolarized carbon-13 MRI requires specialized methods because, unlike conventional MRI, the signal decays rapidly and is unrecoverable. This project proposes rapid and efficient methods for dynamic metabolic imaging to provide localized perfusion, uptake and rate information that are unavailable in current techniques. New sources of contrast with hyperpolarized carbon-13 are also proposed, including a method to distinguish flowing metabolites from those within tissues and development of specialized techniques for multiple carbon-13 agents. Preclinical studies in normal animals will be used for investigation of the new imaging methods. This will facilitate the translation of the methods from development to future clinical application. PUBLIC HEALTH RELEVANCE: MRI with hyperpolarized carbon-13 can non-invasively probe tissue functions that are altered in cancer and other disease states, and the first human trial with prostate cancer patients is shortly forthcoming. The new hyperpolarized carbon-13 imaging methods proposed in this project will provide unprecedented tissue function contrast to improve cancer imaging and potentially enable new clinical applications.