Development of an Optimal MRI Platform for Prostate Investigations at 7 Tesla

描述(申请人提供)：这项提议的中心假设是，利用7特斯拉(7T)的超高磁场提高空间、光谱和时间分辨率的技术发展将允许开发定量和敏感的MRI标记物，更好地识别前列腺癌并区分病理上迟钝的疾病和侵袭性疾病。超高磁场磁共振成像的优势已经在人脑中得到了充分的证明，因为它具有信噪比(SNR)、并行成像性能和新颖的和/或改进的对比机制。然而，到目前为止，与人体躯干相关的器官系统和疾病一直被排除在这些进步之外，因为当射频波长变得明显小于物体尺寸时会出现困难，就像在7T的人体躯干上所做的那样。最近的发展，主要来自我们的实验室，表明这些挑战是可以克服的。因此，我们建议开展旨在利用MRI在较高磁场中可用的潜在收益来研究人体躯干的临床问题的开发。我们关注的临床问题是前列腺癌，这是美国男性最常见的非皮肤恶性肿瘤，其中六分之一的人会在一生中被诊断出患有这种疾病。尽管其流行，但很少有诊断工具，主要是活检和血清PSA，存在着监测疾病进展和确定治疗成功的工具。活检虽然能够局部监测前列腺，但具有侵袭性，而且容易受到固有的抽样误差的影响，导致低估了肿瘤的分级和疾病的程度，而PSA缺乏对恶性肿瘤的特异性。改进的疾病状态监测方法将极大地有利于前列腺癌的管理，因为它可以区分患有侵袭性疾病的患者和可能不需要治疗的小的、受前列腺限制的非侵袭性肿瘤的患者，从而避免患有非侵袭性肿瘤的男性出现与治疗相关的疾病。此外，需要改进方法来识别治疗后早期疾病的复发。我们的长期目标是确定定量和非侵入性的解剖和功能MRI标记物，用于识别前列腺癌和区分生物学上侵袭性和惰性疾病，并使用这些标记物来评估个体化治疗的治疗反应。为了实现这些长期目标，这项应用的主要目标是a)开发一个7特斯拉(7T)前列腺平台，包括开发和评估几种相互依赖的组件(射频线圈、DCE-MRI方法、光谱成像方法和新的光谱量化技术)；b)评估测量前列腺癌定量标志物的重复性，以确定其潜在的变化敏感度；c)评估成像方法和定量标志物以病理为金标准检测癌症的能力；d)通过与3T进行现场比较，确定7T作为检测和监测前列腺癌的强大工具的真正优势。

DESCRIPTION (provided by applicant): The central hypothesis of this proposal is that technological developments that enable increased spatial, spectral and temporal resolution using the ultrahigh magnetic field of 7 Tesla (7T) will allow the development of quantitative and sensitive MRI markers that better identify prostate cancer and differentiate pathologically indolent from aggressive disease. Advantages of ultrahigh magnetic field MRI, due to gains of signal-to-noise- ratio (SNR), parallel imaging performance and novel and/or improved contrast mechanism have been amply demonstrated in the human brain. However, the organ systems and diseases associated with the human torso have been excluded from these advances to date due to difficulties that arise when the RF wavelength becomes significantly smaller than the object size, as it does in the human torso at 7T. Recent developments, largely coming from our laboratory, demonstrate that these challenges can be overcome. Therefore, we propose to undertake developments aimed at exploiting the potential gains available at higher magnetic fields for MRI to investigate a clinical problem in the human torso. The clinical problem we focus on is prostate cancer, which is the most common non-cutaneous malignancy of American men, one in six of whom will be diagnosed with the disease in their lifetime. Despite its prevalence, few diagnostic tools, mainly biopsy and serum PSA, exist for monitoring disease progression and determining treatment success. Biopsies, while able to locally monitor the prostate, are both invasive and subject to inherent sampling error leading to underestimation of tumor grade and extent of disease, while PSA lacks specificity for malignancy. Improved methods to monitor the disease state would greatly benefit prostate cancer management by distinguishing between patients with aggressive disease who would benefit from treatment versus patients with small, prostate-confined, nonaggressive tumors that may not require treatment, and thus avoiding treatment- associated morbidities in men with nonaggressive tumors. Further, improved methods are needed to identify early disease recurrence after treatment. Our long term goals are to identify quantitative and non-invasive anatomic and functional MRI markers useful for the identification of prostate cancer and for distinguishing biologically aggressive versus indolent disease, and to use these markers to evaluate treatment responses to individualized therapies. To achieve these long term goals, the main objectives of this application are to a) develop a 7 Tesla (7T) prostate platform including the development and evaluation of several interdependent components (RF coils, DCE-MRI methods, spectroscopic imaging methods and new spectral quantification techniques), b) evaluate the reproducibility of measuring quantitative prostate cancer markers to determine their potential sensitivity to change, c) evaluate the ability of the imaging methods and quantitative markers to detect cancer using pathology as a gold standard and d) determine the true advantage of 7T as a powerful tool to detect and monitor prostate cancer by performing a field comparison with 3T.