Development of Direct Metabolite Imaging for Human Breast Cancer

描述（由申请人提供）：乳房的磁共振成像（MRI），使用无线电波和磁铁而不是X射线，通过其外观及其对注射物质的反应来识别异常，并且可以检测X射线乳房X线摄影术上不可见的癌症。然而，像后者一样，它通常无法区分癌症和非癌性病变。非癌性活检会导致焦虑、风险并且成本高昂。减少大量的活检良性病变进行今天是一个重要的目标，乳腺影像学研究。质子（1H）磁共振波谱（MRS）使用与MRI相同的设备非侵入性地观察组织代谢，但提供完全独立的生化信息。通过1H MRS上胆碱（Cho）信号的显著增加，已将乳腺癌与良性病变和正常乳腺组织区分开来，这与来自乳腺细胞系的体外MRS的证据一致，即Cho水平随着从正常细胞到永生化细胞到癌基因转化细胞到肿瘤衍生细胞的进展而增加。常规应用体内乳腺1H MRS的挑战是需要高空间分辨率、强大的脂质/水抑制和稳健的技术，所有这些都在临床可接受的采集时间内。我们假设双回波滤波代谢物成像（DEFMI）技术可以克服目前的1H MRS方法相关的所有障碍。我们的长期目标是允许高空间分辨率的1H分子成像，以进行乳腺MRI时，被下令。我们的具体目标是：1）开发和优化DEFMI用于人类乳腺癌; 2）确定DEFMI是否有望降低MRI阳性或不确定MRI结果的女性样本中的MRI假阳性率。该提案的技术方面将进一步发展DEFMI技术，以便在临床可接受的采集时间内获得超高空间分辨率。该提案的临床方面将证明，DEFMI提高了在统计学上有意义的乳腺癌患者数量中检测新发、残留或复发乳腺癌的特异性。活检将是黄金标准。总之，我们将开发一种1H分子成像技术，该技术1）使用短TE和高场提供超高空间分辨率代谢物图像，2）允许直接代谢物成像，3）快速且稳健，4）可以容易地集成到MRI技术人员可操作的标准乳腺MRI方案中，以及5）使放射科医生立即获得代谢物图像，就像传统MRI一样。如果成功的话，它应该成为常规临床乳腺MRI方案的一部分，从而1）通过提供关于病变的独立生化信息、检测“隐藏”癌症、帮助选择活检部位以及同时检查多个病变来改善诊断，2）减少良性病变的活检次数及其伴随的焦虑、风险和成本，以及3）帮助早期识别化疗应答者，从而改善局部晚期乳腺肿瘤的治疗。将开发一种超高空间分辨率质子（1H）代谢物成像技术，以克服与当前方法相关的障碍。如果成功的话，它应该成为常规临床乳腺MRI检查的一部分，从而降低MRI假阳性的高发生率和相关的焦虑，风险和良性活检的成本。

DESCRIPTION (provided by applicant): Magnetic resonance imaging (MRI) of the breasts, which uses radio waves and magnets rather than x-rays, identifies abnormalities by their appearance and their response to an injected substance, and can detect cancers not visible on x-ray mammography. However, like the latter, it is often unable to distinguish a cancer from a non-cancerous lesion. Non-cancerous biopsies cause anxiety, risk and are costly. Reducing the large number of biopsies of benign-lesions performed today is an important goal of breast imaging research. Proton (1H) magnetic resonance spectroscopy (MRS) non-invasively looks at tissue metabolism using the same equipment as MRI but provides completely independent biochemical information. Breast cancers have been distinguished from benign lesions and from normal breast tissue by dramatic increase of a choline (Cho) signal on 1H MRS, which is consistent with evidence from in vitro MRS of breast cell lines that Cho levels increase with progression from normal to immortalized to oncogene-transformed to tumor-derived cells. The challenge of routinely applying in vivo breast 1H MRS is the need for high spatial resolution, powerful lipid/water suppression, and robust technique, all in a clinically acceptable acquisition time. We hypothesize that the double echo-filter metabolite imaging (DEFMI) technique can overcome all obstacles associated with current 1H MRS methods. Our long-term goal is to allow high spatial resolution 1H molecular imaging to be performed whenever a breast MRI is ordered. Our specific aims are: 1) to develop and optimize DEFMI for human breast cancer; 2) to determine whether DEFMI shows promise in reducing the false positive rate of MRI in a sample of women with positive or indeterminate MRI findings. The technical aspect of this proposal will further develop the DEFMI technique so that ultra high spatial resolution can be acquired within clinically acceptable acquisition time. The clinical aspect of this proposal will demonstrate that DEFMI improves specificity in detection of new, residual or recurrent breast cancer in a statistically meaningful number of breast cancer patients. Biopsy will be the gold standard. In summary, we will develop a 1H molecular imaging technique that 1) provides ultra high spatial resolution metabolite images using a short TE and high field, 2) allows direct metabolite imaging, 3) is fast and robust, 4) can be readily integrated into a standard breast MRI protocol operable by an MRI technologist, and 5) makes metabolite images immediately available to a radiologist just like a conventional MRI. If successful, it should become part of the routine clinical breast MRI protocol and thereby 1) improve diagnosis by providing independent biochemical information on lesions, detecting "hidden" cancer, helping selection of a biopsy site, and examining multiple lesions simultaneously, 2) reduce the number of biopsies of benign lesions and their concomitant anxiety, risk and cost, and 3) help early identification of chemotherapy responders, thereby improving the management of locally advanced breast tumors. An ultra high spatial resolution proton (1H) metabolite imaging technique will be developed to overcome obstacles associated with current methods. If successful, it should become part of the routine clinical breast MRI exams, and thereby reduce the high incidence of false positive MRI and associated anxiety, risk and cost of benign biopsies.