Development of Direct Metabolite Imaging for Human Breast Cancer

人类乳腺癌直接代谢成像的发展

• 批准号: 7480999
• 负责人: JIANI HU
• 金额: $ 15.05万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-06 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480999
• 关键词: Anxiety; Appearance; Benign; Biochemical; Biopsy; Brain; Breast; Breast Cancer Detection; Cancer Patient; Cancerous; Cell Line; Cells; Chemicals; Choline; Clinical; Cold Therapy; Detection; Development; Diagnosis; Diagnostic Specificity; Early identification; Equipment; Evolution; Goals; Gold; Human; Image; Imaging Techniques; In Vitro; Incidence; Invasive; Lesion; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Mammography; Metabolism; Methods; Monitor; Neoadjuvant Therapy; Noise; Numbers; Oncogenes; Operative Surgical Procedures; Patients; Protocols documentation; Protons; Radio Waves; Rate; Recurrence; Research; Residual Tumors; Residual state; Resolution; Risk; Sampling; Signal Transduction; Site; Specificity; Speed; Standards of Weights and Measures; Techniques; Time; Tissues; Today; Tumor-Derived; Water; Woman; breast lesion; chemotherapy; clinically relevant; cost; desire; improved; in vivo; interest; magnetic field; malignant breast neoplasm; molecular imaging; novel; radiologist; response; tool

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.

描述(申请人提供)：乳房的磁共振成像(MRI)，它使用无线电波和磁铁而不是x射线，通过它们的外观和对注射物质的反应来识别异常，并可以检测在x射线乳房X光检查中看不到的癌症。然而，像后者一样，它通常无法区分癌症和非癌症病变。非癌性活组织检查会引起焦虑和风险，而且成本高昂。减少今天良性病变的大量活检是乳腺影像研究的一个重要目标。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新陈代谢，但提供完全独立的生化信息。乳腺癌与良性病变和正常乳腺组织的区别在于1HMRS上胆碱(Cho)信号的显著增加，这与来自乳腺细胞系体外MRS的证据一致，即CHO水平随着从正常到永生化到癌基因转化到肿瘤来源细胞的过程而增加。常规应用活体乳腺1H MRS的挑战是需要高空间分辨率、强大的脂肪/水抑制和稳健的技术，所有这些都需要在临床可接受的采集时间内进行。我们假设双回波滤波代谢物成像(DEFMI)技术可以克服当前1H MRS方法的所有障碍。我们的长期目标是，只要订购了乳腺MRI，就可以进行高空间分辨率的1H分子成像。我们的具体目标是：1)开发和优化用于人类乳腺癌的DEFMI；2)确定在MRI阳性或不确定的女性样本中，DEFMI是否有希望降低MRI的假阳性率。这项提议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。这项建议的临床方面将证明，在具有统计意义的数量的乳腺癌患者中，DEFMI提高了检测新的、残留的或复发的乳腺癌的特异性。活组织检查将是金标准。总而言之，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的代谢物图像，2)允许直接代谢物成像，3)快速和稳健，4)可以很容易地集成到标准的乳腺MRI协议中，由MRI技术专家操作，以及5)使代谢物图像立即可供放射科医生使用，就像传统的MRI一样。如果成功，它将成为常规临床乳腺MRI方案的一部分，从而1)通过提供有关病变的独立生化信息、检测“隐藏的”癌症、帮助选择活检部位并同时检查多个病变来提高诊断水平，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)帮助化疗反应人员早期识别化疗反应，从而改善局部晚期乳腺肿瘤的管理。将开发一种超高空间分辨率质子(1H)代谢物成像技术，以克服现有方法的障碍。如果成功，它将成为常规临床乳腺MRI检查的一部分，从而降低MRI假阳性的高发生率以及与良性活检相关的焦虑、风险和成本。