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    Awarded Grants
    Improving Specificity of Breast Cancer Diagnosis with Proton MRSI

    Scientific Abstract:
    BACKGROUND Dynamic contrast-enhanced (DCE) MRI of the breast has demonstrated improved sensitivity for detection of breast cancer compared to x-ray mammography, particularly in settings problematic for the latter such as the dense, augmented, irradiated or post-surgical breast. However specificity remains poor; biopsies of breast lesions seen only on DCE MRI prove benign in 53-80% of cases. Similar difficulties arise in determining the presence of residual tumor in patients treated with neoadjuvant chemotherapy or minimally invasive treatment such as cryotherapy. Contrary to DCE MRI, which characterizes lesions by their morphology and contrast kinetics, magnetic resonance spectroscopy (MRS) reflects lesion metabolism. Distinctive alterations in metabolite content have been observed in breast cancer. Early experience with proton (1H) MRS yielded sensitivity and specificity for detection of breast cancer of 83% and 85% respectively with near 100% for both in a subgroup of young women. However, the low spatial resolution of currently used techniques has precluded the applicability of 1H MRS to small lesions -- the very lesions which may be detected only by DCE MRI and, if malignant, with the best chance for cure. The combination of high spatial resolution and multi-voxel MRS technique (MRSI) should enable evaluation of even small lesions, both in the setting of initial diagnosis and in detection of residual or recurrent tumor following therapy. OBJECTIVES Our objectives are to demonstrate that 1) the combination of band-selective, weighted k-space sampling, and multi-voxel technique improves spatial resolution without sacrificing SNR within a clinically feasible examination time, and 2) high spatial resolution 1H MRSI improves specificity in detection of new, residual or recurrent breast cancer. SPECIFIC AIMS 1. Develop short TE high spatial resolution breast 1H MRSI. 2. Determine whether our 1H MRSI technique used in conjunction with MRI reduces the false positive rate of MRI alone. STUDY DESIGN The technical aspect of this proposal will: 1) further develop our successful MRSI techniques to improve spatial resolution by a factor of more than two, to 0.5 cm3, at 1.5 Tesla in a clinically feasible examination time by utilizing band- selective, weighted k-space sampling and multi-voxel techniques, 2) modify these techniques to achieve spatial resolution of 0.2 cm3 at 4 Tesla, and 3) develop a post-processing software package to correct potential metabolite amplitude modulation due to B0 inhomogeneity. The clinical aspect of this proposal is a cross-sectional observational study of women with positive findings on breast MRI. All participants will undergo proton MRSI and biopsy for evaluation of lesions detected on MRI. Biopsy findings will be the gold standard. POTENTIAL OUTCOMES AND BENEFITS OF THE RESEARCH If successful, the proposed research will develop in vivo 1H MRSI methods that 1) improve early detection and treatment monitoring of breast cancer, 2) allow simultaneous comparison between cancer and normal breast tissue thereby improving detection of new/additional lesions and local heterogeneity, and 3) are robust and practical, adding only 15 minutes to the MRI, operable by an MR technologist, and usable on any imager capable of 1H MRS. This would allow 1H MRS of the breast to be performed whenever a breast MRI is ordered.

    Lay Abstract:
    BACKGROUND 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 benign (non-cancerous) lesion. Consequently 53-80% of biopsies prompted by MRI prove benign. Similar difficulties arise in determining the presence of residual tumor in patients treated with chemotherapy or minimally invasive treatment such as cryotherapy (freezing). Magnetic resonance spectroscopy (MRS) uses the same equipment to look at tissue metabolism, thus providing completely independent biochemical information. Distinctive metabolites have been observed in breast cancer, allowing better discrimination between cancer and benign lesions. Biopsy could be avoided if a lesion were clearly benign. However, low spatial resolution with currently used techniques has precluded applying MRS to small lesions -- the very lesions that may be detected only by MRI and, if cancerous, have the best chance of cure. We propose developing and testing a high spatial resolution multi-voxel MRS technique (MRSI) capable of evaluating small lesions, both in the setting of initial diagnosis and in detection of residual or recurrent tumor following therapy. If successful, this approach will not only avoid many “unnecessary” biopsies, but also provide guidance to optimal patient management and thus improve outcomes. OBJECTIVES Our objectives are to demonstrate that 1) an MRSI technique can be developed that permits high spatial resolution information to be obtained in a clinically feasible examination time, and 2) application of this technique improves correct identification of new, residual or recurrent breast cancer. SPECIFIC AIMS 1. Develop high spatial resolution breast proton MRSI. 2. Determine whether the addition of this MRSI technique improves correct identification of breast cancer in lesions detected by MRI and recommended for biopsy. STUDY DESIGN The technical aspect of this proposal will: 1) further develop our successful MRSI techniques to improve spatial resolution by a factor of more than 2, to 0.5 cm3, at 1.5 Tesla (magnet strength in common use), in a clinically feasible examination time, 2) modify these techniques to achieve spatial resolution of 0.2 cm3 at 4 Tesla (higher magnet strength, currently limited to research), and 3) develop corresponding post-processing software. The clinical aspect of this proposal will: 1) apply these techniques to breast lesions detected by MRI which are scheduled for biopsy, and 2) compare the results of MRS with MRI and biopsy findings in the same lesion. Biopsy findings will be the gold standard. POTENTIAL OUTCOMES AND BENEFITS OF THE RESEARCH If successful, the proposed research will develop MRS methods that 1) improve early detection and treatment monitoring of breast cancer, 2) allow easy comparison between cancer and normal breast tissue in an individual patient thereby improving detection of new/additional lesions, and 3) provide a robust and practical technique which is simple to operate and applicable on any imager capable of MRS. This would allow MRS of the breast to be performed whenever a breast MRI is ordered.