Project 2: Specificity of MRI with Optimal Temporal, Spatial, and Spectral Sampling for Early Breast Cancer
High spectral and spatial resolution MRI (HiSS) of the breast has been shown to improve functional and anatomic water proton images. In addition, high temporal and spatial resolution MRI during contrast media uptake and washout improves measurements of physiologic parameters and increases lesion conspicuity. We propose to combine these two approaches to breast MRI to increase specificity while maintaining high sensitivity for detection of early cancers in the ‘high risk’ population. This new approach is referred to in the following as MRI with improved spectral, spatial and temporal sampling (MRITSS). The proposed work is likely to have a rapid and significant impact on patient care by introducing improvements in MRI technology. To accomplish we will study 1) Women who are referred for MRI as part of standard clinical practice because of a primary lesion found on mammography. These women receive MRI scans primarily to determine whether there are other lesions present that are occult on mammography. 2) Women from the University of Chicago Cancer Risk Clinic who receive routine MRI scans for screening purposes. In cases where small, incidental breast lesions are found by MRI in these patients, we will ask the patients to volunteer for a research scan. The research scan will use MRITSS to scan one or more of the incidental lesions. The specificity of the conventional clinical MRI scans and the MRITSS scan will be evaluated and compared using diagnosis by pathologists as the gold standard. In addition, molecular markers will be correlated with MRI parameters. The specific aims are as follows:
1. Use MRI with improved spectral, spatial, and temporal sampling (MRITSS) to acquire images of suspicious incidental lesions found in high risk women. Determine whether MRITSS increases specificity while maintaining adequate sensitivity. MRITSS will be compared to conventional MRI and pathology will be used as the gold standard.
2. Determine whether conventional and/or MRITSS MRI can distinguish between invasive and intralobular/intraductal cancers.
3. Determine whether breast lesions in African American women who are at risk for high grade, estrogen receptor negative breast cancer are significantly different from those of the other women in the study.
4. Test whether there are specific biological markers that are strongly correlated with MRI parameters, and explain the appearance of functional and anatomic MR images of early breast cancers. We will determine whether i) microvessel density correlates with contrast media uptake rate, ii) irregular tumor margins correlate with rapid tumor growth as indicated by Ki67 iii) prognostic markers for outcome including P53 and HER2 expression correlate with the morphology of tumor margins and with contrast media uptake patterns. We will also determine whether gene mutations that are known to increase cancer risk – BRCA1 and BRCA2 – correlate with functional and anatomic features on MRI, and whether characteristics of germ-line DNA should be considered in the evaluation of MRI data in order to increase diagnostic accuracy.
Accomplishments for Project 2 in the 2006-2011 period
- Established utility of pre-contrast MRITSS in characterization of small breast lesions
- Established sensitivity of MRITSS to tumor vasculature in animal model
- Implemented parallel imaging acceleration for MRITSS imaging, allowing complete bilateral coverage of breasts
- Developed several quantities derived from water resonance structure complexity as potential markers for breast lesion malignancy and evaluated their sensitivity and specificity for lesion characterization
- Showed that computer-aided diagnostic (CADx) analysis of pre-contrast MRITSS images of breast lesions has equivalent performance to CADx analysis of dynamic contrast-enhanced MRI