We propose to test whether HiSS MRI estimates breast cancer risk more accurately than conventional fat- suppressed MRI and X-ray mammography. Reliable measurements of breast density, which is one of the strongest independent risk factors for breast cancer, could significantly improve management of risk and preventive treatment. X-ray mammography predicts increased cancer risk on a population basis but has limited value for guiding treatment of individual patients, due to errors in separation of parenchyma and fat, and errors in measurement of the parenchymal volume. MRI allows 3D imaging of breast parenchyma and detects independent signals from water and fat. MRI detects significant decreases in breast density due to tamoxifen and raloxifen. However, conventional MRI requires suppression of signals from fat in the breast. Fat suppression is sometimes non-uniform and fat suppression pulses affect the water resonance, reducing the accuracy of parenchymal volume measurements. Therefore we propose an innovative approach to measurement of breast cancer risk: We will use high spectral and spatial resolution MR imaging (HiSS MRI) to reliably separate water and fat signals, and to quantitatively measure parenchymal density and changes in breast density due to tamoxifen. We hypothesize that use of quantitative HiSS imaging will reduce variability, standardize measurements, and increase sensitivity to variations in parenchymal volume. In addition, HiSS may provide new markers for risk based on the novel computer-aided diagnosis (CAD) analysis of the enhanced texture of HiSS images, and HiSS images of fat distribution. This proposal builds on work in this laboratory that implemented HiSS MRI on clinical magnets and demonstrated significant advantages of this approach. We propose the following Specific Aims:
Aim #1 : Implement quantitative full bilateral measurements of breast parenchymal density and morphology with HiSS MRI. Phantoms attached to the breast will be used to accurately measure MRI- detectable proton density. Novel software will evaluate parenchymal volume and texture. Fat distribution and composition will be tested as additional markers for risk.
Aim #2. Compare HiSS with conventional approaches: We will compare breast density measured with HiSS, conventional fat-suppressed MRI, Dixon MRI methods, and X-ray mammography. Measures of breast density will include absolute and fractional parenchymal volume, and MRI-detectable water proton density. The variability of HiSS and conventional MRI measurements will be compared.
Aim #3. Measure changes in parenchymal density due to selective estrogen receptor modulator (SERM) therapy: As a measure of the sensitivity of HiSS MRI to changes in breast cancer risk, we propose to image response to preventive therapy that is known to reduce risk. We will compare the sensitivity of HiSS MRI to effects of tamoxifen therapy with that of 2D X-ray mammography and conventional MRI.

Public Health Relevance

The goal of this research is the development and validation of quantitative, robust functional and anatomical imaging methods to predict and assess response of breast parenchyma to preventive therapy. Such tools would allow faster and cheaper drug trials, facilitating discoveries of new therapeutic agents. In addition, it may be possible to predct a specific patient's response to therapy, allowing individualized, more effective treatment plans.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA167785-03
Application #
8792350
Study Section
Special Emphasis Panel (ZRG1-DTCS-A (81))
Program Officer
Zhang, Yantian
Project Start
2013-02-08
Project End
2018-01-31
Budget Start
2015-02-01
Budget End
2016-01-31
Support Year
3
Fiscal Year
2015
Total Cost
$484,087
Indirect Cost
$177,703
Name
University of Chicago
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Mustafi, Devkumar; Fernandez, Sully; Markiewicz, Erica et al. (2017) MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple-negative breast cancer. NMR Biomed 30:
Medved, Milica; Li, Hui; Abe, Hiroyuki et al. (2017) Fast bilateral breast coverage with high spectral and spatial resolution (HiSS) MRI at 3T. J Magn Reson Imaging 46:1341-1348
Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar et al. (2017) MRI ductography of contrast agent distribution and leakage in normal mouse mammary ducts and ducts with in situ cancer. Magn Reson Imaging 40:48-52
Pineda, Federico D; Medved, Milica; Wang, Shiyang et al. (2016) Ultrafast Bilateral DCE-MRI of the Breast with Conventional Fourier Sampling: Preliminary Evaluation of Semi-quantitative Analysis. Acad Radiol 23:1137-44
Abe, Hiroyuki; Mori, Naoko; Tsuchiya, Keiko et al. (2016) Kinetic Analysis of Benign and Malignant Breast Lesions With Ultrafast Dynamic Contrast-Enhanced MRI: Comparison With Standard Kinetic Assessment. AJR Am J Roentgenol 207:1159-1166
Li, Hui; Weiss, William A; Medved, Milica et al. (2016) Breast density estimation from high spectral and spatial resolution MRI. J Med Imaging (Bellingham) 3:044507
Pineda, Federico D; Medved, Milica; Fan, Xiaobing et al. (2016) B1 and T1 mapping of the breast with a reference tissue method. Magn Reson Med 75:1565-73
Weiss, William A; Medved, Milica; Karczmar, Gregory S et al. (2015) Preliminary assessment of dispersion versus absorption analysis of high spectral and spatial resolution magnetic resonance images in the diagnosis of breast cancer. J Med Imaging (Bellingham) 2:024502
Pineda, F D; Medved, M; Fan, X et al. (2015) Comparison of dynamic contrast-enhanced MRI parameters of breast lesions at 1.5 and 3.0?T: a pilot study. Br J Radiol 88:20150021
Mustafi, Devkumar; Zamora, Marta; Fan, Xiaobing et al. (2015) MRI accurately identifies early murine mammary cancers and reliably differentiates between in situ and invasive cancer: correlation of MRI with histology. NMR Biomed 28:1078-86

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