Multinuclear MRI of Breast Tumors

Institution: Stanford University
Investigator(s): Brian  Hargreaves , Ph.D. -
Award Cycle: 2007 (Cycle 13) Grant #: 13IB-0074 Award: $236,771
Award Type: IDEA
Research Priorities
Detection, Prognosis and Treatment>Imaging, Biomarkers, and Molecular Pathology: improving detection and diagnosis

Initial Award Abstract (2007)

Earlier and more accurate diagnosis, as well as better selection and assessment of treatments could dramatically improve survival of breast cancer. Numerous diagnostic modalities exist, including physical examination, x-ray mammography, ultrasound and magnetic resonance imaging (MRI). Proton MRI has been demonstrated as a more sensitive method than x-ray mammography, but suffers from limited specificity. Recent technology advances enable diagnostic quality MR images of sodium in vivo. Since sodium levels are significantly elevated in tumors, simultaneous multinuclear MRI, of both protons and sodium, offers a potentially more specific overall imaging modality. The development of multinuclear MRI as a clinical tool for evaluation of breast cancer will require technical developments, thorough characterization of sodium MRI in the breast, and clinical evaluation in patients.

There are two major hypotheses in the overall research topic. First, we hypothesize that MRI can quantitatively detect differences in sodium concentrations between tumors and normal tissue. This will be tested by the development of new hardware, software and analysis techniques, followed by in vivo imaging in volunteers to characterize normal tissue, and finally by a preliminary study in patients with suspected tumors. We further hypothesize that quantitative sodium MRI will improve the specificity of current breast MRI exams, which will be tested in follow-on research to the proposed project.

There are three specific aims in this research. First, we will develop new receive coil hardware and pulse sequence software for multinuclear MRI, and new analysis techniques to quantify sodium concentrations. Second, we will characterize MRI relaxation properties of sodium in normal breast tissue. Finally, we will develop a sodium/proton MRI protocol based on these properties and perform a preliminary patient study evaluating the benefits of multinuclear MRI for breast imaging, enabling broader clinical studies in future projects. To accomplish these aims, we will design and build a dual-tuned, bilateral breast coil to receive the MRI signal from both sodium and water at 3T. We will develop new MRI pulse sequences for multinuclear imaging using this coil, including methods to separate macromolecule-bound sodium from free sodium. To measure sodium concentrations in breast tissue which includes diffuse fat, we will combine sodium measurements with quantification of fat using proton MRI. After carefully measuring relaxation parameters of sodium in normal tissue, we will perform a preliminary patient study.

High quality quantitative sodium and proton imaging could significantly improve the specificity of MRI for detection of breast cancer. These new imaging methods ultimately have the potential to increase survival rates through earlier diagnosis and better treatment management.

Final Report (2009)

The purpose of this project was to develop methods for sodium breast magnetic resonance imaging (MRI), to test these methods in healthy volunteers, and to perform an early validation study to determine the diagnostic utility of sodium MRI for detection of breast cancer in patients. Sodium MRI is challenging because the signal is much lower than that of standard "proton" MRI.

At the conclusion of the project (and no-cost extension) we have built different MRI hardware appropriate for the combination of sodium MRI with standard proton MRI. Two different sets of MRI hardware are targeted at (1) imaging a single breast with both sodium and proton MRI, and (2) imaging sodium in one breast, while performing a standard bilateral proton MRI exam in both breasts. The latter hardware is achieved by building a sodium insert coil that works with any standard proton breast coil. Both sets of sodium/proton hardware allow acquisition of both sodium and proton MR images without moving the subject, so that the images can be co-registered. This is important, as it allows the higher-resolution proton image to be used as an anatomic reference for sodium images, and also allows direct comparison between different imaging techniques.

Using the new hardware we have developed an imaging protocol that allows us to obtain different types of proton images as well as sodium images. The proton images are fairly standard types of images that identify show bright fluid regions, such as edema and cysts, as well as images acquired during contrast injection that show the increased perfusion common in tumors, and are the primary method used to diagnose breast cancer with MRI. Our sodium imaging allows imaging of sodium density as well as sodium characteristics that may indicate the fraction of sodium that is inside or outside the individual cells.

In the final phase of the project, we aimed to demonstrate that elevated sodium MRI was associated with malignancy of tumors. Although we are only halfway towards completing this study, the early results suggest that there are more complex reasons for elevated sodium levels detected with MRI than we originally suspected. In future we hope to complete this study and learn more about what information sodium MRI can provide about the environment around tumor cells including extracellular matrix and stroma cells.