The aim of this project is to develop a multi nuclei Magnetic Resonance (MRI) Imaging breast examination with enough sensitivity and specificity for tumor grading, which would result in a reduction of the need for needle biopsies. Current MRI techniques have good sensitivity, but the specificity is inadequate to allow an evaluation of tumor malignancy. This would improve if one of the parameters measured in the MRI exam were a tumor specific metabolic marker. An elevated [Na]i as a result of the altered changed Na exchange kinetics typical of proliferating cells, is an excellent metabolic marker for tumor malignancy. With 23Na MRI the tissue sodium concentration (TSC) can be quantified, but in breast lesions the TSC contains a large component from the extracellular volume fraction (EVF), masking intracellular changes that may correlate with tumor malignancy. We propose to use a combination of 23Na MRI and dynamic contrast enhancement 1H MR imaging (1H MRI) to improve the specificity of the MRI exam for evaluating tumor malignancy. This will be achieved through using the sensitivity of 23Na MRI for [Na]i in tumors together with the sensitivity of dynamic contrast enhanced 1H MRI for the extracellular volume fraction (EVF). This is the first proposed method to extract information on [Na]i without sacrificing signal to noise ratio (SNR) or resolution, and this is accomplished by using an independent measurement of the EVF. Although washout kinetics of Gd contrast agent are particularly sensitive to EVF, high resolution three dimensional coverage of the breast prohibits accurate determination of EVF. The time course of Gd contrast enhancement also depends on microvascular permeability. Therefore dynamic contrast enhancement 1H MR data and 23Na MRI measurement of TSC in tumors will be used to create a single parameter combining the best features of 23Na MRI and dynamic contrast enhancement studies. By effectively adding a measure for [Na]i, to state of the art dynamic contrast enhancement studies the specificity of tumor grading with MRI methods will be improved to a point where the need for needle biopsies may be reduced.
| Ouwerkerk, Ronald; Jacobs, Michael A; Macura, Katarzyna J et al. (2007) Elevated tissue sodium concentration in malignant breast lesions detected with non-invasive 23Na MRI. Breast Cancer Res Treat 106:151-60 |
| Ouwerkerk, Ronald (2007) Sodium magnetic resonance imaging: from research to clinical use. J Am Coll Radiol 4:739-41 |
| Macura, Katarzyna J; Ouwerkerk, Ronald; Jacobs, Michael A et al. (2006) Patterns of enhancement on breast MR images: interpretation and imaging pitfalls. Radiographics 26:1719-34; quiz 1719 |
| Jacobs, Michael A; Ouwerkerk, Ronald; Wolff, Antonio C et al. (2004) Multiparametric and multinuclear magnetic resonance imaging of human breast cancer: current applications. Technol Cancer Res Treat 3:543-50 |
