Distinction between the Preneoplastic and Neoplastic State of Murine Mammary Glands by spin-echo NMR

We have, using spin-echo nuclear magnetic resonance spectroscopy, measured the relaxation times and diffusion coefficient of water protons in primary mammary adenocarcinomas of mice. In our biological model, three morphological stages were defined: (a) mammary gland tissue from pregnant mice, (b) preneoplastic nodules, and (c) neoplastic tissue. It was found that neoplastic tissues could be distinguished from normal and prenoeplastic tissue. Spin-spin and spin-lattice relaxation times and the diffusion coefficient of water protons are increased in the neoplastic tissue relative to mammary gland tissue from pregnant mice and preneoplastic nodule tissue. These results suggested that one can use a pulsed NMR method to detect and even predict breast cancer. Damadian reported recently that the spin-lattice (T1) and spin-spin (T2) relaxation times of water protons in tumors were distinguishable from those in normal tissue or in benign tumors (1). These studies used tumor cell lines (Walker sarcoma and Novikoff hepatoma) that have been serially transplanted for many years, and, therefore, have had ample opportunity to undergo biochemical and morphological changes associated with tumor progression. In order to establish whether the increased motional state of tissue water demonstrated by nuclear magnetic resonance (NMR) measurements exists in primary tumors or whether these changes are a consequence of a tumor progression seen only in highly transplantable tumor lines, we chose to look at primary mammary adenocarcinomas of the mouse. The mouse mammary tumor preparation has several advantages that are useful for investigation of discriminating changes in neoplastic compared to normal tissues. First, one can define at least three morphological states of mammary tissue―normal, preneoplastic nodules, and neoplastic tissue (2, 3). The hyperplastic alveolar nodule is considered preneoplastic in the sense that it gives rise to mammary tumors earlier and with greater frequency than normal mammary tissue. In addition, most Abbreviations: NMR, nuclear magnetic resonance; T1, spin-lattice relaxation time; T2, spin-spin relaxation time; D, diffusion coefficient of water.