The anisotropy of the spin-diffusion coefficient Ds of water protons in skeletal muscle has been studied by pulsed NMR methods. The mid-portion of the tibialis anterior muscle of mature male rats was placed in a special sample holder by means of which the muscle fiber orientation theta relative to the diffusion direction could be varied over the range 0 degrees less than or equal to theta less than or equal to 90 degrees. The value of Ds(theta) was determined for theta = 0 degrees, 45 degrees, and 90 degrees. The measured anisotropy Ds(0)/Ds(90) was 1.39, and the value of Ds(0) was 1.39 X 10(-5) cm2/s. These results are interpreted within the framework of a model calculation in which the diffusion equation is solved for a regular hexagonal network similar to the actin-myosin filament network. The large anisotropy, and the large reduction in the value of Ds measured parallel to the filament axes lead to two major conclusions: (a) interpretations in which the reduction in Ds is ascribed to the effect of geometrical obstructions on the diffusion of "free" water are ruled out; and, (b) there is a large fraction of the cellular water associated with the proteins in such a way that its diffusion coefficient is substantially reduced.

We have, using 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.Damadian reported recently that the spin-lattice (T1) and sp)in-sl)in (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.

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