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Proton NMR Microscopy of Multicellular Tumor Spheroid Morphology
Author(s) -
Sillerud Laurel O.,
Freyer James P.,
Neeman Michal,
Mattingly Mark A.
Publication year - 1990
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/j.1522-2594.1990.tb00001.x
Subject(s) - spheroid , microscopy , nuclear magnetic resonance , chemistry , biophysics , biology , pathology , in vitro , physics , medicine , biochemistry
We report proton NMR images obtained at microscopic (<30 μm) resolution of EMT6/Ro and HT1080 multicellular tumor spheroids 1.2–1.7 mm in diameter. T 1 ‐weighted images showed little contrast across a slice through the spheroid. There was also no difference between the inner and outer spheroid regions when signal intensity was measured as a function of the repitition time (TR), showing that T 1 was the same across the spheroid. Conversely, T 2 ‐weighted and multiecho images clearly revealed the central necrosis that occurs as the spheroids develop. Measurements of the thickness of the viable cell zone made on NMR images agreed with those made on standard histology sections for two different cell lines. The basis for the NMR discrimination of the necrotic region from the viable rim cells was found to be a shortened apparent T 2 in the necrotic region (132 ± 17 ms) with respect to that in the viable cells (173 ± 9 ms). These results illustrate the applicability of NMR microscopy to assaying conditions inside intact tumor spheroids and suggest that this technology will allow the use of spheroids to investigate several important questions in tumor biology and pathophysiology.