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MRI‐measured water mobility increases in response to chemotherapy via multiple cell‐death mechanisms
Author(s) -
Morse David L.,
Galons JeanPhilippe,
Payne Claire M.,
Jennings Dominique L.,
Day Sam,
Xia Guowei,
Gillies Robert J.
Publication year - 2007
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1127
Subject(s) - mitotic catastrophe , programmed cell death , apoptosis , necrosis , mitotic index , effective diffusion coefficient , cancer research , chemotherapy , pathology , mitosis , medicine , chemistry , biology , magnetic resonance imaging , microbiology and biotechnology , radiology , biochemistry
Numerous pre‐clinical and clinical reports have demonstrated that the MRI‐measured apparent diffusion coefficient of water (ADC) increases early in the response to a wide variety of anti‐cancer therapies. It has been proposed that this increase in ADC generally results from an increase in the tumor extracellular volume fraction leading to a greater degree of unrestricted water motion. Furthermore, an increase in extracellular volume has been ascribed to the cell shrinkage that occurs early in the process of programmed cell death. However, other modes of death can be initiated soon after beginning therapy. These other modes of death include mitotic catastrophe and necrosis, and may also involve changes in the fraction of water with unrestricted motion. This work examines whether MRI‐measured ADC is altered in response to therapies that induce cell death via non‐apoptotic mechanisms and correlates ADC changes with cell death modalities regionally within the tumor. Apoptotic responses were limited to the tumor periphery in apoptosis‐proficient tumors. Apoptosis was not observed in deficient tumors. Mitotic catastrophe was observed after treatment at the periphery and deeper into the tumor. Necrosis was the predominant response in the center of the tumor. ADC changes were moderate in the periphery and larger in the center. The results indicate that early and significant changes in ADC can occur in concert with mitotic catastrophe and lytic necrosis in the absence of apoptosis. Hence, changes in ADC may be a generalized measure of cytotoxic response to chemotherapy. Copyright © 2007 John Wiley & Sons, Ltd.