The ultimate goal of any
cancer therapy is to target the elimination of neoplastic cells. Although newer therapeutic strategies are in constant development, therapeutic assessment has been hampered by the inability to assess, rapidly and quantitatively, efficacy in vivo. Diffusion imaging and, more recently,
sodium MRI have demonstrated their distinct abilities to detect
therapy-induced alterations in
tumor cellularity, which has been demonstrated to be indicative of therapeutic efficacy. More importantly, both imaging modalities detect
tumor response much earlier than traditional methodologies that rely on macroscopic volumetric changes. In this study, the correlation between
tumor sodium and diffusion was further tested to demonstrate the sensitivity of
sodium imaging to gauge
tumor response to
therapy by using a 9L rat
gliosarcoma treated with varying doses of
BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea]. This orthotopic model has been demonstrated to display variability in response to
BCNU therapy where initial insult has been shown to lead to drug-resistance. In brief, a single 26.6 mg/kg
BCNU dose yielded dramatic responses in both diffusion and
sodium MRI. However, a second equivalent
BCNU dose yielded a much smaller change in diffusion and
sodium, suggesting a drop in
tumor sensitivity to
BCNU. The MRI responses of animals treated with 13.3 mg/kg
BCNU were much lower and similar responses were observed after the initial and secondary applications of
BCNU. Furthermore, these results were further validated using volumetric measurements of the
tumor and also ex vivo determination of
tumor sensitivity to
BCNU. Overall, these experiments demonstrate the sensitivity and applicability of
sodium and diffusion MRI as tools for dynamic assessment of
tumor response to
therapy.