Dynamic contrast enhanced 1H-magnetic resonance imaging in assessment of skeletal muscle and fibrosarcoma perfusion

Abstract

Background. The detection of neoplastic transformation and prediction of the thera­peutic response are very important for effective cancer therapy. Current assessment of tumor treatment efficacy relies on evaluating changes in the tumor size or volume, weeks to months after the assumption of a therapeutic protocol. The tissue perfusion is one of the most important parameter to estimate the neoplastic progress and the efficacy of antitumor therapy. ¹H-magnetic resonance imaging (MRI) is an effective tool that provides distinctive information related to structural, cellular, apoptotic, and necrotic changes in tumor tissue. The technique can be used widely for tumor detection and monitoring of the response to treatment. Methods. Dynamic contrast enhanced ¹H-MRI was used for the assessment of tumor perfusion parameters in normal muscle and in subcutaneous Radiation Infused Fibrosarcoma – 1 (RIF-1) developed under the skin in C3H mice. Gadolinium (20 mM) was used as a capillaries perfusion tracer. Therapy of RIF-1 was administered by a single intraperitoneal injection of 5-fluorouracil (150 mg/kg). MRI experiments were performed before and 3 days after the treatment. Results. Dynamic contrast enhanced ¹H-MRI has shown a much lower perfusion rate in RIF-1 tumor compared to skeletal muscle. 5-fluorouracil caused a significant decrease in subcutaneous RIF-1 volume on days 2 and 3 post-treatment, as well as an increase in tumor inflow measured by Dynamic contrast enhanced ¹H-MRI. An increase in tumor tissue perfusion correlated with an increase in tissue apparent diffusion coefficient and total Na⁺ concentration following 5-fluorouracil chemotherapy reflect an increase in extracellular space and vasodilatation. On the other hand, as it was shown in our previous publications, the lower intracellular Na⁺ concentration and glucose uptake in treated by 5-fluorouracil tumors compared with control tumors suggest a shift in tumor metabolism from glycolysis to oxidation and/or a decrease in cell density. Conclusions. Method of dynamic contrast enhanced ¹H-MRI in combination with other NMR methods, positron emission tomography, histology, etc. should prove useful in assessment of neoplastic transformation of tumor capillaries and efficacy of chemotherapy. Keywords: muscle, perfusion, Gadolinium, fibrosarcoma, 5-fluorouracil, ¹H-MRI