Cryotherapy of malignant tumors. MR imaging in comparison with pathological changes in mice

Purpose: Aim of our study was to investigate the efficacy of 7 F cryoprobes for percutaneous use morpho- and histologically, to examine the role of ap optosis after cryotherapy, and to compare contrast-enhanced MRI with histop athological findings at different time intervals in a tumor-mouse model. Me thods: Percutaneous cryotherapy was performed in 15 immunocompromised nude mice with subcutaneously implanted tumors using the nonsmall-cell lung canc er cell line Lu 1. In group a) 7 mice were sacrificed after definite time i ntervals and histological examinations were done for evaluation of necrosis and apoptosis (HE; TUNEL assay); 2 mice are in long-term follow-up. in gro up b) in 6 mice tumor destruction and perfusion before and after freezing w ere investigated with native and contrast-enhanced MR imaging (T-1- and T-2 -weighted spin-echo) and compared with histopathological findings. Histolog ical control were done in 2 untreated mice. Results: We observed fast tumor -reduction within two weeks (ca. 50%). On long-term follow-up (> 6 months) no recurrence has been noticed so far. Tumors were well vascularized prior to treatment and did not-show contrast enhancement an any time after cryoth erapy. A narrow contrast-enhanced zone was seen on the tumor border subcuta neously as a sign of peripheral hyperemia and central vascular stasis after cryotherapy. On histology there was evidence of both apoptosis and necrosi s. Conclusion: We have established a tumor-mouse model for further investig ations. Two minutes freezing of a 2-cm tumor in the mouse model is sufficie nt for tumor ablation with scarred healing. Apoptosis may play a role in cr yotherapy of experimental tumors. Contrast-enhanced MRI is suitable for the estimation of the cryolasion.