Visualization of thermal washout due to spatiotemporally heterogenous perfusion in the application of a model-based control algorithm for MR-HIFU mediated hyperthermia.

PURPOSE: This article will report results from the in-vivo application of a previously published model-predictive control algorithm for MR-HIFU hyperthermia. The purpose of the investigation was to test the controller's in-vivo performance and behavior in the presence of heterogeneous perfusion. MATERIALS AND METHODS: Hyperthermia at 42°C was induced and maintained for up to 30 min in a circular section of a thermometry slice in the biceps femoris of German landrace pigs (n=5) using a commercial MR-HIFU system and a recently developed MPC algorithm. The heating power allocation was correlated with heat sink maps and contrast-enhanced MRI images. The temporal change in perfusion was estimated based on the power required to maintain hyperthermia. RESULTS: The controller performed well throughout the treatments with an absolute average tracking error of 0.27 ± 0.15 °C and an average difference of 1.25 ± 0.22 °C between T10 and T90. The MPC algorithm allocates additional heating power to sub-volumes with elevated heat sink effects, which are colocalized with blood vessels visible on contrast-enhanced MRI. The perfusion appeared to have increased by at least a factor of ∼1.86 on average. CONCLUSIONS: The MPC controller generates temperature distributions with a narrow spectrum of voxel temperatures inside the target ROI despite the presence of spatiotemporally heterogeneous perfusion due to the rapid thermometry feedback available with MR-HIFU and the flexible allocation of heating power. The visualization of spatiotemporally heterogeneous perfusion presents new research opportunities for the investigation of stimulated perfusion in hypoxic tumor regions.

Intravesical radiofrequency induced hyperthermia enhances mitomycin C accumulation in tumour tissue.

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a highly recurrent disease with potential progression to muscle invasive disease despite the standard bladder instillations with mitomycin C (MMC) or Bacille Calmette-Guérin immunotherapy. Therefore, alternatives such as radiofrequency-induced chemohyperthermia (RF-CHT) with MMC are being investigated. The mechanism explaining the efficacy of RF-CHT is only partly understood. We examined whether RF-CHT results in higher MMC tissue concentrations as compared to cold MMC instillation. PATIENTS AND METHODS: Prior to a planned transurethral resection of bladder tumour (TURBT), patients with stage Ta NMIBC were allocated to either (1) cold MMC instillation or (2) RF-CHT. After MMC instillation, three biopsies were taken of both normal and tumour tissue. Biopsies were snap-frozen and MMC tissue concentrations were analysed using ultra-performance liquid chromatography. RESULTS: Eleven patients were included of which six received RF-CHT. Ten patients had TaG2-LG/HG papillary tumours at pathology. One patient in the RF-CHT group appeared to be free of malignancy and was excluded from the analysis as no tumour biopsies were available. The median MMC concentration in tumour tissue was higher in the RF-CHT group (median 665.00 ng/g vs. 63.75 ng/g, U = 51.0, p = 0.018). Moreover, in both techniques the MMC concentration was lower in normal tissue compared to tumour tissue. Tissue MMC concentration measurements varied substantially within, and between, different patients from the same group. CONCLUSION: Intravesical RF-CHT results in higher tumour MMC concentrations vs. cold MMC instillation which contributes to its superior efficacy.