The Application of Three–Dimensional Contrast–Enhanced Ultrasound to Measure Volume of Affected Tissue after HIFU Treatment for Localized Prostate Cancer

Introduction: Adequate monitoring of volume and location of affected tissue might provide helpful information when performing localized ablative therapy for prostate cancer. We hypothesize that the change in blood flow patterns after therapy in comparison to the blood flow pattern prior to therapy can be used to locate and quantify the amount of affected tissue due to the therapy. We describe the use of three–dimensional contrast–enhanced power Doppler ultrasound (3D–CE–PDU) to determine its additive value to visualize the extent of tissue defects created by high–intensity focused ultrasound (HIFU) in correlation with the histopathology of the prostatectomy specimen.Materials and Methods: Nine patients with biopsy–proven localized prostate cancer, who gave informed consent, were included in the protocol. HIFU treatment was performed 1 week in advance of radical retropubic prostatectomy (RRP) as part of a protocol to study the value of HIFU treatment as local ablative therapy for clinical T1–2N₀M₀ prostate carcinoma. 3D–CE–PDU was performed 1 day prior to unilateral HIFU treatment of the affected lobe on biopsy indication and 1 day before RRP using 2.5 g Levovist® (Schering AG, Germany) microbubble ultrasound contrast agent and a Kretz® Voluson 530D ultrasound scanner (Kretztechnik AG, Austria). Ultrasound data and pathology whole–mount sections were stored digitally to allow off–line processing. Human interpretations of HIFU measurements in three–dimensional ultrasound data were based on gray–scale information (local increase in gray level) in combination with power Doppler mode (absence of blood flow). Histopathological analysis of the whole–mount section revealed a broad band of hemorrhagic necrosis in the HIFU–treated area. Using both the ultrasound data and the pathology sections, the total volume of the prostate and of the HIFU–treated area was measured, and relative volumes were obtained.Results: Visual inspection of the three–dimensional reconstruction of contrast–enhanced Doppler measurements revealed the HIFU–affected prostate tissue by the absence of a blood flow pattern. Paired t tests of the relative HIFU volume indicated that Doppler results (mean 21.7%, SD ±10.8%) differed from the pathology results (mean 32.6%, SD ±16.0%), but a good correlation was found between the relative pathology HIFU volume (Pearson correlation r = 0.94, p<0.0015) and mean 3D–CE–PDU HIFU. Closer inspection of the pathology specimen revealed that the outer ring of the macroscopic hemorrhagic necrosis overestimated the actually dead tissue. On microscopy, the border of dead tissue appeared to be 1–2 mm inside the macroscopically identified red hemorrhagic band. 3D–CE–PDU HIFU volumes indicated by the single observers were not statistically different and correlated very well (Pearson correlation r = 0.98, p<0.001).Conclusion: The results illustrate that 3D–CE–PDU is a promising method to determine the size of the defect of HIFU ablative therapy for prostate carcinoma. The absence of blood flow indicated by three–dimensional power Doppler ultrasound images reflects affected tissue after HIFU treatment, and volume measurements of these areas can quantify the amount of affected tissue.