Extended System Transfer Compensation for Parametric Imaging in Ultrasonic Response Assessment of Anti-Cancer Therapies
The assessment of the tissue response in anti cancer therapy is a time critical process. The early recognition of a failing treatment might allow an adjustment to increase the success rate and spare unnecessary side effects. Today biopsy and nuclear medicine are commonly used procedures for assessing the treatment success. However biopsies are invasive and provide a limited sample volume and nuclear medicine on the other hand requires the application of radioactive agents. It has been observed that ultrasound backscatter properties of cell collections are altered when the cells are respond to an oncological treatment. In previous studies we have estimated spectral properties of ultrasound backscatter using commonly accepted procedures for eliminating system specific transfer properties. These methods proved to be sufficient when investigating regions close to the transducers focus. However, the application in a clinical environment will require the parameter estimation in an extended area combined with parametric imaging. The purpose of this work is to implement more accurate methods for the determination of the effective scatterer size in quantitative high frequency ultrasound. To improve the accuracy but also extend the axial image depth for parametric imaging we developed an algorithm for eliminating the transfer properties of the equipment. It accounts for the distortion of the incident pulse due to the relative defocus position of a time gate and the corresponding alterations in the spectral shape. Two different methods for estimating the transfer properties were applied. One method used the echoes obtained from a plane reflector at 51 positions within the ± 5mm range around the transducers focus. The second method derived the required compensation function from the signal variation within a pellet of untreated cells. Both, the axial amplitude variation and the alterations of the spectral shape were derived as a function of the defocus position. The slope of the normalized power spectrum, the effective scatterer size and integrated backscatter coefficients were computed from ultrasound backscatter of cervix carcinoma (HeLa) cells after applying the compensation algorithms. Chemotherapy was applied to induce apoptosis in HeLa cells. At 6 time points after treatment cells were harvested and ultrasound backscatter was recorded using a 20MHz (f# 2.35) and a 40MHz (f# 3) transducer. Within the axial -12dB range of the transducer slope differences of up to -1.2 dB/MHz were observed and compensated. Integrated backscatter coefficients increased by over 300% of the initial values. This study contributes towards a non-invasive method for estimating tissue responses in anti-cancer therapy.
Keywords: quantitative ultrasound; high frequency ultrasound, HeLa, treatment response, transfer characteristic