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Role of Cavitation during Bulk ultrasound Ablation: Ex vivo and In vivo Studies

Karunakaran, Chandrapriya

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2012, PhD, University of Cincinnati, Engineering and Applied Science: Biomedical Engineering.
Bubble activity can complicate ultrasound treatment by shielding ultrasound energy from the focus or by increasing local ultrasound absorption, rendering the treatment unpredictable. In this thesis, the role of bubble activity was evaluated for ex vivo and in vivo bulk ultrasound ablation experiments. Overpressure was used to suppress cavitation and tissue vaporization in the ex vivo studies. Ex vivo bovine liver was ablated with unfocused ultrasound (3.1 MHz or 4.8 MHz) at 31 W/cm2 for 10 or 20 minutes. A passive cavitation detector (PCD) was used to record acoustic emissions throughout the treatment. Subharmonic, broadband and low-frequency emissions were quantified by processing signals recorded by the PCD. The treated liver was sliced and stained with 2% triphenyl tetrazolium chloride (TTC) to evaluate lesion geometry. Multivariate multiple regression models were computed to predict lesion areas and depths based on the three acoustic emission levels. Results confirm that the three acoustic emissions were significant in predicting lesion dimensions. It was concluded that subharmonic activity may increase lesion area by redistributing ultrasound energy locally, while tissue vaporization may decrease lesion area and depth by shielding energy from the treatment zone. TTC uptake of ultrasound treated tissue was compared to TTC uptake of thermally heated tissue, with comparable thermal doses, to evaluate the contribution of nonthermal bioeffects in bulk ultrasound ablation. Logistic regression modeling was performed to estimate and compare the probability of tissue coagulation, for range of thermal doses, among the two experimental groups (ultrasound and thermally heated). Results suggested no significant differences between TTC uptake levels of thermally heated and ultrasound treated tissue, suggesting that cavitation during bulk ultrasound ablation may translate to thermal bioeffects evident in the tissue. To validate TTC staining as a method to evaluate ultrasound treatment success, tissue from multiple TTC uptake regions of ultrasound ablated liver and VX2 tumor were stained with 4', 6-diamidino-2-phenylindole (DAPI). Nuclear size distributions among the three TTC uptake regions were quantified and compared to evaluate changes in histology among the three regions. Results suggest that TTC uptake levels correspond to distinguishable differences in nuclear size distribution. Cells in the region of partial TTC uptake may undergo apoptosis. The role of cavitation in ultrasound ablation in vivo was investigated by employing passive cavitation imaging to record and monitor cavitation during treatment of swine liver with ultrasound (2700-6000 W/cm2, 20 sec-2 minutes). Passive cavitation imaging can spatially and temporally resolve cavitation signals including subharmonic, broadband and harmonic emissions. Spatial localization of subharmonic, broadband, low-frequency and harmonic activity was compared to local tissue ablation through receiver operating characteristic (ROC) curve analysis. The results suggest that for these in vivo experiments, with no significant subharmonic or broadband emissions, harmonic emissions were the most significant in predicting tissue ablation. Results from this thesis suggest that cavitation can play opposing roles in bulk ultrasound ablation. Cavitation detection and imaging can be used to predict thermal lesion formation. TTC uptake levels correlate to thermal dose and thermal bioeffects in ultrasound ablation and can be used to evaluate treatment success. The results from this thesis can be extended to aid in planning and monitoring of ultrasound treatments and increase the efficiency of ultrasound ablation.
T. Douglas Mast, PhD (Committee Chair)
Christy Holland, PhD (Committee Member)
Daria Narmoneva, PhD (Committee Member)
Marepalli Rao, PhD (Committee Member)
181 p.

Recommended Citations

Citations

  • Karunakaran, C. (2012). Role of Cavitation during Bulk ultrasound Ablation: Ex vivo and In vivo Studies [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1343051845

    APA Style (7th edition)

  • Karunakaran, Chandrapriya. Role of Cavitation during Bulk ultrasound Ablation: Ex vivo and In vivo Studies. 2012. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1343051845.

    MLA Style (8th edition)

  • Karunakaran, Chandrapriya. "Role of Cavitation during Bulk ultrasound Ablation: Ex vivo and In vivo Studies." Doctoral dissertation, University of Cincinnati, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1343051845

    Chicago Manual of Style (17th edition)