Previous work has shown ultrasound echo decorrelation imaging can track and quantify changes in echo signals to predict thermal damage during in vitro radiofrequency ablation (RFA). In the in vivo studies reported here, the feasibility of using echo decorrelation imaging as a treatment monitoring tool is assessed. RFA was performed on a normal swine liver (N = 5) and ultrasound ablation using image-ablate arrays was performed on a rabbit liver implanted with VX2 tumors (N = 2). Echo decorrelation and integrated backscatter were computed from Hilbert transformed pulse-echo data acquired during RFA and ultrasound ablation treatments. Receiver operating characteristic (ROC) curves were employed to assess the ability of echo decorrelation imaging and integrated backscatter to predict ablation. Area under the ROC curves (AUROC) was determined for RFA and ultrasound ablation using echo decorrelation imaging. Ablation was predicted more accurately using echo decorrelation imaging (AUROC 0.832 and 0.776 for RFA and ultrasound ablation respectively) than using integrated backscatter (AUROC 0.734 and 0.494).

Quantitative ultrasound (QUS) imaging is hypothesized to map temperature elevations induced in tissue with high spatial and temporal resolution. To test this hypothesis, QUS techniques were examined to monitor high-intensity focused ultrasound (HIFU) exposure of tissue. In situ experiments were conducted on mammary adenocarcinoma tumors grown in rats and lesions were formed using a HIFU system. A thermocouple was inserted into the tumor to provide estimates of temperature at one location. Backscattered time-domain waveforms from the tissue during exposure were recorded using a clinical ultrasonic imaging system. Backscatter coefficients were estimated using a reference phantom technique. Two parameters were estimated from the backscatter coefficient (effective scatterer diameter (ESD) and effective acoustic concentration (EAC). The changes in the average parameters in the regions corresponding to the HIFU focus over time were correlated to the temperature readings from the thermocouple. The changes in the EAC parameter were consistently correlated to temperature during both heating and cooling of the tumors. The changes in the ESD did not have a consistent trend with temperature. The mean ESD and EAC before exposure were 120 ± 16 μm and 32 ± 3 db/cm3, respectively, and changed to 144 ± 9 μm and 51 ± 7 db/cm3, respectively, just before the last HIFU pulse was delivered to the tissue. After the tissue cooled down to 37°C, the mean ESD and EAC were 126 ± 8 μm and 35 ± 4 db/cm3, respectively. Peak temperature in the range of 50–60°C was recorded by a thermocouple placed just behind the tumor. These results suggest that QUS techniques have the potential to be used for non-invasive monitoring of HIFU exposure.

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During application of high intensity focused ultrasound (HIFU) with therapy arrays, the existence of grating lobes can cause heating at unintended tissue regions. Therefore, the reduction of grating lobes in therapeutic arrays is an important goal. One way to reduce the grating lobes in therapy arrays is to excite the arrays with broadband signals (defined here as >10% fractional bandwidth). To achieve a reduction in grating lobe levels in an ultrasonic array, coded waveforms can be utilized that reduce the grating lobe levels while maintaining the spatial peak temporal average intensity. In this study, a 5-MHz, 9-element, 1.25 mm inter-elemental spacing linear array was excited by a sinusoidal waveform, a conventional linear chirp, and a modified linear chirp. Both chirps spanned the −3-dB bandwidth of the transducer. The conventional chirp was a broadband signal with a linear sweep of frequencies between 2.5 and 7.5 MHz, with all frequency components excited with equal amplitude. The modified chirp signal also swept the frequencies between 2.5 and 7.5 MHz, but the amplitude was weighted such that the edges (low and high frequencies of the band) were excited with more energy than the center of the band. In simulations, the field patterns for the sinusoidal, conventional chirp and modified chirp excitations were produced from the array using Field II and compared. For experiments, the beam pattern from a 5-MHz single-element transducer was mapped using a hydrophone for the sinusoidal, conventional chirp and modified chirp excitation. Each field from the transducer was repeated and summed to produce a field from an array of 9 elements. The difference in the time averaged intensity (in dB) in the main lobe and grating lobes were estimated for each excitation and compared. The results demonstrated that the chirp signals resulted in decreases in grating lobe levels compared to the main lobe, i.e. 10 dB down for focusing and 6 dB down for focusing and steering. A further 1 dB decrease in grating lobe levels was observed for the modified chirp excitation compared to the conventional chirp excitation, which corresponds to ~21% reduction in energy deposition at the grating lobe location.

The success of any minimally invasive treatment procedure can be enhanced significantly if combined with a robust noninvasive imaging modality that can monitor therapy in real time. Quantitative ultrasound (QUS) imaging has been widely investigated for monitoring various treatment responses such as chemotherapy, radiation, and thermal therapy. Previously, we demonstrated the feasibility of using spectral-based QUS parameters to monitor high-intensity focused ultrasound (HIFU) treatment of in situ tumors in euthanized rats [Ultrasonic Imaging 36(4), 239–255, 2014]. In the present study, we examined the use of spectral-based QUS parameters to monitor HIFU treatment of in vivo rat mammary adenocarcinoma tumors (MAT) where significant tissue motion was present. HIFU was applied to tumors in rats using a single-element transducer. During the off part of the HIFU duty cycle, ultrasound backscatter was recorded from the tumors using a linear array co-aligned with the HIFU focus. A total of 10 rats were treated with HIFU in this study with an additional sham-treated rat. Spectral parameters from the backscatter coefficient, i.e., effective scatterer diameter (ESD) and effective acoustic concentration (EAC), were estimated. The changes of each parameter during treatment were compared with a temperature profile recorded by a fine-needle thermocouple inserted into the tumor a few millimeters behind the focus of the HIFU transducer. The mean ESD changed from 121 ± 6 to 81 ± 8 μm(p-value = 0.0002), and the EAC changed from 33 ± 2 to 46 ± 3 dB/cm3 (p-value = 0.0002) during HIFU exposure as the temperature increased on average from 38.7 ± 1.0° C to 64.2 ± 2.7° C. The changes in ESD and EAC were linearly correlated with the changes in tissue temperature during the treatment. When HIFU was turned off, the ESD increased from 81 ± 8 to 121 ± 7 μm and the EAC dropped from 46 ± 3 to 36 ± 2 dB/cm3 as the temperature decreased from 64.2 ± 2.7° C to 45 ± 2.7° C. QUS was demonstrated in vivo to track temperature elevations caused by HIFU exposure.