Quantitative Ultrasound Imaging for Monitoring In Situ High-Intensity Focused Ultrasound Exposure

Abstract

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.

Thermometry and ablation monitoring with ultrasound

“…In the hyperthermia range below 50° C, attenuation changes up to 10–20%, BSC changes of an order of magnitude, and 30% changes in ESD and EAC were all reported as more sensitive than thermally-induced changes in speed of sound. In their most recent work (144), the relationship between ESD, EAC, and temperature was extended up to 80° C in experiments with in situ rat tumors. Good linear regression with temperature was observed in three out of four rats.…”

Noninvasive Quantitative Imaging of Collagen Microstructure in Three-Dimensional Hydrogels Using High-Frequency Ultrasound

“…[15][16][17] Ultrasound tissue characterization techniques have been developed to overcome the limitations of B-scan imaging, and enable quantitative assessments of tissue properties of both normal and diseased tissues. 17 Quantitative ultrasound techniques have employed various parameters to characterize tissues, including the speed of sound, 18,19 absorption and attenuation coefficients, 18,20 nonlinearity parameter, 21 angular scattering, 22 backscatter coefficient, 23-25 integrated backscatter coefficient (IBC), 18,25,26 effective scatterer diameter, 27 midband fit, 16,28,29 spectral intercept, 28 and spectral slope. 16,28,29 These parameters can provide estimates of the density, size, and spatial organization of acoustic scatterers in tissue.…”

“…17 As examples, quantitative ultrasound techniques have been used to characterize various tumors, 19,30 evaluate cardiac abnormalities, 31 monitor cell death, 29,32 characterize human dermis and subcutaneous fat, 33 and assess therapeutic responses in diseased tissues. 27,34,35 Several recent studies have shown that quantitative ultrasound can provide an important tool for the field of tissue engineering. 36 The midband fit and spectral slope parameters were employed to evaluate the mineral content of collagen constructs with hydroxyapatite 16 and monitor osteoblastic differentiation in engineered tissues in vitro.…”

Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials

“…35 A second group is comprised of parameters that can be extracted from the power spectrum of the backscattered RF signals. These frequency-dependent parameters include the midband fit, 36,37 spectral intercept, 37 spectral slope, 33,37 backscatter coefficient, 33,38 effective scatterer diameter, 38 and integrated backscatter coefficient (IBC). 34,39,40 The absorption and attenuation coefficients of materials can be measured by analyzing either the amplitude or the frequency spectrum of the backscattered RF signals.…”

“…31,41-43 In native tissues, quantitative ultrasound techniques have been used to characterize tumors, 43 monitor cell death, 37,44 assess cardiac abnormalities, 45 characterize ultrasound contrast agents, 46 and evaluate therapeutic responses of diseased tissues after treatments with high intensity focused ultrasound or chemotherapeutic agents. 38,47,48 Furthermore, employing high-frequency ultrasound increases the backscatter coefficient of sub-resolution scatterers in tissues, such as cells and collagen fibers. High-frequency ultrasound has been employed to investigate the backscatter coefficient of blood during clotting, 39 to assess backscatter properties of cells and isolated nuclei, 34,49 to characterize human dermis, 39,50 and to monitor cell death in vitro.…”