In vitro assessment of stiffness-dependent histotripsy bubble cloud activity in gel phantoms and blood clots.

As a bubble-based ablative therapy, the efficacy of histotripsy has been demonstrated in healthy or acutely diseased models. Chronic conditions associated with stiff tissues may require additional bubble activity prior to histotripsy liquefaction. In this study, histotripsy pulses were generated in agarose phantoms of Young's moduli ranging from 12.3 to 142 kPa, and in vitro clot models with mild and strong platelet-activated retraction. Bubble cloud emissions were tracked with passive cavitation imaging, and the threshold acoustic power associated with phantom liquefaction was extracted with receiver operator characteristic analysis. The power of histotripsy-generated emissions and the degree of liquefaction were tabulated for both clot models. For the agarose phantoms, the acoustic power associated with liquefaction increased with Young's modulus. When grouped based on agarose concentration, only two arms displayed a significant difference in the liquefaction threshold acoustic power (22.1 kPa versus 142 kPa Young's modulus). The bubble cloud dynamics tracked with passive cavitation imaging indicated no strong changes in the bubble dynamics based on the phantom stiffness. For identical histotripsy exposure, the power of acoustic emissions and degree of clot lysis did not vary based on the clot model. Overall, these results indicate that a fixed threshold acoustic power mapped with passive cavitation imaging can be utilized for predicting histotripsy liquefaction over a wide range of tissue stiffness.

Observation and modulation of the dissolution of histotripsy-induced bubble clouds with high-frame rate plane wave imaging.

Focused ultrasound therapies are a noninvasive means to ablate tissue. Histotripsy utilizes short ultrasound pulses with sufficient tension to nucleate bubble clouds that impart lethal strain to the surrounding tissues. Tracking bubble cloud dissolution between the application of histotripsy pulses is critical to ensure treatment efficacy. In this study, plane wave B-mode imaging was employed to monitor bubble cloud motion and grayscale at frame rates up to 11.25 kHz. Minimal changes in the area or position of the bubble clouds were observed 50 ms post excitation. The bubble cloud grayscale was observed to decrease with the square root of time, indicating a diffusion-driven process. These results were qualitatively consistent with an analytic model of gas diffusion during the histotripsy process. Finally, the rate of bubble cloud dissolution was found to be dependent on the output of the imaging pulse, indicating an interaction between the bubble cloud and imaging parameters. Overall, these results highlight the utility of plane wave B-mode imaging for monitoring histotripsy bubble clouds.

Assessment of histotripsy-induced liquefaction with diagnostic ultrasound and magnetic resonance imaging in vitro and ex vivo.

Histotripsy is a therapeutic ultrasound modality under development to liquefy tissue mechanically via bubble clouds. Image guidance of histotripsy requires both quantification of the bubble cloud activity and accurate delineation of the treatment zone. In this study, magnetic resonance (MR) and diagnostic ultrasound imaging were combined to assess histotripsy treatment in vitro and ex vivo. Mechanically ablative histotripsy pulses were applied to agarose phantoms or porcine livers. Bubble cloud emissions were monitored with passive cavitation imaging (PCI), and hyperechogenicity via plane wave imaging. Changes in the medium structure due to bubble activity were assessed with diagnostic ultrasound using conventional B-mode imaging and T 1-, T 2-, and diffusion-weighted MR images acquired at 3 Tesla. Liquefaction zones were correlated with diagnostic ultrasound and MR imaging via receiver operating characteristic (ROC) analysis and Dice similarity coefficient (DSC) analysis. Diagnostic ultrasound indicated strong bubble activity for all samples. Histotripsy-induced changes in sample structure were evident on conventional B-mode and T 2-weighted images for all samples, and were dependent on the sample type for T 1- and diffusion-weighted imaging. The greatest changes observed on conventional B-mode or MR imaging relative to baseline in the samples did not necessarily indicate the regions of strongest bubble activity. Areas under the ROC curve for predicting phantom or liver liquefaction were significantly greater than 0.5 for PCI power, plane wave and conventional B-mode grayscale, T 1, T 2, and ADC. The acoustic power mapped via PCI provided a better prediction of liquefaction than assessment of the liquefaction zone via conventional B-mode or MR imaging for all samples. The DSC values for T 2-weighted images were greater than those derived from conventional B-mode images. These results indicate diagnostic ultrasound and MR imaging provide complimentary sets of information, demonstrating that multimodal imaging is useful for assessment of histotripsy liquefaction.

MRI-guided transurethral insonation of silica-shell phase-shift emulsions in the prostate with an advanced navigation platform.

PURPOSE: In this study, the efficacy of transurethral prostate ablation in the presence of silica-shell ultrasound-triggered phase-shift emulsions (sUPEs) doped with MR contrast was evaluated. The influence of sUPEs on MR imaging assessment of the ablation zone was also investigated. METHODS: sUPEs were doped with a magnetic resonance (MR) contrast agent, Gd2 O3 , to assess ultrasound transition. Injections of saline (sham), saline and sUPEs alone, and saline and sUPEs with Optison microbubbles were performed under guidance of a prototype interventional MRI navigation platform in a healthy canine prostate. Treatment arms were evaluated for differences in lesion size, T1  contrast, and temperature. In addition, non-perfused areas (NPAs) on dynamic contrast-enhanced (DCE) MRI, 55°C isotherms, and areas of 240 cumulative equivalent minutes at 43°C (CEM43 ) dose or greater computed from MR thermometry were measured and correlated with ablated areas indicated by histology. RESULTS: For treatment arms including sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area ranged from 0.96-0.99, 0.98-0.99, and 0.91-0.99, respectively. In the absence of sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area were 0.69, 0.54, and 0.50, respectively. Across all treatment arms, the areas of thermal tissue damage and NPAs were not significantly different (P = 0.47). Areas denoted by 55°C isotherms and 240 CEM43 dose boundaries were significantly larger than the areas of thermal damage, again for all treatment arms (P = 0.009 and 0.003, respectively). No significant differences in lesion size, T1 contrast, or temperature were observed between any of the treatment arms (P > 0.0167). Lesions exhibiting thermal fixation on histological analysis were present in six of nine insonations involving sUPE injections and one of five insonations involving saline sham injections. Significantly larger areas (P = 0.002), higher temperatures (P = 0.004), and more frequent ring patterns of restricted diffusion on ex vivo diffusion-weighted imaging (P = 0.005) were apparent in lesions with thermal fixation. CONCLUSIONS: T1 contrast suggesting sUPE transition was not evident in sUPE treatment arms. The use of MR imaging metrics to predict prostate ablation was not diminished by the presence of sUPEs. Lesions generated in the presence of sUPEs exhibited more frequent thermal fixation, though there were no significant changes in the ablation areas when comparing arms with and without sUPEs. Thermal fixation corresponded to some qualitative imaging features.

Comparison between whole-body and head and neck neurovascular coils for 3-T magnetic resonance proton resonance frequency shift thermography guidance in the head and neck region.

The purpose of this study is to compare the image quality of magnetic resonance (MR) treatment planning images and proton resonance frequency (PRF) shift thermography images and inform coil selection for MR-guided laser ablation of tumors in the head and neck region. Laser ablation was performed on an agar phantom and monitored via MR PRF shift thermography on a 3-T scanner, following acquisition of T1-weighted (T1W) planning images. PRF shift thermography images and T2-weighted (T2W) planning images were also performed in the neck region of five normal human volunteers. Signal-to-noise ratios (SNR) and temperature uncertainty were calculated and compared between scans acquired with the quadrature mode body integrated coil and a head and neck neurovascular coil. T1W planning images of the agar phantom produced SNRs of 4.0 and 12.2 for the quadrature mode body integrated coil and head and neck neurovascular coil, respectively. The SNR of the phantom MR thermography magnitude images obtained using the quadrature mode body integrated coil was 14.4 versus 59.6 using the head and neck coil. The average temperature uncertainty for MR thermography performed on the phantom with the quadrature mode body integrated coil was 1.1 versus 0.3 °C with the head and neck coil. T2W planning images of the neck in five human volunteers produced SNRs of 28.3 and 91.0 for the quadrature mode body integrated coil and head and neck coil, respectively. MR thermography magnitude images of the neck in the volunteers obtained using the quadrature mode body integrated coil had a signal-to-noise ratio of 8.3, while the SNR using the head and neck coil was 16.1. The average temperature uncertainty for MR thermography performed on the volunteers with the body coil was 2.5 versus 1.6 °C with the head and neck neurovascular coil. The quadrature mode body integrated coil provides inferior image quality for both basic treatment planning sequences and MR PRF shift thermography compared with a neurovascular coil, but may nevertheless be adequate for clinical purposes.

Incorporation of pre-therapy 18 F-FDG uptake data with CT texture features into a radiomics model for radiation pneumonitis diagnosis.

PURPOSE: To determine whether the addition of standardized uptake value (SUV) from PET scans to CT lung texture features could improve a radiomics-based model of radiation pneumonitis (RP) diagnosis in patients undergoing radiotherapy. METHODS AND MATERIALS: Anonymized data from 96 esophageal cancer patients (18 RP-positive cases of Grade ≥ 2) were collected including pre-therapy PET/CT scans, pre-/post-therapy diagnostic CT scans and RP status. Twenty texture features (first-order, fractal, Laws' filter and gray-level co-occurrence matrix) were calculated from diagnostic CT scans and compared in anatomically matched regions of the lung. Classifier performance (texture, SUV, or combination) was assessed by calculating the area under the receiver operating characteristic curve (AUC). For each texture feature, logistic regression classifiers consisting of the average change in texture feature value and the pre-therapy SUV standard deviation (SUVSD ) were created and compared with the texture feature as a lone classifier using ANOVA with correction for multiple comparisons (P < 0.0025). RESULTS: While clinical parameters (mean lung dose, smoking history, tumor location) were not significantly different among patients with and without symptomatic RP, SUV and texture parameters were significantly associated with RP status. AUC for single-texture feature classifiers alone ranged from 0.58 to 0.81 and 0.53 to 0.71 in high-dose (≥ 30 Gy) and low-dose (< 10 Gy) regions of the lungs, respectively. AUC for SUVSD alone was 0.69 (95% confidence interval: 0.54-0.83). Adding SUVSD into a logistic regression model significantly improved model fit for 18, 14 and 11 texture features and increased the mean AUC across features by 0.08, 0.06, and 0.04 in the low-, medium-, and high-dose regions, respectively. CONCLUSIONS: Addition of SUVSD to a single-texture feature improves classifier performance on average, but the improvement is smaller in magnitude when SUVSD is added to an already effective classifier using texture alone. These findings demonstrate the potential for more accurate assessment of RP using information from multiple imaging modalities.