Initial clinical experience building a dual CT- and MR-guided adaptive radiotherapy program.

Introduction: Our institution was the first in the world to clinically implement MR-guided adaptive radiotherapy (MRgART) in 2014. In 2021, we installed a CT-guided adaptive radiotherapy (CTgART) unit, becoming one of the first clinics in the world to build a dual-modality ART clinic. Herein we review factors that lead to the development of a high-volume dual-modality ART program and treatment census over an initial, one-year period. Materials and Methods: The clinical adaptive service at our institution is enabled with both MRgART (MRIdian, ViewRay, Inc, Mountain View, CA) and CTgART (ETHOS, Varian Medical Systems, Palo Alto, CA) platforms. We analyzed patient and treatment information including disease sites treated, radiation dose and fractionation, and treatment times for patients on these two platforms. Additionally, we reviewed our institutional workflow for creating, verifying, and implementing a new adaptive workflow on either platform. Results: From October 2021 to September 2022, 256 patients were treated with adaptive intent at our institution, 186 with MRgART and 70 with CTgART. The majority (106/186) of patients treated with MRgART had pancreatic cancer, and the most common sites treated with CTgART were pelvis (23/70) and abdomen (20/70). 93.0% of treatments on the MRgART platform were stereotactic body radiotherapy (SBRT), whereas only 72.9% of treatments on the CTgART platform were SBRT. Abdominal gated cases were allotted a longer time on the CTgART platform compared to the MRgART platform, whereas pelvic cases were allotted a shorter time on the CTgART platform when compared to the MRgART platform. Our adaptive implementation technique has led to six open clinical trials using MRgART and seven using CTgART. Conclusions: We demonstrate the successful development of a dual platform ART program in our clinic. Ongoing efforts are needed to continue the development and integration of ART across platforms and disease sites to maximize access and evidence for this technique worldwide.

Knowledge-based adaptive planning quality assurance using dosimetric indicators for stereotactic adaptive radiotherapy for pancreatic cancer.

INTRODUCTION: We aimed to develop knowledge-based tools for robust adaptive radiotherapy (ART) planning to determine on-table adaptive DVH metric variations or planning process errors for stereotactic pancreatic ART. We developed volume-based dosimetric identifiers to identify deviations of ART plans from simulation plans. MATERIALS AND METHODS: Two patient cohorts who were treated on MR-Linac for pancreas cancer were included in this retrospective study; a training cohort and a validation cohort. All patients received 50 Gy in 5 fractions. PTV-OPT was generated by subtracting the critical organs plus a 5 mm-margin from PTV. Several metrics that potentially can identify failure-modes were calculated including PTV & PTV_OPT V95% and PTV & PTV_OPT D95%/D5%. The difference between each DVH metric in each adaptive plan with the DVH metric in simulation plan was calculated. The 95% confidence interval (CI) of the variations in each DVH metric was calculated for the patient training cohort. Variations in DVH metrics that exceeded the 95% CI for all fractions in training and validation cohort were flagged for retrospective investigation for root-cause analysis to determine their predictive power for identifying failure-modes. RESULTS: The CIs for the PTV & PTV_OPT V95% and PTV & PTV_OPT D95%/D5% were ± 13%, ± 5%, ± 0.1, ± 0.03, respectively. We estimated the positive predictive value and negative predictive value of our method to be 77% and 89%, respectively, for the training cohort, and 80% for both in the validation cohort. DISCUSSION: We developed dosimetric indicators for ART planning QA to identify population-based deviations or planning errors during online adaptive process for stereotactic pancreatic ART. This technology may be useful as an ART clinical trial QA tool and improve overall ART quality at an institution.

Patient specific contouring region of interest for abdominal stereotactic adaptive radiotherapy.

Contouring during adaptive radiotherapy (ART) can be a time-consuming process. This study describes the generation of patient specific contouring regions of interest (CRoI) for evaluating the high dose fall-off in stereotactic abdominal ART. An empirical equation was derived to determine the radius of a cylindrical patient specific CRoIs. These CRoIs were applied to 60 patients and their adaptive fractions (301 unique treatment plans). Out of the 301 unique treatment plans, 284 (94%) treatment plans contained the high dose fall-off within the CRoI. There was an expected predicted average timesaving of 2.9-min-per case. Patient specific CRoIs improves the efficiency of ART.

A pilot study of same-day MRI-only simulation and treatment with MR-guided adaptive palliative radiotherapy (MAP-RT).

We conducted a prospective pilot study evaluating the feasibility of same day MRI-only simulation and treatment with MRI-guided adaptive palliative radiotherapy (MAP-RT) for urgent palliative indications (NCT#03824366). All (16/16) patients were able to complete 99% of their first on-table attempted fractions, and no grades 3-5 toxicities occurred.

Phantom-based Quality Assurance of a Clinical Dose Accumulation Technique Used in an Online Adaptive Radiation Therapy Platform.

Purpose: This study aimed to develop a routine quality assurance method for a dose accumulation technique provided by a radiation therapy platform for online treatment adaptation. Methods and Materials: Two commonly used phantoms were selected for the dose accumulation QA: Electron density and anthropomorphic pelvis. On a computed tomography (CT) scan of the electron density phantom, 1 target (gross tumor volume [GTV]; insert at 6 o'clock), a subvolume within this target, and 7 organs at risk (OARs; other inserts) were contoured in the treatment planning system (TPS). Two adaptation sessions were performed in which the GTV was recontoured, first at 7 o'clock and then at 5 o'clock. The accumulated dose was exported from the TPS after delivery. Deformable vector fields were also exported to manually accumulate doses for comparison. For the pelvis phantom, synthetic Gaussian deformations were applied to the planning CT image to simulate organ changes. Two single-fraction adaptive plans were created based on the deformed planning CT and cone beam CT images acquired onboard the radiation therapy platform. A manual dose accumulation was performed after delivery using the exported deformable vector fields for comparison with the system-generated result. Results: All plans were successfully delivered, and the accumulated dose was both manually calculated and derived from the TPS. For the electron density phantom, the average mean dose differences in the GTV, boost volume, and OARs 1 to 7 were 0.0%, -0.2%, 92.0%, 78.4%, 1.8%, 1.9%, 0.0%, 0.0%, and 2.3%, respectively, between the manually summed and platform-accumulated doses. The gamma passing rates for the 3-dimensional dose comparison between the manually generated and TPS-provided dose accumulations were >99% for both phantoms. Conclusions: This study demonstrated agreement between manually obtained and TPS-generated accumulated doses in terms of both mean structure doses and local 3-dimensional dose distributions. Large disagreements were observed for OAR1 and OAR2 defined on the electron density phantom due to OARs having lower deformation priority over the target in addition to artificially large changes in position induced for these structures fraction-by-fraction. The tests applied in this study to a commercial platform provide a straightforward approach toward the development of routine quality assurance of dose accumulation in online adaptation.

First treatments for Lattice stereotactic body radiation therapy using magnetic resonance image guided radiation therapy.

Two abdominal patients were treated with Lattice stereotactic body radiation therapy (SBRT) using magnetic resonance guided radiation therapy (MRgRT). This is one of the first reported treatments of Lattice SBRT with the use of MRgRT. A description of the treatment approach and planning considerations were incorporated into this report. MRgRT Lattice SBRT delivered similar planning quality metrics to established dosimetric parameters for Lattice SBRT. Increased signal intensity were seen in the MRI treatments for one of the patients during the course of treatment.

Assessment of a novel commercial large field of view phantom for comprehensive MR imaging quality assurance of a 0.35T MRgRT system.

Consistent quality assurance (QA) programs are vital to MR-guided radiotherapy (MRgRT), for ensuring treatment is delivered accurately and the onboard MRI system is providing the expected image quality. However, daily imaging QA with a dedicated phantom is not common at many MRgRT centers, especially with large phantoms that cover a field of view (FOV), similar to the human torso. This work presents the first clinical experience with a purpose-built phantom for large FOV daily and periodic comprehensive quality assurance (QUASAR™ MRgRT Insight Phantom (beta)) from Modus Medical Devices Inc. (Modus QA) on an MRgRT system. A monthly American College of Radiology (ACR) QA phantom was also imaged for reference. Both phantoms were imaged on a 0.35T MR-Linac, a 1.5T Philips wide bore MRI, and a 3.0T Siemens MRI, with T1-weighted and T2-weighted acquisitions. The Insight phantom was imaged in axial and sagittal orientations. Image quality tests including geometric accuracy, spatial resolution accuracy, slice thickness accuracy, slice position accuracy, and image intensity uniformity were performed on each phantom, following their respective instruction manuals. The geometric distortion test showed similar distortions of -1.7 mm and -1.9 mm across a 190 mm and a 283 mm lengths for the ACR and MRgRT Insight phantoms, respectively. The MRgRT Insight phantom utilized a modulation transform function (MTF) for spatial resolution evaluation, which showed decreased performance on the lower B0 strength MRIs, as expected, and could provide a good daily indicator of machine performance. Both the Insight and ACR phantoms showed a match with scan parameters for slice thickness analysis. During the imaging and analysis of this novel MRgRT Insight phantom the authors found setup to be straightforward allowing for easy acquisition each day, and useful image analysis parameters for tracking MRI performance.

Filmless quality assurance of a Leksell Gamma Knife® Icon™.

PURPOSE: The annual quality assurance (QA) of Leksell Gamma Knife® (LGK) systems are typically performed using films. Film is a good candidate for small field dosimetry due to its high spatial resolution and availability. However, there are multiple challenges with using film; film does not provide real-time measurement and requires batch-specific calibration. Our findings show that active detector-based QA can simplify the procedure and save time without loss of accuracy. METHODS: Annual QA tests for a LGK Icon™ system were performed using both film-based and filmless techniques. Output calibration, relative output factors (ROF), radiation profiles, sector uniformity/source counting, and verification of the unit center point (UCP) and radiation focal point (RFP) coincidence tests were performed. Radiochromic films, two ionization chambers, and a synthetic diamond detector were used for the measurements. Results were compared and verified with the treatment planning system (TPS). RESULTS: The measured dose rate of the LGK Icon was within 0.4% of the TPS value set at the time of commissioning using an ionization chamber. ROF for the 8 and 4-mm collimators were found to be 0.3% and 1.8% different from TPS values using the MicroDiamond detector and 2.6% and 1.9% different for film, respectively. Excellent agreement was found between TPS and measured dose profiles using the MicroDiamond detector which was within 1%/1 mm vs 2%/1 mm for film. Sector uniformity was found to be within 1% for all eight sectors measured using an ionization chamber. Verification of UCP and RFP coincidence using the MicroDiamond detector and pinprick film test was within 0.3 mm at isocenter for both. CONCLUSION: The annual QA of a LGK Icon was successfully performed by employing filmless techniques. Comparable results were obtained using radiochromic films. Utilizing active detectors instead of films simplifies the QA process and saves time without loss of accuracy.

Quantitative proton radiation therapy dosimetry using the storage phosphor europium-doped potassium chloride.

PURPOSE: To (a) characterize the fundamental optical and dosimetric properties of the storage phosphor europium-doped potassium chloride for quantitative proton dosimetry, and (b) investigate if its dose radiation response can be described by an analytic radiation transport model. METHODS: Cylindrical KCl:Eu2+ dosimeters with dimensions of 6 mm diameter and 1 mm thickness were fabricated in-house. The dosimeters were irradiated using both a Mevion S250 passive scattering proton therapy system and a Varian Clinac iX linear accelerator. Photostimulated luminescence (PSL) emission spectra, excitation spectra, and luminescence lifetimes were measured for both proton and photon irradiations. Dosimetric properties including radiation hardness, dose linearity, signal stabilization, dose rate sensitivity, and energy dependence were studied using a laboratory optical reader after irradiations. The dosimeters were modeled using physical quantities including mass stopping powers in the storage phosphor and water for a given proton beam, and mass energy absorption coefficients and massing stopping powers in detector and water for a given photon beam. RESULTS: KCl:Eu2+ exhibited optical emission and stimulation peaks at 421 and 560 nm, respectively, for both proton and photon irradiations, enabling postirradiation readouts using a visible light source while detecting the PSL using a photomultiplier tube. KCl:Eu2+ showed a linear response from 0 to 8 Gy absorbed dose-to-water, a large dynamic range up to 60 Gy, dose-rate independence measured from 83 to 500 MU/min, and a PSL lifetime of <5 ms that is sufficiently short for supporting rapid scanning in a two-dimensional geometry. KCl:Eu2+ was highly reusable with only a slight signal decrease of ~3% at accumulated doses over 100 Gy, which could be managed by a periodic recalibration. The detected PSL signal strength of the dosimeter in the proton field had been calculated accurately to a maximum discrepancy of 2% using known physical quantities along with its prior signal strength as measured in a photon field at the same dose-to-water. This discrepancy might be attributed to an under-response due to linear energy transfer (LET) effect. However, comparisons of depth-dose measurements in a spread-out Bragg peak (SOBP) field with a parallel-plate ionization chamber showed no clear evidence of LET effects. Furthermore, range measurements agreed with ionization chamber measurements to within 1 mm. CONCLUSIONS: KCl:Eu2+ showed linear response over a large dynamic range for proton irradiations and reliably reproduced SOBP measurements as measured by ionization chambers. Its relatively low atomic number of 18 and near LET independence make it suited for quantitative proton dosimetry. In addition, its high radiation hardness means that it can be reused numerous times. Any potential measurement artifacts encountered in complex irradiation conditions should be able to be corrected for using known physical quantities.

Influence of 0.35 T magnetic field on the response of EBT3 and EBT-XD radiochromic films.

PURPOSE: To investigate the inconsistency of recent literature on the effect of magnetic field on the response of radiochromic films, we studied the influence of 0.35 T magnetic field on dosimetric response of EBT3 and EBT-XD GafchromicTM films. METHODS: Two different models of radiochromic films, EBT3 and EBT-XD, were investigated. Pieces of films samples from two different batches for each model were irradiated at different dose levels ranging from 1 to 20 Gy using 6 MV flattening filter free (FFF) x-rays generated by a clinical MR-guided radiotherapy system (B = 0.35 T). Film samples from the same batch were irradiated at corresponding dose levels using 6 MV FFF beam from a conventional linac (B = 0) for comparison. The net optical density was measured 48 h postirradiation using a flatbed scanner. The absorbance spectra were also measured over 500-700 nm wavelength range using a fiber-coupled spectrometer with 2.5 nm resolution. To study the effect of fractionated dose delivery to EBT3 (/EBT-XD) films, 8 (/16) Gy dose was delivered in four 2 (/4) Gy fractions with 24 h interval between fractions. RESULTS: No significant difference was found in the net optical density and net absorbance of the films irradiated with or without the presence of magnetic field. No dependency on the orientation of the film during irradiation with respect to the magnetic field was observed. The fractionated dose delivery resulted in the same optical density as delivering the whole dose in a single fraction. CONCLUSIONS: The 0.35 T magnetic field employed in the ViewRay® MR-guided radiotherapy system did not show any significant influence on the response of EBT3 and EBT-XD GafchromicTM films.

Implementation of a Novel Remote Physician Stereotactic Body Radiation Therapy Coverage Process during the Coronavirus Pandemic.

PURPOSE: During the coronavirus 2019 disease (COVID-19) pandemic, alternative methods of care are needed to reduce the relative risk of transmission in departments. Also needed is the ability to provide vital radiation oncological care if radiation oncologists (RO) are reallocated to other departments. We implemented a novel remote RO stereotactic body radiation therapy (SBRT) coverage practice, requiring it to be reliable, of high audio and visual quality, timely, and the same level of specialty care as our current in-person treatment coverage practice. METHODS AND MATERIALS: All observed failure modes were recorded during implementation over the first 15 sequential fractions. The time from cone beam computed tomography to treatment was calculated before and after implementation to determine timeliness of remote coverage. Image quality metrics were calculated between the imaging console screen and the RO's shared screen. Comfort levels with audio and visual communication as well as overall comfort in comparison to in-person RO coverage was evaluated using Likert scale surveys after treatment. RESULTS: Remote RO SBRT coverage was successfully implemented in 14 of 15 fractions with 3 observed process failures that were all corrected before treatment. Average times of pretreatment coverage before and after implementation were 8.74 and 8.51 minutes, respectively. The cross correlation between the imaging console screen and RO's shared screen was r = 0.96 and lag was 0.05 seconds. The average value for all survey questions was more than 4.5, approaching in-person RO coverage comfort levels. CONCLUSION: Our novel method of remote RO SBRT coverage permits reduced personnel and patient interactions surrounding radiation therapy procedures. This may help to reduce transmission of COVID-19 in our department and provides a means for SBRT coverage if ROs are reallocated to other areas of the hospital for COVID-19 support.

Dose uncertainty and resolution of polymer gel dosimetry using an MRI guided radiation therapy system's onboard 0.35 T scanner.

Magnetic Resonance Imaging (MRI) scanners are widely used for 3D gel dosimeters readout. However, limited access to MRI scanners is a challenge in MRI-based gel dosimetry. Recent clinical implementation of MRI-guided radiation therapy machines provides potential opportunities for onboard gel dosimetry using its MRI subsystem. The objective of this study was to investigate the feasibility of gel dosimetry using ViewRay's onboard 0.35 T MRI scanner. A BANG® polymer gel dosimeter was irradiated by three beams of 3 × 3 cm2 field size. The T2 relaxation rate (R2) of the irradiated gel was measured using a Philips 1.5 T Ingenia MRI and a ViewRay 0.35 T onboard MRI and spin-echo pulse sequences. The number of signal averages (NSA) was set to 16 for the ViewRay acquisitions and one for the Philips 1.5 T MRI to achieve similar signal-to-noise ratios. The in-plane spatial resolution was 1.5 × 1.5 mm2 and the slice thickness was 5 mm. The relative dose uncertainty was obtained using R2 versus dose curves to compare the performance of dosimetry using the two different MRIs and field strengths. The dose uncertainty decreased from 12% at 2 Gy to 3.5% at 7.5 Gy at 1.5 T. The dose uncertainty decreased from 13% at 2 Gy to 4% at 7.5 Gy with NSA = 16 and 3 × 3 mm2 pixel size, and from 10.5% at 2 Gy to 3.2% at 7.5 Gy with NSA = 16 and denoised R2 maps (1.5 × 1.5 mm2 pixel size) at 0.35 T. The mean of dose resolution was 0.4 Gy at 1.5 T while the mean of dose resolution was 0.8 Gy and 0.64 Gy at 0.35 T by downsampling and denoising the R2 map, respectively. Therefore, comparable dose uncertainty was achievable using the ViewRay's onboard 0.35 T and Philips 1.5 T MRI scanners. 3D gel dosimetry using onboard low-field MRI scanner provides ViewRay users a 3D high resolution dosimetry option besides film and ionization chamber.

Characterizing MR Imaging isocenter variation in MRgRT.

We characterized MRI isocenter variation at various gantry positions in two 0.35 T MRgRT systems using two independent methods. First, image center-based quantification was employed on 3D volumetric and 2D cine images of a 24 cm diameter spherical phantom at various gantry positions in the MRI QA mode. The center of the phantom images was identified to quantify the variation of the imaging center at each gantry position. Second, image registration-based quantification was used in radiotherapy mode. 3D volumetric MRIs of a cylindrical phantom were acquired and corresponding image registration from MRI to planning CT was performed. The shifts of the couch were identified to quantify the variation of the imaging center. For verification of noticeable MRI isocenter variation, star-shot pattern measurements with five beams were delivered on the radio-chromic film inserted into the phantom after the couch was shifted. The center of the star-shot pattern was identified to quantify the variation of the imaging center. The proposed methods for measuring MRI isocenter variation were demonstrated with MR-LINAC and MR-60Co systems. Both of the MRgRT systems had field inhomogeneities <5 ppm over a 24 cm diameter spherical volume (DSV) and spatial integrity distortion: <1 mm within 100 mm radius and <2 mm within 175 mm radius. The MRI isocenter of the MR-LINAC system showed noticeable 3D variation (max magnitude: 1.8 mm) compared to that of MR-60Co system (max magnitude: 0.9 mm) relative to the reference gantry positions. In addition, 2D variations (max magnitude) of the MRI isocenter from sagittal cine images were 0.9 mm for the MR-LINAC system and 0.5 mm for the MR-60Co system. Two proposed methods quantified the MRI isocenter variation for various gantry positions in two 0.35 T MRgRT systems. The results of significant isocenter variation in the MR-LINAC system requires further investigation to determine the cause.

Feasibility of detecting change in backscattered energy of acoustic harmonics in locally heated tissues.

Purpose: A real-time noninvasive thermometry technique is required to estimate the temperature distribution during hyperthermia to monitor and control the treatment. The main objective of this study is to demonstrate the possibility of detecting change in backscatter energy (CBE) of acoustic harmonics in tissue-mimicking gel phantoms and ex vivo bovine muscle tissues in which the temperature was locally increased within the hyperthermia regime. Materials and Methods: A peristaltic pump was used to circulate hot water through a needle inserted inside the samples to locally increase the temperature from 26 °C to 46 °C. The CBE of acoustic harmonics were used to identify the location of temperature changes in the samples. A conventional echo-shift technique was also implemented for comparison. Data collection was performed for two conditions to investigate the effect of motion on both techniques by: (1) inducing vibration in the sample through the peristatic pump and, (2) subsequently with no sample vibration while the pump was off. Results: Harmonics were able to determine the location of temperature rise in the presence and absence of vibration. In gel phantom, the mean contrast to noise ratio (CNR) in CBE maps reduced by a factor of 0.86 due to vibration whereas in gradient maps the CNR reduced by a factor of 8.3. Conclusions: The findings of this study suggest that the change in backscatter energy of acoustic harmonics can potentially be used to develop a noninvasive ultrasound-based thermometry technique with lower susceptibility to motion artifacts compared to the echo-shift method.

MRI quality control for low-field MR-IGRT systems: Lessons learned.

PURPOSE: To present lessons learned from magnetic resonance imaging (MRI) quality control (QC) tests for low-field MRI-guided radiation therapy (MR-IGRT) systems. METHODS: MRI QC programs were established for low-field MRI-60 Co and MRI-Linac systems. A retrospective analysis of MRI subsystem performance covered system commissioning, operations, maintenance, and quality control. Performance issues were classified into three groups: (a) Image noise and artifact; (b) Magnetic field homogeneity and linearity; and (c) System reliability and stability. RESULTS: Image noise and artifacts were attributed to room noise sources, unsatisfactory system cabling, and broken RF receiver coils. Gantry angle-dependent magnetic field inhomogeneities were more prominent on the MRI-Linac due to the high volume of steel shielding in the gantry. B0 inhomogeneities measured in a 24-cm spherical phantom were <5 ppm for both MR-IGRT systems after using MRI gradient offset (MRI-GO) compensation on the MRI-Linac. However, significant signal dephasing occurred on the MRI-Linac while the gantry was rotating. Spatial integrity measurements were sensitive to gradient calibration and vulnerable to shimming. The most common causes of MR-IGRT system interruptions were software disconnects between the MRI and radiation therapy delivery subsystems caused by patient table, gantry, and multi-leaf collimator (MLC) faults. The standard deviation (SD) of the receiver coil signal-to-noise ratio was 1.83 for the MRI-60 Co and 1.53 for the MRI-Linac. The SD of the deviation from the mean for the Larmor frequency was 1.41 ppm for the MRI-60 Co and 1.54 ppm for the MRI-Linac. The SD of the deviation from the mean for the transmitter reference amplitude was 0.90% for the MRI-60 Co and 1.68% for the MRI-Linac. High SDs in image stability data corresponded to reports of spike noise. CONCLUSIONS: There are significant technological challenges associated with implementing and maintaining MR-IGRT systems. Most of the performance issues were identified and resolved during commissioning.

Temperature dependence of acoustic harmonics generated by nonlinear ultrasound wave propagation in water at various frequencies.

Ultrasound-based thermometry requires a temperature-sensitive acoustic parameter that can be used to estimate the temperature by tracking changes in that parameter during heating. The objective of this study is to investigate the temperature dependence of acoustic harmonics generated by nonlinear ultrasound wave propagation in water at various pulse transmit frequencies from 1 to 20 MHz. Simulations were conducted using an expanded form of the Khokhlov-Zabolotskaya-Kuznetsov nonlinear acoustic wave propagation model in which temperature dependence of the medium parameters was included. Measurements were performed using single-element transducers at two different transmit frequencies of 3.3 and 13 MHz which are within the range of frequencies simulated. The acoustic pressure signals were measured by a calibrated needle hydrophone along the axes of the transducers. The water temperature was uniformly increased from 26 °C to 46 °C in increments of 5 °C. The results show that the temperature dependence of the harmonic generation is different at various frequencies which is due to the interplay between the mechanisms of absorption, nonlinearity, and focusing gain. At the transmit frequencies of 1 and 3.3 MHz, the harmonic amplitudes decrease with increasing the temperature, while the opposite temperature dependence is observed at 13 and 20 MHz.

Temperature dependence of acoustic harmonics generated by nonlinear ultrasound beam propagation in ex vivo tissue and tissue-mimicking phantoms.

PURPOSE: Hyperthermia is a cancer treatment technique that could be delivered as a stand-alone modality or in conjunction with chemotherapy or radiation therapy. Noninvasive and real-time temperature monitoring of the heated tissue improves the efficacy and safety of the treatment. A temperature-sensitive acoustic parameter is required for ultrasound-based thermometry. In this paper the amplitude and the energy of the acoustic harmonics of the ultrasound backscattered signal are proposed as suitable parameters for noninvasive ultrasound thermometry. MATERIALS AND METHODS: A commercial high frequency ultrasound imaging system was used to generate and detect acoustic harmonics in tissue-mimicking gel phantoms and ex vivo bovine muscle tissues. The pressure amplitude and the energy content of the backscattered fundamental frequency (p1 and E1), the second (p2 and E2) and the third (p3 and E3) harmonics were detected in pulse-echo mode. Temperature was increased from 26° to 46 °C uniformly through both samples. The amplitude and the energy content of the harmonics and their ratio were measured and analysed as a function of temperature. RESULTS: The average p1, p2 and p3 increased by 69%, 100% and 283%, respectively as the temperature was elevated from 26° to 46 °C in tissue samples. In the same experiment the average E1, E2 and E3 increased by 163%, 281% and 2257%, respectively. A similar trend was observed in tissue-mimicking gel phantoms. CONCLUSIONS: The findings suggest that the harmonics generated due to nonlinear ultrasound beam propagation are highly sensitive to temperature and could potentially be used for noninvasive ultrasound tissue thermometry.