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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 433 records · Page 24
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

SU-E-T-245: MR Guided Focused Ultrasound Increased PARP Related Apoptosis On Prostate Cancer in Vivo

Purpose: Our previous study demonstrated that significant tumor growth delay was observed in the mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to understand the cell killing mechanisms of pHIFU. Methods: Prostate cancer cells (LNCaP), were grown orthotopically in 17 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 25W, pulse width 100msec and 300 pulses in one sonication under MR guidance. Mutiple sonications were used to cover the whole tumor volume. Temperature (less than 40 degree centigrade in the focal spot) was monitored using MR thermometry. Animals were euthanized at pre-determined time points (n=2) after treatment: 0 hours; 6 hrs; 24 hrs; 48 hrs; 4 days and 7 days. Two tumorbearing mice were used as control. Three tumor-bearing mice were treated with radiation (RT, 2 Gy) using 6 MV photon beams. RT treated mice were euthanized at 0 hr, 6 hrs and 24 hrs. The tumors were processed for immunohistochemical (IHC) staining for PARP (a surrogate of apoptosis). A multispectral imaging analysis system was used to quantify the expression of PARP staining. Cell apoptosis was calculated based on the PARP expression level, which is the intensity of the DAB reaction. Results: Our data showed that PARP related apoptosis peaked at 48 hrs and 7 days in pHIFU treated mice, which is comparable to that for the RT group at 24 hrs. The preliminary results from this study were consistent with our previous study on tumor growth delay using pHIFU. Conclusion: Our results demonstrated that non-thermal pHIFU increased apoptotic tumor cell death through the PARP related pathway. MR guided pHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy. This treatment modality might be able to synergize with PARP inhibitors to achieve better result.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

TU-A-9A-02: Analysis of Variations in Clinical Doppler Ultrasound Peak Velocity Measurements

Purpose: Doppler ultrasound (US) peak velocity (Vmax) measurements show considerable variations due to intrinsic spectral broadening with different scanning techniques, machines and manufacturers. We developed a semi-automated Vmax estimation method and used this method to investigate the performance of a US system for clinical Doppler Vmax measurement. Methods: Semi-automated Vmax is defined as the velocity at which the computed mean spectral profile falls to within 1 background standard deviation of the background mean. GE LOGIQ E9 system with 9L and ML6-15 probes were studied with steady flow (5.3 – 12.5 ml/s) in a Gammex OPTIMIZER 1425A phantom. All Doppler spectra were acquired by 1 operator at the distal end of 5 mm angular tube using a modified clinical carotid artery protocol. Repeatability and variation of Vmax to scanning parameters and probes were analyzed and reported as percentage, i.e. (max-min)/mean. Results: Vmax estimation had good repeatability (3.1% over 6 days for 9L, and 3.6% for ML6-15). For 9L probe, varying gain, compression, scale, SV depth and length, and frequency had minimal impact on Vmax (all variations less than 4.0%). Beam steering had slightly higher influence (largest variations across flow rates were 4.9% for 9L and 6.9% for ML6-15). For both probes, Doppler angle had the greatest effect on Vmax. Percentage increase of Vmax was largely independent of actual flow rates. For Doppler angle varied from 30 to 60°, Vmax increased 24% for 9L, and 20% for ML6-15. Vmax measured by ML6-15 were lower than that by 9L at each Doppler angle with differences less than 5%. Conclusion: The proposed Vmax estimation method is shown to be a useful tool to evaluate clinical Doppler US system performance. For the tested system and probes, Doppler angle had largest impact in measured Vmax.

42 ENGINEERING↗
DOE OSTI2014

Sampling strategies for subsampled segmented EPI PRF thermometry in MR guided high intensity focused ultrasound

Purpose: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. Methods: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemes utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. Results: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled “truth.” For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes with variable density sampling implemented in zero and two dimensions in a non-EPI GRE pulse sequence both resulted in accurate temperature measurements (RMSE of 0.70 °C and 0.63 °C, respectively). With sequential sampling in the described EPI implementation, temperature monitoring over a 192 × 144 × 135 mm{sup 3} FOV with a temporal resolution of 3.6 s was achieved, while keeping the RMSE compared to fully sampled “truth” below 0.35 °C. Conclusions: When segmented EPI readouts are used in conjunction with k-space subsampling for MR thermometry applications, sampling schemes with sequential sampling, with or without variable density sampling, obtain accurate phase and temperature measurements when using a TCR reconstruction algorithm. Improved temperature measurement accuracy can be achieved with variable density sampling. Centric sampling leads to phase bias, resulting in temperature underestimations.

42 ENGINEERING↗
DOE OSTI2014

Semiautomatic registration of 3D transabdominal ultrasound images for patient repositioning during postprostatectomy radiotherapy

Purpose: The aim of the present work is to propose and evaluate registration algorithms of three-dimensional (3D) transabdominal (TA) ultrasound (US) images to setup postprostatectomy patients during radiation therapy. Methods: Three registration methods have been developed and evaluated to register a reference 3D-TA-US image acquired during the planning CT session and a 3D-TA-US image acquired before each treatment session. The first method (method A) uses only gray value information, whereas the second one (method B) uses only gradient information. The third one (method C) combines both sets of information. All methods restrict the comparison to a region of interest computed from the dilated reference positioning volume drawn on the reference image and use mutual information as a similarity measure. The considered geometric transformations are translations and have been optimized by using the adaptive stochastic gradient descent algorithm. Validation has been carried out using manual registration by three operators of the same set of image pairs as the algorithms. Sixty-two treatment US images of seven patients irradiated after a prostatectomy have been registered to their corresponding reference US image. The reference registration has been defined as the average of the manual registration values. Registration error has been calculated by subtracting the reference registration from the algorithm result. For each session, the method has been considered a failure if the registration error was above both the interoperator variability of the session and a global threshold of 3.0 mm. Results: All proposed registration algorithms have no systematic bias. Method B leads to the best results with mean errors of −0.6, 0.7, and −0.2 mm in left–right (LR), superior–inferior (SI), and anterior–posterior (AP) directions, respectively. With this method, the standard deviations of the mean error are of 1.7, 2.4, and 2.6 mm in LR, SI, and AP directions, respectively. The latter are inferior to the interoperator registration variabilities which are of 2.5, 2.5, and 3.5 mm in LR, SI, and AP directions, respectively. Failures occur in 5%, 18%, and 10% of cases in LR, SI, and AP directions, respectively. 69% of the sessions have no failure. Conclusions: Results of the best proposed registration algorithm of 3D-TA-US images for postprostatectomy treatment have no bias and are in the same variability range as manual registration. As the algorithm requires a short computation time, it could be used in clinical practice provided that a visual review is performed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Position tracking of moving liver lesion based on real-time registration between 2D ultrasound and 3D preoperative images

Purpose: Registration between 2D ultrasound (US) and 3D preoperative magnetic resonance (MR) (or computed tomography, CT) images has been studied recently for US-guided intervention. However, the existing techniques have some limits, either in the registration speed or the performance. The purpose of this work is to develop a real-time and fully automatic registration system between two intermodal images of the liver, and subsequently an indirect lesion positioning/tracking algorithm based on the registration result, for image-guided interventions. Methods: The proposed position tracking system consists of three stages. In the preoperative stage, the authors acquire several 3D preoperative MR (or CT) images at different respiratory phases. Based on the transformations obtained from nonrigid registration of the acquired 3D images, they then generate a 4D preoperative image along the respiratory phase. In the intraoperative preparatory stage, they properly attach a 3D US transducer to the patient’s body and fix its pose using a holding mechanism. They then acquire a couple of respiratory-controlled 3D US images. Via the rigid registration of these US images to the 3D preoperative images in the 4D image, the pose information of the fixed-pose 3D US transducer is determined with respect to the preoperative image coordinates. As feature(s) to use for the rigid registration, they may choose either internal liver vessels or the inferior vena cava. Since the latter is especially useful in patients with a diffuse liver disease, the authors newly propose using it. In the intraoperative real-time stage, they acquire 2D US images in real-time from the fixed-pose transducer. For each US image, they select candidates for its corresponding 2D preoperative slice from the 4D preoperative MR (or CT) image, based on the predetermined pose information of the transducer. The correct corresponding image is then found among those candidates via real-time 2D registration based on a gradient-based similarity measure. Finally, if needed, they obtain the position information of the liver lesion using the 3D preoperative image to which the registered 2D preoperative slice belongs. Results: The proposed method was applied to 23 clinical datasets and quantitative evaluations were conducted. With the exception of one clinical dataset that included US images of extremely low quality, 22 datasets of various liver status were successfully applied in the evaluation. Experimental results showed that the registration error between the anatomical features of US and preoperative MR images is less than 3 mm on average. The lesion tracking error was also found to be less than 5 mm at maximum. Conclusions: A new system has been proposed for real-time registration between 2D US and successive multiple 3D preoperative MR/CT images of the liver and was applied for indirect lesion tracking for image-guided intervention. The system is fully automatic and robust even with images that had low quality due to patient status. Through visual examinations and quantitative evaluations, it was verified that the proposed system can provide high lesion tracking accuracy as well as high registration accuracy, at performance levels which were acceptable for various clinical applications.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Multiattribute probabilistic prostate elastic registration (MAPPER): Application to fusion of ultrasound and magnetic resonance imaging

Purpose: Transrectal ultrasound (TRUS)-guided needle biopsy is the current gold standard for prostate cancer diagnosis. However, up to 40% of prostate cancer lesions appears isoechoic on TRUS. Hence, TRUS-guided biopsy has a high false negative rate for prostate cancer diagnosis. Magnetic resonance imaging (MRI) is better able to distinguish prostate cancer from benign tissue. However, MRI-guided biopsy requires special equipment and training and a longer procedure time. MRI-TRUS fusion, where MRI is acquired preoperatively and then aligned to TRUS, allows for advantages of both modalities to be leveraged during biopsy. MRI-TRUS-guided biopsy increases the yield of cancer positive biopsies. In this work, the authors present multiattribute probabilistic postate elastic registration (MAPPER) to align prostate MRI and TRUS imagery. Methods: MAPPER involves (1) segmenting the prostate on MRI, (2) calculating a multiattribute probabilistic map of prostate location on TRUS, and (3) maximizing overlap between the prostate segmentation on MRI and the multiattribute probabilistic map on TRUS, thereby driving registration of MRI onto TRUS. MAPPER represents a significant advancement over the current state-of-the-art as it requires no user interaction during the biopsy procedure by leveraging texture and spatial information to determine the prostate location on TRUS. Although MAPPER requires manual interaction to segment the prostate on MRI, this step is performed prior to biopsy and will not substantially increase biopsy procedure time. Results: MAPPER was evaluated on 13 patient studies from two independent datasets—Dataset 1 has 6 studies acquired with a side-firing TRUS probe and a 1.5 T pelvic phased-array coil MRI; Dataset 2 has 7 studies acquired with a volumetric end-firing TRUS probe and a 3.0 T endorectal coil MRI. MAPPER has a root-mean-square error (RMSE) for expert selected fiducials of 3.36 ± 1.10 mm for Dataset 1 and 3.14 ± 0.75 mm for Dataset 2. State-of-the-art MRI-TRUS fusion methods report RMSE of 3.06–2.07 mm. Conclusions: MAPPER aligns MRI and TRUS imagery without manual intervention ensuring efficient, reproducible registration. MAPPER has a similar RMSE to state-of-the-art methods that require manual intervention.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Quantitative analysis of breast echotexture patterns in automated breast ultrasound images

Purpose: Breast tissue composition is considered to be associated with breast cancer risk. This study aimed to develop a computer-aided classification (CAC) system to automatically classify echotexture patterns as heterogeneous or homogeneous using automated breast ultrasound (ABUS) images. Methods: A CAC system was proposed that can recognize breast echotexture patterns in ABUS images. For each case, the echotexture pattern was assessed by two expert radiologists and classified as heterogeneous or homogeneous. After neutrosophic image transformation and fuzzy c-mean clusterings, the lower and upper boundaries of the fibroglandular tissues were defined. Then, the number of hypoechoic regions and histogram features were extracted from the fibroglandular tissues, and the support vector machine model with the leave-one-out cross-validation method was utilized as the classifier. The authors’ database included a total of 208 ABUS images of the breasts of 104 females. Results: The accuracies of the proposed system for the classification of heterogeneous and homogeneous echotexture patterns were 93.48% (43/46) and 92.59% (150/162), respectively, with an overall Az (area under the receiver operating characteristic curve) of 0.9786. The agreement between the radiologists and the proposed system was almost perfect, with a kappa value of 0.814. Conclusions: The use of ABUS and the proposed method can provide quantitative information on the echotexture patterns of the breast and can be used to evaluate whether breast echotexture patterns are associated with breast cancer risk in the future.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-J-03: Characterization of the Precision and Accuracy of a New, Preclinical, MRI-Guided Focused Ultrasound System for Image-Guided Interventions in Small-Bore, High-Field Magnets

Purpose: MRI-guided focused ultrasound (MRgFUS) has many potential and realized applications including controlled heating and localized drug delivery. The development of many of these applications requires extensive preclinical work, much of it in small animal models. The goal of this study is to characterize the spatial targeting accuracy and reproducibility of a preclinical high field MRgFUS system for thermal ablation and drug delivery applications. Methods: The RK300 (FUS Instruments, Toronto, Canada) is a motorized, 2-axis FUS positioning system suitable for small bore (72 mm), high-field MRI systems. The accuracy of the system was assessed in three ways. First, the precision of the system was assessed by sonicating regular grids of 5 mm squares on polystyrene plates and comparing the resulting focal dimples to the intended pattern, thereby assessing the reproducibility and precision of the motion control alone. Second, the targeting accuracy was assessed by imaging a polystyrene plate with randomly drilled holes and replicating the hole pattern by sonicating the observed hole locations on intact polystyrene plates and comparing the results. Third, the practicallyrealizable accuracy and precision were assessed by comparing the locations of transcranial, FUS-induced blood-brain-barrier disruption (BBBD) (observed through Gadolinium enhancement) to the intended targets in a retrospective analysis of animals sonicated for other experiments. Results: The evenly-spaced grids indicated that the precision was 0.11 +/− 0.05 mm. When image-guidance was included by targeting random locations, the accuracy was 0.5 +/− 0.2 mm. The effective accuracy in the four rodent brains assessed was 0.8 +/− 0.6 mm. In all cases, the error appeared normally distributed (p<0.05) in both orthogonal axes, though the left/right error was systematically greater than the superior/inferior error. Conclusions: The targeting accuracy of this device is sub-millimeter, suitable for many preclinical applications including focused drug delivery and thermal therapy. Funding support provided by Philips Healthcare.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

MO-DE-210-04: Repositioning and Monitoring of Prostate Cancer Radiotherapy with a New 4D Ultrasound Intra-Modality IGRT Device

Purpose: We report our clinical experience using a non-invasive transperineal (TP) ultrasound (US) probe dedicated to pre-positioning and monitoring of prostate cancer patients. The accuracy of pre-treatment positioning was compared to CBCT for prostate and post-prostatectomy patients. Intrafraction motions were recorded for both localizations. The dosimetric impact of these displacements was finally investigated on prostate patients. Methods: Differences between CBCT/CT and TP-US/TP-US registrations were analyzed on 427 and 453 sessions for 13 prostate and 14 post-prostatectomy patients, respectively. Ten prostate patients’ dosimetries were retrospectively planned using 2 different protocols: 80Gy in 40 fractions and 36.25Gy in 5 fractions with a 5mm CTV- to- PTV margin. The delivery time was measured in order to analyze ranges of intrafraction motions related to each protocol. Mean prostate displacements were calculated for each patient and applied to the treatment isocenter coordinates to evaluate the dosimetric impact of these motions. Results: CBCT and TP-US shifts agreements at ±5mm were 76.6%, 95.1%, 96.3% and 90.3%, 85.0%, 97.6% in anterior- posterior, superior- inferior and left-right directions, for prostate and post-prostatectomy patients, respectively. Intrafraction motions were analyzed considering delivery times of 140 and 290s with an additional time of 120s for patient installation for doses of 2 and 7.25Gy, respectively. Intrafraction motions were patient-dependent and were larger as the irradiation time increased. Larger displacements were observed for prostate compared to post-prostatectomy localizations. Shifts above 3mm were observed on 17.6% and 4.5% of the 2Gy sessions against 30.6% and 7.3% of the 7.25Gy sessions in the anterior-posterior direction for prostate and post-prostatectomy localizations, respectively. Preliminary dosimetric results showed that intrafraction motions mainly impact the PTV coverage. Conclusion: 4D TP-US modality is a promising alternative to irradiating and/or invasive IGRT modalities for both inter and intrafraction motions management. Preliminary dosimetric results show that intrafraction monitoring is mandatory especially for hypofractionated treatments. M Fargier-Voiron was supported by a PhD grant from Elekta.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

MO-DE-210-06: Development of a Supercompounded 3D Volumetric Ultrasound Image Guidance System for Prone Accelerated Partial Breast Irradiation (APBI)

Purpose: For early-stage breast cancer, accelerated partial breast irradiation (APBI) is a cost-effective breast-conserving treatment. Irradiation in a prone position can mitigate respiratory induced breast movement and achieve maximal sparing of heart and lung tissues. However, accurate dose delivery is challenging due to breast deformation and lumpectomy cavity shrinkage. We propose a 3D volumetric ultrasound (US) image guidance system for accurate prone APBI Methods: The designed system, set beneath the prone breast board, consists of a water container, an US scanner, and a two-layer breast immobilization cup. The outer layer of the breast cup forms the inner wall of water container while the inner layer is attached to patient breast directly to immobilization. The US transducer scans is attached to the outer-layer of breast cup at the dent of water container. Rotational US scans in a transverse plane are achieved by simultaneously rotating water container and transducer, and multiple transverse scanning forms a 3D scan. A supercompounding-technique-based volumetric US reconstruction algorithm is developed for 3D image reconstruction. The performance of the designed system is evaluated with two custom-made gelatin phantoms containing several cylindrical inserts filled in with water (11% reflection coefficient between materials). One phantom is designed for positioning evaluation while the other is for scaling assessment. Results: In the positioning evaluation phantom, the central distances between the inserts are 15, 20, 30 and 40 mm. The distances on reconstructed images differ by −0.19, −0.65, −0.11 and −1.67 mm, respectively. In the scaling evaluation phantom, inserts are 12.7, 19.05, 25.40 and 31.75 mm in diameter. Measured inserts’ sizes on images differed by 0.23, 0.19, −0.1 and 0.22 mm, respectively. Conclusion: The phantom evaluation results show that the developed 3D volumetric US system can accurately localize target position and determine target volume, and is a promising image-guidance tool for prone APBI.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

WE-D-210-04: Radiation-Induced Polymerization of Ultrasound Contrast Agents in View of Non-Invasive Dosimetry in External Beam Radiation Therapy

Purpose: Ultrasound contrast agents (UCA’s) based on gas-filled microbubbles encapsulated by an amphiphilic shell are well established as safe and effective echo-enhancers in diagnostic imaging. In view of an alternative application of UCA’s, we investigated the use of targeted microbubbles as radiation sensors for external beam radiation therapy. As radiation induces permanent changes in the microbubble’s physico-chemical properties, a robust measure of these changes can provide a direct or indirect estimate of the applied radiation dose. For instance, by analyzing the ultrasonic dispersion characteristics of microbubble distributions before and after radiation treatment, an estimate of the radiation dose at the location of the irradiated volume can be made. To increase the radiation sensitivity of microbubbles, polymerizable diacetylene molecules can be incorporated into the shell. This study focuses on characterizing the acoustic response and quantifying the chemical modifications as a function of radiation dose. Methods: Lipid/diacetylene microbubbles were irradiated with a 6 MV photon beam using dose levels in the range of 0–150 Gy. The acoustic response of the microbubbles was monitored by ultrasonic through-transmission measurements in the range of 500 kHz to 20 MHz, thereby providing the dispersion relations of the phase velocity, attenuation and nonlinear coefficient. In addition, the radiation-induced chemical modifications were quantified using UV-VIS spectroscopy. Results: UV-VIS spectroscopy measurements indicate that ionizing radiation induces the polymerization of diacetylenes incorporated in the microbubble shell. The polymer yield strongly depends on the shell composition and the radiation-dose. The acoustic response is inherently related to the visco-elastic properties of the shell and is strongly influenced by the shell composition and the physico-chemical changes in the environment. Conclusion: Diacetylene-containing microbubbles are polymerizable under influence of ionizing radiation and are a promising design concept within the development of a novel non-invasive in-vivo radiation dosimeter for external beam radiation therapy. This work was funded by the Research Foundation - Flanders (FWO)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Monte Carlo modeling of ultrasound probes for image guided radiotherapy

Purpose: To build Monte Carlo (MC) models of two ultrasound (US) probes and to quantify the effect of beam attenuation due to the US probes for radiation therapy delivered under real-time US image guidance. Methods: MC models of two Philips US probes, an X6-1 matrix-array transducer and a C5-2 curved-array transducer, were built based on their megavoltage (MV) CT images acquired in a Tomotherapy machine with a 3.5 MV beam in the EGSnrc, BEAMnrc, and DOSXYZnrc codes. Mass densities in the probes were assigned based on an electron density calibration phantom consisting of cylinders with mass densities between 0.2 and 8.0 g/cm{sup 3}. Beam attenuation due to the US probes in horizontal (for both probes) and vertical (for the X6-1 probe) orientation was measured in a solid water phantom for 6 and 15 MV (15 × 15) cm{sup 2} beams with a 2D ionization chamber array and radiographic films at 5 cm depth. The MC models of the US probes were validated by comparison of the measured dose distributions and dose distributions predicted by MC. Attenuation of depth dose in the (15 × 15) cm{sup 2} beams and small circular beams due to the presence of the probes was assessed by means of MC simulations. Results: The 3.5 MV CT number to mass density calibration curve was found to be linear with R{sup 2} > 0.99. The maximum mass densities in the X6-1 and C5-2 probes were found to be 4.8 and 5.2 g/cm{sup 3}, respectively. Dose profile differences between MC simulations and measurements of less than 3% for US probes in horizontal orientation were found, with the exception of the penumbra region. The largest 6% dose difference was observed in dose profiles of the X6-1 probe placed in vertical orientation, which was attributed to inadequate modeling of the probe cable. Gamma analysis of the simulated and measured doses showed that over 96% of measurement points passed the 3%/3 mm criteria for both probes placed in horizontal orientation and for the X6-1 probe in vertical orientation. The X6-1 probe in vertical orientation caused the highest attenuation of the 6 and 15 MV beams, which at 10 cm depth accounted for 33% and 43% decrease compared to the respective (15 × 15) cm{sup 2} open fields. The C5-2 probe in horizontal orientation, on the other hand, caused a dose increase of 10% and 53% for the 6 and 15 MV beams, respectively, in the buildup region at 0.5 cm depth. For the X6-1 probe in vertical orientation, the dose at 5 cm depth for the 3-cm diameter 6 MV and 5-cm diameter 15 MV beams was attenuated compared to the corresponding open fields to a greater degree by 65% and 43%, respectively. Conclusions: MC models of two US probes used for real-time image guidance during radiotherapy have been built. Due to the high beam attenuation of the US probes, the authors generally recommend avoiding delivery of treatment beams that intersect the probe. However, the presented MC models can be effectively integrated into US-guided radiotherapy treatment planning in cases for which beam avoidance is not practical due to anatomy geometry.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Determinants of the reliability of ultrasound tomography sound speed estimates as a surrogate for volumetric breast density

Purpose: High breast density, as measured by mammography, is associated with increased breast cancer risk, but standard methods of assessment have limitations including 2D representation of breast tissue, distortion due to breast compression, and use of ionizing radiation. Ultrasound tomography (UST) is a novel imaging method that averts these limitations and uses sound speed measures rather than x-ray imaging to estimate breast density. The authors evaluated the reproducibility of measures of speed of sound and changes in this parameter using UST. Methods: One experienced and five newly trained raters measured sound speed in serial UST scans for 22 women (two scans per person) to assess inter-rater reliability. Intrarater reliability was assessed for four raters. A random effects model was used to calculate the percent variation in sound speed and change in sound speed attributable to subject, scan, rater, and repeat reads. The authors estimated the intraclass correlation coefficients (ICCs) for these measures based on data from the authors’ experienced rater. Results: Median (range) time between baseline and follow-up UST scans was five (1–13) months. Contributions of factors to sound speed variance were differences between subjects (86.0%), baseline versus follow-up scans (7.5%), inter-rater evaluations (1.1%), and intrarater reproducibility (∼0%). When evaluating change in sound speed between scans, 2.7% and ∼0% of variation were attributed to inter- and intrarater variation, respectively. For the experienced rater’s repeat reads, agreement for sound speed was excellent (ICC = 93.4%) and for change in sound speed substantial (ICC = 70.4%), indicating very good reproducibility of these measures. Conclusions: UST provided highly reproducible sound speed measurements, which reflect breast density, suggesting that UST has utility in sensitively assessing change in density.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Predicting variation in subject thermal response during transcranial magnetic resonance guided focused ultrasound surgery: Comparison in seventeen subject datasets

Purpose: In transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) treatments, the acoustic and spatial heterogeneity of the skull cause reflection, absorption, and scattering of the acoustic beams. These effects depend on skull-specific parameters and can lead to patient-specific thermal responses to the same transducer power. In this work, the authors develop a simulation tool to help predict these different experimental responses using 3D heterogeneous tissue models based on the subject CT images. The authors then validate and compare the predicted skull efficiencies to an experimental metric based on the subject thermal responses during tcMRgFUS treatments in a dataset of seventeen human subjects. Methods: Seventeen human head CT scans were used to create tissue acoustic models, simulating the effects of reflection, absorption, and scattering of the acoustic beam as it propagates through a heterogeneous skull. The hybrid angular spectrum technique was used to model the acoustic beam propagation of the InSightec ExAblate 4000 head transducer for each subject, yielding maps of the specific absorption rate (SAR). The simulation assumed the transducer was geometrically focused to the thalamus of each subject, and the focal SAR at the target was used as a measure of the simulated skull efficiency. Experimental skull efficiency for each subject was calculated using the thermal temperature maps from the tcMRgFUS treatments. Axial temperature images (with no artifacts) were reconstructed with a single baseline, corrected using a referenceless algorithm. The experimental skull efficiency was calculated by dividing the reconstructed temperature rise 8.8 s after sonication by the applied acoustic power. Results: The simulated skull efficiency using individual-specific heterogeneous models predicts well (R{sup 2} = 0.84) the experimental energy efficiency. Conclusions: This paper presents a simulation model to predict the variation in thermal responses measured in clinical ctMRGFYS treatments while being computationally feasible.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2016

First evaluation of the feasibility of MLC tracking using ultrasound motion estimation

Purpose: To quantify the performance of the Clarity ultrasound (US) imaging system (Elekta AB, Stockholm, Sweden) for real-time dynamic multileaf collimator (MLC) tracking. Methods: The Clarity calibration and quality assurance phantom was mounted on a motion platform moving with a periodic sine wave trajectory. The detected position of a 30 mm hypoechogenic sphere within the phantom was continuously reported via Clarity’s real-time streaming interface to an in-house tracking and delivery software and subsequently used to adapt the MLC aperture. A portal imager measured MV treatment field/MLC apertures and motion platform positions throughout each experiment to independently quantify system latency and geometric error. Based on the measured range of latency values, a prostate stereotactic body radiation therapy (SBRT) delivery was performed with three realistic motion trajectories. The dosimetric impact of system latency on MLC tracking was directly measured using a 3D dosimeter mounted on the motion platform. Results: For 2D US imaging, the overall system latency, including all delay times from the imaging and delivery chain, ranged from 392 to 424 ms depending on the lateral sector size. For 3D US imaging, the latency ranged from 566 to 1031 ms depending on the elevational sweep. The latency-corrected geometric root-mean squared error was below 0.75 mm (2D US) and below 1.75 mm (3D US). For the prostate SBRT delivery, the impact of a range of system latencies (400–1000 ms) on the MLC tracking performance was minimal in terms of gamma failure rate. Conclusions: Real-time MLC tracking based on a noninvasive US input is technologically feasible. Current system latencies are higher than those for x-ray imaging systems, but US can provide full volumetric image data and the impact of system latency was measured to be small for a prostate SBRT case when using a US-like motion input.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-J-215: Non-Thermal Pulsed High Intensity Focused Ultrasound Therapy Combined with 5-Aminolevulinic Acid: An in Vivo Pilot Study

Purpose: It has recently been shown that non-thermal pulsed high intensity focused ultrasound (pHIFU) has a cell-killing effect. The purpose of the study is to investigate the sonosensitizing effect of 5-Aminolevulinic Acid (5-ALA) in non-thermal pHIFU cancer therapy. Methods: FaDu human head and neck squamous cell carcinoma cells were injected subcutaneously in the flanks of nude mice. After one to two weeks, the tumors reached the volume of 112 ± 8 mm3 and were assigned randomly into a non-thermal pHIFU group (n=9) and a non-thermal sonodynamic therapy (pHIFU after 5-ALA administration) group (n=7). The pHIFU treatments (parameters: 1 MHz frequency; 25 W acoustic power; 0.1 duty cycle; 60 seconds duration) were delivered using an InSightec ExAblate 2000 system with a GE Signa 1.5T MR scanner. The mice in the non-thermal sonodynamic group received 5-ALA tail-vein injection 4 hours prior to the pHIFU treatment. The tumor growth was monitored using the CT scanner on a Sofie-Biosciences G8 PET/CT system. Results: The tumors in this study grew very aggressively and about 60% of the tumors in this study developed ulcerations at various stages. Tumor growth delay after treatments was observed by comparing the treated (n=9 in pHIFU group; n=7 in sonodynamic group) and untreated tumors (n=17). However, no statistically significant differences were found between the non-thermal pHIFU and non-thermal sonodynamic group. The mean normalized tumor volume of the untreated tumors on Day 7 after their first CT scans was 7.05 ± 0.54, while the normalized volume of the treated tumors on Day 7 after treatment was 5.89 ± 0.79 and 6.27 ± 0.47 for the sonodynamic group and pHIFU group, respectively. Conclusion: In this study, no significant sonosensitizing effects of 5-ALA were obtained on aggressive FaDu tumors despite apparent tumor growth delay in some mice treated with non-thermal sonodynamic therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-J-225: Histology Study of MR Guided Pulsed Focused Ultrasound On Treatment of Prostate Cancer in Vivo

Purpose: Our previous study demonstrated significant tumor growth delay in the mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to understand the cell killing mechanisms of pHIFU. Methods: Prostate cancer cells (LNCaP), were grown orthotopically in 17 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 25W, pulse width 100msec and 300 pulses in one sonication under MR guidance. Mutiple sonications were used to cover the whole tumor volume. The temperature (less than 40 degree centigrade in the focal spot) was monitored using MR thermometry. Animals were euthanized at pre-determined time points (n=2) after treatment: 0 hours; 6 hrs; 24 hrs; 48 hrs; 4 days and 7 days. Two tumorbearing mice were used as control. Three tumor-bearing mice were treated with radiation (RT, 2 Gy) using 6 MV photon beams. RT treated mice were euthanized at 0 hr, 6 hrs and 24 hrs. The tumors were processed for immunohistochemical (IHC) staining for PARP (a surrogate of apoptosis). A multispectral imaging analysis system was used to quantify the expression of PARP staining. Cell apoptosis was calculated based on the PARP expression level using the DAB analysis software. Results: Our data showed that PARP related apoptosis peaked at 48 hrs and 7 days in pHIFU treated mice, which is comparable to that for the RT group at 24 hrs. The preliminary results from this study were consistent with our previous study on tumor growth delay using pHIFU. Conclusion: Our results demonstrated that non-thermal pHIFU increased apoptotic tumor cell death through the PARP related pathway. MR guided pHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy. This treatment modality may synergize with PARP inhibitors to achieve better therapeutic result.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-G-JeP3-05: Geometry Based Transperineal Ultrasound Probe Positioning for Image Guided Radiotherapy

Purpose: The use of ultrasound (US) imaging in radiotherapy is not widespread, primarily due to the need for skilled operators performing the scans. Automation of probe positioning has the potential to remove this need and minimize operator dependence. We introduce an algorithm for obtaining a US probe position that allows good anatomical structure visualization based on clinical requirements. The first application is on 4D transperineal US images of prostate cancer patients. Methods: The algorithm calculates the probe position and orientation using anatomical information provided by a reference CT scan, always available in radiotherapy workflows. As initial test, we apply the algorithm on a CIRS pelvic US phantom to obtain a set of possible probe positions. Subsequently, five of these positions are randomly chosen and used to acquire actual US volumes of the phantom. Visual inspection of these volumes reveal if the whole prostate, and adjacent edges of bladder and rectum are fully visualized, as clinically required. In addition, structure positions on the acquired US volumes are compared to predictions of the algorithm. Results: All acquired volumes fulfill the clinical requirements as specified in the previous section. Preliminary quantitative evaluation was performed on thirty consecutive slices of two volumes, on which the structures are easily recognizable. The mean absolute distances (MAD) between actual anatomical structure positions and positions predicted by the algorithm were calculated. This resulted in MAD of 2.4±0.4 mm for prostate, 3.2±0.9 mm for bladder and 3.3±1.3 mm for rectum. Conclusion: Visual inspection and quantitative evaluation show that the algorithm is able to propose probe positions that fulfill all clinical requirements. The obtained MAD is on average 2.9 mm. However, during evaluation we assumed no errors in structure segmentation and probe positioning. In future steps, accurate estimation of these errors will allow for better evaluation of the achieved accuracy.

60 APPLIED LIFE SCIENCES↗