Three-dimensional US for Quantification of Volumetric Blood Flow: Multisite Multisystem Results from within the Quantitative Imaging Biomarkers Alliance.

Background Quantitative blood flow (QBF) measurements that use pulsed-wave US rely on difficult-to-meet conditions. Imaging biomarkers need to be quantitative and user and machine independent. Surrogate markers (eg, resistive index) fail to quantify actual volumetric flow. Standardization is possible, but relies on collaboration between users, manufacturers, and the U.S. Food and Drug Administration. Purpose To evaluate a Quantitative Imaging Biomarkers Alliance-supported, user- and machine-independent US method for quantitatively measuring QBF. Materials and Methods In this prospective study (March 2017 to March 2019), three different clinical US scanners were used to benchmark QBF in a calibrated flow phantom at three different laboratories each. Testing conditions involved changes in flow rate (1-12 mL/sec), imaging depth (2.5-7 cm), color flow gain (0%-100%), and flow past a stenosis. Each condition was performed under constant and pulsatile flow at 60 beats per minute, thus yielding eight distinct testing conditions. QBF was computed from three-dimensional color flow velocity, power, and scan geometry by using Gauss theorem. Statistical analysis was performed between systems and between laboratories. Systems and laboratories were anonymized when reporting results. Results For systems 1, 2, and 3, flow rate for constant and pulsatile flow was measured, respectively, with biases of 3.5% and 24.9%, 3.0% and 2.1%, and -22.1% and -10.9%. Coefficients of variation were 6.9% and 7.7%, 3.3% and 8.2%, and 9.6% and 17.3%, respectively. For changes in imaging depth, biases were 3.7% and 27.2%, -2.0% and -0.9%, and -22.8% and -5.9%, respectively. Respective coefficients of variation were 10.0% and 9.2%, 4.6% and 6.9%, and 10.1% and 11.6%. For changes in color flow gain, biases after filling the lumen with color pixels were 6.3% and 18.5%, 8.5% and 9.0%, and 16.6% and 6.2%, respectively. Respective coefficients of variation were 10.8% and 4.3%, 7.3% and 6.7%, and 6.7% and 5.3%. Poststenotic flow biases were 1.8% and 31.2%, 5.7% and -3.1%, and -18.3% and -18.2%, respectively. Conclusion Interlaboratory bias and variation of US-derived quantitative blood flow indicated its potential to become a clinical biomarker for the blood supply to end organs. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Forsberg in this issue.

Acoustic attenuation imaging of tissue bulk properties with a priori information.

Attenuation of ultrasound waves traversing a medium is not only a result of absorption and scattering within a given tissue, but also of coherent scattering, including diffraction, refraction, and reflection of the acoustic wave at tissue boundaries. This leads to edge enhancement and other artifacts in most reconstruction algorithms, other than 3D wave migration with currently impractical, implementations. The presented approach accounts for energy loss at tissue boundaries by normalizing data based on variable sound speed, and potential density, of the medium using a k-space wave solver. Coupled with a priori knowledge of major sound speed distributions, physical attenuation values within broad ranges, and the assumption of homogeneity within segmented regions, an attenuation image representative of region bulk properties is constructed by solving a penalized weighted least squares optimization problem. This is in contradistinction to absorption or to conventional attenuation coefficient based on overall insertion loss with strong dependence on sound speed and impedance mismatches at tissue boundaries. This imaged property will be referred to as the bulk attenuation coefficient. The algorithm is demonstrated on an opposed array setup, with mean-squared-error improvements from 0.6269 to 0.0424 (dB/cm/MHz)2 for a cylindrical phantom, and 0.1622 to 0.0256 (dB/cm/MHz)2 for a windowed phantom.

Conditionally Increased Acoustic Pressures in Nonfetal Diagnostic Ultrasound Examinations Without Contrast Agents: A Preliminary Assessment.

The mechanical index (MI) has been used by the US Food and Drug Administration (FDA) since 1992 for regulatory decisions regarding the acoustic output of diagnostic ultrasound equipment. Its formula is based on predictions of acoustic cavitation under specific conditions. Since its implementation over 2 decades ago, new imaging modes have been developed that employ unique beam sequences exploiting higher-order acoustic phenomena, and, concurrently, studies of the bioeffects of ultrasound under a range of imaging scenarios have been conducted. In 2012, the American Institute of Ultrasound in Medicine Technical Standards Committee convened a working group of its Output Standards Subcommittee to examine and report on the potential risks and benefits of the use of conditionally increased acoustic pressures (CIP) under specific diagnostic imaging scenarios. The term "conditionally" is included to indicate that CIP would be considered on a per-patient basis for the duration required to obtain the necessary diagnostic information. This document is a result of that effort. In summary, a fundamental assumption in the MI calculation is the presence of a preexisting gas body. For tissues not known to contain preexisting gas bodies, based on theoretical predications and experimentally reported cavitation thresholds, we find this assumption to be invalid. We thus conclude that exceeding the recommended maximum MI level given in the FDA guidance could be warranted without concern for increased risk of cavitation in these tissues. However, there is limited literature assessing the potential clinical benefit of exceeding the MI guidelines in these tissues. The report proposes a 3-tiered approach for CIP that follows the model for employing elevated output in magnetic resonance imaging and concludes with summary recommendations to facilitate Institutional Review Board (IRB)-monitored clinical studies investigating CIP in specific tissues.

Superficial ultrasound shear wave speed measurements in soft and hard elasticity phantoms: repeatability and reproducibility using two ultrasound systems.

BACKGROUND: There is a paucity of data available regarding the repeatability and reproducibility of superficial shear wave speed (SWS) measurements at imaging depths relevant to the pediatric population. OBJECTIVE: To assess the repeatability and reproducibility of superficial shear wave speed measurements acquired from elasticity phantoms at varying imaging depths using three imaging methods, two US systems and multiple operators. MATERIALS AND METHODS: Soft and hard elasticity phantoms manufactured by Computerized Imaging Reference Systems Inc. (Norfolk, VA) were utilized for our investigation. Institution No. 1 used an Acuson S3000 US system (Siemens Medical Solutions USA, Malvern, PA) and three shear wave imaging method/transducer combinations, while institution No. 2 used an Aixplorer US system (SuperSonic Imagine, Bothell, WA) and two different transducers. Ten stiffness measurements were acquired from each phantom at three depths (1.0 cm, 2.5 cm and 4.0 cm) by four operators at each institution. Student's t-test was used to compare SWS measurements between imaging techniques, while SWS measurement agreement was assessed with two-way random effects single-measure intra-class correlation coefficients (ICCs) and coefficients of variation. Mixed model regression analysis determined the effect of predictor variables on SWS measurements. RESULTS: For the soft phantom, the average of mean SWS measurements across the various imaging methods and depths was 0.84 ± 0.04 m/s (mean ± standard deviation) for the Acuson S3000 system and 0.90 ± 0.02 m/s for the Aixplorer system (P = 0.003). For the hard phantom, the average of mean SWS measurements across the various imaging methods and depths was 2.14 ± 0.08 m/s for the Acuson S3000 system and 2.07 ± 0.03 m/s Aixplorer system (P > 0.05). The coefficients of variation were low (0.5-6.8%), and interoperator agreement was near-perfect (ICCs ≥ 0.99). Shear wave imaging method and imaging depth significantly affected measured SWS (P < 0.0001). CONCLUSION: Superficial shear wave speed measurements in elasticity phantoms demonstrate minimal variability across imaging method/transducer combinations, imaging depths and operators. The exact clinical significance of this variation is uncertain and may change according to organ and specific disease state.

The functional pitch of an organ: quantification of tissue texture with photoacoustic spectrum analysis.

PURPOSE: To investigate the use of photoacoustic (PA) spectrum analysis (PASA) to identify microstructural changes corresponding to fat accumulation in mouse livers ex vivo and in situ. MATERIALS AND METHODS: The laboratory animal protocol for this work was approved by the university committee on use and care of animals. Six mice with normal livers and six mice with fatty livers were examined ex vivo with a PA system at 1200 nm, and nine similar pairs of mice were examined at 532 nm. To explore the feasibility of this technique for future study in an in vivo mouse model, an additional pair of normal and fatty mouse livers was scanned in situ with an ultrasonographic (US) and PA dual-modality imaging system. The PA signals acquired were analyzed by using the proposed PASA method. Results of the groups were compared by using the Student t test. RESULTS: Prominent differences between the PASA parameters from the fatty and normal mouse livers were observed. The analysis of the PASA parameters from six normal and six fatty mouse livers indicates that there are differences of up to 5 standard deviations between the PASA parameters of the normal livers and those of the fatty livers at 1200 nm; for parameters from nine normal and nine fatty mouse livers at 532 nm, the differences were approximately 2 standard deviations (P < .05) for each PASA parameter. CONCLUSION: The results supported our hypothesis that the PASA allows quantitative identification of the microstructural changes that differentiate normal from fatty livers. Compared with that at 532 nm, PASA at 1200 nm is more reliable for fatty liver diagnosis. Online supplemental material is available for this article.

Acceleration of ultrasound thermal therapy by patterned acoustic droplet vaporization.

One application of acoustic droplet vaporization (ADV), a method of converting biocompatible microdroplets into microbubbles, is to enhance locally high intensity focused ultrasound (HIFU) therapy. Two objectives are pursued here: (1) the controlled creation of a bubble trench prior to HIFU using ADV and (2) use of the trench for increasing ablation volumes, lowering acoustic powers, and decreasing therapy duration. Thermally responsive phantoms were made with perfluorocarbon emulsion. Compound lesions were formed in a laboratory setting and a clinical magnetic resonance imaging (MRI)-guided HIFU system. Linear and spiral patterned compound lesions were generated in trenches. A larger fraction of the HIFU beam is contained to increase the generation of heat. Using the laboratory system, a 90 mm linear length spiral trench was formed in 30 s with mechanical beam steering. Comparatively, the clinical HIFU system formed a 19.9 mm linear length spiral trench in approximately 1 s with electronic beam steering. Lesions were imaged optically and with MRI. A uniform thermal ablation volume of 3.25 mL was achieved in 55.4 s (4-times faster than standard clinical HIFU and 14-times larger volume versus sum of individual lesions). Single lesions showed a 400% volume increase.

Simultaneous viewing of individual cells and ambient microvasculature using optical absorption and fluorescence contrasts.

Viewing individual cells and ambient microvasculature simultaneously is crucial for understanding tumor angiogenesis and microenvironments. We developed a confocal fluorescence microscopy (CFM) and photoacoustic microscopy (PAM) dual-modality imaging system that can assess fluorescent contrast and optical absorption contrast in biologic samples simultaneously. After staining tissues with fluorescent dye at an appropriate concentration, each laser pulse can generate not only sufficient fluorescent signals from cells for CFM but also sufficient photoacoustic signals from microvessels for PAM. To explore the potential of this system for diagnosis of bladder cancer, experiments were conducted on a rat bladder model. The CFM image depicts the morphology of individual cells, showing not only large polygonal umbrella cells but also intracellular components. The PAM image acquired at the same time provides complementary information on the microvascular distribution in the bladder wall, ranging from large vessels to capillaries. This device provides an opportunity to realize both histologic assay and microvascular characterization simultaneously. The combination of the information of individual cells and local microvasculature in the bladder offers the capability of envisioning the viability and activeness of these cells and holds promise for more comprehensive study of bladder cancer in vivo.

Breast mass characterization using 3-dimensional automated ultrasound as an adjunct to digital breast tomosynthesis: a pilot study.

OBJECTIVES: The purpose of this study was to retrospectively evaluate the effect of 3-dimensional automated ultrasound (3D-AUS) as an adjunct to digital breast tomosynthesis (DBT) on radiologists' performance and confidence in discriminating malignant and benign breast masses. METHODS: Two-view DBT (craniocaudal and mediolateral oblique or lateral) and single-view 3D-AUS images were acquired from 51 patients with subsequently biopsy-proven masses (13 malignant and 38 benign). Six experienced radiologists rated, on a 13-point scale, the likelihood of malignancy of an identified mass, first by reading the DBT images alone, followed immediately by reading the DBT images with automatically coregistered 3D-AUS images. The diagnostic performance of each method was measured using receiver operating characteristic (ROC) curve analysis and changes in sensitivity and specificity with the McNemar test. After each reading, radiologists took a survey to rate their confidence level in using DBT alone versus combined DBT/3D-AUS as potential screening modalities. RESULTS: The 6 radiologists had an average area under the ROC curve of 0.92 for both modalities (range, 0.89-0.97 for DBT and 0.90-0.94 for DBT/3D-AUS). With a Breast Imaging Reporting and Data System rating of 4 as the threshold for biopsy recommendation, the average sensitivity of the radiologists increased from 96% to 100% (P > .08) with 3D-AUS, whereas the specificity decreased from 33% to 25% (P > .28). Survey responses indicated increased confidence in potentially using DBT for screening when 3D-AUS was added (P < .05 for each reader). CONCLUSIONS: In this initial reader study, no significant difference in ROC performance was found with the addition of 3D-AUS to DBT. However, a trend to improved discrimination of malignancy was observed when adding 3D-AUS. Radiologists' confidence also improved with DBT/3DAUS compared to DBT alone.

Ultrasound: Imaging, development, application.

A brief summary is given of my work in ultrasound imaging and therapy, with some information on the role of this journal in those fields.

Real-time, volumetric imaging of radiation dose delivery deep into the liver during cancer treatment.

Ionizing radiation acoustic imaging (iRAI) allows online monitoring of radiation's interactions with tissues during radiation therapy, providing real-time, adaptive feedback for cancer treatments. We describe an iRAI volumetric imaging system that enables mapping of the three-dimensional (3D) radiation dose distribution in a complex clinical radiotherapy treatment. The method relies on a two-dimensional matrix array transducer and a matching multi-channel preamplifier board. The feasibility of imaging temporal 3D dose accumulation was first validated in a tissue-mimicking phantom. Next, semiquantitative iRAI relative dose measurements were verified in vivo in a rabbit model. Finally, real-time visualization of the 3D radiation dose delivered to a patient with liver metastases was accomplished with a clinical linear accelerator. These studies demonstrate the potential of iRAI to monitor and quantify the 3D radiation dose deposition during treatment, potentially improving radiotherapy treatment efficacy using real-time adaptive treatment.

Digital breast tomosynthesis is comparable to mammographic spot views for mass characterization.

PURPOSE: To determine if digital breast tomosynthesis (DBT) performs comparably to mammographic spot views (MSVs) in characterizing breast masses as benign or malignant. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant reader study obtained informed consent from all subjects. Four blinded Mammography Quality Standards Act-certified academic radiologists individually evaluated DBT images and MSVs of 67 masses (30 malignant, 37 benign) in 67 women (age range, 34-88 years). Images were viewed in random order at separate counterbalanced sessions and were rated for visibility (10-point scale), likelihood of malignancy (12-point scale), and Breast Imaging Reporting and Data System (BI-RADS) classification. Differences in mass visibility were analyzed by using the Wilcoxon matched-pairs signed-ranks test. Reader performance was measured by calculating the area under the receiver operating characteristic curve (A(z)) and partial area index above a sensitivity threshold of 0.90 (A(z)(0.90)) by using likelihood of malignancy ratings. Masses categorized as BI-RADS 4 or 5 were compared with histopathologic analysis to determine true-positive results for each modality. RESULTS: Mean mass visibility ratings were slightly better with DBT (range, 3.2-4.4) than with MSV (range, 3.8-4.8) for all four readers, with one reader's improvement achieving statistical significance (P = .001). The A(z) ranged 0.89-0.93 for DBT and 0.88-0.93 for MSV (P ≥ .23). The A(z)((0.90)) ranged 0.36-0.52 for DBT and 0.25-0.40 for MSV (P ≥ .20). The readers characterized seven additional malignant masses as BI-RADS 4 or 5 with DBT than with MSV, at a cost of five false-positive biopsy recommendations, with a mean of 1.8 true-positive (range, 0-3) and 1.3 false-positive (range, -1 to 4) assessments per reader. CONCLUSION: In this small study, mass characterization in terms of visibility ratings, reader performance, and BI-RADS assessment with DBT was similar to that with MSVs. Preliminary findings suggest that MSV might not be necessary for mass characterization when performing DBT.

Feasibility of ultrasound tomography-guided localized mild hyperthermia using a ring transducer: Ex vivo and in silico studies.

BACKGROUND: As of 2022, breast cancer continues to be the most diagnosed cancer worldwide. This problem persists within the United States as well, as the American Cancer Society has reported that ∼12.5% of women will be diagnosed with invasive breast cancer over the course of their lifetime. Therefore, a clinical need continues to exist to address this disease from a treatment and therapeutic perspective. Current treatments for breast cancer and cancers more broadly include surgery, radiation, and chemotherapy. Adjuncts to these methods have been developed to improve the clinical outcomes for patients. One such adjunctive treatment is mild hyperthermia therapy (MHTh), which has been shown to be successful in the treatment of cancers by increasing effectiveness and reduced dosage requirements for radiation and chemotherapies. MHTh-assisted treatments can be performed with invasive thermal devices, noninvasive microwave induction, heating and recirculation of extracted patient blood, or whole-body hyperthermia with hot blankets. PURPOSE: One common method for inducing MHTh is by using microwave for heat induction and magnetic resonance imaging for temperature monitoring. However, this leads to a complex, expensive, and inaccessible therapy platform. Therefore, in this work we aim to show the feasibility of a novel all-acoustic MHTh system that uses focused ultrasound (US) to induce heating while also using US tomography (UST) to provide temperature estimates. Changes in sound speed (SS) have been shown to be strongly correlated with temperature changes and can therefore be used to indirectly monitor heating throughout the therapy. Additionally, these SS estimates allow for heterogeneous SS-corrected phase delays when heating complex and heterogeneous tissue structures. METHODS: Feasibility to induce localized heat in tissue was investigated in silico with a simulated breast model, including an embedded tumor using continuous wave US. Here, both heterogenous acoustic and thermal properties were modeled in addition to blood perfusion. We further demonstrate, with ex vivo tissue phantoms, the feasibility of using ring-based UST to monitor temperature by tracking changes in SS. Two phantoms (lamb tissue and human abdominal fat) with latex tubes containing varied temperature flowing water were imaged. The measured SS of the water at each temperature were compared against values that are reported in literature. RESULTS: Results from ex vivo tissue studies indicate successful tracking of temperature under various phantom configurations and ranges of water temperature. The results of in silico studies show that the proposed system can heat an acoustically and thermally heterogenous breast model to the clinically relevant temperature of 42°C while accounting for a reasonable time needed to image the current cross section (200 ms). Further, we have performed an initial in silico study demonstrating the feasibility of adjusting the transmit waveform frequency to modify the effective heating height at the focused region. Lastly, we have shown in a simpler 2D breast model that MHTh level temperatures can be maintained by adjusting the transmit pressure intensity of the US ring. CONCLUSIONS: This work has demonstrated the feasibility of using a 256-element ring array transducer for temperature monitoring; however, future work will investigate minimizing the difference between measured SS and the values shown in literature. A hypothesis attributes this bias to potential volumetric average artifacts from the ray-based SS inversion algorithm that was used, and that moving to a waveform-based SS inversion algorithm will greatly improve the SS estimates. Additionally, we have shown that an all-acoustic MHTh system is feasible via in silico studies. These studies have indicated that the proposed system can heat a tumor within a heterogenous breast model to 42°C within a narrow time frame. This holds great promise for increasing the accessibility and reducing the complexity of a future all-acoustic MHTh system.

Pure optical photoacoustic microscopy.

The concept of pure optical photoacoustic microscopy(POPAM) was proposed based on optical rastering of a focused excitation beam and optically sensing the photoacoustic signal using a microring resonator fabricated by a nanoimprinting technique. After the refinements of the microring's working wavelength and in the resonator structure and mold fabrication, an ultrahigh Q factor of 3.0×10(5) was achieved which provided high sensitivity with a noise equivalent detectable pressure(NEDP) value of 29 Pa. This NEDP is much lower than the hundreds of Pascals achieved with existing optical resonant structures such as etalons, fiber gratings and dielectric multilayer interference filters available for acoustic measurement. The featured high sensitivity allowed the microring resonator to detect the weak photoacoustic signals from micro- or submicroscale objects. The inherent superbroad bandwidth of the optical microring resonator combined with an optically focused scanning beam provided POPAM with high resolution in the axial as well as both lateral directions while the axial resolution of conventional photoacoustic microscopy (PAM) suffers from the limited bandwidth of PZT detectors. Furthermore, the broadband microring resonator showed similar sensitivity to that of our most sensitive PZT detector. The current POPAM system provides a lateral resolution of 5 µm and an axial resolution of 8 µm, comparable to that achieved by optical microscopy while presenting the unique contrast of optical absorption and functional information complementing other optical modalities. The 3D structure of microvasculature, including capillary networks, and even individual red blood cells have been discerned successfully in the proof-of-concept experiments on mouse bladders ex vivo and mouse ears in vivo. The potential of approximately GHz bandwidth of the microring resonator also might allow much higher resolution than shown here in microscopy of optical absorption and acoustic propagation properties at depths in unfrozen tissue specimens or thicker tissue sections, which is not now imageable with current optical or acoustic microscopes of comparable resolution.

Drug delivery monitoring by photoacoustic tomography with an ICG encapsulated double emulsion.

The absorption spectrum of indocyanine green (ICG), a nontoxic dye used for medical diagnostics, depends upon its concentration as well as the nature of its environment, i.e., the solvent medium into which it is dissolved. In blood, ICG binds with plasma proteins, thus causing changes in its photoacoustic spectrum. We successfully encapsulated ICG in an ultrasound-triggerable perfluorocarbon double emulsion that prevents ICG from binding with plasma proteins. Photoacoustic spectral measurements on point target as well as 2-D photoacoustic images of blood vessels revealed that the photoacoustic spectrum changes significantly in blood when the ICG-loaded emulsion undergoes acoustic droplet vaporization (ADV), which is the conversion of liquid droplets into gas bubbles using ultrasound. We propose that these changes in the photoacoustic spectrum of the ICG emulsion in blood, coupled with photoacoustic tomography, could be used to spatially and quantitatively monitor ultrasound initiated drug delivery. In addition, we suggest that the photoacoustic spectral change induced by ultrasound exposure could also be used as contrast in photoacoustic imaging to obtain a background free image.

In vivo flow speed measurement of capillaries by photoacoustic correlation spectroscopy.

We recently proposed photoacoustic correlation spectroscopy (PACS) and demonstrated a proof-of-concept experiment. Here we use the technique for in vivo flow speed measurement in capillaries in a chick embryo model. The photoacoustic microscopy system is used to render high spatial resolution and high sensitivity, enabling sufficient signals from single red blood cells. The probe beam size is calibrated by a blood-mimicking phantom. The results indicate the feasibility of using PACS to study flow speeds in capillaries.

Image quality of microcalcifications in digital breast tomosynthesis: effects of projection-view distributions.

PURPOSE: To analyze the effects of projection-view (PV) distribution on the contrast and spatial blurring of microcalcifications on the tomosynthesized slices (X-Y plane) and along the depth (Z) direction for the same radiation dose in digital breast tomosynthesis (DBT). METHODS: A GE GEN2 prototype DBT system was used for acquisition of DBT scans. The system acquires PV images from 21 angles in 3° increments over a ±30° range. From these acquired PV images, the authors selected six subsets of PV images to simulate DBT of different angular ranges and angular increments. The number of PV images in each subset was fixed at 11 to simulate a constant total dose. These different PV distributions were subjectively divided into three categories: uniform group, nonuniform central group, and nonuniform extreme group with different angular ranges and angular increments. The simultaneous algebraic reconstruction technique (SART) was applied to each subset to reconstruct the DBT slices. A selective diffusion regularization method was employed to suppress noise. The image quality of microcalcifications in the reconstructed DBTs with different PV distributions was compared using the DBT scans of an American College of Radiology phantom and three human subjects. The contrast-to-noise ratio (CNR) and the full width at half maximum (FWHM) of the line profiles of microcalcifications within their in-focus DBT slices (parallel to detector plane) and the FWHMs of the interplane artifact spread function (ASF) in the Z-direction (perpendicular to detector plane) were used as image quality measures. RESULTS: The results indicate that DBT acquired with a large angular range or, for an equal angular range,with a large fraction of PVs at large angles yielded superior ASF with smaller FWHM in the Z-direction. PV distributions with a narrow angular range or a large fraction of PVs at small angles had stronger interplane artifacts. In the X-Y focal planes, the effect of PV distributions on spatial blurring depended on the directions. In the X-direction (perpendicular to the chestwall), the normalized line profiles of the calcifications reconstructed with the different PV distributions were similar in terms of FWHM; the differences in the FWHMs between the different PV distributions were less than half a pixel. In the Y-direction (x-ray source motion), the normalized line profiles of the calcifications reconstructed with PVs acquired with a narrow angular range or a large fraction of PVs at small angles had smaller FWHMs and thus less blurring of the line profiles. In addition, PV distributions with a narrow angular range or a large fraction of PVs at small angles yielded slightly higher CNR than those with a wide angular range for small, subtle microcalcifications; however, PV distributions had no obvious effect on CNR for relatively large microcalcifications. CONCLUSIONS: PV distributions affect the image quality of DBT. The relative importance of the impact depends on the characteristics of the signal and the direction (perpendicular or parallel) relative to the direction of x-ray source motion. For a given number of PVs, the angular range and the distribution of the PVs affect the degree of in-plane and interplane blurring in opposite ways. The design of the scan parameters of tomosynthesis systems would require proper consideration of the characteristics of the signals of interest and the potential trade-off of the image quality of different types of signals.

Characterizing the aggressiveness of prostate cancer using an all-optical needle photoacoustic sensing probe: feasibility study.

In our previous studies, we have developed a prototype interstitial needle sensing probe that can acquire broadband A-line photoacoustic (PA) signals encoding both tissue microarchitecture and histochemical information comparable to that accessible by histology. Paving the road toward clinical translation of this technology, we replaced the piezoelectric hydrophone in the needle PA probe with a fiber optic hydrophone that enabled both broader bandwidth and sufficient signal-to-noise ratio (SNR) for PA signal detection. Such an all-optical design also facilitated disposability and significantly reduced the footprint of the needle PA sensing probe. Experiments were performed on well-controlled phantoms and human prostate tissues. The microarchitectures in each sample were quantitatively evaluated by both the nonlinear spectral slope of the PA signal power spectrum and the generalized gamma (GG) parameter a by implementing envelope statistics to the PA signal. In the studies on phantoms containing optically absorbing microspheres with various sizes and concentrations, the nonlinear spectral slope showed a strong correlation of r=-0.80 with the microsphere dimensions, and a relatively weak correlation of r=-0.54 with the microsphere concentrations, while the GG parameter a showed a strong correlation with the microsphere dimensions (r=0.72) and a moderate correlation with the microsphere concentrations (r=0.63). In the studies on human prostate tissues containing progressive cancer stages, both the nonlinear spectral slope and the GG parameter a demonstrated a statistically significant difference between benign and nonaggressive cancer tissues (p<0.01), and between nonaggressive and aggressive cancer tissues (p<0.01). In addition, a multivariate analysis combining the two quantitative measurements demonstrated the boundaries among the different progressive stages of prostate cancer.

A simulation study of ionizing radiation acoustic imaging (iRAI) as a real-time dosimetric technique for ultra-high dose rate radiotherapy (UHDR-RT).

PURPOSE: Electron-based ultra-high dose rate radiation therapy (UHDR-RT), also known as Flash-RT, has shown the ability to improve the therapeutic index in comparison to conventional radiotherapy (CONV-RT) through increased sparing of normal tissue. However, the extremely high dose rates in UHDR-RT have raised the need for accurate real-time dosimetry tools. This work aims to demonstrate the potential of the emerging technology of Ionized Radiation Acoustic Imaging (iRAI) through simulation studies and investigate its characteristics as a promising relative in vivo dosimetric tool for UHDR-RT. METHODS: The detection of induced acoustic waves following a single UHDR pulse of a modified 6 MeV 21EX Varian Clinac in a uniform porcine gelatin phantom that is brain-tissue equivalent was simulated for an ideal ultrasound transducer. The full 3D dose distributions in the phantom for a 1 × 1 cm2 field were simulated using EGSnrc (BEAMnrc∖DOSXYZnrc) Monte Carlo (MC) codes. The relative dosimetry simulations were verified with dose experimental measurements using Gafchromic films. The spatial dose distribution was converted into an initial pressure source spatial distribution using the medium-dependent dose-pressure relation. The MATLAB-based toolbox k-Wave was then used to model the propagation of acoustic waves through the phantom and perform time-reversal (TR)-based imaging reconstruction. The effect of the various linear accelerator (linac) operating parameters, including linac pulse duration and pulse repetition rate (frequency), were investigated as well. RESULTS: The MC dose simulation results agreed with the film measurement results, specifically at the central beam region up to 80% dose within approximately 5% relative error for the central profile region and a local relative error of <6% for percentage dose depth. IRAI-based FWHM of the radiation beam was within approximately 3 mm relative to the MC-simulated beam FWHM at the beam entrance. The real-time pressure signal change agreed with the dose changes proving the capability of the iRAI for predicting the beam position. IRAI was tested through 3D simulations of its response to be based on the temporal changes in the linac operating parameters on a dose per pulse basis as expected theoretically from the pressure-dose proportionality. The pressure signal amplitude obtained through 2D simulations was proportional to the dose per pulse. The instantaneous pressure signal amplitude decreases as the linac pulse duration increases, as predicted from the pressure wave generation equations, such that the shorter the linac pulse the higher the signal and the better the temporal (spatial) resolutions of iRAI. The effect of the longer linac pulse duration on the spatial resolution of the 3D constructed iRAI images was corrected for linac pulse deconvolution. This correction has improved the passing rate of the 1%/1 mm gamma test criteria, between the pressure-constructed and dosimetric beam characteristics, to as high as 98%. CONCLUSIONS: A full simulation workflow was developed for testing the effectiveness of iRAI as a promising relative dosimetry tool for UHDR-RT radiation therapy. IRAI has shown the advantage of 3D dose mapping through the dose signal linearity and, hence, has the potential to be a useful dosimeter at depth dose measurement and beam localization and, hence, potentially for in vivo dosimetry in UHDR-RT.

Delivery of water-soluble drugs using acoustically triggered perfluorocarbon double emulsions.

PURPOSE: Ultrasound can be used to release a therapeutic payload encapsulated within a perfluorocarbon (PFC) emulsion via acoustic droplet vaporization (ADV), a process whereby the PFC phase is vaporized and the agent is released. ADV-generated microbubbles have been previously used to selectively occlude blood vessels in vivo. The coupling of ADV-generated drug delivery and occlusion has therapeutically synergistic potentials. METHODS: Micron-sized, water-in-PFC-in-water (W(1)/PFC/W(2)) emulsions were prepared in a two-step process using perfluoropentane (PFP) or perfluorohexane (PFH) as the PFC phase. Fluorescein or thrombin was contained in the W(1) phase. RESULTS: Double emulsions containing fluorescein in the W(1) phase displayed a 5.7±1.4-fold and 8.2±1.3-fold increase in fluorescein mass flux, as measured using a Franz diffusion cell, after ADV for the PFP and PFH emulsions, respectively. Thrombin was stably retained in four out of five double emulsions. For three out of five formulations tested, the clotting time of whole blood decreased, in a statistically significant manner (p < 0.01), when incubated with thrombin-loaded emulsions exposed to ultrasound compared to emulsions not exposed to ultrasound. CONCLUSIONS: ADV can be used to spatially and temporally control the delivery of water-soluble compounds formulated in PFC double emulsions. Thrombin release could extend the duration of ADV-generated, microbubble occlusions.

Effect of a gel retainment dam on automated ultrasound coverage in a dual-modality breast imaging system.

OBJECTIVE: The goal of this work was to evaluate a possible improvement in ultrasound coverage for a dual-modality breast imaging system in the mammographic geometry. METHODS: A pilot study was performed to evaluate use of a rubber dam to retain ultrasound gel and improve imaging coverage at the breast periphery on a combined imaging system consisting of an ultrasound scanner and a digital x-ray tomosynthesis unit. Several dams were constructed to encompass the shapes of various sizes of compressed breasts. Visual tracings of the breast-to-paddle contact area and breast periphery were made for 8 breasts to estimate coverage area. Two readers independently reviewed the resulting images and were asked to rate the overall breast image quality. RESULTS: The percentages of breast in contact with the paddle were greater (P < .01) and the linear dimensions of breast in contact with the paddle were larger (P < .05) with the rubber dam than without it. With the dam, the mean estimated area of the breast in contact with the paddle increased 14%, whereas the mean increase in the fraction of the total breast area in contact with paddle was 30%. The difference was due to the mean total projected area of the breast decreasing 12% as the dam was pressed against it. The image quality of automated ultrasound with the rubber dam was consistently judged to be superior to that without the dam. CONCLUSIONS: This method can enhance the absolute and percentage area of the breast in contact with the paddle, reducing noncontact gaps at the breast periphery. Gently pressing the breast periphery with the dam inserted toward the chest wall improves coverage in automated breast ultrasound scanning.