Machine Independence of Ultrasound-Based Quantification of Vitreous Echodensities.

Purpose: Quantitative ultrasound (QUS) provides objective indices of Vision Degrading Myodesopsia (VDM) that correlate with contrast sensitivity (CS). To date, QUS methods were only tested on a single ultrasound machine. Here, we evaluate whether QUS measurements are machine independent. Methods: In this cross-sectional study, 47 eyes (24 subjects; age = 53.2 ± 14.4 years) were evaluated with Freiburg acuity contrast testing (%Weber), and ultrasonography using 2 machines: one with a 15-MHz single-element transducer and one with a 5-ring, 20-MHz annular-array. Images were acquired from each system in sequential scans. Artifact-free, log-compressed envelope data were processed to yield three parameters (mean amplitude, M; energy, E; and percentage filled by echodensities, P50) and a composite score (C). A B-mode normalization method was applied to the 20-MHz datasets to match QUS parameters at both frequencies. Statistical analyses were performed to evaluate correlations among CS, E, M, P50, and C for both machines. Results: QUS parameters from each machine correlated with CS (R ≥ 0.57, P < 0.001) and there was correlation between machines (R ≥ 0.84, P < 0.001). Correlations between CS and QUS parameters were statistically similar for both machines (P ≥ 0.14) except when the 20-MHz data were normalized (P = 0.04). Reproducibility of QUS parameters computed from 20-MHz data were satisfactory (52.3%-96.3%) with intraclass correlation values exceeding 0.80 (P < 0.001). Conclusions: The high correlation between QUS parameters from both machines combined with a statistically similar correlation to CS suggests QUS is an effective, machine-independent, quantitative measure of vitreous echodensities. Translational Relevance: QUS may be applied across clinical ophthalmic ultrasound scanners and imaging frequencies to effectively evaluate VDM.

RECURRENT FLOATERS AFTER LIMITED VITRECTOMY FOR VISION DEGRADING MYODESOPSIA.

PURPOSE: Limited vitrectomy improves vision degrading myodesopsia, but the incidence of recurrent floaters postoperatively is not known. We studied patients with recurrent central floaters using ultrasonography and contrast sensitivity (CS) testing to characterize this subgroup and identify the clinical profile of patients at risk of recurrent floaters. METHODS: A total of 286 eyes (203 patients, 60.6 ± 12.9 years) undergoing limited vitrectomy for vision degrading myodesopsia were studied retrospectively. Sutureless 25G vitrectomy was performed without intentional surgical posterior vitreous detachment (PVD) induction. CS (Freiburg Acuity Contrast test: Weber index, %W) and vitreous echodensity (quantitative ultrasonography) were assessed prospectively. RESULTS: No eyes (0/179) with preoperative PVD experienced new floaters. Recurrent central floaters occurred in 14/99 eyes (14.1%) without complete preoperative PVD (mean follow-up = 39 months vs. 31 months in 85 eyes without recurrent floaters). Ultrasonography identified new-onset PVD in all 14 (100%) recurrent cases. Young (younger than 52 years; 71.4%), myopic (≥-3D; 85.7%), phakic (100%) men (92.9%) predominated. Reoperation was elected by 11 patients, who had partial PVD preoperatively in 5/11 (45.5%). At study entry, CS was degraded (3.55 ± 1.79 %W) but improved postoperatively by 45.6% (1.93 ± 0.86 %W, P = 0.033), while vitreous echodensity reduced by 86.6% ( P = 0.016). New-onset PVD postoperatively degraded CS anew, by 49.4% (3.28 ± 0.96 %W; P = 0.009) in patients electing reoperation. Repeat vitrectomy normalized CS to 2.00 ± 0.74%W ( P = 0.018). CONCLUSION: Recurrent floaters after limited vitrectomy for vision degrading myodesopsia are caused by new-onset PVD, with younger age, male sex, myopia, and phakic status as risk factors. Inducing surgical PVD at the primary operation should be considered in these select patients to mitigate recurrent floaters.

Longitudinal in Utero Analysis of Engrailed-1 Knockout Mouse Embryonic Phenotypes Using High-Frequency Ultrasound.

Large-scale international efforts to generate and analyze loss-of-function mutations in each of the approximately 20,000 protein-encoding gene mutations are ongoing using the "knockout" mouse as a model organism. Because one-third of gene knockouts are expected to result in embryonic lethality, it is important to develop non-invasive in utero imaging methods to detect and monitor mutant phenotypes in mouse embryos. We describe the utility of 3-D high-frequency (40-MHz) ultrasound (HFU) for longitudinal in utero imaging of mouse embryos between embryonic days (E) 11.5 and E14.5, which represent critical stages of brain and organ development. Engrailed-1 knockout (En1-ko) mouse embryos and their normal control littermates were imaged with HFU in 3-D, enabling visualization of morphological phenotypes in the developing brains, limbs and heads of the En1-ko embryos. Recently developed deep learning approaches were used to automatically segment the embryonic brain ventricles and bodies from the 3-D HFU images, allowing quantitative volumetric analyses of the En1-ko brain phenotypes. Taken together, these results show great promise for the application of longitudinal 3-D HFU to analyze knockout mouse embryos in utero.

Slow-Flow Ultrasound Localization Microscopy Using Recondensation of Perfluoropentane Nanodroplets.

Ultrasound localization microscopy (ULM) is an emerging, super-resolution imaging technique for detailed mapping of the microvascular structure and flow velocity via subwavelength localization and tracking of microbubbles. Because microbubbles rely on blood flow for movement throughout the vascular space, acquisition times can be long in the smallest, low-flow microvessels. In addition, detection of microbubbles in low-flow regions can be difficult because of minimal separation of microbubble signal from tissue. Nanoscale, phase-change contrast agents (PCCAs) have emerged as a switchable, intermittent or persisting contrast agent for ULM via acoustic droplet vaporization (ADV). Here, the focus is on characterizing the spatiotemporal contrast properties of less volatile perfluoropentane (PFP) PCCAs. The results indicate that at physiological temperature, nanoscale PFP PCCAs with diameters less than 100 nm disappear within microseconds after ADV with high-frequency ultrasound (16 MHz, 5- to 6-MPa peak negative pressure) and that nanoscale PFP PCCAs have an inherent deactivation mechanism via immediate recondensation after ADV. This "blinking" on-and-off contrast signal allowed separation of flow in an in vitro flow phantom, regardless of flow conditions, although with a need for some replenishment at very low flow conditions to maintain count rate. This blinking behavior allows for rapid spatial mapping in areas of low or no flow with ULM, but limits velocity tracking because there is no stable bubble formation with nanoscale PFP PCCAs.

High-Frequency Ultrasound Activation of Perfluorocarbon Nanodroplets for Treatment of Glaucoma.

Elevated intraocular pressure (IOP) is the most prevalent risk factor for initiation and progression of neurodegeneration in glaucoma. Ocular hypertension results from increased resistance to aqueous fluid outflow caused by reduced porosity and increased stiffness of tissues of the outflow pathway. Acoustic activation and resulting bioeffects of the perfluorocarbon (PFC) nanodroplets (NDs) introduced into the anterior chamber (AC) of the eye could potentially represent a treatment for glaucoma by increasing permeability in the aqueous outflow track. To evaluate the potential of NDs to enter the outflow track, 100-nm diameter perfluoropentane (PFP) NDs with a lipid shell were injected into the AC of ex vivo pig eyes and in vivo rat eyes. The NDs were activated and imaged with 18- and 28-MHz linear arrays to assess their location and diffusion. NDs in the AC could also be visualized using optical coherence tomography (OCT). Because of their higher density with respect to aqueous humor, some NDs settled into the iridocorneal angle where they entered the outflow pathway. After acoustic activation of the NDs at the highest acoustic pressure, small gas bubbles were observed in the AC. After two days, no acoustic activation events were visible in the AC of the rats and their eyes showed no evidence of inflammation.

Retrobulbar blood flow in rat eyes during acute elevation of intraocular pressure.

Most studies of the effect of acute elevation of intraocular pressure (IOP) on ocular blood-flow have utilized optical coherence tomography (OCT) to characterize retinal and choroidal flow and vascular density. This study investigates the effect of acute IOP elevation on blood flow velocity in the retrobulbar arteries and veins supplying and draining the eye, which, unlike the retinal and choroidal vasculature, are not directly compressed as IOP is increased. By cannulation of the anterior chamber of 20 Sprague-Dawley rats, we increased IOP in 10 mmHg steps from 10 to 60 mmHg and returned to 10 mmHg. After 1 min at each IOP (and 3 min after return to 10 mmHg), we acquired 18 MHz plane-wave ultrasound data at 3000 compound images/sec for 1.5 s. We produced color-flow Doppler images by digital signal processing of the ultrasound data, identified retrobulbar arteries and veins, generated spectrograms depicting flow velocity over the cardiac cycle and characterized changes of vascular density and perfusion in the orbit overall. Systolic, diastolic and mean velocities and resistive and pulsatile indices were determined from arterial spectrograms at each IOP level. Baseline mean arterial and mean venous velocities averaged 30.9 ±â€¯10.8 and 8.5 ±â€¯3.3 mm/s, respectively. Arterial velocity progressively decreased and resistance indices increased at and above an IOP of 30 mmHg. Mean arterial velocity at 60 mmHg dropped by 55% with respect to baseline, while venous velocity decreased by 20%. Arterial and venous velocities and resistance returned to near baseline after IOP was restored to 10 mmHg. Both vascular density and orbital perfusion decreased with IOP, but while perfusion returned to near normal when IOP returned to 10 mmHg, density remained reduced. Our findings are consistent with OCT-based studies showing reduced perfusion of the retina at levels comparable to retrobulbar arterial flow velocity change with increased IOP. The lesser effect on venous flow is possibly attributable to partial collapse of the venous lumen as volumetric venous outflow decreased at high IOP. The continued reduction in orbital vascular density 3 min after restoration of IOP to 10 mmHg might be attributable to persisting narrowing of capillaries, but this needs to be verified in future studies.

A Deep Learning Approach for Segmentation, Classification, and Visualization of 3-D High-Frequency Ultrasound Images of Mouse Embryos.

Segmentation and mutant classification of high-frequency ultrasound (HFU) mouse embryo brain ventricle (BV) and body images can provide valuable information for developmental biologists. However, manual segmentation and identification of BV and body requires substantial time and expertise. This article proposes an accurate, efficient and explainable deep learning pipeline for automatic segmentation and classification of the BV and body. For segmentation, a two-stage framework is implemented. The first stage produces a low-resolution segmentation map, which is then used to crop a region of interest (ROI) around the target object and serve as the probability map of the autocontext input for the second-stage fine-resolution refinement network. The segmentation then becomes tractable on high-resolution 3-D images without time-consuming sliding windows. The proposed segmentation method significantly reduces inference time (102.36-0.09 s/volume ≈ 1000× faster) while maintaining high accuracy comparable to previous sliding-window approaches. Based on the BV and body segmentation map, a volumetric convolutional neural network (CNN) is trained to perform a mutant classification task. Through backpropagating the gradients of the predictions to the input BV and body segmentation map, the trained classifier is found to largely focus on the region where the Engrailed-1 (En1) mutation phenotype is known to manifest itself. This suggests that gradient backpropagation of deep learning classifiers may provide a powerful tool for automatically detecting unknown phenotypes associated with a known genetic mutation.

Characterization of Vortex Flow in a Mouse Model of Ventricular Dyssynchrony by Plane-Wave Ultrasound Using Hexplex Processing.

The rodent heart is frequently used to study human cardiovascular disease (CVD). Although advanced cardiovascular ultrasound imaging methods are available for human clinical practice, application of these techniques to small animals remains limited due to the temporal and spatial-resolution demands. Here, an ultrasound vector-flow workflow is demonstrated that enables visualization and quantification of the complex hemodynamics within the mouse heart. Wild type (WT) and fibroblast growth factor homologous factor 2 (FHF2)-deficient mice (Fhf2 KO/Y ), which present with hyperthermia-induced ECG abnormalities highly reminiscent of Brugada syndrome, were used as a mouse model of human CVD. An 18-MHz linear array was used to acquire high-speed (30 kHz), plane-wave data of the left ventricle (LV) while increasing core body temperature up to 41.5 °C. Hexplex (i.e., six output) processing of the raw data sets produced the output of vector-flow estimates (magnitude and phase); B-mode and color-Doppler images; Doppler spectrograms; and local time histories of vorticity and pericardium motion. Fhf2 WT/Y mice had repeatable beat-to-beat cardiac function, including vortex formation during diastole, at all temperatures. In contrast, Fhf2 KO/Y mice displayed dyssynchronous contractile motion that disrupted normal inflow vortex formation and impaired LV filling as temperature rose. The hexplex processing approach demonstrates the ability to visualize and quantify the interplay between hemodynamic and mechanical function in a mouse model of human CVD.

DEEP MOUSE: AN END-TO-END AUTO-CONTEXT REFINEMENT FRAMEWORK FOR BRAIN VENTRICLE & BODY SEGMENTATION IN EMBRYONIC MICE ULTRASOUND VOLUMES.

The segmentation of the brain ventricle (BV) and body in embryonic mice high-frequency ultrasound (HFU) volumes can provide useful information for biological researchers. However, manual segmentation of the BV and body requires substantial time and expertise. This work proposes a novel deep learning based end-to-end auto-context refinement framework, consisting of two stages. The first stage produces a low resolution segmentation of the BV and body simultaneously. The resulting probability map for each object (BV or body) is then used to crop a region of interest (ROI) around the target object in both the original image and the probability map to provide context to the refinement segmentation network. Joint training of the two stages provides significant improvement in Dice Similarity Coefficient (DSC) over using only the first stage (0.818 to 0.906 for the BV, and 0.919 to 0.934 for the body). The proposed method significantly reduces the inference time (102.36 to 0.09 s/volume ≈1000x faster) while slightly improves the segmentation accuracy over the previous methods using slide-window approaches.

Contrast-enhanced plane-wave ultrasound imaging of the rat eye.

Preclinical imaging, especially of rodent models, plays a major role in experimental ophthalmology. Our aim was to determine if ultrasound can be used to visualize and measure flow dynamics in the retrobulbar vessels supplying and draining the eye and the potential of contrast microbubbles to provide image and measurement enhancement. To accomplish this, we used a 128-element, 18 MHz linear array ultrasound probe and performed plane-wave imaging of the eyes of Sprague Dawley rats. Compound images were acquired by emitting unfocused wavefronts at multiple angles and combining echo data from all angles to form individual B-scans. Multiple imaging sequences were utilized, compounding up to six angles, with imaging rate of up to 3000 compound B-scans per second and sequence durations from 1.5 to 180 s. Data were acquired before and after intravenous introduction of contrast microbubbles. We found the total power of the Doppler signal in the image plane to increase approximately 20 fold after injection of contrast, followed by an exponential decay to baseline in about 90 s, The best-fit time constant of the decay averaged 41 s. While major vessels and the retinal/choroidal complex were evident pre-contrast, they were dramatically enhanced with contrast present, with details such as choroidal arterioles seen only with contrast. Ocular arteriovenous transit time determined from comparative enhancement curves in arteries and veins was approximately 0.2 s. In conclusion, plane wave ultrasound, especially with enhancement by contrast microbubbles, offers a means for the study of ocular hemodynamics using the rat eye as a model.

Improved evaluation of backscatter characteristics of soft tissue using high-frequency annular array.

Clinical ultrasound is widely used for quantitative diagnosis. To clarify the relationship between anatomical and acoustic properties, high resolution imaging using high-frequency ultrasound (HFU) is required. However, when tissue properties are evaluated using HFU, the depth of field (DOF) is limited. To overcome this problem, an annular array transducer, which has a simple structure and produces high-quality images, is applied to HFU measurement. In previous phantom experiments, we demonstrated that the HFU annular array extends the DOF compared to that of a single-element transducer for quantitative ultrasound (QUS) analysis. Here, we extend that work by applying QUS methods to an ex vivo rat liver. The present study demonstrates that an annular array extends the region and improves the resolution for tissue characterization for an excised healthy rat liver. Amplitude envelope statistics and spectral-based analysis are used as QUS methods.

High-Frequency Multipulse, Plane-Wave Acoustic Contrast Imaging.

Multipulse (MP) ultrasound contrast agent (UCA) imaging is a method to increase the contrast-to-background (CBR) ratio in regions of blood flow. Plane-wave imaging allows high frame rates, and with high-frequency ultrasound, fine-spatial and temporal resolution. MP and plane-wave imaging have not been applied to high-frequency ultrasound. Here, an 18-MHz linear array was employed to implement the MP methods of pulse inversion (PI) and amplitude modulation (AM) using high-speed, multiangle, compound plane-wave imaging. A flow of the UCA DEFINITY© at a dilution ratio of 2000:1 circulating through a 2-mm-diameter flow channel in a tissue-mimicking phantom was used to characterize CBR and compared with cases of standard, multiangle compound plane-wave imaging. The relative improvement of PI and AM versus standard plane-wave imaging ranged from 5 to 10 dB. The CBR was observed to be stable over a 60-min time duration for a 2000:1 dilution ratio and a 2000:1 dilution ratio provided an optimal CBR.

Comprehensive backscattering characteristics analysis for quantitative ultrasound with an annular array: a basic study on homogeneous scattering phantom.

High-frequency ultrasound (HFU, >20 MHz) and quantitative ultrasound (QUS) methods permit a means to understand the relationship between anatomical and acoustic characteristics. In our previous research, we showed that analyzing the acoustic scattering with HFU was an effective method for noninvasive diagnosis. However, the depth of field (DOF) of HFU transducers was limited, which constrains the range of QUS analysis. In this study, we seek to improve the accuracy of HFU, QUS-based parameters on the envelope statistics and frequency-based analysis by using an annular array that allows for an extended DOF. A 20-MHz annular-array transducer with five elements was employed to obtain signals which were beamformed in post-processing. Two kinds of low concentration scattering phantoms were scanned with 30-µm step size. Two QUS analysis techniques were employed: the Nakagami distribution and the reflector method. The results demonstrated that the annular array provides a stable analysis over an extended axial range.

Ultrasound Imaging and Measurement of Choroidal Blood Flow.

PURPOSE: The choroid is a vascular network providing the bulk of the oxygen and nutrient supply to the retina and may play a pivotal role in retinal disease pathogenesis. While optical coherence tomography angiography provides an en face depiction of the choroidal vasculature, it does not reveal flow dynamics. In this report, we describe the use of plane-wave ultrasound to image and characterize choroidal blood flow. METHODS: We scanned both eyes of 12 healthy subjects in a horizontal plane superior to the optic nerve head using an 18-MHz linear array. Plane-wave data were acquired over 10 transmission angles that were coherently compounded to produce 1000 images/sec for 3 seconds. These data were processed to produce a time series of power Doppler images and spectrograms depicting choroidal flow velocity. Analysis of variance was used to characterize peak systolic, and end diastolic velocities and resistive index, and their variability between scans, eyes, and subjects. RESULTS: Power Doppler images showed distinct arterioles within a more diffuse background. Choroidal flow was moderately pulsatile, with peak systolic velocity averaging approximately 10 mm/sec and resistive index of 0.55. There was no significant difference between left and right eyes, but significant variation among subjects. CONCLUSIONS: Plane-wave ultrasound visualized individual arterioles and allowed measurement of flow over the cardiac cycle. Characterization of choroidal flow dynamics offers a novel means for assessment of the choroid's role in ocular disease. TRANSLATIONAL RELEVANCE: Characterization of choroidal flow dynamics offers a novel means for assessment of the choroid's role in ocular disease.

High-Frame-Rate Doppler Ultrasound Using a Repeated Transmit Sequence.

The maximum detectable velocity of high-frame-rate color flow Doppler ultrasound is limited by the imaging frame rate when using coherent compounding techniques. Traditionally, high quality ultrasonic images are produced at a high frame rate via coherent compounding of steered plane wave reconstructions. However, this compounding operation results in an effective downsampling of the slow-time signal, thereby artificially reducing the frame rate. To alleviate this effect, a new transmit sequence is introduced where each transmit angle is repeated in succession. This transmit sequence allows for direct comparison between low resolution, pre-compounded frames at a short time interval in ways that are resistent to sidelobe motion. Use of this transmit sequence increases the maximum detectable velocity by a scale factor of the transmit sequence length. The performance of this new transmit sequence was evaluated using a rotating cylindrical phantom and compared with traditional methods using a 15-MHz linear array transducer. Axial velocity estimates were recorded for a range of ±300 mm/s and compared to the known ground truth. Using these new techniques, the root mean square error was reduced from over 400 mm/s to below 50 mm/s in the high-velocity regime compared to traditional techniques. The standard deviation of the velocity estimate in the same velocity range was reduced from 250 mm/s to 30 mm/s. This result demonstrates the viability of the repeated transmit sequence methods in detecting and quantifying high-velocity flow.

High-speed, high-frequency ultrasound, in utero vector-flow imaging of mouse embryos.

Real-time imaging of the embryonic murine cardiovascular system is challenging due to the small size of the mouse embryo and rapid heart rate. High-frequency, linear-array ultrasound systems designed for small-animal imaging provide high-frame-rate and Doppler modes but are limited in regards to the field of view that can be imaged at fine-temporal and -spatial resolution. Here, a plane-wave imaging method was used to obtain high-speed image data from in utero mouse embryos and multi-angle, vector-flow algorithms were applied to the data to provide information on blood flow patterns in major organs. An 18-MHz linear array was used to acquire plane-wave data at absolute frame rates ≥10 kHz using a set of fixed transmission angles. After beamforming, vector-flow processing and image compounding, effective frame rates were on the order of 2 kHz. Data were acquired from the embryonic liver, heart and umbilical cord. Vector-flow results clearly revealed the complex nature of blood-flow patterns in the embryo with fine-temporal and -spatial resolution.

Subharmonic Response of Polymer Contrast Agents Based on the Empirical Mode Decomposition.

The subharmonic threshold for ultrasound contrast agents has been defined as a 20-25 dB difference between the fundamental and subharmonic (2/1) spectral components of the backscatter signal. However, this Fourier-based criterion assumes a linear time-invariant signal. A more appropriate criterion for short cycle and frequency-modulated waveforms is proposed with an adaptive signal-processing approach based on the empirical mode decomposition (EMD) method. The signal is decomposed into an orthogonal basis known as intrinsic mode functions (IMFs) and a subharmonic threshold is defined with respect to the energy ratio of the subharmonic IMF component to that of the incident signal. The method is applied to backscatter data acquired from two polymer-shelled contrast agents, Philips (#38, mean diameter 2.0 [Formula: see text]) and Point Biomedical (#12027, mean diameter 3.9 [Formula: see text]). The acoustic backscatter signals are investigated for a single contrast agent subjected to monofrequency (20 MHz, 20 cycles) and chirp (15-25 MHz, 20 cycles) forcing for incident pressures ranging from 0.5 to 2.4 MPa. In comparison to the spectral peak difference (20 dB) criterion, the EMD method is more sensitive in determining subharmonic signals.

Ultrafast Ultrasound Imaging of Ocular Anatomy and Blood Flow.

PURPOSE: Ophthalmic ultrasound imaging is currently performed with mechanically scanned single-element probes. These probes have limited capabilities overall and lack the ability to image blood flow. Linear-array systems are able to detect blood flow, but these systems exceed ophthalmic acoustic intensity safety guidelines. Our aim was to implement and evaluate a new linear-array-based technology, compound coherent plane-wave ultrasound, which offers ultrafast imaging and depiction of blood flow at safe acoustic intensity levels. METHODS: We compared acoustic intensity generated by a 128-element, 18-MHz linear array operated in conventionally focused and plane-wave modes and characterized signal-to-noise ratio (SNR) and lateral resolution. We developed plane-wave B-mode, real-time color-flow, and high-resolution depiction of slow flow in postprocessed data collected continuously at a rate of 20,000 frames/s. We acquired in vivo images of the posterior pole of the eye by compounding plane-wave images acquired over ±10° and produced images depicting orbital and choroidal blood flow. RESULTS: With the array operated conventionally, Doppler modes exceeded Food and Drug Administration safety guidelines, but plane-wave modalities were well within guidelines. Plane-wave data allowed generation of high-quality compound B-mode images, with SNR increasing with the number of compounded frames. Real-time color-flow Doppler readily visualized orbital blood flow. Postprocessing of continuously acquired data blocks of 1.6-second duration allowed high-resolution depiction of orbital and choroidal flow over the cardiac cycle. CONCLUSIONS: Newly developed high-frequency linear arrays in combination with plane-wave techniques present opportunities for the evaluation of ocular anatomy and blood flow, as well as visualization and analysis of other transient phenomena such as vessel wall motion over the cardiac cycle and saccade-induced vitreous motion.

In vivo imaging of ocular blood flow using high-speed ultrasound.

Clinical ophthalmic ultrasound is currently performed with mechanically scanned, single-element probes, but these are unable to provide useful information about blood flow with Doppler techniques. Linear arrays are well-suited for the detection of blood flow, but commercial systems generally exceed FDA ophthalmic safety limits. A high-speed plane-wave ultrasound approach with an 18-MHz linear array was utilized to characterize blood flow in the orbit and choroid. Acoustic intensity was measured and the plane-wave mode was within FDA limits. Data were acquired for up to 2 sec and up to 20,000 frames/s with sets of steered plane-wave transmissions that spanned 2*θ degrees where 0 degrees was normal to the array. Lateral resolution was characterized using compounding from 1 to 50 transmissions and -6-dB lateral beamwidths ranged from 320 to 180 µm, respectively. Compounded high-frame-rate data were post-processed using a singular value decomposition spatiotemporal filter and then flow was estimated at each pixel using standard Doppler processing methods. A 1-cm diameter rotating scattering phantom and a 2-mm diameter tube with a flow of blood-mimicking fluid were utilized to validate the flow-estimation algorithms. In vivo data were obtained from the posterior pole of the human eye which revealed regions of flow in the choroid and major orbital vessels supplying the eye.

Coherence-Weighted Synthetic Focusing Applied to Photoacoustic Imaging Using a High-Frequency Annular-Array Transducer.

This paper presents an adaptive synthetic-focusing scheme that, when applied to photoacoustic (PA) data acquired using an annular array, improves focusing across a greater imaging depth and enhances spatial resolution. The imaging system was based on a 40-MHz, 5-element, annular-array transducer with a focal length of 12 mm and an 800-µm diameter hole through its central element to facilitate coaxial delivery of 532-nm laser. The transducer was raster-scanned to facilitate 3D acquisition of co-registered ultrasound and PA image data. Three synthetic-focusing schemes were compared for obtaining PA A-lines for each scan location: delay-and-sum (DAS), DAS weighted with a coherence factor (DAS + CF), and DAS weighted with a sign-coherence factor (DAS + SCF). Bench-top experiments that used an 80-µm hair were performed to assess the enhancement provided by the two coherence-based schemes. Both coherence-based schemes increased the signal-to-noise ratio by approximately 10 dB. When processed using the DAS-only scheme, the lateral dimension of the hair in a PA image with 20 dB dynamic range was between 300 µm and 1 mm for imaging depth ranging from 8 to 20 mm. In comparison, the DAS + CF scheme resulted in a lateral dimension of 200 to 450 µm over the same range. The DAS + SCF synthetic focusing further improved the smallest-resolvable dimension, which was between 150 and 400 µm over the same range of imaging depth. When used on PA data obtained from a 12-day-old mouse embryo, the DAS + SCF processing improved visualization of neurovasculature.