Relationship between transmission/reception conditions of high-frequency plane wave compounding and evaluation accuracy of extended amplitude envelope statistics.

The double-Nakagami (DN) model provides a method for analyzing the amplitude envelope statistics of quantitative ultrasound (QUS). In this study, the relationship between the sound field characteristics and the robustness of QUS evaluation was evaluated using five HF linear array probes and tissue-mimicking phantoms. Compound plane-wave imaging (CPWI) was used to acquire echo data. Five phantoms containing two types of scatterers were used to mimic fatty liver tissue. After clarifying the relationship between the sound field characteristics of the probes and QUS parameters, DN QUS parameters in 10 rat livers with different lipidification were evaluated using one HF linear array probe. For both phantom and in situ liver analyses, correlations between fat content and multiple QUS parameters were confirmed, suggesting that the combination of CPWI using a HF linear array probe with the DN model is a robust method for quantifying fatty liver and has potential clinical diagnostic applications.

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.

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.

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.

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.

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.

Single-shot measurements of the acoustic field of an electrohydraulic lithotripter using a hydrophone array.

Piezopolymer-based hydrophone arrays consisting of 20 elements were fabricated and tested for use in measuring the acoustic field from a shock-wave lithotripter. The arrays were fabricated from piezopolymer films and were mounted in a housing to allow submersion into water. The motivation was to use the array to determine how the shot-to-shot variability of the spark discharge in an electrohydraulic lithotripter affects the resulting focused acoustic field. It was found that the dominant effect of shot-to-shot variability was to laterally shift the location of the focus by up to 5 mm from the nominal acoustic axis of the lithotripter. The effect was more pronounced when the spark discharge was initiated with higher voltages. The lateral beamwidth of individual, instantaneous shock waves were observed to range from 1.5 mm to 24 mm. Due to the spatial variation of the acoustic field, the average of instantaneous beamwidths were observed to be 1 to 2 mm narrower than beamwidths determined from traditional single-point measurements that average the pressure measured at each location before computing beamwidth.

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.

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.

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.

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.

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.

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.

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.

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.

Subharmonic analysis using singular-value decomposition of ultrasound contrast agents.

Ultrasound contrast agents (UCAs) are designed to be used below 10 MHz, but interest is growing in studying the response of agents to high-frequency ultrasound. In this study, the subharmonic response of polymer-shelled UCAs with a mean diameter of 1.1 mum excited with 40-MHz tone-bursts of 1-20 cycles was analyzed. UCAs were diluted in water and streamed through a flow phantom that permitted single-bubble backscatter events to be acquired at peak-negative pressures from 0.75 to 5.0 MPa. At each exposure condition, 1000 single-bubble-backscatter events were digitized. Subharmonic content at 20 MHz was screened using a conventional and a singular-value-decomposition (SVD) method. The conventional method evaluated each event spectrum individually while the SVD method treated the 1000-event data set at one time. A subharmonic score (SHS) indicative of how much subharmonic content a 1000-event data set contained was computed for both methods. Empirical-simulation results indicated that SHSs obtained from the two methods were linearly related. Also, experimental data with both methods indicated that subharmonic likelihood increased with pulse duration and peaked near 2 MPa. The SVD method also yielded quantitative information about subharmonic events not available with the conventional method.

Beamwidth measurement of individual lithotripter shock waves.

New lithotripters with narrower foci and higher peak pressures than the original Dornier HM3 electrohydraulic lithotripter have proven to be less effective and less safe. Hence, accurate measurements of the focal characteristics of lithotripter shock waves are important. The current technique for measuring beamwidth requires a collection of single-point measurements over multiple shock waves, thereby introducing error as a result of any shock-to-shock variability. This work reports on the construction of a hydrophone array sensor and on array measurements of individual lithotripter shock waves. Beamwidths for an electrohydraulic lithotripter with a broad-focus HM3-style reflector and a narrow-focus modified reflector were measured using both new and worn electrodes as well as two different electrical charging potentials. The array measured the waveform, beamwidth, and focal location of individual shock waves. The HM3-style reflector produced repeatable focal waveforms and beam profiles at an 18 kV charging potential with new and worn electrodes. Corresponding measurements suggest a narrower beamwidth than reported previously from averaged point measurements acquired under the same conditions. In addition, a lack of consistency in the measured beam profiles at 23 kV underscores the value of measuring individual shock waves.

Improved high-resolution ultrasonic imaging of the eye.

Currently, virtually all clinical diagnostic ultrasound systems used in ophthalmology are based on fixed-focus, single-element transducers. High-frequency (> or = 20-MHz) transducers introduced to ophthalmology during the last decade have led to improved resolution and diagnostic capabilities for assessment of the anterior segment and the retina. However, single-element transducers are restricted to a small depth of field, limiting their capacity to image the eye as a whole. We fabricated a 20-MHz annular array probe prototype consisting of 5 concentric transducer elements and scanned an ex vivo human eye. Synthetically focused images of the bank eye showed improved depth of field and sensitivity, allowing simultaneous display of the anterior and posterior segments and the full lens contour. This capability may be useful in assessment of vitreoretinal pathologies and investigation of the accommodative mechanism.

In vitro mitral chordal cutting by high intensity focused ultrasound.

Mitral regurgitation, when it arises from functional restriction of mitral leaflet closure, can be relieved by surgical cutting of the mitral tendineae chordae. We hypothesized that high intensity focused ultrasound (HIFU) might be useful as a noninvasive extracorporeal technique for cutting mitral chordae. As a pilot study to test this hypothesis, we examined the in vitro feasibility of using HIFU to cut calf mitral chordae with diameters from 0.2 to 1.6 mm. Sixty-seven percent of chordae were completely cut with HIFU, operated at 4.67 MHz and 45 W acoustic power, with up to 120 pulses of 0.3-s duration at 2-s intervals. Forty-five percent were completely cut when the pulse duration was reduced to 0.2 s. The average diameter of those chordae, which were completely cut, was significantly smaller than that of incompletely cut chordae (0.59 +/- 0.30 versus 1.14 +/- 0.30 mm with a pulse duration of 0.2 s, p < 0.0001; 0.68 +/- 0.29 versus 1.32 +/- 0.20 mm with a pulse duration of 0.3 s, p < 0.0001). For each pulse duration, the number of pulses required for complete cutting exhibited a strong positive correlation with the chordae diameter. In conclusion, in vitro feasibility of mitral chordal cutting by HIFU depended on the diameter of chordae but was controllable by HIFU settings. (E-mail: abeyukio@aol.com).