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PURPOSE: Our goal was to test transcutaneous focused ultrasound in the form of ultrasonic propulsion and burst wave lithotripsy to reposition ureteral stones and facilitate passage in awake subjects. MATERIALS AND METHODS: Adult subjects with a diagnosed proximal or distal ureteral stone were prospectively recruited. Ultrasonic propulsion alone or with burst wave lithotripsy was administered by a handheld transducer to awake, unanesthetized subjects. Efficacy outcomes included stone motion, stone passage, and pain relief. Safety outcome was the reporting of associated anticipated or adverse events. RESULTS: Twenty-nine subjects received either ultrasonic propulsion alone (n = 16) or with burst wave lithotripsy bursts (n = 13), and stone motion was observed in 19 (66%). The stone passed in 18 (86%) of the 21 distal ureteral stone cases with at least 2 weeks follow-up in an average of 3.9±4.9 days post-procedure. Fragmentation was observed in 7 of the burst wave lithotripsy cases. All subjects tolerated the procedure with average pain scores (0–10) dropping from 2.1±2.3 to 1.6±2.0 (P = .03). Anticipated events were limited to hematuria on initial urination post-procedure and mild pain. In total, 7 subjects had associated discomfort with only 2.2% (18 of 820) propulsion bursts. CONCLUSIONS: This study supports the efficacy and safety of using ultrasonic propulsion and burst wave lithotripsy in awake subjects to reposition and break ureteral stones to relieve pain and facilitate passage.

INTRODUCTION AND OBJECTIVE: In clinical trial NCT03873259, a 2.6-mm lower pole stone was treated transcutaneously and ex vivo with 390-kHz burst wave lithotripsy (BWL) for 40 minutes and failed to break. The stone was subsequently fragmented with 650-kHz BWL after a 4-minute exposure. This study investigated how to fragment small stones and why varying the BWL frequency may more effectively fragment stones to dust. METHODS: A linear elastic theoretical model was used to calculate the stress created inside stones from shock wave lithotripsy (SWL) and different BWL frequencies mimicking the stone's size, shape, lamellar structure, and composition. To test model predictions about the impact of BWL frequency, matched pairs of stones (1–5 mm) were treated at (1) 390 kHz, (2) 830 kHz, and (3) 390 kHz followed by 830 kHz. The mass of fragments >1 and 2 mm was measured over 10 minutes of exposure. RESULTS: The linear elastic model predicts that the maximum principal stress inside a stone increases to more than 5.5 times the pressure applied by the ultrasound wave as frequency is increased, regardless of the composition tested. The threshold frequency for stress amplification is proportionate to the wave speed divided by the stone diameter. Thus, smaller stones may be likely to fragment at a higher frequency, but not at a lower frequency below a limit. Unlike with SWL, this amplification in BWL occurs consistently with spherical and irregularly shaped stones. In water tank experiments, stones smaller than the threshold size broke fastest at high frequency (p = 0.0003), whereas larger stones broke equally well to submillimeter dust at high, low, or mixed frequencies. CONCLUSIONS: For small stones and fragments, increasing frequency of BWL may produce amplified stress in the stone causing the stone to break. Using the strategies outlined here, stones of all sizes may be turned to dust efficiently with BWL.

Purpose: To test the effectiveness (Participant A) and tolerability (Participant B) of urinary stone comminution in the first-in-human trial of a new technology, burst-wave lithotripsy (BWL). Materials and Methods: An investigational BWL and ultrasonic propulsion system was used to target a 7-mm kidney stone in the operating room before ureteroscopy (Participant A). The same system was used to target a 7.5 mm ureterovesical junction stone in clinic without anesthesia (Participant B). Results: For Participant A, a ureteroscope inserted after 9 minutes of BWL observed fragmentation of the stone to

Despite the growing incidence of urinary stones, the fundamental interventions for urinary stones have remained the same for several decades. However, technical innovations in ultrasound have enabled new strategies for stone management. Our team aims to employ these methods to establish a new paradigm to treat stones in an office or clinic rather than a surgical suite. Technologies include new imaging methods to detect and characterize stones, burst wave lithotripsy to fragment stones using focused ultrasound rather than shock waves, and ultrasonic propulsion to promote clearance of fragments, all using a single ultrasound platform. This presentation will describe the principles and development of these technologies, as well as the fruitful partnerships between teams of basic scientists, engineers, physicians, and industry that have enabled rapid development of these concepts to successful clinical trials. [Work supported by NIDDK P01 DK043881 and the Focused Ultrasound Foundation.]

Objective: Our goals were to validate stone comminution with an investigational burst wave lithotripsy (BWL) system in patient-relevant conditions and to evaluate the use of ultrasonic propulsion to move a stone or fragments to aid in observing the treatment endpoint. Materials and Methods: The Propulse-1 system, used in clinical trials of ultrasonic propulsion and upgraded for BWL trials, was used to fragment 46 human stones (5–7 mm) in either a 15-mm or 4-mm diameter calix phantom in water at either 50% or 75% dissolved oxygen level. Stones were paired by size and composition, and exposed to 20-cycle, 390-kHz bursts at 6-MPa peak negative pressure (PNP) and 13-Hz pulse repetition frequency (PRF) or 7-MPa PNP and 6.5-Hz PRF. Stones were exposed in 5-minute increments and sieved, with fragments >2 mm weighed and returned for additional treatment. Effectiveness for pairs of conditions was compared statistically within a framework of survival data analysis for interval censored data. Three reviewers blinded to the experimental conditions scored ultrasound imaging videos for degree of fragmentation based on stone response to ultrasonic propulsion. Results: Overall, 89% (41/46) and 70% (32/46) of human stones were fully comminuted within 30 and 10 minutes, respectively. Fragments remained after 30 minutes in 4% (1/28) of calcium oxalate monohydrate stones and 40% (4/10) of brushite stones. There were no statistically significant differences in comminution time between the two output settings (p = 0.44), the two dissolved oxygen levels (p = 0.65), or the two calyx diameters (p = 0.58). Inter-rater correlation on endpoint detection was substantial (Fleiss' kappa = 0.638, p

Renal colic encounters are common; in the United States alone, they represent greater than one million annual emergency department (ED) visits. Most of these stones are managed conservatively with a trial of passage. However, some lead to repeat colic episodes, secondary ED visits, increased anxiety, and increased cost. Of the 5%–10% of symptomatic stones that become lodged at the ureteropelvic junction and are larger than 5 mm, most require operative intervention. In the process of executing a NASA‐funded study of ultrasonic repositioning of kidney stones, the subject was administered fluid to dilate the collecting system, placed in Trendelenburg bed positioning, and rolled to both sides. During this process a symptomatic, obstructing 9‐mm ureteropelvic junction stone moved back into the kidney's lower pole/infundibulum and symptoms were immediately resolved. The patient remained asymptomatic for a period of 5 weeks at which point elective intervention was scheduled. This case demonstrates that ureteropelvic junction stones may be repositioned in a non‐invasive manner, turning a stone that requires urgent intervention into one that can be managed electively.

INTRODUCTION AND OBJECTIVE:The feasibility of ultrasonic propulsion and burst wave lithotripsy (BWL) to noninvasively reposition distal ureteral stones to facilitate passage and relieve pain was te...

INTRODUCTION AND OBJECTIVE:We report stone comminution in the first human subjects by burst wave lithotripsy (BWL), which is the transcutaneous application of focused, cyclic ultrasound pulses.METH...

Purpose: Ultrasonic propulsion is an investigative modality to noninvasively image and reposition urinary stones. Our goals were to test safety and effectiveness of new acoustic exposure conditions from a new transducer, and to use simultaneous ureteroscopic and ultrasonic observation to quantify stone repositioning. Materials and Methods: During operation, ultrasonic propulsion was applied transcutaneously, whereas stone targets were visualized ureteroscopically. Exposures were 350 kHz frequency, ≤200 W/cm(2) focal intensity, and ≤3-second bursts per push. Ureteroscope and ultrasound (US) videos were recorded. Video clips with and without stone motion were randomized and scored for motion ≥3 mm by independent reviewers blinded to the exposures. Subjects were followed with telephone calls, imaging, and chart review for adverse events. Results: The investigative treatment was used in 18 subjects and 19 kidneys. A total of 62 stone targets were treated ranging in size from a collection of “dust” to 15 mm. Subjects received an average of 17 ± 14 propulsion bursts (per kidney) for a total average exposure time of 40 ± 40 seconds. Independent reviewers scored at least one stone movement ≥3 mm in 18 of 19 kidneys (95%) from the ureteroscope videos and in 15 of 19 kidneys (79%) from the US videos. This difference was probably because of motion out of the US imaging plane. Treatment repositioned stones in two cases that would have otherwise required basket repositioning. No serious adverse events were observed with the device or procedure. Conclusions: Ultrasonic propulsion was shown to be safe, and it effectively repositioned stones in 95% of kidneys despite positioning and access restrictions caused by working in an operating room on anesthetized subjects.

The number and distribution of lung ultrasound (LUS) imaging artifacts—B-lines—is correlated with the presence of lung interstitial syndrome such as viral infection and pulmonary edema. The detection and quantification of B-lines is machine and operator dependent, and the mechanisms for B-line formation are not fully understood. The goals of this work were to collect RF data during LUS exams in patients with pulmonary edema and to compare to the signals and corresponding images simulated numerically to elucidate the B-line formation process. Verasonics ultrasound engine (VUE) with a phased array probe (4.5 MHz) was used to perform standard 10-zone LUS in ten patients with confirmed pulmonary edema. The RF data corresponding to each B-mode image and a series of 35 plane wave acquisitions were collected for off-line analyses. Finite element modeling of LUS pulse propagation was performed in COMSOL with fluid-filled inclusions of variable sizes and shapes in air-like medium simulating edematous lung areas. The B-mode image resulting from the simulated RF signals was reconstructed using VUE beamforming. The B-lines similar to those observed experimentally formed in simulated images only under specific conditions of sizes and shapes of water-filled areas relatively to LUS imaging wavelength. [Work supported by NIH R01EB023910.]

Burst wave lithotripsy (BWL) is a new non-invasive method for stone comminution using bursts of sub-megahertz ultrasound. A porcine model of urolithiasis and techniques to implement BWL treatment has been developed to evaluate its effectiveness and acute safety. Six human calcium oxalate monohydrate stones (6–7 mm) were hydrated, weighed, and surgically implanted into the kidneys of three pigs. Transcutaneous stone treatments were performed with a BWL transducer coupled to the skin via an external water bath. Stone targeting and treatment monitoring were performed with a co-aligned ultrasound imaging probe. Treatment exposures were applied in three 10-minute intervals for each stone. If sustained cavitation in the parenchyma was observed by ultrasound imaging feedback, treatment was paused and the pressure amplitude was decreased for the remaining time. Peak negative focal pressures between 6.5 and 7 MPa were applied for all treatments. After treatment, stone fragments were removed from the kidneys. At least 50% of each stone was reduced to

INTRODUCTION: A considerable publication record exists comparing sensitivity and specificity of radiological ultrasound (including point of care ultrasound) to computerized tomography for stone disease. However, the practical application of in-office ultrasound to support the growing number of kidney stone centers around the world represents a nuanced topic that is ripe for study and discussion. METHODS: We provide a descriptive analysis of how in-office ultrasound is being used as an adjunct to clinical care based on our experience during 50 days in clinic at an institutionally affiliated, multidisciplinary kidney stone center. Clinic subjects gave consent and underwent ultrasound as part of research studies. Ultrasonograms were shared with and verified by the treating physician before the patient was discharged from care. We counted the number of times research imaging altered the care plan. RESULTS: Of the 60 patients enrolled the clinician used the information obtained from the studies in 20 (33%) to determine the course of clinical care that resulted in a change in treatment or process. CONCLUSIONS: Ultrasound has the potential to be a cost-effective and valuable tool that can provide more efficient workflow within a kidney stone center or urology clinic.

B-Flow imaging directly displays the flowing intravascular echoes during real-time gray-scale ultrasound without using Doppler techniques. The objective of our study was to evaluate the feasibility of B-Flow imaging in the placenta and to evaluate the artifacts seen on B-Flow imaging. After IRB approval, 36 women (17 normal and 19 high risk women) were enrolled in our study. B-Flow images were acquired on GE LOGIC E9 machine. Retrospective analysis of the B-Flow and cine capture images was performed for artifacts and for vessels visualized. Pregnant women enrolled in the study ranged from 19 to 43 years of age with an average age of 31.7 years. Gestational age varied from 17 weeks and five days to 36 weeks and three days with an average of 26 weeks and three days. From a total of 161 B-Flow images reviewed by one researcher, 15 images were acceptable with no evidence of artifact. The remainder of the images had some artifact in them. For the 36 women with color Doppler and B-Flow images reviewed by the two independent blinded reviewers, a total of 144 reads were obtained. More small horizontal (p = 0.046) and small vertical running vessels (p

Greater visual contrast between calculi and tissue would improve ultrasound (US) imaging of urolithiasis and potentially expand clinical use. The color Doppler twinkling artifact has been suggested to provide enhanced contrast of stones compared with brightness mode (B-mode) imaging, but results are variable. This work provides the first quantitative measure of stone contrast in humans for B-mode and color Doppler mode, forming the basis to improve US for the detection of stones.Using a research ultrasound system, B-mode imaging was tuned for detecting stones by applying a single transmit angle and reduced signal compression. Stone twinkling with color Doppler was tuned by using low-frequency transmit pulses, longer pulse durations, and a high-pulse repetition frequency. Data were captured from 32 subjects, with 297 B-mode and Doppler images analyzed from 21 subjects exhibiting twinkling signals. The signal to clutter ratio (i.e., stone to background tissue) (SCR) was used to compare the contrast of a stone on B-mode with color Doppler, and the contrast between stone twinkling and blood-flow signals within the kidney.The stone was the brightest object in only 54% of B-mode images and 100% of Doppler images containing stone twinkling. On average, stones were isoechoic with the tissue clutter on B-mode (SCR = 0 dB). Stone twinkling averaged 37 times greater contrast than B-mode (16 dB, p 0.0001) and 3.5 times greater contrast than blood-flow signals (5.5 dB, p = 0.088).This study provides the first quantitative measure of US stone to tissue contrast in humans. Stone twinkling contrast is significantly greater than the contrast of a stone on B-mode. There was also a trend of stone twinkling signals having greater contrast than blood-flow signals in the kidney. Dedicated optimization of B-mode and color Doppler stone imaging could improve US detection of stones.

Feasibility of ultrasonic propulsion and burst wave lithotripsy (BWL) to noninvasively reposition distal ureteral stones to facilitate passage and relieve pain was tested. Patients presenting to the clinic or emergency department were recruited. Thirteen subjects underwent ultrasonic propulsion (lower amplitude, longer duration pulses) alone, and 10 subjects also received intermittent BWL (higher amplitude, shorter duration pulses). All participants were awake and underwent a pain assessment pre- and post-procedure. For analysis, subjects were sub-categorized based on whether their stone was acute or chronic (present for ≤10 days or >10 days from their initial ED or symptomatic presentation, respectively). Seventeen subjects were enrolled in the acute study population and 6 subjects were enrolled in the chronic population. Overall, 94% of acute stones passed in an average of 3.4 days post-procedure relative to 54% in 7.5 days in the American Urological Association guidelines. 67% of chronic cases passed stones or fragments, and two surgeries were cancelled. Pain reduction was statistically significant ( p = 0.0215). Adverse events were limited to hematuria on initial urination post-procedure (BWL only, n = 3) and a mild sensation, akin to a pinprick, associated with fewer than 10 of 620 propulsion bursts ( n = 3). [Work supported by NIH-P01-DK04331.]

We report stone comminution in the first 18 human subjects by burst wave lithotripsy (BWL). Subjects undergoing clinical ureteroscopy (URS) for at least one stone ≤12 mm on computed tomography (CT) are recruited. During the planned URS, either before or after ureteroscope insertion, BWL is administered with a handheld probe for 10 min, and any stone fragmentation and tissue injury are observed. The primary effectiveness outcome is the volume percent comminution of the stone into fragments ≤2 mm, where fragment volume is determined by μCT of basketed fragments or image processing of the URS video using the laser fiber as a size reference. The primary safety outcome is independent, blinded grading of tissue injury from the URS video. Overall, 10 of 22 stones (45%) fragmented completely in 10 min. 64% and 73% were projected to fragment completely in 15 and 40 min, respectively. For reference, shock wave lithotripsy success is about 65% to fragments ≤4 mm in 40 min. Of the other six stones, one was larger than the beamwidth, two were smaller than the wavelength, and the ureteroscope introduced air bubbles around another. Only mild reddening with some hematuria was observed ureteroscopically. [Work supported by NIH-P01-DK04331.]

It is hypothesized a 2.6-mm stone was too small to break with 390-kHz burst wave lithotripsy (BWL). In clinical trial NCT03873259, a 2.6-mm stone failed to break after 10 min of 390-kHz BWL and was removed intact. Ex vivo, the stone failed to break after another 30 min at 390 kHz but broke into four pieces in 4 min at 650 kHz. A linear elastic model was used to calculate the stress created inside stones of different sizes, shapes, and compositions by shock wave lithotripsy (SWL) and different BWL frequencies. The model predicts above a threshold frequency proportionate to wave speed over stone length, the maximum principal stress inside a stone increases to more than five times the acoustic pressure applied. Thus, smaller stones may fragment at higher but not lower frequency. Amplification remains with irregularly shaped stones but is not seen with an SWL waveform. Ex vivo, stones smaller than 3 mm broke fastest at 830 kHz while larger stones broke fastest with 390 kHz followed by 830 kHz. For small stones and fragments, increasing BWL frequency many produce, amplified stress in the stone causing the stone to break to smaller fragments to pass. [Work supported by NIH-P01-DK04331 and NIH-K01-DK104854.]

The goal is to test effectiveness and safety of transcutaneous ultrasound pulses for facilitating clearance of residual urinary stone fragments in a randomized control trial (RCT). The study is conducted in a clinic setting with the control and treatment arms undergoing all the same activities with the exception of the ultrasonic propulsion procedure and associated pain questionnaire. Subjects are followed 90 days for assessment of adverse events and for up to 5 years for stone growth and symptomatic stone visits. Twenty-six of 33 subjects have been recruited in each arm The most recent treatment is reported. The subject received shock wave lithotripsy and did not pass any fragments for 17 months. The subject was randomized to the treatment arm. Fragments began moving with the third 3-s propulsion pulse at output 2 of 5 levels. Fifty-two percent of propulsion pulses (41 of 79) resulted in fragment movement. The subject reported no pain at the beginning or end of the procedure and telephoned within 2 h to report passing 9 fragments, no hematuria, and no adverse events. The treatment results of this RCT are compelling as an immediate and casual effect was measured. [Work supported by NIH-P01-DK043881 and VA Puget Sound resources.]

Objectives To assess the effect of orientation on the stiffness measurement by shear wave elastography (SWE) within a thyroid nodule. Methods Forty-five patients with 50 thyroid nodules were enrolled in this study. After a short sonographic examination, SWE images were acquired in transverse and longitudinal orientations. Multiple elastograms of each nodule were obtained in both orientations. Mean and maximum stiffness values were recorded from each region of interest. The overall mean and maximum stiffness values of each nodule were calculated for both orientations separately. The concordance correlation coefficient was used to assess overall agreement between measurements. A receiver operating characteristic curve analysis was conducted to assess diagnostic performance for benign versus malignant nodules. Results The 45 patients included 6 men and 39 women (mean age, 53 years; range, 23–84 years). The mean stiffness values ± SD were 19.1 ± 18.4 and 20.9 ± 21.5 kPa for transverse and longitudinal measurements, respectively, with a small overall bias between the orientations (1.8 kPa; P = .09). Overall agreement was good (concordance correlation coefficient, 0.93) although moderated somewhat after the stiffness values were log transformed to reduce skewness (concordance correlation coefficient, 0.76). Of the 50 nodules, 6 were classified as malignant. The area under the curve based on the mean stiffness value from longitudinal images tended to be better than for transverse images, but the difference was not statistically significant (0.93 versus 0.83; P = .17). Conclusions Our study has shown that good diagnostic performance can be achieved by using SWE in longitudinal and transverse orientations. Moderate to good agreement in mean and maximum stiffness values for both orientations was observed, with only a small bias. Diagnostic performance for benign and malignant nodules was similar. The similar performance of both orientations gives flexibility in imaging patients with anatomic or physical limitations.

Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones.Subjects underwent ultrasonic propulsion while awake without sedation in clinic, or during ureteroscopy while anesthetized. Ultrasound and a pain questionnaire were completed before, during and after propulsion. The primary outcome was to reposition stones in the collecting system. Secondary outcomes included safety, controllable movement of stones and movement of stones less than 5 mm and 5 mm or greater. Adverse events were assessed weekly for 3 weeks.Kidney stones were repositioned in 14 of 15 subjects. Of the 43 targets 28 (65%) showed some level of movement while 13 (30%) were displaced greater than 3 mm to a new location. Discomfort during the procedure was rare, mild, brief and self-limited. Stones were moved in a controlled direction with more than 30 fragments passed by 4 of the 6 subjects who had previously undergone a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of a large stone at the ureteropelvic junction. In 4 subjects a seemingly large stone was determined to be a cluster of small passable stones after they were moved.Ultrasonic propulsion was able to successfully reposition stones and facilitate the passage of fragments in humans. No adverse events were associated with the investigational procedure.

PURPOSE The aim of the study was to assess intrareader and interreader variability in placing a region of interest in the elastography color map in the thyroid nodule. METHOD AND MATERIALS After institutional review board approval, elastograms were obtained by shear wave elastography from 38 individuals, with a total of 60 thyroid nodules. Two readers reviewed all images while blinded to the cytopathology or final histopathology results and to each other's measurements. For each image, readers first performed a qualitative assessment and recorded presence of stiff region(s) and number of stiff regions. Then, they placed a 3-mm circular region of interest on the stiffest region to quantify the mean and maximum stiffness in kilopascals. Intrareader and interreader agreement was summarized for categorical variables using Cohen κ and for continuous variables using the concordance correlation coefficient (CCC) and coefficient of variation. RESULTS There was good overall intrareader and interreader agreement for the presence of stiff regions and number of stiff regions after classifying them as 0, 1, and greater than 1 regions (κ = 0.78-0.81 and 0.74-0.79, respectively). There was also good overall agreement for the the following quantitative measurements: mean kPa (CCC = 0.97 and 0.93) and max kPa (CCC = 0.97 and 0.93). The intrareader and interreader coefficient of variation was 13% and 21% for mean kPa and 14% and 21% for max kPa. CONCLUSIONS There can be differences in measurement of stiffness by 2 different operators in softer nodules with shear wave imaging because of the lack of brighter areas on the color elastograms. A standardized technique is necessary to be able to compare results from 1 study to the next.

The purpose of the study described here was to evaluate the presence and types of artifacts seen in color elastograms in thyroid elastography using shear wave elastography. This Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant study was approved by the ethics committee of our institution, and all patients provided written informed consent. One hundred seventy-eight patients (40 men and 138 women; mean age, 49 y; range, 19–84 y) were enrolled for a total of 241 thyroid nodules. After a short ultrasound (US) examination, SWE images were acquired at multiple levels in the nodule in transverse and longitudinal orientations. A total of 1297 images were obtained from 241 nodules for an average of 5.4 ± 2.7 (mean ± standard deviation) images per nodule. A retrospective review of all images was performed by one reviewer experienced in thyroid elastography. Two hundred eighty images (21.6%) were rated as good quality, and 112 (8.6%) were rated as moderate quality without artifacts. A total of 905 (69.8%) images had some artifact present, though most of these images (73.4%) were still interpretable. Two hundred forty-one images (18.6% of all images) were considered uninterpretable because of artifact. The most common types of artifacts were due to operator error (44.6% of all images), primarily compression (36.5% of all images). Other artifacts seen were due to anatomy (presence of carotid pulsation or adjacent to thyroid or location in isthmus, 11% of all images), nodule characteristics (cystic and calcified nodules or large nodules with lack of penetration, 17% of all images) and other artifacts that could not be explained by the prior mentioned causes (13% of all images). Our study indicates that artifacts are common in elastography images. Operator error was the most common type of artifact we saw. This should be easily correctable by adequate knowledge and recognition with subsequent correction of the artifacts.

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

PURPOSE: Posterior acoustic shadow width has been proposed as a more accurate measure of kidney stone size compared to direct measurement of stone width on ultrasound (US). Published data in humans to date have been based on a research US system. Herein, we compare these two measurements in clinical US images. METHODS: Thirty patient image sets where computed tomography (CT) and US images were captured less than one day apart were retrospectively reviewed. Five blinded reviewers independently assessed the largest stone in each image set for shadow presence and size. Shadow size was compared to US and CT stone sizes. RESULTS: Eighty percent of included stones demonstrated anacoustic shadow; 83% of stones without a shadow were ≤ 5 mm on CT. Average stone size was 6.5 mm ± 4.0 on CT, 10.3 mm ± 4.1 on US, and 7.5 mm ± 4.2 by shadow width. On average, US overestimated stone size by 3.8 mm ± 2.4 based on stone width (p < 0.001) and 1.0 mm ± 1.4 based on shadow width (p < 0.0098). Shadow measurements decreased misclassification of stones by 25% among three clinically relevant size categories (≤ 5 mm, 5.1 – 10 mm, > 10 mm), and by 50% for stones ≤ 5 mm. CONCLUSIONS: US overestimates stone size compared to CT. Retrospective measurement of the acoustic shadow from the same clinical US images is a more accurate reflection of true stone size than direct stone measurement. Most stones without a posterior shadow are ≤ 5 mm.

In the first-in-human trial of ultrasonic propulsion, subjects passed collections of residual stone fragments after repositioning with a C5-2 probe. Here, effectiveness and safety in moving multiple fragments is compared between the C5-2 and a custom SC-50 probe that produces a longer beam and burst duration.

In the first-in-human trial of ultrasonic propulsion, subjects passed collections of residual stone fragments repositioned with a C5-2 probe. Here, effectiveness and safety in moving multiple fragments are compared between the C5-2 and a custom (SC-50) probe that produces a longer focal beam and burst duration.Effectiveness was quantified by the number of stones expelled from a calyx phantom consisting of a 30-mm deep, water-filled well in a block of tissue mimicking material. Each probe was positioned below the phantom to move stones against gravity. Single propulsion bursts of 50 ms or 3 s duration were applied to three separate targets: 10 fragments of 2 different sizes (1-2 and 2-3 mm) and a single 4 × 7 mm human stone. Safety studies consisted of porcine kidneys exposed to an extreme dose of 10-minute burst duration, including a 7-day survival study and acute studies with surgically implanted stones.Although successful in the clinical trial, the shorter focal beam and maximum 50 ms burst duration of the C5-2 probe moved stones, but did not expel any stones from the phantom's 30-mm deep calyx. The results were similar with the SC-50 probe under the same 50 ms burst duration. Longer (3 s) bursts available with the SC-50 probe expelled all stones at both 4.5 and 9.5 cm "skin-to-stone" depths with lower probe heating compared to the C5-2. No abnormal behavior, urine chemistry, serum chemistry, or histological findings were observed within the kidney or surrounding tissues for the 10 min burst duration used in the animal studies.A longer focal beam and burst duration improved expulsion of a stone and multiple stone fragments from a phantom over a broad range of clinically relevant penetration depths and did not cause kidney injury in animal studies.

The purpose of this study was to measure the accuracy of stone-specific algorithms (S-mode) and the posterior acoustic shadow for determining kidney stone size with ultrasound (US) in vivo.Thirty-four subjects with 115 renal stones were prospectively recruited and scanned with S-mode on a research US system. S-mode is gray-scale US adjusted to enhanced stone contrast and resolution by minimizing compression and averaging, and increasing line density and frequency. Stone and shadow width were compared with a recent CT scan and, in 5 subjects with 18 stones, S-mode was compared with a clinical US system.Overall, 84% of stones identified on CT were detected on S-mode and 66% of these shadowed. Seventy-three percent of the stone measurements and 85% of the shadow measurements were within 2 mm of the size on CT. A posterior acoustic shadow was present in 89% of stones over 5 mm versus 53% of stones under 5 mm. S-mode visualized 78% of stones, versus 61% for the clinical system. S-mode stone and shadow measurements differed from CT by 1.6 ± 1.0 mm and 0.8 ± 0.6 mm, respectively, compared with 2.0 ± 1.5 mm and 1.6 ± 1.0 mm for the clinical system.S-mode offers improved visualization and sizing of renal stones. With S-mode, sizing of the stone itself and the posterior acoustic shadow were similarly accurate. Stones that do not shadow are most likely5 mm and small enough to pass spontaneously.

We describe the development of fetal brain lesions after Zika virus (ZIKV) inoculation in a pregnant pigtail macaque. Periventricular lesions developed within 10 d and evolved asymmetrically in the occipital-parietal lobes. Fetal autopsy revealed ZIKV in the brain and significant cerebral white matter hypoplasia, periventricular white matter gliosis, and axonal and ependymal injury. Our observation of ZIKV-associated fetal brain lesions in a nonhuman primate provides a model for therapeutic evaluation.

Background: Patients undergoing mastectomy and prosthetic breast reconstruction have significant acute postsurgical pain, routinely mandating inpatient hospitalization. Liposomal bupivacaine (LB) (Exparel; Pacira Pharmaceuticals, Inc., Parsippany, N.J.) has been shown to be a safe and effective pain reliever in the immediate postoperative period and may be advantageous for use in mastectomy and breast reconstruction patients. Methods: Retrospective review of 90 immediate implant-based breast reconstruction patient charts was completed. Patients were separated into 3 groups of 30 consecutively treated patients who received 1 of 3 pain treatment modalities: intravenous/oral narcotic pain control (control), bupivacaine pain pump, or LB injection. Length of hospital stay, patient-reported Visual Analog Scale (VAS) pain scores, postoperative patient-controlled analgesia usage, and nausea-related medication use were abstracted and subjected to analysis of variance and multiple linear-regression analysis, as appropriate. Results: Subjects were well-matched for age (P = 0.24) regardless of pain-control modality. Roughly half (53%) of control and pain pump–treated subjects had bilateral procedures, as opposed to 80% of LB subjects. Mean length of stay for LB subjects was significantly less than control (1.5 days vs 2.00 days; P = 0.016). LB subjects reported significantly lower VAS pain scores at 4, 8, 12, 16, and 24 hours compared with pain pump and control (P < 0.01). There were no adverse events in the LB group. Conclusion: Use of LB in this group of immediate breast reconstruction patients was associated with decreased patient VAS pain scores in the immediate postoperative period compared with bupivacaine pain pump and intravenous/oral narcotic pain management and reduced inpatient length of stay.

Preliminary investigational use of ultrasound to reposition human kidney stones is reported. The three study arms include: de novo stones, post-lithotripsy fragments, and large stones within the preoperative setting. A pain questionnaire is completed immediately prior to and following propulsion. A maximum of 40 push attempts are administered. Movement is classified as no motion, movement with rollback or jiggle, or movement to a new location. Seven subjects have been enrolled and undergone ultrasonic propulsion to date. Stones were identified, targeted, and moved in all subjects. Subjects who did not have significant movement were in the de novo arm. None of the subjects reported pain associated with the treatment. One subject in the post-lithotripsy arm passed two small stones immediately following treatment corresponding to the two stones displaced from the interpolar region. Three post-lithotripsy subjects reported passage of multiple small fragments within two weeks of treatment. In four subjects, ultrasonic propulsion identified a collection of stones previously characterized as a single stone on KUB and ultrasound. There have been no treatment related adverse events reported with mean follow-up of 3 months. [Trial supported by NSBRI through NASA NCC 9-58. Development supported by NIH DK043881and DK092197.]

Sensitivity and specificity data show users have more difficulty in identifying stones accurately in B-mode ultrasound than x-ray CT. Our goal was to evaluate the signal to noise (SNR) of a new stone specific imaging algorithm, S-mode based on Color Doppler twinkling artifact, to B-mode. Forty sets of B- and S-mode imaging data were collected from 16 subjects using a Philips HDI C5-2 imaging probe and Verasonics ultrasound system. Two ways S-mode differs from Doppler is that it filters out blood flow signal and uses reverse color write priority to add color to echogenic regions only. For both B- and S-mode raw data, we calculate SNR of the magnitude (brightness) of the stone signal compared to the second highest magnitude in the image. The mean and standard deviation of the SNR was 1.6 ± 0.7 for B-mode and 37 ± 24 for S-mode, with 1 being the stone is equally bright as, and difficult to distinguish from, background. In this human study of S-mode, stones appeared over 30 times brighter than background and with over 20 times the contrast to background seen in B-mode. [Work supported by NIH NIDDK grants DK043881 and DK092197, and NSBRI through NASA NCC 9-58.]