Application of novel burst wave lithotripsy and ultrasonic propulsion technology for the treatment of ureteral calculi in a bottlenose dolphin (Tursiops truncatus) and renal calculi in a harbor seal (Phoca vitulina).

Marine mammals may develop kidney stones, which can be challenging to treat. We describe burst wave lithotripsy (BWL) and ultrasonic propulsion to treat ureteral calculi in a 48-year-old female bottlenose dolphin (Tursiops truncatus) and to reduce renal stone burden in a 23-year-old male harbor seal (Phoca vitulina). BWL and ultrasonic propulsion were delivered transcutaneously in sinusoidal ultrasound bursts to fragment and reposition stones. Targeting and monitoring were performed with real-time imaging integrated within the BWL system. Four dolphin stones were obtained and fragmented ex vivo. The dolphin case received a 10-min and a 20-min BWL treatment conducted approximately 24 h apart to treat two 8-10 mm partially obstructing right mid-ureteral stones, using oral sedation alone. For the harbor seal, while under general anesthesia, retrograde ureteroscopy attempts were unsuccessful because of ureteral tortuosity, and a 30-min BWL treatment was targeted on one 10-mm right kidney stone cluster. All 4 stones fragmented completely to < 2-mm fragments in < 20 min ex vivo. In the dolphin case, the ureteral stones appeared to fragment, spread apart, and move with ultrasonic propulsion. On post-treatment day 1, the ureteral calculi fragments shifted caudally reaching the ureteral orifice on day 9. On day 10, the calculi fragments passed, and the hydroureter resolved. In the harbor seal, the stone cluster was observed to fragment and was not visible on the post-operative computed tomography scan. The seal had gross hematuria and a day of behavior indicating stone passage but overall, an uneventful recovery. BWL and ultrasonic propulsion successfully relieved ureteral stone obstruction in a geriatric dolphin and reduced renal stone burden in a geriatric harbor seal.

Development of an Automated Ultrasound Signal Indicator of Lung Interstitial Syndrome.

OBJECTIVES: The number and distribution of lung ultrasound (LUS) imaging artifacts termed B-lines correlate with the presence of acute lung disease such as infection, acute respiratory distress syndrome (ARDS), and pulmonary edema. Detection and interpretation of B-lines require dedicated training and is machine and operator-dependent. The goal of this study was to identify radio frequency (RF) signal features associated with B-lines in a cohort of patients with cardiogenic pulmonary edema. A quantitative signal indicator could then be used in a single-element, non-imaging, wearable, automated lung ultrasound sensor (LUSS) for continuous hands-free monitoring of lung fluid. METHODS: In this prospective study a 10-zone LUS exam was performed in 16 participants, including 12 patients admitted with acute cardiogenic pulmonary edema (mean age 60 ± 12 years) and 4 healthy controls (mean age 44 ± 21). Overall,160 individual LUS video clips were recorded. The LUS exams were performed with a phased array probe driven by an open-platform ultrasound system with simultaneous RF signal collection. RF data were analyzed offline for candidate B-line indicators based on signal amplitude, temporal variability, and frequency spectrum; blinded independent review of LUS images for the presence or absence of B-lines served as ground truth. Predictive performance of the signal indicators was determined with receiving operator characteristic (ROC) analysis with k-fold cross-validation. RESULTS: Two RF signal features-temporal variability of signal amplitude at large depths and at the pleural line-were strongly associated with B-line presence. The sensitivity and specificity of a combinatorial indicator were 93.2 and 58.5%, respectively, with cross-validated area under the ROC curve (AUC) of 0.91 (95% CI = 0.80-0.94). CONCLUSION: A combinatorial signal indicator for use with single-element non-imaging LUSS was developed to facilitate continuous monitoring of lung fluid in patients with respiratory illness.

Tissue properties and respiratory kinematics of the tongue base and soft palate in the obese OSA minipig.

Obesity is a common finding and a major pathogenetic factor in obstructive sleep apnea (OSA) in adults. To understand the mechanisms behind this, the present study investigated the tissue properties and respiratory kinematics of the tongue base and soft palate in the obese OSA minipig model. In 4 verified obese/OSA and 3 non-obese/non-OSA control minipigs, MRI fat-weighted images, ultrasound elastography (USE), and sleep video-fluoroscopy (SVF) were performed to quantify the fat composition, tissue stiffness, and respiratory kinematics of the tongue base and soft palate during sedated sleep. The results indicated that the fat composition gradually increased from the rostral to caudal tongue base, particularly in the posterior 1/3 of the tongue base, regardless of the presence of obesity and OSA. However, this trend was not seen in the soft palate and pharyngeal wall. The pharyngeal wall presented the highest fat composition as compared with the tongue base and soft palate. Overall, obese OSA minipigs showed stiffer tongue tissue than the controls, particularly in the rostral region of the tongue in obese Yucatan minipigs. The respiratory moving ranges of the soft palate were greater in both dorsal-ventral and rostral-caudal directions and during both respiratory and expiratory phases in OSA obese than control minipigs, and the largest moving ranges were seen in OSA obese Panepinto minipigs. The moving range of the tongue base was significantly smaller. These results suggest more fat infiltration in the caudal region of the tongue base regardless of the presence of obesity and/or OSA. The greater tissue stiffness of the tongue in obese OSA minipigs may result from altered neuromuscular drive.

First Series Using Ultrasonic Propulsion and Burst Wave Lithotripsy to Treat Ureteral Stones.

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.

Fragmentation of Stones by Burst Wave Lithotripsy in the First 19 Humans.

PURPOSE: We report stone comminution in the first 19 human subjects by burst wave lithotripsy (BWL), which is the transcutaneous application of focused, cyclic ultrasound pulses. MATERIALS AND METHODS: This was a prospective multi-institutional feasibility study recruiting subjects undergoing clinical ureteroscopy (URS) for at least 1 stone ≤12 mm as measured on computerized tomography. During the planned URS, either before or after ureteroscope insertion, BWL was administered with a handheld transducer, and any stone fragmentation and tissue injury were observed. Up to 3 stones per subject were targeted, each for a maximum of 10 minutes. The primary effectiveness outcome was the volume percent comminution of the stone into fragments ≤2 mm. The primary safety outcome was the independent, blinded visual scoring of tissue injury from the URS video. RESULTS: Overall, median stone comminution was 90% (IQR 20, 100) of stone volume with 21 of 23 (91%) stones fragmented. Complete fragmentation (all fragments ≤2 mm) within 10 minutes of BWL occurred in 9 of 23 stones (39%). Of the 6 least comminuted stones, likely causative factors for decreased effectiveness included stones that were larger than the BWL beamwidth, smaller than the BWL wavelength or the introduction of air bubbles from the ureteroscope. Mild reddening of the papilla and hematuria emanating from the papilla were observed ureteroscopically. CONCLUSIONS: The first study of BWL in human subjects resulted in a median of 90% comminution of the total stone volume into fragments ≤2 mm within 10 minutes of BWL exposure with only mild tissue injury.

Improving Burst Wave Lithotripsy Effectiveness for Small Stones and Fragments by Increasing Frequency: Theoretical Modeling and Ex Vivo Study.

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.

First In-Human Burst Wave Lithotripsy for Kidney Stone Comminution: Initial Two Case Studies.

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 <2 mm fragments. Participant B tolerated the procedure without pain from BWL, required no anesthesia, and passed the stone on day 15. Conclusions: The first-in-human tests of BWL pulses were successful in that a renal stone was comminuted in <10 minutes, and BWL was also tolerated by an awake subject for a distal ureteral stone. Clinical Trial NCT03873259 and NCT02028559.

In-Office Ultrasound Facilitates Timely Clinical Care at a Multidisciplinary Kidney Stone Center.

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.

Pearl-unjammed: the Seattle stone maneuver for ureteropelvic junction urolithiasis.

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.

In Vitro Evaluation of Urinary Stone Comminution with a Clinical Burst Wave Lithotripsy System.

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 < 0.0001), with individual reviewer sensitivities of 95%, 86%, and 100%. Conclusions: Eighty-nine percent of human stones were comminuted with a clinical BWL system within 30 minutes under conditions intended to reflect conditions in vivo. The results demonstrate the advantage of using ultrasonic propulsion to disperse fragments when making a visual determination of breakage endpoint from the real-time ultrasound image.

Quantitative Assessment of Effectiveness of Ultrasonic Propulsion of Kidney Stones.

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/cm2 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.

B-Flow imaging of the placenta: A feasibility study.

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 < 0.001) were identified with B-Flow than color Doppler images. B-Flow is capable of showing perfusion in a human placenta; however, recognizing artifacts and modifying the image acquisition to reduce artifacts is necessary with this new technique to acquire the best images for interpretation.

Artifacts in Shear Wave Elastography Images of Thyroid Nodules.

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.

Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.

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.

Peritraumatic distress fully mediates the relationship between posttraumatic stress symptoms preoperative and three months postoperative in patients undergoing spine surgery.

Background: Growing evidence shows the significance of illness and surgical procedures as traumatizing stressors. Risk factors are widely investigated in various settings and samples, using numerous measures of posttraumatic stress and posttraumatic stress disorder (PTSD). While pretrauma psychological distress is acknowledged as an influential factor, peritraumatic experiences are controversially still being discussed as relevant to the development of PTSD. Objective: In a group of patients consecutively undergoing elective spine surgery (N = 89) in a German hospital, this longitudinal study addressed the question of how pretrauma PTSD symptoms and peritrauma distress interact with one another in regard to the amount of posttrauma symptoms of PTSD. Methods: Pre- and posttrauma symptoms of PTSD as well as peritrauma distress were assessed through questionnaires one week before, one week after or three months after surgery. Results: Even though all three variables showed significant correlations with one another, mediation analysis revealed that peritrauma distress fully mediated the relationship between pre- and posttrauma PTSD symptoms. Conclusions: These results add new insights to the controversial discussion on the role peritraumatic experiences play in the development of PTSD, especially in medical settings.

Contexto: Evidencias crecientes muestran el significado de la enfermedad y de los procedimientos quirúrgicos como estresores traumatizantes en si mismos. Los factores de riesgo son ampliamente investigados en varios contextos y muestras, usando numerosas medidas de estrés postraumático y del trastorno de estrés postraumático (TEPT). Mientras que el estrés psíquico pretraumático es reconocido como un factor influyente, las experiencias peritraumáticas están siendo aun objeto de controversia como elementos relevantes para el desarrollo de un TEPT. Objetivo: En un grupo de pacientes sometidos a cirugía selectiva espinal (N=89) en un hospital alemán, este estudio longitudinal iba dirigido a estudiar la cuestión de en qué medida tanto los síntomas de TEPT pretraumáticos como el estrés pretraumático, interactúan uno con el otro en relación con la aparición de síntomas postraumáticos de un TEPT. Métodos: Los síntomas pre y postraumáticos de TEPT así como el estrés pretraumático fueron evaluados y determinados a través de cuestionarios, una semana antes, una después y tres meses después de la intervención quirúrgica. Resultados: Aunque las tres variables mostraron correlaciones significativas entre sí, el análisis de la mediación revela que el estrés peritraumático es el mayor mediador de la relación entre síntomas de TEPT, pre y postraumáticos. Conclusiones: estos resultados añaden nuevas perspectivas a la controvertida discusión sobre el papel que juegan las experiencias peritraumáticas en el desarrollo del TEPT, especialmente en contextos médicos.

Retrospective comparison of measured stone size and posterior acoustic shadow width in clinical ultrasound images.

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 using US system. Herein, we compared these two measurements in clinical US images. METHODS: Thirty patient image sets where computed tomography (CT) and US images were captured less than 1 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 an acoustic shadow; 83% of stones without a shadow were ≤ 5 mm on CT. Average stone size was 6.5 ± 4.0 mm on CT, 10.3 ± 4.1 mm on US, and 7.5 ± 4.2 mm by shadow width. On average, US overestimated stone size by 3.8 ± 2.4 mm based on stone width (p < 0.001) and 1.0 ± 1.4 mm based on shadow width (p < 0.0098). Shadow measurements decreased misclassification of stones by 25% among three clinically relevant size categories (≤ 5, 5.1-10, > 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.

Quantification of Renal Stone Contrast with Ultrasound in Human Subjects.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Safety and Effectiveness of a Longer Focal Beam and Burst Duration in Ultrasonic Propulsion for Repositioning Urinary Stones and Fragments.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate.

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.

Stone-Mode Ultrasound for Determining Renal Stone Size.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 likely <5 mm and small enough to pass spontaneously.