Postoperative Urinary Retention Rates after Autofill versus Backfill Void Trial following Total Laparoscopic Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To compare the rate of postoperative urinary retention (POUR) after total laparoscopic hysterectomy (TLH) using the autofill vs the backfill void trial. Secondary objectives were to compare the time to discharge from the recovery room, rate of postoperative urinary tract infection (UTI), perceived bladder condition, the effect of bladder function on life, and patient satisfaction. DESIGN: Randomized controlled trial. SETTING: Single academic medical center. PATIENTS: Women who underwent TLH by conventional laparoscopy or robotic-assisted laparoscopy for benign non-urogynecologic indications. INTERVENTIONS: After TLH, participants were randomized to have an autofill void trial (group A) or a backfill void trial once they were able to ambulate (group B). Failure rate, time to discharge, and UTI rate were assessed. Participants completed the patient perception of bladder condition and the incontinence impact questionnaire-short form questionnaires. Patient satisfaction was assessed. Multiple regression analysis was performed to determine the predictors of POUR. MEASUREMENTS AND MAIN RESULTS: Eighty-two participants completed the study after randomization, 42 in group A and 40 in group B. There were no statistically significant differences in demographic or perioperative outcomes. Seven participants had POUR in group A (16.7%) and 11 in group B (27.5%) (p = .36), respectively. The median time to discharge was 176 minutes for group A (160.5, 255.5) and 218 minutes for group B (180, 265) (p = .01), respectively. There were no statistically significant differences in rate of postoperative UTI (p >.99), patient perception of bladder condition scores (p = .24), incontinence impact questionnaire-short form scores (p = .23), and patient satisfaction scores (p = .26). A stepwise logistic regression analysis did not demonstrate any predictors of POUR. CONCLUSION: Backfill void trial once the participant was able to ambulate was not superior to the autofill void trial with respect to the rate of POUR. The autofill void trial resulted in faster same-day discharge.

Exascale applications: skin in the game.

As noted in Wikipedia, skin in the game refers to having 'incurred risk by being involved in achieving a goal', where 'skin is a synecdoche for the person involved, and game is the metaphor for actions on the field of play under discussion'. For exascale applications under development in the US Department of Energy Exascale Computing Project, nothing could be more apt, with the skin being exascale applications and the game being delivering comprehensive science-based computational applications that effectively exploit exascale high-performance computing technologies to provide breakthrough modelling and simulation and data science solutions. These solutions will yield high-confidence insights and answers to the most critical problems and challenges for the USA in scientific discovery, national security, energy assurance, economic competitiveness and advanced healthcare. This article is part of a discussion meeting issue 'Numerical algorithms for high-performance computational science'.

Fallopian tube perfusion in ex-vivo and in-vivo laparoscopic hysterectomy specimens: potential application for uterine transplantation.

STUDY QUESTION: Is there perfusion to the fallopian tubes in ex-vivo and in-vivo uteri at the time of total laparoscopic hysterectomy (TLH), as observed using laser angiography with indocyanine green (ICG)? SUMMARY ANSWER: The fallopian tubes may have perfusion from the utero-ovarian vasculature alone. WHAT IS KNOWN ALREADY: The fallopian tubes are perfused by the uterine and utero-ovarian vessels. Perfusion can be measured using laser angiography with ICG. STUDY DESIGN, SIZE, DURATION: This prospective pilot cohort study included 15 women, ages 32-59 years old, who underwent TLH with bilateral salpingectomy for benign indications. PARTICIPANTS/MATERIALS, SETTING, METHODS: In five participants, TLH was performed and the utero-ovarian artery was cannulated ex vivo and injected with ICG. The other 10 participants underwent the in-vivo protocol. The mesosalpinx and uterine vessels were transected in the partial protocol. Colpotomy was also performed in the complete protocol. All fallopian tubes were imaged using laser angiography with ICG. The relative fluorescence and the fluorescence intensity ratio (length of fluorescent fallopian tube/total length of fallopian tube) of the fallopian tubes were measured in the ex-vivo and in-vivo protocols, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Ex vivo, the fimbria of the ipsilateral fallopian tube had 47% median relative fluorescence as compared to the contralateral fallopian tube, which had 2.4% median relative fluorescence. In vivo, the post-ICG fluorescence intensity ratios were 0.61 ± 0.40 for the partial protocol, and 0.78 ± 0.30 for the complete protocol, with mean differences of 0.37 (95% CI: 0.23-0.50, P < .0001) and 0.22 (95% CI: 0.12-0.31, P < 0.0001), respectively, between the pre-procedure and the post-ICG fluorescence intensity ratios. Greater than 0.75 fluorescence intensity ratios (i.e. >75% tubal length fluorescence) was seen in 60% of fallopian tubes. LIMITATIONS, REASONS FOR CAUTION: This is a pilot study with a small sample size and pathologic uteri, which would not be appropriate for uterine transplantation. No conclusions can be made regarding the functionality of the fallopian tubes. WIDER IMPLICATIONS OF THE FINDINGS: The fallopian tubes may have perfusion with the utero-ovarian vasculature alone, potentially allowing for future animal studies regarding tubal viability in recipients of uterine-tubal transplants. If successful, human uterine-tubal transplantation may allow for spontaneous conception rather than IVF. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. S.F., P.F.P., K.A.S. and R.F. have no conflicts of interest to report. M.L.S. is an educational consultant for Medtronic (Dublin, Republic of Ireland) and Applied Medical (Rancho Santa Margarita, CA, USA), as well as a stockholder for SynDaver Labs (Tampa, FL, USA). S.E.Z. is an educational consultant for Applied Medical (Rancho Santa Margarita, CA, USA) and is on the advisory board for AbbVie Inc. (Chicago, IL, USA). TRIAL REGISTRATION NUMBER: Not applicable.

Development and Validation of a Simulation Model for Laparoscopic Colpotomy.

OBJECTIVE: To develop a realistic simulation model for performance of laparoscopic colpotomy and evaluate its construct and face validity. METHODS: A simulation model was developed and constructed using polyvinyl chloride piping, a uterine manipulator, and synthetic vaginal tissue paired with a commercially available laparoscopic trainer. An observational study was conducted to validate the simulation model for use as a teaching tool. Construct validity was measured through performance evaluation of novice and expert surgeons using a standard and modified Global Operative Assessment of Laparoscopic Skills scale with possible score ranges of 5-25 and 5-40, respectively. Expert surgeons included attending surgeons across various gynecologic subspecialties who teach total laparoscopic hysterectomy to trainees and perform more than 50 total laparoscopic hysterectomies annually. Novice surgeons included residents who perform total laparoscopic hysterectomy as part of their training. Standards were set using a modified contrasting groups approach. Interrater reliability was calculated using Kendall's τ correlation coefficient. Participants were surveyed regarding the realism of the model and its utility as a teaching tool to assess face validity. RESULTS: Five expert and 15 novice surgeons volunteered to participate. Expert surgeons scored higher than novice surgeons on the Global Operative Assessment of Laparoscopic Skills scale (22.8±1.52 vs 13.53±2.69, respectively) with a mean difference of 9.27 (95% CI 7.12-11.4, P<.01) and on a modified Global Operative Assessment of Laparoscopic Skills scale (36.9±2.19 vs 22.6±3.95, respectively) with a mean difference of 14.30 (95% CI 11.2-17.4, P<.01). Suggested passing range was set at 30.5-32.5 out of 40 total points. Kendall's τ interrater reliability was 0.86 (95% CI 0.798-0.923) and 0.87 (95% CI 0.818-0.922), respectively. All participants agreed that the training model was useful for teaching and learning laparoscopic colpotomy and for assessing the learner's ability to perform colpotomy before live surgery. CONCLUSION: This validated simulation system offers novice surgeons an opportunity to practice the skill set necessary to perform laparoscopic colpotomy efficiently and may be used as an educational tool.

Laser Angiography to Assess the Vaginal Cuff During Robotic Hysterectomy.

BACKGROUND AND OBJECTIVES: Vaginal cuff dehiscence may be a vascular-mediated event, and reports show a higher incidence after robot-assisted total laparoscopic hysterectomy (RATLH), when compared with other surgical routes. This study was conducted to determine the feasibility of using laser angiography to assess vaginal cuff perfusion during RATLH. METHODS: This was a pilot feasibility trial incorporating 20 women who underwent RATLH for benign disease. Colpotomy was made with ultrasonic or monopolar instruments, whereas barbed or nonbarbed suture was used for cuff closure. Time of instrument activation during colpotomy was recorded. Images were captured of vaginal cuff perfusion before and after cuff closure. Reviewers evaluated these images and determined areas of adequate cuff perfusion. RESULTS: Indocyanine green (ICG) was visible at the vaginal cuff in all participants. Optimal dosage was determined to be 7.5 mg of ICG per intravenous dose. Mean time to appearance for ICG was 18.4 ± 7.3 s (mean ± SD) before closure and 19.0 ± 8.7 s after closure. No significant difference (P = .19) was noted in judged perfusion in open cuffs after colpotomy with a monopolar (48.9 ± 26.0%; mean ± SD) or ultrasonic (40.2 ± 14.1%) device. No difference was seen after cuff closure (P = .36) when a monopolar (70.9 ± 21.1%) or ultrasonic (70.5 ± 20.5%) device was used. The use of barbed (74.1 ± 20.1%) or nonbarbed (66.4 ± 20.9%) sutures did not significantly affect estimated closed cuff perfusion (P = .19). Decreased cuff perfusion was observed with longer instrument activation times in open cuffs (R2 = 0.3175). CONCLUSION: Laser angiography during RATLH allows visualization of vascular perfusion of the vaginal cuff. The technology remains limited by the lack of quantifiable fluorescence and knowledge of clinically significant levels of fluorescence.

Management, Prevention, and Sequelae of Adhesions in Women Undergoing Laparoscopic Gynecologic Surgery: A Systematic Review.

Surgical adhesions can lead to significant consequences including abdominopelvic pain, bowel obstruction, subfertility, and subsequent surgery. Although laparoscopic surgery is associated with a decreased risk of adhesion formation, methods to further decrease adhesions are warranted. We systematically reviewed literature addressing the management, prevention, and sequelae of adhesions in women undergoing laparoscopic gynecologic surgery. We searched PubMed, EMBASE, EBSCOhost, and Cochrane Central Register of Controlled Trials and found 6566 records. The primary outcome was adhesion formation. The secondary outcomes were abdominopelvic pain, quality of life, subfertility, pregnancy, bowel obstruction, urinary symptoms, and subsequent surgery. After applying inclusion and exclusion criteria, 52 studies remained for qualitative synthesis. Risk of bias assessments were applied independently by 2 authors. There was evidence that Hyalobarrier Gel (Anika Therapeutics, Bedford, MA), HyaRegen NCH Gel (Bilar Medikal, Istanbul, Turkey), Oxiplex/AP Gel (Fziomed, Inc., San Luis Obispo, CA), SprayGel (Confluent Surgical Inc., Waltham, MA), and Beriplast (CSL Behring, LLCm King of Prussia, PA) all decrease the incidence of adhesions. Adept (Baxter, Deerfield, IL) significantly decreased de novo adhesion scores of the posterior uterus. Using an integrated treatment approach to pelvic pain significantly improved pain and quality of life compared with standard laparoscopic treatment. Lastly, Hyalobarrier Gel Endo (Anika Therapeutics, Bedford, MA) placement led to a higher pregnancy rate than no barrier usage. Our findings underscore the need for high-quality trials to evaluate the efficacy of surgical techniques, adhesion barriers, and other treatment modalities on the management and prevention of adhesions and their clinical sequelae. This review was registered on PROSPERO (ID = CRD42017068053).

Anatomy of the Internal Iliac Vein: Implications for Uterine Transplant.

STUDY OBJECTIVE: Uterine transplantation has proven feasible since the first live birth reported in 2014. To enable attachment of the uterus in the recipient, long vascular pedicles of the uterine and internal iliac vessels were obtained during donor hysterectomy, which required a prolonged laparotomy to the living donors. To assist further attempts at uterine transplantation, our video serves to review literature reports of internal iliac vein anatomy and demonstrate a laparoscopic dissection of cadaver pelvic vascular anatomy. DESIGN: Observational (Canadian Task Force Classification III). SETTING: Academic anatomic laboratory. Institutional Review Board ruled that approval was not required for this study. INTERVENTION: Literature review and laparoscopic dissection of cadaveric pelvic vasculature, focusing on the internal iliac vein. MEASUREMENTS AND MAIN RESULTS: Although the internal iliac artery tends to have minimal anatomic variation, its counterpart, the internal iliac vein, shows much variation in published studies [1,2]. Relative to the internal iliac artery, the vein can lie medially or laterally. Normal anatomy is defined as some by meeting 2 criteria: bilateral common iliac vein formed by ipsilateral external and internal iliac vein at a low position and bilateral common iliac vein joining to form a right-sided inferior vena cava [2]. Reports show 79.1% of people have normal internal iliac vein anatomy by these criteria [2]. The cadaver dissection revealed internal iliac vein anatomy meeting criteria for normal anatomy. CONCLUSION: Understanding the complexity and variations of internal iliac vein anatomy can assist future trials of uterine transplantation.

Sterility of Selected Operative Sites During Total Laparoscopic Hysterectomy.

STUDY OBJECTIVE: To describe the type and quantity of bacteria found intraoperatively on the abdomen, vagina, surgical gloves, instrument tips, and uterus at distinct time points during total laparoscopic hysterectomy (TLH). DESIGN: Observational study (Canadian Task Force classification III). SETTING: Academic affiliated hospital. PATIENTS: Thirty-one women undergoing TLH for benign indications in 2016. INTERVENTIONS: After antibiotic prophylaxis and chlorhexidine preparation, swabs were collected from the vaginal fornices and abdomen. During subsequent TLH, additional swabs were collected from the following sites: surgeon's gloves after placement of the uterine manipulator, tips of instruments used to close the vaginal cuff, uterine fundus after extraction, and surgeon's gloves after removal of the uterus. A calibrated loop was used to inoculate each specimen onto 5% blood and chocolate agars for growth of aerobes and onto Brucella blood, phenylethyl alcohol, kanamycin vancomycin, and Bacteroides bile esculin agars for growth of anaerobes. Manual colony counts were tabulated for all positive cultures and reported in colony-forming units per milliliter (CFU/mL). MEASUREMENTS AND MAIN RESULTS: Anaerobic growth was not seen on the instrument tips, in the vagina, or on the abdomen of any patient. Aerobic bacterial growth was not seen in the vagina of any patient. On the surgeon's gloves after uterine manipulator placement, no patients demonstrated sufficient bacterial growth to potentially cause surgical site infection (≥5000 CFU/mL). On the surgeon's gloves following uterine extraction, 1 patient demonstrated sufficient growth to potentially cause infection. None of the patients developed surgical site infections postoperatively. CONCLUSION: Cultures from multiple operative sites yielded bacterial growth, but the bacterial concentrations did not exceed the threshold for infection in 98.9% of cultures. Given absent growth from vaginal cultures and rare growth from abdominal cultures, chlorhexidine gluconate 4% is considered an appropriate surgical preparation for use in laparoscopic hysterectomy.

Uterine viability in the baboon after ligation of uterine vasculature: a pilot study to assess alternative perfusion and venous return for uterine transplantation.

OBJECTIVE: To assess, in two separate groups of baboons, uterine viability after ligation of the uterine veins and uterine viability after ligation of both the uterine arteries and veins, respectively. DESIGN: Prospective, observational study. SETTING: Baboon breeding colony. ANIMAL(S): Six naïve female Papio hamadryas baboons with indicators of normal reproductive function. INTERVENTION(S): Three baboons underwent surgical interruption of the uterine veins bilaterally, and three baboons underwent surgical interruption of the uterine arteries and the uterine veins bilaterally. All baboons also underwent colpotomy, cervico-vaginal reanastomosis, and intraoperative near-infrared fluorescence imaging after vessel ligation. In the postoperative period, transabdominal sonography, vaginoscopy, and endocervical biopsy were performed on all animals. MAIN OUTCOME MEASURE(S): Postoperative uterine and ovarian viability. RESULT(S): Near-infrared imaging confirmed intraoperative perfusion of the uterus and cervico-vaginal anastomosis in all cases. In all subjects, sonography revealed normal uteri, and vaginoscopy revealed well-healed anastomoses. Endocervical biopsies (five of six) demonstrated pathologically normal endocervical tissue without evidence of necrosis. Cyclical sex skin turgescence and menstruation were unanimously observed. CONCLUSION(S): Disruption of bilateral uterine vessels does not affect uterine or ovarian viability in the baboon. Bilateral uterine artery and vein ligation furthers development of a minimally invasive approach to donor hysterectomy.

Laser Angiography with Indocyanine Green to Assess Vaginal Cuff Perfusion during Total Laparoscopic Hysterectomy: A Pilot Study.

STUDY OBJECTIVE: To determine feasibility of using laser angiography with indocyanine green (ICG) to assess vaginal cuff vascular perfusion during total laparoscopic hysterectomy (TLH). DESIGN: Pilot feasibility trial (Canadian Task Force classification II-2). SETTING: Academic-affiliated hospital. PATIENTS: Twenty women undergoing TLH for benign disease. INTERVENTIONS: Participants underwent 1:1 randomization of energy method used for colpotomy (ultrasonic vs monopolar) and vaginal cuff closure suture (barbed vs nonbarbed). After intravenous administration of ICG, laser angiography was used to capture images of the vaginal cuff before and after closure. Three reviewers analyzed fluorescent images of vaginal cuffs to determine percent of cuff perimeter with adequate perfusion when open and length of vaginal cuff adequately perfused when closed. MEASUREMENTS AND MAIN RESULTS: ICG fluorescence was visible at the vaginal cuff in all participants. Mean time to appearance of ICG in the pelvis after administration was 19.8 ± 6.8 seconds (mean ± SD) preclosure, and 26.0 ± 22.2 seconds postclosure. With ultrasonic energy 67.5% ± 17.4% of open cuff perimeter and 74.4% ± 20.5% of closed cuff length were adequately perfused, whereas with monopolar energy use 59.1% ± 17.4% of the open cuff perimeter and 66.3% ± 15.4% of closed cuff length were adequately perfused. Cuffs closed with barbed suture showed adequate perfusion along 71.5% ± 15.1% of the length, whereas those closed with nonbarbed suture showed 68.9% ± 20.9% adequate perfusion. When normalized to cervical cup circumference, ultrasonic energy required 1.0 ± .2 s/mm, whereas monopolar energy required .8 ± .3 s/mm (p = .162). Linear regression showed no association of normalized time of energy activation to percentage of perimeter of open cuff (R2 = .007) or length of closed cuff (R2 = .005) with adequate perfusion. No complications related to intravenous ICG administration occurred. CONCLUSION: Laser angiography with ICG allows evaluation of vascular perfusion at the vaginal cuff during TLH. This technique may facilitate future prospective studies examining causes for vaginal cuff dehiscence, a complication with potential for severe morbidity.

Utility of indocyanine green (ICG) intra-operative angiography to determine uterine vascular perfusion at the time of radical trachelectomy.

OBJECTIVES: The aim of our study was to measure and analyze uterine perfusion utilizing laser angiography with ICG during uterine artery sparing and non-sparing radical trachelectomy. METHODS: Data were collected from all patients diagnosed with early-stage cervical cancer that underwent laser angiography with ICG during open or laparoscopic radical trachelectomy from June 2012 to December 2015. Regression analysis was use to determine the p values and R-squares on fluorescence, surgical time, hospital stay, age and BMI; a p-value<0.05 was considered statistically significant. RESULTS: A total of 20 patients met the inclusion criteria and were included in this study. Ten patients underwent uterine artery-sparing surgery, and ten patients underwent uterine artery non-sparing surgery. The most frequent stage for the entire cohort was IA2 (55%), and the most common histologic subtype was squamous cell carcinoma (49%). Lymph-vascular invasion was noted in 30% of the patients. There was no statistical significance difference in the mean ICG fundal fluorescence intensity between the uterine artery-sparing group 162.5 (range, 137-188) and the uterine artery non-sparing group 160.5 (range, 135-186), p=0.22. In both groups, 100% of the patients regained their menstrual function by postoperative week 8. A total of 4 (40%) pregnancies have occurred in the uterine artery-sparing group and 3 (30%) in the non-uterine artery-sparing group. CONCLUSIONS: Based on our real-time intraoperative angiography observations, there is no need to preserve the uterine artery during radical trachelectomy to maintain uterine viability.

Giant cystic degeneration of a uterine leiomyoma in a patient with autosomal dominant polycystic kidney disease.

OBJECTIVE: To report the management of a large uterine leiomyoma with diffuse cystic degeneration in a patient with autosomal dominant polycystic kidney disease (ADPKD). DESIGN: Case Report. SETTING: Cleveland Clinic Florida, Department of Gynecology, Section of Minimally Invasive Gynecologic surgery, Weston Florida. PATIENTS: A 52-year old woman with ADPKD with a large abdominal mass, abnormal uterine bleeding and symptomatic anemia. Imaging revealed a giant intramural cystic lesion of the uterus compressing the inferior vena cava. INTERVENTIONS: Uterine artery embolization and blood transfusion followed by a computed tomography guided cyst aspiration were performed on admission to alleviate anemia and abdominal pain and distension. Total laparoscopic hysterectomy with bilateral salpingectomy was performed in an outpatient setting. MAIN OUTCOME MEASURES: Management of large cystic degeneration of leiomyoma. RESULTS: Normal recovery from definitive surgery. Surgical pathology confirmed a benign, cystically dilated leiomyoma. CONCLUSION: This case demonstrates the management of giant intramural cyst lesion of the uterus using a minimally invasive surgical approach, as opposed to emergency surgery via laparotomy. CAPSULE: Large uterine leiomyoma with diffuse cystic degeneration in a patient with autosomal dominant polycystic kidney disease, in which step-wise treatments allows successful minimally invasive hysterectomy.

Ultrahigh and persistent optical depths of cesium in Kagomé-type hollow-core photonic crystal fibers.

Alkali-filled hollow-core fibers are a promising medium for investigating light-matter interactions, especially at the single-photon level, due to the tight confinement of light and high optical depths achievable by light-induced atomic desorption (LIAD). However, until now these large optical depths could only be generated for seconds, at most once per day, severely limiting the practicality of the technology. Here we report the generation of the highest observed transient (>10(5) for up to a minute) and highest observed persistent (>2000 for hours) optical depths of alkali vapors in a light-guiding geometry to date, using a cesium-filled Kagomé-type hollow-core photonic crystal fiber (HC-PCF). Our results pave the way to light-matter interaction experiments in confined geometries requiring long operation times and large atomic number densities, such as generation of single-photon-level nonlinearities and development of single photon quantum memories.

Parameter determination and validation for a mechanistic model of the enzymatic saccharification of cellulose-Iß.

Cost-effective production of fuels and chemicals from lignocellulosic biomass often involves enzymatic saccharification, which has been the subject of intense research and development. Recently, a mechanistic model for the enzymatic saccharification of cellulose has been developed that accounts for distribution of cellulose chain lengths, the accessibility of insoluble cellulose to enzymes, and the distinct modes of action of the component cellulases [Griggs et al. (2012) Biotechnol. Bioeng., 109(3):665-675; Griggs et al. (2012) Biotechnol. Bioeng., 109(3):676-685]. However, determining appropriate values for the adsorption, inhibition, and rate parameters required further experimental investigation. In this work, we performed several sets of experiments to aid in parameter estimation and to quantitatively validate the model. Cellulosic materials differing in degrees of polymerization and crystallinity (α-cellulose-Iß and highly crystalline cellulose-Iß ) were digested by component enzymes (EGI/CBHI/ßG) and by mixtures of these enzymes. Based on information from the literature and the results from these experiments, a single set of model parameters was determined, and the model simulation results using this set of parameters were compared with the experimental data of total glucan conversion, chain-length distribution, and crystallinity. Model simulations show significant agreement with the experimentally derived glucan conversion and chain-length distribution curves and provide interesting insights into multiple complex and interacting physico-chemical phenomena involved in enzymatic hydrolysis, including enzyme synergism, substrate accessibility, cellulose chain length distribution and crystallinity, and inhibition of cellulases by soluble sugars.

A new transducer receive transfer function calibration method: application to microbubble backscattering cross-section measurements at high frequency.

When comparing acoustic scattering experiments with theory, the relationship between the pressure generated by a scatterer at the surface of a transducer and the induced voltage must be known. Methods have been previously proposed to measure the receive transfer function that rely on several assumptions. A new, experimental method for measuring the acoustic response of a spherically-focused transducer, using a hydrophone at twice the focal distance, is proposed that requires a minimum number of assumptions and calculations. The receive transfer function of a spherically-focused, high-frequency transducer was calculated, and found to be within 10% of the receive transfer function calculated assuming reciprocity. Further, using the receive transfer function, the effective backscattering cross-section of bound microbubbles interrogated at 30 MHz was measured to be, on average, 65% of the geometric backscattering cross-section, with significant size-independent variability. These results give insight into selecting the optimal microbubble size distribution for linear microbubble imaging at high frequencies.

A residual-potential boundary for time-dependent, infinite-domain problems in computational acoustics.

A theoretically exact computational boundary is introduced, that is based on modal residual potentials for the spherical geometry. The boundary produces a set of first-order, uncoupled ordinary differential equations for nodal boundary responses, and a set of uncoupled time-stepping equations for modal boundary responses. The two sets are coupled through nodal-modal transformation based on the orthogonal surface functions for the spherical boundary. Numerical results generated with the boundary are presented for a step-wave-excited, elastic, spherical shell submerged in an infinite acoustic medium. Extension of the method to other separable geometries for partial differential equations defined in unbounded domains is mentioned.

Nonlinear emission from individual bound microbubbles at high frequencies.

Targeted microbubbles detected with high-frequency ultrasound can establish the molecular expression of blood vessels with submillimeter resolution. To improve microbubble-specific imaging at high frequencies, the subharmonic and second harmonic signal from individual microbubbles were measured as a function of size and pressure. Single phospholipid-shell microbubbles (1.1 to 5.0 microm in diameter) bound to gelatin, co-aligned with an optical microscope and transducer, were insonated with 30 MHz Gaussian-enveloped pulses at pressures from 20 kPa to 1 MPa with -6 dB one-way bandwidths of 11%, 20% and 45%. A subharmonic signal (15 MHz) was detected above a pressure threshold of 110 kPa--independent of bandwidth. The signal peaked for microbubbles 1.60 microm in diameter subject to 20% and 11% bandwidth pulses, and 1.80 microm for 45% bandwidth pulses, for pressures up to 400 kPa, agreeing with the notion that microbubbles insonated at twice their resonant frequency preferentially emit a subharmonic component. For pressures between 400 kPa and 1 MPa, a broader range of microbubbles emitted a subharmonic signal, and microbubbles below 1.70 mum in diameter were disrupted. The second harmonic signal measured, within the limited experimental conditions, was consistent with nonlinear propagation. Further, the results shed light on the effect of the shell on the phase of the subharmonic signal with respect to the fundamental signal.

Reflection from bound microbubbles at high ultrasound frequencies.

Targeted contrast agents and ultrasound imaging are now used in combination for the assessment and tracking of biomarkers in animal models in vivo. These applications have triggered interest in the understanding and prediction of the ultrasound echoes from contrast agents attached to cells. This study describes the reflection enhancement due to microbubbles bound on a gelatin surface. The reflection enhancement was measured using ultrasound pulses at high frequency (40 MHz) and low pressure (38 kPa peak-negativepressure) allowing a linear approximation to be applied. The observed reflection coefficient increased with the number of microbubbles, until reaching saturation at 0.9 when the surface coverage fraction was 35%. A multiple scattering model assuming that the targeted microbubbles are confined within an infinitesimally thin layer appeared suitable in predicting the reflection coefficient even at very high surface densities. These results could permit the optimization of the sensitivity of highfrequency ultrasound to targeted contrast agents.