Pulmonary Transit Time Assessment by CEUS in Healthy Rabbits: Feasibility, and the Effects of UCAs Dilution Concentration.

To evaluate the inter-observer variability and the intra-observer repeatability of pulmonary transit time (PTT) measurement using contrast-enhanced ultrasound (CEUS) in healthy rabbits, and assess the effects of dilution concentration of ultrasound contrast agents (UCAs) on PTT. Thirteen healthy rabbits were selected, and five concentrations UCAs of 1:200, 1:100, 1:50, 1:10, and 1:1 were injected into the right ear vein. Five digital loops were obtained from the apical 4-chamber view. Four sonographers obtained PTT by plotting the TIC of right atrium (RA) and left atrium (LA) at two time points (T1 and T2). The frame counts of the first appearance of UCAs in RA and LA had excellent inter-observer agreement, with intra-class correlations (ICC) of 0.996, 0.988, respectively. The agreement of PTT among four observers was all good at five different concentrations, with an ICC of 0.758-0.873. The reproducibility of PTT obtained by four observers at T1 and T2 was performed well, with ICC of 0.888-0.961. The median inter-observer variability across 13 rabbits was 6.5% and the median variability within 14 days for 4 observers was 1.9%, 1.7%, 2.2%, 1.9%, respectively; The PTT of 13 healthy rabbits is 1.01 ± 0.18 second. The difference of PTT between five concentrations is statistically significant. The PTT obtained by a concentration of 1:200 and 1:100 were higher than that of 1:1, while there were no significantly differences in PTT of a concentration of 1:1, 1:10, and 1:50. PTT measured by CEUS in rabbits is feasible, with excellent inter-observer and intra-observer reliability and reproducibility, and dilution concentration of UCAs influences PTT results.

Intravasation Affects the Diagnostic Image Quality of Transvaginal 4-Dimensional Hysterosalpingo-Contrast Sonography With SonoVue.

OBJECTIVES: We aim to retrospectively analyze the diagnostic image quality of transvaginal 4-dimensional hysterosalpingo-contrast sonography from infertile patients and determine the significant influencing factors. METHODS: A total of 445 patients visiting infertility clinics were included in the study, of which 167 were primary infertile and 278 were secondary infertile. The factors were recorded, including age; examination time; infertility type; history of pelvic inflammatory disease, pelvic surgery, intrauterine surgery, and ectopic pregnancy; endometrial thickness; uterine position; ovarian position; 2-dimensional image quality; intravasation quantity, position, and time; balloon volume; and the dosage of contrast agent or the sterile saline solution. All the factors were compared among different diagnostic image quality groups. The method of rank logistic regression analysis was adopted to analyze the risk factors affecting the diagnostic image quality. RESULTS: Among the 445 infertile patients, 124 (27.9%) patients had intravasation occur during transvaginal 4-dimensional hysterosalpingo-contrast sonography. The diagnostic image quality between the 2 sonographers was consistent (Cronbach's alpha, 0.993). Different intravasation quantities, positions, and times; increased of balloon volume; and history of pelvic surgery were substantial risk factors for the diagnostic image quality. The diagnostic image quality diminished with the increase of intravasation. In the patient with cornual intravasation, the diagnostic image quality was substantially worse than that with non-cornual intravasation. Moreover, early onset of intravasation seriously affected the diagnostic image quality. CONCLUSIONS: In conclusion, intravasation affected the diagnostic image quality, especially early cornual massive intravasation.

Acoustic Characterization and Enhanced Ultrasound Imaging of Long-Circulating Lipid-Coated Microbubbles.

OBJECTIVES: A long-circulating lipid-coated ultrasound (US) contrast agent was fabricated to achieve a longer wash-out time and gain more resistance against higher-mechanical index sonication. Systemic physical, acoustic, and in vivo imaging experiments were performed to better understand the underlying mechanism enabling the improvement of contrast agent performance by adjusting the physical and acoustic properties of contrast agent microbubbles. METHODS: By simply altering the gas core, a kind of US contrast agent microbubble was synthesized with a similar lipid-coating shell as SonoVue microbubbles (Bracco SpA, Milan, Italy) to achieve a longer wash-out time and higher inertial cavitation threshold. To bridge the structure-performance relationship of the synthesized microbubbles, the imaging performance of the microbubbles was assessed in vivo with SonoVue as a control group. The size distribution and inertial cavitation threshold of the synthesized microbubbles were characterized, and the shell parameters of the microbubbles were determined by acoustic attenuation measurements. All of the measurements were compared with SonoVue microbubbles. RESULTS: The synthesized microbubbles had a spherical shape, a smooth, consistent membrane, and a uniform distribution, with an average diameter of 1.484 µm. According to the measured attenuation curve, the synthesized microbubbles resonated at around 2.8 MHz. Although the bubble's shell elasticity (0.2 ± 0.09 N/m) was comparable with SonoVue, it had relatively greater viscosity and inertial cavitation because of the different gas core. Imaging studies showed that the synthesized microbubbles had a longer circulation time and a better chance of fighting against rapid collapse than SonoVue. CONCLUSIONS: Nano/micrometer long-circulating lipid-coated microbubbles could be fabricated by simply altering the core composition of SonoVue microbubbles with a higher-molecular weight gas. The smaller diameter and higher inertial cavitation threshold of the synthesized microbubbles might make it easier to access deep-seated organs and give prolonged imaging enhancement in the liver.

Reliability, repeatability, and reproducibility of pulmonary transit time assessment by contrast enhanced echocardiography.

BACKGROUND: The aim of this study is to investigate the inter and intra-rater reliability, repeatability, and reproducibility of pulmonary transit time (PTT) measurement in patients using contrast enhanced ultrasound (CEUS), as an indirect measure of preload and left ventricular function. METHODS: Mean transit times (MTT) were measured by drawing a region of interest (ROI) in right and left cardiac ventricle in the CEUS loops. Acoustic intensity dilution curves were obtained from the ROIs. MTTs were calculated by applying model-based fitting on the dilution curves. PTT was calculated as the difference of the MTTs. Eight raters with different levels of experience measured the PTT (time moment 1) and repeated the measurement within a week (time moment 2). Reliability and agreement were assessed using intra-class correlations (ICC) and Bland-Altman analysis. Repeatability was tested by estimating the variance of means (ANOVA) of three injections in each patient at different doses. Reproducibility was tested by the ICC of the two time moments. RESULTS: Fifteen patients with heart failure were included. The mean PTT was 11.8 ± 3.1 s at time moment 1 and 11.7 ± 2.9 s at time moment 2. The inter-rater reliability for PTT was excellent (ICC = 0.94). The intra-rater reliability per rater was between 0.81-0.99. Bland-Altman analysis revealed a bias of 0.10 s within the rater groups. Reproducibility for PTT showed an ICC = 0.94 between the two time moments. ANOVA showed no significant difference between the means of the three different doses F = 0.048 (P = 0.95). The mean and standard deviation for PTT estimates at three different doses was 11.6 ± 3.3 s. CONCLUSIONS: PTT estimation using CEUS shows a high inter- and intra-rater reliability, repeatability at three different doses, and reproducibility by ROI drawing. This makes the minimally invasive PTT measurement using contrast echocardiography ready for clinical evaluation in patients with heart failure and for preload estimation.

Straight Vessel Pattern and Rapid Filling Time: Characteristic Findings on Contrast-Enhanced Sonography of Testicular Lymphoma.

Six patients with 7 lesions that were histologically confirmed as primary testicular lymphoma were preoperatively investigated with a standardized sonographic protocol including contrast-enhanced sonography. Duplex and contrast-enhanced sonography showed marked hypervascularization in all 7 lesions. On contrast-enhanced sonography, the filling time of lymphomatous lesions was significantly shorter than the filling time of a size-matched sample of 10 patients with seminomas (P < .0001). The sonographic hallmarks of testicular lymphoma in our case series were as follows: (1) sharply demarcated homogeneous hypoechoic testicular lesions with marked hypervascularization; (2) a rapid (<7 seconds) filling time of contrast bubbles; and (3) a straight and parallel course of intralesional vessels on contrast-enhanced sonography.

Ventilation/perfusion ratios measured by multiple inert gas elimination during experimental cardiopulmonary resuscitation.

BACKGROUND: During cardiopulmonary resuscitation (CPR) the ventilation/perfusion distribution (VA /Q) within the lung is difficult to assess. This experimental study examines the capability of multiple inert gas elimination (MIGET) to determine VA /Q under CPR conditions in a pig model. METHODS: Twenty-one anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0, 0.7 or 0.21). VA/ Q by micropore membrane inlet mass spectrometry-derived MIGET was determined at baseline and during CPR following induction of ventricular fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical impedance tomography and return of spontaneous circulation were assessed. Intergroup differences were analysed by non-parametric testing. RESULTS: MIGET measurements were feasible in all animals with an excellent correlation of measured and predicted arterial oxygen partial pressure (R(2) = 0.96, n = 21 for baseline; R(2) = 0.82, n = 21 for CPR). CPR induces a significant shift from normal VA /Q ratios to the high VA /Q range. Electrical impedance tomography indicates a dorsal to ventral shift of the ventilation distribution. Diverging pulmonary shunt fractions induced by the three inspired oxygen levels considerably increased during CPR and were traceable by MIGET, while 100% oxygen most negatively influenced the VA /Q. Return of spontaneous circulation were achieved in 52% of the animals. CONCLUSIONS: VA /Q assessment by MIGET is feasible during CPR and provides a novel tool for experimental purposes. Changes in VA /Q caused by different oxygen fractions are traceable during CPR. Beyond pulmonary perfusion deficits, these data imply an influence of the inspired oxygen level on VA /Q. Higher oxygen levels significantly increase shunt fractions and impair the normal VA /Q ratio.

Doppler perfusion index and contrast-enhanced ultrasound in patients with colorectal cancer liver metastases.

BACKGROUND/AIMS: To assess the value of the Doppler perfusion index (DPI) and contrast agent for the detection of liver metastases in patients with colorectal cancer. METHODOLOGY: DPI was measured in 18 patients with colorectal cancer liver metastases and 18 control subjects. Sixteen patients were underwent contrast-enhanced ultrasonography (CEUS). RESULTS: patients with liver metastases had significantly greater DPI than control group (0.39 +/- 0.10 vs. 0.19 +/- 0.07, p < 0.05). Sixteen liver metastasis lesions underwent a rapid wash-out of contrast agent during the portal venous phase followed by a complete wash-out of SonoVue during the sinusoidal phase and were differentiated as "fast-in and fast-out" contrast enhancement patter. Another 3 lesions which were not found by baseline ultrasonography were detected to be enhancement defects at sinusoidal phases by CEUS. CONCLUSIONS: DPI is a sensitive index in detection of colorectal liver metastases; if used combined with contrast agent, much more occult liver metastasis would be detected by ultrasonography.

Prolonged heterogeneous liver enhancement on contrast-enhanced ultrasound.

INTRODUCTION: Prolonged heterogeneous liver enhancement (PHLE) is a rare phenomenon that is similar to the ultrasound findings of portal venous gas. The purpose of this report is to describe the phenomenon of PHLE after the injection of the ultrasound contrast agent SonoVue(®). PATIENTS AND METHODS: From 2000 to 2013, 13 patients with PHLE ("cloudy", "wool-like") after bolus injection of SonoVue(®) were observed. The height, weight, and body mass index (BMI) of the patients, and the number of injections were analyzed. In addition, the literature was reviewed. RESULTS: The phenomenon occurred as early as 2 minutes after bolus contrast administration and lasted up to 5 hours on both B-mode and contrast-specific ultrasound. 8/13 (62 %) patients received two or more boluses. None of the patients experienced SonoVue(®)-related side effects or health problems. The phenomenon was not reproducible in 3 patients who received a second SonoVue(®) injection 24 hours after receiving the first. CONCLUSION: This phenomenon is more likely to occur in patients who receive high-dose (or multiple) injections of UCA. It may occur as early as 2 minutes after contrast administration, and therefore, may affect the evaluation of focal liver lesions in the late phase. This phenomenon should not be misdiagnosed as a pathological finding of the liver.

Percutaneous removal of sentinel lymph nodes in a swine model using a breast lesion excision system and contrast-enhanced ultrasound.

OBJECTIVES: To investigate the feasibility of percutaneous removal of the entire sentinel lymph node (SLN) in an animal model using a breast lesion excision system after identifying these nodes using contrast-enhanced ultrasound (CEUS) and intradermal microbubbles. METHODS: Animal studies approval was obtained. SLNs were identified using CEUS and intradermal injection of microbubbles in two young pigs. Microbubbles were mixed with blue dye and injected around the mammary papillae to access lymphatic drainage to the superficial inguinal lymph nodes. When enhancing nodes were identified, the breast lesion excision system (BLES) was used to remove these nodes percutaneously. Both animals then underwent surgical lymph node dissection. Histopathological examination of all the samples was performed. RESULTS: Removal of the entire SLN was successful in three groins in the pigs. All three nodes were stained with blue dye. No other stained nodes were observed in the node dissection specimens. The nodal architecture of removed lymph nodes was well preserved on microscopy. There were no signs of excess trauma within the biopsy bed. CONCLUSION: The results obtained from the swine model demonstrated that it is feasible to remove the entire SLN percutaneously under the guidance of CEUS and microbubbles. KEY POINTS: Intradermal injection of microbubbles and CEUS can identify sentinel lymph nodes • Ultrasound could then guide percutaneous removal of intact and complete SLNs • We have shown this was feasible in pigs but not yet in humans • This technique may eventually have the potential to reduce futile SLN biopsies.

Differentiation between benign and malignant breast tumors using kinetic features of real-time harmonic contrast-enhanced ultrasound.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has gained interest because of its ability to gather vascular information in diverse organs. There is still a subject of debate concerning its value in breast lesions, especially as a differential diagnostic tool. PURPOSE: To investigate whether kinetic parameters of CEUS can differentiate between malignant and benign breast lesions. MATERIAL AND METHODS: We evaluated 75 malignant and 21 benign lesions in the breast or axilla. Contrast harmonic imaging (CHI) US was performed after the injection of a bolus dose of 2.4 mL of Sono Vue® (Bracco, Milano, Italy). The following parameters were calculated for kinetic analysis: initial slope, time to peak enhancement, wash-out ratios W(21) and W(50) (relative decrease in signal intensity from the peak enhancement to 21 s and 50 s, respectively). RESULTS: A significant difference was found between the benign and malignant lesions in time-to-peak (P value <0.05) and wash-out ratios W(21) (P value <0.001) and W(50) (P value <0.001). The mean time-to-peak was 9.3 s for malignant and 14.6 s for benign lesions. The mean signal drop from peak to signal intensity measured at 50 s was 85% for malignant and 66% for benign lesions. There was no difference in absolute values of peak signal intensity and initial slope. The most significant difference between standardized benign and malignant wash-out curves was found at 21 s but statistical significance was reached in the range of 14-50 s. CONCLUSION: Real-time CEUS can evolve into a new non-invasive option for differentiate malignant from benign breast lesions.

An EFSUMB introduction into Dynamic Contrast-Enhanced Ultrasound (DCE-US) for quantification of tumour perfusion.

Dynamic Contrast Enhanced Ultrasound (DCE-US) is an imaging technique that utilizes microbubble contrast agents in diagnostic ultrasound. The EFSUMB guidelines published in 2004, updated in 2008 and 2011 focused on the use of DCE-US, including essential technical requirements, training, investigational procedures and steps, guidance on image interpretation, established and recommended clinical indications and safety considerations. However the quantification of images acquired with ultrasound contrast agents (UCAs) is not discussed in the guidelines. The purpose of this EFSUMB document is to provide some recommendations and descriptions of the quantification of ultrasound images, technical requirements for analysis of time-intensity curves (TICs), methodology for data analysis, and interpretation of the results.

Intraocular gas dynamics after 20-gauge and 23-gauge vitrectomy with sulfur hexafluoride gas tamponade.

PURPOSE: The purpose of this study was to evaluate the intraocular gas dynamics after 23-gauge transconjunctival sutureless vitrectomy (TSV) as compared with 20-gauge pars plana vitrectomy (PPV). METHODS: A consecutive series of 290 eyes that experienced 20-gauge or 23-gauge vitrectomy with 25% sulfur hexafluoride (SF6) gas tamponade were retrospectively reviewed. Intraocular gas bubble size on postoperative Day 1 and Gas50, the interval to dissipate to a 50% gas fill, were evaluated. RESULTS: The mean intraocular bubble size on postoperative Day 1 was 92.0 ± 8.3% in the 20-gauge PPV cases and 83.8 ± 13.7% in the 23-gauge TSV cases (P < 0.001). The mean Gas50 was 8.6 ± 1.6 days in the 20-gauge PPV cases and 6.6 ± 2.2 days in the 23-gauge TSV cases (P < 0.001). Thorough peripheral vitrectomy and 23-gauge TSV were significantly associated with Gas50 ≤ 4 days (odds ratio, 4.62 and 16.8; P = 0.036 and P = 0.007, respectively). Among thoroughly vitrectomized eyes, 13 eyes treated with 23-gauge PPV with intraoperative suture placement at the sclerotomy sites had gas longevity comparative to those with 20-gauge PPV. CONCLUSION: Eyes treated with 23-gauge TSV tend to have earlier gas disappearance or incomplete gas fill. Intraoperative suture placement would be a solution.

Outcome of autologous platelet concentrate and gas tamponade compared to heavy silicone oil tamponade in persistent macular hole surgery.

PURPOSE: Persistence represents the major reason for failure of primary macular hole repair. A variety of surgical approaches are available for treating persistent macular holes. To compare clinical outcome of re-pars plana vitrectomy combined with autologous platelet concentrate and sulfur hexafluoride 20% gas tamponade with heavy silicone oil in persistent macular hole. METHODS: Records of 48 consecutive eyes with persistent macular holes which underwent re-pars plana vitrectomy with either heavy silicone oil (35 eyes, persistent macular-hole minimum linear diameter: 518.8 ± 171.1 µm) or autologous platelet concentrate and sulfur hexafluoride 20% (13 eyes, persistent macular hole-minimum linear diameter: 454.1 ± 211.3 µm) were reviewed retrospectively. All patients underwent measurements of anatomical persistent macular hole characteristics evaluated by optical coherence tomography and visual function. Cases in which anatomical success failed after first re-pars plana vitrectomy were treated with the other surgical techniques, comparable to a cross-over design. RESULTS: Persistent macular hole closure rate was 57.1% with autologous platelet concentrate and sulfur hexafluoride 20% and 45.7% with heavy silicone oil (p = 0.102). Functional results were comparable when persistent macular hole closure was achieved (p ⩾ 0.741), but significantly better for the autologous platelet concentrate with sulfur hexafluoride 20% group when persistent macular hole closure failed (p = 0.019). CONCLUSION: Re-pars plana vitrectomy combined with autologous platelet concentrate and sulfur hexafluoride 20% seems to achieve at least non-inferior persistent macular hole closure rates and comparable functional results when compared to heavy silicone oil, suggesting autologous platelet concentrate and sulfur hexafluoride 20% as a safe surgical alternative in persistent macular hole. Especially when persistent macular hole closure failed, autologous platelet concentrate with sulfur hexafluoride 20% seems to be superior regarding visual outcome.

Characterization of focal liver lesions by means of assessment of hepatic transit time with contrast-enhanced US.

PURPOSE: To assess whether hepatic transit times (HTTs), as measured with contrast material-enhanced ultrasonography (US), can help predict the nature of focal liver lesions. MATERIALS AND METHODS: The study was approved by the local institutional ethics committee, with written informed patient consent. A total of 402 patients were enrolled in the study. HTT, the time between the appearance of the microbubble contrast agent in the hepatic artery and its appearance in the hepatic vein, was measured in the contrast pulse sequencing mode after injection of a sulphur hexafluoride microbubble US contrast agent. Logistic regression was used to identify factors indicative of the malignant or nonmalignant status of focal liver lesions. Receiver operating characteristic (ROC) analysis was performed to determine the predictive value of the HTT. RESULTS: Observed HTTs for malignant focal liver lesions (mean, 6.2 seconds; range, 2-10 seconds) were significantly lower than those for nonmalignant lesions (mean, 9.5 seconds; range, 4-25 seconds; P < .001). ROC analysis revealed cutoff values of 7 seconds for HTT and 0.879 for area under the ROC curve. For HTTs of 7 seconds or shorter, hepatic malignancies were detected with a sensitivity of 79%, a specificity of 80%, a positive predictive value of 53%, and a negative predictive value of 93%. No malignant lesions had an HTT longer than 10 seconds. CONCLUSION: HTT alone could be a good predictor for nonmalignancy of focal liver lesions.

Diagnostic features of real-time contrast-enhanced ultrasound in focal nodular hyperplasia of the liver.

PURPOSE: The typical appearance of focal nodular hyperplasia (FNH) in radiological contrast techniques (helical CT or MRI) includes homogeneous enhancement in the arterial phase, but the exact timing for the best visualization of this pattern is unknown. The aim of the present study was to assess the ultrasound pattern of FNH with special attention to real-time contrast-enhanced ultrasonography (CEUS) appearance and specifically to the timing of perfusion patterns. MATERIALS AND METHODS: 72 patients (60 females, 12 males) with a total of 90 FNH nodules with a diameter ranging from 8 to 100 mm (mean +/- SD, 40.6 +/- 21.5 mm) were examined continuously for at least 4 minutes using CnTI and CPS methods (ESAOTE, Genoa, Italy and Acuson-Siemens) after bolus injection of SonoVue (BRACCO, Milan, Italy). RESULTS: 87 of 90 nodules showed the typical coin-like hyperechogenicity in the arterial phase. The remaining three nodules were all in the same patient and were diagnosed as FNH after resection. Contrast started to appear within the lesions after a mean of 15.7 +/- 4.6 seconds (range 7 - 27 s) and reached peak signal intensity, with the greatest differentiation between the lesion and the surrounding parenchyma, at around 22.6 +/- 7.0 seconds (range 14 - 72 s). In the late phase, 65 lesions (72.2 %) became isoechoic (after a mean of 80.8 +/- 85.7 s, range 20 - 300 s), 22 (24.4 %) slightly hyperechoic and 3 (3.3 %) faintly hypoechoic. CONCLUSION: FNH shows a typical homogeneous hyperechoic pattern during the arterial phase in real-time CEUS which disappears slowly on average but occasionally even as soon as 20 seconds after contrast injection. If the first scans are taken later than 20 seconds after injection (which is still considered to be a full arterial phase), the ultrasound hyperechogenicity may be missed in some cases. Real-time study of these lesions is therefore strongly recommended to avoid possible false-negative results.

[A comparative study of the hepatic transit time (HTT) of different ultrasound contrast agents in patients with liver metastases and healthy controls]. / Vergleich der hepatischen Transitzeit (HTT) verschiedener Ultraschallkontrastmittel (USKM) bei Patienten mit Lebermetastasen und gesunden Probanden.

PURPOSE: Liver metastases lead to a shortening of the HTT of an echo enhancer. Studies using SonoVue™ also showed a shortening of the HTT in healthy controls. Hence the HTT depends on the applied contrast agent. We examined whether the HTT of SonoVue™, Luminity™ und Levovist™ is useful to discriminate between patients with and without liver metastases. MATERIALS AND METHODS: We compared the arteriovenous HTT of Levovist™, Sonovue™ und Luminity™ in 20 patients with liver metastases and in 15 controls. An Acuson Sequoia™ ultrasound system was used. The HTT results from the difference of the arrival time of the microbubbles in the hepatic artery and a hepatic vein. RESULTS: Using Levovist™ six patients and three controls had to be excluded from further analysis. The arrival time was undetectable. The mean HTT values in healthy controls were: Levovsit™ 14.75 sec (SD ± 2.53 sec), SonoVue™ 9.27 sec (SD ± 2.41 sec) and Luminity™ 9.2 sec (SD ± 2.34 sec). In patients the mean HTT values were: Levovist™ 9.89 sec (SD ± 1.04 sec), SonoVue™ 6.28 sec (SD ± 2.41 sec) and Luminity™ 6.33 sec (SD ± 1.37 sec). Using a cut off of 8 sec for SonoVue™ and Luminity™, the sensitivity to exclude liver metastases was 75% and 80%. CONCLUSION: The mean HTT values of all contrast agents were shorter in patients. Levovist™ showed a longer HTT in patients and controls than Luminity™ and SonoVue™. Levovist™ showed the best separation between patients and controls but some patients and controls had to be excluded. The HTT could still be a useful tool to exclude liver metastases but the HTT depends on the contrast agent and the applied contrast technique.

Effect of Aqueous Dynamics on Gas Behavior Following Retinal Reattachment Surgery.

BACKGROUND AND OBJECTIVE: To determine how the gas concentration in air required to achieve full postoperative vitreous cavity fill varies in different aqueous outflow states. MATERIALS AND METHODS: A mathematical model was used to estimate gas dynamics. The change in gas bubble volume over time was calculated in an eye with normal aqueous outflow, ocular hypertension (OHT), and OHT with apraclonidine treatment. RESULTS: The concentration required was higher for all gases to achieve a full postoperative fill in OHT eyes versus normal eyes. Optimal gas concentrations were 22.6% for SF6, 13.9% for C2F6, and 11.6% for C3F8. Despite this, in OHT, the fill achieved was 95%, 95%, and 94% for SF6, C2F6, and C3F8, respectively. With apraclonidine, percentage fill improved for all gases. CONCLUSIONS: This is the first study to show aqueous outflow affects bubble size and indicates eyes with reduced outflow are at risk of underfill. This can ultimately affect surgical success. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:522-528.].

In vitro labeling of mesenchymal stem cells with superparamagnetic iron oxide by means of microbubble-enhanced US exposure: initial experience.

PURPOSE: To investigate the feasibility of magnetically labeling stem cells with superparamagnetic iron oxide (SPIO) by means of microbubble-enhanced ultrasonographic (US) exposure (MUE) and to study the effects of this approach--without secondary transfection agents--on the viability, proliferation activity, and differentiation capability of MUE-labeled stem cells. MATERIALS AND METHODS: Institutional review board approval was obtained for this study. Human mesenchymal stem cells (MSCs) ([1 to 2] x 10(6)/mL) were studied in four experiment groups: sham exposure to US with microbubbles and SPIO (group A), exposure to US with SPIO but without microbubbles (group B), exposure to US with microbubbles and SPIO (group C), and sham exposure to US without SPIO or microbubbles (group D). Intracellular iron uptake was analyzed qualitatively at light and electron microscopy. The viability and proliferation activity of MSCs were evaluated. The adipogenic and osteogenic differentiation capability of the labeled MSCs was also evaluated. Ninety-five percent confidence intervals were derived for assessment of differences in cell viability and proliferation activity between groups C and D. RESULTS: Light and electron microscopy revealed intracytoplasmic iron uptake and nearly 100% cell labeling efficiency. The MUE-labeled MSCs had unaltered viability and uncompromised proliferation activity compared with the nonlabeled MSCs. Similar to the nonlabeled MSCs, the MUE-labeled MSCs differentiated into adipogenic and osteogenic lineages. CONCLUSION: Initial study results show that stem cells can be effectively labeled with SPIO by using MUE without secondary transfection agents and thus that MUE labeling is an appealing alternative cell-labeling approach that warrants investigation for intracellular magnetic labeling of stem cells. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2531081974/-/DC1.

Ultrasonic microbubble contrast agents and the transplant kidney.

AIM: To evaluate the potential application of microbubble agents in the immediate post-transplant period, by studying contrast uptake and washout, and to correlate these values with clinical indices, and thus, assess the potential prognostic value of this technique. MATERIALS AND METHODS: The study group comprised 20 consecutive renal transplant patients within 7 days of transplantation. Sonovue was administered as an intravenous bolus with continuous imaging of the transplant kidney at low mechanical index (MI) for 1 min post-injection. These data were analysed off-line by two observers, and time intensity curves (TIC) for the upper, mid, and lower poles constructed. Within each pole, a region of interest (5 mm square) was placed over the cortex, medullary pyramid, and interlobar artery, resulting in a total of nine TIC for each patient. TIC parameters included the arrival time (AT), time to peak (TTP), peak intensity (Max), gradient of the slope (M), and the area under curve (AUC). RESULTS: For both observers there was good agreement for all values measured from the cortex and medulla, but poor interobserver correlation for the vascular values. In addition, there was only agreement for these values in the upper and mid-pole of the transplant with poor agreement for the lower pole values. The mid-pole of the transplant kidney was chosen as the point of measurement for subsequent studies. Mid-pole values were correlated with clinical data and outcome over the 3-month post-transplant period. Renal microbubble perfusion correlated with the transplant estimated glomerular filtration rate (eGFR) at 3 months post-transplantation (p=0.016). DISCUSSION: In conclusion, this is the first study to confirm reproducibility of the Sonovue TIC data in transplant patients and to quantify regional variation and perfusion. The statistically significant estimates of transplant perfusion may be of future benefit to transplant recipients and potentially utilized as a prognostic tool. However, a more in depth study will be required to support or refute these early study findings.