Contrast-enhanced ultrasound identifies early extrahepatic collateral contributing to residual hepatocellular tumor viability after transarterial chemoembolization.

The mainstay of treatment for unresectable hepatocellular carcinoma is locoregional therapy including percutaneous ablation and transarterial chemo- and radioembolization. While monitoring for tumor response after transarterial chemoembolization is crucial, current imaging strategies are suboptimal. The standard of care is contrast-enhanced magnetic resonance imaging or computed tomography imaging performed at least 4 to 6 weeks after therapy. We present a case in which contrast-enhanced ultrasound identified a specific extra-hepatic collateral from the gastroduodenal artery supplying residual viable tumor and assisting with directed transarterial management

Monitoring Progression of Ductal Carcinoma In Situ Using Photoacoustics and Contrast-Enhanced Ultrasound.

Breast cancer is the leading form of cancer in women, accounting for approximately 41,400 deaths in 2018. While a variety of risk factors have been identified, physical exercise has been linked to reducing both the risk and aggressiveness of breast cancer. Within breast cancer, ductal carcinoma in situ (DCIS) is a common finding. However, less than 25% of DCIS tumors actually progress into invasive breast cancer, resulting in overtreatment. This overtreatment is due to a lack of predictive precursors to assess aggressiveness and development of DCIS. We hypothesize that tissue oxygenation and perfusion measured by photoacoustic and contrast-enhanced ultrasound imaging, respectively, can predict DCIS aggressiveness. To test this, 20 FVB/NJ and 20 SV40Tag mice that genetically develop DCIS-like breast cancers were divided evenly into exercise and control groups and imaged over the course of 6 weeks. Tissue oxygenation was a predictive precursor to invasive breast cancer for FVB/NJ mice (P = 0.015) in the early stages of tumor development. Meanwhile, perfusion results were inconclusive (P \u3e 0.2) as a marker for disease progression. Moreover, voluntary physical exercise resulted in lower weekly tumor growth and significantly improved median survival (P = 0.014)

Evaluation of Hepatocellular Carcinoma Transarterial Chemoembolization using Quantitative Analysis of 2D and 3D Real-time Contrast Enhanced Ultrasound.

Quantitative 2D and 3D contrast-enhanced ultrasound (CEUS) was assessed to evaluate early transarterial chemoembolization (TACE) treatment response. Seventeen patients scheduled for TACE for the treatment of hepatocellular carcinoma participated in the study. 2D and 3D CEUS were performed for each patient at three time points: Prior to TACE, 1-2 weeks post TACE, and 1 month post TACE. Peak-intensities of the tumor and surrounding liver tissue were calculated from 2D and 3D data before and after TACE and used to evaluate tumor treatment response. Residual tumor percentages were calculated from 2D and 3D CEUS acquired 1-2 weeks and 1 month post TACE and compared with results from MRI 1 month post TACE. Nine subjects had complete response while 8 had incomplete response. Peak-intensities of the tumor from 3D CEUS prior to TACE were similar between the complete and incomplete treatment groups (p = 0.70), while 1-2 weeks (p \u3c 0.01) and 1 month post treatment (p \u3c 0.01) were significantly lower in the complete treatment group than in the incomplete treatment group. For 2D CEUS, only the peak-intensity values of the tumor from 1 month post TACE were significantly different (p \u3c 0.01). The correlation coefficients between 2D and 3D residual tumor estimates 1-2 weeks post TACE and the estimates from MRI were 0.73 and 0.94, respectively, while those from 2D and 3D CEUS 1 month post TACE were 0.66 and 0.91, respectively. Quantitative analysis on 2D and 3D CEUS shows potential to differentiate patients with complete versus incomplete response to TACE as early as 1-2 weeks post treatment

Subharmonic and Endoscopic Contrast Imaging of Pancreatic Masses: A Pilot Study.

OBJECTIVES: To use subharmonic imaging (SHI) to depict the vascularity of pancreatic masses compared to contrast-enhanced endoscopic ultrasound (EUS) and pathologic results. METHODS: Sixteen patients scheduled for biopsy of a pancreatic mass were enrolled in an Institutional Review Board-approved study. Pulse-inversion SHI (transmitting/receiving at 2.5/1.25 MHz) was performed on a LOGIQ 9 system (GE Healthcare, Milwaukee, WI) with a 4C transducer, whereas contrast harmonic EUS (transmitting/receiving at 4.7/9.4 MHz) was performed with a radial endoscope (GF-UTC180; Olympus Corporation, Tokyo, Japan) connected to a ProSound SSD α-10 scanner (Hitachi Aloka, Tokyo, Japan). Two injections of the contrast agent Definity (Lantheus Medical Imaging, North Billerica, MA) were administrated (0.3-0.4 and 0.6-0.8 mL for EUS and SHI, respectively). Contrast-to-tissue ratios (CTRs) in the mass and an adjacent vessel were calculated. Four physicians independently scored the images (benign to malignant) for diagnostic accuracy and inter-reader agreement. RESULTS: One patient dropped out before imaging, leaving 11 adenocarcinomas, 1 gastrointestinal stromal tumor with pancreatic infiltration, and 3 benign masses. Marked subharmonic signals were obtained in all patients, with intratumoral blood flow clearly visualized with SHI. Significantly greater CTRs were obtained in the masses with SHI than with EUS (mean ± SD, 1.71 ± 1.63 versus 0.63 ± 0.89; P = .016). There were no differences in the CTR in the surrounding vessels or when grouped by pathologic results (P \u3e .60). The accuracies for contrast EUS and SHI were low (\u3c53%), albeit with a greater κ value for SHI (0.34) than for EUS (0.13). CONCLUSIONS: Diagnostic accuracy of contrast EUS and transabdominal SHI for assessment of pancreatic masses was quite low in this pilot study. However, SHI had improved tumoral CTRs relative to contrast EUS

Effect of Pulse Shaping on Subharmonic Aided Pressure Estimation In Vitro and In Vivo.

OBJECTIVES: Subharmonic imaging (SHI) is a technique that uses the nonlinear oscillations of microbubbles when exposed to ultrasound at high pressures transmitting at the fundamental frequency ie, f METHODS: Eight waveforms with different envelopes were optimized with respect to acoustic power at which the SHAPE study is most sensitive. The study was run with four input transmit cycles, first in vitro and then in vivo in three canines to select the waveform that achieved the best sensitivity for detecting changes in portal pressures using SHAPE. A Logiq 9 scanner with a 4C curvi-linear array was used to acquire 2.5 MHz radio-frequency data. Scanning was performed in dual imaging mode with B-mode imaging at 4 MHz and a SHI contrast mode transmitting at 2.5 MHz and receiving at 1.25 MHz. Sonazoid, which is a lipid stabilized gas filled bubble of perfluorobutane, was used as the contrast agent in this study. RESULTS: A linear decrease in subharmonic amplitude with increased pressure was observed for all waveforms (r from -0.77 to -0.93; P \u3c .001) in vitro. There was a significantly higher correlation of the SHAPE gradient with changing pressures for the broadband pulses as compared to the narrowband pulses in both in vitro and in vivo results. The highest correlation was achieved with a Gaussian windowed binomial filtered square wave with an r-value of -0.95. One of the three canines was eliminated for technical reasons, while the other two produced very similar results to those obtained in vitro (r from -0.72 to -0.98; P CONCLUSIONS: Using this waveform is an improvement to the existing SHAPE technique (where a square wave was used) and should make SHAPE more sensitive for noninvasively determining portal hypertension

Subdermal Ultrasound Contrast Agent Injection for Sentinel Lymph Node Identification: An Analysis of Safety and Contrast Agent Dose in Healthy Volunteers.

Objectives—Mapping of the lymphatic chain for identification of the sentinel lymph node (SLN) is an important aspect of predicting outcomes for breast cancer patients, and it is usually performed as an intraoperative procedure using blue dye and/or radiopharmaceuticals agents. Recently the use of contrast-enhanced ultrasound (CEUS) has been proposed as an alternative imaging technique for this mapping. The objective of this study was to evaluate the use of subdermal administration of the ultrasound contrast agent Sonazoid (GE Healthcare) in terms of patient safety and to select the dose to be used for lymphatic applications in humans. Methods—This study was performed in 12 female volunteers that received bilateral subdermal injections of Sonazoid (1 or 2 ml doses) in the mid-upper outer quadrant of their breasts at two different time-points. CEUS was performed 0, 0.25, 0.5, 1, 2, 4, 6 and 24 hours post-injection to identify SLNs. Results—SLNs were identified within the first hour post-injection as enhanced structures and there was no significant difference by dose in the number of SLNs identified (p=0.74). Volunteers only experienced minor adverse experiences (AEs) that resolved completely without intervention by study completion. Conclusion—The subdermal use of Sonazoid in this study showed only minor local and non-significant AEs that were completely resolved without any intervention. Two different doses were compared with no significant differences observed between them. Hence, the lower dose studied (1 ml) was selected for use in future clinical studies

Prognostic impact of combined fludarabine, treosulfan and mitoxantrone resistance profile in childhood acute myeloid leukemia

Background: The role of cellular drug resistance in childhood acute myeloid leukemia (AML) has not yet been established. The aim of the study was the analysis of the clinical value of ex vivo drug resistance in pediatric AML. Patients and Methods: A cohort of 90 children with de novo AML were assayed for drug resistance profile by the 3-4,5- dimethylthiazol-2-yl-2,5-difenyl tetrazolium bromide (MTT) assay and prognostic model of in vitro drug sensitivity was analyzed. Results: Children who relapsed during follow-up showed higher in vitro resistance of leukemic blasts to most of the drugs tested, except for cytarabine, cladribine, vincristine, mercaptopurine and thioguanine. A combined in vitro drug resistance profile to fludarabine, treosulfan and mitoxantrone (FTM score) was defined and it had an independent prognostic significance for disease free survival in pediatric AML. Conclusion: The combined fludarabine, treosulfan and mitoxantrone resistance profile to possibly may be used for better stratification of children with AML or indicate the necessity for additional therapy

How to perform Contrast-Enhanced Ultrasound (CEUS)

"How to perform contrast-enhanced ultrasound (CEUS)" provides general advice on the use of ultrasound contrast agents (UCAs) for clinical decision-making and reviews technical parameters for optimal CEUS performance. CEUS techniques vary between centers, therefore, experts from EFSUMB, WFUMB and from the CEUS LI-RADS working group created a discussion forum to standardize the CEUS examination technique according to published evidence and best personal experience. The goal is to standardise the use and administration of UCAs to facilitate correct diagnoses and ultimately to improve the management and outcomes of patients

Microbubble Cavitation Restores Staphylococcus Aureus Antibiotic Susceptibility in Vitro and in a Septic Arthritis Model

Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using ultrasound-triggered microbubble destruction (UTMD), in vitro and in a porcine model of septic arthritis. In vitro, when bacterially laden SynF is diluted, akin to the dilution achieved clinically with lavage and local injection of antibiotics, amikacin and ultrasound application result in increased bacterial metabolism, aggregate permeabilization, and a 4-5 log decrease in colony forming units, independent of microbubble destruction. Without SynF dilution, amikacin + UTMD does not increase antibiotic activity. Importantly, in the porcine model of septic arthritis, no bacteria are recovered from the SynF after treatment with amikacin and UTMD-ultrasound without UTMD is insufficient. Our data suggest that UTMD + antibiotics may serve as an important adjunct for the treatment of septic arthritis