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

Progress of In-stent Restenosis after Vertebral Artery Ostium Stenosis and Imaging Assessments

Stenting has become one of the primary procedure to treat vertebral artery ostium stenosis patients. Postoperative in­stent restenosis (ISR) of the stenting is still one of the unsolved issues and requires systematic and further investigation. Through imaging assessments, ISR could be identified and evaluated in clinical practice and researches

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

Effect of a poloxamer 407-based thermosensitive gel on minimization of thermal injury to diaphragm during microwave ablation of the liver.

AIM: To assess the insulating effect of a poloxamer 407 (P407)-based gel during microwave ablation of liver adjacent to the diaphragm. METHODS: We prepared serial dilutions of P407, and 22.5% (w/w) concentration was identified as suitable for ablation procedures. Subsequently, microwave ablations were performed on the livers of 24 rabbits (gel, saline, control groups, n = 8 in each). The P407 solution and 0.9% normal saline were injected into the potential space between the diaphragm and liver in experimental groups. No barriers were applied to the controls. After microwave ablations, the frequency, size and degree of thermal injury were compared histologically among the three groups. Subsequently, another 8 rabbits were injected with the P407 solution and microwave ablation was performed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cr) in serum were tested at 1 d before microwave ablation and 3 and 7 d after operation. RESULTS: In vivo ablation thermal injury to the adjacent diaphragm was evaluated in the control, saline and 22.5% P407 gel groups (P = 0.001-0.040). However, there was no significant difference in the volume of ablation zone among the three groups (P \u3e 0.05). Moreover, there were no statistical differences among the preoperative and postoperative gel groups according to the levels of ALT, AST, BUN and Cr in serum (all P \u3e 0.05). CONCLUSION: Twenty-two point five percent P407 gel could be a more effective choice during microwave ablation of hepatic tumors adjacent to the diaphragm. Further studies for clinical translation are warranted

Emerging Applications of Contrast-enhanced Ultrasound in Trauma

The use of contrast-enhanced ultrasound (CEUS) has expanded over the past decade to include a variety of diagnostic and therapeutic applications. These include urgent clinical situations that require timely diagnosis and subsequent treatment. With the introduction of microbubble ultrasound contrast agents (UCAs), CEUS provides increased sensitivity and specificity over conventional ultrasound. Within the trauma setting, CEUS benefits include point of care imaging and an ability to monitor perfusion in real-time. Additionally, UCAs are non-nephrotoxic, and can be used when contrast enhanced CT is contraindicated. In this review, we discuss recent advancements of CEUS within trauma settings

Ultrasound-triggered antibiotic release from PEEK clips to prevent spinal fusion infection: Initial evaluations.

Despite aggressive peri-operative antibiotic treatments, up to 10% of patients undergoing instrumented spinal surgery develop an infection. Like most implant-associated infections, spinal infections persist through colonization and biofilm formation on spinal instrumentation, which can include metal screws and rods for fixation and an intervertebral cage commonly comprised of polyether ether ketone (PEEK). We have designed a PEEK antibiotic reservoir that would clip to the metal fixation rod and that would achieve slow antibiotic release over several days, followed by a bolus release of antibiotics triggered by ultrasound (US) rupture of a reservoir membrane. We have found using human physiological fluid (synovial fluid), that higher levels (100–500 μg) of vancomycin are required to achieve a marked reduction in adherent bacteria vs. that seen in the common bacterial medium, trypticase soy broth. To achieve these levels of release, we applied a polylactic acid coating to a porous PEEK puck, which exhibited both slow and US-triggered release. This design was further refined to a one-hole or two-hole cylindrical PEEK reservoir that can clip onto a spinal rod for clinical use. Short-term release of high levels of antibiotic (340 ± 168 μg), followed by US-triggered release was measured (7420 ± 2992 μg at 48 h). These levels are sufficient to prevent adhesion of Staphylococcus aureus to implant materials. This study demonstrates the feasibility of an US-mediated antibiotic delivery device, which could be a potent weapon against spinal surgical site infection. Statement of Significance: Spinal surgical sites are prone to bacterial colonization, due to presence of instrumentation, long surgical times, and the surgical creation of a dead space (≥5 cm 3 ) that is filled with wound exudate. Accordingly, it is critical that new approaches are developed to prevent bacterial colonization of spinal implants, especially as neither bulk release systems nor controlled release systems are available for the spine. This new device uses non-invasive ultrasound (US) to trigger bulk release of supra-therapeutic doses of antibiotics from materials commonly used in existing surgical implants. Thus, our new delivery system satisfies this critical need to eradicate surviving bacteria, prevent resistance, and markedly lower spinal infection rates

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

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

LC-MS based stability-indicating method for studying the degradation of lonidamine under physical and chemical stress conditions

Background and purpose: Lonidamine is a hexokinase II inhibitor, works as an anticancer molecule, and is extensively explored in clinical trials. Limited information prevails about the stability-indicating methods which could determine the forced degradation of lonidamine under stressed conditions. Hence, we report the use of a rapid, sensitive, reproducible, and highly accurate liquid chromatography and mass spectrometry method to analyze lonidamine degradation. Experimental approach: The Xbridge BEH shield reverse phase C18 column (2.5 μm, 4.6 × 75 mm) using isocratic 50:50 water: acetonitrile with 0.1% formic acid can detect lonidamine with help of mass spectrometer in tandem with an ultraviolet (UV) detector at 260 nm wavelength. Findings/ Results: A linear curve with r2\u3e 0.99 was obtained for tandem liquid chromatography-mass spectrometry (LC-MS)-UV based detections. This study demonstrated (in the present set up of isocratic elution) that LC-MS based detection has a relatively high sensitivity (S/N (10 ng/mL): 220 and S/N (20 ng/mL): 945) and accuracy at lower detection and quantitation levels, respectively. In addition to developing the LC-MS method, we also report that the current method is stability-indicating and shows that lonidamine gets degraded over time under all three stress conditions; acidic, basic, and oxidative. Conclusion and implications: LC-MS based quantitation of lonidamine proved to be a better method compared to high-performance liquid chromatography (HPLC)-UV detections for mapping lonidamine degradation. This is the first report on the stability-indicating method for studying the forced degradation of lonidamine using LC-MS method