Developing a Microbubble-Based Contrast Agent for Synchrotron Multiple-Image Radiography.

PURPOSE: Multiple-image radiography (MIR) is an analyzer-based synchrotron X-ray imaging approach capable of dissociating absorption, refraction, and scattering components of X-ray interaction with the material. It generates additional image contrast mechanisms (besides absorption), especially in the case of soft tissues, while minimizing absorbed radiation dose. Our goal is to develop a contrast agent for MIR using ultrasound microbubbles by carrying out a systematic assessment of size, shell material, and concentration. PROCEDURES: Microbubbles were synthesized with two different shell materials: phospholipid and polyvinyl-alcohol. Polydisperse perfluorobutane-filled lipid microbubbles were divided into five size groups using centrifugation. Two distributions of air-filled polymer microbubbles were generated: 2-3 µm and 3-4 µm. A subset of polymer microbubbles 3-4 µm had iron oxide nanoparticles incorporated into their shell or coated on their surface. Microbubbles were immobilized in agar with different concentrations: 5 × 107, 5 × 106, and 5 × 105 MBs/ml. MIR was conducted on the BioMedical Imaging and Therapy beamline at the Canadian Light Source. Three images were generated: Gaussian amplitude, refraction, and ultra-small-angle X-ray scattering (USAXS). The contrast signal was quantified by measuring mean pixel values and comparing them with agar. RESULTS: No difference was detected in absorption or refraction images of all tested microbubbles. Using USAXS, a significant signal increase was observed with lipid microbubbles 6-10 µm at the highest concentration (p = 0.02), but no signal was observed at lower concentrations. CONCLUSIONS: These data indicate that lipid microbubbles 6-10 µm are candidates as contrast agents for MIR, specifically for USAXS. A minimum concentration of 5 × 107 microbubbles (lipid-shell 6-10 µm) per milliliter was needed to generate a detectable signal.

Developing a Microbubble-Based Contrast Agent for Synchrotron In-Line Phase Contrast Imaging.

OBJECTIVE: X-ray phase contrast imaging generates contrast from refraction of X-rays, enhancing soft tissue contrast compared to conventional absorption-based imaging. Our goal is to develop a contrast agent for X-ray in-line phase contrast imaging (PCI) based on ultrasound microbubbles (MBs), by assessing size, shell material, and concentration. METHODS: Polydisperse perfluorobutane-core lipid-shelled MBs were synthesized and size separated into five groups between 1 and 10 µm. We generated two size populations of polyvinyl-alcohol (PVA)-MBs, 2-3 µm and 3-4 µm, whose shells were either coated or integrated with iron oxide nanoparticles (SPIONs). Microbubbles were then embedded in agar at three concentrations: 5 × 107, 5 × 106 and 5 × 105 MBs/ml. In-line phase contrast imaging was performed at the Canadian Light Source with filtered white beam micro-computed tomography. Phase contrast intensity was measured by both counting detectable MBs, and comparing mean pixel values (MPV) in minimum and maximum intensity projections of the overall samples. RESULTS: Individual lipid-MBs 6-10 µm, lipid-MBs 4-6 µm and PVA-MBs coated with SPIONs were detectable at each concentration. At the highest concentration, lipid-MBs 6-10 µm and 4-6 µm showed an overall increase in positive contrast, whereas at a moderate concentration, only lipid-MBs 6-10 µm displayed an increase. Negative contrast was also observed from two largest lipid-MBs at high concentration. CONCLUSION: These data indicate that lipid-MBs larger than 4 µm are candidates for PCI, and 5 × 106 MBs/ml may be the lowest concentration suitable for generating visible phase contrast in vivo. SIGNIFICANCE: Identifying a suitable MB for PCI may facilitate future clinical translation.

Contrast-enhanced ultrasound imaging for assessing organ perfusion in rainbow trout (Oncorhynchus mykiss).

Contrast-enhanced ultrasound (CEUS) imaging has great potential as a non-lethal, inexpensive monitoring tool in aquatic toxicology. It is a well-established clinical imaging approach that combines real-time, quantitative assessment of organ blood flow, with morphological data. In humans, it has been extensively used to measure changes in blood flow that can be attributed to cancer, inflammation, and other biological abnormalities. However, it has yet to be explored as a tool for fish physiology or environmental toxicology. In this study, our goal was to determine if CEUS could be used to visualize and measure blood flow in the liver of a rainbow trout. All rainbow trout received two injections of an ultrasound contrast agent, microbubbles. A subset received a third injection after administration of propranolol, a non-specific beta1 & 2-blocker, to determine if changes in blood flow could be detected. Ultrasound contrast time-intensity curves (TIC) were obtained, fit to a lognormal model, and different perfusion parameters were calculated. Contrast enhancement was observed in all rainbow trout livers, with high percentage between repeated measurements, including blood flow (80.6 ± 27.3%), area under the curve (73.2 ± 14%), blood volume (84 ± 14.2%) and peak enhancement (86.7 ± 7.5%). After administration of propranolol, we detected a non-significant (p > 0.05) increase in area under the curve (102.6 ± 44.2%), peak enhancement (77.3 ± 106.4), blood volume (48.2 ± 74.5%), and decrease in hepatic blood flow (-17.3 ± 37.1%). These data suggest that CEUS imaging is suitable to measure organ blood flow in fish, and demonstrates tremendous potential for exploring different organs, fish species, and effects of chemical contaminants in future studies.

Comparative Clinical Observation of Arthroscopic Microfracture in the Presence and Absence of a Stromal Vascular Fraction Injection for Osteoarthritis.

Osteoarthritis (OA) is a degenerative cartilage disease that is characterized by a local inflammatory reaction. Consequently, many studies have been performed to identify suitable prevention and treatment interventions. In recent years, both arthroscopic microfracture (AM) and stem cell therapy have been used clinically to treat OA. This study aimed to evaluate the clinical effects of AM in the presence and absence of a stromal vascular fraction (SVF) injection in the management of patients with OA. Thirty patients with grade 2 or 3 (Lawrence scale) OA of the knee participated in this study. Placebo group patients (n = 15) received AM alone; treatment group patients (n = 15) received AM and an adipose tissue-derived SVF injection. The SVF was suspended in platelet-rich plasma (PRP) before injection into the joint. Patient groups were monitored and scored with the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Lysholm, Visual Analog Pain Scale (VAS), and modified Outerbridge classifications before treatment and at 6, 12, and 18 months post-treatment. Bone marrow edema was also assessed at these time points. Patients were evaluated for knee activity (joint motion amplitude) and adverse effects relating to surgery and stem cell injection. Treatment efficacy was significantly different between placebo and treatment groups. All treatment group patients had significantly reduced pain and WOMAC scores, and increased Lysholm and VAS scores compared with the placebo group. These findings suggest that the SVF/PRP injection efficiently improved OA for 18 months after treatment. This study will be continuously monitored for additional 24 months. Stem Cells Translational Medicine 2017;6:187-195.

Perception of anesthesia safety and postoperative symptoms of surgery patients in Ho Chi Minh City, Vietnam: a pioneering trial of postoperative care assessment in a developing nation.

OBJECTIVES: Vietnamese patients' views on healthcare are changing as surgical interventions become more commonplace, but their views on perioperative care have remained largely unstudied during this period of rapid change. This study assesses Vietnamese patients' impression of anesthesia safety and postoperative pain in relation to clinical outcomes with the aim of improving patient-centered perioperative care. METHODS: The study cohort consisted of 180 hospitalized patients who were followed for 24 h following abdominal surgery. The assessments of these patients on the use of anesthesia and postoperative pain were measured by means of a 5-point Likert scale survey. Perioperative events were recorded on standardized forms by medical staff. The relationship between relevant factors affecting the patients' perceptions of anesthesia safety, postoperative symptoms, and pain was examined using multiple logistic regression analysis. RESULTS: The perception of a low level of anesthesia safety by 105 patients (59%) was associated with a low satisfaction in terms of preoperative anesthesia education [odds ratio (OR) 15.03], poor interaction with family (OR 21.80), and absence of perioperative adverse effects (OR 6.10). The occurrence of three or more postoperative symptoms (59%) was associated with a surgery ≥3 h (OR 2.00). Severe pain at 2 h (25%) post-surgery was associated with male gender (OR 2.08) and open surgery (OR 3.30), no reduction in pain at 24 h (51%) was associated with female gender (OR 2.08), and experiencing as much or more pain than expected (46%) was associated with blood loss ≥100 ml (OR 1.04) and low satisfaction with staff communication (OR 1.90). CONCLUSION: Our results suggest that facilitating patients' communication with staff and families and paying attention to gender differences in pain management are important factors to take into consideration when the aim is to improve perioperative care in the rapidly developing healthcare environment of Vietnam.