Objective This study investigated methods of evaluating the bone fracture healing process using superb microvascular imaging (SMI; two modes color SMI [cSMI] and monochromeSMI [mSMI]), and shear wave elastography (SWE), relative to X‐ray, dual‐energy X‐ray absorptiometry (DXA), and platelet endothelial cell adhesion molecule 1 (PECAM‐1) also know as cluster of differentiation 31 (CD‐31) staining in a rabbit model. Methods This IACUC‐approved study involved eight rabbits that underwent a bilateral fibula osteotomy and were followed for 7 or 21 days (Groups 1 and 2 with 4 rabbits in each). Ultrasound examinations using cSMI, mSMI, and SWE were performed on Days 0, 4, 7, 14, and 21 post‐surgery. At the final time point, rabbits had X‐ray imaging followed by euthanasia and DXA scan. Finally, the fracture areas underwent decalcification, and specimens were stained with CD‐31 for pathological analysis. Ultrasound and X‐ray findings were compared using ANOVAs or paired t ‐tests with CD‐31 stains and DXA was used as a reference. Results Comparing SMI ultrasound images between the last time points for Group 1 (Day 7) and Group 2 (Day 21) showed no statistical significance difference for cSMI ( P = .14) and mSMI ( P = .06), similarly when compared with CD‐31 stains there was no statistical significance difference for cSMI in Group 2 ( P = .13). The SWE ultrasound images from the last time points in Groups 1 and showed no statistical significance difference ( P = .33), the same results were then compared with DXA and also showed no statistical significance difference ( P = .14). When comparing results of the X‐ray images from the last time points for Groups 1 and 2 a statistical significance difference was found ( P = .01), and when X‐ray images were compared with DXA there was a statistical significance difference ( P < .001). Conclusion Compared with CD‐31 stains cSMI on Day 21 was not statistically significant ( P = .13). Results comparing SWE with DXA were also not statistically significant ( P = .14). These results indicate the potential of using certain ultrasound imaging techniques to monitor the bone fracture healing process.
ULTRASOUND CONTRAST AGENTS : basic principles and clinical applications , ULTRASOUND CONTRAST AGENTS : basic principles and clinical applications , کتابخانه مرکزی دانشگاه علوم پزشکی ایران
Gas-filled microbubbles are used as contrast agents in diagnostic ultrasound imaging. A preclinical, acute toxicity study of 2 surfactant-stabilized ultrasound contrast agents (ST68 and ST44) was conducted. Subjects were 104 Sprague-Dawley rats (experimental doses, 0.1, 0.2, 0.8, and 1.0 mL/kg; control, 1.0 mL/kg saline) that were studied for 14 days after contrast; clinical signs, weight, blood, and urine were evaluated. Histopathology was performed following euthanasia. Of the 40 animals receiving ST44, 4 died prematurely and a dose dependency was demonstrated ( P = .011), whereas in the ST68 groups only 1 death occurred (no dose dependency; P = .48). Only the weight of rats injected with ST44 varied significantly ( P = .0003). This dependency was also found for 3 of 5 urine parameters and 4 of 36 blood parameters ( P < .05). For ST68, only 1 urine parameter showed significance ( P < .0001). Giant cell infiltration in the lungs was significantly higher than controls in the ST44 0.1 mL/kg and the ST68 0.8-1.0 mL/kg groups ( P < .01). It is concluded that the prudent choice for future nonrodent, toxicology studies and potentially for human clinical trials is ST68 (given the deaths in the ST44 groups).
Abstract : Neoadjuvant chemotherapy is currently the standard of care for locally advanced breast cancer (LABC). Monitoring tumor response is advantageous for patients. This project aims at establishing noninvasive monitoring of neoadjuvant chemotherapy in the breast using subharmonic aided pressure estimation (SHAPE) to estimate the interstitial fluid pressure (IFP) in LABC. In vitro experiments with the ultrasound contrast agent Definity have showed an inverse linear relationship between the change in subharmonic amplitude and hydrostatic pressure (r2=0.63-0.95, p0.01) over the pressure range associated with breast tumors (0 50 mmHg). In vivo proof of concept for SHAPE as a noninvasive monitor of IFP (r2=0.67-0.96, p0.01) has been provided based on a swine model. The work on in vivo SHAPE measurements of IFP was selected for the final of the American Institute of Ultrasound in Medicine (AIUM) 2011 Young Investigator Award (for VG Halldorsdottir) and was awarded FIRST place out of 90 abstracts submitted for this competition. In total, 97 female, nude rats were implanted with MDA-MB-231 cells and 51 animals were successfully studied with SHI and SHAPE 21, 24 or 28 days after tumor inoculation. However, the comparisons between SHAPE and Stryker IFP measurements have yet to be completed. The SHI images of tumor vascularity were compared to immunohistochemical markers of angiogenesis (CD31, COX-2 and VEGF). The strongest correlation determined by linear regression in this breast cancer model was between SHI and percent area stained with VEGF (r=0.53).
