Histological Observation of Islet Hemorrhage Induced by Diagnostic Ultrasound with Contrast Agent in Rat Pancreas

Miller, Douglas L.; Dou, Chunyan; Sorenson, Dorothy R.; Liu, Ming

doi:10.1371/journal.pone.0021617

Cited by 9 publications

(8 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These are manifest primarily as significant hemorrhage in conjunction with vascular disruption (Miller et al, 2011). In the work here, we used a lower pressure of 570 kPa, which caused endothelial cell death and vascular collapse as before (Czarnota et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Cellular characterization of ultrasound-stimulated microbubble radiation enhancement

Al‐Mahrouki

Iradji

Tran

et al. 2014

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Tumor radiation resistance poses a major obstacle in achieving an optimal outcome in radiation therapy. In the current study, we characterize a novel therapeutic approach that combines ultrasound-driven microbubbles with radiation to increase treatment responses in a prostate cancer xenograft model in mice. Tumor response to ultrasound-driven microbubbles and radiation was assessed 24 hours after treatment, which consisted of radiation treatments alone (2 Gy or 8 Gy) or ultrasound-stimulated microbubbles only, or a combination of radiation and ultrasound-stimulated microbubbles. Immunohistochemical analysis using in situ end labeling (ISEL) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) revealed increased cell death within tumors exposed to combined treatments compared with untreated tumors or tumors exposed to radiation alone. Several biomarkers were investigated to evaluate cell proliferation (Ki67), blood leakage (factor VIII), angiogenesis (cluster of differentiation molecule CD31), ceramide-formation, angiogenesis signaling [vascular endothelial growth factor (VEGF)], oxygen limitation (prolyl hydroxylase PHD2) and DNA damage/repair (γH2AX). Results demonstrated reduced vascularity due to vascular disruption by ultrasound-stimulated microbubbles, increased ceramide production and increased DNA damage of tumor cells, despite decreased tumor oxygenation with significantly less proliferating cells in the combined treatments. This combined approach could be a feasible option as a novel enhancing approach in radiation therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Cellular characterization of ultrasound-stimulated microbubble radiation enhancement

Al‐Mahrouki

Iradji

Tran

et al. 2014

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…The extravascular fibrinogen might bind to cellular antigens, such as intercellular adhesion molecule 1 (ICAM-1) related to early immune responses to injury (Boyd, et al 2008), and would then be labeled immunohistochemically. There were no apparent regions with extensive thrombus formation, such as were seen for contrast enhanced diagnostic ultrasound of rat kidney in Bowman’s capsule (Miller et al 2009) and pancreas around the effected islets (Miller et al 2011a). …”

Section: Discussionmentioning

confidence: 99%

Frequency Dependence of Petechial Hemorrhage and Cardiomyocyte Injury Induced during Myocardial Contrast Echocardiography

Miller

Fabiilli

et al. 2016

Ultrasound in Medicine & Biology

Self Cite

View full text Add to dashboard Cite

Myocardial contrast echocardiography (MCE) for perfusion imaging can induce microscale bioeffects during intermittent high Mechanical Index (MI) scans. The dependence of MCE induced bioeffects on the ultrasonic frequency was examined in rats at 1.6, 2.5 and 3.5 MHz. Premature complexes were counted in the ECG, petechial hemorrhages (PH) with microvascular leakage on the heart surface were observed at the time of exposure, plasma troponin elevation was measured after 4 h and cardiomyocyte injury was detected at 24 h. Increasing response to exposure above an apparent threshold was observed for all endpoints at each frequency. The effects decreased with increasing ultrasonic frequency, and the thresholds increased. Linear regressions for frequency dependent thresholds indicated coefficients and exponents of 0.6 and 1.07 for PH, respectively, and 1.02 and 0.8 for cardiomyocyte death, compared to 1.9 and 0.5 (square root) for the guideline limit of the MI. The results clarify the dependence of cardiac bioeffects on frequency, and should allow development of theoretical descriptions of the phenomena and improved safety guidance for MCE.

show abstract

“…Although clinical trials and meta-analyses have recently dispelled concerns over the safety of UCAs in human patients, [18][19][20][21][22][23] there is a large body of experimental research literature that has not been controverted. Ultrasound and UCAs have induced capillary rupture and hemorrhage, [24][25][26] cardiac damage, 27 and arrhythmias 28 and impaired vascular endothelial function 29 in animal studies. Ultrasound has been shown to mechanically disturb cell membranes, inducing temporary permeability in a phenomenon known as sonoporation.…”

Section: Discussionmentioning

confidence: 99%

Contrast Ultrasound Imaging Does Not Affect Heat Shock Protein 70 Expression in Cholesterol‐Fed Rabbit Aorta

Smith

Simpson

Miller

et al. 2015

J of Ultrasound Medicine

View full text Add to dashboard Cite

Objectives Diagnostic ultrasound imaging is enhanced by the use of circulating microbubble contrast agents (UCAs), but the interactions between ultrasound, UCAs, and vascular tissue are not fully understood. We hypothesized that ultrasound with a UCA would stress the vascular tissue and increase levels of heat shock protein 70 (Hsp70), a cellular stress protein. Methods Male New Zealand White rabbits (n = 32) were fed a standard chow diet (n = 4) or a 1% cholesterol, 10% fat, and 0.11% magnesium diet (n = 28). At 21 days, 24 rabbits on the cholesterol diet were either exposed to ultrasound (3.2-MHz f/3 transducer; 2.1 MPa; mechanical index, 1.17; 10 Hz pulse repetition frequency; 1.6 micro -seconds pulse duration; 2 minutes exposure duration at 4 sites along the aorta) with the UCA Definity (1× concentration, 1 mL/min; Lantheus Medical Imaging, North Billerica, MA) or sham exposed with a saline vehicle injection (n = 12 per group). Four rabbits on the cholesterol diet and 4 on the chow diet served as cage controls and were not exposed to ultrasound or restrained for blood sample collection. Animals were euthanized 24 hours after exposure, and aortas were quickly isolated and frozen in liquid nitrogen. Aorta lysates from the area of ultrasound exposure were analyzed for Hsp70 level by Western blot. Blood plasma was analyzed for cholesterol, Hsp70, and von Willebrand factor, a marker of endothelial function. Results Plasma total cholesterol levels increased to an average of 705 mg/dL. Ultrasound did not affect plasma von Willebrand factor, plasma Hsp70, or aorta Hsp70. Restraint increased Hsp70 (P < .001, analysis of variance). Conclusions Restraint, but not ultrasound with the UCA or cholesterol feeding, significantly increased Hsp70.

show abstract

Histological Observation of Islet Hemorrhage Induced by Diagnostic Ultrasound with Contrast Agent in Rat Pancreas

Cited by 9 publications

References 16 publications

Cellular characterization of ultrasound-stimulated microbubble radiation enhancement

Cellular characterization of ultrasound-stimulated microbubble radiation enhancement

Frequency Dependence of Petechial Hemorrhage and Cardiomyocyte Injury Induced during Myocardial Contrast Echocardiography

Contrast Ultrasound Imaging Does Not Affect Heat Shock Protein 70 Expression in Cholesterol‐Fed Rabbit Aorta

Contact Info

Product

Resources

About