High-Resolution Ultrasound Perfusion Imaging of Therapeutic Angiogenesis

Rissanen, Tuomas T.; Korpisalo, Petra; Karvinen, Henna; Liimatainen, Timo; Laidinen, Svetlana; Gröhn, Olli; Ylä‐Herttuala, Seppo

doi:10.1016/j.jcmg.2007.10.009

Cited by 52 publications

(25 citation statements)

References 17 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Targeted imaging signals (in linear arbitrary units [lau]) in the ROIs were then calculated with the destruction-replenishment method (see Appendix E1 [online]) (31–34). Colorimetric maps of peak enhancement perfusion profiles were analyzed for patterns of peripheral or uniform distribution of functional vascularity (see Appendix E1 [online]) (35). …”

Section: Methodsmentioning

confidence: 99%

Vascular Endothelial Growth Factor Receptor Type 2–targeted Contrast-enhanced US of Pancreatic Cancer Neovasculature in a Genetically Engineered Mouse Model: Potential for Earlier Detection

Pysz¹,

Machtaler

Seeley

et al. 2015

Radiology

View full text Add to dashboard Cite

Purpose To test ultrasonographic (US) imaging with vascular endothelial growth factor receptor type 2 (VEGFR2)-targeted microbubble contrast material for the detection of pancreatic ductal adenocarcinoma (PDAC) in a transgenic mouse model of pancreatic cancer development. Materials and Methods Experiments involving animals were approved by the Institutional Administrative Panel on Laboratory Animal Care at Stanford University. Transgenic mice (n = 44; Pdx1-Cre, KRasG12D, Ink4a−/−) that spontaneously develop PDAC starting at 4 weeks of age were imaged by using a dedicated small-animal US system after intravenous injection of 5 × 107 clinical-grade VEGFR2-targeted microbubble contrast material. The pancreata in wild-type (WT) mice (n = 64) were scanned as controls. Pancreatic tissue was analyzed ex vivo by means of histologic examination (with hematoxylin-eosin staining) and immunostaining of vascular endothelial cell marker CD31 and VEGFR2. The Wilcoxon rank sum test and linear mixed-effects model were used for statistical analysis. Results VEGFR2-targeted US of PDAC showed significantly higher signal intensities (26.8-fold higher; mean intensity ± standard deviation, 6.7 linear arbitrary units [lau] ± 8.5; P < .001) in transgenic mice compared with normal, control pancreata of WT mice (mean intensity, 0.25 lau ± 0.25). The highest VEGFR2-targeted US signal intensities were observed in smaller tumors, less than 3 mm in diameter (30.8-fold higher than control tissue with mean intensity of 7.7 lau ± 9.3 [P < .001]; and 1.7-fold higher than lesions larger than 3 mm in diameter with mean intensity of 4.6 lau ± 5.8 [P < .024]). Ex vivo quantitative VEGFR2 immunofluorescence demonstrated that VEGFR2 expression was significantly higher in pancreatic tumors (P < .001; mean fluorescent intensity, 499.4 arbitrary units [au] ± 179.1) compared with normal pancreas (mean fluorescent intensity, 232.9 au ± 83.7). Conclusion US with clinical-grade VEGFR2-targeted microbubbles allows detection of small foci of PDAC in transgenic mice.

show abstract

Section: Methodsmentioning

confidence: 99%

Vascular Endothelial Growth Factor Receptor Type 2–targeted Contrast-enhanced US of Pancreatic Cancer Neovasculature in a Genetically Engineered Mouse Model: Potential for Earlier Detection

Pysz¹,

Machtaler

Seeley

et al. 2015

Radiology

View full text Add to dashboard Cite

show abstract

“…A control vector (AdCMV) was used in three doses 1 × 10 9 , 1 × 10 10 and 1 × 10 11 vp. Blood perfusion in the target muscle was analyzed before and 6 days after the gene transfers using a contrast pulse sequence (CPS) ultrasound method, that is suitable for detecting blood flow in the capillary level vessels in addition to the larger vessels 20 . All three VEGF encoding vectors induced significant increases in blood perfusion (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Contrast pulse sequence (CPS) ultrasound imaging was performed before and at d6 after gene transfer for the analysis of changes in perfusion in the treated muscles as described previously 20 . Acuson Sequoia 512 and 15 L8 transducer (Siemens AG, Erlangen, Germany) with Sonovue (Bracco, Milano, Italy) contrast agent were used to measure the perfusion in the muscles and the peak intensities were analyzed.…”

Section: Methodsmentioning

confidence: 99%

Snake venom VEGF Vammin induces a highly efficient angiogenic response in skeletal muscle via VEGFR-2/NRP specific signaling

Toivanen

Nieminen

Laakkonen

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Vascular Endothelial Growth Factors (VEGFs) are promising molecules for the treatment of ischemic diseases by pro-angiogenic therapy. Snake venom VEGFs are a novel subgroup with unique receptor binding profiles and as such are potential new therapeutic agents. We determined the ligand-receptor interactions, gene regulation and angiogenic properties of Vipera ammodytes venom VEGF, Vammin, and compared it to the canonical angiogenic factor VEGF-A to evaluate the use of Vammin for therapeutic angiogenesis. Vammin efficiently induced VEGFR-2 mediated proliferation and expression of genes associated with proliferation, migration and angiogenesis. VEGF-A165 and especially VEGF-A109 induced less pronounced effects. Vammin regulates a number of signaling pathways by inducing the expression of NR4A family nuclear receptors and regulators of calcium signaling and MAP kinase pathways. Interestingly, MARC1, which encodes an enzyme discovered to catalyze reduction of nitrate to NO, was identified as a novel VEGFR-2 regulated gene. In rabbit skeletal muscle adenoviral delivery of Vammin induced prominent angiogenic responses. Both the vector dose and the co-receptor binding of the ligand were critical parameters controlling the type of angiogenic response from sprouting angiogenesis to vessel enlargement. Vammin induced VEGFR-2/NRP-1 mediated signaling more effectively than VEGF-A, consequently it is a promising candidate for development of pro-angiogenic therapies.

show abstract

“…It was shown to be associated with disease severity in children with asthma 4, 6. In recent years, several noninvasive imaging techniques have been developed and used as tools to evaluate angiogenesis 8. Of particular interest, high magnification endoscopy provides an adequate assessment of the submucosal vascular network in asthmatic patients 7.…”

Section: Discussionmentioning

confidence: 99%

Endoscopic Evaluation of Angiogenesis in the Large Airways of Horses with Heaves Using Narrow Band Imaging

Herteman

Bullone

Lavoie

2016

Veterinary Internal Medicne

View full text Add to dashboard Cite

BackgroundHeaves is a severe debilitating condition of horses, characterized by lower airway inflammation and permanent structural changes of the bronchial wall. Chronic inflammation promotes the formation of new vessels, a phenomenon known as angiogenesis. Narrow band imaging (NBI) endoscopy is a noninvasive technique that enhances the visualization of submucosal vessels, and commonly is employed for the study of angiogenesis in human patients.ObjectivesUsing NBI, we aimed to determine whether or not the central airways of horses with heaves undergo angiogenesis.AnimalsHorses with heaves during exacerbation of the disease (n = 5) and healthy controls (n = 6).MethodsA library of NBI images was established from previously recorded videoendoscopies. Images were acquired by an operator blinded to horse ID. Images were obtained from 3 sites: 130 from the trachea (14 ± 9.3 [mean ± SD] images per horse with heaves and 10 ± 5.4 from controls; P = .45), 58 from the carina (5.4 ± 3.2 from horses with heaves and 5.2 ± 2.8 fromn controls; P > .99) and 167 from the intermediate bronchi (17.8 ± 6.7 from horses with heaves and 13 ± 5.6 from controls; P = .17). Using dedicated stereology software (NewCAST, Visiopharm; Denmark), the volume density of superficial and deep vessels was calculated blindly by point counting at each site for all horses.ResultsIn the trachea, the volume density of superficial vessels was increased in horses with heaves compared to controls (P = .02). No difference was found between groups for the volume density of both superficial and deep vessels at the carina or intermediate bronchi.Conclusion and Clinical Relevance NBI imaging of the airways was easily performed in standing sedated horses.

show abstract

High-Resolution Ultrasound Perfusion Imaging of Therapeutic Angiogenesis

Abstract: Contrast pulse sequence ultrasound is an efficient and accurate noninvasive real-time perfusion imaging modality in small laboratory animals and also offers a means for the assessment of muscle perfusion in future clinical trials of therapeutic angiogenesis.

Cited by 52 publications

References 17 publications

Vascular Endothelial Growth Factor Receptor Type 2–targeted Contrast-enhanced US of Pancreatic Cancer Neovasculature in a Genetically Engineered Mouse Model: Potential for Earlier Detection

Vascular Endothelial Growth Factor Receptor Type 2–targeted Contrast-enhanced US of Pancreatic Cancer Neovasculature in a Genetically Engineered Mouse Model: Potential for Earlier Detection

Snake venom VEGF Vammin induces a highly efficient angiogenic response in skeletal muscle via VEGFR-2/NRP specific signaling

Endoscopic Evaluation of Angiogenesis in the Large Airways of Horses with Heaves Using Narrow Band Imaging

Contact Info

Product

Resources

About