Contrast-enhanced ultrasound for examining tumor biology

Delorme, Stefan; Krix, Martin

doi:10.1102/1470-7330.2006.0023

Cited by 50 publications

(50 citation statements)

References 27 publications

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“…This agent has a strong nonlinear harmonic response when it is insonated with low acoustic power. The safety and effectiveness of this agent in vascular and parenchymal diagnostic applications have been proved in preliminary experimental and clinical investigations (Delorme and Krix, 2006). SonoVue (5 mg ml À1 ) was mixed with a solution of sodium chloride 0.9% w v À1 solution to form a dispersion containing millions of tiny bubbles of sulphur hexafluoride gas.…”

Section: Power Doppler Ultrasonographic Imagingmentioning

confidence: 99%

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

et al. 2008

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Electrochemotherapy has a direct cytotoxic effect on tumour cells, and presumably, a vascular disrupting effect. In this study, on the basis of the prediction of the mathematical model, histological evaluation and physiological measurements of the tumours were carried out to confirm that electroporation and electrochemotherapy of tumours have a vascular disrupting action. In the study, SA-1 solid subcutaneous sarcoma tumours in A/J mice were treated by bleomycin (BLM) given intravenously (1 mg kg À1 ), application of electric pulses (8 pulses, 1040 V, 100 ms, 1 Hz) or a combination of both -electrochemotherapy. The vascular effect was determined by laser Doppler flowmetry, power Doppler ultrasonographic imaging and Patent blue staining. The extent of tumour hypoxia was determined immunohistochemically by hypoxia marker pimonidazole and partial pressure of oxygen (pO 2 ) in tumours by electron paramagnetic resonance oximetry. Electrochemotherapy with BLM induced good antitumour effect with 22 days, tumour growth delay and 38% tumour cures. The application of electric pulses to the tumours induced instant but transient tumour blood flow reduction (for 70%) that was recovered in 24 h. During this tumour blood flow reduction, we determined an increase in hypoxic tumour area for up to 30%, which was also reflected in reduced tumour oxygenation (for 70%). According to the described mathematical model, endothelial cells lining in tumour blood vessels are exposed to a B40% higher electric field than the surrounding tumour cells, and therefore easily electroporated, allowing access of high BLM concentration to the cytosol. Consequently, electrochemotherapy has, besides the immediate vascular disrupting action, also a delayed one (after 24 h), as a consequence of endothelial cell swelling and apoptosis demonstrated by extensive tumour necrosis, tumour hypoxia, prolonged reduction of tumour blood flow and significant tumour growth delay, and tumour cures. Our results demonstrate that in addition to the well-established direct cytotoxic effect on tumour cells, electrochemotherapy also has an indirect vascular disrupting action resulting altogether in extensive tumour cell necrosis leading to complete regression of tumours.

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Section: Power Doppler Ultrasonographic Imagingmentioning

confidence: 99%

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

et al. 2008

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“…Contrast agents are used to achieve contrast enhancement of perfused areas [66,126] Electron paramagnetic resonance oximetry A method related to NMR for absolute pO 2 measurement. When tissue is exposed to appropriate external magnetic excitation, the resulting electron paramagnetic resonance spectra of the paramagnetic material implanted in tissue depends on local oxygenation and can be measured by a surface coil resonator [81,89,[127][128][129] Luminescence-based fiber-optic oximetry A novel method for absolute pO 2 monitoring.…”

Section: Blood Flow-modifying Effects Of Epmentioning

confidence: 99%

Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases

Jarm

Čemažar

Miklavčič

et al. 2010

Expert Review of Anticancer Therapy

192

132

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“…Doppler ultrasound has been used to monitor antiangiogenic therapy, but its sensitivity for the assessment of changes in the vascularization was shown to be limited [5,11]. This may be due to the fact that conventional Doppler ultrasound is relatively insensitive for slow blood flow values, which predominantly occur in vessels of less than 100 μm in diameter [5].…”

Section: Introductionmentioning

confidence: 97%

“…Ultrasound contrast agents consist of gas-filled microbubbles with a size of 1-6 μm that remain strictly intravascular [11,12]. The advantages of using contrast agents in ultrasound are the highly increased sensitivity to detect even small blood vessels down to a size of 10 μm [13].…”

Section: Introductionmentioning

confidence: 99%

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Volumetric high-frequency Doppler ultrasound enables the assessment of early antiangiogenic therapy effects on tumor xenografts in nude mice

et al. 2007

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The sensitivity of Doppler ultrasound below 10 MHz to assess antiangiogenic therapy effects in tumor xenografts has been shown to be limited. Thus, our aim was to evaluate high-frequency volumetric power-Doppler ultrasound (HF-VPDU) for monitoring antiangiogenic treatments. Squamous cell carcinoma xenografts grown in nude mice were scanned with HF-VPDU at a center frequency of 30 MHz. Images with 200-microm slice thicknesses were recorded and merged into a three-dimensional dataset, of which the relative color pixel density was determined. Animals received either VEGFR2 antibodies or 0.9% NaCl and were examined at days 0, 3 and 6 of treatment. After the last examination, tumors were resected and their vascularization characterized by immunohistology. At day 6, the volumes of treated and untreated tumors were not significantly different yet. In contrast, mean tumor vascularization in treated animals had decreased to 44%, while in the control group it had increased to 152% (P < 0.01). In correspondence, vessel density, as determined by CD31 staining, was 0.19 +/- 0.10% in treated and 0.92 +/- 0.41% in untreated tumors (P < 0.01). Additionally, the fraction of mature (SMA-positive) vessels increased under therapy. Thus, HF-VPDU can be considered as an easily applicable and fast method to screen high animal numbers for antiangiogenic therapy effects.

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Contrast-enhanced ultrasound for examining tumor biology

Cited by 50 publications

References 27 publications

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases

Volumetric high-frequency Doppler ultrasound enables the assessment of early antiangiogenic therapy effects on tumor xenografts in nude mice

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