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  • 1
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    Springer
    Tumor Angiogenesis 529-544 
    Keywords: TUMOR ANGIOGENESIS ; imaging ; ANGIOGENESIS ; tumor
    Type of Publication: Book chapter
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  • 3
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    Springer
    Keywords: intensity ; CONTRAST-MEDIA ; MEDIA ; imaging ; TIME ; contrast media ; CONTRAST
    Type of Publication: Book chapter
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  • 4
    Keywords: RECEPTOR ; SPECTRA ; ANGIOGENESIS ; CANCER ; GROWTH ; GROWTH-FACTOR ; IN-VITRO ; INHIBITOR ; proliferation ; SURVIVAL ; tumor ; ADVANCED SOLID TUMORS ; AGENTS ; ANGIOSTATIN ; BLOOD ; carcinoma ; CELL ; CELL LUNG-CANCER ; CELL-PROLIFERATION ; CLINICAL-TRIAL ; COMBINATION ; DOPPLER ; ENDOTHELIAL GROWTH-FACTOR ; evaluation ; FACTOR RECEPTOR ; Germany ; human ; IN-VIVO ; INHIBITION ; KINASE ; LUNG ; MICROSCOPY ; MICROVESSEL DENSITY ; MODEL ; MODELS ; neoplasms ; PATHWAY ; PATHWAYS ; PERFUSION ; PHASE-I ; PROSTATE ; RECOMBINANT HUMAN ENDOSTATIN ; THERAPY ; TOXICITY ; tumor growth ; TYROSINE KINASE ; VITRO ; VIVO
    Abstract: The multifaceted nature of the angiogenic process in malignant neoplasms suggests that protocols that combine antiangiogenic agents may be more effective than single-agent therapies. However it is unclear which combination of agents would be most efficacious and will have the highest degree of synergistic activity while maintaining low overall toxicity. Here we investigate the concept of combining a "direct" angiogenesis inhibitor (endostatin) with an "indirect" antiangiogenic compound [SU5416, a vascular endothelial growth factor receptor 2 (VEGFR2) receptor tyrosine kinase (RTK) inhibitor]. These angiogenic agents were more effective in combination than when used alone in vitro (endothelial cell proliferation, survival, migration/invasion, and tube formation tests) and in vivo. The combination of SU5416 and low-dose endostatin further reduced tumor growth versus monotherapy in human prostate (M), lung (A459), and glioma (U87) xenograft models, and reduced functional microvessel density, tumor microcirculation, and blood perfusion as detected by intravital microscopy and contrast-enhanced Doppler ultrasound. One plausible explanation for the efficacious combination could be that, whereas SU5416 specifically inhibits vascular endothelial growth factor signaling, low-dose endostatin is able to inhibit a broader spectrum of diverse angiogenic pathways directly in the endothelium. The direct antiangiogenic agent might be able to suppress alternative angiogenic pathways up-regulated by the tumor in response to the indirect, specific pathway inhibition. For future clinical evaluation of the concept, a variety of agents with similar mechanistic properties could be tested
    Type of Publication: Journal article published
    PubMed ID: 14695206
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  • 5
    Keywords: measurement ; ANGIOGENESIS ; Germany ; PERFUSION ; CLASSIFICATION ; CT ; imaging ; INFORMATION ; QUANTIFICATION ; liver ; TISSUE ; TUMORS ; computed tomography ; PATIENT ; BLOOD-FLOW ; INDEX ; primary ; INJECTION ; SIGNAL ; LESIONS ; PATTERNS ; DIFFERENCE ; metastases ; US ; tomography ; COMPUTED-TOMOGRAPHY ; LIVER METASTASES ; POWER DOPPLER SONOGRAPHY ; VASCULARIZATION ; contrast-enhanced ultrasound,liver metastases,arterial perfusion,low-MI imaging,SonoVue ; MICROBUBBLE CONTRAST ; SHU 508A
    Abstract: Rationale and Objectives: We investigated whether observing the arterial vascularization of liver metastases by contrast-enhanced ultrasound with low mechanical index (low-MI) imaging offers additional diagnostic information for the characterization of the liver lesions.Methods: Twenty nine patients with untreated liver metastases of different primaries were examined. Measurements were performed using a low frame rate, low-MI pulse inversion technique after injection of 2.4 mL SonoVue. The relative maximum signal intensity of the liver lesions related to the normal liver tissue was quantified. Ultrasound findings were compared with contrast-enhanced, dual-phase computed tomography (CT) using a pattern-based classification scheme.Results: Compared with contrast-enhanced CT, this modality better detects arterial perfusion. Metastases, even those usually considered hypovascularized, often showed homogeneous enhancement (66%) and higher arterial vascularization than normal liver tissue. CT did not show a comparable vascularization pattern (P 〈 0.001) or any similarly early signal intensity (P 〈 0.001).Conclusions: Contrast-enhanced CT may not be able to visualize short-lasting but large differences of the arterial perfusion of liver metastases, as does contrast-enhanced low-MI ultrasound. This offers new methods for their characterization and for monitoring of therapeutic effects
    Type of Publication: Journal article published
    PubMed ID: 15021325
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  • 6
    Keywords: brain ; SPECTRA ; CANCER ; CANCER CELLS ; CELLS ; GROWTH ; IRRADIATION ; radiotherapy ; tumor ; carcinoma ; CELL ; Germany ; human ; MICROVESSEL DENSITY ; MODEL ; PERFUSION ; PROSTATE ; THERAPY ; tumor growth ; imaging ; METABOLISM ; TUMORS ; SURGERY ; radiation ; RAT ; RATS ; CONTRAST ; MRI ; MAGNETIC-RESONANCE ; PROTON ; RESONANCE SPECTROSCOPY ; SPECTROSCOPY ; magnetic resonance imaging ; ACID ; PROSTATE-CANCER ; CANCER-CELLS ; EXCHANGE ; PARAMETERS ; tomography ; CARCINOMAS ; TCR ; prostate carcinoma ; VASCULARIZATION ; MAPS ; prostate cancer,dynamic MRI,proton MR spectroscopy,radiotherapy
    Abstract: Rationale and Objectives: To establish an experimental setting for monitoring perfusion and metabolism in orthotopic prostate cancer at 1.5 T using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and H-1-MR spectroscopy (MRS).Methods: Dunning rat prostate cancer cells were injected into the prostate by open surgery. Twelve tumor-bearing rats (5 of these irradiated) and 6 healthy controls were followed up using gadolinium-diethylenetriaminepentaacetic acid -enhanced dynamic MRI and H-1-MRS. Amplitude and the exchange rate constant k(ep) were calculated (2-compartment model). From H-1-MR spectra, ratios of choline (Cho) and creatine (tCr) were calculated. All tumors were examined histologically.Results: On DCE MRI parameter maps, tumors showed increased vascularization. k(ep) and microve.ssel density were correlated (r = 0.97). Tumors showed elevated Cho/tCr and an unexpected lipid fraction (2.0-2.2 parts per million). Irradiation slowed tumor growth significantly. Changes of perfusion and metabolism could be detected in all tumors during follow up.Conclusion: DCE MRI and H-1-MRS has potential to characterize orthotopic Dunning prostate cancer in rats, which is a promising model similar to human prostate carcinomas
    Type of Publication: Journal article published
    PubMed ID: 14701987
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  • 7
    Keywords: GROWTH ; radiotherapy ; tumor ; Germany ; PERFUSION ; CT ; FOLLOW-UP ; HEPATOCELLULAR-CARCINOMA ; liver ; TISSUE ; TUMORS ; PATIENT ; BLOOD-FLOW ; RADIATION-THERAPY ; metastases ; tomography ; COMPUTED-TOMOGRAPHY ; LIVER METASTASES ; contrast media ; APPEARANCE ; ultrasound ; RE ; TUMOR-GROWTH ; monitoring ; ENHANCEMENT ; MICROBUBBLE CONTRAST ; TUMOR PERFUSION ; ARTERIAL ; PHASE ; SIZE ; contrast-enhanced ; ARTERIAL PHASE ; KUPFFER CELLS ; liver neoplasms
    Abstract: The purpose of this study was to monitor liver metastases after radiotherapy using contrast-enhanced ultrasound (CEUS). In 15 patients, follow-up examinations after stereotactic, single-dose radiotherapy were performed using CEUS (low mechanical index (MI), 2.4-ml SonoVue) and computed tomography (CT). Besides tumor size, the enhancement of the liver and the metastases was assessed at the arterial, portal venous, and delayed phases. The sizes of the tumor and of a perifocal liver reaction after radiotherapy measured with CEUS significantly correlated with those measured at CT (r=0.93, p〈0.001). CEUS found a significant reduction of the arterial vascularization in treated tumors (p〈0.05). In the arterial phase, the perifocal liver tissue was hypervascularized compared to the treated tumor (p〈0.001); in the late phase, it was less enhanced than the liver (p〈0.001) and more than the tumor (p〈0.01). The perifocal liver reaction was also seen in CT, but with a variable enhancement at the arterial (50% hyperdense compared to normal liver tissue), venous, or delayed phase (each with 70% hyperdense reactions). CEUS allows for the assessment of tumor and liver perfusion, in addition to morphological tumor examination, which was comparable with CT. Thus, changes of tumor perfusion, which may indicate tumor response, as well as the perifocal liver reaction after radiotherapy, which must be differentiated from perifocal tumor growth, can be sensitively visualized using CEUS
    Type of Publication: Journal article published
    PubMed ID: 15729565
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  • 8
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    Cancer Imaging 6 (), 148-152 
    Keywords: radiotherapy ; tumor ; BLOOD ; MODEL ; MODELS ; PERFUSION ; THERAPY ; TOOL ; liver ; TISSUE ; TUMORS ; PATIENT ; BLOOD-FLOW ; blood flow ; FLOW ; BIOLOGY ; treatment ; metastases ; chemotherapy ; KINETICS ; LIVER METASTASES ; BEHAVIOR ; SONOGRAPHY ; ultrasound ; COLOR DOPPLER ; replenishment kinetics ; SIZE ; technique ; COMPOUND ; animal ; contrast-enhanced ultrasound ; viability ; PREDICT ; animal model ; blood supply
    Abstract: his paper reviews the potential of ultrasound for assessing the viability and biological behavior of tumors. Unlike color Doppler sonography, modern techniques for contrast-enhanced ultrasound permit the measurement of tissue perfusion irrespective of vessel size or flow velocity. Perfusion can also be assessed quantitatively, using replenishment kinetics or derivates thereof. The perfusion of tumors is a surrogate parameter of their viability and may mirror their response to therapy. Furthermore, the degree of vascularity in a tumor may express its aggressiveness and help to predict its response to treatment. In animal models, a decrease in blood flow has been shown to precede a shrinkage of tumors treated with anti-angiogenic compounds. In liver metastases, arterial and portal blood supply can be assessed separately, and a response to stereotactic radiotherapy was found to go along with a decrease in arterial perfusion. Moreover, a relatively high arterial perfusion of liver metastases may predict a response to chemotherapy. Contrast-enhanced ultrasound may be a potent tool for assessing the effects of anti-angiogenic treatment in patients
    Type of Publication: Journal article published
    PubMed ID: 17015239
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  • 9
    Keywords: BLOOD ; Germany ; MODEL ; PERFUSION ; DIAGNOSIS ; IMAGES ; QUANTIFICATION ; VOLUME ; PATIENT ; BLOOD-FLOW ; blood flow ; FLOW ; MR ; MRI ; SIGNAL ; magnetic resonance imaging ; AGE ; WOMEN ; MEN ; MUSCLE ; PARAMETERS ; SKELETAL-MUSCLE ; ULTRASONOGRAPHY ; KINETICS ; sensitivity ; specificity ; BIOPSY ; ultrasound ; INCREASE ; replenishment kinetics ; analysis ; methods ; MYOPATHY ; muscle perfusion ; replenishment kinetics of microbubbles ; Sensitivity and Specificity ; EVALUATE ; UNIT ; myopathies ; MR-IMAGES ; contrast-enhanced ultrasound ; BIOPSIES ; DERMATOMYOSITIS ; INFLAMMATORY MYOPATHIES ; POLYMYOSITIS ; MYOSITIS ; SKELETAL-MUSCLE PERFUSION
    Abstract: Objective To evaluate prospectively contrast-enhanced ultrasound (CEUS) in patients suspected of having dermatomyositis or polymyositis. Methods In 35 patients (23 women, 12 men; mean age, 51 years +/- 16 years) who were suspected of having dermatomyositis or polymyositis, perfusion in clinically affected skeletal muscles was quantified with contrast-enhanced intermittent power Doppler ultrasound. By applying a modified model that analyzed the replenishment kinetics of microbubbles, the perfusion-related parameters blood flow, local blood volume and blood flow velocity were measured. Findings were compared with muscle biopsy appearances and with the results of MRI that was performed with a 1.5-Tesla unit. Receiver operating characteristic analysis was performed and optimum thresholds for diagnosis of myositis were determined. Results Eleven patients had histologically confirmed dermatomyositis or polymyositis and showed significantly higher blood flow velocity (P = .01 for dermato- and P 〈 .001 for polymyositis), blood flow (P 〈 .001 for dermato- and polymyositis), and blood volume (P = .007 for dermato- and P 〈 .001 for polymyositis) on contrast-enhanced ultrasound than those who did not have myositis. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis. MRI had a sensitivity, specificity, positive (PPV), and negative predicting values (NPV) of 100%, 88%, 77%, and 100% for diagnosis of myositis, respectively. CEUS blood flow was the best ultrasound measure for diagnosis of dermato- or polymyositis with sensitivity, specificity, PPV, and NPV of 73%, 91%, 80%, and 88%, respectively. Conclusions Increased skeletal muscle perfusion measured by CEUS could serve as an additional measurer for the diagnosis of an inflammatory myopathy
    Type of Publication: Journal article published
    PubMed ID: 17219033
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  • 10
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    Radiologe 47 (9), 800-807 
    Keywords: IN-VITRO ; AGENTS ; Germany ; human ; IN-VIVO ; VITRO ; imaging ; NEW-YORK ; DRUG ; NUCLEAR-MEDICINE ; PATIENT ; DNA ; CONTRAST ; CONTRAST AGENT ; NO ; TRIAL ; TRIALS ; DAMAGE ; DNA-DAMAGE ; SAFETY ; CONTRAST AGENTS ; echocardiography ; FAILURE ; nuclear medicine ; SONOGRAPHY ; CAVITATION ; ultrasound ; MICROBUBBLES ; AGENT ; radiology ; SINGLE ; END ; INCREASE ; DESTRUCTION ; NUCLEAR ; USA ; DRUGS ; RECOMMENDATIONS ; animal ; BLOOD-BRAIN-BARRIER ; MEDICINE ; bioeffects ; nephrotoxity ; ultrasound contrast agents (USCA) ; WFUMB SAFETY SYMPOSIUM
    Abstract: In this overview safety aspects of ultrasound contrast agents (USCA) are described and discussed. In general USCA are very safe drugs. However, allergic adverse reactions can rarely occur, particularly due to the colloidal structure of USCA. In addition, the use of USCA could reduce the threshold for acoustically induced bioeffects and has the potential to increase these effects. In in vitro studies and animal trials USCA caused petechial hemorrhages, vascular damage, and the formation of free radicals. Even DNA damage with single strand breaks could be demonstrated. In human studies and clinical practice none of these bioeffects could be observed. In contrast-enhanced echocardiography a higher rate of premature ventricular contractions has been reported when imaging was triggered at the end systole. Compared with other contrast agents contrast-enhanced ultrasound showed no nephrotoxic effects and could prove to be an alternative diagnostic method for patients with renal failure
    Type of Publication: Journal article published
    PubMed ID: 17876626
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