Publications (5)28.76 Total impact
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Article: Contrast-enhanced microcomputed tomography using intraperitoneal contrast injection for the assessment of tumor-burden in liver metastasis models.
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ABSTRACT: To determine if intraperitoneally (IP) administered contrast (iohexol), used in conjunction with a liver-specific agent (Fenestra), can improve measurement precision and accuracy when quantifying tumor volume from micro-CT images of a liver metastasis model. We compared images acquired with Fenestra alone to images acquired with the combination of Fenestra and IP iohexol. The variability in tumor volume and tumor-burden measurement was evaluated for both techniques. The tumor-burden measurement accuracy of both in vivo techniques was determined by comparison with tumor-burden quantified from ex vivo images. : The addition of IP iohexol decreased measurement variability for individual tumors and overall tumor-burden by 4-8 fold and 2-3 fold, respectively. IP iohexol significantly improved the accuracy of tumor-burden measurement for both low and high tumor-burdened animals. The combination of IP iohexol with Fenestra provides superior delineation of liver tumors, in comparison to Fenestra alone. The complete tumor delineation provided by this imaging strategy allows for noninvasive quantification of liver tumor-burden.Investigative radiology 08/2008; 43(7):488-95. · 4.85 Impact Factor -
Article: Noninvasive quantification of tumor volume in preclinical liver metastasis models using contrast-enhanced x-ray computed tomography.
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ABSTRACT: To determine a timepoint after contrast injection that yields equal liver parenchymal and vascular enhancement in micro-computed tomography images. To evaluate the utility of images acquired during this time period for the noninvasive measurement of liver-tumor volume. The imaging timepoint was determined by quantifying the enhancement kinetics of Fenestra VC (0.015 mL/g) in NIH III mice. In respiratory-gated images of tumor bearing mice, the ability to measure tumor volume was evaluated with a measurement variability study, and by comparing in vivo and histologically measured tumor volume. Eight hours after contrast injection the liver parenchyma and vasculature were equally enhanced allowing for clear delineation of the unenhanced tumors. The smallest tumor detected in this study was 1.1 mm in diameter. The coefficient of variation for tumor-volume measurement ranged from 3.6% to 12.9% and from 6.3% to 25.8% for intra and interobserver variability, respectively. In vivo and histologic tumor-volume measurements were closely correlated (r = 0.98, P < 0.0001). Imaging at a time period of equal liver parenchyma and vascular enhancement after contrast injection allows for clear delineation of liver-tumor borders, thereby enabling quantitative tumor-volume monitoring.Investigative Radiology 02/2008; 43(2):92-9. · 4.59 Impact Factor -
Article: Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo.
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ABSTRACT: Myxoma virus (MV) is a rabbit-specific poxvirus, whose unexpected tropism to human cancer cells has led to studies exploring its potential use in oncolytic therapy. MV infects a wide range of human cancer cells in vitro, in a manner intricately linked to the cellular activation of Akt kinase. MV has also been successfully used for treating human glioma xenografts in immunodeficient mice. This study examines the effectiveness of MV in treating primary and metastatic mouse tumors in immunocompetent C57BL6 mice. We have found that several mouse tumor cell lines, including B16 melanomas, are permissive to MV infection. B16F10 cells were used for assessing MV replication and efficacy in syngeneic primary tumor and metastatic models in vivo. Multiple intratumoral injections of MV resulted in dramatic inhibition of tumor growth. Systemic administration of MV in a lung metastasis model with B16F10LacZ cells was dramatically effective in reducing lung tumor burden. Combination therapy of MV with rapamycin reduced both size and number of lung metastases, and also reduced the induced antiviral neutralizing antibody titres, but did not affect tumor tropism. These results show MV to be a promising virotherapeutic agent in immunocompetent animal tumor models, with good efficacy in combination with rapamycin.Molecular Therapy 02/2008; 16(1):52-9. · 6.87 Impact Factor -
Article: Time-course characterization of the computed tomography contrast enhancement of an iodinated blood-pool contrast agent in mice using a volumetric flat-panel equipped computed tomography scanner.
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ABSTRACT: The objective of this study was to determine the time-course of computed tomography (CT) contrast enhancement of an iodinated blood-pool contrast agent. Five C57BL/6 mice were anesthetized, imaged at baseline, and given an iodinated blood-pool contrast agent. Micro-CT scans were acquired at 0, 0.25, 0.5, 1, 2, 4, 8, and 24 hours after injection. The mean CT number was determined in a region of interest in 7 organs. The CT contrast enhancement was plotted as a function of time for each organ. We identified an imaging window immediately after injection suitable for visualizing the vascular system and a second imaging window at 24 hours for visualizing liver and spleen. A single injection of the blood-pool contrast agent can be used for dual-phase investigations of the vasculature (t = 0 hours) and liver (t = 24 hours), which can be applied to studies of liver tumors or disease.Investigative Radiology 05/2006; 41(4):384-90. · 4.59 Impact Factor -
Article: Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models.
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ABSTRACT: Liver metastasis is a clinically significant contributor to the mortality associated with melanoma, colon, and breast cancer. Preclinical mouse models are essential to the study of liver metastasis, yet their utility has been limited by the inability to study this dynamic process in a noninvasive and longitudinal manner. This study shows that three-dimensional high-frequency ultrasound can be used to noninvasively track the growth of liver metastases and evaluate potential chemotherapeutics in experimental liver metastasis models. Liver metastases produced by mesenteric vein injection of B16F1 (murine melanoma), PAP2 (murine H-ras-transformed fibroblast), HT-29 (human colon carcinoma), and MDA-MB-435/HAL (human breast carcinoma) cells were identified and tracked longitudinally. Tumor size and location were verified by histologic evaluation. Tumor volumes were calculated from the three-dimensional volumetric data, with individual liver metastases showing exponential growth. The importance of volumetric imaging to reduce uncertainty in tumor volume measurement was shown by comparing three-dimensional segmented volumes with volumes estimated from diameter measurements and the assumption of an ellipsoid shape. The utility of high-frequency ultrasound imaging in the evaluation of therapeutic interventions was established with a doxorubicin treatment trial. These results show that three-dimensional high-frequency ultrasound imaging may be particularly well suited for the quantitative assessment of metastatic progression and the evaluation of chemotherapeutics in preclinical liver metastasis models.Cancer Research 07/2005; 65(12):5231-7. · 7.86 Impact Factor
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Institutions
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2005–2008
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The University of Western Ontario
- Department of Medical Biophysics
London, Ontario, Canada
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