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A New Three-Dimensional Ultrasound Microimaging Technology for Preclinical Studies Using a Transgenic Prostate Cancer Mouse Model

¹ Biomedical Engineering Graduate Program and Departments of ² Surgery, ³ Pathology, ⁴ Diagnostic Radiology and Nuclear Medicine, ⁵ Medical Biophysics, and ⁶ Electrical and Computer Engineering, University of Western Ontario; ⁷ Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada; ⁸ Department of Urology, Nagasaki University School of Medicine, Nagasaki, Japan; and ⁹ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington

Requests for requests: Jim W. Xuan, Urology Research Laboratory, London Health Sciences Centre, 375 South Street, London, Ontario, Canada N6A 4G5. Phone: 519-667-6682; Fax: 519-432-7367; E-mail: jim.xuan{at}lhsc.on.ca and James C. Lacefield, Department of Electrical and Computer Engineering, University of Western Ontario, 279 Thompson Engineering Building, London, Ontario, Canada N6A 5B9. Phone: 519-661-2111, ext. 84303; Fax: 519-850-2436; E-mail: jlacefield{at}eng.uwo.ca.

Prostate cancer is the most common cancer in adult men in North America. Preclinical studies of prostate cancer employ genetically engineered mouse models, because prostate cancer does not occur naturally in rodents. Widespread application of these models has been limited because autopsy was the only reliable method to evaluate treatment efficacy in longitudinal studies. This article reports the first use of three-dimensional ultrasound microimaging for measuring tumor progression in a genetically engineered mouse model, the 94–amino acid prostate secretory protein gene-directed transgenic prostate cancer model. Qualitative comparisons of three-dimensional ultrasound images with serial histology sections of prostate tumors show the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. Ultrasound imaging identified tumors ranging from 2.4 to 14 mm maximum diameter. The correlation coefficient of tumor diameter measurements done in vivo with three-dimensional ultrasound and at autopsy was 0.998. Prospective tumor detection sensitivity and specificity were both >90% when diagnoses were based on repeated ultrasound examinations done on separate days. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated volume doubling times of 5 and 13 days for two prostate tumors. Compared with other microimaging and molecular imaging modalities, the application of three-dimensional ultrasound imaging to prostate cancer in mice showed advantages, such as high spatial resolution and contrast in soft tissue, fast and uncomplicated protocols, and portable and economical equipment that will likely enable ultrasound to become a new microimaging modality for mouse preclinical trial studies.

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