Background: Micro-computed tomography offers numerous advantages for small animal imaging, including the ability to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects of x-ray dose accumulated over the course of the experiment. In this study, we scan C57BL/6 mice multiple times per week for six weeks, to determine the effect of the cumulative dose on pulmonary tissue at the end of the study. Methods/Results: C57BL/6 male mice were split into two groups (irradiated group=10, control group=10). The irradiated group was scanned (80kVp/50mA) each week for 6 weeks; the weekly scan session had three scans. This resulted in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final week. Scans from weeks 1 and 6 were reconstructed and analyzed: overall, there was no significant difference in lung volume or lung density between the control group and the irradiated group. Similarly, there were no significant differences between the week 1 and week 6 scans in the irradiated group. Histological samples taken from excised lung tissue also showed no evidence of inflammation or fibrosis in the irradiated group. Conclusion: This study demonstrates that a 5 Gy x-ray dose accumulated over six weeks during a longitudinal micro-CT study has no significant effects on the pulmonary tissue of C57BL/6 mice. As a result, the many advantages of micro- CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken advantage of in longitudinal studies without concern for negative dose-related effects.
Supplementary Figure Legends 1-6 from Functional Neoangiogenesis Imaging of Genetically Engineered Mouse Prostate Cancer Using Three-Dimensional Power Doppler Ultrasound
Supplementary Figure 6 from Functional Neoangiogenesis Imaging of Genetically Engineered Mouse Prostate Cancer Using Three-Dimensional Power Doppler Ultrasound
Micro-computed tomography (micro-CT) offers numerous advantages for small animal imaging, including the ability to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects of X-ray dose accumulated over the course of the experiment. To scan C57BL/6 mice multiple times per week for 6 weeks, in order to determine the effect of the cumulative dose on pulmonary and cardiac tissue at the end of the study. C57BL/6 male mice were split into two groups (irradiated group = 10, control group = 10). The irradiated group was scanned (80 kVp/50 mA) three times weekly for 6 weeks, resulting in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final week. Scans from week 6 were reconstructed and the lungs and heart were analyzed. Overall, there was no significant difference in lung volume or lung density or in left ventricular volume or ejection fraction between the control group and the irradiated group. Histological samples taken from excised lung and myocardial tissue also showed no evidence of inflammation or fibrosis in the irradiated group. This study demonstrated that a 5 Gy X-ray dose accumulated over 6 weeks during a longitudinal micro-CT study had no significant effects on the pulmonary and myocardial tissue of C57BL/6 mice. As a result, the many advantages of micro-CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken advantage of in longitudinal studies without concern for negative dose-related effects.
High-frequency ultrasound techniques are introduced for three-dimensional imaging and thickness estimation of fresh heart valve cusps. Images of porcine aortic valve specimens were acquired within a 12 × 8 × 8 mm3 volume using a VisualSonics VS40 micro-imaging system operating at a 40 MHz centre frequency. Two image volumes were obtained from each of six left coronary cusps. One volume was acquired with the specimen submerged in distilled water and the second volume was acquired through either Hanks physiologic solution or coronary perfusion solution (CPS). The fibrosa, spongiosa and ventricularis were most readily distinguished when the specimen was imaged in distilled water. Colour thickness maps were computed from B-mode image data, and the mean and standard deviations of the thickness were determined for each cusp. In 11 of 12 trials, the image analysis algorithm yielded valid thickness estimates over greater than 98% of the region examined. Mean thickness estimates obtained with specimens submerged in Hanks solution or CPS ranged from 0.66 to 1.03 mm, and submersion in distilled water increased the mean thickness by 20–40%. This observation suggests that the cusps osmotically absorbed water. Information provided by high-frequency ultrasound is expected be valuable for characterizing the morphological properties of heart valves.
<div>Abstract<p>We report the first application of high-frequency three-dimensional power Doppler ultrasound imaging in a genetically engineered mouse (GEM) prostate cancer model. We show that the technology sensitively and specifically depicts functional neoangiogenic blood flow because little or no flow is measurable in normal prostate tissue or tumors smaller than 2–3 mm diameter, the neoangiogenesis “switch-on” size. Vascular structures depicted by power Doppler were verified using Microfil-enhanced micro-computed tomography (micro-CT) and by correlation with microvessel distributions measured by immunohistochemistry and enhanced vascularity visualized by confocal microscopy in two GEM models [transgenic adenocarcinoma of the mouse prostate (TRAMP) and PSP94 gene-directed transgenic mouse adenocarcinoma of the prostate (PSP-TGMAP)]. Four distinct phases of neoangiogenesis in cancer development were observed, specifically, (<i>a</i>) an early latent phase; (<i>b</i>) establishment of a peripheral capsular vascular structure as a neoangiogenesis initiation site; (<i>c</i>) a peak in tumor vascularity that occurs before aggressive tumor growth; and (<i>d</i>) rapid tumor growth accompanied by decreasing vascularity. Microsurgical interventions mimicking local delivery of antiangiogenesis drugs were done by ligating arteries upstream from feeder vessels branching to the prostate. Microsurgery produced an immediate reduction of tumor blood flow, and flow remained low from 1 h to 2 weeks or longer after treatment. Power Doppler, in conjunction with micro-CT, showed that the tumors recruit secondary blood supplies from nearby vessels, which likely accounts for the continued growth of the tumors after surgery. The microsurgical model represents an advanced angiogenic prostate cancer stage in GEM mice corresponding to clinically defined hormone-refractory prostate cancer. Three-dimensional power Doppler imaging is completely noninvasive and will facilitate basic and preclinical research on neoangiogenesis in live animal models. [Cancer Res 2007;67(6):2830–9]</p></div>
Abstract We report the first application of high-frequency three-dimensional power Doppler ultrasound imaging in a genetically engineered mouse (GEM) prostate cancer model. We show that the technology sensitively and specifically depicts functional neoangiogenic blood flow because little or no flow is measurable in normal prostate tissue or tumors smaller than 2–3 mm diameter, the neoangiogenesis “switch-on” size. Vascular structures depicted by power Doppler were verified using Microfil-enhanced micro-computed tomography (micro-CT) and by correlation with microvessel distributions measured by immunohistochemistry and enhanced vascularity visualized by confocal microscopy in two GEM models [transgenic adenocarcinoma of the mouse prostate (TRAMP) and PSP94 gene-directed transgenic mouse adenocarcinoma of the prostate (PSP-TGMAP)]. Four distinct phases of neoangiogenesis in cancer development were observed, specifically, (a) an early latent phase; (b) establishment of a peripheral capsular vascular structure as a neoangiogenesis initiation site; (c) a peak in tumor vascularity that occurs before aggressive tumor growth; and (d) rapid tumor growth accompanied by decreasing vascularity. Microsurgical interventions mimicking local delivery of antiangiogenesis drugs were done by ligating arteries upstream from feeder vessels branching to the prostate. Microsurgery produced an immediate reduction of tumor blood flow, and flow remained low from 1 h to 2 weeks or longer after treatment. Power Doppler, in conjunction with micro-CT, showed that the tumors recruit secondary blood supplies from nearby vessels, which likely accounts for the continued growth of the tumors after surgery. The microsurgical model represents an advanced angiogenic prostate cancer stage in GEM mice corresponding to clinically defined hormone-refractory prostate cancer. Three-dimensional power Doppler imaging is completely noninvasive and will facilitate basic and preclinical research on neoangiogenesis in live animal models. [Cancer Res 2007;67(6):2830–9]
Supplementary Figure 3 from Functional Neoangiogenesis Imaging of Genetically Engineered Mouse Prostate Cancer Using Three-Dimensional Power Doppler Ultrasound
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