No abstract

These findings suggest that smoke can induce growth factor and procollagen production in small airways in a time frame that initially is too short for a significant inflammatory response and that profibrotic growth factor and procollagen gene expression become self-sustaining with repeated smoke exposures. These results imply that the pathogenesis of and possible treatment approaches to emphysema and small airway remodeling might be quite different.

Rodent models of cardiac pathophysiology represent a valuable research tool to investigate mechanism of disease as well as test new therapeutics. 1 Echocardiography provides a powerful, non-invasive tool to serially assess cardiac morphometry and function in a living animal. 2 However, using this technique on mice poses unique challenges owing to the small size and rapid heart rate of these animals. 3 Until recently, few ultrasound systems were capable of performing quality echocardiography on mice, and those generally lacked the image resolution and frame rate necessary to obtain truly quantitative measurements. Newly released systems such as the VisualSonics Vevo2100 provide new tools for researchers to carefully and non-invasively investigate cardiac function in mice. This system generates high resolution images and provides analysis capabilities similar to those used with human patients. Although color Doppler has been available for over 30 years in humans, this valuable technology has only recently been possible in rodent ultrasound. 4,5 Color Doppler has broad applications for echocardiography, including the ability to quickly assess flow directionality in vessels and through valves, and to rapidly identify valve regurgitation. Strain analysis is a critical advance that is utilized to quantitatively measure regional myocardial function. 6 This technique has the potential to detect changes in pathology, or resolution of pathology, earlier than conventional techniques. Coupled with the addition of three-dimensional image reconstruction, volumetric assessment of whole-organs is possible, including visualization and assessment of cardiac and vascular structures. Murine-compatible contrast imaging can also allow for volumetric measurements and tissue perfusion assessment. Begin by securing an isoflurane anesthetized mouse to an animal-handling platform in the supine position. Place a nose cone over the animal's nose and mouth to deliver 0.5-1% isoflurane to maintain the anesthesia. 2. Secure the paws of the mouse to the electrode pads with conducting gel. Ensure appropriate ECG, body temperature at 37°C and check respiratory rate for physiological assessment during imaging. 3. Apply depilatory cream to the chest and upper abdomen of the mouse. 4. After 2 minutes, use wet gauze remove to the cream.1. Once the mouse has been prepared for imaging, tilt the left side of the platform to rotate the animal handling platform 30 degrees about the anterioposterior axis. 2. Orient the transducer in the vertical position and rotate 10 degrees counterclockwise with the notch pointed toward the posterior of the mouse. 3. Next, while in the two-dimensional viewing/video "B-mode", lower the transducer over the left parasternal line until the heart comes into view.Once the pulmonary artery comes into view, collect images and store them. 4. Still in B-mode, move the transducer left or right until the aortic outflow and apex come into view. Some rotation of the probe may be necessary to ensure proper alignment with t...

There was a positive linear correlation between sonographic tumor measurements and histologic tumor burden in the mouse ocular melanoma model. Contrast-enhanced intensity corresponded with microvascular density and blood volume. HF-CE-US is a real-time, noninvasive, reliable method for in vivo evaluation of experimental intraocular melanoma tumor area and relative blood volume.

Background The overall goal of this study was to non-invasively monitor changes in blood flow of squamous cell carcinoma of the head and neck (SCCHN) xenografts using contrast-enhanced magnetic resonance (MR) and ultrasound (US) imaging. Methods Experimental studies were performed on mice bearing FaDu tumors and SCCHN xenografts derived from human surgical tissue. MR examinations were performed using gadofosveset trisodium at 4.7T. Change in T1-relaxation rate of tumors (ΔR1) and tumor enhancement parameters (amplitude, area under the curve - AUC) were measured at baseline and 24 hours after treatment with a tumor-vascular disrupting agent (tumor-VDA), 5,6-dimethylxanthenone-4-acetic acid (DMXAA; ASA404) and correlated with tumor necrosis and treatment outcome. CE-US was performed using microbubbles (Vevo MicroMarker®) to assess the change in relative tumor blood volume following VDA treatment. Results A marked decrease (up to 68% of baseline) in T1-enhancement of FaDu tumors was observed one day after VDA therapy indicative of a reduction in blood flow. Early (24h) vascular response of individual tumors to VDA therapy detected by MRI correlated with tumor necrosis and volume estimates at 10 days post treatment. VDA treatment also resulted in a significant reduction in AUC and amplitude of patient tumor-derived SCCHN xenografts. Consistent with MRI observations, CE-US revealed a significant reduction in tumor blood volume of patient tumor-derived SCCHN xenografts after VDA therapy. Treatment with VDA resulted in a significant tumor growth inhibition of patient tumor derived SCCHN xenografts. Conclusions These findings demonstrate that both CE-MRI and CE-US allow monitoring of early changes in vascular function following VDA therapy. The results also demonstrate, for the first time, potent vascular disruptive and antitumor activity of DMXAA against patient tumor-derived head and neck carcinoma xenografts.