Murine model for non-invasive imaging to detect and monitor ovarian cancer recurrence.

Epithelial ovarian cancer is the most lethal gynecologic malignancy in the United States. Although patients initially respond to the current standard of care consisting of surgical debulking and combination chemotherapy consisting of platinum and taxane compounds, almost 90% of patients recur within a few years. In these patients the development of chemoresistant disease limits the efficacy of currently available chemotherapy agents and therefore contributes to the high mortality. To discover novel therapy options that can target recurrent disease, appropriate animal models that closely mimic the clinical profile of patients with recurrent ovarian cancer are required. The challenge in monitoring intra-peritoneal (i.p.) disease limits the use of i.p. models and thus most xenografts are established subcutaneously. We have developed a sensitive optical imaging platform that allows the detection and anatomical location of i.p. tumor mass. The platform includes the use of optical reporters that extend from the visible light range to near infrared, which in combination with 2-dimensional X-ray co-registration can provide anatomical location of molecular signals. Detection is significantly improved by the use of a rotation system that drives the animal to multiple angular positions for 360 degree imaging, allowing the identification of tumors that are not visible in single orientation. This platform provides a unique model to non-invasively monitor tumor growth and evaluate the efficacy of new therapies for the prevention or treatment of recurrent ovarian cancer.

Broad based tissue uptake of polycationic near-infrared polymeric nanoparticles in living mice.

A near infrared (NIR) fluorescent polymeric nanoparticle, commercialized under the name X-Sight 761 (X761), was tested for compatibility with pre-clinical in vivo imaging applications. In one experiment, an optical clearance profile was obtained by performing whole animal fluorescence imaging over the course of 48 hours on mice injected intravenously with X761. In a second trial, a temporal biodistribution was assessed by conducting necropsy and ex vivo analysis of X761 tissue accumulation at selected time points over a 48 hours period after i.v. injection. Taken together, the data demonstrate a sustained distribution of X761 into all major tissues over the time course, with an extremely low net clearance from the animal. This unique behavior is attributed to cell uptake mediated by the polycationic surface of X761. These properties negate the use of X761 as a reporter within a classical targeted molecular probe construct, in which selective concentration at a target site and rapid clearance from background tissues are needed to develop contrast. Nevertheless, the brightness and stability of X761 is well suited for a range of other applications, ranging from broad based in vivo drug delivery to in vitro fluorescence assays.

Segmentation and measurement of fat volumes in murine obesity models using X-ray computed tomography.

Obesity is associated with increased morbidity and mortality as well as reduced metrics in quality of life. Both environmental and genetic factors are associated with obesity, though the precise underlying mechanisms that contribute to the disease are currently being delineated. Several small animal models of obesity have been developed and are employed in a variety of studies. A critical component to these experiments involves the collection of regional and/or total animal fat content data under varied conditions. Traditional experimental methods available for measuring fat content in small animal models of obesity include invasive (e.g. ex vivo measurement of fat deposits) and non-invasive (e.g. Dual Energy X-ray Absorptiometry (DEXA), or Magnetic Resonance (MR)) protocols, each of which presents relative trade-offs. Current invasive methods for measuring fat content may provide details for organ and region specific fat distribution, but sacrificing the subjects will preclude longitudinal assessments. Conversely, current non-invasive strategies provide limited details for organ and region specific fat distribution, but enable valuable longitudinal assessment. With the advent of dedicated small animal X-ray computed tomography (CT) systems and customized analytical procedures, both organ and region specific analysis of fat distribution and longitudinal profiling may be possible. Recent reports have validated the use of CT for in vivo longitudinal imaging of adiposity in living mice. Here we provide a modified method that allows for fat/total volume measurement, analysis and visualization utilizing the Carestream Molecular Imaging Albira CT system in conjunction with PMOD and Volview software packages.

Analytical radiography for planar radiographic images implemented with a multi-modal system.

A radiographic system is optimized for the contrast inherent to small animals and is developed for a multi-modal imaging system devised for in-vivo studies. The range of X-ray energies utilized (generally considered "soft X-rays") enables enhanced spatial resolution and superior contrast for detailed study of the mouse anatomy and smaller specimens. Despite the difficulties presented by the complicated energy spectrum of soft X-rays, relevant system calibrations for bone measures are described in detail and applied to the mouse. Further, long-bone symmetry modeling using a cylindrical projection is applied to the planar density image, providing convenient bone density estimates that are consistent with other methodologies.