Cellular immunoisolation using semi-permeable barriers has been investigated over the past several decades as a promising treatment approach for diseases such as Parkinson's, Alzheimer's, and Type 1 diabetes. Typically, polymeric membranes are used for immunoisolation applications; however, recent advances in technology have led to the development of more robust membranes that are able to more completely meet the requirements for a successful immunoisolation device, including well controlled pore size, chemical and mechanical stability, non-biodegradability, and biocompatibility with both the graft tissue as well as the host. It has been shown previously that nanoporous alumina biocapsules can act effectively as immunoisolation devices, and support the viability and functionality of encapsulated β cells. The aim of this investigation was to assess the biocompatibility of the material with host tissue. The cytotoxicity of the capsule, as well as its ability to activate complement and inflammation was studied. Further, the effects of PEGmodification on the tissue response to implanted capsules were studied. Our results have shown that the device is non-toxic and does not induce significant complement activation. Further, in vivo work has demonstrated that implantation of these capsules into the peritoneal cavity of rats induces a transient inflammatory response, and that PEG is useful in minimizing the host response to the material.

Contrast-enhanced (CE)-

Inflammatory bowel disease, including ulcerative colitis, is characterized by persistent or recurrent inflammation and can progress to colon cancer. Colitis is difficult to detect and monitor noninvasively. The goal of this work was to develop a preclinical imaging method for evaluating colitis. Herein, we report improved MRI methods for detecting and characterizing colitis noninvasively in mice, using high-resolution in vivo MR images and dynamic contrast-enhanced MRI studies, which were confirmed by histologic studies in a murine model of colitis. C57Bl6/J male mice were treated with 2.5% dextran sulfate sodium in their drinking water for 5 days to induce colitis. MR images were acquired using a 9.4-T Bruker scanner from 5–25 days following dextran sulfate sodium treatment. In dynamic contrast-enhanced MRI studies, Gd uptake (Ktrans) and its distribution (ve) were measured in muscle and normal and inflamed colons after administering Gd-diethyltriaminepentaacetic acid (Gd-DTPA). T2-weighted MR images distinguished normal colon from diffusely thickened colonic wall occurring in colitis (P < 0.0005) and correlated with histologic features. Values of Ktrans and ve obtained from dynamic contrast-enhanced MRI were also significantly different in inflamed colons compared to normal colon (P < 0.0005). The results demonstrate that both T2-weighted anatomic imaging and quantitative analysis of dynamic contrast-enhanced MRI data can successfully distinguish colitis from normal colon in mice.

Accurate measurement of the arterial input function is critical for quantitative evaluation of dynamic contrast enhanced magnetic resonance imaging data. Use of the reference tissue method to derive a local arterial input function avoided large errors associated with direct arterial measurements, but relied on literature values for Ktrans and ve. We demonstrate that accurate values of Ktrans and ve in a reference tissue can be measured by comparing contrast media concentration in a reference tissue to plasma concentrations measured directly in a local artery after the 1–2 passes of the contrast media bolus—when plasma concentration is low and can be measured accurately. The values of Ktrans and ve calculated for the reference tissue can then be used to derive a more complete arterial input function including the first pass of the contrast bolus. This new approach was demonstrated using dynamic contrast enhanced magnetic resonance imaging data from rodent hind limb. Values obtained for Ktrans and ve in muscle, and the shape and amplitude of the derived arterial input function are consistent with published results. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.

MRI methods that accurately identify various stages of mouse mammary cancer could provide new knowledge that directly impacts management of breast cancer in patients. This research evaluates whether MRI can accurately follow the progression from in situ to invasive cancer, by evaluating in vivo and ex vivo MRI, and compared to histology as the gold standard for diagnosing and staging cancer. Six C3(1)SV40Tag virgin female mice between the age of 12-16 weeks were studied. At this age, these mice develop in situ cancer that resembles human DCIS. Fast spin echo images of inguinal mammary glands were acquired at 9.4 Tesla. After in vivo MRI, mice were sacrificed; inguinal mammary glands were excised and fixed in formalin for ex vivo MRI. 3D volume-rendered in vivo and ex vivo MR images were then correlated with histology. High resolution ex vivo scans facilitated comparison of in vivo scans with histology. The sizes of mammary cancers classified as in situ based on histology ranged from 150 to 400 microns in largest diameter, and average signal intensity relative to muscle was 1.40±0.18 on T2-weighted images. Cancers classified as invasive based on histology were >400 microns in largest diameter, and average intensity relative to muscle on T2-weighted images was 2.34±0.26. Using a cutoff of 400 microns in largest diameter to distinguish between in situ and invasive cancers, T2-weighted signal intensity of at least 1.4 times that of muscle for in situ cancer, and at least 2.3 times that of muscle for invasive cancer, 96% of in situ and 100% of invasive cancers were correctly identified on in vivo MRI, using histology as the gold standard. Precise MRI-histology correlation demonstrates that MRI reliably detects early in situ cancer and differentiates in situ from invasive cancers in the SV40Tag mouse model of human breast cancer.