Successful Orthotopic Liver Transplantation in Mice Utilizing Microcomputed Tomography Angiography.

Microcomputed tomography (microCT) angiography is an invaluable resource to researchers. New advances in this technology have allowed for high-quality images to be obtained of micro-vasculature and are high-fidelity tools in the field of organ transplantation. In this model of orthotopic liver transplantation (OLT) in mice, microCT affords the opportunity to evaluate allograft anastomosis in real time and has the added benefit of not having to sacrifice study animals. The choice of contrast, as well as image acquisition settings, create a high-definition image, which gives researchers invaluable information. This allows for evaluation of the technical aspects of the procedure as well as potentially evaluating different therapeutics over an extended duration of time. In this protocol, we detail an OLT model in mice in a stepwise fashion and finally describe a microCT protocol that can give high-quality images, which aid researchers in in-depth analysis of solid organ transplantation. We provide a step-by-step guide for liver transplantation in a mouse, as well as briefly discuss a protocol for evaluating the patency of the graft through microCT angiography.

PATET ratio by Doppler echocardiography: noninvasive detection of pediatric pulmonary arterial hypertension.

Pulmonary artery acceleration time (PAT) and PAT: ejection time (PATET) ratio are echocardiographic measurements of pulmonary arterial hypertension (PAH). These noninvasive quantitative measurements are ideal to follow longitudinally through the clinical course of PAH, especially as it relates to the need for and/or response to treatment. This review article focuses on the current literature of PATET measurement for infants and children as it relates to the shortening of the PATET ratio in PAH. At the same time, further development of PATET as an outcome measure for PAH in preclinical models, particularly mice, such that the field can move forward to human clinical studies that are both safe and effective. Here, we present what is known about PATET in infants and children and discuss what is known in preclinical models with particular emphasis on neonatal mouse models. In both animal models and human disease, PATET allows for longitudinal measurements in the same individual, leading to more precise determinations of disease/model progression and/or response to therapy. IMPACT: PATET ratio is a quantitative measurement by a noninvasive technique, Doppler echocardiography, providing clinicians a more precise/accurate, safe, and longitudinal assessment of pediatric PAH. We present a brief history/state of the art of PATET ratio to predict PAH in adults, children, infants, and fetuses, as well as in small animal models of PAH. In a preliminary study, PATET shortened by 18% during acute hypoxic exposure compared to pre-hypoxia. Studies are needed to establish PATET, especially in mouse models of disease, such as bronchopulmonary, as a routine measure of PAH.

Oncolytic measles virus efficacy in murine xenograft models of atypical teratoid rhabdoid tumors.

BACKGROUND: Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly malignant pediatric tumor of the central nervous system that is usually refractory to available treatments. The aggressive growth, propensity to disseminate along the neuroaxis, and young age at diagnosis contribute to the poor prognosis. Previous studies have demonstrated the efficacy of using oncolytic measles virus (MV) against localized and disseminated models of medulloblastoma. The purpose of this study was to evaluate the oncolytic potential of MV in experimental models of AT/RT. METHODS: Following confirmation of susceptibility to MV infection and killing of AT/RT cells in vitro, nude mice were injected with BT-12 and BT-16 AT/RT cells stereotactically into the caudate nucleus (primary tumor model) or lateral ventricle (disseminated tumor model). Recombinant MV was administered either intratumorally or intravenously. Survival was determined for treated and control animals. Necropsy was performed on animals showing signs of progressive disease. RESULTS: All cell lines exhibited significant killing when infected with MV, all formed syncytia with infection, and all generated infectious virus after infection. Orthotopic xenografts displayed cells with rhabdoid-like cellular morphology, were negative for INI1 expression, and showed dissemination within the intracranial and spinal subarachnoid spaces. Intratumoral injection of live MV significantly prolonged the survival of animals with intracranial and metastatic tumors. CONCLUSION: These data demonstrate that AT/RT is susceptible to MV killing and suggest that the virus may have a role in treating this tumor in the clinical setting.