High-Resolution Ultrasound Including Contrast-Enhanced Ultrasound (CEUS) for the Detection of Gas Formation during Aspergillus Fumigatus Infection in Mice.

PURPOSE: A. fumigatus infections represent a major threat for patients with a suppressed immune system. Early diagnosis is of importance for a favorable outcome but appears to be difficult due to limited diagnostic procedures. Here we investigated the sensitivity of high-resolution ultrasound (HRU) for the detection of A. fumigatus infection in the liver. MATERIALS AND METHODS: BALB/c mice were intravenously infected with A. fumigatus and monitored by HRU, Doppler sonography (CCDS), contrast-enhanced ultrasound (CEUS), and real-time strain color-coded elastography (CCE) using a multi-frequency probe (6 - 15 MHz). Contrast media bolus injection of sulfur-hexafluoride micro-bubbles was applied and digital cine-loops from the arterial phase, as well as the portal venous phase up to the late phase of the whole liver were analyzed. All data were correlated to the histopathological findings. RESULTS: Using HRU and CEUS, a sonic shadow was detected in all infected animals. All Aspergillus-infected nodes from 3 - 6 mm in the liver showed a shadow with rim enhancement and no intranodal enhancement when using CEUS. A. fumigatus infection was confirmed by CFU assessment and histopathological analysis. Granulomas were not associated with shadowing on B-mode. In contrast, granulomas with a diameter above 5 mm and a higher stiffness in CCE generated particularly an arterial rim enhancement and portal venous washout without contrast media uptake in the late phase. In addition, CEUS was able to define dynamic capillary microvascularization of infected liver areas. CONCLUSION: Liver lesions associated with A. fumigatus infection can be detected in mice when combined with CEUS and CCE in vivo.

Functional and phenotypic characterization of the humanized BLT mouse model.

T cells play a central role in the development of immune responses. Patients lacking T cells because of genetic defects such as DiGeorge or Nezelof syndromes and patients infected with the human immunodeficiency virus are highly susceptible to infections and cancers. The lack of adequate in vivo models of T cell neogenesis have hindered the development and clinical implementation of effective therapeutic modalities aimed at treating these and other clinically important maladies. Transplantation of severe combined immunodeficient (SCID) mice with human hematopoietic stem cells results in long-term engraftment and systemic reconstitution with human progenitor, B, and myeloid cells, but curiously, human T cells are rarely present in any tissue. While the implantation of SCID mice with human fetal thymus and liver (SCID-hu thy/liv mice) allows the development of abundant thymocytes that are localized in the human organoid implant, there is minimal systemic repopulation with human T cells. However, we have recently shown that transplantation of autologous human hematopoietic fetal liver CD34+ cells into the nonobese diabetic (NOD)/SCID mouse background previously implanted with fetal thymic and liver tissues results in long-term, systemic human T cell homeostasis. In addition to human T cells, these mice have systemic repopulation with human B cells, monocytes/macrophages, and dendritic cells (DC). Importantly, in these mice the T cells developed in the human thymic implant are capable of being activated by human antigen-presenting cells and mount potent human MHC-restricted T cell immune responses.

High resolution ultrasound including elastography and contrast-enhanced ultrasound (CEUS) for early detection and characterization of liver lesions in the humanized tumor mouse model.

PURPOSE: In this study we investigated the sensitivity of high resolution ultrasound (HRU) in the detection of small liver tumors and its microcirculation in a humanized tumor mouse model (HTM). These mice develop a complete human immune system and human breast cancer growth in the liver which allows the investigation of antibody based immunotherapies under human like conditions. METHOD: HTM were generated by the co-transplantation of human breast cancer cells and human hematopoietic stem cells. HRU, Doppler sonography (CCDS), contrast enhanced ultrasound (CEUS) and color-coded elastography were performed on all HTM and confirmed by histopathological assessment. RESULTS: Using HRU and CEUS, noncystic solid liver lesions between 2 and 11 mm (mean 3.5 mm) size were detectable in HTM. Granulomatous areas were identified by B-scan imaging, showing areas of higher stiffness in elastography and areas without contrast media uptake in the late phase (CEUS). In addition, CEUS detected capillary microcirculation of benign and malignant liver lesions smaller than 10 mm. CONCLUSION: Beyond human breast cancer HTM additionally developed small parenchymal liver lesions, which could be characterized by HRU in combination with CEUS and elastography in-vivo. Nevertheless, the defined diagnoses of solid liver lesions less than 5 mm require confirmation by histopathology.