Lung tumour growth kinetics in SPC-c-Raf-1-BB transgenic mice assessed by longitudinal in-vivo micro-CT quantification

<p>Abstract</p> <p>Background</p> <p>SPC-c-Raf-1-BxB transgenic mice develop genetically induced disseminated lung adenocarcinoma allowing examination of carcinogenesis and evaluation of novel treatment strategies. We report on assessment of lung tumour growth kinetics using a semiautomated region growing segmentation algorithm.</p> <p>Methods</p> <p>156 non contrast-enhanced respiratory gated micro-CT of the lungs were obtained in 12 SPC-raf transgenic (n = 9) and normal (n = 3) mice at different time points. Region-growing segmentation of the aerated lung areas was obtained as an inverse surrogate for tumour burden. Time course of segmentation volumes was assessed to demonstrate the potential of the method for follow-up studies.</p> <p>Results</p> <p>Micro-CT allowed assessment of tumour growth kinetics and semiautomated region growing enabled quantitative analysis. Significant changes of the segmented lung volumes over time could be shown (<it>p </it>= 0.009). Significant group differences could be detected between transgenic and normal animals for time points 8 to 13 months (<it>p </it>= 0.043), when marked tumour progression occurred.</p> <p>Conclusion</p> <p>The presented region-growing segmentation algorithm allows in-vivo quantification of multifocal lung adenocarcinoma in SPC-raf transgenic mice. This enables the assessment of tumour load and progress for the study of carcinogenesis and the evaluation of novel treatment strategies.</p

Evaluation of CT vascularization patterns for survival prognosis in patients with hepatocellular carcinoma treated by conventional TACE

PURPOSE:Transarterial chemoembolization (TACE) is an established treatment for intermediate stage hepatocellular carcinoma (HCC). The aim of this retrospective study was to evaluate the power of lesion vascularization criteria based on computed tomography for prognosis of overall survival before initiation of treatment.METHODS:A total of 59 patients with intermediate stage HCC treated with TACE as first-line treatment were retrospectively evaluated. TACE procedures were performed using doxorubicin, cisplatin, and lipiodol. Response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) were used to determine the initial tumor response. Four vascularization patterns (VP) of the largest target lesion (homogeneous vascularization [VP1], homogeneous vascularization with additional arterial hypervascularization [VP2], heterogeneous vascularization with [VP3] and without zones of hypervascularization [VP4]) were assessed prior to the first TACE and correlated to survival.RESULTS:Kaplan-Meier analysis yielded a median overall survival of 608 days (standard error [SE], 120.5 days). Survival analysis showed significant differences depending on the vascularization patterns (P = 0.012; hazard ratio, 0.327): patients with homogeneously vascularized lesions (VP1, VP2) had a median overall survival of 1091 days (SE, 235.5 days). Patients with heterogeneous vascularization of the lesion (VP3 and VP4) showed a median overall survival of 508 days (SE, 113.9 days).CONCLUSION:The vascularization pattern of the largest HCC lesion is helpful for survival prognosis under TACE treatment and therefore has the potential to be used as an additional parameter for treatment stratification

Effective hematopoietic stem cell-based gene therapy in a murine model of hereditary pulmonary alveolar proteinosis

Hereditary pulmonary alveolar proteinosis due to GM-CSF receptor deficiency (herPAP) constitutes a life-threatening lung disease characterized by alveolar deposition of surfactant protein secondary to defective alveolar macrophage function. As current therapeutic options are primarily symptomatic, we have explored the potential of hematopoietic stem cell-based gene therapy. Using Csf2rb−/− mice, a model closely reflecting the human herPAP disease phenotype, we here demonstrate robust pulmonary engraftment of an alveolar macrophage population following intravenous transplantation of lentivirally corrected hematopoietic stem and progenitor cells. Engraftment was associated with marked improvement of critical herPAP disease parameters, including bronchoalveolar fluid protein, cholesterol and cytokine levels, pulmonary density on computed tomography scans, pulmonary deposition of Periodic Acid-Schiff+ material as well as respiratory mechanics. These effects were stable for at least nine months. With respect to engraftment and alveolar macrophage differentiation kinetics, we demonstrate the rapid development of CD11c+/SiglecF+ cells in the lungs from a CD11c–/SiglecF+ progenitor population within four weeks after transplantation. Based on these data, we suggest hematopoietic stem cell-based gene therapy as an effective and cause-directed treatment approach for herPAP

PET/CT Imaging of c-Myc Transgenic Mice Identifies the Genotoxic N-Nitroso-Diethylamine as Carcinogen in a Short-Term Cancer Bioassay

Background: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. Methodology/Principal Findings: mCT and 18 F-FDG mPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced mCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis. Conclusions/Significance: The present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgeni

CIRSE Standards of Practice on Below-the-Knee Revascularisation

The CIRSE Standards of Practice Committee established a writing group that was tasked with producing up-to-date recommendations for performing below-the-knee revascularisation, taking into account data on novel techniques, devices, and long-term outcomes that have emerged over the last decade. CIRSE Standards of Practice documents are not clinical practice guidelines or systematic reviews of the literature. This document is not intended to impose a standard of clinical patient care but recommends a reasonable approach to and best practices for performing below-the-knee revascularisation

Large scan field, high spatial resolution flat-panel detector based volumetric CT of the whole human skull base and for maxillofacial imaging

Objectives: To assess the feasibility of flat-panel detector based volumetric CT (fpVCT) scanning of the whole human skull base and maxillofacial region, which has thus far only been demonstrated on small, excised specimens. Flat-panel detectors offer more favourable imaging properties than image intensifiers. It is therefore likely that they will replace them in cone-beam CT scanners that are currently used to scan parts of the skull base and maxillofacial region. Furthermore, the resolution of current CT imaging limits diagnosis, surgical planning and intraoperative navigation within these regions. fpVCT might overcome these limitations because it offers higher resolution of high contrast structures than current CT. Methods: Three embalmed cadaver heads were scanned in two scanners: an experimental fpVCT that offers a scan field large enough for a whole human head, and in a current multislice CT (MSCT). 28 structures were compared. Results: Both scanners produced bone images of diagnostic quality. Small high contrast structures such as parts of the ossicular chain and thin bony laminas were better delineated in fpVCT than in MSCT. fpVCT of maxillofacial region and skull base was rated superior to MSCT (P = 0.002) as found in this limited, experimental study. Conclusions: High spatial resolution fpVCT scanning of both regions in a whole human head is feasible and might be slightly superior to MSCT. fpVCT could improve diagnostic accuracy in selected cases, as well as surgical planning and intraoperative navigation accuracy

Clinical and endovascular practice in interventional radiology: a contemporary European analysis

Abstract Background The purpose of this survey was to determine the current trends in endovascular practice by Interventional Radiologists (IR’s) across Europe and to understand the engagement by Interventional Radiology (IR) with clinical practice. CIRSE European members were invited to participate in an online survey between July 11th, 2016 and August 8th, 2016. A 54 question survey was created to capture a comprehensive overview of IR endovascular practice and clinical engagement. Results Four hundred and five valid responses were received (9.9%) from a broad geographic distribution from across Europe. 76% of IR’s practised in centres with more than 400 beds as 60% worked in an academic or university teaching hospital. 36% dedicated 80–100% of their time to IR and 59% dedicated at least 60% of their time to IR. 24/7 IR on-call was available in the hospitals of 73% or respondents. 78% had dedicated IR nursing staff and 67% had nursing support on-call, 55% had inpatient admission privileges and 27% had dedicated IR inpatient beds. 65% of IR’s had admitting rights to day-case beds. 42% ran IR outpatient clinics and 36% performed ward rounds. 81% of respondents performed peripheral arterial disease (PAD) intervention and IR was the main provider of PAD intervention in 67% of centres. Vascular Surgery or Medicine were the main referrers (71%) to IR for PAD intervention. 37% of centres had a hybrid operating theatre and 80% of IR’s had access to this. Conclusion IR remains a substantial player in the field of PAD Intervention. The continued evolution of outpatient clinics and clinical practice is key to retention and future expansion in the field of endovascular therapy for PAD