Restrictions of VC and DLCO in relation to asbestos-related computed tomographic findings quantified by ICOERD-based parameters.

BACKGROUND: Even almost 30 years after the ban on the use of asbestos in Germany, the effects of asbestos are still highly relevant in everyday clinical practice in occupational medicine. The aim of this study was to further investigate the significance of essential parameters of both pulmonary function diagnostics and imaging techniques (low-dose HR-TCT) for the prevention and early detection of asbestos-related morphological and functional lung changes. METHODS: Data from spirometry, body plethysmography and diffusion capacity, as well as CT images of the thorax, were retrospectively studied from 72 patients examined between 2017 and 2019 at the Institute for Occupational and Maritime Medicine (ZfAM), Hamburg, Germany. The subjects were divided into four subgroups according to the presence of comorbidities (concomitant cardiac diseases, obstructive ventilatory disorder, pulmonary function pattern consistent with emphysema, and no other pulmonary or cardiac diseases). These subgroups were analysed in addition to the overall collective. The CT images were evaluated according to the International Classification of Occupational and Environmental Respiratory Diseases (ICOERD) with radiological expertise. In addition, some asbestos-related parameters were newly quantified, and corresponding scores were defined based on ICOERD. Statistical analysis included the use of correlations and fourfold tables with calculation of Spearman's rho (ρ), Cohen's κ, and accuracy. RESULTS: Vital capacity (VC) is slightly reduced in the total collective compared to the normal population (mean 92% of predicted value), while diffusion capacity for CO (DLCO) shows predominantly pathological values, mean 70% of the respective predicted value. The CO transfer coefficient (DLCO/VA), which refers to alveolar volume (VA), also shows slightly decreased values (mean 87% pred.). Seventy-nine percent of patients (n = 57) had signs of pulmonary fibrosis on CT scans, and pleural plaques appeared in 58 of 72 patients (81%). Of the newly quantified additional parameters, particularly frequently described findings are subpleural curvilinear lines (SC, n = 39) and parenchymal bands (PB, n = 29). VC correlates well with the expression of pleural plaques (ρ = - 0.273, P < 0.05), and DLCO measures show a better correlation with fibrosis score (ρ = - 0.315, P < 0.01). A third, newly developed score, which includes the extent of pleural plaques and additional subpleural parameters instead of fibrosis parameters, shows significant correlations for both VC and DLCO (ρ = - 0.283, - 0.274, resp.; both P < 0.05). DISCUSSION: The importance of spirometry (VC) and diffusion capacity measurement (DLCO) as essential diagnostic procedures for the early detection of asbestos-related changes ‒ also including patients with relevant concomitant cardiac or pulmonary diseases ‒ was confirmed. Significant and better correlations between lung function changes (VC and DLCO) and abnormal CT findings are seen when parenchymal bands (PB), subpleural curvilinear lines (SC), and rounded atelectasis (RA) are quantitatively included into the evaluation, in addition to assessing the extent of pleural plaques alone. Therefore, when assessing CT images according to ICOERD, these parameters should also be quantified.

Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice.

Induced overexpression of the secretory protein YKL-40 promotes tumor growth in xenograft experiments. We investigated if targeting YKL-40 with a monoclonal antibody could inhibit tumor growth. YKL-40 expressing human melanoma cells (LOX) were injected subcutenously in Balb/c scid mice. Animals were treated with intraperitoneal injections of anti-YKL-40, isoptype control or PBS. Non-YKL-40 expressing human pancreatic carcinoma cell line PaCa 5061 served as additional control. MR imaging was used for evaluation of tumor growth. Two days after the first injections of anti-YKL-40, tumor volume had increased significantly compared with controls, whereas no effects were observed for control tumors from PaCa 5061 cells lacking YKL-40 expression. After 18 days, mean tumor size of the mice receiving repeated anti-YKL-40 injections was 1.82 g, >4 times higher than mean tumor size of the controls (0.42 g). The effect of anti-YKL-40 on the increase of tumor volume started within hours after injection and was dose dependent. Intratumoral hemorrhage was observed in the treated animals. The strong effect on tumor size indicates important roles for YKL-40 in melanoma growth and argues for a careful evaluation of antibody therapy directed against YKL-40.

68Ga DOTA-TATE PET/CT allows tumor localization in patients with tumor-induced osteomalacia but negative 111In-octreotide SPECT/CT.

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia and low calcitriol levels as well as clinical symptoms like diffuse bone and muscle pain, fatigue fractures or increased fracture risk. Conventional imaging methods, however, often fail to detect the small tumors. Lately, tumor localization clearly improved by somatostatin-receptor (SSTR) imaging, such as octreotide scintigraphy or octreotide SPECT/CT. However, recent studies revealed that still a large number of tumors remained undetected by octreotide imaging. Hence, studies focused on different SSTR imaging methods such as 68Ga DOTA-NOC, 68Ga DOTA-TOC and 68Ga DOTA-TATE PET/CT with promising first results. Studies comparing different SSTR imaging methods for tumor localization in TIO are rare and thus little is known about diagnostic alternatives once a particular method failed to detect a tumor in patients with TIO. Here, we report the data of 5 consecutive patients suffering from TIO, who underwent both 111Indium-octreotide scintigraphy (111In-OCT) SPECT/CT as well as 68Ga DOTA-TATE PET/CT for tumor detection. While 111In-OCT SPECT/CT allowed tumor detection in only 1 of 5 patients, 68Ga DOTA-TATE PET/CT was able to localize the tumor in all patients. Afterwards, anatomical imaging of the region of interest was performed with CT and MRI. Thus, successful surgical resection of the tumor was achieved in all patients. Serum phosphate levels returned to normal and all patients reported relief of symptoms within weeks. Moreover, an iliac crest biopsy was obtained from every patient and revealed marked osteomalacia in all cases. Follow-up DXA revealed an increase in BMD of up to 34.5% 1-year postoperative, indicating remineralization. No recurrence was observed. In conclusion our data indicates that 68Ga DOTA-TATE PET/CT is an effective and promising diagnostic tool in the diagnosis of TIO, even in patients in whom 111In-OCT prior failed to detect a tumor.

Ultrasound-guided intracardial injection and in vivo magnetic resonance imaging of single cells in mice as a paradigm for hematogenous metastases.

Magnetic resonance imaging (MRI) has become an important technique for noninvasive cell tracking in preclinical research. Following appropriate cell labeling MRI can be used to detect larger cell cohorts and also single cells in vivo in mice. Cell distribution to different organs such as brain, liver, spleen, and kidneys can be visualized, semi-quantified, and followed over time. Thus, the fate of single tumor cells and their eventual development to solid metastases could be investigated. Mesenchymal stromal cells can be used as a paradigm for metastasizing tumor cells. We have demonstrated a strategy for magnetic and fluorescent co-labeling of mesenchymal stromal cells (MSC), ultrasound-guided intracardial cell injection with efficient systemic cell delivery, and high-resolution MRI for repetitive visualization of disseminated co-labeled MSC on a single-cell level in vivo in mice. Furthermore, the fluorescent labeling of cells enabled effective histopathological validation.

Magnetic resonance imaging of metastases in xenograft mouse models of cancer.

Magnetic resonance imaging (MRI) of small animals has emerged as a valuable tool to noninvasively monitor tumor growth in mouse models of cancer. However, imaging of metastases in mouse models is difficult due to the need for high spatial resolution. We have demonstrated MRI of metastases in the liver, brain, adrenal glands, and lymph nodes in different xenograft mouse models of cancer. MRI of mice was performed with a clinical 3.0 T magnetic resonance scanner and a commercially available small-animal receiver coil. The imaging protocol consisted of T1- and T2-weighted fat-saturated spin echo sequences with a spatial resolution of 200 µm × 200 µm × 500 µm. Total acquisition time was 30 min per mouse. The technique allowed for repetitive examinations of larger animal cohorts to observe the development of metastases.

Interaction of magnetically labeled multipotent mesenchymal stromal cells and E-and P-selectins monitored by magnetic resonance imaging in mice.

The purpose of this study was to analyze the influence of E- and P-selectins on the migratory pattern of magnetically labeled multipotent mesenchymal stromal cells (MSCs) in mice using magnetic resonance imaging (MRI). Murine MSCs were labeled with fluorescent iron oxide microparticles and carboxyfluorescein succinidyl ester (CFSE). Expression of common MSC markers, CD44, CD90, CD105, and Sca-1, as well as of selectin ligands, CD15s and CD162, was assessed using flow cytometry and immunocytochemistry. Labeled MSCs were injected into E-/P-selectin-deficient and wild-type mice applying doses of 5 × 10(4) cells intracardially, 1 × 10(6) cells intravenously, and 5 × 10(6) cells intraperitoneally. After cell administration, mice underwent MRI repeatedly and histologic evaluation after 7 days. The results demonstrate that magnetically labeled murine MSCs retain their expression of the above-mentioned surface markers and their ability to interact with P-selectin. Furthermore, MRI examinations and histologic analysis revealed that E-/P-selectin deficiency in mice significantly alters the distribution of labeled MSCs after cell injection via different routes.

Selectin binding is essential for peritoneal carcinomatosis in a xenograft model of human pancreatic adenocarcinoma in pfp--/rag2-- mice.

BACKGROUND AND OBJECTIVE: E- and P-selectins expressed on the luminal surface of mesodermally derived endothelial cells play a crucial role in the formation of haematogenous metastases in a number of malignancies. As peritoneal mesothelial cells are also derived form the mesoderm, it was hypothesised that selectins are also of importance in peritoneal tumour spread. METHODS: Immunohistochemistry was used to identify selectin expression on normal human peritoneum and isolated mesothelial cells. E- and P-selectin interactions with human pancreatic adenocarcinoma cells were investigated in dynamic flow assays and flow cytometry; the latter was also used to determine the main selectin ligands on pancreatic adenocarcinoma cell lines PaCa 5061, BxPC-3 and PaCa 5072, and selectin expression on human mesothelial cells. All cell lines were xenografted into the peritoneum of E- and P-selectin-deficient pfp/rag2 mice and selectin wild-type controls. Peritoneal carcinomatosis was quantified using MRI or a scoring system. RESULTS: E- and P-selectin were constitutively expressed on human mesothelial and endothelial cells in the peritoneum. PaCa 5061 and BxPC-3 cells interacted with E- and P-selectins in dynamic flow assays and flow cytometry, with CA19-9 (Sialyl Lewis a) being the main E-selectin ligand. For xenografted PaCa 5061 and BxPC-3 cells, peritoneal metastasis was significantly reduced in E- and P-selectin double knockout mice compared with wild-type pfp/rag2 animals. In contrast, PaCa 5072 cells were almost devoid of selectin binding sites and no intraperitoneal tumour growth was observed. CONCLUSION: Interactions of tumour cells with peritoneal selectins play an important role in the peritoneal spread of pancreatic adenocarcinoma.

Comparative diagnostic performance of ¹8F-FDG PET/CT versus whole-body MRI for determination of remission status in multiple myeloma after stem cell transplantation.

OBJECTIVES: To compare the diagnostic performance of whole-body magnetic resonance imaging (WBMRI) versus (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for determination of remission status in patients with multiple myeloma (MM) after stem cell transplantation (SCT). METHODS: Thirty-one patients were examined by both WBMRI and PET/CT after SCT. Imaging results and clinical remission status as determined by the clinical gold standard (Uniform Response Criteria) were compared. RESULTS: One hundred four lesions were detected in 21 patients. PET/CT had a sensitivity of 50.0 %, a specificity of 85.7 %, a positive predictive value of 62.5 %, a negative predictive value of 78.3 %, and an overall accuracy of 74.2 % for determination of remission status. MRI had a sensitivity of 80.0 %, a specificity of 38.1 %, a positive predictive value of 38.1 %, a negative predictive value of 80 %, and an overall accuracy of 51.6 %. Concordant results were observed in only 12 (11.5 %) of the 104 lesions. CONCLUSIONS: In the post-treatment setting, both FDG PET/CT and WBMRI provide information about the extent of disease, allowing for a more comprehensive evaluation of persisting or recurrent myeloma. MRI may often be false positive because of persistent non-viable lesions. Therefore, PET/CT might be more suitable than MRI for determination of remission status.

Tailor-made quantum dot and iron oxide based contrast agents for in vitro and in vivo tumor imaging.

The biofunctionalization of CdSe/CdS/ZnS quantum dots and Fe(3)O(4) nanocrystals using a novel ligand system based on polyisoprene-block-poly(ethylene oxide) ligands is described. The synthesis includes a partial ligand exchange of the hydrophobic nanocrystals with amino-functionalized polyisoprene ligands, followed by seeded micelle formation of the diblock-copolymers in water. The resulting water-soluble quantum dots showed fluorescence quantum efficiencies in the 40 to 50% range and extraordinary fluorescence stability in the biological environment after cross-linking of the polyisoprene moiety of the ligand shell. No toxicity was detected by water-soluble tetrazolium (WST8) and lactate dehydrogenase (LDH) assays, even at very high nanoparticle concentrations, and almost no nonspecific cell adhesion was detected. The ligand shell was further coupled to the antigen-related cell adhesion molecule (CEACAM) specific monoclonal antibody T84.1. The so-conjugated Fe(3)O(4) nanocrystals allowed in vitro and in vivo tumor targeting by magnetic resonance imaging.

Investigations on the usefulness of CEACAMs as potential imaging targets for molecular imaging purposes.

Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs) family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well.In order to test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM expression was analysed using this antibody. Twelve human cancer cell lines from different entities were screened for their CEACAM expression using qPCR, Western Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines showed the highest expression levels with good correlation of mRNA and protein level. However, when grown in vivo, the CEACAM expression was generally downregulated except for the melanoma cell lines. As the CEACAM expression showed pronounced expression in FemX-1 primary tumours, this model system was used for further experiments. As the accessibility of the antibody after i.v. application is critical for its use in molecular imaging, the binding of the T84.1 monoclonal antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1 primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to tumour cells in the vicinity of blood vessels. This binding pattern was particularly pronounced in the periphery of the tumour xenograft, however, some antibody binding was also observed in the central areas of the tumour around blood vessels. Still, a general penetration of the tumour by i.v. application of the anti CEACAM antibody could not be achieved despite homogenous CEACAM expression of all melanoma cells when analysed in tissue sections. This lack of penetration is probably due to the increased interstitial fluid pressure in tumours caused by the absence of functional lymphatic vessels.

Brown adipose tissue activity controls triglyceride clearance.

Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold and has recently been shown to be present in humans. Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL). Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease. However, the precise biological role of BAT for TRL clearance remains unclear. Here we show that increased BAT activity induced by short-term cold exposure controls TRL metabolism in mice. Cold exposure drastically accelerated plasma clearance of triglycerides as a result of increased uptake into BAT, a process crucially dependent on local LPL activity and transmembrane receptor CD36. In pathophysiological settings, cold exposure corrected hyperlipidemia and improved deleterious effects of insulin resistance. In conclusion, BAT activity controls vascular lipoprotein homeostasis by inducing a metabolic program that boosts TRL turnover and channels lipids into BAT. Activation of BAT might be a therapeutic approach to reduce elevated triglyceride concentrations and combat obesity in humans.

Quantitative magnetic resonance imaging of enzyme activity on the cell surface: in vitro and in vivo monitoring of ADP-ribosyltransferase 2 on T cells.

The objective of this study was to quantify enzymatic activity on the surface of T cells by magnetic resonance imaging (MRI) using R2 and R2* relaxometry. Lymphoma cells expressing adenosine diphosphate (ADP)-ribosyltransferase 2 (ART2) were incubated with increasing doses of its substrate etheno-nicotinamide adenine dinucleotide (NAD), resulting in increasing amounts of surface protein ADP-ribosylation. Etheno-ADP-ribosylated proteins were detected with monoclonal antibody 1G4 and superparamagnetic iron oxide conjugated secondary antibodies (Ab-SPIO). Labeling efficiency was determined with R2 and R2* relaxometry on a clinical 3.0 T scanner. Parallel aliquots of cells were analyzed by flow cytometry. Cell-bound SPIO conjugates were detected by immunofluorescence and electron microscopy and quantified by atomic absorption spectroscopy. To mimic an inflammatory site in vivo, Ab-SPIO-labeled cells were injected subcutaneously in mice and analyzed by MRI. Immunofluorescence and electron microscopy confirmed cell-surface localization of Ab-SPIO. MRI of Ab-SPIO-labeled cells showed a corresponding signal reduction. Increases in R2 and R2* determined by magnetic resonance relaxometry correlated linearly with the expression level of ART2 and the concentration of the ART2 substrate etheno-NAD. R2 and R2* increases correlated linearly with the results from flow cytometry and atomic absorption spectroscopy analyses. Quantitative R2 and R2* mapping enable noninvasive determination of enzymatic activity on T cells and holds promise for characterization of inflammatory sites in vivo by MRI.

Effective therapeutic targeting of the overexpressed HER-2 receptor in a highly metastatic orthotopic model of esophageal carcinoma.

This study aimed to determine the targeted efficacy of trastuzumab (Herceptin) on human epidermal growth factor receptor 2 (HER-2)-overexpressing metastatic esophageal cancer in an orthotopic mouse model. HER-2 overexpression and amplification of human esophageal primary and metastatic tumors were shown with HER-2-fluorescence in situ hybridization analysis and HER-2 immunostaining. Following orthotopic implantation with the HER-2-overexpressing OE19 human esophageal cancer cell line, mice were treated with trastuzumab. Sequential magnetic resonance imaging was used to monitor primary tumor and metastasis during treatment. After six weeks, a significant inhibition of primary tumor development was imaged in trastuzumab-treated animals in comparison with the control group. Trastuzumab treatment also led to a reduction of lymphatic metastasis. Thus, HER-2 targeted therapy with trastuzumab resulted in a significant primary tumor growth reduction as well as a decrease of lymph node metastases in the orthotopic model of metastatic esophageal carcinoma. The results of the present study suggest the clinical use of trastuzumab for HER-2-overexpressing esophageal cancer, which is a significant fraction of the patient population. Treatment of this highly treatment-resistant disease with trastuzumab in the adjuvant setting to prevent lymph node metastasis after primary tumor resection is suggested by the data in this report.

Quantitative MR imaging of targeted SPIO particles on the cell surface and comparison to flow cytometry.

PURPOSE: To detect anti-CEACAM5 targeted superparamagnetic iron oxide (SPIO) particles in vitro on the cell surface by quantitative magnetic resonance (MR) imaging and to compare with flow cytometry. MATERIALS AND METHODS: The monoclonal mouse antibody T84.1 and an appropriate IgG isotype antibody were conjugated to dextran-coated SPIO particles. HT29 cells expressing carcinoembryonic antigen (CEACAM5) were treated with antibody-conjugated SPIO particles. Purified cell samples were examined on a 3.0-T MR scanner using a multi-echo spin-echo sequence for MR relaxometry. Aliquots of the cell samples were further treated with a fluorescein isothiocyanate (FITC) anti-dextran antibody and an Alexa Fluor 488 anti-mouse antibody for the corresponding flow cytometry. RESULTS: MR relaxometry revealed a dose-dependent binding of T84.1-conjugated SPIO particles with a positive correlation between R(2) relaxation rate of cell samples and SPIO particle concentration during incubation (r=0.993, P<.01). Positive correlations were also observed between R(2) relaxation rate and flow cytometry (geometric mean) with both fluorescent antibodies (r=0.972 and r=0.953, both P<.01), respectively. CONCLUSION: The study revealed the feasibility of quantitative MR imaging of targeted SPIO particles on the cell surface comparable to flow cytometry.

Complementary use of fluorescence and magnetic resonance imaging of metastatic esophageal cancer in a novel orthotopic mouse model.

We describe the development of an aggressive orthotopic metastatic model of esophageal cancer, which is visualized in real time with combined magnetic resonance imaging (MRI) and fluorescence imaging. The aim of the study was to describe the development of a novel model of metastatic tumor disease of esophageal carcinoma and use this model to evaluate fluorescence and MRI in early detection of local and metastatic disease. The human esophageal adenocarcinoma cell line PT1590 was stably transfected with green fluorescent protein (GFP). Nude mice were orthotopically implanted with PT1590-GFP cells. Orthotopic tumor growth as well as metastatic spread was examined by fluorescence imaging and high-resolution MRI at defined intervals after orthotopic implantation. Highly aggressive novel fluorescent cell lines were isolated from metastatic tissues and put into culture. After implantation of these cells, 100% of the animals developed orthotopic primary tumors. In 83% of animals, metastatic spread to liver, lung and lymph nodes was observed. Primary tumor growth could be visualized with fluorescence imaging and with MRI with high correlation between the 2 methods. Fluorescence imaging allows fast, sensitive, and economical imaging of the primary and metastatic tumor without anesthesia. With MRI, anatomical structures are visualized more precisely and tumors can be more accurately localized to specific organs. This model should prove highly useful to understand esophageal carcinoma and to identify novel therapeutics for this treatment-resistant disease.

Magnetic resonance imaging of melanoma metastases in a clinical relevant human melanoma xenograft scid mouse model.

This study aimed to analyse (i) the metastatic behaviour of human melanoma FEMX-1 cells in scid mice after surgical excision of the PT and (ii) to evaluate the feasibility of magnetic resonance imaging (MRI) for the detection of melanoma metastases. Histology proved both high specificity (95%), and high sensitivity of MRI detection of melanoma metastasis. CEACAM1, L1, and HPA-binding site expression, all markers predicting metastasis in clinical studies, were preserved in the metastatic nodules. Thus, our xenograft model closely resembles the clinical situation of post-operative development of distant organ metastasis and demonstrates that MRI is a sensitive and highly qualified technology for intra-vital monitoring of melanoma progression.

[18F]FDG and [18F]FLT PET-CT and MR imaging of human neuroblastomas in a SCID mouse xenograft model.

BACKGROUND: Finding new therapeutic agents is of great clinical interest in neuroblastoma research because prognosis of children with disseminated stages of disease is still poor. As xenograft mouse models are frequently used for studying anticancer drugs in vivo, small animal imaging is an important method of monitoring in anticancer research. MATERIALS AND METHODS: SCID mice inoculated with human neuroblastoma SK-N-SH cells were examined with positron-emission tomography-computed tomography (PET-CT) using [18F]fluorodeoxyglucose (FDG) or [18F]fluoro-L-thymidine (FLT) and with magnetic resonance imaging (MRI). RESULTS: All neuroblastomas were detected by MRI. In PET-CT imaging, no tumour was visualized with [18F]FDG, but 13 out of 14 (93%) were found with [18F]FLT. Uptake of [18F]FLT was significantly associated with tumour weight. Necrotic areas could not be identified either by MR imaging or on PET-CT scans. CONCLUSION: Both MR and PET-CT imaging with [18F]FLT are highly qualified for the detection of neuroblastomas grown in SCID mice. However, [18F]FDG, which is the standard tracer in clinical PET-CT imaging, is not suited for PET-CT imaging in the neuroblastoma model.

Gene expression patterns and tumor uptake of 18F-FDG, 18F-FLT, and 18F-FEC in PET/MRI of an orthotopic mouse xenotransplantation model of pancreatic cancer.

UNLABELLED: Our aim was to use PET/MRI to evaluate and compare the uptake of 18F-FDG, 3-deoxy-3-18F-fluorothymidine (18F-FLT), and 18F-fluorethylcholine (18F-FEC) in human pancreatic tumor cell lines after xenotransplantation into SCID mice and to correlate tumor uptake with gene expression of membrane transporters and rate-limiting enzymes for tracer uptake and tracer retention. METHODS: Four weeks after orthotopic inoculation of human pancreatic carcinoma cells (PancTuI, Colo357, and BxPC3) into SCID mice, combined imaging was performed with a small-animal PET scanner and a 3-T MRI scanner using a dedicated mouse coil. Tumor-to-liver uptake ratios (TLRs) of the tracers were compared with gene expression profiles of the tumor cell lines and both normal pancreatic tissue and pancreatic tumor tissue based on gene microarray analysis and quantitative polymerase chain reaction. RESULTS: 18F-FLT showed the highest tumor uptake, with a mean TLR of 2.3, allowing correct visualization of all 12 pancreatic tumors. 18F-FDG detected only 4 of 8 tumors and had low uptake in tumors, with a mean TLR of 1.1 in visible tumors. 18F-FEC did not show any tumor uptake. Gene array analysis revealed that both hexokinase 1 as the rate-limiting enzyme for 18F-FDG trapping and pancreas-specific glucose transporter 2 were significantly downregulated whereas thymidine kinase 1, responsible for 18F-FLT trapping, was significantly upregulated in the tumor cell lines, compared with normal pancreatic duct cells and pancreatic tumor tissue. Relevant genes involved in the uptake of 18F-FEC were predominantly unaffected or downregulated in the tumor cell lines. CONCLUSION: In comparison to 18F-FDG and 18F-FEC, 18F-FLT was the PET tracer with the highest and most consistent uptake in various human pancreatic tumor cell lines in SCID mice. The imaging results could be explained by gene expression patterns of membrane transporters and enzymes for tracer uptake and retention as measured by gene array analysis and quantitative polymerase chain reaction in the respective cell lines. Thus, standard molecular techniques provided the basis to help explain model-specific tracer uptake patterns in xenotransplanted human tumor cell lines in mice as observed by PET.

Computer-aided diagnosis as a second reader: spectrum of findings in CT studies of the chest interpreted as normal.

STUDY OBJECTIVES: To assess the performance of an automated computer-aided detection (CAD) system as a second reader on chest CT studies interpreted as normal at routine clinical interpretation. DESIGN: Chest CT studies were processed using a prototype CAD system for automated detection of lung lesions. Three experienced radiologists analyzed each CAD finding and confirmed or dismissed the marked image features as lung lesions. Noncalcified, focal lung lesions were classified according to size as being of high (> or = 10 mm), intermediate (5 to 9 mm), or low (< or = 4 mm) significance. SETTING: Two sub-specialized academic tertiary referral centers in the United States and Germany. PATIENTS: Chest CT studies were performed in 100 patients, with results initially reported as normal at clinical double reading. Indications for chest CT were suspected pulmonary embolism (PE) [n = 33], lung cancer screening in a high-risk population (n = 28), or follow-up for a cancer history (n = 39). INTERVENTIONS: Reevaluation of all chest CT studies for focal lung lesions with the CAD system as a second reader. MEASUREMENTS: Prevalence and spectrum of lung lesions missed at routine clinical interpretation but found by the CAD system. RESULTS: In 33% (33 of 100 patients), CAD detected significant lung lesions that were not previously reported. Fifty-three significant lesions were detected (mean, 1.6 lesions per case), of which 5 lesions (9.4%) were of high significance, 21 lesions (39.6%) were of intermediate significance, and 27 lesions (50.9%) were of low significance. In the PE group, the lung cancer screening group, and the group with a cancer history, four patients (12.1%), six patients (21.4%), and nine patients (23.1%), respectively, had focal lung lesions of high and/or intermediate significance. The false-positive rate of the CAD system was an average of 1.25 per case (range, 0 to 11). CONCLUSIONS: Significant lung lesions are frequently missed at routine clinical interpretation of chest CT studies but may be detected if CAD is used as an additional reader.

Registration and fusion of CT and MRI of the temporal bone.

OBJECTIVE: To present and evaluate a registration method to fuse complementary information of CT and MRI of the temporal bone. METHODS: CT and MRI of the temporal bone of 26 patients were independently registered 4 times. A manual, iterative, intrinsic, rigid, and retrospective registration method was used. Mean CREm (consistency registration error) was calculated as a reproducibility measurement. RESULTS: CREm was 0.6 mm (95% CI = 0.52-0.68 mm). T-test revealed no difference between pathologic and normal cases (t[102] = -1.71; P = 0.09). Time needed: 13 minutes. In the registered and fused datasets, important bony surgical landmarks (eg, facial nerve canal, inner ear) could be assessed in 3 dimensions relatively to tumor tissue (eg, acoustic schwannoma). Fluid distribution within partially obliterated cochleae could be assigned to either scalae. CONCLUSION: An accurate, reproducible registration and fusion method that improves tumor surgery and cochlea implantation planning with only minor changes to the clinical workflow was presented and described. We suggest this method in selected cases.