共查询到20条相似文献,搜索用时 31 毫秒
1.
Ralf S. Eschbach Wolfgang P. Fendler Philipp M. Kazmierczak Marcus Hacker Axel Rominger Janette Carlsen Heidrun Hirner-Eppeneder Jessica Schuster Matthias Moser Lukas Havla Moritz J. Schneider Michael Ingrisch Lukas Spaeth Maximilian F. Reiser Konstantin Nikolaou Clemens C. Cyran 《PloS one》2015,10(2)
ObjectivesTo investigate a multimodal, multiparametric perfusion MRI / 18F-fluoro-deoxyglucose-(18F-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation.ResultsRegorafenib significantly (p<0.01) suppressed PF (81.1±7.5 to 50.6±16.0 mL/100mL/min), PV (12.1±3.6 to 7.5±1.6%) and PS (13.6±3.2 to 7.9±2.3 mL/100mL/min) as well as TTB (3.4±0.6 to 1.9±1.1) between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03) lower tumor microvascular density (CD-31, 7.0±2.4 vs. 16.1±5.9) and tumor cell proliferation (Ki-67, 434.0 ± 62.9 vs. 663.0 ± 98.3) in the therapy group. Perfusion MRI parameters ΔPF, ΔPV and ΔPS showed strong and significant (r = 0.67-0.78; p<0.01) correlations to the PET parameter ΔTTB and significant correlations (r = 0.57-0.67; p<0.03) to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55; p<0.05).ConclusionsA multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and 18F-FDG-PET validated by immunohistochemistry. 相似文献
2.
Manuela C. Felix Jens Fleckenstein Stefanie Kirschner Linda Hartmann Frederik Wenz Marc A. Brockmann Gerhard Glatting Frank A. Giordano 《PloS one》2015,10(5)
Purpose/ObjectiveAlthough radiotherapy is a key component of cancer treatment, its implementation into pre-clinical in vivo models with relatively small target volumes is frequently omitted either due to technical complexity or expected side effects hampering long-term observational studies. We here demonstrate how an affordable industrial micro-CT can be converted into a small animal IGRT device at very low costs. We also demonstrate the proof of principle for the case of partial brain irradiation of mice carrying orthotopic glioblastoma implants.Methods/MaterialsA commercially available micro-CT originally designed for non-destructive material analysis was used. It consists of a CNC manipulator, a transmission X-ray tube (10–160 kV) and a flat-panel detector, which was used together with custom-made steel collimators (1–5 mm aperture size). For radiation field characterization, an ionization chamber, water-equivalent slab phantoms and radiochromic films were used. A treatment planning tool was implemented using a C++ application. For proof of principle, NOD/SCID/γc−/− mice were orthotopically implanted with U87MG high-grade glioma cells and irradiated using the novel setup.ResultsThe overall symmetry of the radiation field at 150 kV was 1.04±0.02%. The flatness was 4.99±0.63% and the penumbra widths were between 0.14 mm and 0.51 mm. The full width at half maximum (FWHM) ranged from 1.97 to 9.99 mm depending on the collimator aperture size. The dose depth curve along the central axis followed a typical shape of keV photons. Dose rates measured were 10.7 mGy/s in 1 mm and 7.6 mGy/s in 5 mm depth (5 mm collimator aperture size). Treatment of mice with a single dose of 10 Gy was tolerated well and resulted in central tumor necrosis consistent with therapeutic efficacy.ConclusionA conventional industrial micro-CT can be easily modified to allow effective small animal IGRT even of critical target volumes such as the brain. 相似文献
3.
Heling Zhou Kate Luby-Phelps Bruce E. Mickey Amyn A. Habib Ralph P. Mason Dawen Zhao 《PloS one》2009,4(11)
Background
It is recognized that cancer cells exhibit highly elevated glucose metabolism compared to non-tumor cells. We have applied in vivo optical imaging to study dynamic uptake of a near-infrared dye-labeled glucose analogue, 2-deoxyglucose (2-DG) by orthotopic glioma in a mouse model.Methodology and Principal Findings
The orthotopic glioma model was established by surgically implanting U87-luc glioma cells into the right caudal nuclear area of nude mice. Intracranial tumor growth was monitored longitudinally by bioluminescence imaging and MRI. When tumor size reached >4 mm diameter, dynamic fluorescence imaging was performed after an injection of the NIR labeled 2-DG, IRDye800CW 2-DG. Real-time whole body images acquired immediately after i.v. infusion clearly visualized the near-infrared dye circulating into various internal organs sequentially. Dynamic fluorescence imaging revealed significantly higher signal intensity in the tumor side of the brain than the contralateral normal brain 24 h after injection (tumor/normal ratio, TNR = 2.8±0.7). Even stronger contrast was achieved by removing the scalp (TNR = 3.7±1.1) and skull (TNR = 4.2±1.1) of the mice. In contrast, a control dye, IRDye800CW carboxylate, showed little difference (1.1±0.2). Ex vivo fluorescence imaging performed on ultrathin cryosections (20 µm) of tumor bearing whole brain revealed distinct tumor margins. Microscopic imaging identified cytoplasmic locations of the 2-DG dye in tumor cells.Conclusion and Significance
Our results suggest that the near-infrared dye labeled 2-DG may serve as a useful fluorescence imaging probe to noninvasively assess intracranial tumor burden in preclinical animal models. 相似文献4.
Stéphanie Tan Gilles Soulez Patricia Diez Martinez Sandra Larrivée Louis-Mathieu Stevens Yves Goussard Samer Mansour Carl Chartrand-Lefebvre 《PloS one》2016,11(4)
PurposeMetallic artifacts can result in an artificial thickening of the coronary stent wall which can significantly impair computed tomography (CT) imaging in patients with coronary stents. The objective of this study is to assess in vivo visualization of coronary stent wall and lumen with an edge-enhancing CT reconstruction kernel, as compared to a standard kernel.MethodsThis is a prospective cross-sectional study involving the assessment of 71 coronary stents (24 patients), with blinded observers. After 256-slice CT angiography, image reconstruction was done with medium-smooth and edge-enhancing kernels. Stent wall thickness was measured with both orthogonal and circumference methods, averaging thickness from diameter and circumference measurements, respectively. Image quality was assessed quantitatively using objective parameters (noise, signal to noise (SNR) and contrast to noise (CNR) ratios), as well as visually using a 5-point Likert scale.ResultsStent wall thickness was decreased with the edge-enhancing kernel in comparison to the standard kernel, either with the orthogonal (0.97 ± 0.02 versus 1.09 ± 0.03 mm, respectively; p<0.001) or the circumference method (1.13 ± 0.02 versus 1.21 ± 0.02 mm, respectively; p = 0.001). The edge-enhancing kernel generated less overestimation from nominal thickness compared to the standard kernel, both with the orthogonal (0.89 ± 0.19 versus 1.00 ± 0.26 mm, respectively; p<0.001) and the circumference (1.06 ± 0.26 versus 1.13 ± 0.31 mm, respectively; p = 0.005) methods. The edge-enhancing kernel was associated with lower SNR and CNR, as well as higher background noise (all p < 0.001), in comparison to the medium-smooth kernel. Stent visual scores were higher with the edge-enhancing kernel (p<0.001).ConclusionIn vivo 256-slice CT assessment of coronary stents shows that the edge-enhancing CT reconstruction kernel generates thinner stent walls, less overestimation from nominal thickness, and better image quality scores than the standard kernel. 相似文献
5.
Patricia Coutinho de Souza Samantha Mallory Nataliya Smith Debra Saunders Xiao-Nan Li Rene Y. McNall-Knapp Kar-Ming Fung Rheal A. Towner 《PloS one》2015,10(8)
Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients. 相似文献
6.
Ryutaro Kakinuma Noriyuki Moriyama Yukio Muramatsu Shiho Gomi Masahiro Suzuki Hirobumi Nagasawa Masahiko Kusumoto Tomohiko Aso Yoshihisa Muramatsu Takaaki Tsuchida Koji Tsuta Akiko Miyagi Maeshima Naobumi Tochigi Shun-ichi Watanabe Naoki Sugihara Shinsuke Tsukagoshi Yasuo Saito Masahiro Kazama Kazuto Ashizawa Kazuo Awai Osamu Honda Hiroyuki Ishikawa Naoya Koizumi Daisuke Komoto Hiroshi Moriya Seitaro Oda Yasuji Oshiro Masahiro Yanagawa Noriyuki Tomiyama Hisao Asamura 《PloS one》2015,10(9)
PurposeThe image noise and image quality of a prototype ultra-high-resolution computed tomography (U-HRCT) scanner was evaluated and compared with those of conventional high-resolution CT (C-HRCT) scanners.ResultsThe image noise for U-HRCT (100.87 ± 0.51 Hounsfield units [HU]) was greater than that for C-HRCT (40.41 ± 0.52 HU; P < .0001). The image quality of U-HRCT was graded as superior to that of C-HRCT (P < .0001) for all of the following parameters that were examined: margins of subsolid and solid nodules, edges of solid components and pulmonary vessels in subsolid nodules, air bronchograms, pleural indentations, margins of pulmonary vessels, edges of bronchi, and interlobar fissures.ConclusionDespite a larger image noise, the prototype U-HRCT scanner had a significantly better image quality than the C-HRCT scanners. 相似文献
7.
Moritz J?rg Schneider Clemens Christian Cyran Konstantin Nikolaou Heidrun Hirner Maximilian F. Reiser Olaf Dietrich 《PloS one》2014,9(9)
Objectives
To evaluate the use of diffusion-weighted MRI (DW-MRI) and volume measurements for early monitoring of antiangiogenic therapy in an experimental tumor model.Materials and Methods
23 athymic nude rats, bearing human colon carcinoma xenografts (HT-29) were examined before and after 6 days of treatment with regorafenib (n = 12) or placebo (n = 11) in a clinical 3-Tesla MRI. For DW-MRI, a single-shot EPI sequence with 9 b-values (10–800 s/mm2) was used. The apparent diffusion coefficient (ADC) was calculated voxelwise and its median value over a region of interest, covering the entire tumor, was defined as the tumor ADC. Tumor volume was determined using T2-weighted images. ADC and volume changes between first and second measurement were evaluated as classifiers by a receiver-operator-characteristic (ROC) analysis individually and combined using Fisher''s linear discriminant analysis (FLDA).Results
All ADCs and volumes are stated as median±standard deviation. Tumor ADC increased significantly in the therapy group (0.76±0.09×10−3 mm2/s to 0.90±0.12×10−3 mm2/s; p<0.001), with significantly higher changes of tumor ADC than in the control group (0.10±0.11×10−3 mm2/s vs. 0.03±0.09×10−3 mm2/s; p = 0.027). Tumor volume increased significantly in both groups (therapy: 347.8±449.1 to 405.3±823.6 mm3; p = 0.034; control: 219.7±79.5 to 443.7±141.5 mm3; p<0.001), however, the therapy group showed significantly reduced tumor growth (33.30±47.30% vs. 96.43±31.66%; p<0.001). Area under the curve and accuracy of the ADC-based ROC analysis were 0.773 and 78.3%; and for the volume change 0.886 and 82.6%. The FLDA approach yielded an AUC of 0.985 and an accuracy of 95.7%.Conclusions
Regorafenib therapy significantly increased tumor ADC after 6 days of treatment and also significantly reduced tumor growth. However, ROC analyses using each parameter individually revealed a lack of accuracy in discriminating between therapy and control group. The combination of both parameters using FLDA substantially improved diagnostic accuracy, thus highlighting the potential of multi-parameter MRI as an imaging biomarker for non-invasive early tumor therapy monitoring. 相似文献8.
Matthias Brendel Anna Jaworska Eric Grie?inger Christina R?tzer Steffen Burgold Franz-Josef Gildehaus Janette Carlsen Paul Cumming Karlheinz Baumann Christian Haass Harald Steiner Peter Bartenstein Jochen Herms Axel Rominger 《PloS one》2015,10(2)
We aimed to compare [18F]-florbetaben PET imaging in four transgenic mouse strains modelling Alzheimer’s disease (AD), with the main focus on APPswe/PS2 mice and C57Bl/6 mice serving as controls (WT). A consistent PET protocol (N = 82 PET scans) was used, with cortical standardized uptake value ratio (SUVR) relative to cerebellum as the endpoint. We correlated methoxy-X04 staining of β-amyloid with PET results, and undertook ex vivo autoradiography for further validation of a partial volume effect correction (PVEC) of PET data. The SUVR in APPswe/PS2 increased from 0.95±0.04 at five months (N = 5) and 1.04±0.03 (p<0.05) at eight months (N = 7) to 1.07±0.04 (p<0.005) at ten months (N = 6), 1.28±0.06 (p<0.001) at 16 months (N = 6) and 1.39±0.09 (p<0.001) at 19 months (N = 6). SUVR was 0.95±0.03 in WT mice of all ages (N = 22). In APPswe/PS1G384A mice, the SUVR was 0.93/0.98 at five months (N = 2) and 1.11 at 16 months (N = 1). In APPswe/PS1dE9 mice, the SUVR declined from 0.96/0.96 at 12 months (N = 2) to 0.91/0.92 at 24 months (N = 2), due to β-amyloid plaques in cerebellum. PVEC reduced the discrepancy between SUVR-PET and autoradiography from −22% to +2% and increased the differences between young and aged transgenic animals. SUVR and plaque load correlated highly between strains for uncorrected (R = 0.94, p<0.001) and PVE-corrected (R = 0.95, p<0.001) data. We find that APPswe/PS2 mice may be optimal for longitudinal amyloid-PET monitoring in planned interventions studies. 相似文献
9.
Toru Ishikawa Satoshi Abe Asami Hoshii Yumi Yamada Akihiko Iiduka Takeo Nemoto Keiko Takeda Toshiaki Yoshida 《PloS one》2016,11(1)
Background & Aims
The amount of drug-loaded lipiodol in an HCC tumor post-transarterial chemoembolization (TACE) correlates with the risk of local tumor recurrence. Lipiodol enhancement of a tumor on conventional CT, measured in Hounsfield units (HU), can predict tumor response. Here we investigate whether cone-beam CT (CBCT) can also be used to predict tumor response, providing the benefit of being able to optimize the patient’s treatment plan intra-procedurally.Methods
A total of 82 HCC nodules (82 patients), ≤5 cm in diameter, were treated with balloon-occluded TACE using miriplatin between December 2013 and November 2014. For each patient, both CBCT and conventional CT images were obtained post-TACE. The degree of correlation between CBCT and conventional CT was determined by comparing identical regions of interest for each imaging modality using pixel values.Results
The pixel values from conventional CT and CBCT were highly correlated, with a Pearson correlation coefficient of 0.912 (p<0.001). The location of the nodules within the liver did not affect the results; the correlation coefficient was 0.891 (p<0.001) for the left lobe and 0.926 (p<0.001) for the right lobe. The mean pixel value for conventional CT was 439 ± 279 HU, and the mean pixel value for CBCT was 416 ± 311 HU.Conclusions
CBCT may be used as a substitute for conventional CT to quantitatively evaluate the amount of drug-loaded lipiodol within an HCC nodule and, hence, the efficacy of TACE treatment. The major benefit of using CBCT is the ability to predict the likelihood of local recurrence intra-procedurally, enabling subsequent treatment optimization. 相似文献10.
Florian St?ckigt Klara Brixius Lars Lickfett René Andrié Markus Linhart Georg Nickenig Jan Wilko Schrickel 《PloS one》2012,7(11)
Introduction
Beta-adrenoceptors (β-AR) play an important role in the neurohumoral regulation of cardiac function. Three β-AR subtypes (β1, β2, β3) have been described so far. Total deficiency of these adrenoceptors (TKO) results in cardiac hypotrophy and negative inotropy. TKO represents a unique mouse model mimicking total unselective medical β-blocker therapy in men. Electrophysiological characteristics of TKO have not yet been investigated in an animal model.Methods
In vivo electrophysiological studies using right heart catheterisation were performed in 10 TKO mice and 10 129SV wild type control mice (WT) at the age of 15 weeks. Standard surface ECG, intracardiac and electrophysiological parameters, and arrhythmia inducibility were analyzed.Results
The surface ECG of TKO mice revealed a reduced heart rate (359.2±20.9 bpm vs. 461.1±33.3 bpm; p<0.001), prolonged P wave (17.5±3.0 ms vs. 15.1±1.2 ms; p = 0.019) and PQ time (40.8±2.4 ms vs. 37.3±3.0 ms; p = 0.013) compared to WT. Intracardiac ECG showed a significantly prolonged infra-Hisian conductance (HV-interval: 12.9±1.4 ms vs. 6.8±1.0 ms; p<0.001). Functional testing showed prolonged atrial and ventricular refractory periods in TKO (40.5±15.5 ms vs. 21.3±5.8 ms; p = 0.004; and 41.0±9.7 ms vs. 28.3±6.6 ms; p = 0.004, respectively). In TKO both the probability of induction of atrial fibrillation (12% vs. 24%; p<0.001) and of ventricular tachycardias (0% vs. 26%; p<0.001) were significantly reduced.Conclusion
TKO results in significant prolongations of cardiac conduction times and refractory periods. This was accompanied by a highly significant reduction of atrial and ventricular arrhythmias. Our finding confirms the importance of β-AR in arrhythmogenesis and the potential role of unspecific beta-receptor-blockade as therapeutic target. 相似文献11.
Peter Nordbeck Leoni B?nhof Karl-Heinz Hiller Sabine Voll Paula Arias-Loza Lea Seidlmayer Tatjana Williams Yu-Xiang Ye Daniel Gensler Theo Pelzer Georg Ertl Peter M. Jakob Wolfgang R. Bauer Oliver Ritter 《PloS one》2013,8(8)
Background
Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies.Methods
Female Wistar rats (n = 6 per group) were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition.Results
Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05) and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05) after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease.Conclusion
Cardio-thoracic surgical procedures in experimental myocardial infarction cause distinct alterations upon the global integrity of the organism, which in the long term also induce circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective animal studies and transferring these findings to conditions in patients. 相似文献12.
Hu-bing Wu Zhen Wang Quan-shi Wang Yan-jian Han Meng Wang Wen-lan Zhou Hong-sheng Li 《PloS one》2015,10(9)
Background
Neuropilin (NRP) receptors are overexpressed in glioma tumor tissue, and therefore may be a potential target for imaging markers. We investigated whether labelled tLyP-1, an NRP targeting peptide, could be used as the targeting ligand for developing reagents for imaging glioma tumors.Methods
The tLyP-1 peptide (CGNKRTR) was labeled with 5-carboxyfluorescein (FAM) or 18F-fluoride. A control peptide (MAQKTSH) was also labeled with FAM. The in vitro binding between FAM-tLyP-1 and U87MG cells and in vivo biodistribution of FAM-tLyP-1 in a U87MG glioblastoma xenograft model (nude mouse) were determined. The in vivo biodistribution of 18F-tLyP-1 was also determined by microPET/CT.Results
In vitro, FAM-tLyP-1 was strongly taken up by U87MG cells at very low concentrations (1μM). In vivo, FAM-tLyP-1 accumulated in glioma (U87MG) tumors, but uptake was minimal in the normal brain tissue 1 h after administration. The distribution of FAM-tLyP-1 in the tumor tissue was consistent with expression of NRP1. The tumor/brain fluorescence intensity ratio in mice treated with FAM-tLyP-1 was significantly higher than the control FAM-labeled peptide 1 h after administration (3.44 ± 0.83 vs. 1.32 ± 0.15; t = 5.547, P = 0.001). Uptake of FAM-tLyP-1 in glioma tumors could be blocked by administering an excess of non-conjugated tLyP-1 peptide. [Lys4] tLyP-1 was labeled with 18F to synthesis a PET (18F-tLyP-1). MicroPET/CT imaging showed the tumor was visualized clearly with a high tumor/brain radiolabel ratio at 60 min (2.69 ± 0.52) and 120 min (3.11±0.25).Conclusion
Taken together, our results suggest that tLyP-1 could be developed as a novel fluorescent or radio labelled tracer for imaging glioma. 相似文献13.
Previously, we reported a [99mTc(ǀ)]+ labeled d-glucoamine derivative (99mTc-CN5DG) and evaluated it as a tumor imaging agent in mice bearing A549 tumor xenografts. In this paper, 99mTc-CN5DG was further studied in U87 MG (human glioma cells), HCT-116 (human colon cancer cells), PANC-1 (human pancreatic cancer cells) and TE-1 (human esophageal cancer cells) tumor xenografts models to verify its potential application for imaging of different kinds of tumors. The biodistribution data showed that 99mTc-CN5DG had a similar biodistribution pattern in four tumor models at 2 h post-injection with high accumulation in tumors and kidneys. The tumor/muscle ratios (from 4.08 ± 0.42 to 9.63 ± 3.53) and tumor/blood ratios (from 17.18 ± 7.40 to 53.17 ± 16.16) of 99mTc-CN5DG in four tumor models were high. All four kinds of tumors could be clearly seen on their corresponding SPECT/CT images. Pharmacokinetic study in healthy CD-1 mice demonstrated that 99mTc-CN5DG cleared fast from blood (2 min, 12.97 ± 0.88%ID/g; 60 min, 0.33 ± 0.06%ID/g) and the blood distribution, elimination half-life was 5.81 min and 21.16 min, respectively. No abnormality was observed through the abnormal toxicity study. All of the above results demonstrated that 99mTc-CN5DG could be a broad-spectrum SPECT probe for tumor imaging and its further clinical application is warranted. 相似文献
14.
Karsten Beiderwellen Llanos Geraldo Verena Ruhlmann Philipp Heusch Benedikt Gomez Felix Nensa Lale Umutlu Thomas C. Lauenstein 《PloS one》2015,10(9)
Background
The aim of this study was to compare the diagnostic accuracy of [18F]FDG-PET/MRI with PET/CT for the detection of liver metastases.Methods
32 patients with solid malignancies underwent [18F]FDG-PET/CT and subsequent PET/MRI of the liver. Two readers assessed both datasets regarding lesion characterization (benign, indeterminate, malignant), conspicuity and diagnostic confidence. An imaging follow-up (mean interval: 185±92 days) and/-or histopathological specimen served as standards of reference. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both modalities. Accuracy was determined by calculating the area under the receiver operating characteristic (ROC) curve. Values of conspicuity and diagnostic confidence were compared using Wilcoxon-signed-rank test.Results
The standard of reference revealed 113 liver lesions in 26 patients (malignant: n = 45; benign: n = 68). For PET/MRI a higher accuracy (PET/CT: 82.4%; PET/MRI: 96.1%; p<0.001) as well as sensitivity (67.8% vs. 92.2%, p<0.01) and NPV (82.0% vs. 95.1%, p<0.05) were observed. PET/MRI offered higher lesion conspicuity (PET/CT: 2.0±1.1 [median: 2; range 0–3]; PET/MRI: 2.8±0.5 [median: 3; range 0–3]; p<0.001) and diagnostic confidence (PET/CT: 2.0±0.8 [median: 2; range: 1–3]; PET/MRI 2.6±0.6 [median: 3; range: 1–3]; p<0.001). Furthermore, PET/MRI enabled the detection of additional PET-negative metastases (reader 1: 10; reader 2: 12).Conclusions
PET/MRI offers higher diagnostic accuracy compared to PET/CT for the detection of liver metastases. 相似文献15.
Amit Varma Anindita Das Nicholas N. Hoke David E. Durrant Fadi N. Salloum Rakesh C. Kukreja 《PloS one》2012,7(9)
Background
Insulin resistance impairs nitric oxide (NO) bioavailability and obesity promotes a state of chronic inflammation and damages the vascular endothelium. Phosphodiesterase-5 inhibitors restore NO signaling and may reduce circulating inflammatory markers, and improve metabolic parameters through a number of mechanisms. We hypothesized that daily administration of the PDE-5 inhibitor, tadalafil (TAD) will attenuate inflammation, improve fasting plasma glucose and triglyceride levels, body weight, and reduce infarct size after ischemia/reperfusion injury in obese, diabetic mice.Methods
Twenty leptin receptor null (db/db) mice underwent treatment with TAD (1 mg/Kg) or 10% DMSO for 28 days. Body weight and fasting plasma glucose levels were determined weekly. Upon completion, hearts were isolated and subjected to 30 min global ischemia followed by 60 min reperfusion in a Langendorff model. Plasma samples were taken for cytokine analysis and fasting triglyceride levels. Infarct size was measured using computer morphometry of tetrazolium stained sections. Additionally, ventricular cardiomyocytes were isolated and subjected to 40 min of simulated ischemia and reoxygenation. Necrosis was determined using trypan blue exclusion and LDH release assay and apoptosis was assessed by TUNEL assay after 1 h or 18 h of reoxygenation, respectively.Results
Treatment with TAD caused a reduction in infarct size in the diabetic heart (23.2±1.5 vs. 47.8±3.7%, p<0.01, n = 6/group), reduced fasting glucose levels (292±31.8 vs. 511±19.3 mg/dL, p<0.001) and fasting triglycerides (43.3±21 vs. 129.7±29 mg/dL, p<0.05) as compared to DMSO, however body weight was not significantly reduced. Circulating tumor necrosis factor-α and interleukin-1β were reduced after treatment compared to control (257±16.51 vs. 402.3±17.26 and 150.8±12.55 vs. 264±31.85 pg/mL, respectively; P<0.001) Isolated cardiomyocytes from TAD-treated mice showed reduced apoptosis and necrosis.Conclusion
We have provided the first evidence that TAD therapy ameliorates circulating inflammatory cytokines and chemokines in a diabetic animal model while improving fasting glucose levels and reducing infarct size following ischemia-reperfusion injury in the heart. 相似文献16.
17.
Rumas Aslam Nicolas Girerd Beatrice Brembilla-Perrot 《Indian pacing and electrophysiology journal》2015,15(1):32-42
BackgroundSyncope in elderly patients with heart disease is a growing problem. Its aetiological diagnosis is often difficult. We intended to investigate the value of the electrophysiological study (EPS) in old patients with syncope and heart disease.MethodsEPS was performed in 182 consecutive patients with syncope and heart disease, among whom 62 patients were ≥75 years old and 120 patients <75.ResultsLeft ventricular ejection fraction was 43.9±11.7% in patients ≥75 and 41.1±12.6% in patients <75. During EPS, induced sustained ventricular arrhythmias were as frequent in both groups (27.4% in patients ≥75 versus 27.5% in patients <75, p=0.99) whereas AV conduction abnormalities were more frequent in older patients (37.1% in patients ≥75 versus 18.3% in patients<75, p<0.005). Syncope remained unexplained in 35.5% of patients ≥75 and in 51.7% of patients <75 (p<0.04). ICD was more likely to be implanted in younger patients than in patients ≥75 years (37.5% vs 21% respectively, p<0.009). During a mean follow-up period of 3.3±3 years, the 4-year-survival rate was 66.9±6.8 % in patients ≥75 and 75.9±6.2 % in patients <75 years. The main cause of death was heart failure in both groups. The factors related to a worse outcome in a multivariate analysis were low LVEF and higher age.ConclusionComplete EPS allows the identification of treatable causes in a high proportion of elderly patients with syncope and heart disease. Yet, the prognosis of these patients is mainly related to LVEF and age. 相似文献
18.
Luca Rossetti Maurizio Digiuni Montesano Giovanni Marco Centofanti Antonio M. Fea Michele Iester Paolo Frezzotti Michele Figus Antonio Ferreras Francesco Oddone Lucia Tanga Teresa Rolle Valentina Battaglino Chiara Posarelli Ilaria Motolese Pietro Mittica Simone Alex Bagaglia Cristina Menicacci Stefano De Cilla’ Alessandro Autelitano Paolo Fogagnolo 《PloS one》2015,10(8)
PurposeTo evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities.MethodsThis multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (‘controls’). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°.ResultsUnilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1–25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05).ConclusionsIn this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age. 相似文献
19.
Asgeir S. Jakola Erik M. Berntsen P?l Christensen Sasha Gulati Geirmund Unsg?rd Kjell A. Kvistad Ole Solheim 《PloS one》2014,9(7)
Background
Acquired deficits following glioma resection may not only occur due to accidental resection of normal brain tissue. The possible importance of ischemic injuries in causing neurological deficits after brain tumor surgery is not much studied. We aimed to study the volume and frequency of early postoperative circulatory changes (i.e. infarctions) detected by diffusion weighted resonance imaging (DWI) in patients with surgically acquired neurological deficits compared to controls.Methods
We designed a 1∶1 matched case-control study in patients with diffuse gliomas (WHO grade II–IV) operated with 3D ultrasound guided resection. 42 consecutive patients with acquired postoperative dysphasia and/or new motor deficits were compared to 42 matched controls without acquired deficits. Controls were matched with respect to histopathology, preoperative tumor volumes, and eloquence of location. Two independent radiologists blinded for clinical status assessed the postoperative DWI findings.Results
Postoperative peri-tumoral infarctions were more often seen in patients with acquired deficits (63% versus 41%, p = 0.046) and volumes of DWI abnormalities were larger in cases than in controls with median 1.08 cm3 (IQR 0–2.39) versus median 0 cm3 (IQR 0–1.67), p = 0.047. Inter-rater agreement was substantial (67/82, κ = 0.64, p<0.001) for diagnosing radiological significant DWI abnormalities.Conclusion
Peri-tumoral infarctions were more common and were larger in patients with acquired deficits after glioma surgery compared to glioma patients without deficits when assessed by early postoperative DWI. Infarctions may be a frequent and underestimated cause of acquired deficits after glioma resection. DWI changes may be an attractive endpoint in brain tumor surgery with both good inter-rater reliability among radiologists and clinical relevance. 相似文献20.
Bart Lammers Ying Zhao Amanda C. Foks Reeni B. Hildebrand Johan Kuiper Theo J. C. Van Berkel Miranda Van Eck 《PloS one》2012,7(10)