SARS-CoV-2: The Second Wave in Europe.

Although the SARS-CoV-2 virus has already undergone several mutations, the impact of these mutations on its infectivity and virulence remains controversial. In this viewpoint, we present arguments suggesting that SARS-CoV-2 mutants responsible for the second wave have less virulence but much higher infectivity. This suggestion is based on the results of the forecasting and mechanistic models developed by our study group. In particular, in May 2020, the analysis of our mechanistic model predicted that the easing of lockdown measures will lead to a dramatic second wave of the COVID-19 outbreak. However, after the lockdown was lifted in many European countries, the resulting number of reported infected cases and especially the number of deaths remained low for approximately two months. This raised the false hope that a substantial second wave will be avoided and that the COVID-19 epidemic in these European countries was nearing an end. Unfortunately, since the first week of August 2020, the number of reported infected cases increased dramatically. Furthermore, this was accompanied by an increasingly large number of deaths. The rate of reported infected cases in the second wave was much higher than that in the first wave, whereas the rate of deaths was lower. This trend is consistent with higher infectivity and lower virulence. Even if the mutated form of SARS-CoV-2 is less virulent, the very high number of reported infected cases implies that a large number of people will perish.

Discrete Shearlets as a Sparsifying Transform in Low-Rank Plus Sparse Decomposition for Undersampled (k, t)-Space MR Data.

The discrete shearlet transformation accurately represents the discontinuities and edges occurring in magnetic resonance imaging, providing an excellent option of a sparsifying transform. In the present paper, we examine the use of discrete shearlets over other sparsifying transforms in a low-rank plus sparse decomposition problem, denoted by L+S. The proposed algorithm is evaluated on simulated dynamic contrast enhanced (DCE) and small bowel data. For the small bowel, eight subjects were scanned; the sequence was run first on breath-holding and subsequently on free-breathing, without changing the anatomical position of the subject. The reconstruction performance of the proposed algorithm was evaluated against k-t FOCUSS. L+S decomposition, using discrete shearlets as sparsifying transforms, successfully separated the low-rank (background and periodic motion) from the sparse component (enhancement or bowel motility) for both DCE and small bowel data. Motion estimated from low-rank of DCE data is closer to ground truth deformations than motion estimated from L and S. Motility metrics derived from the S component of free-breathing data were not significantly different from the ones from breath-holding data up to four-fold undersampling, indicating that bowel (rapid/random) motility is isolated in S. Our work strongly supports the use of discrete shearlets as a sparsifying transform in a L+S decomposition for undersampled MR data.

A few-shot U-Net deep learning model for lung cancer lesion segmentation via PET/CT imaging.

Over the past few years, positron emission tomography/computed tomography (PET/CT) imaging for computer-aided diagnosis has received increasing attention. Supervised deep learning architectures are usually employed for the detection of abnormalities, with anatomical localization, especially in the case of CT scans. However, the main limitations of the supervised learning paradigm include (i) large amounts of data required for model training, and (ii) the assumption of fixed network weights upon training completion, implying that the performance of the model cannot be further improved after training. In order to overcome these limitations, we apply a few-shot learning (FSL) scheme. Contrary to traditional deep learning practices, in FSL the model is provided with less data during training. The model then utilizes end-user feedback after training to constantly improve its performance. We integrate FSL in a U-Net architecture for lung cancer lesion segmentation on PET/CT scans, allowing for dynamic model weight fine-tuning and resulting in an online supervised learning scheme. Constant online readjustments of the model weights according to the users' feedback, increase the detection and classification accuracy, especially in cases where low detection performance is encountered. Our proposed method is validated on the Lung-PET-CT-DX TCIA database. PET/CT scans from 87 patients were included in the dataset and were acquired 60 minutes after intravenous18F-FDG injection. Experimental results indicate the superiority of our approach compared to other state-of-the-art methods.

Evaluation of the spline reconstruction technique for preclinical PET imaging.

BACKGROUND AND OBJECTIVE: The Spline Reconstruction Technique (SRT) is a fast algorithm based on a novel numerical implementation of an analytic representation of the inverse Radon transform. The purpose of this study is to provide a comparison between SRT, Filtered Back-Projection (FBP), Ordered Subset Expectation Maximization 2D (2D-OSEM), and the Tera-Tomo 3D algorithm, using phantom data at various acquisition durations as well as small-animal data obtained from the Mediso nanoScan® PET/CT scanner. METHODS: For this purpose, the "NEMA NU 4-2008 standards" protocol was employed at five different realizations and acquisition durations. In addition to the image quality metrics described by the NEMA protocol, Cold Region Contrast was also considered as a figure-of-merit. Furthermore, Cold Region Contrast was measured in the myocardial infarction region of six male Wistar rats. The volumetric defect quantification was assessed with dedicated computer software. Lastly, plots of Recovery Coefficient and Spill-Over Ratio as a function of the Percentage Standard Deviation were generated, after smoothing the phantom reconstructions with four different Gaussian filters. Statistical significance was determined by employing the Kruskal-Wallis test or One-way Analysis of Variance depending on the normality of the variable's distribution. RESULTS: The present study revealed that, at the expense of slightly increased noise in the reconstructed images, SRT resulted in higher Recovery Coefficient values for small hot regions of interest, when compared with FBP and 2D-OSEM at all acquisition durations. Furthermore, SRT reconstructed images exhibit higher Recovery Coefficient values, for all hot regions of interest, when compared to the other 2D algorithms at short acquisition durations. In both phantom and animal studies, SRT achieved a significant improvement over 2D-OSEM for the Spill-Over Ratio and the Cold Region Contrast. These advantages were maintained even after comparing the algorithms at equal noise levels. The Tera-Tomo 3D algorithm (4 subsets, iterations≥ 13) performed significantly better compared to the other algorithms for all figures-of-merit. No statistically significant differences regarding the myocardial defect size were observed between the algorithms investigated. CONCLUSIONS: Overall, SRT appears that could be useful for the quantification of small hot regions of interest, cold regions of interest, as well as in low-count imaging applications.

Inspiratory resistive breathing induces acute lung injury.

RATIONALE: Resistive breathing is associated with large negative intrathoracic pressures. Increased mechanical stress induces high-permeability pulmonary edema and lung inflammation. OBJECTIVES: To determine the effects of resistive breathing on the healthy lung. METHODS: Anesthetized rats breathed through a two-way nonrebreathing valve. The inspiratory line was connected to a resistance setting peak inspiratory tracheal pressure at 50% of maximum (inspiratory resistive breathing), while 100% oxygen was supplied to prevent hypoxemia. Quietly breathing animals (100% oxygen) served as controls. Lung injury was evaluated after 3 and 6 hours of resistive breathing. MEASUREMENTS AND MAIN RESULTS: After both 3 and 6 hours of resistive breathing, lung permeability was increased, as assessed by (99m)Tc-diethylenetriaminepentaacetic acid scintigraphy and Evans blue dye extravasation. Tissue elasticity, measured on the basis of static pressure-volume curves and by the low-frequency forced oscillation technique, was also increased. After both 3 and 6 hours of resistive breathing, gravimetric measurements revealed the presence of pulmonary edema and analysis of bronchoalveolar lavage showed increased total protein content, whereas the total cell count was elevated only after 6 hours of resistive breathing. Cytokine levels were assessed in bronchoalveolar lavage fluid and lung tissue by ELISA and were increased after 6 hours compared with controls. Western blot analysis showed early activation of Src kinase via phosphorylation (at 30 min), and Erk1/2 and IκBα (nuclear factor-κB inhibitor) were phosphorylated at 3 and 6 hours. Pathology revealed the presence of lung injury after resistive breathing. CONCLUSIONS: Resistive breathing induces acute lung injury and inflammation.

Covid-19: predictive mathematical formulae for the number of deaths during lockdown and possible scenarios for the post-lockdown period.

In a recent article, we introduced two novel mathematical expressions and a deep learning algorithm for characterizing the dynamics of the number of reported infected cases with SARS-CoV-2. Here, we show that such formulae can also be used for determining the time evolution of the associated number of deaths: for the epidemics in Spain, Germany, Italy and the UK, the parameters defining these formulae were computed using data up to 1 May 2020, a period of lockdown for these countries; then, the predictions of the formulae were compared with the data for the following 122 days, namely until 1 September. These comparisons, in addition to demonstrating the remarkable predictive capacity of our simple formulae, also show that for a rather long time the easing of the lockdown measures did not affect the number of deaths. The importance of these results regarding predictions of the number of Covid-19 deaths during the post-lockdown period is discussed.

Quantification of T1, T2 relaxation times from Magnetic Resonance Fingerprinting radially undersampled data using analytical transformations.

Quantitative magnetic resonance imaging (MRI) estimates magnetic parameters related to tissue, such as T1, T2 relaxation times and proton density. MR fingerprinting (MRF) is a new concept that uses pseudo-random, incoherent measurements to create a unique fingerprint for each tissue type to quantify magnet parameters. This paper aims to enhance MRF performance by investigating (i) the most suitable acquisition trajectory, and (ii) analytical transformations, suitable for radial acquisitions. Highly undersampled MRF brain (k, t)-space data have been simulated and non-linearly reconstructed to exploit the low-rank property of dynamic imaging. Based on our findings, the radial trajectory is the most suitable for MRF compared to Cartesian and spiral acquisitions. Perhaps this is due to the fact that its aliasing artifacts are more noise-like, and that unlike spiral trajectories, it can use analytical transformations that do not require re-gridding. One such analytical algorithm is the spline reconstruction technique (SRT) that is based on a novel numerical implementation of an analytic representation of the inverse Radon transform. Here, for the first time, this algorithm is applied to MR radial data. Reconstructions using SRT were compared to the ones using filtered back-projection. SRT provided images of higher contrast, lower bias, which resulted in more accurate T1, T2 values.

The attenuated spline reconstruction technique for single photon emission computed tomography.

We present the attenuated spline reconstruction technique (aSRT) which provides an innovative algorithm for single photon emission computed tomography (SPECT) image reconstruction. aSRT is based on an analytic formula of the inverse attenuated Radon transform. It involves the computation of the Hilbert transforms of the linear attenuation function and of two sinusoidal functions of the so-called attenuated sinogram These computations are achieved by employing the attenuation information provided by computed tomography (CT) scans and by utilizing custom-made cubic spline interpolation. The purpose of this work is: (i) to present the mathematics of aSRT, (ii) to reconstruct simulated and real SPECT/CT data using aSRT and (iii) to evaluate aSRT by comparing it to filtered backprojection (FBP) and to ordered subsets expectation minimization (OSEM) reconstruction algorithms. Simulation studies were performed by using an image quality phantom and an appropriate attenuation map. Reconstructed images were generated for 45, 90 and 180 views over 360 degrees with 20 realizations and involved Poisson noise of three different levels (NL), namely 100% (NL1), 50% (NL2) and 10% (NL3) of the total counts, respectively. Moreover, real attenuated SPECT sinograms were reconstructed from a real study of a Jaszczak phantom, as well as from a real clinical myocardial SPECT/CT study. Comparisons between aSRT, FBP and OSEM reconstructions were performed using contrast, bias and image roughness. The results suggest that aSRT can efficiently produce accurate attenuation-corrected reconstructions for simulated and real phantoms, as well as for clinical data. In particular, in the case of the clinical myocardial study, aSRT produced reconstructions with higher cold contrast than both FBP and OSEM. aSRT, by incorporating the attenuation correction within itself, may provide an improved alternative to FBP. This is particularly promising for 'cold' regions as those occurring in myocardial ischaemia.

Radiolabeled methotrexate as a diagnostic agent of inflammatory target sites: A proof-of-concept study.

Methotrexate (MTX), as a pharmaceutical, is frequently used in tumor chemotherapy and is also a part of the established treatment of a number of autoimmune inflammatory disorders. Radiolabeled MTX has been studied as a tumor­diagnostic agent in a number of published studies. In the present study, the potential use of technetium­99m­labelled MTX (99mTc­MTX) as a radiotracer was investigated for the identification of inflammatory target sites. The labelling of MTX was carried out via a 99mTc­gluconate precursor. Evaluation studies included in vitro stability, plasma protein binding assessment, partition­coefficient estimation, in vivo scintigraphic imaging and ex vivo animal experiments in an animal inflammation model. MTX was successfully labelled with 99mTc, with a radiochemical purity of >95%. Stability was assessed in plasma, where it remained intact up to 85% at 4 h post­incubation, while protein binding of the radiotracer was observed to be ~50% at 4 h. These preclinical ex vivo and in vivo studies indicated that 99mTc­MTX accumulates in inflamed tissue, as well as in the spinal cord, joints and bones; all areas with relatively high remodeling activity. The results are promising, and set the stage for further work on the development and application of 99mTc­MTX as a radiotracer for inflammation associated with rheumatoid arthritis.

A Novel Metal-Based Imaging Probe for Targeted Dual-Modality SPECT/MR Imaging of Angiogenesis.

Superparamagnetic iron oxide nanoparticles with well-integrated multimodality imaging properties have generated increasing research interest in the past decade, especially when it comes to the targeted imaging of tumors. Bevacizumab (BCZM) on the other hand is a well-known and widely applied monoclonal antibody recognizing VEGF-A, which is overexpressed in angiogenesis. The aim of this proof-of-concept study was to develop a dual-modality nanoplatform for in vivo targeted single photon computed emission tomography (SPECT) and magnetic resonance imaging (MRI) of tumor vascularization. Iron oxide nanoparticles (IONPs) have been coated with dimercaptosuccinic acid (DMSA), for consequent functionalization with the monoclonal antibody BCZM radiolabeled with 99mTc, via well-developed surface engineering. The IONPs were characterized based on their size distribution, hydrodynamic diameter and magnetic properties. In vitro cytotoxicity studies showed that our nanoconstruct does not cause toxic effects in normal and cancer cells. Fe3O4-DMSA-SMCC-BCZM-99mTc were successfully prepared at high radiochemical purity (>92%) and their stability in human serum and in PBS were demonstrated. In vitro cell binding studies showed the ability of the Fe3O4-DMSA-SMCC-BCZM-99mTc to bind to the VEGF-165 isoform overexpressed on M-165 tumor cells. The ex vivo biodistribution studies in M165 tumor-bearing SCID mice showed high uptake in liver, spleen, kidney and lungs. The Fe3O4-DMSA-SMCC-BCZM-99mTc demonstrated quick tumor accumulation starting at 8.9 ± 1.88%ID/g at 2 h p.i., slightly increasing at 4 h p.i. (16.21 ± 2.56%ID/g) and then decreasing at 24 h p.i. (6.01 ± 1.69%ID/g). The tumor-to-blood ratio reached a maximum at 24 h p.i. (~7), which is also the case for the tumor-to-muscle ratio (~18). Initial pilot imaging studies on an experimental gamma-camera and a clinical MR camera prove our hypothesis and demonstrate the potential of Fe3O4-DMSA-SMCC-BCZM-99mTc for targeted dual-modality imaging. Our findings indicate that Fe3O4-DMSA-SMCC-BCZM-99mTc IONPs could serve as an important diagnostic tool for biomedical imaging as well as a promising candidate for future theranostic applications in cancer.

Automatic cumulative sums contour detection of FBP-reconstructed multi-object nuclear medicine images.

The problem of determining the contours of objects in nuclear medicine images has been studied extensively in the past, however most of the analysis has focused on a single object as opposed to multiple objects. The aim of this work is to develop an automated method for determining the contour of multiple objects in positron emission tomography (PET) and single photon emission computed tomography (SPECT) filtered backprojection (FBP) reconstructed images. These contours can be used for computing body edges for attenuation correction in PET and SPECT, as well as for eliminating streak artifacts outside the objects, which could be useful in compressive sensing reconstruction. Contour detection has been accomplished by applying a modified cumulative sums (CUSUM) scheme in the sinogram. Our approach automatically detects all objects in the image, without requiring a priori knowledge of the number of distinct objects in the reconstructed image. This method has been tested in simulated phantoms, such as an image-quality (IQ) phantom and two digital multi-object phantoms, as well as a real NEMA phantom and a clinical thoracic study. For this purpose, a GE Discovery PET scanner was employed. The detected contours achieved root mean square accuracy of 1.14 pixels, 1.69 pixels and 3.28 pixels and a Hausdorff distance of 3.13, 3.12 and 4.50 pixels, for the simulated image-quality phantom PET study, the real NEMA phantom and the clinical thoracic study, respectively. These results correspond to a significant improvement over recent results obtained in similar studies. Furthermore, we obtained an optimal sub-pattern assignment (OSPA) localization error of 0.94 and 1.48, for the two-objects and three-objects simulated phantoms, respectively. Our method performs efficiently for sets of convex objects and hence it provides a robust tool for automatic contour determination with precise results.

Investigation of Image Reconstruction Parameters of the Mediso nanoScan PC Small-Animal PET/CT Scanner for Two Different Positron Emitters Under NEMA NU 4-2008 Standards.

PURPOSE: The Tera-Tomo 3D image reconstruction algorithm (a version of OSEM), provided with the Mediso nanoScan® PC (PET8/2) small-animal positron emission tomograph (PET)/x-ray computed tomography (CT) scanner, has various parameter options such as total level of regularization, subsets, and iterations. Also, the acquisition time in PET plays an important role. This study aims to assess the performance of this new small-animal PET/CT scanner for different acquisition times and reconstruction parameters, for 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and Ga-68, under the NEMA NU 4-2008 standards. PROCEDURES: Various image quality metrics were calculated for different realizations of [18F]FDG and Ga-68 filled image quality (IQ) phantoms. RESULTS: [18F]FDG imaging produced improved images over Ga-68. The best compromise for the optimization of all image quality factors is achieved for at least 30 min acquisition and image reconstruction with 52 iteration updates combined with a high regularization level. CONCLUSION: A high regularization level at 52 iteration updates and 30 min acquisition time were found to optimize most of the figures of merit investigated.

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin.

BACKGROUND: (99m)Tc-sestamibi (MIBI) and (99m)Tc-tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging. METHODS: Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session. RESULTS: MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62+/-0.15 vs. 0.55+/-0.05, P<.05) for TF and 1.9-fold (1.21+/-0.04 vs. 0.64+/-0.05, P<.05) for MIBI but did not affect MCF7/WT. CONCLUSIONS: The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

The SRT reconstruction algorithm for semiquantification in PET imaging.

PURPOSE: The spline reconstruction technique (SRT) is a new, fast algorithm based on a novel numerical implementation of an analytic representation of the inverse Radon transform. The mathematical details of this algorithm and comparisons with filtered backprojection were presented earlier in the literature. In this study, the authors present a comparison between SRT and the ordered-subsets expectation-maximization (OSEM) algorithm for determining contrast and semiquantitative indices of (18)F-FDG uptake. METHODS: The authors implemented SRT in the software for tomographic image reconstruction (stir) open-source platform and evaluated this technique using simulated and real sinograms obtained from the GE Discovery ST positron emission tomography/computer tomography scanner. All simulations and reconstructions were performed in stir. For OSEM, the authors used the clinical protocol of their scanner, namely, 21 subsets and two iterations. The authors also examined images at one, four, six, and ten iterations. For the simulation studies, the authors analyzed an image-quality phantom with cold and hot lesions. Two different versions of the phantom were employed at two different hot-sphere lesion-to-background ratios (LBRs), namely, 2:1 and 4:1. For each noiseless sinogram, 20 Poisson realizations were created at five different noise levels. In addition to making visual comparisons of the reconstructed images, the authors determined contrast and bias as a function of the background image roughness (IR). For the real-data studies, sinograms of an image-quality phantom simulating the human torso were employed. The authors determined contrast and LBR as a function of the background IR. Finally, the authors present plots of contrast as a function of IR after smoothing each reconstructed image with Gaussian filters of six different sizes. Statistical significance was determined by employing the Wilcoxon rank-sum test. RESULTS: In both simulated and real studies, SRT exhibits higher contrast and lower bias than OSEM at the cold lesions. This improvement is achieved at the expense of increasing the noise in the reconstructed images. For the hot lesions, SRT exhibits a small improvement in contrast and LBR over OSEM with 21 subsets and two iterations; however, this improvement is not statistically significant. As the number of iterations increases, the performance of OSEM improves over SRT but again without statistical significance. The curves of contrast and LBR as a function of IR after Gaussian blurring indicate that the advantage of SRT in the cold regions is maintained even after decreasing the noise level by Gaussian blurring. CONCLUSIONS: SRT, at the expense of slightly increased noise in the reconstructed images, reconstructs images of higher contrast and lower bias than the clinical protocol of OSEM. This improvement is particularly evident for images involving cold regions. Thus, it appears that SRT should be particularly useful for the quantification of low-count and cold regions.

High-resolution imaging with (99m)Tc-glucarate for assessing myocardial injury in rat heart models exposed to different durations of ischemia with reperfusion.

UNLABELLED: (99m)Tc-Glucarate ((99m)Tc-GLA) is a novel infarct-avid imaging agent. The aim of this study was to evaluate the role of (99m)Tc-GLA for assessing the severity of myocardial ischemia-reperfusion injury in rat heart models exposed to varied durations of left coronary artery (LCA) occlusion with reperfusion using a high-resolution SPECT system, FASTSPECT. We also wanted to clarify whether a rapid sequence of 3-dimensional imaging with FASTSPECT can quantify uptake and washout kinetics of cardiovascular imaging agents in small-animal heart models. METHODS: The ischemic-reperfused rat heart models were created by ligating the LCA for 30 min (IR30, n = 12) or 90 min (IR90, n = 6) (IR = ischemia-reperfusion) and releasing the ligature for 30 min. Dynamic images were acquired over a 2-h period after (99m)Tc-GLA was intravenously injected. The ischemic area at risk (IAR) was determined by Evans blue staining. Necrosis was assessed with triphenyltetrazolium chloride (TTC) staining and a transmission electron microscope (TEM). RESULTS: The infarct size of the left ventricle (% IAR) on TTC staining was smaller in IR30 (49.2 +/- 4.3) than in IR90 (73.4 +/- 4.7, P < 0.05), which exhibited evidence of more severe irreversible injury than the IR30 heart on TEM. FASTSPECT images demonstrated hot spot accumulations of (99m)Tc-GLA in all hearts. The washout of (99m)Tc-GLA from the ischemic-reperfused area in IR90 was significantly slower than that in IR30. The ratio of the hot spot to normal myocardial activity was 4.1 +/- 0.3 in IR30 and 7.1 +/- 1.1 in IR90 (P < 0.05). The hot spot size (% IAR) (58.4 +/- 2.7 in IR30 vs. 75.9 +/- 2.7 in IR90, P < 0.05) related significantly to the infarct size. CONCLUSION: The severity of myocardial injury induced by ischemia-reperfusion can be assessed by FASTSPECT imaging with (99m)Tc-GLA. The results suggest that (99m)Tc-GLA will be clinically useful in detecting and quantifying acute necrotic myocardium. The FASTSPECT imaging with the rat heart models provides a solution-specific approach with high-resolution and fast dynamic acquisition for kinetic studies of new myocardial imaging agents.

Quantitative analysis of acute myocardial infarct in rat hearts with ischemia-reperfusion using a high-resolution stationary SPECT system.

UNLABELLED: The purpose of this study was to develop an in vivo imaging protocol for a high-resolution stationary SPECT system, called FASTSPECT, in a rat heart model of ischemia-reperfusion (IR) and to compare 99mTc-sestamibi imaging and triphenyltetrazolium chloride (TTC) staining for reliability and accuracy in the measurement of myocardial infarcts. METHODS: FASTSPECT consists of 24 modular cameras and a 24-pinhole aperture with 1.5-mm spatial resolution and 13.3 cps/microCi (0.359 cps/kBq) sensitivity. The IR heart model was created by ligating the left coronary artery for 90 min and then releasing the ligature for 30 min. Two hours after 99mTc-sestamibi injection (5-10 mCi [185-370 MBq]), images were acquired for 5-10 min for 5 control rats and 11 IR rats. The hearts were excised, and the left ventricle was sectioned into 4 slices for TTC staining. RESULTS: Left and right ventricular myocardium in control rats was shown clearly, with uniform 99mTc-sestamibi distribution and 100% TTC staining for viable myocardium. Nine of 11 rats with IR survived throughout imaging and exhibited 50.8% +/- 2.7% ischemic area and 37.9% +/- 3.9% infarct in the left ventricle on TTC staining. The infarct size measured by FASTSPECT imaging was 37.6% +/- 3.6%, which correlated significantly with that measured by TTC staining (r = 0.974; P < 0.01). CONCLUSION: The results confirmed the accuracy of FASTSPECT imaging for measurement of acute myocardial infarcts in rat hearts. Application of FASTSPECT imaging in small animals may be feasible for investigating myocardial IR injury and the effects of revascularization.

Imaging recognition of multidrug resistance in human breast tumors using 99mTc-labeled monocationic agents and a high-resolution stationary SPECT system.

Imaging recognition of multidrug-resistance by 99mTc-labeled sestamibi, tetrofosmin and furifosmin in mice bearing human breast tumors was evaluated using a high-resolution SPECT, FASTSPECT. Imaging results showed that the washout rates in drug-resistant MCF7/D40 tumors were significantly greater than that in drug-sensitive MCF7/S tumors. Furifosmin exhibited greater washout from both MCF7/S and MCF7/D40 than sestamibi, while tetrofosmin washout was greater than sestamibi in MCF7/D40 only. Feasibility of the monocationic agents for characterizing MDR expression was well clarified with FASTSPECT imaging.

Objective comparison of quantitative imaging modalities without the use of a gold standard.

Imaging is often used for the purpose of estimating the value of some parameter of interest. For example, a cardiologist may measure the ejection fraction (EF) of the heart in order to know how much blood is being pumped out of the heart on each stroke. In clinical practice, however, it is difficult to evaluate an estimation method because the gold standard is not known, e.g., a cardiologist does not know the true EF of a patient. Thus, researchers have often evaluated an estimation method by plotting its results against the results of another (more accepted) estimation method, which amounts to using one set of estimates as the pseudogold standard. In this paper, we present a maximum-likelihood approach for evaluating and comparing different estimation methods without the use of a gold standard with specific emphasis on the problem of evaluating EF estimation methods. Results of numerous simulation studies will be presented and indicate that the method can precisely and accurately estimate the parameters of a regression line without a gold standard, i.e., without the x axis.

Estimation in medical imaging without a gold standard.

RATIONALE AND OBJECTIVES: In medical imaging, physicians often estimate a parameter of interest (eg, cardiac ejection fraction) for a patient to assist in establishing a diagnosis. Many different estimation methods may exist, but rarely can one be considered a gold standard. Therefore, evaluation and comparison of different estimation methods are difficult. The purpose of this study was to examine a method of evaluating different estimation methods without use of a gold standard. MATERIALS AND METHODS: This method is equivalent to fitting regression lines without the x axis. To use this method, multiple estimates of the clinical parameter of interest for each patient of a given population were needed. The authors assumed the statistical distribution for the true values of the clinical parameter of interest was a member of a given family of parameterized distributions. Furthermore, they assumed a statistical model relating the clinical parameter to the estimates of its value. Using these assumptions and observed data, they estimated the model parameters and the parameters characterizing the distribution of the clinical parameter. RESULTS: The authors applied the method to simulated cardiac ejection fraction data with varying numbers of patients, numbers of modalities, and levels of noise. They also tested the method on both linear and nonlinear models and characterized the performance of this method compared to that of conventional regression analysis by using x-axis information. Results indicate that the method follows trends similar to that of conventional regression analysis as patients and noise vary, although conventional regression analysis outperforms the method presented because it uses the gold standard which the authors assume is unavailable. CONCLUSION: The method accurately estimates model parameters. These estimates can be used to rank the systems for a given estimation task.

99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice.

BACKGROUND AND AIM: Previous studies have showed that 99mTc labelled glucarate (GLA) might be an agent for non-invasive detection of breast tumours. In xenografted BT20 breast tumours, GLA was found to have higher uptake than 99mTc sestamibi (MIBI). It is unclear whether GLA can localize in all cell line breast cancer xenografts, as well as breast tumours with multidrug resistance (MDR). The present study aimed to investigate the properties of GLA in detecting drug sensitive and drug resistant MCF7 breast cancer xenografts in mice by using dynamic single photon emission computed tomography (SPECT) imaging. METHODS: MCF7/S cells are drug sensitive breast carcinoma cells. MCF7/D40 cells are 40-fold more resistant to doxorubicin compared to MCF7/S. Subcutaneous tumours were grown in SCID mice for 10-14 days after injection of 1 x 10(6) cells into the right thigh. Anaesthetized mice with MCF7/S (MIBI, n=9; GLA, n=8) and MCF7/D40 (MIBI, n=6; GLA, n=5) tumours were imaged using a high-resolution SPECT system called FASTSPECT. Dynamic images were acquired for 2 h after intravenous injection of GLA or MIBI. Expression of MDR P-glycoprotein (Pgp) in the tumours was demonstrated in the MCF7/D40 tumours by western blotting, not in the MCF7/S tumours. RESULTS: The xenografted tumours were visualized unequivocally within 10-30 min in GLA images and remained detectable for at least 2 h after injection. Drug resistant tumours, from which MIBI was rapidly expelled, retained GLA as readily as did drug sensitive tumours. The biodistribution data of GLA demonstrated significantly higher accumulation (%ID/g) compared to MIBI. CONCLUSION: MCF7 tumour xenografts can be detected by 99mTc glucarate imaging. More importantly, 99mTc glucarate can potentially localize drug resistant breast tumours.