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In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal. Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy. [ABSTRACT FROM AUTHOR]

The importance of integrating research findings is incontrovertible and procedures for coordinate-based meta-analysis (CBMA) such as Activation Likelihood Estimation (ALE) have become a popular approach to combine results of fMRI studies when only peaks of activation are reported. As meta-analytical findings help building cumulative knowledge and guide future research, not only the quality of such analyses but also the way conclusions are drawn is extremely important. Like classical meta-analyses, coordinate-based meta-analyses can be subject to different forms of publication bias which may impact results and invalidate findings. The file drawer problem refers to the problem where studies fail to get published because they do not obtain anticipated results (e.g. due to lack of statistical significance). To enable assessing the stability of meta-analytical results and determine their robustness against the potential presence of the file drawer problem, we present an algorithm to determine the number of noise studies that can be added to an existing ALE fMRI meta-analysis before spatial convergence of reported activation peaks over studies in specific regions is no longer statistically significant. While methods to gain insight into the validity and limitations of results exist for other coordinate-based meta-analysis toolboxes, such as Galbraith plots for Multilevel Kernel Density Analysis (MKDA) and funnel plots and egger tests for seed-based d mapping, this procedure is the first to assess robustness against potential publication bias for the ALE algorithm. The method assists in interpreting meta-analytical results with the appropriate caution by looking how stable results remain in the presence of unreported information that may differ systematically from the information that is included. At the same time, the procedure provides further insight into the number of studies that drive the meta-analytical results. We illustrate the procedure through an example and test the effect of several parameters through extensive simulations. Code to generate noise studies is made freely available which enables users to easily use the algorithm when interpreting their results. [ABSTRACT FROM AUTHOR]

Background: Visceral adiposity is a risk factor for many chronic diseases. Existing methods to quantify visceral adipose tissue volume using computed tomographic (CT) images often use a single slice, are manual, and are time consuming, making them impractical for large population studies. We developed and validated a method to accurately, rapidly, and robustly measure visceral adipose tissue volume using CT images. Methods: In-house software, Medical Executable for the Efficient and Robust Quantification of Adipose Tissue (MEERQAT), was developed to calculate visceral adipose tissue volume using a series of CT images within a manually identified region of interest. To distinguish visceral and subcutaneous adipose tissue, ellipses are drawn through the rectus abdominis and transverse abdominis using manual and automatic processes. Visceral and subcutaneous adipose tissue volumes are calculated by counting the numbers of voxels corresponding to adipose tissue in the region of interest. MEERQAT’s ellipse interpolation method was validated by comparing visceral adipose volume from 10 patients’ CT scans with corresponding results from manually delineated scans. Accuracy of visceral adipose quantification was tested using a phantom consisting of animal fat and tissues. Robustness of the method was tested by determining intra-observer and inter-observer coefficients of variation (CV). Results: The mean difference in visceral adipose tissue volume between manual and elliptical delineation methods was -0.54 ± 4.81%. In the phantom, our measurement differed from the known adipose volume by ≤ 7.5% for all scanning parameters. Mean inter-observer CV for visceral adipose tissue volume was 0.085, and mean intra-observer CV for visceral adipose tissue volume was 0.059. Conclusions: We have developed and validated a robust method of accurately and quickly determining visceral adipose tissue volume in any defined region of interest using CT imaging. [ABSTRACT FROM AUTHOR]

Purpose: To identify the impact of reconstruction algorithms on CT radiomic features of pulmonary tumors and to reveal and compare the intra- and inter-reader and inter-reconstruction algorithm variability of each feature. Methods: Forty-two patients (M:F = 19:23; mean age, 60.43±10.56 years) with 42 pulmonary tumors (22.56±8.51mm) underwent contrast-enhanced CT scans, which were reconstructed with filtered back projection and commercial iterative reconstruction algorithm (level 3 and 5). Two readers independently segmented the whole tumor volume. Fifteen radiomic features were extracted and compared among reconstruction algorithms. Intra- and inter-reader variability and inter-reconstruction algorithm variability were calculated using coefficients of variation (CVs) and then compared. Results: Among the 15 features, 5 first-order tumor intensity features and 4 gray level co-occurrence matrix (GLCM)-based features showed significant differences (p<0.05) among reconstruction algorithms. As for the variability, effective diameter, sphericity, entropy, and GLCM entropy were the most robust features (CV≤5%). Inter-reader variability was larger than intra-reader or inter-reconstruction algorithm variability in 9 features. However, for entropy, homogeneity, and 4 GLCM-based features, inter-reconstruction algorithm variability was significantly greater than inter-reader variability (p<0.013). Conclusions: Most of the radiomic features were significantly affected by the reconstruction algorithms. Inter-reconstruction algorithm variability was greater than inter-reader variability for entropy, homogeneity, and GLCM-based features. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. Methods: The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. Results: The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Conclusion: Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials. [ABSTRACT FROM AUTHOR]

Graph analysis is a promising tool to quantify brain connectivity. However, an essential requirement is that the graph measures are reproducible and robust. We have studied the reproducibility and robustness of various graph measures in group based and in individual binary and weighted networks derived from a task fMRI experiment during explicit associative-semantic processing of words and pictures. The nodes of the network were defined using an independent study and the connectivity was based on the partial correlation of the time series between any pair of nodes. The results showed that in case of binary networks, global graph measures exhibit a good reproducibility and robustness for networks which are not too sparse and these figures of merit depend on the graph measure and on the density of the network. Furthermore, group based binary networks should be derived from groups of sufficient size and the lower the density the more subjects are required to obtain robust values. Local graph measures are very variable in terms of reproducibility and should be interpreted with care. For weighted networks, we found good reproducibility (average test-retest variability <5% and ICC values >0.4) when using subject specific networks and this will allow us to relate network properties to individual subject information. [ABSTRACT FROM AUTHOR]

We propose an automatic algorithm for the reconstruction of patient-specific cardiac mesh models with 1-to-1 vertex correspondence. In this framework, a series of 3D meshes depicting the endocardial surface of the heart at each time step is constructed, based on a set of border delineated magnetic resonance imaging (MRI) data of the whole cardiac cycle. The key contribution in this work involves a novel reconstruction technique to generate a 4D (i.e., spatial–temporal) model of the heart with 1-to-1 vertex mapping throughout the time frames. The reconstructed 3D model from the first time step is used as a base template model and then deformed to fit the segmented contours from the subsequent time steps. A method to determine a tree-based connectivity relationship is proposed to ensure robust mapping during mesh deformation. The novel feature is the ability to handle intra- and inter-frame 2D topology changes of the contours, which manifests as a series of merging and splitting of contours when the images are viewed either in a spatial or temporal sequence. Our algorithm has been tested on five acquisitions of cardiac MRI and can successfully reconstruct the full 4D heart model in around 30 minutes per subject. The generated 4D heart model conforms very well with the input segmented contours and the mesh element shape is of reasonably good quality. The work is important in the support of downstream computational simulation activities. [ABSTRACT FROM AUTHOR]

High quality segmentation of diffusion tensor images (DTI) is of key interest in biomedical research and clinical application. In previous studies, most efforts have been made to construct predefined metrics for different DTI segmentation tasks. These methods require adequate prior knowledge and tuning parameters. To overcome these disadvantages, we proposed to automatically learn an adaptive distance metric by a graph based semi-supervised learning model for DTI segmentation. An original discriminative distance vector was first formulated by combining both geometry and orientation distances derived from diffusion tensors. The kernel metric over the original distance and labels of all voxels were then simultaneously optimized in a graph based semi-supervised learning approach. Finally, the optimization task was efficiently solved with an iterative gradient descent method to achieve the optimal solution. With our approach, an adaptive distance metric could be available for each specific segmentation task. Experiments on synthetic and real brain DTI datasets were performed to demonstrate the effectiveness and robustness of the proposed distance metric learning approach. The performance of our approach was compared with three classical metrics in the graph based semi-supervised learning framework. [ABSTRACT FROM AUTHOR]