A Multi-Variate framework to assess reliability and discrimination power of Bayesian estimation of Intravoxel Incoherent Motion parameters.

PURPOSE: To propose a multivariate multi-step framework for a systematic assessment of the estimation reliability and discriminability of Intravoxel Incoherent Motion (IVIM) model parameters. METHODS: Monte-Carlo simulations were generated on a range of SNRs and in different IVIM combinations considering: i) a dense discretization with 24 b-values; ii) a discretization with 9 b-values. A state-of-the-art Bayesian fitting method was adopted. The framework assessed: i) the best model between mono- and bi-exponential, through the BIC index; ii) the fitting accuracy; iii) the power in discriminating two different IVIM parameters distributions of estimated coefficients, using a multivariate test. Exemplificative oncologic cases were also presented. RESULTS: The bi-exponential fitting was reliable for perfusion fraction higher than 5%, with high accuracy in D estimation, acceptable error for f, but high uncertainty in D*. The discrimination of two distributions is generally feasible if differences in D values (at least 0.3 x10-3 mm2/s) are present; in the case of similar D values, a minimal difference of 5% in f can be discriminated just in case of balanced sample size and dense b-values discretization, whereas the impact of D* is quite negligible. These results were also supported by clinical examples. CONCLUSIONS: IVIM model is generally accurate in estimating diffusion, but uncertainties related to perfusion estimation are not negligible and compromise the discrimination power when different populations should be differentiated. The proposed framework should be adopted as interpretative guidelines to better understand when IVIM model applied on real data can provide reliable findings.

High quality surface reconstruction in radiotherapy: Cross-sectional contours to 3D mesh using wavelets.

A novel approach for three-dimensional (3D) surface reconstruction of anatomical structures in radiotherapy (RT) is presented. This is obtained from manual cross-sectional contours by combining both image voxel segmentation processing and implicit surface streaming methods using wavelets. 3D meshes reconstructed with the proposed approach are compared to those obtained from traditional triangulation algorithm. Qualitative and quantitative evaluations are performed in terms of mesh quality metrics. Differences in smoothness, detail and accuracy are observed in the comparison, considering three different anatomical districts and several organs at risk in radiotherapy. Overall best performances were recorded for the proposed approach, regardless the complexity of the anatomical structure. This demonstrates the efficacy of the proposed approach for the 3D surface reconstruction in radiotherapy and allows for further specific image analyses using real biomedical data.

Texture analysis to assess structural modifications induced by radiotherapy.

Texture analysis is an emerging tool employed in Radiotherapy (RT) to improve tumor characterization for planning and to evaluate treatment effects. In the treatment of Head and Neck Cancer, parotid glands can receive high dose that may compromise gland functionality and structure. Texture analysis was here applied on CT images of Head and Neck to evaluate changes in parotid gland structure during RT. CT images at the beginning, at the intermediate stage and at the end of RT were considered and in each time point different features (i.e. mean intensity, variance, entropy, homogeneity, local entropy, fractal dimension and volume) were extracted within parotid volume. A general decrease in tissue complexity and heterogeneity was found, with different time trend for textural features. This is explainable by different biological mechanisms associated to the variation of each index. Volume and mean intensity variation are also correlated with some pre-treatment dosimetric parameters, indicating a relationship between the dose plan and the structural variation estimated after RT.

The Shape of Parotid DVH Predicts the Entity of Gland Deformation During IMRT for Head and Neck Cancers.

The Jacobian of the deformation field of the registration between images taken during Radiotherapy is a measure of compression/expansion of the voxels within an organ. The Jacobian mean value was applied to investigate possible correlations between parotid deformation and anatomical, clinical and dosimetric parameters. Data of 84 patients were analyzed. Parotid deformation was evaluated through Jacobian maps of images taken at the start and at the end of the treatment. Several clinical, geometrical and dosimetric factors were considered. Correlation between Jacobian mean value and these parameters was assessed through Spearman's test. Univariate and multivariate logistic analyses were performed by considering as the end point the first quartile value of the Jacobian mean value. Parotid dose volume histograms were stratified according to gland deformation, assessing the most predictive dose-volume combination. At multivariate analysis, age (p = 0.02), overlap between tumor volume and parotid gland (p = 0.0006) and the parotid volume receiving more than 10 Gy (p = 0.02) were found as the best independent predictors, by considering Jacobian mean value fist quartile, the parotid volume receiving more than 10 Gy and 40 Gy were found as the most predictive dosimetric parameters. Parotid glands were divided in three different sub-groups (bad-, medium- and good dose volume histogram). The risk to have Jacobian means value lower than first quartile was 39.6% versus 19.6% versus 11.3% in these three groups. By including in the multivariate analysis this "dose volume grouping" parameter, age and bad dose volume histogram were found as the most predictive parameters for large shrinkage. The pattern of parotid deformation may be well predicted by some pre-treatment variables; a bad dose volume histogram seems the most important predictor.

Comparative high-resolution pQCT analysis of femoral neck indicates different bone mass distribution in osteoporosis and osteoarthritis.

SUMMARY: Osteoarthritis is linked to a reduced risk of femoral fracture despite osteoporosis. Different bone distribution in the femoral neck in osteoarthritis and fracture was revealed using a peripheral quantitative computed tomography (pQCT) comparative analysis. Our findings sustain the presence of an adaptive mechanism of bone structure providing fracture protection in osteoarthritis. INTRODUCTION: Although osteoarthritis is associated with reduced femoral fracture risk, it does not protect from bone loss. We investigated whether adaptive mechanisms are present at the arthritic joint, leading to reduced fracture risk, despite the presence of low bone mass density. METHODS: We performed pQCT comparative analyses of human femoral neck specimens derived from 32 postmenopausal women who received hip prostheses for osteoarthritis (n = 19) or femoral fracture (n = 13) by applying an in-house automated software to extract bone structure descriptors, characterize trabecular and cortical bone distribution, and evaluate their mutual relationships. RESULTS: The cortical bone volume and trabecular thickness were significantly (p < 0.05) higher in the osteoarthritis group than in the fracture group. Trabecular bone volume was also significantly (p < 0.05) higher in the osteoarthritis group than the fracture group at the inferior and anterior quadrants. Significance was maintained after adjusting for age, cortical bone volume, and cortical porosity thickness. Multiple linear regression analysis showed that thickness, volume, and apparent density of the trabecular region significantly (p < 0.05) correlated with the same cortical descriptors in osteoarthritis, but no significant relationship was found in the fracture group. Age differentially affected the mutual relationships in the two groups, showing a significant correlation with trabecular thickness in both groups and with apparent trabecular density only in femoral fracture group. CONCLUSIONS: Starting from these differences in the structural descriptors, our study sustains the presence of a compensatory mechanism in osteoarthritis to preserve the mechanical competence of bone structure, despite the loss of trabecular bone, underlying lower fracture risk.

An automatic contour propagation method to follow parotid gland deformation during head-and-neck cancer tomotherapy.

We developed an efficient technique to auto-propagate parotid gland contours from planning kVCT to daily MVCT images of head-and-neck cancer patients treated with helical tomotherapy. The method deformed a 3D surface mesh constructed from manual kVCT contours by B-spline free-form deformation to generate optimal and smooth contours. Deformation was calculated by elastic image registration between kVCT and MVCT images. Data from ten head-and-neck cancer patients were considered and manual contours by three observers were included in both kVCT and MVCT images. A preliminary inter-observer variability analysis demonstrated the importance of contour propagation in tomotherapy application: a high variability was reported in MVCT parotid volume estimation (p = 0.0176, ANOVA test) and a larger uncertainty of MVCT contouring compared with kVCT was demonstrated by DICE and volume variability indices (Wilcoxon signed rank test, p < 10(-4) for both indices). The performance analysis of our method showed no significant differences between automatic and manual contours in terms of volumes (p > 0.05, in a multiple comparison Tukey test), center-of-mass distances (p = 0.3043, ANOVA test), DICE values (p = 0.1672, Wilcoxon signed rank test) and average and maximum symmetric distances (p = 0.2043, p = 0.8228 Wilcoxon signed rank tests). Results suggested that our contour propagation method could successfully substitute human contouring on MVCT images.

An automatic segmentation method for regional analysis of femoral neck images acquired by pQCT.

We developed an automatic method for regional analysis of femoral neck images acquired by peripheral quantitative computed tomography (pQCT), based on automatic spatial re-alignment and segmentation; the segmentation method, based on a morphological approach, explicitly accounts for the presence of three different bone compartments: cortical region, trabecular region, and transition zone between cortical and trabecular compartments. The proposed method was applied on 13 femoral neck sections derived from female donors who were undergoing hip replacement surgery for primary degenerative arthritis or fracture, and a typical densitometric and structural analysis was performed both globally and regionally. The proposed segmentation method was quantitatively evaluated by comparing automatic contour and the corresponding manual contours delineated by three operators using metrics based on surface distance (average symmetric distance, ASD) and volumetric overlapping (dice similarity coefficient, DSC). The same approach was used to validate the automatic spatial orientation, considering as metric the difference between manual and automatic angle orientation. Results confirm a satisfactory agreement between automatic and manual performances (ASD < 0.41 mm, DSC > 0.91, orientation difference = 3.61°) and show that globally our algorithm performs very well. Concerning regional analysis application, from our results we can observe that significant differences are present among the four bone quadrants.

Elastic registration based on particle filter in radiotherapy images with brain deformations.

This paper presents the evaluation of the accuracy of an elastic registration algorithm, based on the particle filter and an optical flow process. The algorithm is applied in brain CT and MRI simulated image datasets, and MRI images from a real clinical radiotherapy case. To validate registration accuracy, standard indices for registration accuracy assessment were calculated: the dice similarity coefficient (DICE), the average symmetric distance (ASD) and the maximal distance between pixels (Dmax). The results showed that this registration process has good accuracy, both qualitatively and quantitatively, suggesting that this method may be considered as a good new option for radiotherapy applications like patient's follow up treatment.

Automatic segmentation of cortical and trabecular components of bone specimens acquired by pQCT.

Peripheral Quantitative Computerized Tomography (pQCT) allows the acquisition of bone specimens with a spatial resolution adequate to visualize the 3D structure of the bone cortex and the trabecular network. At present, pQCT scanners are equipped with image processing software that limits the bone analysis in two dimensions and requires strong user interaction. In this work, a method is proposed to automatically segment, in 3D, cortical and trabecular components of bone specimens acquired by pQCT, in order to facilitate and enhance the quantitative evaluation of densitometric properties of the bone.

High intensity physical exercise induced effects on plasma levels of copper and zinc.

Physical exercise leads to many metabolic, cardiovascular, and muscular changes in the body. The trace elements (TE) zinc and copper are directly involved, as enzymatic cofactors, in many of these processes, especially those related to nutrients metabolism, oxygen transport, and formation of usable energy. The effects of high-intensity physical exercise on plasma levels of CU2+ and Zn2+ in 19 subjects are investigated (9 males and 10 females). Plasma copper concentration decreases, and plasma zinc concentration increases, after exercise, in both sexes. After 30 min recovery, both TE concentration values shifts toward rest values in both sexes. These results only partially agree with literature data, probably because we used the treadmill exercise, which makes many muscles work, whereas other authors made their subjects perform a cycloergometer exercise. Physical exercise causes a marked redistribution of TE (copper and zinc) between body stores, bloodstream, and tissues. The condition of high metabolism may lead to a deficiency of TE, requiring supplementation in order to maintain high level performance.