Alessandro Bevilacqua

A 0.18-μm CMOS Squarer Circuit for a Non-Coherent UWB Receiver

Squaring circuits are an important building block for impulse-radio UWB non-coherent receivers. This work proposes a squarer, based on the quadratic law of saturated transistors. Such a circuit has already been proposed for lower frequency applications, therefore this work focuses on the extension to ultra wide bandwidth, with particular care to the consequences related to the deviation from the ideal quadratic law of 0.18μm CMOS transistors. Simulation results prove that the proposed squarer can accommodate the whole UWB bandwidth, with a total power consumption of 1.7mW.

A novel approach for semi-quantitative assessment of reliability of blood flow values in DCE-CT perfusion

Abstract In the last few years, cancer treatments have improved significantly with the introduction of new therapies aiming at reducing tumour angiogenesis, a process leading to disease progression and metastasis formation. Computed tomography perfusion (CTp) is being emerged as a promising functional technique for assessing tumour response to these new treatments, which yield a reduction of perfusion heterogeneity, occurring long before morphological reduction. However, several factors, such as noise induced by respiratory and physiological involuntary motion, prevent a reliable quantitative assessment, hence the clinical use of CTp. Currently, the assessment strategies rely on global measurements that fail in discriminating between noise and heterogeneity of tumour perfusion, both characterized by a wide value dispersion. This paper presents a new approach for reliability estimation by introducing a novel local-based index, which is able to discriminate between tumour heterogeneity, featured by locally structured patterns, and noise, characterised by sparse and unstructured values. This index enables a proper comparison between perfusion maps and can replace the parameters based on the global mean, thus improving the overall reliability of CTp studies and favouring the translation into clinical routine.

Cell Counting and Viability Assessment of 2D and 3D Cell Cultures: Expected Reliability of the Trypan Blue Assay

BackgroundWhatever the target of an experiment in cell biology, cell counting and viability assessment are always computed. The Trypan Blue (TB) assay was proposed about a century ago and is still the most widely used method to perform cell viability analysis. Furthermore, the combined use of TB with a haemocytometer is also considered the standard approach to estimate cell population density. There are numerous research articles reporting the use of TB assays to compute cell number and viability of 2D and 3D cultures. However, the literature still lacks studies regarding the reliability of the TB assay in terms of assessment of its repeatability and reproducibility.MethodsWe compared the TB assays measurements obtained by two biologists who analysed 105 different samples in double-blind for a total of 210 counts performed. We measured: (a) the repeatability of the count performed by the same operator; (b) the reproducibility of counts performed by the two operators.ResultsThere were no significant differences in the results obtained with 2D and 3D cell cultures: we estimated an approximate variability of 5% when the TB assay was used to assess the viability of the culture, and a variability of around 20% when it was used to determine the cell population density.ConclusionsThe main aim of this study was to make researchers aware of potential measurement errors when TB is used with a haemocytometer for counting and viability measurements in 2D and 3D cultures. We believe that these results can help researchers to determine whether the expected reliability of the TB assay is compliant with their applications.

Multislice Analysis of Blood Flow Values in CT Perfusion Studies of Lung Cancer

Objectives. Tumour heterogeneity represents a key issue in CT perfusion (CTp), where all studies are usually based on global mean or median values of perfusion maps, often computed on whole tumour. We sought to determine whether, and to what extent, such global values can be representative of tumour heterogeneity, with respect to single slices, and could be used for therapy assessment. Materials and Methods. Twelve patients with one primary non-small cell lung cancer lesion were enrolled in this study, for a total amount of 26 CTp examinations and 118 slices. Mean and median blood flow (BF) values, calculated voxel-based, were computed on each slice and the whole tumour. To measure functional heterogeneity, entropy was calculated on BF values as well. Results. Most of the slices were not represented by the global BF values computed on the whole tumour. In addition, there are a number of lesions having equivalent global BF values, but they are composed of slices having very different heterogeneity distributions, that is, entropy values. Conclusions. Global mean/median BF values of the single slices separately should be considered for clinical assessment, only if interpreted through entropy computed on BF values. The numerical equivalence between global BF values of different lesions may correspond to different clinical status, thus inducing possible errors in choice of therapy when considering global values only.

Automatic computation of liver and lung perfusion parameters through the analysis of CT image sequences

Computed Tomography perfusion (CTp) is a promising technique for early assessment of the effectiveness of the new anti-angiogenic therapies for cancer treatment. Nonetheless, some difficulties to achieve standardized results in the examinations have slowed down its application in the daily clinical practice. This Thesis addresses three important open issues: a lack of methods to measure results reliability, the clinical relevance of the global perfusion parameter values commonly utilised, a critical revision of protocols of the multi-centre studies. In this work, lung and liver CTp examinations were considered, being among the most studied sites in oncology. nFirst, I set up and validated an error index capable to measure the quality of perfusion results. After that, structured regions affected by noise (e.g., artefacts), vessels or bronchi have been looked for on whole slices. Also exploiting a new error index, an adaptive algorithm has allowed detecting and excluding all those regions automatically. nThe common practice in CTp perfusion studies is providing one averaged value only for each perfusion parameter, computed on the whole tumour, to reduce data variability, but at the expense of tumour heterogeneity. Accordingly, whole lung lesions were considered to inquire into the clinical representativeness of global perfusion values. After proposing a statistical index to quantify tumour functional heterogeneity, it has been proved that using one global value even misleads clinical considerations. nThe last part of the Thesis regards the activities carried out in the widest European multi-centre study on liver CT. Some algorithms to improve the accuracy of perfusion results were developed to favour comparisons of multi-centre CTp examinations. Some meaningful results regarding baseline and blood flow values of liver are discussed, highlighting whether different CT scanners affect CTp outcomes. Finally, tentative guidelines are provided to help considering all the concealable sources of heterogeneity in advance, before planning the protocols.

CT Perfusion in Patients with Lung Cancer: Squamous Cell Carcinoma and Adenocarcinoma Show a Different Blood Flow

Objectives To characterize tumour baseline blood flow (BF) in two lung cancer subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC), also investigating those “borderline” cases whose perfusion value is closer to the group mean of the other histotype. Materials and Methods 26 patients (age range 36-81 years) with primary Non-Small Cell Lung Cancer (NSCLC), subdivided into 19 AC and 7 SCC, were enrolled in this study and underwent a CT perfusion, at diagnosis. BF values were computed according to the maximum-slope method and unreliable values (e.g., arising from artefacts or vessels) were automatically removed. The one-tail Welchs t-test (p-value <0.05) was employed for statistical assessment. Results At diagnosis, mean BF values (in [mL/min/100g]) of AC group [(83.5 ± 29.4)] are significantly greater than those of SCC subtype [(57.0 ± 27.2)] (p-value = 0.02). However, two central SCCs undergoing artefacts from vena cava and pulmonary artery have an artificially increased mean BF. Conclusions The different hemodynamic behaviour of AC and SCC should be considered as a biomarker supporting treatment planning to select the patients, mainly with AC, that would most benefit from antiangiogenic therapies. The significance of results was achieved by automatically detecting and excluding artefactual BF values.

Colour Vignetting Correction for Microscopy Image Mosaics Used for Quantitative Analyses

Image mosaicing permits achieving one high-resolution image, extending the visible area of the sample while keeping the same resolution. However, intensity inhomogeneity of the stitched images can alter measurements and the right perception of the original sample. The problem can be solved by flat-field correcting the images through the vignetting function. Vignetting correction has been widely addressed for grey-level images, but not for colour ones. In this work, a practical solution for the colour vignetting correction in microscopy, also facing the problem of saturated pixels, is described. In order to assess the quality of the proposed approach, five different tonal correction approaches were quantitatively compared using state-of-the-art metrics and seven pairs of partially overlapping images of seven different samples. The results obtained proved that the proposed approach allows obtaining high quality colour flat-field corrected images and seamless mosaics without employing any blending adjustment. In order to give the opportunity to easily obtain seamless mosaics ready for quantitative analysis, the described vignetting correction method has been implemented in an upgraded release of MicroMos (version 3.0), an open-source software specifically designed to automatically obtain mosaics of partially overlapped images.

Baseline values of DCE-CT of liver in patients with colorectal cancer

Poster: ECR 2017 / B-0195 / Baseline values of DCE-CT of liver in patients with colorectal cancer by: A. Bevilacqua1, S. Malavasi1, M. Ronot2, J.-L. Daire2, B. Van Beers2, V. Vilgrain2; 1Bologna/IT, 2Clichy/FR