New methodologies in CT perfusion and MRI analysis to develop cancer imaging biomarkers

Quantitative imaging in oncology aims at developing imaging biomarkers for diagnosis and prediction of cancer aggressiveness and therapy response before any morphological change become visible. This Thesis exploits Computed Tomography perfusion (CTp) and multiparametric Magnetic Resonance Imaging (mpMRI) for investigating diverse cancer features on different organs. I developed a voxel-based image analysis methodology in CTp and extended its use to mpMRI, for performing precise and accurate analyses at single-voxel level. This is expected to improve reproducibility of measurements and cancer mechanisms’ comprehension and clinical interpretability. CTp has not entered the clinical routine yet, although its usefulness in the monitoring of cancer angiogenesis, due to different perfusion computing methods yielding unreproducible results. Instead, machine learning applications in mpMRI, useful to detect imaging features representative of cancer heterogeneity, are mostly limited to clinical research, because of results’ variability and difficult interpretability, which make clinicians not confident in clinical applications. In hepatic CTp, I investigated whether, and under what conditions, two widely adopted perfusion methods, Maximum Slope (MS) and Deconvolution (DV), could yield reproducible parameters. To this end, I developed signal processing methods to model the first pass kinetics and remove any numerical cause hampering the reproducibility. In mpMRI, I proposed a new approach to extract local first-order features, aiming at preserving spatial reference and making their interpretation easier. In CTp, I found out the cause of MS and DV non-reproducibility: MS and DV represent two different states of the system. Transport delays invalidate MS assumptions and, by correcting MS formulation, I have obtained the voxel-based equivalence of the two methods. In mpMRI, the developed predictive models allowed (i) detecting rectal cancers responding to neoadjuvant chemoradiation showing, at pre-therapy, sparse coarse subregions with altered density, and (ii) predicting clinically significant prostate cancers stemming from the disproportion between high- and low- diffusivity gland components.

Hyperspectral imaging and other optical techniques for (in-field/in-lab) physico-chemical attributes estimation of agri-food vegetal products

In the agri-food sector, measurement and monitoring activities contribute to high quality end products. In particular, considering food of plant origin, several product quality attributes can be monitored. Among the non-destructive measurement techniques, a large variety of optical techniques are available, including hyperspectral imaging (HSI) in the visible/near-infrared (Vis/NIR) range, which, due to the capacity to integrate image analysis and spectroscopy, proved particularly useful in agronomy and food science. Many published studies regarding HSI systems were carried out under controlled laboratory conditions. In contrast, few studies describe the application of HSI technology directly in the field, in particular for high-resolution proximal measurements carried out on the ground. Based on this background, the activities of the present PhD project were aimed at exploring and deepening knowledge in the application of optical techniques for the estimation of quality attributes of agri-food plant products. First, research activities on laboratory trials carried out on apricots and kiwis for the estimation of soluble solids content (SSC) and flesh firmness (FF) through HSI were reported; subsequently, FF was estimated on kiwis using a NIR-sensitive device; finally, the procyanidin content of red wine was estimated through a device based on the pulsed spectral sensitive photometry technique. In the second part, trials were carried out directly in the field to assess the degree of ripeness of red wine grapes by estimating SSC through HSI, and finally a method for the automatic selection of regions of interest in hyperspectral images of the vineyard was developed. The activities described above have revealed the potential of the optical techniques for sorting-line application; moreover, the application of the HSI technique directly in the field has proved particularly interesting, suggesting further investigations to solve a variety of problems arising from the many environmental variables that may affect the results of the analyses.

Collection and real-time analysis of images from aircraft to support civil protection operational activities

This report describes the realization of a system, in which an object detection model will be implemented, whose aim is to detect the presence of people in images. This system could be used for several applications: for example, it could be carried on board an aircraft or a drone. In this case, the system is designed in such a way that it can be mounted on light/medium weight helicopters, helping the operator to find people in emergency situations. In the first chapter the use of helicopters for civil protection is analysed and applications similar to this case study are listed. The second chapter describes the choice of the hardware devices that have been used to implement a prototype of a system to collect, analyse and display images. At first, the PC necessary to process the images was chosen, based on the characteristics of the algorithms that are necessary to run the analysis. In the further, a camera that could be compatible with the PC was selected. Finally, the battery pack was chosen taking into account the electrical consumption of the devices. The third chapter illustrates the algorithms used for image analysis. In the fourth, some of the requirements listed in the regulations that must be taken into account for carrying on board all the devices have been briefly analysed. In the fifth chapter the activity of design and modelling, with the CAD Solidworks, the devices and a prototype of a case that will house them is described. The sixth chapter discusses the additive manufacturing, since the case was printed exploiting this technology. In the seventh chapter, part of the tests that must be carried out on the equipment to certificate it have been analysed, and some simulations have been carried out. In the eighth chapter the results obtained once loaded the object detection model on a hardware for image analyses were showed. In the ninth chapter, conclusions and future applications were discussed.

Synthetic generation of amyloid PET images by non-linear dimensionality reduction inversion

Privacy issues and data scarcity in PET field call for efficient methods to expand datasets via synthetic generation of new data that cannot be traced back to real patients and that are also realistic. In this thesis, machine learning techniques were applied to 1001 amyloid-beta PET images, which had undergone a diagnosis of Alzheimer’s disease: the evaluations were 540 positive, 457 negative and 4 unknown. Isomap algorithm was used as a manifold learning method to reduce the dimensions of the PET dataset; a numerical scale-free interpolation method was applied to invert the dimensionality reduction map. The interpolant was tested on the PET images via LOOCV, where the removed images were compared with the reconstructed ones with the mean SSIM index (MSSIM = 0.76 ± 0.06). The effectiveness of this measure is questioned, since it indicated slightly higher performance for a method of comparison using PCA (MSSIM = 0.79 ± 0.06), which gave clearly poor quality reconstructed images with respect to those recovered by the numerical inverse mapping. Ten synthetic PET images were generated and, after having been mixed with ten originals, were sent to a team of clinicians for the visual assessment of their realism; no significant agreements were found either between clinicians and the true image labels or among the clinicians, meaning that original and synthetic images were indistinguishable. The future perspective of this thesis points to the improvement of the amyloid-beta PET research field by increasing available data, overcoming the constraints of data acquisition and privacy issues. Potential improvements can be achieved via refinements of the manifold learning and the inverse mapping stages during the PET image analysis, by exploring different combinations in the choice of algorithm parameters and by applying other non-linear dimensionality reduction algorithms. A final prospect of this work is the search for new methods to assess image reconstruction quality.

Ecological status of mesophotic biogenic reefs off Chioggia

This study investigated the coralligenous reefs' benthic assemblages at 6 sites off Chioggia, in the northern Adriatic Sea, comparing 2 different methods of analysis of photographic samples: the grid method (overlapping a grid of 400 cells) and the random point method (random distribution of 100 points on the photo). For the first method, taxonomic recognition and the percentage coverage estimations were performed manually using photoQuad software. In the second, CoralNet semi-automated web-based annotation system was applied. This allows for assisted and supervised identification, the success rate of which gradually improves after initial software training. The results obtained with the two methods of analysing photographic samples are slightly different. The random points method gives lower species richness values and some differences in coverage estimations; all of this is reflected in the calculation of the biotic index. NAMBER values are significantly lower with the random points method and provide locally different classifications (3 out of 6 sites). However, the results obtained with the two methods are closely related to each other and depict a similar spatial trend. These results rise caution in applying different, albeit similar, methods in the analysis of benthic assemblages aimed to environmental quality assessment.

Changes In Chromatin Structure In Nih 3t3 Cells Induced By Valproic Acid And Trichostatin A.

Valproic acid (VPA) and trichostatin A (TSA) are known histone deacetylase inhibitors (HDACIs) with epigenetic activity that affect chromatin supra-organization, nuclear architecture, and cellular proliferation, particularly in tumor cells. In this study, chromatin remodeling with effects extending to heterochromatic areas was investigated by image analysis in non-transformed NIH 3T3 cells treated for different periods with different doses of VPA and TSA under conditions that indicated no loss of cell viability. Image analysis revealed chromatin decondensation that affected not only euchromatin but also heterochromatin, concomitant with a decreased activity of histone deacetylases and a general increase in histone H3 acetylation. Heterochromatin protein 1-α (HP1-α), identified immunocytochemically, was depleted from the pericentromeric heterochromatin following exposure to both HDACIs. Drastic changes affecting cell proliferation and micronucleation but not alteration in CCND2 expression and in ratios of Bcl-2/Bax expression and cell death occurred following a 48-h exposure of the NIH 3T3 cells particularly in response to higher doses of VPA. Our results demonstrated that even low doses of VPA (0.05 mM) and TSA (10 ng/ml) treatments for 1 h can affect chromatin structure, including that of the heterochromatin areas, in non-transformed cells. HP1-α depletion, probably related to histone demethylation at H3K9me3, in addition to the effect of VPA and TSA on histone H3 acetylation, is induced on NIH 3T3 cells. Despite these facts, alterations in cell proliferation and micronucleation, possibly depending on mitotic spindle defects, require a longer exposure to higher doses of VPA and TSA.

Desenhos de estruturas químicas correlacionam-se com propriedades biológicas: MIA-QSAR

Descriptors in multivariate image analysis applied to quantitative structure-activity relationship (MIA-QSAR) are pixels of bidimensional images of chemical structures (drawings), which were used to model the trichomonicidal activities of a series of benzimidazole derivatives. The MIA-QSAR model showed good predictive ability, with r², q² and r val. ext.² of 0.853, 0.519 and 0.778, respectively, which are comparable to the best values obtained by CoMFA e CoMSIA for the same series. A MIA-based analysis was also performed by using images of alphabetic letters with the corresponding numeric ordering as dependent variables, but no correlation was found, supporting that MIA-QSAR is not arbitrary.

O jogo de futebol : investigação de sua estrutura, de seus modelos e da inteligencia de jogo, do ponto de vista da complexidade

Universidade Estadual de Campinas . Faculdade de Educação Física

Pedagogia do treinamento : metodo, procedimentos pedagogicos e as multiplas competencias do tecnico nos jogos desportivos coletivos

Universidade Estadual de Campinas. Faculdade de Educação Física

Educação fisica na 1ª serie do ensino medio : uma pratica por compromisso

Universidade Estadual de Campinas . Faculdade de Educação Física

Effect of phosphate-bonded investments on titanium reaction layer and crown fit

This study analyzed the reaction layer and measured the marginal crown fit of cast titanium applied to different phosphate-bonded investments, prepared under the following conditions (liquid concentration/casting temperature): Rema Exakt (RE) - 100%/237°C, 75%/287°C, Castorit Super C (CS)-100%/70°C, 75%/141°C and Rematitan Plus (RP)- 100%/430°C (special to titanium cast, as the control group). The reaction layer was studied using the Vickers hardness test, and analyzed by two way ANOVA and Tukey's HSD tests (α = 0.05). Digital photographs were taken of the crowns seated on the die, the misfit was measured using an image analysis system and One-way ANOVA, and Tukey's test was applied (α = 0.05). The hardness decreased from the surface (601.17 VHN) to 150 μm (204.03 VHN). The group CS 75%/141°C presented higher hardness than the other groups, revealing higher surface contamination, but there were no differences among the groups at measurements deeper than 150 μm. The castings made with CS - 100%/70°C presented the lowest levels of marginal misfit, followed by RE -100%/237°C. The conventional investments CS (100%) and RE (100%) showed better marginal fit than RP, but the CS (75%) had higher surface contamination.

Bone quality associated with daily intake of coffee: a biochemical, radiographic and histometric study

Caffeine induces loss of calcium and influences the normal development of bone. This study investigated the effects of coffee on bone metabolism in rats by biochemical measurement of calcium, bone densitometry and histometry. Male rats, born of female treated daily with coffee and with coffee intake since born, were anesthetized, subjected to extraction of the upper right incisor, and sacrificed 7, 21 and 42 days after surgery. Blood and urine samples were taken, and their maxilla radiographed and processed to obtain 5-µm-thick semi-serial sections stained with hematoxylin and eosin. The volume and bone quality were estimated using an image-analysis software. The results showed significantly greater amount of calcium in the plasma (9.40 ± 1.73 versus 9.80 ± 2.05 mg%) and urine (1.00 ± 0.50 versus 1.25 ± 0.70 mg/24 h) and significantly less amount in bone (90.0 ± 1.94 versus 86.0 ± 2.12 mg/mg bone), reduced bone mineral density (1.05 ± 0.11 versus 0.65 ± 0.15 mmAL), and lower amount of bone (76.19 ± 1.6 versus 53.41 ± 2.1 %) (ANOVA; p≤0.01) in animals treated with coffee sacrificed after 42 days. It may be concluded that coffee/caffeine intake caused serious adverse effects on calcium metabolism in rats, including increased levels of calcium in the urine and plasma, decreased bone mineral density and lower volume of bone, thus delaying the bone repair process.

Effectiveness of different final irrigation protocols in removing debris in flattened root canals

This study evaluated in vitro the capacity of debris removal from the apical third of flattened root canals, using different final irrigation protocols. Thirty human mandibular central incisors with a mesiodistal flattened root were prepared using rotary instrumentation by Endo-Flare 25.12 and Hero 642 30.06, 35.02, 40.02 files, irrigated with 2 mL of 1% NaOCl after each file. The specimens were randomly distributed into 5 groups according to the final irrigation of root canals: Group I: 10 mL of distilled water (control), Group II: 10 mL of 1% NaOCl for 8 min, Group III: 2 mL of 1% NaOCl for 2 min (repeated 4 times), Group IV: 10 mL of 2.5% NaOCl for 8 min, and Group V: 10 mL of 2.5% NaOCl for 2 min (repeated 4 times). The apical thirds of the specimens were subjected to histological processing and 6-μm cross-sections were obtained and stained with hematoxylin-eosin. The specimens were examined under optical microscopy at ×40 magnification and the images were subjected to morphometric analysis using the Scion image-analysis software. The total area of root canal and the area with debris were measured in square millimeters. Analysis of variance showed no statistically significant difference (p>0.05) among the groups GI (2.39 ± 3.59), GII (2.91 ± 2.21), GIII (0.73 ± 1.36), GIV (0.95 ± 0.84) and GV (0.51 ± 0.22). In conclusion, the final irrigation protocols evaluated in this study using the Luer syringe presented similar performance in the removal of debris from the apical third of flattened root canals.

Evaluation of the dental structure loss produced during maintenance and replacement of occlusal amalgam restorations

The aim of this in vitro study was to evaluate four different approaches to the decision of changing or not defective amalgam restorations in first primary molar teeth concerning the loss of dental structure. Ditched amalgam restorations (n = 11) were submitted to four different treatments, as follows: Control group - polishing and finishing of the restorations were carried out; Amalgam group - the ditched amalgam restorations were replaced by new amalgam restorations; Composite resin group - the initial amalgam restorations were replaced by composite resin restorations; Flowable resin group - the ditching around the amalgam restorations was filled with flowable resin. Images of the sectioned teeth were made and the area of the cavities before and after the procedures was determined by image analysis software to assess structural loss. The data were submitted to ANOVA complemented by the Student Newman Keuls test (p < 0.05). The cavities in all the groups presented significantly greater areas after the procedures. However, the amalgam group showed more substantial dental loss. The other three groups presented no statistically significant difference in dental structure loss after the re-treatments. Thus, replacing ditched amalgam restorations by other similar restorations resulted in a significant dental structure loss while maintaining them or replacing them by resin restorations did not result in significant loss.

Phototherapy Improves Healing of Chronic Venous Ulcers

Objective: We tested the hypothesis that LED phototherapy with combined 660-nm and 890-nm light will promote healing of venous ulcers that failed to respond to other forms of treatment. Background Data: A variety of dressings, growth factors, and adjunct therapies are used to treat venous ulcers, but none seems to yield satisfactory results. Materials and Methods: We used a randomized placebo-controlled double-blind study to compare a total of 20 patients divided with 32 chronic ulcers into three groups. In group 1 the ulcers were cleaned, dressed with 1% silver sulfadiazine (SDZ) cream, and treated with placebo phototherapy (<.03 J/cm(-3)) using a Dynatron Solaris 705 phototherapy research device. In group 2 the ulcers were treated similarly but received real phototherapy (3 J/cm(-2)) instead of placebo. In group 3 (controls), the ulcers were simply cleaned and dressed with SDZ without phototherapy. The ulcers were evaluated with digital photography and computer image analysis over 90 d or until full healing was attained. Results: Ulcers treated with phototherapy healed significantly faster than controls when compared at day 30 (p < 0.01), day 60 (p < 0.05), and day 90 (p < 0.001), and similarly healed faster than the placebo-treated ulcers at days 30 and 90 (p < 0.01), but not at day 60. The beneficial effect of phototherapy was more pronounced when the confounding effect of small-sized ulcers was removed from the analysis. Medium- and large-sized ulcers healed significantly faster with treatment (>= 40% rate of healing per month) than placebo or control ulcers (p < 0.05). Conclusion: Phototherapy promotes healing of chronic venous ulcers, particularly large recalcitrant ulcers that do not respond to conventional treatment.