Morphological aspects in the diagnosis of skin lesions

En col·laboració amb la Universitat de Barcelona (UB), la Universitat Autònoma de Barcelona (UAB) i l’Institut de Ciències Fotòniques (ICFO)The ABCDE (Asymmetry, Border, Color, Rambla de Sant Nebridi, 10, Diameter and Elevation) rule represents a commonly used clinical guide for the early identification of melanoma. Here we develop a methodology based on an Artificial Neural Network which is trained to stablish a clear differentiation between benign and m lesions. This machine learning approach improves prognosis and diagnosis accuracy rates. align In order to obtain the 6 morphological feature data set for each of the 69 lesions considered, a 3D handheld system is used for acquiring the skin images and an image processing algorithm is applied

Quantitative Assessment of Cancer Vascular Architecture by Skeletonization of High-resolution 3-D Contrast-enhanced Ultrasound Images: Role of Liposomes and Microbubbles.

The accurate characterization and description of the vascular network of a cancer lesion is of paramount importance in clinical practice and cancer research in order to improve diagnostic accuracy or to assess the effectiveness of a treatment. The aim of this study was to show the effectiveness of liposomes as an ultrasound contrast agent to describe the 3-D vascular architecture of a tumor. Eight C57BL/6 mice grafted with syngeneic B16-F10 murine melanoma cells were injected with a bolus of 1,2-Distearoyl-sn-glycero-3-phosphocoline (DSPC)-based non-targeted liposomes and with a bolus of microbubbles. 3-D contrast-enhanced images of the tumor lesions were acquired in three conditions: pre-contrast, after the injection of micro bubbles, and after the injection of liposomes. By using a previously developed reconstruction and characterization image processing technique, we obtained the 3-D representation of the vascular architecture in these three conditions. Six descriptive parameters of these networks were also computed: the number of vascular trees (NT), the vascular density (VD), the number of branches, the 2-D curvature measure, the number of vascular flexes of the vessels, and the 3-D curvature. Results showed that all the vascular descriptors obtained by liposome-based images were statistically equal to those obtained by using microbubbles, except the VD which was found to be lower for liposome images. All the six descriptors computed in pre-contrast conditions had values that were statistically lower than those computed in presence of contrast, both for liposomes and microbubbles. Liposomes have already been used in cancer therapy for the selective ultrasound-mediated delivery of drugs. This work demonstrated their effectiveness also as vascular diagnostic contrast agents, therefore proving that liposomes can be used as efficient “theranostic” (i.e. therapeutic 1 diagnostic) ultrasound probes

Biomedical overview of melanin. 2. Updating molecular modeling, synthesis mechanism, and supramolecular properties regarding melanoma therapy

Melanins represent one of the most ancient and important group of natural macromolecular pigments. They have multiple biological roles in almost all organisms across the Phyla, examples being photoprotection, anti-oxidative action, radical scavenger activity, and heavy metal removal. From the biomedical point of view, melanocytes are involved in the origin of melanoma tumors, and the main therapeutic advances for their treatment have been revised in Part 1 of this review. The chemical structure of eumelanin is a biological concern of great importance, and therefore, exploring theoretical molecular models and synthesis mechanisms will be here described, as well as molecular orbital features and supramolecular organization, which are responsible for the key properties that make these biological pigments so important, and so fascinating. Ultimately, this updated overview is devoted to describe present structural models and physico-chemical characteristics of eumelanin, in order to explain and utilize melanin properties on which new photothermal and ultrasonic protocols for melanoma treatment can be devised and applie

High Resolution Imaging and Digital Characterization of Skin Pathology By Scanning Acoustic Microscopy

Skin cancer represents the most common worldwide malignancy with a widely varying prognosis. Most of the diagnostic tools used for skin imaging are still limited to provide a definite diagnosis of skin cancer, especially melanoma. Easy access to the skin to biopsy and excision made skin underexplored using ultrasonic diagnostic imaging. Given the fact that speed of sound and acoustic impedance are related to elastic modulus, quantitative acoustic microscopy shows great potential as a useful tool for skin cancer diagnosis. The high-frequency acoustic microscopy method was used to evaluate properties of the cancer lesions for melanoma, basal cell carcinoma, and squamous cell carcinoma. The algorithm for quantitative characterization of individual cells in the histological slices has been developed. All cancer cells regardless of the cancer type have lower sound speed comparing to healthy skin cells. The melanoma cells have the lowest values of sound speed (1360 ± 50 m/s) comparing to basal cell carcinoma and squamous cell carcinoma. It was demonstrated on thickly cut skin specimens that melanoma lesions have lower acoustic impedance compared to healthy skin. These findings may become the basis for a new ultrasonic method for melanoma diagnosis or for margin status verification during the surgery helting to reduce the mortality rate from melanoma and improve healthcare in Canada and worldwide

Melanin-binding colorants: updating molecular modeling, staining and labeling mechanisms, and biomedical perspectives

Melanin and melanoma tumors are two fields of increasing interest in biomedical research. Melanins are ubiquitous biopigments with adaptive value and multiple functions, and occur in the malignant melanoma. Although several chemical structures have been proposed for eumelanin, molecular modeling and orbitals indicate that a planar or spiral benzoquinone-porphycene polymer would be the model that better explains the broad-band light and ultrasound absorption, electric conductivity, and graphite-like organization shown by X-ray crystallography and electron microscopy. Lysosomes and melanosomes are selectively labeled by vital probes, and melanin also binds to metal cations, colorants, and drugs, with important consequences in pharmacology, pathology, and melanoma therapy. In addition to traditional and recent oncologic treatments, photodynamic, photothermal, and ultrasound protocols represent novel modalities for melanoma therapy. Since eumelanin is practically the ideal photothermal and ultrasound sensitizer, the vibrational decay from photo-excited electrons after NIR irradiation, or the electrochemical production of ROS and radicals after ultrasound absorption, induce an efficient heating or oxidative response, resulting in the damage and death of tumor cells. This allows repetitive treatments due to the remaining melanin contained in tumoral melanophages. Given that evolution and prognosis of the advanced melanoma is still a concern, new biophysical procedures based on melanin properties can now be developed and applie

Novel melanoma diagnosis and prognosis methods based on 3D fringe projection

This project aims to find an effective and non-invasive methodology to assist in the diagnosis of skin lesions using 3D profile features.Este proyecto tiene como objetivo el desarrollo de una metodología eficaz y no invasiva para la asistencia en el diagnóstico de lesiones cutáneas utilizando sus características 3D.Aquest projecte té com a objectiu desenvolupar una metodologia no invasiva i eficaç per ajudar en el diagnòstic de lesions de la pell mitjançant caraterístiques 3D

Superhydrophobic lab-on-chip measures secretome protonation state and provides a personalized risk assessment of sporadic tumour

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual’s diagnosis and/or help clarify risk in healthy populations

Engineered biomaterials as extracellular microenvironments for guiding cell programming and reprogramming

The interface between cells and materials is a dynamic and complex environment where cells in contact with materials can sense their properties such as stiffness, matrix protein, and geometry and respond to these cues in multiple ways including through mechanical forces exerted on the matrix by the cells. Cells incorporate these cues via signal propagation through integrins, and translate this information through intracellular signal transduction cascades to regulate gene expression and cell fate decisions. Advances in biomaterials to direct stem cell lineage decisions have focused on designing biomimetic materials that realize the ‘‘in vivo” microenvironments’ ability to interact with cells. However, not only is designing tailored biomaterials that present multiple signals challenging, but the precise roles of physical and biochemical cues in coordinating cellular processes such as migration, proliferation, and differentiation remains difficult to dissect. After a short introduction we explore using model polyacrylamide hydrogel systems in Chapter 2-5 to study the effects of biophysical (elasticity and geometry) and chemical (matrix protein) cues on mesenchymal stem cell (MSC) fate decisions, showing these cues can play a large role in differentiation. In Chapter 6 we explore how switching the biophysical microenvironment (matrix stiffness and cell shape) can be used to understand the plasticity of MSC lineage specification. Finally, in Chapter 7-9, we demonstrate how geometric cues at the interface of tissue, where interfacial energy and curvature can be modulated in vitro, will dictate cancer cell tumorigenicity, metastatic potential, and the regulation of tumorangiogenesis. Moreover, we reveal a mechanism where perimeter features initiate α5β1 adhesion and epithelial-to-mesenchymal transition, Mitogen Activated Protein Kinase (MAPK) and Signal Transducer and Activator of Transcription (STAT) pathways, and regulation of distinct histone marks, to guide gene expression underlying the phenotypic alterations of malignant melanoma. Overall, we believe the work presented here demonstrates the importance and utility of extracellular properties in modulating cell programming and reprogramming, and should aid in the development of biomaterials for more efficiently directing distinct cellular states for the development of synthetic model systems that more accurately recapitulate the in vivo microenvironment

Computer Aided Diagnostic Support System for Skin cancer: Review of techniques and algorithms

Image-based computer aided diagnosis systems have significant potential for screening and early detection of malignant melanoma. We review the state of the art in these systems and examine current practices, problems, and prospects of image acquisition, pre-processing, segmentation, feature extraction and selection, and classification of dermoscopic images. This paper reports statistics and results from the most important implementations reported to date. We compared the performance of several classifiers specifically developed for skin lesion diagnosis and discussed the corresponding findings. Whenever available, indication of various conditions that affect the technique’s performance is reported. We suggest a framework for comparative assessment of skin cancer diagnostic models and review the results based on these models. The deficiencies in some of the existing studies are highlighted and suggestions for future research are provided