A review of bioengineering techniques applied to breast tissue: Mechanical properties, tissue engineering and finite element analysis

Female breast cancer was the most prevalent cancer worldwide in 2020, according to the Global Cancer Observatory. As a prophylactic measure or as a treatment, mastectomy and lumpectomy are often performed at women. Following these surgeries, women normally do a breast reconstruction to minimize the impact on their physical appearance and, hence, on their mental health, associated with self-image issues. Nowadays, breast reconstruction is based on autologous tissues or implants, which both have disadvantages, such as volume loss over time or capsular contracture, respectively. Tissue engineering and regenerative medicine can bring better solutions and overcome these current limitations. Even though more knowledge needs to be acquired, the combination of biomaterial scaffolds and autologous cells appears to be a promising approach for breast reconstruction. With the growth and improvement of additive manufacturing, three dimensional (3D) printing has been demonstrating a lot of potential to produce complex scaffolds with high resolution. Natural and synthetic materials have been studied in this context and seeded mainly with adipose derived stem cells (ADSCs) since they have a high capability of differentiation. The scaffold must mimic the environment of the extracellular matrix (ECM) of the native tissue, being a structural support for cells to adhere, proliferate and migrate. Hydrogels (e.g., gelatin, alginate, collagen, and fibrin) have been a biomaterial widely studied for this purpose since their matrix resembles the natural ECM of the native tissues. A powerful tool that can be used in parallel with experimental techniques is finite element (FE) modeling, which can aid the measurement of mechanical properties of either breast tissues or scaffolds. FE models may help in the simulation of the whole breast or scaffold under different conditions, predicting what might happen in real life. Therefore, this review gives an overall summary concerning the human breast, specifically its mechanical properties using experimental and FE analysis, and the tissue engineering approaches to regenerate this particular tissue, along with FE models

Towards an in-plane methodology to track breast lesions using mammograms and patient-specific finite-element simulations

In breast cancer screening or diagnosis, it is usual to combine different images in order to locate a lesion as accurately as possible. These images are generated using a single or several imaging techniques. As x-ray-based mammography is widely used, a breast lesion is located in the same plane of the image (mammogram), but tracking it across mammograms corresponding to different views is a challenging task for medical physicians. Accordingly, simulation tools and methodologies that use patient-specific numerical models can facilitate the task of fusing information from different images. Additionally, these tools need to be as straightforward as possible to facilitate their translation to the clinical area. This paper presents a patient-specific, finite-element-based and semi-automated simulation methodology to track breast lesions across mammograms. A realistic three-dimensional computer model of a patient''s breast was generated from magnetic resonance imaging to simulate mammographic compressions in cranio-caudal (CC, head-to-toe) and medio-lateral oblique (MLO, shoulder-to-opposite hip) directions. For each compression being simulated, a virtual mammogram was obtained and posteriorly superimposed to the corresponding real mammogram, by sharing the nipple as a common feature. Two-dimensional rigid-body transformations were applied, and the error distance measured between the centroids of the tumors previously located on each image was 3.84 mm and 2.41 mm for CC and MLO compression, respectively. Considering that the scope of this work is to conceive a methodology translatable to clinical practice, the results indicate that it could be helpful in supporting the tracking of breast lesions

Multi-Modality Breast MRI Segmentation Using nn-UNet for Preoperative Planning of Robotic Surgery Navigation

Segmentation of the chest region and breast tissues is essential for surgery planning and navigation. This paper proposes the foundation for preoperative segmentation based on two cascaded architectures of deep neural networks (DNN) based on the state-of-the-art nnU-Net. Additionally, this study introduces a polyvinyl alcohol cryogel (PVA-C) breast phantom based on the segmentation of the DNN automated approach, enabling the experiments of navigation system for robotic breast surgery. Multi-modality breast MRI datasets of T2W and STIR images were acquired from 10 patients. Segmentation evaluation utilized the Dice Similarity Coefficient (DSC), segmentation accuracy, sensitivity, and specificity. First, a single class labeling was used to segment the breast region. Then it was employed as an input for three-class labeling to segment fat, fibroglandular (FGT) tissues, and tumorous lesions. The first architecture has a 0.95 DCS, while the second has a 0.95, 0.83, and 0.41 for fat, FGT, and tumor classes, respectively

Differently stained whole slide image registration technique with landmark validation

Abstract. One of the most significant features in digital pathology is to compare and fuse successive differently stained tissue sections, also called slides, visually. Doing so, aligning different images to a common frame, ground truth, is required. Current sample scanning tools enable to create images full of informative layers of digitalized tissues, stored with a high resolution into whole slide images. However, there are a limited amount of automatic alignment tools handling large images precisely in acceptable processing time. The idea of this study is to propose a deep learning solution for histopathology image registration. The main focus is on the understanding of landmark validation and the impact of stain augmentation on differently stained histopathology images. Also, the developed registration method is compared with the state-of-the-art algorithms which utilize whole slide images in the field of digital pathology. There are previous studies about histopathology, digital pathology, whole slide imaging and image registration, color staining, data augmentation, and deep learning that are referenced in this study. The goal is to develop a learning-based registration framework specifically for high-resolution histopathology image registration. Different whole slide tissue sample images are used with a resolution of up to 40x magnification. The images are organized into sets of consecutive, differently dyed sections, and the aim is to register the images based on only the visible tissue and ignore the background. Significant structures in the tissue are marked with landmarks. The quality measurements include, for example, the relative target registration error, structural similarity index metric, visual evaluation, landmark-based evaluation, matching points, and image details. These results are comparable and can be used also in the future research and in development of new tools. Moreover, the results are expected to show how the theory and practice are combined in whole slide image registration challenges. DeepHistReg algorithm will be studied to better understand the development of stain color feature augmentation-based image registration tool of this study. Matlab and Aperio ImageScope are the tools to annotate and validate the image, and Python is used to develop the algorithm of this new registration tool. As cancer is globally a serious disease regardless of age or lifestyle, it is important to find ways to develop the systems experts can use while working with patients’ data. There is still a lot to improve in the field of digital pathology and this study is one step toward it.Eri menetelmin värjättyjen virtuaalinäytelasien rekisteröintitekniikka kiintopisteiden validointia hyödyntäen. Tiivistelmä. Yksi tärkeimmistä digitaalipatologian ominaisuuksista on verrata ja fuusioida peräkkäisiä eri menetelmin värjättyjä kudosleikkeitä toisiinsa visuaalisesti. Tällöin keskenään lähes identtiset kuvat kohdistetaan samaan yhteiseen kehykseen, niin sanottuun pohjatotuuteen. Nykyiset näytteiden skannaustyökalut mahdollistavat sellaisten kuvien luonnin, jotka ovat täynnä kerroksittaista tietoa digitalisoiduista näytteistä, tallennettuna erittäin korkean resoluution virtuaalisiin näytelaseihin. Tällä hetkellä on olemassa kuitenkin vain kourallinen automaattisia työkaluja, jotka kykenevät käsittelemään näin valtavia kuvatiedostoja tarkasti hyväksytyin aikarajoin. Tämän työn tarkoituksena on syväoppimista hyväksikäyttäen löytää ratkaisu histopatologisten kuvien rekisteröintiin. Tärkeimpänä osa-alueena on ymmärtää kiintopisteiden validoinnin periaatteet sekä eri väriaineiden augmentoinnin vaikutus. Lisäksi tässä työssä kehitettyä rekisteröintialgoritmia tullaan vertailemaan muihin kirjallisuudessa esitettyihin algoritmeihin, jotka myös hyödyntävät virtuaalinäytelaseja digitaalipatologian saralla. Kirjallisessa osiossa tullaan siteeraamaan aiempia tutkimuksia muun muassa seuraavista aihealueista: histopatologia, digitaalipatologia, virtuaalinäytelasi, kuvantaminen ja rekisteröinti, näytteen värjäys, data-augmentointi sekä syväoppiminen. Tavoitteena on kehittää oppimispohjainen rekisteröintikehys erityisesti korkearesoluutioisille digitalisoiduille histopatologisille kuville. Erilaisissa näytekuvissa tullaan käyttämään jopa 40-kertaista suurennosta. Kuvat kudoksista on järjestetty eri menetelmin värjättyihin peräkkäisiin kuvasarjoihin ja tämän työn päämääränä on rekisteröidä kuvat pohjautuen ainoastaan kudosten näkyviin osuuksiin, jättäen kuvien tausta huomioimatta. Kudosten merkittävimmät rakenteet on merkattu niin sanotuin kiintopistein. Työn laatumittauksina käytetään arvoja, kuten kohteen suhteellinen rekisteröintivirhe (rTRE), rakenteellisen samankaltaisuuindeksin mittari (SSIM), sekä visuaalista arviointia, kiintopisteisiin pohjautuvaa arviointia, yhteensopivuuskohtia, ja kuvatiedoston yksityiskohtia. Nämä arvot ovat verrattavissa myös tulevissa tutkimuksissa ja samaisia arvoja voidaan käyttää uusia työkaluja kehiteltäessä. DeepHistReg metodi toimii pohjana tässä työssä kehitettävälle näytteen värjäyksen parantamiseen pohjautuvalle rekisteröintityökalulle. Matlab ja Aperio ImageScope ovat ohjelmistoja, joita tullaan hyödyntämään tässä työssä kuvien merkitsemiseen ja validointiin. Ohjelmointikielenä käytetään Pythonia. Syöpä on maailmanlaajuisesti vakava sairaus, joka ei katso ikää eikä elämäntyyliä. Siksi on tärkeää löytää uusia keinoja kehittää työkaluja, joita asiantuntijat voivat hyödyntää jokapäiväisessä työssään potilastietojen käsittelyssä. Digitaalipatologian osa-alueella on vielä paljon innovoitavaa ja tämä työ on yksi askel eteenpäin taistelussa syöpäsairauksia vastaan

Biomechanical properties of breast tissue, a state-of-the-art review

This paper reviews the existing literature on the tests used to determine the mechanical properties of women breast tissues (fat, glandular and tumour tissue) as well as the different values of these properties. The knowledge of the mechanical properties of breast tissue is important for cancer detection, study and planning of surgical procedures such as surgical breast reconstruction using pre-surgical methods and improving the interpretation of clinical tests. Based on the data collected from the analysed studies, some important conclusions were achieved: (1) the Young’s modulus of breast tissues is highly dependent on the tissue preload compression level, and (2) the results of these studies clearly indicate a wide variation in moduli not only among different types of tissue but also within each type of tissue. These differences were most evident in normal fat and fibroglandular tissues

Machine learning methods for the analysis and interpretation of images and other multi-dimensional data

L'abstract è presente nell'allegato / the abstract is in the attachmen

Soft volume simulation using a deformable surface model

The aim of the research is to contribute to the modelling of deformable objects, such as soft tissues in medical simulation. Interactive simulation for medical training is a concept undergoing rapid growth as the underlying technologies support the increasingly more realstic and functional training environments. The prominent issues in the deployment of such environments centre on a fine balance between the accuracy of the deformable model and real-time interactivity. Acknowledging the importance of interacting with non-rigid materials such as the palpation of a breast for breast assessment, this thesis has explored the physics-based modelling techniques for both volume and surface approach. This thesis identified that the surface approach based on the mass spring system (MSS) has the benefits of rapid prototyping, reduced mesh complexity, computational efficiency and the support for large material deformation compared to the continuum approach. However, accuracy relative to real material properties is often over looked in the configuration of the resulting model. This thesis has investigated the potential and the feasibility of surface modelling for simulating soft objects regardless of the design of the mesh topology and the non-existence of internal volume discretisation. The assumptions of the material parameters such as elasticity, homogeneity and incompressibility allow a reduced set of material values to be implemented in order to establish the association with the surface configuration. A framework for a deformable surface model was generated in accordance with the issues of the estimation of properties and volume behaviour corresponding to the material parameters. The novel extension to the surface MSS enables the tensile properties of the material to be integrated into an enhanced configuration despite its lack of volume information. The benefits of the reduced complexity of a surface model are now correlated with the improved accuracy in the estimation of properties and volume behaviour. Despite the irregularity of the underlying mesh topology and the absence of volume, the model reflected the original material values and preserved volume with minimal deviations. Global deformation effect which is essential to emulate the run time behaviour of a real soft material upon interaction, such as the palpation of a generic breast, was also demonstrated, thus indicating the potential of this novel technique in the application of soft tissue simulation