Academic literature on the topic 'Breast infrared imaging'

This descriptive study investigates breast thermal characteristics in females histologically diagnosed with unilateral breast cancer and in their contralateral normal breasts. The multi-institutional clinical pilot study was reviewed and approved by the Institutional Review Boards (IRBs) at participating institutions. Eleven female subjects with radiologic breast abnormalities were enrolled in the study between June 2019 and September 2019 after informed consent was obtained. Static infrared images were recorded for each subject. The Wilcoxon signed rank test was used to conduct paired comparisons in temperature data between breasts among the eight histologically diagnosed breast cancer subjects (n = 8). Localized temperatures of cancerous breast lesions were significantly warmer than corresponding regions in contralateral breasts (34.0 ± 0.9 °C vs. 33.2 ± 0.5 °C, p = 0.0142, 95% CI 0.25–1.5 °C). Generalized temperatures over cancerous breasts, in contrast, were not significantly warmer than corresponding regions in contralateral breasts (33.9 ± 0.8 °C vs. 33.4 ± 0.4 °C, p = 0.0625, 95% CI −0.05–1.45 °C). Among the breast cancers enrolled, breast cancers elevated temperatures locally at the site of the lesion (localized hyperthermia), but not over the entire breast (generalized hyperthermia).

Breast cancer is a major public health problem worldwide. Important advances have improved survival, but early detection remains the main clinical challenge in reducing mortality. Currently, mammography is the ‘gold standard’ tool for breast cancer screening. However, the search for an early breast cancer detection method is the subject of extensive research. Although infrared imaging or breast thermography for early breast cancer detection has been evaluated since the late 1950s, the negative results reported in 1979 by the Breast Cancer Detection and Demonstration Project decreased interest in this imaging modality. Advances in infrared imaging and reduced equipment costs have, however, renewed interest in breast thermography. Breast cancer in developing countries requires new strategies to increase early detection and access to care. In this article, we highlight the principles and advances of infrared imaging technology and describe our experience with new-generation infrared imaging for early breast cancer detection in rural communities in southern Mexico.

Women’s breasts are susceptible to developing cancer; this is supported by a recent study from 2016 showing that 2.8 million women worldwide had already been diagnosed with breast cancer that year. The medical care of a patient with breast cancer is costly and, given the cost and value of the preservation of the health of the citizen, the prevention of breast cancer has become a priority in public health. Over the past 20 years several techniques have been proposed for this purpose, such as mammography, which is frequently used for breast cancer diagnosis. However, false positives of mammography can occur in which the patient is diagnosed positive by another technique. Additionally, the potential side effects of using mammography may encourage patients and physicians to look for other diagnostic techniques. Our review of the literature first explored infrared digital imaging, which assumes that a basic thermal comparison between a healthy breast and a breast with cancer always shows an increase in thermal activity in the precancerous tissues and the areas surrounding developing breast cancer. Furthermore, through our research, we realized that a Computer-Aided Diagnostic (CAD) undertaken through infrared image processing could not be achieved without a model such as the well-known hemispheric model. The novel contribution of this paper is the production of a comparative study of several breast cancer detection techniques using powerful computer vision techniques and deep learning models.

Breast cancer is the most common form of cancer in women. Its aggressive nature has made it one of the chief factors of high female mortality. Therefore, this has motivated research to achieve early diagnosis since it is the best strategy for patient survival. Currently, mammography is the gold standard for detecting breast cancer. However, it is expensive, unsuitable for dense breasts, and an invasive process that exposes the patient to radiation. Infrared thermography is gaining popularity as a screening modality for the early detection of breast cancer. It is a noninvasive and cost-effective modality that allows health practitioners to observe the temperature profile of the breast region for signs of cancerous tumors. Deep learning has emerged as a powerful computational tool for the early detection of breast cancer in radiology. As such, this study presents a review that shows existing work on deep learning-based Computer-aided Diagnosis (CADx) systems for breast cancer detection. In the same context, it reflects on classification utilizing breast thermograms. It first provides an overview of infrared thermography, details on available breast thermogram datasets, and then segmentation techniques applied to these thermograms. We also provide a brief overview of deep neural networks. Finally, it reviews works adopting Deep Neural Networks (DNNs) for breast thermogram classification.

Breast cancer has been reported to be the first deadly disease that affects women worldwide. This type of cancer has been reported to be the second leading cause of death in women worldwide. Medical reports have also reported that every woman is exposed to having breast cancer with an average probability of about 12%. It has also been reported to be the most common cancer that affects women. Fatality could be due to the cancer detection delay; in other words, early detection of the tumor can increase the survival rate of patients. Routine techniques of imaging modalities for cancer screening such as Mammography, Computated Tomography (CT) scan, Magnetic Resonance Imaging (MRI) and ultrasound are impractical tools for many reasons such as the irreproducible nature, the high error rate in cases of thick breasts, the pain and the annoyance they cause. Consequently, there is a need for more convincing strategies with high accuracy rates in breast cancer detection. Therefore, among the large variety of medical breast scanning techniques, thermography has attracted attention in applications related to detection and diagnosis. It is capable of providing helpful and useful information about the physiological variations and accordingly, it can detect tumors even in early stages. In addition, it is a very safe scanning tool, so as many needed tests can be held in proper time and manner. Thermography relies on the fact that human body temperature generally is a natural norm for the diagnosis of diseases. Thermography in medical applications applies infrared body examination tool which is fast, noninvasive, noncontact, pain free, radiation free and flexible to monitor the temperature of the human body. The fundamental principle of thermography relies on physiology such as the distribution of temperature on the skin surface. Infrared thermography scanning for breasts is an imaging technique which essentially searches for temperature change in human body. Temperature variance could be considered as a good indicator of tumor occurrence in the scanned area. Tumor mainly causes a noteworthy increase in blood vessel circulation and metabolic activity, so it causes higher radiations emitted from the human body around the regions of tumor. The paper surveys the literature work conducted in the field of breast cancer detection from thermogram scans. The survey is followed by a discussion of the strengths and weaknesses of thermography-based tumor detection. A new research idea and some considerations are then suggested based on that discussion to achieve better results in this critical area.

This work presents a case study of a 75-year-old woman breast withcancer. The investigation process used infrared image, mammography,computerized tomography (CT) and ultrasound guided biopsy toassess, stage and final diagnostic of the tumor. Each one of theseevaluations brings an isolated piece of information that results in thecorrect diagnostic, and treatment. As early diagnostic of breast cancergoes towards improvement in diagnostics and better therapeutics, it isreasonable to state that breast cancer diagnostics must be achieved asearly as possible. An association between infrared image abnormalitiesand computerized tomography is acknowledged and is assumed that acorrelation could exist. The technical literature demonstrated thattumor depth could be inferred from infrared images, but criticalinformation such as breast perfusion for accurate predictions are notavailable yet. Considering that a mathematical model could modelbreast perfusion, this study proposes that tumor morphology and depthin breast cancer could be adequately determined using mathematicalmodeling, infrared imaging, and computerized tomography incomplementary actions.

Nowadays, breast cancer is one of the most common cancers diagnosed in women. Mammography is the standard screening imaging technique for the early detection of breast cancer. However, thermal infrared images (thermographies) can be used to reveal lesions in dense breasts. In these images, the temperature of the regions that contain tumors is warmer than the normal tissue. To detect that difference in temperature between normal and cancerous regions, a dynamic thermography procedure uses thermal infrared cameras to generate infrared images at fixed time steps, obtaining a sequence of infrared images. In this paper, we propose a novel method to model the changes on temperatures in normal and abnormal breasts using a representation learning technique called learning-to-rank and texture analysis methods. The proposed method generates a compact representation for the infrared images of each sequence, which is then exploited to differentiate between normal and cancerous cases. Our method produced competitive (AUC = 0.989) results when compared to other studies in the literature.

Breast cancer is the most crucial cancer type among all other cancer types. There are many imaging techniques used to screen breast carcinoma. These are mammography, ultrasound, computed tomography, magnetic resonance imaging, infrared imaging, positron emission tomography and electrical impedance tomography. However, there is no gold standard in breast carcinoma diagnosis. The object of this study is to create a hybrid system that uses thermal and electrical imaging methods together for breast cancer diagnosis. Body tissues have different electrical conductivity values depending on their state of health and types. Consequently, one can get information about the anatomy of the human body and tissue&rsquo
s health by imaging tissue conductivity distribution. Due to metabolic heat generation values and thermal characteristics that differ from tissue to tissue, thermal imaging has started to play an important role in medical diagnosis. To increase the temperature contrast in thermal images, the characteristics of the two imaging modalities can be combined. This is achieved by implementing thermal imaging applying electrical currents from the body surface within safety limits (i.e., thermal imaging in active mode). Electrical conductivity of tissues changes with frequency, so it is possible to obtain more than one thermal image for the same body. Combining these images, more detailed information about the tumor tissue can be acquired. This may increase the accuracy in diagnosis while tumor can be detected at deeper locations. Feasibility of the proposed technique is investigated with analytical and numerical simulations and experimental studies. 2-D and 3-D numerical models of the female breast are developed and feasibility work is implemented in the frequency range of 10 kHz and 800 MHz. Temporal and spatial temperature distributions are obtained at desired depths. Thermal body-phantoms are developed to simulate the healthy breast and tumor tissues in experimental studies. Thermograms of these phantoms are obtained using two different infrared cameras (microbolometer uncooled and cooled Quantum Well Infrared Photodetectors). Single and dual tumor tissues are determined using the ratio of uniform (healthy) and inhomogeneous (tumor) images. Single tumor (1 cm away from boundary) causes 55 °
mC temperature increase and dual tumor (2 cm away from boundary) leads to 50 °
mC temperature contrast. With multi-frequency current application (in the range of 10 kHz-800 MHz), the temperature contrast generated by 3.4 mm3 tumor at 9 mm depth can be detected with the state-of-the-art thermal imagers.

Optical imaging is an emerging technology towards non-invasive breast cancer diagnostics. In recent years, portable and patient comfortable hand-held optical imagers are developed towards two-dimensional (2D) tumor detections. However, these imagers are not capable of three-dimensional (3D) tomography because they cannot register the positional information of the hand-held probe onto the imaged tissue. A hand-held optical imager has been developed in our Optical Imaging Laboratory with 3D tomography capabilities, as demonstrated from tissue phantom studies. The overall goal of my dissertation is towards the translation of our imager to the clinical setting for 3D tomographic imaging in human breast tissues. A systematic experimental approach was designed and executed as follows: (i) fast 2D imaging, (ii) coregistered imaging, and (iii) 3D tomographic imaging studies. (i) Fast 2D imaging was initially demonstrated in tissue phantoms (1% Liposyn solution) and in vitro (minced chicken breast and 1% Liposyn). A 0.45 cm3 fluorescent target at 1:0 contrast ratio was detectable up to 2.5 cm deep. Fast 2D imaging experiments performed in vivo with healthy female subjects also detected a 0.45 cm3 fluorescent target superficially placed ~2.5 cm under the breast tissue. (ii) Coregistered imaging was automated and validated in phantoms with ~0.19 cm error in the probe’s positional information. Coregistration also improved the target depth detection to 3.5 cm, from multi-location imaging approach. Coregistered imaging was further validated in-vivo, although the error in probe’s positional information increased to ~0.9 cm (subject to soft tissue deformation and movement). (iii) Three-dimensional tomography studies were successfully demonstrated in vitro using 0.45 cm3 fluorescence targets. The feasibility of 3D tomography was demonstrated for the first time in breast tissues using the hand-held optical imager, wherein a 0.45 cm3 fluorescent target (superficially placed) was recovered along with artifacts. Diffuse optical imaging studies were performed in two breast cancer patients with invasive ductal carcinoma. The images showed greater absorption at the tumor cites (as observed from x-ray mammography, ultrasound, and/or MRI). In summary, my dissertation demonstrated the potential of a hand-held optical imager towards 2D breast tumor detection and 3D breast tomography, holding a promise for extensive clinical translational efforts.

Breast cancer is the most common cancer in women. It is a highly heterogeneous disease in terms of histology, therapeutic response and patient outcomes. Early and accurate detection of breast cancer is crucial as the patient prognosis varies greatly depending on the diagnosis of the disease. Nonetheless current breast cancer classification methods fail to precisely sub-classify the disease, resulting in potential inadequate therapeutic management of patients and subsequent poor clinical outcomes. Substantial effort is therefore put in cancer research to develop methods and find new biomarkers efficiently identifying and characterizing breast tumor cells. Moreover it is now well-recognized that the intensive cross-talk between cancer cells and their microenvironment (including non-tumor cells) highly influences cancer progression. Recently, a growing body of clinical evidence reported the prognostic and predictive value associated with the presence of tumor infiltrating lymphocytes (TILs) in the microenvironment of breast tumors. Although the evaluation of TILs would be of great value for the management of patients and the development of new immunotherapies, it is currently not assessed in routine practice. Furthermore Fourier transform infrared (FTIR) imaging has shown its usefulness to study a panel of human cancers. Infrared (IR) spectroscopy coupled to microscopy provides images composed of multiple spectra reflecting the biochemical composition and subtle modifications within biological samples. IR imaging therefore provides useful information to improve breast cancer identification and characterization. The ultimate aim of this thesis is to improve breast cancer diagnosis using FTIR imaging to better identify and characterize cancer cells and the tumor microenvironment of breast cancers. In a first step we carried out a feasibility study aiming at evaluating the impact of the sample fixation process on IR spectra. While spectra were undeniably influenced by this biochemical alteration, our results indicated that closely-related cell types were influenced similarly and could still be discriminated on the basis of their spectral features. We then demonstrated the capability of IR imaging to discriminate a tumor from a normal tissue environment based on the spectral features of tumor cells and the surrounding extracellular matrix. A particular focus was placed on the identification of lymphocyte spectral signatures of cells isolated from blood or present within secondary lymphoid organs such as tonsils. Our results revealed that IR imaging was sensitive enough to discriminate lymphocyte subpopulations and to identify a particular spectral signature that we assigned to lymphocyte activation. Finally we highlighted the potential value of IR imaging as complementary tool to identify and characterize TILs in breast tumor samples. Altogether, our results suggest that IR imaging provides interesting and reliable information to improve breast cancer characterization and to assess the immune microenvironment of breast tumors.

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Le cancer du sein est le carcinome le plus fréquent chez la femme. C’est une maladie très hétérogène du point de vue histologique, de la réponse thérapeutique et de l’évolution clinique. Une détection rapide et précise de la maladie est cruciale, un diagnostic du cancer du sein dès les premiers stades de la maladie permet une meilleure prise en charge du patient et est directement associé à un meilleur pronostic. Néanmoins la classification actuelle des cancers du sein ne permet souvent pas de caractériser la maladie de manière précise, ce qui donne lieu à la mise en place de traitements moins ciblés et une évolution clinique peu favorable. Pour remédier à cela, des efforts conséquents sont réalisés en recherche, dans le but de mettre au point des méthodes capables d’identifier et de caractériser les cellules tumorales. De plus il est actuellement reconnu que le micro-environnement tumoral (composé des cellules non-tumorales) influence fortement la progression du cancer. Récemment de nombreuses études ont montré que la présence de lymphocytes au niveau des tumeurs mammaires (TILs) était corrélée à un meilleur facteur pronostic et prédictif. Bien que l’évaluation des TILs soit de grande importance dans le cadre des immunothérapies, cet élément n’est actuellement pas pris en compte dans les analyses de routine. Par ailleurs, l’imagerie infrarouge par transformée de Fourier (FTIR) a démontré son utilité dans l’étude de plusieurs cancers humains. La spectroscopie infrarouge (IR) couplée à la microscopie fourni des images composées de multiples spectres qui reflètent la composition biochimique et les modifications dans les échantillons biologiques. De ce fait l’imagerie infrarouge procure des informations utiles pour améliorer l’identification et la caractérisation du cancer du sein. L’objectif général de cette thèse est d’améliorer le diagnostic du cancer du sein par imagerie FTIR pour mieux identifier et caractériser les cellules cancéreuses et le micro-environnement tumoral des tumeurs mammaires. Dans un premier temps nous avons effectué une étude de faisabilité afin d’évaluer l’impact du protocole de fixation des tissus sur les spectres IR. Bien que les spectres soient indéniablement influencés par cette altération biochimique, nos résultats indiquent que des types cellulaires proches sont influencés de manière similaire et peuvent donc être discriminés sur base de leurs caractéristiques spectrales. Nous avons ensuite démontré la capacité de l’imagerie IR de distinguer un environnement tumoral d’un environnement normal sur base des particularités spectrales des cellules tumorales et de la matrice extracellulaire. Une attention particulière a ensuite été portée afin d’identifier des signatures spectrales de cellules immunitaires du sang et au sein d’organes lymphoïdes secondaires, tels que les amygdales. Nos résultats ont révélé que l’imagerie IR permet d'identifier une signature spectrale particulière, que nous avons associée à une stimulation lymphocytaire. Finalement nous avons mis en évidence l’utilité de l’imagerie IR en tant qu’outil complémentaire pour identifier et caractériser les TILs dans les échantillons tumoraux mammaires. De manière générale, nos résultats suggèrent que l’imagerie IR fournit des informations intéressantes et fiables pour améliorer la caractérisation et l’évaluation du micro-environnement immunitaire dans les tumeurs mammaires.
Doctorat en Sciences agronomiques et ingénierie biologique
info:eu-repo/semantics/nonPublished

Despite the possible common histopathological features at diagnosis, cancer cells present within breast carcinomas are highly heterogeneous in their molecular signatures. This heterogeneity is responsible for disparate clinical behaviors, treatment responses and long-term outcomes in breast cancer patients. Although the few histopathological markers can partially describe the diversity of cells found in tumor tissue sections, the full molecular characterization of individual cancer cells is currently impossible in routine clinical practice. In this respect, Fourier transform infrared (FTIR) microspectroscopic imaging of histological sections allows obtaining, for each pixel of tissue images, hundreds of independent potential markers, which makes this technique a particularly powerful tool to distinguish cell types and subtypes. As a complement to the conventional clinicopathological evaluation, this spectroscopic approach has the potential to directly reveal molecular descriptors that should allow identifying different clonal lineages found within a single tumor and therefore provide knowledge relevant to diagnosis, prognosis and treatment personalization. Yet, interpretation of infrared (IR) spectra acquired on tissue sections requires a well-established calibration, which is currently missing. Conventionally, mammary epithelial cells are studied in vitro as adherent two-dimensional (2D) monolayers, which lead to the alteration of cell-microenvironmental interplay and consequently to the loss of tissue structure and function. A number of key in vivo-like interactions may be re-established with the use of three-dimensional (3D) laminin-rich extracellular matrix (lrECM)-based culture systems. The aim of this thesis is to investigate by FTIR imaging the influence of the in vitro growth environment (2D culture versus 3D lrECM culture and 3D monoculture versus 3D co-culture with fibroblasts) on a series of thirteen well-characterized human breast cancer cell lines and to determine culture conditions generating spectral phenotypes that are closer to the ones observed in malignant breast tissues. The reference cell lines cultured in a physiologically relevant basement membrane model and having undergone formalin fixation, paraffin embedding (FFPE), a routine treatment used to preserve clinical tissue specimens, could contribute to the construction of a spectral database. The latter could be ultimately employed as a valuable tool to interpret IR spectra of cells present in tumor tissue sections, particularly through the recognition of unique spectral markers.To achieve the goal, we developed and optimized, in a first step, the preparation of samples derived from traditional 2D and 3D lrECM cell cultures in order to preserve their morphological and molecular relevance for FTIR microspectroscopic analysis. We then highlighted the importance of the influence of the growth environment on the cellular phenotype by comparing spectra of 2D- and 3D-cultured breast cancer cell lines between them. A particular focus was placed to establish a correlation between FTIR spectral data and publicly available microarray-based gene expression patterns of the whole series of breast cancer cell lines grown in 2D and 3D lrECM cultures. Our results revealed that, although based on completely different principles, gene expression profiling and FTIR spectroscopy are similarly sensitive to both the cell line identity and the phenotypes induced by cell culture conditions. We also identified by FTIR imaging changes in the chemical content occurring in the microenvironment surrounding cell spheroids grown in 3D lrECM culture model. Finally, we illustrated the impact of the in vivo-like microenvironment on the IR spectra of breast cancer cell lines grown in 3D lrECM co-culture with fibroblasts and compared them with spectra of cell lines grown in 3D lrECM monoculture. Unsupervised statistical data analyses reported that cells grown in 3D co-cultures produce spectral phenotypes similar to the ones observed in FFPE tumor tissue sections from breast carcinoma patients. Altogether, our results suggest that FFPE samples prepared from 3D lrECM cultures of breast cancer cell lines and studied by FTIR microspectroscopic imaging provide reliable information that could be integrated in the setting up of a recognition model aiming to identify and interpret specific spectral signatures of cells present in breast tumor tissue sections.
Le cancer du sein est une maladie très hétérogène, tant au niveau clinique que biologique. Cette hétérogénéité rend impossible la caractérisation moléculaire complète des cellules cancéreuses individuelles dans la pratique clinique courante. Dans ce contexte, l’imagerie infrarouge à transformée de Fourier (FTIR) des coupes tissulaires permet d'obtenir pour chaque pixel d'une image de tissu des centaines de marqueurs potentiels indépendants, ce qui pourrait faire de cette technique un outil particulièrement puissant pour identifier des différents types et sous-types cellulaires. L'interprétation des spectres infrarouges (IR) enregistrés à partir des coupes histologiques nécessite cependant une calibration qui fait actuellement défaut. Cette calibration pourrait être obtenue à partir de lignées cellulaires tumorales bien caractérisées. Traditionnellement, les cellules épithéliales mammaires sont étudiées in vitro sous forme de monocouches adhérentes bidimensionnelles (2D), ce qui conduit à l'altération de la communication entre les cellules et leur environnement et, par conséquent, à la perte de l’architecture et de la fonction du tissu épithélial. Un certain nombre d'interactions physiologiques clés peuvent être rétablies en utilisant des systèmes de culture tridimensionnelle (3D) dans une matrice extracellulaire riche en laminine (lrECM). L'objectif de cette thèse consiste à étudier par imagerie FTIR l'influence du microenvironnement (via une comparaison entre les cultures 2D et 3D lrECM ou les cultures 3D lrECM en présence ou en l’absence de fibroblastes) sur une série de treize lignées de cellules tumorales mammaires humaines bien caractérisées et à déterminer les conditions de culture générant des phénotypes spectraux qui se rapprochent le plus de ceux observés dans les tissus tumoraux. Au cours de ce travail, nous avons mis au point la culture des lignées cellulaires dans un modèle 3D lrECM ainsi qu’une méthodologie de préparation des échantillons offrant la possibilité de les comparer de manière pertinente avec les cellules cancéreuses présentes dans les coupes histologiques. De même, nous avons étudié par imagerie FTIR les effets du microenvironnement sur les lignées de cellules tumorales et inversement. Pour les lignées investiguées, le passage d’une culture 2D à une culture 3D lrECM s’accompagne, en effet, de modifications du spectre IR étroitement corrélées aux modifications du transcriptome. Les marqueurs spectraux indiquent également que l’environnement 3D génère un phénotype cellulaire proche de celui trouvé dans les coupes histologiques. De manière intéressante, cette proximité est d’autant plus renforcée en présence de fibroblastes dans le milieu de culture.
Doctorat en Sciences agronomiques et ingénierie biologique
info:eu-repo/semantics/nonPublished

Hand-held optical imagers are developed towards clinical breast cancer imaging. Herein, a Gen-2 hand-held optical imager has been developed with unique features: (i) image curved breast tissues with ~86% surface contact, and (ii) perform reflectance and transillumination imaging using the novel forked probe heads. Extensive phantom studies were performed using 1% Liposyn solution (background, ~ 300 ml and 1000 ml volumes) and 0.45 cc India Ink (absorption) targets, under different target:background contrast ratios and target depths. Two-dimensional surface images detected target(s) up to 2.5 cm deep via reflectance imaging, and up to 5 cm deep via transillumination imaging. Preliminary studies on gel-based breast phantoms (~700 ml) detected targets via reflectance and transillumination imaging. Preliminary in-vivo reflectance studies on normal and cancerous breast tissues also detected targets, although with artifacts. In future, the portable Gen-2 imager has potential for clinical breast imaging via reflectance and transillumination approach after extensive in-vivo studies.

A significant challenge in the surgical resection of tumors is accurate identification of tumor margins. Current methods for margin detection are time-intensive and often result in incomplete tumor excision and recurrence of disease. The objective of this project was to develop a near-infrared narrowband imaging (NIR NBI) system to image tumor and its margins in real-time during surgery utilizing the contrast provided by gold nanoparticles (GNPs). NIR NBI images narrow wavelength bands to enhance contrast from plasmonic particles in a widefield, portable and non-contact device that is clinically compatible for real-time tumor margin demarcation. GNPs have recently gained significant traction as nanovectors for combined imaging and photothermal therapy of tumors. Delivered systemically, GNPs preferentially accumulate at the tumor site via the enhanced permeability and retention effect, and when irradiated with NIR light, produce sufficient heat to treat tumor tissue. The NIR NBI system consists of 1) two LED's: green (530 nm) and NIR (780 nm) LED for illuminating the blood vessels and GNP, respectively, 2) a filter wheel for wavelength selection, and 3) a CCD to collect reflected light from the sample. The NIR NBI system acquires and processes images at a rate of at least 6 frames per second. We have developed custom control software with a graphical user interface that handles both image acquisition and processing/display in real-time. We used mice with a subcutaneous tumor xenograft model that received intravenous administration and topical administration of gold nanoshells and gold nanorods. We determined the GNP's distribution and accumulation pattern within tumors using NIR NBI. Ex vivo NIR NBI of tumor xenografts accumulated with GNPs delivered systemically, demonstrated a highly heterogeneous distribution of GNP within the tumor with higher accumulation at the cortex. GNPs were observed in unique patterns surrounding the perivascular region. The GNPs clearly defined the tumor while surrounding normal tissue did not indicate the presence of particles. In addition, we present results from NBI of tumors that received topical delivery of conjugated GNPs. We determined that tumor labeling using topical delivery approach resulted in a more homogenous distribution of GNPs compared to the systemic delivery approach. Finally, we present results from the on-going in vivo tumor margin imaging studies using NIR NBI. Our results demonstrate the feasibility of NIR NBI in demarcating tumor margins during surgical resection and potentially guiding photo-thermal ablation of tumors.
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Breast cancer is fast becoming the leading cause of mortality in women worldwide. As of this year, there are more than 3.1 million women with a history of breast cancer in the U.S., and about 41,760 women are expected to die from this disease. Neoadjuvant chemotherapy (NAC) has become a well-established therapy in the treatment of patients with locally advanced or primarily inoperable breast cancer. It consists of 3-9 months of drug treatment to shrink the tumor size before surgical removal of any remaining mass. A pathological complete response (pCR) is defined as complete disappearance of the tumor before surgery and correlates with 5-year overall survival of the treated patient. However, only 15-40% of subjects who undergo NAC will achieve a pCR, while the remaining patients do not benefit from a therapy that has considerable side effects. In this Ph.D. thesis, I explore the potential of diffuse optical tomography (DOT) for breast cancer imaging and NAC monitoring. The overall objective is two-fold. First, I seek to identify breast cancer patients who will not respond to NAC shortly after the initiation of a 5-9 months therapy regimen. Identifying these patients early will allow a switch to a more promising therapy and avoiding months of ineffective therapy with a drug regimen that has considerable side effects. Second, I use the optical data simultaneously obtained from the contralateral, non-tumor bearing breast to better understand the factors that modulate breast density and the source of its contrast in DOT. This work analyzed DOT data from 105 patients with stage II-III breast cancer under NAC regimen. Data processing and image analysis protocols were developed to more effectively evaluate static tissue contrast and dynamic functional imaging of the breast. Notably, we observed that there are differences in the time evolution of DOT features between pCR and non-pCR tumors under NAC, and DOT features can contribute to the successful prediction of pCR status from pretreatment imaging. Lastly, our analysis demonstrated a positive correlation between DOT feature and mammographic density classification, which could lead to research on the potential use of DOT as a predictor of breast cancer as well as an assessment tool to longitudinally evaluate the efficacy of chemoprevention strategies. These findings represent important steps towards the translation of DOT into current clinical workflow to contribute to better-personalized breast cancer therapies and breast cancer risk management.

Nationalism: Past as Prologue began as a single volume being compiled by Ad Akande, a scholar from South Africa, who proposed it to me as co-author about two years ago. The original idea was to examine how the damaging roots of nationalism have been corroding political systems around the world, and creating dangerous obstacles for necessary international cooperation. Since I (Bruce E. Johansen) has written profusely about climate change (global warming, a.k.a. infrared forcing), I suggested a concerted effort in that direction. This is a worldwide existential threat that affects every living thing on Earth. It often compounds upon itself, so delays in reducing emissions of fossil fuels are shortening the amount of time remaining to eliminate the use of fossil fuels to preserve a livable planet. Nationalism often impedes solutions to this problem (among many others), as nations place their singular needs above the common good. Our initial proposal got around, and abstracts on many subjects arrived. Within a few weeks, we had enough good material for a 100,000-word book. The book then fattened to two moderate volumes and then to four two very hefty tomes. We tried several different titles as good submissions swelled. We also discovered that our best contributors were experts in their fields, which ranged the world. We settled on three stand-alone books:” 1/ nationalism and racial justice. Our first volume grew as the growth of Black Lives Matter following the brutal killing of George Floyd ignited protests over police brutality and other issues during 2020, following the police assassination of Floyd in Minneapolis. It is estimated that more people took part in protests of police brutality during the summer of 2020 than any other series of marches in United States history. This includes upheavals during the 1960s over racial issues and against the war in Southeast Asia (notably Vietnam). We choose a volume on racism because it is one of nationalism’s main motive forces. This volume provides a worldwide array of work on nationalism’s growth in various countries, usually by authors residing in them, or in the United States with ethnic ties to the nation being examined, often recent immigrants to the United States from them. Our roster of contributors comprises a small United Nations of insightful, well-written research and commentary from Indonesia, New Zealand, Australia, China, India, South Africa, France, Portugal, Estonia, Hungary, Russia, Poland, Kazakhstan, Georgia, and the United States. Volume 2 (this one) describes and analyzes nationalism, by country, around the world, except for the United States; and 3/material directly related to President Donald Trump, and the United States. The first volume is under consideration at the Texas A & M University Press. The other two are under contract to Nova Science Publishers (which includes social sciences). These three volumes may be used individually or as a set. Environmental material is taken up in appropriate places in each of the three books. * * * * * What became the United States of America has been strongly nationalist since the English of present-day Massachusetts and Jamestown first hit North America’s eastern shores. The country propelled itself across North America with the self-serving ideology of “manifest destiny” for four centuries before Donald Trump came along. Anyone who believes that a Trumpian affection for deportation of “illegals” is a new thing ought to take a look at immigration and deportation statistics in Adam Goodman’s The Deportation Machine: America’s Long History of Deporting Immigrants (Princeton University Press, 2020). Between 1920 and 2018, the United States deported 56.3 million people, compared with 51.7 million who were granted legal immigration status during the same dates. Nearly nine of ten deportees were Mexican (Nolan, 2020, 83). This kind of nationalism, has become an assassin of democracy as well as an impediment to solving global problems. Paul Krugman wrote in the New York Times (2019:A-25): that “In their 2018 book, How Democracies Die, the political scientists Steven Levitsky and Daniel Ziblatt documented how this process has played out in many countries, from Vladimir Putin’s Russia, to Recep Erdogan’s Turkey, to Viktor Orban’s Hungary. Add to these India’s Narendra Modi, China’s Xi Jinping, and the United States’ Donald Trump, among others. Bit by bit, the guardrails of democracy have been torn down, as institutions meant to serve the public became tools of ruling parties and self-serving ideologies, weaponized to punish and intimidate opposition parties’ opponents. On paper, these countries are still democracies; in practice, they have become one-party regimes….And it’s happening here [the United States] as we speak. If you are not worried about the future of American democracy, you aren’t paying attention” (Krugmam, 2019, A-25). We are reminded continuously that the late Carl Sagan, one of our most insightful scientific public intellectuals, had an interesting theory about highly developed civilizations. Given the number of stars and planets that must exist in the vast reaches of the universe, he said, there must be other highly developed and organized forms of life. Distance may keep us from making physical contact, but Sagan said that another reason we may never be on speaking terms with another intelligent race is (judging from our own example) could be their penchant for destroying themselves in relatively short order after reaching technological complexity. This book’s chapters, introduction, and conclusion examine the worldwide rise of partisan nationalism and the damage it has wrought on the worldwide pursuit of solutions for issues requiring worldwide scope, such scientific co-operation public health and others, mixing analysis of both. We use both historical description and analysis. This analysis concludes with a description of why we must avoid the isolating nature of nationalism that isolates people and encourages separation if we are to deal with issues of world-wide concern, and to maintain a sustainable, survivable Earth, placing the dominant political movement of our time against the Earth’s existential crises. Our contributors, all experts in their fields, each have assumed responsibility for a country, or two if they are related. This work entwines themes of worldwide concern with the political growth of nationalism because leaders with such a worldview are disinclined to co-operate internationally at a time when nations must find ways to solve common problems, such as the climate crisis. Inability to cooperate at this stage may doom everyone, eventually, to an overheated, stormy future plagued by droughts and deluges portending shortages of food and other essential commodities, meanwhile destroying large coastal urban areas because of rising sea levels. Future historians may look back at our time and wonder why as well as how our world succumbed to isolating nationalism at a time when time was so short for cooperative intervention which is crucial for survival of a sustainable earth. Pride in language and culture is salubrious to individuals’ sense of history and identity. Excess nationalism that prevents international co-operation on harmful worldwide maladies is quite another. As Pope Francis has pointed out: For all of our connectivity due to expansion of social media, ability to communicate can breed contempt as well as mutual trust. “For all our hyper-connectivity,” said Francis, “We witnessed a fragmentation that made it more difficult to resolve problems that affect us all” (Horowitz, 2020, A-12). The pope’s encyclical, titled “Brothers All,” also said: “The forces of myopic, extremist, resentful, and aggressive nationalism are on the rise.” The pope’s document also advocates support for migrants, as well as resistance to nationalist and tribal populism. Francis broadened his critique to the role of market capitalism, as well as nationalism has failed the peoples of the world when they need co-operation and solidarity in the face of the world-wide corona virus pandemic. Humankind needs to unite into “a new sense of the human family [Fratelli Tutti, “Brothers All”], that rejects war at all costs” (Pope, 2020, 6-A). Our journey takes us first to Russia, with the able eye and honed expertise of Richard D. Anderson, Jr. who teaches as UCLA and publishes on the subject of his chapter: “Putin, Russian identity, and Russia’s conduct at home and abroad.” Readers should find Dr. Anderson’s analysis fascinating because Vladimir Putin, the singular leader of Russian foreign and domestic policy these days (and perhaps for the rest of his life, given how malleable Russia’s Constitution has become) may be a short man physically, but has high ambitions. One of these involves restoring the old Russian (and Soviet) empire, which would involve re-subjugating a number of nations that broke off as the old order dissolved about 30 years ago. President (shall we say czar?) Putin also has international ambitions, notably by destabilizing the United States, where election meddling has become a specialty. The sight of Putin and U.S. president Donald Trump, two very rich men (Putin $70-$200 billion; Trump $2.5 billion), nuzzling in friendship would probably set Thomas Jefferson and Vladimir Lenin spinning in their graves. The road of history can take some unanticipated twists and turns. Consider Poland, from which we have an expert native analysis in chapter 2, Bartosz Hlebowicz, who is a Polish anthropologist and journalist. His piece is titled “Lawless and Unjust: How to Quickly Make Your Own Country a Puppet State Run by a Group of Hoodlums – the Hopeless Case of Poland (2015–2020).” When I visited Poland to teach and lecture twice between 2006 and 2008, most people seemed to be walking on air induced by freedom to conduct their own affairs to an unusual degree for a state usually squeezed between nationalists in Germany and Russia. What did the Poles then do in a couple of decades? Read Hlebowicz’ chapter and decide. It certainly isn’t soft-bellied liberalism. In Chapter 3, with Bruce E. Johansen, we visit China’s western provinces, the lands of Tibet as well as the Uighurs and other Muslims in the Xinjiang region, who would most assuredly resent being characterized as being possessed by the Chinese of the Han to the east. As a student of Native American history, I had never before thought of the Tibetans and Uighurs as Native peoples struggling against the Independence-minded peoples of a land that is called an adjunct of China on most of our maps. The random act of sitting next to a young woman on an Air India flight out of Hyderabad, bound for New Delhi taught me that the Tibetans had something to share with the Lakota, the Iroquois, and hundreds of other Native American states and nations in North America. Active resistance to Chinese rule lasted into the mid-nineteenth century, and continues today in a subversive manner, even in song, as I learned in 2018 when I acted as a foreign adjudicator on a Ph.D. dissertation by a Tibetan student at the University of Madras (in what is now in a city called Chennai), in southwestern India on resistance in song during Tibet’s recent history. Tibet is one of very few places on Earth where a young dissident can get shot to death for singing a song that troubles China’s Quest for Lebensraum. The situation in Xinjiang region, where close to a million Muslims have been interned in “reeducation” camps surrounded with brick walls and barbed wire. They sing, too. Come with us and hear the music. Back to Europe now, in Chapter 4, to Portugal and Spain, we find a break in the general pattern of nationalism. Portugal has been more progressive governmentally than most. Spain varies from a liberal majority to military coups, a pattern which has been exported to Latin America. A situation such as this can make use of the term “populism” problematic, because general usage in our time usually ties the word into a right-wing connotative straightjacket. “Populism” can be used to describe progressive (left-wing) insurgencies as well. José Pinto, who is native to Portugal and also researches and writes in Spanish as well as English, in “Populism in Portugal and Spain: a Real Neighbourhood?” provides insight into these historical paradoxes. Hungary shares some historical inclinations with Poland (above). Both emerged from Soviet dominance in an air of developing freedom and multicultural diversity after the Berlin Wall fell and the Soviet Union collapsed. Then, gradually at first, right wing-forces began to tighten up, stripping structures supporting popular freedom, from the courts, mass media, and other institutions. In Chapter 5, Bernard Tamas, in “From Youth Movement to Right-Liberal Wing Authoritarianism: The Rise of Fidesz and the Decline of Hungarian Democracy” puts the renewed growth of political and social repression into a context of worldwide nationalism. Tamas, an associate professor of political science at Valdosta State University, has been a postdoctoral fellow at Harvard University and a Fulbright scholar at the Central European University in Budapest, Hungary. His books include From Dissident to Party Politics: The Struggle for Democracy in Post-Communist Hungary (2007). Bear in mind that not everyone shares Orbán’s vision of what will make this nation great, again. On graffiti-covered walls in Budapest, Runes (traditional Hungarian script) has been found that read “Orbán is a motherfucker” (Mikanowski, 2019, 58). Also in Europe, in Chapter 6, Professor Ronan Le Coadic, of the University of Rennes, Rennes, France, in “Is There a Revival of French Nationalism?” Stating this title in the form of a question is quite appropriate because France’s nationalistic shift has built and ebbed several times during the last few decades. For a time after 2000, it came close to assuming the role of a substantial minority, only to ebb after that. In 2017, the candidate of the National Front reached the second round of the French presidential election. This was the second time this nationalist party reached the second round of the presidential election in the history of the Fifth Republic. In 2002, however, Jean-Marie Le Pen had only obtained 17.79% of the votes, while fifteen years later his daughter, Marine Le Pen, almost doubled her father's record, reaching 33.90% of the votes cast. Moreover, in the 2019 European elections, re-named Rassemblement National obtained the largest number of votes of all French political formations and can therefore boast of being "the leading party in France.” The brutality of oppressive nationalism may be expressed in personal relationships, such as child abuse. While Indonesia and Aotearoa [the Maoris’ name for New Zealand] hold very different ranks in the United Nations Human Development Programme assessments, where Indonesia is classified as a medium development country and Aotearoa New Zealand as a very high development country. In Chapter 7, “Domestic Violence Against Women in Indonesia and Aotearoa New Zealand: Making Sense of Differences and Similarities” co-authors, in Chapter 8, Mandy Morgan and Dr. Elli N. Hayati, from New Zealand and Indonesia respectively, found that despite their socio-economic differences, one in three women in each country experience physical or sexual intimate partner violence over their lifetime. In this chapter ther authors aim to deepen understandings of domestic violence through discussion of the socio-economic and demographic characteristics of theit countries to address domestic violence alongside studies of women’s attitudes to gender norms and experiences of intimate partner violence. One of the most surprising and upsetting scholarly journeys that a North American student may take involves Adolf Hitler’s comments on oppression of American Indians and Blacks as he imagined the construction of the Nazi state, a genesis of nationalism that is all but unknown in the United States of America, traced in this volume (Chapter 8) by co-editor Johansen. Beginning in Mein Kampf, during the 1920s, Hitler explicitly used the westward expansion of the United States across North America as a model and justification for Nazi conquest and anticipated colonization by Germans of what the Nazis called the “wild East” – the Slavic nations of Poland, the Baltic states, Ukraine, and Russia, most of which were under control of the Soviet Union. The Volga River (in Russia) was styled by Hitler as the Germans’ Mississippi, and covered wagons were readied for the German “manifest destiny” of imprisoning, eradicating, and replacing peoples the Nazis deemed inferior, all with direct references to events in North America during the previous century. At the same time, with no sense of contradiction, the Nazis partook of a long-standing German romanticism of Native Americans. One of Goebbels’ less propitious schemes was to confer honorary Aryan status on Native American tribes, in the hope that they would rise up against their oppressors. U.S. racial attitudes were “evidence [to the Nazis] that America was evolving in the right direction, despite its specious rhetoric about equality.” Ming Xie, originally from Beijing, in the People’s Republic of China, in Chapter 9, “News Coverage and Public Perceptions of the Social Credit System in China,” writes that The State Council of China in 2014 announced “that a nationwide social credit system would be established” in China. “Under this system, individuals, private companies, social organizations, and governmental agencies are assigned a score which will be calculated based on their trustworthiness and daily actions such as transaction history, professional conduct, obedience to law, corruption, tax evasion, and academic plagiarism.” The “nationalism” in this case is that of the state over the individual. China has 1.4 billion people; this system takes their measure for the purpose of state control. Once fully operational, control will be more subtle. People who are subject to it, through modern technology (most often smart phones) will prompt many people to self-censor. Orwell, modernized, might write: “Your smart phone is watching you.” Ming Xie holds two Ph.Ds, one in Public Administration from University of Nebraska at Omaha and another in Cultural Anthropology from the Chinese Academy of Social Sciences, Beijing, where she also worked for more than 10 years at a national think tank in the same institution. While there she summarized news from non-Chinese sources for senior members of the Chinese Communist Party. Ming is presently an assistant professor at the Department of Political Science and Criminal Justice, West Texas A&M University. In Chapter 10, analyzing native peoples and nationhood, Barbara Alice Mann, Professor of Honours at the University of Toledo, in “Divide, et Impera: The Self-Genocide Game” details ways in which European-American invaders deprive the conquered of their sense of nationhood as part of a subjugation system that amounts to genocide, rubbing out their languages and cultures -- and ultimately forcing the native peoples to assimilate on their own, for survival in a culture that is foreign to them. Mann is one of Native American Studies’ most acute critics of conquests’ contradictions, and an author who retrieves Native history with a powerful sense of voice and purpose, having authored roughly a dozen books and numerous book chapters, among many other works, who has traveled around the world lecturing and publishing on many subjects. Nalanda Roy and S. Mae Pedron in Chapter 11, “Understanding the Face of Humanity: The Rohingya Genocide.” describe one of the largest forced migrations in the history of the human race, the removal of 700,000 to 800,000 Muslims from Buddhist Myanmar to Bangladesh, which itself is already one of the most crowded and impoverished nations on Earth. With about 150 million people packed into an area the size of Nebraska and Iowa (population less than a tenth that of Bangladesh, a country that is losing land steadily to rising sea levels and erosion of the Ganges river delta. The Rohingyas’ refugee camp has been squeezed onto a gigantic, eroding, muddy slope that contains nearly no vegetation. However, Bangladesh is majority Muslim, so while the Rohingya may starve, they won’t be shot to death by marauding armies. Both authors of this exquisite (and excruciating) account teach at Georgia Southern University in Savannah, Georgia, Roy as an associate professor of International Studies and Asian politics, and Pedron as a graduate student; Roy originally hails from very eastern India, close to both Myanmar and Bangladesh, so he has special insight into the context of one of the most brutal genocides of our time, or any other. This is our case describing the problems that nationalism has and will pose for the sustainability of the Earth as our little blue-and-green orb becomes more crowded over time. The old ways, in which national arguments often end in devastating wars, are obsolete, given that the Earth and all the people, plants, and other animals that it sustains are faced with the existential threat of a climate crisis that within two centuries, more or less, will flood large parts of coastal cities, and endanger many species of plants and animals. To survive, we must listen to the Earth, and observe her travails, because they are increasingly our own.

Near infrared (NIR) spectroscopy (650-1100 nm) has been applicated for monitoring of brain and muscle oxygenation. Although optical breast imaging instrumentation, using one to four wavelengths in the NIR range, has been developed, very few in vivo breast spectral data are available. This study reports the optical map of breasts and an accurate characterization of spectroscopic fatures by derivative and difference spectroscopy. The bands due to water, lipids and deoxy-hemoglobin have been precisely identified. Results indicate that there is a large variability of breast composition at different locations in the same subject as well as amongst subjects.

Review question / Objective: Whether is indocyanine green fluorescence imaging-guided lymphadenectomy feasible to improve the number of lymph node dissections during radical gastrectomy in patients with gastric cancer undergoing curative resection? Condition being studied: Gastric cancer was the sixth most common malignant tumor and the fourth leading cause of cancer-related death in the world. Radical lymphadenectomy was a standard procedure in radical gastrectomy for gastric cancer. The retrieval of more lymph nodes was beneficial for improving the accuracy of tumor staging and the long-term survival of patients with gastric cancer. Indocyanine green(ICG) near-infrared fluorescent imaging has been found to provide surgeons with effective visualization of the lymphatic anatomy. As a new surgical navigation technique, ICG near-infrared fluorescent imaging was a hot spot and had already demonstrated promising results in the localization of lymph nodes during surgery in patients with breast cancer, non–small cell lung cancer, and gastric cancer. In addition, ICG had increasingly been reported in the localization of tumor, lymph node dissection, and the evaluation of anastomotic blood supply during radical gastrectomy for gastric cancer. However, it remained unclear whether ICG fluorescence imaging would assist surgeons in performing safe and sufficient lymphadenectomy.

The necessity to improve broiler thermotolerance and live performance led to the following hypothesis: Appropriate comprehensive incubation treatments that include significant temperature management changes will promote angiogenesis and will improve acquisition of thermotolerance and carcass quality of heavy broilers through epigenetic adaptation. It was based on the following questions: 1. Can TM during embryogenesis of broilers induce a longer-lasting thermoregulatory memory (up to marketing age of 10 wk) that will improve acquisition of thermotolerance as well as increased breast meat yield in heavy broilers? 2. The improved sensible heat loss (SHL) suggests an improved peripheral vasodilation process. Does elevated temperature during incubation affect vasculogenesis and angiogenesis processes in the chick embryo? Will such create subsequent advantages for heavy broilers coping with adverse hot conditions? 3. What are the changes that occur in the PO/AH that induce the changes in the threshold response for heat production/heat loss based on the concept of epigenetic temperature adaptation? The original objectives of this study were as follow: a. to assess the improvement of thermotolerance efficiency and carcass quality of heavy broilers (~4 kg); b. toimproveperipheral vascularization and angiogenesis that improve sensible heat loss (SHL); c. to study the changes in the PO/AH thermoregulatory response for heat production/losscaused by modulating incubation temperature. To reach the goals: a. the effect of TM on performance and thermotolerance of broilers reared to 10 wk of age was studied. b. the effect of preincubation heating with an elevated temperature during the 1ˢᵗ 3 to 5 d of incubation in the presence of modified fresh air flow coupled with changes in turning frequency was elucidated; c.the effect of elevated temperature on vasculogenesis and angiogenesis was determined using in ovo and whole embryo chick culture as well as HIF-1α VEGF-α2 VEGF-R, FGF-2, and Gelatinase A (MMP2) gene expression. The effects on peripheral blood system of post-hatch chicks was determined with an infrared thermal imaging technique; c. the expression of BDNF was determined during the development of the thermal control set-point in the preoptic anterior hypothalamus (PO/AH). Background to the topic: Rapid growth rate has presented broiler chickens with seriousdifficulties when called upon to efficiently thermoregulate in hot environmental conditions. Being homeotherms, birds are able to maintain their body temperature (Tb) within a narrow range. An increase in Tb above the regulated range, as a result of exposure to environmental conditions and/or excessive metabolic heat production that often characterize broiler chickens, may lead to a potentially lethal cascade of irreversible thermoregulatory events. Exposure to temperature fluctuations during the perinatal period has been shown to lead to epigenetic temperature adaptation. The mechanism for this adaptation was based on the assumption that environmental factors, especially ambient temperature, have a strong influence on the determination of the “set-point” for physiological control systems during “critical developmental phases.” Recently, Piestunet al. (2008) demonstrated for the first time that TM (an elevated incubation temperature of 39.5°C for 12 h/d from E7 to E16) during the development/maturation of the hypothalamic-hypophyseal-thyroid axis (thermoregulation) and the hypothalamic-hypophyseal-adrenal axis (stress) significantly improved the thermotolerance and performance of broilers at 35 d of age. These phenomena raised two questions that were addressed in this project: 1. was it possible to detect changes leading to the determination of the “set point”; 2. Did TM have a similar long lasting effect (up to 70 d of age)? 3. Did other TM combinations (pre-heating and heating during the 1ˢᵗ 3 to 5 d of incubation) coupled with changes in turning frequency have any performance effect? The improved thermotolerance resulted mainly from an efficient capacity to reduce heat production and the level of stress that coincided with an increase in SHL (Piestunet al., 2008; 2009). The increase in SHL (Piestunet al., 2009) suggested an additional positive effect of TM on vasculogenesis and angiogensis. 4. In order to sustain or even improve broiler performance, TM during the period of the chorioallantoic membrane development was thought to increase vasculogenesis and angiogenesis providing better vasodilatation and by that SHL post-hatch.