Optical spectroscopy-based imaging techniques for the diagnosis of breast cancer: A novel approach

There have been substantial advancements in optical spectroscopy-based imaging techniques in recent years. These developments can potentially herald a transformational change in the diagnostic pathway for diseases such as cancer. In this paper, we review the clinical and engineering aspects of novel optical spectroscopy-based imaging tools. We provide a comprehensive analysis of optical and non-optical spectroscopy-based breast cancer diagnosis techniques vis-à-vis the current standard techniques such as X-Ray mammography, ultrasonography, and tissue biopsy. The recent advancements in optical spectroscopy-based imaging systems such as Transillumination Imaging (TI) and the various types of Diffuse Optical Imaging (DOI) systems (parallel-plate, bed-based, and handheld) are examined. The engineering aspects, including mechanical, electronics, optics, automatic interpretation using artificial intelligence (AI), and ergonomics are discussed. The abilities of these technologies for measuring several cancer biomarkers such as hemoglobin, water, lipid, collagen, oxygen saturation (SO2), and tissue oxygenation index (TOI) are investigated. This article critically assesses the diagnostic ability and practical deployment of these new technologies to differentiate between the normal and cancerous tissue

One-dimensional convolutional neural network model for breast cancer subtypes classification and biochemical content evaluation using micro-FTIR hyperspectral images

Breast cancer treatment still remains a challenge, where molecular subtypes classification plays a crucial role in selecting appropriate and specific therapy. The four subtypes are Luminal A (LA), Luminal B (LB), HER2 subtype, and Triple-Negative Breast Cancer (TNBC). Immunohistochemistry is the gold-standard evaluation, although interobserver variations are reported and molecular signatures identification is time-consuming. Fourier transform infrared micro-spectroscopy with machine learning approaches have been used to evaluate cancer samples, presenting biochemical-related explainability. However, this explainability is harder when using deep learning. This study created a 1D deep learning tool for breast cancer subtype evaluation and biochemical contribution. Sixty hyperspectral images were acquired from a human breast cancer microarray. K-Means clustering was applied to select tissue and paraffin spectra. CaReNet-V1, a novel 1D convolutional neural network, was developed to classify breast cancer (CA) and adjacent tissue (AT), and molecular subtypes. A 1D adaptation of Grad-CAM was applied to assess the biochemical impact to the classifications. CaReNet-V1 effectively classified CA and AT (test accuracy of 0.89), as well as HER2 and TNBC subtypes (0.83 and 0.86), with greater difficulty for LA and LB (0.74 and 0.68). The model enabled the evaluation of the most contributing wavenumbers to the predictions, providing a direct relationship with the biochemical content. Therefore, CaReNet-V1 and hyperspectral images is a potential approach for breast cancer biopsies assessment, providing additional information to the pathology report. Biochemical content impact feature may be used for other studies, such as treatment efficacy evaluation and development new diagnostics and therapeutic methods.Comment: 23 pages, 5 figures, 2 table

A study of Raman spectroscopy for the early detection and characterization of prostate cancer using blood plasma and prostate tissue biopsy.

Prostate cancer (PC) is the most common cancer in men after non-melanoma skin cancer in the United Kingdom (Cancer Research UK, 2019). Current diagnostic methods (PSA, DRE, MRI & prostate biopsy) have limitations as these are unable to distinguish between low-risk cancers that do not need active treatment from cancers which are more likely to progress. In addition, prostate biopsy is invasive with potential side effects. There is an urgent need to identify new biomarkers for early diagnosis and prognostication in PC. Raman spectroscopy (RS) is an optical technique that utilises molecular-specific, inelastic scattering of light photons to interrogate biological samples. When laser light is incident on a biological sample, the photons from the laser light can interact with the intramolecular bonds present within the sample. The Raman spectrum is a direct function of the molecular composition of the tissue, providing a molecular fingerprint of the phenotypic expression of the cells and tissues, which can give good objective information regarding the pathological state of the biological sample under interrogation. We applied a technique of drop coating deposition Raman (DCDR) spectroscopy using both blood plasma and sera to see if a more accurate prediction of the presence and progression of prostate cancer could be achieved than PSA which would allow for blood sample triage of patients into at risk groups. 100 participants were recruited for this study (100 blood plasma and 100 serum samples). Secondly, 79 prostate tissue samples (from the same cohort) were interrogated with the aid of Raman micro-spectroscopy to ascertain if Raman spectroscopy can provide molecular fingerprint that can be utilised for real time in vivo analysis. Multivariate analysis of support vector machine (SVM) learning and linear discriminant analysis (LDA) were utilised differently to test the performance accuracy of the discriminant model for distinguishing between benign and malignant mean plasma spectra. SVM gave a better performance accuracy than LDA with sensitivity and specificity of 96% and 97% respectively and an area under the curve (AUC) of 0.98 as opposed to sensitivity and specificity of 51% and 80% respectively with AUC of 0.74 using LDA. Slightly lower performance accuracy was also observed when blood serum mean spectra analysis was compared with blood plasma mean spectra analysis for both machine learning algorithms (SVM & LDA). Tissue spectral analysis on the other hand recorded an overall accuracy of 80.8% and AUC of 0.82 with the SVM algorithm compared to performance accuracy of 75% and AUC of 0.77 with LDA algorithm (better performance noted with the SVM algorithm). The small sample size of 79 prostate biopsy tissues was responsible for the low sensitivity and specificity. Therefore, the tissues were insufficient to describe all the variances in each group as well as the variability of the gold standard technique. Conclusion: Raman spectroscopy could be a potentially useful technique in the management of Prostate Cancer in areas such as tissue diagnosis, assessment of surgical margin after radical prostatectomy, detection of metastasis, Prostate Cancer screening as well as monitoring and prognosticating patients with Prostate Cancer. However, more needs to be done to validate the approaches outlined in this thesis using prospective collection of new samples to test the classification models independently with sufficient statistical power. At this stage only the fluid-based models are likely to be large enough for this validation process

Optical biopsy identification and grading of gliomas using label-free visible resonance Raman spectroscopy.

Glioma is one of the most refractory types of brain tumor. Accurate tumor boundary identification and complete resection of the tumor are essential for glioma removal during brain surgery. We present a method based on visible resonance Raman (VRR) spectroscopy to identify glioma margins and grades. A set of diagnostic spectral biomarkers features are presented based on tissue composition changes revealed by VRR. The Raman spectra include molecular vibrational fingerprints of carotenoids, tryptophan, amide I/II/III, proteins, and lipids. These basic in situ spectral biomarkers are used to identify the tissue from the interface between brain cancer and normal tissue and to evaluate glioma grades. The VRR spectra are also analyzed using principal component analysis for dimension reduction and feature detection and support vector machine for classification. The cross-validated sensitivity, specificity, and accuracy are found to be 100%, 96.3%, and 99.6% to distinguish glioma tissues from normal brain tissues, respectively. The area under the receiver operating characteristic curve for the classification is about 1.0. The accuracies to distinguish normal, low grade (grades I and II), and high grade (grades III and IV) gliomas are found to be 96.3%, 53.7%, and 84.1% for the three groups, respectively, along with a total accuracy of 75.1%. A set of criteria for differentiating normal human brain tissues from normal control tissues is proposed and used to identify brain cancer margins, yielding a diagnostic sensitivity of 100% and specificity of 71%. Our study demonstrates the potential of VRR as a label-free optical molecular histopathology method used for in situ boundary line judgment for brain surgery in the margins

Dual-path convolutional neural network using micro-FTIR imaging to predict breast cancer subtypes and biomarkers levels: estrogen receptor, progesterone receptor, HER2 and Ki67

Breast cancer molecular subtypes classification plays an import role to sort patients with divergent prognosis. The biomarkers used are Estrogen Receptor (ER), Progesterone Receptor (PR), HER2, and Ki67. Based on these biomarkers expression levels, subtypes are classified as Luminal A (LA), Luminal B (LB), HER2 subtype, and Triple-Negative Breast Cancer (TNBC). Immunohistochemistry is used to classify subtypes, although interlaboratory and interobserver variations can affect its accuracy, besides being a time-consuming technique. The Fourier transform infrared micro-spectroscopy may be coupled with deep learning for cancer evaluation, where there is still a lack of studies for subtypes and biomarker levels prediction. This study presents a novel 2D deep learning approach to achieve these predictions. Sixty micro-FTIR images of 320x320 pixels were collected from a human breast biopsies microarray. Data were clustered by K-means, preprocessed and 32x32 patches were generated using a fully automated approach. CaReNet-V2, a novel convolutional neural network, was developed to classify breast cancer (CA) vs adjacent tissue (AT) and molecular subtypes, and to predict biomarkers level. The clustering method enabled to remove non-tissue pixels. Test accuracies for CA vs AT and subtype were above 0.84. The model enabled the prediction of ER, PR, and HER2 levels, where borderline values showed lower performance (minimum accuracy of 0.54). Ki67 percentage regression demonstrated a mean error of 3.6%. Thus, CaReNet-V2 is a potential technique for breast cancer biopsies evaluation, standing out as a screening analysis technique and helping to prioritize patients.Comment: 32 pages, 3 figures, 6 table

Infrared Thermography for the Assessment of Lumbar Sympathetic Blocks in Patients with Complex Regional Pain Syndrome

[ES] El síndrome de dolor regional complejo (SDRC) es un trastorno de dolor crónico debilitante que suele afectar a una extremidad, y se caracteriza por su compleja e incomprendida fisiopatología subyacente, lo que supone un reto para su diagnóstico y tratamiento. Para evitar el deterioro de la calidad de vida de los pacientes, la consecución de un diagnóstico y tratamiento tempranos marca un punto de inflexión. Entre los diferentes tratamientos, los bloqueos simpáticos lumbares (BSLs) tienen como objetivo aliviar el dolor y reducir algunos signos simpáticos de la afección. Este procedimiento intervencionista se lleva a cabo inyectando anestesia local alrededor de los ganglios simpáticos y, hasta ahora, se realiza frecuentemente bajo el control de diferentes técnicas de imagen, como los ultrasonidos o la fluoroscopia. Dado que la termografía infrarroja (TIR) ha demostrado ser una herramienta eficaz para evaluar la temperatura de la piel, y teniendo en cuenta el efecto vasodilatador que presentan los anestésicos locales inyectados, se ha considerado el uso de la IRT para la evaluación de los BSLs. El objetivo de esta tesis es, estudiar la capacidad de la TIR como una técnica complementaria para la evaluación de la eficacia en la ejecución de los BSLs. Para cumplir este objetivo, se han realizado tres estudios implementando la TIR en pacientes diagnosticados de SDRC de miembros inferiores sometidos a BSLs. El primer estudio se centra en la viabilidad de la TIR como herramienta complementaria para la evaluación de la eficacia ejecución de los BSLs. Cuando se realizan los BSLs, la colocación correcta de la aguja es crítica para llevar realizar el procedimiento técnicamente correcto y, en consecuencia, para lograr los resultados clínicos deseados. Para verificar la posición de la aguja, tradicionalmente se han utilizado técnicas de imagen, sin embargo, los BSLs bajo control fluoroscópico no siempre aseguran su exacta ejecución. Por este motivo, se han aprovechado las alteraciones térmicas inducidas por los anestésicos locales y se han evaluado mediante la TIR. Así, cuando en las imágenes infrarrojas se observaron cambios térmicos en la planta del pie afectado tras la inyección de lidocaína, se consideró que el BSL era exitoso. El segundo estudio trata del análisis cuantitativo de los datos térmicos recogidos en el entorno clínico a partir de diferentes parámetros basados en las temperaturas extraídas de ambos pies. Según los resultados, para predecir adecuadamente los BSLs exitosos, se deberían analizar las temperaturas de las plantas de los pies durante los primeros cuatro minutos tras la inyección del anestésico local. Así, la aplicación de la TIR en el entorno clínico podría ser de gran ayuda para evaluar la eficacia de ejecución de los BSLs mediante la evaluación de las temperaturas de los pies en tiempo real. Por último, el tercer estudio aborda el análisis cuantitativo mediante la implementación de herramientas de machine learning (ML) para evaluar su capacidad de clasificar automáticamente los BSLs. En este estudio se han utilizado una serie de características térmicas extraídas de las imágenes infrarrojas para evaluar cuatro algoritmos de ML para tres momentos diferentes después del instante de referencia (inyección de lidocaína). Los resultados indican que los cuatro modelos evaluados presentan buenos rendimientos para clasificar automáticamente los BSLs entre exitosos y fallidos. Por lo tanto, la combinación de parámetros térmicos junto con de clasificación ML muestra ser eficaz para la clasificación automática de los procedimientos de BSLs. En conclusión, el uso de la TIR como técnica complementaria en la práctica clínica diaria para la evaluación de los BSLs ha demostrado ser totalmente eficaz. Dado que es un método objetivo y relativamente sencillo de implementar, puede permitir que los médicos especialistas en dolor identifiquen los bloqueos realizados fallidos y, en consecuencia, puedan revertir esta situación.[CA] La síndrome de dolor regional complex (SDRC) és un trastorn de dolor crònic debilitant que sol afectar una extremitat, i es caracteritza per la seua complexa i incompresa fisiopatologia subjacent, la qual cosa suposa un repte per al seu diagnòstic i tractament. Per a evitar la deterioració de la qualitat de vida dels pacients, la consecució d'un diagnòstic i tractament primerencs marca un punt d'inflexió. Entre els diferents tractaments , els bloquejos simpàtics lumbars (BSLs) tenen com a objectiu alleujar el dolor i reduir alguns signes simpàtics de l'afecció. Aquest procediment intervencionista es duu a terme injectant anestèsia local al voltant dels ganglis simpàtics i, fins ara, es realitza freqüentment sota el control de diferents tècniques d'imatge, com els ultrasons o la fluoroscopia. Atés que la termografia infraroja (TIR) ha demostrat ser una eina eficaç per a avaluar la temperatura de la pell, i tenint en compte l'efecte vasodilatador que presenten els anestèsics locals injectats, s'ha considerat l'ús de la TIR per a l'avaluació dels BSLs. L'objectiu d'aquesta tesi és, estudiar la capacitat de la TIR com una tècnica complementària per a l'avaluació de l'eficàcia en l'execució dels BSLs. Per a complir aquest objectiu, s'han realitzat tres estudis implementant la TIR en pacients diagnosticats de SDRC de membres inferiors sotmesos a BSLs. El primer estudi avalua la viabilitat de la TIR com a eina complementària per a l'analisi de l'eficàcia en l'execució dels BSLs. Quan es realitzen els BSLs, la col·locació correcta de l'agulla és crítica per a dur a terme el procediment tècnicament correcte i, en conseqüència, per a aconseguir els resultats clínics desitjats. Per a verificar la posició de l'agulla, tradicionalment s'han utilitzat tècniques d'imatge, no obstant això, els BSLs baix control fluoroscòpic no sempre asseguren la seua exacta execució. Per aquest motiu, s'han aprofitat les alteracions tèrmiques induïdes pels anestèsics locals i s'han avaluat mitjançant la TIR. Així, quan en les imatges infraroges es van observar canvis tèrmics en la planta del peu afectat després de la injecció de lidocaIna, es va considerar que el BSL era exitós. El segon estudi tracta de l'anàlisi quantitativa de les dades tèrmiques recollides en l'entorn clínic a partir de diferents paràmetres basats en les temperatures extretes d'ambdós peus. Segons els resultats, per a predir adequadament l'execució exitosa d'un BSL, s'haurien d'analitzar les temperatures de les plantes dels peus durant els primers quatre minuts després de la injecció de l'anestèsic local. Així, l'implementació de la TIR en l'entorn clínic podria ser de gran ajuda per a avaluar l'eficàcia d'execució dels BSLs mitjançant l'avaluació de les temperatures dels peus en temps real. El tercer estudi aborda l'anàlisi quantitativa mitjançant la implementació d'eines machine learning (ML) per a avaluar la seua capacitat de classificar automàticament els BSLs. En aquest estudi s'han utilitzat una sèrie de característiques tèrmiques extretes de les imatges infraroges per a avaluar quatre algorismes de ML per a tres moments diferents després de l'instant de referència (injecció de lidocaïna). Els resultats indiquen que els quatre models avaluats presenten bons rendiments per a classificar automàticament els BSLs en exitosos i fallits. Per tant, la combinació de paràmetres tèrmics juntament amb models de classificació ML mostra ser eficaç per a la classificació automàtica dels procediments de BSLs. En conclusió, l'ús de la TIR com a tècnica complementària en la pràctica clínica diària per a l'avaluació dels BSLs ha demostrat ser totalment eficaç. Atés que és un mètode objectiu i relativament senzill d'implementar, pot ajudar els metges especialistes en dolor a identificar els bloquejos realitzats fallits i, en conseqüència, puguen revertir aquesta situació.[EN] Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that usually affects one limb, and it is characterized by its misunderstood underlying pathophysiology, resulting in both challenging diagnosis and treatment. To avoid the patients' impairment quality of life, the achievement of both an early diagnosis and treatment marks a turning point. Among the different treatment approaches, lumbar sympathetic blocks (LSBs) are addressed to alleviate the pain and reduce some sympathetic signs of the condition. This interventional procedure is performed by injecting local anaesthetic around the sympathetic ganglia and, until now, it has been performed under different imaging techniques, including the ultrasound or the fluoroscopy approaches. Since infrared thermography (IRT) has proven to be a powerful tool to evaluate skin temperatures and taking into account the vasodilatory effects of the local anaesthetics injected in the LSB, the use of IRT has been considered for the LSBs assessment. Therefore, the purpose of this thesis is to evaluate the capability of IRT as a complementary assessment technique for the LSBs procedures performance. To fulfil this aim, three studies have been conducted implementing the IRT in patients diagnosed with lower limbs CRPS undergoing LSBs. The first study focuses on the feasibility of IRT as a complementary assessment tool for LSBs performance, that is, for the confirmation of the proper needle position. When LSBs are performed, the correct needle placement is critical to carry out the procedure technically correct and, consequently, to achieve the desired clinical outcomes. To verify the needle placement position, imaging techniques have traditionally been used, however, LSBs under radioscopic guidance do not always ensure an exact performance. For this reason, the thermal alterations induced by the local anaesthetics, have been exploited and assessed by means of IRT. Thus, the LSB procedure was considered successfully performed when thermal changes within the affected plantar foot were observed in the infrared images after the lidocaine injection. The second study deals with the quantitative analysis of the thermal data collected in the clinical setting through the evaluation of different temperature-based parameters extracted from both feet. According to the results, the proper LSB success prediction could be achieved in the first four minutes after the block through the evaluation of the feet skin temperatures. Therefore, the implementation of IRT in the clinical setting might be of great help in assessing the LSBs performance by evaluating the plantar feet temperatures in real time. Finally, the third study addresses the quantitative analysis by implementing machine learning (ML) tools to assess their capability to automatically classify LSBs. In this study, a set of thermal features retrieved from the infrared images have been used to evaluate four ML algorithms for three different moments after the baseline time (lidocaine injection). The results indicate that all four models evaluated present good performance metrics to automatically classify LSBs into successful and failed. Therefore, combining infrared features with ML classification models shows to be effective for the LSBs procedures automatic classification. In conclusion, the use of IRT as a complementary technique in daily clinical practice for LSBs assessment has been evidenced entirely effective. Since IRT is an objective method and it is not very demanding to perform, it is of great help for pain physicians to identify failed procedures, and consequently, it allow them to reverse this situation.Cañada Soriano, M. (2022). Infrared Thermography for the Assessment of Lumbar Sympathetic Blocks in Patients with Complex Regional Pain Syndrome [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/181699TESI

Raman spectroscopic characterization and analysis of agricultural and biological systems

Technical progresses in the past two decades in instrumental design, laser and electronic technology, and computer-based data analysis have made Raman spectroscopy, a noninvasive, nondestructive optical molecular spectroscopic imaging technique, an attractive choice for analytical tasks. Raman spectroscopy provides chemical structural information at molecular level with minimal sample preparation in a quick, easy-to-operate and reproducible fashion. In recent years it has been applied more and more to the analysis and characterization of agricultural products and biological samples. This dissertation documents the innovative research in Raman spectroscopic characterization and analysis in both biomedical and agricultural systems that I have been working on throughout my PhD training. The biomedical research conducted was focused on glaucoma. Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of pathological changes and progression in glaucoma and other neuroretinal diseases, which is critical for the prevention of permanent structural damage and irreversible vision loss, remains a great challenge. In my research, the Raman spectra from canine retinal tissues were subjected to multivariate discriminant analysis with a support vector machine algorithm to differentiate disease tissues versus healthy tissues. The high classification accuracy suggests that Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue not only at late stage but also at early stage with high specificity. To expand the scope of application of Raman analysis, it was also applied to characterize agricultural and food materials. More specifically, Raman spectroscopy was applied to analyze meat. Existing objective methods (e.g., mechanical stress/strain analysis, near infrared spectroscopy) to predict sensory attributes of pork in general do not yield satisfactory correlation to panel evaluations. Raman spectroscopic methodology was investigated in this study to evaluate and predict tenderness, juiciness and chewiness of fresh, uncooked pork loins from 169 pigs. The method developed in this thesis yielded good prediction of sensory attributes such as tenderness and chewiness, and it has the potential to become a rapid objective assay for tenderness and chewiness of pork products that may find practical applications in pork industry. In addition, a Raman spectroscopic screening method in conjunction with discriminant modeling was developed for rapid evaluation of boar taint level in pork. Through the research demonstrated in this dissertation, Raman spectroscopy has been shown to have great potential to address analytical needs in new fields with great potential for innovative applications

OCM 2021 - Optical Characterization of Materials : Conference Proceedings

The state of the art in the optical characterization of materials is advancing rapidly. New insights have been gained into the theoretical foundations of this research and exciting developments have been made in practice, driven by new applications and innovative sensor technologies that are constantly evolving. The great success of past conferences proves the necessity of a platform for presentation, discussion and evaluation of the latest research results in this interdisciplinary field