Diabetic foot ulcers monitoring by employing super resolution and noise reduction deep learning techniques

Diabetic foot ulcers (DFUs) constitute a serious complication for people with diabetes. The care of DFU patients can be substantially improved through self-management, in order to achieve early-diagnosis, ulcer prevention, and complications management in existing ulcers. In this paper, we investigate two categories of image-to-image translation techniques (ItITT), which will support decision making and monitoring of diabetic foot ulcers: noise reduction and super-resolution. In the former case, we investigated the capabilities on noise removal, for convolutional neural network stacked-autoencoders (CNN-SAE). CNN-SAE was tested on RGB images, induced with Gaussian noise. The latter scenario involves the deployment of four deep learning super-resolution models. The performance of all models, for both scenarios, was evaluated in terms of execution time and perceived quality. Results indicate that applied techniques consist a viable and easy to implement alternative that should be used by any system designed for DFU monitoring

Shear-promoted drug encapsulation into red blood cells: a CFD model and μ-PIV analysis

The present work focuses on the main parameters that influence shear-promoted encapsulation of drugs into erythrocytes. A CFD model was built to investigate the fluid dynamics of a suspension of particles flowing in a commercial micro channel. Micro Particle Image Velocimetry (μ-PIV) allowed to take into account for the real properties of the red blood cell (RBC), thus having a deeper understanding of the process. Coupling these results with an analytical diffusion model, suitable working conditions were defined for different values of haematocrit

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

Influencing the Inflammatory Response Through Multi-Scale Geometry, Antibiotic Release, and Fluid Management in a Textile-Based Biomaterial Wound Dressing

The total population of diagnosed and undiagnosed diabetes mellitus in the United states is expected to rise by 54% between the years of 2015 and 2030 contributing to $200 billion in health care expense. The exponential rise in common diabetic wounds, such as diabetic foot ulcers, puts a large population at risk for complications such as infection, amputation, and even death. Peripheral neuropathy leading to late diagnoses, patient non-compliance, and lack of holistic treatment options all contribute to complications with the incidence of new ulcer formation after treatment reaching 50%. This work explores the design, development, and in vitro evaluation of a multicomponent textile-based biomaterial and absorptive dressing that combines the need to manage infection, eliminate excess exudate levels, and provide an ideal environment for healthy tissue to repair and remodel the wound site. Melt-splun poly-l-lactide (PLLA) yarn of fibers with round or 4-deep-grooved (4DG) geometry were knitted into the skin-contact layer, the first layer of the dressing. Different methods of gentamicin sulfate (GS) incorporation, along with the impact of fiber geometry, were studied to explore optimal antibiotic release and efficacy. Results indicated that an increase in surface area as well as heat-enabled diffusion allowed for higher release of GS. Because each factorial treatment, with the exception of exhaustion dyeing method of incorporation, released GS at or above the minimum inhibitory concentration, there showed no difference in geometry and method of incorporation on antibacterial efficacy. The GS incorporated skin contact layer also appeared to be biocompatible in cultures of mouse bone marrow stromal D1 cells. Cell adhesion studies showed that a polyethylene glycol (PEG) surface treatment is needed to prevent non-specific protein and cellular attachment upon dressing changes. A microscopically thin layer of PEG was added to the surface of the contact layer and showed less cell attachment as seen in fluorescently labeled LIVE/DEADTM analysis, while showing no impact on GS release and antibacterial efficacy. In this aim, it can be concluded that the combination of GS release and a PEG surface coat can simultaneously kill and prevent infection while providing a non-adhesive surface upon removal from the wound. Polyurethane (PU) foam was characterized in a two-factor analysis based on foam density and mixing speed used to create the foam layer. PU foam V was chosen as the absorptive layer of the dressing and a comparative analysis was conducted using commercialized absorptive dressings. The PU foam layer was exposed to different time durations of ultra-violet ozone to increase the surface wettability and initiate moisture absorption. To prevent saturation, PLLA yarn of 4DG fibers was braided into an evaporative and moisture wicking layer. The braided fabric was able to vertically wick porcine serum at a rate of 0.88 mm/sec. The combination of absorptive and moisture wicking layers stimulate wound healing by removing moisture from the ulcer, while preventing maceration and premature saturation of the dressing, leading to fewer dressing changes. Additionally, an in vitro chronic wound model was constructed to verify the efficacy of the combined layers of the dressing. After applying the dressing for a duration of 48 hours, the dressing inhibited bacterial infection, while acting as a superabsorbent material without causing saturation. Further work explored healthy cell viability and any oxidative stress levels after exposing cells to both bacterial infection and the dressing. Although the in vitro model maintains some limitations and assumptions at the present time, it can be concluded that with the addition of the wound dressing, cell viability increased over time, and therefore promoted tissue repair. Future work will explore alternative antimicrobials for a more gradual release as well as improving the in vitro model by discovering the interaction between the co-culture in different types of medias and substrates while including proinflammatory biomarkers that could affect oxidative stress

Generalizable automated pixel-level structural segmentation of medical and biological data

Over the years, the rapid expansion in imaging techniques and equipments has driven the demand for more automation in handling large medical and biological data sets. A wealth of approaches have been suggested as optimal solutions for their respective imaging types. These solutions span various image resolutions, modalities and contrast (staining) mechanisms. Few approaches generalise well across multiple image types, contrasts or resolution. This thesis proposes an automated pixel-level framework that addresses 2D, 2D+t and 3D structural segmentation in a more generalizable manner, yet has enough adaptability to address a number of specific image modalities, spanning retinal funduscopy, sequential fluorescein angiography and two-photon microscopy. The pixel-level segmentation scheme involves: i ) constructing a phase-invariant orientation field of the local spatial neighbourhood; ii ) combining local feature maps with intensity-based measures in a structural patch context; iii ) using a complex supervised learning process to interpret the combination of all the elements in the patch in order to reach a classification decision. This has the advantage of transferability from retinal blood vessels in 2D to neural structures in 3D. To process the temporal components in non-standard 2D+t retinal angiography sequences, we first introduce a co-registration procedure: at the pairwise level, we combine projective RANSAC with a quadratic homography transformation to map the coordinate systems between any two frames. At the joint level, we construct a hierarchical approach in order for each individual frame to be registered to the global reference intra- and inter- sequence(s). We then take a non-training approach that searches in both the spatial neighbourhood of each pixel and the filter output across varying scales to locate and link microvascular centrelines to (sub-) pixel accuracy. In essence, this \link while extract" piece-wise segmentation approach combines the local phase-invariant orientation field information with additional local phase estimates to obtain a soft classification of the centreline (sub-) pixel locations. Unlike retinal segmentation problems where vasculature is the main focus, 3D neural segmentation requires additional exibility, allowing a variety of structures of anatomical importance yet with different geometric properties to be differentiated both from the background and against other structures. Notably, cellular structures, such as Purkinje cells, neural dendrites and interneurons, all display certain elongation along their medial axes, yet each class has a characteristic shape captured by an orientation field that distinguishes it from other structures. To take this into consideration, we introduce a 5D orientation mapping to capture these orientation properties. This mapping is incorporated into the local feature map description prior to a learning machine. Extensive performance evaluations and validation of each of the techniques presented in this thesis is carried out. For retinal fundus images, we compute Receiver Operating Characteristic (ROC) curves on existing public databases (DRIVE & STARE) to assess and compare our algorithms with other benchmark methods. For 2D+t retinal angiography sequences, we compute the error metrics ("Centreline Error") of our scheme with other benchmark methods. For microscopic cortical data stacks, we present segmentation results on both surrogate data with known ground-truth and experimental rat cerebellar cortex two-photon microscopic tissue stacks.Open Acces

Recent Advances in Wound Healing

The human wound-healing process could be divided into four discrete phases, which have also been indicated as the hemostasis, the inflammatory, the proliferation, and the remodeling phase. For a wound to be healed efficaciously, all four phases must sequentially happen at an expected time setting. Numerous aspects can hinder one or more stages of this procedure, thus can cause inappropriate or diminished wound healing. This book reviews the recent literature on the most significant factors that affect wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include physiology of wound healing, interferon, stem cells and photobiomodulation, chronic venous ulcer, chronic fistula, bionanomaterials, topical antiseptic agents, including silver and sodium hypochlorite solution, diabetic ulcers, and nutritional supplements such as copper