3-D lung deformation and function from respiratory-gated 4-D x-ray CT images : application to radiation treatment planning.

Many lung diseases or injuries can cause biomechanical or material property changes that can alter lung function. While the mechanical changes associated with the change of the material properties originate at a regional level, they remain largely asymptomatic and are invisible to global measures of lung function until they have advanced significantly and have aggregated. In the realm of external beam radiation therapy of patients suffering from lung cancer, determination of patterns of pre- and post-treatment motion, and measures of regional and global lung elasticity and function are clinically relevant. In this dissertation, we demonstrate that 4-D CT derived ventilation images, including mechanical strain, provide an accurate and physiologically relevant assessment of regional pulmonary function which may be incorporated into the treatment planning process. Our contributions are as follows: (i) A new volumetric deformable image registration technique based on 3-D optical flow (MOFID) has been designed and implemented which permits the possibility of enforcing physical constraints on the numerical solutions for computing motion field from respiratory-gated 4-D CT thoracic images. The proposed optical flow framework is an accurate motion model for the thoracic CT registration problem. (ii) A large displacement landmark-base elastic registration method has been devised for thoracic CT volumetric image sets containing large deformations or changes, as encountered for example in registration of pre-treatment and post-treatment images or multi-modality registration. (iii) Based on deformation maps from MOFIO, a novel framework for regional quantification of mechanical strain as an index of lung functionality has been formulated for measurement of regional pulmonary function. (iv) In a cohort consisting of seven patients with non-small cell lung cancer, validation of physiologic accuracy of the 4-0 CT derived quantitative images including Jacobian metric of ventilation, Vjac, and principal strains, (V?1, V?2, V?3, has been performed through correlation of the derived measures with SPECT ventilation and perfusion scans. The statistical correlations with SPECT have shown that the maximum principal strain pulmonary function map derived from MOFIO, outperforms all previously established ventilation metrics from 40-CT. It is hypothesized that use of CT -derived ventilation images in the treatment planning process will help predict and prevent pulmonary toxicity due to radiation treatment. It is also hypothesized that measures of regional and global lung elasticity and function obtained during the course of treatment may be used to adapt radiation treatment. Having objective methods with which to assess pre-treatment global and regional lung function and biomechanical properties, the radiation treatment dose can potentially be escalated to improve tumor response and local control

Multi-contrast Photoacoustic Microscopy

Photoacoustic microscopy is a hybrid imaging modality with high spatial resolution, moderate imaging depth, excellent imaging contrast and functional imaging capability. Taking full advantage of this powerful weapon, we have investigated different anatomical, functional, flow dynamic and metabolic parameter measurements using photoacoustic microscopy. Specifically, Evans-blue dye was used to enhance photoacoustic microscopy of capillaries; label-free transverse and axial blood flow was measured based on bandwidth broadening and time shift of the photoacoustic signals; metabolic rate of oxygen was quantified in vivo from all the five parameters measured by photoacoustic microcopy; whole cross-sectional imaging of small intestine was achieved on a double-illumination photoacoustic microscopy with extended depth of focus and imaging depth; hemodynamic imaging was performed on a MEMS-mirror enhanced photoacoustic microscopy with a cross-sectional imaging rate of 400 Hz. As a maturing imaging technique, PAM is expected to find new applications in both fundamental life science and clinical practice

Bioactive Molecules from Extreme Environments II

This Special Issue, as a continuation of the previous Special Issue, “Bioactive Molecules from Extreme Environments” (https://www.mdpi.com/journal/marinedrugs/special_issues/Extreme_Environments accessed on 4 November 2021), includes 10 research articles and 2 reviews, providing a wide overview of the chemical biodiversity offered by different marine organisms inhabiting extreme environments to be used for biotechnological and pharmaceutical applications. The six articles in this Special Issue are focused on the polar regions, which represent an untapped source of marine natural products and are still largely unexplored compared to more accessible sites. Many of these articles refer to Antarctica, which is the coldest and most inaccessible continent on the Earth, where extreme temperatures, light and ice have selected biological communities with a unique suite of bioactive metabolites. The marine organisms of Arctic and Antarctic environments are a reservoir of natural compounds, exhibiting huge structural diversity and significant bioactivities that could be used in human applications

Effect of curing conditions and harvesting stage of maturity on Ethiopian onion bulb drying properties

The study was conducted to investigate the impact of curing conditions and harvesting stageson the drying quality of onion bulbs. The onion bulbs (Bombay Red cultivar) were harvested at three harvesting stages (early, optimum, and late maturity) and cured at three different temperatures (30, 40 and 50 oC) and relative humidity (30, 50 and 70%). The results revealed that curing temperature, RH, and maturity stage had significant effects on all measuredattributesexcept total soluble solids

Biodegradable Magneto-Luminescent Mesoporous Nanoparticles As New Nanobiomedical Tools In Cancer Treatment

Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide and 2nd in mortality rate, accounting to 1.93 million cases and 916 000 deaths just in 2020. The development of CRC targeted therapies has been a hot topic in recent medical forums and among researchers, with the demand for non-invasive approaches, like oral ones, capable of preserving their therapeutic properties from administration to local action drastically increasing in the last decade. Its body location makes CRC a usually silent disease, whose commonly later detection and action usually lead to severe aggravations and even death. Targetability, drugs' resistance and toxicity of the said therapies are thus three of the key points for the development of effective therapies. On the other hand, the presence of cancerassociated bacterial infections and inflammations has been positively correlated with low treatment success rates and associated complications, with bacterial infections being particularly damaging in gastric and colorectal cancer. Some of the metabolites/toxins of these opportunistic bacteria have been linked to tumorigenesis and CRC drug-resistance. A conjoint therapy capable of addressing both CRC and associated bacteria, where drug preservation, null secondary toxicity and targetability are ensured. In light of the above-mentioned, herein we cover the synthesis of a new magnetofluorescent nanotherapy against both CRC and associated bacterial strains, going from the synthesis of sustainable, biocompatible, biodegradable and cheap nanocomposite particles (NANO3) to the testing of its dual drug cargo and delivery capacities, magneto-fluorescent properties and later assessment of its combined antibacterial and anti-tumor activity. The successful synthesis of new anti-CA IX targeting inhibitor as potential directing agent is also covered as a cheaper alternative to the commonly used and expensive antibodies. From an antimicrobial point of view, NANO3 showed significant activity against CRC-related bacterial strains, with their intrinsic magnetic properties potentiating a hyperthermia-assisted pH responsive release and antimicrobial therapy. The combined release of an antibiotic (i.e., ofloxacin) and an anti-tumor drug (i.e., doxorubicin) showed no hinderance on the activity of both active drugs. Accordingly, NANO3 anti-tumoral activity, arising solely from the loaded doxorubicin, was conserved and competitive to that of the free model drug. Targetability was conferred by successfully functionalizing of NANO3 with anti-EGFR and and/or anti-CA IX, the later favoring higher NANO3 uptake in HCT-116 cell line. A proof-of-concept oral delivery was also simulated, where a dual Eudragit® enteric coating successfully protected NANO3 formulations from stomachal and small intestine conditions, selectively dispensing it in colon environment and potentiating their use in a future anti-CRC oral therapy. In this thesis an optimization of a luminescent antimicrobial activity assay specific for nanoparticles was also carried out along with the evaluation of other cyanine-based antimicrobial scaffolds for a potential biomedical and food-based application.O cancro colorrectal (CRC) é o 3º tipo de cancro mais comum a nível mundial e o 2º na taxa de mortalidade, contabilizando 1,93 milhões de casos e 916 000 mortes apenas em 2020. O desenvolvimento de terapias orientadas para CRC tem sido um tema recorrente no meio médico e entre investigadores, tendo a procura de abordagens não invasivas, tais como as orais, capazes de preservar as suas propriedades terapêuticas desde a administração até à acção local, aumentado drasticamente na última década. A sua localização corporal faz do CRC uma doença geralmente silenciosa, cuja detecção e acção tardias conduzem a agravamentos do quadro clinico ou mesmo à morte. A capacidade de carga, a resistência dos medicamentos e a toxicidade das referidas terapias são assim três dos pontos-chave para o desenvolvimento de terapias eficazes. Por outro lado, a presença de infecções e inflamações bacterianas associadas ao cancro têm sido positivamente correlacionadas com baixas taxas de sucesso de tratamento e ao aumento de complicações, com particular impacto prejudicial em situações de cancro gástrico e colorrectal. Alguns dos metabolitos/toxinas destas bactérias oportunistas têm sido ligados à tumorigenese e à resistência aos medicamentos em CRC. Uma terapia conjunta capaz de tratar tanto CRC como as bactérias associadas, onde a preservação do medicamento, a toxicidade secundária nula e a capacidade de carga são asseguradas. Tendo em conta o acima mencionado, na presente tese detalha-se a síntese de uma nova nanoterapia magneto-fluorescente tanto contra CRC como contra estirpes bacterianas associadas. Indo assim, desde a síntese de partículas nanocompósitas sustentáveis, biocompatíveis, biodegradáveis e baratas (NANO3) até à dupla carga e entrega de medicamentos; bem como da avaliação das suas propriedades magneto-fluorescentes até à sua actividade antibacteriana e antitumoral combinada. A síntese bem-sucedida do novo inibidor de CA IX como potencial agente dirigente é também coberta como uma alternativa mais barata aos anticorpos normalmente utilizados. De um ponto de vista antimicrobiano, NANO3 mostrou uma actividade significativa contra estirpes bacterianas relacionadas com CRC, com as suas propriedades magnéticas intrínsecas potenciando uma libertação pHresponsiva, assistida por hipertérmia, e por fim a uma terapia antimicrobiana. A libertação combinada de um antibiótico (i.e.,, ofloxacina) e de um medicamento anti-tumoral (i.e., doxorubicina) não levou a qualquer redução da actividade de ambos os medicamentos. Assim, a actividade anti-tumoral de NANO3, proveniente unicamente da doxorubicina carregada, foi conservada e competitiva em relação à do medicamento livre. A capacidade de atuar especificamente sobre células de CRC foi conferida pela funcionalização das NANO3 com anti-EGFR e / ou anti-CA IX, o último dos quais favorecendo uma maior internalização de NANO3 na linha celular HCT-116. Foi também simulada uma prova de conceito de uma toma oral, onde um revestimento entérico duplo de Eudragit® protegeu com sucesso as formulações de NANO3 das condições estomacais e do intestino delgado, dispensando-o selectivamente em ambiente de cólon e potenciando a sua utilização numa futura terapia oral anti-CRC. Na presente tese foi também realizada uma optimização de um ensaio de actividade antimicrobiana luminescente específico para nanopartículas, juntamente com a avaliação de outros substratos antimicrobianos à base de cianina para uma potencial aplicação biomédica e alimentar