An optimized ultrasound detector for photoacoustic breast tomography

Photoacoustic imaging has proven to be able to detect vascularization-driven optical absorption contrast associated with tumors. In order to detect breast tumors located a few centimeter deep in tissue, a sensitive ultrasound detector is of crucial importance for photoacoustic mammography. Further, because the expected photoacoustic frequency bandwidth (a few MHz to tens of kHz) is inversely proportional to the dimensions of light absorbing structures (0.5 to 10+ mm), proper choices of materials and their geometries, and proper considerations in design have to be made for optimal photoacoustic detectors. In this study, we design and evaluate a specialized ultrasound detector for photoacoustic mammography. Based on the required detector sensitivity and its frequency response, a selection of active material and matching layers and their geometries is made leading to a functional detector models. By iteration between simulation of detector performances, fabrication and experimental characterization of functional models an optimized implementation is made and evaluated. The experimental results of the designed first and second functional detectors matched with the simulations. In subsequent bare piezoelectric samples the effect of lateral resonances was addressed and their influence minimized by sub-dicing the samples. Consequently, using simulations, the final optimized detector could be designed, with a center frequency of 1 MHz and a -6 dB bandwidth of ~80%. The minimum detectable pressure was measured to be 0.5 Pa, which will facilitate deeper imaging compared to the currrent systems. The detector should be capable of detecting vascularized tumors with resolution of 1-2 mm. Further improvements by proper electrical grounding and shielding and implementation of this design into an arrayed detector will pave the way for clinical applications of photoacoustic mammography.Comment: Accepted for publication in Medical Physics (American Association of Physicists in Medicine

Automated retinal analysis

Diabetes is a chronic disease affecting over 2% of the population in the UK [1]. Long-term complications of diabetes can affect many different systems of the body including the retina of the eye. In the retina, diabetes can lead to a disease called diabetic retinopathy, one of the leading causes of blindness in the working population of industrialised countries. The risk of visual loss from diabetic retinopathy can be reduced if treatment is given at the onset of sight-threatening retinopathy. To detect early indicators of the disease, the UK National Screening Committee have recommended that diabetic patients should receive annual screening by digital colour fundal photography [2]. Manually grading retinal images is a subjective and costly process requiring highly skilled staff. This thesis describes an automated diagnostic system based oil image processing and neural network techniques, which analyses digital fundus images so that early signs of sight threatening retinopathy can be identified. Within retinal analysis this research has concentrated on the development of four algorithms: optic nerve head segmentation, lesion segmentation, image quality assessment and vessel width measurements. This research amalgamated these four algorithms with two existing techniques to form an integrated diagnostic system. The diagnostic system when used as a 'pre-filtering' tool successfully reduced the number of images requiring human grading by 74.3%: this was achieved by identifying and excluding images without sight threatening maculopathy from manual screening

Aerospace Medicine and Biology: A continuing bibliography, supplement 216

One hundred twenty reports, articles, and other documents introduced into the NASA scientific and technical information system in January 1981 are listed. Topics include: sanitary problems; pharmacology; toxicology; safety and survival; life support systems; exobiology; and personnel factors

Dual microcapsule system for autonomous self-healing coatings

Polymer coatings are vulnerable to external and internal damage. Formation of microcracks can occur because of an impact event or through oscillatory stresses such as thermal expansion and contraction. Self-healing offers a solution to respond to internal damage and repair the polymeric structure. This work utilizes a dual microcapsule system as the autonomous self-healing mechanism for use in an epoxy coating. The system is comprised of an epoxy resin microcapsule and an amine adduct capsule embedded in an epoxy matrix. Encapsulation of the epoxy resin was achieved, however encapsulation of the amine adduct is very challenging, and was the main focus of this work. The amine adduct has been successfully encapsulated, resulting in a satisfactory microcapsule payload and size, but reproducibility has proven to be difficult. Though reproducibility is an issue, the adhesive properties of amine adduct and epoxy capsules have been successful by adhering two pieces of epoxy together

Revealing Real-Time Emotional Responses: a Personalized Assessment based on Heartbeat Dynamics

Emotion recognition through computational modeling and analysis of physiological signals has been widely investigated in the last decade. Most of the proposed emotion recognition systems require relatively long-time series of multivariate records and do not provide accurate real-time characterizations using short-time series. To overcome these limitations, we propose a novel personalized probabilistic framework able to characterize the emotional state of a subject through the analysis of heartbeat dynamics exclusively. The study includes thirty subjects presented with a set of standardized images gathered from the international affective picture system, alternating levels of arousal and valence. Due to the intrinsic nonlinearity and nonstationarity of the RR interval series, a specific point-process model was devised for instantaneous identification considering autoregressive nonlinearities up to the third-order according to the Wiener-Volterra representation, thus tracking very fast stimulus-response changes. Features from the instantaneous spectrum and bispectrum, as well as the dominant Lyapunov exponent, were extracted and considered as input features to a support vector machine for classification. Results, estimating emotions each 10 seconds, achieve an overall accuracy in recognizing four emotional states based on the circumplex model of affect of 79.29%, with 79.15% on the valence axis, and 83.55% on the arousal axis

Vacuolation, proliferation and neoplasia in the liver of Boston Harbor winter flounder (Pseudopleuronectes americanus)

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution July 1991Neoplasia has been found in the livers of bottom-feeding fish taken from heavily contaminated freshwater and marine habitats. This study examined the progressive development and ultimate diversity of liver neoplasia in winter flounder (Pseudopleuronectes americanus) from Deer Island Flats, Boston Harbor, MA., U.S.A., and encompassed histopathology, ultrastructural pathology, immunohistochemistry and experimental toxicology. It was found that liver neoplasia was most prevalent adjacent to a major sewage outfall, and that the predominant neoplastic cell type was cholangiocellular. Cholangiocellular neoplasms ranged from non-invasive tubular cholangiomas to invasive anaplastic cholangiocellular carcinomas. The latter were solid, tubular, cystic and scirrhous in form. Hepatocellular adenomas and carcinomas were also present, but only infrequently. Abnormally vacuolated hepatic epithelia were intimately associated with neoplastic lesions of all types. These vacuolated cells were first seen in the center of the hepatic tubule, as vacuolated preductular biliary epithelial cells. Later, cells of the entire hepatic tubule were vacuolated. Foci of vacuolated cells were visible grossly, and often contained or were adjacent to neoplastic lesions. Vacuolation, biliary hyperplasia, aggregation of macrophages and necrosis were first seen in two year old fish. These lesions then appeared to progress, becoming more severe and prevalent as the fish grew. Of the fish for which age data were available, the youngest fish to contain a liver neoplasm was 5 years old. Prevalence of neoplasia did not differ between gender of fish. Liver neoplasia and vacuolation persisted in fish that were maintained in clean water on clean food for five months. However, the prevalence of vacuolation decreased with increasing distance from urban contamination, being absent in fish from Georges Bank. Ultrastructural examination of winter flounder liver from clean and contaminated sites revealed a loss of hepatic glycogen and lipid stores with increasing environmental contamination, with a concomitant increase of abnormal proliferated endoplasmic reticulum (ER). Fluid accumulation in the cisternal space of the ER, and the perinuclear space and mitochondra led to vesicle formation. These vesicles coalesced, to form large cellular vacuoles that compressed the nucleus and residual cytoplasm to the margins of the cell. Vacuolation appeared to be a process that affected preductular cells, hepatocytes, cholangiocytes, neoplastic cells, and exocrine pancreatic cells. To assess the role of vacuolated cells in the progression to neoplasia, evidence for replicative nuclear DNA synthesis was sought by assaying for the nuclear incorporation of a nucleotide analog, bromodeoxyuridine (BrdU). Tissue sections from fish labeled with BrdU were stained imunohistochemically using an anti-BrdU monoclonal antibody. Constitutive DNA synthesis was observed in basal gill and intestinal epithelia, and renal hemopoietic cells. Increased levels of DNA synthesis were observed in vacuolated cells, hyperplastic biliary epithelia, and most particularly in neoplastic cells, some of which were vacuolated. These observations were taken to suggest that vacuolated cells were capable of DNA synthesis, and that this, along with their intimate spatial relationship with neoplastic cells implied that they may be involved in the progression to neoplasia. To further investigate these observations, attempts were made to recreate the feral disease in the laboratory. Methods were developed for atraumatic capture, transport and year round maintenance of winter flounder. Long term colonies were established and experiments designed to reproduce the situation in wild-caught fish. The long latency between first exposure of larvae to genotoxic carcinogens in the native fish from Boston, and the actual appearance of neoplasia many years later, leads to the assumption that chronic exposure to epigenetic carcinogens was the rate limiting step in this neoplastic progression. Technical grade chlordane was chosen as representative of the hepatotoxic epigenetic carcinogens present in Boston Harbor sediments. Acute and subacute exposures were conducted, to establish the toxicity of the fish to chlordane, and to examine the resultant histopathology. A chronic feeding study was then conducted for one year, using chlordane and benzo(a)pyrene. Histological alterations induced in treated fish included elevated levels of macrophage aggregations, perisinusoidal edema, necrosis, and a proliferative reaction that involved the formation of structures that were apparently primitive biliary tubules. These studies have shown that winter flounder exposed to chemical contaminants appear to undergo a set of histopathological changes that precede neoplastic change. Cellular vacuolation is a significant change that may be directly involved in the progression to neoplasia. It is a relatively common lesion and is an excellent marker in winter flounder for the detection of the chronic biological effects of the particular chemical contaminants in the Boston Harbor environment, at a stage long before overt neoplasia is evident.This research was funded by the Massachusetts Institute of Technology/ Woods Hole Oceanographic Institution Joint Program, U.S.P.H.S. grant CA/ES44306, the WHOI Ocean Ventures Fund, a Sea Grant New Initiative grant, The Donaldson Chartable Trust, and the Massachusetts Water Resources Authority

Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control

The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson?s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity

An application of functional magnetic resonance in medicine : optimization of fMRI and rsfMRI studies

Novel functional magnetic resonance techniques based on variation of the blood-oxygenated-level-dependent (BOLD) signal during the performance of a task or in response to a stimulus (fMRI) as well as at the rest (rsfMRI) are compared. These techniques play a significant role in the investigation of functional architecture of the brain. There is a good overlap between the areas of fMRI activation elicited by motor, language, visual or other task studies and the corresponding rsfMRI networks (RSNs). Progress in statistical approaches for processing is presented particularly for rsfMRI data. Both fMRI techniques as completely non-invasive can be successfully used in medical diagnostics and neurosurgery. In recent years, research has focused on the rsfMRI technique since it represents a promising and cost-effective alternative to task-based fMRI for scientific needs as well as for medical applications

Angiocardiología por rayos X

La radiología permite obtener una películaradiográfica de la imagen de una parte delcuerpo humano, por su exposición a los rayosX. Cuando la radiación X atraviesa el objetobajo estudio, sufre una atenuación que depende dela densidad y el espesor del objeto. Los rayos atenuadosllegan a un a un receptor que puede ser la película fotográfica,produciendo así una imagen cuyo contraste facilitaráel diagnóstico médico. La angiografía es un procedimientoradiológico usado para observar el flujo de sangre,en cualquier órgano del cuerpo. Bajo este procedimientodestacan la angiografía cardiaca para observar las arteriascoronarias, la angiografía vascular para estudiar la irrigacióndel cerebro, y la ventriculografía, para observar la cavidadventricular. En el presente artículo, se presentan unconjunto de técnicas desarrolladas para el procesamientode imágenes adquiridas durante procedimientos de angiografíacardiaca

Development of an alternative ventricular catheter and an in vitro model of its obstruction

This thesis was previously held under moratorium from 5th November 2014 until 2nd June 2020.Intracranial pressure and volume varies considerably between hydrocephalic patients, and with age, health and haemodynamic status; if left untreated intracranial pressure rises and the ventricular system expands to accommodate the excess cerebrospinal fluid (CSF), with significant morbidity and mortality. Although considerable improvements in design have been made since their introduction all CSF shunts in use today have a high incidence of failure with shunt obstruction being the most serious. Conventional proximal shunt catheters are made from poly (di-methyl) siloxane (PDMS), the walls of which are perforated with holes for the CSF to pass through. The limited range of catheters, in terms of material selection and flow distribution, is responsible in large part for their poor performance.;The aim of the study is to design and fabricate an alternative design of proximal catheter with permeable walls, and to evaluate its performance in the presence of glial cells, which are responsible for blockage. Electrospun Poly-ether Urethane (EPU) samples were fabricated from solvent, by means of an electrospinning technique, to yield microfibrous polymer conduits. The hydrodynamic properties of EPU and conventional shunt were studied using a purpose-built shunt testing system.;The viability and growth of cells on candidate catheter materials such as PDMS and polyurethane in the form of cast films, microfibrous mats and porous sponges were studied in presence of proteins present in CSF after 48h and 96h in culture. The number of viable cells was significantly less on EPU samples compared to the other substrates, which suggests that the fibrous form of the material from which the catheter is made has a bearing on the cell growth. A cell culture model of shunt obstruction was developed in which the cells were subjected to flow during culture in vitro, and the degree of obstruction quantified in terms of hydraulic permeability post static and perfusion culture. The results indicate that a catheter made of EPU would be able to maintain CSF flow even with the presence of cells for the time period chosen for this study. These findings have implications for the design and deployment of micro porous shunt catheter systems for the treatment of hydrocephalus.Intracranial pressure and volume varies considerably between hydrocephalic patients, and with age, health and haemodynamic status; if left untreated intracranial pressure rises and the ventricular system expands to accommodate the excess cerebrospinal fluid (CSF), with significant morbidity and mortality. Although considerable improvements in design have been made since their introduction all CSF shunts in use today have a high incidence of failure with shunt obstruction being the most serious. Conventional proximal shunt catheters are made from poly (di-methyl) siloxane (PDMS), the walls of which are perforated with holes for the CSF to pass through. The limited range of catheters, in terms of material selection and flow distribution, is responsible in large part for their poor performance.;The aim of the study is to design and fabricate an alternative design of proximal catheter with permeable walls, and to evaluate its performance in the presence of glial cells, which are responsible for blockage. Electrospun Poly-ether Urethane (EPU) samples were fabricated from solvent, by means of an electrospinning technique, to yield microfibrous polymer conduits. The hydrodynamic properties of EPU and conventional shunt were studied using a purpose-built shunt testing system.;The viability and growth of cells on candidate catheter materials such as PDMS and polyurethane in the form of cast films, microfibrous mats and porous sponges were studied in presence of proteins present in CSF after 48h and 96h in culture. The number of viable cells was significantly less on EPU samples compared to the other substrates, which suggests that the fibrous form of the material from which the catheter is made has a bearing on the cell growth. A cell culture model of shunt obstruction was developed in which the cells were subjected to flow during culture in vitro, and the degree of obstruction quantified in terms of hydraulic permeability post static and perfusion culture. The results indicate that a catheter made of EPU would be able to maintain CSF flow even with the presence of cells for the time period chosen for this study. These findings have implications for the design and deployment of micro porous shunt catheter systems for the treatment of hydrocephalus