Predicting and auralizing acoustics in classrooms

Although classrooms have fairly simple geometries, this type of room is known to cause problems when trying to predict their acoustics using room acoustics computer modeling. Some typical features from a room acoustics point of view are: Parallel walls, low ceilings (the rooms are flat), uneven distribution of absorption, and most of the floor being covered with furniture which at long distances act as scattering elements, and at short distance provide strong specular components. The importance of diffraction and scattering is illustrated in numbers and by means of auralization, using ODEON 8 Beta

Placental Protein 13 (PP13) – a placental immunoregulatory galectin protecting pregnancy

Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a jelly-roll fold, carbohydrate-recognition domain and sugar-binding preference resembling to other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low first trimester maternal serum concentrations are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is an increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure d

Predicting the risk to develop preeclampsia in the first trimester combining promoter variant -98A/C of LGALS13 (placental protein 13), Black ethnicity, previous preeclampsia, obesity, and maternal age

BACKGROUND: We studied LGALS13 [Placental Protein 13 (PP13)] promoter DNA polymorphisms in preeclampsia (PE) prediction, given PP13’s effects on hypotension, angiogenesis and immunotolerance. METHODS: We retrieved 67 PE (49 term, 18 preterm) cases and 196 matched controls from first trimester plasma samples prospectively collected at King's College Hospital, London. Cell-free DNA was extracted and the four LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs were determined in BeWo trophoblast-like cells with luciferase assays. RESULTS: A/C genotype in –98 position was the lowest in term PE compared to controls (p<0.032), similar to a South African cohort. Control but not all PE allele frequencies were in Hardy-Weinberg equilibrium (p=0.036). The Odds ratio for term PE calculated from prior risk, the A/A genotype and black ethnicity was 14 (p<0.001). In luciferase assays, the LGALS13 promoter “-98A" variant had 13% (p=0.04) and 26% (p<0.001) lower expression than the "-98C" variant in non-differentiated and differentiated BeWo cells, respectively. After 48-hour differentiation, there was 4.55- fold increase in expression of "-98C" variant versus 3.85-fold of "-98A" variant (p<0.001). CONCLUSION: Lower LGALS13 (PP13) expression by the "-98A/A" genotype appears to impose higher risk to develop PE and could aid in PE prediction

Methods and Algorithms for Cardiovascular Hemodynamics with Applications to Noninvasive Monitoring of Proximal Blood Pressure and Cardiac Output Using Pulse Transit Time

Advanced health monitoring and diagnostics technology are essential to reduce the unrivaled number of human fatalities due to cardiovascular diseases (CVDs). Traditionally, gold standard CVD diagnosis involves direct measurements of the aortic blood pressure (central BP) and flow by cardiac catheterization, which can lead to certain complications. Understanding the inner-workings of the cardiovascular system through patient-specific cardiovascular modeling can provide new means to CVD diagnosis and relating treatment. BP and flow waves propagate back and forth from heart to the peripheral sites, while carrying information about the properties of the arterial network. Their speed of propagation, magnitude and shape are directly related to the properties of blood and arterial vasculature. Obtaining functional and anatomical information about the arteries through clinical measurements and medical imaging, the digital twin of the arterial network of interest can be generated. The latter enables prediction of BP and flow waveforms along this network. Point of care devices (POCDs) can now conduct in-home measurements of cardiovascular signals, such as electrocardiogram (ECG), photoplethysmogram (PPG), ballistocardiogram (BCG) and even direct measurements of the pulse transit time (PTT). This vital information provides new opportunities for designing accurate patient-specific computational models eliminating, in many cases, the need for invasive measurements. One of the main efforts in this area is the development of noninvasive cuffless BP measurement using patient’s PTT. Commonly, BP prediction is carried out with regression models assuming direct or indirect relationships between BP and PTT. However, accounting for the nonlinear FSI mechanics of the arteries and the cardiac output is indispensable. In this work, a monotonicity-preserving quasi-1D FSI modeling platform is developed, capable of capturing the hyper-viscoelastic vessel wall deformation and nonlinear blood flow dynamics in arbitrary arterial networks. Special attention has been dedicated to the correct modeling of discontinuities, such as mechanical properties mismatch associated with the stent insertion, and the intertwining dynamics of multiscale 3D and 1D models when simulating the arterial network with an aneurysm. The developed platform, titled Cardiovascular Flow ANalysis (CardioFAN), is validated against well-known numerical, in vitro and in vivo arterial network measurements showing average prediction errors of 5.2%, 2.8% and 1.6% for blood flow, lumen cross-sectional area, and BP, respectively. CardioFAN evaluates the local PTT, which enables patient-specific calibration and its application to input signal reconstruction. The calibration is performed based on BP, stroke volume and PTT measured by POCDs. The calibrated model is then used in conjunction with noninvasively measured peripheral BP and PTT to inversely restore the cardiac output, proximal BP and aortic deformation in human subjects. The reconstructed results show average RMSEs of 1.4% for systolic and 4.6% for diastolic BPs, as well as 8.4% for cardiac output. This work is the first successful attempt in implementation of deterministic cardiovascular models as add-ons to wearable and smart POCD results, enabling continuous noninvasive monitoring of cardiovascular health to facilitate CVD diagnosis

Signiture analysis of fetal blood velocity waveforms

Doppler blood velocity waveform analysis is conducted to affect clinical diagnosis. Current analysis codes developed at RIT posses the capability to assess gross hemodynamic parameters such as heart rate, mean pulse velocity, peak systolic velocity and also the beat to beat variability of these parameters. These computer algorithms have, however, lacked the ability to determine hemodynamic indices such as the pulsatility and resistance index as well as the AB ratio. This latter deficiency stems from an algorithmic need to accurately determine end diastolic velocity in every cardiac cycle. The current thesis specifically augments current algorithms to accurately compute end diastolic velocity. The end diastolic velocity, peak systolic velocity and mean pulse velocity determined in each cardiac cycle are then used to compute the various pulsevelocity waveform indices noted above. In addition, the use of end diastolic velocity in conjunction with peak systolic velocity allows the velocity waveform to be dissected into diastolic subsections, which resemble decaying exponential curves. These exponential decay curves will be characterized via curve fitting. The goal of this thesis is to assess whether traditional pulsatility indices and/or the decay curve parameters are adequate to assess fetal developmental age between 10-13 weeks gestation. Discrimination assessment is conducted using neural network analysis techniques. Whether entire pulsevelocity waveforms extracted between successive end-diastolic velocities provides a more robust data set for gestational age discrimination is also explored. The results suggest that hemodynamic indices computed for fetuses between 10 to 13 weeks gestation provide insufficient data for effective neural network classification. Use of the entire pulse-velocity waveform data in neural network analysis showed better fetal gestational age classification than use of waveform indices. However, similarity of waveforms between 10-13 weeks gestation prevented robust classification using either hemodynamic indices or entire pulse-velocity waveforms based on the fetal data records used for this study

An investigation of real time ultrasound Doppler techniques for tissue motion and deformation analysis

Cardiovascular disease accounts for more than 50% of all deaths in the Western world. Atherosclerosis is responsible for the vast majority of these diseases. There are a range of risk factors for atherosclerosis that affect the endothelial lining vessel wall cells to cause endothelial dysfunction, which then predisposes to a localized build-up of 'plaque' tissue that narrows the lumen of the arteries. Plaque rupture promotes localized vasospasm, thrombosis and embolism causing downstream tissue death, resulting in severe disability or death from, for instance, heart attack (in the coronary circulation) or stroke (in the cerebral circulation). Narrowing of the lumen and plaque rupture are associated with high tissue stresses and tissue under perfusion, which will alter local arterial and myocardial wall dynamics and elastic properties. Hence visualization of tissue dynamic and deformation property changes is crucial to detect atherosclerosis in the earliest stages to prevent acute events.The objective of this dissertation research is to develop new techniques based on Doppler ultrasound to investigate and visualize changes in tissue dynamic and deformation properties due to atherosclerosis in cardiac and vascular applications. A new technique, to correct for the Doppler angle dependence for tissue motion analysis has been developed. It is based on multiple ultrasound beams, and has been validated in vitro to study tissue dynamic properties. It can measure tissue velocity magnitude with low bias (5%) and standard deviation (10%), and tissue velocity orientation with a bias less than 5 degrees and a standard deviation below 5 degrees. A new Doppler based method, called strain rate, has also been developed and validated in vitro for the quantification of regional vessel or myocardial wall deformation. Strain rate is derived from the velocity information and can assess tissue deformation with an accuracy of 5% and a standard deviation less than 10%. Some examples of cardiac strain rate imaging have been gathered and are described in this thesis. Strain rate, as all Doppler based techniques, suffers from angle dependence limitation. A method to estimate one-component strain rate in any direction in the two-dimensional image not necessarily along the ultrasound beam has been developed. The method allows correcting for the strain rate bias along any user-defined direction. It is also shown that the full strain rate tensor can theoretically be extracted from the velocity vector field acquired by multiple beam tissue vector velocity technique. In vitro experiments have shown that qualitative two-component strain rate tensor can be derived. Two-component vector velocity from the moving tissue was acquired and two two-component strain rate images were derived. The images showed agreement with the expected deformation pattern

The use of Fluid Haemodynamics in the Diagnosis of Cardiovascular Disease

Currently the diagnostic methods used to detect cardiovascular disease largely rely on the inference of the presence of arterial stenosis. There is a clinical interest in the development of a diagnostic screening technique which can indicate the risk of developing cardiovascular disease at an early stage so that non-surgical treatments can be applied. The goal of this work was to develop and validate a diagnostic screening technique for cardiovascular disease using the mechanical biomarker wall shear stress. Improvements in wall shear stress measurements were made by using a 2D Fourier transform to extract additional spectral information from the ultrasound pulse and decrease the spectral variance by integrating across the bandwidth of transmitted frequencies. This technique was validated for a series of anatomically realistic flow phantoms which precisely mimicked the progression of wall stiffening that characterises cardiovascular disease. The newly developed spectral analysis technique demonstrated a higher diagnostic performance than the other techniques tested, both in terms of a greater degree of significance in detecting differences in vessel wall stiffness and in terms of the sensitivity and specificity of the technique. The technique could not be tested in pulsatile flow due to hardware limitations, but preliminary testing indicated that the increased performance of the technique would likely transfer to a physiological flow regime. The results of this work indicated that the algorithm had the potential to rival the diagnostic power of the current gold standard while being applicable at an earlier stage of cardiovascular disease