Noninvasive ambient pressure estimation using ultrasound contrast agents – invoking subharmonics for cardiac and hepatic applications

Ultrasound contrast agents (UCAs) are encapsulated microbubbles that provide a source for acoustic impedance mismatch with the blood, due to difference in compressibility between the gas contained within these microbubbles and the blood. When insonified by an ultrasound beam, these UCAs act as nonlinear scatterers and enhance the echoes of the incident pulse, resulting in scattering of the incident ultrasound beam and emission of fundamental (f0), subharmonic (f0/2), harmonic (n*f0; n ) and ultraharmonic (((2n-1)/2)*f0; n & n > 1) components in the echo response.A promising approach to monitor in vivo pressures revolves around the fact that the ultrasound transmit and receive parameters can be selected to induce an ambient pressure amplitude dependent subharmonic signal. This subharmonic signal may be used to estimate ambient pressure amplitude; such technique of estimating ambient pressure amplitude is referred to as subharmonic aided pressure estimation or SHAPE. This project develops and evaluates the feasibility of SHAPE to noninvasively monitor cardiac and hepatic pressures (using commercially available ultrasound scanners and UCAs) because invasive catheter based pressure measurements are used currently for these applications.Invasive catheter based pressure measurements pose risk of introducing infection while the catheter is guided towards the region of interest in the body through a percutaneous incision, pose risk of death due to structural or mechanical failure of the catheter (which has also triggered product recalls by the USA Food and Drug Administration) and may potentially modulate the pressures that are being measured. Also, catheterization procedures require fluoroscopic guidance to advance the catheter to the site of pressure measurements and such catheterization procedures are not performed in all clinical centers. Thus, a noninvasive technique to obtain ambient pressure values without the catheterization process is clinically helpful.While an intravenous injection is required to inject the UCAs into the body, this procedure is considered noninvasive as per the definition provided by the Center for Medicare and Medicaid Services; invasive procedures include surgical procedures as well as catheterization procedures while minor procedures such as drawing blood (which requires a similar approach as injecting UCAs) are considered noninvasive.In vitro results showed that the standard error between catheter pressures and SHAPE results is below 10 mmHg with a correlation coefficient value of above 0.9 – this experimental error of 10 mmHg is less than the errors associated with other techniques utilizing UCAs for ambient pressure estimation. In vivo results proved the feasibility of SHAPE to noninvasively estimate clinically relevant left and right ventricular (LV and RV) pressures. The maximum error in estimating the LV and RV systolic and diastolic pressures was 3.5 mmHg. Thus, the SHAPE technique may be useful for systolic and diastolic pressure estimation given that the standard recommendations require the errors for these pressure measurements to be within 5 mmHg. The ability of SHAPE to identify induced portal hypertension (PH) was also proved. The changes in the SHAPE data correlated significantly (p < 0.05) with the changes in the portal vein (PV) pressures and the absolute amplitudes of the subharmonic signal also correlated with absolute PV pressures.The SHAPE technique provides the ability to noninvasively obtain in vivo pressures. This technique is applicable not only for critically ill patients, but also for screening symptomatic patients and potentially for other clinical pressure monitoring applications, as well.Ph.D., Biomedical Engineering -- Drexel University, 201

Implementation of differential self-mixing interferometry systems for the detection of nanometric vibrations

In this Thesis, we explore Self-mixing interferometry (SMI ), a method capable of producing high resolution optical path related measurements in a simple, compact and cost-effective way. Even with a notably less complex setup than traditional interferometric methods, SMI can produce measurements with a resolution well below the micrometric scale (N'2) which is sufficient for most industrial applications. The SMI effect is produced when a small part of the laser power impacting a target is back-scattered and re-injected into the laser cavity. As a result, the phase and amplitude of the laser wave is modified generating a signature beat, which can be "easily" related to different optical path-related dynamics. The main advantage of this method in relation to other interferometric methods is the simple setup consisting mainly of a single mode laser diode (LO) equipped with a simple electronic system readout a simple optical system may be used to collimate/focus the beam allowing measurements at larger distances. Because of the small amount of reflected optical power required to allow the effect, the technique can produce high resolution measurements even with diffusive targets. While the SMI method has been largely studied in the last three decades, there are still several topics worth the development of further research. One of those topics, how to increase the resolution on displacement measurements, is one of the main topics covered in this work. Classical SMI methods allow the reconstruction of displacement measurement with a resolution of N'2. The use of special processing algorithms can push further this limit reaching values in the order of e.g. N32. In this work, we propose a method to increase even further this limit reach values better than N100.The idea discussed, differential self-mixing interferometry (OSMI) proposes the use of a reference modulation (mechanical or electrical) to be used as a reference for the measurement. Simulated results have shown that under ideal conditions, it may be possible to reach resolutions in the order of N1000. In practice, however, this limit is much smaller (N100) because of LO dynamics, and different practical limitations present in the amplification and readout electronics. Experiments and measurements are presented along the second chapter of this work to present proof of the proposed method. After exploring the basics of OSMI, possible applications for classic SMI and DSMI were pursued. The obtained results are presented in the following sections. First, a review on potential biomedical measurements using SMI is discussed. The obtained results suggest that it is possible to obtain some key values related to biomedical constants (e.g. P.PW) using a displacement SMI measurement. The method, however, may not be reliable enough especially on long time measurements. Moreover, the use of certain wavelengths must be avoided during long exposures as they may prove harmful to the soft tissue due to the requirements of a small laser spot. lt is observed that SNR may lead to difficulties during the signal processing stage which may impact the results of the reconstructed signal. Next, the DSMI method was tested in an AFM-like cantilever system. The results suggest that is possible to follow the motion of a micrometric size cantilever oscillating at low frequencies with a high resolution. Higher frequencies may be achieved by using an electronic reference modulation configuration. The proposed system was able to detect some artefacts on the motion which maybe attributed to possible deflections on the cantilever surface. Possible enhancements to the method are suggested for any researcher who wants to expand the topic.En esta Tesis, se explora la interferometría auto-mezclante, mejor conocida por su nombre en inglés Self-m ixing interferometry (SMI), un método capaz de producir mediciones relativas al cambio del camino óptico en un haz laser. La técnica está caracterizada por su tamaño compacto, bajo coste y alta resolución. Pese a su simplicidad, la resolución alcanzada por sistemas basados en SMI se encuentra por debajo de la escala micrométrica (N2), lo cual es suficiente para la mayoría de las aplicaciones industriales. El efecto SMI se genera cuando una pequeña parte de la potencia óptica del láser es retro reflectada por un blanco y reinyectada en la cavidad láser. Como resultado, se genera una modulación de la amplitud y fase del láser, la cual puede ser "fácilmente" relacionada con diferentes efectos relativos al camino óptico del láser. La principal ventaja del método SMI es la simplicidad del sistema de medición el cual está compuesto de un diodo láser (LO) equipado con una tarjeta de procesamiento electrónico. una lente de enfoque o colimación puede ser utilizada con el fin de regular la reinyección de potencia y la distancia al blanco. Debido a que el SMI se genera con una pequeña cantidad de potencia es posible realizar mediciones incluso en blancos con reflexión difusa. . Si bien el método SMI ha sido estudiado ampliamente durante las 3 últimas décadas, aún existen diversos puntos de interés en su estudio. Uno de estos puntos corresponde a la mejora de resolución en la medida de desplazamiento, el cuál es uno de los temas abordados en el presente trabajo. Los métodos clásicos SMI para la medición de desplazamiento permiten alcanzar una resolución en el orden de A/2. El uso de algoritmos de procesamiento especializados puede permitir mejorar el límite de la técnica alcanzando resoluciones (por ejemplo) en el orden de N32. En este trabajo proponemos un método que teóricamente permitiría alcanzar resoluciones mejores que N1OO. La discusión en este punto se sitúa sobre la técnica differential self-mixing interferometry (DSMI), la cual hace uso de una modulación de referencia (mecánica o electrónica) para realizar la medición. Los resultados de diversas simulaciones sugieren que, en condiciones ideales, la técnica es capaz de producir una resolución superior a N1000. En la práctica, el límite encontrado es menor (N100), lo cual puede ser atribuido a condiciones de ruido y efectos de no linealidad en el láser. Para apoyar la idea propuesta diversas medidas simuladas y experimentales son presentadas a lo largo de esta Tesis. Después de explorar las ideas básicas de DSMI, un grupo de posibles aplicaciones para SMI y DSMI fueron exploradas en este trabajo. Una revisión de posibles aplicaciones biomédicas utilizando SMI fue explorada. Los resultados obtenidos sugieren que es posible obtener valores relacionados con constantes biomédicas de interés (p.e. APW) utilizando medidas de desplazamiento basadas en SMI. El método, sin embargo, no es lo suficientemente fiable como para producir medidas estables en un uso prolongado. El SNR de la señal puede introducir complicaciones durante el procesado SMI que puede derivar en errores de reconstrucción de la señal original. . El método DSMI fue probado en un prototipo de sistema AFM equipado con un cantiléver. Los resultados obtenidos sugieren que la técnica es capaz de medir movimientos producidos por un cantiléver de dimensiones micrométricas con alta resolución en bajas frecuencias. La medición de oscilaciones de mayor frecuencia podría ser alcanzada utilizando una configuración basada en modulación electrónica. El sistema propuesto fue capaz de detectar artefactos en el movimiento que podrían ser atribuidos a deflexiones en el cantiléver. Algunas posibles mejoras a esta implementación son sugeridas como puntos para futuras investigaciones alrededor de este tema.Postprint (published version

Aerospace medicine and biology, an annotated bibliography. volume xi- 1962-1963 literature

Aerospace medicine and biology - annotated bibliography for 1962 and 196

Molecular phylogeny of horseshoe crab using mitochondrial Cox1 gene as a benchmark sequence

An effort to assess the utility of 650 bp Cytochrome C oxidase subunit I (DNA barcode) gene in delineating the members horseshoe crabs (Family: xiphosura) with closely related sister taxa was made. A total of 33 sequences were extracted from National Center for Biotechnological Information (NCBI) which include horseshoe crabs, beetles, common crabs and scorpion sequences. Constructed phylogram showed beetles are closely related with horseshoe crabs than common crabs. Scorpion spp were distantly related to xiphosurans. Phylogram and observed genetic distance (GD) date were also revealed that Limulus polyphemus was closely related with Tachypleus tridentatus than with T.gigas. Carcinoscorpius rotundicauda was distantly related with L.polyphemus. The observed mean Genetic Distance (GD) value was higher in 3rd codon position in all the selected group of organisms. Among the horseshoe crabs high GC content was observed in L.polyphemus (38.32%) and lowest was observed in T.tridentatus (32.35%). We conclude that COI sequencing (barcoding) could be used in identifying and delineating evolutionary relatedness with closely related specie