A Framework for Tumor Localization in Robot-Assisted Minimally Invasive Surgery

Manual palpation of tissue is frequently used in open surgery, e.g., for localization of tumors and buried vessels and for tissue characterization. The overall objective of this work is to explore how tissue palpation can be performed in Robot-Assisted Minimally Invasive Surgery (RAMIS) using laparoscopic instruments conventionally used in RAMIS. This thesis presents a framework where a surgical tool is moved teleoperatively in a manner analogous to the repetitive pressing motion of a finger during manual palpation. We interpret the changes in parameters due to this motion such as the applied force and the resulting indentation depth to accurately determine the variation in tissue stiffness. This approach requires the sensorization of the laparoscopic tool for force sensing. In our work, we have used a da Vinci needle driver which has been sensorized in our lab at CSTAR for force sensing using Fiber Bragg Grating (FBG). A computer vision algorithm has been developed for 3D surgical tool-tip tracking using the da Vinci \u27s stereo endoscope. This enables us to measure changes in surface indentation resulting from pressing the needle driver on the tissue. The proposed palpation framework is based on the hypothesis that the indentation depth is inversely proportional to the tissue stiffness when a constant pressing force is applied. This was validated in a telemanipulated setup using the da Vinci surgical system with a phantom in which artificial tumors were embedded to represent areas of different stiffnesses. The region with high stiffness representing tumor and region with low stiffness representing healthy tissue showed an average indentation depth change of 5.19 mm and 10.09 mm respectively while maintaining a maximum force of 8N during robot-assisted palpation. These indentation depth variations were then distinguished using the k-means clustering algorithm to classify groups of low and high stiffnesses. The results were presented in a colour-coded map. The unique feature of this framework is its use of a conventional laparoscopic tool and minimal re-design of the existing da Vinci surgical setup. Additional work includes a vision-based algorithm for tracking the motion of the tissue surface such as that of the lung resulting from respiratory and cardiac motion. The extracted motion information was analyzed to characterize the lung tissue stiffness based on the lateral strain variations as the surface inflates and deflates

A centrifugal microfluidic platform for capturing, assaying and manipulation of beads and biological cells

Microfluidics is deemed a field with great opportunities, especially for applications in medical diagnostics. The vision is to miniaturize processes typically performed in a central clinical lab into small, simple to use devices - so called lab-on-a-chip (LOC) systems. A wide variety of concepts for liquid actuation have been developed, including pressure driven flow, electro-osmotic actuation or capillary driven methods. This work is based on the centrifugal platform (lab-on-a-disc). Fluid actuation is performed by the forces induced due to the rotation of the disc, thus eliminating the need for external pumps since only a spindle motor is necessary to rotate the disc and propel the liquids inside of the micro structures. Lab-on-a-disc systems are especially promising for point-of-care applications involving particles or cells due to the centrifugal force present in a rotating system. Capturing, assaying and identification of biological cells and microparticles are important operations for lab-on-a-disc platforms, and the focus of this work is to provide novel building blocks towards an integrated system for cell and particle based assays. As a main outcome of my work, a novel particle capturing and manipulation scheme on a centrifugal microfluidic platform has been developed. To capture particles (biological cells or micro-beads) I designed an array of V-shaped micro cups and characterized it. Particles sediment under stagnant flow conditions into the array where they are then mechanically trapped in spatially well-defined locations. Due to the absence of flow during the capturing process, i.e. particle sedimentation is driven by the artificial gravity field on the centrifugal platform, the capture efficiency of this approach is close to 100% which is notably higher than values reported for typical pressure driven systems. After capturing the particles, the surrounding medium can easily be exchanged to expose them to various conditions such as staining solutions or washing buffers, and thus perform assays on the captured particles. By scale matching the size of the capturing elements to the size of the particles, sharply peaked single occupancy can be achieved. Since all particles are arrayed in the same focal plane in spatially well defined locations, operations such as counting or fluorescent detection can be performed easily. The application of this platform to perform multiplexed bead-based immunoassays as well as the discrimination of various cell types based on intra cellular and membrane based markers using fluorescently tagged antibodies is demonstrated. Additionally, methods to manipulate captured particles either in batch mode or on an individual particle level have been developed and characterized. Batch release of captured particles is performed by a novel magnetic actuator which is solely controlled by the rotation frequency of the disc. Furthermore, the application of this actuator to rapidly mix liquids is shown. Manipulation of individual particles is performed using an optical tweezers setup which has been developed as part of this work. Additionally, this optical module also provides fluorescence detection capabilities. This is the first time that optical tweezers have been combined with a centrifugal microfluidic system. This work presents the core technology for an integrated centrifugal platform to perform cell and particle based assays for fundamental research as well as for point-of- care applications. The key outputs of my specific work are: 1. Design, fabrication and characterization of a novel particle capturing scheme on a centrifugal microfluidic platform (V-cups) with very high capture efficiency (close to 100%) and sharply peaked single occupancy (up to 99.7% single occupancy). 2. A novel rotation frequency controlled magnetic actuator for releasing captured particles as well as for rapidly mixing liquids has been developed, manufactured and characterized. 3. The V-cup platform has successfully been employed to capture cells and perform multi-step antibody staining assays for cell discrimination. 4. An optical tweezers setup has been built and integrated into a centrifugal teststand, and successful manipulation of individual particles trapped in the V-cup array is demonstrated

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Investigating the build-up of precedence effect using reflection masking

The auditory processing level involved in the build‐up of precedence [Freyman et al., J. Acoust. Soc. Am. 90, 874–884 (1991)] has been investigated here by employing reflection masked threshold (RMT) techniques. Given that RMT techniques are generally assumed to address lower levels of the auditory signal processing, such an approach represents a bottom‐up approach to the buildup of precedence. Three conditioner configurations measuring a possible buildup of reflection suppression were compared to the baseline RMT for four reflection delays ranging from 2.5–15 ms. No buildup of reflection suppression was observed for any of the conditioner configurations. Buildup of template (decrease in RMT for two of the conditioners), on the other hand, was found to be delay dependent. For five of six listeners, with reflection delay=2.5 and 15 ms, RMT decreased relative to the baseline. For 5‐ and 10‐ms delay, no change in threshold was observed. It is concluded that the low‐level auditory processing involved in RMT is not sufficient to realize a buildup of reflection suppression. This confirms suggestions that higher level processing is involved in PE buildup. The observed enhancement of reflection detection (RMT) may contribute to active suppression at higher processing levels

Wearable and BAN Sensors for Physical Rehabilitation and eHealth Architectures

The demographic shift of the population towards an increase in the number of elderly citizens, together with the sedentary lifestyle we are adopting, is reflected in the increasingly debilitated physical health of the population. The resulting physical impairments require rehabilitation therapies which may be assisted by the use of wearable sensors or body area network sensors (BANs). The use of novel technology for medical therapies can also contribute to reducing the costs in healthcare systems and decrease patient overflow in medical centers. Sensors are the primary enablers of any wearable medical device, with a central role in eHealth architectures. The accuracy of the acquired data depends on the sensors; hence, when considering wearable and BAN sensing integration, they must be proven to be accurate and reliable solutions. This book is a collection of works focusing on the current state-of-the-art of BANs and wearable sensing devices for physical rehabilitation of impaired or debilitated citizens. The manuscripts that compose this book report on the advances in the research related to different sensing technologies (optical or electronic) and body area network sensors (BANs), their design and implementation, advanced signal processing techniques, and the application of these technologies in areas such as physical rehabilitation, robotics, medical diagnostics, and therapy

High-throughput estimation of crop traits: A review of ground and aerial phenotyping platforms

Crop yields need to be improved in a sustainable manner to meet the expected worldwide increase in population over the coming decades as well as the effects of anticipated climate change. Recently, genomics-assisted breeding has become a popular approach to food security; in this regard, the crop breeding community must better link the relationships between the phenotype and the genotype. While high-throughput genotyping is feasible at a low cost, highthroughput crop phenotyping methods and data analytical capacities need to be improved. High-throughput phenotyping offers a powerful way to assess particular phenotypes in large-scale experiments, using high-tech sensors, advanced robotics, and imageprocessing systems to monitor and quantify plants in breeding nurseries and field experiments at multiple scales. In addition, new bioinformatics platforms are able to embrace large-scale, multidimensional phenotypic datasets. Through the combined analysis of phenotyping and genotyping data, environmental responses and gene functions can now be dissected at unprecedented resolution. This will aid in finding solutions to currently limited and incremental improvements in crop yields

Identification and validation of target pathways influencing outcome after traumatic brain injury

Traumatic brain injury (TBI) involves both an initial primary insult to the brain and a delayed secondary injury in the hours and days thereafter. The delayed nature of secondary brain injury leaves open the possibility for a window of therapeutic intervention to prevent neurodegeneration. As there are currently no approved drugs for the treatment and prevention of secondary injury after TBI, my approach has been to first identify molecular pathways associated with a differential outcome from injury, followed by validation of these pathways by targeting them with a variety of therapeutic strategies ranging from genetic manipulation to novel drug compounds, and dietary supplementation. The Apolipoprotein E (APOE) gene has three major alleles, APOE2, APOE3 and APOE4, the latter of which confers risk for poor outcome following TBI. Using quantitative Liquid Chromatography-Mass Spectrometry, large proteomic datasets can be generated, and the difference in protein expression in response to TBI between transgenic mice expressing APOE3 or APOE4 can reveal changes that reflect a "better" or "worse" outcome, respectively. Analyzing such datasets from APOE3 and APOE4 transgenic mice at a wide range of time points, we examined the differential response to TBI and identified several protein pathways of interest, including: CD40 signaling, NF-kB signaling, and APP related proteins. Optimizing several behavioral I testing paradigms (Rotarod, Morris Water Maze, and Barnes Maze), we characterized spatial memory and motor function deficits resulting from TBI in order to quantify a "good" or "poor" response. Using a variety of targeted intervention strategies (CD40L knockout, administration of (-)-Nllvadipine, or anatabine) to modulate the protein pathways of interest, we showed improvement in response to TBI. Overall, these experiments provide demonstrate the effectiveness of using a systems biology approach to find potential targets for therapeutic intervention