Robotically Steered Needles: A Survey of Neurosurgical Applications and Technical Innovations

This paper surveys both the clinical applications and main technical innovations related to steered needles, with an emphasis on neurosurgery. Technical innovations generally center on curvilinear robots that can adopt a complex path that circumvents critical structures and eloquent brain tissue. These advances include several needle-steering approaches, which consist of tip-based, lengthwise, base motion-driven, and tissue-centered steering strategies. This paper also describes foundational mathematical models for steering, where potential fields, nonholonomic bicycle-like models, spring models, and stochastic approaches are cited. In addition, practical path planning systems are also addressed, where we cite uncertainty modeling in path planning, intraoperative soft tissue shift estimation through imaging scans acquired during the procedure, and simulation-based prediction. Neurosurgical scenarios tend to emphasize straight needles so far, and span deep-brain stimulation (DBS), stereoelectroencephalography (SEEG), intracerebral drug delivery (IDD), stereotactic brain biopsy (SBB), stereotactic needle aspiration for hematoma, cysts and abscesses, and brachytherapy as well as thermal ablation of brain tumors and seizure-generating regions. We emphasize therapeutic considerations and complications that have been documented in conjunction with these applications

Lab-on-a-chip Thermoelectric and Solid-phase Immunodetection of Biochemical Analytes and Extracellular Vesicles: Experimental and Computational Analysis

Microfluidics is the technology of controlling and manipulating fluids at the microscale. Microfluidic platforms provide precise fluidic control coupled with low sample volume and an increase in the speed of biochemical reactions. Lab-on-a-chip platforms are used for detection and quantification of biochemical analytes, capture, and characterization of various proteins, sensitive analysis of cytokines, and isolation and detection of extracellular vesicles (EVs). This study focuses on the development of microfluidic and solid-phase capture pin platforms for the detection of cytokines, extracellular vesicles, and cell co-culture. The fabrication processes of the devices, experimental workflows, numerical analysis to identify optimal design parameters, and reproducibility studies have been discussed. Layer-by-layer assembly of polyelectrolytes has been developed to functionalize glass and stainless-steel substrates with biotin for the immobilization of streptavidinconjugated antibodies for selective capture of cytokines or EVs. Microstructure characterization techniques (SEM, EDX, and fluorescence microscopy) have been implemented to assess the efficiency of substrate functionalization. A detailed overview of current methods for purification and analysis of EVs is discussed as well. Additionally, the dissertation demonstrates the feasibility of a calorimetric microfluidic immunosensor with an integrated antimony-bismuth (Sb/Bi) thermopile sensor for the detection of cytokines with picomolar sensitivity. The developed platform can be used for the universal detection of both exothermic or endothermic reactions. A three-dimensional numerical model was developed to define the critical design parameters that enhance the sensitivity of the platform. Mathematical analyses identified the optimal combinations of substrate material and dimensions that will maximize the heat transfer to the sensor. Lab-on-a-chip cell co-culture platform with integrated pneumatic valve was designed, numerically characterized, and fabricated. This device enables the reversible separation of two cell culture chambers and serves as a tool for the effective analysis of cell-to-cell communication. Intercellular communication is mediated by extracellular vesicles. A protocol for the functionalization of stainless-steel probe with exosomespecific CD63 antibody was developed. The efficiency of the layer-by-layer deposition of polyelectrolytes and the effectiveness of biotin and streptavidin covalent boding were characterized using fluorescent and scanning electron microscopy

Vocal fold vibratory and acoustic features in fatigued Karaoke singers

Session 3aMU - Musical Acoustics and Speech Communication: Singing Voice in Asian CulturesKaraoke is a popular singing entertainment particularly in Asia and is gaining more popularity in the rest of world. In Karaoke, an amateur singer sings with the background music and video (usually guided by the lyric captions on the video screen) played by Karaoke machine, using a microphone and an amplification system. As the Karaoke singers usually have no formal training, they may be more vulnerable to vocal fatigue as they may overuse and/or misuse their voices in the intensive and extensive singing activities. It is unclear whether vocal fatigue is accompanied by any vibration pattern or physiological changes of vocal folds. In this study, 20 participants aged from 18 to 23 years with normal voice were recruited to participate in an prolonged singing task, which induced vocal fatigue. High speed laryngscopic imaging and acoustic signals were recorded before and after the singing task. Images of /i/ phonation were quantitatively analyzed using the High Speed Video Processing (HSVP) program (Yiu, et al. 2010). It was found that the glottis became relatively narrower following fatigue, while the acoustic signals were not sensitive to measure change following fatigue. © 2012 Acoustical Society of Americapublished_or_final_versio

Effective treatment of solid tumors via Cryosurgery

Ph.DDOCTOR OF PHILOSOPH

Optical dosimetry tools and Monte Carlo based methods for applications in image guided optical therapy in the brain

Purpose: The long-term goal of this research is to determine the feasibility of using near infra-red light to stimulate drug release in metastatic lesions within the brain. In this work, we focused on developing the tools needed to quantify and verify photon fluence distribution in biological tissue. To accomplish this task, an optical dosimetry probe and Monte Carlo based simulation code were fabricated, calibrated and developed to predict light transport in heterogeneous tissue phantoms of the skull and brain. Empirical model (EM) of photon transport using CT images as input were devised to provide real-time calculations capable of being translated to preclinical and clinical applications. Methods and Materials: A GPU based 3D Monte Carlo code was customized to simulate the photon transport within head phantoms consisting of skull bone, white and gray matter with differing laser beam properties, including flat, Gaussian, and super-Gaussian profiles that are converging, parallel, or diverging. From these simulations, the local photon fluence and tissue dosimetric distribution was simulated and validated through the implementation of a novel titanium-based optical dosimetry probe with an isotropic acceptance and 1.5mm diameter. Empirical models (EM) of photon transport were devised and calibrated to MC simulated data to provide 3D fluence and optical dosimetric maps in real-time developed around on a voxel-based convolution technique. Optical transmission studies were performed using human skull bone samples to determine the optical transmission characteristics of heterogeneous bone structures and the effectiveness of the Monte Carlo in simulating this heterogeneity. These tools provide the capability to develop and optimize treatment plans for optimal release of pharmaceuticals to metastatic breast cancer in the brain. Results: At the time of these experiments, the voxel-based CUDA MC code implemented and further developed in this study had not been validated by measurement. A novel optical dosimetry probe was fabricated and calibrated to measure the absolute photon fluence (mW/mm2) in phantoms resembling white matter, gray matter and skull bone and compared to 3D Monte Carlo simulated data. The TiO2-based dosimetry probe was shown to have superior linearity and isotropicity of response to previous Nylon based probes, and was better suited to validate the Monte Carlo using localized 3D measurement (\u3c 25% systematic error for white matter, gray matter and skull bone phantoms along illumination beam axis up to a depth of 2cm in homogeneous tissue and 3.8cm in heterogeneous head phantom). Next, the transport parameters of the empirical algorithm was calibrated using the 3D Monte Carlo and EMs and validated by optical dosimetry probe measurements (with error of 10.1% for White Matter, 45.1% for Gray Matter and 22.1% for Skull Bone phantoms) along illumination beam axis. Conclusions: The design and validation of the Monte Carlo, the optical dosimetry probe and the Empirical algorithm increases the clinical feasibility of optical therapeutic planning to narrow down the complex possibilities of illumination conditions, further compounded by the heterogeneous structure of the brain, such as varying skull thicknesses and densities. Our ultimate goal is to design a fast Monte Carlo based optical therapeutic protocol to treat brain metastasis. The voxelated nature of the MC and EM provides the necessary 3D photon distribution to within 25% error to guide future clinical studies involving optically triggered drug release

A Patient-Specific Infrared Imaging Technique for Adjunctive Breast Cancer Screening: A Clinical and Simulation - Based Approach

Breast cancer is currently the most prevalent form of cancer in women with over 266,000 new diagnoses every year. The various methods used for breast cancer screening range in accuracy and cost, however there is no easily reproducible, reliable, low-cost screening method currently available for detecting cancer in breasts, especially with dense tissue. Steady-state Infrared Imaging (IRI) is unaffected by tissue density and has the potential to detect tumors in the breast by measuring and capturing the thermal profile on the breast surface induced by increased blood perfusion and metabolic activity in a rapidly growing malignant tumor. The current work presents a better understanding of IRI as an accurate breast cancer detection modality. A detailed study utilizing IRI-MRI approach with clinical design and validation of an elaborate IRI-Mammo study are presented by considering patient population, clinical study design, image interpretation, and recommended future path. Clinical IRI images are obtained in this study and an ANSYS-based modeling process developed earlier at RIT is used to localize and detect tumor in seven patients without subjective human interpretation. Further, the unique thermal characteristics of tumors that make their signatures distinct from benign conditions are identified. This work is part of an ongoing multidisciplinary collaboration between a team of thermal engineers and numerical modelers at the Rochester Institute of Technology and a team of clinicians at the Rochester General Hospital. The following components were developed to ensure valid experimentation while considering ethical considerations: IRB documentation, patient protocols, an image acquisition system (camera setup and screening table), and the necessary tools needed for image analysis without human interpretation. IRI images in the prone position were obtained and were used in accurately detecting the presence of a cancerous tumor in seven subjects. The size and location of tumor was also confirmed within 7 mm as compared to biopsy-proven pathology information. The study indicates that the IRI-Mammo approach has potential to be a highly effective adjunctive screening tool that can improve the breast cancer detection rates especially for subjects with dense breast tissue. This method is low cost, no-touch, radiation-free and highly portable, making it an attractive candidate as a breast cancer detection modality. Further, the developed method provided insight into infrared features corresponding to other biological images, pathology reports and patient history