Low bandwidth eye tracker for scanning laser ophthalmoscopy

Use of adaptive optics with scanning laser ophthalmoscopes (AOSLOs) has allowed for in vivo, noninvasive imaging of the human rod and cone pho- toreceptor mosaic. This modality could prove to be a valuable tool for clin- icians in early diagnosis of retinal disease as well as provide invaluable incite for researchers. In order for these instruments to become practical in a clinical environment, many challenges must be overcome. Involuntary eye motion makes the use of AOSLOs particularly difficult as it increases imaging time, post-processing time, data storage requirements, and, most importantly, subject\u27s chances of retinal damage due to light exposure. The goal of this thesis is to develop a real time eye tracking and com- pensation system capable of overcoming slow eye drift. Data acquisition and synchronization software and electronics were developed for use with an AOSLO. A motion estimation technique based on normalized cross cor- relation NCC accelerated by CUDA enabled graphics cards was used as a basis for the tracking system. Motion prediction methods were developed and evaluated in order to increase the system bandwidth. Specifically, lin- ear and quadratic extrapolation, discrete cosine transform extrapolation, and Kalman filtering techniques were used. These tracking methods were evaluated using simulated motion and real subjects

Single Camera Spectral Domain Polarization-sensitive Optical Coherence Tomography Using Offset B-scan Modulation

doi:10.1364/OE.18.007281We report a simple implementation to acquire spectral domain polarization-sensitive optical coherence tomography (PSOCT) using a single camera. By combining a dual-delay assembly in the reference arm and offset B-scan in the sample arm, the orthogonal vertical- and horizontalpolarized images were acquired in parallel and spatially separated by a fixed distance in the full range image space. The two orthogonal polarization images were recombined to calculate the intensity, retardance and fast-axis images. This system was easy to implement and capable of acquiring highspeed in vivo 3D polarization-sensitive OCT images

Distributed Network, Wireless and Cloud Computing Enabled 3-D Ultrasound; a New Medical Technology Paradigm

Medical technologies are indispensable to modern medicine. However, they have become exceedingly expensive and complex and are not available to the economically disadvantaged majority of the world population in underdeveloped as well as developed parts of the world. For example, according to the World Health Organization about two thirds of the world population does not have access to medical imaging. In this paper we introduce a new medical technology paradigm centered on wireless technology and cloud computing that was designed to overcome the problems of increasing health technology costs. We demonstrate the value of the concept with an example; the design of a wireless, distributed network and central (cloud) computing enabled three-dimensional (3-D) ultrasound system. Specifically, we demonstrate the feasibility of producing a 3-D high end ultrasound scan at a central computing facility using the raw data acquired at the remote patient site with an inexpensive low end ultrasound transducer designed for 2-D, through a mobile device and wireless connection link between them. Producing high-end 3D ultrasound images with simple low-end transducers reduces the cost of imaging by orders of magnitude. It also removes the requirement of having a highly trained imaging expert at the patient site, since the need for hand-eye coordination and the ability to reconstruct a 3-D mental image from 2-D scans, which is a necessity for high quality ultrasound imaging, is eliminated. This could enable relatively untrained medical workers in developing nations to administer imaging and a more accurate diagnosis, effectively saving the lives of people

Optical imaging of the chorioretinal vasculature in the living human eye

Detailed visualization of microvascular changes in the human retina is clinically limited by the capabilities of angiography imaging, a 2D fundus photograph that requires an intravenous injection of fluorescent dye. Whereas current angiography methods enable visualization of some retinal capillary detail, they do not adequately reveal the choriocapillaris or other microvascular features beneath the retina. We have developed a noninvasive microvascular imaging technique called phase-variance optical coherence tomography (pvOCT), which identifies vasculature three dimensionally through analysis of data acquired with OCT systems. The pvOCT imaging method is not only capable of generating capillary perfusion maps for the retina, but it can also use the 3D capabilities to segment the data in depth to isolate vasculature in different layers of the retina and choroid. This paper demonstrates some of the capabilities of pvOCT imaging of the anterior layers of choroidal vasculature of a healthy normal eye as well as of eyes with geographic atrophy (GA) secondary to age-related macular degeneration. The pvOCT data presented permit digital segmentation to produce 2D depth-resolved images of the retinal vasculature, the choriocapillaris, and the vessels in Sattler’s and Haller’s layers. Comparisons are presented between en face projections of pvOCT data within the superficial choroid and clinical angiography images for regions of GA. Abnormalities and vascular dropout observed within the choriocapillaris for pvOCT are compared with regional GA progression. The capability of pvOCT imaging of the microvasculature of the choriocapillaris and the anterior choroidal vasculature has the potential to become a unique tool to evaluate therapies and understand the underlying mechanisms of age-related macular degeneration progression

Detection of Intra-Tumor Self Antigen Recognition during Melanoma Tumor Progression in Mice Using Advanced Multimode Confocal/Two Photon Microscope

Determining how tumor immunity is regulated requires understanding the extent to which the anti-tumor immune response “functions” in vivo without therapeutic intervention. To better understand this question, we developed advanced multimodal reflectance confocal/two photon fluorescence intra-vital imaging techniques to use in combination with traditional ex vivo analysis of tumor specific T cells. By transferring small numbers of melanoma-specific CD8+ T cells (Pmel-1), in an attempt to mimic physiologic conditions, we found that B16 tumor growth alone was sufficient to induce naive Pmel-1 T cell proliferation and acquisition of effector phenotype. Tumor -primed Pmel-1 T cells, are capable of killing target cells in the periphery and secrete IFNγ, but are unable to mediate tumor regression. Within the tumor, Pmel-1 T cells have highly confined mobility, displaying long term interactions with tumor cells. In contrast, adoptively transferred non tumor-specific OT-I T cells show neither confined mobility, nor long term interaction with B16 tumor cells, suggesting that intra-tumor recognition of cognate self antigen by Pmel-1 T cells occurs during tumor growth. Together, these data indicate that lack of anti-tumor efficacy is not solely due to ignorance of self antigen in the tumor microenvironment but rather to active immunosuppressive influences preventing a protective immune response

Near real time confocal microscopy of Ex Vivo cervical tissue: detection of dysplasia

textRecent studies have shown the ability of confocal microscopy to noninvasively image cells in vivo in real time. This ability to visualize nuclei in vivo shows the potential of confocal microscopy to dramatically improve the prevention, detection and therapy of epithelial cancers. More exciting is the potential to quantitatively measure nuclear morphometry providing a basis to automate the cancer detection process. This dissertation describes studies exploring this potential in ex vivo cervical tissue using acetic acid as a nuclear contrast agent. First the use of acetic acid was demonstrated to improved contrast in confocal images of cervical tissue sufficiently to allow segmentation. Segmentation is robust throughout the epithelium in most normal tissue and upper portions of tissue diagnosed with severe dysplasia. Based upon this segmentation, quantitative feature measurements were extracted from confocal images of cervical tissue in a pilot study to determine if the features would aide in the detection of dysplasia. Simultaneously, a qualitative review of confocal images was performed by untrained reviewers and compared with clinical colposcopic impressions, the standard clinical tool aiding in dysplasia detection. The sensitivity and specificity of both the qualitative (95% and 69%) and quantitative (100% and 91%) review were improved compared to colposcopic review (91% and 62%). Finally the ability of confocal microscopy to produce 3D images was explored as a further means to improve dysplasia detection. Based upon Beer’s equation for light attenuation, the scattering coefficient was extracted from 3D image sets of ex vivo cervical tissue and compared with histology from the same precancerous lesion. The results suggested a possible correlation between high scattering values and the presence of dysplasia. Quantitative 3D features were also extracted from 3D image sets and correlated with the presence of CIN 2/3. Increased separation between normal and CIN 2/3 biopsies was produced using the 3D features as compared to the 2D. More importantly, when additional information (scattering coefficient) is combined with the 2D features, the ability to distinguish between normal and CIN 2/3 is 100% accurate in this small sample set.Electrical and Computer Engineerin

Image processing in medical ultrasound

This Ph.D project addresses image processing in medical ultrasound and seeks to achieve two major scientific goals: First to develop an understanding of the most significant factors influencing image quality in medical ultrasound, and secondly to use this knowledge to develop image processing methods for enhancing the diagnostic value of medical ultrasound. The project is an industrial Ph.D project co-sponsored by BK Medical ApS., with the commercial goal to improve the image quality of BK Medicals scanners. Currently BK Medical employ a simple conventional delay-and-sum beamformer to generate B-mode images. This is a simple and well understood method that allows dynamic receive focusing for an improved resolution, the drawback is that only optimal focus is achieved in the transmit focus point. Synthetic aperture techniques can overcome this drawback, but at a cost of increased system complexity and computational demands. The development goal of this project is to implement, Synthetic Aperture Sequential Beamforming (SASB), a new synthetic aperture (SA) beamforming method. The benefit of SASB is an improved image quality compared to conventional beamforming and a reduced system complexity compared to conventional synthetic aperture techniques. The implementation is evaluated using both simulations and measurements for technical and clinical evaluations. During the course of the project three sub-projects were conducted. The first project were development and implementation of a real-time data acquisition system. The system were implemented using the commercial available 2202 ProFocus BK Medical ultrasound scanner equipped with a research interface and a standard PC. The main feature of the system is the possibility to acquire several seconds of interleaved data, switching between multiple imaging setups. This makes the system well suited for development of new processing methods and for clinical evaluations, where acquisition of the exact same scan location for multiple methods is important. The second project addressed implementation, development and evaluation of SASB using a convex array transducer. The evaluation were performed as a three phased clinical trial. In the first phase, the prototype phase, the technical performance of SASB were evaluated using the ultrasound simulation software Field II and Beamformation toolbox III (BFT3) and subsequently evaluated using phantom and in-vivo measurements. The technical performance were compared to conventional beamforming and gave motivation to continue to phase two. The second phase evaluated the clinical performance of abdominal imaging in a pre-clinical trial in comparison with conventional imaging, and were conducted as a double blinded study. The result of the pre-clinical trialmotivated for a larger scale clinical trial. Each of the two clinical trials were performed in collaboration with Copenhagen University Hospital, Rigshospitalet, and Copenhagen University, Department of Biostatistic. Evaluations were performed by medical doctors and experts in ultrasound, using the developed Image Quality assessment program (IQap). The study concludes that the image quality in terms of spatial resolution, contrast and unwanted artifacts is statistically better using SASB imaging than conventional imaging. The third and final project concerned simulation of the acoustic field for high quality imaging systems. During the simulation study of SASB, it was noted that the simulated results did not predict the measured responses with an appropriate confidence for simulated systemperformance evaluation. Closer inspection of themeasured transducer characteristics showed a sever time-offlight phase error, sensitivity deviations, and deviating frequency responses between elements. Simulations combined with experimentally determined element pulse echo wavelets, showed that conventional simulation using identical pulse echo wavelets for all elements is too simplistic to capture the true performance of the imaging system, and that the simulations can be improved by including individual pulse echo wavelets for each element. Using the improved model the accuracy of the simulated response is improved significantly and is useful for simulated systemevaluation. Itwas further shown that conventional imaging is less sensitive to phase and sensitivity errors than SASB imaging. This shows that for simulated performance evaluation a realistic simulation model is important for a reliable evaluation of new high quality imaging systems

360-deg profilometry: new techniques for display and acquisition

Two optical methods are proposed for shape measurement and defect detection of curved surfaces in the form of a complete 360- deg profile of the object. The first one is the standard structured light approach. Display of the resulting data is the emphasis of this section. The second approach uses modulated structured light with a scanning digital camera for faster and simpler data acquisition. Quantitative processing is done off-line while real-time moire produces enhanced display of the defects for qualitative analysis.published_or_final_versio