The Stanford Symposium on Biomedical Imaging was designed to bring together scientists, engineers and physicians who are developing and using novel imaging technologies for the enhancement of human health and for the advancement of science.
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Sebastian Wachsmann Hogiu
(University of California, Davis)
Optics in Pathology: from Superresolution Microscopy to Point of Care Devices
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Date: 04/05/2012
Description:
In this talk I will present our group’s work to develop and apply novel optical technologies for pathology. One such technology is aimed at improving spatial resolution in optical microscopy. This technique (called super‐resolution optical microscopy) utilize either patterned illumination or photo‐physical processes in molecules, and can, in certain situations, resolve objects as small as tens of nanometers. We will make use of a super‐resolution microscope that is based on structured illumination for analysis of blood and other types of cells on pathology slides. The spatial resolution that can be achieved with this microscope is approximately 100nm, and allows for the morphological investigation of fluorescent structures within cells. Another example is the development of two attachments to a commercial cell phone that transform the phone’s integrated lens and image sensor into a 350x microscope and visible‐light spectrometer. The microscope is capable of transmission and polarized microscopy modes and is shown to have 1.5 micron resolution and a usable field‐of‐view of ~150×150 microns with no image processing, and approximately 350×350 microns when post‐processing is applied. The spectrometer has a 300 nm bandwidth with a limiting spectral resolution of close to 5nm. We show applications of the devices to medically relevant problems. In the case of the microscope, we image both stained and unstained blood‐smears showing the ability to acquire images of similar quality to commercial microscope platforms, thus allowing diagnosis of clinical pathologies.
Marc Fournelle
(Fraunhofer Institute for Biomedical Technology)
Multimodal Skin Imaging Combining Optics, Ultrasound and Optoacoustic Techniques – The SKINSPECTION project
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Date: 05/05/2012
Description:
The incidence of skin cancer in Europe, US, and Australia is rising rapidly. One in five will develop some form of skin cancer during the lifetime. A person has a 1:33 chance to develop melanoma, the most aggressive skin cancer. Melanoma is the second most common cancer in women aged 20‐29, and the sixth most common cancer in men and women. In 2007, more than 1 million new cases were diagnosed in the US alone. About 90% of skin cancers are caused by ultraviolet (UV) sunlight. A significant improvement of the current diagnostic tools of dermatologists is required in order to identify dermal disorders at a very early stage as well as to monitor directly the effects of treatment. In the context of the SKINSPECTION project, a European consortium has developed a novel multimodal hybrid diagnostic imaging system with the capability to perform non‐invasive high resolution three‐dimensional imaging in‐vivo. The SKINSPECTION approach combines two‐photon imaging with time‐correlated single photon detection, autofluorescence lifetime imaging, high‐frequency ultrasound and optoacoustic imaging. The innovative combination of these modalities allows to obtain a wide‐field view with quantitative depth information of skin lesions and a close‐look into particular intratissue compartments with quantitative hyperspectral information and subcellular resolution. The goal of the project is to provide a novel unique tool for early diagnosis and treatment control of skin cancer and skin disease. For achieving this objective, two systems for microscopic and macroscopic imaging of lesions were developed in the last 3 years by the partners JenLab GmbH and Imperial College London (two‐photon microscopy/FLIM) and Fraunhofer IBMT and kibero GmbH (Optoacoustic/Ultrasound imaging). The systems were successfully certified for clinical studies and are currently being evaluated for imaging of skin lesions in a bicentric clinical trial at Hammersmith Hospital and Universita di Modena.
Louis D. Silverstein
(VCD Sciences, Inc.)
Emerging Applications and Associated Requirements for Color Reproduction Accuracy in Medical Imaging
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Date: 04/05/2012
Description:
The use of color displays in medical imaging is growing as more clinical specialties use digital images as a resource in diagnosis and treatment decisions. Telemedicine applications such as telepathology, teledermatology and teleophthalmology rely heavily on color images. However, standard methods for calibrating, characterizing and profiling medical color displays do not exist, resulting in inconsistent presentation. To address this, we developed a calibration, characterization and profiling protocol for color‐critical medical imaging applications. Supporting analyses reveal very high color reproduction accuracy as determined by CIE DE2000 color differences for 210 test colors uniformly distributed in CIE Lab color space. The impact of the display tone‐reproduction curve on color reproduction accuracy is compared for two tone‐reproduction curves of special interest in medical imaging, the DICOM gray‐scale standard display function and the CIE L* standard lightness function. We report the results from a psychophysical investigation of the diagnostic performance of trained pathologists viewing “virtual” breast biopsy slides and compare the diagnostic performance achieved with calibrated, color‐managed LCDs with un‐calibrated LCDs without the benefits of color management.
Elizabeth A. Krupinski
(University of Arizona)
Medical Teleconferencing
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Date: 04/05/2012
Description:
Medical images represent a significant source of information that clinicians utilize to render diagnostic and treatment decisions. The first specialty that typically comes to mind when thinking about medical imaging is radiology. Recently however, medical imaging has come to cover a much broader range of specialties through the growth of telemedicine including cardiology, radiation oncology, pathology, and ophthalmology. The interpretation of medical images relies on a combination of many factors including perception, cognition, human factors, and technology. When one considers how clinicians read medical images, three basic stages are typically regarded as being involved: seeing, recognizing and interpreting. It may sound simple, but the potential for failure at any point in the interpretation process is actually quite high ‐ errors are made. Whenever new technologies are introduced into the clinic, we need to thoroughly evaluate them to insure that patient will not be impacted negatively. Physical evaluation of the images and their quality is critical of course, but the ultimate test of their quality and utility is whether they improve diagnostic performance and/or workflow efficiency. We need to understand not only the images and the technologies used to acquire and display them; we need to understand the interpreter of those images – the clinician. As the clinical environment changes and more and more various types of images become a part of the patient record this becomes even more critical. This talk will summarize some of the ways we have used to evaluate the impact of new imagingtechnologies in the growing arena of telemedicine.
Daniel Razansky
(Technical University Munich)
Multi-Spectral Optoacoustic Tomography – Volumetric Color Hearing in Real-time
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Date: 04/05/2012
Description:
The main‐stream of optical interrogations in living tissues are still limited to surface‐limited microscopic imaging or otherwise low resolution diffusion tomographies. Despite significant progress in both fields, those methods do not allow exploration of the full potential of novel classes of fluorescent and other molecular agents for high‐resolution volumetric quantitative imaging of entire organs, small animals or human tissues. Biomedical optoacoustics has emerged in the recent decade as a powerful tool for high‐resolution visualization of optical contrast, overcoming a variety of longstanding limitations imposed by light scattering in deep tissues. But true performance of optoacoustic imaging techniques can only be exploited when excitation at multiple wavelengths is used in order to enable highly sensitive spectral differentiation of intrinsic biomarkers and extrinsically administered contrast agents. By detecting tiny sound vibrations, resulting from selective absorption of light at multiple wavelengths, multispectral optoacoustic tomography (MSOT) can now “hear color” in three dimensions, i.e., deliver volumetric spectrally enriched (color) images from deep living tissues at high spatial resolution and in real time. These new‐found imaging abilities directly relate to preclinical screening applications in animal models and are foreseen to significantly impact clinical decision making as well. The talk provides the technical essentials of MSOT, including latest developments in the inverse theory,spectral processing algorithms, and imaging instrumentation. Several in‐vivo imaging studies, involving gene expression and other molecular agents, are showcased in small animals with performance that forecasts MSOT as a method of choice for biological imaging and select clinical segments.
Daniel A. Fletcher
(University of California, Berkeley)
Mobile Phone Based Clinical Microscopy
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Date: 04/05/2012
Description:
Microscopy is a critical tool for disease research, screening, and diagnosis. Presently, use of microscopy for health care is often limited to well‐equipped medical laboratory settings staffed by qualified personnel. In the developing world and other underserved regions, the lack of equipment and expertise required for diagnostic microscopy contributes to poor health, spread of treatable diseases, and emergence of drug‐resistant disease strains. While medical resources are scarce in many developing countries and rural communities, the widespread availability of wireless communication and camera‐enabled mobile phones has the potential to fundamentally change the way medical diagnoses are performed. A compact and portable microscopy system based on a mobile phone and capable of image capture, image processing, and communication with medical experts could dramatically increase access to basic health care by delivering services closer to where patients live and work. This talk will describe recent progress developing and implementing such a device, which we call CellScope, to improve diagnosis of infectious diseases.
Aydogan Ozcan
(University of California, Los Angeles)
Lensless On-chip Imaging of Cells
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Date: 04/05/2012
Description:
Today there are more than 5 billion cell‐phone users in the world, and the majority of these cellphones are being used in the developing parts of the world. This massive volume of wireless phone communication brings an enormous cost‐reduction to cellphones despite their sophisticated hardware and software capabilities. Quite importantly, most of these existing cellphones are also already equipped with advanced digital imaging and sensing platforms that can be utilized for various health monitoring applications. This impressive advancement is one of the central building blocks of the emerging fields of “Telemedicine” and “Wireless Health”.
Centered on this vision, in this talk I will introduce fundamentally new imaging and detection architectures that can compensate in the digital domain for the lack of complexity of optical components by use of novel theories and numerical algorithms to address the immediate needs and requirements of Telemedicine for Global Health Problems. Specifically, I will present an on‐chip cytometry and microscopy platform that utilizes cost‐effective and compact components to enable digital recognition and 3D microscopic imaging of cells with sub‐cellular resolution over a large field of view without the need for any lenses, bulky optical components or coherent sources such as lasers.
Further, I will discuss lens‐free implementations of various other computational imaging modalities on the same platform such as pixel super‐resolution imaging, lens‐free on‐chip tomography, holographic opto‐fluidic microscopy/tomography. Finally, I will demonstrate lens‐free on‐chip imaging of fluorescently labeled cells over an ultra wide field of view of >8 cm2, which could be especially important for rare cell analysis (e.g., detection of circulating tumor cells), as well as for high‐throughput screening of DNA/protein micro‐arrays.
Butrus T. Khuri Yakub
(Stanford University)
Capacitive Micromachined Ultrasound Transducers (CMUTs) Enabling Advanced 3-D Imaging
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Date: 04/05/2012
Description:
The advent of silicon micromachining enables the realization of the full potential of these transducers and provides performance that makes CMUTs competitive and superior to piezoelectric transducers. In immersion applications, CMUTs are possible with fractional bandwidth of over 100 %, an electromechanical coupling coefficient close to unity; are made in the form of single element or one‐dimensional (1D) or two‐dimensional (2D) arrays of tens of thousand of elements, as well as annular arrays. They have been operated in the frequency range of 100 kHz to 50 MHz, and included in systems with a dynamic range of the order of 150 dB/V/Hz. Custom electronics have been developed and integrated with arrays of transducers to form compact imaging catheters. This presentation will first review the operation of CMUTs, the technology used to make them, and applications in medical imaging.
Yukako Yagi
(Harvard University)
Digital Pathology - Beyond Pathology
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Description:
Conventional histopathology is rapidly shifting towards digital integration. The ability to digitize histopathology slides automatically, rapidly and a high resolution has been advanced by numerous investigators around the world over the past approximately fifteen years. We provide an overview of current digital pathology applications and research with emphasis on whole slide imaging (WSI) and beyond. Static or interactive digital pathology work stations already can be used for many purposes, e.g. telepathology expert consultations, frozen section diagnosis in remote areas, cytology screening, quality assurance, diagnostic validations for clinical trials, quantitation of hormone receptor in cancer, or three‐dimensional visualization of anatomical structures, among others. Changes of workflow in histology laboratories are beginning to enable digital image acquisition and WSI in a routine setting. WSI plays an increasingly important roles in pathology education, glass slide boxes in medical schools are being replaced by digital slide collections (virtual slide box); digital slide seminars and virtual microscopy are used for postgraduate and continuing medical education in pathology. Research to improve WSI in many ways and efforts to validate WSI systems for diagnostic settings are ongoing. The advanced versions of Optical Coherence Tomography (OCT) for in –vivo biopsy, Microtomography (Micro CT) for the frozen sections, and Light CT have joined in Digital Pathology world. It may bring new era in Pathology.
Hakho Lee
(Harvard University)
Chip-based Sensors for Molecular Imaging
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Date: 04/05/2012
Description:
Biosensors based on magnetic detection emerge as a promising diagnostic platform. Due to the intrinsically negligible magnetic susceptibilities of biological entities, magnetic detection experiences little interference from native biological samples; even optically turbid samples will often appear transparent to magnetic fields. Biomolecules or cells of interests, when magnetically labeled, however, can attain a high contrast against complex biological background. This presentation will review such magnetic sensing technologies, specifically focusing on a general detection platform termed diagnostic magnetic resonance (DMR). Similar to clinical MRI, the DMR utilizes magnetic nanoparticles to modulate the spinspin relaxation time of neighboring water molecules. Numerous assay configurations and nanoparticles have been designed to detect a wide range of targets including DNA, mRNA, proteins, enzymatic activity, metabolites, drugs, pathogens, and tumor cells. Recently, the capabilities of DMR technology have been considerably advanced with the development of a miniaturized, chip‐based NMR detector system that is capable of performing highly sensitive measurements on microliter sample volumes and in a multiplexed format. With these and on‐going advances in system design, the DMR technology holds great promise as a high‐throughput, low‐cost, and portable platform in clinical and point‐of‐care settings.