David Benaron, Ilian Parachikov, Wai-Fung Cheong, Shai Friedland, Boris Rubinsky, David Otten, Frank Liu, Carl Levinson, Aileen Murphy, Yair Talmi, James Weersing, Joshua Duckworth, Uwe Hörchner, Eben Kermit
We develop a clinical visible-light spectroscopy (VLS) tissue oximeter. Unlike currently approved near-infrared spectroscopy (NIRS) or pulse oximetry (SpO2%), VLS relies on locally absorbed, shallow-penetrating visible light (475 to 625 nm) for the monitoring of microvascular hemoglobin oxygen saturation (StO2%), allowing incorporation into therapeutic catheters and probes. A range of probes is developed, including noncontact wands, invasive catheters, and penetrating needles with injection ports. Data are collected from: 1. probes, standards, and reference solutions to optimize each component; 2. ex vivo hemoglobin solutions analyzed for StO2% and pO2 during deoxygenation; and 3. human subject skin and mucosal tissue surfaces. Results show that differential VLS allows extraction of features and minimization of scattering effects, in vitro VLS oximetry reproduces the expected sigmoid hemoglobin binding curve, and in vivo VLS spectroscopy of human tissue allows for real-time monitoring (e.g., gastrointestinal mucosal saturation 69±4%, n=804; gastrointestinal tumor saturation 45±23%, n=14; and p<0.0001), with reproducible values and small standard deviations (SDs) in normal tissues. FDA approved VLS systems began shipping earlier this year. We conclude that VLS is suitable for the real-time collection of spectroscopic and oximetric data from human tissues, and that a VLS oximeter has application to the monitoring of localized subsurface hemoglobin oxygen saturation in the microvascular tissue spaces of human subjects.
David Benaron, Ilian Parachikov, Wai-Fung Cheong, Shai Friedland, Joshua Duckworth, David Otten, Boris Rubinsky, Uwe Horchner, Eben Kermit, Frank Liu, Carl Levinson, Aileen Murphy, John Price, Yair Talmi, James Weersing
We report the development of a general, quantitative, and localized visible light clinical tissue oximeter, sensitive to both hypoxemia and ischemia. Monitor design and operation were optimized over four instrument generations. A range of clinical probes were developed, including non-contact wands, invasive catheters, and penetrating needles with injection ports. Real-time data were collected (a) from probes, standards, and reference solutions to optimize each component, (b) from ex vivo hemoglobin solutions co-analyzed for StO2% and pO2 during deoxygenation, and (c) from normoxic human subject skin and mucosal tissue surfaces. Results show that (a) differential spectroscopy allows extraction of features with minimization of the effects of scattering, (b) in vitro oximetry produces a hemoglobin saturation binding curve of expected sigmoid shape and values, and (c) that monitoring human tissues allows real-time tissue spectroscopic features to be monitored. Unlike with near-infrared (NIRS) or pulse oximetry (SpO2%) methods, we found non-pulsatile, diffusion-based tissue oximetry (StO2%) to work most reliably for non-contact reflectance monitoring and for invasive catheter- or needle-based monitoring, using blue to orange light (475-600 nm). Measured values were insensitive to motion artifact. Down time was non-existent. We conclude that the T-Stat oximeter design is suitable for the collection of spectroscopic data from human subjects, and that the oximeter may have application in the monitoring of regional hemoglobin oxygen saturation in the capillary tissue spaces of human subjects.
David Benaron, Boris Rubinski, Susan Hintz, Joshua Duckworth, Aileen Murphy, John Price, Frank Liu, David Otten, David Stevenson, Wai-Fung Cheong, Eben Kermit
Each tissue has a unique spectral signature (e.g. liver looks distinct from bowel due to differences in both absorbance and in the way the tissue scatters light). Therefore, we suspect that automated discrimination among tissue types (e.g. blood, nerve, artery, vein, muscle) or tissue state (frozen, unfrozen, viable, dead) is feasible. In this study, we investigated our ability to detect hidden structures (such as blood vessels) or events (such as tissue ablation via freezing) using optical systems. For blood vessel localization, a key step in vascular access, we resolved the component concentration of hemoglobin measured within the tissue, and found that blood vessel depth and direction could be determined. For freezing detection, we found that changes in effective absorbance during freezing allowed the freezing process to be monitored spectroscopically. Such optical techniques may usher in use of light-assisted medical diagnosis, leading to automated and portable diagnostic devices which enable real-time diagnostics and monitoring during medical interventions, such as cryoablation or vascular access.
David Benaron, Wai-Fung Cheong, Joshua Duckworth, Kenneth Noles, Camran Nezhat, Daniel Seidman, Susan Hintz, Carl Levinson, Aileen Murphy, John Price, Frank Liu, David Stevenson, Eben Kermit
Each tissue type has a unique spectral signature (e.g. liver looks distinct from bowel due to differences in both absorbance and in the way the tissue scatters light). While differentiation between normal tissues and tumors is not trivial, automated discrimination among normal tissue types (e.g. nerve, artery, vein, muscle) is feasible and clinically important, as many medical errors in medicine involve the misidentification of normal tissues. In this study, we have found that spectroscopic differentiation of tissues can be successfully applied to tissue samples (kidney and uterus) and model systems (fruit). Such optical techniques may usher in use of optical tissue diagnosis, leading to automated and portable diagnostic devices which can identify tissues, and guide use of medical instruments, such as during ablation or biopsy.
Medical optical imaging (MOI) and spectroscopy (MOS) use light emitted into opaque tissues in order to determine the interior structure and chemical content. These optical techniques have been developed in an attempt to prospectively identify impending brain injuries before they become irreversible, thus allowing injury to be avoided or minimized. Optical imaging and spectroscopy center around the simple idea that light passes through the body in small amounts, and emerges bearing clues about tissues through which it passed. Images can be reconstructed from such data, and this is the basis of optical tomography. We have used a time-of-flight system reported earlier to monitor oxygenation and image hemorrahage in neonatal brain. This chapter summarizes our early results.
Medical optical imaging (MOI) uses light emitted into opaque tissues in order to determine the interior structure and chemical content. These optical techniques have been developed in an attempt to prospectively identify impending brain injuries before they become irreversible, thus allowing injury to be avoided or minimized. Optical imaging and spectroscopy center around the simple idea that light passes through the body in small amounts, and emerges bearing clues about tissues through which it passed. Images can be reconstructed from such data, and this is the basis of optical tomography. Over the past few years, techniques have been developed to allow construction of images from such optical data at the bedside. We have used a time-of-flight system reported earlier to monitor oxygenation and image hemorrhage in neonatal brain. This article summarizes the problems that we believe can be addressed by such techniques, and reports on some of our early results.
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