Performance Assessment of a Commercial Continuous-Wave Near-Infrared Spectroscopy Tissue Oximeter for Suitability for Use in an International, Multi-Center Clinical Trial.

Despite the wide range of clinical and research applications, the reliability of the absolute oxygenation measurements of continuous wave near-infrared spectroscopy sensors is often questioned, partially due to issues of standardization. In this study, we have compared the performances of 13 units of a continuous wave near-infrared spectroscopy device (PortaMon, Artinis Medical Systems, NL) to test their suitability for being used in the HEMOCOVID-19 clinical trial in 10 medical centers around the world. Detailed phantom and in vivo tests were employed to measure the precision and reproducibility of measurements of local blood oxygen saturation and total hemoglobin concentration under different conditions: for different devices used, different operators, for probe repositioning over the same location, and over time (hours/days/months). We have detected systematic differences between devices when measuring phantoms (inter-device variability, <4%), which were larger than the intra-device variability (<1%). This intrinsic variability is in addition to the variability during in vivo measurements on the forearm muscle resulting from errors in probe positioning and intrinsic physiological noise (<9%), which was also larger than the inter-device differences (<3%) during the same test. Lastly, we have tested the reproducibility of the protocol of the HEMOCOVID-19 clinical trial; that is, forearm muscle oxygenation monitoring during vascular occlusion tests over days. Overall, our conclusion is that these devices can be used in multi-center trials but care must be taken to characterize, follow-up, and statistically account for inter-device variability.

Massively parallel simulator of optical coherence tomography of inhomogeneous turbid media.

BACKGROUND AND OBJECTIVE: An accurate and practical simulator for Optical Coherence Tomography (OCT) could be an important tool to study the underlying physical phenomena in OCT such as multiple light scattering. Recently, many researchers have investigated simulation of OCT of turbid media, e.g., tissue, using Monte Carlo methods. The main drawback of these earlier simulators is the long computational time required to produce accurate results. We developed a massively parallel simulator of OCT of inhomogeneous turbid media that obtains both Class I diffusive reflectivity, due to ballistic and quasi-ballistic scattered photons, and Class II diffusive reflectivity due to multiply scattered photons. METHODS: This Monte Carlo-based simulator is implemented on graphic processing units (GPUs), using the Compute Unified Device Architecture (CUDA) platform and programming model, to exploit the parallel nature of propagation of photons in tissue. It models an arbitrary shaped sample medium as a tetrahedron-based mesh and uses an advanced importance sampling scheme. RESULTS: This new simulator speeds up simulations of OCT of inhomogeneous turbid media by about two orders of magnitude. To demonstrate this result, we have compared the computation times of our new parallel simulator and its serial counterpart using two samples of inhomogeneous turbid media. We have shown that our parallel implementation reduced simulation time of OCT of the first sample medium from 407 min to 92 min by using a single GPU card, to 12 min by using 8 GPU cards and to 7 min by using 16 GPU cards. For the second sample medium, the OCT simulation time was reduced from 209 h to 35.6 h by using a single GPU card, and to 4.65 h by using 8 GPU cards, and to only 2 h by using 16 GPU cards. Therefore our new parallel simulator is considerably more practical to use than its central processing unit (CPU)-based counterpart. CONCLUSIONS: Our new parallel OCT simulator could be a practical tool to study the different physical phenomena underlying OCT, or to design OCT systems with improved performance.

Depth-Resolved Multispectral Sub-Surface Imaging Using Multifunctional Upconversion Phosphors with Paramagnetic Properties.

Molecular imaging is very promising technique used for surgical guidance, which requires advancements related to properties of imaging agents and subsequent data retrieval methods from measured multispectral images. In this article, an upconversion material is introduced for subsurface near-infrared imaging and for the depth recovery of the material embedded below the biological tissue. The results confirm significant correlation between the analytical depth estimate of the material under the tissue and the measured ratio of emitted light from the material at two different wavelengths. Experiments with biological tissue samples demonstrate depth resolved imaging using the rare earth doped multifunctional phosphors. In vitro tests reveal no significant toxicity, whereas the magnetic measurements of the phosphors show that the particles are suitable as magnetic resonance imaging agents. The confocal imaging of fibroblast cells with these phosphors reveals their potential for in vivo imaging. The depth-resolved imaging technique with such phosphors has broad implications for real-time intraoperative surgical guidance.

A coaxial optrode as multifunction write-read probe for optogenetic studies in non-human primates.

BACKGROUND: Advances in optogenetics have led to first reports of expression of light-gated ion-channels in non-human primates (NHPs). However, a major obstacle preventing effective application of optogenetics in NHPs and translation to optogenetic therapeutics is the absence of compatible multifunction optoelectronic probes for (1) precision light delivery, (2) low-interference electrophysiology, (3) protein fluorescence detection, and (4) repeated insertion with minimal brain trauma. NEW METHOD: Here we describe a novel brain probe device, a "coaxial optrode", designed to minimize brain tissue damage while microfabricated to perform simultaneous electrophysiology, light delivery and fluorescence measurements in the NHP brain. The device consists of a tapered, gold-coated optical fiber inserted in a polyamide tube. A portion of the gold coating is exposed at the fiber tip to allow electrophysiological recordings in addition to light delivery/collection at the tip. RESULTS: Coaxial optrode performance was demonstrated by experiments in rodents and NHPs, and characterized by computational models. The device mapped opsin expression in the brain and achieved precisely targeted optical stimulation and electrophysiology with minimal cortical damage. COMPARISON WITH EXISTING METHODS: Overall, combined electrical, optical and mechanical features of the coaxial optrode allowed a performance for NHP studies which was not possible with previously existing devices. CONCLUSIONS: Coaxial optrode is currently being used in two NHP laboratories as a major tool to study brain function by inducing light modulated neural activity and behavior. By virtue of its design, the coaxial optrode can be extended for use as a chronic implant and multisite neural stimulation/recording.

Improved importance sampling for Monte Carlo simulation of time-domain optical coherence tomography.

We developed an importance sampling based method that significantly speeds up the calculation of the diffusive reflectance due to ballistic and to quasi-ballistic components of photons scattered in turbid media: Class I diffusive reflectance. These components of scattered photons make up the signal in optical coherence tomography (OCT) imaging. We show that the use of this method reduces the computation time of this diffusive reflectance in time-domain OCT by up to three orders of magnitude when compared with standard Monte Carlo simulation. Our method does not produce a systematic bias in the statistical result that is typically observed in existing methods to speed up Monte Carlo simulations of light transport in tissue. This fast Monte Carlo calculation of the Class I diffusive reflectance can be used as a tool to further study the physical process governing OCT signals, e.g., obtain the statistics of the depth-scan, including the effects of multiple scattering of light, in OCT. This is an important prerequisite to future research to increase penetration depth and to improve image extraction in OCT.

Influence of tissue absorption and scattering on the depth dependent sensitivity of Raman fiber probes investigated by Monte Carlo simulations.

We present a Monte Carlo model, which we use to calculate the depth dependent sensitivity or sampling volume of different single fiber and multi-fiber Raman probes. A two-layer skin model is employed to investigate the dependency of the sampling volume on the absorption and reduced scattering coefficients in the near infrared wavelength range (NIR). The shape of the sampling volume is mainly determined by the scattering coefficient and the wavelength dependency of absorption and scattering has only a small effect on the sampling volume of a typical fingerprint spectrum. An increase in the sampling depth in nonmelanoma skin cancer, compared to normal skin, is obtained.