Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no ...

Tyndall National Institute

Phantoms play a critical role in the development of biophotonics techniques. There is a lack of novel phantom tools in the emerging field of upconverting nanoparticles (UCNPs) for biophotonics application. This work provides a range of UCNP-based phantom tools and a manufacturing recipe to bridge the gap and accelerate the development of UCNP-based biophotonics applications.

Solid optical tissue phantom tools based on upconverting nanoparticles for biomedical applications.

Rapid advancement of novel optical spectroscopy and imaging systems relies on the availability of well-characterised and reproducible protocols for phantoms as a standard for the validation of the technique. The tissue-mimicking phantoms are also used to investigate photon transport in biological samples before clinical trials that require well-characterized phantoms with known optical properties (reduced scattering (') and absorption () coefficients). However, at present, there is limited literature available providing well-characterized phantom recipes considering various biomarkers and tested over a wide range of optical properties covering most of the human organs and applicable to multimodal optical spectroscopy. In this study, gelatin-based phantoms were designed to simulate tissue optical properties where India ink and Intralipid were used as absorbing and scattering agents, respectively. Multiple biomarkers were simulated by varying the gelatin concentration to mimic the change in tissue hydration and hydroxyapatite concentration to mimic bone signature. The recipe along with biomarkers were optimized and characterised over a wide range of optical properties ( from 0.1 to 0.5 cm; ' from 5 to 15 cm) relevant to human tissue using a broadband time-domain diffuse optical spectrometer. The data collected showed a linear relationship between the concentration of ink/lipids and /' values with negligible coupling between  and ' values. While being stored in a refrigerator post-fabrication, the  and ' did not change significantly (<4% coefficient of variation, 'CV') over three weeks. The reproducibility in three different sets was validated experimentally and found to be strong with a variation of ≤6% CV in  and ≤9% CV in '. From the 3 × 3 data of  and ' matrices, one can deduce the recipe for any target absorption or reduced scattering coefficient. The applicability of the phantoms was tested using diffuse reflectance and Raman spectrometers. A use case application was demonstrated for Raman spectroscopy where hydration and hydroxyapatite phantoms were designed to characterize the Raman instrument. The Raman instrument could detect the change in 1% of HA and 5% of hydration. This study presents a first-of-its-kind robust, well-characterized, multi-biomarker phantom recipe for calibration and benchmarking of multimodal spectroscopy devices assisting in their clinical translation.

Fabrication and characterization of multi-biomarker optimized tissue-mimicking phantoms for multi-modal optical spectroscopy.

In this work, we used a hybrid time domain near-infrared spectroscopy (TD-NIRS) and diffuse correlation spectroscopy (DCS) device to retrieve hemoglobin and blood flow oscillations of skeletal muscle microvasculature. We focused on very low (VLF) and low-frequency (LF) oscillations ( frequency lower than 0.145 Hz), that are related to myogenic, neurogenic and endothelial activities. We measured power spectral density (PSD) of blood flow and hemoglobin concentration in four muscles (thenar eminence, plantar fascia, sternocleidomastoid and forearm) of 14 healthy volunteers to highlight possible differences in microvascular hemodynamic oscillations. We observed larger PSDs for blood flow compared to hemoglobin concentration, in particular in case of distal muscles ( thenar eminence and plantar fascia). Finally, we compared the PSDs measured on the thenar eminence of healthy subjects with the ones measured on a septic patient in the intensive care unit: lower power in the endothelial-dependent frequency band, and larger power in the myogenic ones were observed in the septic patient, in accordance with previous works based on laser doppler flowmetry.

Assessment of power spectral density of microvascular hemodynamics in skeletal muscles at very low and low-frequency via near-infrared diffuse optical spectroscopies.

Phantoms simultaneously mimicking anatomical and optical properties of real tissues can play a pivotal role for improving dosimetry algorithms. The aim of the paper is to design and develop a hybrid phantom model that builds up on the strengths of solid and liquid phantoms for mimicking various anatomical structures for prostate cancer photodynamic therapy (PDT) dosimetry validation. The model comprises of a photosensitizer-embedded gelatin lesion within a liquid Intralipid prostate shape that is surrounded by a solid silicone outer shell. The hybrid phantom was well characterized for optical properties. The final assembled phantom was also evaluated for fluorescence tomographic reconstruction in conjunction with SpectraCure's IDOSE software. The developed model can lead to advancements in dosimetric evaluations. This would improve PDT outlook as a clinical treatment modality and boost phantom based standardization of biophotonic devices globally.

Claudia Nunzia Guadagno

BioPixS-Biophotonics Standards,
IPIC,
BioPixS-Biophotonics Standards, IPIC

Tyndall National Institute

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care

Claudia Nunzia Guadagno

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Tyndall National Institute

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care

BioPixS-Biophotonics Standards,
IPIC,
BioPixS-Biophotonics Standards, IPIC