Hyperspectral imaging solutions for brain tissue metabolic and hemodynamic monitoring: past, current and future developments

Hyperspectral imaging (HSI) technologies have been used extensively in medical research, targeting various biological phenomena and multiple tissue types. Their high spectral resolution over a wide range of wavelengths enables acquisition of spatial information corresponding to different light-interacting biological compounds. This review focuses on the application of HSI to monitor brain tissue metabolism and hemodynamics in life sciences. Different approaches involving HSI have been investigated to assess and quantify cerebral activity, mainly focusing on: (1) mapping tissue oxygen delivery through measurement of changes in oxygenated (HbO₂) and deoxygenated (HHb) hemoglobin; and (2) the assessment of the cerebral metabolic rate of oxygen (CMRO₂) to estimate oxygen consumption by brain tissue. Finally, we introduce future perspectives of HSI of brain metabolism, including its potential use for imaging optical signals from molecules directly involved in cellular energy production. HSI solutions can provide remarkable insight in understanding cerebral tissue metabolism and oxygenation, aiding investigation on brain tissue physiological processes

MAESTROS: A multi-wavelength time domain NIRS system to monitor changes in oxygenation and oxidation state of cytochrome-c-oxidase

CCBY We present a multi-wavelength, multi-channel, time domain near-infrared spectroscopy (NIRS) system named MAESTROS. This instrument can measure absorption and scattering coefficients and can quantify the concentrations of oxy- and deoxy-haemoglobin ([HbO2] , [HHb]), and oxidation state of cytochrome-c-oxidase ([oxCCO] ). This system is composed of a supercontinuum laser source coupled with two acousto-optic tuneable filters (AOTF). The light is collected by four photomultipliers tubes (PMT), connected to a router to redirect the signal to a single TCSPC card. The interface between the system and the tissue is based on optical fibres. This arrangement allows us to resolve up to sixteen wavelengths, within the range of 650 to 900 nm, at a sampling rate compatible with the physiology (from 0.5 to 2 Hz). In this paper, we describe the system and assess its performance based on two specifically designed protocols for photon migration instruments, the BIP and nEUROPt protocols, and on a well characterized liquid phantom based on Intralipid and water. Then, the ability to resolve [HbO2], [HHb] and [oxCCO] is demonstrated on a homogeneous liquid phantom, based on blood for [HbO2] , [HHb] and yeast for [oxCCO] . In the future, the system could be used to monitor brain tissue physiology

Investigation of the quantification of hemoglobin and cytochrome-c-oxidase in the exposed cortex with near-infrared hyperspectral imaging: a simulation study

SIGNIFICANCE: We present a Monte Carlo (MC) computational framework that simulates near-infrared (NIR) hyperspectral imaging (HSI) aimed at assisting quantification of the in vivo hemodynamic and metabolic states of the exposed cerebral cortex in small animal experiments. This can be done by targeting the NIR spectral signatures of oxygenated (HbO2) and deoxygenated (HHb) hemoglobin for hemodynamics as well as the oxidative state of cytochrome-c-oxidase (oxCCO) for measuring tissue metabolism. AIM: The aim of this work is to investigate the performances of HSI for this specific application as well as to assess key factors for the future design and operation of a benchtop system. APPROACH: The MC framework, based on Mesh-based Monte Carlo (MMC), reproduces a section of the exposed cortex of a mouse from an in vivo image and replicates hyperspectral illumination and detection at multiple NIR wavelengths (up to 121). RESULTS: The results demonstrate: (1) the fitness of the MC framework to correctly simulate hyperspectral data acquisition; (2) the capability of HSI to reconstruct spatial changes in the concentrations of HbO2, HHb, and oxCCO during a simulated hypoxic condition; (3) that eight optimally selected wavelengths between 780 and 900 nm provide minimal differences in the accuracy of the hyperspectral results, compared to the "gold standard" of 121 wavelengths; and (4) the possibility to mitigate partial pathlength effects in the reconstructed data and to enhance quantification of the hemodynamic and metabolic responses. CONCLUSIONS: The MC framework is proved to be a flexible and useful tool for simulating HSI also for different applications and targets

A near-infrared hyperspectral imaging system for quantitative monitoring of hemodynamics and metabolism on the exposed cortex of mice

A near-infrared (NIR) hyperspectral imaging (HSI) system has been developed to measure the hemodynamic (changes in concentration of oxyhemoglobin and deoxyhemoglobin) and the metabolic (changes in concentration of oxidised cytochrome-c-oxidase) responses in the exposed cortex of small animals. Using the extended spectral information of multiple wavelengths in the NIR range between 780 and 900 nm optimal differentiation between the optical signatures of the chromophores (hemoglobin and cytochrome-c-oxidase) can be achieved. The system, called hNIR, is composed of: (1) a high-frame rate, large-format scientific CMOS (sCMOS) camera for image acquisition and (2) a broadband source coupled with a Pellin-Broca prism mounted on a rotating motor for sequential, fast-rate illumination of the target at different spectral bands. The system characterisation highlights the capability of the setup to achieve high spatial resolution over a ~1x1 mm field of view (FOV). Hyperspectral data analysis also includes simulations using a Monte Carlo optical model of HSI, to estimate the average photon pathlength and improve image reconstruction and quantification. The hNIR system described here is an improvement over a previously tested commercial snapshot HSI solution both in terms of spatial resolution and signal-to-noise ratio (SNR). This setup will be used to monitor brain hemodynamic and metabolic changes in the exposed cortex of mice during systemic oxygenation changes

The Use of Supercontinuum Laser Sources in Biomedical Diffuse Optics: Unlocking the Power of Multispectral Imaging

Optical techniques based on diffuse optics have been around for decades now and are making their way into the day-to-day medical applications. Even though the physics foundations of these techniques have been known for many years, practical implementation of these technique were hindered by technological limitations, mainly from the light sources and/or detection electronics. In the past 20 years, the developments of supercontinuum laser (SCL) enabled to unlock some of these limitations, enabling the development of system and methodologies relevant for medical use, notably in terms of spectral monitoring. In this review, we focus on the use of SCL in biomedical diffuse optics, from instrumentation and methods developments to their use for medical applications. A total of 95 publications were identified, from 1993 to 2021. We discuss the advantages of the SCL to cover a large spectral bandwidth with a high spectral power and fast switching against the disadvantages of cost, bulkiness, and long warm up times. Finally, we summarize the utility of using such light sources in the development and application of diffuse optics in biomedical sciences and clinical applications

Quantum Correction in Exact Quantization Rules

An exact quantization rule for the Schr\"{o}dinger equation is presented. In the exact quantization rule, in addition to $N\pi$, there is an integral term, called the quantum correction. For the exactly solvable systems we find that the quantum correction is an invariant, independent of the number of nodes in the wave function. In those systems, the energy levels of all the bound states can be easily calculated from the exact quantization rule and the solution for the ground state, which can be obtained by solving the Riccati equation. With this new method, we re-calculate the energy levels for the one-dimensional systems with a finite square well, with the Morse potential, with the symmetric and asymmetric Rosen-Morse potentials, and with the first and the second P\"{o}schl-Teller potentials, for the harmonic oscillators both in one dimension and in three dimensions, and for the hydrogen atom.Comment: 10 pages, no figure, Revte

Magnetic Soret effect: Application of the ferrofluid dynamics theory

The ferrofluid dynamics theory is applied to thermodiffusive problems in magnetic fluids in the presence of magnetic fields. The analytical form for the magnetic part of the chemical potential and the most general expression of the mass flux are given. By employing these results to experiments, global Soret coefficients in agreement with measurements are determined. Also an estimate for a hitherto unknown transport coefficient is made.Comment: 7 pages, 2 figure

Satisfying the Einstein-Podolsky-Rosen criterion with massive particles

In 1935, Einstein, Podolsky and Rosen (EPR) questioned the completeness of quantum mechanics by devising a quantum state of two massive particles with maximally correlated space and momentum coordinates. The EPR criterion qualifies such continuous-variable entangled states, where a measurement of one subsystem seemingly allows for a prediction of the second subsystem beyond the Heisenberg uncertainty relation. Up to now, continuous-variable EPR correlations have only been created with photons, while the demonstration of such strongly correlated states with massive particles is still outstanding. Here, we report on the creation of an EPR-correlated two-mode squeezed state in an ultracold atomic ensemble. The state shows an EPR entanglement parameter of 0.18(3), which is 2.4 standard deviations below the threshold 1/4 of the EPR criterion. We also present a full tomographic reconstruction of the underlying many-particle quantum state. The state presents a resource for tests of quantum nonlocality and a wide variety of applications in the field of continuous-variable quantum information and metrology.Comment: 8 pages, 7 figure

0.75 atoms improve the clock signal of 10,000 atoms

Since the pioneering work of Ramsey, atom interferometers are employed for precision metrology, in particular to measure time and to realize the second. In a classical interferometer, an ensemble of atoms is prepared in one of the two input states, whereas the second one is left empty. In this case, the vacuum noise restricts the precision of the interferometer to the standard quantum limit (SQL). Here, we propose and experimentally demonstrate a novel clock configuration that surpasses the SQL by squeezing the vacuum in the empty input state. We create a squeezed vacuum state containing an average of 0.75 atoms to improve the clock sensitivity of 10,000 atoms by 2.05 dB. The SQL poses a significant limitation for today's microwave fountain clocks, which serve as the main time reference. We evaluate the major technical limitations and challenges for devising a next generation of fountain clocks based on atomic squeezed vacuum.Comment: 9 pages, 6 figure

Investigation of a direction sensitive sapphire detector stack at the 5 GeV electron beam at DESY-II

Extremely radiation hard sensors are needed in particle physics experiments to instrument the region near the beam pipe. Examples are beam halo and beam loss monitors at the Large Hadron Collider, FLASH or XFEL. Currently artificial diamond sensors are widely used. In this paper single crystal sapphire sensors are considered as a promising alternative. Industrially grown sapphire wafers are available in large sizes, are of low cost and, like diamond sensors, can be operated without cooling. Here we present results of an irradiation study done with sapphire sensors in a high intensity low energy electron beam. Then, a multichannel direction-sensitive sapphire detector stack is described. It comprises 8 sapphire plates of 1 cm^2 size and 525 micro m thickness, metallized on both sides, and apposed to form a stack. Each second metal layer is supplied with a bias voltage, and the layers in between are connected to charge-sensitive preamplifiers. The performance of the detector was studied in a 5 GeV electron beam. The charge collection efficiency measured as a function of the bias voltage rises with the voltage, reaching about 10 % at 950 V. The signal size obtained from electrons crossing the stack at this voltage is about 22000 e, where e is the unit charge. The signal size is measured as a function of the hit position, showing variations of up to 20 % in the direction perpendicular to the beam and to the electric field. The measurement of the signal size as a function of the coordinate parallel to the electric field confirms the prediction that mainly electrons contribute to the signal. Also evidence for the presence of a polarisation field was observed.Comment: 13 pages, 7 figures, 3 table