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

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

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

The flash flood of the Bisagno Creek on 9th October 2014: An “unfortunate” combination of spatial and temporal scales

SummaryOn the 9th October, 2014 a strong event hit the central part of Liguria Region producing disastrous consequences to the city of Genoa where the Bisagno Creek flooded causing one death and lots of damage. The precipitation pattern responsible for the event had peculiar spatial and temporal characteristics that led to an unexpected flash flood. The temporal sequence of rainfall intensities and the particular severity of rainfall showers at small temporal scale, together with the size of the sub-basin hit by the most intense part of the rainfall were the unfortunate concurrent ingredients that led to an “almost perfect” flash flood. The peak flow was estimated to be a 100–200years order return period.The effects of the spatial and temporal scales of the precipitation pattern were investigated by coupling a rainfall downscaling model with a hydrological model setting up an experiment that follows a probabilistic approach.Supposing that the correct volume of precipitation at different spatial and temporal scales is known, the experiment provided the probability of generating events with similar effects in terms of streamflow.Furthermore, the study gives indications regarding the goodness and reliability of the forecasted rainfall field needed, not only in terms of total rainfall volume, but even in spatial and temporal pattern, to produce the observed ground effects in terms of streamflow

A hyperspectral imaging system for mapping haemoglobin and cytochrome-c-oxidase concentration changes in the exposed cerebral cortex

We present a novel hyperspectral imaging (HSI) system using visible and near-infrared (NIR) light on the exposed cerebral cortex of animals, to monitor and quantify in vivo changes in the oxygenation of haemoglobin and in cellular metabolism via measurement of the redox states of cytochrome-c-oxidase (CCO). The system, named hNIR, is based on spectral scanning illumination at 11 bands (600, 630, 665, 784, 800, 818, 835, 851, 868, 881 and 894 nm), using a supercontinuum laser coupled with a rotating Pellin-Broca prism. Image reconstruction is performed with the aid of a Monte Carlo framework for photon pathlength estimation and post-processing correction of partial volume effects. The system is validated on liquid optical phantoms mimicking brain tissue haemodynamics and metabolism, and finally applied in vivo on the exposed cortex of mice undergoing alternating oxygenation challenges. The results of the study demonstrate the capacity of hNIR to map and quantify the haemodynamic and metabolic states of the exposed cortex at microvascular levels. This represents (to the best of our knowledge) the first example of simultaneous mapping and quantification of cerebral haemoglobin and CCO in vivo using visible and NIR HSI, which can potentially become a powerful tool for better understanding brain physiology

Activity of drugs against dormant Mycobacterium tuberculosis

AbstractObjective/backgroundHeterogeneous mixtures of cellular and caseous granulomas coexist in the lungs of tuberculosis (TB) patients, with Mycobacterium tuberculosis (Mtb) existing from actively replicating (AR) to dormant, nonreplicating (NR) stages. Within cellular granulomas, the pH is estimated to be less than 6, whereas in the necrotic centres of hypoxic, cholesterol/triacylglycerol-rich, caseous granulomas, the pH varies between 7.2 and 7.4. To combat TB, we should kill both AR and NR stages of Mtb. Dormant Mtb remodels lipids of its cell wall, and so lipophilic drugs may be active against NR Mtb living in caseous, lipid-rich, granulomas. Lipophilicity is expressed as logP, that is, the logarithm of the partition coefficient (P) ratio Poctanol/Pwater. In this study, the activity of lipophilic drugs (logP>0) and hydrophilic drugs (logP⩽0) against AR and NR Mtb was measured in hypoxic conditions under acidic and slightly alkaline pHs.MethodsThe activity of drugs was determined against AR Mtb (5-day-old aerobic cells: A5) and NR Mtb (12- and 19-day-old hypoxic cells: H12 and H19) in a Wayne dormancy model of Mtb H37Rv at pH 5.8, to mimic the environment of cellular granulomas. Furthermore, AR and NR bacilli were grown for 40days in Wayne models at pH 6.6, 7.0, 7.4, and 7.6, to set up conditions mimicking the caseous granulomas (hypoxia+slightly alkaline pH), to measure drug activity against NR cells. Mtb viability was determined by colony-forming unit (CFU) counts.ResultsAt pH 5.8, lipophilic drugs (rifampin, rifapentine, bedaquiline, PA-824, clofazimine, nitazoxanide: logP⩾2.14) reduced CFU of all cells (H12, H19, and A5) by ⩾2log10. Among hydrophilic drugs (isoniazid, pyrazinamide, ethambutol, amikacin, moxifloxacin, metronidazole: logP⩽0.01), none reduced H12 and H19 CFUs by ⩾2log10, with the exception of metronidazole. When Mtb was grown at different pHs the following Mtb growth was noted: at pH 6.6, AR cells grew fluently while NR cells grew less, with a CFU increase up to Day 15, followed by a drop to Day 40. AR and NR Mtb grown at pH 7.0, 7.4, and 7.6 showed up to 1 log10 CFU lower than their growth at pH 6.6. The pHs of all AR cultures tended to reach pH 7.2–7.4 on Day 40. The pHs of all NR cultures remained stable at their initial values (6.6, 7.0, 7.4, and 7.6) up to Day 40. The activity of drugs against H12 and H19 cells was tested in hypoxic conditions at a slightly alkaline pH. Under these conditions, some lipophilic drugs were more active (>5 log CFU decrease after 21days of exposure) against H12 and H19 cells than clofazimine, nitazoxanide, isoniazid, pyrazinamide, amikacin (<1 log CFU decrease after 21days of exposure). Testing of other drugs is in progress.ConclusionLipophilic drugs were more active than hydrophilic agents against dormant Mtb in hypoxic conditions at pH 5.8. The Wayne model under slightly alkaline conditions was set up, and in hypoxic conditions at a slightly alkaline pH some lipophilic drugs were more active than other drugs against NR Mtb. Overall, these models can be useful for testing drug activity against dormant Mtb under conditions mimicking the environments of cellular and caseous granulomas