Optical coherence tomography measurements of biological fluid flows with picolitre spatial localization

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Interest in studying the human and animal microcirculation has burgeoned in recent years. In part this has been driven by recent advances in volumetric microscopy modalities, which allow the study of the 3-D morphology of the microcirculation without the limitations of 2-D intra-vital microscopy. In this paper we highlight the power of optical coherence tomography (OCT) to image the normal and pathological microcirculation with picolitre voxel sizes. Both Doppler and speckle-variance methods are employed to characterize complex rheological flows both in-vitro and in-vivo. GPU accelerated image registration methods are demonstrated in order to mitigate problems of bulk tissue motion in methods based on speckle decorrelation. In-vivo images of the human nailfold microcirculation are shown

Improvements in Skeletal Muscle Can Be Detected Using Broadband NIRS in First-Time Marathon Runners

Skeletal muscle metabolic function is known to respond positively to endurance exercise interventions, such as marathon training. Studies investigating skeletal muscle have typically used muscle biopsy samples or magnetic resonance spectroscopy (MRS) to interrogate metabolic function. We aimed to non-invasively detect exercise-training-induced improvements in muscle function using broadband near-infrared spectroscopy (NIRS). We used NIRS to determine concentration changes in oxygenated haemoglobin (HbO2) and the oxidation state of cytochrome-c-oxidase (oxCCO) in gastrocnemius during arterial occlusion in 14 volunteers. We also used a cardio-pulmonary exercise test (CPET) to assess peak total body oxygen uptake (peakVO2; a measure of fitness). Measurements were made at baseline (BL) which was prior to a period of at least 16 weeks of training for the 2017 London Marathon, and then within 3 weeks after completion of the marathon, follow-up (FU). We observed an increase in locally measured muscle oxygen consumption and rate of oxCCO concentration change, but not in cardio-respiratory fitness measured as whole-body peak oxygen consumption (peakVO2)

Hyperspectral Imaging of the Hemodynamic and Metabolic States of the Exposed Cortex: Investigating a Commercial Snapshot Solution

Hyperspectral imaging (HSI) systems have the potential to retrieve in vivo hemodynamic and metabolic signals from the exposed cerebral cortex. The use of multiple narrow wavelength bands in the near infrared (NIR) range theoretically allows not only to image brain tissue oxygenation and hemodynamics via mapping of hemoglobin concentration changes, but also to directly quantify cerebral metabolism via measurement of the redox states of mitochondrial cytochrome-c-oxidase (CCO). The aim of this study is to assess the possibility of performing hyperspectral imaging of in vivo cerebral oxyhemoglobin (HbO2), deoxyhemoglobin (HHb) and oxidized CCO (oxCCO) using commercially available HSI devices. For this reason, a hyperspectral snapshot solution based on Cubert GmbH technology (S185 FireflEYE camera) has been tested on the exposed cortex of mice during normoxic, hypoxic and hyperoxic conditions. The system allows simultaneous acquisition of 138 wavelength bands between 450 and 998 nm, with spectral sampling and resolution of ~4 to 8 nm. From the hyperspectral data, relative changes in concentration of hemoglobin and oxCCO are estimated and hemodynamic and metabolic maps of the imaged cortex are calculated for two different NIR spectral ranges. Spectroscopic analysis at particular regions of interest is also performed, showing typical oxygen-dependent hemodynamic responses. The results highlight some of the potentials of the technology, but also the limitations of the tested commercial solution for such specific application, in particular regarding spatial resolution

Evaluation of Haemoglobin and Cytochrome Responses During Forearm Ischaemia Using Multi-wavelength Time Domain NIRS

We demonstrate the ability of a 16-wavelength time domain near-infrared spectroscopy system to monitor changes in oxy- and deoxy haemoglobin ([HbO2] [HHb]) and the oxidation of cytochrome-c-oxidase ([oxCCO]), during forearm ischaemia. We tested two methods to retrieve the concentration changes. The first uses the measured changes in light attenuation and the modified Beer-Lambert law, and the second uses the absorption and scattering estimated by the measured time-point spread function. The system is able to retrieve the concentration changes with both methods, giving similar results. At the end of forearm ischaemia (t = 5 min), we measured an increase in [HHb] of 16.77 ± 2.52 and 16.37 ± 2.33 μMol, and a decrease in [HbO2] of -6.12 ± 1.62 and -5.57 ± 2.02 μMol for method 1 and 2, respectively. At that same time, the changes in [oxCCO] were -0.36 ± 0.33 and -1.40 ± 1.20 μMol, for method 1 and 2, respectively. These small changes in [oxCCO], despite a huge change in haemoglobin, demonstrate the absence of crosstalk and are comparable to previous measurements using broadband NIRS

Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy

We have evaluated the ability of steady-state, radially-resolved, broad-band near infrared diffuse reflectance spectroscopy to measure carbogen-induced changes in haemoglobin oxygen saturation (SO2) and total haemoglobin concentration in a rat R3230 mammary adenocarcinoma model in vivo. Detectable shifts toward higher saturations were evident in all tumours (n = 16) immediately after the onset of carbogen breathing. The SO2 reached a new equilibrium within 1 min and remained approximately constant during 200–300 s of administration. The return to baseline saturation was more gradual when carbogen delivery was stopped. The degree to which carbogen increased SO2 was variable among tumours, with a tendency for tumours with lower initial SO2 to exhibit larger changes. Tumour haemoglobin concentrations at the time of peak enhancement were also variable. In the majority of cases, haemoglobin concentration decreased in response to carbogen, indicating that increased tumour blood volume was not responsible for the observed elevation in SO2. We observed no apparent relationship between the extent of the change in tumour haemoglobin concentration and the magnitude of the change in the saturation. Near infrared diffuse reflectance spectroscopy provides a rapid, non-invasive means of monitoring spatially averaged changes in tumour haemoglobin oxygen saturation induced by oxygen modifiers. © 1999 Cancer Research Campaig

Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia

Hypoxia-ischaemia (HI) is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS), and the model simulates the circulatory and metabolic processes that give rise to the measured signals. Model extensions include simulation of the carotid arterial occlusion used to induce HI, inclusion of cytoplasmic pH, and loss of metabolic function due to cell death. Model behaviour is compared to data from two piglets, one of which recovered following HI while the other did not. Behaviourally-important model parameters are identified via sensitivity analysis, and these are optimised to simulate the experimental data. For the non-recovering piglet, we investigate several state changes that might explain why some MRS and NIRS signals do not return to their baseline values following the HI insult. We discover that the model can explain this failure better when we include, among other factors such as mitochondrial uncoupling and poor cerebral blood flow restoration, the death of around 40% of the brain tissue. Copyright

Laser-induced modification of the patellar ligament tissue: comparative study of structural and optical changes

The effects of non-ablative infrared (IR) laser treatment of collagenous tissue have been commonly interpreted in terms of collagen denaturation spread over the laser-heated tissue area. In this work, the existing model is refined to account for the recently reported laser-treated tissue heterogeneity and complex collagen degradation pattern using comprehensive optical imaging and calorimetry toolkits. Patella ligament (PL) provided a simple model of type I collagen tissue containing its full structural content from triple-helix molecules to gross architecture. PL ex vivo was subjected to IR laser treatments (laser spot, 1.6 mm) of equal dose, where the tissue temperature reached the collagen denaturation temperature of 60 ± 2°C at the laser spot epicenterin the first regime, and was limited to 67 ± 2°C in the second regime. The collagen network was analyzed versus distance from the epicenter. Experimental characterization of the collagenous tissue at all structural levels included cross-polarization optical coherence tomography, nonlinear optical microscopy, light microscopy/histology, and differential scanning calorimetry. Regressive rearrangement of the PL collagen network was found to spread well outside the laser spot epicenter (>2 mm) and was accompanied by multilevel hierarchical reorganization of collagen. Four zones of distinct optical and morphological properties were identified, all elliptical in shape, and elongated in the direction perpendicular to the PL long axis. Although the collagen transformation into a random-coil molecular structure was occasionally observed, it was mechanical integrity of the supramolecular structures that was primarily compromised. We found that the structural rearrangement of the collagen network related primarily to the heat-induced thermo-mechanical effects rather than molecular unfolding. The current body of evidence supports the notion that the supramolecular collagen structure suffered degradation of various degrees, which gave rise to the observed zonal character of the laser-treated lesion

Development of a Near Infrared Multi-Wavelength, Multi-Channel, Time-Resolved Spectrometer for Measuring Brain Tissue Haemodynamics and Metabolism

We present a novel time domain functional near infrared spectroscopy system using a supercontinuum laser allowing us to measure the coefficient of absorption and scattering of up to 16 multiplexed wavelengths in the near infrared region. This is a four detector system that generates up to 3 mW of light for each wavelength with a narrow 2-3 nm FWHM bandwidth between 650 and 890 nm; each measurement of 16 wavelengths per channel can be performed up to a rate of 1 Hz. We can therefore quantify absolute haemoglobin changes in tissue and are currently investigating which and how many wavelengths are needed to resolve additional chromophores in tissue, such as water and the oxidation state of cytochrome-c-oxidase

The effect of basic assumptions on the tissue oxygen saturation value of near infrared spectroscopy

Tissue oxygen saturation (StO(2)), a potentially important parameter in clinical practice, can be measured by near infrared spectroscopy (NIRS). Various devices use the multi-distance approach based on the diffusion approximation of the radiative transport equation [1, 2]. When determining the absorption coefficient (μ (a)) by the slope over multiple distances a common assumption is to neglect μ (a) in the diffusion constant, or to assume the scattering coefficient [Formula: see text] to be constant over the wavelength. Also the water influence can be modeled by simply subtracting a water term from the absorption. This gives five approaches A1-A5. The aim was to test how these different methods influence the StO(2) values. One data set of 30 newborn infants measured on the head and another of eight adults measured on the nondominant forearm were analyzed. The calculated average StO(2) values measured on the head were (mean ± SD): A1: 79.99 ± 4.47%, A2: 81.44 ± 4.08%, A3: 84.77 ± 4.87%, A4: 85.69 ± 4.38%, and A5: 72.85 ± 4.81%. The StO(2) values for the adult forearms are: A1: 58.14 ± 5.69%, A2: 73.85 ± 4.77%, A3: 58.99 ± 5.67%, A4: 74.21 ± 4.76%, and A5: 63.49 ± 5.11%. Our results indicate that StO(2) depends strongly on the assumptions. Since StO(2) is an absolute value, comparability between different studies is reduced if the assumptions of the algorithms are not published