Mamadou Diop

Quantifying the cerebral metabolic rate of oxygen by combining diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy

Abstract. Preterm infants are highly susceptible to ischemic brain injury; consequently, continuous bedside monitoring to detect ischemia before irreversible damage occurs would improve patient outcome. In addition to monitoring cerebral blood flow (CBF), assessing the cerebral metabolic rate of oxygen (CMRO2) would be beneficial considering that metabolic thresholds can be used to evaluate tissue viability. The purpose of this study was to demonstrate that changes in absolute CMRO2 could be measured by combining diffuse correlation spectroscopy (DCS) with time-resolved near-infrared spectroscopy (TR-NIRS). Absolute CBF was determined using bolus-tracking TR-NIRS to calibrate the DCS measurements. Cerebral venous blood oxygenation (SvO2) was determined by multiwavelength TR-NIRS measurements, the accuracy of which was assessed by directly measuring the oxygenation of sagittal sinus blood. In eight newborn piglets, CMRO2 was manipulated by varying the anesthetics and by injecting sodium cyanide. No significant differences were found between the two sets of SvO2 measurements obtained by TR-NIRS or sagittal sinus blood samples and the corresponding CMRO2 measurements. Bland–Altman analysis showed a mean CMRO2 difference of 0.0268±0.8340  mL O2/100  g/min between the two techniques over a range from 0.3 to 4 mL O2/100  g/min.

Quantifying cerebral blood flow in an adult pig ischemia model by a depth-resolved dynamic contrast-enhanced optical method

Dynamic contrast-enhanced (DCE) near-infrared (NIR) methods have been proposed for bedside monitoring of cerebral blood flow (CBF). These methods have primarily focused on qualitative approaches since scalp contamination hinders quantification. In this study, we demonstrate that accurate CBF measurements can be obtained by analyzing multi-distance time-resolved DCE data with a combined kinetic deconvolution optical reconstruction (KDOR) method. Multi-distance time-resolved DCE-NIR measurements were made in adult pigs (n=8) during normocapnia, hypocapnia and ischemia. The KDOR method was used to calculate CBF from the DCE-NIR measurements. For validation, CBF was measured independently by CT under each condition. The mean CBF difference between the techniques was -1.7 mL/100 g/min with 95% confidence intervals of -16.3 and 12.9 mL/100 g/min; group regression analysis revealed a strong agreement between the two techniques (slope=1.06±0.08, y-intercept=-4.37±4.33 mL/100 g/min, p<0.001). The results of an error analysis suggest that little a priori information is needed to recover CBF, due to the robustness of the analytical method and the ability of time-resolved NIR to directly characterize the optical properties of the extracerebral tissue (where model mismatch is deleterious). The findings of this study suggest that the DCE-NIR approach presented is a minimally invasive and portable means of determining absolute hemodynamics in neurocritical care patients.

Model-independent dynamic constraint to improve the optical reconstruction of regional kinetic parameters.

Optical dye-dilution techniques can quantify kinetic parameters in a region of tissue, but currently rely on a two-step process-spatial reconstruction of the dye concentration, repeated at every time-point, and subsequent kinetic analysis of the time-dependent change in dye concentration. Inaccuracies, in this approach, are due mainly to the ill-posed nature of the spatial reconstruction problem, which propagates into kinetic analysis and result in errors in extracted dynamic parameters. We present a hybrid kinetic deconvolution optical reconstruction algorithm, effectively combining optical reconstruction and model-independent kinetic analysis into a single inverse problem that is better posed. Kinetic parameters of multiple tissue regions can be quantified simultaneously. As proof of principle, we provide numerical experiments in reflectance-based and fluorescence molecular tomography scenarios.

Time-resolved near-infrared technique for bedside monitoring of absolute cerebral blood flow

A primary focus of neurointensive care is monitoring the injured brain to detect harmful events that can impair cerebral blood flow (CBF). Since current non-invasive bedside methods can only indirectly assess blood flow, the goal of this research was to develop an optical technique for measuring absolute CBF. A time-resolved near-infrared (NIR) apparatus was built and its ability to accurately measure changes in optical properties was demonstrated in tissue-mimicking phantoms. The time-resolved system was combined with a bolus-tracking method for measuring CBF using the dye indocyanine green (ICG) as an intravascular flow tracer. Cerebral blood flow was measured in newborn piglets and for comparison, CBF was concurrently measured using a previously developed continuous-wave NIR method. Measurements were acquired with both techniques under three conditions: normocapnia, hypercapnia and following occlusion of the carotid arteries. Mean CBF values (N = 3) acquired with the TR-NIR system were 31.9 ± 11.7 ml/100g/min during occlusion, 39.7 ± 1.6 ml/100g/min at normocapnia, and 58.8 ± 9.9 ml/100g/min at hypercapnia. Results demonstrate that the developed TR-NIR technique has the sensitivity to measure changes in CBF; however, the CBF measurements were approximately 25% lower than the values obtained with the CW-NIRS technique.

Kinetic model optimization for characterizing tumour physiology by dynamic contrast-enhanced near-infrared spectroscopy

Dynamic contrast-enhanced (DCE) methods are widely used with magnetic resonance imaging and computed tomography to assess the vascular characteristics of tumours since these properties can affect the response to radiotherapy and chemotherapy. In contrast, there have been far fewer studies using optical-based applications despite the advantages of low cost and safety. This study investigated an appropriate kinetic model for optical applications to characterize tumour haemodynamics (blood flow, F, blood volume, V(b), and vascular heterogeneity) and vascular leakage (permeability surface-area product, PS). DCE data were acquired with two dyes, indocyanine green (ICG) and 800 CW carboxylate (IRD(cbx)), from a human colon tumour xenograph model in rats. Due to the smaller molecular weight of IRD(cbx) (1166 Da) compared to albumin-bound ICG (67 kDa), PS of IRD(cbx) was significantly larger; however, no significant differences in F and V(b) were found between the dyes as expected. Error analysis demonstrated that all parameters could be estimated with an uncertainty less than 5% due to the high temporal resolution and signal-to-noise ratio of the optical measurements. The next step is to adapt this approach to optical imaging to generate haemodynamics and permeability maps, which should enhance the clinical interest in optics for treatment monitoring.

Development of a combined broadband near-infrared and diffusion correlation system for monitoring cerebral blood flow and oxidative metabolism in preterm infants.

Neonatal neuromonitoring is a major clinical focus of near-infrared spectroscopy (NIRS) and there is an increasing interest in measuring cerebral blood flow (CBF) and oxidative metabolism (CMRO2) in addition to the classic tissue oxygenation saturation (StO2). The purpose of this study was to assess the ability of broadband NIRS combined with diffusion correlation spectroscopy (DCS) to measured changes in StO2, CBF and CMRO2 in preterm infants undergoing pharmaceutical treatment of patent ductus arteriosus. CBF was measured by both DCS and contrast-enhanced NIRS for comparison. No significant difference in the treatment-induced CBF decrease was found between DCS (27.9 ± 2.2%) and NIRS (26.5 ± 4.3%). A reduction in StO2 (70.5 ± 2.4% to 63.7 ± 2.9%) was measured by broadband NIRS, reflecting the increase in oxygen extraction required to maintain CMRO2. This study demonstrates the applicability of broadband NIRS combined with DCS for neuromonitoring in this patient population.

Improved light collection and wavelet de-noising enable quantification of cerebral blood flow and oxygen metabolism by a low-cost, off-the-shelf spectrometer

Abstract. Broadband continuous-wave near-infrared spectroscopy (CW-NIRS) is an attractive alternative to time-resolved and frequency-domain techniques for quantifying cerebral blood flow (CBF) and oxygen metabolism in newborns. However, efficient light collection is critical to broadband CW-NIRS since only a small fraction of the injected light emerges from any given area of the scalp. Light collection is typically improved by optimizing the contact area between the detection system and the skin by means of light guides with large detection surface. Since the form-factor of these light guides do not match the entrance of commercial spectrometers, which are usually equipped with a narrow slit to improve their spectral resolution, broadband NIRS spectrometers are typically custom-built. Nonetheless, off-the-shelf spectrometers have attractive advantages compared to custom-made units, such as low cost, small footprint, and wide availability. We demonstrate that off-the-shelf spectrometers can be easily converted into suitable instruments for deep tissue spectroscopy by improving light collection, while maintaining good spectral resolution, and reducing measurement noise. The ability of this approach to provide reliable cerebral hemodynamics was illustrated in a piglet by measuring CBF and oxygen metabolism under different anesthetic regimens.

Monitoring brain temperature by time-resolved near-infrared spectroscopy: pilot study

Abstract. Mild hypothermia (HT32°C−33°C) is an effective neuroprotective strategy for a variety of acute brain injuries. However, the wide clinical adaptation of HT32−33°C has been hampered by the lack of a reliable noninvasive method for measuring brain temperature, since core measurements have been shown to not always reflect brain temperature. The goal of this work was to develop a noninvasive optical technique for measuring brain temperature that exploits both the temperature dependency of water absorption and the high concentration of water in brain (80%–90%). Specifically, we demonstrate the potential of time-resolved near-infrared spectroscopy (TR-NIRS) to measure temperature in tissue-mimicking phantoms (in vitro) and deep brain tissue (in vivo) during heating and cooling, respectively. For deep brain tissue temperature monitoring, experiments were conducted on newborn piglets wherein hypothermia was induced by gradual whole body cooling. Brain temperature was concomitantly measured by TR-NIRS and a thermocouple probe implanted in the brain. Our proposed TR-NIRS method was able to measure the temperature of tissue-mimicking phantoms and brain tissues with a correlation of 0.82 and 0.66 to temperature measured with a thermometer, respectively. The mean difference between the TR-NIRS and thermometer measurements was 0.15°C±1.1°C for the in vitro experiments and 0.5°C±1.6°C for the in vivo measurements.

Time-resolved subtraction method for measuring optical properties of turbid media

Near-infrared spectroscopy is a noninvasive optical method used primarily to monitor tissue oxygenation due to the absorption properties of hemoglobin. Accurate estimation of hemoglobin concentrations and other light absorbers requires techniques that can separate the effect of absorption from the much greater effect of light scattering. One of the most advanced methods is time-resolved near-infrared spectroscopy (TR-NIRS), which measures the absorption and scattering coefficients of a turbid medium by modeling the recorded distribution time of flight of photons. A challenge with TR-NIRS is that it requires accurate characterization of the dispersion caused by the system. In this study, we present a method for circumventing this problem by applying statistical moment analysis to two time-of-flight distributions measured at separated source-detector distances. Simulations based on analytical models and Monte Carlo code, and tissue-mimicking phantoms, were used to demonstrate its accuracy for source-detector distances typically used in neuroimaging applications. The simplicity of the approach is well suited to real-time applications requiring accurate quantification of the optical properties of a turbid medium.

Assessing the feasibility of time-resolved fNIRS to detect brain activity during motor imagery

Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical technique for detecting brain activity, which has been previously used during motor and motor executive tasks. There is an increasing interest in using fNIRS as a brain computer interface (BCI) for patients who lack the physical, but not the mental, ability to respond to commands. The goal of this study is to assess the feasibility of time-resolved fNIRS to detect brain activity during motor imagery. Stability tests were conducted to ensure the temporal stability of the signal, and motor imagery data were acquired on healthy subjects. The NIRS probes were placed on the scalp over the premotor cortex (PMC) and supplementary motor area (SMA), as these areas are responsible for motion planning. To confirm the fNIRS results, subjects underwent functional magnetic resonance imaging (fMRI) while performing the same task. Seven subjects have participated to date, and significant activation in the SMA and/or the PMC during motor imagery was detected by both fMRI and fNIRS in 4 of the 7 subjects. No activation was detected by either technique in the remaining three participants, which was not unexpected due to the nature of the task. The agreement between the two imaging modalities highlights the potential of fNIRS as a BCI, which could be adapted for bedside studies of patients with disorders of consciousness.