Intralipid Suspensions Research Articles

Development and optimisation of a near-infrared spectroscopic system for glucose quantification in aqueous and intralipid-based samples

A non-invasive glucose sensing device could revolutionise diabetes treatment. Near Infrared (NIR) spectroscopy is a promising technology for glucose sensing; however, the design and choice of components for NIR spectroscopy can greatly affect the sensing accuracy. We aimed to develop a NIR absorption spectroscopy system to determine liquid glucose concentrations in the physiological range, by evaluating a range of NIR photodetector components and light sources. Three detection assemblies were tested: (i) a dispersive spectrometer with photodiode array, (ii) a Czerny–Turner monochromator with InGaAs photodiode and (iii) a miniature Fourier Transform Infrared (FTIR) spectrometer. A halogen lamp and NIR globar were trialled as potential light sources. The components were systematically tested by comparing the coefficient of determination and standard error of prediction (SEP) for the same set of aqueous glucose samples through 10 mmol l−1 concentration steps. The Czerny–Turner monochromator with InGaAs photodiode, along with the globar, were identified as the optimal components for the system. A range of concentration steps (1–10 mmol l−1) were scanned to identify the physiologically relevant limit of detection, which was identified as 5 mmol/l for glucose in solution. Spectra were then collected from glucose samples in 10% intralipid suspension in the 10–20 mmol l−1 range and the equivalent concentrations in solution. The SEP was greater for the intralipid samples due to strong scattering. Scattering was dominant above 1300 nm, whilst absorption was dominant below 1300 nm. Although alternative approaches achieve better resolution, our system uses simple and readily-available components and presents a platform for a non-invasive NIR glucose sensing device.

Optical Characterization of Homogeneous and Heterogeneous Intralipid-Based Samples

Different scattering processes take place when photons propagate inside turbid media. Many powerful experimental techniques exploiting these processes have been developed and applied over the years in a large variety of situations from fundamental and applied research to industrial applications. In the present paper, we intend to take advantage of Static Light Scattering (SLS), Dynamic Light Scattering (DLS), and Time-Resolved Transmittance (TRT) for investigating all the different scattering regimes by using scattering suspensions in a very large range of scatterer concentrations. The suspensions were prepared using Intralipid 20%, a material largely employed in studies of the optical properties of turbid media, with concentrations from 10−5% to 50%. By the analysis of the angular and temporal dependence of the scattered light, a more reliable description of the scattering process occurring in these samples can be obtained. TRT measurements allowed us to obtain information on the reduced scattering coefficient, an important parameter largely used in the description of the optical properties of turbid media. TRT was also employed for the detection of inclusions embedded in Intralipid suspensions, by using a properly designed data analysis. The present study allowed us to better elucidate the dependence of scattering properties of Intralipid suspensions in a very large concentration range and the occurrence of the different scattering processes involved in the propagation of light in turbid media for the first time to our knowledge. In so doing, the complementary contribution of SLS, DLS, and TRT in the characterization of turbid media from an optical and structural point of view is strongly evidenced.

Designing phantoms to accurately replicate circular depolarization in biological scattering media.

We introduce an iterative method for designing optical phantoms that are able to replicate the depolarization profiles of various target media, including colloidal suspensions of Intralipid, bovine milk, and ex vivo samples of ovine kidney cortex tissue. The designed phantoms comprise spherical scattering particles with fine-tuned size distributions and are capable of simultaneously reproducing spatially resolved intensity measurements and depolarization measurements of target media when illuminated with circularly polarized light.

Reducing the spectral nonlinearity error caused by varying integration time

In the spectral analysis, it is very common to adjust the grating spectrometer's integration time to make it at the appropriate sensitivity, which can get high signal-to-noise ratio (SNR) and unsaturated spectrum. However, varying the integration time during measurement will introduce errors. The influence of varying spectrometer integration time on the spectral analysis was studied in this work, and a method was proposed to formulate a calibration model to inhibit the effect of different sensitivity spectrum due to different integration time. The strategy is to construct a model that is insensitive to the variation of integration time. This method involves the use of collected spectra under different integration time for the model establishment where the obtained model is found to satisfactorily inhibit the influence of integration time variation. An experiment was designed: Collecting the transmission spectra of Intra-lipid suspension by setting different integration time, the obtained spectral data were then processed by “Interactive-Validation method”that can evaluate the error caused by different integration, and processed by the“new modeling method”. The experimental results showed that when the integration time was varied to achieve high SNR spectra acquisition, the model established via the novel modeling strategy was clearly a viable method of improving its robustness by incorporating varying integration time, and it could well inhibit the error caused by integration time variation.

Reduction of flexible container induced error for the composition analysis of in-flexible-container liquid based on differential optical-path spectrum

The influence of flexible container on the spectral analysis of in-flexible-container liquid was investigated in this study. A method was proposed to formulate a model to inhibit the influence due to the difference of the flexible container. Based on the modified Longbow Bill’s Law (Beer–Lambert law), a model insensitive to the difference of the flexible container was constructed. This method involves the use of differential optical-path spectrum for studying the model of in-flexible-container liquid. The obtained model was found to satisfactorily inhibit the influence caused by the variation of the flexible container. An experiment was designed using a mixed solution of Intra-lipid suspension and India ink as the analytical sample, and a polyvinyl chloride sample tube was used to simulate the flexible container of the analytical sample. Analysis of the experimental data shows that the model established via the differential optical-path spectrum modeling strategy could well inhibit the error caused by variation of the flexible container. Therefore, this study provides a basis for the quantitative analysis of blood or other liquids in flexible containers.

The influence of different integration time on stoichiometric analysis in near infrared grating spectrometers

Grating spectrometers are widely used in NIR spectroscopic analysis asa spectrum acquisition instrument. The sensitivity of the spectrometer can be varied by changing the integration time. In this paper, we study the influence of varying integration time on Stoichiometric analysis. The NIR spectra of different intralipid suspensions measured at five integration time were collected, which were then used to establish a model to predict the intralipid suspensions concentration by using the partial least squares regression (PLSR) method. “Cross-validation method” was used to evaluate the errors caused by the different integration times. Experimental results showed that the model accuracy is different based on the root-mean-square error of the calibration set (RMSEC), which ranged from 0.0016 to 0.3488. With the method of “Cross-validation,” all the root-mean-square errors of the prediction set (RMSEP) were larger than the RMSECs, up to two orders of magnitude. This study demonstrates that the integration time has a nonlinear relationship with the light intensity obtained by the spectrometer, this nonlinearity will affect the measurement accuracy. Therefore, we should pay attention to the influence by varying integration time on the measurement in the stoichiometric analysis.

High power visible light emitting diodes as pulsed excitation sources for biomedical photoacoustics.

The use of visible light emitting diodes (LEDs) as an alternative to Q-switched lasers conventionally used as photoacoustic excitation sources has been explored. In common with laser diodes, LEDs offer the advantages of compact size, low cost and high efficiency. However, laser diodes suitable for pulsed photoacoustic generation are typically available only at wavelengths greater than 750nm. By contrast, LEDs are readily available at visible wavelengths below 650nm where haemoglobin absorption is significantly higher, offering the prospect of increased SNR for superficial vascular imaging applications. To demonstrate feasibility, a range of low cost commercially available LEDs operating in the 420-620nm spectral range were used to generate photoacoustic signals in physiologically realistic vascular phantoms. Overdriving with 200ns pulses and operating at a low duty cycle enabled pulse energies up to 10µJ to be obtained with a 620nm LED. By operating at a high pulse repetition frequency (PRF) in order to rapidly signal average over many acquisitions, this pulse energy was sufficient to generate detectable signals in a blood filled tube immersed in an Intralipid suspension (µs’ = 1mm−1) at a depth of 15mm using widefield illumination. In addition, a compact four-wavelength LED (460nm, 530nm, 590nm, 620nm) in conjunction with a coded excitation scheme was used to illustrate rapid multiwavelength signal acquisition for spectroscopic applications. This study demonstrates that LEDs could find application as inexpensive and compact multiwavelength photoacoustic excitation sources for imaging superficial vascular anatomy.Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.

Stimulated Raman photoacoustic spectroscopy for chemical-contrast imaging of a sample deeply buried in scattering media.

The development of a stimulated Raman scattering photoacoustic (SRS-PA) spectrometer is presented. In the apparatus, a molecular vibrational mode is excited by the SRS process. The vibrational excitation energy is converted to heat by vibrational relaxation. The volumes around the excited molecules including the surrounding solvent molecules expand by heating, resulting in the generation of an ultrasonic wave. The ultrasonic wave can be used as a molecular-selective signal. Because the ultrasonic wave is scarcely scattered by media, SRS-PA is expected to be applied for obtaining molecular-selective signals from deeply buried samples. In the present study, a SRS-PA spectrometer was developed and applied to obtain molecular-selective signals from test samples. The SRS-PA signals from water and lipid, which are important components in biological systems, were first obtained. The SRS-PA signal from a polystyrene film buried in a highly light-scattering intralipid suspension was also measured. We succeeded in obtaining the signal from the film when it was buried with a depth of up to 1.8 mm. The results indicate that SRS-PA can be effectively applied for the chemical-contrast imaging of deeply buried samples.

Measuring flow dynamics in a microfluidic chip using optical coherence tomography with 1 µm axial resolution

An experimental verification of simulated flow dynamics in a novel design of microfluidic device can be difficult, especially, in devices such as mixers or deterministic lateral displacement (DLD) arrays. Doppler optical coherence tomography (DOCT) is one of the visualization modalities used to measure flow velocity profiles in microfluidic channels, capillaries and microvascular networks. Previously conducted flow measurements with high speed spectral-domain optical coherence tomography (SD-OCT) devices have had typical axial resolution in the range few microns which can be insufficient for accurate mapping of flow dynamics in microchannels. This paper introduces a high-speed SD-OCT system with an axial resolution of 1.2µm in air (below 1µm in water) to evaluate flow in a microfluidic chip. The A-line acquisition rate of the device is 123kHz. Flow velocities from 1% Intralipid suspension are obtained across the microfluidic channel with the specified height of 20µm and the width of 50µm. The results show that the utilized SD-OCT device can visualize flows as close as 1µm from the channel wall. The flow rate of 0.63µl/min, determined from the cross-sectional velocity map, agreed well with the value of 0.67µl/min set to the syringe pump.

Fiber-optic polarization diversity detection for rotary probe optical coherence tomography

We report a polarization diversity detection scheme for optical coherence tomography with a new, custom, miniaturized fiber coupler with single mode (SM) fiber inputs and polarization maintaining (PM) fiber outputs. The SM fiber inputs obviate matching the optical lengths of the X and Y OCT polarization channels prior to interference and the PM fiber outputs ensure defined X and Y axes after interference. Advantages for this scheme include easier alignment, lower cost, and easier miniaturization compared to designs with free-space bulk optical components. We demonstrate the utility of the detection system to mitigate the effects of rapidly changing polarization states when imaging with rotating fiber optic probes in Intralipid suspension and during in vivo imaging of human airways.

Light Propagation in NIR Spectroscopy of the Human Brain

In study of the brain, oxygenation changes in the cerebral cortex are of great interest, since the concentrations of oxyhaemoglobin and deoxyhaemoglobin change due to coupling of hemodynamics to cortical neural activity. In order to non-invasively monitor oxygenation in the cerebral cortex by near-infrared spectroscopy (NIRS), light should penetrate into brain tissue to a depth of approximately 1-2 cm. Many studies show that by increasing the source-detector distance, illuminating light penetrates deeper into brain tissue. Using tissue-mimicking phantom measurements, forehead in vivo measurements, and Monte Carlo (MC) simulations, this paper estimates light propagation in the brain and the minimum source-detector distance to allow sensing of the cerebral cortex. We present optical sensing of a pulsating aqueous intralipid suspension in a vessel located at different depths within a multilayered phantom of the human forehead. Experimental results are compared with the MC simulations accounting for the optical properties of the phantom. The thickness and morphology of the different tissue layers were obtained from an anatomical magnetic resonance image of a test subject's head. Results from these three methods correlate with each other and show that the brain cortex can be sensed with optical methods based on NIRS.

Optical Scattering Properties of Intralipid Phantom in Presence of Encapsulated Microbubbles

In imaging, contrast agents are utilized to enhance sensitivity and specificity of diagnostic modalities. In ultrasound imaging, microbubbles (MBs)—a gas-core shell-encapsulated agent—are used clinically as contrast agents. The working hypothesis of this study is that microbubbles can be employed as an intravascular contrast agent in optical imaging systems. In this work, the interaction of light and microbubbles in a turbid medium (intralipid) was investigated, particularly, the effect of MBs on the reduced scattering and absorption coefficients. Diffuse reflectance (DR) and total transmittance (TT) measurements of highly scattering intralipid suspension (0.5–5%) were measured using spectroscopic integrating sphere system in the absence and presence of Definity microbubbles. The optical properties were computed using the inverse adding doubling (IAD) software. The presence of microbubbles increased DR and decreased TT of intralipid phantoms. In the presence of MBs (0.5% volume concentration), the reflectance of the intralipid phantom increased from 35% to 100%. The reduced scattering coefficient increased significantly (30%) indicating potential use of MBs as optical contrast agents in light based modalities.

Effect of surface roughness on measurement of light distribution in intralipid suspension

Light distribution in the biological tissue phantom intralipid suspension with different interface roughness was measured for quantitative understanding of surface roughness effect. The results show that the surface roughness strongly affects light distribution inside the approximately semi-infinite biological tissue phantom. The phantom surface possesses a certain degree roughness and the effect of the surface roughness on measurement results of light distribution in tissue is substantial, so the measurement of light distribution in biological tissue needs to take surface roughness into account.

EFFICIENT FITTING RANGE FOR GLUCOSE MEASUREMENT WITH OPTICAL COHERENCE TOMOGRAPHY

Studies of non-invasive glucose measurement with optical coherence tomography (OCT) in tissue-simulating phantoms and biological tissues show that glucose has an effect on the OCT signal slope. Choosing an efficient fitting range to calculate the OCT signal slope is important because it helps to improve the precision of glucose measurement. In this paper, we study the problem in two ways: (1) scattering-induced change of OCT signal slope versus depth in intralipid suspensions with different concentrations based on Monte Carlo (MC) simulations and experiments and (2) efficient fitting range for glucose measurement in 3% and 10% intralipid. The results show that the OCT signal slope expresses a contrary change with scattering coefficient below a certain depth in high intralipid concentrations, so that there is an effective fitting depth. With an efficient fitting range from 100 μm to the effective fitting depth, the precision of glucose measurement can be 4.4 mM for 10% intralipid and 2.2 mM for 3% intralipid.

Illustration of a bimodal system in Intralipid-20% by polarized light scattering: experiments and modeling

Intralipid suspensions behave like phantoms of human tissues concerning their light scattering properties. We present experimental measurements of the angular distribution of polarized light scattering at various incidence angles on Intralipid-20%. A comparison of the absolute values of these measurements with simulations using a vector radiative transfer model (N-flux) developed for multilayered media demonstrates a stratified structure of the samples with a double distribution of the size of scatterers. This result is confirmed by polarimetry imaging.

Quantification of scattering changes using polarization-sensitive optical coherence tomography

We demonstrate that changes in the degree of polarization (DOP) depend on changes in the scattering coefficient, and they can be quantified by using a polarization-sensitive optical coherence tomography (PS-OCT) system. We test our hypothesis using liquid and solid phantoms made from Intralipid suspensions and gelatin, respectively. We also quantify the DOP changes with depth caused by changes in the concentration of scatterers in the liquid and solid phantoms. It is clearly shown that the DOP change has a linear relationship with the scattering change. In our previous study, we showed that the axial slope of the DOP is different between normal and pathologic cervical tissues. Our results demonstrate that the quantification of the axial DOP slope can be used for the systematic diagnosis of certain tissue pathology.

Near-infrared laser tomographic imaging with right-angled scattered coherent light using an optical heterodyne-detection-based confocal scanning system

We demonstrate, what is to the best of our knowledge, a novel optical tomographic method for the visualization of the inner structure of scattering media such as biological tissue in the near-infrared region. We constructed a scanning confocal imaging system with a cross-axes arrangement using optical fibers. This system is based on the optical heterodyne technique and enables the detection of very weak coherence photons that are generated in the spatially restricted confocal region and scattered laterally (90 degrees ) against an incident beam. To evaluate the fundamental imaging capabilities of the system, we assessed measurements from scattering phantoms composed of an Intralipid suspension with varying volume concentrations. The results of this study demonstrate that the right-angled scattered light adheres to the Lambert-Beer law and that the present system can detect light propagating through a distance of approximately 31l of the mean free path. An inclusion as small as 100 microm can be discriminated in a scattering media with an optical thickness of 4. We investigated the potential of the proposed system for imaging biological tissues in preliminary experiments using samples of chicken breast tissue.

Scattering photoacoustic study of weakly-absorbing substances in aqueous suspensions

This study explores the application of the scattering photoacoustic (SPA) technique to the study of weakly-absorbing substances in suspensions. The technique allows the scattering and PA properties of weakly absorbing materials to be examined simultaneously. The experiment reported here measured the reduced scattering coefficients of milk, intralipid and polystyrene suspensions with and without glucose. It turned out that in milk the SPA method has a higher detection sensitivity for fat than for glucose. Nonetheless, glucose was observed to have a larger effect on scattering in light milk and intralipid-1% bases than in non-fat milk and polystyrene-0.5% bases, although the scattering effect contributed little to the PA signal produced in the suspensions.

Glucose-induced changes in the optical properties of Intralipid

Photoacoustic and optical measurement techniques were used in this paper to study glucose-induced changes in Intralipid suspensions. Optical energy was provided by a Nd:YAG laser at 1064 and 532 nm and a picosecond laser module at 906 nm. As detectors, the setup employed a photoacoustic detector, PIN diode, and streak camera. Increasing the glucose content of the suspensions increased the refractive indices of the studied media. This served to decrease the refractive index mismatch between the background and the scattering particles and led consequently to decreased scattering, which then affected both the peak-to-peak value of the photoacoustic signals and the transmitted optical pulses. At 1064 nm, glucose changed the peak-to-peak value of the photoacoustic signal more in 1% than in 2% Intralipid. In addition, the glucose-induced change in the transmitted pulse amplitude was less noticeable at 532 than at 1064 nm in 1% Intralipid.

On the renormalisation of the diffusion asymptotics in the problem of reflection of a narrow optical beam from a biological medium

An analytic hybrid method is considered for solving the stationary radiation transfer equation in the problem on reflection of a narrow laser beam from biological media such as the 2% aqueous solution of intralipid and erythrocyte suspension with the volume concentration (hematocrit) H=0.41. The method is based on the reciprocity of the Green function in the radiation transfer theory and on the iteration solution of the integral equation for this function. As a result, the ray intensity is represented as a sum of two terms. The first of them describes the contribution of finite-order scattering to the intensity of a beam diffusely reflected from the medium. The second term contains the explicit analytic expression for a spatially distributed effective source of diffuse radiation emerging from the deep layers of the medium to the surface. This approach substantially improves the diffusion approximation for the problem under study and allows one to obtain the uniform asymptotics of the reflection coefficient at the specified interval of distances between the radiation source and detector on the medium surface with the relative error within ±6% for the 2% intralipid emulsion and erythrocyte suspension (H=0.41).