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Short-wave Infrared Photoacoustic Spectroscopy for Lipid and Water Detection
... A limitation of this study was that no direct validation with histology was performed to quantify the presence of LWC. Studies which implement spectral-unmixing algorithms 24,[45][46][47][48] to identify LWC and other constituents in tissue may find a benefit in the increased SNR at chosen wavelengths provided through HWG; however, future validation studies are needed to determine the accuracy of these HWG-enabled spectral unmixing algorithms in the SWIR. One potential drawback of heavy water coupling is its relatively high cost compared to regular water that primarily depends on purity and volume. ...
Significance
Changes in lipid, water, and collagen (LWC) content in tissue are associated with numerous medical abnormalities (cancer, atherosclerosis, and Alzheimer’s disease). Standard imaging modalities are limited in resolution, specificity, and/or penetration for quantifying these changes. Short-wave infrared (SWIR) photoacoustic imaging (PAI) has the potential to overcome these challenges by exploiting the unique optical absorption properties of LWC>1000 nm.
Aim
This study’s aim is to harness SWIR PAI for mapping LWC changes in tissue. The focus lies in devising a reflection-mode PAI technique that surmounts current limitations related to SWIR light delivery.
Approach
To enhance light delivery for reflection-mode SWIR PAI, we designed a deuterium oxide (D2O, “heavy water”) gelatin (HWG) interface for opto-acoustic coupling, intended to significantly improve light transmission above 1200 nm.
Results
HWG permits light delivery >1 mJ up to 1850 nm, which was not possible with water-based coupling (>1 mJ light delivery up to 1350 nm). PAI using the HWG interface and the Visualsonics Vevo LAZR-X reveals a signal increase up to 24 dB at 1720 nm in lipid-rich regions.
Conclusions
By overcoming barriers related to light penetration, the HWG coupling interface enables accurate quantification/monitoring of biomarkers like LWC using reflection-mode PAI. This technological stride offers potential for tracking changes in chronic diseases (in vivo) and evaluating their responses to therapeutic interventions.
Brain disorders seriously affect life quality. Therefore, non-invasive neuroimaging has received attention to monitoring and early diagnosing neural disorders to prevent their progress to a severe level. This short review briefly describes the current MRI and PET/CT techniques developed for non-invasive neuroimaging and the future direction of optical imaging techniques to achieve higher resolution and specificity using the second near-infrared (NIR-II) region of wavelength with organic molecules.
Lipids, as the basic component of cell membranes, play an important role in human health as well as brain function. The brain is highly enriched in lipids, and disruption of lipid homeostasis is related to neurologic disorders as well as neurodegenerative diseases such as Alzheimer’s disease (AD). Aging is associated with changes in lipid composition. Alterations of fatty acids at the level of lipid rafts and cerebral lipid peroxidation were found in the early stage of AD. Genetic and environmental factors such as apolipoprotein and lipid transporter carrying status and dietary lipid content are associated with AD. Insight into the connection between lipids and AD is crucial to unraveling the metabolic aspects of this puzzling disease. Recent advances in lipid analytical methodology have led us to gain an in-depth understanding on lipids. As a result, lipidomics have becoming a hot topic of investigation in AD, in order to find biomarkers for disease prediction, diagnosis, and prevention, with the ultimate goal of discovering novel therapeutics.
Neutral lipids have been implicated in a host of potentially debilitating human diseases, such as heart disease, type-2 diabetes, and metabolic syndrome. Matrix-assisted laser desorption ionization (MALDI), the method-of-choice for mass spectrometry imaging (MSI), has led to remarkable success in imaging several lipid classes from biological tissue sections. However, due to ion suppression by phospholipids, MALDI has limited ability to efficiently ionize and image neutral lipids, such as triglycerides (TGs). To help overcome this obstacle, we have utilized silicon nanopost arrays (NAPA), a matrix-free laser desorption ionization (LDI) platform. Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease of the apocrine sweat glands. The ability of NAPA to efficiently ionize lipids is exploited in the analysis of human skin samples from sufferers of HS. Ionization by LDI from NAPA allows for the detection and imaging of a number of neutral lipid species, including TGs comprised of shorter, odd-chain fatty acids, which strongly suggests an increased bacterial load within the host tissue, as well as hexosylceramides (HexCers) and galabiosyl-/lactosylceramides that appear to be correlated with the presence of HS. Our results demonstrate that NAPA-LDI-MSI is capable of imaging and potentially differentiating healthy and diseased human skin tissues based on changes in detected neutral lipid composition.
Background:
There are now significant evidences that lipid metabolism is affected in numerous neurodegenerative diseases including Alzheimer's disease. These dysfunctions lead to abnormal levels of certain lipids in the brain, cerebrospinal fluid and plasma. It is consequently of interest to establish lipid profiles in neurodegenerative diseases. This approach, which can contribute to identify lipid biomarkers of Alzheimers' disease, can also permit to identify new therapeutic targets. It was therefore of interest to focus on central and peripheral biomarkers in Alzheimer's disease.
Methods:
A review of the literature on 148 papers was conducted. Based on this literature, the involvement of lipids (cholesterol and oxysterols, fatty acids, phospholipids) in Alzheimer's disease has been proposed.
Results:
Of the 148 references cited for lipid biomarkers for Alzheimer's disease, 65 refer to cholesterol and oxysterols, 35 to fatty acids and 40 to phospholipids. Among these lipids, some of them such as 24S-hydroxyckolesterol, open up new therapeutic perspectives in gene therapy, in particular. The results on the very long-chain fatty acids suggest the potential of peroxisomal dysfunctions in Alzheimer's disease. As for the phospholipids, they could constitute interesting biomarkers for detecting the disease at the prodromal stage.
Conclusion:
There are now several lines of evidence that lipids play fundamental roles in the pathogenesis of AD and that some of them have a prognostic and diagnosis value. This may pave the way for the identification of new therapeutic targets, new effective drugs and / or new treatments.
We present a review of short-wave infrared (SWIR, defined here as similar to 1000 to 2000 nm) spectroscopy and imaging techniques for biological tissue optical property characterization. Studies indicate notable SWIR absorption features of tissue constituents including water (near 1150, 1450, and 1900 nm), lipids (near 1040, 1200, 1400, and 1700 nm), and collagen (near 1200 and 1500 nm) that are much more prominent than corresponding features observed in the visible and near-infrared (VIS-NIR, defined here as similar to 400 to 1000 nm). Furthermore, the wavelength dependence of the scattering coefficient has been observed to follow a power-law decay from the VIS-NIR to the SWIR region. Thus, the magnitude of tissue scattering is lower at SWIR wavelengths than that observed at VIS or NIR wavelengths, potentially enabling increased penetration depth of incident light at SWIR wavelengths that are not highly absorbed by the aforementioned chromophores. These aspects of SWIR suggest that the tissue spectroscopy and imaging in this range of wavelengths have the potential to provide enhanced sensitivity (relative to VIS-NIR measurements) to chromophores such as water and lipids, thereby helping to characterize changes in the concentrations of these chromophores due to conditions such as atherosclerotic plaque, breast cancer, and burns. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)
The objective is derived from the need for a reliable absorption spectrum of lipids for component analysis of in vivo tissue spectra. NIR in vivo spectroscopy enables to derive the concentration of the key tissue constituents absorbing in the 600-1100 nm range, that is oxy- and deoxy- hemoglobin, water and lipids. Yet, although the first three constituents are already well characterized in literature, quite few data are available on mammalian lipids. In the present proceeding we report the absorption spectrum of a clear purified oil obtained from pig lard. Absorption coefficients were measured with time resolved and spatially resolved diffuse reflectance spectroscopy techniques. At temperatures of 37 °C and higher it is a clear transparent liquid thus suitable for collimated transmission measurements. In total three independent measurement techniques were employed the determine the absorption coefficients of mammalian lipids. The absorption spectra obtained from NIR spectroscopic techniques are supposed to be a linear combination of the absorption spectra of the chromophores present in the tissue. Decomposition of the measured absorption spectra into its components can be used to quantify absolute tissue chromophore concentrations. Furthermore, tissue oxygenation and total haemoglobin content can be calculated from these quantities. It is therefore essential to have detailed knowledge of the intrinsic absorption spectra of these 4 components. Oxy, de-oxy hemoglobin spectra and water are well-quantified en commonly applied. A basic tissue fat spectrum however has not been determined so far. The fat spectra used for spectral decomposition vary among the different research groups. These spectra all differ from each other with respect to their spectral shape as well as the magnitude of the main absorption peaks and may contain chlorophylls, making absolute comparison and interpretation of results and techniques impossible. The reason for the absence of a basic fat spectrum in the literature is that saturated mammalian fat is not available as a pure clear liquid. In the present paper we report the absorption spectrum of a clear oil obtained from mammalian pig lard. At room temperature this oil is a solid grease that displays strong scattering properties. Absorption and scattering properties of this solid grease were measured using time resolved and spatially resolved diffuse reflectance spectroscopy (TRS and DRS). At temperatures of 37°C and higher it is a clear liquid with only minimal scattering properties. Hence, an independent measurement of the absorption spectrum can be made using collimated transmission measurements.
Obtaining absolute chromophore concentrations from photoacoustic images obtained at multiple wavelengths is a nontrivial aspect of photoacoustic imaging but is essential for accurate functional and molecular imaging. This topic, known as quantitative photoacoustic imaging, is reviewed here. The inverse problems involved are described, their nature (nonlinear and ill-posed) is discussed, proposed solution techniques and their limitations are explained, and the remaining unsolved challenges are introduced.
In this paper we present the absorption coefficient mu(a) and the isotropic scattering coefficient mu(s)(') for 22 human skin samples measured using a double integrating sphere apparatus in the wavelength range of 1000-2200 nm. These in vitro results show that values for mua) follow 70% of the absorption coefficient of water and values for mu(s)(') range from 3 to 16 cm(-1). From the measured optical properties, it was found that a 2% Intralipid solution provides a suitable skin tissue phantom.
Linear spectroscopic inversions, in which photoacoustic amplitudes are assumed to be directly proportional to absorption coefficients, are widely used in photoacoustic imaging to estimate blood oxygen saturation because of their simplicity. Unfortunately, they do not account for the spatially varying wavelength-dependence of the light fluence within the tissue, which introduces "spectral coloring," a potentially significant source of error. However, accurately correcting for spectral coloring is challenging, so we investigated whether there are conditions, e.g., sets of wavelengths, where it is possible to ignore the spectral coloring and still obtain accurate oxygenation measurements using linear inversions. Accurate estimates of oxygenation can be obtained when the wavelengths are chosen to (i) minimize spectral coloring, (ii) avoid ill-conditioning, and (iii) maintain a sufficiently high signal-to-noise ratio (SNR) for the estimates to be meaningful. It is not obvious which wavelengths will satisfy these conditions, and they are very likely to vary for different imaging scenarios, making it difficult to find general rules. Through the use of numerical simulations, we isolated the effect of spectral coloring from sources of experimental error. It was shown that using wavelengths between 500 nm and 1000 nm yields inaccurate estimates of oxygenation and that careful selection of wavelengths in the 620- to 920-nm range can yield more accurate oxygenation values. However, this is only achievable with a good prior estimate of the true oxygenation. Even in this idealized case, it was shown that considerable care must be exercised over the choice of wavelengths when using linear spectroscopic inversions to obtain accurate estimates of blood oxygenation. This suggests that for a particular imaging scenario, obtaining accurate and reliable oxygenation estimates using linear spectroscopic inversions requires careful modeling or experimental studies of that scenario, taking account of the instrumentation, tissue anatomy, likely sO
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range, and image formation process.
Photoacoustic imaging using a focused, scanning detector in combination with a pulsed light source is a common technique to visualize light-absorbing structures in biological tissue. In the acoustic resolution mode, where the imaging resolution is given by the properties of the transducer, there are various challenges related to the choice of sensors and the optimization of the illumination. These are addressed by linking a Monte Carlo simulation of energy deposition to a time-domain model of acoustic propagation and detection. In this model, the spatial and electrical impulse responses of the focused transducer are combined with a model of acoustic attenuation in a single response matrix, which is used to calculate detector signals from a volumetric distribution of absorbed energy density. Using the radial symmetry of the detector, the calculation yields a single signal in less than a second on a standard personal computer. Various simulation results are shown, comparing different illumination geometries and demonstrating spectral imaging. Finally, simulation results and experimental images of an optically characterized phantom are compared, validating the accuracy of the model. The proposed method will facilitate the design of photoacoustic imaging devices and will be used as an accurate forward model for iterative reconstruction techniques.
Pathology and autopsy studies have demonstrated that sudden disruption of vulnerable atherosclerotic plaque is responsible for most acute coronary syndromes. These plaques are characterized by a lipid-rich core with abundant inflammatory cells and a thin fibrous cap. Thermal strain imaging (TSI) using intravascular ultrasound (IVUS) has been proposed for high-risk arterial plaque detection, in which image contrast results from the temperature dependence of sound speed. It has the potential to distinguish a lipid-laden lesion from the arterial vascular wall due to its strong contrast between water-bearing and lipid-bearing tissue. Initial simulations indicate plaque identification is possible for a 1 degrees C temperature rise. A phantom experiment using an IVUS imaging array further supports the concept, and results agree reasonably well with prediction.
Lipids and Alzheimer's Disease
- Yc Kao
- Y K Ho
- Tu
- K J Jou
- Tsai