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Attenuation spectra measured using time frequency analysis from phantoms imaged within 1mm path length cuvette. (a) Attenuation spectra of phantoms composed of distilled water and varying concentrations of cholesterol. (b) Attenuation of phantoms composed of distilled water and various concentrations of calcium. (c) Attenuation of phantoms composed of distilled water, collagen, and various concentrations of cholesterol. (d-f) Preprocessing of attenuation spectra using SVN and a Savasky Golay filter corresponding to attenuation spectra in a-c. Preprocessing reduced intensity bias and high frequency oscillations to highlight spectral shape. The mean is plotted as a solid line with the shaded area representing the standard error.
Source publication
Optical frequency domain imaging (OFDI) can identify key components related to plaque vulnerability but can suffer from artifacts that could prevent accurate identification of lipid rich regions. In this paper, we present a model of depth resolved spectral analysis of OFDI data for improved detection of lipid. A quadratic Discriminant analysis mode...
Citations
... To make the artificial lipid-rich plaque, fresh bovine cardiac muscle was trimmed into a 5 × 5cm 2 sample with a surgical blade. Mayonnaise (Kraft) as a rich source of lipid (> 80%) was injected into this sample with an insulin needle with a gauge of 30 G at a depth about 70-500 μm beneath the surface, to mimic the cap thickness of typical coronary arterial plaques 42,45 . The aorta specimen was obtained through the National disease research interchange (NDRI) from an 88-year-old female who died of cardiac disease. ...
Optical coherence tomography (OCT) is a medical imaging method that generates micron-resolution 3D volumetric images of tissues in-vivo. Photothermal (PT)-OCT is a functional extension of OCT with the potential to provide depth-resolved molecular information complementary to the OCT structural images. PT-OCT typically requires long acquisition times to measure small fluctuations in the OCT phase signal. Here, we use machine learning with a neural network to infer the amplitude of the photothermal phase modulation from a short signal trace, trained in a supervised fashion with the ground truth signal obtained by conventional reconstruction of the PT-OCT signal from a longer acquisition trace. Results from phantom and tissue studies show that the developed network improves signal to noise ratio (SNR) and contrast, enabling PT-OCT imaging with short acquisition times and without any hardware modification to the PT-OCT system. The developed network removes one of the key barriers in translation of PT-OCT (i.e., long acquisition time) to the clinic.
... Apart from the telecommunication applications, the short-wavelength part (1650-1800 nm) is also interesting in terms of bio-photonics or material processing because of existing prominent absorption peaks of water [14], cholesterol [15], or hydrocarbon-containing materials [16]. The long-wavelength tail (1800-2050 nm) is significant for applications in free-space optical communication [17], LIDAR-based gas sensing [18], pumping of solid-state lasers, and generation of supercontinuum [19], label-free biological imaging using nonlinear microscopy [20], or for defense applications [21]. ...
We present the development of a pair of silica-based thulium-doped fiber amplifiers working together in a broad spectral range from 1.65 µm to 2.02 µm. For the one optimized for shorter wavelengths, we designed and prepared optical fiber with a depressed cladding. We show the performance of the amplifiers achieving small-signal gain of at least 10 dB over 350 nm range from 1670 nm to 2020 nm, maximum gain of 40.7 dB with a noise figure as low as 6.45 dB and an optical signal-to-noise ratio of up to 50 dB. To the best of our knowledge, it is the first time that thulium fiber amplifiers of straightforward design without using redundant spectral filters operating efficiently in such a wide spectral region are demonstrated.
... The spectral range 1625-1800 nm is of interest for applications in medicine, where a suitable absorption line of lipids at around 1720 nm exists in a region of low absorption and scattering of water [1][2][3][4][5], and material processing, where strong absorption of plastic materials allows for efficient polymer welding [6]. Interesting opportunities have also recently arisen for extending the bandwidth of optical telecommunications beyond the conventional L-band (1565-1625 nm) [7], mainly thanks to the advancement of hollow-core fiber technology [8,9], which allows for low-loss transmission at wavelengths, where traditional silica fibers experience higher losses due to material absorption and bend-induced losses. ...
We present a thulium-doped silica fiber, featuring a depressed cladding, for applications at wavelengths below 1800 nm. The depressed cladding is used as a distributed filter suppressing amplified spontaneous emission at longer wavelengths, which helps promote emission at shorter wavelengths. We describe the fiber design process that was carried out by using a combination of numerical methods. The fiber was prepared in-house by a combination of the standard modified chemical vapor deposition method and nanoparticle doping. We demonstrate the effectiveness and tunability of ASE filtering, which is influenced by fiber bend radius and its variation.
... One of the first works validating the utilization of OCT in the prediction of atherosclerotic plaque vulnerability was accomplished by Fleming and co-workers [71]. They have prepared various phantom samples, differing in their composition, and have placed them into quartz cuvettes for imaging. ...
... Cholesterol, collagen, calcium, glycerol trioleate, and water were used to produce mixtures approximately similar to the chemical compositions of plaques. A combined spectral and attenuation model was applied to predict the presence of specific molecules accurately [71]. With this cuvette approach, authors could evaluate the contribution of each component in resulting signals. ...
... To do so, mayonnaise was injected into the tunica media of fresh, healthy swine aorta. Mayonnaise was chosen due to its favorable composition and scattering signature [71]. Results indicated that the proposed imaging model was able to detect the presence of lipids below varying depths of material tissue, which demonstrates the utility of the system [71]. ...
Atherosclerosis represents the etiologic source of several cardiovascular events, including myocardial infarction, cerebrovascular accidents, and peripheral artery disease, which remain the leading cause of mortality in the world. Numerous strategies are being delineated to revert the non-optimal projections of the World Health Organization, by both designing new diagnostic and therapeutic approaches or improving the interventional procedures performed by physicians. Deeply understanding the pathological process of atherosclerosis is, therefore, mandatory to accomplish improved results in these trials. Due to their availability, reproducibility, low expensiveness, and rapid production, biomimicking physical models are preferred over animal experimentation because they can overcome some limitations, mainly related to replicability and ethical issues. Their capability to represent any atherosclerotic stage and/or plaque type makes them valuable tools to investigate hemodynamical, pharmacodynamical, and biomechanical behaviors, as well as to optimize imaging systems and, thus, obtain meaningful prospects to improve the efficacy and effectiveness of treatment on a patient-specific basis. However, the broadness of possible applications in which these biomodels can be used is associated with a wide range of tissue-mimicking materials that are selected depending on the final purpose of the model and, consequently, prioritizing some materials’ properties over others. This review aims to summarize the progress in fabricating biomimicking atherosclerotic models, mainly focusing on using materials according to the intended application.
... Beyond cap thickness, lipid-rich necrotic cores serve as significant indicators of high-risk plaques [97]. A study employed a discriminant analysis ML model on spectral and attenuation data, based on acquired OCT spectra to quantify key chemicals, such as lipid, collagen, and calcium, in phantoms and swine ex vivo tissue [98]. This advancement has significant implications for personalized medicine, as it enables precise depth localization of lipids and necrotic cores in coronary plaques, improving the interpretation of IV-OCT data and facilitating tailored treatment approaches. ...
Personalized medicine transforms healthcare by adapting interventions to individuals’ unique genetic, molecular, and clinical profiles. To maximize diagnostic and/or therapeutic efficacy, personalized medicine requires advanced imaging devices and sensors for accurate assessment and monitoring of individual patient conditions or responses to therapeutics. In the field of biomedical optics, short-wave infrared (SWIR) techniques offer an array of capabilities that hold promise to significantly enhance diagnostics, imaging, and therapeutic interventions. SWIR techniques provide in vivo information, which was previously inaccessible, by making use of its capacity to penetrate biological tissues with reduced attenuation and enable researchers and clinicians to delve deeper into anatomical structures, physiological processes, and molecular interactions. Combining SWIR techniques with machine learning (ML), which is a powerful tool for analyzing information, holds the potential to provide unprecedented accuracy for disease detection, precision in treatment guidance, and correlations of complex biological features, opening the way for the data-driven personalized medicine field. Despite numerous biomedical demonstrations that utilize cutting-edge SWIR techniques, the clinical potential of this approach has remained significantly underexplored. This paper demonstrates how the synergy between SWIR imaging and ML is reshaping biomedical research and clinical applications. As the paper showcases the growing significance of SWIR imaging techniques that are empowered by ML, it calls for continued collaboration between researchers, engineers, and clinicians to boost the translation of this technology into clinics, ultimately bridging the gap between cutting-edge technology and its potential for personalized medicine.
... 16,22 Recent investigations have focused on the postprocessing-based SOCT for the characterization of lipid-rich plaque in tissues and phantoms using the absorption features of lipids. 23,24 However, the data were acquired using OCT systems operated at a center wavelength of 1310 nm, where the lipid absorption coefficient is relatively small and lacks clearly discerning structures. This demands much reference data and training or a representative metric to visualize the property of the spectrum. ...
... Since the scattering and absorption coefficients of a material are wavelength-dependent parameters, the measurement of spectral-dependent OCT intensity profiles ½Iðλ; zÞ can offer material classification based on either scattering or absorption features. 23,31,32 In this study, we exploited the distinct absorption features of water and lipid containing samples for the classification of materials. ...
Significance:
Spectroscopic analysis of optical coherence tomography (OCT) data can yield added information about the sample's chemical composition, along with high-resolution images. Typical commercial OCT systems operate at wavelengths that may not be optimal for identifying lipid-containing samples based on absorption features.
Aim:
The main aim of this study was to develop a 1200 nm spectroscopic OCT (SOCT) for the classification of lipid-based and water-based samples by extracting the lipid absorption peak at 1210 nm from the OCT data.
Approach:
We developed a 1200 nm OCT system and implemented a signal processing algorithm that simultaneously retrieves spectroscopic and structural information from the sample. In this study, we validated the performance of our OCT system by imaging weakly scattering phantoms with and without lipid absorption features. An orthogonal projections to latent structures-discriminant analysis (OPLS-DA) model was developed and applied to classify weakly scattering samples based on their absorption features.
Results:
The OCT system achieved an axial resolution of 7.2 μm and a sensitivity of 95 dB. The calibrated OPLS-DA model on weakly scattering samples with lipid and water-based absorption features correctly classified 19/20 validation samples.
Conclusions:
The 1200 nm SOCT system can discriminate the lipid-containing weakly scattering samples from water-based weakly scattering samples with good predictive ability.
... Validation of proposed model was carried out using experimental PT-OCT results of mayonnaise (mayo)-ultrasound gel mixtures at various component ratios. Mayo was chosen to mimic the lipid-rich necrotic-core material present in atheromatous coronary atherosclerotic lesions [25,32]. Mayo, indeed, is primarily composed of lipids, which provide an absorption signature that can be targeted with PT-OCT, and its lipid composition is similar to that of the atherosclerotic plaques [25,32]. ...
... Mayo was chosen to mimic the lipid-rich necrotic-core material present in atheromatous coronary atherosclerotic lesions [25,32]. Mayo, indeed, is primarily composed of lipids, which provide an absorption signature that can be targeted with PT-OCT, and its lipid composition is similar to that of the atherosclerotic plaques [25,32]. In this model, a solution for the bio-heat equation (Eq. 3) was presented as a function of concentration-dependent material properties as follow [30]: ...
Photo-thermal optical coherence tomography (PT-OCT) is a functional extension of conventional OCT with the ability to generate maps of light absorption co-registered with the micron resolution structural tomograms of OCT. Potentially, signal analysis of such light absorption maps can be used to obtain refined depth-resolved insight into the chemical composition of tissue. Such analysis, however, is complex because the underlying physics of PT-OCT is multifactorial. That is, aside from tissue chemical composition, optical, thermal, and mechanical properties of tissue affect PT-OCT signals; certain system/instrumentation parameters also influence PT-OCT signals. As such, obtaining refined depth-resolved insight into tissue chemical composition requires in-depth understanding of the interplay between sample and system parameters and the induced signals. Moreover, translation of PT-OCT to clinics requires introduction of new experimentation strategies for enhancing the detection specificity and imaging speed of PT-OCT. In this review paper, we present and discuss our recent works aimed at addressing the above theoretical and technological challenges.
... This is because of the strong optical absorption of lipid at 1210 and 1720 nm wavelengths agreeing with that of the reference optical absorption spectrum [41]. In contrast, displacement can be seen over the 1400-1525 nm range on the artery wall, which is due to a combination of the optical absorption of collagen, elastin and water at this wavelength range [42,43]. However, in a recent paper by Salimi et al. [44], they report that water, though highly absorbing at 1210 nm, shows little change in optical path length due to its large heat capacity which acts against temperature rise and thermal expansion. ...
... However, in a recent paper by Salimi et al. [44], they report that water, though highly absorbing at 1210 nm, shows little change in optical path length due to its large heat capacity which acts against temperature rise and thermal expansion. This translates to only a small contribution to the measured displacement in the 1450 nm region corresponding to the large absorption peak of water [43]. On one hand, TE-OCT reveals unique spectral features of specific tissue types, while on the other hand, tissue type could possibly be identified in the TE-OCT images by choosing a proper excitation wavelength. ...
Optical imaging techniques that provide free space, label free imaging are powerful tools in obtaining structural and biochemical information in biological samples. To date, most of the optical imaging technologies create images with a specific contrast and require multimodality integration to add additional contrast. In this study, we demonstrate spectroscopic Thermo-elastic Optical Coherence Tomography (TE-OCT) as a potential tool in tissue identification. TE-OCT creates images based on two different forms of contrast: optical reflectance and thermo-elastic deformation. TE-OCT uses short laser pulses to induce thermo-elastic tissue deformation and measures the resulting surface displacement using phase-sensitive OCT. In this work we characterized the relation between thermo-elastic displacement and optical absorption, excitation, fluence and illumination area. The experimental results were validated with a 2-dimensional analytical model. Using spectroscopic TE-OCT, the thermo-elastic spectra of elastic phantoms and tissue components in coronary arteries were extracted. Specific tissue components, particularly lipid, an important biomarker for identifying atherosclerotic lesions, can be identified in the TE-OCT spectral response. As a label-free, free-space, dual-contrast, all-optical imaging technique, spectroscopic TE-OCT holds promise for biomedical research and clinical pathology diagnosis.
... A potentially unifying hypothesis is that deposit formation involves dysregulation of lipid transfer among cones and supporting RPE and Müller glia, as follows. Among other factors, reflectivity involves light scattering from lipid-water interfaces in a size-dependent manner (organelles, lipid droplets, lipoproteins, and emulsions [74][75][76][77] ). The homogeneous reflectivity Features were evaluated at different time points (ie, before AVL formation, at maximum lesion volume, and during regression). ...
Purpose
: To evaluate hypotheses about the role of acquired vitelliform lesion (AVL) in age-related macular degeneration (AMD) pathophysiology.
Design
: Laboratory histology study; retrospective, observational case series
Methods
: Two donor eyes in a research archive with AVL and AMD were analyzed with light and electron microscopy for AVL content at locations matched to ex vivo B-scans. A retrospective, observational clinical cohort study of 42 eyes of 30 patients at two referral clinics) determined the frequency of optical coherence tomography (OCT) features stratified by AVL fate.
Results
: Histologic and clinical cases showed subretinal drusenoid deposit (SDD) and drusen. Ultrastructural AVL components in two donor eyes included retinal pigment epithelium (RPE) organelles (3–22% of volume), outer segments (2–10%), lipid droplets (0.2–12%), and a flocculent material (57–59%). Of 48 AVL (mean follow-up 46 ± 39 months), 50% collapsed to complete RPE and outer retinal atrophy (cRORA), 38% were stable, 10% resorbed, and 2% developed neovascularization. The ETDRS grid central subfield contained 77% of AVL. Hyperreflective foci, ellipsoid zone disruption, and hyperreflective thickening of the RPE-basal lamina-Bruch's membrane band were common at maximum AVL expansion. Collapsing and non-collapsing AVL had different growth rates (rapid vs slow, respectively).
Conclusions
: AVL deposits contain unexpectedly low levels of RPE organelles and outer segments. Subfoveal predilection, reflectivity on OCT, hyperautofluorescence, yellow color, and growth-regression phases suggest dysregulation of lipid transfer pathways specific to cone photoreceptors and supporting cells in formation of AVL deposit, analogous to drusen and SDD. Prediction of AVL outcomes via growth rates should be confirmed in larger clinical studies.
... The concentration, spatial distribution, and molecular composition of lipids are essential biomarkers for investigating atherosclerosis, coronary heart disease, obesity, and diabetes, among other diseases, as they define the onset, severity, and progression of the disease course. Technologies typically employed for studying lipids such as histopathology [1], mass spectroscopy [2][3][4], optical frequency domain imaging [5][6][7], and Raman [8,9] or near-and mid-infrared microscopy [10][11][12][13] require biopsy extraction, harmful labelling strategies, are based on indirect lipid detection, or are characterized by poor spatial resolution and penetration depths and, thus, prevent application in cells, animals, and humans in vivo. As a new emerging modality, photoacoustics has a unique capability for label-free and dynamic monitoring lipids at high resolution and penetration depth in biological tissue by accessing the intrinsic molecular absorption contrast [14][15][16][17][18][19][20]. ...
Near-infrared photoacoustics receives increasing interest as an intravital modality to sense key biomolecules crucial. One of the most central types of biomolecules of interest are lipids as they constitute essential bio-hallmarks of cardiovascular and metabolic diseases and their in-vivo detection holds insightful information about disease progression and treatment monitoring. However, the full potential of near-infrared photoacoustic for high-resolution and high-sensitivity biomedical studies of lipids has so far not been exploited due a lack of appropriate excitation sources delivering short-pulses at high-repetition-rate, high-pulse-energy, and wavelength around 1200 nm. Here, we demonstrate a custom-built SRS fiber amplifier that provides optical excitations at 1192.7 nm, repetition rates of 200 kHz, pulse durations below 2 ns, and pulse energies beyond 5 μJ. We capitalize on the performance of our excitation source and show near-infrared photoacoustics resolving intrinsic lipid contrast in biomedically relevant specimens ranging from single cells to lipid-rich tissue with subcellular resolution.
