Atopic dermatitis (AD) and psoriasis are the two most prevalent skin disorders, often assessed through subjective questionnaires or visual evaluations conducted by clinicians, which can be subject to interpersonal variations. This study aims to explore the distinctions between these skin conditions and healthy skin using a portable confocal Raman spectroscopy (CRS) system for objective assessment. Spectral measurements at 671 nm and 785 nm on 9 AD, 6 psoriasis, and 11 healthy subjects reveal lower water content in AD compared to psoriasis and healthy skin. Ceramide subclasses show disease-specific trends, distinguishing AD, and psoriasis. Cholesterol levels further differentiate these conditions, with lower concentrations in lesional AD and significantly higher concentrations in lesional psoriasis compared to healthy skin. These differences contribute to the objective differentiation of skin conditions aiding in thorough assessment and treatment monitoring. Furthermore, it offers valuable insights for developing targeted disease-specific topical treatments.
Vulvar skin, distinct from other areas, undergoes changes due to aging, causing symptoms like dryness and itchiness. While much research focuses on facial or forearm skin, vulva skin properties are underexplored. This study uses an in-house developed fiber-based Diffuse Reflectance Spectroscopy (DRS) system to assess vulva skin changes in 100 women. This objective evaluation includes analyzing tissue chromophores—water, lipid, oxyhemoglobin, and deoxyhemoglobin providing insights into moisture content, lipid levels, oxygen saturation, and blood fraction. DRS, compared to invasive methods, achieved a 65% accuracy in estimating estrogen levels, suggesting its potential for objective diagnosis and monitoring of genitourinary skin conditions.
Non-melanoma skin cancers (NMSC) pose challenges with current clinical approaches. In this context, Multispectral Optoacoustic Tomography (MSOT) offers a promising non-invasive imaging solution. With high isotropic resolution and contrast-enhanced capabilities, MSOT provides a 3D tumor map by resolving melanin and haemoglobin signals. Our feature extraction and automated level-set image segmentation algorithm enables tumor profiling and precise boundary delineation of width, depth, and volume. Validated against histology, these metrics aid preoperative tumor mapping and surgical planning as it fosters a comprehensive understanding of tumor morphology and metabolic activities. Thus, clinicians can optimize NMSC management, revolutionizing diagnostics and treatment for improved patient outcomes.
We introduce a compact, non-contact multimodal imaging platform that integrates ultrasound (US) imaging, inclusive of photoacoustic (PA) detection, with optical coherence tomography (OCT). This integration is achieved through a novel virtual acoustic detector array (VADA) technique for all-optical US sensing, utilizing the temporal and spatial resolving capabilities of swept-source optical interferometry. The technique extracts US signals from the phase time evolution of a swept-source OCT's spectral sweep. It enables the virtual construction of the VADA along both lateral and depth directions on the imaging target for non-contact detection of acoustic waves from surrounding US sources. The platform's high-speed scanning (MHz OCT A-scan rate) and ultra-sensitive phase detection (nm displacement sensitivity) allow for the customization of the spatial density of the VADA and the collection of wideband acoustic signals, which are essential for the reconstruction of US images. In our pilot study, we successfully demonstrated the feasibility of this technique. We used a conventional US transducer as an acoustic source. The acoustic field distribution within the imaging target and the morphology and position of the piezoelectric layer were successfully reconstructed, which is based on US waveforms obtained from the VADA.
Auretek is the first of its kind portable Confocal Raman Spectroscopy (CRS) system equipped with fiber based handheld probe, that cascades dual-wavelength lasers. With its flexible probe, Auretek can acquire CRS data of skin from various parts of the human body with depth profiling. A clinical study was conducted to investigate the effects of ceramide-based moisturizer (CBM) on skin physiology and biochemistry. Quantitative skin component characterization in different epidermal layers was done with spectral unmixing analysis of the CRS data. Even though the analysis revealed a significant increase in ceramide content on the side of CBM application, the increase was in the layers within the stratum corneum.
Confocal Raman spectroscopy (CRS) technology has wide applications, especially in the biomedical field. CRS provides non-destructive, contrast-free and molecule-specific quantitative measurement of samples, including biological tissues. These advantages make it ideal for human skin characterization. We present a portable dual-wavelength CRS system with a handheld measurement probe which connected to the console by optical fibers. To achieve fast switching between the two wavelengths, a fast 2-to-1 fiber array multiplexing module was used. A large bandwidth could be covered at each measurement point in real time. We performed system characterization for this proposed CRS system and measured different samples.
Blood flow measurement in deep tissue is important because the circulatory system transports oxygen and nutrition to the tissue and removes carbon dioxide out from the tissue. Several non-invasive optical methods were developed for blood flow measurement in deep tissue, such as diffuse correlation spectroscopy (DCS) and diffuse speckle contrast analysis (DSCA). In this paper we will introduce a new speckle-based method for fast blood flow measurement in deep tissue: diffuse speckle pulsatile flowmetry (DSPF). By using a multi-mode fiber for speckle pattern detection, DSPF achieves high blood flow measurement rate of 300 Hz. It has one of the fastest measurement rates of blood flow among non-invasive modalities.
Inflammatory skin disorder, eczema, is usually assessed by subjective disease scoring systems such as SCORAD and EASI. These scoring systems are based on clinical observations and questionnaires and hence it is subjected to inter and intra-assessor variability. Here, for the first time, we used optoacoustic imaging to image the structural and morphological changes of the skin in a non-invasive manner. Through a clinical study, we computed specific metrics such as epidermis thickness, total blood volume, vessel diameter in the dermis, ratio of low and high frequency signals. We trained a linear kernel-based support vector machine model for eczema classification using these metrics. We could achieve an accuracy of 86.6% and high sensitivity and specificity of 96.2% and 82.1% respectively. We also formulated a novel Eczema Vascular and Structural Index (EVSI) to objectively assess the severity of eczema.
Significance: Noninvasive in vivo fast pulsatile blood flow measurement in deep tissue is important because the blood flow waveform is correlated with physiological parameters, such as blood pressure and elasticity of blood vessels. Compromised blood flow may cause diseases, such as stroke, foot ulcer, and myocardial ischemia. There is great clinical demand for a portable and cost-effective device for noninvasive pulsatile blood flow measurement.
Aim: A diffuse-optics-based method, diffuse speckle pulsatile flowmetry (DSPF), was developed for fast measurement (∼300 Hz) of deep tissue blood flow noninvasively. To validate its performance, both a phantom experiment and in vivo demonstration were conducted.
Approach: Over the past two decades, single-mode fibers have been used as detection fibers in most diffuse-optics-based deep tissue blood flow measurement modalities. We used a multimode (MM) detection fiber with a core size of 200 μm for diffused speckle pattern detection. A background intensity correction algorithm was implemented for speckle contrast calculation. The MM detection fiber helped to achieve a level of deep tissue blood flow measurement similar to that of conventional modalities, such as diffuse correlation spectroscopy and diffuse speckle contrast analysis, but it increases the measurement rate of blood flow to 300 Hz.
Results: The design and implementation of the DSPF system were introduced. The theory of the background intensity correction for the diffused speckle pattern detected by the MM fiber was explained. A flow phantom was built for validation of the performance of the DSPF system. An in vivo cuff-induced occlusion experiment was performed to demonstrate the capability of the proposed DSPF system.
Conclusions: An MM detection fiber can help to achieve fast (∼300 Hz) pulsatile blood flow measurement in the proposed DSPF method. The cost-effective device and the fiber-based flexible probe increase the usability of the DSPF system significantly.
We present a dual-wavelength fast mechanical scanning optical-resolution photoacoustic microscopy system (OR-PAM) in this paper. Conventional mechanical scanning OR-PAM system takes ~ 30 min for one frame of single wavelength imaging. The acquisition of two wavelengths will double the total imaging time. By using a fast-linear stage, a high signal-to-noise (SNR) optical and acoustic combiner and 2 lasers at different wavelengths, we achieved a B-scan rate of 12 Hz and reduced the acquisition time to ~1.5 min for dual-wavelength imaging. This system can be used in large field optical resolution imaging. Contrast-free vascular and functional imaging can be achieved using this system. Both ex vivo and in vivo imaging results are demonstrated.
Photoacoustic microscopy (PAM) is a fast-growing biomedical imaging technique that provides high-resolution in vivo imaging beyond the optical diffusion limit. Depending on the scalable lateral resolution and achievable penetration depth, PAM can be classified into optical resolution PAM (OR-PAM) and acoustic resolution PAM (AR-PAM). The use of a microelectromechanical systems (MEMS) scanner has improved OR-PAM imaging speed significantly and is highly beneficial in the development of miniaturized handheld devices. The shallow penetration depth of OR-PAM limits the use of such devices for a wide range of clinical applications. We report the use of a high-speed MEMS scanner for both OR-PAM and AR-PAM. A high-speed, wide-area scanning integrated OR-AR-PAM system combining MEMS scanner and raster mechanical movement was developed. A lateral resolution of 5 μm and penetration depth ∼0.9-mm in vivo was achieved using OR-PAM at 586 nm, whereas a lateral resolution of 84 μm and penetration depth of ∼2-mm in vivo was achieved using AR-PAM at 532 nm.
The hemodynamics and oxygen saturation status of vascular are very important biomarkers for disease, such as brain glioma tumor and ischemia-reperfusion ulcer. Therefore, a high spatial resolution imaging tool for vascular imaging is demanded. Conventional optical imaging modalities, including confocal microscopy and two-photon microscopy, require external contrast agent to image blood vessels and are not sensitive to oxygen saturation. The development of photoacoustic microscopy provides a contrast-free, high-spatial resolution and functional vascular imaging tool. It’s gaining more and more popularity in biomedical research. In this paper, we introduce a dual-wavelength opticalresolution photoacoustic microscopy (OR-PAM) system for functional imaging of vasculature. This system has demonstrated its application in brain glioma tumor imaging, as well as skin ischemia-reperfusion imaging.
A Microelectromechanical Systems (MEMS)-based rapid scanning photoacoustic microscopy (PAM) is available to help life science research in neuroscience, cell biology, and in vivo imaging. MicroPhotoAcoustics (MPA; Ronkonkoma, NY), the only manufacturer and vendor of Optical Resolution (OR)-PAM systems, has developed a commercial PAM system with switchable optical and acoustic resolution (OR- and AR-PAM). To achieve real-time imaging capability without sacrificing high signal-to-noise ratios (SNRs), a 2-axis water-proofing MEMS scanner made of flexible polydimethylsiloxane (PDMS) was demonstrated by collaboration with Pohang University of Science and Technology (South Korea) that promises to dramatically increase the system’s imaging speed. This flexible scanner results in a wide scanning range and a fast imaging speed (5 B-scan images per second). Equipped with different excitation sources, in vivo PA images of microvasculatures in a mouse ear was obtained. The lateral and axial resolutions of the OR-PAM system are 4.38 μm. It is expected that this MEMS-based fast OR-PAM system can be significantly useful in both preclinical and clinical applications. With the continuation of new technological advancements and discoveries, MPA plans to further advance PAM to achieve faster imaging speed, higher spatial resolution at deeper tissue layer, and address a broader range of biomedical applications.
A focused-scanning photoacoustic microscopy (PAM) is available to help advancing life science research in neuroscience, cell biology, and in vivo imaging. At this early stage, the only one manufacturer of PAM systems, MicroPhotoAcoustics (MPA; Ronkonkoma, NY), MPA has developed a commercial PAM system with switchable optical and acoustic resolution (OR- and AR-PAM), using multiple patents licensed from the lab of Lihong Wang, who pioneered photoacoustics. The system includes different excitation sources. Two kilohertz-tunable, Q-switched, Diode Pumped Solid-State (DPSS) lasers offering a up to 30kHz pulse repetition rate and 9 ns pulse duration with 532 and 559 nm to achieve functional photoacoustic tomography for sO2 (oxygen saturation of hemoglobin) imaging in OR-PAM. A Ti:sapphire laser from 700 to 900 nm to achieve deep-tissue imaging. OR-PAM provides up to 1 mm penetration depth and 5 μm lateral resolution. while AR-PAM offers up to 3 mm imaging depth and 45 μm lateral resolution. The scanning step sizes for OR- and AR-PAM are 0.625 and 6.25 μm, respectively. Researchers have used the system for a range of applications, including preclinical neural imaging; imaging of cell nuclei in intestine, ear, and leg; and preclinical human imaging of finger cuticle. With the continuation of new technological advancements and discoveries, MPA plans to further advance PAM to achieve faster imaging speed, higher spatial resolution at deeper tissue layer, and address a broader range of biomedical applications.
We present a water-proof Microelectromechanical systems (MEMS) based scanning optical resolution Photoacoustic Microscopy (OR-PAM) system and its application in glioma tumor mouse model study. The presented OR-PAM system has high optical resolution (~3 μm) and high scanning speed (up to 50 kHz A-scan rate), which is ideal for cerebral vascular imaging. In this study, the mice with glioma tumor are treated with vascular disrupting agent (VDA). OR-PAM system is utilized to image the cerebral with the whole skull intact before and after the injection of VDA. By image registration, the response of every single blood vessel can be traced. This will provide us deeper understanding of the drug effect.
Diffuse correlation spectroscopy (DCS) is an emerging noninvasive technique that probes the deep tissue blood flow, by using the time-averaged intensity autocorrelation function of the fluctuating diffuse reflectance signal. We present a fast Fourier transform (FFT)-based software autocorrelator that utilizes the graphical programming language LabVIEW (National Instruments) to complete data acquisition, recording, and processing tasks. The validation and evaluation experiments were conducted on an in-house flow phantom, human forearm, and photodynamic therapy (PDT) on mouse tumors under the acquisition rate of ∼400 kHz . The software autocorrelator in general has certain advantages, such as flexibility in raw photon count data preprocessing and low cost. In addition to that, our FFT-based software autocorrelator offers smoother starting and ending plateaus when compared to a hardware correlator, which could directly benefit the fitting results without too much sacrifice in speed. We show that the blood flow index (BFI) obtained by using a software autocorrelator exhibits better linear behavior in a phantom control experiment when compared to a hardware one. The results indicate that an FFT-based software autocorrelator can be an alternative solution to the conventional hardware ones in DCS systems with considerable benefits.
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