0000000000014338
AUTHOR
Janis Spigulis
showing 91 related works from this author
Multispectral and autofluorescence RGB imaging for skin cancer diagnostics
2019
This paper presents the results of statistical clinical data, combining two diagnostic methods. A combination of two skin imaging methods – diffuse reflectance and autofluorescence – has been applied for skin cancer diagnostics. Autofluorescence (AF) and multispectral diffuse reflectance images were acquired by custom made prototype with 405 nm, 526 nm, 663 nm and 964 nm LEDs and RGB CMOS camera. Parameter p’ was calculated from diffuse reflectance images under green, red and infrared illumination, AF intensity (I’) was calculated from AF images exited at 405nm wavelength. Obtained results show that criterion p` > 1 gives possibility to discriminate melanomas and different kind of keratosis…
Compact dielectric reflective elements II Multichannel filter of closely spaced spectral bands
1994
The optical design of an interference wedge filter providing the simultaneous separation of a number of closely spaced spectral bands is studied. Multiple reflections of the incident collimated beam within the wedge are initiated, each of them characterized by a different angle of incidence and consequently by specific spectral parameters of the transmitted band. Model calculations based on the measured angular dependences of filter transmission parameters have been performed. The design is proposed for applications in optical communications (wavelength division demultiplexing), analytical spectroscopy (minipolychromators), color analysis, and similar areas.
Lasers for in-vivo skin diagnostics: some recent developments
2019
The recent advancements of three laser-based diagnostic technologies developed at the Riga group are briefly reviewed: (i) RGB imaging of cw-laser excited skin autofluorescence intensity and photobleaching rate distributions, (ii) ps-laser excited skin autofluorescence and diffuse reflectance kinetics analysis, (iii) snapshot RGB skin chromophore mapping under triple-laser illumination. These techniques have passed preliminary laboratory and clinical tests which have demonstrated a promising potential for further implementation in portable devices for routine clinical applications. Operation principles, set-up schemes and some clinical results obtained by the above-mentioned techniques are …
Application of colour magnification technique for revealing skin microcirculation changes under regional anaesthetic input
2013
In this work the colour magnification technique was applied for monitoring of palm skin microcirculation changes under peripheral (Plexus Brachialis with axiliary access) Regional Anaesthesia (RA). During the RA procedure 20 minute video of patient’s forearm was taken at steady light conditions. Video content was processed offline by custom developed Matlab software with build-in colour magnification algorithm that performs temporal filtering of video sequence near-heartbeat frequency, spatial decomposition of video and amplification of pulsatile signal in every pixel of skin image. Using this method, we are able to visualize the subcutaneous microcirculation changes in high spatial resolut…
Multispectral, Fluorescent and Photoplethysmographic Imaging for Remote Skin Assessment
2017
Optical tissue imaging has several advantages over the routine clinical imaging methods, including non-invasiveness (does not change the structure of tissues), remote operation (avoids infection) and ability to quantify the tissue condition by means of specific image parameters. Dermatologists and other skin experts need compact (preferably pocket-size), self-sustained and easy-to-use imaging devices. The operational principles and designs of ten portable in-vivo skin imaging prototypes developed at the Biophotonics Laboratory of Institute of Atomic Physics and Spectroscopy, University of Latvia during the recent five years are presented in this paper. Four groups of imaging devices are con…
Water detection in skin by dual-band photodiodes
2013
Purpose of this study was to develop a simple model for possibilities to detect water in skin by diffuse reflectance spectra. The model is based on comparison of diffuse reflectance spectra when illuminating water sample with LEDs of different wavelengths (1200 nm, and 1450 nm). The illumination LEDs were chosen due to water absorption differences in near-infrared spectral range. For detection, dual-band photodiode DSD2 by Thorlabs was used. Due to differences of water absorption at different wavelengths in the near-infrared spectral region, this correlation could be used for mapping of water content in skin or, in other words, determine relative moisture level in skin. Simple experimental …
Melanoma-nevus differentiation by multispectral imaging
2011
A clinical trial on multi-spectral imaging of malignant and non-malignant skin pathologies comprising 22 melanomas and 59 pigmented nevi was performed in Latvian Oncology Center. Analysis of data obtained in the spectral range 450–950 nm using multispectral camera have led to a novel image processing algorithm capable to distinguish melanoma from pigmented nevi and different areas of activity of melanoma. The proposed methodology and potential clinical applications are discussed.
A multispectral imaging approach for diagnostics of skin pathologies
2013
Noninvasive multispectral imaging method was applied for different skin pathology such as nevus, basal cell carcinoma, and melanoma diagnostics. Developed melanoma diagnostic parameter, using three spectral bands (540 nm, 650 nm and 950 nm), was calculated for nevus, melanoma and basal cell carcinoma. Simple multispectral diagnostic device was established and applied for skin assessment. Development and application of multispectral diagnostics method described further in this article.
Optical Studies of the Capillary Refill Kinetics in Fingertips
2009
A new methodology for temporal analysis of the capillary refill processes by means of photoplethysmography (PPG) contact probe operating in the blue region of spectrum has been developed. A corresponding prototype device for finger measurements has been created and clinically tested. Results demonstrated that both AC and DC components of the blue PPG bio-signals are sensitive to the capillary occlusion and refill. Real-time measurements of the skin capillary refill kinetics by this technology can be used for noninvasive diagnostics of the peripheral perfusion disorders.
Evaluation of Skin Vascular Malformations’ Laser Treatment by RGB and Multi-spectral Imaging
2012
RGB imaging system for mapping and monitoring of hemoglobin changes in skin has been tested for evaluation of vascular malformations’ laser treatment. The multi-spectral imaging system was used as the reference.
<title>High-frequency electrodeless light sources for application</title>
2001
The high-frequency electrodes light sources (HFELS) are widely used as bright radiators of narrow and intensive spectral lines covering spectral region from VUV to IR. In this work we shall give a short overview of our experience in preparation of HFELS, containing He, H, Rb, Hg, Zn, Pb, As, Sb, Bi, Tl, Hg-Cd, Hg-Zn, Hg-Cd-Zn, Se-Te for different applications. Special attention would be paid for HFELS use in Zeeman mercury analyzer, in Atomic absorption analyzer and Angle and glass refractive index measurement system.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
A snapshot multi-wavelengths imaging device for in-vivo skin diagnostics
2020
A portable proof-of-concept prototype device for single snapshot capturing of four spectral line images has been designed, assembled and laboratory-tested. It comprises optical unit that ensures even illumination of the skin target area simultaneously at four laser wavelengths - 450 nm, 523 nm, 638 nm and 850 nm, double-camera image recording system, micro-computer managed operation system and a touch-screen display for image control and displaying the concentration distribution maps of four skin chromophores - melanin, oxy-hemoglobin, deoxy-hemoglobin and bilirubin. Besides, the device captures skin auto fluorescence image at 405 nm laser excitation to separate seborrheic keratosis from ot…
Application of principal component analysis to multispectral imaging data for evaluation of pigmented skin lesions
2013
Non-invasive and fast primary diagnostics of pigmented skin lesions is required due to frequent incidence of skin cancer – melanoma. Diagnostic potential of principal component analysis (PCA) for distant skin melanoma recognition is discussed. Processing of the measured clinical multi-spectral images (31 melanomas and 94 nonmalignant pigmented lesions) in the wavelength range of 450-950 nm by means of PCA resulted in 87 % sensitivity and 78 % specificity for separation between malignant melanomas and pigmented nevi.
Monitoring soft tissue coagulation by optical spectroscopy
2017
Laser tissue welding (LTW) or laser tissue soldering (LTS) is investigated since many years for treatment of incisions, wound closure and anastomosis of vessels [1, 2]. Depending on the process, a certain temperature in the range between 65 °C to 85 °C must be reached and held for a few seconds. Care has to be taken not to overheat the tissue, otherwise necrosis or tissue carbonization may occur and will impair wound healing. Usually the temperature is monitored during the process to control the laser power [3]. This requires either bulky equipment or expensive and fragile infrared fibers to feed the temperature signal to an infrared detector. Alternatively, changes in tissue morphology can…
Beer-Lambert law for optical tissue diagnostics: current state of the art and the main limitations.
2021
Abstract. Significance: Beer–Lambert law (BLL) is a widely used tool for contact and remote determination of absorber concentration in various media, including living tissues. Originally proposed in the 18th century as a simple exponential expression, it has survived numerous modifications and updates. The basic assumptions of this law may not be fulfilled in real measurement conditions. This can lead to mistaken or misinterpreted results. In particular, the effects to be additionally taken into account in the tissue measurements include anisotropy, scattering, fluorescence, chemical equilibria, interference, dichroism, spectral bandwidth disagreements, stray radiation, and instrumental eff…
LASCA and PPG imaging for non-contact assessment of skin blood supply
2013
Laser speckle contrast analysis (LASCA) offers a non-contact, full-field, and real-time mapping of capillary blood flow and can be considered as an alternative method to Laser Doppler perfusion imaging (LDPI). Photoplethysmography (PPG) is well known technique for assessment of skin blood pulsations that can be related to blood flow. In recent years several studies have been done on development of non-contact PPG imaging (PPGI). LASCA and PPGI techniques are simpler and cheaper compared with LDPI. LASCA technique has been implemented in several commercial instruments. However, these systems are still too expensive and bulky to be widely available. Several optical techniques have found new i…
Skin chromophore mapping by modified video-microscope
2013
Possibilities to map skin chromophores using a modified low-cost digital video-microscope is discussed. The device comprises CMOS digital imaging sensor, four-colour LED illumination system and image acquisition optics. The main goal is to obtain a set of spectral images of the skin area of interest for further conversion into maps of the main skin chromophores
Micro-circulation of skin blood: optical monitoring by advanced photoplethysmography techniques
2003
Blood micro-circulation in upper skin layers has been studied experimentally in real time by advanced two-channel photoplethysmography (PPG) techniques. The blood volume changes caused by micro-vessel expansion and dilution during the cardiac cycles have been detected by infrared optical contact sensors. A newly developed portable monitoring device comprising a lap-top computer was used for accumulation and processing of the bio-signals. Shapes of the PPG signals detected at different sites of the body were compared with these obtained by computer modeling.
Real-time analysis of skin capillary-refill processes using blue LED
2010
A method for analysis of skin capillary-refill processes in real time by means of reflection photoplethysmography (PPG) contact probe operating in the blue (438nm ± 30 nm) and infrared (938 nm ± 20 nm) regions of spectrum is proposed. The corresponding prototype hardware and software for measurements have been developed and tested in laboratory. Realtime measurements of finger capillary refill kinetics by this technology have been taken and analyzed. Results demonstrated that both AC and DC components of the blue PPG biosignal are sensitive to capillary occlusion and refill.
Time of flight for photon in human skin
2016
The time of flight for photons in human skin was measured using picosecond diode laser. Two different wavelength lasers were used - 405 nm and 510 nm. A difference for time of flight in normal skin and in nevus was observed as well as a difference for different wavelength laser irradiation was observed. For 405 nm laser irradiation the difference was 41 ps while comparison of time of flights skin and nevi using 510 nm irradiation showed a result of 32 ps. Results allow to conclude that the time photon travels in skin might depend on the characteristics of the medium and wavelength of the irradiation. This can be related to known data for light penetration depth in human skin for different w…
Optical fiber diffusive tip designs for medical laser-lightguide delivery systems
1994
Medical laser radiation delivery instruments with diffusive tips on the distal ends of plastic-clad silica optical fibers have been designed, tested, and manufactured. The instruments are optimized for endoscopic, therapeutic, dermatologic and surgical laser treatment. The diffusive tips provide radial, cylindrical and aside-conical spatial distributions of the output radiation. Optical schemes concerning each type of the tip and the corresponding spatial distribution functions of the output radiation are presented and analyzed. Designs of the lightguide instruments for surgical and dermatological procedures demanding local high-power laser irradiation are also discussed.
<title>Optical sensing for early cardiovascular diagnostics</title>
2000
A sensor device for noninvasive detection and analysis of the pulsating blood flow waveforms by means of the reflective single-period photoplethysmorgraphy (SPPPG) technique has been designed and clinically tested. The sensor is operated jointly with any standard PC, by connecting the sensor head to the AD-card and using a separate hard disc with the signal processing software; all circuits are fed by the PC power supply. After processing, normalized shape of the mean SPPPG signal and its parameters are calculated and displayed; the measurement/processing time does not exceed 2 minutes. The clinically detected SPPPG signal shapes and corresponding parameters are presented and discussed. The…
Skin Erythema Assessment by an RGB Imaging Device: a Clinical Study
2015
In this study, skin erythema assessment of 90 rosacea patients was estimated by a simple, low-cost RGB imaging device. A new erythema index assessment algorithm is proposed and clinically validated. Comparison with dermatologist’s visual assessment shows high correlation.
Combined multi-wavelength laser speckle contrast imaging and diffuse reflectance imaging for skin perfusion assessment
2019
Abstract Laser Speckle Contrast Imaging (LSCI) is a powerful low-cost method for visualization of flow, microcirculation and blood perfusion. Due to the fact that diseased and healthy tissues has different blood perfusion, LSCI can be a perspective tool for cancer diagnostics and discrimination between different types of tissues. Previously, multispectral diffuse reflectance imaging method for melanoma diagnostics has been introduced. In this work, multi-wavelength (532-, 655- and 850- nm) LSCI technique combined with hyperspectral camera and diffuse reflectance imaging method will be used for assessment of tissues with different skin perfusion properties. An in vivo experiment with occlusi…
Multispectral autoflourescence detection of skin neoplasia using steady-state techniques
2019
In the current study were used excitation-emission matrices (EEMs) and synchronous fluorescence spectroscopy (SFS) steady-state techniques in a broad spectral regions (excitation at 220-500 nm and emission at 280-850 nm) to achieve the whole set of endogenous fluorophores, existed in normal and neoplastic cutaneous tissues. Several types of benign, dysplastic and malignant types of skin lesions were investigated ex vivo using both EEM and SFS modalities, namely the basal cell papilloma and carcinoma, pigmented nevi, dysplastic nevi, squamous cell carcinoma and malignant melanoma. Histological analysis was used as a “gold standard” for evaluation of clinical diagnosis of the lesions investig…
Novel laser technologies for human skin in-vivo assessment
2007
Two experimental methodologies for human skin optical non-invasive in-vivo assessment have been developed and clinically tested - imaging of the laser-excited autofluorescence fading rate, and simultaneous recording of the reflectance photoplethysmography signals at several laser wavelengths with different skin penetration depths. Details of both equipments are described along with some measurement results illustrating feasibility of the novel technologies.
<title>Potential of advanced photoplethysmography sensing for noninvasive vascular diagnostics and early screening</title>
2002
Advanced sensor device for shape analysis of the tissue- reflected mean single period photoplethysmography (SPPPG) signals has been designed and clinically tested. The SPPPG signal shape reveals individual features of the patient's cardio-vascular state. Clinical studies of several patient groups (e.g. diabetes mellitus, atherosclerosis obliterans, Raynaud's syndrome) made possible to specify components of the SPPPG signal that are sensitive to the corresponding organic or functional pathologies. Comparison of the right and left arm finger SPPPG signal shapes, for instance, appears to be efficient tool for early screening of unilateral atherosclerosis obliterans.© (2002) COPYRIGHT SPIE--The…
Spectral imaging system for money counterfeit detection
2019
A prototype with three different wavelength lasers (448nm, 532nm and 659nm) for money counterfeit illumination, analyzation and detection using RGB crosstalk correction and comparing spectral image ration for different banknote elements will be presented.
Towards noncontact skin melanoma selection by multispectral imaging analysis
2011
A clinical trial comprising 334 pigmented and vascular lesions has been performed in three Riga clinics by means of multispectral imaging analysis. The imaging system Nuance 2.4 (CRi) and self-developed software for mapping of the main skin chromophores were used. Spe- cific features were observed and analyzed for malignant skin melanomas: notably higher absorbance (especially as the difference of optical density relative to the healthy skin), uneven chromophore distribution over the lesion area, and the possibility to select the "melanoma areas" in the correla- tion graphs of chromophores. The obtained results indicate clinical potential of this technology for noncontact selec- tion of mel…
Skin cancer screening – better safe than sorry
2020
Skin cancer is the most common type of cancers. In Latvia, on average there are approximately 200 new melanoma and 1300 non-melanoma cancer cases per year. Non-melanoma cancers are: Basal Cell Carcinoma, Squamous Cell Carcinoma and others. It is essential to discover skin cancer at an early stage when it is treatable. For this reason, a reliable, non-invasive and quantitative skin cancer screening method is necessary in order to discover skin cancer as early as possible and to help physicians such as general practitioners and dermatologists assign patients to the best treatment as soon as possible. In this article, the current skin cancer incidence as well as the screening situation in Latv…
Wearable wireless photoplethysmography sensors
2008
Wearable health monitoring sensors may support early detection of abnormal conditions and prevention of their consequences. Recent designs of three wireless photoplethysmography monitoring devices embedded in hat, glove and sock, and connected to PC or mobile phone by means of the Bluetooth technology, are described. First results of distant monitoring of heart rate and pulse wave transit time using the newly developed devices are presented.
Rosacea assessment by erythema index and principal component analysis segmentation maps
2017
RGB images of rosacea were analyzed using segmentation maps of principal component analysis (PCA) and erythema index (EI). Areas of segmented clusters were compared to Clinician’s Erythema Assessment (CEA) values given by two dermatologists. The results show that visible blood vessels are segmented more precisely on maps of the erythema index and the third principal component (PC3). In many cases, a distribution of clusters on EI and PC3 maps are very similar. Mean values of clusters’ areas on these maps show a decrease of the area of blood vessels and erythema and an increase of lighter skin area after the therapy for the patients with diagnosis CEA = 2 on the first visit and CEA=1 on the …
Benign &#x2014; A typical nevi discrimination using diffuse reflectance and fluorescence multispectral imaging system
2015
Early diagnostics of skin cancer is of interest for dermatologists. Atypical nevi are not considered to be malignant, but are suspects that should be detected and monitored over time. The multispectral imaging system Nuance operating in spectral range 450–950 nm was adapted for clinical in vivo measurements in diffuse reflectance and fluorescence mode. Mean and standard deviation values of optical density and fluorescence intensity were extracted from segmented pigmented lesions (21 benign and 26 atypical nevi) and used for further analysis. It was possible to achieve 62% sensitivity and 67% specificity for discrimination between atypical and benign lesions using averaged fluorescence mean …
<title>A portable device for optical assessment of the cardiovascular condition</title>
2003
A hand-held prototype device for detection and processing of the tissue-remitted optical signals has been developed and tested. The photoplethysmography (PPG) principle was applied to follow the dilation and contraction of skin blood vessels during the cardiac cycle. Cardiovascular condition of the monitored person was assessed by temporal analysis of the recorded PPG signals as well as by shape analysis of the mean single-period PPG signals.© (2003) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Implementation of laser speckle contrast analysis as connection kit for mobile phone for assessment of skin blood flow
2014
Laser speckle contrast analysis (LASCA) offers a non-contact, full-field, and real-time mapping of capillary blood flow and can be considered as an alternative method to Laser Doppler perfusion imaging. LASCA technique has been implemented in several commercial instruments. However, these systems are still too expensive and bulky to be widely available. Several optical techniques have found new implementations as connection kits for mobile phones thus offering low cost screening devices. In this work we demonstrate simple implementation of LASCA imaging technique as connection kit for mobile phone for primary low-cost assessment of skin blood flow. Stabilized 650 nm and 532 nm laser diode m…
Simultaneous detection of tissue autofluorescence decay distribution and time-gated photo-bleaching rates
2015
ABSTRACT Experimental methodology for parallel measurements of in-vivo skin autofluorescence (AF) lifetimes and photo-bleaching dynamic has been developed and tested. The AF lifetime decay distributio ns were periodically collected from fixed tissue area with subsequent detection of the fluorescence intensity decrease dynamic at different time gates after the pulse excitation. Temporal distributions of human in-vivo skin AF lifetimes and bleaching kinetics were collected and analyzed by means of commercial time-corr elated single photon counting system. Keywords: TCSPC, skin autofluoresc ence, and photo-bleaching. 1. INTRODUCTION Laser induced time-resolved autofluorescence (AF) spectroscop…
Diffuse reflectance and fluorescence multispectral imaging system for assessment of skin
2014
The diffuse reflectance multispectral imaging technique has been used for distant mapping of in vivo skin chromophores (hemoglobin and melanin). The fluorescence multispectral imaging is not so common for skin applications due to complicity of data acquisition and processing, but could provide additional information about skin fluorophores. Both techniques are compatible, and could be combined into a multimodal solution. The multispectral imaging system Nuance based on liquid crystal tunable filters was adapted for diffuse reflectance and fluorescence spectral imaging of in vivo skin. Uniform illumination was achieved by LED ring light. Combination of four LEDs (warm white, 770 nm, 830 nm a…
Comparison of single-spot technique and RGB imaging for erythema index estimation
2016
A commercially available point measurement device, the Mexameter(®), and an experimental RGB imaging prototype device were used for erythema index estimation of 50 rosacea patients by analysing the level of skin redness on the forehead, both cheeks and both sides of a nose. Results are compared with Clinician's Erythema Assessment (CEA) values given by two dermatologists. The Mexameter uses 568 nm and 660 nm LEDs and a photodetector for estimation of erythema index, while the used prototype device acquired RGB images at 460 nm, 530 nm and 665 nm LED illumination. Several erythema index estimation algorithms were compared to determine which one gives the best contrast between increased eryth…
Semi-automatic detection of skin malformations by analysis of spectral images
2013
The multi-spectral imaging technique to reveal skin malformations has been described in this work. Four spectral images taken at polarized monochromatic LED illumination (450nm, 545nm, 660nm and 940 nm) and polarized white LED light imaged by CMOS sensor via cross-oriented polarizing filter were analyzed to calculate chromophore maps. The algorithm based on skin color analysis and user-defined threshold selection allows highlighting of skin areas with predefined chromophore concentration semi-automatically. Preliminary results of clinical tests are presented.
Bilateral photoplethysmography studies of the leg arterial stenosis.
2005
A newly developed portable multi-channel photoplethysmography (PPG) device has been used for comparative studies of 20 healthy control subjects and 45 patients with diagnosed arterial stenosis in a leg. The peripheral blood pulsations were detected simultaneously at four body sites-the same fingers and toes of both arms and legs. The PPG pulses recorded at the periphery of the stenotic leg, if compared with those of the healthy leg, were much weaker, with delayed arrival as a consequence of increased pulse wave transit time (PWTT) due to higher vascular resistance. The specific PWTT delays for the occluded legs were in the range of 20-80 ms, while in the case of healthy subjects the leg PPG…
Clinical measurements with multi-spectral photoplethysmography sensors
2012
A portable multi-spectral photoplethysmography device has been used for studies of 40 subjects. Multi-spectral monitoring was performed by means of a four - wavelengths (465 nm, 530 nm, 630 nm and 870 nm) light emitted diodes (LED) and a single photodiode with multi-channel signal output processing. The proposed methodology and potential clinical applications are discussed.
<title>Pressure sensitivity of the side-glowing optical fibers</title>
2001
Remarkable impact of external mechanical pressure to the transmitted radiation intensity has been observed for glowing fibers with various silica core diameters and side- scattering efficiencies. A physical model on deformation- simulated light scattering has been developed and discussed. The results of experimental studies confirmed the basic model assumptions.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Snapshot multi-spectral-line imaging for applications in dermatology and forensics
2019
Performance of multi-spectral imaging critically depends on image acquisition time and working spectral bandwidths. Ultimate performance can be achieved if a set of monochromatic (single-wavelength) spectral images is obtained by a single snapshot - a technique provisionally called “snapshot multi-spectral-line imaging” or SMSLI. The SMSLI principle and the developed prototype devices for 3, 4 and 5 spectral line snapshot imaging are described. Two potential practical applications of SMSLI are discussed – for fast mapping of the main in-vivo skin chromophores and for detection of counterfeit banknotes and documents.
Multi-spectral photoplethysmography technique for parallel monitoring of pulse shapes at different tissue depths
2011
A photoplethysmography (PPG) signal can provide very useful information about a subject's hemodynamic status in a hospital or home environment. A newly developed portable multi-spectral photoplethysmography device has been used for studies of 11 healthy subjects. Multi-spectral photoplethysmography (MS-PPG) biosensor intended for analysis of peripheral blood volume pulsations at different vascular depths has been designed and experimentally tested. Multi-spectral monitoring was performed by means of a three–wavelengths (405 nm, 660 nm and 780 nm) laser diode and a single photodiode with multi-channel signal output processing. The proposed methodology and potential clinical applications are …
Photoplethysmography Device for Detection of Changes in the Vasomotor Parameters of Small Laboratory Animals
2008
A device for observation of changes in vasomotor parameters of small laboratory animals with limited blood amount has been developed. The device contains cw laser sources (635 nm, 650nm or 980 nm), photodetector, amplifier of the absorption photoplethysmography signal and special software for data recording.
2-D mapping of skin chromophores in the spectral range 500 - 700 nm
2009
The multi-spectral imaging technique has been used for distant mapping of in-vivo skin chromophores by analyzing spectral data at each reflected image pixel and constructing 2-D maps of the relative concentrations of oxy-/deoxy-haemoglobin and melanin. Instead of using a broad visible-NIR spectral range, this study focuses on narrowed spectral band 500–700 nm, speeding-up the signal processing procedure. Regression analysis confirmed that superposition of three Gaussians is optimal analytic approximation for the oxy-haemoglobin absorption tabular spectrum in this spectral band, while superposition of two Gaussians fits well for deoxy-haemoglobin absorption and exponential function – for mel…
Multi-spectral imaging analysis of pigmented and vascular skin lesions: results of a clinical trial
2011
A clinical trial comprising 266 pigmented lesions and 49 vascular lesions has been performed in three Riga clinics by means of multi-spectral imaging analysis. The imaging system Nuance 2.4 (CRI) and self-developed software for mapping of the main skin chromophores were used. The obtained results confirm clinical potential of this technology for non-contact quantitative assessment of skin pathologies.
Multispectral fluorescence detection of pigmented cutaneous tumours
2020
We investigated pigmented skin tumour lesions in vivo and ex vivo, including benign and dysplastic nevi, as well as malignant lesions, such as pigmented basal cell carcinoma (BCC) and malignant melanoma (MM) lesions, to obtain a complex view about the feasibility of different excitation sources solely and/or in combination to induce fluorescence signal useful for diagnosis of various low-fluorescent cutaneous neoplasia. A specialized multispectral analysis of the data obtained was applied by using excitation in broad spectral range, covering ultraviolet, visible and near-infrared spectral range, that contribute considerably to: (1) fundamental determination of tumour tissues’ spectral prope…
Photobleaching effects onin vivoskin autofluorescence lifetime
2015
The autofluorescence lifetime of healthy human skin was measured using excitation provided by a picosecond diode laser operating at a wavelength of 405 nm and with fluorescence emission collected at 475 and 560 nm. In addition, spectral and temporal responses of healthy human skin and intradermal nevus in the spectral range 460 to 610 nm were studied before and after photobleaching. A decrease in the autofluorescences lifetimes changes was observed after photobleaching of human skin. A three-exponential model was used to fit the signals, and under this model, the most significant photoinduced changes were observed for the slowest lifetime component in healthy skin at the spectral range 520 …
Towards combined multispectral, FLIM and Raman imaging for skin diagnostics
2020
To explore challenges for further improvement of diagnostic performance, a project aimed at development of technology for tri-modal skin imaging by combining multispectral, fluorescence lifetime and Raman band imaging was initiated. In this study, each of the mentioned imaging modalities has been preliminary tested and updated. Four different multispectral imaging devices were tested on color standards. Picosecond laser-excited fluorescence lifetime imaging equipment was examined on ex-vivo skin samples. Finally, a new Raman spectroscopy setup with 785 nm laser was launched and tested on cell cultures and ex-vivo skin. Advantages and specific features of the tri-modal skin imaging are discu…
RGB imaging of laser-excited skin autofluorescence bleaching rates
2010
In-vivo skin photo-bleaching (intensity decrease during irradiation) has been investigated at 405 nm cw laser excitation. Digital RGB photo-camera was used for studies of the bleaching features by analysis of fluorescent images at separated R, G and B spectral bands. Diagnostic potential based on correlations between skin pigmentation and bleaching rates is discussed.
Influence of low power CW laser irradiation on skin hemoglobin changes
2012
Influence of low power laser irradiance on healthy skin using diffuse reflectance spectroscopy and multispectral imaging was studied. Changes of diffuse reflectance spectra in spectral range from 500 to 600 nm were observed after 405 nm, 473 nm and 532 nm laser provocation, leading to conclusion that the content of skin hemoglobin has changed. Peaks in spectral absorbance (optical density) curves corresponded to well-known oxy-hemoglobin absorbance peaks at 542 and 577 nm.
Imaging of Laser-Excited Autofluorescence Fading Rates: Novel Technique for Tissue Surface Structure Studies
2008
Experimental methodology for imaging of laser-excited tissue autofluorescence fading rates has been developed and clinically tested. Details of the equipment and image processing are described, along with measurement results confirming feasibility of the novel technology.
Comparison of a near-infrared reflectance spectroscopy system and skin conductance measurements for in vivo estimation of skin hydration: a clinical …
2017
Diffuse reflectance spectroscopy system was developed for estimation of skin hydration in the near-infrared spectral range of 900-1700 nm. Experimental setup consisted of a near-infrared spectrometer, Y-type fiber optics probe with 1 detection and 6 illumination fibers, halogen-tungsten light source and a PC. By analyzing diffuse reflectance spectrum, a parameter representing skin hydration by performing baseline correction and calculating the area under the 1450 nm water absorption maximum is proposed. A clinical study was performed acquiring data of skin hydration of 39 patients' forearm skin. Results of the developed system are compared to results obtained by a commercial device based on…
Teaching of laser medical topics: Latvian experience
2002
Pilot program for Master's studies on Biomedical Optics has been developed and launched at University of Latvia in 1995. The Curriculum contains several basic subjects like Fundamentals of Biomedical Optics, Medical Lightguides, Anatomy and Physiology, Lasers and Non-coherent Light Sources, Optical Instrumentation for Healthcare, Optical Methods for Patient Treatment, Basic Physics, etc. Special English Terminology and Laboratory-Clinical Praxis are also involved, and the Master Theses is the final step for the degree award. Recently a new extensive short course for medical laser users "Lasers and Bio-optics in Medicine" has been prepared in the PowerPoint format and successfully presented …
Mobile phone based laser speckle contrast imager for assessment of skin blood flow
2014
Assessment of skin blood flow is of interest for evaluation of skin viability as well as for reflection of the overall condition of the circulatory system. Laser Doppler perfusion imaging (LDPI) and laser speckle contrast imaging (LASCI) are optical techniques used for assessment of skin perfusion. However, these systems are still too expensive and bulky to be widely available. Implementation of such techniques as connection kits for mobile phones have a potential for primary diagnostics. In this work we demonstrate simple and low cost LASCI connection kit for mobile phone and its comparison to laser Doppler perfusion imager. Post-occlusive hyperemia and local thermal hyperemia tests are us…
Multi-spectral photoplethysmography biosensor
2011
A photoplethysmography (PPG) signal can provide very useful information about a subject's hemodynamic status in a hospital or home environment. A newly developed portable multi-spectral photoplethysmography device has been used for studies of 11 healthy subjects. The developed optical fiber biosensor comprises one multi-wavelength laser diode (405nm, 660nm and 780nm) and a single photodiode with multi-channel signal output processing and built in Li-ion accumulator; special software was created for visualization and measuring of the MS-PPG signals. ARM7TDMI-S LPC2148, NXP (founded by Philips) 32 bit processor with clock frequency of 60 MHz performs measurement and analysis of the signal.
LED-bed therapy of cardiovascular disorders: a volunteer study
2020
Studies of the physiological response of human half-body illumination by a specially designed bed comprising large number of LEDs emitting in the red and near infrared spectral range were carried out in a group of 32 volunteers comprising healthy subjects and hypertension patients. Blood pressure, heart rate and arterial blood oxygen saturation, as well as the bed surface temperature were continuously monitored during the measurement sessions with and without aluminum foil cover on the bed surface. None of the volunteers exhibited any notable changes in the heart rate and blood oxygenation during the procedures. The LightStim LED-bed session did not produce changes of arterial pressure in n…
Mobile platform for online processing of multimodal skin optical images: Using online Matlab server for processing remission, fluorescence and laser …
2015
Mobile platform for multimodal skin assessment has been developed. Different illumination sources allow switching between modalities. Diffuse reflectance spectral imaging is provided by five LEDs, fluorescence is excited by 405 nm LEDs, and laser speckle by 650 nm laser diode. Handheld, battery powered device includes all light sources and color camera with USB. The core of the system is Linux OS embedded microcontroller. USB, FTP and HTML with JavaScript combination is used to create standard image transfer and control interface. In combination with built in WiFi access point it allows online skin images storage and processing. It means that data processing algorithms are located and updat…
Noncontact monitoring of vascular lesion phototherapy efficiency by RGB multispectral imaging.
2013
A prototype low-cost RGB imaging system consisting of a commercial RGB CMOS sensor, RGB light-emitting diode ring light illuminator, and a set of polarizers was designed and tested for mapping the skin erythema index, in order to monitor skin recovery after phototherapy of vascular lesions, such as hemangiomas and telangiectasias. The contrast of erythema index (CEI) was proposed as a parameter for quantitative characterization of vascular lesions. Skin recovery was characterized as a decrease of the CEI value relative to the value before the treatment. This approach was clinically validated by examining 31 vascular lesions before and after phototherapy.
Glowing optical fiber designs and parameters
1997
Side-emitting optical fiber designs and main parameters have been studied. A simplified model to describe emission of the 'glowing' fiber is developed. Basic expressions for the emission parameters as functions of the input radiation intensity, distance along the fiber axis and scattering efficiency longitudinal distribution are given for several design modifications. The model assumptions have been checked experimentally by testing silica core side-glowing optical fiber samples.
Application prospects of silica core side-glowing optical fibers
2005
The side-emitting optical fibers are specially designed to stimulate leakage of the core-transmitted radiation via their side surfaces, so creating the effect of glowing tiny wires. The basic design concepts for this kind of optical fibers are discussed, as well as some of the present and potential future applications.
Smartphone single-snapshot mapping of skin chromophores
2016
Suitability of smartphone for single-snapshot mapping of skin melanin, oxy-hemoglobin and deoxy-hemoglobin under 3-wavelengths illumination was demonstrated. Simultaneous 448-532-659 nm illumination was provided by a portable laser-based prototype.
3×3 Technique for RGB Snapshot Mapping of Skin Chromophores
2015
Three monochromatic spectral images have been extracted from a single RGB image data set at simultaneous illumination of skin by 473nm, 532nm and 609nm spectral lines. They were further transformed into distribution maps of three skin chromophores - melanin, oxy-hemoglobin and deoxy-hemoglobin, related to pigmented and vascular skin malformations. Performance and clinical potential of the proposed 3×3 technique is discussed.
Optical multichannel sensing of skin blood pulsations
2004
Time resolved detection and analysis of the skin back-scattered optical signals (reflection photoplethysmography or PPG) provide information on skin blood volume pulsations and can serve for cardiovascular assessment. The multi-channel PPG concept has been developed and clinically verified in this study. Portable two- and four-channel PPG monitoring devices have been designed for real-time data acquisition and processing. The multi-channel devices were successfully applied for cardiovascular fitness tests and for early detection of arterial occlusions in extremities. The optically measured heartbeat pulse wave propagation made possible to estimate relative arterial resistances for numerous …
Biophotonics Master studies: teaching and training experience at University of Latvia
2015
Two-year program for Master's studies on Biophotonics (Biomedical Optics) has been originally developed and carried out at University of Latvia since 1995. The Curriculum contains basic subjects like Fundamentals of Biomedical Optics, Medical Lightguides, Anatomy and Physiology, Lasers and Non-coherent Light Sources, Basic Physics, etc. Student laboratories, special English Terminology and Laboratory-Clinical Praxis are also involved as the training components, and Master project is the final step for the degree award. Life-long learning is supported by several E-courses and an extensive short course for medical laser users “Lasers and Bio-optics in Medicine”. Recently a new inter-universit…
Clinical measurements analysis of multi-spectral photoplethysmograph biosensors
2014
The developed portable multi-spectral photoplethysmograph (MS-PPG) optical biosensor device, intended for analysis of peripheral blood volume pulsations at different vascular depths, has been clinically verified. Multi-spectral monitoring was performed by means of a four – wavelengths (454 nm, 519 nm, 632 nm and 888 nm) light emitted diodes and photodiode with multi-channel signal output processing. Two such sensors can be operated in parallel and imposed on the patient’s skin. The clinical measurements confirmed ability to detect PPG signals at four wavelengths simultaneously and to record temporal differences in the signal shapes (corresponding to different penetration depths) in normal a…
Real-Time Photoplethysmography Imaging System
2011
Real-time non-contact photoplethysmography imaging (PPGI) system for high-resolution blood perfusion mapping in human skin has been proposed. The PPGI system comprises of LED lamp, webcam and computer with video processing software. The purpose of this study is to evaluate the reliability of the PPGI system when measuring blood perfusion. The validation study of PPGI and laser-Doppler perfusion imager (LDPI) was performed during local warming of palm skin. Results showed that the amplitude of PPGI increases immediately after warming and well correlated with the mean LDPI amplitude (R=0.92+-0.03, p<0.0001). We found that PPGI technique has good potential for non-contact monitoring of blood p…
Riga Group’s recent results on laser applications for skin diagnostics
2021
Abstract The laser-related activities are reviewed of the Biophotonics Laboratory at UL Institute of Atomic Physics and Spectroscopy following the previous ICSQE-2018 conference. Four recent research projects are considered, including one EC Horizon-2020 project, two European Regional Development Fund (ERDF) projects and one project funded by the Latvian Council of Science (LCS). The projects are generally aimed at developing new optical methods and technologies for non-invasive in-vivo skin assessment to facilitate the early diagnostics of skin malformations (including cancers). Most of the projects explore novel approaches of camera-based biomedical imaging to the clinical diagnostics and…
Contact and contactless diffuse reflectance spectroscopy: potential for recovery monitoring of vascular lesions after intense pulsed light treatment.
2011
Optical fiber contact probe diffuse reflectance spectroscopy and remote multispectral imaging methods in the spectral range of 400 to 1100 nm were used for skin vascular malformation assessment and recovery tracing after treatment by intense pulsed light. The results confirmed that oxy-hemoglobin relative changes and the optical density difference between lesion and healthy skin in the spectral region 500 to 600 nm may be successfully used for objective appraisal of the therapy effect. Color redness parameter a* = 2 is suggested as a diagnostic border to distinguish healthy skin and vascular lesions, and as the indicator of phototreatment efficiency. Valuable diagnostic information on large…
Differentiation of seborrheic keratosis from basal cell carcinoma, nevi and melanoma by RGB autofluorescence imaging
2018
A clinical trial on the autofluorescence imaging of skin lesions comprising 16 dermatologically confirmed pigmented nevi, 15 seborrheic keratosis, 2 dysplastic nevi, histologically confirmed 17 basal cell carcinomas and 1 melanoma was performed. The autofluorescence spatial properties of the skin lesions were acquired by smartphone RGB camera under 405 nm LED excitation. The diagnostic criterion is based on the calculation of the mean autofluorescence intensity of the examined lesion in the spectral range of 515 nm–700 nm. The proposed methodology is able to differentiate seborrheic keratosis from basal cell carcinoma, pigmented nevi and melanoma. The sensitivity and specificity of the prop…
Analysis of skin basalioma and melanoma by multispectral imaging
2012
A clinical trial involving multi-spectral imaging of histologically confirmed 8 basaliomas and 30 melanomas was performed. Parametric maps of the melanin index, erythema index and melanoma-nevus differentiation parameter have been constructed and mutually compared. Specific features of basalioma and melanoma images were analyzed and discussed.
RGB imaging system for monitoring of skin vascular malformation's laser therapy
2012
A prototype RGB imaging system for mapping of skin chromophores consists of a commercial RGB CMOS sensor, RGB LEDs ring-light illuminator and orthogonally orientated polarizers for reducing specular reflectance. The system was used for monitoring of vascular malformations (hemagiomas and telangiectasias) therapy.
Skin haemoglobin mapping: comparison of multi-spectral imaging and selective R-G-B analysis
2010
The multi-spectral imaging technique has been used for distant mapping of in-vivo skin haemoglobin. Besides, potential of selective R-G-B analysis of skin images has been studied under bi-chromatic (532 nm and 635 nm) laser illumination.
Smartphone snapshot mapping of skin chromophores under triple-wavelength laser illumination
2017
Abstract Chromophore distribution maps are useful tools for skin malformation severity assessment and for monitoring of skin recovery after burns, surgeries, and other interactions. The chromophore maps can be obtained by processing several spectral images of skin, e.g., captured by hyperspectral or multispectral cameras during seconds or even minutes. To avoid motion artifacts and simplify the procedure, a single-snapshot technique for mapping melanin, oxyhemoglobin, and deoxyhemoglobin of in-vivo skin by a smartphone under simultaneous three-wavelength (448–532–659 nm) laser illumination is proposed and examined. Three monochromatic spectral images related to the illumination wavelengths …
RGB mapping of hemoglobin distribution in skin
2011
An experimental RGB imaging system based on commercial color camera was constructed, and its potential for mapping of hemoglobin distribution in skin was studied. Two types of LEDs (RGB and white “warm” LEDs) were compared as illuminators for acquiring images of vascular and pigmented skin malformations. A novel approach for studies of skin capillary refill by RGB analysis has been proposed and discussed.
<title>Compact multi-functional skin spectrometry set-up</title>
2006
A portable fibre-optic spectrometry set-up has been assembled and tested for applications in skin diffuse reflectance spectrometry, laser fluorescence spectrometry and multi-wavelength reflection photoplethysmography (multi-PPG) studies. The spectrometry set was tested by diffuse reflectance and fluorescence measurements for diagnostics of skin vascular malformations and pigmented diseases such as nevi and melanoma . In addition, studies of microcirculation in blood vessels located at different depths from the skin surface were performed by the multi-PPG method. The results of skin diffuse reflectance and autofluorescence showed differences in spectra of healthy and pathologic skin. The par…
Study of smartphone suitability for mapping of skin chromophores.
2015
RGB (red-green-blue) technique for mapping skin chromophores by smartphones is proposed and studied. Three smartphones of different manufacturers were tested on skin phantoms and in vivo on benign skin lesions using a specially designed light source for illumination. Hemoglobin and melanin indices obtained by these smartphones showed differences in both tests. In vitro tests showed an increment of hemoglobin and melanin indices with the concentration of chromophores in phantoms. In vivo tests indicated higher hemoglobin index in hemangiomas than in nevi and healthy skin, and nevi showed higher melanin index compared to the healthy skin. Smartphones that allow switching off the automatic cam…
<title>Fiber optical intensity-ratio refractometer with digital display</title>
1994
Simplicity, cost efficiency, and higher fidelity compared to the single-channel design are the main advantages stimulating the recent interest on fiber optic intensity-ratio sensors. Optical and electronic designs of refractometric sensors of this kind are discussed here. Two optical schemes of retroreflective probes with one input and two output fibers are proposed. The probe sensitivity to liquid refractivity changes in the interval 1.33 < n < 1.41 is studied by computer simulation. An originally developed one-ADC-based signal processing circuit providing digital display of the intensity-ratio determined n-values is described as well.
Multimodal device for assessment of skin malformations
2013
A variety of multi-spectral imaging devices is commercially available and used for skin diagnostics and monitoring; however, an alternative cost-efficient device can provide an advanced spectral analysis of skin. A compact multimodal device for diagnosis of pigmented skin lesions was developed and tested. A polarized LED light source illuminates the skin surface at four different wavelengths – blue (450 nm), green (545 nm), red (660 nm) and infrared (940 nm). Spectra of reflected light from the 25 mm wide skin spot are imaged by a CMOS sensor. Four spectral images are obtained for mapping of the main skin chromophores. The specific chromophore distribution differences between different skin…
Multi-spectral Reflection Photoplethysmography: Potential for Skin Microcirculation Assessment
2006
Technique for simultaneous recording of reflection photoplethysmography signals in broad spectral band (violet to NIR) has been developed, and its potential for assessment of blood microcirculation at various depths from the skin surface is discussed.
Optical systems for non-invasive cardiovascular biosensing
2005
Three portable prototype devices for cardiovascular biosensing based on reflection-type photoplethysmography (PPG) principle have been designed and clinically tested. The single-channel PPG finger sensor provides real-time measurements with fast calculation of the mean single-period PPG signal shape ("cardiovascular fingerprint", potentially useful for recognition). The dual-channel PPG system gives additional possibility to monitor on-line the arterial pulse wave transit time and its responses to physical exercises. The four-channel PPG system proved to be applicable for fast detection of cardiovascular pathologies, e.g. arterial occlusions in extremities. Design principles and software al…
Phantoms Used for Mapping of Skin Chromophores by Multi-spectral Imaging
2014
Skin phantoms can be used for better understanding of diffuse reflectance imaging of skin. In this study, skin phantoms of hemoglobin, bilirubin and melanin were developed and studied for possibilities to calibrate chromophore concentration values.
Monitoring of blood pulsation using non-contact technique
2009
Time resolved detection and analysis of the skin back-scattered optical signals (reflection photoplethysmography or contact PPG) provide rich information on skin blood volume pulsations and can serve for cardiovascular assessment. The widely used contact PPG technique has many limitations, like high sensitivity to sensor movement etc. The newly developed non-contact PPG technique has been developed in this work. Potential of the new technique for express-assessment of human cardio-vascular condition has been demonstrated.
Assessment of efficiencies of electroporation and sonoporation methods by using fluorescence RGB imaging method
2013
Simple RGB method for fluorescence in vivo imaging is presented to assess efficiency of electroporation and sonoporation methods by measuring distribution and accumulation of green fluorescence protein (GFP) concentration. 20 laboratory measurements were performed on mice to test the method.
Portable two-channel PPG cardiovascular sensor device
2003
A portable sensor device for simultaneous detection and processing of skin-remitted optical signals from any two sites of the body has been developed and tested. The photoplethysmography (PPG) principle was applied to follow the dilatation and contraction of skin blood vessels during the cardiac cycle. The newly developed two-channel approach allows to estimate the vascular blood flow resistance by analysis of time shifts between the PPG pulses detected at different body sites. Potential of the sensor device for express-assessment of human cardio-vascular condition and for body fitness tests has been demonstrated.
Fluorescence spectroscopy for estimation of anticancer drug sonodestruction in vitro
2013
The effect of ultrasound exposure on bleomycin fluorescence and pharmacological properties is studied. Bleomycin was treated by ultrasound for 7 min. Bleomycin fluorescence was measured during ultrasound exposure by means of fiber-optic spectrometry. Cell colony test was used to evaluate blemycin cytotoxity before and after ultrasound exposure.
Wireless photoplethysmography finger sensor probe
2010
A sensitive, digital, wireless sensor probe has been developed for photoplethysmography (PPG) measurements. It uses standard light emitting source and detector. The main advantage of this approach is to measure discharge time of the photodiode as amplitude of PPG signal. It reduces the cost, dimensions, power consumption and filtering of the device. First results of distant monitoring of heart rate using the newly developed sensor probe are presented.
Investigating different skin and gastrointestinal tract (GIT) pathologies ex vivo by autofluorescence spectroscopy and optical imaging
2017
The skin neoplasias are on a second place in the world statistics of cancer incidence, and gastrointestinal tract (GIT) tumours are also in the “top ten” list. For the most of cutaneous and gastrointestinal tumours could be obtained better prognoses for patients, if an earlier and precise diagnostics procedure is applied. One of the most promising approaches for development of improved diagnostic techniques, is based on optical detection, and analysis of the signatures of biological tissues for detecting the presence of pathological alterations in the investigated objects. It is important to develop and combine novel diagnostic techniques for an accurate early stage diagnosis to improve the…
Remitted photon path lengths in human skin: in-vivo measurement data
2020
The remitted photon path lengths in human skin can be estimated by modelling; however, there are very few experimental data available to validate the simulations. This study exploited the photon time of flight method where picosecond laser pulses at seven wavelength bands in the spectral range 560-800 nm were launched into in-vivo forearm skin of 10 volunteers via an optical fiber. The pulses of back-scattered light were detected via another optical fiber placed at variable distance (1, 8, 12, 16 or 20 mm) from the input fiber, with subsequent analysis of their shapes for all 35 spectral-spatial combinations. Using a deconvolution algorithm, the distribution functions of remitted photon arr…
Skin chromophore mapping from multi-spectral laser line images
2020
Skin chromophore maps can be used for assessment of various skin malformations and early cancer diagnostics. Commercially available devices are bulky and expensive. We present two portable proof-of-concept device prototypes for multi-spectral laser line imaging with three (448 nm, 532 nm and 659 nm) and four (450 nm, 523 nm, 638 nm and 850 nm) wavelength laser illumination. Laser modules and special optics that ensure uniform light distribution over the region of interest have been exploited. Skin chromophore maps were calculated using Beer-Lambert law, considering light scattering properties in the skin and including photon path length evaluated from the directly measured photon-time-of-fl…