Perfusion measured by laser speckle contrast imaging as a predictor for expansion of psoriasis lesions.

BACKGROUND: Skin microvasculature changes are crucial in psoriasis development and correlate with perfusion. The noninvasive Handheld Perfusion Imager (HAPI) examines microvascular skin perfusion in large body areas using laser speckle contrast imaging (LSCI). OBJECTIVES: To (i) assess whether increased perilesional perfusion and perfusion inhomogeneity are predictors for expansion of psoriasis lesions and (ii) assess feasibility of the HAPI system in a mounted modality. METHODS: In this interventional pilot study in adults with unstable plaque psoriasis, HAPI measurements and color photographs were performed for lesions present on one body region at week 0, 2, 4, 6 and 8. The presence of increased perilesional perfusion and perfusion inhomogeneity was determined. Clinical outcome was categorized as increased, stable or decreased lesion surface between visits. Patient feedback was collected on a 10-point scale. RESULTS: In total, 110 lesions with a median follow-up of 6 (IQR 6.0) weeks were assessed in 6 patients with unstable plaque psoriasis. Perfusion data was matched to 281 clinical outcomes after two weeks. A mixed multinomial logistic regression model revealed a predictive value of perilesional increased perfusion (OR 9.90; p < 0.001) and perfusion inhomogeneity (OR 2.39; p = 0.027) on lesion expansion after two weeks compared to lesion stability. HAPI measurements were considered fast, patient-friendly and important by patients. CONCLUSION: Visualization of increased perilesional perfusion and perfusion inhomogeneity by noninvasive whole field LSCI holds potential for prediction of psoriatic lesion expansion. Furthermore, the HAPI is a feasible and patient-friendly tool.

Correction: Bulsink et al. Oxygen Saturation Imaging Using LED-Based Photoacoustic System. Sensors 2021, 21, 283.

The authors wish to make the following corrections to this paper [...].

Oxygen Saturation Imaging Using LED-Based Photoacoustic System.

Oxygen saturation imaging has potential in several preclinical and clinical applications. Dual-wavelength LED array-based photoacoustic oxygen saturation imaging can be an affordable solution in this case. For the translation of this technology, there is a need to improve its accuracy and validate it against ground truth methods. We propose a fluence compensated oxygen saturation imaging method, utilizing structural information from the ultrasound image, and prior knowledge of the optical properties of the tissue with a Monte-Carlo based light propagation model for the dual-wavelength LED array configuration. We then validate the proposed method with oximeter measurements in tissue-mimicking phantoms. Further, we demonstrate in vivo imaging on small animal and a human subject. We conclude that the proposed oxygen saturation imaging can be used to image tissue at a depth of 6-8 mm in both preclinical and clinical applications.

Tomographic Ultrasound and LED-Based Photoacoustic System for Preclinical Imaging.

Small animals are widely used as disease models in medical research. Noninvasive imaging modalities with functional capability play an important role in studying the disease state and treatment progress. Photoacoustics, being a noninvasive and functional modality, has the potential for small-animal imaging. However, the conventional photoacoustic tomographic systems use pulsed lasers, making it expensive, bulky, and require long acquisition time. In this work, we propose the use of photoacoustic and ultrasound tomographic imaging with LEDs as the light source and acoustic detection using a linear transducer array. We have demonstrated full-view tomographic imaging of a euthanized mouse and a potential application in liver fibrosis research.

Quantitative blood oxygen saturation imaging using combined photoacoustics and acousto-optics.

In photoacoustic spectroscopy (PAS), wavelength dependent optical attenuation of biological tissue presents a challenge to measure the absolute oxygen saturation of hemoglobin (sO2). Here, we employ the combination of photoacoustics and acousto-optics (AO) at two optical wavelengths to achieve quantification, where AO serves as a sensor for the relative local fluence. We demonstrate that our method enables compensation of spatial as well as wavelength dependent fluence variations in PAS without a priori knowledge about the optical properties of the medium. The fluence compensated photoacoustic images at two excitation wavelengths are used to estimate the absolute oxygen saturation of blood in a spatially and spectroscopically heterogeneous phantom.

The state of the art in breast imaging using the Twente Photoacoustic Mammoscope: results from 31 measurements on malignancies.

OBJECTIVES: Photoacoustic mammography is potentially an ideal technique, however, the amount of patient data is limited. To further our understanding of the in vivo performance of the method and to guide further research and development, we imaged 33 breast malignancies using the research system - the Twente Photoacoustic Mammoscope (PAM). METHODS: Thirty-one patients participated in this retrospective, observational study. The study and informed consent procedure were approved by the local ethics committee. PAM uses 1,064 nm light for excitation with a planar, 588-element, 1-MHz ultrasound array for detection. Photoacoustic lesion visibility and appearance were compared with conventional imaging (x-ray mammography and ultrasonography) findings, histopathology and patient demographics. RESULTS: Of 33 malignancies 32 were visualized with high contrast and good co-localization with conventional imaging. The contrast of the detected malignancies was independent of radiographic breast density, and size estimation was reasonably good with an average 28 % deviation from histology. However, the presence of contrast areas outside the malignant region is suggestive for low specificity of the current system. Statistical analyses did not reveal any further relationship between PAM results and patient demographics nor lesion characteristics. CONCLUSIONS: The results confirm the high potential of photoacoustic mammography in future breast care. KEY POINTS: • Photoacoustic breast imaging visualizes malignancies with high imaging contrast. • Photoacoustic lesion contrast is independent of the mammographically estimated breast density. • No clear relationship exists between photoacoustic characteristics and lesion type, grade, etc. • Photoacoustic specificity to breast cancer from some cases is not yet optimal.

Measuring absorption coefficient of scattering liquids using a tube inside an integrating sphere.

A method for measuring the absorption coefficient µa of absorbing and scattering liquid samples is presented. The sample is injected into a small transparent tube mounted through an integrating sphere. Two models for determining the absorption coefficient using the relative optical output signal are described and validated using aqueous ink absorbers of 0.5 vol.% (0.3 mm-1<µa<1.55 mm-1) and 1.0 vol.% (1.0 mm-1<µa<4.0 mm-1) concentrations with 1 vol.% (µs'≈1.4 mm-1) and 10 vol.% (µs'≈14 mm-1) Intralipid dilutions. The low concentrations give µa and µs values, which are comparable with those of biological tissues. One model assumes a uniform light distribution within the sample, which is valid for low absorption. Another model considers light attenuation that obeys Lambert-Beer's law, which may be used for relatively high absorption. Measurements with low and high scattering samples are done for the wavelength range of 400-900 nm. Measured spectra of purely absorbing samples are within 15% agreement with measurements using standard transmission spectrophotometry. For 0.5 vol.% ink absorbers and at wavelengths below 700 nm, measured µa values are higher for samples with low scattering and lower for those with high scattering. At wavelengths above 700 nm, measured µa values do not vary significantly with amount of scattering. For 1.0 vol.% ink absorbers, measured spectra do not change with low scattering. These results indicate that the method can be used for measuring absorption spectra of scattering liquid samples with optical properties similar to biological absorbers, particularly at wavelengths above 700 nm, which is difficult to accomplish with standard transmission spectrophotometry.

Perfusion Intensity Correlates with Expression Levels of Psoriasis-Related Genes and Proteins.

BACKGROUND: Previous research revealed heterogeneity in the perfusion intensity within clinically homogenous-appearing plaques, without differences in erythema. In addition, an increased perfusion was found within the perilesional skin. This raises the question whether the heterogeneity in perfusion found both inside and outside a lesion influences the expression levels of genes and proteins involved in the pathogenesis of psoriasis. OBJECTIVES: To correlate the perfusion intensity to mRNA and protein expression of genes associated with the pathogenesis of psoriasis and to visualize the dynamics of the perfusion intensity over time using laser Doppler perfusion imaging. METHODS: Fourteen patients with plaque psoriasis were included. The superficial microcirculation and clinical local scores (single usability metric, SUM, scores) were analysed in one representative lesion every 2 weeks. After 8 weeks 4 biopsies were taken, one from a highly perfused area (hotspot) and one from a low perfusion area (coldspot) of the lesional skin, one biopsy from the highly perfused perilesional skin and one from the distant uninvolved skin. RESULTS: Statistically significant differences in mRNA and protein expression, including IL-17 and TBX21/T-Bet, were found between hotspots and coldspots, and between the highly perfused perilesional and the uninvolved skin. Hotspots tend to remain on the same location during 8 weeks of follow-up. CONCLUSIONS: Within homogenous-appearing psoriatic plaques, there are remarkable differences in mRNA and protein levels, which are correlated with the perfusion intensity and can be detected by using laser Doppler perfusion imaging. In addition, differences in mRNA and protein expression between the highly perfused perilesional skin and the uninvolved skin were found, indicating that several biological changes occur well before clinical changes become manifest.

Solving the speckle decorrelation challenge in acousto-optic sensing using tandem nanosecond pulses within the ultrasound period.

We present a novel acousto-optic (AO) method, based on a nanosecond laser system, which will enable us to obtain AO signals in liquid turbid media. By diverting part of the light in a delay line, we inject tandem pulses with 27 ns separation. The change of the speckle pattern, caused by the ultrasound phase shift, reduces the speckle contrast of the integrated speckle pattern captured in a single camera frame. With these tandem pulses, we were able to perform AO on a 2 cm liquid turbid medium in transmission mode. We show the raw signal and a spatial AO scan of a homogenous water-intralipid sample. This approach is potentially capable of AO probing in vivo, since the acquisition time (of approximately 40 ns) is four orders of magnitude less than the typical time scales of speckle decorrelation found in vivo. The method may eventually enable us to obtain fluence compensated photoacoustic signals generated by the same laser.

Laser speckle contrast analysis for quantifying the Allen test: a feasibility study.

BACKGROUND AND OBJECTIVE: The radial artery has become a routinely used conduit for coronary artery bypass graft surgery (CABG). Prior to surgery the Allen test is performed to test the patency of the ulnar artery. A positive Allen test, reperfusion >5 seconds, suggests an insufficient perfusion of the hand by the ulnar artery. In this study we investigated if laser speckle contrast analysis (LASCA) provides an objective determination of the reperfusion time. MATERIALS AND METHODS: When the hand is illuminated with coherent laser light, the backscattered light will result in an interference pattern consisting of bright and dark areas called speckles. This speckle pattern will change due to movement of red blood cells. LASCA uses these changes to visualize the perfusion during the Allen test. Reperfusion is measured on the palmar side of the hand. The reperfusion time is defined as the time from onset of reperfusion to maximum perfusion calculated by a polynomial curve fit. The reperfusion time of the hand of patients undergoing CABG (n = 30) is measured using LASCA and is compared to the conventional Allen test performed by the nurse practitioner. RESULTS: LASCA measurements showed a negative Allen test of both hands of 16 patients. Fourteen had a borderline reperfusion time of 5-6 seconds and/or a positive Allen test of one or both hands. No statistical significant difference was observed for the LASCA Allen test compared to the conventional Allen test, P = 0.549 for the left hand and P = 0.223 for the right hand. CONCLUSION: LASCA is able to visualize perfusion of the hand and measure a quick, moderate, slow reperfusion response or no reperfusion. It is technically feasible to determine the reperfusion time of the hand. LASCA can be a useful and objective tool to assess ulnar collateral blood supply to the hand prior to harvesting of the radial artery as a bypass graft.

Mitigation of Motion Artifacts in Handheld Laser Speckle Contrast Imaging Illustrated on Psoriasis Lesions.

BACKGROUND: Handheld laser speckle contrast imaging (LSCI) is crucial in clinical settings, but motion artifacts (MA) can compromise perfusion image reliability. Current prevention and suppression methods are often impractical or complex. Machine vision techniques, promising in medical imaging, could improve signal quality, but their use in suppressing MA is still unexplored. OBJECTIVE: We propose an innovative method based on linear regression for MA correction (MAC) in LSCI and validate it in vivo. METHODS: We performed paired handheld and mounted LSCI measurements on 14 subjects with psoriasis using the previously validated handheld perfusion imager (HAPI). By marking lesion boundaries for clinical purposes, the HAPI used a monochromatic camera for both speckle imaging and motion detection, simplifying hardware requirements. Accurate estimation of relative displacements between the test object and LSCI probe allowed us to apply MAC to the perfusion images. RESULTS: Local perfusion values correlated with applied speed were used to calculate and correct MA. The difference between mean perfusion in handheld and mounted modes after MAC significantly decreased (median error 14.2 perfusion units (p.u.) on lesions before correction ( ) and 0.5 p.u. after correction ( p=0.2)). CONCLUSION: The findings provide evidence for robust handheld LSCI and validate the MA technique in psoriasis case. Of the two causes of MA-onsurface speeds and wavefront tilt-we address the former and correct mean perfusion, assuming constant temporal perfusion at each location. SIGNIFICANCE: We describe a practical, non-contact, marker-free technique for reliable handheld perfusion imaging, supporting further clinical translation in plastic surgery and burns.

Photoacoustic guided ultrasound wavefront shaping for targeted acousto-optic imaging.

To overcome speed of sound aberrations that negatively impact the acoustic focus in acousto-optic imaging, received photoacoustic signals are used to guide the formation of ultrasound wavefronts to compensate for acoustic inhomogeneities. Photoacoustic point sources composed of gold and superparamagnetic iron oxide nanoparticles are used to generate acoustic waves that acoustically probe the medium as they propagate to the detector. By utilizing cross-correlation techniques with the received photoacoustic signal, transmitted ultrasound wavefronts compensate for the aberration, allowing for optimized and configurable ultrasound transmission to targeted locations. It is demonstrated that utilizing a portable commercially available ultrasound system using customized software, photoacoustic guided ultrasound wavefront shaping for targeted acousto-optic imaging is robust in the presence of large, highly attenuating acoustic aberration.

Optical techniques for the intraoperative assessment of nodal status.

The lymphatic system is an important pathway in the metastatic spread of many malignancies and a key prognostic indicator. Nondestructive assessment of the nodal status during surgery could limit the amount of lymph nodes that need to be resected and allow for immediate regional lymphadenectomy during sentinel lymph node biopsy procedures. This review looks into the possibilities of conventional medical imaging methods that are capable of intraoperative nodal assessment and discusses multiple newly developed optical techniques. The physical background behind these techniques is reviewed and a concise overview of their main advantages and disadvantages is provided. These recent innovations show that while the application of optical modalities for intraoperative nodal staging is not yet applied routinely, there is reason enough to expect their introduction in the near future.

Prediction of motion artifacts caused by translation in handheld laser speckle contrast imaging.

Significance: In handheld laser speckle contrast imaging (LSCI), motion artifacts (MA) are inevitable. Suppression of MA leads to a valid and objective assessment of tissue perfusion in a wide range of medical applications including dermatology and burns. Our study shines light on the sources of these artifacts, which have not yet been explored. We propose a model based on optical Doppler effect to predict speckle contrast drop as an indication of MA. Aim: We aim to theoretically model MA when an LSCI system measuring on static scattering media is subject to translational displacements. We validate the model using both simulation and experiments. This is the crucial first step toward creating robustness against MA. Approach: Our model calculates optical Doppler shifts in order to predict intensity correlation function and contrast of the time-integrated intensity as functions of applied speed based on illumination and detection wavevectors. To validate the theoretical predictions, computer simulation of the dynamic speckles has been carried out. Then experiments are performed by both high-speed and low-framerate imaging. The employed samples for the experiments are a highly scattering matte surface and a Delrin plate of finite scattering level in which volume scattering occurs. Results: An agreement has been found between theoretical prediction, simulation, and experimental results of both intensity correlation functions and speckle contrast. Coefficients in the proposed model have been linked to the physical parameters according to the experimental setups. Conclusions: The proposed model provides a quantitative description of the influence of the types of illumination and media in the creation of MA. The accurate prediction of MA caused by translation based on Doppler shifts makes our model suitable to study the influence of rotation. Also the model can be extended for the case of dynamic media, such as live tissue.

Speed-of-sound compensated photoacoustic tomography for accurate imaging.

PURPOSE: In most photoacoustic (PA) tomographic reconstructions, variations in speed-of-sound (SOS) of the subject are neglected under the assumption of acoustic homogeneity. Biological tissue with spatially heterogeneous SOS cannot be accurately reconstructed under this assumption. The authors present experimental and image reconstruction methods with which 2D SOS distributions can be accurately acquired and reconstructed, and with which the SOS map can be used subsequently to reconstruct highly accurate PA tomograms. METHODS: The authors begin with a 2D iterative reconstruction approach in an ultrasound transmission tomography setting, which uses ray refracted paths instead of straight ray paths to recover accurate SOS images of the subject. Subsequently, they use the SOS distribution in a new 2D iterative PA reconstruction approach, where refraction of rays originating from PA sources is accounted for in accurately retrieving the distribution of these sources. Both the SOS reconstruction and SOS-compensated PA reconstruction methods utilize the Eikonal equation to model acoustic wavefront propagation. The equation is solved using a high accuracy fast marching method. RESULTS: The authors validated the new reconstruction algorithms using numerical phantoms. For experiments they utilized the recently introduced PER-PACT method which can be used to simultaneously acquire SOS and PA data from subjects. CONCLUSIONS: It is first confirmed that it is important to take SOS inhomogeneities into account in high resolution PA tomography. The iterative reconstruction algorithms, that model acoustic refractive effects, in reconstructing SOS distributions, and subsequently using these distributions to correct PA tomograms, yield artifact-free highly accurate images. The approach of using the hybrid measurement method and the new reconstruction algorithms is successful in substantially improving the quality of PA images with a minimization of blurring and artifacts.

Passive element enriched photoacoustic computed tomography (PER PACT) for simultaneous imaging of acoustic propagation properties and light absorption.

We present a 'hybrid' imaging approach which can image both light absorption properties and acoustic transmission properties of an object in a two-dimensional slice using a computed tomography (CT) photoacoustic imager. The ultrasound transmission measurement method uses a strong optical absorber of small cross-section placed in the path of the light illuminating the sample. This absorber, which we call a passive element acts as a source of ultrasound. The interaction of ultrasound with the sample can be measured in transmission, using the same ultrasound detector used for photoacoustics. Such measurements are made at various angles around the sample in a CT approach. Images of the ultrasound propagation parameters, attenuation and speed of sound, can be reconstructed by inversion of a measurement model. We validate the method on specially designed phantoms and biological specimens. The obtained images are quantitative in terms of the shape, size, location, and acoustic properties of the examined heterogeneities.

Multiple passive element enriched photoacoustic computed tomography.

Recently, we presented a method using laser-induced ultrasound from an external absorber (passive element) to image the ultrasound transmission parameters of an object under photoacoustic tomographic investigation. The method suffers from long measurement times due to the requirement for a large number of views and consequently physical projections around the object. Here we propose and validate an approach that permits a multitude of views to be obtained within a limited projection scenario. The approach uses a plurality of spatially distributed external absorbers in the path of the light, that results in multiple laser-induced ultrasound sources to interrogate the object from a number of angles. This reduces the required number of rotation angles or physical projections around the object, permitting a considerable reduction in imaging time without significant degradation in image quality. The approach brings the concept of hybrid imaging of ultrasound transmission parameters together with photoacoustic imaging, into the realm of practical application.

Reflection-mode acousto-optic imaging using plane wave ultrasound pulses.

SIGNIFICANCE: Performance of an acousto-optic imaging system is limited by light fluence rate and acoustic pressure field distributions characteristics. In optically scattering media, the former determines the achievable contrast, whereas the latter the imaging resolution. The system parameters can be shaped by changing relative positions of ultrasound (US) transducer array and optodes. However, in the case of many potential clinical applications, optimization possibilities in this regard are limited, as a sample is accessible from one side only and using a water tank for coupling is not feasible. AIM: We investigate the possibilities of improving performance of an acousto-optic imaging system operating in reflection mode geometry with linear US array in direct contact with a sample using plane wave instead of focused US pulses. APPROACH: Differences in acoustic pressure field distributions for various transducer excitation patterns were determined numerically and experimentally. Acousto-optic images of phantoms with and without optically absorbing inclusions were acquired by measuring laser speckle contrast decrease due to the light modulation by plane wave and focused US pulses with different apodization patterns. RESULTS: The residual acoustic pressure field components occupy relatively large volume and contribute to light modulation. Using nonsteered plane wave US pulses instead of focused ones allows one to mitigate their influence. It also allows one to obtain clear two-dimensional reconstructions of light fluence rate maps by shifting transducer apodization along the lateral direction. CONCLUSIONS: Using nonsteered plane wave US pulses allows one to achieve better imaging performance than with focused pulses in the assumed system geometry.