A Phosphenotron Device for Sensoric Spatial Resolution of Phosphenes within the Visual Field Using Non-Invasive Transcranial Alternating Current Stimulation.

This study presents phosphenotron, a device for enhancing the sensory spatial resolution of phosphenes in the visual field (VF). The phosphenotron employs a non-invasive transcranial alternating current stimulation (NITACS) to modulate brain activity by applying weak electrical currents to the scalp or face. NITACS's unique application induces phosphenes, a phenomenon where light is perceived without external stimuli. Unlike previous invasive methods, NITACS offers a non-invasive approach to create these effects. The study focused on assessing the spatial resolution of NITACS-induced phosphenes, crucial for advancements in visual aid technology and neuroscience. Eight participants were subjected to NITACS using a novel electrode arrangement around the eye orbits. Results showed that NITACS could generate spatially defined phosphene patterns in the VF, varying among individuals but consistently appearing within their VF and remaining stable through multiple stimulations. The study established optimal parameters for vibrant phosphene induction without discomfort and identified electrode positions that altered phosphene locations within different VF regions. Receiver Operating characteristics analysis indicated a specificity of 70.7%, sensitivity of 73.9%, and a control trial accuracy of 98.4%. These findings suggest that NITACS is a promising, reliable method for non-invasive visual perception modulation through phosphene generation.

Observation of Tissue Oxygenation Changes Using Remote Photoplesysmography with a Smartphone.

BACKGROUND: Tissue oxygenation is a critical marker of tissue status and can be used to evaluate and track wound progress, the viability of transplanted tissue, and burns. Thus, the determination of tissue oxygenation (preferably remotely) is of great importance. AIM: Explore the impact of oxygenation changes on tissue color. MATERIAL AND METHODS: The rPPG of both hands was acquired using a stand-mounted smartphone (iPhone 8) placed about 10 cm above the hands. A 60 s baseline was followed by occlusion of one arm using a cuff inflated to 200 mmHg for approximately 2 min. The cuff was then rapidly deflated, followed by a 60 s recovery period. The reference muscle oxygenation signal (SmO2) was acquired using the near-infrared contact Moxy device (Fortiori Design LLC) placed on the forearm distal to the occlusion. The data were collected on both hands of 28 healthy volunteers. RESULTS: rPPG can observe changes in tissue oxygenation, which was confirmed across 28 participants using a robust reference standard. CONCLUSION: We have an initial confirmation of the notion that rPPG can monitor changes in tissue oxygenation. However, a spectrum of rPPG and SmO2 reductions is observed, which should be explored in future work.

Remote Photoplethysmography with a High-Speed Camera Reveals Temporal and Amplitude Differences between Glabrous and Non-Glabrous Skin.

Photoplethysmography (PPG) is a noninvasive optical technology with applications including vital sign extraction and patient monitoring. However, its current use is primarily limited to heart rate and oxygenation monitoring. This study aims to demonstrate the utility of PPG for physiological investigations. In particular, we sought to demonstrate the utility of simultaneous data acquisition from several regions of tissue using remote/contactless PPG (rPPG). Specifically, using a high-speed scientific-grade camera, we collected rPPG from the hands (palmar/dorsal) of 22 healthy volunteers. Data collected through the red and green channels of the RGB CMOS sensor were analyzed. We found a statistically significant difference in the amplitude of the glabrous skin signal over the non-glabrous skin signal (1.41 ± 0.85 in the red channel and 2.27 ± 0.88 in the green channel). In addition, we found a statistically significant lead of the red channel over the green channel, which is consistent between glabrous (17.13 ± 10.69 ms) and non-glabrous (19.31 ± 12.66 ms) skin. We also found a statistically significant lead time (32.69 ± 55.26 ms in the red channel and 40.56 ± 26.97 ms in the green channel) of the glabrous PPG signal over the non-glabrous, which cannot be explained by bilateral variability. These results demonstrate the utility of rPPG imaging as a tool for fundamental physiological studies and can be used to inform the development of PPG-based devices.

Feasibility Study of Remote Contactless Perfusion Imaging with Consumer-Grade Mobile Camera.

A non-invasive, contactless, inexpensive and easy-to-operate perfusion imaging method using a consumer-grade mobile camera (iPhone 8) developed in our group can visualise blood flow in tissue. METHODS: Ischemia was induced in one hand using a blood pressure cuff inflated over the systolic blood pressure to stop the blood flow. Using an iPhone, data was collected from 5 subjects, beginning with no occlusion (a baseline), followed by one hand occluded, and then release of the occlusion to restore blood circulation. This protocol was repeated for each hand for a total of 10 videos. The data were analysed to extract the oscillating and quasi-constant components of the photoplethysmogram signal representing blood flow. In addition, we introduced a scoring parameter to reflect perfusion (i.e., perfusion score). RESULTS: The proposed perfusion score was used to create a pseudo colour map of perfusion across the protocol, demonstrating the ability to detect ischemia caused by occlusion. The difference in perfusion score was statistically significant between ischemia and baseline/recovery. CONCLUSIONS: Pilot results on healthy volunteers demonstrate the feasibility of perfusion imaging using a consumer-grade camera. A further developed method can be used to assess the viability of transplanted tissue.

Towards Development of Specular Reflection Vascular Imaging.

Specular reflection from tissue is typically considered as undesirable, and managed through device design. However, we believe that specular reflection is an untapped light-tissue interaction, which can be used for imaging subcutaneous blood flow. To illustrate the concept of subcutaneous blood flow visualization using specular reflection from the skin, we have developed a ray tracing for the neck and identified conditions under which useful data can be collected. Based on our model, we have developed a prototype Specular Reflection Vascular Imaging (SRVI) device and demonstrated its feasibility by imaging major neck vessels in a case study. The system consists of a video camera that captures a video from a target area illuminated by a rectangular LED source. We extracted the SRVI signal from 5 × 5 pixels areas (local SRVI signal). The correlations of local SRVIs to the SRVI extracted from all pixels in the target area do not appear to be randomly distributed, but rather form cohesive sub-regions with distinct boundaries. The obtained waveforms were compared with the ECG signal. Based on the time delays with respect to the ECG signal, as well as the waveforms themselves, the sub-regions can be attributed to the jugular vein and carotid artery. The proposed method, SRVI, has the potential to contribute to extraction of the diagnostic information that the jugular venous pulse can provide.

Feasibility of photoacoustic imaging for the non-invasive quality management of stored blood bags.

BACKGROUND AND OBJECTIVES: During the in vitro storage of red blood cells (RBCs), unfavourable changes (storage lesions) cause a rapid consumption of intracellular diphosphoglycerate. The latter deregulates the oxygen-haemoglobin binding potential, subsequently increasing oxygen saturation (SO2 ) and membrane degradation, transforming RBCs from biconcave discs to rigid spherical bodies (spheroechinocytes). Current laboratory techniques invasively extract RBC samples to assess the quality of red cell concentrate (RCC) units. Optical technologies could provide a means of assessing quality non-invasively. MATERIALS AND METHODS: A photoacoustic (PA) imaging technique was developed for acquiring the SO2 of blood bags non-invasively. Seven RCC units were monitored every 3-5 days until expiry (6 weeks). Measurements were validated against a conventional blood gas analyzer (BGA). Using an image flow cytometry assay, morphological profile trends were compared against the SO2 trends during blood bag storage. RESULTS: A strong correlation (r2  ≥ 0·95) was found when comparing temporal data between PA and BGA SO2 measurements. Inter-sample PA variability was found to be similar to that produced by BGA (±0·8%). A strong correlation was found to exist between the temporal changes in SO2 and relative spheroechinocyte population (0·79 ≤ r2  ≤ 0·97). CONCLUSION: This study suggests that PA imaging can non-invasively track the SO2 of stored RBCs non-invasively. By longitudinally monitoring the change in SO2 , it is possible to infer the effects of the storage lesion on RBC morphology. This non-invasive monitoring technique allows for the assessment of blood bags, without compromising sterility pre-transfusion.

Integrated catheter for simultaneous radio frequency ablation and optoacoustic monitoring of lesion progression.

Radio frequency (RF) catheter ablation is commonly used to eliminate dysfunctional cardiac tissue by heating via an alternating current. Clinical outcomes are highly dependent on careful anatomical guidance, electrophysiological mapping, and careful RF power titration during the procedure. Yet, current treatments rely mainly on the expertise of the surgeon to assess lesion formation, causing large variabilities in the success rate. We present an integrated catheter design suitable for simultaneous RF ablation and real-time optoacoustic monitoring of the forming lesion. The catheter design utilizes copper-coated multimode light guides capable of delivering both ablation current and near-infrared pulsed-laser illumination to the target tissue. The generated optoacoustic responses were used to visualize the ablation lesion formation in an ex-vivo bovine heart specimen in 3D. The presented catheter design enables the monitoring of ablation lesions with high spatiotemporal resolution while the overall therapy-monitoring approach remains compatible with commercially available catheter designs.

Mathematical Model of an Innate Immune Response to Cutaneous Wound in the Presence of Local Hypoxia.

We developed a 2D multi-agent stochastic model of interaction between cellular debris, bacteria and neutrophils in the surface cutaneous wound with local hypoxia. Bacteria, which grow logistically with a maximum carrying capacity, and debris are phagocytosed by neutrophils with probability determined by the partial pressure of oxygen in the tissue, pO 2 = 4-400 mmHg, according to the Michaelis-Menten equation with K m = 40 mmHg. The influx of new neutrophils depends linearly (k = 0.05-0.2) on the amount of (a) platelets and (b) neutrophils, which are in contact with bacteria or debris. Each activated neutrophil can accomplish a certain amount of phagocytosis, n max = 5-20, during its lifespan, T = 1-5 days. The universe of outcomes consists of (a) bacteria clearance (high k and n max ), (b) infection is not cleared by neutrophils (low k and nmax), and (c) intermittent (quasiperiodic) bursts of inflammation. In the absence of infection, phagocytosis stops within 48 h. We found that pO 2 alone did not change the type of outcome, but affects the number of recruited neutrophils and inflammation duration (in the absence of infection by up to 10 and 5 %, respectively).

Decoupling and tuning the light absorption and scattering resonances in metallic composite nanostructures.

Utilizing the localized surface plasmon resonance (LSPR) effect of metallic nanoparticles enables their usage as contrast agents in a variety of applications for medical diagnostics and treatment. Those applications can use both the very strong absorption and scattering properties of the metallic nanoparticle due to their LSPR effects. There are certain applications where domination of the scattering over absorption or vice versa would be an advantage. However, the scattering and absorption resonance peaks have practically the same spectral location for solid noble metal nanoparticles at a certain domination of one over the other. In this paper we present gold nanoparticles coated with silicon that switches the order between the scattering and the absorption magnitude at the resonance peak by up to 34% in scattering-absorption ratio and tune the plasmon resonance over the spectrum by up to 56nm. This is obtained by modifying the refractive index of the silicon coating of the nanoparticle by illuminating it with a pumping light due to the plasma dispersion effect in silicon.

Optoacoustic monitoring of cutting efficiency and thermal damage during laser ablation.

Successful laser surgery is characterized by a precise cut and effective hemostasis with minimal collateral thermal damage to the adjacent tissues. Consequently, the surgeon needs to control several parameters, such as power, pulse repetition rate, and velocity of movements. In this study we propose utilizing optoacoustics for providing the necessary real-time feedback of cutting efficiency and collateral thermal damage. Laser ablation was performed on a bovine meat slab using a Q-switched Nd-YAG laser (532 nm, 4 kHz, 18 W). Due to the short pulse duration of 7.6 ns, the same laser has also been used for generation of optoacoustic signals. Both the shockwaves, generated due to tissue removal, as well as the normal optoacoustic responses from the surrounding tissue were detected using a single broadband piezoelectric transducer. It has been observed that the rapid reduction in the shockwave amplitude occurs as more material is being removed, indicating decrease in cutting efficiency, whereas gradual decrease in the optoacoustic signal likely corresponds to coagulation around the ablation crater. Further heating of the surrounding tissue leads to carbonization accompanied by a significant shift in the optoacoustic spectra. Our results hold promise for real-time monitoring of cutting efficiency and collateral thermal damage during laser surgery. In practice, this could eventually facilitate development of automatic cut-off mechanisms that will guarantee an optimal tradeoff between cutting and heating while avoiding severe thermal damage to the surrounding tissues.

Observation of blood motion in the internal jugular vein by contact and contactless photoplethysmography during physiological testing: case studies.

Central venous pressure is an estimate of right atrial pressure and is often used to assess hemodynamic status. However, since it is measured invasively, non-invasive alternatives would be of great utility. The aim of this preliminary study was a) to investigate whether photoplethysmography (PPG) can be used to characterize venous system fluid motion and b) to find the model for venous blood volume modulations. For this purpose, we monitored the internal jugular veins using contact (cPPG) and video PPG during clinically validated physiological tests: abdominojugular test (AJT) and breath holding (BH). Video PPG and cPPG signals were captured simultaneously on the left and right sides of the neck, respectively. ECG was also captured using the same clinical monitor as cPPG. Two volunteers underwent AJT and BH with head up/down, each with: baseline (15s), experiment (15s), and recovery (15s). Video PPG was split into remote PPG (rPPG) and micromotion detection. All signal modalities were significantly affected by physiological testing. Moreover, cPPG and micromotion waveforms exhibited primary features of jugular vein waveforms and, therefore, have great potential for venous blood flow monitoring. Specifically, remote patient monitoring applications may be enabled by this methodology, facilitating physical collection without a specially trained care provider.

Non-invasive transcranial alternating current stimulation of spatially resolved phosphenes.

This study focused on the use of Non-Invasive Transcranial Alternating Current Stimulation (NITACS) to induce and map phosphenes (spark-like percepts in the visual field) in healthy individuals. The study found optimal stimulation parameters to induce reliable phosphenes without skin irritation or pain. The results suggest NITACS can be used as a tool to investigate the relationship between facial stimulation location and phosphene localization within the field of vision (FOV) and raise questions about the origin of phosphenes generated through NITACS. The outcomes of this study could serve as a source of inspiration for creating non-invasive visual aids in the future.

Remote photoplethysmography with consumer smartphone reveals temporal differences between glabrous and nonglabrous skin: Pilot in vivo study.

Photoplethysmography (PPG) is a noninvasive optical technology, with applications including vital sign extraction and patient monitoring. The PPG acquisition skin type may be of importance. Skin is either nonglabrous (~90%) or glabrous (~10%). Clinical PPG collection is typically from glabrous (fingerpad), while proliferating wearables collecting PPG, which may perform critical functions like arrythmia detection, often acquire from atypical sites. Glabrous skin has significant differences from nonglabrous, including microcirculation, yet comparisons between their PPG signals have not been well reported. Using a smartphone-based remote/contactless PPG, a pilot dataset was collected from the hands (palmar/dorsal) of five healthy volunteers. The data shows statistically significant lead time (52 ± 36 ms) of glabrous over nonglabrous. Further, a trend of glabrous amplitude increase over nonglabrous (31%) was found. Although our study has a small number of participants, these results further the characterization of PPG skin differences, and can be used to inform development of PPG-based devices.

Prospective for creating a near-field scalpel for laser surgery.

The efficient electric field enhancement due to coating a dielectric wedge by plasmon-carrying nanowires has been demonstrated numerically within the framework of the finite-difference frequency-domain method. The numerical simulations show increasing of electric field intensity in the near-field region of the dielectric wedge coated by silver nanowires in the regime of local plasmon excitation up to 100 times versus the uncoated case.

In vivo optical tissue differentiation by diffuse reflectance spectroscopy: preliminary results for tissue-specific laser surgery.

OBJECTIVES: Laser surgery requires feedback to avoid the accidental destruction of critically important tissues. It was the aim of the authors to identify different tissue types in vivo by diffuse reflectance spectroscopy to set the basis for tissue-specific control of laser surgery. METHODS: Tissue differentiation was performed on in vivo tissue of rats (skin, fat, muscle, and nerve) by diffuse reflectance spectroscopy between 350 and 650 nm. Data analysis was done using principal components analysis, followed by linear discriminant analysis (LDA). The differentiation performance was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: ROC analysis showed a tissue differentiation of 100%, with a high sensitivity of more than 99%. Only the tissue pair skin/fat showed a reduced differentiation performance and specificity. CONCLUSION: The results show the general viability of in vivo optical tissue differentiation and create a basis for the further development of a control system for tissue-specific laser surgery.

Feasibility of Specular Reflection Imaging for Extraction of Neck Vessel Pressure Waveforms.

Cardiovascular disease (CVD) is a leading cause of death worldwide and was responsible for 31% of all deaths in 2015. Changes in fluid pressures within the vessels of the circulatory system reflect the mechanical function of the heart. The jugular venous (JV) pulse waveform is an important clinical sign for assessing cardiac function. However, technology able to aid evaluation and interpretation are currently lacking. The goal of the current study was to develop a remote monitoring tool that aid clinicians in robust measurements of JV pulse waveforms. To address this need, we have developed a novel imaging modality, Specular Reflection Vascular Imaging (SRVI). The technology uses specular reflection for visualization of skin displacements caused by pressure pulsations in blood vessels. SRVI has been tested on 10 healthy volunteers. 10-seconds videos of the neck illuminated with a diffuse light source were captured at 250 fps. SRVI was able to identify and discriminate skin displacements caused by carotid artery and jugular vein pulsations to extract both carotid artery and jugular vein waveforms, making them easier to be visualized and interpreted. The method provided a 6-fold improvement in signal strength over a comparator remote PPG dataset. The current pilot study is a proof-of-concept demonstration of the potential of Specular Reflection Vascular Imaging for extraction of JV pulse waveforms.

Optical nerve detection by diffuse reflectance spectroscopy for feedback controlled oral and maxillofacial laser surgery.

BACKGROUND: Laser surgery lacks haptic feedback, which is accompanied by the risk of iatrogenic nerve damage. It was the aim of this study to investigate diffuse reflectance spectroscopy for tissue differentiation as the base of a feedback control system to enhance nerve preservation in oral and maxillofacial laser surgery. METHODS: Diffuse reflectance spectra of nerve tissue, salivary gland and bone (8640 spectra) of the mid-facial region of ex vivo domestic pigs were acquired in the wavelength range of 350-650 nm. Tissue differentiation was performed using principal component (PC) analysis followed by linear discriminant analysis (LDA). Specificity and sensitivity were calculated using receiver operating characteristic (ROC) analysis and the area under curve (AUC). RESULTS: Five PCs were found to be adequate for tissue differentiation with diffuse reflectance spectra using LDA. Nerve tissue could be differed from bone as well as from salivary gland with AUC results of greater than 88%, sensitivity of greater than 83% and specificity in excess of 78%. CONCLUSIONS: Diffuse reflectance spectroscopy is an adequate technique for nerve identification in the vicinity of bone and salivary gland. The results set the basis for a feedback system to prevent iatrogenic nerve damage when performing oral and maxillofacial laser surgery.

Diffuse reflectance spectroscopy for optical soft tissue differentiation as remote feedback control for tissue-specific laser surgery.

BACKGROUND AND OBJECTIVE: Laser surgery does not provide haptic feedback for operating layer-by-layer and thereby preserving vulnerable anatomical structures like nerve tissue or blood vessels. Diffuse reflectance spectra can facilitate remote optical tissue differentiation. It is the aim of the study to use this technique on soft tissue samples, to set a technological basis for a remote optical feedback system for tissue-specific laser surgery. MATERIALS AND METHODS: Diffuse reflectance spectra (wavelength range: 350-650 nm) of ex vivo types of soft tissue (a total of 10,800 spectra) of the midfacial region of domestic pigs were remotely measured under reduced environmental light conditions and analyzed in order to differentiate between skin, mucosa, muscle, subcutaneous fat, and nerve tissue. We performed a principal components (PC) analysis (PCA) to reduce the number of variables. Linear discriminant analysis (LDA) was utilized for classification. For the tissue differentiation, we calculated the specificity and sensitivity by receiver operating characteristic (ROC) analysis and the area under curve (AUC). RESULTS: Six PCs were found to be adequate for tissue differentiation with diffuse reflectance spectra using LDA. All of the types of soft tissue could be differentiated with high specificity and sensitivity. Only the tissue pairs nervous tissue/fatty tissue and nervous tissue/mucosa showed a decline of differentiation due to bio-structural similarity. However, both of these tissue pairs could still be differentiated with a specificity and sensitivity of more than 90%. CONCLUSIONS: Analyzing diffuse reflectance spectroscopy with PCA and LDA allows for remote differentiation of biological tissue. Considering the limitations of the ex vivo conditions, the obtained results are promising and set a basis for the further development of a feedback system for tissue-specific laser surgery.

Assessment of photobleaching during endoscopic autofluorescence imaging of the lower GI tract.

BACKGROUND AND OBJECTIVES: In autofluorescence endoscopy, the difference in the fluorescence of intrinsic fluorophores is imaged to help visualize pre-malignant lesions, as in the system evaluated here. In this, blue light is used for excitation and the green autofluorescence is normalized by the red diffuse reflectance and presented using a false color scale. The present study was designed to quantify the degree of fluorescence photobleaching induced by the excitation light during use in the colon, since significant photobleaching could lead to false interpretation of the images, particularly false-positive lesions. STUDY DESIGN: Measurements were made ex vivo and in vivo, both using the endoscopic imaging system and a separate fiberoptic spectroscopy probe in externalized rat jejunum and in patients undergoing routine colonoscopy, using exposures typical of autofluorescence endoscopic examination. RESULTS: Photobleaching could be potentially caused at blue light exposure. However, at light intensities and exposure times that are typically used in clinical practice, the average photobleaching (% loss of peak fluorescence intensity) was <1% and <6% in the rat and human tissues, respectively. Nevertheless, the range was large: from -17% to +18% in rats and -33% to +43% in patients, where negative values denote an apparent increase in fluorescence. Both the large positive and negative deviations are believed in part to be due to a measurement artifact caused by uncontrollable tissue motility. SUMMARY AND CONCLUSIONS: It is concluded that, using exposures typically encountered in clinical practice, there is minimal photobleaching during fluorescence endoscopy at exposure such as are used in the Onco-LIFE and comparable systems. The small changes in fluorescence intensity and spectral shift that do occur are not likely to be detectable by eye, and so should not impact significantly on the diagnostic accuracy of the technique.

Silicon nanoparticles produced by femtosecond laser ablation in water as novel contamination-free photosensitizers.

We report the synthesis of novel inorganic contamination-free photosensitizers based on colloidal silicon nanoparticles prepared by laser ablation in pure deionized water. We show that such nanoparticles are capable of generating singlet oxygen ((1)O(2)) under laser irradiation with a yield estimated at 10% of that of photofrin, which makes them a potential candidate for therapeutics, antiseptics, or disinfectants. We also discuss a model of (1)O(2) generation and the possibility for optimizing its release. Potential advantages of such novel inorganic photosensitizers include stable and nonphotobleaching (1)O(2) release, easy removal, and low dark toxicity.