Non-invasive Optical Technology Research Articles

Reference Ranges for Regional Cerebral Oxygen Saturation with Masimo O3® after Birth and Differences with Other Devices.

Cerebral oximetry using near-infrared spectroscopy (NIRS) is a noninvasive optical technology widely used in neonatology. The present study aimed to define reference ranges for cerebral tissue oxygen saturation (crSO2) with a new four-wavelength NIRS device, Masimo O3® oximeter, during immediate transition after birth and compare values with those obtained previously with NIRO 200NX®. This was a prospective observational study using Masimo O3 device to measure crSO2 and regional cerebral fractional tissue oxygen extraction (cFTOE) in healthy term newborns delivered by primary cesarean section, during the 15 minutes after cord clamping. The neonates who required any medical support were excluded. The NIRS sensor was placed on the right forehead. Peripheral oxygen saturation and heart rate were continuously measured by pulse oximetry. Previous studies which established centiles for crSO2 with NIRO 200NX were used for comparison. A total of 44 newborns were included. The median crSO2 and cFTOE (interquartile range) at 2, 5, and 7 minutes was 54% (49-54), 71% (64-86), and 79% (73-84) and 0,25 (0,18-0,33), 0,19 (0,15-0,23), and 0,16 (0,12-0,21), respectively, with no further changes afterwards. The crSO2 measurements were significantly higher with Masimo O3 compared with NIRO-200NX. The present observational study presented reference ranges for crSO2 and cFTOE measured with Masimo O3 oximeter during the immediate neonatal transition. Values obtained with O3 were higher than those obtained with other oximeters. For this reason, crSO2 is device-specific so there must be known reference values for each oximeter to define therapeutic interventions based on crSO2 and assess cerebral oxygenation in clinical studies. · Masimo O3 uses four wavelengths to measure regional oxygen saturation value.. · O3 values of crSO2 and cFTOE differ with other neonatal oximeters at birth.. · Knowledge of reference range of O3 at birth is essential to guide resuscitation..

FRI606 Changes In The Pedal Microcirculation Of Diabetic Patients With Poor Glycemic Control Detected Using Non Invasive Optical Imaging

Abstract Disclosure: I.K. Bolakale-Rufai: None. S. French: None. J.C. Arias: None. K. Concha-Moore: None. T. Tan: None. D.G. Armstrong: None. A. Mazhar: Employee; Self; Modulim. C.C. Weinkauf: None. Background: Microvascular disease (MVD) describes systemic changes in the small vessels (∼100 υm diameter) that impair tissue oxygenation and perfusion. Emerging evidence has shown that MVD (which is prevalent in diabetics) is clinically relevant as it synergistically acts with peripheral arterial disease to increase the risk of limb loss by 22.7-fold. Poor glycemic control has been linked to clinical microvascular disease (nephropathy and retinopathy) However, the direct impact of poor glycemic control on the microcirculation of the feet is unknown as there are currently no standardized non-invasive methods used clinically to assess and quantify MVD of the lower limbs. Spatial frequency domain imaging (SFDI) is a novel non-invasive optical technology that can detect and quantify microvascular disease of the foot by measuring the amount of hemoglobin(HbT1) in the capillaries of the superficial dermis up to 1-2mm deep and oxygenation (StO2) in the dermal micro-circulation. We hypothesize that poor glycemic control in DM affects pedal microcirculation and the changes can be detected using the SFDI technology. Methods: 307 patients (600 lower extremity limbs) were prospectively enrolled at a single institution, Banner University Medicine, Tucson, AZ from 2016- 2023. Diabetic patients were stratified into three groups based on their HbA1c level: ≤6.7%, 6.8-9.9%, and ≥10%. Mann U Whitney test and Spearman rank correlation were used in testing the association between HbA1C and SFDI-metrics with p<.05 considered as statistical significance. Results: We included 230 lower limbs belonging to diabetic patients. The mean age of the patients was 61.7 years. Clinical neuropathy and retinopathy were found in 79% and 30.7% of patients, respectively. SFDI-derived biomarkers of microcirculation were compared among diabetics categorized by HbA1C levels. We observed a significant reduction in papillary dermal perfusion (HbT1) as the glycemic control (HbA1C) of the patients worsened (p<0.001). Although tissue oxygenation (StO2) was not statistically different across diabetic groups, the St02/HbT1 ratio which represents the ratio of tissue oxygenation to perfusion, increased with elevated HbA1C levels. This indicated that poorly controlled diabetics had less oxygen being extracted from their poorly perfused micro-circulation. Conclusions: This study suggests that poor glycemic control directly affects the microcirculation of the feet in diabetic patients. The SFDI technology is a promising noninvasive tool to evaluate microvascular disease of the feet and potentially may be utilized clinically to stratify diabetic patients at risk for foot ulceration or limb loss based on glycemic control over time. Presentation: Friday, June 16, 2023

Microendoscopy in vivo for the pathological diagnosis of cervical precancerous lesions and early cervical cancer

BackgroundCervical cancer is an important public health problem. Conventional colposcopy is inefficient in the diagnosis of cervical lesions and massive biopsies result in trauma. There is an urgent need for a new clinical strategy to triage women with abnormal cervical screening results immediately and effectively. In this study, the high-resolution microendoscopy combined with methylene blue cell staining technology was used to perform real-time in vivo imaging of the cervix for the first time.MethodsA total of 41 patients were enrolled in the study. All patients underwent routine colposcopy and cervical biopsy, and high-resolution images of methylene blue-stained cervical lesions were obtained in vivo using microendoscopy. The cell morphological features of benign and neoplastic cervical lesions stained with methylene blue under microendoscopy were analyzed and summarized. The microendoscopy and histopathology findings of the high-grade squamous intraepithelial lesion (HSIL) and more severe lesions were compared.ResultsThe overall consistency of microendoscopy diagnosis with pathological diagnosis was 95.12% (39/41). Diagnostic cell morphological features of cervicitis, low-grade squamous intraepithelial lesion (LSIL), HSIL, adenocarcinoma in situ, and invasive cancer were clearly demonstrated in methylene blue stained microendoscopic images. In HSIL and more severe lesions, microendoscopic methylene blue cell staining technology can show the microscopic diagnostic features consistent with histopathology.ConclusionsThis study was an initial exercise in the application of the microendoscopy imaging system combined with methylene blue cell staining technology to cervical precancerous lesions and cervical cancer screening. The results provided the basis for a novel clinical strategy for triage of women with abnormal cervical screening results using in vivo non-invasive optical diagnosis technology.

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.

Developments and Clinical Applications of Noninvasive Optical Technologies for Skin Cancer Diagnosis.

Skin cancer has shown a sharp increase in prevalence over the past few decades and currently accounts for one-third of all cancers diagnosed. The most lethal form of skin cancer is melanoma, which develops in 4% of individuals. The rising prevalence and increased number of fatalities of skin cancer put a significant burden on healthcare resources and the economy. However, early detection and treatment greatly improve survival rates for patients with skin cancer. Since the rising rates of both the incidence and mortality have been particularly noticeable with melanoma, significant resources have been allocated to research aimed at earlier diagnosis and a deeper knowledge of the disease. Dermoscopy, reflectance confocal microscopy, optical coherence tomography, multiphoton-excited fluorescence imaging, and dermatofluorescence are only a few of the optical modalities reviewed here that have been employed to enhance noninvasive diagnosis of skin cancer in recent years. This review article discusses the methodology behind newly emerging noninvasive optical diagnostic technologies, their clinical applications, and advantages and disadvantages of these techniques, as well as the potential for their further advancement 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.

Usability Evaluation of a Noninvasive Neutropenia Screening Device (PointCheck) for Patients Undergoing Cancer Chemotherapy: Mixed Methods Observational Study.

Patients with cancer undergoing cytotoxic chemotherapy face an elevated risk of developing serious infection as a consequence of their treatment, which lowers their white blood cell count and, more specifically, their absolute neutrophil count. This condition is known as neutropenia. Neutropenia accompanied by a fever is referred to as febrile neutropenia, a common side effect of chemotherapy with a high mortality rate. The timely detection of severe neutropenia (<500 absolute neutrophil count/μL) is critical in detecting and managing febrile neutropenia. Current methods rely on blood draws, which limit them to clinical settings and do not allow frequent or portable monitoring. In this study, we demonstrated the usability of PointCheck, a noninvasive device for neutropenia screening, in a simulated home environment without clinical supervision. PointCheck automatically performs microscopy through the skin of the finger to image the blood flowing through superficial microcapillaries and enables the remote monitoring of neutropenia status, without requiring venipuncture. This study aimed to evaluate the usability of PointCheck, a noninvasive optical technology for screening severe neutropenia, with the goal of identifying potential user interface, functionality, and design issues from the perspective of untrained users. We conducted a multicenter study using quantitative and qualitative approaches to evaluate the usability of PointCheck across 154 untrained participants. We used a mixed method approach to gather usability data through user testing observations, a short-answer qualitative questionnaire, and a standardized quantitative System Usability Scale (SUS) survey to assess perceived usability and satisfaction. Of the 154 participants, we found that 108 (70.1%) scored above 80.8 on the SUS across all sites, with a mean SUS score of 86.1 across all sites. Furthermore, the SUS results indicated that, out of the 151 users who completed the SUS survey, 145 (96%) found that they learned how to use PointCheck very quickly, and 141 (93.4%) felt very confident when using the device. We have shown that PointCheck, a novel technology for noninvasive, home-based neutropenia detection, can be safely and effectively operated by first-time users. In a simulated home environment, these users found it easy to use, with a mean SUS score of 86.1, indicating an excellent perception of usability and placing this device within the top tenth percentile of systems evaluated for usability by the SUS. ClinicalTrials.gov NCT04448314; https://clinicaltrials.gov/ct2/show/NCT04448314 (Hospital Universitario 12 de Octubre registration) and NCT04448301; https://clinicaltrials.gov/ct2/show/NCT04448301 (Boston Medical Center registration).

A Handheld Fiber-Optic Probe to Enable Optical Coherence Tomography of Oral Soft Tissue.

This study presents a highly miniaturized, handheld probe developed for rapid assessment of soft tissue using optical coherencetomography (OCT). OCT is a non-invasive optical technology capable of visualizing the sub-surface structural changes that occur in soft tissue disease such as oral lichen planus. However, usage of OCT in the oral cavity has been limited, as the requirements for high-quality optical scanning have often resulted in probes that are heavy, unwieldy and clinically impractical. In this paper, we present a novel probe that combines an all-fiber optical design with a light-weight magnetic scanning mechanism to provide easy access to the oral cavity. The resulting probe is approximately the size of a pen (10 mm × 140 mm) and weighs only 10 grams. To demonstrate the feasibility and high image quality achieved with the probe, imaging was performed on the buccal mucosa and alveolar mucosa during routine clinical assessment of six patients diagnosed with oral lichen planus. Results show the loss of normal tissue structure within the lesion, and contrast this with the clear delineation of tissue layers in adjacent inconspicuous regions. The results also demonstrate the ability of the probe to acquire a three-dimensional data volume by manually sweeping across the surface of the mucosa. The findings of this study show the feasibility of using a small, lightweight probe to identify pathological features in oral soft tissue.

Influence of source-detector separation on diffuse correlation spectroscopy measurements of cerebral blood flow with a multilayered analytical model.

.Significance: Diffuse correlation spectroscopy (DCS) is an emerging noninvasive optical technology for bedside monitoring of cerebral blood flow. However, extracerebral hemodynamics can significantly influence DCS estimations of cerebral perfusion. Advanced analytical models can be used to remove the contribution of extracerebral hemodynamics; however, these models are highly sensitive to measurement noise. There is a need for an empirical determination of the optimal source–detector separation(s) (SDS) that improves the accuracy and reduces sensitivity to noise in the estimation of cerebral blood flow with these models.Aim: To determine the influence of SDS on solution uniqueness, measurement accuracy, and sensitivity to inaccuracies in model parameters when using the three-layer model to estimate cerebral blood flow with DCS.Approach: We performed a series of in silico simulations on samples spanning a wide range of physiologically-relevant layer optical properties, thicknesses, and flow. Data were simulated at SDS ranging from 0.5 to 3.0 cm using the three-layer solution to the correlation diffusion equation (with and without noise added) and using three-layer slab Monte Carlo simulations. We quantified the influence of SDS on uniqueness, accuracy, and sensitivity to inaccuracies in model parameters using the three-layer inverse model.Results: Two SDS are required to ensure a unique solution of cerebral blood flow index (CBFi). Combinations of 0.5/1.0/1.5 and 2.5 cm provide the optimal choice for balancing the depth penetration with signal-to-noise ratio to minimize the error in CBFi across a wide range of samples with varying optical properties, thicknesses, and dynamics.Conclusions: These results suggest that the choice of SDS is critical for minimizing the estimated error of cerebral blood flow when using the three-layer model to analyze DCS data.

Short Circuit and Broken Rotor Faults Severity Discrimination in Induction Machines Using Non-invasive Optical Fiber Technology

Multiple techniques continue to be simultaneously utilized in the condition monitoring and fault detection of electric machines, as there is still no single technique that provides an all-round solution to fault finding in these machines. Having various machine fault-detection techniques is useful in allowing the ability to combine two or more in a manner that will provide a more comprehensive application-dependent condition-monitoring solution; especially, given the increasing role these machines are expected to play in man’s transition to a more sustainable environment, where many more electric machines will be required. This paper presents a novel non-invasive optical fiber using a stray flux technique for the condition monitoring and fault detection of induction machines. A giant magnetostrictive transducer, made of terfenol-D, was bonded onto a fiber Bragg grating, to form a composite FBG-T sensor, which utilizes the machines’ stray flux to determine the internal condition of the machine. Three machine conditions were investigated: healthy, broken rotor, and short circuit inter-turn fault. A tri-axial auto-data-logging flux meter was used to obtain stray magnetic flux measurements, and the numerical results obtained with LabView were analyzed in MATLAB. The optimal positioning and sensitivity of the FBG-T sensor were found to be transverse and 19.3810 pm/μT, respectively. The experimental results showed that the FBG-T sensor accurately distinguished each of the three machine conditions using a different order of magnitude of Bragg wavelength shifts, with the most severe fault reaching wavelength shifts of hundreds of picometres (pm) compared to the healthy and broken rotor conditions, which were in the low-to-mid-hundred and high-hundred picometre (pm) range, respectively. A fast Fourier transform (FFT) analysis, performed on the measured stray flux, revealed that the spectral content of the stray flux affected the magnetostrictive behavior of the magnetic dipoles of the terfenol-D transducer, which translated into strain on the fiber gratings.

Biopsy-free in vivo virtual histology of skin using deep learning

An invasive biopsy followed by histological staining is the benchmark for pathological diagnosis of skin tumors. The process is cumbersome and time-consuming, often leading to unnecessary biopsies and scars. Emerging noninvasive optical technologies such as reflectance confocal microscopy (RCM) can provide label-free, cellular-level resolution, in vivo images of skin without performing a biopsy. Although RCM is a useful diagnostic tool, it requires specialized training because the acquired images are grayscale, lack nuclear features, and are difficult to correlate with tissue pathology. Here, we present a deep learning-based framework that uses a convolutional neural network to rapidly transform in vivo RCM images of unstained skin into virtually-stained hematoxylin and eosin-like images with microscopic resolution, enabling visualization of the epidermis, dermal-epidermal junction, and superficial dermis layers. The network was trained under an adversarial learning scheme, which takes ex vivo RCM images of excised unstained/label-free tissue as inputs and uses the microscopic images of the same tissue labeled with acetic acid nuclear contrast staining as the ground truth. We show that this trained neural network can be used to rapidly perform virtual histology of in vivo, label-free RCM images of normal skin structure, basal cell carcinoma, and melanocytic nevi with pigmented melanocytes, demonstrating similar histological features to traditional histology from the same excised tissue. This application of deep learning-based virtual staining to noninvasive imaging technologies may permit more rapid diagnoses of malignant skin neoplasms and reduce invasive skin biopsies.

Accuracy of diffuse correlation spectroscopy measurements of cerebral blood flow when using a three-layer analytical model.

Diffuse correlation spectroscopy (DCS) is a non-invasive optical technology for the assessment of an index of cerebral blood flow (CBFi). Analytical methods that model the head as a three-layered medium (i.e., scalp, skull, brain) are becoming more commonly used to minimize the contribution of extracerebral layers to the measured DCS signal in adult cerebral blood flow studies. However, these models rely on a priori knowledge of layer optical properties and thicknesses. Errors in these values can lead to errors in the estimation of CBFi, although the magnitude of this influence has not been rigorously characterized. Herein, we investigate the accuracy of measuring cerebral blood flow with a three-layer model when errors in layer optical properties or thicknesses are present. Through a series of in silico experiments, we demonstrate that CBFi is highly sensitive to errors in brain optical properties and skull and scalp thicknesses. Relative changes in CBFi are less sensitive to optical properties but are influenced by errors in layer thickness. Thus, when using the three-layer model, accurate estimation of scalp and skull thickness are required for reliable results.

When the human brain goes diving: using near-infrared spectroscopy to measure cerebral and systemic cardiovascular responses to deep, breath-hold diving in elite freedivers.

Continuous measurements of haemodynamic and oxygenation changes in free living animals remain elusive. However, developments in biomedical technologies may help to fill this knowledge gap. One such technology is continuous-wave near-infrared spectroscopy (CW-NIRS)-a wearable and non-invasive optical technology. Here, we develop a marinized CW-NIRS system and deploy it on elite competition freedivers to test its capacity to function during deep freediving to 107 m depth. We use the oxyhaemoglobin and deoxyhaemoglobin concentration changes measured with CW-NIRS to monitor cerebral haemodynamic changes and oxygenation, arterial saturation and heart rate. Furthermore, using concentration changes in oxyhaemoglobin engendered by cardiac pulsation, we demonstrate the ability to conduct additional feature exploration of cardiac-dependent haemodynamic changes. Freedivers showed cerebral haemodynamic changes characteristic of apnoeic diving, while some divers also showed considerable elevations in venous blood volumes close to the end of diving. Some freedivers also showed pronounced arterial deoxygenation, the most extreme of which resulted in an arterial saturation of 25%. Freedivers also displayed heart rate changes that were comparable to diving mammals both in magnitude and patterns of change. Finally, changes in cardiac waveform associated with heart rates less than 40 bpm were associated with changes indicative of a reduction in vascular compliance. The success here of CW-NIRS to non-invasively measure a suite of physiological phenomenon in a deep-diving mammal highlights its efficacy as a future physiological monitoring tool for human freedivers as well as free living animals. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

Lower Limb Dynamic Activity Significantly Reduces Foot Skin Perfusion: Exploring Data with Different Optical Sensors in Age-Grouped Healthy Adults

Introduction: The human lower limb is widely used as a model to study in vivo microcirculatory physiology and pathophysiology. It is a preferential target for critical comorbidities (overweight, diabetes, and peripheral vascular disease). Movement and activity are consistently regarded as beneficial, but the related adaptive physiology is still poorly understood. Our goal was to better identify the foot microcirculatory changes after a regular walking gait activity in healthy subjects of different ages. Methods: Twelve healthy participants of both sexes, with normal BMI and Ankle-Brachial Index, were selected and grouped according to age – group I (21.0 ± 1 y.o.) and group II (55.8 ± 3 y.o.). The protocol involved 2 phases of 5-min duration each – phase 1, a static standing position, and phase 2, 5-min walking with a comfortable pace on a pre-established circuit. Perfusion changes were assessed in the dorsal region of both feet before (baseline, phase 1) and after (phase 2) the gait period by noninvasive optical technologies – laser Doppler flowmetry (LDF), photoplethysmography, and polarized spectroscopy (PSp). Comparative statistics were performed with a 95% confidence level. Results: All instruments detected an asymmetric nonsignificant perfusion between right and left feet during rest in all participants with values in females consistently lower than men. Older participants exhibited lower baseline values than the younger group. Gait evoked a perfusion reduction in all participants relative to phase 1 detected with all technologies, with statistically significant changes recorded with LDF (group I, p = 0.033, and group II, p = 0.028) and PSp (group II, p = 0.041). Furthermore, LDF revealed that gait significantly reduced perfusion velocity in the older group (p = 0.003). Corresponding changes in the younger group were present but discrete. Recovery to baseline levels was also slower in the older group. Discussion/Conclusions: Our results confirm that perfusion is age dependent and demonstrate the clinical relevance of simple dynamic activities such as gait. This reduction of the dorsal foot perfusion occurs in depth, being more pronounced with the movement intensity, suggesting a wide application potential in early diagnostics as for rehabilitation.

Non-invasive Optical Technical Identification of Red Pigments on Chinese Paper Notes

Red pigments with bright colors were widely used in ancient Chinese painted pottery, books, antiques, calligraphy, and paintings. Herein, red pigments of traditional paper notes were investigated by non-invasive optical technology in order to enrich the Chinese historical pigments knowledge base. The results of laser Raman spectroscopy tests on five paper notes clearly identified the inorganic mineral pigments including ocher and cinnabar. Infrared spectroscopy measurements indicated that an artificial synthetic magenta was employed as the organic pigment. Inorganic and organic red pigments were applied together on the same samples 2 and 5 which can be speculated to serve an anti-counterfeiting function. In addition, SEM-EDS analysis of sample 5 clearly showed that the red pigment was composed of lead oxides and ZnS was added as color modulator. Combined with the abovementioned non-invasive techniques, analysis of printed pigments can provide a feasible method to authenticate and conserve paper notes.

On a Feature Extraction and Classification Study for PPG Signal Analysis

Photoplethysmography (PPG) is a low cost, non-invasive optical technology to detect the volumetric changes of blood circulation at the surface of skin. While the medical indication of components of PPG signals in the form of pulse wave are not yet fully understood, it is vastly agreed that they carry valuable pathophysiological information related to the cardiovascular system. Going beyond just dealing with frequency and time domain features of the pulse wave, as well as the first and second derivatives of the wave commonly seen in many of the relevant work, we applied a K-MEANS improved algorithm for feature extraction based on selected time domain parameters: K1 (systolic area), K2 (diastolic area) and K (entire pulse wave area). The extracted characteristic waveforms under the same light intensity could achieve average confidence level of 90% or higher. The stationary wavelet transform was adopted to further analyze the characteristic waveform by calculating the wavelet entropy; We then trained a Probability Neural Network (PNN) model using the wavelet entropy and other time domain characteristic parameters. It is found that the trained PNN model performs well in analyzing characteristic waveform to distinguish between health condition and severe arterial stenosis.

Hemodynamics of Prefrontal Cortex in Ornithine Transcarbamylase Deficiency: A Twin Case Study.

Ornithine transcarbamylase deficiency (OTCD) is the most common form of urea cycle disorder characterized by the presence of hyperammonemia (HA). In patients with OTCD, HA is known to cause impairments in domains of executive function and working memory. Monitoring OTCD progression and investigating neurocognitive biomarkers can, therefore, become critical in understanding the underlying brain function in a population with OTCD. We used functional near infrared spectroscopy (fNIRS) to examine the hemodynamics of prefrontal cortex (PFC) in a fraternal twin with and without OTCD. fNIRS is a non-invasive and wearable optical technology that can be used to assess cortical hemodynamics in a realistic clinical setting. We quantified the hemodynamic variations in total-hemoglobin as assessed by fNIRS while subjects performed the N-back working memory (WM) task. Our preliminary results showed that the sibling with OTCD had higher variation in a very low frequency band (<0.03 Hz, related to mechanism of cerebral autoregulation) compared to the control sibling. The difference between these variations was not as prominent in the higher frequency band, indicating the possible role of impaired autoregulation and cognitive function due to presence of HA. We further examined the functional connectivity in PFC, where the OTCD sibling showed lower interhemispheric functional connectivity as the task load increased. Our pilot results are the first to show the utility of fNIRS in monitoring OTCD cortical hemodynamics, indicating the possibility of inefficient neurocognitive function. This study provides a novel insight into the monitoring of OTCD focusing on the contribution of physiological process and neurocognitive function in this population.

Oxygen Monitor to Study Vascularization of Medical Devices

Prevascularized medical devices can improve cell therapy. Such devices may replace whole organ transplantation with hosting only the necessary therapeutic cells. We have developed a noninvasive optical technology to study the vascularization into such medical devices. In our technique, oxygen partial pressure within a device is monitored by Oxygen Sensitive Tubes (OSTs), comprising oxygen permeable silicone tubing with inner luminal surfaces coated by an oxygen-sensitive porphyrin dye. OSTs were placed within a PDMS device and transplanted into the subcutaneous space of athymic nude mice. An optical probe placed over the skin excites the OSTs with a pulse of light and detects the luminescent lifetime of emitted light, which is uniquely related to oxygen partial pressure. Furthermore, we developed a Dynamic Inhalation Gas Test (DIGT) to determine the oxygen transport rate between the microvasculature and the device. DIGT works by monitoring oxygen partial pressure in a device following a step change in inhaled-gas oxygen content. We report DIGT oxygen dynamics measured intermittently over eight weeks. Our study shows DIGT dynamics are unique to each implant, supporting the important role of the host tissue response in the availability of oxygen over time.

Emerging Optical Techniques for the Diagnosis of Onychomycosis

Onychomycosis is the most prevalent nail infection. Although it is not a life-threatening condition, it impacts the quality of life for many patients and often imposes a challenging diagnostic problem. The causative agents are dermatophytes, yeasts and non-dermatophytic moulds. Accurate and early diagnosis, including the identification of the causative species, is the key factor for rational therapy. Still, early diagnosis is not optimal as the current gold standard for the differentiation of the infectious agents is culture-based approaches. On the other hand, noninvasive optical technologies may enable differential diagnosis of nail pathologies including onychomycosis. When light penetrates and propagates along the nail tissue, it interacts in different ways with the components of either infected or healthy nail segments, providing a wealth of diagnostic information upon escaping the tissue. This review aims to assess alternative optical techniques for the rapid diagnosis of onychomycosis with a potential to monitor therapeutic response or even identify the fungal agent non-invasively and in real time in a clinical setting.

Validation of a Second-Generation Near-Infrared Spectroscopy Monitor in Children With Congenital Heart Disease.

Cerebral oximetry using near-infrared spectroscopy is a noninvasive optical technology to detect cerebral hypoxia-ischemia and develop interventions to prevent and ameliorate hypoxic brain injury. Cerebral oximeters are calibrated and validated by comparison of the near-infrared spectroscopy-measured cerebral O2 saturation (SctO2) to a "field" or reference O2 saturation (REF CX) calculated as a weighted average from arterial and jugular bulb oxygen saturations. In this study, we calibrated and validated the second-generation, 5 wavelength, FORE-SIGHT Elite with the medium sensor (source-detector separation 12 and 40 mm) for measurement of SctO2 in children with congenital heart disease. After institutional review board approval and written informed consent, 63 children older than 1 month and ≥2.5 kg scheduled for cardiac catheterization were enrolled. Self-adhesive FORE-SIGHT Elite medium sensors were placed on the right and left sides of the forehead. Blood samples for calculation of REF CX were drawn simultaneously from the aorta or femoral artery and the jugular bulb before (T1) and shortly after (T2) baseline hemodynamic measurements. FORE-SIGHT Elite SctO2 measurements were compared to the REF CX (REF CX = [0.3 SaO2] + [0.7 SjbO2]) using Deming regression, least squares linear regression, and Bland-Altman analysis. Sixty-one subjects (4.5 [standard deviation 4.4] years of age; 17 [standard deviation 13] kg, male 56%) completed the study protocol. Arterial oxygen saturation ranged from 64.7% to 99.1% (median 96.0%), jugular bulb venous oxygen saturation from 34.1% to 88.1% (median 68.2%), the REF CX from 43.8% to 91.4% (median 76.9%), and the SctO2 from 47.8% to 90.8% (median 76.3%). There was a high degree of correlation in SctO2 between the right and left sensors at a given time point (within subject between sensor correlation r = 0.91 and 95% confidence interval [CI], 0.85-0.94) or between T1 and T2 for the right and left sensors (replicates, within subject between time point correlation r = 0.95 and 95% CI, 0.92-0.96). By Deming regression, the estimated slope was 0.966 (95% CI, 0.786-1.147; P = .706 for testing against null hypothesis of slope = 1) with a y intercept of 2.776 (95% CI, -11.102 to 16.654; P = .689). The concordance correlation coefficient was 0.873 (95% CI, 0.798-0.922). Bland-Altman analysis for agreement between SctO2 and REF CX that accounted for repeated measures (both in times and sensors) found a bias of -0.30% (95% limits of agreement: -10.56% to 9.95%). This study calibrated and validated the FORE-SIGHT Elite tissue oximeter to accurately measure SctO2 in pediatric patients with the medium sensor.