Diffuse Reflectance Spectroscopy System Research Articles

Noninvasive hemoglobin quantification across different cohorts using a wearable diffuse reflectance spectroscopy system.

Quantifying hemoglobin is vital yet invasive through blood draws. We developed a wearable diffuse reflectance spectroscopy device comprising control and sensor boards with photodiodes and light-emitting diodes to noninvasively determine hemoglobin. Neural networks enabled recovery of optical parameters for chromophore fitting to calculate hemoglobin. Testing healthy and elderly subjects revealed strong correlation (r=0.9) between our system and invasive methods after data conversion. Bland-Altman analysis demonstrated tight 95% limits of agreement from -1.98 to 1.98 g/dL between the DRS and invasive hemoglobin concentrations. By spectroscopically isolating hemoglobin absorption, interference from melanin was overcome. Our device has the potential for future integration into wearable technology, enabling hemoglobin level tracking.

Evaluation of NIR LED and laser diode as a light source in diffuse reflectance spectroscopy system for intravenous fluid infiltration detection under dermis layer of skin phantom

This study evaluates the performance of near-infrared (NIR) LED and laser diode as light sources for detecting intravenous fluid (IV) infiltration under dermis layer of skin phantom using diffuse reflectance spectroscopy (DRS). A commercially available and relatively cheap NIR LED (950 nm) and laser diode (980 nm) were employed, and a laboratory DRS system was transformed into a portable prototype with Internet of Things (IoT) integration for smartphone data acquisition. The results demonstrate that both laboratory and prototype DRS systems successfully detected IV fluid as low as 0.1 ml beneath the dermis layer of skin phantom. Notably, the DRS sensitivity using the laser diode light source surpassed that of the LED, both in the laboratory and prototype DRS systems. These findings highlight the high potential of NIR laser diodes in DRS systems for highly sensitive infiltration detection.

Noninvasive transcutaneous bilirubin measurement in adults using skin diffuse reflectance.

Accurate measurement of bilirubin concentration in adults is crucial for the diagnosis and management of liver and biliary tract diseases. Traditional methods relying on central laboratory testing pose challenges such as invasiveness, patient discomfort, and time consumption. Non-invasive alternatives have been explored, but their applicability to adult populations remains uncertain. This study aimed to develop and validate a portable non-invasive optical system based on spatially resolved diffuse reflectance spectroscopy (DRS) specifically tailored for adult transcutaneous bilirubin measurement. Forty-two adult patients with various underlying conditions were included in the study. Comparisons between transcutaneous bilirubin values measured by the DRS system and total serum bilirubin concentrations obtained through blood tests revealed strong correlations, particularly at the neck (r = 0.872) and the medial side of the right upper arm (r = 0.940). Bland-Altman analyses demonstrated substantial agreement between the transcutaneous bilirubin values and total serum bilirubin concentrations. The results highlight the potential of the non-invasive DRS system as a convenient and reliable tool for monitoring bilirubin values in adults.

A Clinical Study to Assess Diffuse Reflectance Spectroscopy with an Auto-Calibrated, Pressure-Sensing Optical Probe in Head and Neck Cancer.

Diffuse reflectance spectroscopy (DRS) is a powerful tool for quantifying optical and physiological tissue properties such as hemoglobin oxygen saturation and vascularity. DRS is increasingly used clinically for distinguishing cancerous lesions from normal tissue. However, its widespread clinical acceptance is still limited due to uncontrolled probe-tissue interface pressure that influences reproducibility and introduces operator-dependent results. In this clinical study, we assessed and validated a pressure-sensing and automatic self-calibration DRS in patients with suspected head and neck squamous cell carcinoma (HNSCC). The clinical study enrolled nineteen patients undergoing HNSCC surgical biopsy procedures. Patients consented to evaluation of this improved DRS system during surgery. For each patient, we obtained 10 repeated measurements on one tumor site and one distant normal location. Using a Monte Carlo-based model, we extracted the hemoglobin saturation data along with total hemoglobin content and scattering properties. A total of twelve cancer tissue samples from HNSCC patients and fourteen normal tissues were analyzed. A linear mixed effects model tested for significance between repeated measurements and compared tumor versus normal tissue. These results demonstrate that cancerous tissues have a significantly lower hemoglobin saturation compared to normal controls (p < 0.001), which may be reflective of tumor hypoxia. In addition, there were minimal changes over time upon probe placement and repeated measurement, indicating that the pressure-induced changes were minimal and repeated measurements did not differ significantly from the initial value. This study demonstrates the feasibility of conducting optical spectroscopy measurements on intact lesions prior to removal during HNSCC procedures, and established that this probe provides diagnostically-relevant physiologic information that may impact further treatment.

Handheld diffuse reflectance spectroscopy system for noninvasive quantification of neonatal bilirubin and hemoglobin concentrations: a pilot study.

The prevalence rate of neonatal jaundice can reach 80%, of which 5% may develop dangerous hemolytic jaundice. The blood test for obtaining bilirubin and hemoglobin concentration is the gold standard for diagnosing hemolytic jaundice; however, frequently drawing blood from jaundice neonates for the screening purpose is not practical. We have developed a handheld diffuse reflectance spectroscopy system to noninvasively determine the bilirubin and hemoglobin levels in neonates. Our study showed that the correlation coefficients were 0.95 and 0.80 for bilirubin and hemoglobin between the results from the blood tests and our handheld system, respectively. This handheld system could be an effective tool for screening hemolytic jaundice.

Investigating the clinical implication of corneometer and mexameter readings towards objective, efficient evaluation of psoriasis vulgaris severity.

In clinical settings, although Psoriasis Area and Severity Index (PASI) scoring system can provide a quick visual assessment of the severity of psoriasis vulgaris, there is still a strong demand for higher efficiency and accuracy in quantifying the inflammation status of psoriatic lesions. Currently, there are already commercial systems, such as the Courage + Khazaka Corneometer and Mexameter that measure skin capacitance and optical reflectance, for conveniently quantifying the status of skin barrier function and erythema of skin. Despite numerous comparisons of the Courage + Khazaka system with the PASI scoring system, they are rarely compared on parity with diffuse reflectance spectroscopy (DRS) based systems. In this study, we employed a custom-built DRS system shown to be able to determine the skin water-protein binding status and the hemoglobin concentration, and we performed cross-validation of the DRS measurement results with the readings derived from the Corneometer and Mexameter as well as a portion of the PASI scores. Our results revealed that the erythema readings from the Mexameter were a good representation of skin oxygenated hemoglobin but not the deoxygenated hemoglobin. On the other hand, the dermatologists recruited in this study were inclined to rate higher scores on the “erythema” category as skin’s deoxygenated hemoglobin level was higher. Thus, the Mexameter derived erythema readings may not be coherent with the PASI erythema scores. Further, the Corneometer derived skin capacitance readings were well correlated to the PASI “desquamation” and “thickness” scores, while the PASI “desquamation” evaluation was a dominating factor contributing to the DRS deduced water-protein binding status. We conclude that the DRS method could be a valuable addition to existing skin capacitance/reflectance measurement systems and the PASI scoring system toward achieving a more efficient and objective clinical psoriasis vulgaris severity evaluation.

Accurate nondestructive prediction of soluble solids content in citrus by near‐infrared diffuse reflectance spectroscopy with characteristic variable selection

This study employs a near-infrared diffuse reflectance spectroscopy (NIRDRS) system to accurate nondestructive determine citrus soluble solids content (SSC). The penetration experiment results showed that the interference of thick peel is large and NIRDRS light has the ability to penetrate the peel to a certain extent. Partial least squares with different characteristic variable selection methods were used to establish the quantitative model of SSC. The results demonstrated that characteristic variable selection methods can select targeted characteristic variables and improve the accuracy with few variables. Monte Carlo-uninformative variable elimination method was selected as the optimal prediction performance. In the best prediction model, the correlation coefficient and root mean square error of prediction of the prediction set are 0.854 and 0.7%Brix, respectively, while the variable number decreases to 440 from 1557. Furthermore, the models using the average spectra of four points on the equator are the most appropriate. Novelty impact statement The penetrating ability of near-infrared diffuse reflectance spectroscopy (NIRDRS) light to thick peel and the prediction of internal quality of citrus is still unsatisfactory with traditional partial least squares (PLS) algorithm due to the interference of thick peel. In this study, a nondestructive method for the analysis of soluble solids content (SSC) in citrus was established by NIRDRS with characteristic variable selection algorithms. The results demonstrated that NIRDRS light has the ability to penetrate the peel to a certain extent, while characteristic variable selection methods can select targeted characteristic variables and improve the accuracy of quantitative analysis models with fewer variables.

A centrosymmetric Dy2 compound derived from acylhydrazone Schiff base ligand exhibiting zero-field single-molecule magnet behavior

Based on acylhydrazone Schiff base ligand (2,3′-Hpcad, N3-(2-pyridoyl)-3-pyridinecarboxamidrazone), a binuclear DyIII compound, [Dy2(2,3′-pcad)2(C6H5COO)4(H2O)2] (1), has been successfully prepared by the hydrothermal synthesis method, and fully characterized by single-crystal X-ray diffraction, elemental analysis, Raman spectra, diffuse reflectance spectroscopy and magnetic property measurement system. Compond 1 exhibits a centrosymmetric binuclear structure bridged by benzoate groups and each eight-coordinated DyIII ion is located in a slightly distorted biaugmented trigonal prism configuration (C2v-BTPR). In addition, alternating-current magnetic susceptibility measurements illustrate that 1 exhibits zero-field single-molecule magnet behavior with the higher effective energy barrier (Ueff) value of 114.0 K compared to other Dy2 compounds with C2v-BTPR configuration. In addition, this study reveals configuration of each DyIII ion and intra-molecular magnetic coupling of two DyIII ions may synergistically effect Dy2-SMMs properties. Furthermore, the band gap energy of 1 is found to be 2.65 eV, which proves 1 could be used as the wide-gap semiconductor.

SP7.1.6 Using Diffuse Reflectance Spectroscopy (DRS) to Identify Tumour and Non-tumour Tissue in Upper Gastrointestinal Specimens

Abstract Aim Cancers of the upper gastrointestinal (GI) tract remain a major contributor to the global cancer risk. Surgery aims to completely resect tumour with clear margins, whilst preserving as much surrounding tissue. Diffuse reflectance spectroscopy (DRS) is a novel technique that presents a promising advancement in cancer diagnosis. We have developed a novel DRS system with tracking capability. Our aim is to classify tumour and non-tumour GI tissue in real-time using this device to aid intra-operative analysis of resection margins. Method An ex-vivo study was undertaken in which data was collected from consecutive patients undergoing upper GI cancer resection surgery between August 2020- January 2021. A hand-held DRS probe and tracking system was used on normal and cancerous tissue to obtain spectral information. After acquisition of all spectra, a classification system using histopathology results was created. A user interface was developed using Python 3.6 and Qt5. A support vector machine was used to classify the results. Results The data included 4974 normal spectra and 2108 tumour spectra. The overall accuracy of the DRS probe in differentiating normal versus tumour tissue was 88.08% for the stomach (sensitivity 84.8%, specificity 89.3%), and 91.42% for the oesophagus (sensitivity 76.3%, specificity 98.9%). Conclusion We have developed a successful DRS system with tracking capability, able to process thousands of spectra in a small timeframe, which can be used in real-time to distinguish tumour and non-tumour tissue. This can be used for intra-operative decision-making during upper GI cancer surgery to help select the best resection plane.

Investigation of water bonding status of normal and psoriatic skin in vivo using diffuse reflectance spectroscopy

Psoriasis affects more than 125 million people worldwide, and the diagnosis and treatment efficacy evaluation of the disease mainly rely on clinical assessments that could be subjective. Our previous study showed that the skin erythema level could be quantified using diffuse reflectance spectroscopy (DRS), and the hemoglobin concentration of most psoriatic lesion was higher than that of its adjacent uninvolved skin. While the compromised epidermal barrier function has been taken as the major cause of clinical manifestation of skin dryness and inflammation of psoriasis, very few methods can be used to effectively evaluate this function. In this study, we investigate the near infrared spectroscopic features of psoriatic (n = 21) and normal (n = 21) skin that could link to the epidermal barrier function. From the DRS measurements, it was found that the water bonding status and light scattering properties of psoriasis are significantly different from those of uninvolved or normal skin. The connection between these parameters to the epidermal barrier function and morphology will be discussed. Our results suggest that objective evaluation of epidermal barrier function of psoriasis could be achieved using a simple DRS system.

Skin erythema and pigmentation: a review of optical assessment techniques.

Skin erythema may present due to many causes. One of the common causes is prolonged exposure to sun rays. Other than sun exposure, skin erythema is an accompanying sign of dermatological diseases such as acne, psoriasis, melasma, post inflammatory hyperpigmentation, fever, as well as exposure to specific electromagnetic wave bands. Quantifying skin erythema in patients enables the dermatologist to assess the patient's skin health. Therefore, quantitative assessment of skin erythema was the target of several studies. The clinical standard for erythema evaluation is visual assessment. However, the former standard has some imperfections. For instance, it is subjective, and unqualified for precise color information exchange. To overcome these shortcomings, the past three decades witnessed various methodologies that aimed to achieve erythema objective assessment, such as diffuse reflectance spectroscopy (DRS), and both optical and non-optical systems. This review article reports on the studies published in the past three decades where the performance, the mathematical tactics for computation, and the capabilities of erythema assessment techniques for cutaneous diseases are discussed. In particular, the achievements and limitations of the current techniques in erythema assessment are presented. The profits and development trends of optical and non-optical methods are displayed to provide the researcher with awareness into the present technological advances and its potential for dermatological diseases research.

Abstract 2776: Real-time measurement of temperature and tissue damage during laser photothermal ablation

Abstract Hepatocellular carcinoma (HCC) is the sixth most common cancer and tumor resection is feasible in only 25±30% of these patients. Thermal ablation therapies using lasers, radiofrequency waves and microwaves are considered as an alternative treatment for unresectable tumors. Our goal was to develop optical fiber-based laser ablation while monitoring the changes in temperature and tissue properties in real-time. A portable diffuse reflectance spectroscopy (DRS) system consisting of a DRS probe with self-calibration and fiber optic temperature sensor was made. Tissue mimicking phantoms using human hemoglobin powders and polystyrene particles with fixed total number of scatterers were used to calibrate the system. In vivo studies were performed in 8 rats orthotopically implanted with HCC. Temperature sensor was inserted in the center of the tumor via hypodermic needle and DRS fiber was overlaid on the temperature sensor. Ablation was performed by a fiber optic diffuser connected to an 808nm laser using different power settings in pulse mode. The tissue temperature and optical properties were continuously monitored until both plateaued using a custom LabVIEW program. Rats were immediately euthanized, and the ablated liver tissues were collected for histological analysis. The DRS showed average errors of 6.31% and 4.74% in measuring the absorption (μa) and reduced scattering coefficients (μs) of the phantoms respectively. Tumor bearing liver tissues showed a decreasing trend in both μa and μs irrespective of the laser power (1W-2.5W) and the temperatures recorded (50°C to 88°C) in different animals. Histological analysis showed discrete zones of tissue damage from treated regions with hemorrhage in the outer most zone. Changes in optical properties of the ablated tumors with temperatures and histological changes needs further correlation by performing more in vivo studies. Citation Format: Faraneh Fathi, Dilip R. Maddirela, Venkateswara Rao Gogineni, Sarah B. White, Bing Yu. Real-time measurement of temperature and tissue damage during laser photothermal ablation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2776.

Estimation of Chronological Age of Cattle Using Spatially Resolved Diffuse Reflectance Measurements of Hide

Determining the age of the cattle is important in the cattle industry especially for trading purposes. Dentition and ossification scores are currently used to estimate the age of cattle. Both these methods have limitations which can create significant differences in carcass value. In this study, a fibre-optic probe-based spatially resolved diffuse reflectance spectroscopy system was used to investigate the possibility of using visible-near-infrared spectra for predicting the chronological age of beef cattle. This investigation was carried out on hide samples taken from 80 cattle with accurate date of birth and of the same breed. Spectra of hide samples taken from the neck area were used to build partial least squares models to estimate the age of the cattle. Various empirical pre-processing methods and wavelength selection using genetic algorithm (GA) were used to investigate whether these approaches could enhance model performance. Model performance was evaluated using the repeated learning-testing (RLT) method. A model with the lowest average root mean square error of prediction (ARMSEP) of 2.0 years was obtained when reflected intensity spectra collected from a source-detector distance of 1.0 mm was used after pre-processing with automatic Whittaker filter and applying wavelength selection using GA indicating the feasibility of this method for estimating the age of cattle. Two approaches for utilising measurements from all the source-detector distances collected by the spatially resolved measurement system were also considered. Both these approaches, co-adding and data fusion through augmentation, led to poorer model performance compared to using measurements from only one source-to-detector distance.

Photodynamic therapy dosimetry using multiexcitation multiemission wavelength: toward real-time prediction of treatment outcome.

.Evaluating the optical properties of biological tissues is needed to achieve accurate dosimetry during photodynamic therapy (PDT). Currently, accurate assessment of the photosensitizer (PS) concentration by fluorescence measurements during PDT is typically hindered by the lack of information about tissue optical properties. In the present work, a hand-held fiber-optic probe instrument monitoring fluorescence and reflectance is used for assessing blood volume, reduced scattering coefficient, and PS concentration facilitating accurate dosimetry for PDT. System validation was carried out on tissue phantoms using nonlinear least squares support machine regression analysis. It showed a high correlation coefficient () in the prediction of the PS concentration upon a large variety of phantom optical properties. In vivo measurements were conducted in a PDT chlorine e6 dose escalating trial involving 36 male Swiss mice with Ehrlich solid tumors in which fluences of 5, 15, and were delivered at two fluence rates (100 and ). Remarkably, quantitative measurement of fluorophore concentration was achieved in the in vivo experiment. Diffuse reflectance spectroscopy (DRS) system was also used to independently measure the physiological properties of the target tissues for result comparisons. Then, blood volume and scattering coefficient measured by the fiber-optic probe system were compared with the corresponding result measured by DRS and showed agreement. Additionally, tumor hemoglobin oxygen saturation was measured using the DRS system. Overall, the system is capable of assessing the implicit photodynamic dose to predict the PDT outcome.

Nondestructive Evaluation of Apple Fruit Quality by Frequency-Domain Diffuse Reflectance Spectroscopy: Variations in Apple Skin and Flesh

The optical properties of fruits, such as light absorption and scattering characteristics, change with biochemical activities during storage. Diffuse reflectance spectroscopy (DRS) systems have been widely applied for noninvasively observing biological tissues. In this study, we used a frequency-domain DRS system to measure the optical properties of apples. Results showed that variations in the chlorophyll, water, and flesh-texture of apples could be noninvasively monitored over time. We also observed substantial differences in the absorption and reduced scattering coefficients between injured and normal apples. The DRS techniques could be used for apple grading, and, by extension, for monitoring the quality of other fruits.

Assessing effects of pressure on tumor and normal tissue physiology using an automated self-calibrated, pressure-sensing probe for diffuse reflectance spectroscopy.

Diffuse reflectance spectroscopy (DRS) represents a quantitative, noninvasive, nondestructive means of assessing vascular oxygenation, vascularity, and structural properties. However, it is known that such measurements can be influenced by the effects of pressure, which is a major concern for reproducible and operator-independent assessment of tissues. Second, regular calibration is a necessary component of quantitative DRS to account for factors such as lamp decay and fiber bending. Without a means of reliably controlling for these factors, the accuracy of any such assessments will be reduced, and potentially biased. To address these issues, a self-calibrating, pressure-controlled DRS system is described and applied to both a patient-derived xenograft glioma model, as well as a set of healthy volunteers for assessments of oral mucosal tissues. It was shown that pressure had a significant effect on the derived optical parameters, and that the effects on the optical parameters were magnified with increasing time and pressure levels. These findings indicate that not only is it critical to integrate a pressure sensor into a DRS device, but that it is also important to do so in an automated way to trigger a measurement as soon as possible after probe contact is made to minimize the perturbation to the tissue site.

Smartphone based optical spectrometer for diffusive reflectance spectroscopic measurement of hemoglobin

We report a miniature, visible to near infrared G-Fresnel spectrometer that contains a complete spectrograph system, including the detection hardware and connects with a smartphone through a microUSB port for operational control. The smartphone spectrometer is able to achieve a resolution of ~5 nm in a wavelength range from 400 nm to 1000 nm. We further developed a diffuse reflectance spectroscopy system using the smartphone spectrometer and demonstrated the capability of hemoglobin measurement. Proof of concept studies of tissue phantoms yielded a mean error of 9.2% on hemoglobin concentration measurement, comparable to that obtained with a commercial benchtop spectrometer. The smartphone G-Fresnel spectrometer and the diffuse reflectance spectroscopy system can potentially enable new point-of-care opportunities, such as cancer screening.

Skin collagen can be accurately quantified through noninvasive optical method: Validation on a swine study.

Diffuse reflectance spectroscopy (DRS) is a noninvasive optical technology characterized by relatively low system cost and high efficiency. In our previous study, we quantified the relative concentration of collagen for the individual keloid patient. However, no actual value of collagen concentration can prove the reliability of collagen detection by our DRS system. Skin-mimicking phantoms were prepared using different collagen and coffee concentrations, and their chromophore concentrations were quantified using the DRS system to analyze the influence of collagen and other chromophores. Moreover, we used the animal study to compare the DRS system with the collagen evaluation of biopsy section by second-harmonic generation (SHG) microscopy at four different skin parts. In the phantom study, the result showed that coffee chromophore did not severely interfere with collagen concentration recovery. In the animal study, a positive correlation (r=.902) between the DRS system and collagen evaluation with SHG microscopy was found. We have demonstrated that the DRS system can quantify the actual values of collagen concentration and excluded the interference of other chromophores in skin-mimicking phantoms. Furthermore, a high positive correlation was found in the animal study with SHG microscopy. We consider that the DRS is a potential technique and can evaluate skin condition objectively.

In vivo preclinical verification of a multimodal diffuse reflectance and correlation spectroscopy system for sensing tissue perfusion.

In reconstructive surgery, impeded blood flow in microvascular free flaps due to a compromise in arterial or venous patency secondary to blood clots or vessel spasms can rapidly result in flap failures. Thus, the ability to detect changes in microvascular free flaps is critical. In this paper, we report progress on in vivo pre-clinical testing of a compact, multimodal, fiber-based diffuse correlation and reflectance spectroscopy system designed to quantitatively monitor tissue perfusion in a porcine model's surgically-grafted free flap. We also describe the device's sensitivity to incremental blood flow changes and discuss the prospects for continuous perfusion monitoring in future clinical translational studies.

Design verification of a compact system for detecting tissue perfusion using bimodal diffuse optical technologies.

It is essential to monitor tissue perfusion during and after reconstructive surgery, as restricted blood flow can result in graft failures. Current clinical procedures are insufficient to monitor tissue perfusion, as they are intermittent and often subjective. To address this unmet clinical need, a compact, low-cost, multimodal diffuse correlation spectroscopy and diffuse reflectance spectroscopy system was developed. We verified system performance via tissue phantoms and experimental protocols for rigorous bench testing. Quantitative data analysis methods were employed and tested to enable the extraction of tissue perfusion parameters. This design verification study assures data integrity in future in vivo studies.