Spatial Frequency Domain Imaging Research Articles

Multi-frequency spatial frequency domain imaging: a depth-resolved optical scattering model to isolate scattering contrast in thin layers of skin.

Current methods for wound healing assessment rely on visual inspection, which gives qualitative information. Optical methods allow for quantitative non-invasive measurements of optical properties relevant to wound healing. Spatial frequency domain imaging (SFDI) measures the absorption and reduced scattering coefficients of tissue. Typically, SFDI assumes homogeneous tissue; however, layered structures are present in skin. We evaluate a multi-frequency approach to process SFDI data that estimates depth-specific scattering over differing penetration depths. Multi-layer phantoms were manufactured to mimic wound healing scattering contrast in depth. An SFDI device imaged these phantoms and data were processed according to our multi-frequency approach. The depth sensitive data were then compared with a two-layer scattering model based on light fluence. The measured scattering from the phantoms changed with spatial frequency as our two-layer model predicted. The performance of two models solutions for SFDI was consistently better than the standard diffusion approximation. We presented an approach to process SFDI data that returns depth-resolved scattering contrast. This method allows for the implementation of layered optical models that more accurately represent physiologic parameters in thin tissue structures as in wound healing.

MicroRNA-155 mediates multiple gene regulations pertinent to the role of human adipose-derived mesenchymal stem cells in skin regeneration.

Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds. Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data. Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24h post-transfection. Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo.

Spatial frequency domain imaging combining profile correction enables accurate real-time quantitative mapping of optical properties of apples

Spatial frequency domain imaging technology enables non-contact, wide-field quantitative analysis of optical properties in strong turbid media, thereby enhancing bruise detection in fruits based on changes in optical property values. However, precise and real-time measurement of the optical properties of curved biological materials is challenging due to the significant influence of tissue contours. This paper primarily presents a research study on real-time correction method based on the property that DC component diffuse reflectance (Rd_DC) and AC component diffuse reflectance (Rd_AC) are influenced by the contour trend of the tissue in a similar manner. The aim of this method is to eliminate the significant impact of sample contour angle on demodulation and enhance the detection of apple bruise. Sinusoidal illumination at a spatial frequency of 0.2 mm−1 was projected at 730 nm, with the experiments carried out on standard reflector, polytetrafluoroethylene sphere, and non-bruised and bruised apples. The results showed that, the relative error of the planar standard reflector decreased from the maximum value of 52.85–4.74%. The median of the Rd_AC for the polytetrafluoroethylene spherical standard, which fluctuated between 0.6 and 0.8, was corrected to the theoretical value of 1. For normal apples, the maximum fluctuation in the standard deviation of Rd_AC, after median filtering, reduced from 172.94% at 300×300 pixels to 18.69%. The boxplot of Rd_AC for bruised apples became smaller, with the lower fence being corrected from nearly 0–0.1750, which closely matched the theoretical value of 0.17. Additionally, the correlation of reduced scattering coefficient (μs′) in the ideal region of interest (100×100 pixels) remained at 0.9785 before and after correction, while other areas were corrected, making the bruising more pronounced. The correction method did not require additional experiments, with the consumed time in millisecond level.

Deep-learning approach to stratified reconstructions of tissue absorption and scattering in time-domain spatial frequency domain imaging.

The conventional optical properties (OPs) reconstruction in spatial frequency domain (SFD) imaging, like the lookup table (LUT) method, causes OPs aliasing and yields only average OPs without depth resolution. Integrating SFD imaging with time-resolved (TR) measurements enhances space-TR information, enabling improved reconstruction of absorption () and reduced scattering () coefficients at various depths. To achieve the stratified reconstruction of OPs and the separation between and , using deep learning workflow based on the temporal and spatial information provided by time-domain SFD imaging technique, while enhancing the reconstruction accuracy. Two data processing methods are employed for the OPs reconstruction with TR-SFD imaging, one is full TR data, and the other is the featured data extracted from the full TR data (, continuous-wave component, , mean time of flight). We compared their performance using a series of simulation and phantom validations. Compared to the LUT approach, utilizing full TR, and datasets yield high-resolution OPs reconstruction results. Among the three datasets employed, full TR demonstrates the optimal accuracy. Utilizing the data obtained from SFD and TR measurement techniques allows for achieving high-resolution separation reconstruction of and at different depths within 5mm.

Extended Kalman filtering for enhancing a cyclic pattern-updating scheme of single-pixel dynamic fluorescence spatial frequency domain imaging: publisher's note.

This publisher's note contains a correction to Opt. Lett.48, 5443 (2023)10.1364/OL.495099.

Wide-field illumination diffuse optical tomography within a framework of single-pixel time-domain spatial frequency domain imaging.

We present a wide-field illumination time-domain (TD) diffusion optical tomography (DOT) for three-dimensional (3-D) reconstruction within a shallow region under the illuminated surface of the turbid medium. The methodological foundation is laid on the single-pixel spatial frequency domain (SFD) imaging that facilitates the adoption of the well-established time-correlated single-photon counting (TCSPC)-based TD detection and generalized pulse spectrum techniques (GPST)-based reconstruction. To ameliorate the defects of the conventional diffusion equation (DE) in the forward modeling of TD-SFD-DOT, mainly the low accuracy in the near-field region and in profiling early-photon migration, we propose a modified model employing the time-dependent δ-P1 approximation and verify its improved accuracy in comparison with both the Monte Carlo and DE-based ones. For a simplified inversion process, a modified GPST approach is extended to TD-SFD-DOT that enables the effective separation of the absorption and scattering coefficients using a steady-state equivalent strategy. Furthermore, we set up a single-pixel TD-SFD-DOT system that employs the TCSPC-based TD detection in the SFD imaging framework. For assessments of the reconstruction approach and the system performance, phantom experiments are performed for a series of scenarios. The results show the effectiveness of the proposed methodology for rapid 3-D reconstruction of the absorption and scattering coefficients within a depth range of about 5 mean free pathlengths.

Ultra-miniature dual-wavelength spatial frequency domain imaging for micro-endoscopy.

There is a need for a cost-effective, quantitative imaging tool that can be deployed endoscopically to better detect early stage gastrointestinal cancers. Spatial frequency domain imaging (SFDI) is a low-cost imaging technique that produces near-real time, quantitative maps of absorption and reduced scattering coefficients, but most implementations are bulky and suitable only for use outside the body. We aim to develop an ultra-miniature SFDI system comprising an optical fiber array (diameter 0.125mm) and a micro camera ( package) to displace conventionally bulky components, in particular, the projector. First, we fabricated a prototype with an outer diameter of 3mm, although the individual component dimensions could permit future packaging to a diameter. We developed a phase-tracking algorithm to rapidly extract images with fringe projections at three equispaced phase shifts to perform SFDI demodulation. To validate the performance, we first demonstrate comparable recovery of quantitative optical properties between our ultra-miniature system and a conventional bench-top SFDI system with an agreement of 15% and 6% for absorption and reduced scattering, respectively. Next, we demonstrate imaging of absorption and reduced scattering of tissue-mimicking phantoms providing enhanced contrast between simulated tissue types (healthy and tumour), done simultaneously at wavelengths of 515 and 660nm. Using a support vector machine classifier, we estimate that sensitivity and specificity values of are feasible for detecting simulated squamous cell carcinoma. This device shows promise as a cost-effective, quantitative imaging tool to detect variations in optical absorption and scattering as indicators of cancer.

Motion-resistant three-wavelength spatial frequency domain imaging system with ambient light suppression using an 8-tap CMOS image sensor.

We present a motion-resistant three-wavelength spatial frequency domain imaging (SFDI) system with ambient light suppression using an 8-tap complementary metal-oxide semiconductor (CMOS) image sensor (CIS) developed at Shizuoka University. The system addresses limitations in conventional SFDI systems, enabling reliable measurements in challenging imaging scenarios that are closer to real-world conditions. Our study demonstrates a three-wavelength SFDI system based on an 8-tap CIS. We demonstrate and evaluate the system's capability of mitigating motion artifacts and ambient light bias through tissue phantom reflectance experiments and in vivo volar forearm experiments. We incorporated the Hilbert transform to reduce the required number of projected patterns per wavelength from three to two per spatial frequency. The 8-tap image sensor has eight charge storage diodes per pixel; therefore, simultaneous image acquisition of eight images based on multi-exposure is possible. Taking advantage of this feature, the sensor simultaneously acquires images for planar illumination, sinusoidal pattern projection at three wavelengths, and ambient light. The ambient light bias is eliminated by subtracting the ambient light image from the others. Motion artifacts are suppressed by reducing the exposure and projection time for each pattern while maintaining sufficient signal levels by repeating the exposure. The system is compared to a conventional SFDI system in tissue phantom experiments and then in vivo measurements of human volar forearms. The 8-tap image sensor-based SFDI system achieved an acquisition rate of 9.4 frame sets per second, with three repeated exposures during each accumulation period. The diffuse reflectance maps of three different tissue phantoms using the conventional SFDI system and the 8-tap image sensor-based SFDI system showed good agreement except for high scattering phantoms. For the in vivo volar forearm measurements, our system successfully measured total hemoglobin concentration, tissue oxygen saturation, and reduced scattering coefficient maps of the subject during motion (16.5cm/s) and under ambient light (28.9lx), exhibiting fewer motion artifacts compared with the conventional SFDI. We demonstrated the potential for motion-resistant three-wavelength SFDI system with ambient light suppression using an 8-tap CIS.

Quantifying tissue properties and absolute hemodynamics using coherent spatial imaging.

Measuring hemodynamic function is crucial for health assessment. Optical signals provide relative hemoglobin concentration changes, but absolute measurements require costly, bulky technology. Speckleplethysmography (SPG) uses coherent light to detect speckle fluctuations. Combining SPG with multispectral measurements may provide important physiological information on blood flow and absolute hemoglobin concentration. To develop an affordable optical technology to measure tissue absorption, scattering, hemoglobin concentrations, tissue oxygen saturation (), and blood flow. We integrated reflectance spectroscopy and laser speckle imaging to create coherent spatial imaging (CSI). CSI was validated against spatial frequency domain imaging (SFDI) using phantom-based measurements. In vivo arterial and venous occlusion experiments compared CSI with diffuse optical spectroscopy/diffuse correlation spectroscopy (DOS/DCS) measurements. CSI and SFDI agreed on tissue absorption and scattering in phantom tests. CSI and DOS/DCS showed similar trends and agreement in arterial occlusion results. During venous occlusion, both uncorrected and corrected blood flow decreased with increasing pressure, with an difference in overall blood flow decrease between the methods. CSI and DOS/DCS data showed expected hemoglobin concentrations, , and blood flow trends. CSI provides affordable and comprehensive hemodynamic information. It can potentially detect dysfunction and improve measurements, such as blood pressure, , and metabolism.

Monte Carlo simulations and phantom modeling for spatial frequency domain imaging of surgical wound monitoring.

Postoperative surgical wound infection is a serious problem around the globe, including in countries with advanced healthcare systems, and a method for early detection of infection is urgently required. We explore spatial frequency domain imaging (SFDI) for distinguishing changes in surgical wound healing based on the tissue scattering properties and surgical wound width measurements. A comprehensive numerical method is developed by applying a three-dimensional Monte Carlo simulation to a vertical heterogeneous wound model. The Monte Carlo simulation results are validated using resin phantom imaging experiments. We report on the SFDI lateral resolution with varying reduced scattering value and wound width and discuss the partial volume effect at the sharp vertical boundaries present in a surgical incision. The detection sensitivity of this method is dependent on spatial frequency, wound reduced scattering coefficient, and wound width. We provide guidelines for future SFDI instrument design and explanation for the expected error in SFDI measurements.

Development of a multispectral spatial-frequency domain imaging system for property and quality assessment of fruits and vegetables

Thanks to the unique features of wide-field, label-free and depth-resolved imaging, spatial-frequency domain imaging (SFDI) technique has witnessed rapid and considerable progress in biomedical, agricultural and food engineering. This paper reports on the design, characterization and calibration of a multipurpose, multispectral SFDI system (550, 600, 630, 675, 710 and 730 nm) for property and quality assessment of fruits and vegetables. The system was mainly composed of illumination unit, imaging unit and sample stage. Customized software was developed to synchronously control pattern generation and shift, light illuminating, image acquisition and saving. Multiple parameters, including field of view, spatial resolution, uniformity, linearity, repeatability and stability, were used to characterize or calibrate the multispectral SFDI system from a systematic view, based on a set of experiments using optical phantoms. The results indicate that the constructed multispectral SFDI system can be used to collect optical property parameters of common fruits and vegetables after calibration. Then the multispectral SFDI system was applied to measure the optical properties of six types of fruits and vegetables (apple, pear, cucumber, tomato, white and green radish), and the measured optical property mappings were utilized for detecting early-stage bruise, which cannot be observed by naked eyes or even conventional uniform lighting imaging. The results demonstrated that the multispectral SFDI system was capable of measuring optical properties, and the reduced scattering coefficient mapping was superior to the absorption coefficient mapping in detecting early-stage bruise. Selection of effective characteristic wavelength could further enhance the bruise detection.

Extended Kalman filtering for enhancing a cyclic pattern-updating scheme of single-pixel dynamic fluorescence spatial frequency domain imaging.

A single-pixel imaging technique applied to fluorescence spatial frequency domain imaging (f-SFDI) brings many positive benefits, but its low frame rate will also lead to severe quantitative degradation when dynamically imaging a vibrant target. This work presents a novel, to the best of our knowledge, single-pixel imaging approach that combines the extended Kalman filtering (EKF) and a cyclic one-pattern updating for an enhanced dynamic f-SFDI. The cyclic one-pattern updating scheme enables the dynamic imaging at a high frame rate, and on this basis, the imaging process of an intensity temporally varying target (assuming no structure motion in the scene) is dynamically modelled, and accordingly, the surface intensities and images at each sampling time point simultaneously estimated via the EKF. Simulation and phantom validations demonstrate that the method can improve the quantitative accuracy of the results. An in vivo experiment performed on two mice for dynamic monitoring of photosensitizer doses in a photodynamic therapy further demonstrates the clinical feasibility of the proposed method.

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

Quantitative hemodynamic imaging: a method to correct the effects of optical properties on laser speckle imaging.

Studying cerebral hemodynamics may provide diagnostic information on neurological conditions. Wide-field imaging techniques, such as laser speckle imaging (LSI) and optical intrinsic signal imaging, are commonly used to study cerebral hemodynamics. However, they often do not account appropriately for the optical properties of the brain that can vary among subjects and even during a single measurement. Here, we describe the combination of LSI and spatial-frequency domain imaging (SFDI) into a wide-field quantitative hemodynamic imaging (QHI) system that can correct the effects of optical properties on LSI measurements to achieve a quantitative measurement of cerebral blood flow (CBF). We describe the design, fabrication, and testing of QHI. The QHI hardware combines LSI and SFDI with spatial and temporal synchronization. We characterized system sensitivity, accuracy, and precision with tissue-mimicking phantoms. With SFDI optical property measurements, we describe a method derived from dynamic light scattering to obtain absolute CBF values from LSI and SFDI measurements. We illustrate the potential benefits of absolute CBF measurements in resting-state and dynamic experiments. QHI achieved a 50-Hz raw acquisition frame rate with a field of view and flow sensitivity up to . The extracted SFDI optical properties agreed well with a commercial system (). The system showed high stability with low coefficients of variations over multiple sessions within the same day () and over multiple days (). When optical properties were considered, the in-vivo hypercapnia gas challenge showed a slight difference in CBF ( to 0.5% difference). The in-vivo resting-state experiment showed a change in CBF ranking for nine out of 13 animals when the correction method was applied to LSI CBF measurements. We developed a wide-field QHI system to account for the confounding effects of optical properties on CBF LSI measurements using the information obtained from SFDI.

Generic and Model-Based Calibration Method for Spatial Frequency Domain Imaging with Parameterized Frequency and Intensity Correction.

Spatial frequency domain imaging (SFDI) is well established in biology and medicine for non-contact, wide-field imaging of optical properties and 3D topography. Especially for turbid media with displaced, tilted or irregularly shaped surfaces, the reliable quantitative measurement of diffuse reflectance requires efficient calibration and correction methods. In this work, we present the implementation of a generic and hardware independent calibration routine for SFDI setups based on the so-called pinhole camera model for both projection and detection. Using a two-step geometric and intensity calibration, we obtain an imaging model that efficiently and accurately determines 3D topography and diffuse reflectance for subsequently measured samples, taking into account their relative distance and orientation to the camera and projector, as well as the distortions of the optical system. Derived correction procedures for position- and orientation-dependent changes in spatial frequency and intensity allow the determination of the effective scattering coefficient μs' and the absorption coefficient μa when measuring a spherical optical phantom at three different measurement positions and at nine wavelengths with an average error of 5% and 12%, respectively. Model-based calibration allows the characterization of the imaging properties of the entire SFDI system without prior knowledge, enabling the future development of a digital twin for synthetic data generation or more robust evaluation methods.

Diabetic Foot Ulcer Imaging: An Overview and Future Directions.

Diabetic foot ulcers (DFUs) affect one in every three people with diabetes. Imaging plays a vital role in objectively complementing the gold-standard visual yet subjective clinical assessments of DFUs during the wound treatment process. Herein, an overview of the various imaging techniques used to image DFUs is summarized. Conventional imaging modalities (e.g., computed tomography, magnetic resonance imaging, positron emission tomography, single-photon emitted computed tomography, and ultrasound) are used to diagnose infections, impact on the bones, foot deformities, and blood flow in patients with DFUs. Transcutaneous oximetry is a gold standard to assess perfusion in DFU cases with vascular issues. For a wound to heal, an adequate oxygen supply is needed to facilitate reparative processes. Several optical imaging modalities can assess tissue oxygenation changes in and around the wounds apart from perfusion measurements. These include hyperspectral imaging, multispectral imaging, diffuse reflectance spectroscopy, near-infrared (NIR) spectroscopy, laser Doppler flowmetry or imaging, and spatial frequency domain imaging. While perfusion measurements are dynamically monitored at point locations, tissue oxygenation measurements are static two-dimensional spatial maps. Recently, we developed a spatio-temporal NIR-based tissue oxygenation imaging approach to map for the extent of asynchrony in the oxygenation flow patterns in and around DFUs. Researchers also measure other parameters such as thermal maps, bacterial infections (from fluorescence maps), pH, collagen, and trans-epidermal water loss to assess DFUs. A future direction for DFU imaging would ideally be a low-cost, portable, multi-modal imaging platform that can provide a visual and physiological assessment of wounds for comprehensive wound care intervention and management.

Profile-based diffuse reflectance corrections for improved optical property measurement of spherical fruit with spatial frequency domain imaging

Diffuse reflectance (Rd), demodulated from spatial frequency domain imaging (SFDI), is strongly influenced by the surface profile of target sample, and the optical properties (absorption coefficient μa and reduced scattering coefficient μ's) extracted from the Rd are prone to large estimation errors caused by curved surface of the fruit. This study proposes a profile-based Rd correction method, aiming to improve the accuracy of optical property measurement for spherical fruit, such as apples, as well as enhance fruit bruise detection through improved optical properties. Firstly, the surface height of the test object was obtained by performing the phase-measuring profilometry (PMP) in SFDI. Secondly, the object surface reflection angle was calculated using the proposed angle calculation method for spherical samples. The Modified Lambertian Correction (MLC) method was then refined to minimize the effect of the incident angle on the Rd correction. The performance of the Rd correction method was validated using standard reflector and Teflon spheres. The results showed that the average error of the PMP measurement with the height range of 0–50 mm was within 1 mm, the relative error of the corrected Rd was within 2 %, and the standard deviation of the Rd for the Teflon sphere was reduced by about 60 % after correction. Finally, the proposed Rd correction method was applied to measure the optical properties of four spherical fruit (‘Golden Delicious’, ‘Red Fuji’ apples, lemons, and oranges). The results revealed that the standard deviations of the measured μa and μ's of the spherical fruit were greatly reduced by about 70 % and 40 % after correction. The improved optical property mappings enhanced the early bruise detection of apples due to the fact that the optical property contrast between the non-bruised and bruised tissues were significantly increased.

Spatial frequency domain imaging for the assessment of scleroderma skin involvement.

Systemic sclerosis (SSc) is an autoimmune disease characterized by the widespread deposition of excess collagen in the skin and internal organs, as well as vascular dysfunction. The current standard of care technique used to quantify the extent of skin fibrosis in SSc patients is the modified Rodnan skin score (mRSS), which is an assessment of skin thickness based on clinical palpation. Despite being considered the gold standard, mRSS testing requires a trained physician and suffers from high inter-observer variability. In this study, we evaluated the use of spatial frequency domain imaging (SFDI) as a more quantitative and reliable method for assessing skin fibrosis in SSc patients. SFDI is a wide-field and non-contact imaging technique that utilizes spatially modulated light to generate a map of optical properties in biological tissue. The SFDI data were collected at six measurement sites (left and right forearms, hands, and fingers) of eight control subjects and ten SSc patients. mRSS were assessed by a physician, and skin biopsies were collected from subject's forearms and used to assess for markers of skin fibrosis. Our results indicate that SFDI is sensitive to skin changes even at an early stage, as we found a significant difference in the measured optical scattering () between healthy controls and SSc patients with a local mRSS score of zero (no appreciable skin fibrosis by gold standard). Furthermore, we found a strong correlation between the diffuse reflectance (Rd) at a spatial frequency of 0.2 mm-1 and the total mRSS between all subjects (Spearman correlation coefficient = -0.73, p-value < 0.0028), as well as high correlation with histology results. The healthy volunteer results show excellent inter- and intra-observer reliability (ICC > 0.8). Our results suggest that the measurement of tissue and Rd at specific spatial frequencies and wavelengths can provide an objective and quantitative assessment of skin involvement in SSc patients, which could greatly improve the accuracy and efficiency of monitoring disease progression and evaluating drug efficacy.

A Comparison of Spectroscopy and Imaging Techniques Utilizing Spectrally Resolved Diffusely Reflected Light for Intraoperative Margin Assessment in Breast-Conserving Surgery: A Systematic Review and Meta-Analysis.

Up to 19% of patients require re-excision surgery due to positive margins in breast-conserving surgery (BCS). Intraoperative margin assessment tools (IMAs) that incorporate tissue optical measurements could help reduce re-excision rates. This review focuses on methods that use and assess spectrally resolved diffusely reflected light for breast cancer detection in the intraoperative setting. Following PROSPERO registration (CRD42022356216), an electronic search was performed. The modalities searched for were diffuse reflectance spectroscopy (DRS), multispectral imaging (MSI), hyperspectral imaging (HSI), and spatial frequency domain imaging (SFDI). The inclusion criteria encompassed studies of human in vivo or ex vivo breast tissues, which presented data on accuracy. The exclusion criteria were contrast use, frozen samples, and other imaging adjuncts. 19 studies were selected following PRISMA guidelines. Studies were divided into point-based (spectroscopy) or whole field-of-view (imaging) techniques. A fixed-or random-effects model analysis generated pooled sensitivity/specificity for the different modalities, following heterogeneity calculations using the Q statistic. Overall, imaging-based techniques had better pooled sensitivity/specificity (0.90 (CI 0.76-1.03)/0.92 (CI 0.78-1.06)) compared with probe-based techniques (0.84 (CI 0.78-0.89)/0.85 (CI 0.79-0.91)). The use of spectrally resolved diffusely reflected light is a rapid, non-contact technique that confers accuracy in discriminating between normal and malignant breast tissue, and it constitutes a potential IMA tool.

Designing and simulating realistic spatial frequency domain imaging systems using open-source 3D rendering software.

Spatial frequency domain imaging (SFDI) is a low-cost imaging technique that maps absorption and reduced scattering coefficients, offering improved contrast for important tissue structures such as tumours. Practical SFDI systems must cope with various imaging geometries including imaging planar samples ex vivo, imaging inside tubular lumen in vivo e.g. for endoscopy, and measuring tumours or polyps of varying morphology. There is a need for a design and simulation tool to accelerate design of new SFDI systems and simulate realistic performance under these scenarios. We present such a system implemented using open-source 3D design and ray-tracing software Blender that simulates media with realistic absorption and scattering in a wide range of geometries. By using Blender's Cycles ray-tracing engine, our system simulates effects such as varying lighting, refractive index changes, non-normal incidence, specular reflections and shadows, enabling realistic evaluation of new designs. We first demonstrate quantitative agreement between Monte-Carlo simulated absorption and reduced scattering coefficients with those simulated from our Blender system, achieving discrepancy in absorption coefficient and in reduced scattering coefficient. However, we then show that using an empirically derived look-up table the errors reduce to and respectively. Next, we simulate SFDI mapping of absorption, scattering and shape for simulated tumour spheroids, demonstrating enhanced contrast. Finally we demonstrate SFDI mapping inside a tubular lumen, which highlighted a important design insight: custom look-up tables must be generated for different longitudinal sections of the lumen. With this approach we achieved absorption error and scattering error. We anticipate our simulation system will aid in the design of novel SFDI systems for key biomedical applications.