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A critical need exists for early, accurate diagnosis of burn wound severity to help identify the course of treatment and outcome of the wound. Laser speckle imaging (LSI) is a promising blood perfusion imaging approach, but it does not account for changes in tissue optical properties that can occur with burn wounds, which are highly dynamic environments. Here, we studied optical property dynamics following burn injury and debridement and the associated impact on interpretation of LSI measurements of skin perfusion. We used spatial frequency domain imaging (SFDI) measurements of tissue optical properties to study the impact of burn-induced changes in these properties on LSI measurements. An established preclinical porcine model of burn injury was used (n = 8). SFDI and LSI data were collected from burn wounds of varying severity. SFDI measurements demonstrate that optical properties change in response to burn injury in a porcine model. We then apply theoretical modeling to demonstrate that the measured range of optical property changes can affect the interpretation of LSI measurements of blood flow, but this effect is minimal for most of the measured data. Collectively, our results indicate that, even with a dynamic burn wound environment, blood-flow measurements with LSI can serve as an appropriate strategy for accurate assessment of burn severity.

High positive margin rates in oncologic breast-conserving surgery are a pressing clinical problem. Volumetric X-ray scanning is emerging as a powerful ex vivo specimen imaging technique for analyzing resection margins, but X-rays lack contrast between non-malignant and malignant fibrous tissues. In this study, combined micro-CT and wide-field optical image radiomics were developed to classify malignancy of breast cancer tissues, demonstrating that X-ray/optical radiomics improve malignancy classification. Ninety-two standardized features were extracted from co-registered micro-CT and optical spatial frequency domain imaging samples extracted from 54 breast tumors exhibiting seven tissue subtypes confirmed by microscopic histological analysis. Multimodal feature sets improved classification performance versus micro-CT alone when adipose samples were included (AUC = 0.88 vs. 0.90; p-value = 3.65e−11) and excluded, focusing the classification task on exclusively non-malignant fibrous versus malignant tissues (AUC = 0.78 vs. 0.85; p-value = 9.33e−14). Extending the radiomics approach to high-dimensional optical data—termed “optomics” in this study—offers a promising optical image analysis technique for cancer detection. Radiomic feature data and classification source code are publicly available.

Background: Microvascular disease (MVD) describes systemic changes in the small vessels (~100 um diameter) that impair tissue oxygenation and perfusion. MVD is a common but poorly monitored complication of diabetes. Recent studies have demonstrated that MVD: (i) is an independent risk factor for ulceration and amputation and (ii) increases risk of adverse limb outcomes synergistically with PAD. Despite the clinical relevance of MVD, microvascular evaluation is not standard in a vascular assessment. Methods: We evaluated 299 limbs from 153 patients seen clinically for possible lower extremity PAD. The patients were assessed by ankle brachial index (ABI), toe brachial index (TBI), and spatial frequency domain imaging (SFDI). These measurements were evaluated and compared to patient MVD status, defined by clinical diagnoses of (in ascending order of severity) no diabetes; diabetes; diabetes + neuropathy; diabetes + neuropathy + retinopathy. Results: SFDI-derived parameters HbT1 and StO2 were significantly different across the MVD groups ( P < .001). A logistic regression model based on HbT1 and StO2 differentiated limbs with severe MVD (diabetes+neuropathy+retinopathy) from the larger group of limbs from patients with only diabetes ( P = .001, area under the curve = 0.844). Neither ABI nor TBI significantly differentiated these populations. Conclusions: Standard assessment of PAD using ABI and TBI are inadequate for detecting MVD in at-risk populations. SFDI-defined HbT1 and StO2 are promising tools for evaluating MVD. Prospective studies with wound-based outcomes would be useful to further evaluate the role MVD assessment could play in routine clinical evaluation of patients at risk for lower extremity complications.

It was demonstrated that confocal Raman microscopy (CRM) could be used for domain imaging in the calcium orthovanadate Ca3(VO4)2 single crystals. The domain contrast could be achieved using noticea...

The purpose of this study was to assess early and late vascular healing in response to bioresorbable-polymer sirolimus-eluting stents (BP-SESs) for the treatment of patients with ST-elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). A total of 106 patients with STEMI and 101 patients with stable-CAD were enrolled. Optical frequency-domain images were acquired at baseline, at 1- or 3-month follow-up, and at 12-month follow-up. In the STEMI and CAD cohorts, the percentage of uncovered struts (%US) was significantly and remarkably decreased during early two points and at 12-month (the STEMI cohort: 1-month: 18.75 ± 0.78%, 3-month: 10.19 ± 0.77%, 12-month: 1.80 ± 0.72%; p p p ≤ 0.001), whereas the one in the CAD cohort was not significantly changed (0.89 ± 1.24, 0.67 ± 1.07, and 0.64 ± 0.72; p = 0.59). In comparison with both groups, differences of %US and PLIA score at early two points were almost disappeared or close at 12 months. The strut-coverage and healing processes in the early phase after BP-SES implantation were significantly improved in both cohorts, especially markedly in STEMI patients. At 1 year, qualitatively and quantitatively consistent neointimal coverage was achieved in both pathogenetic groups.

Whether predicting the rotational atherectomy (RA) effect based on the position of optical frequency domain imaging (OFDI) is accurate remains uncertain. The aim of this study was to evaluate the predictive accuracy of OFDI in identifying RA location and area. Twenty-five patients who underwent RA with OFDI were included. On pre-RA OFDI images, a circle with the dimension of a Rota burr was drawn at the center of the OFDI catheter. The area where the circle overlapped with the vessel wall was defined as the predicted ablation area (P-area), and the actual ablated area (A-area) was measured. The predictive accuracy of OFDI was evaluated as follows: overlapped ablation area (O-area: overlapping P- and A-areas) divided by P-area = %Correct-area, and A-area − O-area divided by A-area = %Error-area. Cross-sections were separated into four categories based on the median values of %Correct- and %Error-area. Among 334 cross-sections, RA effects were confirmed in the predicted location in 87% of them. The median %Correct- and %Error-areas were 43.1% and 64.2%, respectively. Floppy wire, narrow lumen area, OFDI catheter close to the intima, and large arc of calcium were independently associated with good prediction (high %Correct-/low %Error-areas). Non-left anterior descending lesions, OFDI catheter far from the wire, and OFDI catheter and wire far from the intima were associated with irrelevant ablation (low %Correct-/ high %Error-areas). The accuracy of the OFDI-based predictions for RA effects was acceptable with regard to location, but not high with regard to area. Wire types, target vessels, and OFDI catheter and wire positions are important determinants for accurately predicting RA effect using pre-procedural OFDI.

Background Here we report the application of optical frequency domain imaging (OFDI), a new optical coherence tomography device, for intravascular visualization in the treatment of a recanalized unruptured internal carotid artery aneurysm that was treated initially by stent-assisted coil embolization. Case Description OFDI revealed malapposition of the stent and lack of neointimal growth at the aneurysm neck, which was treated by deployment of a Pipeline Embolization Device to overlap the stent. An angiogram performed 1 year after the procedure revealed perfect healing of the aneurysm, and OFDI clearly demonstrated good stent apposition and total endothelialization over the aneurysm neck. Conclusions OFDI/OCT appears to be a useful diagnostic tool for evaluating stent-strut apposition over the vessel wall and the grade of neointimal endothelialization across the neck of the aneurysm in aneurysmal recanalization.

Early stage dental caries can be remineralized without the need for “drill-and-fill” treatments that are more invasive and less permanent. However, early stage caries lesions typically present as a white spot on a white background, resulting in many lesions only being identified after they have developed beyond the point of remineralization as cavities. We present a spatial frequency domain imaging technique to characterize the optical properties of dental tissue. This technique enables different dental tissue types (healthy enamel, healthy dentin and damaged or demineralized enamel) to be easily distinguished from one another and allows quantification of the reduced scattering coefficients of dental tissue. The use of near-infrared light at 850 nm allows high depth penetration into the tissue and suppression of absorption effects, ensuring only changes in the reduced scattering coefficient that result directly from demineralization of enamel are observed and simplifying the analysis method. This technique provides a tool to both guide the attention of dentists to areas of interest and potential demineralization, and to provide longitudinal quantified assessments to monitor caries lesion behaviour over time.

We present a spatial frequency domain imaging (SFDI) system based on single- pixel imaging (SPI) techniques with a single digital micromirror device (DMD) modulating simultaneously the sinusoidal pattern and the spatial sampling masks.

We considered the experimentally observed variety of domain shapes in crystals of lithium niobate and lithium tantalate family. The shapes were classified, and their formation was discussed in term...

Supplemental Digital Content is available in the text., Background: Clinical implications of online 3-dimensional optical frequency domain imaging (3D-OFDI)-guided stenting for bifurcation lesions have not been investigated in the randomized controlled trials. The purpose of this study was to determine whether online 3D-OFDI-guided stenting is superior to angiography-guided percutaneous coronary intervention (PCI) in terms of incomplete stent apposition at the bifurcation segment. Methods: The OPTIMUM trial (Online 3-Dimensional Optical Frequency Domain Imaging to Optimize Bifurcation Stenting Using UltiMaster Stent) was a randomized, multicenter clinical trial. Eligible patients had an angiographically significant stenosis in the bifurcation lesion treated with a provisional single stent strategy using the Ultimaster sirolimus eluting stent. Patients were randomly allocated to either online 3D-OFDI-guided or angiography-guided PCI. Patients randomized to 3D-OFDI guidance underwent online 3D-OFDI assessment after rewiring into the jailed side branch after stenting and proximal optimization technique, while in the angiography guidance arm, rewiring was performed using conventional fluoroscopic/angiographic guidance. The primary end point of this trial was the postprocedural average percentage of malapposed struts per lesion assessed by OFDI in the confluence zone of the main and side branches. Results: Between June 8, 2017 and September 26, 2018, 110 patients with 111 bifurcation lesions were randomized at 4 Japanese centers. Of these, 56 patients with 57 lesions were treated with 3D-OFDI-guided PCI, whereas 54 patients with 54 lesions were treated with angiography-guided PCI. In the 3D-OFDI guidance arm, the feasibility of online 3D-OFDI was 98.2%. The average percentage of incomplete stent apposition per lesion at bifurcation was lower in the 3D-OFDI guidance arm than that in the angiography guidance arm (19.5±15.8% versus 27.5±14.2%, P=0.008). The superiority of the 3D-OFDI guidance arm was also confirmed in the strut level analysis (odds ratio: 0.54 [95% CI, 0.36–0.81]; P=0.003). Conclusions: Online 3D-OFDI-guided bifurcation PCI was superior to angiography-guided bifurcation PCI in terms of acute incomplete stent apposition at bifurcation. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02972489.

Purpose To analyze the difference in morphological patterns between in-stent restenosis (ISR) lesions of overlapping segments and ISR lesions of non-overlapping segments with second- and third-generation drug-eluting stents (DESs) using optical frequency domain imaging (OFDI). Methods We analyzed 23 consecutive ISR lesions after second- or third-generation DES implantation using OFDI. Results A total of 18 men and 5 women (median age, 68.0 years; interquartile range, 51.0–74.0 years) were included in the analysis. Fourteen and nine patients underwent second- and third-generation DES implantation, respectively. The median ISR detection timepoint was 10.0 months after implantation (interquartile range, 9.0–34.0 months). In 9 out of 23 lesions, ISR was found in the stent overlap area (overlapping segment group); the remaining 14 cases were categorized as the non-overlapping segment group. In OFDI analysis, homogeneous, layered, and heterogeneous patterns were found in 22%, 55%, and 22%, respectively, of lesions in the overlapping segment group and 14%, 50%, and 35%, respectively, of lesions in the non-overlapping segment group. There was no difference in the distribution of restenotic tissue structure patterns between the groups (p = .756). Conclusions Morphological assessments of ISR tissue using OFDI showed no difference between the overlapping and non-overlapping segment groups with second and third-generation DESs in this hypothesis generating study.

Collagen fiber networks provide the structural strength of tissues, such as tendons, skin and arteries. Quantifying the fiber architecture in response to mechanical loads is essential towards a better understanding of the tissue-level mechanical behaviors, especially in assessing disease-driven functional changes. To enable novel investigations into these load-dependent fiber structures, a polarized spatial frequency domain imaging (pSFDI) device was developed and, for the first time, integrated with a biaxial mechanical testing system. The integrated instrument is capable of a wide-field quantification of the fiber orientation and the degree of optical anisotropy (DOA), representing the local degree of fiber alignment. The opto-mechanical instrument''s performance was assessed through uniaxial loading on tendon tissues with known collagen fiber microstructures. Our results revealed that the bulk fiber orientation angle of the tendon tissue changed minimally with loading (median ± 0.5*IQR of 52.7° ± 3.3° and 51.9° ± 3.3° under 0 and 3% longitudinal strains, respectively), whereas on a micro-scale, the fibers became better aligned with the direction of loading: the DOA (mean ± SD) increased from 0.149 ± 0.032 to 0.198 ± 0.056 under 0 and 3% longitudinal strains, respectively, p 0.001. The integrated instrument was further applied to study two representative mitral valve anterior leaflet (MVAL) tissues subjected to various biaxial loads. The fiber orientations within these representative MVAL tissue specimens demonstrated noticeable heterogeneity, with the local fiber orientations dependent upon the sample, the spatial and transmural locations, and the applied loading. Our results also showed that fibers were generally better aligned under equibiaxial (DOA = 0.089 ± 0.036) and circumferentially-dominant loading (DOA = 0.086 ± 0.037) than under the radially-dominant loading (DOA = 0.077 ± 0.034), indicating circumferential predisposition. These novel findings exemplify a deeper understanding of the load-dependent collagen fiber microstructures obtained through the use of the integrated opto-mechanical instrument. STATEMENT OF SIGNIFICANCE: In this study, a novel quantitative opto-mechanical system was developed by combining a polarized Spatial Frequency Domain Imaging (pSFDI) device with a biaxial mechanical tester. The integrated system was used to quantify the load-dependent collagen fiber microstructures in representative tendon and mitral valve anterior leaflet (MVAL) tissues. Our results revealed that MVAL's fiber architectures exhibited load-dependent spatial and transmural heterogeneities, suggesting further microstructural complexity than previously reported in heart valve tissues. These novel findings were possible through the system's ability to, for the first time, capture the load-dependent collagen architecture in the mitral valve anterior leaflet tissue over a wide field of view (e.g., 10 × 10 mm for the MVAL tissue specimens). Such capabilities afford unique future opportunities to improve patient outcomes through concurrent mechanical and microstructural assessments of healthy and diseased tissues in conditions such as heart valve regurgitation and calcification.

Purpose Optical frequency domain imaging (OFDI) is widely used to characterize lipidic-atherosclerotic plaques, shown as signal-poor regions with diffuse borders, in clinical setting. Given that lipid components are common to both fibroatheroma (FA) and pathological intimal thickening (PIT), it is unclear whether OFDI can be used to accurately distinguish between FA and PIT. This study evaluated the differences in OFDI findings between FA and PIT in comparison with histopathology. Methods A total of 631 histological cross-sections from 14 autopsy hearts were analyzed for the comparison between OFDI and histological images. Of those, 190 (30%) sections were diagnosed with PIT and 120 (19%) with FA. All OFDI images were matched with histology and the OFDI signal attenuation rate was calculated from an exponential. The lipid length was measured longitudinally, and the lipid arc was measured with a protractor centered in the center of the lumen. Results There was no significant difference in the OFDI signal attenuation rate between FA and PIT (3.09 ± 1.04 versus 2.79 ± 1.20, p = 0.13). However, the lipid length was significantly longer and the maximum lipid arc was significantly larger in FA than in PIT (7.5 [4.3–10.3] mm versus 4.3 [2.7–5.8] mm, p < 0.0001, and 125 [101–174]° versus 96 [74–131]°, p < 0.0001, respectively). Conclusions OFDI may be capable of discriminating advanced lipid plaques from early stage atherosclerosis based on the longitudinal and circumferential extent of signal-poor region.

Introduction The present study aimed to compare the accuracy of quantitative measurements by contemporary intravascular imaging systems including optical frequency domain imaging (OFDI), frequency domain optical coherence tomography (FD-OCT), and 6 intravascular ultrasound (IVUS) systems. Methods We imaged five cylindrical phantom models made from an acrylic resin with known lumen diameters (1.51, 2.03, 3.04, 4.04, and 5.04 mm, respectively) using OFDI (FastView and LUNAWAVE, Terumo), FD-OCT (Dragonfly JP and ILUMIEN OPTIS, Abbott Vascular), and 6 mechanically rotating IVUS systems including a system, two 40-MHz, one 45-MHz, two 60-Mhz and one broad-band frequency IVUS systems. The OFDI, FD-OCT, and IVUS images were obtained using automated motorized pullback in a tank filled with 37-degree Celsius saline and, in cases of OFDI and FD-OCT, contrast-saline mixture (1:1 ratio) and contrast under the system setting of the refractive index for the corresponding flush medium. Results All the imaging systems showed good accuracy and excellent precision of lumen measurement with the relative differences between the measured diameter and actual phantom diameter being ranging from −2.9% to 8.0% and minimum standard deviations of the measured diameters (≤0.02 mm). Conclusion The present study demonstrated that contemporary intravascular imaging systems including OFDI, FD-OCT, and IVUS provided clinically acceptable accuracy and excellent precision of quantitative lumen measurement in phantom models in vitro across a wide range of dimensions. Future research to confirm these findings in vivo are warranted.

Background Burns are devastating injuries, carry significant morbidity, and require long-term treatment or multiple reconstructive procedures. Wound healing and secondary insults caused by burn wound conversion are amendable to therapeutic intervention, where ischemia has been cited as one of the major factors (Dermatol Surg. 2008;34:1159-1169). Halting injury progression in the zone of stasis is crucial as conversion creates increased burn surface area and depth, leading to local and systemic consequences (J Burns Wounds. 2006;5:e2). Oxygen-carrying micro/nanobubbles, MNB(O2), offer a novel technology that can be used to effectively deliver oxygen to burn wounds and potentially counteract burn wound ischemia. Methods Topical irrigation with MNB(O2) of full-thickness burn wounds on a rodent model (n = 3) was compared against saline-treated controls (n = 3). Tissue structure (reduced scattering coefficient, μs'), oxyhemoglobin concentration (cHbO2), and tissue perfusion were quantified over the course of 28 days through spatial frequency domain imaging and laser speckle imaging. Histological samples taken at the end of the experiment were examined for evidence of wound healing. Results Findings in this preliminary study showed hastened healing with significant differences in spatial frequency domain imaging-measured μs' during wound healing (days 11-28) in MNB(O2) group. The healing "tipping point" seemed to occur at days 9 to 11 with increased collagen organization and increased cHbO2 occurring around that period confirming the gross healing improvements observed. In addition, histological evidence indicated that only the MNB(O2) burns had reached the remodeling phase by the end of 28-day study period. Conclusions These preliminary findings propose the potential of MNB(O2) as a topical method for improving burn wound healing.

Purpose While optical frequency domain imaging (OFDI) can delineate calcium modification and fracture, the capability of high-definition intravascular ultrasound (HD-IVUS) for detecting these remains unclear. This study evaluated the diagnostic accuracy of HD-IVUS for assessing calcium modification and fracture as compared to OFDI. Methods HD-IVUS and OFDI were used during orbital or rotational atherectomy procedures conducted for 21 heavily calcified coronary lesions in 19 patients. With OFDI assessment used as the gold standard, diagnostic accuracies of HD-IVUS for calcium modification and fracture were compared every 1 mm to the matched pre-stenting images (n=1,129). Calcium modification, as assessed by OFDI, was defined as polished and concave-shaped calcium. For HD-IVUS, calcium modification was defined as the presence of reverberation with concave-shaped calcium. In both assessments, the definition of calcium fracture was defined as a slit or complete break in the calcium plate. Results Calcified plaque was found in 86.4% of analyzed OFDI images. Calcium modification and fracture were detected in 20.6% and 11.0% of detected calcified plaques. Sensitivity, specificity, positive and negative predictive values of HD-IVUS detection for calcium modification and fracture were 54.4%, 97.8%, 86.7%, 89.1% and 86.0%, 94.5%, 58.2%, 96.8%, respectively. Discordance cases between both assessments demonstrated that heterogeneous calcium visualized by OFDI, separated calcium and guide wire artifact can be misdiagnosed. Conclusion Diagnostic accuracies of HD-IVUS for assessing calcium modification and fracture were modest as compared to OFDI. These results suggest that OFDI guidance is more feasible during treatment of heavily calcified coronary lesions versus HD-IVUS guidance.

Significance: Sub-diffuse optical properties may serve as useful cancer biomarkers, and wide-field heatmaps of these properties could aid physicians in identifying cancerous tissue. Sub-diffuse spatial frequency domain imaging (sd-SFDI) can reveal such wide-field maps, but the current time cost of experimentally validated methods for rendering these heatmaps precludes this technology from potential real-time applications. Aim: Our study renders heatmaps of sub-diffuse optical properties from experimental sd-SFDI images in real time and reports these properties for cancerous and normal skin tissue subtypes. Approach: A phase function sampling method was used to simulate sd-SFDI spectra over a wide range of optical properties. A machine learning model trained on these simulations and tested on tissue phantoms was used to render sub-diffuse optical property heatmaps from sd-SFDI images of cancerous and normal skin tissue. Results: The model accurately rendered heatmaps from experimental sd-SFDI images in real time. In addition, heatmaps of a small number of tissue samples are presented to inform hypotheses on sub-diffuse optical property differences across skin tissue subtypes. Conclusion: These results bring the overall process of sd-SFDI a fundamental step closer to real-time speeds and set a foundation for future real-time medical applications of sd-SFDI such as image guided surgery.

Spatial frequency domain imaging (SFDI) is a non-contact wide-field optical imaging technique for optical property detection. This study aimed to establish an SFDI system and investigate the effects of system calibration, error analysis and correction on the measurement of optical properties. Optical parameter characteristic measurements of normal pears with three different damage types were performed using the calibrated system. The obtained absorption coefficient μa and the reduced scattering coefficient μ’s were used for discriminating pears with different surface damage using a linear discriminant analysis model. The results showed that at 527 nm and 675 nm, the pears’ quadruple classification (normal, bruised, scratched and abraded) accuracy using the SFDI technique was 92.5% and 83.8%, respectively, which has an advantage compared with the conventional planar light classification results of 82.5% and 77.5%. The three-way classification (normal, minor damage and serious damage) SFDI technique was as high as 100% and 98.8% at 527 nm and 675 nm, respectively, while the classification accuracy of conventional planar light was 93.8% and 93.8%, respectively. The results of this study indicated that SFDI has the potential to detect different damage types in fruit and that the SFDI technique has a promising future in agricultural product quality inspection in further research.

The microscopic tissue structure and organization influence the polarization of light. Intravascular polarimetry leverages this compelling intrinsic contrast mechanism by using polarization-sensitive optical frequency domain imaging to measure the polarization properties of the coronary arterial wall. Tissues rich in collagen and smooth muscle cells appear birefringent, while the presence of lipid causes depolarization, offering quantitative metrics related to the presence of important components of coronary atherosclerosis. Here, we review the basic principle, the interpretation of polarization signatures, and first clinical investigations of intravascular polarimetry and discuss how this extension of contemporary intravascular imaging may advance our knowledge and improve clinical practice in the future.

The three-dimensional reconstruction of optical coherence tomography and optical frequency domain imaging (3D-OCT/OFDI) helps optimize bifurcation percutaneous coronary interventions (PCIs) with side branch (SB) dilatation by identifying the optimal rewiring position. 3D-OCT/OFDI’s diagnostic performance for assessing the rewiring position into a jailed SB is unknown. We retrospectively evaluated the diagnostic performances of a conventional (ver. 1.1) and a new (ver. 1.2) online 3D-OFDI reconstruction system based on an offline 3D reconstruction system’s performance. We analyzed 45 patients’ 52 OFDI pullbacks with main vessel stenting followed by rewiring into a jailed SB for coronary bifurcation lesions. We counted the undetected stent struts in the polygon of confluence as the stent detection performance. We assessed the diagnostic agreement regarding the rewiring position into a jailed SB by the three 3D reconstruction systems. The percentage of undetected struts and the diagnostic agreement of ver.1.2 were significantly better than those of ver.1.1 [5.1 ± 5.1% vs. 30.2 ± 14.2%; p p = 0.0120]. The new online 3D-OFDI reconstruction system provides better diagnostic performance than the conventional online system for assessing the rewiring position into a jailed SB.

In this document, the methods for the quantitative measurement and morphological assessment of optical coherence tomography (OCT)/optical frequency domain imaging images (OFDI) are briefly summarized. The focus is on the clinical application of OCT/OFDI to guide percutaneous coronary interventions.

Background. While the evaluation of burr speed was discussed regarding platelet aggregation, the association between platform speed and acute lumen gain of rotational atherectomy remains unknown. Methods. Through the evaluation of the potential of low-speed rotational atherectomy (LSRA) in in-vitro experiments, minimum lumen diameter (MLD) and minimum lumen area (MLA) after conventional high-speed rotational atherectomy (HSRA group) and those after LSRA following HSRA (LSRA+HSRA group) treated by 1.5 mm burrs were measured by optical frequency domain imaging (OFDI) in 30 consecutive human lesions. Results. The in-vitro experiments demonstrated that MLD and MLA after LSRA+HSRA were significantly larger (MLD: LSRA+HSRA=1.50 ±0.05 mm, HSRA= 1.43 ±0.05 mm, p=0.015; MLA: LSRA+HSRA= 1.90 ±0.17 mm2, HSRA= 1.71±0.11 mm2, and p= 0.037), requiring more crossing attempts (LSRA= 134 ±20 times, HSRA= 72 ±11 times, and p< 0.001). In human studies, there was no significance in reference vessel diameter and lesion length before the procedure between two groups. MLDs after LSRA+HSRA were significantly larger than those in HSRA (LSRA+HSRA= 1.22 ±0.16 mm, HSRA= 1.07 ±0.14 mm, and p= 0.0078), while MLAs after LSRA+HSRA tended to be larger (LSRA+HSRA= 1.79 ±0.51 mm2, HSRA= 1.55 ±0.47 mm2, and p= 0.19). There was no significance in the occurrence of in-hospital complication, including slow flow or no reflow, major dissection, and procedural myocardial infarction, between LSRA+HSRA and HSRA. Conclusions. LSRA can achieve larger lumen gain compared, whereas HSRA can pass calcified lesions easily. Combination of LSRA and HSRA is a safe and feasible strategy for severely calcified lesions in clinical practice.

While clinical examination is needed for burn severity diagnosis, several emerging technologies aim to quantify this process for added objectivity. Accurate assessments become easier after burn progression, but earlier assessments of partial thickness burn depth could lead to earlier excision and grafting and subsequent improved healing times, reduced rates of scarring/infection, and shorter hospital stays. Spatial Frequency Domain Imaging (SFDI), Laser Speckle Imaging (LSI) and thermal imaging are three non-invasive imaging modalities that have some diagnostic ability for noninvasive assessment of burn severity, but have not been compared in a controlled experiment. Here we tested the ability of these imaging techniques to assess the severity of histologically confirmed graded burns in a swine model. Controlled, graded burn wounds, 3 cm in diameter were created on the dorsum of Yorkshire pigs (n=3, 45–55kg) using a custom-made burn tool that ensures consistent pressure has been employed by various burn research groups. For each pig, a total of 16 burn wounds were created on the dorsal side. Biopsies were taken for histological analysis to verify the severity of the burn. Clinical analysis, SFDI, LSI and thermal imaging were performed at 24 and 72 hours after burn to assess the accuracy of each imaging technique. In terms of diagnostic accuracy, using histology as a reference, SFDI (85%) and clinical analysis (83%) performed significantly better that LSI (75%) and thermography (73%) 24 hours after the burn. There was no statistically significant improvement from 24 to 72 hours across the different imaging modalities. These data indicate that these imaging modalities, and specifically SFDI, can be added to the burn clinicians’ toolbox to aid in early assessment of burn severity.

Background Noninvasive vascular tests are critical for identifying patients who may benefit from surgical revascularization, but current tests have significant limitations in people with diabetes. This study aimed to evaluate the ability of spatial frequency domain imaging (SFDI), an optical imaging method capable of measuring tissue oxygen saturation (StO2) and tissue hemoglobin, to assess lower extremity blood supply. Methods Ankle-brachial index, toe-brachial index, pedal Doppler waveforms, and SFDI images were prospectively evaluated in 47 consecutive patients with and without diabetes in whom there was concern for peripheral artery disease (PAD). SFDI is a noncontact optical imaging technology that uses structured illumination to quantify subsurface (2-3 mm in depth) StO2 and tissue hemoglobin in the dermal microcirculation (HbT1) and macrocirculation (HbT2) over a large field of view (15 × 20 cm) within 10 seconds. Results This demonstrates the ability of SFDI to capture reliable clinical measurements of perfusion in plantar aspects of the feet. SFDI StO2 values differentiate nondiabetic patients with and without arterial disease, defined as ankle-brachial index Conclusions SFDI is a feasible, rapid, and easy to use widefield measurement of perfusion in a clinical setting. This first-of-use study suggests that the technology has potential to evaluate lower extremity perfusion in people with and without diabetes. Further studies with increased numbers of patients and end points including wound healing will need to be designed to fully evaluate the applicability of this new technology.

Quantitative evaluation of the content of key tissue chromophores is of great importance for biomedical diagnostics. However, in general, it is impossible to estimate the true concentration of chromophore from the diffuse reflected light, as both absorption and scattering contribute to the overall reflected signal. Spatial frequency domain imaging is one of the promising techniques which allows for the disentanglement of scattering and absorption coefficients and further quantitative mapping of tissue chromophores. Yet, spatial frequency domain imaging demands high-cost equipment which hinders its applicability for biomedical diagnostics. In this work, we evaluate the feasibility of spatial frequency domain imaging low-cost implementation using LED-projector both on the optical phantoms in vitro and human skin in vivo. We demonstrate that the relative error achieved by this technique is of ∼5% and allows for rapid quantitative mapping of chromophores in tissues such as oxy- and deoxyhemoglobin, melanin etc.

Significance: Longitudinal tracking of hemodynamic changes in the breast has shown potential for neoadjuvant chemotherapy (NAC) outcome prediction. Spatial frequency domain imaging (SFDI) could be suitable for frequent monitoring of shallow breast tumors, but strong sensitivity to superficial absorbers presents a challenge. Aim: We investigated the efficacy of a two-layer SFDI inverse model that accounts for varying melanin concentration in the skin to improve discrimination of optical properties of deep tissue of the breast. Approach: Hemodynamic changes in response to localized breast compression were measured in 13 healthy volunteers using a handheld SFDI device. Epidermis optical thickness was determined based on spectral fitting of the model output and used to calculate subcutaneous optical properties. Results: Optical properties from a homogeneous model yielded physiologically unreasonable absorption and scattering coefficients for highly pigmented volunteers. The two-layer model compensated for the effect of melanin and yielded properties in the expected range for healthy breast. Extracted epidermal optical thickness was higher for higher Fitzpatrick types. Compression induced a decrease in total hemoglobin consistent with tissue blanching. Conclusions: The handheld SFDI device and two-layer model show potential for imaging hemodynamic responses that potentially could help predict efficacy of NAC in patients of varying skin tones.

Measurement of optical properties is critical for understanding light-tissue interaction, properly interpreting measurement data, and gaining better knowledge of tissue physicochemical properties. However, conventional optical measuring techniques are limited in point measurement, which partly hinders the applications on characterizing spatial distribution and inhomogeneity of optical properties of biological tissues. Spatial-frequency domain imaging (SFDI), as an emerging non-contact, depth-varying and wide-field optical imaging technique, is capable of measuring the optical properties in a wide field-of-view on a pixel-by-pixel basis. This review first describes the typical SFDI system and the principle for estimating optical properties using the SFDI technique. Then, the applications of SFDI in the fields of biomedicine, as well as food and agriculture, are reviewed, including burn assessment, skin tissue evaluation, tumor tissue detection, brain tissue monitoring, and quality evaluation of agro-products. Finally, a discussion on the challenges and future perspectives of SFDI for optical property estimation is presented.

Regular blood lipid screening is recommended for those suffering from cardiovascular disease (CVD). Current blood lipid measurements require invasive blood draws and lab-based testing. We introduce here shortwave infrared spatial frequency domain imaging (SWIR SFDI) as a non-invasive technique for blood lipid monitoring. We will report results from an analysis of SFDI measurement parameters (spatial frequency, wavelength, etc.) and light propagation models that result in accurate optical properties and chromophore extractions in the SWIR. Additionally, we will present results from a healthy volunteer study of longitudinal postprandial blood lipid changes measured in superficial blood vessels with SWIR SFDI.

While visual clinical impression is the standard of care for burn severity assessment, accuracy improves after the injury progresses, leading to patients waiting days for a diagnosis. Spatial Frequency Domain Imaging (SFDI) has shown the potential to assess burn grade as early as 24 hours post-burn. Here, we compared SFDI and Laser Speckle Imaging (LSI) at 24 and 72 hours after burn injury to clinical burn severity diagnosis. Three patients with burns ranging in severity were imaged. Both techniques showed an ability to categorize burn severity 24 hours after the initial injury, well before the outcome was determined by a clinician at 72 hours or later.

Autologous keratinocytes or stem cell based therapies are modern approaches for the treatment of skin loss in burn victims and chronic wound patients. The aim of this study is to identify depth-resolved structural changes in treated burn wounds using Spatial Frequency Domain Imaging (SFDI). When altering the investigated depth into tissue via the spatial frequency used in our calculations, we found changes in the scattering parameters for the treated samples. These scattering changes are correlated with histology, indicating a potential means to monitor re-epithelization and collagen formation during the treatment process across the entire wound area.

In this presentation I will describe our recent work to extend the spectral content of spatial frequency domain imaging (SFDI) to the short wave infrared (SWIR, 900-1300 nm). I will describe the unique instrumentation and methods needed for SWIR-SFDI measurements, and discuss the advantages and tradeoffs of imaging in the SWIR compared to the VIS and NIR. I will also present several preclinical and clinical application examples of SWIR-SFDI, including monitoring of edema, blood lipids, and spatial mapping of lipids in tumors.

Herein, we report on a depth-resolved Macroscopic Fluorescence Lifetime Imaging (MFLI) analytic framework based around machine learning coupled with a computationally efficient Monte Carlo-based data simulation workflow for robust and user-friendly model training. Our Siamese convolutional neural network (CNN) takes both optical properties (OPs) and time-resolved fluorescence decays as input and reconstructs both lifetime maps and depth profiles simultaneously. We validate our approach using phantom embeddings in silico and experimentally using Spatial Frequency Domain Imaging (SFDI) for OP retrieval. To our knowledge, this is the first study reporting the augmentation of MFLI with wide-field SFDI for lifetime topography.

The feasibility of the spatial frequency domain imaging (SFDI) for early treatment assessment in a mouse femoral injury model was investigated. For mice with and without treatment, the revascularization process was monitored by SFDI, which provides the total hemoglobin concentration (THC) of the injured bone and surrounding soft tissues. The biomechanical strength of the healed femurs was measured after 4 weeks of healing. The correlation between the SFDI-derived THC and the biomechanical strength will be investigated. Such correlation will be used to develop a prediction model to estimate the bone healing outcome at an early time point.

Significance: Spatial frequency domain imaging (SFDI), a noncontact wide-field imaging technique using patterned illumination with multiple wavelengths, has been used to quantitatively measure structural and functional parameters of in vivo tissue. Using SFDI in a porcine model, we previously found that scattering changes in skin could potentially be used to noninvasively assess burn severity and monitor wound healing. Translating these findings to human subjects necessitates a better understanding of the variation in “baseline” human skin scattering properties across skin types and anatomical locations. Aim: Using SFDI, we aim to characterize the variation in the reduced scattering coefficient (μs′) for skin across a range of pigmentation and anatomic sites (including common burn locations) for normal human subjects. These measurements are expected to characterize baseline human skin properties to inform our use of SFDI for clinical burn severity and wound healing assessments. Approach: SFDI was used to measure μs′ in the visible- and near-infrared regime (471 to 851 nm) in 15 subjects at 10 anatomical locations. Subjects varied in age, gender, and Fitzpatrick skin type. Results: For all anatomical locations, the coefficient of variation in measured μs′ decreased with increasing wavelength. High intersubject variation in μs′ at visible wavelengths coincided with large values of the melanin extinction coefficient at those wavelengths. At 851 nm, where intersubject variation in μs′ was smallest for all anatomical locations and absorption from melanin is minimal, significant intrasubject differences in μs′ were observed at the different anatomical locations. Conclusions: Our study is the first report of wide-field mapping of human skin scattering properties across multiple skin types and anatomical locations using SFDI. Measured μs′ values varied notably between skin types at wavelengths where absorption from melanin was prominent. Additionally, μs′ varied considerably across different anatomical locations at 851 nm, where the confounding effects from melanin absorption are minimized.

In this work, the effect of the thermo-hydrotherapy procedure on the immerged skin has been evaluated optically by monitoring the skin diffuse transmittance based on spatial frequency domain imaging technique.

Intracranial aneurysms (ICAs) are focal dilatations that imply a weakening of the brain artery. Incidental rupture of an ICA is increasingly responsible for significant mortality and morbidity in the American’s aging population. Previous studies have quantified the pressure-volume characteristics, uniaxial mechanical properties, and morphological features of human aneurysms. In this pilot study, for the first time, we comprehensively quantified the mechanical, collagen fiber microstructural, and morphological properties of one resected human posterior inferior cerebellar artery aneurysm. The tissue from the dome of a right posterior inferior cerebral aneurysm was first mechanically characterized using biaxial tension and stress relaxation tests. Then, the load-dependent collagen fiber architecture of the aneurysm tissue was quantified using an in-house polarized spatial frequency domain imaging system. Finally, optical coherence tomography and histological procedures were used to quantify the tissue’s microstructural morphology. Mechanically, the tissue was shown to exhibit hysteresis, a nonlinear stress-strain response, and material anisotropy. Moreover, the unloaded collagen fiber architecture of the tissue was predominantly aligned with the testing Y-direction and rotated towards the X-direction under increasing equibiaxial loading. Furthermore, our histological analysis showed a considerable damage to the morphological integrity of the tissue, including lack of elastin, intimal thickening, and calcium deposition. This new unified characterization framework can be extended to better understand the mechanics-microstructure interrelationship of aneurysm tissues at different time points of the formation or growth. Such specimen-specific information is anticipated to provide valuable insight that may improve our current understanding of aneurysm growth and rupture potential.

Only 30% of dental caries are detected early enough for restorative remineralization treatments. Here, we present a near infrared spatial frequency domain imaging system that can detect and quantitatively assess early-stage dental caries.

Intravascular polarimetry (IVP) with polarization-sensitive optical frequency domain imaging measures polarization properties of the coronary arterial wall in parallel with the intensity images of conventional optical frequency domain imaging ([1][1],[2][2]). Tissues rich in collagen and smooth