Optical methods for blood perfusion measurement--theoretical comparison among four different modalities.

Blood perfusion in human tissue can be measured in vivo by means of various optical methods, which seem to be very different from one another. The most prominent examples of them are laser Doppler flowmetry, laser speckle contrast imaging, diffuse correlation spectroscopy, and the most recently developed diffuse speckle contrast analysis. In this paper, we claim that these four seemingly different modalities are examining different aspects of the same entity-the temporal autocorrelation function of scattered photons. We will show how the observables in each modality can be theoretically derived from the temporal autocorrelation function, and will discuss the merits and drawbacks of each modality in its practical use.

Multi-channel deep tissue flowmetry based on temporal diffuse speckle contrast analysis.

Recently, diffuse speckle contrast analysis (DSCA) was introduced as a competent modality for deep tissue blood flow measurement, where the speckle contrast is calculated over spatial domain on the CCD image of diffuse reflectance. In this paper, we introduce time-domain DSCA where temporal statistics are used for speckle contrast calculation and results in the same deep tissue flow measurement. This new modality is especially suitable for multi-channel real-time flowmetry, and we demonstrate its performance on human arm during cuff occlusion test. Independent component analysis (ICA) study on multi-channel data shows promising results about underlying physiology.

Deep tissue flowmetry based on diffuse speckle contrast analysis.

Diffuse correlation spectroscopy (DCS) is an emerging modality for noninvasive deep tissue blood flow monitoring that is becoming increasingly popular; it conducts an autocorrelation analysis of fast fluctuating photon count signals from a single speckle. In this Letter, we show that the same level of deep tissue flow information can be obtained from a much simpler analysis on the spatial distribution of the speckles that is obtained by a CCD camera, which we named diffuse speckle contrast analysis (DSCA). Both the flow phantom experiment and in vivo cuff occlusion data are presented. DSCA can be considered a new optical modality that combines DCS and laser speckle contrast imaging (LSCI), which exploits simple instrumentation and analysis and yet is sensitive to deep tissue flow.

Pressure stimulus study on acupuncture points with multi-channel multimode-fiber diffuse speckle contrast analysis (MMF-DSCA).

A multi-channel multimode-fiber deep tissue flowmetry system has been constructed based on diffuse speckle contrast analysis (DSCA) for simultaneous blood flow measurements at different locations on the human body. This system has been utilized in an acupuncture study within the field of traditional Chinese medicine (TCM), primarily focusing on acupuncture points along the large intestine meridian. Deep tissue blood flow was monitored at four different acupuncture points (LI1, LI5, LI10, and ST25) with a sampling rate of 60 Hz while applying pressure stimulus on LI4 (hegu or hapgok). Although the blood flow index (BFI) and blood volume (BV) did not exhibit significant changes after the pressure stimulus, an increase in the amplitude and complexity of low-frequency oscillations (LFOs) in microcirculation was observed.

A Review on Progress, Challenges, and Prospects of Material Jetting of Copper and Tungsten.

Copper (Cu) and tungsten (W) possess exceptional electrical and thermal conductivity properties, making them suitable candidates for applications such as interconnects and thermal conductivity enhancements. Solution-based additive manufacturing (SBAM) offers unique advantages, including patterning capabilities, cost-effectiveness, and scalability among the various methods for manufacturing Cu and W-based films and structures. In particular, SBAM material jetting techniques, such as inkjet printing (IJP), direct ink writing (DIW), and aerosol jet printing (AJP), present a promising approach for design freedom, low material wastes, and versatility as either stand-alone printers or integrated with powder bed-based metal additive manufacturing (MAM). Thus, this review summarizes recent advancements in solution-processed Cu and W, focusing on IJP, DIW, and AJP techniques. The discussion encompasses general aspects, current status, challenges, and recent research highlights. Furthermore, this paper addresses integrating material jetting techniques with powder bed-based MAM to fabricate functional alloys and multi-material structures. Finally, the factors influencing large-scale fabrication and potential prospects in this area are explored.

Coherent backscattering cone shape depends on the beam size.

Coherent backscattering (CBS) is a beautiful physical phenomenon that takes place in a highly scattering medium, which has potential application in noninvasive optical property measurement. The current model that explains the CBS cone shape, however, assumes the incoming beam diameter is infinitely large compared to the transport length. In this paper, we evaluate the effect of a finite scalar light illumination area on the CBS cone, both theoretically and experimentally. The quantitative relationship between laser beam size and the CBS cone shape is established by using two different finite beam models (uniform top hat and Gaussian distribution). A series of experimental data with varying beam diameters is obtained for comparison with the theory. Our study shows the CBS cone shape begins to show distortion when beam size becomes submillimeter, and this effect should not be ignored in general. In biological tissue where a normal large beam CBS cone is too narrow for detection, this small beam CBS may be more advantageous for more accurate and higher resolution tissue characterization.

Blood flow estimation via numerical integration of temporal autocorrelation function in diffuse correlation spectroscopy.

BACKGROUND AND OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical technique widely used to monitor blood flow. Recently, efforts have been made to derive new signal processing methods to minimize the systems used and shorten the signal processing time. Herein, we propose alternative approaches to obtain blood flow information via DCS by numerically integrating the temporal autocorrelation curves. METHODS: We use the following methods: the inverse of K2 (IK2)-based on the framework of diffuse speckle contrast analysis-and the inverse of the numerical integration of squared g1 (INISg1) which, based on the normalized electric field autocorrelation curve, is more simplified than IK2. In addition, g1 thresholding is introduced to further reduce computational time and make the suggested methods comparable to the conventional nonlinear fitting approach. To validate the feasibility of the suggested methods, studies using simulation, liquid phantom, and in vivo settings were performed. In the meantime, the suggested methods were implemented and tested on three types of Arduino (Arduino Due, Arduino Nano 33 BLE Sense, and Portenta H7) to demonstrate the possibility of miniaturizing the DCS systems using microcotrollers for signal processing. RESULTS: The simulation and experimental results confirm that both IK2 and INISg1 are sufficiently relevant to capture the changes in blood flow information. More interestingly, when g1 thresholding was applied, our results showed that INISg1 outperformed IK2. It was further confirmed that INISg1 with g1 thresholding implemented on a PC and Portenta H7, an advanced Arduino board, performed faster than did the deep learning-based, state-of-the-art processing method. CONCLUSION: Our findings strongly indicate that INISg1 with g1 thresholding could be an alternative approach to derive relative blood flow information via DCS, which may contribute to the simplification of DCS methodologies.

Dataset on transcriptome signature of skeletal muscle of young, adult and aged mice.

This data article reports the level of expression of messenger RNA (mRNA) obtained from a set of 18 skeletal muscle samples using Affymetrix Genechips Exon arrays. Data were obtained from Gastrocnemius muscle of C57BL6 male mice at 3 distinct age groups, 2, 11 and 25 months old representing young, mature adult and aged groups. The data submitted to GEO constitute a large dataset of 15,300 mRNA levels. The data include eighteen .CEL files obtained after scanning mouse exon arrays and one .xls file obtained after processing with Genespring GX 14.9. Three distinct files containing affymetrix data processed using Genespring and analyzed for differences between stages 2 per 2 are provided as supplementary data.

Nanoarray-based biomolecular detection using individual Au nanoparticles with minimized localized surface plasmon resonance variations.

Here, we present a mean to expand the use of individual metallic nanoparticles to two-dimensional plasmonic nanoarrays. An optical detection platform to track down localized surface plasmon resonance (LSPR) signals of individual nanoparticles on substrates was built for the application of plasmonic nanoarrays. A pseudoimage of nanoparticles on a substrate was reconstructed from their scattering spectra obtained by scanning a user-defined area. The spectral and spatial resolutions of the system were also discussed in detail. Most importantly, we present a method to normalize the localized surface plasmon resonance from geometrically different nanoparticles. After normalization, plasmonic responses from different particles become highly consistent, creating well-fitted dose-response curves of both surrounding refractive index changes and receptor-analyte binding to the surface of individual nanoparticles. Finally, the proof-of-concept system for plasmonic nanoarray detection is demonstrated by the measurement of the aptamer-thrombin binding event.

A Scalable Solution Route to Porous Networks of Nanostructured Black Tungsten.

This paper studied the feasibility of a new solution-processed method to manufacture black tungsten nanostructures by laser conversion of tungsten hexacarbonyl precursor on the Inconel 625 substrate under argon atmosphere at ambient pressure. The results show that sublimation of the precursor can be prevented if the decomposition temperature (>170 °C) is achieved using the laser heating method. Three different laser powers from 60-400 W were used to investigate the role of laser parameters on the conversion. It was found that lower laser power of 60 W resulted in a mixture of unconverted precursor and converted tungsten. Higher laser powers >200 W resulted in α-W (BCC) in one step without further heat treatment. Different oxygen concentrations from 0.5 ppm to 21 vol% were used in the laser canister to investigate the effect of oxygen concentration on the conversion. It was found that the hard vacuum (>10-4 torr) or hydrogen is not necessary to obtain α-W (BCC). The solar absorptance varied from 63-97%, depending on the amount of precursor deposited on the substrate and oxygen content in the laser canister. This solution-based laser conversion of tungsten precursor is a scalable method to manufacture tungsten coatings for high-temperature applications.

Low frequency oscillations assessed by diffuse speckle contrast analysis for foot angiosome concept.

An angiosome refers to a 3D tissue volume that is vascularized by a single artery and is a relatively new concept that is useful in vascular surgery; however, the direct relationship between arterial blood flow and micro-perfusion is still controversial. Here, we propose a diffuse speckle contrast analysis (DSCA), which is an emerging tissue perfusion monitoring modality, to investigate the correlations among low frequency oscillations (LFOs) measured from different areas on the feet of healthy subjects. We obtained reproducible results from the correlation analyses of LFOs, and their physiological implications were discussed. In order to confirm the changes in the frequency oscillations, we analyzed and compared the power spectral density changes due to heart rate variability in the electrocardiographic signal during reactive hyperemia and head-up tilt protocols.

Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography.

We have developed a novel parallel-plate diffuse optical tomography (DOT) system for three-dimensional in vivo imaging of human breast tumor based on large optical data sets. Images of oxy-, deoxy-, and total hemoglobin concentration as well as blood oxygen saturation and tissue scattering were reconstructed. Tumor margins were derived using the optical data with guidance from radiology reports and magnetic resonance imaging. Tumor-to-normal ratios of these endogenous physiological parameters and an optical index were computed for 51 biopsy-proven lesions from 47 subjects. Malignant cancers (N=41) showed statistically significant higher total hemoglobin, oxy-hemoglobin concentration, and scattering compared to normal tissue. Furthermore, malignant lesions exhibited a twofold average increase in optical index. The influence of core biopsy on DOT results was also explored; the difference between the malignant group measured before core biopsy and the group measured more than 1 week after core biopsy was not significant. Benign tumors (N=10) did not exhibit statistical significance in the tumor-to-normal ratios of any parameter. Optical index and tumor-to-normal ratios of total hemoglobin, oxy-hemoglobin concentration, and scattering exhibited high area under the receiver operating characteristic curve values from 0.90 to 0.99, suggesting good discriminatory power. The data demonstrate that benign and malignant lesions can be distinguished by quantitative three-dimensional DOT.

Correction: Early assessment of tumor response to photodynamic therapy using combined diffuse optical and diffuse correlation spectroscopy to predict treatment outcome.

[This corrects the article DOI: 10.18632/oncotarget.15720.].

Imaging complex structures with diffuse light.

We use diffuse optical tomography to quantitatively reconstruct images of complex phantoms with millimeter sized features located centimeters deep within a highly-scattering medium. A non-contact instrument was employed to collect large data sets consisting of greater than 10(7) source-detector pairs. Images were reconstructed using a fast image reconstruction algorithm based on an analytic solution to the inverse scattering problem for diffuse light.

Comparison of diffuse optical tomography of human breast with whole-body and breast-only positron emission tomography.

We acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using diffuse optical tomography (DOT) and positron emission tomography (PET). Co-registration of DOT and PET images was facilitated by a mutual information maximization algorithm. We also compared DOT and whole-body PET images of 14 patients with breast abnormalities. Positive correlations were found between total hemoglobin concentration and tissue scattering measured by DOT, and fluorodeoxyglucose (18F-FDG) uptake. In light of these observations, we suggest potential benefits of combining both PET and DOT for characterization of breast lesions.

Muscular blood flow responses as an early predictor of the severity of diabetic neuropathy at a later stage in streptozotocin-induced type I diabetic rats: a diffuse correlation spectroscopy study.

We propose a novel application of diffuse correlation spectroscopy to evaluate microvascular malfunctions of muscle tissue affected by hyperglycemia and determine their correlation with the severity of diabetic neuropathy at a later stage. Microvascular responses of the thigh muscle and the mechanical pain threshold of the hind paw of streptozotocin-induced type I diabetic rats were continuously monitored once per week for 70 days. Significantly decreased baseline blood flow and reactive hyperemia responses were observed as early as 1 week after hyperglycemia induction. The reactive hyperemia response at 2 weeks of hyperglycemia was highly correlated with the mechanical pain threshold at 8 weeks, at which time a decreased pain threshold was statistically confirmed in hyperglycemic rats relative to controls.

Standardized platform for coregistration of nonconcurrent diffuse optical and magnetic resonance breast images obtained in different geometries.

We present a novel methodology for combining breast image data obtained at different times, in different geometries, and by different techniques. We combine data based on diffuse optical tomography (DOT) and magnetic resonance imaging (MRI). The software platform integrates advanced multimodal registration and segmentation algorithms, requires minimal user experience, and employs computationally efficient techniques. The resulting superposed 3-D tomographs facilitate tissue analyses based on structural and functional data derived from both modalities, and readily permit enhancement of DOT data reconstruction using MRI-derived a-priori structural information. We demonstrate the multimodal registration method using a simulated phantom, and we present initial patient studies that confirm that tumorous regions in a patient breast found by both imaging modalities exhibit significantly higher total hemoglobin concentration (THC) than surrounding normal tissues. The average THC in the tumorous regions is one to three standard deviations larger than the overall breast average THC for all patients.

Quantitative comparison of tissue oxygen and motexafin lutetium uptake by ex vivo and noninvasive in vivo techniques in patients with intraperitoneal carcinomatosis.

Near-infrared diffuse reflectance spectroscopy (DRS) has been used to noninvasively monitor optical properties during photodynamic therapy (PDT). This technique has been extensively validated in tissue phantoms; however, validation in patients has been limited. This pilot study compares blood oxygenation and photosensitizer tissue uptake measured by multiwavelength DRS with ex vivo assays of the hypoxia marker, 2-(2-nitroimida-zol-1[H]-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5), and the photosensitizer (motexafin lutetium, MLu) from tissues at the same tumor site of three tumors in two patients with intra-abdominal cancers. Similar in vivo and ex vivo measurements of MLu concentration are carried out in murine radiation-induced fibrosarcoma (RIF) tumors (n=9). The selection of optimal DRS wavelength range and source-detector separations is discussed and implemented, and the association between in vivo and ex vivo measurements is examined. The results demonstrate a negative correlation between blood oxygen saturation (StO(2)) and EF5 binding, consistent with published relationships between EF5 binding and electrode measured pO(2), and between electrode measured pO(2) and StO(2). A tight correspondence is observed between in vivo DRS and ex vivo measured MLu concentration in the RIF tumors; similar data are positively correlated in the human intraperitoneal tumors. These results further demonstrate the potential of in vivo DRS measurements in clinical PDT.

Early assessment of tumor response to photodynamic therapy using combined diffuse optical and diffuse correlation spectroscopy to predict treatment outcome.

Photodynamic therapy (PDT) of cancer involves the use of a photosensitizer that can be light-activated to eradicate tumors via direct cytotoxicity, damage to tumor vasculature and stimulating the body's immune system. Treatment outcome may vary between individuals even under the same regime; therefore a non-invasive tumor response monitoring system will be useful for personalization of the treatment protocol. We present the combined use of diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) to provide early assessment of tumor response. The relative tissue oxygen saturation (rStO2) and relative blood flow (rBF) in tumors were measured using DOS and DCS respectively before and after PDT with reference to baseline values in a mouse model. In complete responders, PDT-induced decreases in both rStO2 and rBF levels were observed at 3 h post-PDT and the rBF remained low until 48 h post-PDT. Recovery of these parameters to baseline values was observed around 2 weeks after PDT. In partial responders, the rStO2 and rBF levels also decreased at 3 h post PDT, however the rBF values returned toward baseline values earlier at 24 h post-PDT. In contrast, the rStO2 and rBF readings in control tumors showed fluctuations above the baseline values within the first 48 h. Therefore tumor response can be predicted at 3 to 48 h post-PDT. Recovery or sustained decreases in the rBF at 48 h post-PDT corresponded to long-term tumor control. Diffuse optical measurements can thus facilitate early assessment of tumor response. This approach can enable physicians to personalize PDT treatment regimens for best outcomes.

Avian embryo monitoring during incubation using multi-channel diffuse speckle contrast analysis.

Determining the survival rate of avian embryos during incubation is essential for cost-saving in the poultry industry. A multi-channel diffuse speckle contrast analysis (DSCA) system, comprising four optical fiber channels, is proposed to achieve noninvasive in vivo measurements of deep tissue flow. The system was able to monitor chick embryo vital signs over the entire incubation period. Moreover, it proved useful in distinguishing between chick embryos in healthy and weakened conditions.