Deep Tissue Blood Flow Research Articles

Sustained acoustic medicine treatment of discogenic chronic low back pain: A randomized, multisite, double-blind, placebo-controlled trial.

Sustained acoustic medicine (SAM) is a noninvasive long-term treatment that provides essential mechanical and thermal stimulus to accelerate soft tissue healing, alleviate pain, and improve physical activity. SAM increases localized deep tissue temperature, blood flow, cellular proliferation, migration, and nutrition exchange, resulting in reduced inflammation and an increased rate of tissue regeneration. To assess the efficacy of SAM treatment of discogenic back pain in the lower spinal column to reduce pain, improve quality of life, and lower pharmacotherapy use. Sixty-five subjects with chronic low back pain were randomly assigned to SAM (N= 33) or placebo (N= 32) groups. Subjects self-applied SAM device bilaterality on the lower lumbar region for 4 hours daily for 8 weeks and completed daily pain diaries before, during, and after treatment. Subjects recorded pain reduction using a numeric rating scale (NRS), medication use, and physical activity using the Global Rating of Change (GROC) and Oswestry Disability Index (ODI). SAM treatment significantly reduced chronic lower back pain from baseline relative to placebo treatment (p< 0.0001). SAM treated subjects reported significantly lower back pain at 4 weeks, with the highest pain reduction (-2.58 points NRS, p< 0.0001) reported at 8 weeks. Similar trends were observed in improved physical activity (3.48 GROC, p< 0.0001, 69-88% ODI, p< 0.0001) and 22.5% (15.2 morphine milligram equivalent) reduction in the use of opioid medication from baseline to 8 weeks. Daily, home-use SAM treatment significantly improves the clinical symptoms of chronic lower back pain, improves physical mobility, and reduces daily medication use. SAM treatment is well-tolerated by patients and may be considered a safe, non-invasive treatment option for chronic discogenic, lower back pain.

Tunable dynamical tissue phantom for laser speckle imaging.

We introduce a novel method to design and implement a tunable dynamical tissue phantom for laser speckle-based in-vivo blood flow imaging. This approach relies on stochastic differential equations (SDE) to control a piezoelectric actuator which, upon illuminated with a laser source, generates speckles of pre-defined probability density function and auto-correlation. The validation experiments show that the phantom can generate dynamic speckles that closely replicate both surfaces as well as deep tissue blood flow for a reasonably wide range and accuracy.

Pathlength-selective, interferometric diffuse correlation spectroscopy (PaLS-iDCS).

Diffuse correlation spectroscopy (DCS) is an optical method that offers non-invasive assessment of blood flow in tissue through the analysis of intensity fluctuations in diffusely backscattered coherent light. The non-invasive nature of the technique has enabled several clinical applications for deep tissue blood flow measurements, including cerebral blood flow monitoring as well as tumor blood flow mapping. While a promising technique, in measurement configurations targeting deep tissue hemodynamics, the standard DCS implementations suffer from insufficient signal-to-noise ratio (SNR), depth sensitivity, and sampling rate, limiting their utility. In this work, we present an enhanced DCS method called pathlength-selective, interferometric DCS (PaLS-iDCS), which improves upon both the sensitivity of the measurement to deep tissue hemodynamics and the SNR of the measurement using pathlength-specific coherent gain. Through interferometric detection, PaLS-iDCS can provide time-of-flight (ToF) specific blood flow information without the use of expensive time-tagging electronics and low-jitter detectors. The new technique is compared to time-domain DCS (TD-DCS), another enhanced DCS method able to resolve photon ToF in tissue, through Monte Carlo simulation, phantom experiments, and human subject measurements. PaLS-iDCS consistently demonstrates improvements in SNR (>2x) for similar measurement conditions (same photon ToF), and the SNR improvements allow for measurements at extended photon ToFs, which have increased sensitivity to deep tissue hemodynamics (~50% increase). Further, like TD-DCS, PaLS-iDCS allows direct estimation of tissue optical properties from the sampled ToF distribution without the need for a separate spectroscopic measurement. This method offers a relatively straightforward way to allow DCS systems to make robust measurements of blood flow with greatly enhanced sensitivity to deep tissue hemodynamics, enabling further applications of this non-invasive technology.

A portable optical pulsatile flowmetry demonstrates strong clinical relevance for diabetic foot perfusion assessment.

We present a robust, cost-effective (<2000 USD), and portable optical diffuse speckle pulsatile flowmetry (DSPF) device with a flexible handheld probe for deep tissue blood flow measurement in the human foot as well as a first-in-man observational clinical study using the proposed optical device for tissue ischemia assessment and peripheral artery disease (PAD) diagnosis. Blood flow in tissue is inherently pulsatile in nature. However, most conventional methods cannot measure deep tissue-level pulsatile blood flow noninvasively. The proposed optical device can measure tissue-level pulsatile blood flow ∼6 mm underneath the skin surface. A new quantitative tissue perfusion index (TPIDSPF) based on frequency domain analysis of the pulsatile blood flow waveform is defined to assess tissue ischemia status. Through a clinical study involving 66 subjects, including healthy individuals and diabetes patients with and without PAD, TPIDSPF demonstrated strong correlations of 0.720 with transcutaneous tissue partial oxygen pressure (TcPO2) and 0.652 with toe-brachial index (TBI). Moreover, among the three methods, TPIDSPF demonstrated the highest area under the curve for PAD diagnosis among diabetes patients, with a notable value of 0.941. The promising clinical results suggest that the proposed optical method has the potential to be an effective clinical tool for identifying PAD among the diabetic cohort.

Non-invasive low-cost deep tissue blood flow measurement with integrated Diffuse Speckle Contrast Spectroscopy.

Diffuse Correlation Spectroscopy (DCS) is a widely used non-invasive measurement technique to quantitatively measure deep tissue blood flow. Conventional implementations of DCS use expensive single photon counters as detecting elements and optical probes with bulky fiber optic cables. In recent years, newer approaches to blood flow measurement such as Diffuse Speckle Contrast Analysis (DSCA) and Speckle Contrast Optical Spectroscopy (SCOS), have adapted speckle contrast analysis methods to simplify deep tissue blood flow measurements using cameras and single photon counting avalanche detector arrays as detectors. Here, we introduce and demonstrate integrated Diffuse Speckle Contrast Spectroscopy (iDSCS), a novel optical sensor setup which leverages diffuse speckle contrast analysis for probe-level quantitative measurement of tissue blood flow. iDSCS uses a standard photodiode configured in photovoltaic mode to integrate photon intensity fluctuations over multiple integration durations using a custom electronic circuit, as opposed to the high frequency sampling of photon counts with DCS. We show that the iDSCS device is sensitive to deep-tissue blood flow measurements with experiments on a human forearm and compare the sensitivity and dynamic range of the device to a conventional DCS instrument. The iDSCS device features a low-cost, low-power, small form factor instrument design that will enable wireless probe-level measurements of deep tissue blood 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.

Deep-learning-based separation of shallow and deep layer blood flow rates in diffuse correlation spectroscopy.

Diffuse correlation spectroscopy faces challenges concerning the contamination of cutaneous and deep tissue blood flow. We propose a long short-term memory network to directly quantify the flow rates of shallow and deep-layer tissues. By exploiting the different contributions of shallow and deep-layer flow rates to auto-correlation functions, we accurately predict the shallow and deep-layer flow rates (RMSE = 0.047 and 0.034 ml/min/100 g of simulated tissue, R2 = 0.99 and 0.99, respectively) in a two-layer flow phantom experiment. This approach is useful in evaluating the blood flow responses of active muscles, where both cutaneous and deep-muscle blood flow increase with exercise.

SpeckleCam: high-resolution computational speckle contrast tomography for deep blood flow imaging.

Laser speckle contrast imaging is widely used in clinical studies to monitor blood flow distribution. Speckle contrast tomography, similar to diffuse optical tomography, extends speckle contrast imaging to provide deep tissue blood flow information. However, the current speckle contrast tomography techniques suffer from poor spatial resolution and involve both computation and memory intensive reconstruction algorithms. In this work, we present SpeckleCam, a camera-based system to reconstruct high resolution 3D blood flow distribution deep inside the skin. Our approach replaces the traditional forward model using diffuse approximations with Monte-Carlo simulations-based convolutional forward model, which enables us to develop an improved deep tissue blood flow reconstruction algorithm. We show that our proposed approach can recover complex structures up to 6 mm deep inside a tissue-like scattering medium in the reflection geometry. We also conduct human experiments to demonstrate that our approach can detect reduced flow in major blood vessels during vascular occlusion.

Editorial: Advanced photonic devices and sensing systems

The Diffuse Speckle Pulsatile Flowmetry provides an high monitoring rates of around 300 Hz for non-invasive measurement of blood flow in deep tissue, exhibiting promising potential for the monitoring various pathologies associated with abnormal blood flow.In the reported article author examined the parameter comprises this technique including speckle size and exposure time on measuere flow reading experimentally and reported how the flow measurement sensitivity was affected by these parameters.3. Che, Zonglun, Jun Wang, Pan Xu, Xijia Gu, Lina Ma, Jing Zhu, and Chunyan Cao. "A spatially non-overlapping dual-wavelength 2D FBG for the measurement of temperature and strain." Frontiers in Physics ( 2022): 925.In the reported work auhtor proposed designing of a dual-wavelength 2D fiber Bragg grating (FBG) written on a standard single-mode fiber to monitor temperature and strain simultanously. The sensor showed an high sensitivty for temperature and strain of 10.64pm/°C and 0.882731pm/uε at the central wavelength of 1548nm, while 10.74pm/°C and 0.916080pm/uε at the central wavelength of 1550nm.4. Shi, Weihua, Rongqiu Mu, Xiaochen Guo, Rushan Jiang, Mingyu Shangguan, Qing Feng Li, Huiyi Zhang, Ling Zhang, and

Development of single photon avalanche detectors for NIR light detection

Near-infrared (NIR) light is used in several non-invasive biomedical techniques to measure the blood flow in deep tissues. The BIOSPAD project targets the development of SPAD arrays specifically designed for Diffuse Correlation Spectroscopy (DCS) in the NIR to measure deep tissue microvascular blood flow. In the first stage of the project, single SPADs with multiplication layers buried at different depths have been designed at IFAE and produced in a 150 nm CMOS technology. In this study, we present results of the characterization of SPAD devices with an area of 50 × 50 µm2 operated with an external passive quenching circuit. We compared properties, such as Dark Count Rate (DCR) and Photon Detection Efficiency (PDE) of the different SPAD designs. The PDE for 780 nm light of SPADs with a buried multiplication layer was observed to be in the range of 10–20% with a DCR of the order of 2 kHz. The results of these first prototypes are promising and are being followed up by the development of a new generation of CMOS SPADs designed to further improve the NIR light response.

Laser speckle simulation tool based on stochastic differential equations for bio imaging applications.

Laser speckle-based blood flow imaging is a well-accepted and widely used method for pre-clinical and clinical applications. Although it was introduced as a method to measure only superficial blood flow (< 1mm depth), several recently introduced variants resulted in measuring deep tissue blood flow (a few cm) as well. A means of simulating laser speckles is often necessary for the analysis and development of these imaging modalities, as evident from many such attempts towards developing simulation tools in the past. Such methods often employ Fourier transforms or statistical tools to simulate speckles with desired statistical properties. We present the first method to use a stochastic differential equation to generate laser speckles with a pre-determined probability density function and a temporal auto-correlation. The method allows the choice of apriori gamma distribution along with simple exponential or more complex temporal auto-correlation statistics for simulated speckles, making it suitable for different blood flow profiles. In contrast to the existing methods that often generate speckles associated with superficial flow, we simulate both superficial and diffuse speckles leading to applications in deep tissue blood flow imaging. In addition, we have also incorporated appropriate models for noise associated with the detectors to simulate realistic speckles. We have validated our model by comparing the simulated speckles with those obtained from in-vivo studies in mice and healthy human subject.

Experimental characterization of diffuse speckle pulsatile flowmetry system

The recently developed Diffuse Speckle Pulsatile Flowmetry (DSPF) technique offers high measurement rates of around 300 Hz for non-invasive blood flow measurement of blood flow in deep tissue (up to a depth of approximately 15 mm), showing promising potential for the monitoring of various pathologies associated with abnormal blood flow. The effects of various parameters associated with this technique such as speckle size and exposure time on the measured flow readings, however, have yet to be studied. In this work, we examine these relationships experimentally, observing that the number of pixels per speckle (a measure of speckle size) and exposure time have a strong inverse relationship and a positive relationship respectively with the measured DSPF readings in no-flow setups using both static single light scattering and multiple light scattering mediums. We also studied how the sensitivity of DSPF readings to flow is affected by these parameters, finding that the number of pixels per speckle and exposure time have an inverse relationship and strong positive linear relationship respectively with the gradient of the regression line between the actual and measured flow rates in a dynamic setup using a tissue-mimicking flow phantom. It is hoped that these results would enable researchers using the DSPF technique to select and utilize the most optimized settings for their specific use applications.

Evaluation of Local Skeletal Muscle Blood Flow in Manipulative Therapy by Diffuse Correlation Spectroscopy.

Manipulative therapy (MT) is applied to motor organs through a therapist’s hands. Although MT has been utilized in various medical treatments based on its potential role for increasing the blood flow to the local muscle, a quantitative validation of local muscle blood flow in MT remains challenging due to the lack of appropriate bedside evaluation techniques. Therefore, we investigated changes in the local blood flow to the muscle undergoing MT by employing diffuse correlation spectroscopy, a portable and emerging optical measurement technology that non-invasively measures blood flow in deep tissues. This study investigated the changes in blood flow, heart rate, blood pressure, and autonomic nervous activity in the trapezius muscle through MT application in 30 volunteers without neck and shoulder injury. Five minutes of MT significantly increased the median local blood flow relative to that of the pre-MT period (p < 0.05). The post-MT local blood flow increase was significantly higher in the MT condition than in the control condition, where participants remained still without receiving MT for the same time (p < 0.05). However, MT did not affect the heart rate, blood pressure, or cardiac autonomic nervous activity. The post-MT increase in muscle blood flow was significantly higher in the participants with muscle stiffness in the neck and shoulder regions than in those without (p < 0.05). These results suggest that MT could increase the local blood flow to the target skeletal muscle, with minimal effects on systemic circulatory function.

Lossless Compressed Sensing of Photon Counts for Fast Diffuse Correlation Spectroscopy.

Diffuse Correlation Spectroscopy (DCS), a noninvasive optical technique, measures deep tissue blood flow using avalanche photon counting modules and data acquisition devices such as FPGAs or correlator boards. Conventional DCS instruments use in-processor counter modules that consume 32 bits/channel which is inefficient for low-photon budget situations prevalent in diffuse optics. Scaling these photon counters for large-scale imaging applications is difficult due to bandwidth and processing time considerations. Here, we introduce a new, lossless compressed sensing approach for fast and efficient detection of photon counts. The compressed DCS method uses an array of binary-coded-decimal counters to record photon counts from 8 channels simultaneously as a single 32-bit number. We validate the compressed DCS approach by comparisons with conventional DCS in experiments on tissue simulating phantoms and in-vivo arm cuff occlusion. Lossless compressed DCS was implemented with 87.5% compression efficiency. In tissue simulating phantoms, it was able to accurately estimate a tissue blood flow index, with no statistically significant difference compared to conventional DCS. Compressed DCS also recorded blood flow in vivo, in human forearm, with signal-to-noise ratio and dynamic range comparable to conventional DCS. Lossless 87.5% efficient compressed sensing counting of photon counts meets and exceeds benchmarks set by conventional DCS systems, offering a low-cost alternative for fast (~100 Hz) deep tissue blood flow measurement with optics.

Extraction of tissue optical property and blood flow from speckle contrast diffuse correlation tomography (scDCT) measurements.

Measurement of blood flow in tissue provides vital information for the diagnosis and therapeutic monitoring of various vascular diseases. A noncontact, camera-based, near-infrared speckle contrast diffuse correlation tomography (scDCT) technique has been recently developed for 3D imaging of blood flow index (αDB) distributions in deep tissues up to a centimeter. A limitation with the continuous-wave scDCT measurement of blood flow is the assumption of constant and homogenous tissue absorption coefficient (μ a ). The present study took the advantage of rapid, high-density, noncontact scDCT measurements of both light intensities and diffuse speckle contrast at multiple source-detector distances and developed two-step fitting algorithms for extracting both μ a and αDB. The new algorithms were tested in tissue-simulating phantoms with known optical properties and human forearms. Measurement results were compared against established near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) techniques. The accuracies of our new fitting algorithms with scDCT measurements in phantoms (up to 16% errors) and forearms (up to 23% errors) are comparable to relevant study results (up to 25% errors). Knowledge of μ a not only improved the accuracy in calculating αDB but also provided the potential for quantifying tissue blood oxygenation via spectral measurements. A multiple-wavelength scDCT system with new algorithms is currently developing to fit multi-wavelength and multi-distance data for 3D imaging of both blood flow and oxygenation distributions in deep tissues.

Time resolved speckle contrast optical spectroscopy at quasi-null source-detector separation for non-invasive measurement of microvascular blood flow.

Time (or path length) resolved speckle contrast optical spectroscopy (TD-SCOS) at quasi-null (2.85 mm) source-detector separation was developed and demonstrated. The method was illustrated by in vivo studies on the forearm muscle of an adult subject. The results have shown that selecting longer photon path lengths results in higher hyperemic blood flow change and a faster return to baseline by a factor of two after arterial cuff occlusion when compared to SCOS without time resolution. This indicates higher sensitivity to the deeper muscle tissue. In the long run, this approach may allow the use of simpler and cheaper detector arrays compared to time resolved diffuse correlation spectroscopy that are based on readily available technologies. Hence, TD-SCOS may increase the performance and decrease cost of devices for continuous non-invasive, deep tissue blood flow monitoring.

Simultaneous measurements of tissue blood flow and oxygenation using a wearable fiber-free optical sensor.

.Significance: There is an essential need to develop wearable multimodality technologies that can continuously measure both blood flow and oxygenation in deep tissues to investigate and manage various vascular/cellular diseases.Aim: To develop a wearable dual-wavelength diffuse speckle contrast flow oximetry (DSCFO) for simultaneous measurements of blood flow and oxygenation variations in deep tissues.Approach: A wearable fiber-free DSCFO probe was fabricated using 3D printing to confine two small near-infrared laser diodes and a tiny CMOS camera in positions for DSCFO measurements. The spatial diffuse speckle contrast and light intensity measurements at the two different wavelengths enable quantification of tissue blood flow and oxygenation, respectively. The DSCFO was first calibrated using tissue phantoms and then tested in adult forearms during artery cuff occlusion.Results: Phantom tests determined the largest effective source–detector distance (15 mm) and optimal camera exposure time (10 ms) and verified the accuracy of DSCFO in measuring absorption coefficient variations. The DSCFO detected substantial changes in forearm blood flow and oxygenation resulting from the artery occlusion, which meet physiological expectations and are consistent with previous study results.Conclusions: The wearable DSCFO may be used for continuous and simultaneous monitoring of blood flow and oxygenation variations in freely behaving subjects.

Interferometric speckle visibility spectroscopy (ISVS) for human cerebral blood flow monitoring

Infrared light scattering methods have been developed and employed to non-invasively monitor human cerebral blood flow (CBF). However, the number of reflected photons that interact with the brain is low when detecting blood flow in deep tissue. To tackle this photon-starved problem, we present and demonstrate the idea of interferometric speckle visibility spectroscopy (ISVS). In ISVS, an interferometric detection scheme is used to boost the weak signal light. The blood flow dynamics are inferred from the speckle statistics of a single frame speckle pattern. We experimentally demonstrated the improvement in the measurement of fidelity by introducing interferometric detection when the signal photon number is low. We apply the ISVS system to monitor the human CBF in situations where the light intensity is ∼100-fold less than that in common diffuse correlation spectroscopy (DCS) implementations. Due to the large number of pixels (∼2 × 105) used to capture light in the ISVS system, we are able to collect a similar number of photons within one exposure time as in normal DCS implementations. Our system operates at a sampling rate of 100 Hz. At the exposure time of 2 ms, the average signal photoelectron number is ∼0.95 count/pixel, yielding a single pixel interferometric measurement signal-to-noise ratio (SNR) of ∼0.97. The total ∼2 × 105 pixels provide an expected overall SNR of 436. We successfully demonstrate that the ISVS system is able to monitor the human brain pulsatile blood flow, as well as the blood flow change when a human subject is doing a breath-holding task.

Diffuse correlation spectroscopy measurements of blood flow using 1064nm light.

.Significance: Diffuse correlation spectroscopy (DCS) is an established optical modality that enables noninvasive measurements of blood flow in deep tissue by quantifying the temporal light intensity fluctuations generated by dynamic scattering of moving red blood cells. Compared with near-infrared spectroscopy, DCS is hampered by a limited signal-to-noise ratio (SNR) due to the need to use small detection apertures to preserve speckle contrast. However, DCS is a dynamic light scattering technique and does not rely on hemoglobin contrast; thus, there are significant SNR advantages to using longer wavelengths () for the DCS measurement due to a variety of biophysical and regulatory factors.Aim: We offer a quantitative assessment of the benefits and challenges of operating DCS at 1064 nm versus the typical 765 to 850 nm wavelength through simulations and experimental demonstrations.Approach: We evaluate the photon budget, depth sensitivity, and SNR for detecting blood flow changes using numerical simulations. We discuss continuous wave (CW) and time-domain (TD) DCS hardware considerations for 1064 nm operation. We report proof-of-concept measurements in tissue-like phantoms and healthy adult volunteers.Results: DCS at 1064 nm offers higher intrinsic sensitivity to deep tissue compared with DCS measurements at the typically used wavelength range (765 to 850 nm) due to increased photon counts and a slower autocorrelation decay. These advantages are explored using simulations and are demonstrated using phantom and in vivo measurements. We show the first high-speed (cardiac pulsation-resolved), high-SNR measurements at large source–detector separation (3 cm) for CW-DCS and late temporal gates (1 ns) for TD-DCS.Conclusions: DCS at 1064 nm offers a leap forward in the ability to monitor deep tissue blood flow and could be especially useful in increasing the reliability of cerebral blood flow monitoring in adults.

Fast pulsatile blood flow measurement in deep tissue through a multimode detection fiber.

.Significance: Noninvasive in vivo fast pulsatile blood flow measurement in deep tissue is important because the blood flow waveform is correlated with physiological parameters, such as blood pressure and elasticity of blood vessels. Compromised blood flow may cause diseases, such as stroke, foot ulcer, and myocardial ischemia. There is great clinical demand for a portable and cost-effective device for noninvasive pulsatile blood flow measurement.Aim: A diffuse-optics-based method, diffuse speckle pulsatile flowmetry (DSPF), was developed for fast measurement () of deep tissue blood flow noninvasively. To validate its performance, both a phantom experiment and in vivo demonstration were conducted.Approach: Over the past two decades, single-mode fibers have been used as detection fibers in most diffuse-optics-based deep tissue blood flow measurement modalities. We used a multimode (MM) detection fiber with a core size of for diffused speckle pattern detection. A background intensity correction algorithm was implemented for speckle contrast calculation. The MM detection fiber helped to achieve a level of deep tissue blood flow measurement similar to that of conventional modalities, such as diffuse correlation spectroscopy and diffuse speckle contrast analysis, but it increases the measurement rate of blood flow to 300 Hz.Results: The design and implementation of the DSPF system were introduced. The theory of the background intensity correction for the diffused speckle pattern detected by the MM fiber was explained. A flow phantom was built for validation of the performance of the DSPF system. An in vivo cuff-induced occlusion experiment was performed to demonstrate the capability of the proposed DSPF system.Conclusions: An MM detection fiber can help to achieve fast () pulsatile blood flow measurement in the proposed DSPF method. The cost-effective device and the fiber-based flexible probe increase the usability of the DSPF system significantly.