Measurement Of Tissue Blood Flow Research Articles

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.

Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice.

Much of what we know about insulin resistance is based on studies from metabolically active tissues such as the liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance; however, the underlying mechanisms remain incompletely understood. Arf6 (ADP ribosylation factor 6) is a small GTPase that plays a critical role in endothelial cell function. Here, we tested the hypothesis that the deletion of endothelial Arf6 will result in systemic insulin resistance. We used mouse models of constitutive endothelial cell-specific Arf6 deletion (Arf6f/- Tie2Cre+) and tamoxifen-inducible Arf6 knockout (Arf6f/f Cdh5CreER+). Endothelium-dependent vasodilation was assessed using pressure myography. Metabolic function was assessed using a battery of metabolic assessments including glucose and insulin tolerance tests and hyperinsulinemic-euglycemic clamps. We used a fluorescence microsphere-based technique to measure tissue blood flow. Skeletal muscle capillary density was assessed using intravital microscopy. Endothelial Arf6 deletion impaired insulin-stimulated vasodilation in white adipose tissue and skeletal muscle feed arteries. The impairment in vasodilation was primarily due to attenuated insulin-stimulated nitric oxide bioavailability but independent of altered acetylcholine-mediated or sodium nitroprusside-mediated vasodilation. Endothelial cell-specific deletion of Arf6 also resulted in systematic insulin resistance in normal chow-fed mice and glucose intolerance in high-fat diet-fed obese mice. The underlying mechanisms of glucose intolerance were reductions in insulin-stimulated blood flow and glucose uptake in the skeletal muscle and were independent of changes in capillary density or vascular permeability. Results from this study support the conclusion that endothelial Arf6 signaling is essential for maintaining insulin sensitivity. Reduced expression of endothelial Arf6 impairs insulin-mediated vasodilation and results in systemic insulin resistance. These results have therapeutic implications for diseases that are associated with endothelial cell dysfunction and insulin resistance such as diabetes.

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.

Quantitative Evaluation of Manipulative Therapy Effects by Tissue Blood Flow and Muscle Stiffness Measurements

Quantitative Evaluation of Manipulative Therapy Effects by Tissue Blood Flow and Muscle Stiffness Measurements

Improved spatial speckle contrast model for tissue blood flow imaging: effects of spatial correlation among neighboring camera pixels.

Speckle contrast analysis is the basis of laser speckle imaging (LSI), a simple, inexpensive, noninvasive technique used in various fields of medicine and engineering. A common application of LSI is the measurement of tissue blood flow. Accurate measurement of speckle contrast is essential to correctly measure blood flow. Variables, such as speckle grain size and camera pixel size, affect the speckle pattern and thus the speckle contrast. We studied the effects of spatial correlation among adjacent camera pixels on the resulting speckle contrast values. We derived a model that accounts for the potential correlation of intensity values in the common experimental situation where the speckle grain size is larger than the camera pixel size. In vitro phantom experiments were performed to test the model. Our spatial correlation model predicts that speckle contrast first increases, then decreases as the speckle grain size increases relative to the pixel size. This decreasing trend opposes what is observed with a standard speckle contrast model that does not consider spatial correlation. Experimental data are in good agreement with the predictions of our spatial correlation model. We present a spatial correlation model that provides a more accurate measurement of speckle contrast, which should lead to improved accuracy in tissue blood flow measurements. The associated correlation factors only need to be calculated once, and open-source software is provided to assist with the calculation.

Continuous monitoring of tissue oxygen metabolism based on multi-wavelength diffuse correlation spectroscopy using LSTM-based RNN model

Growing incidences of cardiovascular diseases have driven demand for continuous tissue oxygen metabolism monitoring. Diffuse optical spectroscopy (DOS) or near-infrared spectroscopy (NIRS) is typically employed to measure oxygenated and de-oxygenated hemoglobin, while diffuse correlation spectroscopy (DCS) provides a direct measure of tissue blood flow noninvasively. Traditionally, combined DCS and DOS/NIRS approaches are utilized for monitoring oxygen metabolism, which needs two different numerical models to calculate blood flow and oxygen saturation. In this paper, we evaluate the utility of multi-wavelength diffuse correlation spectroscopy (mwDCS) using a proposed deep learning approach, i.e., long short-term memory (LSTM) based recurrent neural network (RNN). Arterial occlusion experiments were performed in vivo to generate the data from 6 healthy individuals. Further, based on the dataset acquired by mwDCS, a LSTM-based RNN model was developed to directly assess changes of blood flow and oxygen saturation. Compared to conventional methods, the in vivo experiments in this study demonstrated a more portable system with promising results. Pearsons correlation coefficients of the proposed model reached 0.82 and 0.64 for the changes of blood flow and oxygen saturation, respectively. Our results shows that mwDCS using LSTM-based RNN model provides an alternative method for continuous tissue oxygen metabolism monitoring.

Pseudocontinuous Arterial Spin Labeling: Clinical Applications and Usefulness in Head and Neck Entities.

Simple SummaryConventional imaging methods, such as ultrasonography, computed tomography, and magnetic resonance imaging may be inadequate to accurately diagnose lesions of the head and neck because they vary widely. Recently, the arterial spin labeling technique, especially pseudocontinuous arterial spin labeling (pCASL) with the three-dimensional (3D) readout method, has been dramatically developed to improve diagnostic performance for lesion differentiation, which can show prominent blood flow characteristics. Here, we demonstrate the clinical usefulness of 3D pCASL for diagnosing various entities, including inflammatory lesions, hypervascular lesions, and neoplasms in the head and neck, for evaluating squamous cell carcinoma (SCC) treatment responses, and for predicting SCC prognosis.As functional magnetic resonance imaging, arterial spin labeling (ASL) techniques have been developed to provide quantitative tissue blood flow measurements, which can improve the performance of lesion diagnosis. ASL does not require contrast agents, thus, it can be applied to a variety of patients regardless of renal impairments and contrast agent allergic reactions. The clinical implementation of head and neck lesions is limited, although, in recent years, ASL has been increasingly utilized in brain lesions. Here, we review the development of the ASL techniques, including pseudocontinuous ASL (pCASL). We compare readout methods between three-dimensional (3D) turbo spin-echo and 2D echo planar pCASL for the clinical applications of pCASL to head and neck lesions. We demonstrate the clinical usefulness of 3D pCASL for diagnosing various entities, including inflammatory lesions, hypervascular lesions, and neoplasms; for evaluating squamous cell carcinoma (SCC) treatment responses, and for predicting SCC prognosis.

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.

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.

Diagnosis of skin and soft tissue infections using near-infrared spectroscopy.

AimSkin and soft tissue infections are classified into cellulitis and necrotizing fasciitis, which are difficult to distinguish. Necrotizing fasciitis has a poor prognosis and requires immediate intensive care. The diagnostic gold standard is to incise the lesion to determine whether necrosis has reached the fascia. We aimed to show that these infections can be differentiated using near‐infrared spectroscopy.MethodsWe describe two cases in an observational study about the utility of near‐infrared spectroscopy. Case 1 involved a 77‐year‐old man with a chief complaint of pain, redness, and swelling in the right lower leg for 1 week. Computed tomography of his legs showed no gas formation. Case 2 involved an 82‐year‐old man. He visited another hospital because of pain, redness, and swelling in the right thigh. Based on the X‐ray examination, necrotizing fasciitis was suspected, and he was transferred to our hospital.ResultsIn Case 1, the regional oxygen saturation value was lower on the lesion side (41%) than on the healthy side (55%). We confirmed the depth of invasion by incision, leading to a diagnosis of necrotizing fasciitis. In Case 2, the thigh’s regional oxygen saturation was higher on the affected side (76%) than on the healthy side (61%). An incision was made for diagnosis, but the fascia was not necrotized. Thus, we diagnosed cellulitis and provided conservative treatment using antibiotics.ConclusionNear‐infrared spectroscopy can be utilized to measure tissue blood flow, and it could be useful as a non‐invasive diagnostic tool for skin and soft tissue infections.

Involvement of microcirculation in critical ischemia: how to identify it?

Critical limb ischemia represents the most severe pattern of peripheral arterial disease (PAD) associated with the high risk of major amputation, cardiovascular events and death. The diagnosis and management of critical limb ischemia (CLI) is often challenging. Systolic ankle and toe pressure measurements are considered to be the basic techniques for the identification of PAD. However, they provide rough insight into the dependent local tissue perfusion. Furthermore, those techniques do not enable investigation of microcirculation which has crucial role in the pathogenesis of CLI. Some patients with mild deterioration of macrocirculation develop CLI if microcirculation is affected. Investigation of perfusion on macro- and local microcirculatory level enables more effective treatment: revascularization of the angiosome-related artery. The technologies capable of assessing limb tissue oxygenation or perfusion on microcirculatory level enable direct assessment of distant tissue oxygenation. Transcutaneous oxygen tension (TcPO2) measurement which was introduced in clinical practice represents one of the objective criteria for the diagnosis of CLI. Main weakness of this technique as well as laser Doppler flow measurement is low penetrance from the skin surface. Measurement of tissue blood flow on microcirculatory level can be performed with indocyanine green fluorescent imaging (ICG), contrast-enhanced magnetic resonance and vital microscopy. ICG is promising method which provides excellent informative image of tissue perfusion. However, it offers little quantitative information. Investigation of microcirculation in patients with CLI is of outmost importance because it enables insight in local tissue perfusion and oxygenation, which represents the basis of identification of most ischemic regions and provide more successful angiosome related revascularization of an affected artery.

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.

Efficacy of wheat hot pack (dry heat) and pottery hot pack (moist heat) on eyelid temperature and tissue blood flow in healthy eyes: a randomized control trial.

To investigate the eyelid temperature (Temp) and tissue blood flow (TBF) changes in healthy eyes using wheat hot pack (WHP) and pottery hot pack (PHP). A randomized, double-blind, within-subject crossover study design was conducted in a Thai tertiary care center. All healthy subjects received warm compress treatment with WHP and PHP. The subjects were randomized to receive the WHP or the PHP at the first sequence. Temp and TBF measurements were taken at baseline, and every 2min during the 10-min application of the heated compresses, and every 2min for a 10-min duration after the compresses were removed. There were 29 females (96.7%) and 1 male. The mean (SD) age of the subjects was 33.17 (5.21) years. Two warm compresses were able to increase the surface lid Temp significantly from the baseline Temp at every time point of measurement and location. For the WHP application, the maximum surface Temp (SD) of the outer upper lid, outer lower lid, and inner lower lid were 40.07 (0.80)°C, 38.44 (0.91)°C, and 35.83 (0.71)°C, respectively (all P value < 0.001) and under the PHP application, the highest surface Temp (SD) were 40.63 (0.97)°C, 38.32 (1.27)°C, and 35.82 (0.71)°C, respectively (all P value < 0.001). Both WHP and PHP were able to increase TBF significantly with no adverse events and these effects can be sustained until 20min. The results of this study suggest the potential of using these warm compresses for meibomian gland dysfunction. Further clinical research is needed.

Enhancement of diffuse correlation spectroscopy tissue blood flow measurement by acoustic radiation force.

The current research on acousto-optic effects focuses on the interactions of acoustic waves with static optical properties rather than dynamic features such as tissue blood flow. Diffuse correlation spectroscopy (DCS) is an emerging technology capable of direct measurements of tissue blood flow by probing the movements of red blood cells (RBCs). In this article, we investigated the relations between the acoustic radiation force (ARF) and ultrasonic patterns by the finite element simulations. Based on the outcomes, we experimentally explored how the ultrasound-generated ARF enhance the DCS data as well as the blood flow measurements. The results yield the optimal pattern to generate ARF and elucidate the relations between the ultrasonic emission and flow elevations. The flow modality combing the DCS with ARF modulations, which was proposed in this study for the first time, would promote disease diagnosis and therapeutic assessment in the situation wherein the blood flow contrast between healthy and pathological tissues is insufficient.

Optimal repetition time for free breathing myocardial arterial spin labeling.

The aim of this study was to improve the scan efficiency of ASL in the myocardium. Free breathing FAIR-ASL scans with different TRs were compared, while keeping the acquisition time constant. Scans were named by the trigger pulse that started each acquisition: every two (TP1), four (TP2) and six (TP3) cardiac cycles. TP2 offered the best alternative with a coefficient of variation of 17.15% intrasession and 36.85% intersession. Mean MBF increased by 0.22±0.41ml/g/min with mild stress.

Portable Near-Infrared Technologies and Devices for Noninvasive Assessment of Tissue Hemodynamics.

Tissue hemodynamics, including the blood flow, oxygenation, and oxygen metabolism, are closely associated with many diseases. As one of the portable optical technologies to explore human physiology and assist in healthcare, near-infrared diffuse optical spectroscopy (NIRS) for tissue oxygenation measurement has been developed for four decades. In recent years, a dynamic NIRS technology, namely, diffuse correlation spectroscopy (DCS), has been emerging as a portable tool for tissue blood flow measurement. In this article, we briefly describe the basic principle and algorithms for static NIRS and dynamic NIRS (i.e., DCS). Then, we elaborate on the NIRS instrumentation, either commercially available or custom-made, as well as their applications to physiological studies and clinic. The extension of NIRS/DCS from spectroscopy to imaging was depicted, followed by introductions of advanced algorithms that were recently proposed. The future prospective of the NIRS/DCS and their feasibilities for routine utilization in hospital is finally discussed.

Near-Infrared Spectroscopy (NIRS)-based Digit Skin Tissue Blood Flow Measurement System

The tissue blood flow (BF) and vascular resistance are the important information for consult peripheral vascular system which related to cardiovascular disease. Unfortunately, most of the current BF monitors are costly, built in huge size and preferable use in hospital and clinic. In the present study, a portable digit skin tissue BF measurement system had been developed using Near-infrared spectroscopy (NIRS) method with simple circuitry and low cost that can be afforded by patients to monitor their cardiovascular information. This system consists of a self-developed NIRS probe; LED and a photodiode, and an Arduino Uno board with MATLAB software as the processing unit. The NIR LED transmits 810 nm light source through biological tissue then detected by the photodiode. The output signal from the NIRS probe is based on resistance changes in the photodiode and by applying the voltage divider law, the signal is further processed by the Arduino with the MATLAB software. Then, according to the modified Lambert-Beer Law in scattering medium, the change in total concentration of haemoglobin ( ) is plotted in order to get a quantitative BF reading which based on its maximum change during venous occlusion. To evaluate the proposed BF measurement system, BF measurement tests had been conducted on four healthy subjects during resting and after exercise. The study had shown that the results of BF after the exercise were in average of 1.5 time higher than the resting BF and this finding agrees with previous research works.

Approaches to denoise the diffuse optical signals for tissue blood flow measurement

Various diseases are relevant to the abnormal blood flow in tissue. Diffuse correlation spectroscopy (DCS) is an emerging technology to extract the blood flow index (BFI) from light electric field temporal autocorrelation data. To account for tissue heterogeneity and irregular geometry, we developed an innovative DCS algorithm (i.e., the Nth order linear algorithm, or simply the NL algorithm) previously, in which the DCS signals are fully utilized through iterative linear regressions. Under the framework of NL algorithm, the BFI to be extracted is significantly influenced by the linear regression approach adopted. In this study, three approaches were proposed and evaluated for performing the iterative linear regressions, in order to understand what are the appropriate regression methods for BFI estimation. The three methods are least-squared minimization (L2 norm), least-absolute minimization (L1 norm) and support vector regression (SVR), where L2 norm is a conventional approach to perform linear regression. L1 norm and SVR are the approaches newly introduced here to process the DCS data. Computer simulations and the autocorrelation data collected from liquid phantom and human tissues are utilized to evaluate the three approaches. The results show that the best performance is achieved by the SVR approach in extracting the BFI values, with an error rate of 2.23% at 3.0 cm source-detector separation. The L1 norm method gives a medium error of 2.81%. In contrast, the L2 norm method leads to the largest error (3.93%) in extracting the BFI values. The outcomes derived from this study will be very helpful for the tissue blood flow measurements, which is critical for translating the DCS technology to the clinic.

Seizure epicenter depth and translaminar field potential synchrony underlie complex variations in tissue oxygenation during ictal initiation

Whether functional hyperemia during epileptic activity is adequate to meet the heightened metabolic demand of such events is controversial. Whereas some studies have demonstrated hyperoxia during ictal onsets, other work has reported transient hypoxic episodes that are spatially dependent on local surface microvasculature. Crucially, how laminar differences in ictal evolution can affect subsequent cerebrovascular responses has not been thus far investigated, and is likely significant in view of possible laminar-dependent neurovascular mechanisms and angioarchitecture. We addressed this open question using a novel multi-modal methodology enabling concurrent measurement of cortical tissue oxygenation, blood flow and hemoglobin concentration, alongside laminar recordings of neural activity, in a urethane anesthetized rat model of recurrent seizures induced by 4-aminopyridine. We reveal there to be a close relationship between seizure epicenter depth, translaminar local field potential (LFP) synchrony and tissue oxygenation during the early stages of recurrent seizures, whereby deep layer seizures are associated with decreased cross laminar synchrony and prolonged periods of hypoxia, and middle layer seizures are accompanied by increased cross-laminar synchrony and hyperoxia. Through comparison with functional activation by somatosensory stimulation and graded hypercapnia, we show that these seizure-related cerebrovascular responses occur in the presence of conserved neural-hemodynamic and blood flow-volume coupling. Our data provide new insights into the laminar dependency of seizure-related neurovascular responses, which may reconcile inconsistent observations of seizure-related hypoxia in the literature, and highlight a potential layer-dependent vulnerability that may contribute to the harmful effects of clinical recurrent seizures. The relevance of our findings to perfusion-related functional neuroimaging techniques in epilepsy are also discussed.