A comprehensive overview of diffuse correlation spectroscopy: Theoretical framework, recent advances in hardware, analysis, and applications.

Diffuse correlation spectroscopy (DCS) is a powerful tool for assessing microvascular hemodynamic in deep tissues. Recent advances in sensors, lasers, and deep learning have further boosted the development of new DCS methods. However, newcomers might feel overwhelmed, not only by the already-complex DCS theoretical framework but also by the broad range of component options and system architectures.

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.

Flexible circuit-based spatially aware modular optical brain imaging system for high-density measurements in natural settings.

Significance: Functional near-infrared spectroscopy (fNIRS) presents an opportunity to study human brains in everyday activities and environments. However, achieving robust measurements under such dynamic conditions remains a significant challenge.

Aim: The modular optical brain imaging (MOBI) system is designed to enhance optode-to-scalp coupling and provide a real-time probe three-dimensional (3D) shape estimation to improve the use of fNIRS in everyday conditions.

Choosing a camera and optimizing system parameters for speckle contrast optical spectroscopy.

Speckle contrast optical spectroscopy (SCOS) is an emerging camera-based technique that can measure human cerebral blood flow (CBF) with high signal-to-noise ratio (SNR). At low photon flux levels typically encountered in human CBF measurements, camera noise and nonidealities could significantly impact SCOS measurement SNR and accuracy. Thus, a guide for characterizing, selecting, and optimizing a camera for SCOS measurements is crucial for the development of next-generation optical devices for monitoring human CBF and brain function.

Functional hemodynamic imaging markers for the prediction of pathological outcomes in breast cancer patients treated with neoadjuvant chemotherapy.

Significance: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes.

Aim: We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT.

Flexible-circuit-based 3-D aware modular optical brain imaging system for high-density measurements in natural settings.

Significance: Functional near-infrared spectroscopy (fNIRS) presents an opportunity to study human brains in everyday activities and environments. However, achieving robust measurements under such dynamic condition remains a significant challenge.

Aim: The modular optical brain imaging (MOBI) system is designed to enhance optode-to-scalp coupling and provide real-time probe 3-D shape estimation to improve the use of fNIRS in everyday conditions.

Multi-wavelength multi-distance diffuse correlation spectroscopy system for assessment of premature infants' cerebral hemodynamics.

Infants born at an extremely low gestational age (ELGA, < 29 weeks) are at an increased risk of intraventricular hemorrhage (IVH), and there is a need for standalone, safe, easy-to-use tools for monitoring cerebral hemodynamics. We have built a multi-wavelength multi-distance diffuse correlation spectroscopy device (MW-MD-DCS), which utilizes time-multiplexed, long-coherence lasers at 785, 808, and 853 nm, to simultaneously quantify the index of cerebral blood flow (CBF) and the hemoglobin oxygen saturation (SO). We show characterization data on liquid phantoms and demonstrate the system performance on the forearm of healthy adults, as well as clinical data obtained on two preterm infants.

Comparing the performance potential of speckle contrast optical spectroscopy and diffuse correlation spectroscopy for cerebral blood flow monitoring using Monte Carlo simulations in realistic head geometries.

Significance: The non-invasive measurement of cerebral blood flow based on diffuse optical techniques has seen increased interest as a research tool for cerebral perfusion monitoring in critical care and functional brain imaging. Diffuse correlation spectroscopy (DCS) and speckle contrast optical spectroscopy (SCOS) are two such techniques that measure complementary aspects of the fluctuating intensity signal, with DCS quantifying the temporal fluctuations of the signal and SCOS quantifying the spatial blurring of a speckle pattern. With the increasing interest in the use of these techniques, a thorough comparison would inform new adopters of the benefits of each technique.

Fluorescence lifetime of injected indocyanine green as a universal marker of solid tumours in patients.

The surgical resection of solid tumours can be enhanced by fluorescence-guided imaging. However, variable tumour uptake and incomplete clearance of fluorescent dyes reduces the accuracy of distinguishing tumour from normal tissue via conventional fluorescence intensity-based imaging. Here we show that, after systemic injection of the near-infrared dye indocyanine green in patients with various types of solid tumour, the fluorescence lifetime (FLT) of tumour tissue is longer than the FLT of non-cancerous tissue.

scatterBrains: an open database of human head models and companion optode locations for realistic Monte Carlo photon simulations.

Significance: Monte Carlo (MC) simulations are currently the gold standard in the near-infrared and diffuse correlation spectroscopy (NIRS/DCS) communities for generating light transport paths through tissue. However, realistic and diverse models that capture complex tissue layers are not easily available to all; moreover, manually placing optodes on such models can be tedious and time consuming. Such limitations may hinder the adoption of representative models for basic simulations and the use of these models for large-scale simulations, e.

Enhancing diffuse correlation spectroscopy pulsatile cerebral blood flow signal with near-infrared spectroscopy photoplethysmography.

Significance: Combining near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) allows for quantifying cerebral blood volume, flow, and oxygenation changes continuously and non-invasively. As recently shown, the DCS pulsatile cerebral blood flow index () can be used to quantify critical closing pressure (CrCP) and cerebrovascular resistance ().

Aim: Although current DCS technology allows for reliable monitoring of the slow hemodynamic changes, resolving pulsatile blood flow at large source-detector separations, which is needed to ensure cerebral sensitivity, is challenging because of its low signal-to-noise ratio (SNR).

Portable, high speed blood flow measurements enabled by long wavelength, interferometric diffuse correlation spectroscopy (LW-iDCS).

Diffuse correlation spectroscopy (DCS) is an optical technique that can be used to characterize blood flow in tissue. The measurement of cerebral hemodynamics has arisen as a promising use case for DCS, though traditional implementations of DCS exhibit suboptimal signal-to-noise ratio (SNR) and cerebral sensitivity to make robust measurements of cerebral blood flow in adults. In this work, we present long wavelength, interferometric DCS (LW-iDCS), which combines the use of a longer illumination wavelength (1064 nm), multi-speckle, and interferometric detection, to improve both cerebral sensitivity and SNR.

FDU-Net: Deep Learning-Based Three-Dimensional Diffuse Optical Image Reconstruction.

Near-infrared diffuse optical tomography (DOT) is a promising functional modality for breast cancer imaging; however, the clinical translation of DOT is hampered by technical limitations. Specifically, conventional finite element method (FEM)-based optical image reconstruction approaches are time-consuming and ineffective in recovering full lesion contrast. To address this, we developed a deep learning-based reconstruction model (FDU-Net) comprised of a Fully connected subnet, followed by a convolutional encoder-Decoder subnet, and a U-Net for fast, end-to-end 3D DOT image reconstruction.

Diffuse correlation spectroscopy: current status and future outlook.

Diffuse correlation spectroscopy (DCS) has emerged as a versatile, noninvasive method for deep tissue perfusion assessment using near-infrared light. A broad class of applications is being pursued in neuromonitoring and beyond. However, technical limitations of the technology as originally implemented remain as barriers to wider adoption.

Method to improve the localization accuracy and contrast recovery of lesions in separately acquired X-ray and diffuse optical tomographic breast imaging.

Near-infrared diffuse optical tomography (DOT) has the potential to improve the accuracy of breast cancer diagnosis and aid in monitoring the response of breast tumors to chemotherapy by providing hemoglobin-based functional imaging. The use of structural lesion priors derived from clinical breast imaging methods, such as mammography, can improve recovery of tumor optical contrast; however, accurate lesion prior placement is essential to take full advantage of prior-guided DOT image reconstruction. Simultaneous optical and anatomical imaging may not always be possible or desired, which can make the accurate registration of the lesion prior challenging.

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.

Functional Time Domain Diffuse Correlation Spectroscopy.

Time-domain diffuse correlation spectroscopy (TD-DCS) offers a novel approach to high-spatial resolution functional brain imaging based on the direct quantification of cerebral blood flow (CBF) changes in response to neural activity. However, the signal-to-noise ratio (SNR) offered by previous TD-DCS instruments remains a challenge to achieving the high temporal resolution needed to resolve perfusion changes during functional measurements. Here we present a next-generation optimized functional TD-DCS system that combines a custom 1,064 nm pulse-shaped, quasi transform-limited, amplified laser source with a high-resolution time-tagging system and superconducting nanowire single-photon detectors (SNSPDs).

Open-source FlexNIRS: A low-cost, wireless and wearable cerebral health tracker.

Currently, there is great interest in making neuroimaging widely accessible and thus expanding the sampling population for better understanding and preventing diseases. The use of wearable health devices has skyrocketed in recent years, allowing continuous assessment of physiological parameters in patients and research cohorts. While most health wearables monitor the heart, lungs and skeletal muscles, devices targeting the brain are currently lacking.

Erratum: Improved accuracy of cerebral blood flow quantification in the presence of systemic physiology cross-talk using multi-layer Monte Carlo modeling.

[This corrects the article DOI: 10.1117/1.NPh.

In Vivo Absolute Metabolite Quantification Using a Multiplexed ERETIC-RX Array Coil for Whole-Brain MR Spectroscopic Imaging.

Background: Absolute quantification of metabolites in MR spectroscopic imaging (MRSI) requires a stable reference signal of known concentration. The Electronic REference To access In vivo Concentrations (ERETIC) has shown great promise but has not been applied in patients and 3D MRSI. ERETIC hardware has not been integrated with receive arrays due to technical challenges, such as coil combination and unwanted coupling between multiple ERETIC and receive channels, for which we developed mitigation strategies.

Diffuse Correlation Spectroscopy Beyond the Water Peak Enabled by Cross-Correlation of the Signals From InGaAs/InP Single Photon Detectors.

Objective: Diffuse correlation spectroscopy (DCS) is an optical technique that allows for the non-invasive measurement of blood flow. Recent work has shown that utilizing longer wavelengths beyond the traditional NIR range provides a significant improvement to signal-to-noise ratio (SNR). However, current detectors both sensitive to longer wavelengths and suitable for clinical applications (InGaAs/InP SPADs) suffer from suboptimal afterpulsing and dark noise characteristics.

Superconducting nanowire single-photon sensing of cerebral blood flow.

The ability of diffuse correlation spectroscopy (DCS) to measure cerebral blood flow (CBF) in humans is hindered by the low signal-to-noise ratio (SNR) of the method. This limits the high acquisition rates needed to resolve dynamic flow changes and to optimally filter out large pulsatile oscillations and prevents the use of large source-detector separations ( ), which are needed to achieve adequate brain sensitivity in most adult subjects. To substantially improve SNR, we have built a DCS device that operates at 1064 nm and uses superconducting nanowire single-photon detectors (SNSPD).

Optimization of time domain diffuse correlation spectroscopy parameters for measuring brain blood flow.

Time domain diffuse correlation spectroscopy (TD-DCS) can offer increased sensitivity to cerebral hemodynamics and reduced contamination from extracerebral layers by differentiating photons based on their travel time in tissue. We have developed rigorous simulation and evaluation procedures to determine the optimal time gate parameters for monitoring cerebral perfusion considering instrumentation characteristics and realistic measurement noise. We simulate TD-DCS cerebral perfusion monitoring performance for different instrument response functions (IRFs) in the presence of realistic experimental noise and evaluate metrics of sensitivity to brain blood flow, signal-to-noise ratio (SNR), and ability to reject the influence of extracerebral blood flow across a variety of time gates to determine optimal operating parameters.