The Siegert relationship is an important tool in biomedical optics to infer statistics of temporal field fluctuations from observations of intensity fluctuations. The Siegert relationship derivation assumes dynamic Gaussian fields with zero mean. To accommodate a non-ergodic or static field, a modification of the Siegert relationship is often invoked. We show that conventional forms of the modified Siegert relationship, which assume that the coherence factor of dynamic fields also determines mutual coherence between dynamic and static fields, are incorrect in general. We propose a more general form of the modified Siegert relationship and validate it experimentally.
Interferometric DOS (iDOS) is a new class of approaches that promises to improve the quantitative accuracy and depth specificity of blood flow index (BFI). iDOS techniques have alternatively achieved either time-of-flight (TOF) discrimination or highly parallel detection, but not both at once. Here, we break this barrier with a single iDOS instrument. Specifically, we show that rapid tuning of a temporally coherent laser during the sensor integration time increases the effective linewidth seen by a highly parallel interferometer. With a deep TOF filter applied to a high throughput interferometer, we demonstrate brain-specific BFI imaging.
KEYWORDS: Interferometry, Heterodyning, Signal to noise ratio, Brain, Diffuse optical imaging, Homodyne detection, Sensors, Cameras, Signal detection, Near infrared spectroscopy
The field of diffuse optics has provided a rich set of neurophotonic tools to measure the human brain noninvasively. Interferometric detection is a recent, exciting methodological development in this field. The approach is especially promising for the measurement of diffuse fluctuation signals related to blood flow. Benefitting from inexpensive sensor arrays, the interferometric approach has already dramatically improved throughput, enabling the measurement of brain blood flow faster and deeper. The interferometric approach can also achieve time-of-flight resolution, improving the accuracy of acquired signals. We provide a historical perspective and summary of recent work in the nascent area of interferometric diffuse optics. We predict that the convergence of interferometric technology with existing economies of scale will propel many advances in the years to come.
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.
Maintenance of cerebral blood flow (CBF) is required for normal brain function. Yet, measuring CBF in adult humans requires high-end medical instrumentation. Here, leveraging two-dimensional (2D) complementary metal-oxide-semiconductor (CMOS) technology, we present and validate an optical approach, called multi-exposure interferometric Diffusing Wave Spectroscopy (MiDWS), to monitor blood flow index (BFI), a proxy for CBF, via the adult human forehead. MiDWS employs interferometry to detect low light levels, and probes the optical field autocorrelation by varying the sensor exposure time. This approach may enable human brain optical BFI monitoring with 2D CMOS sensors, with associated economies of scale.
Interferometric Near-Infrared Spectroscopy (iNIRS) is a time-of-flight- (TOF-) resolved method to measure diffuse optical field dynamics from the human brain. Here we demonstrate a non-contact, null source-collector separation iNIRS approach based on polarization splitting, which enables galvanometer-based scanning across large spatial fields-of-view and suppresses single and few-scattered superficial light that degrades the effective dynamic range for deep measurements. We present, for the first time, multi-dimensional TOF- and laterally-resolved data sets that describe human forehead dynamics. The resulting blood flow index images show significant spatial heterogeneity in superficial dynamics, helping to identify optimal regions for subsequent monitoring with improved brain specificity.
Interferometric near-infrared spectroscopy (iNIRS) is a time-of-flight- (TOF-) resolved sensing method for direct and simultaneous quantification of tissue optical properties (absorption and reduced scattering) and dynamics (blood flow index) in vivo with a single modality. The technique has previously been validated in Intralipid phantoms, and applied to continuously and non-invasively monitor optical properties and blood flow index in the brains of head-fixed, anesthetized mice. A demonstration of robust iNIRS measurements in human tissues with motion would support the viability of iNIRS for clinical applications. Here, we perform non-contact iNIRS in human tissues. We show that phase drift caused by involuntary motion during acquisition significantly distorts the optical field autocorrelation, particularly at early TOFs. To solve this issue, we present a novel numerical phase drift correction method to isolate field dynamics due to just red blood cell motion within the sample. Upon correction, TOF-resolved autocorrelations exhibit exponential decay behavior, whether acquired from Intralipid, the human forearm, or the human forehead. We confirm the link between bulk motion artifacts and phase drift by simultaneous, co-registered iNIRS and Optical Coherence Tomography measurements. By applying conventional, time-resolved diffusion theory and diffusing wave spectroscopy theory, we quantify optical properties and time-of-flight-resolved dynamics in Intralipid, the human forearm, and the human brain. Finally, we explore strategies for increased photon collection through parallelization of iNIRS, to probe greater depths in the human brain. This work conclusively shows that diffuse optical measurements of field dynamics are possible, even in the presence of motion artifacts.
Interferometric near-infrared spectroscopy (iNIRS) is a recently introduced time-of-flight- (TOF-) resolved sensing method for quantifying optical and dynamical properties of turbid media non-invasively. iNIRS measures the interference spectrum of light traversing a turbid medium using a rapidly tunable, or frequency swept, light source. While the modality was successfully demonstrated in vivo in the nude mouse brain for monitoring absorption, reduced scattering, and blood flow index, translation towards human measurements requires improving light collection efficiency. Particularly, interrogating cortical tissue beneath the adult human scalp and skull remains challenging due to the limited core size and throughput of the single mode fiber currently used for detection. To tackle this problem, we implement a short to null source-detector separation geometry setup to significantly improve the number of detected diffuse photons. We discuss both hardware and post-processing improvements to isolate the desired diffuse signal from the large, non-diffuse and specular signals. Furthermore, key improvements in the iNIRS optical system, including higher TOF resolution (22-60 ps), optimized dynamic range (36-47 dB), faster sweep rate (50-500 kHz), and a technique for combining the forward and backward sweeps to double the effective optical field autocorrelation sampling rate, are presented. These allow for more precise and quantitative extraction of in vivo optical properties and TOF-resolved dynamics at long path lengths. Collectively, these key advances in the technology pave the way for translating iNIRS towards non-invasive, real-time, and quantitative measurements of oxygen metabolism and blood perfusion in deep human tissues.
Sensing and imaging methods based on the dynamic scattering of coherent light, including laser speckle, laser Doppler, and diffuse correlation spectroscopy quantify scatterer motion using light intensity (speckle) fluctuations. The underlying optical field autocorrelation (OFA), rather than being measured directly, is typically inferred from the intensity autocorrelation (IA) through the Siegert relationship, by assuming that the scattered field obeys Gaussian statistics. In this work, we demonstrate interferometric near-infrared spectroscopy (iNIRS) for measurement of time-of-flight (TOF) resolved field and intensity autocorrelations in fluid tissue phantoms and in vivo. In phantoms, we find a breakdown of the Siegert relationship for short times-of-flight due to a contribution from static paths whose optical field does not decorrelate over experimental time scales, and demonstrate that eliminating such paths by polarization gating restores the validity of the Siegert relationship.
Inspired by these results, we developed a method, called correlation gating, for separating the OFA into static and dynamic components. Correlation gating enables more precise quantification of tissue dynamics. To prove this, we show that iNIRS and correlation gating can be applied to measure cerebral hemodynamics of the nude mouse in vivo using dynamically scattered (ergodic) paths and not static (non-ergodic) paths, which may not be impacted by blood. More generally, correlation gating, in conjunction with TOF resolution, enables more precise separation of diffuse and non-diffusive contributions to OFA than is possible with TOF resolution alone. Finally, we show that direct measurements of OFA are statistically more efficient than indirect measurements based on IA.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.