Diffuse correlation spectroscopy (DCS) is an emerging optical modality used to measure cortical cerebral blood flow. This outlook presents a brief overview of the technology, summarizing the advantages and limitations of the method, and describing its recent applications to animal, adult, and infant cohorts. At last, the paper highlights future applications where DCS may play a pivotal role individualizing patient management and enhancing our understanding of neurovascular coupling, activation, and brain development.

We have come a long way since Jöbsis first demonstrated that noninvasive cerebral monitoring was possible in humans within the near-infrared light window (approximately 700 to 1000 nm) in the late 1970s.¹ What started as a tool to quantify blood oxygenation in the brain has exploded into a whole field of study that aims to exploit this window to reveal a battery of information related to human brain physiology, including brain metabolism, blood flow, autoregulation, perfusion pressure, water concentration, light scattering, exogenous contrast agents, and more. In this text, we use the term “diffuse optics” to broadly describe any technique that employs a near-infrared light source and a photodetector to capture multiply scattered photons in the diffusion limit (i.e., in the limit wherein the absorption coefficient, ${\mu }_a$, is much less than the reduced scattering coefficient, ${\mu }_s^{\prime }$, and the source-detector separation is much greater than the photon mean free path). The term “diffuse” has historical connotations in the field and reflects how near-infrared photons propagate through biological tissue. However, it should be noted that this term is in no way associated with how the field/community is organized or conducts its science. On the contrary, the breadth and depth of the progress made in the field over the past decade could only be accomplished by a cohesive, focused, and tight-knit community of researchers!

Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) are two noninvasive diffuse optical technologies that provide information about microvascular cerebral hemodynamic processes. NIRS is sensitive to variations in absorption by oxy- and deoxy-hemoglobin of near-infrared light propagating diffusively in the head, providing a measure of cerebral blood volume (CBV) and oxygenation changes.¹ 2. 3. ^{– 4} DCS uses a long coherence length source and measures the decorrelation time scale of the intensity fluctuations of the multiple-scattered light, which relates to the motion of moving scattering centers, mostly consisting of red blood cells.⁵ 6. ^{– 7} Unlike indocyanine green bolus tracking methods that require the injection of a contrast agent,⁸ 9. ^{– 10} DCS provides a noninvasive and fast measure of blood flow relative changes. It quantifies a blood flow index that has been shown to correlate with cerebral blood flow (CBF) as assessed by other modalities such as transcranial Doppler (TCD) ultrasonography,¹¹ 12. ^{– 13} phase-encoded velocity mapping magnetic resonance imaging (MRI),¹⁴ and Xenon-enhanced computed tomography.¹⁵ NIRS, and more recently and sporadically DCS, has been applied to a broad range of functional imaging and monitoring studies, including developmental studies in infants and children,¹⁶ 17. 18. ^{– 19} cognitive and memory assessment in mental disorders,²⁰ 21. ^{– 22} and monitoring of cerebrovascular health in brain injured patients.^15,23 24. 25. ^{– 26}

Approximately 30,000 infants are born each year in the United States with congenital heart disease (CHD), with about a third requiring major surgical repair in the first few months of life.¹ Recent advances in cardiac surgery for complex CHD have minimized infant mortality. Thus, the current focus in the clinical community is oriented toward preventing neurologic injury and improving neurocognitive outcome in these high-risk babies who grow up to face various medical and academic challenges.^{2, 3}

Diffuse correlation spectroscopy (DCS) is a novel optical technique that appears to be an excellent tool for assessing cerebral blood flow in a continuous and non-invasive manner at the bedside. We present new clinical validation of the DCS methodology by demonstrating strong agreement between DCS indices of relative cerebral blood flow and indices based on phase-encoded velocity mapping magnetic resonance imaging (VENC MRI) of relative blood flow in the jugular veins and superior vena cava. Data were acquired from 46 children with single ventricle cardiac lesions during a hypercapnia intervention. Significant increases in cerebral blood flow, measured both by DCS and by VENC MRI, as well as significant increases in oxyhemoglobin concentration, and total hemoglobin concentration, were observed during hypercapnia. Comparison of blood flow changes measured by VENC MRI in the jugular veins and by DCS revealed a strong linear relationship, R = 0.88, p<0.001, slope = 0.91±0.07. Similar correlations were observed between DCS and VENC MRI in the superior vena cava, R = 0.77, slope = 0.99±0.12, p<0.001. The relationship between VENC MRI in the aorta and DCS, a negative control, was weakly correlated, R = 0.46, slope = 1.77±0.45, p<0.001.

The Neuron Doctrine formulated by Ramón y Cajal at the turn of the 19th century is an embodiment of neuroscience discovery empowered by optics. Cajal used Camillo Golgi’s “black reaction” to sparsely impregnate neurons with light-absorbing silver nitrate in histological brain sections. Inspecting these sections with a light microscope, Cajal concluded that information was flowing in one specific direction—from dendrites to axons—within a network of discrete nerve cells connected by synapses. This conceptual advance, enabled through utilization of a light-absorbing probe in combination with widefield microscopy, laid the foundation for modern neuroscience. Fast-forward to the present day, and optical tools for measurement and manipulation of neuronal activity are so ubiquitous and versatile that “neurophotonics” has become a common word in the scientific vocabulary: we talk about neurophotonic technologies and research centers, we have the Neurophotonics journal, and recognize neurophotonics as its own field of research.