This special section of Neurophotonics evolved from a shared interest between SPIE and the Society for Brain Mapping and Therapeutics (SBMT)1 in advancing the ways in which photonics can be applied to the understanding of the physiological structure and function of the brain and improving the diagnosis and treatment of brain disorders. The collection of papers presented here captures some of the multidisciplinary work in these areas that is typical of what is presented at SBMT annual meetings.1

We are pleased to present an excellent collection of papers including overviews of the field and original research with cutting edge data and technological innovations. The common theme in this collection is the interaction of technology, engineering, and science to further our understanding of the brain as a fundamental science and to work together toward treating, curing, and perhaps preventing neurological disease and disorders.

The number of neural connections in a cubic millimeter of the human brain has been compared to the number of stars in the Milky Way. What we know about the universe changes every day as astronomers use more and more powerful telescopes and sensors, but the idea is intriguing. The human brain with its hundred billion neurons and hundred trillion connections rivals the cosmos in sheer complexity, and the future of neuroscience will certainly depend on multidisciplinary approaches and advances in technology.

The paper by Segev et al. takes the complexity head on. Optogenetics has enabled optical activation and suppression of specific neuronal activities, but the field has been hampered by fundamental limitations posed by light scattering in neural tissue which prevent deep brain stimulation. Segev et al.’s innovative approach seeks to overcome this significant limitation by developing neurophotonic probes that take advantage of integrated nanophotonics and microelectromechanical systems (MEMS). The paper demonstrates the delivery of complex illumination patterns deep within brain tissue using these mass-producible ultranarrow silicon-based probes. Inspired by the revolution in silicon microelectronics, the authors argue that large-scale integration of such neurophotonic probes is necessary to understand the complexity of the human brain.

Visualization of neuronal activity in vivo is of great importance for understanding brain functions. Localizing neural activities is a critical step in understanding the functional characteristics of neuronal interactions in the brain. Light scattering as a challenge and opportunity for this visualization has been discussed in the paper by Tang et al. as a review of laminar optical tomography (LOT) which is based on light transport in tissue. While scattering, absorption, and fluorescence are the primary processes of light transport in tissue, scattering is the prevalent phenomenon for this in vivo imaging. By detecting the emerging light for a range of positions with different source–detector separations, it is possible to perform depth-resolved imaging of subsurface tissue structures through a proportional relationship between the source–detector separations and the average investigation depths. The detection geometry used in LOT allows collection of information from a relatively shallow depth (millimeter or mesoscopic scale), enabling higher resolution tomographic imaging.

Neurofeedback-based learning studies have been performed using real-time analysis of brain signals with various neuroimaging techniques to enable self-regulation of brain function. Electroencephalography (EEG) has been used since the 1960s as a way of providing feedback to allow control of brain activity. Neurofeedback has since been extended to other neuroimaging techniques, such as functional near-infrared spectroscopy (fNIRS) to take advantage of better spatial resolution source location accuracy, smaller instrumentation footprint, and ease of use of optical-based neuroimaging techniques when compared with functional magnetic resonance imaging (fMRI). Liu et al. have used fNIRS in a proof of concept human subject study. Impaired facial processing may contribute to social dysfunction in certain individuals with autism spectrum disorder (ASD). Prior studies show that EEG-based and fMRI-based neurofeedback might help some individuals with ASD learn to modulate regional brain activity and thus reduce symptoms. This paper reports on the feasibility of employing fNIRS-based neurofeedback training in children with ASD. In another paper, Kashou et al. use fNIRS in a study to elucidate functional developmental processes in the newborn brain with reference to the effects of somatic stimulation and to assess the feasibility of NIRS in the clinical intensive care unit setting.

Three papers in this special section relate the use of the eye-brain connection for neurofeedback, for understanding the disease and abnormality, and ultimately for understanding the brain, and for therapeutic purposes: Hu et al. study age-related macular degeneration through special analysis of retina in three-dimensional spectral-domain optical coherence tomography (OCT) images, while Makarov et al. offer a fundamental and quantum-mechanics basis of understanding the transparency of certain cells by studying the retinal cell transparency through their quantum mechanics (QM)-based model. Zelinsky and Feinberg used EEG to investigate cortical effects from wearing therapeutic eyeglasses, hypothesizing that they can create measureable changes in EEG. Their hypothesis is based on the idea that the brain is equipped with a complex system for processing sensory information, including retinal circuitry comprising part of the central nervous system. Retinal stimulation can influence brain function via customized eyeglasses at both subcortical and cortical levels.

Gottschalk et al. discuss the importance of visualization of whole brain activity during epileptic seizures as fundamental for both understanding of the underlying disease mechanism, as well as the development of treatment strategies. They further present the challenge of studying deep brain neural activity with the existing functional neuroimaging methods due to lack of adequate resolution and low penetration into subcortical areas. The authors use temporal correlation between the real-time volumetric optoacoustics imaging and electrophysiological recordings of the whole-brain responses as functional neuroimaging. The authors use this technique’s ability to noninvasively visualize real-time thalamo-cortical activity inducing epileptic seizures in mice.

Precise delineation of normal tissue from tumor tissue for a complete resection of brain tumor mass is a significant challenge in neurosurgery. In a review paper, Vasefi et al. discuss various optical and thermal imaging as potential techniques for cancer diagnosis in neurosurgery. They discuss OCT, thermal infrared imaging, and various fluorescence-based imaging while correlating the advancement of the brain mapping field with the advances in optical technologies. C. J. Liu et al. use a serial optical coherence scanner, which integrates a vibratome slicer and polarization-sensitive OCT for ex vivo imaging for visualization of the mouse cerebellum and adjacent brainstem. The scanner provides intrinsic optical contrasts to distinguish the cerebellar cortical layers and white matter. Images from serial scans reveal the large-scale anatomy in detail and map the nerve fiber pathways in the cerebellum and brainstem. They show high-resolution tiled images for delineation of fine structures in the cerebellum and brainstem by incorporating a water-immersion microscope objective. Huang et al. present a review of use of a specific fluorescence technique for tumor surgery. In their paper, they discuss aminolevulinic acid (ALA)-mediated exogenous fluorescence of protoporphyrin IX (PpIX) as a sensitive approach for tumor imaging. This review paper highlights the challenges and progress in PpIX-mediated fluorescence-guided resection.

The last two papers in the collection show the power of imaging as an intraoperative guide during neurosurgery. In the first paper, a review of long-wavelength infrared imaging with quantum well infrared photodetector or QWIP arrays—originally developed for space-based observation— Khoshakhlagh and Gunapala describe how their uniform and high-resolution images can provide an additional tool for neurosurgeons in delineating tumor cells. Bae et al. describe the innovation of 4-mm diameter stereoscopic imaging endoscope with tilt control that is based on a single CMOS camera for minimally invasive brain tumor surgery. In addition to use of photonic imaging as intraoperative tools, these two papers are examples of space technology for neurophotonics and intraoperative neurosurgery.

In accepting the 2015 SBMT Beacon Award, Stephen Hawking, the preeminent cosmologist and amyotrophic lateral sclerosis (ALS) patient, stated, “I have spent my life thinking about the universe, its inception, its destiny, its seeming anomalies and how it can all be explained. Understanding one’s own brain is … a different type of challenge… and it is hard to emphasize enough how important technology can be in diagnosing and treating neurological diseases.” We agree. We hope that you enjoy this special section.