Chong Huang

Adequate cerebral blood flow (CBF) is essential for delivering oxygen and nutrients and removing metabolic waste to maintain normal brain function. Hypoperfusion reduces oxygen and nutrient delivery, leading to tissue ischemia and neuronal death, whereas hyperperfusion can cause excessive vascular pressure, increasing the risk of blood-brain barrier disruption and intracranial hemorrhage.^1,2 Continuous and longitudinal monitoring of CBF is crucial for understanding cerebral pathological conditions and developing effective interventions.^3,4

To address many of the deficiencies in optical neuroimaging technologies, such as poor tempo-spatial resolution, low penetration depth, contact-based measurement, and time-consuming image reconstruction, a novel, noncontact, portable, time-resolved laser speckle contrast imaging (TR-LSCI) technique has been developed for continuous, fast, and high-resolution 2D mapping of cerebral blood flow (CBF) at different depths of the head. TR-LSCI illuminates the head with picosecond-pulsed, coherent, widefield near-infrared light and synchronizes a fast, high-resolution, gated single-photon avalanche diode camera to selectively collect diffuse photons with longer pathlengths through the head, thus improving the accuracy of CBF measurement in the deep brain. The reconstruction of a CBF map was dramatically expedited by incorporating convolution functions with parallel computations. The performance of TR-LSCI was evaluated using head-simulating phantoms with known properties and in-vivo rodents with varied hemodynamic challenges to the brain. TR-LSCI enabled mapping CBF variations at different depths with a sampling rate of up to 1 Hz and spatial resolutions ranging from tens/hundreds of micrometers on rodent head surfaces to 1-2 millimeters in deep brains. With additional improvements and validation in larger populations against established methods, we anticipate offering a noncontact, fast, high-resolution, portable, and affordable brain imager for fundamental neuroscience research in animals and for translational studies in humans.

Malignant glioma (MG) is the most common type of primary malignant brain tumors. Surgical resection of MG remains the cornerstone of therapy and the extent of resection correlates with patient survival. A limiting factor for resection, however, is the difficulty in differentiating the tumor from normal tissue during surgery. Fluorescence imaging is an emerging technique for real-time intraoperative visualization of MGs and their boundaries. However, most clinical grade neurosurgical operative microscopes with fluorescence imaging ability are hampered by low adoption rates due to high cost, limited portability, limited operation flexibility, and lack of skilled professionals with technical knowledge. To overcome the limitations, we innovatively integrated miniaturized light sources, flippable filters, and a recording camera to the surgical eye loupes to generate a wearable fluorescence eye loupe ( FLoupe ) device for intraoperative imaging of fluorescent MGs. Two FLoupe prototypes were constructed for imaging of Fluorescein and 5-aminolevulinic acid (5-ALA), respectively. The wearable FLoupe devices were tested on tumor-simulating phantoms and patients with MGs. Comparable results were observed against the standard neurosurgical operative microscope (PENTERO® 900) with fluorescence kits. The affordable and wearable FLoupe devices enable visualization of both color and fluorescence images with the same quality as the large and expensive stationary operative microscopes. The wearable FLoupe device allows for a greater range of movement, less obstruction, and faster/easier operation. Thus, it reduces surgery time and is more easily adapted to the surgical environment than unwieldy neurosurgical operative microscopes.

Editorial: Functional near-infrared diffuse optical spectroscopy (fNIRS) to explore mental health

Three-dimensional (3D) reconstruction techniques have been widely used in the preoperative evaluation of hepatectomy. Here we used a 3D reconstruction technique to estimate the remnant liver volume and clarify a clinical speculation that limited functional liver tissue would be excised in hepatectomy for large hepatic tumors. Hepatectomy simulation by IQQA-Liver software was applied to 108 patients of hemihepatectomy divided into two groups (tumor diameter ≥ 10 cm vs.40%, accounting for the overwhelming majority of all patients. There was no hepatic failure or death within 30 days of surgery. In summary, it is better to use a 3D reconstruction method for preoperative safety assessment of liver resection for large hepatic tumors, through the hepatectomy simulation and volume calculation. In the same range of anatomical hepatectomy, a larger tumor mass meant less excised functional liver volume and more remnant liver volume. Our results indicated that neither ELV nor RLV/LV, but RLV/SLV was the better determinant of safety of hepatectomy.

Oxygen is a critical component of the microenvironment required for supporting cellular activities. Tissue oxygen alteration is a vital sign for the assessment of cardiovascular diseases such as heart failure, septic shock, and cerebral hypoxia.^{1 – 3} Tissue oxygenation level reflects the balance between oxygen supply and consumption.⁴ Blood flow affects the efficiency of oxygen delivery to and waste removal from tissues. Blood flow is highly sensitive to pathophysiological alterations,⁵ thus could be an indicator for the detection of diseases that are associated with tissue ischemia such as peripheral artery disease, cerebral vascular disease, neurological disorders, and cancers.^{6 – 11} There are also growing interests in simultaneous measurements of blood flow and oxygenation alterations as more comprehensive biomarkers for tissue health/injury than one single parameter alone.^{12 – 14} Furthermore, a combination of tissue blood flow and oxygenation allows to estimate the metabolic rate of tissue oxygen consumption,^12,15 another important functional parameter highly associated with tissue pathology.

We adapted and tested an innovative noncontact speckle contrast diffuse correlation tomography (scDCT) system for 3D imaging of cerebral blood flow (CBF) variations in perinatal disease models utilizing neonatal piglets, which closely resemble human neonates. CBF variations were concurrently measured by the scDCT and an established diffuse correlation spectroscopy (DCS) during global ischemia, intraventricular hemorrhage, and asphyxia; significant correlations were observed. Moreover, CBF variations associated reasonably with vital pathophysiological changes. In contrast to DCS measurements of mixed signals from local scalp, skull and brain, scDCT generates 3D images of CBF distributions at prescribed depths within the head, thus enabling specific determination of regional cerebral ischemia. With further optimization and validation in animals and human neonates, scDCT has the potential to be a noninvasive imaging tool for both basic neuroscience research in laboratories and clinical applications in neonatal intensive care units.

Extremely preterm infants’ hemodynamic instability places them at high risk of brain injury. Currently there is no reliable bedside method to continuously monitor cerebral hemodynamics in the neonatal intensive care unit (NICU). This paper reports a feasibility study to adapt and test an innovative speckle contrast diffuse correlation tomography (scDCT) device for noncontact, high-density, 3D imaging of cerebral blood flow (CBF) in preterm infants. The scDCT scans a focused point near-infrared illumination to multiple source positions for deep tissue penetration, and controls an electron multiplying charge-coupled-device camera with thousands of pixels to achieve a high-density sampling. The optimized scDCT for use in preterm infants was first evaluated against an established diffuse correlation spectroscopy in an infant-head-simulating phantom with known properties. The observed significant correlation between the two measurements verified the capability of scDCT for transcranial brain imaging. The insignificant influence of transparent incubator wall on scDCT measurements was then confirmed by comparing adult forearm blood flow responses to artery cuff occlusions measured inside and outside the incubator. Finally, the scDCT device was moved to the NICU to image CBF variations in two preterm infants. Infant #1 with no major organ deficits showed little CBF fluctuation over the first 3 weeks of life. Infant #2 showed a significant CBF increase after the 2 h pharmacotherapy for patent ductus arteriosus closure. While these CBF variations meet physiological expectations, the fact that no significant changes are noted with peripheral monitoring of blood oxygen saturation suggests necessity of direct cerebral monitoring. This feasibility study with timely technology development is an important and necessary step towards larger clinical studies with more subjects to further validate it for continuous monitoring and instant management of cerebral pathologies and interventions in the NICU.