This PDF file contains the front matter associated with SPIE Proceedings Volume 11225 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

We hypothesized that generation of nitric oxide (NO) was associated with persistent hemodynamic abnormalities observed in the rat cortex exposed to a shock wave. To examine this speculation, we performed in vivo imaging of NO in the rat cortex exposed to a laser-induced shock wave (LISW). An NO sensitive fluoroprobe (DAF-2 DA) was applied to the cortical surface, and NO-originating fluorescence was observed under the stereoscopic fluorescence microscope. We observed that the fluorescence intensity in perivascular spaces as well as in parenchyma was drastically increased after LISW application. Intense fluorescence spots in the parenchyma probably indicate NO generation from neurons.

One of the goals of the Neural Engineering System Design (NESD) program in the United States and of similar programs around the world is to develop an interface able to read from one million neurons in parallel. This is well beyond the capabilities of traditional multi-electrode arrays (MEAs), which are inherently limited in both spatial resolution and number of channels, due to issues with power dissipation and wiring.^{1, 2} To overcome these roadblocks our group has proposed a novel optrode array that measures electrical activity and uses light for both signal transduction and transmission, thus decoupling the bio-potentials from the signal acquisition circuitry.³ The technology relies on the sensitivity of a particular class of liquid crystals (LCs) to small electric fields and is analogous to a LC display, where the intensity of each pixel (optrode, in our case) is controlled by the electrical activity of the biological tissue. Here, we present the first use of such a transduction mechanism to record from cardiac tissue and investigate stimulus artifact suppression in rabbit sciatic nerve. Our results pave the way to the development of high-density high-channel-count optrode arrays for electrophysiology studies and brain-machine interfaces.

Tumors in the central nervous system (CNS) can produce significant behavior deficits. These deficits significantly reduce the quality of life of long-term brain tumor survivors. Motor deficits can be the main presenting symptoms that brings a brain tumor patient into the hospital. Additionally, motor deficits can either improve or worsen after treatment. Its poorly understood how tumor phenotype (e.g infiltrative or circumscribed) contributes to the development and evolution of motor deficits. Resting state functional connectivity magnetic resonance imaging (rsfc-MRI) could help determine a relationship between brain function and tumor phenotype. rsfc-MRI provides measurements of functional connectivity (FC), which is a measure of brain activity and has been shown to correlate with neurological function (e.g. cognitive and motor deficit) in many disease states. Additional studies are needed before rsfc-MRI can be included in the standard of care for brain tumor patients because it is largely unknown how important clinical factors, such as tumor location and tumor burden (e.g. tumor volume), modulate the association between FC measurements and neurological performance. However, human studies are unlikely to have the statistical power to determine the relationships between FC, clinical factors, and neurological function because it is difficult to enroll many human subjects while controlling for a factor. Fortunately, mice can be used to control for a factor in many genetically identical specimens. Therefore, FC assessments need to be applied to studies in mouse models of brain tumors to assess the interactions be specific clinical factors, FC measurements and neurological function. FC measurements are infrequently obtained in mouse models because it is technically difficult to perform rsfc-MRI on the small mouse brain. Fortunately, functional connectivity optical intrinsic signal imaging (fcOISI) can be used obtain FC measurements in mice. In this study, we investigated how tumor phenotype modulates the relationship between tumor burden measures and motor function. We injected in two groups of mice with human brain tumor cell lines that exhibit different growth phenotypes. We assessed the motor function of the mice by their performance on a battery of sensorimotor tests. We determined tumor burden with bioluminescence and MRI and assessed FC with fcOISI. Lastly, we performed linear regression analysis to determine how these measured factors interact in the prediction of performance on the motor tests.

Although the neural basis underlying visuospatial reasoning has been widely explored by neuroimaging techniques, the brain activation patterns during naturalistic visuospatial reasoning such as tangram remains unclear. In this study, the directional functional connectivity of fronto-parietal networks during the tangram task was carefully inspected by using combined functional near-infrared spectroscopy (fNIRS) and conditional Granger causality analysis (GCA). Meanwhile, the causal networks during the traditional spatial reasoning task were also characterized to exhibit the differences with those during the tangram task. We discovered that the tangram task in a natural environment showed enhanced activation in the fronto-parietal regions, particularly the frontal cortex. In addition, a strong directional connectivity from the right prefrontal cortex to left angular gyrus was detected for the complex spatial reasoning condition of spatial reasoning task, whereas no effective connectivity was identified between the frontal and parietal cortices during the tangram task. Further correlation analyses showed that the behavioral performance in the spatial reasoning rather than the tangram task manifested the relationship with the connectivity between the frontal and parietal cortex. Our findings demonstrate that the tangram task measures a different aspect of the visuospatial reasoning ability which requires more trial-and-error strategies and creative thinking rather than inductive reasoning. In particular, the frontal cortex is mostly involved in tangram puzzle-solving, whereas the interaction between frontal and parietal cortices might be disrupted by the hands-on experience during the tangram task. Our study also indicates that conditional GCA combined with fNIRS neuroimaging technique is a robust tool for constructing the causal networks associated with natural visuospatial reasoning, which paves a new avenue for an improved understanding of the neural mechanism underlying tangram

Childhood Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder whose symptoms include the inability to focus, impulsivity, and extremely active behavior. Advanced Test of Attention (ATA) is used to diagnose ADHD by measuring the patient’s impulse rate, average response rate, standard deviation rate, and omission rate during visual and auditory stimulation. However, ATA metrics are often skewed due to long task times and level of difficulty. We recruited healthy and ADHD children to monitor their performance during ATA. This work highlights diffuse optical tomography’s capability in providing cerebral perfusion changes to supplement ATA results for monitoring the cognitive effects of ADHD.

The acquisition of narrow wavelength bands in the Near-Infrared (NIR) range using hyperspectral imaging have the potential to yield functional and metabolic information during a neurosurgical operation. The analysis of the reflectance spectra through the modified Beer-Lambert law and Monte Carlo simulations enable us to measure the concentration changes of oxy, deoxygenated hemoglobin and cytochrome-c-oxidase during the video acquisition. A functional model has been implemented to evaluate the functional brain areas following neuronal activation by physiological stimuli. The results show a good correlation between the computed quantitative functional maps and the brain areas identified by electrical brain stimulation. This work demonstrates that a quantitative modeling of the brain hemodynamic and metabolic biomarkers could evaluate in a robust way the functional areas and the cellular energy metabolism during neurosurgery.

The ability to differentiate healthy and tumorous tissue is vital during the surgical removal of tumors. This ability is especially critical during neurosurgical tumor resection due to the risk associated with removing healthy brain tissue. In this paper, we present an epifluorescence spectroscopy guided device that is not only capable of autonomously classifying a region of tissue as tumorous or healthy in real-time–but is also able to differentiate between different tumor types. For this study, glioblastoma and melanoma were chosen as the two different tumor types. Six mice were utilized in each of the three classes (healthy, glioblastoma, melanoma) for a total of eighteen mice. A “one-vs-the-all” approach was used to create a multi-class classifier. The multi-class classifier was capable of classifying with 100% accuracy. Future work includes increasing the number of mice in each of the three tumor classes to create a more robust classifier and expanding the number of tumor types beyond glioblastoma and melanoma.

Gliomas are diffuse brain tumors still hardly curable due to the difficulties to identify margins. 5-ALA induced PpIX fluorescence measurements enable to gain in sensitivity but are still limited to discriminate margin from healthy tissue. In this fluorescence spectroscopic study, we compare an expert-based model assuming that two states of PpIX contribute to total fluorescence and machine learning-based models. We show that machine learning retrieves the main features identified by the expert approach. We also show that machine learning approach slightly overpasses expert-based model for the identification of healthy tissues. These results might help to improve fluorescence-guided resection of gliomas by discriminating healthy tissues from tumor margins.

Conducting polymer are a promising class of biomaterials owing to their mechanical compliance and energy density. However, slow electrochemical processes have hindered widespread application. In this work, we make microscopic arrays of fs/ps laser patterned holes in relatively thick, easy to handle conducting polymer films in order to reduce charging time. A single-step, top-down, non-contact and template-free approach is used, employing femto and picosecond lasers to texturize polypyrrole films while preserving the total capacitance. A wide range of hole separations and diameters (pitch/diameter from 9.75/5.17 μm to 24.7/13.2 μm) are explored to reduce the diffusion path length in the bulk polymer, which achieved a speed increase of between 2 and 30 times. Fast charging conducting polymer electrodes such as ones achieved in this work may be useful in creating highly efficient (extremely low impedance and high fidelity) implantable electrodes for neural monitoring/stimulating app

Dura mater repair represents a final and crucial step in cranial surgery: an inadequate dural reconstruction determines dreadful consequences that significantly increase morbidity and mortality rates. Different dural substitutes have been used with poor results. To overcome this issue, in previous studies we proposed a laser-based approach to the bonding of porcine dura mater, evidencing the feasibility of the laser assisted procedure. In this work, we present the optimization of the laser bonding approach ex vivo in porcine dura mater and in vivo in rats. An 810 nm cw laser was used to weld the ICG stained chitosan patch to the dura. The ex vivo tests enabled to optimize the laser parameters, using histology and leak pressure evaluation to study the bonding effect. The in vivo tests were performed on 32 adult Wistar rats: laser bonding was carried out in 16 rats, while a collagen matrix was used for duroplasty in the control group. After the treatment, the animals were left to recover and were observed in a 15 and 90 days follow up study. At sacrifice, the rats were anesthetized for fluid leakage pressure test; treated tissue was harvested and underwent standard histology. The results of this study pointed out that the laser bonding procedure can be used to close the dura mater, both ex vivo and in vivo. The thermal effect is limited and spatially confined. The technique can thus be proposed as a valid alternative to standard method for the closuring of dura mater in cranial surgery.

The development of improved Augmented Reality (AR) Head-Mounted Devices (HMDs) have led to increasing use cases for AR applications. In the case of surgery, an HMD can be used as an assistive tool to help surgeons operate. With a triplanar surgical navigation system as an industry standard, the use of an HMD can improve the surgeon’s comfort, and overall experience. An HMD can offer the surgeon a consistent flow of information in front of their eyes with medically relevant images, such as craniospinal computed tomography (CT) data that can be displayed as they operate. This paper aims to bring an HMD-based overlay framework that can be used in the operating room. With a combination of Android Studio, OpenCV, and OpenGL, an inside-out localization method with Aruco Markers is demonstrated. The framework estimates the head pose of the user and subsequently renders a patient specific CT scan that will be spatially anchored to the real world. The CT reconstruction can then be virtually superimposed onto the physical patient. The HMD’s (ODG R9) fisheye lens will also be used to enhance and enable a larger field of view for better object detection. This paper also introduces a “focus mode” that improves the localization accuracy. The framework will be evaluated in each of the 3-axes for translational and rotational movement error. It will be evaluated on the detection accuracy of different numbers of markers and at different distances. It will also be evaluated using an ultra-high definition (UHD) camera.

In humans, the pupillary light reflex (PLR) is the change in diameter of the pupil as a response to changes in light intensity. By quantitatively monitoring the pupillary light reflex, there is potential to gain diagnostic knowledge for patients in a variety of situations including those suffering from a traumatic brain injury as well as those undergoing invasive neurosurgery proximal to the optic nerves. To improve the diagnostic capabilities of the PLR, a novel pupillometer was developed. The pupillometer is intended for direct placement on the eye and allows for the continuous stimulation and monitoring of pupillary light reflexes. Tests on anesthetized rabbits demonstrate real-time data acquisition and display, including the pupil diameter and velocities of constriction and dilation. The sensor is in development for implementation as a clinical device to monitor the status of the oculomotor nerves, and may also find applications in the diagnostic assessment of traumatic brain injury or changes in intracranial pressure.

Nerve injuries that significantly affect a patient’s quality of life are a common complication of major surgeries. Fluorescence-guided surgery (FGS) has become increasingly popular because it allows physicians to position their instruments precisely during surgeries to spare nerves, for example, in radical prostatectomies. Visualization of nerves during oncological surgeries is an unmet clinical need that is under investigation. Here, we address this unmet need with a contrast agent that is selective for peripheral nerves. Our contrast agent combines an existing near infrared (NIR) dye that fluoresces in the 800 region with a naturally-occurring protein of the human nervous system, nerve growth factor (NGF) – a combination termed Nervelight. Due to the fact that exogenously administered NGF localizes to the distal ends of nerves due to guidance by high affinity receptors, our contrast agent binds specifically to, then is endocytosed, and is transported up the nerve via retrograde axonal transport. In the clinical setting during nerve sparing surgeries, the area in question would be incised, and the surgeon could intra-operatively apply the agent to at-risk nerves before removing the tumor. In preliminary studies, after we directly applied the contrast agent to the nerve of interest, the targeted nerve was clearly labeled by this fluorescent imaging agent. In these experiments, visualization was obtained after 10 minutes. Other studies suggest that nerves may be seen for the duration of at least one hour and likely longer. These results suggest that Nervelight can serve as a fluorescence-guided surgical tool that will improve the visualization of at-risk nerves during radical prostatectomies, and possibly other oncological surgeries.