This PDF file contains the front matter associated with SPIE Proceedings Volume 10050, including the Title Page, Copyright information, Table of Contents, and Conference Committee listing.

In glioma resection surgery, the detection of tumour is often guided by using intraoperative fluorescence imaging notably with 5-ALA-PpIX, providing fluorescent contrast between normal brain tissue and the gliomas tissue to achieve improved tumour delineation and prolonged patient survival compared with the conventional white-light guided resection. However, the commercially available fluorescence imaging system relies on surgeon’s eyes to visualise and distinguish the fluorescence signals, which unfortunately makes the resection subjective. In this study, we developed a novel multi-scale spectrally-resolved fluorescence imaging system and a computational model for quantification of PpIX concentration. The system consisted of a wide-field spectrally-resolved quantitative imaging device and a fluorescence endomicroscopic imaging system enabling optical biopsy. Ex vivo animal tissue experiments as well as human tumour sample studies demonstrated that the system was capable of specifically detecting the PpIX fluorescent signal and estimate the true concentration of PpIX in brain specimen.

In the routine of stereotactic biopsy on suspected tumors located deep in the brain or patients with multiple lesions, tissue samples are harvested to determine the type of malignancy. Biopsies are taken from pre-calculated positions based on the preoperative radiologic images susceptible to brain shift. In such cases the biopsy procedure may need to be repeated leading to a longer operation time. To provide guidance for targeting diagnostic tumor tissue and to avoid vessel rupture on the insertion path of the tumor, an application specific fiber optic probe was developed. The setup incorporated spectroscopy for 5-aminolevulinic acid induced protopophyrin IX (PpIX) fluorescence in the tumor and laser Doppler for measuring microvascular blood flow which recorded backscattered light (TLI) at 780 nm and blood perfusion. The recorded signals were compared to the histopathologic diagnosis of the tissue samples (n=16) and to the preoperative radiologic images. All together 146 fluorescence and 276 laser Doppler signals were recorded along 5 trajectories in 4 patients. On all occasions strong PpIX fluorescence peaks were visible during real-time guidance. Comparing the gliotic tumor marginal zone with the tumor, the PpIX (51 vs. 528 a.u., [0-1790], p < 0.05) was higher and TLI (2.9 vs. 2.0 a.u., [0-4.1], p < 0.05) was lower in tumor. The autofluorescence (104 vs.70 a.u., [0-442], p > 0.05) and blood perfusion (8.3 vs. 17 a.u., [0-254], p > 0.05) were not significantly different. In conclusion, the optical guidance probe made real-time tumor detection and vessel tracking possible during the stereotactic biopsy procedures. Moreover, the fluorescence and blood perfusion in the tumor could be studied at controlled positions in the brain and the tumor.

Focal cortical dysplasia (FCD) is an abnormality in the cerebral cortex that is caused by malformations during cortical development. Currently, magnetic resonance imaging (MRI) and electro-corticography (ECoG) are used for detecting FCD. On the downside, MRI is very much insensitive to small malformations in the brain, while ECoG is an invasive and time consuming procedure. Recently, optical techniques were widely exploited as a minimally invasive and quantitative approaches for disease diagnosis. These techniques include fluorescence and Raman spectroscopy. The aim of this investigation is to study the diagnostic performances of optical spectroscopy incorporating fluorescence (at 378 nm and 445 nm excitation wavelengths) and Raman spectroscopy (at 785 nm excitation) for the discrimination of FCD from normal brain in pediatric subjects. The study included 10 normal and 17 FCD tissue sites from 3 normal and 7 FCD samples. The emission spectra of FCD at 378 nm excitation wavelength presented a blue-shifted peak with respect to normal tissue. Prominent spectral differences between normal and FCD tissue were observed at 1298 cm^-1, 1302 cm^-1, 1445 cm^-1 and 1660 cm^-1 using Raman spectroscopy. Tissue classification models were developed using a multivariate statistical method, principal component analysis. This study demonstrates that a combined spectroscopic approach can provide a better diagnostic capability for classifying normal and FCD tissues. Further, the implementation of the technology within a fiber probe could open the way for in vivo diagnostics and intra-operative surgical guidance.

The human brain is made up of functional regions governing movement, sensation, language, and cognition. Unintentional injury during neurosurgery can result in significant neurological deficits and morbidity. The current standard for localizing function to brain tissue during surgery, intraoperative electrical stimulation or recording, significantly increases the risk, time, and cost of the procedure. There is a need for a fast, cost-effective, and high-resolution intraoperative technique that can avoid damage to functional brain regions. We propose that optical coherence tomography (OCT) can fill this niche by imaging differences in the cellular composition and organization of functional brain areas. We hypothesized this would manifest as differences in the attenuation coefficient measured using OCT. Five functional regions (prefrontal, somatosensory, auditory, visual, and cerebellum) were imaged in ex vivo porcine brains (n=3), a model chosen due to a similar white/gray matter ratio as human brains. The attenuation coefficient was calculated using a depth-resolved model and quantitatively validated with Intralipid phantoms across a physiological range of attenuation coefficients (absolute difference < 0.1cm-1). Image analysis was performed on the attenuation coefficient images to derive quantitative endpoints. We observed a statistically significant difference among the median attenuation coefficients of these five regions (one-way ANOVA, p<0.05). Nissl-stained histology will be used to validate our results and correlate OCT-measured attenuation coefficients to neuronal density. Additional development and validation of OCT algorithms to discriminate brain regions are planned to improve the safety and efficacy of neurosurgical procedures such as biopsy, electrode placement, and tissue resection.

In this work, we analyzed the clinical applicability of NIRS for use during Quantitative Autonomic Testing (QAT). QAT is a protocol consisting of deep breathing, Valsalva maneuver, and tilt table examination. It is used to diagnose a patient with disorders of the autonomic nervous system (ANS). Disorders of ANS includes orthostatic hyper/hypotension, vasovagal syncope, and postural orthostatic tachycardia syndrome. The results of QAT are typically analyzed with the use of blood pressure and heart rate data, however these metrics may be influenced by factors such as arrhythmia, making the data interpretation and diagnosis difficult for clinicians. We tested our custom built 108-channel NIRS probe on 26 elderly patients during the QAT protocol with various ANS disorders. We found that prefrontal cerebral oxygenation correlated well with blood pressure and heart rate changes for all three tasks, making it a clinically feasible tool for observing ANS functionality. During the Valsalva maneuver, we observed a longer delayed and lower amplitude response of cerebral oxygenation to the prefrontal area in orthostatic intolerant patients. During the tilt table examination, we saw a larger response in cerebral oxygenation and less equal transient cerebral oxygenation during tilt up and tilt down in tilt table examinations that were positive (unhealthy), compared to tilt table examinations that were negative (healthy). Overall, our study showcases NIRS as an enhanced tool for understanding ANS disorders.

Our goal was to use 2-channel frequency domain near-infrared spectroscopy (NIRS) to investigate the hemodynamic and metabolic mechanisms underlying hyperglycemia-associated long-term memory impairment. We hypothesized that prefrontal cortex (PFC) oxygen saturation (%Sat) and perfusion (tHb, i.e. total hemoglobin) would decrease due to hyperglycemia during learning, and then increase during recall. During learning, participants’ blood glucose was manipulated with beverages containing either 47.4 mg saccharine control (CON, n = 10), or 50 g dextrose + 23.7 mg saccharine (GLC, n = 10). In the Symbol-Digit Modalities Test (SMDT) participants matched nine symbols to corresponding digits (1-9 inclusive), completing 105 learning and 15 testing trials on day 1 and 15 testing trials on day 2. From learning to recall, CON SMDT performance was unchanged, but GLC SMDT performance was decreased 11% (P = 0.0173). There were significant interactions (2-way ANOVA) between the CON-GLC treatment effects and the learning-recall effects for both PFC perfusion and oxygen saturation. Specifically, comparing learning to recall, CON exhibited no tHb differences but for GLC there was a large tHb decrease during learning with a partial recovery toward CON values during recall (P = 0.0012); and, comparing learning to recall, CON exhibited a large %Sat decrease but GLC exhibited a large %Sat increase (P = 0.021). We speculate that, during learning, after overnight fasting (CON) the PFC demands more hemodynamic and metabolic resources and “works” harder, but with readily available sugar (GLC) the PFC exhibits decreased “effort.”

Inline optical coherence tomography (OCT) has proven to be an ideal feedback mechanism for real-time depth control of high-power ablation lasers. This has found use in industrial laser ablation applications, but it has the potential to truly change the use of laser ablation in medicine. Previously, we have presented a novel design that is able to place the OCT beam ( λc = 1310nm) coaxially with the beam of a high-powered fiber laser (λ = 1064nm, Pavg=10W, Ppeak = 1kW) without the need of a dichroic mirror on the output stage. This design successfully demonstrated real-time ablation depth feedback. Development of this design was continued and further refinements have been made to improve performance and form factor, with the ultimate goal being to create a compact, low-cost, high-precision laser scalpel to be used for various surgical osteotomies. We present an improved design that, unlike before, removes the need for bulk optics in the entire system other than a single collimator and doublet lens on the output. Strategies for dispersion mismatch compensation will be discussed to optimize resolution of OCT feedback. Initial results for depth-controlled ablation of tissue is presented.

Tissue removal using electrocautery is standard practice in neurosurgery since tissue can be cut and cauterized simultaneously. Thermally mediated tissue ablation using lasers can potentially possess the same benefits but with increased precision. However, given the critical nature of the spine, brain, and nerves, the effects of direct photo-thermal interaction on neural tissue needs to be known, yielding not only high precision of tissue removal but also increased control of peripheral heat damage. The proposed use of lasers as a neurosurgical tool requires that a common ground is found between ablation rates and resulting peripheral heat damage. Most surgical laser systems rely on the conversion of light energy into heat resulting in both desirable and undesirable thermal damage to the targeted tissue. Classifying the distribution of thermal energy in neural tissue, and thus characterizing the extent of undesirable thermal damage, can prove to be exceptionally challenging considering its highly inhomogenous composition when compared to other tissues such as muscle and bone. Here we present the characterization of neural tissue ablation rate and heat affected zone of a 1.94 micron thulium doped fiber laser for neural tissue ablation. In-Vivo ablation of porcine cerebral cortex is performed. Ablation volumes are studied in association with laser parameters. Histological samples are taken and examined to characterize the extent of peripheral heat damage.

Targeted delivery of chemotherapeutic drugs to tumor sites is a major challenge in cancer chemotherapy. Cell-based vectorization of therapeutic agents has great potential for cancer therapy in that it can target and maintain an elevated concentration of therapeutic agents at the tumor site and prevent their spread into healthy tissue. The use of circulating cells such as monocytes/macrophages (Ma) offers several advantages compared to nanoparticles as targeted drug delivery vehicles. Ma can be easily obtained from the patient, loaded in vitro with drugs and reinjected into the blood stream. Ma can selectively cross the partially compromised blood-brain barrier surrounding brain tumors and are known to actively migrate to tumors, drawn by chemotactic factors, including hypoxic regions where conventional chemo and radiation therapy are least effective. The utility of Ma as targeted drug delivery vehicles for photochemical internalization (PCI) of tumors was investigated in this study. In vitro studies were conducted using a mixture of F98 rat glioma cells and rat macrophages loaded with a variety of chemotherapeutic agents including bleomycin and 5-fluorouracil. Preliminary data show that macrophages are resistant to both chemotherapeutics while significant toxicity is observed for F98 cells exposed to both drugs. Co-incubation of F98 cells with loaded Ma results in significant F98 toxicity suggesting that Ma are releasing the drugs and, hence providing the rationale for their use as delivery vectors for cancer therapies such as PCI.

Depression is a common psychiatric disorder that its prevalence has been reported to be 16% among adults. In recent years, transcranial near-infrared laser therapy (NILT) has gained considerable attention as a novel non-pharmaceutical method for depression. The present study was designed to compare the efficacy of two different treatment strategies in a rat model of depression. Forty male Wistar rats (180-200 g) divided into 4 groups: control, depressive, depressive-NILT, and depressive-Citalopram. All animals excepted control group was exposed to chronic mild stress (CMS) for 4 weeks. Rats in laser group received 10-Hz pulsed NILT (810 nm, energy density 1.2 J/cm² per session) transcranially for a total of 12 sessions over a three-week period. Citalopram (10 mg/kg, Intraperitoneal) was administered for 21 consecutive days. Depressive-like behavior was tested in the forced swimming test (FST) model. Serum cortisol levels were also determined. The results of FST showed an increase in swimming and decrease in immobility period, for both NILT and Citalopram groups compared to the stress group. There was also no significant difference between the experimental groups in climbing behavior. The induction of CMS significantly increased serum cortisol levels and treatments with NILT and Citalopram decreased it. Our findings showed that NILT will be more beneficial to improve the depressive-like behaviors in the rat. Our data also showed that transcranial NILT was as effective as Citalopram in the treatment of depression. Therefore, these pieces of evidence may help improve NILT as an alternative non-pharmaceutical method for depression therapy.

Cranial neurosurgical procedures are especially delicate considering that the surgeon must localize the subsurface anatomy with limited exposure and without the ability to see beyond the surface of the surgical field. Surgical accuracy is imperative as even minor surgical errors can cause major neurological deficits. Traditionally surgical precision was highly dependent on surgical skill. However, the introduction of intraoperative surgical navigation has shifted the paradigm to become the current standard of care for cranial neurosurgery. Intra-operative image guided navigation systems are currently used to allow the surgeon to visualize the three-dimensional subsurface anatomy using pre-acquired computed tomography (CT) or magnetic resonance (MR) images. The patient anatomy is fused to the pre-acquired images using various registration techniques and surgical tools are typically localized using optical tracking methods. Although these techniques positively impact complication rates, surgical accuracy is limited by the accuracy of the navigation system and as such quantification of surgical error is required. While many different measures of registration accuracy have been presented true navigation accuracy can only be quantified post-operatively by comparing a ground truth landmark to the intra-operative visualization. In this study we quantified the accuracy of cranial neurosurgical procedures using a novel optical surface imaging navigation system to visualize the three-dimensional anatomy of the surface anatomy. A tracked probe was placed on the screws of cranial fixation plates during surgery and the reported position of the centre of the screw was compared to the co-ordinates of the post-operative CT or MR images, thus quantifying cranial neurosurgical error.

Computer-assisted navigation (CAN) may guide spinal surgeries, reliably reducing screw breach rates. Definitions of screw breach, if reported, vary widely across studies. Absolute quantitative error is theoretically a more precise and generalizable metric of navigation accuracy, but has been computed variably and reported in fewer than 25% of clinical studies of CAN-guided pedicle screw accuracy. We reviewed a prospectively-collected series of 209 pedicle screws placed with CAN guidance to characterize the correlation between clinical pedicle screw accuracy, based on postoperative imaging, and absolute quantitative navigation accuracy. We found that acceptable screw accuracy was achieved for significantly fewer screws based on 2mm grade vs. Heary grade, particularly in the lumbar spine. Inter-rater agreement was good for the Heary classification and moderate for the 2mm grade, significantly greater among radiologists than surgeon raters. Mean absolute translational/angular accuracies were 1.75mm/3.13° and 1.20mm/3.64° in the axial and sagittal planes, respectively. There was no correlation between clinical and absolute navigation accuracy, in part because surgeons appear to compensate for perceived translational navigation error by adjusting screw medialization angle. Future studies of navigation accuracy should therefore report absolute translational and angular errors. Clinical screw grades based on post-operative imaging, if reported, may be more reliable if performed in multiple by radiologist raters.

Computer-assisted navigation is used by surgeons in spine procedures to guide pedicle screws to improve placement accuracy and in some cases, to better visualize patient’s underlying anatomy. Intraoperative registration is performed to establish a correlation between patient’s anatomy and the pre/intra-operative image. Current algorithms rely on seeding points obtained directly from the exposed spinal surface to achieve clinically acceptable registration accuracy. Registration of these three dimensional surface point-clouds are prone to various systematic errors. The goal of this study was to evaluate the robustness of surgical navigation systems by looking at the relationship between the optical density of an acquired 3D point-cloud and the corresponding surgical navigation error. A retrospective review of a total of 48 registrations performed using an experimental structured light navigation system developed within our lab was conducted. For each registration, the number of points in the acquired point cloud was evaluated relative to whether the registration was acceptable, the corresponding system reported error and target registration error. It was demonstrated that the number of points in the point cloud neither correlates with the acceptance/rejection of a registration or the system reported error. However, a negative correlation was observed between the number of the points in the point-cloud and the corresponding sagittal angular error. Thus, system reported total registration points and accuracy are insufficient to gauge the accuracy of a navigation system and the operating surgeon must verify and validate registration based on anatomical landmarks prior to commencing surgery.

Surgical navigation has been more actively deployed in open spinal surgeries due to the need for improved precision during procedures. This is increasingly difficult in minimally invasive surgeries due to the lack of visual cues caused by smaller exposure sites, and increases a surgeon’s dependence on their knowledge of anatomical landmarks as well as the CT or MRI images. The use of augmented reality (AR) systems and registration technologies in spinal surgeries could allow for improvements to techniques by overlaying a 3D reconstruction of patient anatomy in the surgeon’s field of view, creating a mixed reality visualization. The AR system will be capable of projecting the 3D reconstruction onto a field and preliminary object tracking on a phantom. Dimensional accuracy of the mixed media will also be quantified to account for distortions in tracking.

When using surgical loupes and other head mounted surgical instruments for an extended period of time, many surgeons experience fatigue during the procedure, which results in a lot of pain in the neck and upper back. This is primarily due to the surgeon being subjected to long periods of uncomfortable positions, due to the design of the surgical instrument. To combat this issue, the surgeon is required to have a larger freedom of movement, which will reduce the fatigue in the affected areas, and allow the surgeon to comfortably operate for longer periods of time. The proposed design will incorporate an optical magnification system on a surgical head mounted display that will allow the surgeon to freely move their head and neck during the operation, while the optics are focused on the area of interest. The design will also include an infrared tracking system in order to acquire the field of view data, which will be used to control the optics. The reduction in neck pain will also be quantified using a clinically standardized numeric pain rating scale.

Intracranial aneurysms affect a large number of individuals every year. Changes to hemodynamics are thought to be a crucial factor in the initial formation and enlargement of intracranial aneurysms. Previously, surgical clipping – an open an invasive procedure, was the standard of care. More recently, minimally invasive, catheter based therapies, specifically stenting and coiling, has been employed for treatment as it is less invasive and poses fewer overall risks. However, these treatments can further alter hemodynamic patterns of patients, affecting efficacy and prognosis. Doppler optical coherence tomography (DOCT) has shown to be useful for the evaluation of changes to hemodynamic patterns in various vascular pathologies, and intravascular DOCT may provide useful insight in the evaluation and changes to hemodynamic patterns before and during the treatment of aneurysms. In this study, we present preliminary results of DOCT imaging used in three patient-specific aneurysm phantoms located within the Circle of Willis both pre and post-treatment. These results are compared with computational fluid dynamics (CFD) simulations and high-speed camera imaging for further interpretation and validation of results.

We propose a rapid imaging method to monitor the spatial distribution of total hemoglobin concentration (CHbT), the tissue oxygen saturation, and the scattering power b in the expression of μ_s’=aλ^-b as the scattering parameters in cerebral cortex using a digital red-green-blue camera. In the method, the RGB-values are converted into the tristimulus values in CIEXYZ color space which is compatible with the common RGB working spaces. Monte Carlo simulation (MCS) for light transport in tissue is used to specify a relation among the tristimulus XYZ-values and the concentration of oxygenated hemoglobin, that of deoxygenated hemoglobin, and the scattering power b. In the present study, we performed sequential recordings of RGB images of in vivo exposed rat brain during the cortical spreading depolarization evoked by the topical application of KCl. Changes in the total hemoglobin concentration and the tissue oxygen saturation imply the temporary change in cerebral blood flow during CSD. Decrease in the scattering power b was observed before the profound increase in the total hemoglobin concentration, which is indicative of the reversible morphological changes in brain tissue during CSD. The results in this study indicate potential of the method to evaluate the pathophysiological conditions in brain tissue with a digital red-green-blue camera.

Cerebral penetrating arterioles (PAs) are structurally and functionally different from the pial arterioles, as they are an exception group from the collateral circulation. Previous study has demonstrated the PAs are the bottlenecks to the flow from the surface arteries to the deeper microcirculations. However, functional change in PAs after ischemia plays an important role in delivering blood from a highly collateralized pial arteriole network to capillaries. An ability to separately monitor PA flow dynamics is critical to understand flow redistribution mechanism during stroke and refine stroke treatment target. We use optical coherence tomography (OCT)-based microangiography (OMAG) to evaluate flow and velocity change in multiple PAs after middle cerebral artery occlusion (MCAO) in mice across a large cortex region, covering distal branches of arterioles and anastomosis. We also apply OCT-based tissue injury mapping (TIM) method to reveal the potential penumbra development within the imaging region, upon which we observed apparent differences of the PA flow dynamics between core and penumbra regions. Our results suggest that the flow dynamics of PAs can be an important factor regulating the stroke penumbra development, and that stimulatory treatment targeting PAs can be studied under the guidance of OMAG.

The brain relies on a continuous and adequate supply of blood flow, bringing the nutrients that it needs and removing the waste products of metabolism. It is thus one of the most tightly regulated systems in the body, whereby a whole range of mechanisms act to maintain this supply, despite changes in blood pressure etc. Failure of these mechanisms is found in a number of devastating cerebral diseases, including stroke, vascular dementia and brain injury and trauma. Spontaneous contraction and relaxation of arterioles (and in some instances venules) termed vasomotion has been observed in an extensive variety of tissues and species. Vasomotion has a beneficial effect on tissue oxygenation and enhance blood flow. Although vasomotion is strictly a local phenomenon, the regulation of contractile activity of vascular smooth muscle cells is dependent on the complex interplay between vasodilator and vasoconstrictor stimuli from circulating hormones, neurotransmitters, endothelial derived factors, and blood pressure. Therefore, evaluation of the spontaneous oscillations in cerebral vasculatures might be a useful tool for assessing risk and investigating different treatment strategies in neurological disorders, such as traumatic brain injury, seizure, ischemia, and stroke. In the present study, we newly propose a method to visualize the spontaneous low-frequency oscillation of cerebral blood volume based on the sequential RGB images of exposed brain.

Monitoring cerebral energy metabolism at a cellular level is essential to improve our understanding of healthy brain function and its pathological alterations. In this study, we resolve specific alterations in cerebral metabolism utilizing minimally-invasive 2-Photon fluorescence lifetime imaging (2P-FLIM) measurements of reduced nicotinamide adenine dinucleotide (NADH) fluorescence, collected in vivo from anesthetized rats and mice. Time-resolved lifetime measurements enables distinction of different components contributing to NADH autofluorescence. These components reportedly represent different enzyme-bound formulations of NADH. Our observations from this study confirm the hypothesis that NADH FLIM can identify specific alterations in cerebral metabolism. Using time-correlated single photon counting (TCSPC) equipment and a custom-built multimodal imaging system, 2-photon fluorescence lifetime imaging (FLIM) was performed in cerebral tissue with high spatial and temporal resolution. Multi-exponential fits for NADH fluorescence lifetimes indicate 4 distinct components, or 'species.' We observed distinct variations in the relative proportions of these components before and after pharmacological-induced impairments to several reactions involved in anaerobic glycolysis and aerobic oxidative metabolism. Classification models developed with experimental data correctly predict the metabolic impairments associated with bicuculline-induced focal seizures in separate experiments. Compared to traditional intensity-based NADH measurements, lifetime imaging of NADH is less susceptible to the adverse effects of overlying blood vessels. Evaluating NADH measurements will ultimately lead to a deeper understanding of cerebral energetics and its pathology-related alterations. Such knowledge will likely aid development of therapeutic strategies for neurodegenerative diseases such as Alzheimer's Disease, Parkinson's disease, and stroke.

During the last four decades, various optical techniques have been proposed and intensively used for biomedical diagnosis and therapy both in animal model and in human. These techniques have several advantages over the traditional existing methods: simplicity in structure, low-cost, easy to handle, portable, can be used repeatedly over time near the patient bedside for continues monitoring, and offer high spatiotemporal resolution. In this work, we demonstrate the use of two optical imaging modalities namely, spatially modulated illumination and dual-wavelength laser speckle to image the changes in brain tissue chromophores, morphology, and metabolic before, during, and after the onset of focal traumatic brain injury in intact mouse head (n=15). Injury was applied in anesthetized mice by weight-drop apparatus using ~50gram metal rod striking the mouse’s head. Following data analysis, we show a series of hemodynamic and structural changes over time including higher deoxyhemoglobin, reduction in oxygen saturation and blood flow, cell swelling, etc., in comparison with baseline measurements. In addition, to validate the monitoring of cerebral blood flow by the imaging system, measurements with laser Doppler flowmetry were also performed (n=5), which confirmed reduction in blood flow following injury. Overall, our result demonstrates the capability of diffuse optical modalities to monitor and map brain tissue optical and physiological properties following brain trauma.

Intracranial pressure (ICP) monitoring has a key role in the management of neurosurgical and neurological injuries. Currently, the standard clinical monitoring of ICP requires an invasive transducer into the parenchymal tissue or the brain ventricle, with possibility of complications such as hemorrhage and infection. A non-invasive method for measuring ICP, would be highly preferable, as it would allow clinicians to promptly monitor ICP during transport and allow for monitoring in a larger number of patients. We have introduced diffuse correlation spectroscopy (DCS) as a non-invasive ICP monitor by fast measurement of pulsatile cerebral blood flow (CBF). The method is similar to Transcranial Doppler ultrasound (TCD), which derives ICP from the amplitude of the pulsatile cerebral blood flow velocity, with respect to the amplitude of the pulsatile arterial blood pressure. We believe DCS measurement is superior indicator of ICP than TCD estimation because DCS directly measures blood flow, not blood flow velocity, and the small cortical vessels measured by DCS are more susceptible to transmural pressure changes than the large vessels. For fast DCS measurements to recover pulsatile CBF we have developed a custom high-power long-coherent laser and a strategy for delivering it to the tissue within ANSI standards. We have also developed a custom FPGA-based correlator board, which facilitates DCS data acquisitions at 50-100 Hz. We have tested the feasibility of measuring pulsatile CBF and deriving ICP in two challenging scenarios: humans and rats. SNR is low in human adults due to large optode distances. It is similarly low in rats because the fast heart rate in this setting requires a high repetition rate.

Optical Coherence Tomography (OCT) provides a high-resolution imaging technique with limited depth penetration. The current use of OCT is limited to relatively small areas of tissue for anatomical structure diagnosis or minimally invasive guided surgery. In this study, we propose to image a large area of the surface of the cerebral cortex. This experiment aims to evaluate the potential difficulties encountered when applying OCT imaging to large and irregular surface areas. The current state-of-the-art OCT imaging technology uses scanning systems with at most 3 degrees-of-freedom (DOF) to obtain a 3D image representation of the sample tissue. We propose the use of a 7 DOF industrial robotic arm to increase the scanning capabilities of our OCT. Such system will be capable of acquiring data from large samples of tissue that are too irregular for conventional methods. Advantages and disadvantages of our system are discussed.

Endovascular Optical Coherence Tomography (OCT) has previously been used in both bench-top and clinical environments to produce vascular images, and can be helpful in characterizing, among other pathologies, plaque build-up and impedances to normal blood flow. The raw data produced can also be processed to yield high-resolution blood velocity information, but this computation is expensive and has previously only been available a posteriori using post-processing software. Real-time Doppler OCT (DOCT) imaging has been demonstrated before in the skin and eye, but this capability has not been available to vascular surgeons. Graphics Processing Units (GPUs) can be used to dramatically accelerate this type of distributed computation. In this paper we present a software package capable of real-time DOCT processing and circular image display using GPU acceleration designed to operate with catheter-based clinical OCT systems. This image data is overlayed onto structural images providing clinicians with live, high-resolution blood velocity information to complement anatomical data. Further, we validated flow data obtained in real time using a carotid flow phantom -- constructed using 3D structural OCT data -- and controlled flow from an external pump.

In the case of infiltrative brain tumors the surgeon faces difficulties in determining their boundaries to achieve total resection. The aim of the investigation was to evaluate the performance of multimodal OCT (MM OCT) for differential diagnostics of normal brain tissue and glioma using an experimental model of glioblastoma. The spectral domain OCT device that was used for the study provides simultaneously two modes: cross-polarization and microangiographic OCT. The comparative analysis of the both OCT modalities images from tumorous and normal brain tissue areas concurrently with histologic correlation shows certain difference between when accordingly to morphological and microvascular tissue features.