This PDF file contains the front matter associated with SPIE Proceedings Volume 10864, including the Title Page, Copyright Information, Table of Contents, Author and Conference Committee lists.

Background: Pediatric High-grade gliomas (pHGGs) are the No.1 cause of cancer-related deaths in children with median survival of less than a year. pHGGs tend to be infiltrative and appear irregularly shaped with ill-defined borders difficult to be distinguished from surrounding normal brain tissue. As the extent of surgical resection predicts survival, precise tumor removal with more accurate margin delineation means better treatment outcome and less loss of vital functions. While EGFR is one of the most commonly amplified genes in pHGGs, its protein-level expression is not as well characterized as in adult HGGs. Previously, near-infrared (NIR) dye labeled epidermal growth factor receptor (EGFR) antibody has served as contrast agent in fluorescence-guided surgery of head and neck cancer. However, it must overcome the blood-brain barrier (BBB) for effective intratumoral delivery in the case of brain cancer. Therefore, the latest advancement in reversible BBB opening with tight junction protein modulation has the potential to enable the molecular targeted imaging guidance of pHGG resection. Aims: The current study aimed to improve intratumoral delivery of NIR fluorescent EGFR antibody via reversible BBB permeability enhancement with siRNA modulation of tight junction protein in an orthotopic xenograft animal model of high-grade glioma with EGFR overexpression. Furthermore, resected pHGGs were examined for EGFR expression in order to stratify patient subpopulation most likely to benefit from intraoperative molecular imaging strategy that targets EGFR. Methods: An orthotopic high-grade glioma xenograft model was established in 6-15 week old mice (n=3) by intracranial injection of 10^6 EGFR-overexpressing high-grade glioma cells (D270, 10ul) 3mm below the surface of brain. Subsequently, the exposed brain was covered with a glass plate secured to the skull with cyanoacrylate glue. siRNA was selected from those targeting conserved regions of the mouse claudin-5 cDNA sequence. 20μg of claudin-5 siRNA was injected intravenously via the tail vein in an in vivo-Jet-PEI solution (Polyplus Transfection) at a rate of 0.2 ml/sec 10 days post tumor implant. 0.1mL tetramethylrhodamine (250kDa) and various sized FITC-dextran (4.4-150kDa) solutions were injected intravenously to visualize blood vessels and assess extravasation distance through cranial window via 2-photo microscopy. Enhanced permeability of BBB was characterized by increase in KTrans on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the tumor region. Mean fluorescence intensity at 800nm was measured through cranial window with an in vivo NIR imager (Pearl Impulse, LI-COR Biosciences) 0-72 hours following tail vein injection of 200ug panitumumab-IRDye800 (pan800). Immunohistochemical analysis of EGFR expression was performed on surgically resected de novo primary pHGG tumors, from seven GBM and three anaplastic ependymoma patients respectively. Results: The siRNA has shown a reversible 80% suppression of claudin-5 at 48-hrs post-injection that returned to normal levels at 72 hours. More than three-fold increase in penetration distance of 70kDa enhancing agent was observed in extravascular space and a 74% increase in intratumoral permeability was observed on DCE-MRI. Intratumoral delivery of fluorescent EGFR antibody (panitumumab-IRDye800) occurred at 6 hours and peaked at 48 hours post systemic injection following BBB opening. Positive EGFR expression was found in 70% of all surgically removed high-grade pediatric brain tumor samples. The median age of patients with positive EGFR expression was 15 (IQR = 12.75 to 16.50), significantly higher (P = 0.018) than that of EGFR negative patients (median = 0.75, IQR = 0.47 to 5.38). Conclusions: We provided proof-of-concept evidence that the enabling technology of transient BBB modulation and fluorescence-guided imaging with EGFR targeting antibody has great potential for clinical translation to improve surgery outcome by providing tumor-specific precision resection to a significant subpopulation of young patients with pHGGs

The use of monocyte/macrophage (Ma) cells as a biomimetic drug delivery system can be attributed to their involvement in innate immunity and active tumor targeting, by chemotactic factors, to hypoxic regions where conventional therapies such as chemotherapy and radiation are least effective. Furthermore, their ability to readily bypass a partially compromised blood-brain barrier has influenced the utilization of Ma as delivery vectors for brain tumor therapies that can leave other tissues relatively unaffected. Previous studies have confirmed that Ma can efficiently deliver therapeutically meaningful chemotherapeutic concentrations to in-vitro glioma models with limited carrier cytotoxicity. The effectiveness of photochemical internalization (PCI), a light-based approach, by Ma-based vectorization of drug for tumors was investigated in this study. Utilizing glioma and macrophage cell lines, in-vitro studies were conducted to demonstrate the increased efficacy of Ma-delivered chemotherapeutics. Preliminary data show that macrophages are resistant to chemotherapeutics while significant toxicity is observed for tumor cells exposed to the same drug. Further, co-incubation of tumor and Ma cells show significant tumor cell toxicity, suggestive of drug release by Ma. Treatment by PCI utilizing macrophage-mediated drug delivery was shown to enhance chemotherapeutic biological activity in comparison to drug treatment alone.

Successful clinical translation of optical techniques and therapies that advance the detection and treatment of high-grade brain cancer, glioblastoma multiforme (GBM), needs controlled, ethical and practical GBM models that accurately represent the biological reality. However, the available test-beds are not biologically accurate (artificial phantoms); are hindered by complex physiology and ethical concerns (animal models); or involve practical complexity due to rapid biological degradation of the samples ex vivo (surgical biopsies). Here, we present the development and validation of an in vitro, biologically accurate, 3-dimensional living GBM tumour model produced by tissue engineering techniques. Our 3D living equivalents of GBM tumour tissue are in the millimeter size range, consist of brain-specific extracellular matrix and living cells, and exhibit the relevant (often unfavorable) tissue optical properties such as scattering and tissue auto-fluorescence. The model also reproduces essential challenges in translational neurophotonics that are due to uneven tissue surface topography, variation in structural, optical and biochemical properties of matrix, heterogeneous cellular phenotypes and uneven distribution of exogenous contrast and therapeutic agents. We will show results of depth-resolved and wide-field imaging of the living GBM-equivalents in laboratory microscopic and theatre-based imaging systems under normal and fluorescence-guided surgery conditions using the typical 5-ALA to fluorescent PpIX conversion by GBM cells, in addition to 3D mapping of exogenous contrast agents such as fluorescent cell viability markers. These results illustrate the versatility of our 3D-engineered GBM model as macroscopic test-bed for the development of optical tools to improve the detection and treatment of brain cancer.

Peripheral nerve injuries are difficult to treat because axon regeneration is limited and functional recovery is often unsatisfactory in patients. Brief electrical stimulation of injured nerves is emerging as a new promising therapy that can relieve pain or induce better axon regeneration and functional recovery than untreated nerves. In this study, we report an innovative wireless and biocompatible stimulator that is also a scaffold for injured nerves when an autograft is applied to bridge a gap in rat sciatic nerves. We have named this device “graft-antenna” to highlight the double functionality of the implant. The scaffold is made of chitosan and incorporates a gold loop antenna (diameter ~1.3 mm, thickness ~70 nm) powered wirelessly by a transcranial magnetic stimulator (TMS). The device is bonded to tissue non-invasively and without sutures, exploiting the photo-adhesion properties of the chitosan scaffold. The stimulator did not migrate after implantation on healthy sciatic nerves in rats and was able to trigger a steady compound muscle action potential for 12 weeks (CMAP ~1.3 mV). No CMAP was elicited by the TMS when the wireless stimulator was not implanted on nerves. Axon regeneration was facilitated in sciatic nerves that were grafted with the graft-antenna and stimulated for 1 hour, once a week (magnetic field magnitude~0.72 T, pulse duration ~350 μs, repetition rate=1 pulse/sec). Eight weeks post-operatively, myelinated axon count, CMAP and nerve conduction velocity were statistically higher in the graft-antenna group (n=5) than in nerves grafted with the chitosan scaffold without antenna.

Intraoperative diagnosis of brain tumors remains a challenging problem of modern neurosurgery. A complete resection of tumor is the most important factor, determining an efficiency of its treatment, while an incomplete resection, caused by inaccurate detection of tumor margins, increases a probability of the tumor recurrence. The existing methods of the intraoperative neurodiagnosis of tumors are plagued with limited sensitivity and specificity; they remain laborious, time-consuming and/or rather expensive. Therefore, the development of novel methods for the intraoperative diagnosis of gliomas relying on modern instruments of medical imaging is a topical problem of medicine, physics, and engineering. In our research, we studied the ability of dual-modality imaging that combines such methods as optical coherence tomography (OCT) and terahertz (THz) pulsed spectroscopy, for intraoperative diagnosis of brain tumors with a strong emphasize on a human brain gliomas. We performed experimental studies of the frequency-dependent THz dielectric properties and OCT imaging of healthy (intact) and pathological brain tissues ex vivo in order to analyze the prospect for differentiation between tissue classes. The observed results highlight a potential of the considered instruments in the label-free intraoperative neurodiagnostics.

OCT is a perspective method for glial tumor margins detection during surgical operation. The challenging clinical problem of improving the functional outcomes of the surgeries on the central nervous system could be solved with the aid of cross-polarization (CP) OCT, which visualizes light backscattered from the sample in two orthogonal polarizations and gives sensitivity to the myelinated fibers. This study aimed to evaluate CP OCT feasibility to distinguish different types of brain tissue during glioma surgery to assess tumor margins and the proximity to the conductive pathways of the brain. Postoperative human specimens (tumorous tissue and peritumoral tissue, n = 40) for ex vivo СP OCT study were taken with considering the location of eloquent brain areas and tracts. Regions of sampling were also recorded at the neuronavigation station. It was shown, that the quantitative characteristics of the OCT signal of the tumor and peritumoral area have quite good correspondence with the tumor location according to the preoperative MRI, and better correlated with histological data. The same results were demonstrated for comparison of the OCT signal of the peritumoral areas and the normal white matter with the MRI-tractography and histological data. In conclusion, the CP OCT method has a high potential for intraoperative application to clarify the presence of infiltration areas and proximity to eloquent brain areas and tracts. The study was supported by RFBR projects No. 18-29-01049_mk and No. 16-32-60178 mol_а_dk.

Angiogenesis is a key factor for the growth and expansion of malignant tumors. Recently, non-invasive imaging techniques have been largely employed to observe the functional neovascular status of tumor progression. In this study, we present an integrated hybrid-resolution photoacoustic microscopy (PAM) capable of both optical-resolution (OR: a tightly focused beam for finer lateral resolution at shallower region) and acoustic-resolution (AR: a deeper imaging depth based on its ultrasound-dominated detection with relatively large illumination area) imaging for monitoring the progression of angiogenesis. The hybrid-resolution design is achieved by using a liquid lens to adjust the beam size for OR/AR mode selection. A multimode fiber with small core diameter is used to maintain the fine lateral resolution and deliver the laser light with higher energy for OR and AR illumination, respectively. The imaging resolutions of the proposed PAM are demonstrated by phantom experiments: the lateral resolution of OR mode is ~20 μm at a depth of 1 mm, while the resolution of AR mode is ~80 μm at depths of 2 to 3 mm. Additionally, in vivo experiments are conducted to show the capability of this PAM. Angiogenesis imaging of a subcutaneous tumor model in mice is presented using its intrinsic optical contrast (i.e., hemoglobin). Besides, information of oxygen saturation is also acquired using two wavelengths to indicate the hypoxic region of the tumor. In summary, the developed hybrid-resolution PAM is able to monitor the angiogenesis and provide hemodynamic information of tumor covering a broader depth range with high resolutions.

Tumor blood vessels have been known as being heterogeneous because of their chaotic and abundant distribution. Thus, imaging techniques which reveal hemodynamic information of tumor vasculature play significant roles in tumor studies. Photoacoustic (PA) imaging could acquire hemodynamic information based on the intrinsic characteristics of hemoglobin, while ultrasound (US) imaging provides information of structure and blood flow. Therefore, an integrated system was developed for both US microvascular imaging and PA imaging of the tumor region. To further improve the imaging performance, a liquid filled dual-modality microdroplets was designed for both ultrasound flow and PA imaging. The microdroplets were manufactured using the microfluidics technique to produce consistent microbubble with diameters between 23 µm to 25 µm, determining the vascular size for imaging. Additionally, the microdroplets were filled with saline diluted organic nanoparticles as contrast agents for PA imaging, while commercial microbubbles are filled with inert gas. Both in vitro and in vivo studies have been conducted for evaluating the designed contrast agent and system. Results of in vitro experiments, which performed with microtubes submerged in a scattering medium, demonstrated different flow speeds and directions of the designed phantom. Subcutaneous tumor was next tested during in vivo studies. Based on the organic nanoparticle-doped droplet, we were able to obtain the information of total hemoglobin concentration, oxygen saturation and blood flow speed of the tumor angiogenesis region with a higher sensitivity. In the future, our microdroplets could be applied to more applications, such as slow drug release based on its specific structure.

The noninvasive imaging of a brain has led to significant advances for optical techniques in neurosurgery and brain imaging. Previous study reported hemodynamic brain activity is related with neuronal activity. Photoacoustic microscopy (PAM) can detect hemodynamic activity in blood vessels by exciting red blood cells so neuronal activity can be detected by imaging vessels with PAM. Based on the results, we observed the cortical response to electrical stimulations of mouse’s hindlimbs with our functional photoacoustic microscopy (FPAM) system. Especially, based on a fast-speed imaging capability of our FPAM system, we observed instantaneous changes of hemodynamic brain activity by imaging a mouse brain non-invasively with capillary-level resolution while electrically stimulating the mouse’s hindlimbs. For the future studies, the intraoperative surgical photoacoustic microscopy system can be used to monitor the cortical response to electrical stimulations. By integrating FPAM system with surgical microscopy, we developed an intraoperative surgical photoacoustic microscopy system that provides photoacoustic images and enlarged surface view simultaneously. Additionally, by back projecting the acquired photoacoustic images on the ocular lens of the surgical microscopy, surgeons can see both the enlarged surface view and photoacoustic images simultaneously without moving the sight from the ocular lens. Thus, the developed intraoperative surgical photoacoustic microscopy system can be a vital tool for the microsurgeries and neurosurgeries including monitoring the cortical response to electrical stimulations.

We investigated a rapid imaging method to monitor the spatial distribution of total hemoglobin concentration (CHbT), the tissue oxygen saturation (StO2), and the scattering power b in the expression of musp=a(lambda)^-b as the scattering parameters in cerebral cortex using a digital red-green-blue camera. In the method, Monte Carlo simulation (MCS) for light transport in brain tissue is used to specify a relation among the RGB-values and the concentration of oxygenated hemoglobin (CHbO), that of deoxygenated hemoglobin (CHbR), and the scattering power b. In the present study, we performed sequential recordings of RGB images of in vivo exposed brain of rats before, during, and after hindlimb electrical stimulation. The remarkable increases in CHbO, CHbT, and StO2 were induced by hindlimb electrical stimulation whereas significant decreases in the scattering power b and CHbR were observed after the onset of stimulation. It has been reported that cerebral blood flow (CBF) and blood oxygen level-dependent (BOLD) signal responses show better correlation with post-synaptic local field potentials than with spiking activity. Positive CBF and BOLD responses during stimulation are associated with an increase in neuronal activity and decrease in deoxyhemoglobin content. Therefore, the decrease in the scattering power b of somatosensory cortex after hindlimb electrical stimulation is indicative of slow post-synaptic potential change. The results in this study indicate potential of RGB camera-based imaging to evaluate both hemodynamics and synaptic activity in brain tissue.

Diffuse correlation spectroscopy (DCS) is an emerging technique that allows for estimation of the motion of particles. By monitoring the time course of the speckle intensity fluctuations, the motion of the scattering particles, usually red blood cells in the microvasculature of biological tissues, can be quantified. Though these measurements are traditionally taken at near infrared wavelengths, where the attenuation of light by tissue chromophores, primarily hemoglobin, is reduced, the multiply scattered field is still heavily attenuated and expensive photon counting detectors are required to measure the signal intensity. By decreasing the cost of these systems, they may be more applicable in measuring patient hemodynamics at the bedside. Other groups have explored the use of heterodyne techniques [1,2] to amplify the intensity of the scattered field for detection with less expensive detectors, showing the potential for lowering the cost of DCS systems. Here we detail the performance characteristics of a single mode fiber (SMF) interferometer as well as follow through to investigate the theoretical relationship between the measured correlation function and the underlying dynamics. DCS measurements in the traditional homodyne configuration made with photon counting detectors are compared with those made with the interferometer with the photon counting detectors to explore experimental parameters that optimize the SNR of the blood flow index. The feasibility of utilizing fast photodiodes in the detection of the amplified field is also explored. Through the use of amplified optical signals, the detection of the DCS signal using less expensive detectors is shown to be possible. References: 1. Nakaji, H. US Application. No. 15/424581 (2017). 2. Zhou, W., Kholiqov, O., Chong, S. P. & Srinivasan, V. J. Highly parallel, interferometric diffusing wave spectroscopy for monitoring cerebral blood flow dynamics. Optica 5, 518 (2018).

The objective of the present work is to evaluate feasibility of deploying a High-Density Diffuse Optical Tomography (HD-DOT) instrument to a field setting to measure the effects of early life stressors on brain development. This goal was accomplished by imaging a cohort of typical and malnourished children in Cali, Colombia. Feasibility of performing brain imaging in this population using HD-DOT was assessed by replicating known brain responses during both tasks and rest. A total of 22 participants were enrolled in the study (10 male; average age 107.2 months; age range 97-118 months). Participants completed a passive word listening task, and participants were also imaged as they rested quietly for 5 minutes while viewing a movie. Data acquisition was performed using a custom field-ready HD-DOT system with a small footprint optimized for field use. This continuous-wave system consisted of a 30 source by 48 detector array, (S-D separations of 1.3, 2.9, and 3.9 cm; first through third nearest neighbor measurements), sampled at a 10 Hz frame rate. Sources consisted of LEDs illuminating at 750 and 850 nm. The passive word listening task revealed activations in the superior temporal gyrus, demonstrating sufficient data quality and sensitivity to known auditory language processing regions. Functional connectivity (FC) was measured using data collected during passive movie viewing and reveals sensitivity to at least two previously published functional networks. The results of this work confirm feasibility of performing neuroimaging in low-resource settings with HD-DOT. Future work will identify differences in brain function between the two populations.

Intraoperative characterization of blood flow and visualization of microvasculature can have a huge impact on surgical outcomes. Knowledge about vasculature can provide diagnostic leverage, reducing operating times and improving patient recovery. Currently used Doppler-based techniques suffer from various shortcomings such as poor spatial resolution, high susceptibility to motion artifacts, and the inability to detect longitudinal flows. Our aim is to develop a fast, non-invasive approach to intraoperative microvascular imaging of slow-moving blood. In this work, we present a spatio-temporal approach to detect blood flow in vessels on the order of 0.1 mm. Specifically, a speckle-variance flow processing algorithm is used to detect small changes in B-mode pixel intensity on a micro-ultrasound (μUS) system operating in the range of 22-70 MHz. Data used in this study was acquired intraoperatively for patients undergoing neurosurgical procedures. Microcirculation was clearly visible in various anatomical structures and the spatial resolution in flow detection was much superior in comparison to Doppler-based flow detection. Moreover, using infrared optical tracking (Northern Digital Inc., Waterloo, Canada), a three-dimensional reconstruction of the microvasculature was constructed. This 3D vessel map allows for better visualization of the vasculature in the surgical cavity – allowing surgeons to plan their incisions, minimizing blood loss and potentially improving patient outcomes. To our knowledge, this is the first implementation of a three-dimensional, intraoperative microcirculation imaging technique using statistical and optical methods, alongside a non-Doppler high frequency ultrasound.

This study, investigates the relationship between retinal image features and β-amyloid (Aβ) burden in the brain with the aim of developing a non-invasive early detection method for Alzheimer’s disease (AD). 172 retinal images from 20 clinically probable AD and 45 age-matched control cases were acquired using a hyper spectral imaging system. Brain Aβ accumulation was estimated from amyloid PET imaging. Spatial and spectral features from the hyperspectral retinal images were calculated including vessels tortuosity and image textures at different anatomical regions. Retinal veins of amyloid positive subjects (Aβ+) showed a higher mean tortuosity compared to the amyloid negative subjects (p<2.4e-7). Furthermore, a significant difference between texture measures of retinal arteries and their adjacent regions were observed in Aβ+ subjects when compared to the Aβ- (p<1.3e-5).

It has been proposed that there are two alternative strategies for bilinguals to translate between languages, i.e. “transcoding”, which takes the “shortcut” linking translation equivalents between the source language (SL) and the target language (TL), or “transphrasing”, which takes the “long route” involving a monolingual processing of meaning in the SL, a non-verbal conceptual level, and then a monolingual processing of meaning in the TL ^1-4. This study examined the neural mechanism underlying these two translation strategies in the context of Chinese to English simultaneous interpreting (SI) by using optical brain mapping techniques. In particular, brain activation patterns associated with the two forms of bilingual processing are compared with those related to “code-mixing”, which is a strategy that probably has little to do with bilingual processing but available to simultaneous interpreters in certain contexts. We discovered that “transcoding” only elicited significant and almost immediate brain activation in the Broca’s area, whereas “transphrasing” produced more extensive and stronger activation across the whole left prefrontal cortex as compared to “code-mixing”. This pilot study, which provides neurological evidences for the “shortcut” and the “long route” that bilinguals utilize when translating between languages, will definitely pave a new avenue for better understanding of the cognitive mechanism underlying translation, bilingual processing and speech production in general.

Traditional optical imaging systems are designed for imaging with a single contrast mechanism, and therefore can interrogate only a single neurophysiologic variable. However, the biological complexity underlying neurophysiological function and its alteration in neurodegenerative diseases, requires the simultaneous interrogation of multiple neurophysiologic variables to arrive at a better understanding. Today’s multicontrast optical imaging systems satisfy this need, but suffer from some inherent limitations. Owing to the need to integrate multiple contrast mechanisms, these imaging systems tend to be benchtop-based and unportable, often requiring animals to be anesthetized, custom built and expensive. This limits their widespread adoption. Miniaturization, although technically challenging, remains a potential solution to these limitations. To address this unmet need, here we present the design considerations and practical guidelines for building inexpensive, miniaturized, and portable multicontrast optical neuroimaging systems that allow comprehensive interrogation of brain function in freely behaving rodents. We then showcase an example tri-contrast miniature neuroimaging system and demonstrate the implementation of our guidelines. We conclude by demonstrating the utility of such a miniature multicontrast neuroimaging system by interrogating in an awake rodent the tumor extent, angiogenic vascular sprouting, flow establishment in the newly formed vessels, as well as anomalies in resting-state microvascular fluctuations in a preclinical model of brain tumor progression.

A method based on spatial frequency domain imaging platform and different back-processing algorithms are used together to present the refractive index (RI) of mouse brain tissue in the NIR spectral range. Structured light patterns at two frequencies of six wavelengths ranging between 690 and 970 nm were serially projected onto mouse scalp while a camera mounted above the head captures the reflected diffuse light. In the computer, the recorded images at each wavelength were converted to spatial absorption and scattering maps, respectively. Then, algorithms based on Maxell equations, Hilbert Transform, and Kramers-Kronig relations are used separately to calculate the RI. Once the value of RI at each wavelength was obtained, the wavelength dependence of RI was fitted using four well-known dispersion models. In addition, three-dimensional surface-profile distribution of RI was achieved based on phase profilometry principle. During this study, RI was evaluated in mouse model of heatstress (HS) showing a decrease in RI with increasing wavelength and overall differences pre-and-post HS. An in-house system was built to control the body temperature and thermal camera together with IR laser temperature meter gun was used to measure brain temperature. The changes in RI we observed reflect the pathophysiology of the brain during HS and present an additional advantage of spatial frequency domain imaging technique to characterize brain function. Overall, this work demonstrates a proofof- concept of the proposed method which we believe will be beneficial to the Biophotonics' community.

Coupling behavioral information with functional neuroimaging data sets promises to provide comprehensive insight into many medical data analyses. Analyzing the relationship of data sets of such diverse natures across multiple subjects requires special considerations. This enables a much more robust characterization of different data sets. Here, we investigate the relation between psychopathic traits quantified by the Psychopathic Personality Inventory- Revised [PPI-R]; (behavioral data set) and brain functional activities captured by functional near infra-red spectroscopy (fNIRS; neuroimaging data set). Particularly, we wanted to determine the psychopathic core traits most correlated with brain functional activation in personal (emotionally salient) and impersonal (more logical than emotional) moral judgment (MJ) decision-making. Our aim was to fill the gap in neuroimaging research between psychopathic traits and neuroimaging data during moral decision making using fNIRS. Applying Canonical Correlation Analysis (CCA) on brain functional activity recording from 30 healthy subjects and their psychopathic traits revealed coldheartedness and carefree non-planfulness to be highly correlated with prefrontal activation during personal (emotionally salient) MJ, while Machiavellian egocentricity, rebellious nonconformity, coldheartedness, and carefree non-planfulness were the core traits that exhibited the same dynamics as prefrontal activity during impersonal (more logical) MJ. Furthermore, ventromedial prefrontal cortex (vmPFC) and left lateral prefrontal cortex (PFC) were the prefrontal regions most positively correlated with psychopathic traits during personal MJ, and the right vmPFC and right lateral PFC were most correlated with impersonal MJ decision-making.

The temporal evolution of cortical activation patterns during a handgrip task inducing forearm muscle fatigue was studied with functional near-infrared spectroscopy (fNIRS). Brain activation patterns mapped over the prefrontal and sensorimotor cortices (111 channels) and concurrent fatigue measurements, assessed by a force sensor, were studied for a group of physical active subjects versus an age-matched healthy, but non-exercising group. Thirteen young adults (18-35 years old) were recruited who performed intermittent handgrip contractions for 3.5s alternating with 6.5s of rest for 120 blocks with their dominant hand. Observed differences in activation and connectivity in the primary motor cortex (M1), premotor and supplementary motor cortex (PMC/SMA), and prefrontal cortex (PFC) in both hemispheres hinted at differences in compensatory tactics used by the brain based on available physical resources that depend on physical activity. Furthermore, our study demonstrated strengthened FC throughout the entire duration of the fatigue-inducing handgrip task. Ultimately, this ongoing study will provide baseline measurements on the brain’s compensatory patterns for follow-up work on older individuals with impaired cardiovascular health performing the fatiguing handgrip task.

The vascular space occupancy (VASO) fMRI method probes changes in cerebral blood volume (CBV) under various physiological states, including neuronal activation in humans. However, it requires a careful choice of sequence parameters because the blood oxygen-level dependent (BOLD) effect offsets the VASO signal. Assessing this BOLD contamination as a function of pulse sequence parameters would improve the quantification of CBV changes with VASO. However, this task requires knowledge of the cerebral vascular geometry of the MRI voxel. Towards this end, optical microscopy can provide high-resolution 3D images of vasculature. Here, we use detailed angiograms of rodent brain acquired with two-photon microscopy to model fMRI signals (VASO and BOLD) from first principles using Monte Carlo diffusion of water protons. We present quantitative plots of VASO together with intra- and extravascular BOLD fractional signal changes as a function of echo time (TE), for spin echo (SE) and gradient echo (GRE) pulse sequences, at low to ultra-high magnetic fields. Our results indicate that at 3T, the BOLD contamination of the VASO response is under 12% for GRE and 2% for SE up to TE=6 ms, but this contamination is significantly higher at 7T and above. We also found GRE BOLD intravascular contributions of 85% at 1.5T, 55% at 3T and 4% at 7T and SE intravascular contributions of 70% at 1.5T, 40% at 3T and 10% at 7T. These results may provide important information to optimize the pulse sequence timing in human VASO and BOLD fMRI, leading the way to a wider application of these fMRI techniques in healthy and diseased brain.