Mapping Brain Metabolic Connectivity in Awake Rats with PET and Optogenetic Stimulation
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38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
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Multi Modality Brain Mapping System (MBMS) Using Artificial Intelligence and Pattern Recognition
A Multimodality Brain Mapping System (MBMS), comprising one or more scopes (e.g., microscopes or endoscopes) coupled to one or more processors, wherein the one or more processors obtain training data from one or more first images and/or first data, wherein one or more abnormal regions and one or more normal regions are identified; receive a second image captured by one or more of the scopes at a later time than the one or more first images and/or first data and/or captured using a different imaging technique; and generate, using machine learning trained using the training data, one or more viewable indicators identifying one or abnormalities in the second image, wherein the one or more viewable indicators are generated in real time as the second image is formed. One or more of the scopes display the one or more viewable indicators on the second image.
Kateb, Babak↗
Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression
Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing “helpless” behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing “resilient” behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. In conclusion, our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses tostress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.
60 APPLIED LIFE SCIENCES↗
LLNLs Neurotechnology Portfolio Presentation to Society for Brain Mapping and Therapeutics (SBMT) [Slides]
Lawrence Livermore National Laboratory has a long history in Bioengineering. They developed the first-ever bionic eye, as one example given. LLNL works in the Electroceuticals area. ELECTROnic pharmaCEUTICAL: Bioelectronic devices designed to stimulate electrically active tissues to affect biological systems in such a fashion as to alleviate or mitigate symptomatology and/or pathology. The market outlook in the Brain Computer Interface (BCI) area is discussed, as is Polymeric Opto-Electro-Mechanical Systems (POEMS). The presentation ends with iCHIP and Tissue Research topics.
59 BASIC BIOLOGICAL SCIENCES↗
HDAC6 Brain Mapping with [ 18 F]Bavarostat Enabled by a Ru-Mediated Deoxyfluorination
Not Available
59 BASIC BIOLOGICAL SCIENCES↗
Quantifying Mesoscale Neuroanatomy Using X-Ray Microtomography
Methods for resolving the three-dimensional (3D) microstructure of the brain typically start by thinly slicing and staining the brain, followed by imaging numerous individual sections with visible light photons or electrons. In contrast, X-rays can be used to image thick samples, providing a rapid approach for producing large 3D brain maps without sectioning. Here we demonstrate the use of synchrotron X-ray microtomography (µCT) for producing mesoscale (~1 µm 3 resolution) brain maps from millimeter-scale volumes of mouse brain. We introduce a pipeline for µCT-based brain mapping that develops and integrates methods for sample preparation, imaging, and automated segmentation of cells, blood vessels, and myelinated axons, in addition to statistical analyses of these brain structures. Our results demonstrate that X-ray tomography achieves rapid quantification of large brain volumes, complementing other brain mapping and connectomics efforts.
60 APPLIED LIFE SCIENCES↗
X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology
Abstract The brain is a privileged organ with regard to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischaemic changes begin almost immediately, triggering an ischaemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and breakdown of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains <25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl− are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood–brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The change observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.
Biochemistry & Molecular Biology↗
Model of brain activation predicts the neural collective influence map of the brain
Significance Evidence suggests that the brain is arranged in functionally specialized modules to form a network of networks (NoN). Understanding how functionality emerges from the integration of such modular architectures is one of the greatest scientific challenges. We introduce a model of brain NoN, which is robust against random node failures, captures the integration of functionally specialized modules in the brain, and provides falsifiable predictions about the locations of the most influential nodes, called neural collective influencers, in the brain network—predictions that are impossible in existing but fragile models of interdependent NoN. If confirmed by experiment, our results may pave the way for applications of clinical interest.
Morone, Flaviano↗
A three-dimensional thalamocortical dataset for characterizing brain heterogeneity
Neural microarchitecture is heterogeneous, varying both across and within brain regions. The consistent identification of regions of interest is one of the most critical aspects in examining neurocircuitry, as these structures serve as the vital landmarks with which to map brain pathways. Access to continuous, three-dimensional volumes that span multiple brain areas not only provides richer context for identifying such landmarks, but also enables a deeper probing of the microstructures within. Here, we describe a three-dimensional X-ray microtomography imaging dataset of a well-known and validated thalamocortical sample, encompassing a range of cortical and subcortical structures from the mouse brain . In doing so, we provide the field with access to a micron-scale anatomical imaging dataset ideal for studying heterogeneity of neural structure.
60 APPLIED LIFE SCIENCES↗
Patch2Self2: Self-supervised Denoising on Coresets via Matrix Sketching
Diffusion MRI (dMRI) non-invasively maps brain white matter yet necessitates denoising due to low signal-to-noise ratios. Patch2Self (P2S) employing self-supervised techniques and regression on a Casorati matrix effectively denoises dMRI images and has become the new de-facto standard in this field. P2S however is resource intensive both in terms of running time and memory usage as it uses all voxels (n) from all-but-one held-in volumes (d-1) to learn a linear mapping Phi : \mathbb R ^ n x(d-1) \mapsto \mathbb R ^ n for denoising the held-out volume. The increasing size and dimensionality of higher resolution dMRI acquisitions can make P2S infeasible for large-scale analyses. This work exploits the redundancy imposed by P2S to alleviate its performance issues and inspect regions that influence the noise disproportionately. Specifically this study makes a three-fold contribution: (1) We present Patch2Self2 (P2S2) a method that uses matrix sketching to perform self-supervised denoising. By solving a sub-problem on a smaller sub-space so called coreset we show how P2S2 can yield a significant speedup in training time while using less memory. (2) We present a theoretical analysis of P2S2 focusing on determining the optimal sketch size through rank estimation a key step in achieving a balance between denoising accuracy and computational efficiency. (3) We show how the so-called statistical leverage scores can be used to interpret the denoising of dMRI data a process that was traditionally treated as a black-box. Experimental results on both simulated and real data affirm that P2S2 maintains denoising quality while significantly enhancing speed and memory efficiency achieved by training on a reduced data subset.
Fadnavis, Shreyas↗
TU-C-HORIZONS-01: The Expanding Horizons Travel Grant Program: ePosters and Discussion
The Expanding Horizons travel grant program provides opportunity for students and trainees to broaden the scope of scientific meetings they attend and gain insight from research outside traditional domains of medical physics. Through participation in such conferences, early-career researchers are introduced to new topics with relevance to medical physics research as a means to expand the scientific horizons of our discipline. This year, 21 Expanding Horizons travel grants were awarded, granting travel to 17 conferences, including: Radiomics, the World Molecular Imaging Society (WMIS), the 3D Printing Conference and Expo, the GPU Technology Conference, the SIAM Imaging Science Conference, the Human Brain Mapping Conference, the OSA Conference on Clinical and Translational Biophotonics, the Society for Neuroscience, the AACR Conference on Tumor Microenvironment, and the Conference on Knowledge Discovery and Data Mining. The Expanding Horizons electronic poster session gives a venue for AAPM conference attendees to meet and discuss with awardees, learn the hot topics and emerging research areas presented at these conferences, and understand the relevance to future medical physics research.
61 RADIATION PROTECTION AND DOSIMETRY↗
WE-FG-206-05: New Arterial Spin Labeling Method for Simultaneous Estimation of Arterial Cerebral Blood Volume, Cerebral Blood Flow and Arterial Transit Time
Purpose: To demonstrate the feasibility of a novel Arterial Spin Labeling (ASL) method for simultaneously measuring cerebral blood flow (CBF), arterial transit time (ATT), and arterial cerebral blood volume (aCBV) without the use of a contrast agent. Methods: A series of multi-TI ASL images were acquired from one healthy subject on a 3T Siemens Skyra, with the following parameters: PCASL labeling with variable TI [300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000] ms, labeling bolus 1400 ms when TI allows, otherwise 100 ms less than TI, TR was minimized for each TI, two sinc shaped pre-saturation pulses were applied in the imaging plane immediately before 2D EPI acquisition. 64×64×24 voxels, 5 mm slice thickness, 1 mm gap, full brain coverage, 6 averages per TI, no crusher gradients, 11 ms TE, scan time of 4:56. The perfusion weighted time-series was created for each voxel and fit to a novel model. The model has two components: 1) the traditional model developed by Buxton et al., accounting for CBF and ATT, and 2) a box car function characterizing the width of the labeling bolus, with variable timing and height in proportion to the aCBV. All three parameters were fit using a nonlinear fitting routine that constrained all parameters to be positive. The main purpose of the high-temporal resolution TI sampling for the first second of data acquisition was to precisely estimate the blood volume component for better detection of arrival time and magnitude of signal. Results: Whole brain maps of CBF, ATT, and aCBV were produced, and all three parameters maps are consistent with similar maps described in the literature. Conclusion: Simultaneous mapping of CBF, ATT, and aCBV is feasible with a clinically tractable scan time (under 5 minutes).
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Incongruity, incongruity resolution, and mental states: The measure and modification of situational awareness and control
The research reported here describes the process of induction of various mental states. Our goals were to measure and to manipulate both the behavioral and the neurological correlates of particular mental states that have previously been demonstrated to be either beneficial or deleterious to in-flight performance situations. The experimental paradigm involved developing a context of which the participants were aware, followed by the introduction of an incongruity into that context. The empirical questions involved how the incongruity was resolved and the consequent effects on mental state. The dependent variables were measures of both the short-term ERP changes and the longer-term brain mapping indications of predominant mental states. The mission of NASA Flight Management Division and Human/Automation Integration Branch centers on the understanding and improvement of interaction between a complex system and a human operator. Specifically, the goal is improved efficiency through better operative procedures and control strategies. More efficient performance in demanding flight environments depends on improved situational awareness and replanning for fault management.
Derks, Peter L.↗
Brain wave correlates of attentional states: Event related potentials and quantitative EEG analysis during performance of cognitive and perceptual tasks
The increased use of automation in the cockpits of commercial planes has dramatically decreased the workload requirements of pilots, enabling them to function more efficiently and with a higher degree of safety. Unfortunately, advances in technology have led to an unexpected problem: the decreased demands on pilots have increased the probability of inducing 'hazardous states of awareness.' A hazardous state of awareness is defined as a decreased level of alertness or arousal which makes an individual less capable of reacting to unique or emergency types of situations. These states tend to be induced when an individual is not actively processing information. Under such conditions a person is likely to let his/her mind wander, either to internal states or to irrelevant external conditions. As a result, they are less capable of reacting quickly to emergency situations. Since emergencies are relatively rare, and since the high automated cockpit requires progressively decreasing levels of engagement, the probability of being seduced into a lowered state of awareness is increasing. This further decreases the readiness of the pilot to react to unique circumstances such as system failures. The HEM Lab at NASA-Langley Research Center has been studying how these states of awareness are induced and what the physiological correlates of these different states are. Specifically, they have been interested in studying electroencephalographic (EEG) measures of different states of alertness to determine if such states can be identified and, hopefully, avoided. The project worked on this summer involved analyzing the EEG and the event related potentials (ERP) data collected while subjects performed under two conditions. Each condition required subjects to perform a relatively boring vigilance task. The purpose of using these tasks was to induce a decreased state of awareness while still requiring the subject to process information. Each task involved identifying an infrequently presented target stimulus. In addition to the task requirements, irrelevant tones were presented in the background. Research has shown that even though these stimuli are not attended, ERP's to them can still be elicited. The amplitude of the ERP waves has been shown to change as a function of a person's level of alertness. ERP's were also collected and analyzed for the target stimuli for each task. Brain maps were produced based on the ERP voltages for the different stimuli. In addition to the ERP's, a quantitative EEG (QEEG) was performed on the data using a fast Fourier technique to produce a power spectral analysis of the EEG. This analysis was conducted on the continuous EEG while the subjects were performing the tasks. Finally, a QEEG was performed on periods during the task when subjects indicated that they were in an altered state of awareness. During the tasks, subjects were asked to indicate by pressing a button when they realized their level of task awareness had changed. EEG epochs were collected for times just before and just after subjects made this reponse. The purpose of this final analysis was to determine whether or not subjective indices of level of awareness could be correlated with different patterns of EEG.
Freeman, Frederick G.↗
Human Factors and Information Operation for a Nuclear Power Space Vehicle
This paper describes human-interactive systems needed for a crewed nuclear-enabled space mission. A synthesis of aircraft engine and nuclear power plant displays, biofeedback of sensory input, virtual control, brain mapping for control process and manipulation, and so forth are becoming viable solutions. These aspects must maintain the crew's situation awareness and performance, which entails a delicate function allocation between crew and automation.
Trujillo, Anna C.↗
TH-A-BRF-09: Integration of High-Resolution MRSI Into Glioblastoma Treatment Planning
Purpose: Identification of a metabolite signature that shows significant tumor cell infiltration into normal brain in regions that do not appear abnormal on standard MRI scans would be extremely useful for radiation oncologists to choose optimal regions of brain to treat, and to quantify response beyond the MacDonald criteria. We report on integration of high-resolution magnetic resonance spectroscopic imaging (HR-MRSI) with radiation dose escalation treatment planning to define and target regions at high risk for recurrence. Methods: We propose to supplement standard MRI with a special technique performed on an MRI scanner to measure the metabolite levels within defined volumes. Metabolite imaging was acquired using an advanced MRSI technique combining 3D echo-planar spectroscopic imaging (EPSI) with parallel acquisition (GRAPPA) using a multichannel head coil that allows acquisition of whole brain metabolite maps with 108 μl resolution in 12 minutes implemented on a 3T MR scanner. Elevation in the ratio of two metabolites, choline (Cho, elevated in proliferating high-grade gliomas) and N-acetyl aspartate (NAA, a normal neuronal metabolite), was used to image infiltrating high-grade glioma cells in vivo. Results: The metabolite images were co-registered with standard contrast-enhanced T1-weighted MR images using in-house registration software and imported into the treatment-planning system. Regions with tumor infiltration are identified on the metabolic images and used to create adaptive IMRT plans that deliver a standard dose of 60 Gy to the standard target volume and an escalated dose of 75 Gy (or higher) to the most suspicious regions, identified as areas with elevated Cho/NAA ratio. Conclusion: We have implemented a state-of-the-art HR-MRSI technology that can generate metabolite maps of the entire brain in a clinically acceptable scan time, coupled with introduction of an imaging co-registration/ analysis program that combines MRSI data with standard imaging studies in a clinically useful fashion.
60 APPLIED LIFE SCIENCES↗
Synchrotron radiation imaging is a powerful tool to image brain microvasculature
Synchrotron radiation (SR) imaging is a powerful experimental tool for micrometer-scale imaging of microcirculation in vivo. This review discusses recent methodological advances and findings from morphological investigations of cerebral vascular networks during several neurovascular pathologies. In particular, it describes recent developments in SR microangiography for real-time assessment of the brain microvasculature under various pathological conditions in small animal models. It also covers studies that employed SR-based phase-contrast imaging to acquire 3D brain images and provide detailed maps of brain vasculature. In addition, a brief introduction of SR technology and current limitations of SR sources are described in this review. In the near future, SR imaging could transform into a common and informative imaging modality to resolve subtle details of cerebrovascular function.
62 RADIOLOGY AND NUCLEAR MEDICINE↗