Results for “Brain Mapping” — Page 9

DOE OSTI2024

Untargeted Spatial Metabolomics and Spatial Proteomics on the Same Tissue Section

An increasing number of spatial multiomic workflows have been recently developed. Some of these approaches have leveraged initial mass spectrometry imaging (MSI)-based spatial metabolomics to inform region of interest (ROI) selection for downstream spatial proteomics. However, these workflows have been limited by varied substrate requirements between modalities or have required analyzing serial sections (i.e., one section per modality). To mitigate these issues, we present a novel multiomic workflow that uses desorption electrospray ionization (DESI)-MSI to identify representative spatial metabolite patterns on-tissue prior to spatial proteomic analyses on the same tissue section. Further, this workflow is demonstrated here with a model mammalian tissue (coronal rat brain section) mounted on a polyethylene naphthalate-membrane slide. Initial DESI-MSI resulted in 160 annotations (SwissLipids) within to the METASPACE platform (≤20% false discovery rate). A segmentation map from the annotated ion images informed downstream ROI selection for spatial proteomics characterization from the same sample. The unspecific substrate requirements and minimal sample disruption inherent to DESI-MSI allowed for an optimized, downstream spatial proteomics assay, resulting in 3888 ± 240 to 4717 ± 48 proteins being confidently directed per ROI (200 µm x 200 µm). Finally, we demonstrate the integration of multiomic information, where we found ceramide localization to be correlated with SMPD3 abundance (ceramide synthesis protein), and we also utilized protein abundance to resolve metabolite isomeric ambiguity. Overall, the integration of DESI-MSI into the multiomic workflow allows for complementary spatial and molecular-level information to be achieved from optimized implementations of each MS assay inherent to the workflow itself.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

NASA NTRS1984

The APL image processing laboratory

The present and proposed capabilities of the Central Image Processing Laboratory, which provides a powerful resource for the advancement of programs in missile technology, space science, oceanography, and biomedical image analysis, are discussed. The use of image digitizing, digital image processing, and digital image output permits a variety of functional capabilities, including: enhancement, pseudocolor, convolution, computer output microfilm, presentation graphics, animations, transforms, geometric corrections, and feature extractions. The hardware and software of the Image Processing Laboratory, consisting of digitizing and processing equipment, software packages, and display equipment, is described. Attention is given to applications for imaging systems, map geometric correction, raster movie display of Seasat ocean data, Seasat and Skylab scenes of Nantucket Island, Space Shuttle imaging radar, differential radiography, and a computerized tomographic scan of the brain.

Jenkins, J. O.↗

DOE OSTI2016

Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging

Purpose: Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)–induced damage to whole-brain WM bundles. Methods and Materials: An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Six DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT. Results: Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P<.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients. Conclusions: Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2025

Contributions of major tau kinase activation and phospho-tau accumulation to cortical and hippocampal tangle formation and cognition in older adults

Aberrant activation of tau kinases (tauK) has been proposed as a major step in tau hyperphosphorylation and misfolding, and subsequent formation of neurofibrillary tangles (NFT) in Alzheimer's disease (AD). However, evidence of tauK hyperactivation in actual AD brains is scarce and inconsistent, and their role in age-related cognitive decline remains undocumented. We evaluated activated/inhibited species of CDK5/p35/p25, GSK3a/ß, and ERK1/2 as well as ten tau/phospho-tau (ptau) peptides (mapping Ser 202 , Thr 217 , Ser 262 , Ser 305 , and Ser 404 phospho-residues) by Western blot or selected reaction monitoring proteomics, respectively, in postmortem dorsolateral prefrontal cortex (DLPFC) and hippocampal samples of 150 participants from the Rush Memory and Aging Project (MAP). Regression models and mediation analyses assessed the contributions of these variables to tau phosphorylation, NFT deposition and antemortem cognitive status of MAP participants. Surprisingly, greater p25 and p35 (indices for CDK5 activation) and lower pSer 21/9 -GSK3a/ß (inhibited species) immunodensities were associated with lower ptau peptide amounts. Individuals with higher p25 cortical densities displayed better cognitive outcomes, particularly working memory. Statistical mediation analyses indicated that the beneficial effect of CDK5/p25 on cognition was mediated by lower densities of phospho-Thr 217 -tau and NFT deposition in DLPFC, and also identified Thr 217 and Ser 262 as the ptau sites with greatest influence in both NFT accumulation and cognitive impairment. The present data suggest that tau hyperphosphorylation, tangle deposition, and the subsequent cognitive impairment do not rely on aberrant activation of major tauKs. Additionally, novel evidence was provided for the beneficial contribution of cortical CDK5/p25 to the maintenance of working memory.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1994

Innovation and application of ANN in Europe demonstrated by Kohonen maps

One of the most important contributions to neural networks comes from Kohonen, Helsinki/Espoo, Finland, who had the idea of self-organizating maps in 1981. He verified his idea by an algorithm of which many applications make use of. The impetus for this idea came from biology, a field where the Europeans have always been very active at several research laboratories. The challenge was to model the self-organization found in the brain. Today one goal is the development of more sophisticated neurons which model the biological neurons more exactly. They should come to a better performance of neural nets with only a few complex neurons instead of many simple ones. A lot of application concepts arise from this idea: Kohonen himself applied it to speech recognition, but the project did not overcome much more than the recognition of the numerals one to ten at that time. A more promising application for self-organizing maps is process control and process monitoring. Several proposals were made which concern parameter classification of semiconductor technologies, design of integrated circuits, and control of chemical processes. Self-organizing maps were applied to robotics. The neural concept was introduced into electric power systems. At Dortmund we are working on a system which has to monitor the quality and the reliability of gears and electrical motors in equipment installed in coal mines. The results are promising and the probability to apply the system in the field is very high. A special feature of the system is that linguistic rules which are embedded in a fuzzy controller analyze the data of the self-organizing map in regard to life expectation of the gears. It seems that the fuzzy technique will introduce the technology of neural networks in a tandem mode. These technologies together with the genetic algorithms start to form the attractive field of computational intelligence.

Goser, Karl↗

NASA NTRS1987

Tubulinlike protein from Spirochaeta bajacaliforniensis

Tubulin proteins are the fundamental subunits of all polymeric microtubule-based eukaryotic structures. Long, hollow structures each composed of 13 protofilaments as revealed by electron microscopy, microtubules (240 angstroms in diameter) are nearly ubiquitous in eukaryotes. These proteins have been the subject of intense biochemical and biophyiscal interest since the early 1970s and are of evolutionary interest as well. If tubulin-based structures (i.e., neurotubules, mitotic spindle tubules, centrioles, kinetosomes, axonemes, etc.) evolved from spirochetes by way of motility symbioses, tubulin homologies with spirochete proteins should be detectable. Tubulin proteins are widely thought to be limited to eukaryotes. Yet both azotobacters and spirochetes have shown immunological cross-reactivity with antitubulin antibodies. In neither of these studies was tubulin isolated nor any specific antigen identified as responsible for the immunoreactivity. Furthermore, although far less uniform in structure than eukaryotic microtubules, various cytoplasmic fibers and tubules (as seen by electron microscopy) have been reported in several types of prokaryotes (e.g., Spirochaeta; large termite spirochetes; treponemes; cyanobacteria; and Azotobacter. This work forms a part of our long-range study of the possible prokaryotic origin of tubulin and microtubules. Spirochetes are helically shaped gram-negative motile prokaryotes. They differ from all other bacterial in that the position of their flagella is periplasmic: their flagella lie between the inner and outer membranes of the gram-negative cell wall. Some of the largest spirochetes have longitudinally aligned 240 angstrom microtubules. Unfortunately, in spite of many attempts, all of the larger spirochetes (family Pillotaceae) with well-defined cytoplasmic tubules and antitubulin immunoreactivity are not cultivable. However, a newly described spirochete species (Spirochaeta bajacaliforniensis) possessing cytoplasmic fibers displays antitubulin immunoreactivity in whole-cell preparations. Since preliminary observations suggested that Spirochaeta bajacaliforniensis proteins may be related to eukaryotic tubulins, their characterization was undertaken. Brain tubulin can be purified by utilizing its ability to polymerize at warm temperatures and to depolymerize in the cold. After several cycles of sedimentation and redissolution the microtubule fraction is comprised of 75% tubulin and 20% high molecular mass microtubule-associated proteins (MAPs). In this paper we report that components of cell lysates, prepared from a spirochete that contains cytoplasmic fibers (Spirochaeta bajacaliforniensis), also exhibit the property of temperature-dependent cyclical sedimentation. Additionally we report the identification and characterization of the polypeptide responsible for cross-reactivity with antitubulin antiserum.

Non-NASA Center↗

DOE OSTI2014

TH-A-BRF-03: Evaluation of Synthetic CTs Generated Using MR-SIM Data

Purpose: To describe and evaluate a novel algorithm for generating synthetic CT images from MR-SIM data for dose calculations in MR-only treatment planning. Methods: A voxel-based weighted summation method was implemented to generate synthetic CT (synCT) images. MR data were acquired using Philips 1.0T Panorama high-field open MR-SIM. Retrospective patient data from seven prostate patients and one brain patient (three lesions) enrolled in an IRB-approved study were used. 3D T1-weighted fast field echo and 3D T2-weighted turbo spin echo sequences were utilized for all patients. A 3D balanced turbo field echo sequence using spectral presaturation with inversion recovery was acquired for prostate patients, but 3D ultra-short echo time (UTE)-DIXON was instead acquired for the brain patient to amplify bone signal for semi-automatic bone segmentation. Weight optimization was performed using a training subset of patients. HU value differences between planning CT and synCTs were analyzed using mean absolute error (MAE). Original patient CT-based treatment plans were mapped onto synCTs, dose was recalculated using original leaf motion and MU values, and DRRs were generated. Dosevolume metrics and gamma analysis were used for dosimetric evaluation. Results: Average whole-body MAE of synCTs across all patients was 75+12 HU. In prostate cancer patients, average HU difference between planning and synCTs was 0.9±1.0% for soft tissue structures and 4.3±2.5% for bony structures. DRRs were generated from synCTs and qualitatively showed good geometric agreement with planning CT-generated DRRs. D99, mean dose, and maximum dose to CTV calculated using the synCT remained within 1.2% of planning CT-based dose calculations. All gamma analysis evaluated at 2%/2mm dose difference/distance to agreement) pass rates were greater than 95% with an average of 99.9±0.1% for prostate patients and 98.4±2.2% for three brain lesions. Conclusion: SynCTs were generated with clinically acceptable accuracy comparable to planning CTs, enabling dose computations for MR-only simulation. Research supported in part by a grant from Philips HealthCare (Best, Netherlands)

60 APPLIED LIFE SCIENCES↗

DOE OSTI2012

Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI). Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2012

University LDRD student progress report on descriptions and comparisons of brain microvasculature via random graph models

Brain tissue includes a close interaction of neurons, glial cells, and microvasculature. This university LDRD project supported a student, Mr. Nathan Cornelius working with Professor Peter C. Doerschuk of Cornell University, in developing techniques extracting maps of the microvasculature from 2-photon optical 3-D imagery, in describing such maps as random graphs, and in developing statistical tools for comparing the graphs.

Doerschuk, Peter C.↗

DOE OSTI2013

Statistical Assessment of Proton Treatment Plans Under Setup and Range Uncertainties

Purpose: To evaluate a method for quantifying the effect of setup errors and range uncertainties on dose distribution and dose–volume histogram using statistical parameters; and to assess existing planning practice in selected treatment sites under setup and range uncertainties. Methods and Materials: Twenty passively scattered proton lung cancer plans, 10 prostate, and 1 brain cancer scanning-beam proton plan(s) were analyzed. To account for the dose under uncertainties, we performed a comprehensive simulation in which the dose was recalculated 600 times per given plan under the influence of random and systematic setup errors and proton range errors. On the basis of simulation results, we determined the probability of dose variations and calculated the expected values and standard deviations of dose–volume histograms. The uncertainties in dose were spatially visualized on the planning CT as a probability map of failure to target coverage or overdose of critical structures. Results: The expected value of target coverage under the uncertainties was consistently lower than that of the nominal value determined from the clinical target volume coverage without setup error or range uncertainty, with a mean difference of −1.1% (−0.9% for breath-hold), −0.3%, and −2.2% for lung, prostate, and a brain cases, respectively. The organs with most sensitive dose under uncertainties were esophagus and spinal cord for lung, rectum for prostate, and brain stem for brain cancer. Conclusions: A clinically feasible robustness plan analysis tool based on direct dose calculation and statistical simulation has been developed. Both the expectation value and standard deviation are useful to evaluate the impact of uncertainties. The existing proton beam planning method used in this institution seems to be adequate in terms of target coverage. However, structures that are small in volume or located near the target area showed greater sensitivity to uncertainties.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2022

Complex genetics cause and constrain fungal persistence in different parts of the mammalian body

Determining how genetic polymorphisms enable certain fungi to persist in mammalian hosts can improve understanding of opportunistic fungal pathogenesis, a source of substantial human morbidity and mortality. We examined the genetic basis of fungal persistence in mice using a cross between a clinical isolate and the lab reference strain of the budding yeast Saccharomyces cerevisiae. Employing chromosomally encoded DNA barcodes, we tracked the relative abundances of 822 genotyped, haploid segregants in multiple organs over time and performed linkage mapping of their persistence in hosts. Detected loci showed a mix of general and antagonistically pleiotropic effects across organs. General loci showed similar effects across all organs, while antagonistically pleiotropic loci showed contrasting effects in the brain vs the kidneys, liver, and spleen. Persistence in an organ required both generally beneficial alleles and organ-appropriate pleiotropic alleles. This genetic architecture resulted in many segregants persisting in the brain or in nonbrain organs, but few segregants persisting in all organs. These results show complex combinations of genetic polymorphisms collectively cause and constrain fungal persistence in different parts of the mammalian body.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2012

Multicriteria VMAT optimization

Purpose: To make the planning of volumetric modulated arc therapy (VMAT) faster and to explore the tradeoffs between planning objectives and delivery efficiency. Methods: A convex multicriteria dose optimization problem is solved for an angular grid of 180 equi-spaced beams. This allows the planner to navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus organ at risk sparing. The selected plan is then made VMAT deliverable by a fluence map merging and sequencing algorithm, which combines neighboring fluence maps based on a similarity score and then delivers the merged maps together, simplifying delivery. Successive merges are made as long as the dose distribution quality is maintained. The complete algorithm is called VMERGE. Results: VMERGE is applied to three cases: a prostate, a pancreas, and a brain. In each case, the selected Pareto-optimal plan is matched almost exactly with the VMAT merging routine, resulting in a high quality plan delivered with a single arc in less than 5 min on average. Conclusions: VMERGE offers significant improvements over existing VMAT algorithms. The first is the multicriteria planning aspect, which greatly speeds up planning time and allows the user to select the plan, which represents the most desirable compromise between target coverage and organ at risk sparing. The second is the user-chosen epsilon-optimality guarantee of the final VMAT plan. Finally, the user can explore the tradeoff between delivery time and plan quality, which is a fundamental aspect of VMAT that cannot be easily investigated with current commercial planning systems.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2015

Cryo-EM of the pathogenic VCP variant R155P reveals long-range conformational changes in the D2 ATPase ring

Single amino acid mutations in valosin containing protein (VCP/p97), a highly conserved member of the ATPases associated with diverse cellular activities (AAA) family of ATPases has been linked to a severe degenerative disease affecting brain, muscle and bone tissue. Previous studies have demonstrated the role of VCP mutations in altering the ATPase activity of the D2 ring; however the structural consequences of these mutations remain unclear. In this study, we report the three-dimensional (3D) map of the pathogenic VCP variant, R155P, as revealed by single-particle Cryo-Electron Microscopy (EM) analysis at 14 Å resolution. We show that the N-terminal R155P mutation induces a large structural reorganisation of the D2 ATPase ring. Results from docking studies using crystal structure data of available wild-type VCP in the EM density maps indicate that the major difference is localized at the interface between two protomers within the D2 ring. Consistent with a conformational change, the VCP R155P variant shifted the isoelectric point of the protein and reduced its interaction with its well-characterized cofactor, nuclear protein localization-4 (Npl4). Together, our results demonstrate that a single amino acid substitution in the N-terminal domain can relay long-range conformational changes to the distal D2 ATPase ring. Our results provide the first structural clues of how VCP mutations may influence the activity and function of the D2 ATPase ring. - Highlights: • p97{sub R155P} and p97{sub A232E} decrease the ability of p97 to bind to its co-factor Npl4. • p97{sub R155P} has a different isoelectric point than that of p97{sub R95G}, p97{sub A232E} and p97{sub WT}. • Mutation R155P changes principally the conformation of the D2 ring. • Mutation R155P modifies the interface between two protomers within the D2 ring.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-B-210-00: MR-Guided Focused Ultrasound Therapy in Oncology

MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advanced techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: Learn background on devices and techniques for MR guided HIFU for cancer therapy Understand issues and current status of clinical MRg HIFU Understand strategies for compensating for organ movement during MRgHIFU Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-B-210-01: MRg HIFU - Bone and Soft Tissue Tumor Ablation

MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advanced techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: Learn background on devices and techniques for MR guided HIFU for cancer therapy Understand issues and current status of clinical MRg HIFU Understand strategies for compensating for organ movement during MRgHIFU Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-B-210-02: MRg HIFU - Advanced Approaches for Ablation and Hyperthermia

MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advanced techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: Learn background on devices and techniques for MR guided HIFU for cancer therapy Understand issues and current status of clinical MRg HIFU Understand strategies for compensating for organ movement during MRgHIFU Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2012

7-Tesla Susceptibility-Weighted Imaging to Assess the Effects of Radiotherapy on Normal-Appearing Brain in Patients With Glioma

Purpose: To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials: SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results: Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation. These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions: High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2021

Automated Generation of Integrated Digital and Spiking Neuromorphic Machine Learning Accelerators

The growing numbers of application areas for artificial intelligence (AI) methods have led to an explosion of domain-specific accelerators that could support every new machine learning (ML) algorithm advancement, clearly highlighting the need for a capability to quickly and automatically transition from algorithm definition to hardware implementation and explore design space along a variety of SWaP (size, weight and Power). The software defined architectures (SODA) synthesizer implements a compiler-based modular infrastructure for the end-to-end generation of machine learning accelerators from high-level frameworks to hardware description language. At the same time, neuromorphic computing, by mimicking how the brain operates, promises to perform artificial intelligence tasks at efficiencies orders of magnitude higher than the current conventional tensor-processing based accelerators, as demonstrated by a variety of specialized designs leveraging Spiking Neural Networks (SNNs). Nevertheless, the mapping of an artificial neural network (ANN) to solutions supporting SNNs is still a non-trivial and very device-specific task, and completely lack the possibility to design hybrid systems that integrate conventional and spiking neural models. In this paper we discuss the support for such an integrated generation leveraging the SODA Synthesizer framework and its modular structure. In particular, we present a new MLIR dialect (part of the SODA frontend) that allows expressing spiking neural network features (e.g., available resources, spiking sequences, analog signal reading, etc.) and illustrate how it enables mapping to Spiking Neurons and deployment to the related specialized hardware (which, in the digital domain, could be generated through the other existing layers of the SODA Synthesizer). We then discuss the opportunities for even deeper integration afforded by the hardware compilation infrastructure, providing a path towards the generation of complex heterogeneous artificial intelligence systems.

Curzel, Serena↗