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At least 181 records · Page 10

Data-driven Mapping of the Mouse Connectome: The utility of transfer learning to improve the performance of deep learning models performing axon segmentation on light-sheet microscopy images

Light sheet microscopy has made possible the high temporal and spatial 3D imaging of both fixed and live biological tissue, with samples as large as the entire mouse brain. However, segmentation and quantification of that data remains a time-consuming manual process. Machine learning methods promise the possibility of automating this process. This study seeks to advance the performance of prior models through the application of refinements such as transfer learning.

59 BASIC BIOLOGICAL SCIENCES↗

MR/PET quantification tools: Registration, segmentation, classification, and MR-based attenuation correction

Purpose: Combined MR/PET is a relatively new, hybrid imaging modality. A human MR/PET prototype system consisting of a Siemens 3T Trio MR and brain PET insert was installed and tested at our institution. Its present design does not offer measured attenuation correction (AC) using traditional transmission imaging. This study is the development of quantification tools including MR-based AC for quantification in combined MR/PET for brain imaging. Methods: The developed quantification tools include image registration, segmentation, classification, and MR-based AC. These components were integrated into a single scheme for processing MR/PET data. The segmentation method is multiscale and based on the Radon transform of brain MR images. It was developed to segment the skull on T1-weighted MR images. A modified fuzzy C-means classification scheme was developed to classify brain tissue into gray matter, white matter, and cerebrospinal fluid. Classified tissue is assigned an attenuation coefficient so that AC factors can be generated. PET emission data are then reconstructed using a three-dimensional ordered sets expectation maximization method with the MR-based AC map. Ten subjects had separate MR and PET scans. The PET with [{sup 11}C]PIB was acquired using a high-resolution research tomography (HRRT) PET. MR-based AC was compared with transmission (TX)-based AC on the HRRT. Seventeen volumes of interest were drawn manually on each subject image to compare the PET activities between the MR-based and TX-based AC methods. Results: For skull segmentation, the overlap ratio between our segmented results and the ground truth is 85.2 ± 2.6%. Attenuation correction results from the ten subjects show that the difference between the MR and TX-based methods was <6.5%. Conclusions: MR-based AC compared favorably with conventional transmission-based AC. Quantitative tools including registration, segmentation, classification, and MR-based AC have been developed for use in combined MR/PET.

60 APPLIED LIFE SCIENCES↗

Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

In vivo mapping of mutagenesis sensitivity of human enhancers

Distant-acting enhancers are central to human development1. However, our limited understanding of their functional sequence features prevents the interpretation of enhancer mutations in disease2. Here we determined the functional sensitivity to mutagenesis of human developmental enhancers in vivo. Focusing on seven enhancers that are active in the developing brain, heart, limb and face, we created over 1,700 transgenic mice for over 260 mutagenized enhancer alleles. Systematic mutation of 12-base-pair blocks collectively altered each sequence feature in each enhancer at least once. We show that 69% of all blocks are required for normal in vivo activity, with mutations more commonly resulting in loss (60%) than in gain (9%) of function. Using predictive modelling, we annotated critical nucleotides at the base-pair resolution. The vast majority of motifs predicted by these machine learning models (88%) coincided with changes in in vivo function, and the models showed considerable sensitivity, identifying 59% of all functional blocks. Taken together, our results reveal that human enhancers contain a high density of sequence features that are required for their normal in vivo function and provide a rich resource for further exploration of human enhancer logic.

Kosicki, Michael↗

Multi-scale signaling and tumor evolution in high-grade gliomas

Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.

60 APPLIED LIFE SCIENCES↗

Prolonged Blood-Brain Barrier Injury Occurs After Experimental Intracerebral Hemorrhage and Is Not Acutely Associated with Additional Bleeding

Intracerebral hemorrhage (ICH) causes blood-brain barrier (BBB) damage along with altered element levels in the brain. BBB permeability was quantified at 3, 7, and 14 days with Evans Blue dye after collagenase-induced ICH in rat. At peak permeability (day 3), a gadolinium (Gd)-based contrast agent was injected to further characterize BBB disruption, and X-ray fluorescence imaging (XFI) was used to map Gd, Fe, Cl, and other elements. XFI revealed that Ca, Cl, Gd, and Fe concentrations were significantly elevated, whereas K was significantly decreased. Therefore, using Gd-XFI, we co-determined BBB dysfunction with alterations in the metallome, including those that contribute to cell death and functional outcome. Warfarin was administered 3 days post-ICH to investigate whether additional or new bleeding occurs during peak BBB dysfunction, and hematoma volume was assessed on day 4. Warfarin administration prolonged bleeding time after a peripheral cut-induced bleed, but warfarin did not worsen hematoma volume. Accordingly, extensive BBB leakage occurred after ICH, but did not appear to affect total hematoma size.

59 BASIC BIOLOGICAL SCIENCES↗

Ultrafast two-photon fluorescence imaging of cerebral blood circulation in the mouse brain in vivo

Characterizing blood flow dynamics in vivo is critical to understanding the function of the vascular network under physiological and pathological conditions. Existing methods for hemodynamic imaging have insufficient spatial and temporal resolution to monitor blood flow at the cellular level in large blood vessels. By using an ultrafast line-scanning module based on free-space angular chirped enhanced delay, we achieved two-photon fluorescence imaging of cortical blood flow at 1,000 two-dimensional (2D) frames and 1,000,000 one-dimensional line scans per second in the awake mouse. This orders-of-magnitude increase in temporal resolution allowed us to measure cerebral blood flow at up to 49 mm/s and observe pulsatile blood flow at harmonics of heart rate. Directly visualizing red blood cell (RBC) flow through vessels down to >800 µm in depth, we characterized cortical layer–dependent flow velocity distributions of capillaries, obtained radial velocity profiles and kilohertz 2D velocity mapping of multifile blood flow, and performed RBC flux measurements from penetrating blood vessels.

59 BASIC BIOLOGICAL SCIENCES↗

MO-G-17A-04: Internal Dosimetric Calculations for Pediatric Nuclear Imaging Applications, Using Monte Carlo Simulations and High-Resolution Pediatric Computational Models

Purpose: Our purpose is to evaluate the administered absorbed dose in pediatric, nuclear imaging studies. Monte Carlo simulations with the incorporation of pediatric computational models can serve as reference for the accurate determination of absorbed dose. The procedure of the calculated dosimetric factors is described, while a dataset of reference doses is created. Methods: Realistic simulations were executed using the GATE toolkit and a series of pediatric computational models, developed by the “IT'IS Foundation”. The series of the phantoms used in our work includes 6 models in the range of 5–14 years old (3 boys and 3 girls). Pre-processing techniques were applied to the images, to incorporate the phantoms in GATE simulations. The resolution of the phantoms was set to 2 mm3. The most important organ densities were simulated according to the GATE “Materials Database”. Several used radiopharmaceuticals in SPECT and PET applications are being tested, following the EANM pediatric dosage protocol. The biodistributions of the several isotopes used as activity maps in the simulations, were derived by the literature. Results: Initial results of absorbed dose per organ (mGy) are presented in a 5 years old girl from the whole body exposure to 99mTc - SestaMIBI, 30 minutes after administration. Heart, kidney, liver, ovary, pancreas and brain are the most critical organs, in which the S-factors are calculated. The statistical uncertainty in the simulation procedure was kept lower than 5%. The Sfactors for each target organ are calculated in Gy/(MBq*sec) with highest dose being absorbed in kidneys and pancreas (9.29*10{sup 10} and 0.15*10{sup 10} respectively). Conclusion: An approach for the accurate dosimetry on pediatric models is presented, creating a reference dosage dataset for several radionuclides in children computational models with the advantages of MC techniques. Our study is ongoing, extending our investigation to other reference models and evaluating the results with clinical estimated doses.

60 APPLIED LIFE SCIENCES↗

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 biophysical 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 anitubulin 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 bacteria 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 angstroms 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 composed 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↗

Assessing the Dosimetric Accuracy of Magnetic Resonance-Generated Synthetic CT Images for Focal Brain VMAT Radiation Therapy

Purpose: The purpose of this study was to assess the dosimetric accuracy of synthetic CT (MRCT) volumes generated from magnetic resonance imaging (MRI) data for focal brain radiation therapy. Methods and Materials: A study was conducted in 12 patients with gliomas who underwent both MR and CT imaging as part of their simulation for external beam treatment planning. MRCT volumes were generated from MR images. Patients' clinical treatment planning directives were used to create 12 individual volumetric modulated arc therapy (VMAT) plans, which were then optimized 10 times on each of their respective CT and MRCT-derived electron density maps. Dose metrics derived from optimization criteria, as well as monitor units and gamma analyses, were evaluated to quantify differences between the imaging modalities. Results: Mean differences between planning target volume (PTV) doses on MRCT and CT plans across all patients were 0.0% (range: −0.1 to 0.2%) for D{sub 95%}; 0.0% (−0.7 to 0.6%) for D{sub 5%}; and −0.2% (−1.0 to 0.2%) for D{sub max}. MRCT plans showed no significant changes in monitor units (−0.4%) compared to CT plans. Organs at risk (OARs) had average D{sub max} differences of 0.0 Gy (−2.2 to 1.9 Gy) over 85 structures across all 12 patients, with no significant differences when calculated doses approached planning constraints. Conclusions: Focal brain VMAT plans optimized on MRCT images show excellent dosimetric agreement with standard CT-optimized plans. PTVs show equivalent coverage, and OARs do not show any overdose. These results indicate that MRI-derived synthetic CT volumes can be used to support treatment planning of most patients treated for intracranial lesions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Design of Hopfield Networks Based on Superconducting Coupled Oscillators

The global energy shortage has driven the development of many energy-efficient computational platforms beyond Moore's law, among which brain-inspired neuromorphic computing is one of the promising solutions. Associative memory and pattern recognition are important computations solved by brain-inspired Hopfield networks. Classical Hopfield networks store memories via fixed point attractors of their dynamics. In oscillatory Hopfield networks, these attractors are replaced by periodic orbits. Here, we design an oscillatory Hopfield network based on coupled superconducting oscillators. We first employ a mathematical phase reduction approach to map networks of coupled superconducting rapid single flux quantum (RSFQ) ring oscillators to coupled Kuramoto phase-oscillator networks. We use this theory to numerically optimize the hardware's mutual inductances in order to directly match the phase-reduced superconducting oscillators to a model of phase-oscillator-based Hopfield networks. The resulting network can store multiple oscillatory phase-locked memory patterns and recover the patterns based on the initial phase conditions. As different pattern recognition tasks, or learning, require tunable connectivity strengths between the oscillatory nodes, we further employ a coupler circuit that enables tuning the coupling strength between two oscillators by applying an external flux. We demonstrate the functionality of our design through numerical simulations of a small example network with oscillators operating at 86 GHz and recognizing patterns within 10 ns. Our approach enables the learning and retrieval of dynamical memory patterns with a wide range of applications where rhythmic dynamic output is beneficial.

Cheng, Ran↗

Systematic Comparison of High-throughput Single-Cell and Single-Nucleus Transcriptomes during Cardiomyocyte Differentiation

A comprehensive reference map of all cell types in the human body is necessary for improving our understanding of fundamental biological processes and in diagnosing and treating disease. High-throughput single-cell RNA sequencing techniques have emerged as powerful tools to identify and characterize cell types in complex and heterogeneous tissues. However, extracting intact cells from tissues and organs is often technically challenging or impossible, for example in heart or brain tissue. Single-nucleus RNA sequencing provides an alternative way to obtain transcriptome profiles of such tissues. To systematically assess the differences between high-throughput single-cell and single-nuclei RNA-seq approaches, we compared Drop-seq and DroNc-seq, two microfluidic-based 3' RNA capture technologies that profile total cellular and nuclear RNA, respectively, during a time course experiment of human induced pluripotent stem cells (iPSCs) differentiating into cardiomyocytes. Clustering of timeseries transcriptomes from Drop-seq and DroNc-seq revealed six distinct cell types, five of which were found in both techniques. Furthermore, single-cell trajectories reconstructed from both techniques reproduced expected differentiation dynamics. We then applied DroNc-seq to postmortem heart tissue to test its performance on heterogeneous human tissue samples. Our data confirm that DroNcseq yields similar results to Drop-seq on matched samples and can be successfully used to generate reference maps for the human cell atlas.

59 BASIC BIOLOGICAL SCIENCES↗

Prostatome: A combined anatomical and disease based MRI atlas of the prostate

Purpose: In this work, the authors introduce a novel framework, the anatomically constrained registration (AnCoR) scheme and apply it to create a fused anatomic-disease atlas of the prostate which the authors refer to as the prostatome. The prostatome combines a MRI based anatomic and a histology based disease atlas. Statistical imaging atlases allow for the integration of information across multiple scales and imaging modalities into a single canonical representation, in turn enabling a fused anatomical-disease representation which may facilitate the characterization of disease appearance relative to anatomic structures. While statistical atlases have been extensively developed and studied for the brain, approaches that have attempted to combine pathology and imaging data for study of prostate pathology are not extant. This works seeks to address this gap. Methods: The AnCoR framework optimizes a scoring function composed of two surface (prostate and central gland) misalignment measures and one intensity-based similarity term. This ensures the correct mapping of anatomic regions into the atlas, even when regional MRI intensities are inconsistent or highly variable between subjects. The framework allows for creation of an anatomic imaging and a disease atlas, while enabling their fusion into the anatomic imaging-disease atlas. The atlas presented here was constructed using 83 subjects with biopsy confirmed cancer who had pre-operative MRI (collected at two institutions) followed by radical prostatectomy. The imaging atlas results from mapping thein vivo MRI into the canonical space, while the anatomic regions serve as domain constraints. Elastic co-registration MRI and corresponding ex vivo histology provides “ground truth” mapping of cancer extent on in vivo imaging for 23 subjects. Results: AnCoR was evaluated relative to alternative construction strategies that use either MRI intensities or the prostate surface alone for registration. The AnCoR framework yielded a central gland Dice similarity coefficient (DSC) of 90%, and prostate DSC of 88%, while the misalignment of the urethra and verumontanum was found to be 3.45 mm, and 4.73 mm, respectively, which were measured to be significantly smaller compared to the alternative strategies. As might have been anticipated from our limited cohort of biopsy confirmed cancers, the disease atlas showed that most of the tumor extent was limited to the peripheral zone. Moreover, central gland tumors were typically larger in size, possibly because they are only discernible at a much later stage. Conclusions: The authors presented the AnCoR framework to explicitly model anatomic constraints for the construction of a fused anatomic imaging-disease atlas. The framework was applied to constructing a preliminary version of an anatomic-disease atlas of the prostate, the prostatome. The prostatome could facilitate the quantitative characterization of gland morphology and imaging features of prostate cancer. These techniques, may be applied on a large sample size data set to create a fully developed prostatome that could serve as a spatial prior for targeted biopsies by urologists. Additionally, the AnCoR framework could allow for incorporation of complementary imaging and molecular data, thereby enabling their careful correlation for population based radio-omics studies.

60 APPLIED LIFE SCIENCES↗

SU-E-T-799: Verification of a Simultaneous Treatment of Multiple Brain Metastases Using VMAT Technique by a Composite Alanine-Gel Dosimeter Phantom

Purpose: This work presents an end-to-end test using a Gel-Alanine phantom to validate the three-dimensional (3D) dose distribution (DD) delivered by a single isocenter VMAT technique on the simultaneous treatment of multiple brain metastases. Methods: Three cylindrical phantons containing MAGIC-f gel dosimeter were used to measure the 3D DD of a VMAT treatment, the first two were filled with the gel dosimeter (Gel 1 and 2) and the third one was filled with gel and 12 alanine dosimeters distributed along it (Gel 3). Gels 1 and 3 were irradiated and gel 2 was used to map the magnetic resonance image (MRI) scanner field inomogeneities. A CT scan of gel 3 was used for the VMAT treatment planning and 5 alanine pellets were chosen as lesions, around them a PTV was grown and different dose prescriptions were assigned for each one, varying from 5 to 9Gy. Before treatment, the plan was approved in a QA based on an ionization chamber absolute dose measurement, a radiochromic film planar dose measurement and a portal dosimetry per field verification; and also the phantons positioning were verified by ExacTrac 6D correction and OBI kV Cone Beam CT. The gels were irradiated, the MRIs were acquired 24 hours after irradiation and finally, the alanine dosimeters were analysed in a X-band Electron Spin Resonance spectrometer. Results: The association of the two detectors enabled the 3D dose evaluation by gel and punctually inside target volumes by alanine. In the gamma analyses (3%/3mm) comparing the 5 PTVs’ central images DD with TPS expected DD more than 95% of the points were approved. The alanine absolute dose measurements were in agreement with TPS by less than 5%. Conclusion: The gel-alanine phantom enabled the dosimetric validation of multiple brain metastases treatment using VMAT, being an almost ideal tool for this application. This work is partially supported by FAPESP.

60 APPLIED LIFE SCIENCES↗

TH-CD-206-01: Expectation-Maximization Algorithm-Based Tissue Mixture Quantification for Perfusion MRI

Purpose: To investigate the feasibility of estimating the tissue mixture perfusions and quantifying cerebral blood flow change in arterial spin labeled (ASL) perfusion MR images. Methods: The proposed perfusion MR image analysis framework consists of 5 steps: (1) Inhomogeneity correction was performed on the T1- and T2-weighted images, which are available for each studied perfusion MR dataset. (2) We used the publicly available FSL toolbox to strip off the non-brain structures from the T1- and T2-weighted MR images. (3) We applied a multi-spectral tissue-mixture segmentation algorithm on both T1- and T2-structural MR images to roughly estimate the fraction of each tissue type - white matter, grey matter and cerebral spinal fluid inside each image voxel. (4) The distributions of the three tissue types or tissue mixture across the structural image array are down-sampled and mapped onto the ASL voxel array via a co-registration operation. (5) The presented 4-dimensional expectation-maximization (4D-EM) algorithm takes the down-sampled three tissue type distributions on perfusion image data to generate the perfusion mean, variance and percentage images for each tissue type of interest. Results: Experimental results on three volunteer datasets demonstrated that the multi-spectral tissue-mixture segmentation algorithm was effective to initialize tissue mixtures from T1- and T2-weighted MR images. Compared with the conventional ASL image processing toolbox, the proposed 4D-EM algorithm not only generated comparable perfusion mean images, but also produced perfusion variance and percentage images, which the ASL toolbox cannot obtain. It is observed that the perfusion contribution percentages may not be the same as the corresponding tissue mixture volume fractions estimated in the structural images. Conclusion: A specific application to brain ASL images showed that the presented perfusion image analysis method is promising for detecting subtle changes in tissue perfusions, which is valuable for the early diagnosis of certain brain diseases, e.g. multiple sclerosis.

60 APPLIED LIFE SCIENCES↗

Caltech campus executive LDRD.

The environment most brain systems of humans and other animals are almost constantly confronted with is complex and continuously changing, with each time step updating a potentially bewildering set of opportunities and demands for action. Far from the controlled, discrete trials used in most neuro- and psychological investigations, behavior outside the lab at Caltech is a seamless and continuous process of monitoring (and error correction) of ongoing action, and of evaluating persistence in the current activity with respect to opportunities to switch tasks as alternatives become available. Prior work on frontopolar and prefrontal task switching, use tasks within the same modality (View a stream of symbols on a screen and perform certain response mappings depending on task rules). However, in these task switches the effector is constant: only the mapping of visual symbols to the specific button changes. In this task, the subjects are choosing what kinds of future action decisions they want to perform, where they can control either which body part will act, or which direction they will orient an instructed body action. An effector choice task presents a single target and the subject selects which effector to use to reach the target (eye or hand). While the techniques available for humans can be less spatially resolved compared to non-human primate neural data, they do allow for experimentation on multiple brain areas with relative ease. Thus, we address a broader network of areas involved in motor decisions. We aim to resolve a current dispute regarding the specific functional roles of brain areas that are often co-activated in studies of decision tasks, dorsal premotor cortex(PMd) and posterior parietal cortex(PPC). In one model, the PPC distinctly drives intentions for action selection, whereas PMd stimulation results in complex multi-joint movements without any awareness of, nor subjective feeling of, willing the elicited movement, thus seems to merely help execute the chosen action.

Shepodd, Timothy J.↗

SU-G-IeP1-07: Inaccuracy of Lesion Blood Flow Quantification Related to the Proton Density Reference Image in Arterial Spin Labeling MRI of Brain Tumors

Purpose: Cerebral blood flow quantification in arterial spin labeling (ASL) MRI requires an estimate of the equilibrium magnetization of blood, which is often obtained by a set of proton density (PD) reference image. Normally, a constant blood-brain partition coefficient is assumed across the brain. However, this assumption may not be valid for brain lesions. This study aimed to evaluate the impact of lesion-related PD variations on ASL quantification in patients with brain tumors. Methods: MR images for posttreatment evaluation of 42 patients with brain tumors were retrospectively analyzed. These images were acquired on a 3T MRI scanner, including T2-weighted FLAIR, 3D pseudo-continuous ASL and post-contrast T1-weighted images. Anatomical images were coregistered with ASL images using the SPM software. Regions of interest (ROIs) of the enhancing and FLAIR lesions were manually drawn on the coregistered images. ROIs of the contralateral normal appearing tissues were also determined, with the consideration of approximating coil sensitivity patterns in lesion ROIs. Relative lesion blood flow (lesion/contralateral tissue) was calculated from both the CBF map (dependent on the PD) and the ΔM map for comparison. Results: The signal intensities in both enhancing and FLAIR lesions were significantly different than contralateral tissues on the PD reference image (p<0.001). The percent signal difference ranged from −15.9 to 19.2%, with a mean of 5.4% for the enhancing lesion, and from −2.8 to 22.9% with a mean of 10.1% for the FLAIR lesion. The high/low lesion-related PD signal resulted in inversely proportional under-/over-estimation of blood flow in both enhancing and FLAIR lesions. Conclusion: Significant signal differences were found between lesions and contralateral tissues in the PD reference image, which introduced errors in blood flow quantification in ASL. The error can be up to 20% in individual patients with an average of 5- 10% for the group of patients with brain tumors.

60 APPLIED LIFE SCIENCES↗