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Rajiv S Deshpande¹, Michael C Langham¹, Cheng-Chieh Cheng¹, and Felix W Wehrli^1
1University of Pennsylvania, Philadelphia, PA, United States

Keywords: Oxygenation, Kidney, metabolic rate of oxygen

Kidney oxygen consumption rate increases during the early stages of diabetes, ultimately leading to hypoxia of renal tissue. Thus, a reliable non-invasive approach to quantify kidney metabolism has significant clinical potential. Here, an approach to quantify the kidney oxygen utilization of both kidneys is reported. The method relies on the MOTIVE-bSSFP pulse sequence to measure SvO₂ and blood flow rate in the inferior vena cava, above and below the branching of the renal vessels. Conservation of mass yields an expression to compute bilateral renal metabolic rate of oxygen.  

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Yifan Gou¹, Christopher Golden², Zixuan Lin³, Jennifer Shepard², Aylin Tekes³, Zhiyi Hu³, Xin Li³, Kumiko Oishi⁴, Marilyn Albert⁵, Hanzhang Lu³, Peiying Liu^3,6, and Dengrong Jiang^3
1Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States, ²Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Center for Imaging Science, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, United States, ⁵Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁶Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States

Keywords: Oxygenation, Oxygenation

Cerebral venous oxygenation (Y_v) is a biomarker in various brain diseases such as hypoxic-ischemic-encephalopathy in neonates and Alzheimer's disease in the elderly. T₂-Relaxation-Under-Spin-Tagging (TRUST) MRI is a widely used technique to measure global Y_v level. However, subject motion during TRUST scan can cause considerable errors in Y_v quantification. This work developed an automatic algorithm for motion-corrected quantification of Y_v, which showed improved precision of Y_v estimation in both neonates and elderly adults.

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SHUN KISHIMOTO¹, Nallathamby Devasahayam¹, Kota Yamashita¹, Kazumasa Horie¹, Kazutoshi Yamamoto¹, Jeffrey R Brender¹, and Murali C Krishna^1
1NCI, Bethesda, MD, United States

Keywords: Oxygenation, Cancer

Due to the narrow linewidth and slower signal decay, it was expected that Ox071 is suitable for wide range pO2 estimation. In this work, we present our first 3D in vivo EPR oximetry using Ox071 in comparison with Ox063. EPR imaging of  MIA Paca-2 tumor and healthy kidneys were performed on successive days by using either Ox071 or Ox063, resulting in similar spin density, pO2 maps, and pO2 histograms in the tumor regions and more homogeneous pO2 profile with Ox071 in kidney compared with Ox063. The result suggested that Ox071 is applicable for oximetry in tissue at higher pO2.

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Koen P.A. Baas¹, Chau Vu², Jian Shen², Bram F. Coolen³, Gustav J. Strijkers³, John C. Wood^2,4, and Aart J. Nederveen^1
1Radiology and Nuclear Medicine, Amsterdam UMC, Amsterdam, Netherlands, ²Biomedical Engineering, University of Southern California, Los Angeles, CA, United States, ³Biomedical Engineering and Physics, Amsterdam UMC, Amsterdam, Netherlands, ⁴Division of Cardiology, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, United States

Keywords: Oxygenation, Oxygenation

TRUST and T2-TRIR can be used to measure venous blood oxygenation (Y_v) and oxygen extraction fraction (OEF). T2-TRIR also offers simultaneous blood T1 (T1_b) measurements for hematocrit calculation in lieu of invasive blood samples. Here, TRUST and T2-TRIR were compared across a broad Y_v range using hypoxic and hypercapnic challenges in healthy volunteers, while T2-TRIR-derived hematocrit estimates were compared with venipuncture results. T2-TRIR- and TRUST-derived Y_v and OEF values exhibited a small constant bias (-5.4±3.5% and 6.0±4.0% respectively, both p<0.01) across all stimuli. Hematocrit by venipuncture and from T1_b were unbiased but had broad confidence intervals (1.7±6.3%, p=0.20).  

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Raj Kumar Parajuli¹, Megumi Ueno², Saaya Suzuki¹, Akira Sumiyoshi¹, Takayuki Obata¹, Ichio Aoki¹, and Ken-ichiro Matsumoto^2
1Department of Molecular Imaging and Theranostics, National Institutes for Quantum Science and Technology (QST), Chiba, Japan, ²Department of Radiation Regulatory Science Research, National Institutes for Quantum Science and Technology (QST), Chiba, Japan

Keywords: Oxygenation, Brain, Oxidative stress, TOLD, X-ray irradiation

This study aims to evaluate the metabolic changes caused on the brain tissues due to radiation exposure to healthy tissues while tumor treatment. The tissue oxidization and reduction mechanism represented by redox imaging could be a suitable index to evaluate in vivo oxidative stress in living animals that could evaluate metabolic damages due to irradiation. We adopted tissue oxygen level dependent (TOLD) MRI imaging to analyze TOLD signal for the control group mice and the irradiated mice. The result shows the distinct oxygen consumption levels in the control and the irradiated mice.

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Xiaoyi Liu¹, Yayan Yin¹, Juan Wei², and Jie Lu^1
1Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China, Beijing, China, ²GE Healthcare, MR Research China, Beijing, Beijing, China

Keywords: Arterial spin labelling, Metabolism, oxygen extraction fraction

We aimed to improve the accuracy of OEF mapping by using multi-delay arterial spin labeling based on quantitative susceptibility mapping plus quantitative blood oxygen level-dependent magnitude (QSM+qBOLD, or QQ). 3D multi-echo gradient-echo and ASL sequence were performed in 7 healthy subjects. ROIs analysis and paired t-test compared QQ with single-delay ASL and QQ with multi-delay ASL. QQ with multi-delay ASL shows smaller OEFs than QQ with single-delay ASL method. Corresponding OEFs were 38.9±3.4% and 39.6±3.4% (P<0.01) in gray matter, 39.7±2.9% and 40.2±2.9% in whole brain(P<0.01), respectively. Our study suggests that QQ with multi-delay ASL provides more accurate OEF than QQ with single-delay ASL, which may have potential in the use of clinical diseases.

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Ayako Imamura^1,2,3, Rikita Araki⁴, Yukari Takahashi³, Koichi Miyatake², Fusao Kato³, Sakiko Honjoh², and Tomokazu Tsurugizawa^3,5,6
1Ph. D. Program in Humanics, University of Tsukuba, Tsukuba, Japan, ²International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan, ³Department of Neuroscience, The Jikei University School of Medicine, Tokyo, Japan, ⁴Bruker Japan K.K., Yokohama, Japan, ⁵Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan, ⁶Faculty of Engineering,, University of Tsukuba, Tsukuba, Japan

Keywords: fMRI, fMRI

Simultaneous recording of fMRI and EEG is a promising approach to realize functional brain imaging with high temporal and spatial resolution. However, using standard echo planar imaging in conventional fMRI studies, implantation of electrodes on the cortical surface induces strong magnetic susceptibility artifacts in fMRI images. The zero-echo time (ZTE) sequences show a remarkable reduction in sensitivity to magnetic susceptibility artifacts and motion-derived artifacts. In this study, we showed that the ZTE sequence suppressed the susceptibility artifact by electrodes and air in the ear canal in mice. Furthermore, ZTE showed the typical functional connectivity in the mice at resting state.

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Junjian Wen^1,2, Xunda Wang^1,2, Teng Ma^1,2,3, Linshan Xie^1,2, Alex T. L. Leong^1,2, and Ed X. Wu^1,2,4
1Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China, ²Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China, ³Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong SAR, China, ⁴School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, China

Keywords: fMRI (resting state), Neuroscience

In the recent decade, resting-state functional MRI (rsfMRI) has emerged as the most invaluable, non-invasive imaging technique to map long-range, brain-wide functional connectivity networks. Despite the enormous potential inherent in this technique, our present knowledge of the neural underpinnings of rsfMRI connectivity remains generally incomplete given the lack of studies examining the role of the inhibitory neural population, which is the counterpart of the excitatory neurons. In this study, we directly examine the role of zona incerta, which is one of the major source of inhibitory drive to the cortex.

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Sosuke Yoshinaga¹, Yumiko Tsubakihara¹, Takayuki Fukumoto¹, Shotaro Maita¹, Mitsuhiro Takeda¹, and Hiroaki Terasawa^1
1Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

Keywords: New Devices, Preclinical

Muscone, a major component of musk odor, attracts male mice. The odor-evoked behaviors are mediated by neural circuits activated by the stimulation. We have been working on whole-brain BOLD fMRI studies of mice, using a method that employs periodic odor stimulation and independent component analysis. In this study, we investigated the brain regions activated by muscone in mice under medetomidine and low-dose ketamine anesthesia. Ketamine reportedly exhibits disinhibition of glutamate signaling at a low dose. As the result, we identified numerous muscone-evoked activated regions located in the olfactory pathways and higher-order regions in the cerebrum.

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Ana Mafalda Valente¹, Rita Gil¹, and Noam Shemesh^1
1Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal

Keywords: fMRI, Multimodal, NEURO

Neuronal responses are shaped by experiences. Plasticity can occur at single neuron level or at the full population level. Here, we established a novel behavioural task requiring rats to distinguish between continuous and flickering lights. We then performed fMRI in trained vs naive animals and investigated BOLD-fMRI responses along the visual pathway. When light flashes become meaningful in trained animals, the BOLD activation patterns are significantly modulated compared to naive counterparts, in particular in higher visual cortex and associative areas. BOLD-fMRI signals are thus capable of deciphering plasticity arising from strong associations with actions and rewards.

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Junghun Cho¹, Pascal Spincemaille², Thanh D. Nguyen ², and Yi Wang^2
1Biomedical Engineering, SUNY Buffalo, Buffalo, NY, United States, ²Weill Cornell Medicine, New York, NY, United States

Keywords: Oxygenation, Quantitative Imaging

Oxygen extraction fraction (OEF) is critical to evaluate brain tissue viability and function in neurologic disorders. An integrated model of QSM and qBOLD (QSM+qBOLD or QQ) has been developed to map OEF utilizing a routine multi-echo gradient echo (mGRE) acquisition without impractical vascular challenges. This study proposes a novel mGRE acquisition with logarithmic echo spacing that acquires more data points in short echo time regime, which is critical to decouple the model parameters in QQ. The proposed novel mGRE provided more accurate OEF in two simulations, compared to the conventional mGRE. 

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Xiaole Zhong^1,2 and J. Jean Chen^1,2,3
1Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Rotman Research Institute, Baycrest Hospital, Toronto, ON, Canada, ³Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada

Keywords: fMRI, Metabolism

Calibrated BOLD fMRI is becoming a method of choice in assessing baseline cerebral oxidative metabolism (CMRO₂), with gas-free calibrated fMRI being an non-invasive alternative to the more established gas-calibrated fMRI methods. However, the relative repeatabilities of these two approaches are unknown, each depending on a unique set of input measurements.  This study uses analytical simulations to investigate the sensitivity of  baseline OEF and CMRO₂ estimates to the measured inputs of each method. Our results suggest that gas-free calibrated fMRI is substantially less sensitive to input variations than gas-calibrated fMRI, demonstrating the potential for simulation-informed methodological selection.

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Vahid Khalilzad Sharghi¹, Eric Maltbie¹, Wen-Ju Pan¹, Shella Keilholz¹, and Kaundinya Gopinath^1
1Emory University, Atlanta, GA, United States

Keywords: fMRI (resting state), Brain Connectivity

Several studies point to brain slow rhythms as the basis of rsfMRI signal. We recently reported that only vigilance/arousal dependent components of fMRI signal that are not specific to brain function networks (BFNs) decrease after suppression of slow rhythms, while BFNs increase in apparent strength. Default mode network (DMN) is a BFN that exhibits similar dependence on vigilance as slow rhythms. In this study, we examined the effects of slow rhythm suppression on the integrity of DMN. Our results show that DMN is not related to these rhythms and behaves just like other BFNs upon their suppression.

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Grant Hartung^1,2, Avery J. L. Berman^1,2, Divya Varadarajan^1,2, Jingyuan Chen^1,2, and Jonathan R. Polimeni^1,2,3
1Athinoula A. Martinos Center For Biomedical Imaging, MGH, Charlestown, MA, United States, ²Department of Radiology, Harvard Medical School, Boston, MA, United States, ³Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States

Keywords: fMRI, Blood vessels, High-Resolution fMRI, Biophysical Simulation

Here we attempted to estimate a “point-spread function” of blood flow and oxygenation in the cerebral cortex through biophysical simulations based on a reconstructed vascular anatomical network. We stimulated individual pre-capillary arterioles and computed the downstream capillary flow and oxygenation based on fluid dynamics and oxygen transport through blood and tissue. We quantified this spread in the directions radial and tangential to the cortex. While several biases in spread were observed, we found a roughly 400 μm spread in the radial direction and generally narrower spread in the tangential direction, although both varied with cortical depth.

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Jacob Chaussé¹, Avery J. L. Berman^2,3, and J. Jean Chen^1,4
1Rotman Research Institute, North York, ON, Canada, ²Department of Physics, Carleton University, Ottawa, ON, Canada, ³University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada, ⁴Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Keywords: Simulations, Software Tools

Numerical simulations are valuable tools for understanding the transverse relaxation process, but their use is impeded by computational complexities and a lack of standard in simulation pipelines. We present a new software suite (named BOLDSwimSuite) to address these challenges, making numerical simulations accessible to a wider community of researchers. Among its many features, this toolbox is able to accommodate arbitrary magnetic-field perturbers as well as simulate different MRI sequences. This toolbox is useful for investigating BOLD fMRI contrast and MR vascular fingerprinting among other applications.

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Ahlam Alzaidi^1,2, Rafal Panek³, and Nicholas P Blockley^1
1School of Life Sciences, University of Nottingham, Nottingham, United Kingdom, ²Radiology Department, Taif University, Taif, Saudi Arabia, ³Medical Physics and Clinical Engineering, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom

Keywords: Relaxometry, Phantoms

A phantom to produce R₂' (reversible transverse relaxation rate) contrast was developed by inducing subvoxel magnetic susceptibility variations that mimic the quantitative Blood Oxygenation Level Dependant (qBOLD) MRI signal. Microscopic glass bubbles were used for this purpose and offer a cheaper option for making large volume phantoms than existing phantoms that use precision polystyrene microspheres. A linear relationship between R₂' and the glass bubble volume fraction was found. Comparisons of multiparametric qBOLD acquisitions between two MR vendors were also made. In the future, phantoms such as this could facilitate quality assurance for qBOLD acquisition strategies and assist with multicentre harmonization.

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Avery J.L. Berman^1,2, Jacob Chausse³, Grant Hartung^4,5, Jonathan R. Polimeni^4,5,6, and J. Jean Chen^3,7
1Department of Physics, Carleton University, Ottawa, ON, Canada, ²University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada, ³Rotman Research Institute, Baycrest Health Sciences, North York, ON, Canada, ⁴Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ⁵Department of Radiology, Harvard Medical School, Boston, MA, United States, ⁶Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States, ⁷Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Keywords: Simulations, fMRI

Simulations of the BOLD signal have provided invaluable insights into the biophysical underpinnings of BOLD contrast. Typically, infinite cylinders are used to represent the vasculature, although, in reality the vasculature is much more complex. In this study, we compared several biophysical modelling techniques for simulating the BOLD effect, including using Vascular Anatomical Networks (VANs) to model the capillary bed with realistic geometry. We found the majority of the different simulation approaches produced relatively consistent results with each other. The VAN simulations were consistent with the infinite cylinders, suggesting that infinite cylinders are a reasonable approximation to more realistic vascular models.