Evelyn MR Lake¹, Xinxin Ge², Xilin Shen¹, Peter Herman¹, Fahmeed Hyder¹, Jessica A Cardin³, Michael J Higley³, Dustin Scheinost¹, Xenophon Papademetris¹, Michael C Crair², and R Todd Constable^1
1Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States, ²Department of Neurobiology, Yale University, New Haven, CT, United States, ³Department of Neuroscience, Yale University, New Haven, CT, United States

We demonstrate longitudinal simultaneous whole-cortex Ca²⁺ imaging and fMRI in mice expressing GCaMP in one of five different cell types (excitatory, inhibitory, two interneuron subtypes, and astrocytes). The high SNR of our dual-imaging approach is shown by the indistinguishable Ca²⁺ responses to hind-paw or visual stimulation measured inside and outside the scanner. We optimize a spatially variable, three-parameter gamma-variant to investigate the transfer function between the BOLD and Ca²⁺ signals throughout the cortex. This approach is applied in functionally and anatomically defined ROIs. Results show that 1/3^rd of the variance in BOLD is accounted for from spontaneous excitatory Ca²⁺ activity.

Yuanyuan Jiang¹, Xuming Chen², Patricia Pais Roldán², Bruce Rosen¹, and Xin Yu^1,2
1Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Cambridge, MA, United States, ²Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

We established a multi-modal fMRI platform with two-channel fiber optic recording based on a genetically encoded fluorescent reporter, iGluSnFR, for extracellular glutamate (Glu) sensing and intracellular calcium indicator, GCaMP6f. Different from the intracellular neuronal and astrocytic calcium transients, the Glu signal, peak responses of spikes and baseline drift, show unique correlation features to the BOLD fMRI signal. Here, we applied the multi-modal fMRI platform to decipher the cellular and molecular interaction underlying the BOLD fMRI signal through the neuro-glio-vascular network in animal brains.

Corey Cruttenden¹, Wei Zhu², Yi Zhang², Rajesh Rajamani¹, Xiao-Hong Zhu², and Wei Chen^2
1Mechanical Engineering, University of Minnesota, Minneapolis, MN, United States, ²Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

Recording neural signals such as extracellular action potentials during functional magnetic resonance imaging (fMRI) will improve our understanding of neurovascular coupling, which is responsible for the fMRI blood oxygen level dependent (BOLD) signal. Recording electrical neural signals during fMRI is challenging due to interactions between the recording hardware and electromagnetic (EM) fields involved in MRI that introduce noise and artifacts. We developed an adaptive virtual referencing technique to improve the action potential signal quality recorded in the bore of a 16.4T animal scanner during GRASE fMRI. This technique will enable us to further study neurovascular coupling at 16.4T. 

Wenyu Tu¹, Yuncong Ma², Thomas Neuberger², and Nanyin Zhang^2
1The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, United States, ²Biomedical Engineering, Penn State University, University Park, PA, United States

To elucidate the neural basis of resting state functional network, it is important to continuously record neural activity during rsfMRI. In this study, we developed a platform including animal setup and a signal denoising pipeline to achieve continuous measurement of local field potential (LFP) and neuronal spikes with simultaneous whole-brain rsfMRI in rats. 

Yoshifumi Abe^1
1Keio University School of Medicine, Tokyo, Japan

We propose an analytical framework to characterize dynamic brain function in neuropsychiatric conditions by taking advantage of the technical aspects of diffusion functional MRI (DfMRI). The pipeline consists of local activity analysis with apparent diffusion coefficient (ADC) data, functional connectivity (FC) analysis with diffusion-weighted data (S_b1800), and ignition-driven mean integration (IDMI) analysis combining both. We illustrated its utility by analyzing model mice with an obsessive–compulsive disorder (OCD)-related behavior. The framework was successful in detecting hyperactivation and biased connectivity across the cortico-striato-thalamic circuitry. The IDMI analysis found unseen local activity-initiated propagation to the global network.

Xiao Yu^1,2, Bo-Wei Chen³, Xiaojun Tan^1,4, Boyi Qu^1,4, Tingting He^1,2, Ching-Fu Wang³, Yu-Hao Lan³, You-Yin Chen³, and Hsin-Yi Lai^1,2
1Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China, ²Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China, ³Department of Biomedical Engineering, National Yang Ming University, Taipei, Taiwan, ⁴College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China

Simultaneous recording of electrophysiological signals with functional magnetic resonance imaging (fMRI) can provide a solution for investigation of neurovascular coupling. However, this technique is challenged by 2 aspects, image artifact from electrode and electrophysiological noise from magnetic field. We improved our pervious lab-designed microelectrode array and developed a de-noise method for use of its electrophysiological recording in 7T MRI. The results showed better structural image quality and stable acquisition of spike signals and local field potential. The proposed tool and method has the potential to facilitate simultaneous spike-recording during MR scanning in 7T MRI and further study the neurovascular coupling.

Daniel C. Marsh¹, Rodika Sokoliuk², Kevin M. Aquino^1,3, Daisie O. Pakenham¹, Ross Wilson², Rosa Sanchez Panchuelo¹, Matthew J Brookes¹, Simon Hanslmayr², Stephen D. Mayhew², Susan T Francis¹, and Karen J Mullinger^1,2
1Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, ²Centre for Human Brain Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom, ³Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia

EEG alpha (8-13Hz) oscillations occur throughout the cortex but the generating mechanisms are poorly understood. Opinion is divided between alpha being driven by bottom-up, top-down or both these processes. Here we use simultaneous 7T-fMRI-EEG during periods of eyes open/closed to assess the generator of alpha by determining the strongest BOLD-alpha negative layer correlations. We show the feasibility of using high spatial resolution 7T-fMRI with EEG to understand the origin of oscillations. Preliminary analysis shows BOLD-alpha correlations peak in middle layers of V1 (but not in V2/V3) providing suggestion that the alpha oscillations investigated are driven by bottom-up processing.

Patricia S. Lan¹, Kevin J. Glaser², Richard L. Ehman², and Gary H. Glover^3
1Bioengineering, Stanford University, Stanford, CA, United States, ²Radiology, Mayo Clinic, Rochester, MN, United States, ³Radiology, Stanford University, Stanford, CA, United States

In this work, we demonstrate the first fMRE (functional MR elastography) activation in the cerebellum using a motor planning task. A block paradigm of 24s ON (auditory-cued button pressing) and 24s OFF (rest) was used and images were acquired with a single-shot spin-echo EPI MRE sequence. Our results show that tissue stiffness within the cerebellum increases with motor planning. Furthermore, the stiffness and BOLD activation colocalize in the cerebellum but do not match exactly, suggesting that the two modalities may reveal different aspects of the mechanisms for neural activation.

Dengrong Jiang¹, Shengwen Deng², Crystal G. Franklin², Michael O'Boyle², Wei Zhang², Betty L. Heyl², Li Pan³, Paul A. Jerabek², Peter T. Fox², and Hanzhang Lu^1
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ³Siemens Healthineers, Baltimore, MD, United States

Cerebral oxygen extraction fraction (OEF) is a potential biomarker in various diseases. The current gold standard to measure OEF is ¹⁵O-PET, but its clinical applications are impeded by inherent limitations. To facilitate broader clinical applications of OEF as a disease biomarker, in this work, we compared the whole-brain OEF measurement of a non-invasive MRI technique, T₂-relaxation-under-spin-tagging (TRUST), with the gold standard PET measurement, and demonstrated a strong linear correlation and no systematic difference between the two methods.

Martin Tik¹, Michael Woletz¹, Anna-Lisa Schuler¹, Matic Princic¹, Allan Hummer¹, and Christian Windischberger^1
1Medical University of Vienna, Vienna, Austria

We have established and validated a concurrent TMS/fMRI setup to study target engagement of TMS-treatment during stimulation. The proposed marker for target engagement is a change in anti-correlation of the sgACC to the DLPFC. The direct sgACC effect due to DLPFC stimulation can only be observed by concurrent fMRI. We could show that TMS treatment over the left DLPFC leads to lasting effects in RS connectivity and importantly overlap with acute BOLD response during stimulation. We conclude that concurrent TMS/fMRI can be used to investigate efficacy of treatment and thereby propose a translation into clinical medicine.