Laura Lewis^1,2, Kawin Setsompop^2,3, Bruce R Rosen^2,3, and Jonathan R Polimeni^2,3
1Society of Fellows, Harvard University, Cambridge, MA, United States, ²Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, United States, ³Department of Radiology, Harvard Medical School, Boston, MA, United States

            Recent work has suggested that fMRI can detect neural activity on faster timescales than previously thought. We tested the temporal limits of fMRI using oscillating visual stimuli to generate an oscillatory neural response in human visual cortex. Using rapid (TR=227 ms) fMRI acquisition at 7 Tesla, we were able to detect 0.75 Hz oscillations in visual cortex that were an order of magnitude larger than predicted by canonical linear models. Using the balloon/Windkessel model we show that continuous and rapidly varying neural activity can generate larger fMRI signals than expected. We conclude that fMRI can be used to measure oscillations of up to at least 0.75 Hz, and suggest alterations to hemodynamic response models for experiments studying continuous and rapidly varying neural activity.

Louis Gagnon^1,2,3, Sava Sakadzic⁴, Frederic Lesage², Philippe Pouliot², Anders M Dale⁵, Anna Devor⁵, Richard B Buxton⁵, and David A Boas^3
1Department of Medicine, Laval University, Quebec, QC, Canada, ²Department of Electrical Engineering, Ecole Polytechnique Montreal, Montreal, QC, Canada, ³Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States, ⁴Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Chalestown, MA, United States, ⁵Department of Radiology and Neuroscience, UCSD, La Jolla, CA, United States

Calibrated fMRI allows to estimate relative changes in the Cerebral Metabolic Rate of Oxygen Consumption (rCMRO₂) from combined BOLD and ASL measurements during a functional task. Here, we improved the accuracy of the approach by using Two-Photon microscopic measurements of the cortical microvasculature together with first principle Monte Carlo simulations of proton diffusion across the two-photon volumes. Our method allowed (1) to validate Calibrated fMRI from the microscopic point of view and (2) to optimize the free parameters of the biophysical model assumed, therefore increasing the accuracy of this method to estimate rCMRO₂.

Ian D Driver¹, Richard G Wise¹, and Kevin Murphy^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom

We propose a method for correcting for bias introduced by an iso-metabolic assumption in hypercapnia calibrated BOLD studies. A graded hypercapnia design and an assumption of linear CMRO₂ dependence on hypercapnia level are used to separate the calibration parameter M from CMRO₂ changes during hypercapnia. This method avoids intra-subject and experimental variability introduced by making a prior assumption of iso-metabolism or a CMRO₂ decrease with hypercapnia based on literature values. We implement this method using two distinct levels of hypercapnia, measuring lower M values than when making the iso-metabolic assumption, with a significant dose-wise reduction in CMRO₂ with hypercapnia level.

Alberto Merola¹, Michael A Germuska¹, Esther AH Warnert¹, Sharmila Khot^1,2, Daniel Helme², Lewys Richmond², Kevin Murphy¹, and Richard G Wise^1
1CUBRIC, Cardiff University, Cardiff, United Kingdom, ²Department of Anesthesia and Intensive Care Medicine, Cardiff University, Cardiff, United Kingdom

Caffeine acute effects on oxygen metabolism are not well characterized across the brain with MRI. We aim at measuring these in a double-blind, crossover, placebo-controlled study on sixteen healthy, moderate caffeine consumers using a dual calibrated fMRI approach and a novel forward estimation model. Results show spatial variations in OEF₀, CBF, CVR, venous CBV and CMRO₂ across grey matter at different levels of resolution (grey matter, ROI and voxel), in agreement with most of the literature findings. Therefore we propose this approach as the first viable method to assess the effects of drugs on brain metabolism with a voxel-wise resolution.

Celia M. Dong^1,2, Patrick P. Gao^1,2, Leon C. Ho^1,2, Alex T.L. Leong^1,2, Russell W. Chan^1,2, Xunda Wang^1,2, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, China, People's Republic of, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China, People's Republic of

Anesthesia is needed in many neuroscience studies but its effect on brain network response properties has not been fully understood. In particular, how it modulates crossmodal sensory responses remains largely unknown. This study investigated the brain responses to auditory stimulation at different isoflurane levels using large-view BOLD fMRI. Robust responses to multiple pure tone sound stimuli were detected in the bilateral visual cortex at 2.5% isoflurane but not at 1.0% isoflurane level. These results revealed the broad and profound modulation effects of anesthesia on brain crossmodal response properties during external sensory stimulation. 

Pei-Ching Chang ¹, Daniele Procissi², Maria Virginia Centeno¹, and Vania Apkarian^1
1Physiology, Northwestern University, Chicago, IL, United States, ²Radiology, Northwestern University, Chicago, IL, United States

fMRI in rodents is a major tool for basic neuroscience research. It allows investigation of brain networks in different animal models of disease and injury using translational methods with clinical relevance. In many instances it is essential to image animals in an awake condition (i.e. without anesthesia).  While several have shown it is possible to image animals in the awake condition they nearly all require initial anesthesia and forced restraint. In this study we describe a strategy to image rats trained to be "comfortably" restrained and head posted and show how it is possible to enhance the performance of the fMRI experiments. 

Matthias F. Valverde Salzmann¹, Klaus Scheffler¹, and Rolf Pohmann^1
1High-field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

A setup for concurrent functional MRI and intrinsic optical imaging spectroscopy inside a 14.1 T animal scanner was developed, based on a magnetic field proof camera and optics. fMRI and optical imaging were simultaneously performed on rats with electrical forepaw stimulation, resulting in excellent signals for both BOLD and optical reflectance in two wavelengths (red and green). Only minor interactions between both modalities were observed. The combination of these two techniques can be used to investigate the origins of the BOLD effect and to open up novel ways of exploring brain function.

Michaël Bernier¹, Étienne Croteau², Christian-Alexandre Castellano², Stephen C Cunnane², and Kevin Whittingstall^3
1Nuclear medecine and radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada, ²Research center of aging, Université de Sherbrooke, Sherbrooke, QC, Canada, ³Diagnostic radiology, Université de Sherbrooke, Sherbrooke, QC, Canada

Currently, PET is the primary imaging modality used to infer energy metabolism in the brain. It is also known to be a reliable biomarker of aging and cognitive diseases.  However, the cost and invasive nature of PET limits its use in basic research.  There is therefore great interest in developing alternative less invasive approaches for estimating brain glucose metabolism.  Using resting state fMRI metrics such as regional local homogeneity (ReHo), amplitude of low-frequencies fluctuations (ALFF) and regional global connectivity (closeness) we found that both regional- and subject-variations in ReHo strongly correlate with brain glucose uptake in healthy young and aging participants.

Ali Golestani¹, Jonathan Kwinta^1,2, Stephen Strother^1,2, Yasha Khatamian¹, and Jean Chen^1,2
1Rotman Research Institute at Baycrest, Toronto, ON, Canada, ²Medical Biophysics, University of Toronto, Toronto, ON, Canada

Changes in the cerebrovascular reactivity (CVR) in known to alter the amplitude of the task-based blood oxygenation level dependent (BOLD) fMRI signal. The effect of CVR on resting-state functional connectivity however is still unknown. In this study, we altered within-individual CVR by manipulating the end-tidal CO₂ (PETCO₂) level, and in each PETCO₂ level we calculated CVR and resting-state connectivity in the motor and executive control networks. rs-fMRI connectivity is significantly influenced with CVR, irrespective of neural function. The strength of this association varies between motor and executive control networks. This study stresses the importance of vascular measurements to remove biases in interpreting rs-fMRI connectivity.

Maria Guidi¹, Laurentius Huber², Leonie Lampe¹, and Harald E. Möller^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²NIMH, Bethesda, MD, United States

Cortical layer-dependent fMRI can investigate effective connectivity of the brain. However, in order to obtain layer-dependent activity information, the unspecific fMRI sensitivity to draining veins must be accounted for, e.g., with calibrated BOLD methods.  Regional variations of resting-state fMRI signal fluctuations have been suggested to resemble features of baseline physiology, such as venous blood volume and vascular reactivity. In this study, we investigate the possibility to use resting-state signal fluctuations to normalize/calibrate layer-dependent fMRI task-responses. In calibration studies with induced hypercapnia, we validate the new approach to obtain cortical profiles of vascular reactivity by comparisons with the established M-value.