fMRI: Beyond BOLD

Friday 16 May 2014

Xin Yu¹, Stephen J. Dodd¹, Afonso C. Silva¹, and Alan P. Koretsky^1
1National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States

Hemodynamic signal from individual venules can be detected directly with fMRI. Here, the hemodynamic signal from BOLD and CBV fMRI was measured at high temporal (100ms) and spatial (150x150µm) resolution in layers 4/5 of the rat forepaw S1 with a fast gradient-echo MRI sequence. Distinctly different voxels were activated in BOLD vs CBV fMRI. In contrast to the BOLD activated voxels primarily located within penetrating venules, CBV activated voxels were primarily located to penetrating arterioles. This result makes it possible to directly image the CBV and BOLD response at the level of single-vessels to better understand neurovascular coupling.

Lisa C. Krishnamurthy^1,2 and Hanzhang Lu^1
1Advanced Imaging Research Center, UT Southwester Medical Center, Dallas, TX, United States, ²Dept. of Bioengineering, University of Texas at Arlington, Arlington, TX, United States

The ability to generate a “small-vessel map” of Yv may help in better characterizing variations in venous oxygenation across brain regions, identifying regions at risk of ischemia attack or stroke, and may find immediate applications in clinical conditions that affect specific brain regions. The present study aims to optimize a sequence called T2-Relaxation-Under-Phase-Contrst (TRU-PC) MRI to generate a complete Yv map of the vasculature in the mid-sagittal brain, including small veins (1-2 mm in caliber). The optimization includes removing an eddy-current induced artifact to improve the Yv quantification, adding additional scans to sensitize the maps to more vessels, and merging these scans into a single signal map for T2-fitting.

Michael Germuska¹ and Daniel Bulte^2
1Cardiff University Brain Research Imaging Centre, University of Cardiff, Cardiff, United Kingdom, ²Nuffield Dept. of Clinical Neurosciences, Oxford University, Oxford, Oxon, United Kingdom

Recently, respiratory-calibrated MRI methods capable of providing a quantitative assessment of cerebral physiology have been developed. In this study we combine hyperoxic and hypercapnic calibration of the BOLD signal with a simultaneous BOLD measurement of vessel size. The combination of these methods allows for the elimination of significant physiological assumptions from each of the combined techniques. Modelling results show that the new method produces accurate estimates over a wider range of physiological states than each of the combined methods, broadening the scope of such measurements. Results from pilot data in healthy volunteers agrees well with expected mean values.

Qiang Shen¹, Shiliang Huang¹, and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

We previously reported high spatial resolution basal CBF maps of rat brain at 75x56x1000μm. In this study, we further pushed the spatial resolution to 50x38x1000μm for basal CBF imaging. Moreover, we also investigated lamina-specific CBF fMRI responses in a rat forepaw stimulation model. Comparison was made with lamina-specific BOLD fMRI responses. High resolution CBF map showed remarkable columnar and layer specific perfusion information in the cortex. Layer IV and VI showed higher CBF, likely associated with higher basal metabolic needs. The CBF fMRI responses peaked broadly in layer IV-V, whereas the BOLD fMRI responses peaked in the superficial layers.

Laurentius Huber¹, Aneurin Kennerley², Dimo Ivanov³, Claudine Gauthier¹, Harald E. Möller¹, and Robert Turner^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Department of Psychology, The University of Sheffield, United Kingdom, ³Psychology and Neuroscience, Maastricht University, Netherlands

A CBV- and BOLD-sensitive multi-echo VASO sequence is used to estimate arterial and venous CBV changes. Separation between vascular compartments can be achieved by modeling their T2* and oxygenation-dependent signal contribution across TEs in MR images with and without selective blood nulling. Spatiotemporal features of arterial and venous CBV and their interaction with CBF and BOLD responses is considered with respect to position across the cortical ribbon, the post-stimulus undershoot and sustained neural inhibition. It is concluded that these features differ across time, stimulus type and vessel type.

Marta Vidorreta¹, Amaia Benitez¹, Maria Pastor¹, and Maria Fernandez-Seara^1
1Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain

Arterial spin labeled (ASL) perfusion fMRI offers the possibility of measuring cerebral blood flow (CBF) and assessing functional connectivity (FC) by means of evaluating the temporal correlations in the fluctuations of the CBF time series. The goal of this study was to evaluate and compare the reproducibility of FC maps derived from CBF and concurrent BOLD data. The results of this test-retest study show that FC derived from CBF data offers better reproducibility of the connectivity values, although slightly lower reproducibility of the spatial localization of the identified networks.

Valerie E.M. Griffeth¹ and Richard B. Buxton^1
1Keck Center for fMRI, University of California, San Diego, La Jolla, CA, United States

Since the discovery of the blood oxygenation level dependent (BOLD) signal, it has been noted that there is a post-stimulus undershoot. The source of this undershoot is often debated as it is unclear whether it is a neurologic, vascular or metabolic phenomenon. Here we provide evidence for a post-stimulus CBF undershoot by combining data from multiple experiments examining the response in the visual cortex to high contrast flickering checkerboard stimuli. These results suggest that previous publications may have missed CBF undershoots either due to lack of study power or imaging parameters not optimized for detecting the CBF signal.

Alan J Stone¹, Kevin Murphy¹, Nicholas P Blockley², Ashley D Harris^3,4, and Richard G Wise^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom, ²FMRIB, University of Oxford, Oxford, United Kingdom, ³Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ⁴F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States

Traditionally calibrated BOLD is used to measure the maximum BOLD signal change (M) allowing measurement of relative CMRO₂ changes with task. Here an extension of the dual calibrated FMRI methodology is presented which allows regional estimates of absolute CMRO₂ to be made. Asymmetric Spin Echo (ASE) is used to calculate maximum BOLD signal change (M) through the measurement of R₂'. This is then used in a hyperoxic calibrated BOLD experiment allowing the measurement of S_vO₂ and calculation of absolute CMRO₂ using Fick’s principle.

Jack A Wells¹, Isabel N Christie^¹, Nephtali Marina², Melina F Figueiredo³, Anya G Teschemacher³, Sergey Kasparov³, Alexander V Gourine*², and Mark F Lythgoe*^1
1Centre for Advanced Biomedical Imaging, University College London, London, London, United Kingdom, ²Neuroscience, Physiology and Pharmacology, UCL, London, United Kingdom, ³School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom

Understanding the mechanisms of neurovascular coupling is essential to the interpretation of fMRI BOLD signals. Astrocytes communicate via release of ATP, however its role neurovascular coupling has not been considered. To explore the contribution of ATP-mediated signalling in generation of BOLD responses, we developed a lentiviral vector that degrades ATP, effectively preventing its action. During bilateral forepaw stimulation, a smaller BOLD response was observed in the forepaw region transduced to express TMPAP relative to the control side. These novel data indicate that astroglial ATP-signalling is important for neurovascular coupling in the intact brain.

Hsiao-Ying Wey¹, Marjorie Villien¹, Joseph B Mandeville¹, Bruce R Rosen¹, and Jacob M Hooker^1
1A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States

BOLD fMRI only probes neural activity indirectly and the signal reflects a composite change of neurovascular and neurometabolic coupling. Complete measurements of changes in hemodynamic responses and oxidative and non-oxidative glucose metabolisms in response to stimuli or tasks will facilitate our interpretation of brain function. In this study, we circumvent the temporal limitation of FDG PET and reinvent its use to enable a truly dynamic detection of glucose metabolism. In addition, we validate our approaches using global physiological challenges. Together with simultaneously acquired BOLD/ASL data and hypercapnic calibration, a wealth of information can be obtained in one scan.