Thomas Liu¹, and Hongjian He^2
1UCSD Center for Functional MRI, La Jolla, CA, United States, ²Bio-X Laboratory, Zhejiang University, Hangzhou, China

In resting-state functional connectivity MRI (fcMRI), the presence of global signal confounds lead to variability in connectivity maps. A number of global signal correction methods have been proposed, but have their limitations. Here we demonstrate that a portion of the global signal can be viewed as an additive confound that increases with the mean BOLD amplitude. An approach for minimizing the contribution of this additive confound is presented, and an initial comparison with existing global signal correction methods is provided.

Hu Cheng¹, and Aina Puce^1
1Indiana University, Bloomington, IN, United States

A simple method is proposed to estimate the variance of resting state functional network originated from residual noises in the MRI signal. The variance from noise is compared with the total variance between networks from different time periods. The results suggest that a substantial amount of variance of the functional network comes from the intrinsic noise that is not coupled with the coherences of different brain regions. Sampling more time points can effectively reduce the noise-related variance. Another effect of residual noise is reduction of the correlation coefficient, which can be estimated from the variance of network.

Meghan Robinson¹, Javier Gonzalez-Castillo¹, Souheil Inati², Daniel Handwerker¹, and Peter Bandettini^1,2
1Section on Functional Imaging Methods, NIMH, NIH, Bethesda, MD, United States, ²functional MRI Facility, NIMH, NIH, Bethesda, MD, United States

The brain is continuously adapting to respond to the environment. In the course of a rest scan, subjects are expected to engage in different cognitive states for variable periods of time (i.e., relaxing, planning dinner, napping, etc.). Each of these states brings the brain into a different pattern of overall connectivity. Still, some level of stability is expected for the periods when subjects remain in a given cognitive state. Here, we propose a way to automatically identify such cognitive states looking at how the fMRI signal from different cortical regions pass in-and-out of synchrony with each other as time progresses.

Gopikrishna Deshpande^1,2, Hao Jia¹, Zhihao Li³, and Xiaoping Hu^3
1AU MRI research center, Dept. of ECE, Auburn University, Auburn, Alabama, United States, ²Dept. of Psychology, Auburn University, Auburn, Alabama, United States, ³Coulter Dept of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States

Functional connectivity in resting state networks show dynamic patterns in time and frequency.We hypothesized that effective connectivity between resting state fMRI time series may also dynamically evolve across time and frequency. We obtained effective connectivity between 33 regions in 4 RSNs as a function of time and frequency using dynamic multiscale vector autoregressive model based on Kalman filter. We observed that in the 0.1 to 0.01 Hz frequency range, RSNs toggle between 5 distinct states.

Hsu-Lei Lee¹, Benjamin Zahneisen¹, Thimo Hugger¹, Pierre LeVan¹, and Jürgen Hennig^1
1Medical Physics, University Medical Center Freiburg, Freiburg, Germany

MR-Encephalography allows the acquisition of whole brain volume image within 100 msec. With this high sampling rate, we looked at resting-state fMRI BOLD signal at 0.5~0.8 Hz. Independent component analysis revealed several resting-state networks that are similar to the ones observed under 0.1 Hz. These networks at higher frequencies are more stable as we shorten the signal length, therefore can provide the possibility to shorten total scan time and to assess resting-state network dynamics over a period of time.

Ali-Mohammad Golestani¹, and Mariana Lazar^1
1Radiology, New York University Medical Center, New York, NY, United States

Anatomical landmarks are commonly used to identify regions of interest (ROIs) for brain imaging studies that might not reflect functional specialization. Previous studies showed that some of the anatomically defined ROIs can be subdivided into sub-regions based on their connectivity. Most of the parcellation approaches use clustering algorithms in which the number of clusters should be known in advance. We used a new clustering method that estimates the number and size of sub-regions, and parcellate precentral gyrus into posterior and inferior parts. This study highlights the importance of using a parcellation method that can automatically detect the number of clusters.

Clare Kelly¹, Greg J. Siegle², and Michael P. Milham^3,4
1NYU Child Study Center, New York, NY, United States, ²University of Pittsburgh School of Medicine, Pittsburgh, PA, United States, ³Nathan S. Kline Institute for Psychiatric Research, NY, United States, ⁴Child Mind Institute, New York, NY, United States

Studies applying clustering methods to intrinsic (resting-state) functional connectivity (iFC) data have largely avoided white matter (WM), reflecting skepticism regarding the fidelity of WM BOLD signal. In light of mounting evidence supporting the neurophysiological veracity of WM BOLD, we parcellated WM on the basis of iFC, using a multi-site large-n dataset. We obtained a symmetrical topography consistent with DTI tractography atlases. For example, the corpus callosum, the internal capsule, and the superior longitudinal fasciculus were stably identified across sites. We suggest that iFC measures may have utility for the investigation of WM in clinical disorders characterized by WM alterations.

Mingrui Xia¹, Jinhui Wang¹, and Yong He^1
1State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China

With the development of complex network analyzes on human brain neuroimaging data; visualization of the structural and functional connectivity patterns became an important part of the graph theoretical approach. An easy using network visualization tool can help researchers show their results intuitively, and highlight their key point. Therefore we developed this brain network visualization tool termed as ‘BrainNet Viewer’, which can help researchers visualize structural and functional connectivity patterns from different levels in a quick, easy and flexible way. This package can be downloaded from NITRC (www.nitrc.org/projects/bnv/).

Gang Chen¹, B. Douglas Ward¹, Chunming Xie¹, Wenjun Li¹, Guangyu Chen¹, Joseph S Goveas², Piero G Antuono³, and Shi-Jiang Li^1
1Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, ²Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, United States, ³Neurology, Medical College of Wisconsin, Milwaukee, WI, United States

In resting-state functional MRI cross-group studies, the available techniques may bias the results in choosing the specified reference. We introduced an x-guided clustering method to solve this problem. The x-guided clustering method incorporates all of the subject groups by producing group difference information and then creating functional clusters. This method was applied to identify functional clusters that were significantly different between the amnestic mild cognitively impaired and cognitively normal subjects.

Yinan Liu¹, Karl Young^1,2, Yu Zhang^1,2, Michael Weiner^1,2, and Norbert Schuff^1,2
1Department of Veteran Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, United States, ²Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, CA, United States

We examined the value of transient information (TI), a recently introduced information-theoretic quantity that measures the uncertainty in synchronization, for characterizing functional connectivity in fMRI. Specifically, we used TI to capture the process of synchronization between two fMRI signals whose periodicity is initially unknown. We found that TI various markedly across the brain with e.g. posterior cingulate and precuneus synchronizing easier and faster with each other than with the putamen. These preliminary results suggest that TI may be a useful metric for quantifying functional connectivity.

Xiao Liu¹, Xiao-Hong Zhu¹, and Wei Chen^1
1Radiology, Center for Magnetic Resonance Research, Minneapolis, MN, United States

In this study, a recently proposed correlation-matrix-based hierarchical clustering (CMBHC) method was tested and evaluated using human resting-state fMRI datasets, and the results were compared with those obtained using the independent component analysis (ICA). It was found that the CMBHC was able not only to extract more coherent patterns than the ICA, but also to retain a number of weak but consistent functional connections (e.g., cortico-subcortical connections) that were largely missed by the ICA. The overall results suggest that the CMBHC could be a powerful tool for analyzing resting-state fMRI data, especially at the single subject level.

Shantanu Majumdar¹, and David C Zhu^1,2
1Department of Radiology, Michigan State University, East Lansing, Michigan, United States, ²Department of Psychology, Michigan State University, East Lansing, Michigan, United States

Resting-state fMRI has shown great potential towards understanding the spontaneous brain activity at rest in healthy subjects as well as patients with neurological disorders. A viable clinical tool requires a high level of reproducibility. In this work, we investigated quantitative effects of a wavelet-based analysis of resting-state fMRI signal to improve the reproducibility in detecting functionally active brain regions.

Stephen D Mayhew¹, Camillo Porcaro², Dirk Ostwald³, and Andrew P Bagshaw^1
1Birmingham University Imaging Centre, School of Psychology, University of Birmingham, Birmingham, West Mids, United Kingdom, ²Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom, ³Bernstein Centre for Computational Neuroscience, Berlin, Germany

We use simultaneous EEG-fMRI to investigate the relationship between ongoing or "baseline" brain activity, as indexed by pre-stimulus EEG alpha (8-13Hz) power, and the magnitude of the BOLD fMRI response to brief visual stimulation. We report a significant reduction of visual PBR and enhancement of auditory NBR in trials preceded by high alpha power, beyond that predicted by a linear model. This study provides new evidence that both PBR and NBR to visual stimulation are nonlinearly dependent upon electrophysiological characteristics of baseline brain activity and that NBR reflects inhibition of non-task related brain areas as indexed by occipital alpha power.

Georges Hankov¹, Thomas Christen¹, Heiko Schmiedeskamp¹, Roland Bammer¹, and Greg Zaharchuk^1
1Department of Radiology, Stanford University, Stanford, California, United States

The purpose of the study was to follow and analyze the dynamic changes in brain oxygenation induced by a carbogen respiratory challenge in normal human brain. Using a simple model and a multiple spin- and gradient-echo (SAGE) EPI sequence, maps of amplitude, wash-in and wash-out time constants, and arrival time delay of carbogen were computed. In 5 volunteers, we found a homogeneous response to carbogen and low inter-subject variability. This methodology could be used to study pathologies such as stroke or cancer.

Cecil Chern-Chyi Yen¹, Fuqiang Zhao², and Seong-Gi Kim^3,4
1National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States, ²Imaging, Merck, West Point, PA, United States, ³Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States

Cortical layer-specific responses are shown to resemble the neural response of the cortical layers. However, these layer-specific hemodynamic responses may be contaminated by the vascular reactivity, which is known to have layer-specific distribution. To investigate this issue, we performed two cerebral blood volume (CBV)- weighted fMRI studies in cat visual cortex with hypercapnic stimulus as an indicator for vascular reactivity, and visual stimulus. Our results showed that the peak responses of the CBV-weighted layer profile induced by hypercapnic stimulus co-localized with that induced by visual stimulus. Therefore, cautions shall be taken in interpreting layer-specific hemodynamic response as neural response.

Federico De Martino^1,2, Jan Zimmermann², Lars Muckli³, Kamil Ugurbil¹, Pierre-Francois van de Moortele¹, Rainer Goebel², and Essa Yacoub^1
1Radiology, Center for Magnetic Resonance Research, Minneapolis, Minnesota, United States, ²Cognitive Neuroscience, Maastricht University, Maastricht, Netherlands, ³Psychology, University of Glasgow, GLasgow, United Kingdom

Laminar specific fMRI in humans has potential for clinical applications. It has not yet been demonstrated whether gains in high field T2 weighted BOLD would be advantageous in layer specific fMRI investigations and/or in regions outside of V1. We examine layer specific response profiles in two different visual areas (V1 and MT) within the same subjects and compare Gradient Echo and GRASE. We show that GRASE might be preferred to GE when layer specific responses throughout the entire cortical depth are of interest.

Ian D Driver¹, Emma L Hall¹, Paula L Croal¹, Susan T Francis¹, and Penny A Gowland^1
1Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, United Kingdom

The BOLD post-stimulus undershoot (PSU) following a motor task is assessed at 7T through simultaneous measurement of BOLD, CBF, and venous CBV using hyperoxia. This work shows a post-stimulus undershoot in both the BOLD and CBF response, when the venous CBV response had returned to baseline. This suggests a neuronal origin for the PSU, but could also result from a delayed vascular compliance. Results show that at the spatial resolution (2 x 2 x 3 mm³), the PSU is not more localised to the underlying neuronal response, as reported in animal models.

Xiaopeng Zong¹, Tae Kim¹, and Seong-Gi Kim^1
1Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States

Studying the compartment-specific dynamic cerebral blood volume responses is important for quantitative fMRI studies and understanding the dynamic properties of BOLD fMRI responses. In this study, we measured BOLD, arterial (CBV_a), venous (CBV_v), and total cerebral blood volume responses to electrical forepaw stimulation in -chloralose anesthetized rats using a magnetization transfer-varied fMRI technique and injection of paramagnetic contrast agent. We found a fast CBV_a response and a delayed slower CBV_v response. Our findings are consistent with earlier studies under different anesthesia conditions and support the anesthesia independence of the fast CBV_a and slow CBV_v dynamic properties.

Catie Chang¹, Biyu J. He², and Jeff H. Duyn^1
1Advanced MRI section, NINDS, National Institutes of Health, Bethesda, MD, United States, ²NINDS, National Institutes of Health, Bethesda, MD, United States

It was recently demonstrated that the BOLD signal exhibits scale-free temporal dynamics whose autocorrelation/long-range memory is reflected in the Hurst exponent (H). Here, we demonstrate that H and BOLD signal amplitude decrease as a function of increased cognitive effort (working memory load) across widespread regions of the brain. Furthermore, we characterize the sensitivity of H to the manner in which fMRI data are pre-processed. Importantly, removing noise due to physiological processes and head motion was found to enhance the significance of load-dependent changes in the Hurst exponent, increasing the likelihood that the observed dynamic changes are of neural origin.

Jeroen C. W. Siero^1,2, Nick F. Ramsey¹, Hans Hoogduin^1,2, Dennis W. J. Klomp², Peter R. Luijten², and Natalia Petridou^1,2
1Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, ²Radiology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

Gradient-echo BOLD at high fields has opened up the possibility to visualize the cortical columnar and laminar functional organization but its specificity can suffer from contributions of several vessel sizes even at high fields. Here we assess the microvascular contributions of the GE BOLD response (HRF) across the cortical depth at 7T by relating it to the microvascular specific SE BOLD response. We show that the early phase (onset time and rising slope) of the GE HRF is specific to the microvasculature in deep gray matter which presumably contains layers III-V.

Jing Chen¹, Jing An², Yan Zhuo¹, and X. Joe Zhou^3
1State Key Laboratory of Brain and Cognitive Science, Inst. of Biophysics, Chinese Academy of Sciences, Beijing, China, ²MR Collaboration NE Asia, Siemens Healthcare, Siemens Shenzhen Magnetic Resonance, Shenzhen, China, ³Department of Radiology and Center for MR Research, University of Illinois Medical Center, Chicago, IL, United States

Recently, steady-state free precession (SSFP) fMRI has drawn widespread interests, due to its unique ability of providing distortion-free functional images with improved SNR/CNR, especially in regions near susceptibility boundaries. However, to develop SSFP fMRI as a robust tool for a broad range of applications, several practical issues must be carefully examined. In this study, we measure the hemodynamic response function of transition-band SSFP (tb-SSFP) fMRI, describe its temporal characteristics, and evaluate its linearity.

Santosh B. Katwal^1,2, John C. Gore^2,3, and Baxter P. Rogers^2,3
1Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, United States, ²Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ³Biomedical Engineering, Vanderbilt University

We assessed the ability to detect small temporal differences in BOLD responses from fMRI using Granger causality. Task-related-voxels were selected using: i) self-organizing map (SOM), ii) independent component analysis (ICA), iii) statistical parametric mapping (SPM) and iv) localizer scan in conjunction with SPM. Additionally, we fitted curves to average signals with inverse logit functions and estimated the differences in time-to-peak to compare the temporal differences. The combination of SOM and Granger causality detected differences as small as 28 ms. In general, data-driven approach for voxel selection seems to work better than hypothesis-driven approach in detecting small temporal differences from fMRI.

Simo Särkkä¹, Arno Solin¹, Aapo Nummenmaa^1,2, Aki Vehtari¹, Toni Auranen³, Simo Vanni^3,4, and Fa-Hsuan Lin^1,2
1Department of Biomedical Engineering and Computational Science, Aalto University, Espoo, Finland, ²Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, United States, ³Advanced Magnetic Imaging Centre, Aalto University, Espoo, Finland, ⁴Low Temperature Laboratory, Aalto University, Espoo, Finland

We use a Kalman filter and smoother method (DRIFTER) to identify physiological oscillatory signals from fMRI data, and analyze their spatial amplitude and phase structures. The frequencies of the cardiac and respiration signals were identified from external reference signals and the frequency of a physiological 0.1 Hz signal was identified from spatially averaged EPI data with 100 ms TR. The results indicate that the signals indeed have a clear spatial structure, which could be used to aid removal of the physiological signals or for analysis of brain functionality.

Han Yuan¹, Vadim Zotev¹, Raquel Phillips¹, and Jerzy Bodurka^1
1Laureate Institute for Brain Research, Tulsa, OK, United States

We investigated the relationship between the respiration, alpha-band-limited EEG power, and BOLD fMRI from simultaneous recordings in human subjects and have found significant correlation between slow temporal fluctuations of these three sources of signals. In particular, the correlation between respiration and EEG is much stronger in closed-eye resting than in open-eye resting, and is consistently observed from recordings inside and outside scanner. Results suggest that respiration fluctuations reflect and are linked to the underlying brain electrophysiological activity.

Kyle D Steinke¹, David Frakes², Jose Rios³, Gabe Oland², and Leslie C Baxter^1
1Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, ²School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States, ³Biomedical Engineering, Cornell University, Ithaca, NY, United States

Functional MRI is of limited utility in longitudinal studies because it lacks a quantitative baseline. We tested whether a test of interest (e.g., a motor task) could be compared to a generally stable vision task to overcome this weakness. We used approximate entropy (ApEn) to characterize each time series signal. The motor task ApEn was then compared to the vision task ApEn to form a ratio, which remained stable after a caffeine intervention, as expected, but changed in surgical patients that had behavioral decline.

Joseph Mandeville¹, Christin Sander², Bruce Jenkins³, Bruce Rosen³, Jacob Hooker³, Ciprian Catana³, Wim Vanduffel³, Nathaniel Alpert³, and Marc Normandin^4
1Radiology, Massachusetts General Hospital, Boston, MA, United States, ²Massachusetts Institute of Technology, United States, ³Radiology, Massachusetts General Hospital, United States, ⁴Massachusetts General Hospital, United States

fMRI data in an awake monkey during amphetamine challenge were acquired simultaneously with PET measurement of D2 receptor density. A compartment model of the fMRI response, based upon the competing effects of stimulation at D1 and D2 receptors, was developed to describe the temporal shape and magnitude of the fMRI response, while also accurately describing other reported fMRI responses in monkeys and rats at different levels of drug-induced dopamine. The model-inferred D2 contribution to fMRI signal correlated linearly with measured D2 receptor density. Simultaneous PET/MR measurements of dynamic dopaminergic function will be required to further refine the model.

Tynan Reid Stevens¹, David B Clarke², Ryan CN D'Arcy¹, and Steven D Beyea^1
1IBD-Atlantic, NRC, Halifax, Nova Scotia, Canada, ²QEII Health Science Centre, Halifax, Nova Scotia, Canada

Setting activation thresholds remains a significant challenge in fMRI. Fixed threshold levels do not account for individual variability, habituation, or acquisition strategies. We developed a method for determining data-driven thresholds levels based on test-retest ROC-reproducibility (ROC-r) analysis. Eight subjects performed test-retest fMRI at two field strengths (1.5 & 4 Tesla). Optimized ROC-r thresholds were calculated for the template (5.27 +/- 0.22) and retest images (3.71 +/- 0.18). The ROC-r thresholds were significantly higher for 4 Tesla than 1.5 Tesla. Compared to FDR or Bonferroni thresholds, ROC-r thresholds produced more consistent activation extent across field strengths and trials.

Vadim Zotev¹, Han Yuan¹, Raquel Phillips¹, and Jerzy Bodurka^1
1Laureate Institute for Brain Research, Tulsa, OK, United States

EEG performed simultaneously with fMRI with millisecond temporal resolution is particularly sensitive to rapid head rotations. Motion artifacts in EEG-fMRI recordings contain useful real-time information about such rotations. We describe a novel and simple approach for deriving additional fMRI motion regressors directly from EEG motion artifacts, and demonstrate its efficiency for patients with major depression. We show that inclusion of four EEG based motion regressors to the GLM model in addition to six fMRI motion parameters reduces average standard deviation of the GLM fit error by 5-10%, especially in frontal and occipital regions. Possible applications of this approach are discussed.

Pierre LeVan¹, Julian Maclaren¹, Michael Herbst¹, and Jürgen Hennig^1
1Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany

This study investigates the use of accurate motion-tracking to remove ballistocardiographic (BCG) artifacts in EEG recorded inside the MR scanner. These artifacts, due to heartbeat-related head motion in the magnetic field, are usually corrected by an averaged artifact subtraction (AAS) method, which consists of subtracting a template formed by averaging EEG signals from each cardiac cycle. However, AAS cannot model artifact variability across cardiac cycles, preventing a complete removal of BCG artifacts. Motion measurements during scanning were used to regress out residual BCG waveforms, resulting in significantly reduced root-mean-square residuals across cardiac cycles and improved EEG quality.

Jaemin Shin¹, and Xiaoping Hu^1
1Biomedical Engineering, Georgia Tech/Emory University, Atlanta, GA, United States

To overcome cardiac pulsation related artifact, cardiac-gated acquisition has been utilized with correction for T1 effect due to variation of the cardiac cycle but it is only valid for the flip angle of 90°. B1 inhomogeneity can often cause a significant variation in flip angle, e.g., 65° to 105° over the brain volume for a nominal flip angle of 90° at 3 T. In this work, we developed a generalized correction technique for T1 effect incorporating actual flip angle, estimated from fMRI dataset itself using Unscented Kalman filter. The new technique is demonstrated with simulated data and in vivo data.

Patrick W Stroman¹, Rachael L Bosma¹, Michaela Beynon¹, and Christine Dobek^1
1Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada

An improvement in physiological noise removal in spinal cord fMRI data is demonstrated. A combination of phase errors due to flow of cerebrospinal fluid (CSF), and image artefacts at high intensity boundaries between CSF and adjacent tissues, is revealed by means of computer simulations of the spinal fMRI acquisition. Spatially and temporally variant signals are demonstrated that do not match the timing of the CSF flow itself. However, the cause of this physiological noise enables it to be modeled as a convolution of a distortion operator, and the unaffected data, and we demonstrate a means of modeling and removing it.

Rob H.N. Tijssen^1,2, Mark Jenkinson¹, and Karla L. Miller^1
1FMRIB Centre, Oxford University, Oxford, United Kingdom, ²University Medical Center Utrecht, Utrecht, Netherlands

In this work we explore the use of retrospective corrections, in order to remove temporal instabilities from 3D FMRI acquisitions. Using the Bayesian Information Criterion (BIC) to determine an optimal subset, previously proposed for RETROICOR, we aim to optimize the regressor set for various 3D acquisition methods (e.g., SPGR and bSSFP). The results suggest that the optimal number of regressors is highly dependent on the acquisition and can even be zero (i.e., no retrospective correction) in some cases (e.g., when a real-time cardiac synchronized readout is used to correct for cardiac fluctuations prospectively).

Peiying Liu¹, Carolyn Sacco², Yan Fang², Carol Tamminga², and Hanzhang Lu^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas, United States

The power of fMRI in assessing neural activity and detecting group differences are often hampered by variations in fMRI responses across individuals. Normalization of fMRI signals with basal physiologic parameters may be useful in reducing variations and improving sensitivity, but this utility hasn’t been tested in patient populations. The present work extends previous findings in healthy controls, and showed a modulation effect of baseline venous oxygenation on fMRI signals in Schizophrenia patients. The results demonstrated that, by accounting for basal physiologic parameters, the sensitivity of fMRI in differentiating patient population from healthy controls can be enhanced with relatively little cost.

Michael Lührs¹, Charles Müller¹, and Johannes Bernarding^1
1Department of Biometry and Medical Informatics, Otto von Guericke University Magdeburg, Magdeburg, Saxony-Anhalt, Germany

Real-time fMRI communication interface between Turbo-BrainVoyager 3.0 and other software tools, providing transfer of multiple data (ROI's) and datatypes based on the TCP/IP protocol.

M.G. Bleichner¹, J. M. Jansma¹, M. Raemakers¹, J. Sellmeijer¹, E.J. Aarnoutse¹, J.C.W. Siero², N. Petridou², and N.F. Ramsey^1
1Dept. of Neurology and Neurosurgery, University Medical Center Utrecht, Rudolf Magnus Institute of Neuroscience, Utrecht, Netherlands, ²Dept. of Radiology, University Medical Center Utrecht, Rudolf Magnus Institute of Neuroscience, Utrecht, Netherlands

Decoding the neuronal activity of complex hand gestures, as used in sign languages, could be an interesting way to control a brain computer interface. Thinking about hand gestures representing letters could be translated directly into text on a computer screen. Here we study the underlying neuro-physiological changes of executed hand movements using high field fMRI. We show that single trial classification is possible and that different hand gestures can be distinguished based on the underlying neuronal activation pattern. We conclude that complex hand gestures are a promising control signal for brain computer interfaces.

Nagesh Adluru¹, Richard J. Davidson¹, and Andrew L. Alexander^1
1University of Wisconsin-Madison, Madison, WI, United States

Hypothesis testing is one of the most commonly performed statistical analyses in neuroimaging studies. Often the goal is to study the effects of variables such as physiological, behavioral and/or clinical on a variety of neuroimaging measurements e.g., cortical thickness, bold-activation, microstructural properties. A most common approach to test the significance of these effects is to project the measured neuroimaging data onto the linear models defined using the variables of interest via ordinary least squares. In this paper we propose that using a more robust projection can increase sensitivity to the effects and hence can also control for confounding parameters.

Stefan Posse^1,2, and Elena Ackley^1
1Neurology, University of New Mexico, Albuquerque, NM, United States, ²Electrical and Computer Engineering, Physics and Astronomy, University of New Mexico, Albuquerque, NM, United States

Real-time fMRI using multi-slab echo volumar imaging was performed with temporal resolution of 286 ms for whole brain acquisition and 136 ms for partial brain acquisition on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Whole brain EVI with 286 ms temporal resolution of visual and motor tasks significantly increased average and maximum percent BOLD signal change, average and maximum t-score, and extent of activation compared with EPI. Partial brain EVI with 136 ms temporal resolution exhibited comparable percent signal change, enabled nonaliased detection of heartbeat correlated signal fluctuation and improved sampling of the hemodynamic response function.

Benedikt Andreas Poser¹, and V Andrew Stenger^1
1UH-QMC Neuroscience and MR Research Program, University of Hawaii, Honolulu, Hawaii, United States

There is demand for shorter whole-brain fMRI acquisition times to allow clear separation of signals from resting state networks and unwanted phsysiological fluctuations (e.g. motion, respiratory and cardiac noise). “Multiplexed” 2D EPI has been proposed to improve temporal resolution. We investigate multiplexed spiral-in acquisition as a more efficent approach because TE is at the end of the sequence. Factor three multiplexing gave whole brain coverage with 36 slices in 420ms. RS fMRI at 3T showed clear sampling of physiologcial noise in the time courses.

Alan Chu¹, Jon-Fredrik Nielsen¹, and Douglas C. Noll^1
1Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States

Hadamard-encoded fMRI is a multi-slice acquisition method that potentially increases temporal resolution compared to conventional, single-slice fMRI. Because Hadamard-encoded fMRI is relatively more susceptible to signal variations from both physiological and non-physiological sources, it is critical to perform appropriate noise removal for the method to perform well. In this abstract, we outline the proper processing needed for Hadamard-encoded fMRI, and show that the results have increased temporal resolution without a decrease in activation quality.

Mehdi Ordikhani-Seyedlar¹, Benjamin Zahneisen¹, Thimo Hugger¹, Jürgen Hennig¹, and Pierre LeVan^1
1Radiology and Medical Physics, University-Medical Center Freiburg, Freiburg, Germany

Our aim was to use a new technique to acquire the whole brain functional imaging data at a high temporal resolution of 100ms while doing a visuospatial attention task. This study showed that high temporal resolution fMRI can successfully measure small fluctuations in trial-by-trial BOLD signal correlated with reaction time in order to identify the emergence of functional networks in the brain during the execution of a cognitive task.

Liyong Chen^1,2, Audrey Chang^1,2, Junqian Xu³, Steen Moeller³, Edward J Auerbach³, An Thanh Vu^1,2, Kamil Ugurbil³, Essa Yacoub³, and David Feinberg^1,2
1Helen Wills Neuroscience Institute, University of California, Berkeley, CA, United States, ²Advanced MRI Technologies, Sebastopol, CA, United States,³Center for Magnetic Resonance Research (CMRR), Department of Radiology, University of Minnesota, Minneapolis, MN, United States

Multiplexed-EPI is performed using different number of images readout simultaneous in the EPI echo trains. Compared in whole brain imaging, slice accelerations (M) of 6 to 48 images per echo train were evaluated. Results showed observable trade-offs in image quality at highest accelerations using single echo trains to scan the whole brain and good quality images using two or three echo trains.

Moreno Pasin¹, Marios C Yiannakas¹, Ahmed Toosy², and Claudia A M Wheeler-Kingshott^1
1NMR Research Unit, Department of Neuroinflammation, UCL Institute of Neurology, University College London, London, England, United Kingdom, ²NMR Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, University College London, London, United Kingdom

In this study we assess the performance of the ZOnally-magnified Oblique Multislice EPI (ZOOM-EPI) sequence using a reduced field of view for targeted areas of fMRI activation. We compared motor fMRI activations on 5 healthy subjects obtained using ZOOM-EPI with ones obtained using conventional GE-EPI and SE-EPI sequences in terms of their spatial localisation. Moreover we report the dimensions of the activated regions in each subject for the three different sequences. For all subjects the ZOOM-EPI showed good anatomical correspondence with the overlapping activated areas from the more conventional GE-EPI and SE-EPI sequences and more localised activation.

Martin Krämer¹, and Jürgen R Reichenbach^1
1Medical Physics Group, Department of Diagnostic and Interventional Radiology I, Jena University Hospital, Jena, Germany

Using the PROPELLER-EPI technique for functional magnetic resonance imaging has the advantage that, albeit the multi-shot nature of the method, acceptable temporal resolutions can be achieved. At the same time the readout train length is significantly reduced, enabling high in-plane resolutions. In our work we demonstrate that long-axis PROPELLER-EPI can be used for performing fMRI with submillimeter resolution at a clinical field strength of 3T. Results from a finger tapping experiment are presented with an in-plane resolution of 0.7 mm²

Dae-Hun Kang¹, Uk-Su Choi¹, Jun-Young Chung¹, Da-Eun Kim¹, Young-Bo Kim¹, and Zang-Hee Cho^1
1Neuroscience Research Institute, Gachon University of Medicine and Science, Incheon, Korea

Using consecutive interleaved multi-shot EPI scheme (ciEPI) with minimal intersegment delay and parallel imaging is one of methods to obtain less-distorted images. Recently, multiple stimulus-driven retinotopic maps were introduced using conventional EPI schemes in the previous study. In a present paper, a retinotopic response is observed by visual stimuli through ciEPI schemes with high-resolution at 7T.

Wietske van der Zwaag^1,2, Mayur Narsude¹, João Jorge³, José Pedro Marques^1,2, and Rolf Gruetter^1,2
1Université de Lausanne, Lausanne, VD, Switzerland, ²LIFMET, EPFL, Lausanne, VD, Switzerland, ³Instituto Superior Técnico, Lisbonne, Switzerland

Physiological noise can prohibit the detection of BOLD signal variations. The movement of the brainstem during the cardiac cycle amplifies this problem locally. In this study, the effect of (1) temporal resolution of a 3D-EPI acquisition and (2) physiological noise removal on BOLD detection in primary auditory cortex AI and the brainstem were investigated. Physiological noise removal was essential for BOLD signal detection in the brainstem at the axial slice orientation used. In addition, higher temporal resolution increased the number of active voxels significantly. Increases in BOLD sensitivity with shorter TR and physiological noise removal were also found in AI.

David Ress¹, Reswanul Khan², Bharath Chandresekaran³, and Seth Koslov^3
1Neurobiology, Psychology, Imaging Research Center, Center for Perceptual Systems, The University of Texas at Austin, Austin, TX, United States,²Neurobiology, Physics, Imaging Research Center, Center for Perceptual Systems, The University of Texas at Austin, Austin, TX, United States,³Communication Sciences and Disorders, The University of Texas at Austin, Austin, TX, United States

We present a high-resolution sparse-sampling fMRI approach for imaging small auditory brainstem structures. High resolution is obtained with a multi-shot spiral acquisition. Sparse sampling is obtained by two adjustments to the fMRI pulse sequence. First, quiet periods are created by disabling the acquisition gradients for long periods (9 s) to permit delivery of auditory stimuli. Second T1-equilibrium is maintained by continual delivery of slice-selective excitation pulses throughout each scanning run. Using this approach, we have obtained 1.2-mm sampling in human inferior colliculus (IC) with satisfactory contrast-to-noise ratio. The data confirm a laminar organization of stimulus frequency representation in human IC.

Reswanul Khan¹, Sucharit Katyal², Clint Greene², Evan Luther³, and David Ress^2
1Neurobiology, Physics, Imaging Research Center, Center for Perceptual Systems, The University of Texas at Austin, Austin, TX, United States,²Neurobiology, Psychology, Imaging Research Center, Center for Perceptual Systems, The University of Texas at Austin, Austin, TX, United States,³Neurobiology, Biomedical Engineering, Imaging Research Center, Center for Perceptual Systems, The University of Texas at Austin, Austin, TX, United States

At conventional resolutions, BOLD fMRI samples responses from various tissues in cerebral cortex: white matter, gray matter, and extra-pial. Here, we utilize high-resolution fMRI (0.9-mm voxels) to characterize the BOLD hemodynamic response function (HRF), as it varies with depth and tissue type in cortex. Surface-based analysis methods create a normalized depth coordinate that permits characterization throughout the variable thickness of gray matter. The HRF peak response occurs faster in deep gray matter, but is stronger and noisier in more superficial tissue. No significant initial dip is present in the gray matter, but is clearly evident in extra-pial tissues.

Denis Chaimow^1,2, Kamil Ugurbil¹, and Amir Shmuel^1,3
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ³Montreal Neurological Institute, McGill University, Montreal, QC, Canada

The ability of high-field fMRI to truly resolve columnar organization depends on the spatial scale of the pattern, the BOLD point spread, the voxel size and the noise level. To better understand the role of each factor, and to guide the selection of optimal parameters, we developed a mathematical model of imaging cortical columns. We quantified the expected differential functional contrast relative to noise and the expected similarity between the imaged pattern and the true columnar organization as a function of parameters of interest. We found that the voxel width that optimizes differential contrast is larger than the one that optimizes accuracy. Furthermore, we propose a method for confirming that an imaged pattern reflects the true columnar organization.

Xiao Liu¹, Silvina G. Horovitz^1,2, Allen R. Braun³, Walter S. Carr⁴, Dante Picchionie⁵, Masaki Fukunaga¹, and Jeff H. Duyn^1
1Advanced MRI section, LFMI, NINDS, National Institutes of Health, Bethesda, MD, United States, ²Human Motor Control Section, MNB, National Institutes of Health, ³Language Section, Voice, Speech and Language Branch, NIDCD, National Institutes of Health, ⁴Naval Medical Research Center, ⁵Department of Behavioral Biology, Walter Reed Army Institute of Research

In this study, the average temporal correlation of spontaneous BOLD fMRI activity within local brain regions was computed and compared between the wake and slow wave sleep (SWS) stages in human. Significant reductions in local BOLD correlation were primarily found in the prefrontal cortex during the SWS, while increases were limited to posterior brain regions. The finding is consistent with the notion that prefontal activity is an important constituent of higher cognitive function during conscious awareness, and the fact that the latter is reduced during SWS. This suggests that the distribution of local correlation may report on cognitive state.

Maolin Qiu¹, Ramachandran Ramani², and R. Todd Constable^1,3
1Diagnostic Radiology, Yale University, New Haven, CT, United States, ²Anesthesiology, Yale University, New Haven, CT, United States, ³Biomedical Engineering, and Neurosurgery, Yale University

Process-coherence theories have been proposed by anesthesiologists about anesthesia and unconsciousness and they were originally based on clinical observations of neuronal activity in sleep, epileptic, or vegetative patients. It has been difficult to test hypotheses involving disruptions in the coherence of neural activity until very recently with the development of techniques for reliably assessing intrinsic functional connectivity contrast (ICC). We used ICC power to quantify changes in communications between neural networks, upon administration of Propofol, and test the hypothesis of process-coherence theories. Our results demonstrate the enhancement of synchronous oscillations in the DMN in the presence of Propofol, and such increases in synchronous oscillations may be a prerequisite for producing sleepiness and unconsciousness.

Tommaso Gili¹, Neeraj Saxena², Ana Diukova¹, Kevin Murphy¹, Judith E Hall², and Richard G Wise^1
1Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff, United Kingdom, ²Section of Anaesthetics, Intensive Care and Pain Medicine, Cardiff University School of Medicine, Cardiff, United Kingdom

We have examined alterations in functional connectivity induced by propofol sedation in a group of healthy volunteers. Large cortical areas (occipital, temporal, frontal and parietal) were used as seed regions for the functional connectivity analysis. While there appeared to be little involvement of the default-mode network in sedation related changes, thalamo-cortical functional connectivity was modified. This is consistent with previous suggestions of altered thalamo-cortical communication in sedation and pharmacologically induced loss of consciousness.

Benito de Celis Alonso¹, Silke Kreitz², Silvia Hidalgo Tobón³, Carlos Herrera¹, Florian Spiegel², Sebastian Spiegel², Marina Sergeyeva², and Andreas Hess^2
1Faculty of Medicine, BUAP, Benemérita Universidad Autónoma de Puebla, Puebla, PUE, Mexico, ²Pharmacology and Toxicology, FAU Erlagen-Nuremberg, Erlangen, Bayern, Germany, ³UAM Universidad Autónoma de México, Mexico

Resting-state imaging analyzes the low frequency fluctuations of the BOLD signal (0.01-0.1 Hz) when brain is at rest. It is accepted that these fluctuations reflect neuronal activity (1,2) and also a certain degree of structural (3) and functional connectivity (4). It is known that resting states are reproducible in other order of mammalians (5) and that they are not affected by sleep (6) or even sedation (7). Results for rodents are obtained regularly under anesthesia and apparently the narcotic has no effect on resting-states (8,9) even if other authors establish that there should be anesthetic confounds (10, 11). No study tackles the effect on resting-states of total experimental time under anesthesia. In this study, we compared resting states in two scenarios, one before and after an fMRI experiment and other when no fMRI experiment was performed between resting state measurements. Our results show that there is a decay in both cases of correlation strength that depends on the total time animals have been under anesthesia, This decay does not seem to imply a change in the nature of the correlations.

Todd B Harshbarger¹, M. Stephen Melton², Allen W Song¹, and Stephen Klein^2
1Brain Imaging and Analysis Center, Duke University, Durham, NC, United States, ²Anesthesiology, Duke University Medical Center, Durham, NC, United States

Functional connectivity is increasingly used to compare normal brain states with various disorders. In this study, we investigated resting state functional connectivity before and after a peripheral nerve block. We show that cross-hemispheric correlations in motor areas which exist before the block is applied are disrupted by the nerve block. These correlations return immediately after the block wears off. This can have implications in the study of connectivity and correlations between hemispheres, as well as potential implications for studies of how the brain reacts to damage in the peripheral nervous system.

Chunxia Li¹, Zhihao Li², Xiaoping Hu², Jocelyne Bachevalier³, and Xiaodong Zhang^1,4
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States, ²Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States, ³Yerkes National Primate Research Center and Department of Psychology, Emory University, Atlanta, Georgia, United States, ⁴Division of Neuropharmacology and Neurologic Disease, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States

Macaques with neonatal hippocampal lesions showed hippocampal-dependent and prefrontal-dependent memory deficits similar to those reported in schizophrenic patients and are thus an ideal animal model to study the mechanism of the abnormal functional connectivity reported in schizophrenia. In this study, rhesus monkeys with neonatal hippocampal lesions were used to investigate the functional connectivity between the hippocampus (HP) and the dorsolateral prefrontal cortex (DLPFC) with the resting-state functional MRI technique. The results showed weaker functional connectivity between left HP and left DLPFC in animals with neonatal HP lesions, and the degree of abnormal connectivity was significantly correlated with volume of HP lesion.

Iris Y. Zhou^1,2, Y. X. Liang³, Joe S. Cheng^1,2, Russell W. Chan^1,2, Kevin C. Chan^1,4, K. F. So³, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China, ³Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China, ⁴Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA, United States

Resting-state fMRI has been increasingly used in the diagnosis of a variety of brain diseases. However, the underlying mechanism of the spontaneous fluctuations in rsfMRI signals is still under debate. In this study, the effects of complete and partial transection of corpus callosum (CC) on rsfMRI signal were investigated. The loss of interhemispheric functional connections after the complete transection of CC was observed. More importantly, partial CC transection disrupted only the specific intercortical functional connection that is known to be anatomically connected through CC. These findings further indicate that the spontaneous fluctuations in rsfMRI signal largely reflect the anatomical connections.

Ann S Choe^1,2, Visar Belegu^1,2, Cristina Sadowsky^2,3, Peter C van Zijl^4,5, James Pekar^4,5, and John McDonald^1,2
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²International Center for Spinal Cord Injury, Hugo Moser Research Institute at Kennedy Krieger Inc, Baltimore, MD, United States, ³Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁵F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Can MRI inform classification of spinal cord injury (SCI), and assess consequent brain changes? In this study, we used advanced MR methods to report on the structural and functional alterations in the central nervous system of a patient who recovered significant neurological function after SCI. Pattern of changes in diffusion tensor imaging and magnetization transfer imaing-derived parameters in the cord was consistent with the subject¡¯s motor and sensory function evaluations, and the changes in the BNC of the subject was consistent with the subject¡¯s clinical presentation, suggesting that rs-fMRI can be used to observe brain functional changes of SCI subjects.

Molly Claire Chapman¹, Laura Marie Jelsone-Swain², and Robert Cary Welsh^2
1School of Medicine, University of Michigan, Ann Arbor, MI, United States, ²Radiology, University of Michigan, Ann Arbor, MI, United States

We examine diffusion tensor metrics and resting state functional connectivity in an amyotrophic lateral sclerosis population.

Hu Cheng¹, Jerillyn Kent¹, Mallory Klaunig¹, Dae-Jin Kim¹, Brian O'donnell¹, William Hetrick¹, and Aina Puce^1
1Indiana University, Bloomington, IN, United States

Recently, abnormalities in the amplitude of low frequency resting state fMRI signal have been observed in schizophrenia patients. In this report, we examined the variance of the signal in resting state fMRI across the whole brain, and found significant differences between schizophrenia patients and non-patient controls. The controls showed higher temporal SNR mainly in the white matter, clustered in several regions including temporal, frontal, and parietal lobes, cerebellum, anterior cingulate, and major white matter tracts. White matter abnormalities in these regions have been previously reported in schizophrenia patients.

Collin Liu^1,2, Anitha Priya Krishnan³, Lirong Yan¹, Jeffrey R Alger¹, John Ringman⁴, and Danny JJ Wang^1,4
1Ahmanson-Lovelace Brain Mapping Center, UCLA, Los Angeles, CA, United States, ²Neurobehavior Unit, VA Greater LA Healthcare System, Los Angeles, CA, United States, ³Molecular Imaging Center, USC, Los Angeles, CA, ⁴Neurology, UCLA, Los Angeles, CA

Interpretation of biological signals is essential for diagnosing diseases. Pattern recognition and spectral analyses have commonly been used. More recently a non-linear time-series analysis called approximate entropy has been applied to EEG, ECG, and hormonal levels. Here we applied approximate entropy to resting state BOLD fMRI time-series, to characterize the complexity of the signal in normal aging and familial Alzheimer's disease. Similar calculation can be made between the time-series of a seed voxel and that of all other voxels to provide a measure of synchronicity. This is called cross-approximate entropy. These analyses might provide novel measures of functional connectivity, complementary to cross-correlation.

Jeehye Seo¹, Hui-jin Song¹, Seong-Uk Jin¹, Hee-Kyung Kim¹, Jang Woo Park¹, Moon Han¹, Jong Su Baeck¹, Ji-Young Kim², and Yongmin Chang^1,3
1Medical & Biological Engineering, Kyungpook National University, Daegu, Jung-gu, Korea, ²School of Medicine, Kyungpook National University, Daegu, Jung-gu, Korea, ³Molecular Medicine, Kyungpook National University, Daegu, Jung-gu, Korea

Fibromyalgia (FM) is a medical disorder characterized by chronic widespread pain, a heightened and painful response to pressure. Currently, no investigation is available for identifying the power spectral density of low frequency BOLD fluctuations during resting-state functional magnetic resonance imaging (rs-fMRI) while recent study evaluated functional connectivity of low frequency fluctuation in FM patients. Using seed-based analysis of low frequency BOLD fluctuations in pain related networks, our results demonstrated (1) the medial and lateral pain networks of slow fluctuation BOLD signal during rs-fMRI and (2) the differences in the power spectral density within pain-related networks between FM patients and healthy controls.

Albrecht Stroh¹, Florian Schmid², Lydia Wachsmuth², Valentin Riedl¹, Afra Wohlschlaeger³, Jenny Kressel³, Claus Zimmer³, and Cornelius Faber^2
1Technical University Munich, Munich, Germany, ²University Hospital Muenster, Germany, ³Technical University Munich, Germany

Furthering our understanding of the spatiotemporal dynamics of neurovascular coupling requires the simultaneous and unperturbed recording of neuronal spiking and BOLD fMRI. Here, we demonstrate the feasibility of optical recording of neuronal activity with sub-millisecond temporal precision within a 9.4 T small animal scanner and simultaneously recording BOLD fMRI. Using fluorescent indicators for intracellular Ca2+ concentrations, we achieve a direct optical readout of super-threshold neuronal spiking activity, enabling the temporal and spatial correlation of BOLD time course and neuronal firing patterns.

Philipp Lebhardt¹, Wolfgang Kelsch^2,3, Claudia Falfan-Melgoza¹, Gabriele Ende¹, Alexander Sartorius², and Wolfgang Weber-Fahr^1
1NeuroImaging, Central Institute of Mental Health, Mannheim, Germany, ²Clinic of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany, ³Cinical Neurobiology, University of Heidelberg, Hiedelberg, Germany

In this study we were interested in the influence of laser power and stimulation frequency on the optogenetically induced BOLD signal of the hippocampal network in mice. We induced expression of channelrhodopsin-2 in Ca2+/calmodulin-dependent protein kinase II-expressing neurons by virus injection. Laser stimulation was periodically applied through an optical fiber in the left hippocampus with block and event related designs using different power and stimulation characteristics. We found activation and deactivation due to laser heating effects even at low power levels and diverse activation patterns in dependency of stimulation length and frequency

Daniil Aksenov^1,2, Limin Li^1,2, Michael Miller^1,2, George Iordanescu^1,2, and Alice Wyrwicz^1,2
1NorthShore Univ. RI, Center for Basic MR Research, Evanston, IL, United States, ²Pritzker Sch. of Med., Univ. of Chicago, Chicago, IL, United States

Optogenetic control offers great potential for studying the relationship between BOLD and neuronal activity in specific cell populations under a variety of modulatory conditions. In this work, we combine simultaneous fMRI and electrophysiological recording in the whisker barrel cortex with localized pharmacological modulation and optogenetic stimulation to examine the BOLD response in awake rabbits before and after local injection of the GABA-A agonist muscimol. Our results indicate that BOLD area and magnitude are preserved during optical stimulation in the cortex even in the presence of increased inhibition produced by muscimol injection, but thalamic BOLD response decreased after injection.

Hesamoddin Jahanian^1,2, Scott Peltier^1,2, Douglas C Noll^1,2, and Luis Hernandez-Garcia^1,2
1Functional MRI Laboratory, University of Michigan, Ann Arbor, Michigan, United States, ²Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States

Functional magnetic resonance imaging using physiological parameters such as cerebral blood perfusion or cerebral blood volume (CBV), unlike BOLD fMRI, provides a quantifiable contrast and is also more closely related to neural activity. Current Perfusion-based fMRI techniques, however, suffer from poor sensitivity and low temporal resolution. It has recently been shown that the change in CBV during neural activation mainly originates from arterial rather than venous blood volume, but CBV-based fMRI methods (such as VASO and MOTIVE) are also limited by their low signal to noise ratio. We propose a novel method based on pseudocontinuous arterial spin labeling (pCASL) technique to achieve a contrast that depends on arterial cerebral blood volume (CBVa) and can be used for functional imaging experiments. The method proposed here offers sensitivity to brain activation that is on par with BOLD imaging and superior to perfusion ASL, while maintaining most of the advantages of perfusion ASL imaging.

Deqiang Qiu¹, David E Rex¹, Manojkumar Saranathan¹, Robert M Lober², Greg Zaharchuk¹, Michael E Moseley¹, and Kristen W Yeom^1
1Radiology, Stanford University, Stanford, CA, United States, ²Neurosurgery and Division of Child Neurology, Stanford University, Stanford, CA, United States

Functional MRI (fMRI) has commonly been performed using a T2*-based BOLD (Blood oxygenation level dependent) technique, which depends on complex interactions between multiple physiological processes and has inherent resolution limits due to sensitivity to large veins. In this paper, we present the first human demonstration of the use of blood pool agent gadofosveset trisodium (Ablavar) for functional T1-based blood volume MRI. Development of T1 contrast agent based fMRI will lead to high-resolution and distortion-free brain mapping techniques.

Richard Baumgartner¹, William Cho², Alexandre Coimbra², Cynthia Gargano³, Robert Iannone⁴, Arie Struyk⁴, Rebecca Fox⁴, Zaiqi Wang⁴, Fuqiang Zhao⁵, Donald Williams⁵, Torsten Reese⁶, Brian Henry⁷, Esben Petersen⁸, Chris Chen⁹, Dai Feng³, Sofia Apreleva³, and Jeffrey Evelhoch^5
1Biostatistics and Research Decision Sciences (BARDS), Merck Research Laboratories (MRL), Rahway, New Jersey, United States, ²Genentech, ³BARDS, MRL, ⁴Experimental Medicine, MRL, ⁵Imaging, MRL, ⁶Center for Cooperative Research in Biomaterials, Spain, ⁷Translational Medicine Research Center, MRL,⁸Clinical Imaging Center, Singapore, ⁹Singapore National University

 

Yujie Qiu¹, Edmund Kwok², and Joseph P Hornak^1
1Imaging Science, Rochester Institute of Technology, Rochester, NY, United States, ²Imaging Science, University of Rochester Medical Center, Rochester, NY, United States

A new concept for an fMRI phantom is presented where the T₂ of a non-viscous, high dielectric constant liquid is changed by the application of an electric field. The electric field aligns the dipoles in the liquid, thus changing the molecular motions and T₂. The T₂ value of propylene carbonate was changed from 45 to 36 ms by the application of a 116 V/cm electric field. This T₂ change will produce a 15% change in the signal, comparable to the 5-20% seen for the BOLD response. This concept may allow changing the T₂ at rates comparable to the BOLD response.

Mukund Balasubramanian¹, Padma Sundaram¹, William W. Wells², Tobias Loddenkemper³, Robert V. Mulkern¹, and Darren B. Orbach^1
1Department of Radiology, Children's Hospital Boston, Boston, Massachusetts, United States, ²Department of Radiology, Brigham and Women's Hospital,³Department of Neurology, Children's Hospital Boston, Boston, Massachusetts, United States

In order to determine the limits of detecting short-duration currents with the phase of gradient-echo EPI, we imaged a phantom carrying ionic currents of various amplitudes and duty cycles, including those approximating epileptiform activity. Our results demonstrate the feasibility of detecting DC pulses with durations of 200 milliseconds or longer, for current amplitudes that are plausible for interictal discharges. Although our particular focus is on epilepsy, the ability to reliably image neuronal currents in general would provide a novel and important contrast mechanism for fMRI, with widespread applicability.

Michael Germuska¹, Thies Jochimsen², Michael Kelly¹, Tom Okell¹, and Daniel Bulte^1
1Nuffield Dept. of Clinical Neurosciences, University of Oxford, Oxford, Oxon, United Kingdom, ²PET-MR Group, Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany

Of particular interest when assessing neuro-angiogenesis are changes in blood flow, blood volume and vessel size. Here we present an MR imaging protocol that maybe used to make simultaneous measurements of these parameters in humans. The protocol uses a modified pseudo-continuous ASL sequence, with a dual gradient-spin echo EPI readout. Periods of mild hyperoxia are used to modulate the BOLD signal during acquisition. Mean vessel size maps and blood volume are calculated from the change in spin echo and gradient echo images. While the gradient echo signal is used to calculate resting blood flow.

Tomokazu Tsurugizawa¹, Luisa Ciobanu¹, and Denis Le Bihan^1
1Neurospin, Gif sur Yvette, France

Diffusion-weighted functional MRI (DfMRI) has been shown to be sensitive to neural activation in the human brain. In this study, I compared the DfMRI (b=10, 250, and 1800) and BOLD signal changes in rat somatosensory cortex under hyperoxia without neuronal stimulation and forepaw electrical stimulation. The amplitude of the high b-value DfMRI (b=1800) signal was lower than those of BOLD signal during hyperoxia. During the forepaw stimulation, early return-to-baseline of the high b-value DfMRI response was observed compared to BOLD response. These results show that the BOLD and DfMRI signal point out different mechanisms.

Blanca Lizarbe¹, Maria Lusia Garcia-Martin^2,3, Pilar Lopez-Larrubia¹, and Sebastian Cerdan^1
1Instituto Investigaciones Biomedicas "Alberto Sols", Madrid, Spain, ²Magnetic Ressonance Unit, Clinica Nuestra Senora del Rosario, Madrid, Spain, ³Head Nano-Imaging Facility, Parque Tecnológico de Andalucía, Malaga, Spain

We report on the use of functional DWI as a robust marker of hypothalamic activation by fasting in human subjects. Six adult male where imaged (DWI, three directions) in two different situations, fed (after one week of a balanced diet), and after 24 hours of fasting. Two areas of the brain, the hypothalamus and the cortex, were investigated using a biexponential model of diffusion. Fasting is shown to elicit significant, and directionally-dependent, changes of the biexponential diffusion parameters in the hypothalamus, suggesting an activation-induced cell swelling. These results open the possibility to examine feeding disorders and their therapies by DWI.

Nyoman D. Kurniawan¹, John Power², Natalie Alexopoulos¹, Donald J Maillet³, Michael Vogel¹, Ian M. Brereton¹, and David C. Reutens^1
1Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia, ²Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia, ³Centre for Advanced Imaging, University of Queensland, Brisbane, Australia

Diffusion-weighted FMRI (DFMRI) was suggested to provide a more direct measurement of neuronal activation (Le Bihan et al., 2006). DFMRI methods are thought to reflect cell swelling and a reduction in extracellular space accompanying the influx of water and ions in active neurons. However, there is some evidence that in vivo DFMRI signals may be contaminated by haemodynamic/BOLD effects and thus put doubts about the significance and origin of the DFMRI signal. In this study, we aimed to verify the origin of DFMRI signal in vitro using perfused brain slices free from haemodynamic effects. We found that DFMRI could detect activation signal in the absence of hemodynamic effects. In hippocampal slices, K+ stimulation induced changes in DFMRI signal with a similar spatial distribution and time course to that observed with fluorescence microscopy.

Shilpi Modi¹, Manas K Mandal², Prabhjot Kaur¹, Rajendra P Tripathi¹, and Subash Khushu^1
1Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi, Delhi, India, ²Defence Institute of Psychological Research, Delhi, Delhi, India

Anxiety impairs the inhibition function and hence, increased distractibility is found in anxious individuals compared with nonanxious ones. fMRI was carried out to map neural correlates for an attention task that required distracter inhibition. Individual differences in state and trait anxiety levels were regressed with individual BOLD activation patterns. Multiple regression analysis results indicate that the activation in thalamus predicted lower state anxiety and higher trait anxiety levels of subjects Results further suggest that different types of anxiety—state or trait—may influence attention differently.

Sally Eldeghaidy^1,2, Luca Marciani^1,3, Tracey Hollowood⁴, Kay Head¹, Johanneke Busch⁵, Andrew J. Taylor⁴, Tim Foster⁶, Robin C. Spiller³, Joanne Hort⁴, Penny A. Gowland¹, and Susan Francis^1
1Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²Department of Physics, Suez Canal University, Ismailia, Egypt, ³Nottingham Digestive Diseases Centre NIHR Biomedical Research Unit, Nottingham University Hospitals, Nottinghamshire, United Kingdom, ⁴Sensory Science Centre, Division of Food Sciences, University of Nottingham, Loughborough, Leicestershire, United Kingdom, ⁵Unilever R&D, Vlaardingen, Netherlands, ⁶Division of Food Sciences, University of Nottingham, Loughborough, Leicestershire, United Kingdom

The increase understanding of the impact of fat on the flavour perception could assist the design of food products that are lower in fat but still rewarding to eat. Here, we mapped the cortical representation to no flavoured fat, flavoured no fat, iso-release and perceived flavoured fat emulsions. We show that the presence of fat in the oral cavity reduces the cortical response to flavour, particularly in the primary taste areas and anterior cingulate, even when samples are iso-perceived (or volatile release) for sweetness, flavour and thickness.

Kyle K. Xing^1,2, Condon Lau^1,2, Patrick P. Gao^1,2, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, the University of Hong Kong, Hong Kong, China, ²Department of Electrical and Electronic Engineering, the University of Hong Kong, Hong Kong, China

Extensive research has been conducted to understand how the central nervous system receives information from individual sensory channels and converts it into perceptions of sight, sound, touch, smell, and taste. Neurons in the superior colliculus (SC) respond to auditory and visual inputs, but noninvasive fMRI studies have only observed visual responses. In this study, we apply BOLD fMRI on rats to measure the hemodynamic responses in the SC and inferior colliculus following auditory and visual stimulation. Responses are observed in the SC during both stimuli, providing the first fMRI evidence of auditory-visual convergence in the SC.

Youngseob Seo^1,2, Zhiyue J Wang^1,2, Srinivas Rachakonda³, Jonathan M Chia⁴, and Nancy K Rollins^1,2
1Radiology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States, ²Radiology, Children's Medical Center Dallas, Dallas, Texas, United States, ³University of New Mexico, ⁴Philips Healthcare

Dyslexia is referred to as specific reading disability/retardation in spite of conventional instruction and adequate intelligence. Learning to read is one of the most important skills for children to acquire in early education. We compared brain activities between dyslexic children and normal controls for reading and action-related tasks using fMRI and group ICA. We demonstrated there are differences in brain function activities in visual, executive, auditory, motor, sensory cortexes and Broca’s area between the 2 groups.

Ying Hao¹, Zhiyue Xia², Haibin Zhu³, Xiaoying Wang^1,3, Jing Fang^1,4, Jue Zhang^1,4, and Dapeng Bao^2
1Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, Beijing, China, ²Beijing Sport University, ³Peking University First Hospital,⁴Department of Engineering, Peking University

Most studies have utilized noninvasive BOLD-fMRI to depict the central neural adaption to physical fatigue or exhaustion; however, the large-scale effects of exercise on the cardio-pulmonary systems may influence the blood oxygen level dependent (BOLD) signal independent of neuronal activation. Thus, arterial spin labeling (ASL), which is capable of acquiring regional CBF values noninvasively, was proposed here to depict the brain response to exercise fatigue and exhaustion. Eight athletes were conducted the PASL scan pre- and post- the ergometer tasks on fatigue and exhaustion levels. Significant CBF reduction was observed after both kinds of exercises.

Ray Lee^1
1Neuroscience Institute, Princeton University, Princeton, NJ, United States

Taking advantage of emerging dyadic fMRI (dfMRI), a study on two human-brain interactions inside one MRI scanner was conducted. Besides confirmed most of the previous results regarding BOLD effect in social cognition, the probabilistic independent component analysis (PICA) results of our dfMRI data reveal that the basal ganglia coupling between two brains could be an essential stage in social cognition. This is the first time that fMRI shows that a special region of brain during social interaction becomes correlated, while most other BOLD effects due to social interaction are only coherent within each individual brain.

Jevin W. Zhang^1,2, Condon Lau^1,2, Joe S. Cheng^1,2, Kyle K. Xing^1,2, Iris Y. Zhou^1,2, Matthew M. Cheung^1,2, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China

Intensity is an important physical property of the sound wave and is usually reported as sound pressure level (SPL). This study examines the fMRI hemodynamic responses in the rat inferior colliculus (IC), lateral lemniscus (LL), medial geniculate body (MGB) and auditory cortex (AC) over a broad 72dB SPL range using sparse temporal sampling. The BOLD signal change increases significantly with SPL in IC and LL, but not in MGB and AC, which agrees with electrophysiology findings. This is the first fMRI observation of differences in SPL dependences between auditory structures and furthers our understanding of SPL processing.

Hao Jia¹, Oleg Mykolajovych Pustovyy², Paul Waggoner³, Ronald J Beyers¹, John Schumacher⁴, Jay Barrett⁵, Edward Morrison², Robert L Gillette⁴, Thomas S Denney^1,6, Vitaly J Vodyanoy⁵, and Gopikrishna Deshpande^1,6
1AU MRI research center, Dept. of ECE, Auburn University, Auburn, Alabama, United States, ²Dept. of Anatomy, Physiology & Pharmacology, Auburn University, Auburn, Alabama, United States, ³Canine Detection Research Institute, Auburn University, Auburn, Alabama, United States, ⁴Dept. of Clinical Sciences, Auburn University, Auburn, Alabama, United States, ⁵College of Veterinary Medicine, Auburn University, Auburn, Alabama, United States, ⁶Dept. of Psychology, Auburn University, Auburn, Alabama, United States

Canines are used extensively for detecting odors in both civilian and national security contexts, but their olfactory system remains largely unexplored in vivo. We developed and demonstrated the feasibility of an experimental setup for controlled delivery of odorant stimulus to both conscious and lightly anesthetized dogs. We found that in awake dogs, regions modulated by odor concentration were mainly in the frontal cortex, while that in anesthetized dogs were primarily in lower structures such as brain stem. The differential response to concentrations in awake and anesthetized dogs provide in vivo demonstration of previous ex vivo cellular recordings.

Zuyao Y Shan¹, Katie L McMahon¹, Greig I de Zubicaray², Paul M Thompson³, Nicholas G Martin⁴, Margaret J Wright⁴, and David C Reutens^1
1Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD 4072, Australia, ²School of Psychology, The University of Queensland, Brisbane, QLD 4072, ³Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, CA, United States, ⁴Genetic Epidemiology Laboratory, Queensland Insitute of Medical Research, Brisbane, QLD 4029, Australia

Neurovascular coupling is crucial for normal brain function but the contribution of genetic factors to coupling mechanisms is poorly understood. We investigated the heritability of the hemodynamic response function (HRF) of BOLD fMRI in the brain using the twin methodology, in which the degree of concordance between monozygotic (MZ, identical) and dizygotic (DZ, fraternal) twin pairs is compared. We found smaller differences in HRF time to peak in MZ than DZ twin pairs. It suggests that this trait is heritable, perhaps reflecting the genetic influence on neurovascular coupling factors that control the timing of blood entry into the activated area.

Yash Shailesh Shah¹, Luis Hernandez-Garcia¹, Douglas C Noll¹, Kinh Luan Phan¹, Mark K Greenwald², Jon Kar Zubieta¹, and Scott J Peltier^1
1University of Michigan, Ann arbor, Michigan, United States, ²Wayne State University, Detroit, Michigan, United States

Support vector machine learning from fMRI images for application in real-time neurofeedback to regulate craving in nicotine-dependent subjects.

Guang Li^1,2, Yen-Yu I. Shih², Bryan H. De La Garza², Jeffrey W. Kiel^3,4, and Timothy Q. Duong^1,2
1Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ³Ophthalmology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ⁴Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

There are clinical interests in dynamic cerebral autoregulation (DCA) assessment in diseases such as stroke and diabetic. We developed a rat model to assess DCA through transient BF changes during acute hypertension using MRI. We detected normal and impaired CA, and also revealed BF and oxygenation increases associated with acute BP elevation. Our study suggested that CA was established at a higher BF level during acute hypertension under normocapnia but it was impaired under hypercapnia. This method can be used for quick region-specific CA evaluation in normal and diseased physiology and can be extended to other organs such as eye.

Rebecca Susan Dewey^1,2, Olga Pollatos³, Akram A. Hosseini¹, Susan T. Francis², and Dorothee P. Auer^1
1Radiological and Imaging Sciences, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ³Department of Psychology, Potsdam University, Potsdam, Germany

Reduction of peripheral nervous system feedback is hypothesised to be associated with reduced neural response to emotional stimuli. Emotional stimuli typically elicit responses in the limbic system, including the amygdala, brainstem and salience network (anterior insula and anterior cingulate). The peripherally acting beta-blocker, nadolol, reduces peripheral autonomous nervous responses. Simultaneous acquisition of perfusion weighted ASL and BOLD fMRI give novel insight into regional drug induced changes in BOLD and perfusion. This study reports a pharmacologically induced increase in amygdala response to unpleasant emotional visual stimuli as measured using BOLD fMRI. Speculative explanations for paradoxical amygdala behaviour are given.

Julien Bouvier^1,2, Affif Zaccaria^1,3, Irène Troprès⁴, Laurent Selek^3,5, Pierre Bouzat^3,5, David Chechin², François Berger^3,5, Alexandre Krainik^3,5, and Emmanuel Barbier^1,3
1INSERM, U836, Grenoble, Isère, France, ²Philips Healthcare, Suresnes, Ile de France, France, ³Université Joseph Fourier, Grenoble Institute of Neurosciences, Grenoble, France, ⁴3T Facility, SFR Biomedical NMR and Neurosciences, Grenoble, France, ⁵CHU, Grenoble, France

Tissue oxygenation can be characterized by local oxygen saturation (lSO2), which may be mapped by quantitative Blood Oxygen Level Dependent (BOLD) approaches. An approach that combines separate estimates of T2, T2*, BVf, and B0 inhomogeneities has recently been proposed and validated in rats and a preliminary study has been realized in humans. The aim of this study is to evaluate this approach in non human primates under two depth of anesthesia.

Zeenat Atcha¹, Hui Chien Tay¹, Fatima Ali Nasrallah¹, Huang Wei Wei¹, Brian Henry², and Kai-Hsiang Chuang^1
1Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, A*STAR, Singapore, Singapore, Singapore, ²Medicine Research Centre, MSD, Singapore, Singapore

The aim of our study was to investigate the sensitivity and distinct spatiotemporal responses of bicuculine-induced brain activity using three pharmacological magnetic resonance imaging (phMRI) methods: blood-oxygen-level-dependent (BOLD) contrast, cerebral blood volume (CBV) with intravascular contrast agent, and cerebral blood flow (CBF) with arterial spin labeling (ASL). Acute administration of bicuculline produced region-specific hemodynamic responses in the S1, hippocampal, caudate putamen and thalamus regions. Furthermore, we demonstrate that temporal dynamics of CBV and BOLD signals were long lasting, whereas CBF responses were immediate. Information obtained from these complementary imaging techniques provide better insights to underpin neurovascular coupling upon a drug challenge.

Esben Thade Petersen¹, Jill De Vis¹, Thomas Alderliesten², Petra M. Lemmers², Karina J Kersbergen², Manon Benders², C. A. T. van den Berg³, and Jeroen Hendrikse^1
1Department of Radiology, UMC, Utrecht, Netherlands, ²Neonatology, Wilhemina Children's Hospital, Utrecht, Netherlands, ³Department of Radiotherapy, UMC, Utrecht, Netherlands

Bloods oxygen saturation is an important parameter for the evaluation of patients such as stroke or asphyxiated newborns. Here we present a method for measurement of blood T2 in the tissue using a “T2-Prepared Blood IVIM Imaging of Oxygen Saturation” (T2-BIOS) sequence from where bloods oxygen saturation can be estimated. IVIM effects in diffusion-weighted imaging are exploited to separate the blood signal and by using previous determined relationships of T2 versus Y, one can generate an oxygen saturation map. In the neonates this information is obtained from NIRS and similarity is shown, although not significantly correlated in this small population.

Kevin Murphy¹, Ashley D Harris¹, and Richard G Wise^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom

The Grubb exponent, α, describes the non-linear relationship between CBV and CBF changes and is usually assumed to be 0.38. Increases in CBV are reflected in the static magnetisation (M0) changes of the BOLD signal. This study proposes a model to use simultaneously acquired static magnetisation and CBF measurements to determine α. A previous model by Woolrich et al., neglected M0 effects caused by extravascular spins after CBV increases. This new model accounts for both blood and non-blood effects on M0 and removes the need to assume a baseline CBV value when estimating the Grubb exponent.

Richard G Wise¹, Ashley D Harris¹, and Kevin Murphy^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom

We present a method for measuring absolute cerebral metabolic oxygen consumption (CMRO₂). ASL and BOLD FMRI were combined with hypercapnic and hyperoxic respiratory challenges. Under an assumption of iso-metabolism, the BOLD signal calibration parameter (M) established in hypercapnia was used with the hyperoxic BOLD signal changes to estimate the resting venous deoxyhaemoglobin concentration and therefore oxygen extraction fraction and CMRO₂, on a regional basis. This was performed at rest and with continuous visual stimulation. The proposed method may offer a useful marker of cerebral metabolism in health and disease given its non-invasiveness compared to radiotracer methods.

Swati Rane¹, Manus Donahue^1,2, and John C Gore^1,3
1Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Psychiatry, Vanderbilt University, Nashville, TN, United States, ³Biomedical Engineering, Vanderbilt University, Nashville, TN, United States

Multi-echo fMRI experiments were performed at 7T with and without REST slabs. Signal changes upon functional activation were measured at TE = 0 ms as a measure of functional CBV change. Simulations were also conducted to study multi-echo fMRI signal characteristics and its dependence on functional CBV changes

Valerie E.M. Griffeth¹, Nicholas P Blockley², and Richard B Buxton^2
1Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States, ²Department of Radiology, University of California, San Diego, La Jolla, CA, United States

We used a detailed model of the BOLD effect to reexamine the original assumptions of the Davis model for calibrated BOLD, particularly the relationship between the BOLD signal and the change in total deoxyhemoglobin content. A simple heuristic model, as an alternative to the Davis model, incorporates transparent dependency on the underlying physiology, and works remarkably well for CBF/CMRO₂ coupling ratios from 1.3-5. Additionally, it directly defines the null line of the BOLD response while also providing a means by which to directly compare CBF/CMRO₂ coupling ratios between two stimuli without calibrating to measure the scaling parameter, M.

David Thomas Pilkinton¹, and Ravinder Reddy^1
1Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

This work aims to develop a biophysical model that relates blood flow and oxygen consumption to the observed T1 decrease in tissues during hyperoxia. Showing opposite trends compared to hyperoxic effects on R2 (BOLD), hyperoxic R1 enhancement increases as CBF increases and metabolism decreases. Using hypercapnia to induce an isometabolic increase in CBF, our model captures effects on R1 due to this physiological parameter during hyperoxia. Since a comprehensive validation of this model requires measuring hyperoxia as a function of metabolism, future work will focus on altered metabolic states.

David T Pilkinton¹, Victor K Babu¹, Wesley Baker¹, Joel H Greenberg², and Ravinder Reddy^1
1Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States

The aim of this study is to quantify relative metabolic changes using hyperoxic calibrated BOLD/ASL fMRI in a hypermetabolic swine model. Metabolic changes using this large animal model were previously studied by our group using gas that is isotopically-enriched with 17O2. We sought to cross-validate these measurements with hyperoxic dHb dilution methods of relative metabolism and to compare the results of hyperoxia and hypercapnia calibration methods using this animal model.

Xiang He¹, Chan-Hong Moon¹, Serter Gumus¹, Ayaz Aghayev¹, JinHong Wang¹, Dmitriy A Yablonskiy², and Kyongtae Ty Bae^1
1Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ²Mallinckrodt Institute of Radiology, Washington University in St Louis, St Louis, Missouri, United States

The objective of this study is a non-invasive quantification of arteriole oxygenation in human brain in the baseline state and during functional activation. We applied a recently proposed MR-based ASL-qBOLD technique to investigate T2* decay profile of ASL water signal originated from large feeding arteries and small arteries/arterioles. Our data demonstrate a gradual decrease of arteriole blood oxygenation approaching capillaries. We found that in arterioles the mean blood oxygen saturation was 86.9±3.4%. During visual stimulation, no significant change of arteriole blood oxygenation was detected, which is consistent with the results reported in previous studies using invasive methods in rodent models.

Pelin Aksit Ciris¹, Maolin Qiu¹, and Robert Todd Constable^1
1Yale University, New Haven, CT, United States

CBV changes occur across diverse pathologies and during functional challenges, however, measurements have been invasive and difficult especially in humans. In this study, whole brain absolute CBV (mL blood/100mL parenchyma) was measured non-invasively in 13 human volunteers during visual stimulation; by further developing a method based on a biophysical model with rotating multi-slice acquisitions maintaining steady state. Such non-invasive quantification could foster improved understanding of the relationship between neuronal activity, hemodynamic changes and metabolism underlying fMRI signal, provide a reference for calibrated fMRI, and potentially find clinical utility in evaluating vascular state, vascular damage, and/or monitoring treatments.

Feng Xu¹, Peiying Liu¹, Juan Pascual², Xuchen Zhang², and Hanzhang Lu^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United States

The glucose is the primary source of energy for the brain and its effect on brain metabolism is not well understood. With a recently developed technique quantifying cerebral metabolic rate of oxygen (CMRO2), we studied the acute and chronic effect of glucose on healthy controls and GLUT-1 deficiency (GLUT-1 DS) patients who suffer the chronic hypoglycemia in the brain. In healthy subjects, the acute increase of glucose reduced CMRO2. The baseline CMRO2 of Glut-1DS patients is lower than healthy controls, and was elevated after the glucose ingestion.