An Introduction to Normalization and Calibration Methods in Functional MRI

In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.

[1]  Gregory G. Brown,et al.  BOLD and Perfusion Response to Finger-Thumb Apposition after Acetazolamide Administration: Differential Relationship to Global Perfusion , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  F. Hyder,et al.  Total neuroenergetics support localized brain activity: Implications for the interpretation of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Bandettini,et al.  Spatial Heterogeneity of the Nonlinear Dynamics in the FMRI BOLD Response , 2001, NeuroImage.

[4]  Bharat B. Biswal,et al.  Detection and scaling of task-induced fMRI-BOLD response using resting state fluctuations , 2008, NeuroImage.

[5]  Hengyi Rao,et al.  Arterial spin-labeled perfusion MRI in basic and clinical neuroscience , 2009, Current opinion in neurology.

[6]  Thomas T. Liu,et al.  Inter-subject variability in hypercapnic normalization of the BOLD fMRI response , 2009, NeuroImage.

[7]  G. Crelier,et al.  Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: The deoxyhemoglobin dilution model , 1999, Magnetic resonance in medicine.

[8]  Ravi S. Menon,et al.  Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. , 1993, Biophysical journal.

[9]  Todd B. Parrish,et al.  Caffeine's effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism , 2009, NeuroImage.

[10]  Gregory G. Brown,et al.  Measurement of cerebral perfusion with arterial spin labeling: Part 1. Methods , 2007, Journal of the International Neuropsychological Society.

[11]  M. D’Esposito,et al.  Reducing vascular variability of fMRI data across aging populations using a breathholding task , 2007, Human brain mapping.

[12]  A. Dale,et al.  Coupling of Total Hemoglobin Concentration, Oxygenation, and Neural Activity in Rat Somatosensory Cortex , 2003, Neuron.

[13]  Hengyi Rao,et al.  Applications of arterial spin labeled MRI in the brain , 2012, Journal of magnetic resonance imaging : JMRI.

[14]  Thomas T. Liu,et al.  An arteriolar compliance model of the cerebral blood flow response to neural stimulus , 2005, NeuroImage.

[15]  Thomas T. Liu,et al.  Cerebral blood flow and BOLD responses to a memory encoding task: A comparison between healthy young and elderly adults , 2007, NeuroImage.

[16]  Daniel Gallichan,et al.  Flow‐metabolism coupling in human visual, motor, and supplementary motor areas assessed by magnetic resonance imaging , 2007, Magnetic resonance in medicine.

[17]  Fahmeed Hyder,et al.  Neuroimaging With Calibrated fMRI , 2004, Stroke.

[18]  T. L. Davis,et al.  Calibrated functional MRI: mapping the dynamics of oxidative metabolism. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Olli Gröhn,et al.  Coupling between simultaneously recorded BOLD response and neuronal activity in the rat somatosensory cortex , 2008, NeuroImage.

[20]  Douglas C. Noll,et al.  Accounting for nonlinear BOLD effects in fMRI: parameter estimates and a model for prediction in rapid event-related studies , 2005, NeuroImage.

[21]  A. Toga,et al.  Linear and Nonlinear Relationships between Neuronal Activity, Oxygen Metabolism, and Hemodynamic Responses , 2004, Neuron.

[22]  Gary H. Glover,et al.  Controlled inspiration depth reduces variance in breath-holding-induced BOLD signal , 2008, NeuroImage.

[23]  Timothy Q. Duong,et al.  Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals , 2005, NeuroImage.

[24]  D. Heeger,et al.  Linear Systems Analysis of Functional Magnetic Resonance Imaging in Human V1 , 1996, The Journal of Neuroscience.

[25]  Feng Xu,et al.  The Influence of Carbon Dioxide on Brain Activity and Metabolism in Conscious Humans , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  J. J. Chen,et al.  BOLD‐specific cerebral blood volume and blood flow changes during neuronal activation in humans , 2009, NMR in biomedicine.

[27]  G. Bruce Pike,et al.  MRI measurement of the BOLD-specific flow–volume relationship during hypercapnia and hypocapnia in humans , 2010, NeuroImage.

[28]  Bart Rypma,et al.  Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor. , 2007, Magnetic resonance imaging.

[29]  Hellmuth Obrig,et al.  Individual alpha-frequency correlates with amplitude of visual evoked potential and hemodynamic response , 2008, NeuroImage.

[30]  F. Hyder,et al.  Cerebral energetics and spiking frequency: The neurophysiological basis of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Thomas T. Liu,et al.  Calibrated fMRI in the medial temporal lobe during a memory-encoding task , 2008, NeuroImage.

[32]  Gary H Glover,et al.  Calibration of BOLD fMRI using breath holding reduces group variance during a cognitive task , 2007, Human brain mapping.

[33]  Gary H. Glover,et al.  Assessment of Hemodynamic Response during Focal Neural Activity in Human Using Bolus Tracking, Arterial Spin Labeling and BOLD Techniques , 2000, NeuroImage.

[34]  Richard B. Buxton,et al.  A theoretical framework for estimating cerebral oxygen metabolism changes using the calibrated-BOLD method: Modeling the effects of blood volume distribution, hematocrit, oxygen extraction fraction, and tissue signal properties on the BOLD signal , 2011, NeuroImage.

[35]  R A Pigeau,et al.  Steady-state visual evoked responses in high and low alpha subjects. , 1992, Electroencephalography and clinical neurophysiology.

[36]  Jeff H. Duyn,et al.  Hemodynamic nonlinearities affect BOLD fMRI response timing and amplitude , 2009, NeuroImage.

[37]  J A Frank,et al.  Measuring the effects of indomethacin on changes in cerebral oxidative metabolism and cerebral blood flow during sensorimotor activation , 2003, Magnetic resonance in medicine.

[38]  Thomas T. Liu,et al.  Physiological noise reduction for arterial spin labeling functional MRI , 2006, NeuroImage.

[39]  G. Iannetti,et al.  BOLD functional MRI in disease and pharmacological studies: room for improvement? , 2007, Magnetic resonance imaging.

[40]  Jed A. Meltzer,et al.  Individual differences in EEG theta and alpha dynamics during working memory correlate with fMRI responses across subjects , 2007, Clinical Neurophysiology.

[41]  A. Fleisher,et al.  Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation , 2009, Human brain mapping.

[42]  K. Uğurbil,et al.  Effect of Basal Conditions on the Magnitude and Dynamics of the Blood Oxygenation Level-Dependent fMRI Response , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[43]  S. Uijtdehaage,et al.  Relationship between brain electrical activity and cortical perfusion in normal subjects , 1999, Psychiatry Research: Neuroimaging.

[44]  Thomas T. Liu,et al.  Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: A calibrated BOLD fMRI study , 2008, NeuroImage.

[45]  Hanzhang Lu,et al.  Quantitative evaluation of oxygenation in venous vessels using T2‐Relaxation‐Under‐Spin‐Tagging MRI , 2008, Magnetic resonance in medicine.

[46]  John E. W. Mayhew,et al.  The effect of hypercapnia on the neural and hemodynamic responses to somatosensory stimulation , 2005, NeuroImage.

[47]  M. D’Esposito,et al.  The Variability of Human, BOLD Hemodynamic Responses , 1998, NeuroImage.

[48]  E C Wong,et al.  A hypercapnia‐based normalization method for improved spatial localization of human brain activation with fMRI , 1997, NMR in biomedicine.

[49]  Thomas T. Liu,et al.  Caffeine increases the linearity of the visual BOLD response , 2010, NeuroImage.

[50]  Richard B. Buxton,et al.  Test–retest stability of calibrated BOLD-fMRI in HIV− and HIV+ subjects , 2011, NeuroImage.

[51]  Fahmeed Hyder,et al.  Dynamics of Changes in Blood Flow, Volume, and Oxygenation: Implications for Dynamic Functional Magnetic Resonance Imaging Calibration , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[52]  Jean Gotman,et al.  Hemodynamic and metabolic responses to activation, deactivation and epileptic discharges , 2005, NeuroImage.

[53]  Messoud Ashina,et al.  Pharmacological modulation of the bOLD response: A study of acetazolamide and glyceryl trinitrate in humans , 2011, Journal of magnetic resonance imaging : JMRI.

[54]  Seong-Gi Kim,et al.  Arterial versus Total Blood Volume Changes during Neural Activity-Induced Cerebral Blood Flow Change: Implication for BOLD fMRI , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[55]  Richard B. Buxton,et al.  Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: Implications for BOLD-fMRI , 2008, NeuroImage.

[56]  M. D’Esposito,et al.  Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging , 2003, Nature Reviews Neuroscience.

[57]  Polina Golland,et al.  Sources of Variability in MEG , 2007, MICCAI.

[58]  G. Crelier,et al.  Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[59]  J. J. Chen,et al.  Global Cerebral Oxidative Metabolism during Hypercapnia and Hypocapnia in Humans: Implications for BOLD fMRI , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[60]  Karl J. Friston,et al.  Nonlinear event‐related responses in fMRI , 1998, Magnetic resonance in medicine.

[61]  Christine L Larson,et al.  Functional coupling of simultaneous electrical and metabolic activity in the human brain , 2004, Human brain mapping.

[62]  Peter Herman,et al.  Energetics of neuronal signaling and fMRI activity , 2007, Proceedings of the National Academy of Sciences.

[63]  Jeremy F Magland,et al.  Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[64]  Peter A. Bandettini,et al.  Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI , 2006, NeuroImage.

[65]  Riitta Hari,et al.  Predicting stimulus‐rate sensitivity of human somatosensory fMRI signals with MEG , 2009, Human brain mapping.

[66]  D. Noll,et al.  Nonlinear Aspects of the BOLD Response in Functional MRI , 1998, NeuroImage.

[67]  Thomas T. Liu,et al.  A signal processing model for arterial spin labeling functional MRI , 2005, NeuroImage.

[68]  Irene Tracey,et al.  Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal , 2004, NeuroImage.

[69]  Darren R Gitelman,et al.  Hemodynamic response changes in cerebrovascular disease: implications for functional MR imaging. , 2002, AJNR. American journal of neuroradiology.

[70]  Jens Frahm,et al.  The Effect of Acetazolamide on Regional Cerebral Blood Oxygenation at Rest and under Stimulation as Assessed by MRI , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[71]  S. Tobimatsu,et al.  Normal variability of the amplitude and phase of steady-state VEPs. , 1996, Electroencephalography and clinical neurophysiology.

[72]  J. Polich,et al.  On the relationship between EEG and P300: individual differences, aging, and ultradian rhythms. , 1997, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[73]  N. Logothetis,et al.  The Influence of Moderate Hypercapnia on Neural Activity in the Anesthetized Nonhuman Primate , 2008, Cerebral cortex.

[74]  Yulin Ge,et al.  Baseline blood oxygenation modulates response amplitude: Physiologic basis for intersubject variations in functional MRI signals , 2008, Magnetic resonance in medicine.

[75]  J. R. Baker,et al.  The intravascular contribution to fmri signal change: monte carlo modeling and diffusion‐weighted studies in vivo , 1995, Magnetic resonance in medicine.

[76]  Egill Rostrup,et al.  Hypercapnic normalization of BOLD fMRI: comparison across field strengths and pulse sequences , 2004, NeuroImage.

[77]  Guanghua Xiao,et al.  Improving fMRI sensitivity by normalization of basal physiologic state , 2009, Human brain mapping.

[78]  R. Edelman,et al.  Magnetic resonance imaging (2) , 1993, The New England journal of medicine.

[79]  P. Manganotti,et al.  EEG and fMRI Coregistration to Investigate the Cortical Oscillatory Activities During Finger Movement , 2008, Brain Topography.

[80]  Mark D'Esposito,et al.  Variation of BOLD hemodynamic responses across subjects and brain regions and their effects on statistical analyses , 2004, NeuroImage.

[81]  R. Buxton,et al.  Modeling the hemodynamic response to brain activation , 2004, NeuroImage.

[82]  Jason Berwick,et al.  Further nonlinearities in neurovascular coupling in rodent barrel cortex , 2005, NeuroImage.