Multimodal Measurements of Blood Plasma and Red Blood Cell Volumes during Functional Brain Activation

As an alternative to functional magnetic resonance imaging (fMRI) with blood oxygenation level dependent (BOLD) contrast, cerebral blood volume (CBV)-weighted fMRI with intravascular contrast agents in animal models have become popular. In this study, dynamic measurements of CBV were performed by magnetic resonance imaging (MRI) and laser-Doppler flowmetry (LDF) in α-chloralose anesthetized rats during forepaw stimulation. All recordings were localized to the contralateral primary somatosensory cortex as revealed by BOLD at 11.7 T. Ultra-small superparamagnetic iron oxide (15mg/kg)—a plasma-borne MRI contrast agent with a half-life of several hours in blood circulation—was used to quantify changes in magnetic field inhomogeneity in blood plasma. The LDF backscattered laser light (805 nm), which reflects the amount of red blood cells, was used to measure alterations in the non-plasma compartment. Dynamic and layer-specific comparisons of the two CBV signals during functional hyperemia revealed excellent correlations (> 0.86). These results suggest that CBV measurements from either compartment may be used to reflect dynamic changes in total CBV. Furthermore, by assuming steady-state mass balance and negligible counter flow, these results indicate that volume hematocrit is not appreciably affected during functional activation.

[1]  C. Rovainen,et al.  Journal of Cerebral Blood Flow and Metabolism Localized Dynamic Changes in Cortical Blood Flow with Whisker Stimulation Corresponds to Matched Vascular and Neuronal Architecture of Rat Barrels , 2022 .

[2]  Kazuto Masamoto,et al.  Imaging brain vasculature with BOLD microscopy: MR detection limits determined by in vivo two‐photon microscopy , 2008, Magnetic resonance in medicine.

[3]  Hongxia Ren,et al.  CBF, BOLD, CBV, and CMRO2 fMRI signal temporal dynamics at 500‐msec resolution , 2008, Journal of magnetic resonance imaging : JMRI.

[4]  C. Patlak,et al.  Nicotine increases microvascular blood flow and flow velocity in three groups of brain areas. , 1993, The American journal of physiology.

[5]  D. Delpy,et al.  Measurement of Cranial Optical Path Length as a Function of Age Using Phase Resolved Near Infrared Spectroscopy , 1994 .

[6]  Hanbing Lu,et al.  Quantifying the blood oxygenation level dependent effect in cerebral blood volume–weighted functional MRI at 9.4T , 2007, Magnetic resonance in medicine.

[7]  U. Dirnagl,et al.  Laser-Doppler measurements of concentration and velocity of moving blood cells in rat cerebral circulation. , 1997, Acta physiologica Scandinavica.

[8]  H. Merkle,et al.  BOLD and CBV‐weighted functional magnetic resonance imaging of the rat somatosensory system , 2006, Magnetic resonance in medicine.

[9]  J. Detre,et al.  Activation-flow coupling with forepaw stimulation in female and male rats , 1999, Neuroscience Research.

[10]  J C Gore,et al.  Physiological basis for BOLD MR signal changes due to neuronal stimulation: Separation of blood volume and magnetic susceptibility effects , 1998, Magnetic resonance in medicine.

[11]  Peter Herman,et al.  Mathematical model for the estimation of hemodynamic and oxygenation variables by tissue spectroscopy. , 2006, Journal of theoretical biology.

[12]  B. Rosen,et al.  Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation , 1998, Magnetic resonance in medicine.

[13]  K Pettigrew,et al.  The Velocities of Red Cell and Plasma Flows through Parenchymal Microvessels of Rat Brain are Decreased by Pentobarbital , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  F. Hyder,et al.  Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI , 2001, NMR in biomedicine.

[15]  David A. Boas,et al.  Evidence that cerebral blood volume can provide brain activation maps with better spatial resolution than deoxygenated hemoglobin , 2005, NeuroImage.

[16]  A. Popel,et al.  Theory of oxygen transport to tissue. , 1989, Critical reviews in biomedical engineering.

[17]  T A Woolsey,et al.  Blood Flow in Single Surface Arterioles and Venules on the Mouse Somatosensory Cortex Measured with Videomicroscopy, Fluorescent Dextrans, Nonoccluding Fluorescent Beads, and Computer-Assisted Image Analysis , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  F. Hyder,et al.  Frequency‐dependent tactile responses in rat brain measured by functional MRI , 2008, NMR in biomedicine.

[19]  P. Jacobs,et al.  Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. , 1995, Magnetic resonance imaging.

[20]  Peter Herman,et al.  Nonlinear Analysis of Blood Cell Flux Fluctuations in the Rat Brain Cortex during Stepwise Hypotension Challenge , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

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

[22]  Tao Jin,et al.  Improved cortical-layer specificity of vascular space occupancy fMRI with slab inversion relative to spin-echo BOLD at 9.4 T , 2008, NeuroImage.

[23]  D L Rothman,et al.  High-Resolution CMRO2 Mapping in Rat Cortex: A Multiparametric Approach to Calibration of BOLD Image Contrast at 7 Tesla , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  Fahmeed Hyder,et al.  Dynamic Imaging of Perfusion and Oxygenation by Functional Magnetic Resonance Imaging , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  M. Tamura,et al.  Simple peak shift analysis of time-of-flight data with a slow instrumental response function. , 2005, Journal of biomedical optics.

[26]  C. Patlak,et al.  Technique-dependent variations in cerebral microvessel blood volumes and hematocrits in the rat. , 1992, Journal of applied physiology.

[27]  B. Rosen,et al.  MRI measurement of the temporal evolution of relative CMRO2 during rat forepaw stimulation , 1999, Magnetic resonance in medicine.

[28]  B. Rosen,et al.  Functional mapping of the human visual cortex by magnetic resonance imaging. , 1991, Science.

[29]  John A Detre,et al.  Signal averaged laser Doppler measurements of activation–flow coupling in the rat forepaw somatosensory cortex , 1998, Brain Research.

[30]  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.

[31]  Anders M. Dale,et al.  Repeated fMRI Using Iron Oxide Contrast Agent in Awake, Behaving Macaques at 3 Tesla , 2002, NeuroImage.

[32]  I Kanno,et al.  CBF change evoked by somatosensory activation measured by laser-Doppler flowmetry: independent evaluation of RBC velocity and RBC concentration. , 1999, The Japanese journal of physiology.

[33]  D L Rothman,et al.  Image reconstruction of sequentially sampled echo-planar data. , 1995, Magnetic resonance imaging.

[34]  D. Kleinfeld,et al.  Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Sridhar S Kannurpatti,et al.  Regional dynamics of the fMRI‐BOLD signal response to hypoxia‐hypercapnia in the rat brain , 2003, Journal of magnetic resonance imaging : JMRI.

[36]  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.

[37]  Robin Fåhrœus.,et al.  The Suspension‐stability of the Blood. , 2009 .

[38]  Jiabao He,et al.  Simultaneous laser Doppler flowmetry and arterial spin labeling MRI for measurement of functional perfusion changes in the cortex , 2007, NeuroImage.