Intrinsic signal changes accompanying sensory stimulation: Functional brain mapping using MRI (original) (raw)

Intrinsic Signal Changes Accompanying Sensory Stimulation: Functional Brain Mapping with Magnetic Resonance Imaging

Proceedings of The National Academy of Sciences, 1992

We report that visual stimulation produces an easily detectable (5-20%) transient increase in the intensity of water proton magnetic resonance signals in human primary visual cortex in gradient echo images at 4-T magnetic-field strength. The observed changes predominantly occur in areas containing gray matter and can be used to produce highspatial-resolution functional brain maps in humans. Reducing the image-acquisition echo time from 40 msec to 8 msec reduces the amplitude of the fractional signal change, suggesting that it is produced by a change in apparent transverse relaxation time T2. The amplitude, sign, and echo-time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral blood flow and concomitantly increases venous-blood oxygenation.

Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation

Proceedings of the …, 1992

Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter Tl-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P < 0.001) of 1.8% ± 0.8% (GE) and 1.8% ± 0.9% (ID) was observed in the primary visual cortex (Vi) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 ± 2.2 s for the GE images and 8.9 ± 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (Ml) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatialtemporal window onto individual brain physiology.

Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model

Biophysical Journal, 1993

It recently has been demonstrated that magnetic resonance imaging can be used to map changes in brain hemodynamics produced by human mental operations. One method under development relies on blood oxygenation level-dependent (BOLD) contrast: a change in the signal strength of brain water protons produced by the paramagnetic effects of venous blood deoxyhemoglobin. Here we discuss the basic quantitative features of the observed BOLD-based signal changes, including the signal amplitude and its magnetic field dependence and dynamic effects such as a pronounced oscillatory pattern that is induced in the signal from primary visual cortex during photic stimulation experiments. The observed features are compared with the results of Monte Carlo simulations of water proton intravoxel phase dispersion produced by local field gradients generated by paramagnetic deoxyhemoglobin in nearby venous blood vessels. The simulations suggest that the effect of water molecule diffusion is strong for the case of blood capillaries, but, for larger venous blood vessels, water diffusion is not an important determinant of deoxyhemoglobin-induced signal dephasing. We provide an expression for the apparent in-plane relaxation rate constant (R*) in terms of the main magnetic field strength, the degree of the oxygenation of the venous blood, the venous blood volume fraction in the tissue, and the size of the blood vessel.

Dynamic MRI sensitized to cerebral blood oxygenation and flow during sustained activation of human visual cortex

Magnetic Resonance in Medicine, 1996

Changes in cerebral blood oxygenation and flow during prolonged activation of human visual cortex (6-min video projection) were monitored using high-resolution T2*and T,-weighted gradient-echo MRI in identical sessions. Oxygenation-sensitive recordings displayed an initial signal increase (oxygenation "overshoot"), a subsequent signal decrease extending over 4-5 min (relative deoxygenation), and a signal drop after the end of stimulation that mirrored the initial response (oxygenation "undershoot"). Flow-sensitive MRI demonstrated that the inflow effect remained elevated during the entire period of Stimulation. The observation of gradually decreasing cerebral blood oxygenation, despite persisting elevation of blood flow, may be understood to be an accumulation of deoxyhemoglobin due to the progressive up-regulation of oxidative phosphorylation. The present findings support a concept in which transitions between functional states lead to an uncoupling of perfusion (oxygen delivery) from oxidative metabolism (oxygen consumption) whereas steady-state activity achieves their recoupling.

Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging

1993

It recently has been demonstrated that magnetic resonance imaging can be used to map changes in brain hemodynamics produced by human mental operations. One method under development relies on blood oxygenation level-dependent (BOLD) contrast: a change in the signal strength of brain water protons produced by the paramagnetic effects of venous blood deoxyhemoglobin. Here we discuss the basic quantitative features of the observed BOLD-based signal changes, including the signal amplitude and its magnetic field dependence and dynamic effects such as a pronounced oscillatory pattern that is induced in the signal from primary visual cortex during photic stimulation experiments. The observed features are compared with the results of Monte Carlo simulations of water proton intravoxel phase dispersion produced by local field gradients generated by paramagnetic deoxyhemoglobin in nearby venous blood vessels. The simulations suggest that the effect of water molecule diffusion is strong for the case of blood capillaries, but, for larger venous blood vessels, water diffusion is not an important determinant of deoxyhemoglobin-induced signal dephasing. We provide an expression for the apparent in-plane relaxation rate constant (R*) in terms of the main magnetic field strength, the degree of the oxygenation of the venous blood, the venous blood volume fraction in the tissue, and the size of the blood vessel.

Noninvasive MRI measurement of the absolute cerebral blood volume-cerebral blood flow relationship during visual stimulation in healthy humans

Magnetic Resonance in Medicine, 2013

Purpose-The relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF) underlies blood oxygenation level dependent functional MRI signal. This study investigates the potential for improved characterization of the CBV-CBF relationship in humans, and examines gender effects as well as spatial variations in the CBV-CBF relationship. Methods-Healthy subjects were imaged non-invasively at rest and during visual stimulation, constituting the first MRI measurement of the absolute CBV-CBF relationship in humans with complete coverage of the functional areas of interest. Results-CBV and CBF estimates were consistent with literature, and their relationship varied both spatially and with gender. In a region of interest (ROI) with stimulus induced activation in CBV and CBF at the P<0.05 significance level, a power function fit resulted in CBV = 2.1 CBF 0.32 across all subjects, CBV = 0.8 CBF 0.51 in females and CBV = 4.4 CBF 0.15 in males. Exponents decreased in both genders as ROIs were expanded to include less significantly activated regions. Conclusion-Consideration for potential gender related differences, as well as regional variations under a range of physiological states, may reconcile some of the variation across literature and advance our understanding of the underlying cerebrovascular physiology.

Direct detection of neuronal activity with MRI: fantasy, possibility, or reality?

2005

Abstract Hemodynamic-based functional magnetic resonance imaging (fMRI) techniques have proven to be extremely robust and sensitive methods for noninvasive detection and mapping of human brain activation. Nevertheless, limitations in temporal and spatial resolution as well as interpretation remain because hemodynamic changes accompanying brain activation are relatively sluggish and variable and therefore imprecise measures of neuronal activity.

Water-diffusion slowdown in the human visual cortex on visual stimulation precedes vascular responses

Journal of Cerebral Blood Flow & Metabolism, 2009

We used magnetic resonance imaging (MRI) to investigate the temporal dynamics of changes in water diffusion and blood oxygenation level-dependent (BOLD) responses in the brain cortex of eight subjects undergoing visual stimulation, and compared them with changes of the vascular hemoglobin content (oxygenated, deoxygenated, and total hemoglobin) acquired simultaneously from intrinsic optical recordings (near infrared spectroscopy). The group average rise time for the diffusion MRI signal was statistically significantly shorter than those of the BOLD signal and total hemoglobin content optical signal, which is assumed to be the fastest observable vascular signal. In addition, the group average decay time for the diffusion MRI also was shortest. The overall time courses of the BOLD and optical signals were strongly correlated, but the covariance was weaker with the diffusion MRI response. These results suggest that the observed decrease in water diffusion reflects early events that pre...

Vascular imprints of neuronal activity: Relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation

Proceedings of the National Academy of Sciences, 1997

Modern functional neuroimaging methods, such as positron-emission tomography (PET), optical imaging of intrinsic signals, and functional MRI (fMRI) utilize activity-dependent hemodynamic changes to obtain indirect maps of the evoked electrical activity in the brain. Whereas PET and f low-sensitive MRI map cerebral blood f low (CBF) changes, optical imaging and blood oxygenation level-dependent MRI map areas with changes in the concentration of deoxygenated hemoglobin (HbR). However, the relationship between CBF and HbR during functional activation has never been tested experimentally. Therefore, we investigated this relationship by using imaging spectroscopy and laser-Doppler f lowmetry techniques, simultaneously, in the visual cortex of anesthetized cats during sensory stimulation. We found that the earliest microcirculatory change was indeed an increase in HbR, whereas the CBF increase lagged by more than a second after the increase in HbR. The increased HbR was accompanied by a simultaneous increase in total hemoglobin concentration (Hbt), presumably ref lecting an early blood volume increase. We found that the CBF changes lagged after Hbt changes by 1 to 2 sec throughout the response. These results support the notion of active neurovascular regulation of blood volume in the capillary bed and the existence of a delayed, passive process of capillary filling.