The Relationship Between M in "Calibrated fMRI" and the Physiologic Modulators of fMRI

Abstract

The "calibrated fMRI" technique requires a hypercapnia calibration experiment in order to estimate the factor "M". It is desirable to be able to obtain the M value without the need of a gas challenge calibration. According to the analytical expression of M, it is a function of several baseline physiologic parameters, such as baseline venous oxygenation and CBF, both of which have recently been shown to be significant modulators of fMRI signal. Here we studied the relationship among hypercapnia-calibrated M, baseline venous oxygenation and CBF, and assessed the possibility of estimating M from the baseline physiologic parameters. It was found that baseline venous oxygenation and CBF are highly correlated (R(2)=0.77, P<0.0001) across subjects. However, the hypercapnia-calibrated M was not correlated with baseline venous oxygenation or CBF. The hypercapnia-calibrated M was not correlated with an estimation of M based on analytical expression either. The lack of correlation may be explained by the counteracting effect of venous oxygenation and CBF on the M factor, such that the actual M value of an individual may be mostly dependent on other parameters such as hematocrit. Potential biases in hypercapnia-based M estimation were also discussed in the context of possible reduction of CMRO(2) during hypercapnia.

Keywords: Calibrated fMRI; brain.; cerebral blood flow; cerebral metabolic rate of oxygen; venous oxygenation.

Fig. (1)

Experimental protocol for the study. A) Experiment design. Before the subject enters the magnet, breathing apparatus (including mouth piece, nose clip, end-tidal CO₂ sampling tube) was attached to the subject. Following survey and reference scans, TRUST MRI was performed to measure baseline venous oxygenation. Phase-contrast velocity MRI was used to measure CBF. Finally, pseudo-continuous ASL sequence was used with two echoes to simultaneously measure BOLD and CBF signal changes during hypercapnia challenge. During the ASL scan, the subject breathed four minutes of room-air. Then the gas valve was switched to CO₂ gas mixture and the scan continued for another six minutes. The first two minutes after the switching was considered transition time and the data acquired were not used in the analysis. B) Position of imaging slice and labeling slab for TRUST MRI. The labeling slab is above the imaging slice for venous blood labeling. A relatively large gap (2 cm) between the imaging slice and labeling slab was used to minimize the saturation of labeling pulse on the imaging slice. This gap is not expected to affect the venous blood signal intensity as the flow velocity in these veins is relatively high (~16 cm/s) and the blood in the gap would have flown out of the imaging slice by the time of acquisition.

Fig. (2)

Representative data for TRUST MRI and phase-contrast MRI. A) TRUST MRI signal, i.e. control-label, in the sagittal sinus as a function of effective TE. The symbol shows the experimental results. The solid curve shows the fitting of the data to a mono-exponential function. The time constant of the decay, i.e. T2 relaxation time of the blood, is also shown. B) Anatomical image from the phase-contrast scan. C) Posterior portion of the anatomic image highlighted by the orange box. D) Magnitude image of the phase-contrast scan showing large vessels as bright signals. The two bright regions indicate the superior sagittal sinus and the straight sinus, respectively. E) Velocity map. The flow in the veins is shown in dark color because the flow direction is downwards.

Fig. (3)

Scatter plot between baseline venous oxygenation and baseline CBF across subjects (N=11). Each symbol represents data from one subject.

Fig. (4)

A representative map of the M factor. Eight slices are show. The data of BOLD and CBF were first smoothed before being used to calculate the M factor on a voxel-by-voxel basis. Arrows indicate regions where the estimated M values were clearly out of the reasonable range. This may be because of errors in the CBF and BOLD signals (e.g. decreased CBF and increased BOLD signal) which resulted in poor model fitting.

Fig. (5)

Scatter plots between variables in the model for the M factor. A) Scatter plot between hypercapnia-based M and baseline venous oxygenation. B) Scatter plot between hypercapnia-based M and baseline CBF. C) Scatter plot between hypercapnia-based M and baseline-parameter-estimated M. It was found that the hypercapnia-based M was not correlated with any of the variables associated with baseline physiology.