Synopsis

Keywords: fMRI, fMRI (task based), Intravascular fMRI contrast, extravascular fMRI contrast

By using dual-echo DANTE-EPI for functional visual stimulation studies, the contrast of fractions of intravascular signal to total signal change can be generated. We show an intravascular shifted (IVS) contrast can provide simultaneous visualization of intra-extra vascular contrast under different frequencies of visual stimulations at 3T.

Introduction

The blood-oxygenation-level dependent (BOLD) effect consists of intravascular and extravascular components, both of which can arise from small and large blood vessels as well as from the capillary bed. It is desirable to develop a fMRI contrast that can visually and quantifiably differentiate both of intravascular and extravascular components.
Vascular space occupancy (VASO) fMRI¹ is a non-BOLD technique that relies on nulling of the arterial, arteriolar and capillary blood signal with dark blood pulse module such as inversion recovery (IR) or “delay alternating with nutation for tailored excitation” (DANTE) preparation pulses². Based on the opposing effects of intravascular and BOLD signal changes in the microvasculature while dark blood pulse modules were applied, we successfully demonstrated that prepared dual-echo EPI (DANTE-dEPI) may be used for quantification of CBV changes³.
In this work, using functional images from DANTE-dEPI, the pixel-wised contrast of fractions of intravascular to total signal changes can be generated. We show that the averaged fractions of intravascular signal change (∆S₀/S₀)_intra in the total BOLD signal (∆S/S)_tot is determined to be 34.5%, (or extravascular change 65.5% at TE=30ms under 3 Tesla). In addition, we show this fraction is independent of applied visual stimulation frequencies and individual subjects. Finally, using the constant fraction 34.5% of intravascular to total BOLD as a reference fraction, we demonstrate an intravascular shifted (IVS) contrast can provide visually differentiable of intra-extra vascular contrast simultaneously under different frequencies of visual stimulations.

Methods:

1. Fraction of intravascular change to total signal change
When assuming the blood signal is fully suppressed at the ideal case, from the perspective of the vascular components.$$\left(\frac{\Delta S}{S}\right)_{tot} =\left(\frac{\Delta S_0}{S_0}\right)_{intraV}+\left(\frac{\Delta S_{TE_2}}{S_{TE_2}}\right)_{extraV} \left(1\right)$$
$$1=R_{intraV}+R_{extraV} \left(2\right)$$, where the intra-extra vascular components can be normalized by total signal changes; the R_intraV=(∆S₀/S₀)_intraV /(∆S/S)_tot and R_extraV=(∆S₀/S₀)_extraV /(∆S/S)_tot. The (∆S₀/S₀)_intraV is intravascular change extrapolated from DANTE images of two echo times; the (∆S_TE2/S_TE2)_extraV is extravascular signal change equivalent to the BOLD change of DANTE images from second echo time TE=30 ms.
2. Intravascular shifted (IVS) contrast, (analog to the definition of NMR chemical shift)
$$ γ_i = \frac{R_{intraV_i}-R_{ref}}{R_{ref}} \left(3\right)$$
The γ_i in Eq. 3 represents for shifting distance of individual pixel away from a constant reference of intravascular R_ref=0.345. R_{intraV, i} is the fraction of (∆S₀/S₀)_intraV /(∆S/S)_tot in the individual pixel. The R_ref is equal to 0.345 based on our measurement of averaged intravascular component of R_intraV being 34.5% at 3T and, most importantly, this value not varying with different frequencies of visual stimulus and different subjects. We may use averaged R_intraV =34.5% as a constant reference, which is similar to the definition of NMR chemical shift.
3. Imaging methods: Dual-echo DANTE-EPI, DANTE-prepared imaging sequence is shown in Fig. 1, indicating both the DANTE preparation module itself (Fig. 1a ), as well as the proposed method for embedding it within a multi-slice single echo or multi-echo EPI sequence (Fig. 1b). Five healthy volunteers (male, age 35-45 years) underwent fMRI scans in Siemens Prisma 3T. Written informed consent was obtained from all subjects and the study was carried out with the ethical approval of our institutional review board. Tasks of fMRI, flashing checkerboard 1, 5 and 10Hz, 0.5 minutes ON-OFF blocks were performed. A standard Siemens 32-channel head coil was employed. Common parameters used for single echo and multi echo EPI were as follows: FAEPI=70°, GRAPPA (R=3), resolution 2.1´2.1 mm in-plane (92´92 pixels) with field of view 192 mm, 2 mm slice thickness with 50% gap, bandwidth 2074 Hz/pixel. For imaging of DANTE single echo EPI with echo time TE=9 ms, 38 slices were acquired within 3s TR. For imaging of DANTE multi echo EPI with echo time TE=11 and 29 ms, respectively, 32 slices were acquired. DANTE parameters: Number of pulses = 52; Interpulse delay = 700 us, Flip angle = 7.

Results and Discussion:

A linear relationship of averaged fractions (R_intraV) of intravascular changes ((∆S₀/S₀)_intraV) to total BOLD signal changes ((∆S/S)_tot) was shown in Fig. 2, suggesting that averaged intravascular R_intraV =0.345 is a constant independent from stimulation frequencies and subjects. The comparison of intravascular shifted (IVS), or γ contrast with BOLD contrast was shown in Fig. 3. The red and blue pixels in IVS or γ map represent for the intravascular and extravascular components dominated regions, respectively. It can be clearly visualized that under the lower frequencies the activated regions are more extravascular dominated (blue) and intravascular dominated area (red) increases with higher stimulation frequencies. Histograms of one of subjects were shown in Fig. 4, suggesting the shifting of γ values when frequency increases.

Conclusion:

By using dual-echo DANTE-EPI for functional visual stimulation studies, the pixel-wised contrast of fractions of intravascular to total signal change can be generated. Due to the constant of averaged fraction 34.5% of intravascular to total BOLD, we show an intravascular shifted (IVS) contrast can provide differentiable intra-extra vascular contrast simultaneously under different frequencies of visual stimulations at 3T.

Acknowledgements

This work was supported by the Intramural Research Program of the National Institute of Mental Health, USA.