Quantitative cerebral blood volume (CBV) fMRI has the potential to overcome several limitations of BOLD fMRI. In particular, it helps to understand the underlying neuro-vascular coupling in positive and negative BOLD responses and offers superior localization specificity. Non-invasive CBV-fMRI with VASO, however, is inherently a single-slice approach and limited with respect to its field-of-view (FOV) [1]. This limitation can be overcome with advanced readout strategies such as simultaneous multi-slice (SMS) EPI [2] or 3D-EPI [3]. SMS-VASO has recently been used to obtain promising high-resolution CBV maps [4], however, with limited slice resolution. The purpose of this study is to develop and evaluate a new fMRI sampling strategy that combines VASO contrast with a 3D-EPI readout module. The performance of 3D-EPI-VASO is investigated with respect to its sensitivity and specificity to neural activity changes and compared with those of SMS-VASO and also standard BOLD fMRI.Experiments were performed on a 7T Siemens scanner with a 32-channel NOVA head-coil. For simultaneous BOLD and CBV weighting, the SS-SI-VASO inversion preparation scheme was used [5]. We tested the new method in four pilot experiments of two volunteers. Sequence parameters of 3D-EPI and SMS were separately optimized to have the same FOV and were kept as similar as possible. Both approaches had the same TI1/TI2/TR=1.1/2.6/3.0s, bandwidth/Px=1860Hz, #slices=28, in-plane GRAPPA=2, in-plane partial-Fourier=7/8 and in-plane resolution=1.5×1.5mm². To investigate the effective resolution in slice direction, the slice thickness was varied between 1.2-3mm in both SMS and 3D-EPI. SMS-specific parameters were: SMS-factor=4, blipped-CAIPI FOV-shift=1/3, TE=18ms, flip-angle=90°, excitation-pulse bandwidth-time-product=5.2. 3D-EPI-specific parameters were: through-plane GRAPPA=2, slice-partial-Fourier=7/8, TE=22 ms, flip-angle≈15°-25°, #segments=14, slab-selective excitation bandwidth-time-product=25. Please note the different acceleration for 3D-EPI and SMS-EPI, which is a result of advanced partial-Fourier imaging possible in 3D-EPI and the longer possible readout train within the VASO-specific timing constraints (TI/TR) with the 3D-k-space out-center-out (aka ‘linear’) trajectory. SMS-EPI unaliasing is done with split slice GRAPPA (MGH blipCAIPI C2P [2,6] (http://www.nmr.mgh.harvard.edu/software/c2p/sms). To investigate the specificity and sensitivity to neural activity changes, a 6-min finger tapping experiments (blocks of 30 s stimulation and 30 s rest) were conducted. Statistical activation and smoothness was estimated with FSL [7].Figure 1 shows the functional activation maps of CBV and BOLD acquired with 3D-EPI and SMS-EPI from one representative participant. The activation in CBV is on both sides of the central sulcus but not in between, while BOLD activation covers also CSF/vein in the sulcus (orange arrow in Fig. 1). 3D-EPI-VASO provides sufficient contrast-to-noise ratio to detect deactivation in the ipsilateral sensory cortex (blue arrows in Fig. 1) and the small excitatory activity in ipsilateral M1 (red arrows in Fig. 1), similar to BOLD fMRI. Representative maps of tSNR can be seen in Fig. 2. VASO tSNR in 3D-EPI is homogeneous across slices, while the different slice-dependent inversion times in SMS-VASO result in a heterogeneous tSNR (blue arrows in Fig. 2). Table 1 in Fig. 3 shows that 3D-EPI-VASO has approximately the same average tSNR compared to SMS-EPI, while yielding a higher resolution in the slice direction.The superior specificity of CBV-fMRI compared to conventional BOLD-fMRI is consistent with previous VASO studies [4,5]. The lower tSNR of 3D-EPI-VASO in the central imaging region is attributed to the lack of CAIPIRINHA-sampling in the 3D-EPI experiment compared to the blipped-CAIPI SMS-EPI (green arrows in Fig. 2). This results in higher g-factors, which can be addressed by 3D-CAIPI-EPI as previsouly shown [8,9]. The fact that VASO tSNR is comparable for 3D-EPI and SMS-EPI, but not in the BOLD signal, might arise from the different relative physiological and thermal noise contributions in the two contrasts, and the different spin history in BOLD and VASO imaging, when different flip angles are used in 3D-EPI and SMS-EPI. The higher slice resolution in 3D-EPI is consistent with slice profile imperfections in 2D-imaging. The proposed 3D-EPI VASO is currently being evaluated and optimized on a larger number of subjects, in order to more fully characterize its performance and inter-subject stability.We combined VASO with 3D-EPI readout to increase the FOV comparable to conventional BOLD fMRI. 3D-EPI-VASO has superior localization specificity without the sensitivity to large draining veins within the central sulcus. Concurrently, it has enough sensitivity to detect small inhibitory areas in ipsilateral S1. 3D-EPI-VASO offers a higher resolution in the slice direction compared to SMS-VASO with comparable tSNR. Therefore, it may play an important role in high-resolution (layer-dependent) fMRI [5].