Blood nulling versus tissue suppression: Enhancing integrated VASO and perfusion (VAPER) contrast for laminar fMRI

Cerebral blood volume (CBV) and cerebral blood flow (CBF)-based functional magnetic resonance imaging (fMRI) have proven to be more laminar-specific than blood-oxygen-level-dependent (BOLD) contrast fMRI, but they suffer from relatively low sensitivity. In previous work, we integrated CBV and CBF into one contrast using DANTE (Delay Alternating with Nutation for Tailored Excitation) pulse trains combined with 3D echo-planar imaging (EPI) to create an integrated blood volume and perfusion (VAPER)-weighted contrast (Chai et al., 2020). Building on this, we have now introduced a magnetization transfer approach to induce a tissue-suppression-based VASO (vascular space occupancy) effect and incorporated it with the VAPER technique to boost the overall sensitivity while maintaining superior laminar specificity, all without altering the original VAPER sequence timing scheme. This magnetization transfer (MT)–VAPER fMRI acquisition alternates between DANTE blood-nulling and MT-tissue-suppression conditions, generating an integrated VASO and perfusion contrast enhanced by MT. Both theoretical and experimental evaluation demonstrated an approximately 30% enhancement in VAPER sensitivity with MT application. This novel MT–VAPER method was empirically validated in human primary motor and visual cortices, demonstrating its superior laminar specificity and robust reproducibility, establishing it as valuable non-BOLD tool for laminar fMRI in human brain function research.