Hemogenetic functional MRI (fMRI) is a recently developed imaging technique that enables the visualization of neural activity at a brain-wide scale by genetically encoding molecular probes that generate hemodynamic contrast in targeted populations of cells or circuits. This approach overcomes the limitations of conventional fMRI, which relies on indirect blood flow changes linked to general brain activity. The first generation of hemogenetic fMRI is based on engineered nitric oxide synthase-based reporters (NOSTICs) to produce localized hemodynamic signals in genetically targeted neuronal populations. This chapter outlines the principles behind hemogenetic fMRI, describes the molecular engineering of NOSTIC-based hemogenetic reporters, and provides a step-by-step guide to experimental protocols for in vitro evaluations of the reporters’ functions and in vivo imaging procedures to apply hemogenetic fMRI to detect circuit-specific neuronal activity. The advantages, limitations, and future applications of these technologies are discussed in the context of functional neuroimaging.