Currently, clinical brain single photon emission computed tomography (SPECT) is mostly performed using rotating dual-head gamma cameras equipped with low-energy-high-resolution parallel-beam collimators (LEHR PAR). The resolution of these systems is rather poor (8–10 mm) and the rotation of the heavy gamma cameras can introduce misalignment errors. Therefore, we designed a static full-ring multi-lofthole brain SPECT insert for an existing ring of LaBr3 (5% Ce) detectors. The novelty of the design is found in the shutter mechanism that makes the system very flexible and eliminates the need for rotating parts. A stationary SPECT insert is not only more robust, it is also easier to integrate in a magnetic resonance imaging system (MRI) for simultaneous SPECT-MRI. The target spatial resolution of our design is 6 mm. In this study we used analytical calculations to optimize the collimator for an existing ring of LaBr3 (5% Ce) detectors. We fixed the target spatial resolution at 6 mm in the center of the field-of-view and maximized the volume sensitivity by changing the collimator radius, the aperture and the number of loftholes. Based on these optimal parameters we simulated phantom data and evaluated the image quality of our multi-lofthole system. We simulated a noiseless uniform and Defrise phantom to assess artifacts and sampling completeness and a noiseless hot-rod phantom to assess the reconstructed spatial resolution. We visually evaluated a simulated noisy Hoffman phantom with two lesions. Then, we evaluated the non-prewhitening matched filter signal-to-noise ratio (NPW-SNR) in two lesion detectability phantoms: one with hot lesions and one with cold lesions. Finally, a contrast-to-noise (CNR) study was performed on a phantom with both hot and cold lesions of different sizes (6–16 mm). All results were compared to a LEHR PAR system. The optimization resulted in a final collimator design with a volume sensitivity of 1.55 × 10−4 cps Bq−1, which is 2.5 times lower than the sensitivity of a dual-head system with LEHR PAR collimators. Spatial resolution, on the other hand, has clearly improved compared to LEHR PAR: with the multi-lofthole system we successfully reconstructed 4 mm hot rods. Although this improved resolution did not result in an unambiguous improvement in CNR or NPWSNR, we believe that the flexibility of the shutter mechanism opens interesting perspectives toward time-multiplexing and integration with MRI.