TY - JOUR AU - AB - Mapping immediate early gene (IEG) expression across intact mouse brains allows for unbiased identification of brain- wide activity patterns underlying complex behaviors. Accurate registration of sample brains to a common anatomic reference is critical for precise assignment of IEG-positive (“active”) neurons to known brain regions of interest (ROIs). While existing automated voxel-based registration methods provide a high-throughput solution, they require substantial computing power, can be difficult to implement and fail when brains are damaged or only partially imaged. Additionally, it is challenging to cross-validate these approaches or compare them to any preexisting literature based on serial coronal sectioning. Here, we present the open-source R package SMART (Semi-Manual Alignment to Reference Templates) that extends the WholeBrain R package framework to automated segmentation and semi-auto- mated registration of intact mouse brain light-sheet fluorescence microscopy (LSFM) datasets. The SMART package was created for novice programmers and introduces a streamlined pipeline for aligning, registering, and segmenting LSFM volumetric datasets across the anterior-posterior (AP) axis, using a simple “choice game” and interactive menus. SMART provides the flexibility to register whole brains, partial brains or discrete user-chosen images, and is fully compatible with traditional sectioned coronal slice-based analyses. We demonstrate SMART’score functions using example datasets TI - SMART: An open source extension of WholeBrain for iDISCO+ LSFM intact mouse brain registration and segmentation DO - 10.1101/727529 DA - 2019-08-06 UR - https://www.deepdyve.com/lp/unpaywall/smart-an-open-source-extension-of-wholebrain-for-idisco-lsfm-intact-FKZU9R8F0z DP - DeepDyve ER -