Can combined µCT and TOF-MRI assist in neuroanatomical surgery planning in small animal models?

Aims Deep brain stimulation (DBS) for neurological and psychiatric disorders like Parkinson’s disease or major depression disorder requires the implantation of electrodes for the application of electrical pulses in deep brain anatomical locations. For such procedures, preoperative or intra-operative multi-modality brain magnetic resonance imaging (MRI) or computed tomography angiography (CTA) images of the individual patient are extensively investigated to define the optimal trajectory for electrode insertion to avoid vasculature and functionally important brain areas. Unlike DBS in humans, planning of brain interventions in preclinical rodent models is typically restricted to defining the target and entry points in a generalized anatomical small animal brain atlas and transforming these onto the individual animal using a stereotactic reference frame. As current atlases provide limited or no blood vessel information, the outcome of neurosurgical small animal model experiments could be deleteriously influenced when a sub-optimal electrode trajectory ruptures the cerebral vasculature resulting in severe systemic effects. However, the feasibility of individual preoperative imaging-based surgical path planning in animal studies is limited. Therefore, we aim to build a stereotactic (probabilistic) atlas based on anatomical (CT, MRI) and cerebral vasculature (TOF-MRI, CTA) information that can be used for neurosurgical planning (e.g. electrode implantation), without requiring the acquisition of vasculature and anatomical reference images for each individual animal. Here, we validate vasculature information from TOF-MRI with CT(A) and assess the intra-strain variability in skull reference points and cerebral vasculature for neurosurgery planning and subsequent (probabilistic) atlas building. Using this atlas, we aim to evaluate the risk of a user defined electrode trajectory damaging a blood vessel on its path. The use of such a method will be readily applicable to DBS in small animal models and also to a wide range of stereotactic surgeries like targeted injection of viral vectors, contrast agents, cells for the creation of neural disease models and in situ cell labeling applications.