Project Abstract/Summary The objective of this psychological technology SBIR/STTR Fast-Track proposal is to provide an innovative gamified biofeedback solution (software-only) to improve the effectiveness of functional Magnetic Resonance Imaging (fMRI) for pediatric pre-neurosurgical planning. Maximal safe resection of an epileptic focus to optimize outcome is carefully balanced against impact on critical brain regions that could result in neurodevelopmental deficits. To avoid deficits such as aphasia or paralysis, surgeons rely on pre-surgical functional brain mapping to define borders for safe resection. Gold standard, invasive functional brain mapping via electrocortical stimulation (ECS) is complex, time consuming and carries medical risks (e.g. seizures). It is extremely challenging for children, to tolerate the often-uncomfortable electrical stimulation. FDA cleared non- invasive fMRI is a safer alternative for functional mapping. Unfortunately, fMRI has yet to reach its full potential in pediatrics. Motion as low as 0.2 mm causes distortion of the fMRI signal. Clinical fMRI tasks are also performed covertly (i.e., no overt speech, no recording of button presses). Functional maps are generated post-hoc, so scan operators and patients cannot know if sufficient usable data were collected, resulting in 50- 90% clinical pediatric fMRI failure rates due to motion and poor task compliance. NOUS Imaging Inc. has developed FDA 510(k)-cleared Framewise Integrated Real-Time MRI Monitoring (FIRMM) software for tracking motion and its effects. Use of FIRMM can greatly improve the chances of obtaining usable fMRI maps, reducing fMRI data loss rates due to motion by >50% in children. FIRMM currently displays brain motion to the scan operator and patient in real-time, enabling scan operator intervention and patient self-regulation. In this Fast-Track application, we will extend development from FIRMM to FIRMM Qx with gamified biofeedback and task compliance tracking, to provide a new, neuro-developmentally appropriate, biofeedback-based quality improvement solution for pediatric clinical fMRI. In Phase I we will develop and verify FIRMM Qx as a tool to greatly reduce fMRI mapping failures due to non-compliance, motion or both. In Phase II, we will demonstrate that FIRMM Qx is superior to fMRI without real-time QC and biofeedback, providing more accurate maps and lower non-invasive brain mapping fail-rates for pediatric epilepsy surgery planning. NordicNeuroLab (NNL) is the leading supplier of fMRI hardware and software, used for fMRI at > 2000 institutions worldwide. However, NNL fMRI fails whenever insufficient quality fMRI data are collected. A new, synergistic partnership between NOUS and NNL will add FIRMM Qx real-time motion and task compliance improvement to NNL fMRI. NOUS will be providing developmental psychology know-how, while NNL provides best-in-class fMRI hardware, post- processing and a large distribution network. Adding FIRMM Qx, to the NOUS portfolio and NNL user base will make epilepsy surgery for children better and safer.

Project Narrative In children, clinical functional MRI (fMRI) has extremely high fail rates (50-90%) due to excessive head motion and task non-compliance. Despite FDA clearance for neurosurgical planning, the low quality of pediatric fMRI mapping is limiting its use, thus increasing discomfort and the risk of cognitive, language and motor deficits. This psychological technology application overcomes the current insufficiencies of non-invasive pediatric fMRI with FIRMM Qx, a real-time motion and compliance tracking software that uses neuro-developmentally targeted, gamified biofeedback to improve fMRI brain mapping and thus neurosurgical safety for children.