Design and Development of an Advanced Functional MRI Software as Medical Device (SaMD) forClinical Trials and Therapeutic Applications in Neuropsychiatry

ABSTRACT Neuropsychiatric conditions comprise a significant portion of global disease burden, yet approval rates for novel therapies remain low. This stems from a continuing lack of evidence from human subjects on neurobiological target engagement and mechanisms of action, which leads to exorbitant costs and risk of clinical trial failure that together impede successful market entry of effective treatments. Functional magnetic resonance imaging (fMRI) has been a transformative tool for human systems neuroscience, which over 20 years has revealed the functional architecture of the brain in health and disease. It has the potential to support the creation of new treatments for neuropsychiatric disorders with objective biological evidence of treatment effects. In practice, commercial deployment of fMRI has been limited due to enduring challenges related to artifacts, processing, and result reproducibility. To realize its potential, there is a need for a fMRI platform that meets clinical trial and industry requirements for standardization. To address this need, Ceretype Neuromedicine proposes to develop an end-to- end advanced fMRI platform focused on improving sensitivity, reliability, and automation for industry-sponsored trials of neuropsychiatric therapies. This innovative solution builds on our well-validated multi-echo fMRI (ME-fMRI) approach, multi-echo independent component analysis (ME-ICA), which alone quadruples signal-to-noise, doubles statistical power, and triples the time efficiency of fMRI exams. Ceretype has now deployed this technology in commercial clinical trials of novel therapeutics and in exclusive partnership with a leading imaging contract research organization. Here, we propose extensive engineering and testing around ME-ICA for a single, automated pipeline that meets rigorous standards for reproducibility and standardization through FDA 510(k) clearance of a class II software as a medical device. New features will support integration into a wide array of clinical trial environments and corresponding radiological workflows. We also introduce a new quantitative metric of brain activity, which our preliminary evidence suggests controls for unwanted measurement variability that impacts multi-site studies. The two primary objectives of this fast-track SBIR proposal are to 1) engineer a fMRI system for industry-backed trials that meets regulatory requirements (Phase I), and 2) establish standard quantitative fMRI measurements with regulatory guidance, validate the system, and submit to the FDA for 510(k) clearance (Phase II). In Phase I, we aim to conduct design and development around standardization requirements (IEC 62-304, ISO 13485, 21 CFR 820, ISO 14971) and then design and execute verification tests to meet product requirements. In Phase II, we aim to design standard quantitative fMRI measurements with regulatory guidance (FDA’s Technical Performance Assessment of Quantitative Imaging in Radiological Device Premarket Submissions), and conduct validation testing prior to submission for 510(k) clearance. Upon completion, Ceretype will market the cleared product with imaging contract research organization partners, academic researchers, and leading MRI vendors to broaden utility of fMRI and improve the outcomes of clinical trials for groundbreaking neuropsychiatric therapies.