Ultra-high sensitivity, high spatial resolution single photon emission tomography using mechanical flux manipulation

The overall goal of this Phase 2 SBIR proposal is to build on our successfully-implemented Phase 1 STTR work in which we developed, simulated, built, and validated a new philosophy for single photon radionuclide (SPR) imaging. We refer to our new imaging methodology as mechanical flux manipulation (MFM). MFM utilizes high resolution pixelated detectors and a novel image reconstruction methodology utilizing detector flux information to achieve target performance goals of >50% detection efficiency for photons impinging an MFM detector and <2 mm reconstructed image resolution. The two main features that differentiate MFM from traditional SPECT are collimator-less detectors and the use of probability distributions versus line of response (LOR) counts to reconstruct images. MFM does not bin individually detected photons to a LOR. The direction of travel for individual photons is not considered. MFM is further differentiated from SPECT in that it uses a fully 3D image reconstruction and reaps the imaging benefits similar to 3D versus 2D PET data acquisition and image reconstruction. While MFM will support general single photon tomographic imaging protocols, our initial focus is to demonstrate feasibility for human brain imaging. This project is consists of three specific aims. Aims 1 and 2 are an iterative process of building (SA1) and testing (SA2) an MFM tomographic imaging system with 2 detector panels. We will first build a single detector panel for the MFM system (SA1-A) that will be used to acquire phantom data to assess the capabilities of the single-panel MFM system (SA2-A). The single- panel MFM system will be evaluated for usability, machine tolerances, and precision of control. After this evaluation, we will make any necessary changes and build a second MFM detector panel to integrate into the system (SA1-B). The 2-panel MFM system will then be evaluated via phantom studies including the striatal brain phantom and the miniDerenzo Phantom. These will be used to evaluate resolution, contrast, uniformity, noise, and overall image quality (SA2-B). Acquisition and reconstruction settings will be chosen based on phantom imaging performance. Our third aim is to perform human brain imaging using the 2-panel MFM system. We will obtain a minimal-risk IRB and recruit 4 patients that have been referred for I-123 Ioflupane SPECT imaging for differential Parkinson’s diagnosis. We will ask patients to walk a short distance from their SPECT imaging session and be scanned an additional 15-20 minutes in our MFM system while the radiotracer is still in their brain. Human brain images will be evaluated by an experienced radiologist. Project Number: 9R44MH144704-02A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Larry Pierce | Institution: QUANT, INC., EDMONDS, WA | Award Amount: $1,835,001 | Activity Code: R44 | Study Section: Special Emphasis Panel[ZEB1 OSR-E (M2)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11254264