High-resolution and high-sensitivity PET for quantitative molecular imaging of the monoaminergic nuclei: A GATE simulation study

Abstract

Purpose: Quantitative in vivo molecular imaging of fine brain structures requires high-spatial resolution and high-sensitivity. Positron emission tomography (PET) is an attractive candidate to introduce molecular imaging into standard clinical care due to its highly targeted and versatile imaging capabilities based on the radiotracer being used. However, PET suffers from relatively poor spatial resolution compared to other clinical imaging modalities, which limits its ability to accurately quantify radiotracer uptake in brain regions and nuclei smaller than 3 mm in diameter. Here we introduce a new practical and cost-effective high-resolution and high-sensitivity brain-dedicated PET scanner, using our depth-encoding Prism-PET detector modules arranged in a conformal decagon geometry, to substantially reduce the partial volume effect and enable accurate radiotracer uptake quantification in small subcortical nuclei.

Methods: Two Prism-PET brain scanner setups were proposed based on our 4-to-1 and 9-to-1 coupling of scintillators to readout pixels using $1.5\times 1.5\times 20$ mm³ and $0.987\times 0.987\times 20$ mm³ crystal columns, respectively. Monte Carlo simulations of our Prism-PET scanners, Siemens Biograph Vision, and United Imaging EXPLORER were performed using Geant4 application for tomographic emission (GATE). National Electrical Manufacturers Association (NEMA) standard was followed for the evaluation of spatial resolution, sensitivity, and count-rate performance. An ultra-micro hot spot phantom was simulated for assessing image quality. A modified Zubal brain phantom was utilized for radiotracer imaging simulations of 5-HT_1A receptors, which are abundant in the raphe nuclei (RN), and norepinephrine transporters, which are highly concentrated in the bilateral locus coeruleus (LC).

Results: The Prism-PET brain scanner with 1.5 mm crystals is superior to that with 1 mm crystals as the former offers better depth-of-interaction (DOI) resolution, which is key to realizing compact and conformal PET scanner geometries. We achieved uniform 1.3 mm full-width-at-half-maximum (FWHM) spatial resolutions across the entire transaxial field-of-view (FOV), a NEMA sensitivity of 52.1 kcps/MBq, and a peak noise equivalent count rate (NECR) of 957.8 kcps at 25.2 kBq/mL using 450-650 keV energy window. Hot spot phantom results demonstrate that our scanner can resolve regions as small as 1.35 mm in diameter at both center and 10 cm away from the center of the transaixal FOV. Both 5-HT_1A receptor and norepinephrine transporter brain simulations prove that our Prism-PET scanner enables accurate quantification of radiotracer uptake in small brain regions, with a 1.8-fold and 2.6-fold improvement in the dorsal RN as well as a 3.2-fold and 4.4-fold improvement in the bilateral LC compared to the Biograph Vision and EXPLORER, respectively.

Conclusions: Based on our simulation results, the proposed high-resolution and high-sensitivity Prism-PET brain scanner is a promising cost-effective candidate to achieve quantitative molecular neuroimaging of small but important brain regions with PET clinically viable.

Keywords: Prism-PET; depth-of-interaction; high sensitivity; high spatial resolution; monoaminergic nuclei; positron emission tomography; quantitative molecular imaging; time-of-flight.

FIGURE 1

3D GATE models of the EXPLORER (left), Siemens Biograph Vision (middle), and Prism-PET brain scanner (right) with modified Zubal brain phantom at the center of the FOV.

FIGURE 2

Demonstration of LORs rebinned to virtual cylinder (VC). Yellow: VC detector ring. Red dash line: actual LORs. Blue solid line: LORs rebinned to the VC

FIGURE 3

Axial sensitivity profiles of EXPLORER, Biograph Vision, Prism-PET 1 mm, and Prism-PET 1.5 mm.

FIGURE 4

Count rate and NECR performance of EXPLORER, Biograph Vision, Prism-PET 1 mm, and Prism-PET 1.5 mm.

FIGURE 5

Simulated ultra-micro phantom images at the center and edge (i.e., 100 mm offset from the center of the transaxial FOV). Rods’ diameters from smallest to largest are 0.75, 1.0, 1.35, 1.7, 2.0, and 2.4 mm (clockwise). Raw: images without any corrections. DOI: images with DOI-rebinning. ICS-DOI: images with both ICS recovery and DOI-rebinning.

FIGURE 6

5-HT_1A radiotracer GATE simulation using the Biograph Vision, EXPLORER, Prism-PET 1 mm, and Prism-PET 1.5 mm. The insets in these figures show a zoomed-in view of the DRN. Top row represents the corresponding slice in Montreal Neurological Institute (MNI152) space (centered around the DRN).

FIGURE 7

NET radiotracer GATE simulation using the EXPLORER, Biograph Vision, Prism-PET 1 mm, and Prism-PET 1.5 mm. The insets in these figures show a zoomed-in view of the bilateral LC. Top row represents the corresponding slice in MNI152 template images (centered around the LC).

FIGURE 8

Calculated RUR values for each VOI (DRN, LLC, and RLC) using the 5-HT_1A radiotracer (DRN) and NET radiotracer (LLC, RLC) for all four simulated scanners. Ground truth RUR values based on postmortem autoradiographic studies are also displayed for reference.