Online program Overview Session: MIC-12

Abstract

Targeted alpha therapy is a very promising treatment modality for numerous types of cancer. Although PET presents an excellent resolution and signal-to-noise ratio, this modality is limited to radionuclides that emit positrons and cannot be used to image alpha radionuclides such as Ac-225 and Pb-212. Therefore, SPECT is the imaging modality of choice for these radionuclides, despite its poor signal-to-noise ratio and low quantitative accuracy due to the extremely limited sensitivity of this modality. We propose a new approach that enables imaging of alpha-emitting radionuclides in PET/CT scanners: time-of-flight cascade gamma-ray imaging. Our methodology exploits the coincidence detection of gamma-ray cascades emitted by ²²⁵Ac or ²¹²Pb to perform tomography of non-positron emitters in PET/CT scanners. Our technique is evaluated with Ac-225 and Pb-212 phantoms at low concentrations of ~44kBq/mL and short scan sessions under 5-minutes in a commercial clinical PET/CT. We also present the first clinical image of a prostate cancer patient injected with 225Ac-PSMA-617 in a clinical PET/CT system. Lastly, we predict via simulations that next-generation long-axial field-of-view PET/CT scanners will achieve a sensitivity several orders of magnitude higher than SPECT with similar or better spatial resolution.

Abstract

Imaging of theranostic radionuclides that emit high-energy (MeV range) γ rays remains extremely challenging with conventional imaging systems. SPECT performance degrades at MeV energies due to scatter and collimator penetration, while PET is inherently restricted to positron-emitting radionuclides. Pair production tomography (PPT) offers a new approach enabled by the high-energy γ interactions with matter to detectable coincidence signals. When a photon with energy ≥ 2m_ec² (=1.022 MeV) undergoes pair production, the positron generated from this pair production leads to annihilation with the medium electron and emission of two 511 keV photons, enabling PET imaging. In this study, we experimentally demonstrate PPT using the ²¹²Pb decay chain, exploiting 2.617 MeV γ rays from ²⁰⁸Tl. Monte Carlo simulations indicate that, despite long photon transport distances, the spatial distributions of pair production and annihilation events remain localized at the millimeter scale. Phantom experiments were performed on both clinical time-of-flight (TOF) PET and preclinical non-TOF PET systems without hardware modification using clinically and preclinically relevant ²¹²Pb activity levels. Reconstructed PPT images successfully recovered the spatial distribution of activity, with improved contrast observed when TOF information was available. Corresponding SPECT measurements under identical conditions showed reduced visibility for smaller structures. Our results demonstrate the feasibility of PPT for imaging high-energy γ-emitting radionuclides and suggest a route to extend PET beyond conventional principles requiring positron emissions directly from radionuclides.

Abstract

X-ray based radiotherapy is indispensable in modern cancer treatment yet has challenges because it is an open-loop treatment, with limited ability to verify during treatment whether the delivered dose matches the treatment plan. To address this problem, we investigated the use of positrons which are generated in a patient body during X-ray radiotherapy through pair production interactions between matter and MV X-rays, and proposed a novel imaging modality termed pair-production tomography (P2T). This is possible because the X-ray energy used for radiotherapy is a few MeV, and pair production can occur when the photon energy is higher than 1.022 MeV, producing an electron–positron pair. Their simulation results showed opportunities to utilize pair-produced positrons to not only monitor the treatment but also differentiate materials with similar density but different effective atomic numbers, which remains challenging in conventional computed tomography. However, to our best knowledge, there has been no experimental evidence of pair-produced positron detection using a clinical linear accelerator (LINAC).  Therefore, in this study, we performed experimental detection of pair-produced positrons using a LINAC. Experiments were conducted using a LINAC and a pair of radiation detectors composed of photomultiplier tubes and LYSO scintillator crystals. We successfully observed positrons generated in various phantoms via pair production. Furthermore, we quantitatively investigated sensitivity of P2T by adjusting the effective atomic number of phantoms, showing consistent results with the previous simulation results. These results provide an important step toward experimental validation of P2T.

Abstract

Terbium-149 (¹⁴⁹Tb) is a promising radionuclide for targeted α therapy that also emits positrons and prompt photons γ across a wide energy range, which makes it a candidate for ortho-positronium (oPs) lifetime imaging (oPsLI). We present the first demonstration of oPsLI with a therapeutic radionuclide and with γ energies below 511 keV on a commercial long-axial field-of-view PET/CT system. Using a three-lifetime-component Bayesian fitting model, we determined the oPs lifetime for the following three γ energy windows: 310 to 420 keV, 590 to 710 keV and above 720 keV. The medium- and high-energy windows yielded oPs lifetime values consistent with each other and with literature values, while the low-energy window produced systematically lower values. Voxel-wise oPsLI with small voxel size was successfully demonstrated using a single γ energy window. These results establish ¹⁴⁹Tb as a versatile probe for exploring γ energy window effects in oPsLI, with future potential for in vivo microdosimetry and chelator stability studies.

Abstract

We present the first in-vivo imaging of the degree of quantum entanglement in a human subject. The reported investigations were conducted at the Cracow University Hospital in Poland using a 50 cm long, multi-photon J-PET scanner capable of registering and imaging the degree of quantum entanglement of photons originating from electron-positron annihilations in the patient’s body.

A 48-year-old male patient, administered 145 MBq of [68Ga]Ga-DOTA-TATE, was scanned for 20 minutes starting 90 minutes post-injection, following the completion of his routine diagnosis. Data were collected in a triggerless mode, enabling the simultaneous registration of annihilation photons and Compton scattered photons. Event selection was based on the position, time, and energy deposition of the annihilation and scattered photons.

The angular distributions between the scattering planes of annihilation photons in the patient's liver and spleen were determined. These distributions were used to extract the degree of quantum entanglement for these organs. The obtained degree of quantum entanglement is larger than expected for separable photons and lower than expected for maximally entangled photons.

These results demonstrate, for the first time, the feasibility of measuring the degree of quantum entanglement in annihilation photons originating from patients during positron emission tomography. This finding motivates the further development of detectors for the construction of PET systems capable of simultaneously capturing annihilation and Compton-scattered photons, and supports future studies aimed at uncovering medically useful information gained by imaging the degree of quantum entanglement.

Abstract

In addition to medical imaging applications, Positron Emission Tomography (PET) systems can be used to study fundamental physics. One pathway for positron-electron annihilation is the formation of ortho-positronium (oPs), an intermediate bound state that decays to photons after a short lifetime. The lifetime and decay kinematics of oPs can be used to probe material properties and test the Standard Model. Additional sources of charge conjugation-parity (CP) symmetry violation are required to explain the observed matter-antimatter imbalance in the Universe, and CP violation can be constrained by measuring  decays under the reversal of an applied magnetic field. A dedicated physics measurement platform was constructed from the architecture of the NeuroSphere brain PET insert for 7-T MRI, including a PET detector array, positronium target with lifetime trigger, and motorized gantry for control of the system orientation inside the 7-T environment. GATE simulations were used to inform the development of a custom data analysis pipeline for oPs event selection and multi-coincidence processing. Systematics were mitigated by combining runs with various target and detector positions (to average out artificial asymmetries caused by assembly or detector efficiency) and by applying a baseline correction from events in a kinematic region with vanishing analyzing power (to account for drift and more field- and material- related effects).  decays in polyvinyltoluene (PVT) were measured at 7 T, finding a lifetime of 98.7 ± 1.0 ns and constraining CP violation to be zero at a level of 2 × 10⁻². This work demonstrates the unique opportunity provided by PET/MR instrumentation to perform high-field physics measurements, a pathway toward a leading measurement of CP violation in positronium, and proof-of-concept for measuring positronium decays with the full NeuroSphere system.

Abstract

In nuclear medicine, positron emission tomography (PET) and single photon emission computed tomography (SPECT) exhibit high detection sensitivity by detecting γ-rays emitted from radiopharmaceuticals, but they are limited by poor spatial resolution. Conversely, Magnetic Resonance Imaging (MRI) achieves high spatial resolution by encoding positional information through Larmor precession induced by magnetic field gradients. To improve the spatial resolution in nuclear medicine, we propose a novel image reconstruction framework that integrates magnetic field–based spatial encoding, as utilized in MRI, with γ-ray detection as employed in PET and SPECT.
By incorporating the effect of Larmor precession in perturbed angular correlation (PAC), we formulated a forward model that enables image reconstruction as an inverse problem. Numerical simulations demonstrated that our method can stabilize 7 by 7pixels imaging on a small-animal scale. Furthermore, condition number analysis revealed that the imaging process becomes increasingly stable as the neodymium magnets are scanned. However, since each magnetic field distribution requires several hours of measurement, future work will focus on designing more detailed field distributions to reduce measurement time while further enhancing spatial resolution.

Abstract

Task-based adaptive SPECT imaging has long been limited by the computational complexity associated with optimizing acquisition strategies over high-dimensional system configuration spaces. In this work, we present a computational framework for adaptive SPECT imaging based on direct optimization of imaging time distribution (ITD) over discretized detector poses. We have demonstrated the effectiveness of this scheme on a simulated robotic SPECT platform. The framework finds the best imaging strategy by finding an optimized imaging noise property based on the modified uniform Cramér–Rao bound (MUCRB). We further improve the computation efficiency using a non-uniform object-space pixelation (NUOP), which makes it possible to compute the optimum imaging geometry in real time. A StarGuide-inspired multi-head robotic SPECT was simulated and evaluated using a Hoffman brain phantom and hot- and cold-rod resolution-phantoms. Compared with conventional whole-view and uniform ITDs under identical total acquisition time, the optimized ITDs achieved substantially improved region-of-interest (ROI) image quality in all three phantoms and ROIs. These results demonstrate that the proposed framework enables efficient task-specific optimization of acquisition strategies for highly reconfigurable SPECT systems.