World's highest resolution achieved with mouse-brain-dedicated PET

PET (Positron Emission Tomography) is widely used in clinical settings and drug discovery because it can capture the biodistribution of trace amounts of diagnostic imaging agents. However, its low resolution compared to CT and MRI has been a long-standing challenge. A research group including Deputy Director Taiga Yamaya and Senior Researcher Han Gyu Kang of the Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, QST (National Institutes for Quantum Science and Technology), has developed a new technology that achieves the world's highest resolution in a PET system dedicated to mouse heads. The findings were published in the Journal of Nuclear Medicine.

The resolution of PET has historically been limited to approximately 4 mm for clinical use and 1 to 2 mm even for experimental animals such as mice. This is due to a fundamental trade-off when detecting the trace radiation emitted by diagnostic agents. Thinning the sensor reduces sensitivity; while thickening it degrades the resolution.

The research group succeeded in achieving both high sensitivity and high resolution simultaneously by multi-layering the sensor. The newly developed detector, measuring approximately 12 mm square, features a three-layer sensor section (scintillator) with a pixel pitch of 0.8 mm in each layer, enabling the acquisition of fine positional information. The pixel count is configured in a pyramid structure, with 11×12 pixels in the first layer, 12×12 in the second layer, and 13×13 in the third layer.

By adopting this structure, it became possible to specify exactly which pixel in which layer absorbed the radiation based on the light-reception information obtained from the underlying photosensors. However, because there is a limit to processing the data of 445 pixels per detector, the group made it possible to process all detected light signals by compressing the signals optically from 445 down to 25, and then electronically step-by-step from 25 down to 4.

Kang stated: "The crystal pitch was the challenge. While testing various pitches, we improved the reflective material of the crystal pixels. We also reduced the pitch of the photosensor from the conventional 3.2 mm to 2.4 mm. Designing the electronic circuits to compress the signals was what made it work successfully."

The fabricated prototype PET system for mouse heads demonstrated the world's highest performance with a resolution of 0.5 mm. As a result, it has become possible to observe fine structures of less than 1 mm, which could not be visualized by PET until now. This makes it possible to capture functional changes and disease progression in the mouse brain with much higher precision.

Significant efficiency improvements are expected in drug discovery research, including the development of new treatments for cranial nerve diseases. Furthermore, applying this technology to clinical PET systems could lead to the early detection of cancer and dementia.

Yamaya stated: "Research to specify positions three-dimensionally was being conducted worldwide, but that idea had not been realized. By integrating comprehensive technologies, including crystal arrangement, photosensors, and information processing circuits, we achieved an outcome that overwhelms the PET systems of other nations."

Journal Information
Publication: Journal of Nuclear Medicine
Title: Sub-0.5-mm Resolution PET Versus Autoradiography: Comparison of mGluR1 Concentrations in Mouse Brain
DOI: 10.2967/jnumed.125.271600