Imaging and sensing of pH and chemical state with nuclear-spin-correlated cascade gamma rays via radioactive tracer
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2022-01-14 |
| Journal | Communications Physics |
| Authors | Kenji Shimazoe, Mizuki Uenomachi, Hiroyuki Takahashi |
| Institutions | The University of Tokyo |
| Citations | 20 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive Summaryâ- Core Breakthrough: Demonstration of simultaneous molecular accumulation imaging and quantum sensing of local micro-environment (pH and chemical state) using nuclear-spin-correlated cascade gamma rays from the radioactive tracer Indium-111 (111In).
- Sensing Mechanism: The technique leverages the Perturbed Angular Correlation (PAC) phenomenon, where the local electric quadrupole hyperfine interaction affects the intermediate nuclear spin state of 111In, altering the angular distribution of the subsequent cascade gamma rays (171 keV and 245 keV).
- pH Sensitivity: A significant transition in the gamma-ray angular correlation (anisotropic parameter Ax) was observed in 111InCl3 solutions as the pH shifted from 3 to 5, confirming feasibility for local pH mapping.
- Chemical State Detection: The system successfully differentiated between chelated 111In (trapped by Psyche-DOTA) and unchelated 111InCl3, proving the capability to determine the chemical bond state of the radiotracer in solution.
- Imaging Method: Accumulation imaging was achieved using Double Photon Emission Coincidence Imaging (DPECT), which localizes the source position with high sensitivity via the intersection of two back-projected coincidence lines.
- Hardware Implementation: The detection system utilizes high-resolution HR-GAGG scintillators coupled with SiPM arrays and a dynamic time-over-threshold (dToT) signal processing circuit for precise time-and-energy detection.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| Radioactive Tracer | 111In | Nuclide | Used for SPECT and cascade gamma-ray emission. |
| Tracer Half-life | 2.8 | days | Suitable for clinical use in diagnosis. |
| Cascade Gamma 1 Energy | 171 | keV | First photon detected. |
| Cascade Gamma 2 Energy | 245 | keV | Second photon detected. |
| Intermediate State Lifetime (TN) | 84.5 | ns | Time constant of the intermediate nuclear spin state. |
| True Coincidence Timing Window | -50 to +200 | ns | Used to isolate correlated cascade events. |
| Energy Window | ±10 | % | Applied around 171 keV and 245 keV peaks for filtering. |
| Scintillator Material | HR-GAGG | Compound | Ce:Gd3Al2Ga3O12, used for gamma-ray conversion. |
| Scintillator Density | 6.63 | g/cm3 | High density material characteristic. |
| Energy Resolution (HR-GAGG) | 4 | % | Measured with avalanche photodiode sensor. |
| Detector Pixel Size | 2.5 x 2.5 x 4.0 | mm | Dimensions of individual HR-GAGG crystals in the 8x8 arrays. |
| Intrinsic Time Resolution | 50 | ns (FWHM) | Achieved using the dToT signal processing method. |
| Demonstrated Sensitivity | 0.46 to 1.73 | pmol | Activity range (0.8-3 MBq) used in solution experiments. |
| Anisotropy Transition Range | pH 3 to pH 5 | pH | Range where the angular correlation distribution changes significantly for 111InCl3. |
Key Methodologies
Section titled âKey Methodologiesâ-
Tracer and Sample Preparation:
- Standard 111InCl3 solution (pH 1.9) was adjusted using NaOH, HCl, and phosphoric buffer to create seven distinct pH conditions (pH 1 to pH 13).
- Chelated samples (Psyche-DOTA[111In]) were prepared by mixing 111InCl3 with Psyche-DOTA (1:1000 molar ratio) and incubating at 80 °C for 15 minutes.
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Detector System Setup:
- Sensing (Non-imaging): Eight HR-GAGG/SiPM detector modules (512 channels total) were arranged in an octagon around the target solution to maximize solid angle coverage for angular correlation measurement.
- Imaging (DPECT): Four modules, each equipped with 15-mm thick Lead (Pb) parallel hole collimators (2-mm diameter holes), were positioned at 0°, 90°, 180°, and 270° around two 111InCl3 sources.
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Signal Acquisition and Processing:
- Charge signals from SiPMs were processed using the dynamic Time-over-Threshold (dToT) method, providing digital outputs for time stamp and energy (pulse width).
- Data acquisition (DAQ) used an FPGA (Xilinx Kinetex7) synchronized with external clocks (1 kHz) to record time, energy, and position in list mode.
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Coincidence Event Filtering:
- Events were filtered for the cascade gamma-ray energies (171 keV and 245 keV, ±10%).
- True Coincidence Events: Selected within the time window of -50 ns to +200 ns.
- Random Coincidence Events: Selected within the time window of -500 ns to -200 ns, used for normalization and geometry correction.
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Imaging and Sensing Parameter Extraction:
- Imaging: Double Photon Emission Coincidence Imaging (DPECT) was used, reconstructing the source location by identifying the intersection points of the two back-projection lines defined by the coincidence events.
- Sensing: The anisotropic parameter (Ax) was calculated within defined Regions of Interest (ROI) in the reconstructed voxels, using the ratio of coincidence counts at 90° versus 180° (Ax = W(90°)/W(180°)).
Commercial Applications
Section titled âCommercial Applicationsâ- Nuclear Medicine Diagnostics (SPECT/PET Enhancement): Integrating local molecular environment sensing (pH, viscosity, temperature) into standard molecular imaging, providing functional information beyond simple tracer accumulation.
- Targeted Theranostics: Quality control and validation of complex radiolabeled targeting agents (e.g., DOTA conjugates, liposomes) by confirming the chemical bond state (chelation efficiency) in vivo or in situ.
- Deep-Tissue Quantum Sensing: Utilizing high-penetration sub-MeV gamma rays as naturally polarized photons to perform quantum sensing of micro-environments deep within the human body, a capability currently limited by visible-light quantum sensors (like NV centers).
- Biochemical Research: High-sensitivity (pmol level) detection and mapping of local pH changes or molecular interactions in biological systems, relevant for studying disease progression (e.g., tumor microenvironments).
- Advanced Detector Technology: Application of the HR-GAGG/SiPM/dToT detection system in next-generation gamma-ray imagers (DPECT, Compton cameras) requiring high timing and energy resolution for coincidence detection.