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Imaging and sensing of pH and chemical state with nuclear-spin-correlated cascade gamma rays via radioactive tracer

MetadataDetails
Publication Date2022-01-14
JournalCommunications Physics
AuthorsKenji Shimazoe, Mizuki Uenomachi, Hiroyuki Takahashi
InstitutionsThe University of Tokyo
Citations20
AnalysisFull AI Review Included

Technical Analysis & Documentation: Quantum Sensing via Cascade Gamma Rays

Section titled “Technical Analysis & Documentation: Quantum Sensing via Cascade Gamma Rays”

This research demonstrates a novel quantum sensing and imaging technique utilizing the nuclear spin state of the radioactive tracer Indium-111 ($^{111}$In) to detect local molecular environments (pH and chemical state). This breakthrough opens new avenues for highly sensitive nuclear medicine diagnostics, but requires next-generation detector materials to achieve clinical viability.

  • Quantum Sensing Breakthrough: Successful proof-of-concept for simultaneous imaging and quantum sensing of local micro-environments (pH, chelation state) using nuclear-spin-correlated cascade gamma rays.
  • Mechanism: The technique relies on Perturbed Angular Correlation (PAC) spectroscopy, where the electric quadrupole hyperfine interaction in the intermediate nuclear spin state is measured via the angular distribution of cascade photons (171 keV and 245 keV).
  • High Sensitivity: Sensing capability demonstrated at the picomole (pmol) level, aligning with the high sensitivity required for clinical nuclear medicine.
  • Detector Requirements: The method demands extremely high time resolution (currently $\approx$ 50 ns FWHM) and spatial precision for coincidence detection, areas where current scintillator technology (HR-GAGG) faces limitations.
  • 6CCVD Value Proposition: High-purity Single Crystal Diamond (SCD) offers superior radiation hardness, carrier mobility, and timing resolution (sub-nanosecond potential) compared to scintillators, making it the ideal material platform for developing the high-sensitivity, high-speed gamma detectors required to scale this technology for in vivo imaging.
  • Future Integration: The work directly relates to solid-state quantum sensing (e.g., NV centers), positioning 6CCVD’s SCD as the foundational substrate for integrating advanced quantum sensors into medical imaging devices.

ParameterValueUnitContext
Radioactive Tracer$^{111}$InN/AUsed for SPECT and quantum sensing
Tracer Half-Life$\approx$ 2.8daysSuitable for clinical applications
Cascade Gamma Ray 1 ($\gamma_1$)171keVFirst decay photon
Cascade Gamma Ray 2 ($\gamma_2$)245keVSecond decay photon
Intermediate State Lifetime ($T_N$)84.5nsTime constant for PAC measurement
Measured Sensitivity0.46 - 1.73pmolRadioactivity range used in experiments
Intrinsic Time Resolution (FWHM)$\approx$ 50nsAchieved by HR-GAGG/SiPM system
Scintillator MaterialHR-GAGGN/ACe:Gd3Al2Ga3O12
Scintillator Density6.63g/cm3High density for gamma absorption
Critical pH Transition Range3 to 5N/AObserved transition in $\gamma$-ray emission distribution
Detector Array Size8x8pixelsPer module (3.2 mm pitch)
Collimator Thickness15mmLead (Pb) used for physical collimation

The experiment utilized a combination of precise radiotracer chemistry, advanced gamma-ray detection hardware, and specialized coincidence signal processing.

  1. Tracer Preparation: $^{111}$InCl$_{3}$ raw solution (pH 1.9) was mixed with NaOH, HCl, and phosphoric acid buffers to create seven distinct pH conditions (pH 1 to pH 13) for angular correlation studies.
  2. Chelation Study: $^{111}$In atoms were trapped by the chelating molecule Psyche-DOTA by mixing $^{111}$InCl$_{3}$ and Psyche-DOTA (1:1000 molar ratio) and heating to 80 °C for 15 minutes.
  3. Detector Setup (Non-Imaging): Eight 8x8 arrays of HR-GAGG scintillators coupled to SiPMs were arranged in an octagon geometry to surround the target, enabling measurement of the angular correlation across a wide solid angle.
  4. Detector Setup (Imaging): Four detector modules equipped with 15-mm thick Lead (Pb) parallel-hole collimators (2-mm diameter, 3.2-mm pitch) were used to surround two $^{111}$InCl$_{3}$ sources for simultaneous imaging and pH sensing.
  5. Signal Processing: Charge signals were processed using the Dynamic Time-over-Threshold (dToT) method, providing digital outputs for time and energy (pulse width).
  6. Coincidence Detection: Events were filtered for energy (171 keV and 245 keV $\pm 10$%) and time coincidence (true events: -50 ns to +200 ns; random events: -500 ns to -200 ns).
  7. Parameter Extraction: The local pH/chemical state was quantified by calculating the anisotropic parameter ($A_x$), defined as the ratio of coincidence counts at 90° versus 180° angular correlation.
  8. Image Reconstruction: Double Photon Emission Coincidence Tomography (DPECT) was used, localizing the source position by identifying the intersection point of the two back-projection lines corresponding to the coincident photons.

The successful implementation of this quantum sensing technique relies heavily on the performance limits of the gamma-ray detection system, particularly timing resolution and spatial density. 6CCVD’s MPCVD diamond materials are uniquely positioned to address the sensitivity and resolution challenges necessary for clinical translation.

Applicable Materials for Next-Generation DPECT/PAC Detectors

Section titled “Applicable Materials for Next-Generation DPECT/PAC Detectors”

To improve the sensitivity (currently limited by collimation and detector efficiency) and timing resolution (currently 50 ns FWHM) for in vivo imaging, the research requires a shift toward high-performance, solid-state detectors.

  • Single Crystal Diamond (SCD) - Detector Grade:
    • Application: Ideal for direct conversion gamma-ray detectors. SCD offers superior carrier mobility and a wide bandgap, enabling faster signal collection and significantly improving timing resolution (potential for sub-nanosecond timing), crucial for minimizing random coincidence events and increasing sensitivity.
    • Recommendation: High-purity SCD wafers (up to 500 ”m thickness) for high-speed, high-resolution pixelated detector arrays, replacing the current GAGG scintillators.
  • Polycrystalline Diamond (PCD) - Substrate Grade:
    • Application: Cost-effective, large-area substrates for complex detector assemblies or integrated electronics.
    • Recommendation: Large-area PCD plates (up to 125 mm diameter) for mechanical support or as radiation-hard platforms for detector readout electronics.
  • Boron-Doped Diamond (BDD):
    • Application: While the paper focuses on gamma detection, BDD is the gold standard for electrochemical sensing. BDD electrodes could be integrated into the diagnostic system to provide simultaneous, highly localized electrochemical pH measurements, complementing the nuclear spin sensing data.

6CCVD provides the necessary engineering and fabrication services to transition this proof-of-concept into a robust clinical device.

Research Requirement6CCVD CapabilityTechnical Advantage
Custom DimensionsPlates/wafers up to 125 mm (PCD) and custom SCD sizes.Enables fabrication of large, high-density detector arrays (e.g., 8x8 or 16x16 pixel geometries) required for increased solid angle coverage and spatial resolution.
Thickness ControlSCD and PCD thickness control from 0.1 ”m to 500 ”m.Allows optimization of detector thickness for maximum absorption efficiency of sub-MeV gamma rays (171 keV and 245 keV).
MetalizationInternal capability for Au, Pt, Pd, Ti, W, Cu.Essential for creating ohmic contacts and pixel electrodes on diamond detectors (e.g., Ti/Pt/Au contacts mentioned in related PAC literature) for precise charge collection and signal readout.
Surface FinishPolishing to Ra < 1 nm (SCD) and Ra < 5 nm (PCD).Critical for minimizing surface defects that degrade charge collection efficiency and timing performance in solid-state detectors.

6CCVD’s in-house PhD team specializes in MPCVD growth optimization and material integration for extreme environments. We can assist researchers and engineers with material selection and design for similar Nuclear Medicine Quantum Sensing projects, ensuring the diamond substrate meets the stringent requirements for high-speed coincidence detection and radiation hardness.

Call to Action: For custom specifications or material consultation regarding high-performance SCD detectors or integrated quantum sensing platforms, visit 6ccvd.com or contact our engineering team directly.