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Magnetic-susceptibility-dependent ratiometric probes for enhancing quantitative MRI
Cheng Zhang1, Bin Nan1, Juntao Xu1
1State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China.
Abstract:
In magnetic resonance imaging (MRI), quantitative measurements of analytes are hindered by difficulties in distinguishing the MRI signals of activation of the probe by the analyte from those of the accumulation of the intact probe. Here we show that imaging sensitivity and quantitation can be enhanced by ratiometric MRI probes with a high relaxivity-ratio change (more than 2.5-fold at 7 T) via magnetic-susceptibility-dependent magnetic resonance tuning. Specifically, polymeric probes that incorporate paramagnetic Mn-porphyrin and superparamagnetic iron oxide nanoparticles inducing opposite changes in the longitudinal and transverse magnetic relaxivities responded to analyte concentration independently of probe concentration. In mice, the probes allowed for quantitative real-time dynamic imaging of H2O2, H2S or pH in subcutaneous tumours, in livers with drug-induced injury and in orthotropic gliomas. The ratiometric MRI probes may be advantageously used to obtain molecular insight into pathological processes and to circumvent interference from dynamic changes in probe concentration within the body while providing anatomical information.
Insights
New ratiometric magnetic resonance imaging (MRI) probes enable accurate analyte quantification by decoupling probe activation from probe accumulation. These advanced probes offer enhanced sensitivity for real-time molecular imaging in vivo.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Medical Diagnostics
Background:
- Quantitative measurements in magnetic resonance imaging (MRI) are often limited by the inability to differentiate probe activation signals from probe accumulation.
- Existing MRI techniques struggle with distinguishing analyte-induced probe activation from the concentration of the intact probe, hindering accurate quantification.
Purpose of the Study:
- To develop and validate novel ratiometric MRI probes for enhanced sensitivity and quantitative accuracy in analyte detection.
- To overcome the limitations of distinguishing analyte-specific signals from probe concentration variations in MRI.
Main Methods:
- Development of polymeric probes incorporating paramagnetic Mn-porphyrin and superparamagnetic iron oxide nanoparticles.
- Utilizing magnetic-susceptibility-dependent magnetic resonance tuning to achieve a high relaxivity-ratio change (>2.5-fold at 7 T).
- In vivo testing in mice for real-time dynamic imaging of hydrogen peroxide (H2O2), hydrogen sulfide (H2S), and pH in various pathological models.
Main Results:
- The ratiometric probes demonstrated a high relaxivity-ratio change, enabling analyte concentration to be measured independently of probe concentration.
- Quantitative real-time dynamic imaging of H2O2, H2S, and pH was successfully achieved in mice with subcutaneous tumors, drug-induced liver injury, and orthotropic gliomas.
- The probes provided both molecular insights and anatomical information, overcoming interference from dynamic probe concentration changes.
Conclusions:
- Ratiometric MRI probes offer a significant advancement for sensitive and quantitative molecular imaging.
- These probes can provide valuable molecular insights into pathological processes by accurately measuring analyte concentrations in real-time.
- The developed probes circumvent interference from probe accumulation, improving the reliability of MRI-based diagnostics.
