Abstract
Synchronous assessment of multiple MRI contrast agents in a single scanning session would provide a new “multi-color” imaging capability similar to fluorescence imaging but with high spatiotemporal resolution and unlimited imaging depth. This multi-agent MRI technology would enable a whole new class of basic science and clinical MRI experiments that simultaneously explore multiple physiologic/molecular events in vivo. Unfortunately, conventional MRI acquisition techniques are only capable of detecting and quantifying one paramagnetic MRI contrast agent at a time. Herein, the Dual Contrast – Magnetic Resonance Fingerprinting (DC-MRF) methodology was extended for in vivo application and evaluated by simultaneously and dynamically mapping the intra-tumoral concentration of two MRI contrast agents (Gd-BOPTA and Dy-DOTA-azide) in a mouse glioma model. Co-registered gadolinium and dysprosium concentration maps were generated with sub-millimeter spatial resolution and acquired dynamically with just over 2-minute temporal resolution. Mean tumor Gd and Dy concentration measurements from both single agent and dual agent DC-MRF studies demonstrated significant correlations with ex vivo mass spectrometry elemental analyses. This initial in vivo study demonstrates the potential for DC-MRF to provide a useful dual-agent MRI platform.
Highlights
Www.nature.com/scientificreports or more contrast agents in a single MRI scan could provide additional diagnostic and prognostic information
The first step in validating the Dual Contrast – Magnetic Resonance Fingerprinting (DC-MRF) methodology was to assess the in vivo magnetic relaxivities (r1 and r2) of the Gd-BOPTA and Dy-DOTA-azide contrast agents
Either Gd-BOPTA or Dy-DOTA-azide was injected as a single agent over a range of doses (0.1–0.4 mmol/kg for Gd-BOPTA, n = 14; 0.3–1.3 mmol/kg for Dy-DOTA-azide, n = 17) during serially acquired dynamic MRF scans to assess the T1 and T2 relaxation time constants before and after contrast agent administration
Summary
Www.nature.com/scientificreports or more contrast agents in a single MRI scan could provide additional diagnostic and prognostic information. Two molecular MRI contrast agents could be combined to assess both gene expression (e.g., reporter genes6,7) and the downstream effects of the gene’s function such as neurotransmitter release[8], ion concentration[9], protein production[10], or enzymatic activity[11] In this way a “two-color” MRI method could be used in a similar fashion to how multi-agent imaging studies are routinely conducted in basic science fluorescence imaging experiments[12]. Recent in vitro work developed a pathway towards detecting multiple contrast agents by simultaneously assessing both the T1 and T2 relaxation time constants and proposing a new multi-agent relaxation model14: 1/T1 = 1/T10 + r1A × [A] + r1B × [B] With this model, it was shown that simultaneous assessment of T1 and T2 provided by the Magnetic Resonance Fingerprinting methodology could be used to directly solve Eqs. 2a and 2b in order to calculate voxelwise concentration maps for agents A and B. The goal of this study is to further develop and evaluate the DC-MRF methodology to dynamically measure the concentration of two MRI contrast agents in vivo
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