Background: Multi-modal brain image registration is a prerequisite for accurate mapping of brain structure and function in neuroscience. Image registration is commonly performed using automated software; however, its accuracy decreases when images differ in modality, contrast, uniformity, and resolution. This limitation could be overcome by using an external reference point; however, high-contrast agents in multi-modal imaging have not been previously reported. New methods: Here, we propose a novel multi-modal fiducial marker that contains Tungsten solution and provides high contrast in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). The basic characteristics of this multi-modal marker were investigated by assessing major sources of image contrast in the following modalities: density and T1-, T2-relaxivity in comparison with conventional contrast agents. Results: Tungsten solution had lower T1- and T2-relaxivity and high solubility, and showed high contrast in T1- and T2-weighted MR and CT images at a high-density concentration (˜3.0 g/mL), whereas other conventional solutions did not show sufficient contrast in either CT or MRI. Comparison with existing methods: The use of this Tungsten-based multi-modal marker allowed more accurate registration than a software-only method in phantom and animal experiments. Application of this method demonstrated accurate cortical surface mapping of neurotransmitter function (dopamine transporter, DAT) using PET and MRI, and provided a neurobiologically relevant cortical distribution consistent with previous literature on histology-based DAT immunoreactivity. Conclusions: The Tungsten-based multi-modal fiducial marker is non-radioactive, easy to handle, and aids precise registration across different modalities of brain imaging.
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