KEYWORDS: Tumors, Magnetic resonance imaging, Tissues, Skin, In vivo imaging, Mixtures, Body composition, Contrast agents, Signal to noise ratio, Refractive index, Optical clearing
The use of multimodality approaches may benefit from simultaneous or sequential optical and magnetic resonance (MR) imaging applied to the same tissue volume. Previously observed in vivo optical clearing (OC) effect of MRI contrast agent was investigated with a goal of quantifying the effect of gadobutrol (GB) and biocompatible compositions containing GB as means of improving fluorescence intensity imaging (FI) in a rodent model of cancer. MRI was also explored as a technique enabling localization of the tumor volumes affected by intravenous administration of GB performed for the purpose of achieving an OC effect. Xenografting of cells expressing a red fluorescent marker TagRFP in athymic mice resulted in subcutaneous tumors that were subjected to 1H MRI at 1T by applying T1w-3D gradient-echo (GRE) pulse sequences. MRI allowed to measure the longitudinal changes in MR signal intensity that were sufficient for ROI analysis after manual or automated image segmentation. By performing topical application of an OC compositions, which contained 1.0 M or 0.7 M GB mixed with water and dimethyl sulfoxide (DMSO) onto the skin similar tumor MRI signal enhancement by 30–40% within the first 15 min was achieved. Over time, the effect of GB-mediated OC on FI and tumor/background ratio decreased. The application of 0.7 M GB OC mixture in contrast, to concentrated 1.0 M GB resulted in a continuous increase of both tumor red fluorescence as well as of the tumor/background ratio within 15 min and 1 h post cutaneous application. By applying T1w-3D GRE MR it was determined that concentrated 1.0 M GB resulted in MR signal loss measured in the skin due to high magnetic susceptibility. However, the MR signal loss was colocalized with the OC effect in tumor tissue. Intravenous injection of GB at a dose of 0.3 mmol/kg resulted in a rapid and temporary increase of FI by 40%. In conclusion, low-field MRI proved to be useful for performing in vivo imaging of GB-containing OC compositions behavior after local and systemic applications in cancer models and supported the observation of FI longitudinal changes in vivo.
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