Abstract
Although MEMRI (Manganese Enhanced MRI) informations were obtained on primary tumors in small animals, MEMRI data on metastases are lacking. Thus, our goal was to determine if 3D Look-Locker T1 mapping was an efficient method to evaluate Mn ions transport in brain metastases in vivo. The high spatial resolution in 3D (156 × 156 × 218 μm) of the sequence enabled to detect metastases of 0.3 mm3. In parallel, the T1 quantitation enabled to distinguish three populations of MDA-MB-231 derived brain metastases after MnCl2 intravenous injection: one with a healthy blood-tumor barrier that did not internalize Mn2+ ions, and two others, which T1 shortened drastically by 54.2% or 24%. Subsequent scans of the mice, enabled by the fast acquisition (23 min), demonstrated that these T1 reached back their pre-injection values in 24 h. Contrarily to metastases, the T1 of U87-MG glioma remained 26.2% shorter for one week. In vitro results supported the involvement of the Transient Receptor Potential channels and the Calcium-Sensing Receptor in the uptake and efflux of Mn2+ ions, respectively. This study highlights the ability of the 3D Look-Locker T1 mapping sequence to study heterogeneities (i) amongst brain metastases and (ii) between metastases and glioma regarding Mn transport.
Highlights
Calcium is a ubiquitous second messenger that is necessary for tremendous activities especially in tumor cells
Metastases detected on the balanced Steady State Free Precession (bSSFP) image (a) as hyper-intense areas are detected on the T1 map before injection (b), due to their longer T1 than healthy brain
On the bSSFP images, the hyper signal was due to the T2/T1 contrast of the sequence and the watery composition of the metastases which accounted for longer T1 values on the 3D T1 maps
Summary
Calcium is a ubiquitous second messenger that is necessary for tremendous activities especially in tumor cells. The detection of Mn2+ ions in vivo brings anatomical information, it is necessary to quantify the uptake, efflux and residual time of the contrast agent in order to follow longitudinally cancer cell activity and evaluate the efficiencies of therapeutic approaches. Castets et al developed a 3D T1 mapping sequence combining the Look-Locker module with a spiral sampling that lasted only 12 min with a spatial resolution of 208 × 208 × 312 μm on the mouse’s heart[13] This type of sequence would be very useful to localize precisely Mn2+ ions within tumors, to follow the kinetics of Mn2+ ions in the tumors and to detect small early-growing metastases. This rate is affected by the increasing incidence of brain metastases[28]
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