Abstract
PurposeTo assess the uptake, accumulation, temporal stability, and spatial localization of isoflurane (ISO) in the C57BL/6 mouse, and to identify its potential interference with the detection of labeled cardiac progenitor cells using 19F MRI/MR spectroscopy (MRS).Materials and MethodsObjectives are demonstrated using (a) in vitro ISO tests, (b) in vivo temporal accumulation/spatial localization C57BL/6 studies (n = 3), and (c) through injections of perfluoro‐crown‐ether (PFCE) labeled cardiac progenitor cells into femoral muscle areas of the murine hindlimb post‐mortem (n = 1) using 1H/19F MRI/MRS at 9.4 Tesla. Data were acquired using double‐gated spoiled gradient echo images and pulse‐acquire spectra. For the in vivo study, the temporal stability of ISO resonances was quantified using coefficient of variability (CV) (5 min) estimates.ResultsTwo ISO resonances were observed in vivo that correspond to the ‐CF3 and ‐OCHF2 moieties. CV values ranged between 3.2 and 6.4% (‐CF3) and 6.4 and 11.2% (‐OCHF2). Reductions of the ISO dose (2.0 to 1.7%) at 80 min postinduction had insignificant effects on ISO signals (P = 0.23; P = 0.71). PFCE‐labeled cells exhibited a resonance at −16.25 ppm in vitro that did not overlap with the ISO resonances, a finding that is confirmed with MRS post‐mortem using injected, labeled cells. Based on 19F MRI, similar in vivo/post‐mortem ISO compartmentalization was also confirmed in peripheral and thoracic skeletal muscles.ConclusionSignificant ISO accumulation was observed by 19F MRS in vivo with temporally stable signals over 90 min postinduction. ISO effects on PFCE labels are anticipated to be minimal but may be more prominent for perfluoropolyether or perfluorooctyl bromide labels. Level of Evidence: 1 Technical Efficacy: Stage 1J. MAGN. RESON. IMAGING 2017;45:1659–1667
Highlights
Noninvasive imaging and tracking of labeled cells in vivo and their functional impact has taken an increasing role in recent years.[1,2,3] nanoparticles (NPs) containing perfluorocarbons (PFC) have enabled direct tracking and quantification of labeled cell populations using 19F MR spectroscopy (MRS) and MRI.[4,5] Correspondingly, labeling and in vivo MRI tracking of cells has been applied in small animal models of neurovascular disease,[4,6,7,8] exhibiting potential for translational work.[9]
Two distinct ISO resonances are observed in vivo (Fig. 1D) that, respectively, correspond to the -CF3, and -OCHF2 moieties.[14,17,19]
The results demonstrate that the presence of ISO does not constitute a problem for the detection and quantification of PFCE in cardiac labeled cells.[20]
Summary
Noninvasive imaging and tracking of labeled cells in vivo and their functional impact has taken an increasing role in recent years.[1,2,3] nanoparticles (NPs) containing perfluorocarbons (PFC) have enabled direct tracking and quantification of labeled cell populations using 19F MR spectroscopy (MRS) and MRI.[4,5] Correspondingly, labeling and in vivo MRI tracking of cells has been applied in small animal models of neurovascular disease,[4,6,7,8] exhibiting potential for translational work.[9]. Most preclinical studies are routinely conducted using inhalational isoflurane (ISO),[10,11,12,13] the most commonly used volatile anesthetic owing to its minimal cardio-depressive Journal of Magnetic Resonance Imaging effects.[12] Isoflurane (CF3CH2ClOCHF2) contains two groups (moieties) of 19F atoms, which give rise to two peaks (with chemical shifts of -4 and -10.3 ppm with respect to CFCl3) in the NMR spectrum. These peaks may interfere with the detection of fluorinated agents in vivo
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