Enhanced Fluorine-19 MRI Sensitivity using a Cryogenic Radiofrequency Probe: Technical Developments and Ex Vivo Demonstration in a Mouse Model of Neuroinflammation

Neuroinflammation can be monitored using fluorine-19 (19F)-containing nanoparticles and 19F MRI. Previously we studied neuroinflammation in experimental autoimmune encephalomyelitis (EAE) using room temperature (RT) 19F radiofrequency (RF) coils and low spatial resolution 19F MRI to overcome constraints in signal-to-noise ratio (SNR). This yielded an approximate localization of inflammatory lesions. Here we used a new 19F transceive cryogenic quadrature RF probe (19F-CRP) that provides the SNR necessary to acquire superior spatially-resolved 19F MRI. First we characterized the signal-transmission profile of the 19F-CRP. The 19F-CRP was then benchmarked against a RT 19F/1H RF coil. For SNR comparison we used reference compounds including 19F-nanoparticles and ex vivo brains from EAE mice administered with 19F-nanoparticles. The transmit/receive profile of the 19F-CRP diminished with increasing distance from the surface. This was counterbalanced by a substantial SNR gain compared to the RT coil. Intraparenchymal inflammation in the ex vivo EAE brains was more sharply defined when using 150 μm isotropic resolution with the 19F-CRP, and reflected the known distribution of EAE histopathology. At this spatial resolution, most 19F signals were undetectable using the RT coil. The 19F-CRP is a valuable tool that will allow us to study neuroinflammation with greater detail in future in vivo studies.

[1]  B. Engelhardt,et al.  C-C chemokine receptor 6–regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE , 2009, Nature Immunology.

[2]  J. Kipnis Multifaceted interactions between adaptive immunity and the central nervous system , 2016, Science.

[3]  B. Dardzinski,et al.  Rapid tissue oxygen tension mapping using 19F inversion‐recovery echo‐planar imaging of P erfluoro‐15 ‐crown‐5‐ether , 1994, Magnetic resonance in medicine.

[4]  C. Müller,et al.  Selective Activation of Adenosine A2A Receptors on Immune Cells by a CD73-Dependent Prodrug Suppresses Joint Inflammation in Experimental Rheumatoid Arthritis , 2012, Science Translational Medicine.

[5]  J. Schulz-Menger,et al.  Functional and Morphological Cardiac Magnetic Resonance Imaging of Mice Using a Cryogenic Quadrature Radiofrequency Coil , 2012, PloS one.

[6]  E. Ahrens,et al.  Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine-19 MRI , 2014, Magnetic resonance in medicine.

[7]  Rolf Schubert,et al.  Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI: image reconstruction, biological half‐lives and sensitivity , 2014, NMR in biomedicine.

[8]  Boguslaw Tomanek,et al.  Double-frequency birdcage volume coils for 4.7T and 7T , 2005 .

[9]  L. Bolinger,et al.  Mapping of the Radiofrequency Field , 1993 .

[10]  Eric T Ahrens,et al.  In vivo imaging platform for tracking immunotherapeutic cells , 2005, Nature Biotechnology.

[11]  Won-Bin Young,et al.  Rapid quantification of inflammation in tissue samples using perfluorocarbon emulsion and fluorine-19 nuclear magnetic resonance. , 2011, BioTechniques.

[12]  Arno Klein,et al.  A reproducible evaluation of ANTs similarity metric performance in brain image registration , 2011, NeuroImage.

[13]  E. McVeigh,et al.  Signal-to-noise measurements in magnitude images from NMR phased arrays , 1997, Proceedings of the 19th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. 'Magnificent Milestones and Emerging Opportunities in Medical Engineering' (Cat. No.97CH36136).

[14]  P. Sawchenko,et al.  Time course and distribution of inflammatory and neurodegenerative events suggest structural bases for the pathogenesis of experimental autoimmune encephalomyelitis , 2007, The Journal of comparative neurology.

[15]  M. Rudin,et al.  Micro MRI of the mouse brain using a novel 400 MHz cryogenic quadrature RF probe , 2009, NMR in biomedicine.

[16]  A. J. Morton,et al.  Use of magnetic resonance imaging for anatomical phenotyping of the R6/2 mouse model of Huntington's disease , 2009, Neurobiology of Disease.

[17]  E. Ahrens,et al.  In vivo MRI cell tracking using perfluorocarbon probes and fluorine‐19 detection , 2013, NMR in biomedicine.

[18]  J. Lowe,et al.  Regional variations in the extent and pattern of grey matter demyelination in multiple sclerosis: a comparison between the cerebral cortex, cerebellar cortex, deep grey matter nuclei and the spinal cord , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[19]  Sebastian Temme,et al.  19F magnetic resonance imaging of endogenous macrophages in inflammation. , 2012, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[20]  Thoralf Niendorf,et al.  Advancing Cardiovascular, Neurovascular, and Renal Magnetic Resonance Imaging in Small Rodents Using Cryogenic Radiofrequency Coil Technology , 2015, Front. Pharmacol..

[21]  Allan R. Jones,et al.  Genome-wide atlas of gene expression in the adult mouse brain , 2007, Nature.

[22]  Oliver Griesbeck,et al.  Real-time in vivo analysis of T cell activation in the central nervous system using a genetically encoded calcium indicator , 2013, Nature Medicine.

[23]  S. Pacini,et al.  Commentary: Structural and functional features of central nervous system lymphatic vessels , 2015, Front. Neurosci..

[24]  Florian Schmid,et al.  Chapter 1 Pulse Sequence Considerations and Schemes , 2016 .

[25]  Rolf Schubert,et al.  In Vivo Monitoring of Inflammation After Cardiac and Cerebral Ischemia by Fluorine Magnetic Resonance Imaging , 2008, Circulation.

[26]  R. Reynolds,et al.  Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. , 2011, Brain : a journal of neurology.

[27]  D. Lodygin,et al.  Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid , 2016, Nature.

[28]  Guido Gerig,et al.  User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability , 2006, NeuroImage.

[29]  F. Franconi,et al.  Radiofrequency map of an NMR coil by imaging. , 1993, Magnetic resonance imaging.

[30]  Daniel Marek,et al.  Performance of a 200‐MHz cryogenic RF probe designed for MRI and MRS of the murine brain , 2008, Magnetic resonance in medicine.

[31]  H. Wekerle,et al.  Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions , 2009, Nature.

[32]  F. Paul,et al.  Enlargement of Cerebral Ventricles as an Early Indicator of Encephalomyelitis , 2013, PloS one.

[33]  J. Parisi,et al.  Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination , 2000, Annals of neurology.

[34]  Stefan Klein,et al.  Fast parallel image registration on CPU and GPU for diagnostic classification of Alzheimer's disease , 2013, Front. Neuroinform..

[35]  Brian B. Avants,et al.  Explicit B-spline regularization in diffeomorphic image registration , 2013, Front. Neuroinform..

[36]  Sven Junge,et al.  Cryogenic and Superconducting Coils for MRI , 2012 .

[37]  R. Henkelman Measurement of signal intensities in the presence of noise in MR images. , 1985, Medical physics.

[38]  Richard Nicholas,et al.  Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space , 2015, Neuropathology and applied neurobiology.

[39]  Britta Engelhardt,et al.  Vascular, glial, and lymphatic immune gateways of the central nervous system , 2016, Acta Neuropathologica.

[40]  T. Niendorf,et al.  Identification of Cellular Infiltrates during Early Stages of Brain Inflammation with Magnetic Resonance Microscopy , 2012, PloS one.

[41]  Dorothee P. Auer,et al.  Probe-Specific Procedure to Estimate Sensitivity and Detection Limits for 19F Magnetic Resonance Imaging , 2016, PloS one.

[42]  C. Wegner,et al.  Inflammation, demyelination, and degeneration - recent insights from MS pathology. , 2011, Biochimica et biophysica acta.

[43]  G Allan Johnson,et al.  Design of a superconducting volume coil for magnetic resonance microscopy of the mouse brain. , 2008, Journal of magnetic resonance.

[44]  F. Paul,et al.  Perfluorocarbon Particle Size Influences Magnetic Resonance Signal and Immunological Properties of Dendritic Cells , 2011, PloS one.

[45]  E. Ahrens,et al.  In vivo observation of intracellular oximetry in perfluorocarbon‐labeled glioma cells and chemotherapeutic response in the CNS using fluorine‐19 MRI , 2010, Magnetic Resonance in Medicine.

[46]  Hans Lassmann,et al.  Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. , 2006, Brain : a journal of neurology.

[47]  Michael Detmar,et al.  A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules , 2015 .

[48]  T. Niendorf,et al.  Anchoring Dipalmitoyl Phosphoethanolamine to Nanoparticles Boosts Cellular Uptake and Fluorine-19 Magnetic Resonance Signal , 2015, Scientific Reports.

[49]  Thoralf Niendorf,et al.  Visualizing Brain Inflammation with a Shingled-Leg Radio-Frequency Head Probe for 19F/1H MRI , 2013, Scientific Reports.

[50]  H. Gudbjartsson,et al.  The rician distribution of noisy mri data , 1995, Magnetic resonance in medicine.