Keywords: Cest, Mri, Cancer, Magnetization Transfer, Proteins, Spin Diffusion, Frequency Allocation, Irradiation, Neurodegenerative Diseases, Scanning, Chemical Exchange Saturation Transfer, Neurodegenerative Disorders, Radiofrequency Irradiation, Selective Measurements, Magnetic Resonance Imaging, Bulk Mobile Protein, Carnosine, Creatine, Dodecyl Sulfate Sodium, Globular Protein, Unclassified Drug, Adult, Analytic Method, Animal Tissue, Article, Brain Tissue, Brain Tumor, Case Report, Cerebrospinal Fluid, Clinical Article, Conformational Transition, Contrast Enhancement, Controlled Study, Human, Kernel Method, Magnetic Field, Middle Aged, Molecular Size, Molecular Weight, Mouse, Nonhuman, Nuclear Magnetic Resonance Imaging, Priority Journal, Protein Analysis, Protein Conformation, Protein Folding, Spectrofluorometry, Steady State, Tissue Homogenate, White Matter, Macromolecular Substances Analysis
, Proteins Analysis
, Signal Processing, Computer-Assisted,
Affiliations: *** IBB - CNR ***
Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of High-field Magnetic Resonance, Max-Planck-Institute for Biological Cybernetics, Tübingen, Germany
Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Institute of Biostructure and Bioimaging (IBB), National Research Council (CNR), Torino, Italy
Molecular Structure Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany
Faculty of Medicine, University of Heidelberg, Heidelberg, Germany
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Dual-frequency irradiation CEST-MRI of endogenous bulk mobile proteins
A novel MRI contrast is proposed which enables the selective detection
of endogenous bulk mobile proteins in vivo. Such a non-invasive imaging
technique may be of particular interest for many diseases associated
with pathological alterations of protein expression, such as cancer and
neurodegenerative disorders. Specificity to mobile proteins was achieved
by the selective measurement of intramolecular spin diffusion and the
removal of semi-solid macromolecular signal components by a correction
procedure. For this purpose, the approach of chemical exchange
saturation transfer (CEST) was extended to a radiofrequency (RF)
irradiation scheme at two different frequency offsets (dualCEST). Using
protein model solutions, it was demonstrated that the dualCEST technique
allows the calculation of an image contrast which is exclusively
sensitive to changes in concentration, molecular size and the folding
state of mobile proteins. With respect to application in humans,
dualCEST overcomes the selectivity limitations at relatively low
magnetic field strengths, and thus enables examinations on clinical MR
scanners. The feasibility of dualCEST examinations in humans was
verified by a proof-of-principle examination of a brain tumor patient at
3 T. With its specificity for the mobile fraction of the proteome, its
comparable sensitivity to conventional water proton MRI and its
applicability to clinical MR scanners, this technique represents a
further step towards the non-invasive imaging of proteomic changes in
humans.
Dual-frequency irradiation CEST-MRI of endogenous bulk mobile proteins