Dynamic activity‐induced manganese‐dependent contrast magnetic resonance imaging (DAIM MRI)

Activity‐induced manganese‐dependent contrast (AIM) MRI is a hemodynamic‐independent functional MRI method that used manganese ion as an MR‐detectable contrast agent. In AIM, MnCl2 is infused intra‐arterially after the blood‐brain barrier (BBB) is opened with a hyperosmolar agent. Upon functional stimulation of the brain, Mn2+ accumulates in the active region(s) by entering active cells through voltage‐gated Ca2+ channels, causing local signal increases in T1‐weighted images. The contrast of AIM MRI depends strongly on the depth of anesthesia, and the low levels used in somatosensory stimulation studies can lead to significant nonspecific accumulation of manganese ion throughout the brain. The purpose of this study was to produce an AIM functional map of somatosensory stimulation, which separates the stimulation‐specific signal increase from the nonspecific activation due to light anesthesia. A dynamic AIM (DAIM) paradigm was developed, which used sequential MR scans during MnCl2 infusion, prior to and following functional stimulation of the brain. Stimulation‐specific functional maps were produced using time‐course analysis. The new method was tested during glutamate administration and electric stimulation of the rat forepaw. It was shown that DAIM maps are better confined to the specific region of brain activated by somatosensory stimulation as compared to AIM MRI. Magn Reson Med 48:927–933, 2002. © 2002 Wiley‐Liss, Inc.

[1]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[2]  R. H. Evans,et al.  Excitatory amino acid transmitters. , 1981, Annual review of pharmacology and toxicology.

[3]  A. Koretsky,et al.  Manganese‐enhanced MRI of mouse heart during changes in inotropy † , 2001, Magnetic resonance in medicine.

[4]  P C Lauterbur,et al.  Paramagnetic contrast agents in nuclear magnetic resonance medical imaging. , 1983, Seminars in nuclear medicine.

[5]  P. Molinoff,et al.  Basic Neurochemistry: Molecular, Cellular and Medical Aspects , 1989 .

[6]  M. Reivich,et al.  THE [14C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1 , 1977, Journal of neurochemistry.

[7]  M Hoehn-Berlage,et al.  Variation of functional MRI signal in response to frequency of somatosensory stimulation in α‐chloralose anesthetized rats , 1996, Magnetic resonance in medicine.

[8]  P. Renshaw,et al.  Sequential dynamic susceptibility contrast MR experiments in human brain: Residual contrast agent effect, steady state, and hemodynamic perturbation , 1995, Magnetic resonance in medicine.

[9]  Hiroshi Kita,et al.  Mn and Mg influxes through Ca channels of motor nerve terminals are prevented by verapamil in frogs , 1990, Brain Research.

[10]  Afonso C. Silva,et al.  In vivo neuronal tract tracing using manganese‐enhanced magnetic resonance imaging , 1998, Magnetic resonance in medicine.

[11]  W. Douglas,et al.  Indications from Mn-quenching of Fura-2 fluorescence in melanotrophs that dopamine and baclofen close Ca channels that are spontaneously open but not those opened by high [K+]O; and that Cd preferentially blocks the latter. , 1993, Cell calcium.

[12]  E. Hoffman,et al.  TOMOGRAPHIC MEASUREMENT OF LOCAL CEREBRAL GLUCOSE METABOLIC RATE IN HUMANS WITH (F‐18)2‐FLUORO-2‐DEOXY-D‐GLUCOSE: VALIDATION OF METHOD , 1980, Annals of neurology.

[13]  B. Rosen,et al.  Dynamic imaging with lanthanide chelates in normal brain: Contrast due to magnetic susceptibility effects , 1988, Magnetic resonance in medicine.

[14]  Seong-Gi Kim,et al.  Functional MRI of calcium‐dependent synaptic activity: Cross correlation with CBF and BOLD measurements , 2000, Magnetic resonance in medicine.

[15]  S. Ogawa.  Brain magnetic resonance imaging with contrast-dependent oxygenation , 1990 .

[16]  P. Hrdina.  Basic Neurochemistry: Molecular, Cellular and Medical Aspects. , 1996 .

[17]  D. Schwartzentruber,et al.  Ingested manganese chloride as a contrast agent for magnetic resonance imaging. , 1987, Magnetic resonance imaging.

[18]  P. Drapeau,et al.  Manganese fluxes and manganese‐dependent neurotransmitter release in presynaptic nerve endings isolated from rat brain. , 1984, The Journal of physiology.

[19]  R. Haworth,et al.  Comparison of Ca2+, Sr2+, and Mn2+ fluxes in mitochondria of the perfused rat heart. , 1980, Circulation research.

[20]  F. Hyder,et al.  Dynamic Magnetic Resonance Imaging of the Rat Brain during Forepaw Stimulation , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  Hiroshi Kita,et al.  Tetanic stimulation increases the frequency of miniature end-plate potentials at the frog neuromuscular junction in Mn2+-, CO2+-, and Ni2+-saline solutions , 1981, Brain Research.

[22]  E C Wong,et al.  Processing strategies for time‐course data sets in functional mri of the human brain , 1993, Magnetic resonance in medicine.

[23]  D. Fornasiero,et al.  Paramagnetic complexes of manganese(II), iron(III), and gadolinium(III) as contrast agents for magnetic resonance imaging. The influence of stability constants on the biodistribution of radioactive aminopolycarboxylate complexes. , 1987, Investigative radiology.

[24]  Donald S. Williams,et al.  Perfusion imaging , 1992, Magnetic resonance in medicine.

[25]  K. Schmidt.  Effect of Halothane Anesthesia on Regional Acetylcholine Levels in the Rat Brain , 1966, Anesthesiology.

[26]  S. H. Koenig,et al.  Magnetic field dependence of solvent proton relaxation rates induced by Gd3+ and Mn2+ complexes of various polyaza macrocyclic ligands: Implications for NMR imaging , 1986, Magnetic resonance in medicine.

[27]  G L Wolf,et al.  The oral administration of MnCl2: a potential alternative to IV injection for tissue contrast enhancement in magnetic resonance imaging. , 1984, Magnetic resonance imaging.

[28]  A. Koretsky,et al.  Manganese ion enhances T1‐weighted MRI during brain activation: An approach to direct imaging of brain function , 1997, Magnetic resonance in medicine.