Sodium MR Imaging Detection of Mild Alzheimer Disease: Preliminary Study

BACKGROUND AND PURPOSE: There is significant interest in the development of novel noninvasive techniques for the diagnosis of Alzheimer disease (AD) and tracking its progression. Because MR imaging has detected alterations in sodium levels that correlate with cell death in stroke, we hypothesized that there would be alterations of sodium levels in the brains of patients with AD, related to AD cell death. MATERIALS AND METHODS: A total of 10 volunteers (5 with mild AD and 5 healthy control subjects) were scanned with a 20-minute sodium (23Na) MR imaging protocol on a 3T clinical scanner. RESULTS: After normalizing the signal intensity from the medial temporal lobes corresponding to the hippocampus with the ventricular signal intensity, we were able to detect a 7.5% signal intensity increase in the brains of patients with AD (AD group, 68.25% ± 3.4% vs control group, 60.75% ± 2.9%; P < .01). This signal intensity enhancement inversely correlated with hippocampal volume (AD group, 3.22 ± 0.50 cm3 vs control group, 3.91 ± 0.45 cm3; r2 = 0.50). CONCLUSIONS: This finding suggests that sodium imaging may be a clinically useful tool to detect the neuropathologic changes associated with AD.

[1]  Arijitt Borthakur,et al.  23Na MRI accurately measures fixed charge density in articular cartilage , 2002, Magnetic resonance in medicine.

[2]  P. Turski,et al.  Experimental and human brain neoplasms: detection with in vivo sodium MR imaging. , 1987, Radiology.

[3]  Peter Jezzard,et al.  Theoretical and experimental evaluation of detached endcaps for 3 T birdcage coils , 2003, Magnetic resonance in medicine.

[4]  C. Jack,et al.  MR‐based hippocampal volumetry in the diagnosis of Alzheimer's disease , 1992, Neurology.

[5]  C. V. van Echteld,et al.  Assessment of Myocardial Viability by Intracellular 23Na Magnetic Resonance Imaging , 2004, Circulation.

[6]  Arijitt Borthakur,et al.  Sodium and T1ρ MRI for molecular and diagnostic imaging of articular cartilage , 2006, NMR in biomedicine.

[7]  R. Lenkinski,et al.  MR imaging of sodium in the human brain with a fast three-dimensional gradient-recalled-echo sequence at 4 T. , 2003, Academic radiology.

[8]  Andrew J Wheaton,et al.  In vivo measurement of plaque burden in a mouse model of Alzheimer's disease , 2006, Journal of magnetic resonance imaging : JMRI.

[9]  F. Shic,et al.  Reduced glutamate neurotransmission in patients with Alzheimer's disease–an in vivo 13C magnetic resonance spectroscopy study , 2003, Magnetic Resonance Materials in Physics, Biology and Medicine.

[10]  J. Helpern,et al.  Quantitative MR imaging in Alzheimer disease. , 2006, Radiology.

[11]  T. Parrish,et al.  Relationship of elevated 23Na magnetic resonance image intensity to infarct size after acute reperfused myocardial infarction. , 1999, Circulation.

[12]  C. Jack,et al.  Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease , 1998, Neurology.

[13]  Marc Dhenain,et al.  Age-related evolution of amyloid burden, iron load, and MR relaxation times in a transgenic mouse model of Alzheimer's disease , 2006, Neurobiology of Disease.

[14]  R. Reddy,et al.  Triple quantum sodium imaging of articular cartilage , 1997, Magnetic resonance in medicine.

[15]  K R Thulborn,et al.  Comprehensive MR imaging protocol for stroke management: tissue sodium concentration as a measure of tissue viability in nonhuman primate studies and in clinical studies. , 1999, Radiology.

[16]  Terry L. Jernigan,et al.  Cerebral structure on MRI, part II: Specific changes in Alzheimer's and Huntington's diseases , 1991, Biological Psychiatry.

[17]  K. Blennow,et al.  CSF markers for incipient Alzheimer's disease , 2003, The Lancet Neurology.

[18]  A. Haley,et al.  Shortening of hippocampal spin-spin relaxation time in probable Alzheimer's disease: a 1H magnetic resonance spectroscopy study , 2004, Neuroscience Letters.

[19]  S. Neubauer,et al.  Time course of 23Na signal intensity after myocardial infarction in humans , 2004, Magnetic resonance in medicine.

[20]  J. Morris,et al.  The Uniform Data Set (UDS): Clinical and Cognitive Variables and Descriptive Data From Alzheimer Disease Centers , 2006, Alzheimer disease and associated disorders.

[21]  R. Gonzalez,et al.  Quantitative In Vivo 31P Magnetic Resonance Spectroscopy of Alzheimer Disease , 1996, Alzheimer disease and associated disorders.

[22]  K. Strange,et al.  Regulation of solute and water balance and cell volume in the central nervous system. , 1992, Journal of the American Society of Nephrology : JASN.

[23]  F. Boada,et al.  Three‐dimensional triple‐quantum–filtered 23Na imaging of in vivo human brain , 1999, Magnetic resonance in medicine.

[24]  M. F. Falangola,et al.  Quantitative MRI reveals aging‐associated T2 changes in mouse models of Alzheimer's disease , 2007, NMR in biomedicine.

[25]  F E Boada,et al.  Quantitative in vivo tissue sodium concentration maps: The effects of biexponential relaxation , 1994, Magnetic resonance in medicine.

[26]  T. R. Harrison Principles of internal medicine , 1955 .

[27]  E. Rojas,et al.  Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Miller,et al.  Transient Focal Cerebral Ischemia , 2001 .

[29]  M. Horn 23Na magnetic resonance imaging for the determination of myocardial viability: the status and the challenges. , 2004, Current vascular pharmacology.

[30]  A. Borthakur,et al.  In vivo triple quantum filtered twisted projection sodium MRI of human articular cartilage. , 1999, Journal of magnetic resonance.

[31]  Nobuhisa Iwata,et al.  19F and 1H MRI detection of amyloid beta plaques in vivo. , 2005, Nature neuroscience.

[32]  J. Bigby Harrison's Principles of Internal Medicine , 1988 .

[33]  R. Cohen The Application of Positron-Emitting Molecular Imaging Tracers in Alzheimer’s Disease , 2007, Molecular Imaging and Biology.

[34]  Michael Bock,et al.  3D radial projection technique with ultrashort echo times for sodium MRI: Clinical applications in human brain and skeletal muscle , 2007, Magnetic resonance in medicine.

[35]  R. Reddy,et al.  Detection of Residual Quadrupolar Interaction in Human Skeletal Muscle and Brain in vivo via Multiple Quantum Filtered Sodium NMR Spectra , 1995, Magnetic resonance in medicine.

[36]  G H Glover,et al.  Methodology of in vivo human sodium MR imaging at 1.5 T. , 1986, Radiology.

[37]  G. Bartzokis,et al.  Reliability of in vivo volume measures of hippocampus and other brain structures using MRI. , 1993, Magnetic resonance imaging.

[38]  Woodrow D. Deitrich,et al.  The National Alzheimer's Coordinating Center (NACC) Database: An Alzheimer Disease Database , 2004, Alzheimer disease and associated disorders.

[39]  W. Rooney,et al.  The molecular environment of intracellular sodium: 23Na NMR relaxation , 1991, NMR in biomedicine.

[40]  G. Shires,et al.  Thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) as a 23Na shift reagent for the in vivo rat liver. , 1993, Biochemistry.

[41]  R. Martins,et al.  Quantitative MR imaging R2 relaxometry in elderly participants reporting memory loss. , 2006, AJNR. American journal of neuroradiology.

[42]  M. Sugishita,et al.  [Clinical Dementia Rating (CDR)]. , 2011, Nihon rinsho. Japanese journal of clinical medicine.

[43]  C. Jack,et al.  Hippocampal transverse relaxation times in patients with Alzheimer disease. , 1997, Radiology.

[44]  Ravi S. Menon,et al.  Long component time constant of 23Na T  *2 relaxation in healthy human brain , 2004, Magnetic resonance in medicine.

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

[46]  M Alecci,et al.  Practical design of a 4 Tesla double-tuned RF surface coil for interleaved 1H and 23Na MRI of rat brain. , 2006, Journal of magnetic resonance.

[47]  W. Jagust,et al.  Quantitative NMR measurements of hippocampal atrophy in Alzheimer's disease , 1988, Magnetic resonance in medicine.

[48]  John G. Sled,et al.  Magnetization Transfer Ratio in Mild Cognitive Impairment and Dementia of Alzheimer's Type , 2002, NeuroImage.

[49]  F Andermann,et al.  Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging , 1992, Neurology.

[50]  Costin Tanase,et al.  Loss of cell ion homeostasis and cell viability in the brain: what sodium MRI can tell us. , 2005, Current topics in developmental biology.

[51]  Paul A Bottomley,et al.  Tissue sodium concentration in human brain tumors as measured with 23Na MR imaging. , 2003, Radiology.

[52]  H. Naritomi,et al.  Sequential changes on23Na MRI after cerebral infarction , 2004, Neuroradiology.

[53]  M. Mattson,et al.  Amyloid beta-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[54]  Fritz Schick,et al.  Sodium 3-D MRI of the human torso using a volume coil. , 2004, Magnetic resonance imaging.

[55]  Christian Beaulieu,et al.  In vivo sodium magnetic resonance imaging of the human brain using soft inversion recovery fluid attenuation , 2005, Magnetic resonance in medicine.

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

[57]  Christopher Clark,et al.  Disease-modifying therapies for Alzheimer disease , 2007, Neurology.

[58]  F. Jessen,et al.  Treatment monitoring and response prediction with proton MR spectroscopy in AD , 2006, Neurology.

[59]  J. Detre,et al.  Assessment of cerebral blood flow in Alzheimer's disease by spin‐labeled magnetic resonance imaging , 2000, Annals of neurology.

[60]  C. Jack,et al.  MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD , 2003, Neurology.

[61]  Nick C Fox,et al.  Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: power calculations and estimates of sample size to detect treatment effects. , 2000, Archives of neurology.