1naresh
Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

)
1naresh
Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

)
1naresh
Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

)
1naresh
Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

)
1naresh
Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => FreeToRead
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

)


  
    










































































































































    Whole-Brain N-Acetylaspartate as a Surrogate Marker of Neuronal Damage in Diffuse Neurologic Disorders | American Journal of Neuroradiology  
    



















    































    
  
  




    
    

  

      


    

      

  
  
  

    

  

    

  

                
    

      

  

    

  
      
  
  

    


Advertisement



  



  


  
  



  



    

  


  


  


  
  
  
  
  
  

  	      


    
      

    
  
    
        
    

  

    
                        

  

                
    

      

	  

		
		

			

			  

  
      
  
  

    

  
  
      
OtherREVIEW ARTICLE

  
      

  
      
Whole-Brain N-Acetylaspartate as a Surrogate Marker of Neuronal Damage in Diffuse Neurologic Disorders
  
    	
D.J. Rigotti, M. Inglese and O. Gonen

  
    	
American Journal of Neuroradiology November 2007,  28 (10) 1843-1849; DOI: https://doi.org/10.3174/ajnr.A0774 

  
  
  



  


  
  



			

		

	
	
 	
	  
  

		
		

			

			  

  
      
  
  

    
  


  
  



  
      
  
  

    

  

    

  
      
  
  

    
References
  1. ↵
    McFarland H. The lesion in multiple sclerosis: clinical, pathological, and magnetic resonance imaging considerations. J Neurol Neurosurg Psychiatry 1998;64S1:S26–S30
  2. Ferguson B, Matyszak MK, Esiri MM, et al. Axonal damage in acute multiple sclerosis lesions. Brain 1997;120:393–99
    Abstract/FREE Full Text
  3. ↵
    Bitsch A, Bruhn H, Vougioukas V, et al. Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. AJNR Am J Neuroradiol 1999;20:1619–27
    Abstract/FREE Full Text
  4. ↵
    Miller BL. A review of chemical issues in 1H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR Biomed 1991;4:47–52
    CrossRefPubMedWeb of Science
  5. ↵
    Lin A, Ross BD, Harris K, et al. Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapeutic decision making. NeuroRx 12005;2:197–214
  6. ↵
    Tallan HH, Moore S, Stein WH. N-acetyl-L-aspartic acid in brain. J Biol Chem 1956;219:257–64
    FREE Full Text
  7. ↵
    Simmons ML, Frondoza CG, Coyle JT. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 1991;45:37–45
    CrossRefPubMedWeb of Science
  8. Jenkins BG, Klivenyi P, Kustermann E, et al. Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington's disease mice. J Neurochem 2000;74:2108–19
    CrossRefPubMedWeb of Science
  9. ↵
    Moffett JR, Namboodiri MA, Cangro CB, et al. Immunohistochemical localization of N-acetylaspartate in rat brain. Neuroreport 1991;2:131–34
    PubMedWeb of Science
  10. ↵
    Baslow MH, Resnik TR. Canavan disease: analysis of the nature of the metabolic lesions responsible for development of the observed clinical symptoms. J Mol Neurosci 1997;9:109–25
    CrossRefPubMedWeb of Science
  11. ↵
    Danielsen EA, Ross B. Magnetic Resonance Spectroscopy Diagnosis of Neurological Diseases. New York: Marcel Dekker;1999 .
  12. ↵
    Ross BD, Bluml S. Magnetic resonances of the human brain. Anat Rec 2001;265:54–84
    CrossRefPubMed
  13. ↵
    Bjartmar C, Battistuta J, Terada N, et al. N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve. Ann Neurol 2002;51:51–58
    CrossRefPubMedWeb of Science
  14. ↵
    Bjartmar C, Kidd G, Mork S, et al. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 2000;48:893–901
    CrossRefPubMedWeb of Science
  15. ↵
    Goldstein FB. Biosynthesis of N-acetyl-L-aspartic acid. Biochim Biophys Acta 1959;33:583–84
    PubMed
  16. ↵
    Baslow MH, Guilfoyle DN. Effect of N-acetylaspartic acid on the diffusion coefficient of water: a proton magnetic resonance phantom method for measurement of osmolyte-obligated water. Anal Biochem 2002;311:133–38
    CrossRefPubMed
  17. ↵
    Chakraborty G, Mekala P, Yahya D, et al. Intraneuronal N-acetylaspartate supplies acetyl groups for myelin lipid synthesis: evidence for myelin-associated aspartoacylase. J Neurochem 2001;78:736–45
    CrossRefPubMedWeb of Science
  18. ↵
    Madhavarao CN, Chinopoulos C, Chandrasekaran K, et al. Characterization of the N-acetylaspartate biosynthetic enzyme from rat brain. J Neurochem 2003;86:824–35
    CrossRefPubMedWeb of Science
  19. ↵
    Yan HD, Ishihara K, Serikawa T, et al. Activation by N-acetyl-L-aspartate of acutely dissociated hippocampal neurons in rats via metabotropic glutamate receptors. Epilepsia 2003;44:1153–59
    CrossRefPubMed
  20. ↵
    Kreis R, Ernst T, Ross BD. Absolute quantitation of water and metabolites in the human brain. II. metabolite concentrations. J Magn Reson Series B 1993;102:9–19
    CrossRefWeb of Science
  21. Birken DL, Oldendorf WH. N-acetyl-L-aspartic acid: a literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev 1989;13:23–31
    CrossRefPubMedWeb of Science
  22. Arnold DL, de Stefano N, Matthews PM, et al. N-acetylaspartate: usefulness as an indicator of viable neuronal tissue. Ann Neurol 2001;50:823–25
    PubMedWeb of Science
  23. ↵
    Baslow MH. Functions of N-acetyl-L-aspartate and N-acetyl-L-aspartylglutamate in the vertebrate brain: role in glial cell-specific signaling. J Neurochem 2000;75:453–59
    CrossRefPubMedWeb of Science
  24. ↵
    Brooks WM, Friedman SD, Stidley CA. Reproducibility of 1H-MRS in vivo. Magn Reson Med 1999;41:193–97
    CrossRefPubMedWeb of Science
  25. Marshall I, Wardlaw J, Cannon J, et al. Reproducibility of metabolite peak areas in 1H MRS of brain. Magn Reson Imaging 1996;14:281–92
    CrossRefPubMedWeb of Science
  26. ↵
    Bokde AL, Teipel SJ, Zebuhr Y, et al. A new rapid landmark-based regional MRI segmentation method of the brain. J Neurol Sci 2002;194:35–40
    CrossRefPubMedWeb of Science
  27. ↵
    Inglese M, Ge Y, Filippi M, et al. Indirect evidence for early widespread gray matter involvement in relapsing-remitting multiple sclerosis. Neuroimage 2004;21:1825–29
    CrossRefPubMedWeb of Science
  28. ↵
    De Stefano N, Narayanan S, Francis SJ, et al. Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability. Arch Neurol 2002;59:1565–71
    CrossRefPubMedWeb of Science
  29. ↵
    Zaaraoui W, Fleysher L, Fleysher R, et al. Human brain-structure resolved T(2) relaxation times of proton metabolites at 3 Tesla. Magn Reson Med 2007;57:983–89
    CrossRefPubMed
  30. ↵
    Gonen O, Viswanathan AK, Catalaa I, et al. Total brain N-acetylaspartate concentration in normal, age-grouped females: quantitation with non-echo proton NMR spectroscopy. Magn Reson Med 1998;40:684–89
    PubMedWeb of Science
  31. ↵
    Udupa JK, Odhner D, Samarasekera S. 3DVIEWNIX: an open, transportable, multdimensional, multimodality, multiparametric imaging software system. Proc SPIE 1994;2164:58–73
    CrossRef
  32. ↵
    De Santi S, de Leon MJ, Rusinek H, et al. Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging 2001;22:529–39
    CrossRefPubMedWeb of Science
  33. ↵
    Ashburner J, Hutton C, Frackowiak R, et al. Identifying global anatomical differences: deformation-based morphometry. Hum Brain Mapp 1998;6:348–57
    CrossRefPubMedWeb of Science
  34. ↵
    Smith SM, De Stefano N, Jenkinson M, et al. Normalized accurate measurement of longitudinal brain change. J Comput Assist Tomogr 2001;25:466–75
    CrossRefPubMedWeb of Science
  35. ↵
    Smith SM, Zhang Y, Jenkinson M, et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage 2002;17:479–89
    CrossRefPubMedWeb of Science
  36. ↵
    Smith SM, Rao A, De Stefano N, et al. Longitudinal and cross-sectional analysis of atrophy in Alzheimer's disease: cross-validation of BSI, SIENA and SIENAX. Neuroimage 2007;36:1200–06. Epub 2007 Apr 27
    CrossRefPubMedWeb of Science
  37. ↵
    Gonen O, Grossman RI. The accuracy of whole brain N-acetylaspartate quantification. Magn Reson Imaging 2000;18:1255–58
    CrossRefPubMedWeb of Science
  38. ↵
    Filippi M, Bozzali M, Rovaris M, et al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 2003;126:433–37
    Abstract/FREE Full Text
  39. ↵
    Benedetti B, Rigotti DJ, Liu S, et al. Reproducibility of the whole-brain N-acetylaspartate level across institutions, MR scanners, and field strengths. AJNR Am J Neuroradiol 2007;28:72–75
    Abstract/FREE Full Text
  40. ↵
    Rigotti DJ, Inglese M, Babb JS, et al. Serial whole-brain N-acetylaspartate concentration in healthy young adults. AJNR Am J Neuroradiol. 2007;28:1650–51
    Abstract/FREE Full Text
  41. ↵
    Falini A, Bozzali M, Magnani G, et al. A whole brain MR spectroscopy study from patients with Alzheimer's disease and mild cognitive impairment. Neuroimage 2005;26:1159–63
    CrossRefPubMed
  42. ↵
    Scahill RI, Frost C, Jenkins R, et al. A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging. Arch Neurol 2003;60:989–94
    CrossRefPubMedWeb of Science
  43. ↵
    Compston A, Coles A. Multiple sclerosis. Lancet 2002;359:1221–31
    CrossRefPubMedWeb of Science
  44. ↵
    Sayao AL, Devonshire V, Tremlett H. Longitudinal follow-up of “benign” multiple sclerosis at 20 years. Neurology 2007;68:496–500
    Abstract/FREE Full Text
  45. ↵
    Montalban X. Primary progressive multiple sclerosis. Curr Opin Neurol 2005;18:261–66
    PubMedWeb of Science
  46. ↵
    Cree B. Emerging monoclonal antibody therapies for multiple sclerosis. Neurologist 2006;12:171–78
    CrossRefPubMedWeb of Science
  47. Hartung HP, Bar-Or A, Zoukos Y. What do we know about the mechanism of action of disease-modifying treatments in MS? J Neurol 2004;251 (suppl 5):v12–v29
    CrossRefPubMed
  48. ↵
    Fox EJ. Management of worsening multiple sclerosis with mitoxantrone: a review. Clin Ther 2006;28:461–74
    CrossRefPubMedWeb of Science
  49. ↵
    Miller DH, Thompson AJ, Filippi M. Magnetic resonance studies of abnormalities in the normal-appearing white matter and gray matter in multiple sclerosis. J Neurol 2003;250:1407–19
    CrossRefPubMedWeb of Science
  50. ↵
    Gonen O, Catalaa I, Babb JS, et al. Total brain N-acetylaspartate: a new measure of disease load in MS. Neurology 2000;54:15–19
    Abstract/FREE Full Text
  51. ↵
    Rovaris M, Gallo A, Falini A, et al. Axonal injury and overall tissue loss are not related in primary progressive multiple sclerosis. Arch Neurol 2005;62:898–902
    CrossRefPubMedWeb of Science
  52. ↵
    Ge Y, Gonen O, Inglese M, et al. Neuronal cell injury precedes brain atrophy in multiple sclerosis. Neurology 2004;62:624–27
    Abstract/FREE Full Text
  53. ↵
    Lumsden C. The clinical immunology of multiple sclerosis. In: BG Vinken PJ, ed. Handbook of Clinical Neurology. Vol.9 . North-Holland, Amsterdam: Elsevier;1970 :217–309
  54. ↵
    Gonen O, Moriarty DM, Li BS, et al. Relapsing-remitting multiple sclerosis and whole-brain N-acetylaspartate measurement: evidence for different clinical cohorts initial observations. Radiology 2002;225:261–68
    PubMedWeb of Science
  55. ↵
    Gonen O, Oberndorfer TA, Inglese M, et al. Reproducibility of 3 whole-brain N-acetylaspartate decline cohorts in relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 2007;28:267–71
    Abstract/FREE Full Text
  56. ↵
    Weinshenker BG. Natural history of multiple-sclerosis. Ann Neurol 1994;36:S6–S11
    CrossRefPubMedWeb of Science
  57. ↵
    Rovaris M, Gambini A, Gallo A, et al. Axonal injury in early multiple sclerosis is irreversible and independent of the short-term disease evolution. Neurology 2005;65:1626–30
    Abstract/FREE Full Text
  58. ↵
    Patel SH, Inglese M, Glosser G, et al. Whole-brain N-acetylaspartate level and cognitive performance in HIV infection. AJNR Am J Neuroradiol 2003;24:1587–91
    Abstract/FREE Full Text
  59. ↵
    Medana IM, Esiri MM. Axonal damage: a key predictor of outcome in human CNS diseases. Brain 2003;126:515–30
    Abstract/FREE Full Text
  60. ↵
    Cohen BA, Inglese M, Rusinek H, et al. Proton MR spectroscopy and MRI-volumetry in mild traumatic brain injury. AJNR Am J Neuroradiol 2007;28:907–13
    Abstract/FREE Full Text
  61. ↵
    DeAngelis LM. Brain tumors. N Engl J Med 2001;344:114–23
    CrossRefPubMedWeb of Science
  62. ↵
    Surawicz TS, McCarthy BJ, Kupelian V, et al. Descriptive epidemiology of primary brain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990–1994. Neuro Oncol 1999;1:14–25
    PubMed
  63. ↵
    Lunsford LD, Martinez AJ, Latchaw RE. Magnetic resonance imaging does not define tumor boundaries. Acta Radiol Suppl 1986;369:154–56
    PubMed
  64. ↵
    Cohen BA, Knopp EA, Rusinek H, et al. Assessing global invasion of newly diagnosed glial tumors with whole-brain proton MR spectroscopy. AJNR Am J Neuroradiol 2005;26:2170–77
    Abstract/FREE Full Text
  65. ↵
    Inglese M, Brown S, Johnson G, et al. Whole-brain N-acetylaspartate spectroscopy and diffusion tensor imaging in patients with newly diagnosed gliomas: a preliminary study. AJNR Am J Neuroradiol 2006;27:2137–40
    Abstract/FREE Full Text
  66. ↵
    Curnes JT. MR imaging of peripheral intracranial neoplasms: extraaxial vs intraaxial masses. J Comput Assist Tomogr 1987;11:932–37
    PubMed
  67. ↵
    Cohen BA, Knopp EA, Rusinek H, et al. Brain compression without global neuronal loss in meningiomas: whole-brain proton MR spectroscopy report of 2 cases. AJNR Am J Neuroradiol 2005;26:2178–82
    Abstract/FREE Full Text
  68. ↵
    Aupérin A, Arriagada R, PIgnon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341:476–84
    CrossRefPubMedWeb of Science
  69. ↵
    Movsas B, Li BS, Babb JS, et al. Quantifying radiation therapy-induced brain injury with whole-brain proton MR spectroscopy: initial observations. Radiology 2001;221:327–31
    CrossRefPubMedWeb of Science
  


  
  



  




  


  
  



  
      
  
  

    
  


  
  



  
      
  
  

     Back to top  


  
  



			

		

		
		

			

			  

  
        
In this issue

    
  
  

    
  


  
  



  
      
  
  

    

  

    

  
      
  
  

    


Advertisement



  



  


  
  



  



  


  
  



  
      
  
  

    

	  
  

		

          

            

  
      
  
  

     Print  


  
  



  
      
  
  

     Download PDF  


  
  



  
      
  
  

    
 Email Article
  


  
  



  
      
  
  

    
 Citation Tools
  


  
  



          

        

        
        

          

            



  
      
  
  

    

  

    

  
      
  
  

    

  
  
  
  
      
Whole-Brain N-Acetylaspartate as a Surrogate Marker of Neuronal Damage in Diffuse Neurologic Disorders
  
    	
D.J. Rigotti, M. Inglese, O. Gonen

  
    	
American Journal of Neuroradiology Nov 2007, 28 (10) 1843-1849; DOI: 10.3174/ajnr.A0774 

  
  
  



  


  
  



  
      
  
  

    

  
    
  
  
    
  
  
    
  


  


  
  



  
      
  
  

    
del.icio.us logo Twitter logo Facebook logo Mendeley logo
  


  
  



  



  


  
  



  
      
  
  

    
  


  
  



          

        

	
 	
	
	


  


  
  



  
      
  
  

    
              Purchase  


  
  



  
        
Jump to section

    
  
  

    
  


  
  



  
      
  
  

    
  


  
  



			

		

	
	
 	
	
	


    

  



  

                
    

      

  

    

  
      
  
  

    


Advertisement