title: T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease.
abstract: In the current study, we have evaluated the performance of magnetic resonance (MR) T1rho (T1ρ) imaging and CSF biomarkers (T-tau, P-tau and Aβ-42) in characterization of Alzheimer's disease (AD) patients from mild cognitive impairment (MCI) and control subjects. With informed consent, AD (n = 27), MCI (n = 17) and control (n = 17) subjects underwent a standardized clinical assessment and brain MRI on a 1.5-T clinical-scanner. T1ρ images were obtained at four different spin-lock pulse duration (10, 20, 30 and 40 ms). T1ρ maps were generated by pixel-wise fitting of signal intensity as a function of the spin-lock pulse duration. T1ρ values from gray matter (GM) and white matter (WM) of medial temporal lobe were calculated. The binary logistic regression using T1ρ and CSF biomarkers as variables was performed to classify each group. T1ρ was able to predict 77.3% controls and 40.0% MCI while CSF biomarkers predicted 81.8% controls and 46.7% MCI. T1ρ and CSF biomarkers in combination predicted 86.4% controls and 66.7% MCI. When comparing controls with AD, T1ρ predicted 68.2% controls and 73.9% AD, while CSF biomarkers predicted 77.3% controls and 78.3% for AD. Combination of T1ρ and CSF biomarkers improved the prediction rate to 81.8% for controls and 82.6% for AD. Similarly, on comparing MCI with AD, T1ρ predicted 35.3% MCI and 81.9% AD, whereas CSF biomarkers predicted 53.3% MCI and 83.0% AD. Collectively CSF biomarkers and T1ρ were able to predict 59.3% MCI and 84.6% AD. On receiver operating characteristic analysis T1ρ showed higher sensitivity while CSF biomarkers showed greater specificity in delineating MCI and AD from controls. No significant correlation between T1ρ and CSF biomarkers, between T1ρ and age, and between CSF biomarkers and age was observed. The combined use of T1ρ and CSF biomarkers have promise to improve the early and specific diagnosis of AD. Furthermore, disease progression form MCI to AD might be easily tracked using these two parameters in combination.
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar ; Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haris
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Yadav
authors.affiliation: All India Institute of Medical Science, Ansari Nagar East, New Delhi, Delhi 110029, India.
authors.forename: Arshi
authors.initials: A
authors.lastname: Rizwan
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA ; Center for Biomedical Engineering, Indian institute of Technology, New Delhi, India.
authors.forename: Anup
authors.initials: A
authors.lastname: Singh
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA ; Center for Magnetic Resonance Research, Radiology Department, University of Illinois at Chicago, IL, USA.
authors.forename: Kejia
authors.initials: K
authors.lastname: Cai
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaura
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Section of Biomedical Image Analysis, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.affiliation: Department of Pathology & Lab Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Elias R
authors.initials: ER
authors.lastname: Melhem
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Arijitt
authors.initials: A
authors.lastname: Borthakur
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D019540:Area Under Curve; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009483:Neuropsychological Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins
keywords: AD, Alzheimer's disease; Alzheimer's disease; Aβ1-42, amyloid beta 42; CSF biomarkers; CSF, cerebrospinal fluid; FOV, field of view; GM, gray matter; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; MPRAGE, magnetization prepared rapid acquisition gradient-echo; MRI, magnetic resonance imaging; MTL, medial temporal lobe; Medial temporal lobe; Mild cognitive impairment; PET, positron emission tomography; ROC, receiver operating characteristic.; T-tau, total tau; T1rho; T1ρ, T1rho; TE, echo time; TI, inversion time; TR, repetition time; TSL, total spin lock; WM, white matter
references.citation: Neurol Sci. 2001 Feb;22(1):77-8
references.pmid: 11487210
references.citation: Neuroimage. 2011 Sep 15;58(2):469-80
references.pmid: 21718788
references.citation: Neurology. 2000 Mar 14;54(5):1099-102
references.pmid: 10720281
references.citation: J Neurol Sci. 2001 Jan 15;183(1):95-8
references.pmid: 11166802
references.citation: Neurology. 1999 May 12;52(8):1555-62
references.pmid: 10331678
references.citation: Magn Reson Med. 2005 Nov;54(5):1087-93
references.pmid: 16200568
references.citation: Neurology. 2005 Mar 8;64(5):861-5
references.pmid: 15753423
references.citation: Int J Clin Pract. 2012 Feb;66(2):185-98
references.pmid: 22257044
references.citation: Magn Reson Imaging. 1999 Sep;17(7):1001-10
references.pmid: 10463651
references.citation: Neurology. 1997 Sep;49(3):786-94
references.pmid: 9305341
references.citation: Neurology. 1999 Apr 12;52(6):1153-8
references.pmid: 10214736
references.citation: Neurobiol Aging. 2013 Aug;34(8):2003-13
references.pmid: 23540941
references.citation: J Alzheimers Dis. 2012;31 Suppl 3:S5-18
references.pmid: 22233763
references.citation: Arch Neurol. 2001 Mar;58(3):373-9
references.pmid: 11255440
references.citation: J Magn Reson Imaging. 2004 Apr;19(4):403-9
references.pmid: 15065163
references.citation: Methods Mol Biol. 2011;670:169-89
references.pmid: 20967591
references.citation: Neurobiol Aging. 2012 Jan;33(1):198.e1-14
references.pmid: 20688420
references.citation: Lancet Neurol. 2006 Mar;5(3):228-34
references.pmid: 16488378
references.citation: Ann Neurol. 2003 Aug;54(2):263-7
references.pmid: 12891683
references.citation: J Magn Reson Imaging. 2006 Nov;24(5):1011-7
references.pmid: 17036339
references.citation: Neuroimage. 2008 Jul 15;41(4):1199-205
references.pmid: 18479942
references.citation: Arch Neurol. 2001 Dec;58(12):1985-92
references.pmid: 11735772
references.citation: Am J Geriatr Psychiatry. 2012 Nov;20(11):994-1000
references.pmid: 22048323
references.citation: Dialogues Clin Neurosci. 2004 Dec;6(4):379-90
references.pmid: 22034251
references.citation: Nat Rev Neurol. 2010 Feb;6(2):67-77
references.pmid: 20139996
references.citation: Clin Chem. 2007 May;53(5):859-65
references.pmid: 17395712
references.citation: Brain. 2009 Apr;132(Pt 4):1067-77
references.pmid: 19251758
references.citation: JAMA Intern Med. 2014 Jan;174(1):133-4
references.pmid: 24081022
references.citation: J Alzheimers Dis. 2008 May;14(1):51-7
references.pmid: 18525127
references.citation: J Magn Reson Imaging. 2014 Aug;40(2):376-82
references.pmid: 24227659
references.citation: Mt Sinai J Med. 2010 Jan-Feb;77(1):69-81
references.pmid: 20101721
references.citation: Adv Exp Med Biol. 2011;701:137-42
references.pmid: 21445780
references.citation: Biochem Biophys Res Commun. 1997 Jul 18;236(2):262-4
references.pmid: 9240421
references.citation: World J Biol Psychiatry. 2003 Oct;4(4):147-55
references.pmid: 14608585
references.citation: Acad Radiol. 2004 Jul;11(7):741-9
references.pmid: 15217591
references.citation: Neurology. 2008 Dec 9;71(24):1986-92
references.pmid: 19064880
references.citation: Neuropsychiatry Neuropsychol Behav Neurol. 2000 Apr;13(2):83-8
references.pmid: 10780626
references.citation: Arch Neurol. 2005 May;62(5):770-3
references.pmid: 15883264
references.citation: J Neuroimaging. 2011 Apr;21(2):e86-90
references.pmid: 20331502
references.citation: J Intern Med. 2004 Sep;256(3):205-23
references.pmid: 15324364
references.citation: J Intern Med. 2004 Sep;256(3):224-34
references.pmid: 15324365
references.citation: Neurobiol Aging. 2000 Nov-Dec;21(6):845-61
references.pmid: 11124429
references.citation: Neurology. 2010 Jul 13;75(2):143-51
references.pmid: 20625167
references.citation: BMJ Open. 2013 Jun 20;3(6):null
references.pmid: 23794572
references.citation: JAMA. 2009 Jul 22;302(4):385-93
references.pmid: 19622817
references.citation: Neurobiol Aging. 2010 May;31(5):758-64
references.pmid: 18692273
references.citation: Neurobiol Aging. 2008 Apr;29(4):514-23
references.pmid: 17174012
references.citation: PLoS One. 2014;9(5):e97486
references.pmid: 24830386
references.citation: Alzheimers Dement. 2012 Jan;8(1):65-73
references.pmid: 22047631
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: Magn Reson Med. 2010 May;63(5):1376-82
references.pmid: 20432308
references.citation: NMR Biomed. 2006 Nov;19(7):781-821
references.pmid: 17075961