Functional Neuroimaging in Clinical Neurology: A Comprehensive Review of Commonly Used Modalities

Abstract

Functional neuroimaging has revolutionized our understanding of brain physiology and pathophysiology, providing dynamic insights into neural activity that complement structural imaging. This review examines the principal functional neuroimaging modalities used in routine clinical practice, positron emission tomography (PET), single-photon emission computed tomography, magnetic resonance imaging, and their clinical applications in neurology. We present an evidence-based approach to modality selection and interpretation, emphasizing the integration of multimodal imaging data to enhance diagnostic accuracy. Recent advances in molecular imaging have transformed the evaluation of neurodegenerative diseases, moving the field from observing the downstream consequences of disease to visualizing the primary molecular pathologies in vivo. The development of specific PET ligands for amyloid-β plaques, tau neurofibrillary tangles, neurotransmitter system components, and markers of synaptic density and neuroinflammation represents a paradigm shift toward a biological definition of these disorders. This review provides practical algorithms for clinical decision-making, critically evaluates the strengths and limitations of each technique, and highlights emerging applications that promise to further advance neurological diagnosis and management toward an era of precision medicine.

Keywords

functional neuroimaging - PET - SPECT - neurodegenerative disease - epilepsy - molecular imaging

Publikationsverlauf

Eingereicht: 21. Juli 2025

Angenommen: 15. Dezember 2025

Accepted Manuscript online:
19. Dezember 2025

Artikel online veröffentlicht:
30. Dezember 2025

• References

• 1 Raichle ME. A brief history of human brain mapping. Trends Neurosci 2009; 32 (02) 118-126
• 2 Poldrack RA, Farah MJ. Progress and challenges in probing the human brain. Nature 2015; 526 (7573) 371-379
• 3 Sokoloff L. Energetics of functional activation in neural tissues. Neurochem Res 1999; 24 (02) 321-329
• 4 Lammertsma AA. Forward to the past: the case for quantitative PET imaging. J Nucl Med 2017; 58 (07) 1019-1024
• 5 Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron 2009; 62 (01) 42-52
• 6 Mesulam MM. From sensation to cognition. Brain 1998; 121 (Pt 6): 1013-1052
• 7 Bandettini PA. Twenty years of functional MRI: the science and the stories. Neuroimage 2012; 62 (02) 575-588
• 8 Phelps ME. Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci U S A 2000; 97 (16) 9226-9233
• 9 Ametamey SM, Honer M, Schubiger PA. Molecular imaging with PET. Chem Rev 2008; 108 (05) 1501-1516
• 10 Bailey DL, Townsend DW, Valk PE, Maisey MN. Positron Emission Tomography: Basic Sciences. London: Springer-Verlag; 2005
• 11 Miller PW, Long NJ, Vilar R, Gee AD. Synthesis of 11C, 18F, 15O, and 13N radiolabels for positron emission tomography. Angew Chem Int Ed Engl 2008; 47 (47) 8998-9033
• 12 Cherry SR, Sorenson JA, Phelps ME. Physics in Nuclear Medicine. 4th ed. Philadelphia: Elsevier/Saunders; 2012
• 13 Lewellen TK. Recent developments in PET detector technology. Phys Med Biol 2008; 53 (17) R287-R317
• 14 Kinahan PE, Fletcher JW. Positron emission tomography-computed tomography standardized uptake values in clinical practice and assessing response to therapy. Semin Ultrasound CT MR 2010; 31 (06) 496-505
• 15 Herholz K, Heiss WD. Positron emission tomography in clinical neurology. Mol Imaging Biol 2004; 6 (04) 239-269
• 16 Sokoloff L, Reivich M, Kennedy C. 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. J Neurochem 1977; 28 (05) 897-916
• 17 Wong DF, Gjedde A, Wagner Jr HN. Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands. J Cereb Blood Flow Metab 1986; 6 (02) 137-146
• 18 Volkow ND, Fowler JS, Wang GJ. Positron emission tomography and single-photon emission computed tomography in substance abuse research. Semin Nucl Med 2003; 33 (02) 114-128
• 19 Villemagne VL, Fodero-Tavoletti MT, Masters CL, Rowe CC. Tau imaging: early progress and future directions. Lancet Neurol 2015; 14 (01) 114-124
• 20 Clark CM, Pontecorvo MJ, Beach TG. et al; AV-45-A16 Study Group. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol 2012; 11 (08) 669-678
• 21 Herscovitch P, Markham J, Raichle ME. Brain blood flow measured with intravenous H2(15)O. I. Theory and error analysis. J Nucl Med 1983; 24 (09) 782-789
• 22 Turkheimer FE, Edison P, Pavese N. et al. Reference and target region modeling of [11C]-(R)-PK11195 brain studies. J Nucl Med 2007; 48 (01) 158-167
• 23 Magistretti PJ, Pellerin L. Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci 1999; 354 (1387) 1155-1163
• 24 Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 1979; 6 (05) 371-388
• 25 Mosconi L. Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD. Eur J Nucl Med Mol Imaging 2005; 32 (04) 486-510
• 26 Theodore WH. Presurgical focus localization in epilepsy: PET and SPECT. Semin Nucl Med 2017; 47 (01) 44-53
• 27 Henry TR, Engel Jr J, Mazziotta JC. Clinical evaluation of interictal fluorine-18-fluorodeoxyglucose PET in partial epilepsy. J Nucl Med 1993; 34 (11) 1892-1898
• 28 Knowlton RC. The role of FDG-PET, ictal SPECT, and MEG in the epilepsy surgery evaluation. Epilepsy Behav 2006; 8 (01) 91-101
• 29 Willmann O, Wennberg R, May T, Woermann FG, Pohlmann-Eden B. The contribution of 18F-FDG PET in preoperative epilepsy surgery evaluation for patients with temporal lobe epilepsy: a meta-analysis. Seizure 2007; 16 (06) 509-520
• 30 Kim YK, Lee DS, Lee SK, Chung CK, Chung JK, Lee MC. (18)F-FDG PET in localization of frontal lobe epilepsy: comparison of visual and SPM analysis. J Nucl Med 2002; 43 (09) 1167-1174
• 31 Carne RP, O'Brien TJ, Kilpatrick CJ. et al. MRI-negative PET-positive temporal lobe epilepsy: a distinct surgically remediable syndrome. Brain 2004; 127 (Pt 10): 2276-2285
• 32 Chassoux F, Rodrigo S, Semah F. et al. FDG-PET improves surgical outcome in negative MRI Taylor-type focal cortical dysplasias. Neurology 2010; 75 (24) 2168-2175
• 33 Salamon N, Kung J, Shaw SJ. et al. FDG-PET/MRI coregistration improves detection of cortical dysplasia in patients with epilepsy. Neurology 2008; 71 (20) 1594-1601
• 34 Theodore WH, Dickens D, Wiggs EA. et al. Effect of valproate on cerebral metabolism and blood flow: an 18F–2-deoxyglucose and 15O water positron emission tomography study. Epilepsia 2002; 43 (12) 1515-1520
• 35 Herholz K. FDG PET and differential diagnosis of dementia. Alzheimer Dis Assoc Disord 1995; 9 (01) 6-16
• 36 Foster NL, Heidebrink JL, Clark CM. et al. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease. Brain 2007; 130 (Pt 10): 2616-2635
• 37 Mosconi L, Tsui WH, Herholz K. et al. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer's disease, and other dementias. J Nucl Med 2008; 49 (03) 390-398
• 38 Teune LK, Bartels AL, de Jong BM. et al. Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord 2010; 25 (14) 2395-2404
• 39 Nestor PJ, Altomare D, Festari C. et al; EANM-EAN Task Force for the Prescription of FDG-PET for Dementing Neurodegenerative Disorders. Clinical utility of FDG-PET for the differential diagnosis among the main forms of dementia. Eur J Nucl Med Mol Imaging 2018; 45 (09) 1509-1525
• 40 Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol 1997; 42 (01) 85-94
• 41 Drzezga A, Lautenschlager N, Siebner H. et al. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 2003; 30 (08) 1104-1113
• 42 Ishii K, Sakamoto S, Sasaki M. et al. Cerebral glucose metabolism in patients with frontotemporal dementia. J Nucl Med 1998; 39 (11) 1875-1878
• 43 Matias-Guiu JA, Cabrera-Martin MN, Matias-Guiu J. et al. FDG-PET/CT or MRI for the diagnosis of primary progressive aphasia? A pilot study with pathological correlation. J Alzheimers Dis 2015; 47 (04) 873-883
• 44 Imamura T, Ishii K, Hirono N. et al. Occipital glucose metabolism in dementia with Lewy bodies with and without Parkinsonism: a study using positron emission tomography. Dement Geriatr Cogn Disord 2001; 12 (03) 194-197
• 45 Lim SM, Katsifis A, Villemagne VL. et al. The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for diagnosis of dementia with Lewy bodies. J Nucl Med 2009; 50 (10) 1638-1645
• 46 Mielke R, Heiss WD. Positron emission tomography for diagnosis of Alzheimer's disease and vascular dementia. J Neural Transm Suppl 1998; 53: 237-250
• 47 Eckert T, Barnes A, Dhawan V. et al. FDG PET in the differential diagnosis of Parkinsonian disorders. Neuroimage 2005; 26 (03) 912-921
• 48 Niethammer M, Tang CC, Feigin A. et al. A disease-specific metabolic brain network associated with corticobasal degeneration. Brain 2014; 137 (Pt 11): 3036-3046
• 49 Di Chiro G. Positron emission tomography using [18F] fluorodeoxyglucose in brain tumors. A powerful diagnostic and prognostic tool. Invest Radiol 1987; 22 (05) 360-371
• 50 Padma MV, Said S, Jacobs M. et al. Prediction of pathology and survival by FDG PET in gliomas. J Neurooncol 2003; 64 (03) 227-237
• 51 Ricci PE, Karis JP, Heiserman JE, Fram EK, Bice AN, Drayer BP. Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography?. AJNR Am J Neuroradiol 1998; 19 (03) 407-413
• 52 Chao ST, Suh JH, Raja S, Lee SY, Barnett G. The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. Int J Cancer 2001; 96 (03) 191-197
• 53 Nihashi T, Dahabreh IJ, Terasawa T. Diagnostic accuracy of PET for recurrent glioma diagnosis: a meta-analysis. AJNR Am J Neuroradiol 2013; 34 (05) 944-950 , S1–S11
• 54 Mathis CA, Wang Y, Klunk WE. Imaging beta-amyloid plaques and neurofibrillary tangles in the aging human brain. Curr Pharm Des 2004; 10 (13) 1469-1492
• 55 Probasco JC, Solnes L, Nalluri A. et al. Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm 2017; 4 (04) e352
• 56 Mathis CA, Wang Y, Klunk WE. Imaging beta-amyloid plaques and neurofibrillary tangles in the aging human brain. Curr Pharm Des 2004; 10 (13) 1469-1492
• 57 Villemagne VL, Doré V, Burnham SC, Masters CL, Rowe CC. Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions. Nat Rev Neurol 2018; 14 (04) 225-236
• 58 Jack Jr CR, Bennett DA, Blennow K. et al; Contributors. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement 2018; 14 (04) 535-562
• 59 Jack Jr CR, Bennett DA, Blennow K. et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016; 87 (05) 539-547
• 60 Sperling RA, Aisen PS, Beckett LA. et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7 (03) 280-292
• 61 Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002; 297 (5580) 353-356
• 62 Klunk WE, Engler H, Nordberg A. et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 2004; 55 (03) 306-319
• 63 Mathis CA, Wang Y, Holt DP, Huang GF, Debnath ML, Klunk WE. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem 2003; 46 (13) 2740-2754
• 64 Minoshima S, Drzezga AE, Barthel H. et al. SNMMI procedure standard/EANM practice guideline for amyloid PET imaging of the brain 1.0. J Nucl Med 2016; 57 (08) 1316-1322
• 65 Klunk WE, Koeppe RA, Price JC. et al. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement 2015; 11 (01) 1-15.e1 , 4
• 66 Ossenkoppele R, Jansen WJ, Rabinovici GD. et al; Amyloid PET Study Group. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. JAMA 2015; 313 (19) 1939-1949
• 67 Jansen WJ, Ossenkoppele R, Knol DL. et al; Amyloid Biomarker Study Group. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA 2015; 313 (19) 1924-1938
• 68 Schöll M, Maass A, Mattsson N. et al. Biomarkers for tau pathology. Mol Cell Neurosci 2019; 97: 18-33
• 69 Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 1992; 42 (3 Pt 1): 631-639
• 70 Pontecorvo MJ, Devous Sr MD, Navitsky M. et al; 18F-AV-1451-A05 investigators. Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition. Brain 2017; 140 (03) 748-763
• 71 Lowe VJ, Curran G, Fang P. et al. An autoradiographic evaluation of AV-1451 Tau PET in dementia. Acta Neuropathol Commun 2016; 4 (01) 58
• 72 Lohith TG, Bennacef I, Vandenberghe R. et al. Brain imaging of Alzheimer dementia patients and elderly controls with (18)F-MK-6240, a PET tracer targeting neurofibrillary tangles. J Nucl Med 2019; 60 (01) 107-114
• 73 Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82 (04) 239-259
• 74 Ossenkoppele R, Schonhaut DR, Schöll M. et al. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. Brain 2016; 139 (Pt 5): 1551-1567
• 75 Johnson KA, Minoshima S, Bohnen NI. et al; Alzheimer's Association, Society of Nuclear Medicine and Molecular Imaging, Amyloid Imaging Taskforce. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer's Association. Alzheimers Dement 2013; 9 (01) e-1-e-16
• 76 Rabinovici GD, Gatsonis C, Apgar C. et al. Association of amyloid positron emission tomography with subsequent change in clinical management among Medicare beneficiaries with mild cognitive impairment or dementia. JAMA 2019; 321 (13) 1286-1294
• 77 de Wilde A, van der Flier WM, Pelkmans W. et al. Association of amyloid positron emission tomography with changes in diagnosis and patient treatment in an unselected memory clinic cohort: the ABIDE project. JAMA Neurol 2018; 75 (09) 1062-1070
• 78 Shaw LM, Arias J, Blennow K. et al. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer's disease. Alzheimers Dement 2018; 14 (11) 1505-1521
• 79 Jack Jr CR, Wiste HJ, Schwarz CG. et al. Longitudinal tau PET in ageing and Alzheimer's disease. Brain 2018; 141 (05) 1517-1528
• 80 Villemagne VL, Harada R, Doré V. et al. Assessing reactive astrogliosis with 18F-SMBT-1 across the Alzheimer's disease spectrum. J Nucl Med 2022; 63 (10) 1560-1569
• 81 Koga S, Sekiya H, Kondru N, Ross OA, Dickson DW. Neuropathology and molecular diagnosis of Synucleinopathies. Mol Neurodegener 2021; 16 (01) 83
• 82 Korat Š, Bidesi NSR, Bonanno F. et al. Alpha-synuclein PET tracer development-an overview about current efforts. Pharmaceuticals (Basel) 2021; 14 (09) 847
• 83 Maurer A, Leonov A, Ryazanov S. et al. 11C radiolabeling of anle253b: a putative PET tracer for Parkinson's disease that binds to α-synuclein fibrils in vitro and crosses the blood-brain barrier. ChemMedChem 2020; 15 (05) 411-415
• 84 Nelson PT, Dickson DW, Trojanowski JQ. et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain 2019; 142 (06) 1503-1527
• 85 Buée L, Bussière T, Buée-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 2000; 33 (01) 95-130
• 86 Tagai K, Ono M, Kubota M. et al. High-contrast in vivo imaging of tau pathologies in Alzheimer's and non-Alzheimer's disease tauopathies. Neuron 2021; 109 (01) 42-58.e8
• 87 Respondek G, Höglinger GU. The phenotypic spectrum of progressive supranuclear palsy. Parkinsonism Relat Disord 2016; 22 (Suppl. 01) S34-S36
• 88 Brendel M, Barthel H, van Eimeren T. et al. Assessment of 18F-PI-2620 as a biomarker in progressive supranuclear palsy. JAMA Neurol 2020; 77 (11) 1408-1419
• 89 Robinson JL, Lee EB, Xie SX. et al. Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain 2018; 141 (07) 2181-2193
• 90 Volkow ND, Fowler JS, Wang GJ, Baler R, Telang F. Imaging dopamine's role in drug abuse and addiction. Neuropharmacology 2009; 56 (suppl 1): 3-8
• 91 Innis RB, Cunningham VJ, Delforge J. et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 2007; 27 (09) 1533-1539
• 92 Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. Neuroimage 1996; 4 (3 Pt 1): 153-158
• 93 Brooks DJ. Molecular imaging of dopamine transporters. Ageing Res Rev 2016; 30: 114-121
• 94 Jokinen P, Helenius H, Rauhala E, Brück A, Eskola O, Rinne JO. Simple ratio analysis of 18F-fluorodopa uptake in striatal subregions separates patients with early Parkinson disease from healthy controls. J Nucl Med 2009; 50 (06) 893-899
• 95 Antonini A, Schwarz J, Oertel WH, Beer HF, Madeja UD, Leenders KL. [11C]raclopride and positron emission tomography in previously untreated patients with Parkinson's disease: Influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors. Neurology 1994; 44 (07) 1325-1329
• 96 Kuhl DE, Koeppe RA, Minoshima S. et al. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology 1999; 52 (04) 691-699
• 97 Petrou M, Frey KA, Kilbourn MR. et al. In vivo imaging of human cholinergic nerve terminals with (-)-5-(18)F-fluoroethoxybenzovesamicol: biodistribution, dosimetry, and tracer kinetic analyses. J Nucl Med 2014; 55 (03) 396-404
• 98 Bohnen NI, Yarnall AJ, Weil RS. et al. Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches. Lancet Neurol 2022; 21 (04) 381-392
• 99 Meyer JH, Wilson AA, Ginovart N. et al. Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. Am J Psychiatry 2001; 158 (11) 1843-1849
• 100 Savitz J, Lucki I, Drevets WC. 5-HT(1A) receptor function in major depressive disorder. Prog Neurobiol 2009; 88 (01) 17-31
• 101 McGinnity CJ, Hammers A, Riaño Barros DA. et al. Initial evaluation of 18F-GE-179, a putative PET Tracer for activated N-methyl D-aspartate receptors. J Nucl Med 2014; 55 (03) 423-430
• 102 Finnema SJ, Scheinin M, Shahid M. et al. Application of cross-species PET imaging to assess neurotransmitter release in brain. Psychopharmacology (Berl) 2015; 232 (21–22): 4129-4157
• 103 Wong DF, Tauscher J, Gründer G. The role of imaging in proof of concept for CNS drug discovery and development. Neuropsychopharmacology 2009; 34 (01) 187-203
• 104 Wintermark M, Sesay M, Barbier E. et al. Comparative overview of brain perfusion imaging techniques. Stroke 2005; 36 (09) e83-e99
• 105 Raichle ME, Martin WR, Herscovitch P, Mintun MA, Markham J. Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. J Nucl Med 1983; 24 (09) 790-798
• 106 Baron JC, Jones T. Oxygen metabolism, oxygen extraction and positron emission tomography: Historical perspective and impact on basic and clinical neuroscience. Neuroimage 2012; 61 (02) 492-504
• 107 Kuroda S, Houkin K, Kamiyama H, Mitsumori K, Iwasaki Y, Abe H. Long-term prognosis of medically treated patients with internal carotid or middle cerebral artery occlusion: can acetazolamide test predict it?. Stroke 2001; 32 (09) 2110-2116
• 108 Powers WJ, Grubb Jr RL, Darriet D, Raichle ME. Cerebral blood flow and cerebral metabolic rate of oxygen requirements for cerebral function and viability in humans. J Cereb Blood Flow Metab 1985; 5 (04) 600-608
• 109 Derdeyn CP, Videen TO, Yundt KD. et al. Variability of cerebral blood volume and oxygen extraction: stages of cerebral haemodynamic impairment revisited. Brain 2002; 125 (Pt 3): 595-607
• 110 Packard RR, Huang SC, Dahlbom M, Czernin J, Maddahi J. Absolute quantitation of myocardial blood flow in human subjects with or without myocardial ischemia using dynamic flurpiridaz F 18 PET. J Nucl Med 2014; 55 (09) 1438-1444
• 111 Terry RD, Masliah E, Salmon DP. et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991; 30 (04) 572-580
• 112 Chen MK, Mecca AP, Naganawa M. et al. Assessing synaptic density in Alzheimer disease with synaptic vesicle glycoprotein 2A positron emission tomographic imaging. JAMA Neurol 2018; 75 (10) 1215-1224
• 113 Mecca AP, Chen MK, O'Dell RS. et al. In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET. Alzheimers Dement 2020; 16 (07) 974-982
• 114 Bastin C, Bahri MA, Meyer F. et al. In vivo imaging of synaptic loss in Alzheimer's disease with [18F]UCB-H positron emission tomography. Eur J Nucl Med Mol Imaging 2020; 47 (02) 390-402
• 115 van Aalst J, Ceccarini J, Demyttenaere K, Sunaert S, Van Laere K. What has neuroimaging taught us on the neurobiology of yoga? A review. Front Integr Nuerosci 2020; 14: 34
• 116 Heneka MT, Carson MJ, El Khoury J. et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol 2015; 14 (04) 388-405
• 117 Venneti S, Lopresti BJ, Wiley CA. The peripheral benzodiazepine receptor (Translocator protein 18kDa) in microglia: from pathology to imaging. Prog Neurobiol 2006; 80 (06) 308-322
• 118 Owen DR, Yeo AJ, Gunn RN. et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab 2012; 32 (01) 1-5
• 119 Carter SF, Schöll M, Almkvist O. et al. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med 2012; 53 (01) 37-46
• 120 Horti AG, Naik R, Foss CA. et al. PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R). Proc Natl Acad Sci U S A 2019; 116 (05) 1686-1691
• 121 Beaino W, Janssen B, Kooij G. et al. Purinergic receptors P2Y12R and P2 × 7R: potential targets for PET imaging of microglia phenotypes in multiple sclerosis. J Neuroinflammation 2017; 14 (01) 259
• 122 Terada T, Obi T, Bunai T. et al. In vivo mitochondrial and glycolytic impairments in patients with Alzheimer disease. Neurology 2020; 94 (15) e1592-e1604
• 123 Toyohara J, Sakata M, Ishiwata K. Imaging of sigma1 receptors in the human brain using PET and [11C]SA4503. Cent Nerv Syst Agents Med Chem 2009; 9 (03) 190-196
• 124 Ceccarini J, Kuepper R, Kemels D, van Os J, Henquet C, Van Laere K. [18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users. Addict Biol 2015; 20 (02) 357-367
• 125 Catafau AM. Brain SPECT in clinical practice. Part I: perfusion. J Nucl Med 2001; 42 (02) 259-271
• 126 Van Paesschen W, Dupont P, Sunaert S, Goffin K, Van Laere K. The use of SPECT and PET in routine clinical practice in epilepsy. Curr Opin Neurol 2007; 20 (02) 194-202
• 127 Khalil MM, Tremoleda JL, Bayomy TB, Gsell W. Molecular SPECT imaging: an overview. Int J Mol Imaging 2011; 2011: 796025
• 128 Saha GB. Fundamentals of Nuclear Pharmacy. 7th ed. New York: Springer; 2018
• 129 Neirinckx RD, Canning LR, Piper IM. et al. Technetium-99m d,l-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion. J Nucl Med 1987; 28 (02) 191-202
• 130 Tatsch K, Poepperl G. Nigrostriatal dopamine terminal imaging with dopamine transporter SPECT: an update. J Nucl Med 2013; 54 (08) 1331-1338
• 131 Rahmim A, Zaidi H. PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun 2008; 29 (03) 193-207
• 132 Valotassiou V, Malamitsi J, Papatriantafyllou J. et al. SPECT and PET imaging in Alzheimer's disease. Ann Nucl Med 2018; 32 (09) 583-593
• 133 Yeo JM, Lim X, Khan Z, Pal S. Systematic review of the diagnostic utility of SPECT imaging in dementia. Eur Arch Psychiatry Clin Neurosci 2013; 263 (07) 539-552
• 134 Imabayashi E, Matsuda H, Asada T. et al. Superiority of 3-dimensional stereotactic surface projection analysis over visual inspection in discrimination of patients with very early Alzheimer's disease from controls using brain perfusion SPECT. J Nucl Med 2004; 45 (09) 1450-1457
• 135 la Fougère C, Rominger A, Förster S, Geisler J, Bartenstein P. PET and SPECT in epilepsy: a critical review. Epilepsy Behav 2009; 15 (01) 50-55
• 136 Devous Sr MD, Thisted RA, Morgan GF, Leroy RF, Rowe CC. SPECT brain imaging in epilepsy: a meta-analysis. J Nucl Med 1998; 39 (02) 285-293
• 137 O'Brien TJ, So EL, Mullan BP. et al. Subtraction ictal SPECT co-registered to MRI improves clinical usefulness of SPECT in localizing the surgical seizure focus. Neurology 1998; 50 (02) 445-454
• 138 Desai A, Bekelis K, Thadani VM. et al. Interictal PET and ictal subtraction SPECT: sensitivity in the detection of seizure foci in patients with medically intractable epilepsy. Epilepsia 2013; 54 (02) 341-350
• 139 Booij J, Tissingh G, Boer GJ. et al. [123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease. J Neurol Neurosurg Psychiatry 1997; 62 (02) 133-140
• 140 Darcourt J, Booij J, Tatsch K. et al. EANM procedure guidelines for brain neurotransmission SPECT using (123)I-labelled dopamine transporter ligands, version 2. Eur J Nucl Med Mol Imaging 2010; 37 (02) 443-450
• 141 Benamer TS, Patterson J, Grosset DG. et al. Accurate differentiation of Parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord 2000; 15 (03) 503-510
• 142 Kaasinen V, Vahlberg T. Striatal dopamine in Parkinson disease: a meta-analysis of imaging studies. Ann Neurol 2017; 82 (06) 873-882
• 143 Rizzo G, Copetti M, Arcuti S, Martino D, Fontana A, Logroscino G. Accuracy of clinical diagnosis of Parkinson disease: a systematic review and meta-analysis. Neurology 2016; 86 (06) 566-576
• 144 Pirker W. Correlation of dopamine transporter imaging with Parkinsonian motor handicap: how close is it?. Mov Disord 2003; 18 (Suppl. 07) S43-S51
• 145 Ogawa S, Lee TM, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A 1990; 87 (24) 9868-9872
• 146 Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature 2001; 412 (6843) 150-157
• 147 Binder JR, Desai RH, Graves WW, Conant LL. Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. Cereb Cortex 2009; 19 (12) 2767-2796
• 148 Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 1995; 34 (04) 537-541
• 149 Black DF, Vachha B, Mian A. et al. American Society of Functional Neuroradiology-recommended fMRI paradigm algorithms for presurgical language assessment. AJNR Am J Neuroradiol 2017; 38 (10) E65-E73
• 150 Janecek JK, Swanson SJ, Sabsevitz DS. et al. Language lateralization by fMRI and Wada testing in 229 patients with epilepsy: rates and predictors of discordance. Epilepsia 2013; 54 (02) 314-322
• 151 Agarwal S, Sair HI, Yahyavi-Firouz-Abadi N, Airan R, Pillai JJ. Neurovascular uncoupling in resting state fMRI demonstrated in patients with primary brain gliomas. J Magn Reson Imaging 2016; 43 (03) 620-626
• 152 Gotman J, Grova C, Bagshaw A, Kobayashi E, Aghakhani Y, Dubeau F. Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. Proc Natl Acad Sci U S A 2005; 102 (42) 15236-15240
• 153 Laufs H, Hamandi K, Salek-Haddadi A, Kleinschmidt AK, Duncan JS, Lemieux L. Temporal lobe interictal epileptic discharges affect cerebral activity in “default mode” brain regions. Hum Brain Mapp 2007; 28 (10) 1023-1032
• 154 Greicius MD, Srivastava G, Reiss AL, Menon V. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A 2004; 101 (13) 4637-4642
• 155 Brier MR, Thomas JB, Snyder AZ. et al. Loss of intranetwork and internetwork resting state functional connections with Alzheimer's disease progression. J Neurosci 2012; 32 (26) 8890-8899
• 156 Detre JA, Leigh JS, Williams DS, Koretsky AP. Perfusion imaging. Magn Reson Med 1992; 23 (01) 37-45
• 157 Edelman RR, Siewert B, Darby DG. et al. Qualitative mapping of cerebral blood flow and functional localization with echo-planar MR imaging and signal targeting with alternating radio frequency. Radiology 1994; 192 (02) 513-520
• 158 Silva AC, Zhang W, Williams DS, Koretsky AP. Multi-slice MRI of rat brain perfusion during amphetamine stimulation using arterial spin labeling. Magn Reson Med 1995; 33 (02) 209-214
• 159 Dai W, Garcia D, de Bazelaire C, Alsop DC. Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn Reson Med 2008; 60 (06) 1488-1497
• 160 Alsop DC, Detre JA, Golay X. et al. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med 2015; 73 (01) 102-116
• 161 Zaharchuk G. Arterial spin label imaging of acute ischemic stroke and transient ischemic attack. Neuroimaging Clin N Am 2011; 21 (02) 285-301 , x
• 162 Bivard A, Krishnamurthy V, Stanwell P. et al. Arterial spin labeling versus bolus-tracking perfusion in hyperacute stroke. Stroke 2014; 45 (01) 127-133
• 163 Lee M, Zaharchuk G, Guzman R, Achrol A, Bell-Stephens T, Steinberg GK. Quantitative hemodynamic studies in moyamoya disease: a review. Neurosurg Focus 2009; 26 (04) E5
• 164 MacIntosh BJ, Lindsay AC, Kylintireas I. et al. Multiple inflow pulsed arterial spin-labeling reveals delays in the arterial arrival time in minor stroke and transient ischemic attack. AJNR Am J Neuroradiol 2010; 31 (10) 1892-1894
• 165 Du AT, Jahng GH, Hayasaka S. et al. Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI. Neurology 2006; 67 (07) 1215-1220
• 166 Dai W, Lopez OL, Carmichael OT, Becker JT, Kuller LH, Gach HM. Mild cognitive impairment and alzheimer disease: patterns of altered cerebral blood flow at MR imaging. Radiology 2009; 250 (03) 856-866
• 167 Hu WT, Wang Z, Lee VM, Trojanowski JQ, Detre JA, Grossman M. Distinct cerebral perfusion patterns in FTLD and AD. Neurology 2010; 75 (10) 881-888
• 168 Taylor JP, Firbank MJ, He J. et al. Visual cortex in dementia with Lewy bodies: magnetic resonance imaging study. Br J Psychiatry 2012; 200 (06) 491-498
• 169 Pizzini FB, Farace P, Manganotti P. et al. Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase: PASL vs DSC-MRI. Magn Reson Imaging 2013; 31 (06) 1001-1005
• 170 Wolf RL, Alsop DC, Levy-Reis I. et al. Detection of mesial temporal lobe hypoperfusion in patients with temporal lobe epilepsy by use of arterial spin labeled perfusion MR imaging. AJNR Am J Neuroradiol 2001; 22 (07) 1334-1341
• 171 Oz G, Alger JR, Barker PB. et al; MRS Consensus Group. Clinical proton MR spectroscopy in central nervous system disorders. Radiology 2014; 270 (03) 658-679
• 172 Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM. N-acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol 2007; 81 (02) 89-131
• 173 Miller BL. A review of chemical issues in 1H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR Biomed 1991; 4 (02) 47-52
• 174 Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 1992; 281 (Pt 1): 21-40
• 175 Brand A, Richter-Landsberg C, Leibfritz D. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 1993; 15 (3–5): 289-298
• 176 Prichard J, Rothman D, Novotny E. et al. Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation. Proc Natl Acad Sci U S A 1991; 88 (13) 5829-5831
• 177 Mullins PG, McGonigle DJ, O'Gorman RL. et al; Cardiff Symposium on MRS of GABA. Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA. Neuroimage 2014; 86: 43-52
• 178 Sundgren PC, Nagesh V, Elias A. et al. Metabolic alterations: a biomarker for radiation-induced normal brain injury-an MR spectroscopy study. J Magn Reson Imaging 2009; 29 (02) 291-297
• 179 Andronesi OC, Kim GS, Gerstner E. et al. Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy. Sci Transl Med 2012; 4 (116) 116ra4
• 180 Cendes F, Caramanos Z, Andermann F, Dubeau F, Arnold DL. Proton magnetic resonance spectroscopic imaging and magnetic resonance imaging volumetry in the lateralization of temporal lobe epilepsy: a series of 100 patients. Ann Neurol 1997; 42 (05) 737-746
• 181 Malmgren K, Thom M. Hippocampal sclerosis–origins and imaging. Epilepsia 2012; 53 (Suppl. 04) 19-33
• 182 Kantarci K, Jack Jr CR, Xu YC. et al. Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: A 1H MRS study. Neurology 2000; 55 (02) 210-217
• 183 Ernst T, Chang L, Melchor R, Mehringer CM. Frontotemporal dementia and early Alzheimer disease: differentiation with frontal lobe H-1 MR spectroscopy. Radiology 1997; 203 (03) 829-836
• 184 Pioro EP, Majors AW, Mitsumoto H, Nelson DR, Ng TC. 1H-MRS evidence of neurodegeneration and excess glutamate + glutamine in ALS medulla. Neurology 1999; 53 (01) 71-79
• 185 Janson CG, McPhee SW, Francis J. et al. Natural history of Canavan disease revealed by proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted MRI. Neuropediatrics 2006; 37 (04) 209-221
• 186 Jan W, Zimmerman RA, Wang ZJ, Berry GT, Kaplan PB, Kaye EM. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology 2003; 45 (06) 393-399
• 187 Lin DD, Crawford TO, Barker PB. Proton MR spectroscopy in the diagnostic evaluation of suspected mitochondrial disease. AJNR Am J Neuroradiol 2003; 24 (01) 33-41
• 188 Blennow G, Winblad B, Blennow K. Current concepts of mixed pathologies in neurodegenerative diseases. Can J Neurol Sci 2023; 50 (01) 37-47
• 189 Bhattacharya R, Kim J, Grossman K. An update on brain imaging in Parkinsonian dementia. Open Access J. Neurol 2023; 31: 107-114
• 190 Moura S, Nunes LS, Leite JP. Hemodynamic state of periictal hyperperfusion revealed by arterial spin labeling MRI. Epilepsy Behav 2018; 85: 55-62
• 191 Galldiks T, Langen K, Hattingen MM. The emerging role of amino acid PET in neuro-oncology. PET Clin 2018; 13 (03) 313-322
• 192 Whitwell JL, Graff-Radford J, Tosakulwong N. et al. Imaging correlations of tau, amyloid, metabolism, and atrophy in typical and atypical Alzheimer's disease. Alzheimers Dement 2018; 14 (08) 1005-1014
• 193 Chen Z, Jamadar SD, Li S. et al. From simultaneous to synergistic MR-PET brain imaging: a review of hybrid MR-PET imaging methodologies. Hum Brain Mapp 2018; 39 (12) 5126-5144
• 194 Ssali T, Anazodo UC, Thiessen JD, Prato FS, St Lawrence K. A noninvasive method for quantifying cerebral blood flow by hybrid PET/MRI. J Nucl Med 2018; 59 (08) 1329-1334
• 195 Jacobs HIL, Hedden T, Schultz AP. et al. Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nat Neurosci 2018; 21 (03) 424-431
• 196 Chen KT, Salcedo S, Chonde DB. et al. MR-assisted PET motion correction in simultaneous PET/MRI studies of dementia subjects. J Magn Reson Imaging 2018; 48 (05) 1288-1296
• 197 Rathore S, Habes M, Iftikhar MA, Shacklett A, Davatzikos C. A review on neuroimaging-based classification studies and associated feature extraction methods for Alzheimer's disease and its prodromal stages. Neuroimage 2017; 155: 530-548
• 198 Young J, Modat M, Cardoso MJ, Mendelson A, Cash D, Ourselin S. Alzheimer's Disease Neuroimaging Initiative. Accurate multimodal probabilistic prediction of conversion to Alzheimer's disease in patients with mild cognitive impairment. Neuroimage Clin 2013; 2: 735-745
• 199 Spasov S, Passamonti L, Duggento A, Liò P, Toschi N. Alzheimer's Disease Neuroimaging Initiative. A parameter-efficient deep learning approach to predict conversion from mild cognitive impairment to Alzheimer's disease. Neuroimage 2019; 189: 276-287
• 200 Liu F, Jang H, Kijowski R, Bradshaw T, McMillan AB. Deep learning MR imaging-based attenuation correction for PET/MR imaging. Radiology 2018; 286 (02) 676-684
• 201 Lameka K, Farwell MD, Ichise M. Positron emission tomography. Handb Clin Neurol 2016; 135: 209-227
• 202 Sevigny J, Chiao P, Bussière T. et al. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature 2016; 537 (7618) 50-56
• 203 Mecca AP, O'Dell RS, Sharp ES. et al. Synaptic density and cognitive performance in Alzheimer's disease: a PET imaging study with [¹¹ C]UCB-J. Alzheimers Dement 2022; 18 (12) 2527-2536
• 204 Matuskey D, Tinaz S, Wilcox KC. et al. Synaptic changes in Parkinson disease assessed within vivo imaging. Ann Neurol 2020; 87 (03) 329-338
• 205 Ma D, Gulani V, Seiberlich N. et al. Magnetic resonance fingerprinting. Nature 2013; 495 (7440) 187-192