Share：
Share this content in WeChat
X
[Chinese][PDF]2931
• Review •
Study on the application of quantitative susceptibility mapping in the diagnosis and progression tracking of Alzheimer's disease
WANG Ruiqi  ZHAN Yijun  PEI Jian 

Cite this article as WANG R Q, ZHAN Y J, PEI J. Study on the application of quantitative susceptibility mapping in the diagnosis and progression tracking of Alzheimer's disease[J]. Chin J Magn Reson Imaging, 2024, 15(5): 187-191, 197. DOI:10.12015/issn.1674-8034.2024.05.030.


[Abstract] Alzheimer's disease (AD) is a degenerative disease of the central nervous system, and dysregulation of iron homeostasis in the brain is one of the important pathological features of AD. Quantitative susceptibility mapping (QSM), a noninvasive magnetic resonance technique, is sensitive to the presence of iron and can quantify local tissue magnetization with high spatial resolution. In recent years, the QSM technique has been investigated on the magnetization rate of different brain regions and the relationship with other pathological biomarkers. The aim of this paper is to analyze the effect of iron homeostasis dysregulation on the pathology of AD as well as the potential value of the QSM technique in the early diagnosis of AD and tracking of the disease course, to provide objective neuroimaging basis for the early diagnosis and treatment of AD.
[Keywords] Alzheimer's disease；quantitative susceptibility mapping；magnetic resonance imaging；iron homeostasis disorder；brain iron deposition

WANG Ruiqi   ZHAN Yijun   PEI Jian*  

Department of Acupuncture and Moxibustion, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

Corresponding author: PEI J, E-mail: longhuaacup@aliyun.com

Conflicts of interest   None.

Received  2023-12-21
Accepted  2024-04-30
DOI: 10.12015/issn.1674-8034.2024.05.030
Cite this article as WANG R Q, ZHAN Y J, PEI J. Study on the application of quantitative susceptibility mapping in the diagnosis and progression tracking of Alzheimer's disease[J]. Chin J Magn Reson Imaging, 2024, 15(5): 187-191, 197. DOI:10.12015/issn.1674-8034.2024.05.030.

[1]
JACK C J, BENNETT D A, BLENNOW K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease[J]. Alzheimers Dement, 2018, 14(4): 535-562. DOI: 10.1016/j.jalz.2018.02.018.
[2]
PENG Y, CHANG X, LANG M. Iron homeostasis disorder and Alzheimer's disease[J/OL]. Int J Mol Sci, 2021, 22(22): 12443 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/34830326/. DOI: 10.3390/ijms222212442.
[3]
WU Y, TORABI S F, LAKE R J, et al. Simultaneous Fe2+/Fe3+ imaging shows Fe3+ over Fe2+ enrichment in Alzheimer's disease mouse brain[J/OL]. Sci Adv, 2023, 9(16): eade7622 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/37075105/. DOI: 10.1126/sciadv.ade7622.
[4]
HAACKE E M, LIU S, BUCH S, et al. Quantitative susceptibility mapping: current status and future directions[J]. Magn Reson Imaging, 2015, 33(1): 1-25. DOI: 10.1016/j.mri.2014.09.004.
[5]
LIU J, LIU T, DE ROCHEFORT L, et al. Morphology enabled dipole inversion for quantitative susceptibility mapping using structural consistency between the magnitude image and the susceptibility map[J]. Neuroimage, 2012, 59(3): 2560-2568. DOI: 10.1016/j.neuroimage.2011.08.082.
[6]
WANG Y, LIU T. Quantitative susceptibility mapping (QSM): Decoding MRI data for a tissue magnetic biomarker[J]. Magn Reson Med, 2015, 73(1): 82-101. DOI: 10.1002/mrm.25358.
[7]
LANGKAMMER C, SCHWESER F, KREBS N, et al. Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study[J]. Neuroimage, 2012, 62(3): 1593-1599. DOI: 10.1016/j.neuroimage.2012.05.049.
[8]
AILLAUD I, FUNKE S A. Tau aggregation inhibiting peptides as potential therapeutics for Alzheimer disease[J]. Cell Mol Neurobiol, 2023, 43(3): 951-961. DOI: 10.1007/s10571-022-01230-7.
[9]
DIXON S J, LEMBERG K M, LAMPRECHT M R, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072. DOI: 10.1016/j.cell.2012.03.042.
[10]
STREIT W J, ROTTER J, WINTER K, et al. Droplet degeneration of hippocampal and cortical neurons signifies the beginning of neuritic plaque formation[J]. J Alzheimers Dis, 2022, 85(4): 1701-1720. DOI: 10.3233/JAD-215334.
[11]
WANG F, WANG J, SHEN Y, et al. Iron dyshomeostasis and ferroptosis: a new Alzheimer's disease hypothesis?[J/OL]. Front Aging Neurosci, 2022, 14: 830569 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/35391749/. DOI: 10.3389/fnagi.2022.830569.
[12]
ZHANG Y, GAO X, BAI X, et al. The emerging role of furin in neurodegenerative and neuropsychiatric diseases[J/OL]. Transl Neurodegener, 2022, 11(1): 39 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/35996194/. DOI: 10.1186/s40035-022-00313-1.
[13]
GREENOUGH M A. The role of presenilin in protein trafficking and degradation-implications for metal homeostasis[J]. J Mol Neurosci, 2016, 60(3): 289-297. DOI: 10.1007/s12031-016-0826-4.
[14]
LEI P, AYTON S, FINKELSTEIN D I, et al. Tau deficiency induces Parkinsonism with dementia by impairing APP-mediated iron export[J]. Nat Med, 2012, 18(2): 291-295. DOI: 10.1038/nm.2613.
[15]
TSATSANIS A, MCCORKINDALE A N, WONG B X, et al. The acute phase protein lactoferrin is a key feature of Alzheimer's disease and predictor of Aβ burden through induction of APP amyloidogenic processing[J]. Mol Psychiatry, 2021, 26(10): 5516-5531. DOI: 10.1038/s41380-021-01248-1.
[16]
CHIOU B, NEAL E H, BOWMAN A B, et al. Endothelial cells are critical regulators of iron transport in a model of the human blood-brain barrier[J]. J Cereb Blood Flow Metab, 2019, 39(11): 2117-2131. DOI: 10.1177/0271678X18783372.
[17]
AYTON S, WANG Y, DIOUF I, et al. Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology[J]. Mol Psychiatry, 2020, 25(11): 2932-2941. DOI: 10.1038/s41380-019-0375-7.
[18]
BURGETOVA R, DUSEK P, BURGETOVA A, et al. Age-related magnetic susceptibility changes in deep grey matter and cerebral cortex of normal young and middle-aged adults depicted by whole brain analysis[J]. Quant Imaging Med Surg, 2021, 11(9): 3906-3919. DOI: 10.21037/qims-21-87.
[19]
BLACK E, RASCH A, WIMMER T, et al. The effects of age, genotype and diet on hippocampal subfield iron dysregulation and Alzheimer's disease biomarkers in an ApoE mouse model[J]. Eur J Neurosci, 2023, 57(6): 1033-1047. DOI: 10.1111/ejn.15933.
[20]
KAN H, UCHIDA Y, ARAI N, et al. Simultaneous voxel-based magnetic susceptibility and morphometry analysis using magnetization-prepared spoiled turbo multiple gradient echo[J/OL]. NMR Biomed, 2020, 33(5): e4272 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/32043682/. DOI: 10.1002/nbm.4272.
[21]
BULK M, ABDELMOULA W M, GEUT H, et al. Quantitative MRI and laser ablation-inductively coupled plasma-mass spectrometry imaging of iron in the frontal cortex of healthy controls and Alzheimer's disease patients[J/OL]. Neuroimage, 2020, 215: 116808 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/32289451/. DOI: 10.1016/j.neuroimage.2020.116808.
[22]
SACCHI L, CONTARINO V E, SIGGILLINO S, et al. Banks of the superior temporal sulcus in Alzheimer's disease: a pilot quantitative susceptibility mapping study[J]. J Alzheimers Dis, 2023, 93(3): 1125-1134. DOI: 10.3233/JAD-230095.
[23]
YANG A, DU L, GAO W, et al. Associations of cortical iron accumulation with cognition and cerebral atrophy in Alzheimer's disease[J]. Quant Imaging Med Surg, 2022, 12(9): 4570-4586. DOI: 10.21037/qims-22-7.
[24]
KIM H W, LEE S, YANG J H, et al. Cortical iron accumulation as an imaging marker for neurodegeneration in clinical cognitive impairment spectrum: a quantitative susceptibility mapping study[J]. Korean J Radiol, 2023, 24(11): 1131-1141. DOI: 10.3348/kjr.2023.0490.
[25]
GUAN X, GUO T, ZHOU C, et al. Altered brain iron depositions from aging to Parkinson's disease and Alzheimer's disease: a quantitative susceptibility mapping study[J/OL]. Neuroimage, 2022, 264: 119683 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/36243270/. DOI: 10.1016/j.neuroimage.2022.119683.
[26]
TIEPOLT S, RULLMANN M, JOCHIMSEN T H, et al. Quantitative susceptibility mapping in β-Amyloid PET-stratified patients with dementia and healthy controls-A hybrid PET/MRI study[J/OL]. Eur J Radiol, 2020, 131: 109243 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/32916411/. DOI: 10.1016/j.ejrad.2020.109243.
[27]
LI G, TONG R, ZHANG M, et al. Age-dependent changes in brain iron deposition and volume in deep gray matter nuclei using quantitative susceptibility mapping[J/OL]. NeuroImage, 2023, 269: 119923 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/36739101/. DOI: 10.1016/j.neuroimage.2023.119923.
[28]
HUANG C, LI J, LIU C, et al. Investigation of brain iron levels in Chinese patients with Alzheimer's disease[J/OL]. Front Aging Neurosci, 2023, 15: 1168845 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/37284016/. DOI: 10.3389/fnagi.2023.1168845.
[29]
VINAYAGAMANI S, SHEELAKUMARI R, SABARISH S, et al. Quantitative susceptibility mapping: technical considerations and clinical applications in neuroimaging[J]. J Magn Reson Imaging, 2021, 53(1): 23-37. DOI: 10.1002/jmri.27058.
[30]
LI D, LIU Y, ZENG X, et al. Quantitative study of the changes in cerebral blood flow and iron deposition during progression of Alzheimer's disease[J]. J Alzheimers Dis, 2020, 78(1): 439-452. DOI: 10.3233/JAD-200843.
[31]
SATO R, KUDO K, YAMAGUCHI A, et al. Correlation analysis between magnetic susceptibility in MRI and amyloid β in PET[J/OL]. Alzheimer's & Dementia, 2020, 16(S4): e40064 [2023-12-21]. https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.040064. DOI: https://doi.org/10.1002/alz.040064.
[32]
COGSWELL P M, WISTE H J, SENJEM M L, et al. Associations of quantitative susceptibility mapping with Alzheimer's disease clinical and imaging markers[J/OL]. Neuroimage, 2021, 224: 117433 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/33035667/. DOI: 10.1016/j.neuroimage.2020.117433.
[33]
COGSWELL P M, FAN A P. Multimodal comparisons of QSM and PET in neurodegeneration and aging[J/OL]. NeuroImage, 2023, 273: 120068 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/37003447/. DOI: https://doi.org/10.1016/j.neuroimage.2023.120068.
[34]
VAN BERGEN J, LI X, QUEVENCO F C, et al. Simultaneous quantitative susceptibility mapping and Flutemetamol-PET suggests local correlation of iron and β-amyloid as an indicator of cognitive performance at high age[J/OL]. Neuroimage, 2018, 174: 308-316 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/29548847/. DOI: 10.1016/j.neuroimage.2018.03.021.
[35]
AYTON S, FAZLOLLAHI A, BOURGEAT P, et al. Cerebral quantitative susceptibility mapping predicts amyloid-β-related cognitive decline[J]. Brain, 2017, 140(8): 2112-2119. DOI: 10.1093/brain/awx137.
[36]
IKEBE Y, SATO R, AMEMIYA T, et al. Prediction of amyloid positron emission tomography positivity using multiple regression analysis of quantitative susceptibility mapping[J]. Magn Reson Imaging, 2023, 103: 192-197. DOI: 10.1016/j.mri.2023.08.002.
[37]
O'CALLAGHAN J, HOLMES H, POWELL N, et al. Tissue magnetic susceptibility mapping as a marker of tau pathology in Alzheimer's disease[J]. Neuroimage, 2017, 159: 334-345. DOI: 10.1016/j.neuroimage.2017.08.003.
[38]
YANG L, CHENG Y, SUN Y, et al. Combined application of quantitative susceptibility mapping and diffusion kurtosis imaging techniques to investigate the effect of iron deposition on microstructural changes in the brain in Parkinson's disease[J/OL]. Front Aging Neurosci, 2022, 14: 792778 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/35370619/. DOI: 10.3389/fnagi.2022.792778.
[39]
ZACHARIOU V, BAUER C E, PAPPAS C, et al. High cortical iron is associated with the disruption of white matter tracts supporting cognitive function in healthy older adults[J]. Cerebral Cortex, 2023, 33(8): 4815-4828. DOI: 10.1093/cercor/bhac382.
[40]
ZACHARIOU V, BAUER C E, SEAGO E R, et al. Cortical iron disrupts functional connectivity networks supporting working memory performance in older adults[J/OL]. NeuroImage, 2020, 223: 117309 [2023-12-21]. https://pubmed.ncbi.nlm.nih.gov/32861788/. DOI: https://doi.org/10.1016/j.neuroimage.2020.117309.
[41]
FRISONI G B, ALTOMARE D, THAL D R, et al. The probabilistic model of Alzheimer disease: the amyloid hypothesis revised[J]. Nat Rev Neurosci, 2022, 23(1): 53-66. DOI: 10.1038/s41583-021-00533-w.
[42]
SERRANO-POZO A, DAS S, HYMAN B T. APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches[J]. Lancet Neurol, 2021, 20(1): 68-80. DOI: 10.1016/S1474-4422(20)30412-9.
[43]
AYTON S, FAUX N G, BUSH A I. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE[J/OL]. Nat Commun, 2015, 6: 6760 [2023-11-28]. https://pubmed.ncbi.nlm.nih.gov/25988319/. DOI: 10.1038/ncomms7760.
[44]
MA J, QIAN C, BAO Y, et al. Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice[J/OL]. Redox Biology, 2021, 40: 101865 [2023-11-28]. https://pubmed.ncbi.nlm.nih.gov/33493903/. DOI: 10.1016/j.redox.2021.101865.
[45]
YIM Y, CHOI J D, CHO J H, et al. Magnetic susceptibility in the deep gray matter may be modulated by apolipoprotein E4 and age with regional predilections: a quantitative susceptibility mapping study[J]. Neuroradiology, 2022, 64(7): 1331-1342. DOI: 10.1007/s00234-021-02859-9.
[46]
NIR T M, ZHU A H, GARI I B, et al. Effects of ApoE4 and ApoE2 genotypes on subcortical magnetic susceptibility and microstructure in 27, 535 participants from the UK Biobank[J]. Pac Symp Biocomput, 2022, 27: 121-132. DOI: 10.1142/9789811250477_0012.
[47]
KAGERER S M, VAN BERGEN J, LI X, et al. APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults[J/OL]. Alzheimers Dement (Amst), 2020, 12(1): e12002 [2023-11-28]. https://pubmed.ncbi.nlm.nih.gov/32211498/. DOI: 10.1002/dad2.12002.
[48]
UCHIDA Y, KAN H, SAKURAI K, et al. APOE ɛ4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction[J]. J Neurol Neurosurg Psychiatry, 2022, 93: 772-778. DOI: 10.1136/jnnp-2021-328519.
[49]
SPOTORNO N, ACOSTA-CABRONERO J, STOMRUD E, et al. Relationship between cortical iron and tau aggregation in Alzheimer's disease[J]. Brain, 2020, 143(5): 1341-1349. DOI: 10.1093/brain/awaa089.
[50]
BULK M, KENKHUIS B, van der GRAAF L M, et al. Postmortem T2*-Weighted MRI imaging of cortical iron reflects severity of Alzheimer's disease[J]. J Alzheimers Dis, 2018, 65(4): 1125-1137. DOI: 10.3233/JAD-180317.
[51]
KUCHCINSKI G, PATIN L, LOPES R, et al. Quantitative susceptibility mapping demonstrates different patterns of iron overload in subtypes of early-onset Alzheimer's disease[J]. Eur Radiol, 2023, 33(1): 184-195. DOI: 10.1007/s00330-022-09014-9.
[52]
Dementia and Cognitive Impairment Group of Chinese Society of Neurology, Cognitive Disorders Committee of Neurology Branch of Chinese Medical Doctor Association. Chinese expert consensus on brief screening of prodromal Alzheimer's disease (2023)[J]. Chin J Neuromed, 2023, 22(5): 433-444. DOI: 10.3760/cma.j.cn115354-20230330-00191.
[53]
LIU Y, DONG J, SONG Q, et al. Correlation between cerebral venous oxygen level and cognitive status in patients with Alzheimer's disease using quantitative susceptibility mapping[J/OL]. Front Neurosci, 2020, 14: 570848 [2023-11-28]. https://pubmed.ncbi.nlm.nih.gov/33536866/. DOI: 10.3389/fnins.2020.570848.
[54]
YANG A, ZHUANG H, DU L, et al. Evaluation of whole-brain oxygen metabolism in Alzheimer's disease using QSM and quantitative BOLD[J/OL]. Neuroimage, 2023, 282: 120381 [2024-3-28]. https://pubmed.ncbi.nlm.nih.gov/37734476/. DOI: 10.1016/j.neuroimage.2023.120381.
[55]
KIM H G, PARK S, RHEE H Y, et al. Quantitative susceptibility mapping to evaluate the early stage of Alzheimer's disease[J]. Neuroimage Clin, 2017, 16: 429-438. DOI: 10.1016/j.nicl.2017.08.019.
[56]
MANDAL P K, GOEL A, BUSH A I, et al. Hippocampal glutathione depletion with enhanced iron level in patients with mild cognitive impairment and Alzheimer's disease compared with healthy elderly participants[J/OL]. Brain Commun, 2022, 4(5): fcac215 [2023-11-28]. https://pubmed.ncbi.nlm.nih.gov/36072647/. DOI: 10.1093/braincomms/fcac215.
[57]
UCHIDA Y, KAN H, SAKURAI K, et al. Quantitative susceptibility mapping as an imaging biomarker for Alzheimer's disease: The expectations and limitations[J/OL]. Front Neurosci, 2022, 16: 938092 [2023-11-28]. https://pubmed.ncbi.nlm.nih.gov/35992906/. DOI: 10.3389/fnins.2022.938092.
[58]
WANG D, LI Y Y, LUO J H, et al. Age-related iron deposition in the basal ganglia of controls and Alzheimer disease patients quantified using susceptibility weighted imaging[J]. Arch Gerontol Geriatr, 2014, 59(2): 439-449. DOI: 10.1016/j.archger.2014.04.002.
[59]
PARK M, MOON Y, HAN S H, et al. Motor cortex hypointensity on susceptibility-weighted imaging: a potential imaging marker of iron accumulation in patients with cognitive impairment[J]. Neuroradiology, 2019, 61(6): 675-683. DOI: 10.1007/s00234-019-02159-3.
[60]
DEISTUNG A, SCHÄFER A, SCHWESER F, et al. Toward in vivo histology: a comparison of quantitative susceptibility mapping (QSM) with magnitude-, phase-, and R2*-imaging at ultra-high magnetic field strength[J]. Neuroimage, 2013, 65: 299-314. DOI: 10.1016/j.neuroimage.2012.09.055.
[61]
EVERETT J, CÉSPEDES E, SHELFORD L R, et al. Evidence of redox-active iron formation following aggregation of ferrihydrite and the Alzheimer's disease peptide β-amyloid[J]. Inorg Chem, 2014, 53(6): 2803-2809. DOI: 10.1021/ic402406g.
[62]
TUZZI E, BALLA D Z, LOUREIRO J, et al. Ultra-High field MRI in Alzheimer's disease: effective transverse relaxation rate and quantitative susceptibility mapping of human brain in vivo and ex vivo compared to histology[J]. J Alzheimers Dis, 2020, 73(4): 1481-1499. DOI: 10.3233/JAD-190424.
[63]
KIM H G, PARK S, RHEE H Y, et al. Evaluation and prediction of early Alzheimer's disease using a machine learning-based optimized combination-feature set on gray matter volume and quantitative susceptibility mapping[J]. Curr Alzheimer Res, 2020, 17(5): 428-437. DOI: 10.2174/1567205017666200624204427.

PREV Research progress of magnetic resonance 3D-TIWI and diffusion imaging in Alzheimer,s disease
NEXT Advances in the application of DTI-ALPS in brain glymphoid system related neurological diseases
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn