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Research progress of chemical exchange saturation transfer magnetic resonance imaging in neurodegenerative disease
TIAN Yaotian  LI Chunmei  CHEN Min 

Cite this article as: TIAN Y T, LI C M, CHEN M. Research progress of chemical exchange saturation transfer magnetic resonance imaging in neurodegenerative disease[J]. Chin J Magn Reson Imaging, 2023, 14(1): 32-35, 47. DOI:10.12015/issn.1674-8034.2023.01.006.

[Abstract] Chemical exchange saturation transfer (CEST) imaging is a new imaging method developed based on chemical exchange and magnetization transfer technology, which can selectively saturate exchangeable protons in specific metabolites and transfer magnetization to free water. Thus, the signal intensity of specific metabolites can be indirectly reflected by detecting the signal intensity of free water. Based on this, CEST can achieve in vivo non-invasive detection of low concentration of metabolites without the involvement of contrast agents or radioactive tracers, so it has been widely used in central nervous system diseases. Neurodegenerative diseases are an important part of central nervous system diseases. This review will focus on the application and progress of CEST imaging in neurodegenerative diseases.
[Keywords] neurodegenerative disease;Alzheimer's disease;Parkinson's disease;Huntington's disease;amyotrophic lateral sclerosis;multiple sclerosis;magnetic resonance imaging;chemical exchange saturation transfer imaging;amide proton transfer-weighted imaging

TIAN Yaotian1, 2   LI Chunmei1, 2   CHEN Min1, 2*  

1 Department of Radiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China

2 Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China

Corresponding author: Chen M, E-mail:

Conflicts of interest   None.

ACKNOWLEDGMENTS National Natural Science Foundation of China (No. 82071891, 81771826).
Received  2022-09-26
Accepted  2023-01-04
DOI: 10.12015/issn.1674-8034.2023.01.006
Cite this article as: TIAN Y T, LI C M, CHEN M. Research progress of chemical exchange saturation transfer magnetic resonance imaging in neurodegenerative disease[J]. Chin J Magn Reson Imaging, 2023, 14(1): 32-35, 47. DOI:10.12015/issn.1674-8034.2023.01.006.

WARD K M, ALETRAS A H, BALABAN R S. A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST)[J]. J Magn Reson, 2000, 143(1): 79-87. DOI: 10.1006/jmre.1999.1956.
ZHOU Y, BIE C, VAN ZIJL P C M, et al. The relayed nuclear Overhauser effect in magnetization transfer and chemical exchange saturation transfer MRI[J/OL]. NMR Biomed, 2022: e4778 [2022-09-25]. DOI: 10.1002/nbm.4778.
DOU W, LIN C E, DING H, et al. Chemical exchange saturation transfer magnetic resonance imaging and its main and potential applications in pre-clinical and clinical studies[J]. Quant Imaging Med Surg, 2019, 9(10): 1747-1766. DOI: 10.21037/qims.2019.10.03.
ZHANG Y, ZU T, LIU R, et al. Acquisition sequences and reconstruction methods for fast chemical exchange saturation transfer imaging[J/OL]. NMR Biomed, 2022: e4699 [2022-09-25]. DOI: 10.1002/nbm.4699.
JIANG S, WEN Z, AHN S S, et al. Applications of chemical exchange saturation transfer magnetic resonance imaging in identifying genetic markers in gliomas[J/OL]. NMR Biomed, 2022: e4731 [2022-09-25]. DOI: 10.1002/nbm.4731.
HEO H Y, TEE Y K, HARSTON G, et al. Amide proton transfer imaging in stroke[J/OL]. NMR Biomed, 2022: e4734 [2022-09-25]. DOI: 10.1002/nbm.4734.
CHEN L, WEI Z, CHAN K W Y, et al. Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI[J]. Neuroimage, 2019, 188: 380-390. DOI: 10.1016/j.neuroimage.2018.12.018.
JAHNG G H, CHOI W, CHUNG J J, et al. Mapping exchangeable protons to monitor protein alterations in the brain of an Alzheimer's disease mouse model by using MRI[J]. Curr Alzheimer Res, 2018, 15(14): 1343-1353. DOI: 10.2174/1567205015666180911143518.
WELLS J A, O'CALLAGHAN J M, HOLMES H E, et al. In vivo imaging of tau pathology using multi-parametric quantitative MRI[J]. Neuroimage, 2015, 111: 369-378. DOI: 10.1016/j.neuroimage.2015.02.023.
WANG R, LI S Y, CHEN M, et al. Amide proton transfer magnetic resonance imaging of Alzheimer's disease at 3.0 Tesla: a preliminary study[J]. Chin Med J (Engl), 2015, 128(5): 615-619. DOI: 10.4103/0366-6999.151658.
GUO Z, JIANG Y, QIN X, et al. Amide proton transfer-weighted MRI might help distinguish amnestic mild cognitive impairment from a normal elderly population[J/OL]. Front Neurol, 2021, 12: 707030 [2022-09-25]. DOI: 10.3389/fneur.2021.707030.
LI C, PENG S, WANG R, et al. Chemical exchange saturation transfer MR imaging of Parkinson's disease at 3 Tesla[J]. Eur Radiol, 2014, 24(10): 2631-2639. DOI: 10.1007/s00330-014-3241-7.
LI C, CHEN M, ZHAO X, et al. Chemical Exchange Saturation Transfer MRI Signal Loss of the Substantia Nigra as an Imaging Biomarker to Evaluate the Diagnosis and Severity of Parkinson's Disease[J/OL]. Front Neurosci, 2017, 11: 489 [2022-09-25]. DOI: 10.3389/fnins.2017.00489.
LI S, CHAN P, LI C, et al. Changes of Amide Proton Transfer Imaging in Multiple System Atrophy Parkinsonism Type[J/OL]. Front Aging Neurosci, 2020, 12: 572421 [2022-09-25]. DOI: 10.3389/fnagi.2020.572421.
DAI Z, KALRA S, MAH D, et al. Amide signal intensities may be reduced in the motor cortex and the corticospinal tract of ALS patients[J]. Eur Radiol, 2021, 31(3): 1401-1409. DOI: 10.1007/s00330-020-07243-4.
BY S, BARRY R L, SMITH A K, et al. Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T[J]. Magn Reson Med, 2018, 79(2): 806-814. DOI: 10.1002/mrm.26736.
LI C, WANG R, CHEN H, et al. Chemical exchange saturation transfer MR imaging is superior to diffusion-tensor imaging in the diagnosis and severity evaluation of Parkinson's disease: a study on substantia nigra and striatum[J/OL]. Front Aging Neurosci, 2015, 7: 198 [2022-09-25]. DOI: 10.3389/fnagi.2015.00198.
GOERKE S, MILDE K S, BUKOWIECKI R, et al. Aggregation-induced changes in the chemical exchange saturation transfer (CEST) signals of proteins[J/OL]. NMR Biomed, 2017, 30(1): 10.1002/nbm.3665 [2022-09-25]. DOI: 10.1002/nbm.3665.
JONES K M, POLLARD A C, PAGEL M D. Clinical applications of chemical exchange saturation transfer (CEST) MRI[J]. J Magn Reson Imaging, 2018, 47(1): 11-27. DOI: 10.1002/jmri.25838.
CHO N S, HAGIWARA A, YAO J, et al. Amine-weighted chemical exchange saturation transfer magnetic resonance imaging in brain tumors[J/OL]. NMR Biomed, 2022: e4785 [2022-09-25].
CEMBER A T J, NANGA R P R, REDDY R. Glutamate-weighted CEST (gluCEST) imaging for mapping neurometabolism: An update on the state of the art and emerging findings from in vivo applications[J/OL]. NMR Biomed, 2022: e4780 [2022-09-25]. DOI: 10.1002/nbm.4780.
NAM M H, WON W, HAN K S, et al. Signaling mechanisms of μ-opioid receptor (MOR) in the hippocampus: disinhibition versus astrocytic glutamate regulation[J]. Cell Mol Life Sci, 2021, 78(2): 415-426. DOI: 10.1007/s00018-020-03595-8.
COX M F, HASCUP E R, BARTKE A, et al. Friend or Foe? Defining the Role of Glutamate in Aging and Alzheimer's Disease[J/OL]. Front Aging, 2022, 3: 929474 [2022-09-25]. DOI: 10.3389/fragi.2022.929474.
VERMA M, LIZAMA B N, CHU C T. Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration[J/OL]. Transl Neurodegener, 2022, 11(1): 3 [2022-09-25]. DOI: 10.1186/s40035-021-00278-7.
CAI K, HARIS M, SINGH A, et al. Magnetic resonance imaging of glutamate[J]. Nat Med, 2012, 18(2): 302-306. DOI: 10.1038/nm.2615.
IGARASHI H, UEKI S, KITAURA H, et al. Longitudinal GluCEST MRI Changes and Cerebral Blood Flow in 5xFAD Mice[J/OL]. Contrast Media Mol Imaging, 2020, 2020: 8831936 [2022-09-25]. DOI: 10.1155/2020/8831936.
PÉROT J B, CÉLESTINE M, PALOMBO M, et al. Longitudinal multimodal MRI characterization of a knock-in mouse model of Huntington's disease reveals early grey and white matter alterations[J/OL]. Hum Mol Genet, 2022: ddac036 [2022-09-25]. DOI: 10.1093/hmg/ddac036.
BAGGA P, PICKUP S, CRESCENZI R, et al. In vivo GluCEST MRI: Reproducibility, background contribution and source of glutamate changes in the MPTP model of Parkinson's disease[J/OL]. Sci Rep, 2018, 8(1): 2883 [2022-09-25]. DOI: 10.1038/s41598-018-21035-3.
O'GRADY K P, DULA A N, LYTTLE B D, et al. Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis[J]. Mult Scler, 2019, 25(12): 1580-1592. DOI: 10.1177/1352458518799583.
SCHUR G M, DUNN J, NGUYEN S, et al. In vivo assessment of OXPHOS capacity using 3 T CrCEST MRI in Friedreich's ataxia[J]. J Neurol, 2022, 269(5): 2527-2538. DOI: 10.1007/s00415-021-10821-1.
TAKAHASHI Y, SAITO S, KIOKA H, et al. Mouse skeletal muscle creatine chemical exchange saturation transfer (CrCEST) imaging at 11.7T MRI[J]. J Magn Reson Imaging, 2020, 51(2): 563-570. DOI: 10.1002/jmri.26844.
CHUNG J J, JIN T, LEE J H, et al. Chemical exchange saturation transfer imaging of phosphocreatine in the muscle[J]. Magn Reson Med, 2019, 81(6): 3476-3487. DOI: 10.1002/mrm.27655.
LIU Z, YANG Q, LUO H, et al. Demonstration of fast and equilibrium human muscle creatine CEST imaging at 3 T[J]. Magn Reson Med, 2022, 88(1): 322-331. DOI: 10.1002/mrm.29223.
ZAMANI P, PROTO E A, WILSON N, et al. Multimodality assessment of heart failure with preserved ejection fraction skeletal muscle reveals differences in the machinery of energy fuel metabolism[J]. ESC Heart Fail, 2021, 8(4): 2698-2712. DOI: 10.1002/ehf2.13329.
CHEN L, VAN ZIJL P C M, WEI Z, et al. Early detection of Alzheimer's disease using creatine chemical exchange saturation transfer magnetic resonance imaging[J/OL]. Neuroimage, 2021, 236: 118071 [2022-09-25]. DOI: 10.1016/j.neuroimage.2021.118071.
BANJAR M, HORIUCHI S, GEDEON D N, et al. Review of Quantitative Knee Articular Cartilage MR Imaging[J]. Magn Reson Med Sci, 2022, 21(1): 29-40. DOI: 10.2463/mrms.rev.2021-0052.
WOLLSCHLÄGER L M, NEBELUNG S, SCHLEICH C, et al. Evaluating Lumbar Intervertebral Disc Degeneration on a Compositional Level Using Chemical Exchange Saturation Transfer: Preliminary Results in Patients with Adolescent Idiopathic Scoliosis[J/OL]. Diagnostics (Basel), 2021, 11(6): 934 [2022-09-25]. DOI: 10.3390/diagnostics11060934.
MINOSHIMA S, MOSCI K, CROSS D, et al. Brain [F-18]FDG PET for Clinical Dementia Workup: Differential Diagnosis of Alzheimer's Disease and Other Types of Dementing Disorders[J]. Semin Nucl Med, 2021, 51(3): 230-240. DOI: 10.1053/j.semnuclmed.2021.01.002.
CAPRIOGLIO C, GARIBOTTO V, JESSEN F, et al. The clinical use of Alzheimer's disease biomarkers in patients with mild cognitive impairment: A European Alzheimer's disease consortium s urvey[J]. J Alzheimers Dis, 2022, 89(2): 535-551. DOI: 10.3233/JAD-220333.
JIANG J, SHENG C, CHEN G, et al. Glucose metabolism patterns: A potential index to characterize brain ageing and predict high conversion risk into cognitive impairment[J/OL]. Geroscience, 2022: 10.1007/s11357-022-00588-2 [2022-09-25]. DOI: 10.1007/s11357-022-00588-2.
WALKER Z, GANDOLFO F, ORINI S, et al. Clinical utility of FDG PET in Parkinson's disease and atypical parkinsonism associated with dementia[J]. Eur J Nucl Med Mol Imaging, 2018, 45(9): 1534-1545. DOI: 10.1007/s00259-018-4031-2.
HAN Z, LIU G. Sugar-based biopolymers as novel imaging agents for molecular magnetic resonance imaging[J/OL]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2019, 11(4): e1551 [2022-09-25]. DOI: 10.1002/wnan.1551.
CHEN P, SHEN Z, WANG Q, et al. Reduced Cerebral Glucose Uptake in an Alzheimer's Rat Model With Glucose-Weighted Chemical Exchange Saturation Transfer Imaging[J/OL]. Front Aging Neurosci, 2021, 13: 618690 [2022-09-25]. DOI: 10.3389/fnagi.2021.618690.
LENG F, EDISON P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?[J]. Nat Rev Neurol, 2021, 17(3): 157-172. DOI: 10.1038/s41582-020-00435-y.
BOYD R J, AVRAMOPOULOS D, JANTZIE L L, et al. Neuroinflammation represents a common theme amongst genetic and environmental risk factors for Alzheimer and Parkinson diseases[J/OL]. J Neuroinflammation, 2022, 19(1): 223 [2022-09-25]. DOI: 10.1186/s12974-022-02584-x.
LIND A, BORAXBEKK C J, PETERSEN E T, et al. Do glia provide the link between low-grade systemic inflammation and normal cognitive ageing? A 1H magnetic resonance spectroscopy study at 7 tesla[J]. J Neurochem, 2021, 159(1): 185-196. DOI: 10.1111/jnc.15456.
SONG T, SONG X, ZHU C, et al. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer's disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies[J/OL]. Ageing Res Rev, 2021, 72: 101503 [2022-09-25]. DOI: 10.1016/j.arr.2021.101503.
YANEZ LOPEZ M, PARDON M C, BAIKER K, et al. Myoinositol CEST signal in animals with increased Iba-1 levels in response to an inflammatory challenge-preliminary findings[J/OL]. PLoS One, 2019, 14(2): e0212002 [2022-09-25]. DOI: 10.1371/journal.pone.0212002.
HARIS M, SINGH A, CAI K, et al. MICEST: a potential tool for non-invasive detection of molecular changes in Alzheimer's disease[J]. J Neurosci Methods, 2013, 212(1): 87-93. DOI: 10.1016/j.jneumeth.2012.09.025.

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