Chemical Exchange Saturation Transfer (CEST) MRI Technical Development
Chemical exchange saturation transfer (CEST) imaging is a relatively new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through their exchangeable protons. CEST MRI is still under development and one major impediment for more widespread application is limited specificity for a particular metabolite. Recently, our group developed one new MRI technique named as variable delay multi pulse (VDMP) CEST for spectral editing of CEST Z-spectrum (a-c). In this method, the inter-pulse delay of a saturation pulse train is varied to act as an exchange rate filter to separate CEST effects from the confounding factors. Due to the capability of measuring exchange rate precisely, the new technique can separate the fast-exchanging and slow-exchanging compounds unambiguously and provides greater insight into the mechanisms of magnetization transfer and CEST effects in tissue. We also developed several other CEST acquisition, post-processing and quantification methods such as one ultra-short echo time (UTE) CEST that can monitor in vivo protein aggregation process by making use of the saturation transfer signal from aliphatic protons (d).

REFERENCES:

a. Kexin Wang, Sooyeon Park, David Olayinka Kamson, Yuguo Li, Guanshu Liu, Jiadi Xu* “ Guanidinium and amide CEST mapping of human brain by high spectral resolution CEST at 3 T”, Magnetic Resonance in Medicine, (2023) 89 (1), 177-191.

b. Xiang Xu, Nirbhay N Yadav, Haifeng Zeng, Craig K Jones, Jinyuan Zhou, Peter CM van Zijl, Jiadi Xu*, “Magnetization transfer contrast–suppressed imaging of amide proton transfer and relayed nuclear overhauser enhancement chemical exchange saturation transfer effects in the human brain”, Magnetic Resonance in Medicine, 75, 88-96(2016).

c. Kexin Wang, Licheng Ju, Yulu Song, Lindsay Blair, Kevin Xie, Claire Liu, Anna Li, Dan Zhu, Feng Xu, Guanshu Liu, Hye-Young Heo, Nirbhay Yadav, Georg Oeltzschner, Richard A. E. Edden, Qin Qin, David Olayinka Kamson, Jiadi Xu* “ Whole-Cerebrum guanidino and amide CEST mapping at 3T by a 3D stack-of-spiral gradient echo acquisition.”, Magnetic Resonance in Medicine, (2024) 92 , 1456.

d. Lin Chen, Zhiliang Wei, Kannie WY Chan, Shuhui Cai, Guanshu Liu, Hanzhang Lu, Philip C Wong, Peter CM van Zijl, Tong Li*, Jiadi Xu*, “Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI”, Neuroimage, 188, 380-390(2019).

High-resolution creatine and phosphocreatine mapping of brain and muscle by MRI
Creatine (Cr) and phosphocreatine (PCr) are two predominant high-energy molecules present in brain and muscle and are altered by common diseases. Although energy metabolism and PCr play a vital role in cellular homeostasis, there currently are no routine diagnostic tests to noninvasively quantify or map the distribution of PCr with clinically acceptable spatial resolution or/and scan time. In the past few years, Our group developed and validated several noninvasive approaches for quantifying and imaging Cr and PCr energy metabolism, without contrast agents, on MRI scanners with only proton channel. We demonstrated that the exchangeable guanidinium protons of millimolar concentration Cr and PCr can be exploited to detect them via the water signal in MRI with greatly enhanced sensitivity (molar signal) using chemical exchange saturation transfer (CEST) MRI, and its concentration can be quantified using both polynomial and Lorentzian line-shape fitting (PLOF)(a-c) and artificial neural network (ANN)(d) methods.

REFERENCES:

a. Ziqin Zhang+, Kexin Wang+, Sooyeon Park, Anna Li, Yuguo Li, Robert G Weiss, Jiadi Xu* “ The exchange rate of creatine CEST in mouse brain”, Magnetic Resonance in Medicine, (2023) DOI: 10.1002/mrm.29662

b. Lin Chen, Peter B Barker, Robert G Weiss, Peter CM van Zijl, Jiadi Xu*, “Creatine and phosphocreatine mapping of mouse skeletal muscle by a polynomial and Lorentzian line‐shape fitting CEST method”, Magnetic Resonance in Medicine, 81, 69-78(2019).

c. Licheng Ju+, Kexin Wang+, Michael Schär, Su Xu, Joshua Rogers, Dan Zhu, Qin Qin, Robert G. Weiss, Jiadi Xu* “ Simultaneous creatine and phosphocreatine mapping of skeletal muscle by CEST MRI at 3T”, Magnetic Resonance in Medicine, (2024) 91 (3), 942-954.

d. Lin Chen, Michael Schär, Kannie WY Chan, Jianpan Huang, Zhiliang Wei, Hanzhang Lu, Qin Qin, Robert G Weiss, Peter CM van Zijl, Jiadi Xu*, “ In vivo imaging of phosphocreatine with artificial neural networks”, Nature Communications, 11, 1072 (2020).

Cerebrospinal fluid (CSF) and water exchange in brain measured by non-invasive MRI methods
Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. However, the CSF exchange with the parenchyma and ependymal layers and the correlation with brain function was not well documented, which is mainly caused by a lack of non-invasive methods for quantifying this process. Recently, we developed and validated several MRI approaches for quantifying CSF water exchange with other tissues without contrast agents. The spin-labeling based MRI methods, named as magnetization transfer indirect spin labeling (MISL) and phase alternate labeling with null recovery (PALAN), assessing the water exchange by exploiting their significantly different protein concentration and water T1, T2, cand diffusion properties. The PALAN method can also assess the interstitial fluid (ISF) flow in brain without contrast agents.

REFERENCES:

a. Anna M Li, Lin Chen, Hongshuai Liu, Yuguo Li, Wenzhen Duan, Jiadi Xu* “ Age-dependent cerebrospinal fluid-tissue water exchange detected by magnetization transfer indirect spin labeling MRI”, Magnetic Resonance in Medicine, (2022) 87 (5), 2287-2298.

b. Anna M Li, Jiadi Xu* “ Cerebrospinal fluid- tissue exchange revealed by phase alternate labeling with null recovery MRI”, Magnetic Resonance in Medicine, (2022) 87 (3), 1207-1217.

c. Jianpan Huang, Peter CM van Zijl, Xiongqi Han, Celia M Dong, Gerald WY Cheng, Kai-Hei Tse, Linda Knutsson, Lin Chen, Joseph HC Lai, Ed X Wu, Jiadi Xu*, Kannie WY Chan*, “ Altered d-glucose in brain parenchyma and cerebrospinal fluid of early Alzheimer’s disease detected by dynamic glucose-enhanced MRI ”, Science Advances, 6, eaba3884 (2020).

d. Yihan Wu, Feng Xu, Dan Zhu, Anna Li, Kexin Wang, Qin Qin, Jiadi Xu* “ Cerebrospinal Fluid Flow within Ventricles and Subarachnoid Space Evaluated by Velocity Selective Spin Labeling MRI”, NeuroImage, (2025) 309, 121095.

Arterial Spin Labeling (ASL) technical development
Perfusion imaging of rodent animals at high fields often interferences with the magnetization transfer (MT) effect due to the strong MT asymmetry. Usually, a separate neck-labeling coil is applied, which has hampered the wide application of perfusion images in rodents. We developed a Steady Pulsed Imaging and Labeling (SPIL) scheme to obtain high-resolution multi-slice perfusion images using standard preclinical MRI equipment. SPIL significantly extends the label bolus duration, increasing the sensitivity and efficiency of perfusion imaging. It has potential for widespread application to ASL studies in preclinical models.

REFERENCES:

a. Xiang Chen, Wenjing Xu, Xiaoyang Han, Yuting Zhai, Jiadi Xu, and Xiao-Yong Zhang“ A high-resolution whole-brain CBF atlas based on more than 100 adult normal mice ”, ISMRM 2022, 3586.

b. Jiadi Xu*, Qin Qin, Dan Wu, Jun Hua, Xiaolei Song, Michael T McMahon, Frances J Northington, Jiangyang Zhang, Peter CM van Zijl, James J Pekar, “ Steady pulsed imaging and labeling scheme for noninvasive perfusion imaging”, Magnetic Resonance in Medicine, 75, 238-248(2016).

c. L Knutsson+, J Xu+*, A Ahlgren, PCM van Zijl, “Chemical Exchange Saturation Transfer, Magnetization Transfer Contrast, and Arterial Spin Labeling: How Similar Pulse Sequences detect Different Phenomena”, Magnetic Resonance in Medicine, 80, 1320(2018).