Creatine chemical exchange saturation transfer (CrCEST) MRI for Alzheimer's disease detection at 3T
Research output: Conference Papers › Poster › peer-review
Author(s)
Related Research Unit(s)
Detail(s)
Original language | English |
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Publication status | Presented - 6 Sept 2023 |
Conference
Title | World Molecular Imaging Congress (WMIC) 2023 |
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Location | |
Place | Czech Republic |
City | Prague |
Period | 5 - 9 September 2023 |
Link(s)
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(01f8c93a-1dbd-4c85-9e85-7edc9db54875).html |
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Abstract
Alzheimer’s disease (AD) is one of the greatest health concerns, but its early detection remains a challenge. Acidification is universally acknowledged in AD (1,2), and a recent study (3) pointed out that faulty autolysosome acidification leads to amyloid beta deposition, a distinctive hallmark of AD. Therefore, it would be important if early signs of AD could be detected by measuring a pH decrease in the brain. Chemical exchange saturation transfer (CEST) MRI is a non-invasive and sensitive technique for imaging target proteins and metabolites through their exchangeable protons, and is already being applied in vivo for pH mapping (4-6). However, the conventional amide proton transfer CEST contrast may be problematic for specifically probing pH in AD, since it can also be affected by protein aggregation (7-9). Total creatine (Cr + PCr) concentration remains stable in most neurodegenerative diseases (10-12), making the guanidinium protons detected at 2.0 ppm in creatine CEST (CrCEST) a potential pH mapping method for these conditions. However, CrCEST is usually believed invisible at 3T due to rapid guanidinium proton exchange measured in phantoms (13,14). Here, we validate the possibility of in-vivo assignment and detection of CrCEST signal at 3T by comparing wild-type and Guanidinoacetate N-methyltransferase deficiency (GAMT-/-) mice, which exhibit low Cr and PCr concentrations (15,16), using the polynomial and Lorentzian line-shape fitting (PLOF) approach(12,17-19) demonstrated in supplementary Fig. S1 and then applied that detection to AD mice.
Eight age-matched (3-9 months old) pairs of GAMT-/- and wild type (WT) mice were scanned at 3T (Bruker Biospec). Single-slice continuous-wave CEST experiments were performed using a RARE sequence (matrix size: 32 × 32,saturation time 1 s) as a function of B1. Imaging data for ten age-matched (11 months old) pairs of AD model mice (5xFAD) and WT mice were obtained from a previous publication (20). This original study used matrix size 96 × 96, B1 0.6 µT, and saturation time 3 s.
The PLOF method can extract amide proton (amideCEST) and guanidinium proton (GuanCEST) of Cr (CrCEST) and protein-based arginine protons (ArgCEST), as verified in Fig. S2. Taking the difference of the preprocessed Z-spectra of WT (average plots in Figure A) and GAMT-/- mice, the Cr peak at 2 ppm is observed for all B1 values (Figure B), indicating that in-vivo Cr guanidinium protons exchange slower than in PBS-buffered phantoms with an exchange rate of 270 ± 70 s-1 as determined from lineshape and multi-B1 fitting (see Fig. S3A, B). A maximum CrCEST signal of 0.7% was achieved at B1 = 0.8 μT.
By assuming the ratio of arginine and amide (AAR) protons to be constant and acquiring AAR in the GAMT-/-mouse study, CrCEST can be extracted by measuring the amideCEST and GuanCEST: (Figure C). Increased CrCEST signals were observed in the AD mouse brain (WT: (0.0018 0.0027) vs AD: (0.0040 0.0026); p = 0.036) (Figure D). Using the simulations in Fig. S3C, an increase of CrCEST signal in AD mice and be explained by a decrease in pH and exchange rate of the guanidinium protons. The distributions of amideCEST contrasts are found to be homogeneous across the entire brain for both AD and WT mice (Figs. G&H), while the GuanCEST in thalamus was lower than that in cortex (Figs. E&F).
In conclusion, we report the observation of CrCEST in-vivo in the brain at 3T. Changes in CrCEST signal in AD mice suggest CrCEST has potential as a marker for AD detection.
Eight age-matched (3-9 months old) pairs of GAMT-/- and wild type (WT) mice were scanned at 3T (Bruker Biospec). Single-slice continuous-wave CEST experiments were performed using a RARE sequence (matrix size: 32 × 32,saturation time 1 s) as a function of B1. Imaging data for ten age-matched (11 months old) pairs of AD model mice (5xFAD) and WT mice were obtained from a previous publication (20). This original study used matrix size 96 × 96, B1 0.6 µT, and saturation time 3 s.
The PLOF method can extract amide proton (amideCEST) and guanidinium proton (GuanCEST) of Cr (CrCEST) and protein-based arginine protons (ArgCEST), as verified in Fig. S2. Taking the difference of the preprocessed Z-spectra of WT (average plots in Figure A) and GAMT-/- mice, the Cr peak at 2 ppm is observed for all B1 values (Figure B), indicating that in-vivo Cr guanidinium protons exchange slower than in PBS-buffered phantoms with an exchange rate of 270 ± 70 s-1 as determined from lineshape and multi-B1 fitting (see Fig. S3A, B). A maximum CrCEST signal of 0.7% was achieved at B1 = 0.8 μT.
By assuming the ratio of arginine and amide (AAR) protons to be constant and acquiring AAR in the GAMT-/-mouse study, CrCEST can be extracted by measuring the amideCEST and GuanCEST: (Figure C). Increased CrCEST signals were observed in the AD mouse brain (WT: (0.0018 0.0027) vs AD: (0.0040 0.0026); p = 0.036) (Figure D). Using the simulations in Fig. S3C, an increase of CrCEST signal in AD mice and be explained by a decrease in pH and exchange rate of the guanidinium protons. The distributions of amideCEST contrasts are found to be homogeneous across the entire brain for both AD and WT mice (Figs. G&H), while the GuanCEST in thalamus was lower than that in cortex (Figs. E&F).
In conclusion, we report the observation of CrCEST in-vivo in the brain at 3T. Changes in CrCEST signal in AD mice suggest CrCEST has potential as a marker for AD detection.
Bibliographic Note
Information for this record is supplemented by the author(s) concerned.
Citation Format(s)
Creatine chemical exchange saturation transfer (CrCEST) MRI for Alzheimer's disease detection at 3T. / Wang, Kexin; HUANG, Jianpan; Ju, L et al.
2023. Poster session presented at World Molecular Imaging Congress (WMIC) 2023, Prague, Czech Republic.
2023. Poster session presented at World Molecular Imaging Congress (WMIC) 2023, Prague, Czech Republic.
Research output: Conference Papers › Poster › peer-review