Abstract 63: Novel Imaging of Protein Integrity to Better Define Ischemic Injury After Stroke

Introduction: Ischemic injury on MRI is defined acutely by measuring the diffusion of water alone. Chemical exchange saturation transfer imaging (CEST) allows measurement of intracellular pH, and changes in protein structure and mobility using Nuclear Overhauser Enhancement (NOE). When identifying treatment targets, changes to protein integrity have the potential to complement diffusion-weighted imaging (DWI) in distinguishing irreversible from reversible intracellular processes that are amenable to therapeutic intervention. Methods: Patients with non-lacunar ischemic stroke underwent serial MRI over 1 month. The imaging protocol included single slice CEST imaging. NOE was quantified using a 3-pool exchange model relative to the contralateral hemisphere (rNOE*). DWI, ASL perfusion imaging, T1-weighted and FLAIR imaging were used to define the tissue outcome: ischemic core, infarct growth, and oligemic tissue that survived. Infarct growth was classified as early or late (before or after 24 hours). Images and masks were registered to CEST native image space for voxelwise and patient-level serial analyses. Results: 30 patients were included in the analysis. Within 6 hours rNOE* in early infarct growth was significantly lower than ischemic core and late infarct growth (p<0.001 and p<0.001, see Figure). In patient-level analyses, rNOE* dropped over the initial 24 hours in the ischemic core and early infarct growth regions, but not in regions of late infarct growth or oligemia. Conclusion: rNOE* showed a discrete temporal profile in tissue that infarcted by 24 hours in contrast to that which survived or infarcted later. This is additive information to that provided by routine acute stroke MRI at presentation, and demonstrates that the imaging of intracellular protein structure and mobility may have a role alongside DWI in helping to predict tissue fate. Further work is required to understand the potential of NOE as a modifiable imaging biomarker.

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Whole-brain amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging in glioma patients using low-power steady-state pulsed chemical exchange saturation transfer (CEST) imaging at 7T

Journal of Magnetic Resonance Imaging ◽

10.1002/jmri.25108 ◽

2015 ◽

Vol 44 (1) ◽

pp. 41-50 ◽

Cited By ~ 49

Author(s):

Hye-Young Heo ◽

Craig K. Jones ◽

Jun Hua ◽

Nirbhay Yadav ◽

Shruti Agarwal ◽

...

Keyword(s):

Steady State ◽

Proton Transfer ◽

Low Power ◽

Chemical Exchange ◽

Chemical Exchange Saturation Transfer ◽

Amide Proton ◽

Saturation Transfer ◽

Nuclear Overhauser Enhancement ◽

Cest Imaging ◽

Nuclear Overhauser

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Novel nanomedicine with a chemical-exchange saturation transfer effect for breast cancer treatment in vivo

Journal of Nanobiotechnology ◽

10.1186/s12951-019-0557-0 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 5

Author(s):

Yanlong Jia ◽

Chaochao Wang ◽

Jiehua Zheng ◽

Guisen Lin ◽

Dalong Ni ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Treatment ◽

Chemical Exchange ◽

Raft Polymerization ◽

Animal Experiments ◽

Chemical Exchange Saturation Transfer ◽

Saturation Transfer ◽

Cest Imaging

Abstract Background Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. Results To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 μg/mL vs. ~ 5 μg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). Conclusions The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.

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Assessment of a clinically feasible Bayesian fitting algorithm using a simplified description of Chemical Exchange Saturation Transfer (CEST) imaging

Journal of Magnetic Resonance ◽

10.1016/j.jmr.2019.01.006 ◽

2019 ◽

Vol 300 ◽

pp. 120-134 ◽

Cited By ~ 1

Author(s):

Aaron Kujawa ◽

Mina Kim ◽

Eleni Demetriou ◽

Annasofia Anemone ◽

Dario Livio Longo ◽

...

Keyword(s):

Chemical Exchange ◽

Chemical Exchange Saturation Transfer ◽

Saturation Transfer ◽

Cest Imaging ◽

Fitting Algorithm

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pH Mapping of Skeletal Muscle by Chemical Exchange Saturation Transfer (CEST) Imaging

Cells ◽

10.3390/cells9122610 ◽

2020 ◽

Vol 9 (12) ◽

pp. 2610

Author(s):

Yu-Wen Chen ◽

Hong-Qing Liu ◽

Qi-Xuan Wu ◽

Yu-Han Huang ◽

Yu-Ying Tung ◽

...

Keyword(s):

Skeletal Muscle ◽

Electrical Stimulation ◽

Magnetic Resonance ◽

Ph Value ◽

Chemical Exchange ◽

Chemical Exchange Saturation Transfer ◽

Resonance Spectroscopy ◽

Saturation Transfer ◽

Ph Changes ◽

Cest Imaging

Magnetic resonance imaging (MRI) is extensively used in clinical and basic biomedical research. However, MRI detection of pH changes still poses a technical challenge. Chemical exchange saturation transfer (CEST) imaging is a possible solution to this problem. Using saturation transfer, alterations in the exchange rates between the solute and water protons because of small pH changes can be detected with greater sensitivity. In this study, we examined a fatigued skeletal muscle model in electrically stimulated mice. The measured CEST signal ratio was between 1.96 ppm and 2.6 ppm in the z-spectrum, and this was associated with pH values based on the ratio between the creatine (Cr) and the phosphocreatine (PCr). The CEST results demonstrated a significant contrast change at the electrical stimulation site. Moreover, the pH value was observed to decrease from 7.23 to 7.15 within 20 h after electrical stimulation. This pH decrease was verified by 31P magnetic resonance spectroscopy and behavioral tests, which showed a consistent variation over time.

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