Developing imidazoles as CEST MRI pH sensors

Yang, Xing; Song, Xiaolei; Banerjee, Sangeeta Ray; Li, Yuguo; Byun, Youngjoo; Liu, Guanshu; Bhujwalla, Zaver M.; Pomper, Martin G.; McMahon, Michael T.

doi:10.1002/cmmi.1693

Cited by 50 publications

(68 citation statements)

References 74 publications

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“…Anthranylic acids and imidazoles have also shown similar 300–2000 Hz chemical exchange rates and high 4.0–9.3 ppm MR frequencies that can generate unique CEST signals. Similar to aryl amide CT agents, these agents can have CEST signals that are pH‐dependent, and thus can be designed to measure extracellular pH . Derivatives of these agents can undergo enzyme‐catalyzed modification of a ligand, so that the comparison of enzyme‐responsive and unresponsive CEST signals of the agent can then robustly detect enzyme catalysis, which is known as catalyCEST MRI .…”

Section: Exogenous Cest Agentsmentioning

confidence: 99%

Clinical applications of chemical exchange saturation transfer (CEST) MRI

Jones

Pollard

Pagel

2017

Magnetic Resonance Imaging

222

246

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Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has been developed and employed in multiple clinical imaging research centers worldwide. Selective radiofrequency (RF) saturation pulses with standard 2D and 3D MRI acquisition schemes are now routinely performed, and CEST MRI can produce semiquantitative results using magnetization transfer ratio asymmetry (MTRasym) analysis while accounting for B0 inhomogeneity. Faster clinical CEST MRI acquisition methods and more quantitative acquisition and analysis routines are under development. Endogenous biomolecules with amide, amine, and hydroxyl groups have been detected during clinical CEST MRI studies, and exogenous CEST agents have also been administered to patients. These CEST MRI tools show promise for contributing to assessments of cerebral ischemia, neurological disorders, lymphedema, osteoarthritis, muscle physiology, and solid tumors. This review summarizes the salient features of clinical CEST MRI protocols and critically evaluates the utility of CEST MRI for these clinical imaging applications. Level of Evidence: 5 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:11–27.

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Section: Exogenous Cest Agentsmentioning

confidence: 99%

Clinical applications of chemical exchange saturation transfer (CEST) MRI

Jones

Pollard

Pagel

2017

Magnetic Resonance Imaging

222

246

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“…Chemical exchange saturation transfer (CEST) is a novel MRI approach in which the contrast is generated by saturating specific exchangeable protons on either endogenous or exogenous molecules . Owing to the sensitivity of the proton exchange rate to a variety of chemical and physical factors, including pH, several CEST pH‐responsive probes have been demonstrated to measure tissue pH . Among them, iopamidol is a clinical approved radiographic agent that was demonstrated to report accurate renal pH values, independently from the concentration, at both preclinical and clinical levels .…”

Section: Introductionmentioning

confidence: 99%

Noninvasive evaluation of renal pH homeostasis after ischemia reperfusion injury by CEST‐MRI

et al. 2017

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Acute kidney injury (AKI) in mice caused by sustained ischemia followed by reperfusion is associated with acute tubular necrosis and renal dysfunctional blood flow. Although the principal role of the kidney is the maintenance of acid-base balance, current imaging approaches are unable to assess this important parameter, and clinical biomarkers are not robust enough in evaluating the severity of kidney damage. Therefore, novel noninvasive imaging approaches are needed to assess the acid-base homeostasis in vivo. This study investigates the usefulness of MRI-chemical exchange saturation transfer (CEST) pH imaging (through iopamidol injection) in characterizing moderate and severe AKI in mice following unilateral ischemia reperfusion injury. Moderate (20 min) and severe (40 min) ischemia were induced in Balb/C mice, which were imaged at several time points thereafter (Days 0, 1, 2, 7). A significant increase of renal pH values was observed as early as one day after the ischemia reperfusion damage for both moderate and severe ischemia. MRI-CEST pH imaging distinguished the evolution of moderate from severe AKI. A recovery of normal renal pH values was observed for moderate AKI, whereas a persisting renal pH increase was observed for severe AKI on Day 7. Renal filtration fraction was significantly lower for clamped kidneys (0.54-0.57) in comparison to contralateral kidneys (0.84-0.86) following impairment of glomerular filtration. The severe AKI group showed a reduced filtration fraction even after 7 days (0.38 for the clamped kidneys). Notably, renal pH values were significantly correlated with the histopathological score. In conclusion, MRI-CEST pH mapping is a valid tool for the noninvasive evaluation of both acid-base balance and renal filtration in patients with ischemia reperfusion injury.

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“…Our group has developed the imidazole‐4,5‐dicarboxyimides (I45DCs) for kidney imaging. These contain ‐NH exchangeable protons at 7.8 ppm and 4.5 ppm from water allowing two proton ratiometric imaging, with pH maps of kidney generated after injecting the imidazole compound into mice. The in‐vivo results presented in Figure shows the pH maps calculated at 45 min after injection of I45DC CEST agent.…”

Section: Cest Mri Ph Imaging Applicationsmentioning

confidence: 49%

pH Imaging Using Chemical Exchange Saturation Transfer (CEST) MRI

Pavuluri

McMahon

2017

Israel Journal of Chemistry

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Acid‐base homeostasis is an essential process for maintaining proper pH levels in the body, with alterations in this process potentially signaling pathology. While monitoring urine pH, blood gases and other assays can provide information on the overall systemic pH, it is desirable to get more localized knowledge to assist diagnosis. Various non‐invasive methods have been developed with Chemical Exchange Saturation Transfer (CEST) MRI now emerging as a particularly intriguing technology for detecting pH. In this review, we provide an overview of the paramagnetic and diamagnetic CEST probes available for producing pH maps, describe in depth the various methods to collect CEST MRI data and post‐process the resulting images to create pH maps and describe how this has been applied for detecting renal injury, mapping the pH of tumors and monitoring the health of transplanted therapeutic cells. Finally, we will provide an outlook of the possibilities to translate this technology into patients.

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Developing imidazoles as CEST MRI pH sensors

Cited by 50 publications

References 74 publications

Clinical applications of chemical exchange saturation transfer (CEST) MRI

Clinical applications of chemical exchange saturation transfer (CEST) MRI

Noninvasive evaluation of renal pH homeostasis after ischemia reperfusion injury by CEST‐MRI

pH Imaging Using Chemical Exchange Saturation Transfer (CEST) MRI

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