pH Imaging Using Chemical Exchange Saturation Transfer (CEST) MRI

Pavuluri, Kowsalya Devi; McMahon, Michael T.

doi:10.1002/ijch.201700075

Cited by 19 publications

(21 citation statements)

References 123 publications

(166 reference statements)

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“…pH‐sensitive chemical exchange saturation transfer (CEST) MRI is a promising new method for in vivo applications . Exogenous CEST agent pH mapping have already been applied for kidney imaging.…”

Section: Discussionmentioning

confidence: 99%

“…Since the exchange rate of urea is minimal at this pH range, it might be challenging to obtain the pH maps of kidneys using only the quantitative urea‐weighted CEST method. On the other hand, pH could be measured independently using paraCEST (eg, Lanthanide‐DOTA‐tetraamide complexes, Eu3+ based agents) or diaCEST agents (eg, Iopamidol) in order to derive urea concentration by combining Equations 1 and 10 …”

Section: Discussionmentioning

confidence: 99%

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Proton exchange in aqueous urea solutions measured by water‐exchange (WEX) NMR spectroscopy and chemical exchange saturation transfer (CEST) imaging in vitro

Stabinska

Neudecker

Ljimani

et al. 2019

Magnetic Resonance in Med

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Purpose:To characterize the proton exchange in aqueous urea solutions using a modified version of the WEX II filter at high magnetic field, and to assess the feasibility of performing quantitative urea CEST MRI on a 3T clinical MR system. Methods: In order to study the dependence of the exchange-rate constant k sw of urea as a function of pH and T, the WEX-spectra were acquired at 600 MHz from urea solutions in a pH range from 6.4 to 8.0 and a temperature range from T = 22 • C to 37 • C. The CEST experiments were performed on a 3T MRI scanner by applying a train of 50 Gaussian-shaped pulses, each 100-millisecond long with a spacing of 100 milliseconds, for saturation. Exchange rates of urea were calculated using the (extended) AREX metric. Results: The results showed that proton exchange in aqueous urea solutions is acid and base catalyzed with the rate constants: k a = (9.95 ± 1.1) × 10 6 l/(mol·s) and k b = (6.21 ± 0.21) × 10 6 l/(mol·s), respectively. Since the urea protons undergo a slow exchange with water protons, the CEST effect of urea can be observed efficiently at 3T. However, in neutral solutions the exchange rate of urea is minimal and cannot be estimated using the quantitative CEST approach. Conclusions: By means of the WEX-spectroscopy, the kinetic parameters of the proton exchange in urea solutions have been determined. It was also possible to estimate the exchange rates of urea in a broad range of pH values using the CEST method at a clinical scanner. K E Y W O R D SCEST, exchange rate, proton exchange, urea, urCEST, WEX

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proton exchange in aqueous urea solutions measured by water‐exchange (WEX) NMR spectroscopy and chemical exchange saturation transfer (CEST) imaging in vitro

Stabinska

Neudecker

Ljimani

et al. 2019

Magnetic Resonance in Med

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“…In contrast to these methods, magnetic resonance imaging (MRI) approaches do not rely on ionizing radiation, offer a high penetration depth and excellent soft tissue contrast, and allow fast acquisition of high-resolution anatomical images at the same time. Saturation transfer between bulk water and exchangeable protons of molecules with pH-dependent exchange rates [ 11 ] or relaxivities of lanthanide complexes can be used for pH imaging [ 12 ]. Additionally, thermally polarized signals of molecules bearing pH sensitive 1 H, 19 F [ 13 ] and 31 P [ 14 ] nuclei can be exploited for in vivo pH measurements.…”

Section: Introductionmentioning

confidence: 99%

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules

Hundshammer

Düwel

Ruseckas

et al. 2018

Sensors

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pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (pKa). Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the pKa of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1-13C]serine amide and [1-13C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei (13C, 15N, 31P) with high sensitivity up to 4.8 ppm/pH and we show that 13C spins can be hyperpolarized with dissolution dynamic polarization (DNP). Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications.

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“…As a method of generating contrast in MRI scans, the use of exogenous CEST agents has several advantages over the more conventional relaxation agents used in clinical radiology. CEST agents can be turned on and off post-administration (Zhang et al, 2003 ), they can be selectively imaged even in the presence of another CEST agent (Aime et al, 2005 ), they can also be used to ratiometrically sense the concentration of biologically relevant species such as pH, lactate concentration, temperature or enzyme activity (Olatunde et al, 2015 ; Pavuluri and McMahon, 2017 ; Sinharay et al, 2017 ; Zhang et al, 2017a , b ). But for all these advantages CEST still suffers from one very serious drawback: exogenous CEST agents have inherently high detection limits.…”

Section: Introductionmentioning

confidence: 99%

ParaCEST Agents Encapsulated in Reverse Nano-Assembled Capsules (RACs): How Slow Molecular Tumbling Can Quench CEST Contrast

et al. 2018

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Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid (PAA) after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride (PAH) followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. The quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST.

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pH Imaging Using Chemical Exchange Saturation Transfer (CEST) MRI

Cited by 19 publications

References 123 publications

Proton exchange in aqueous urea solutions measured by water‐exchange (WEX) NMR spectroscopy and chemical exchange saturation transfer (CEST) imaging in vitro

Proton exchange in aqueous urea solutions measured by water‐exchange (WEX) NMR spectroscopy and chemical exchange saturation transfer (CEST) imaging in vitro

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules

ParaCEST Agents Encapsulated in Reverse Nano-Assembled Capsules (RACs): How Slow Molecular Tumbling Can Quench CEST Contrast

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