Eleni Demetriou

Bio: Eleni Demetriou is an academic researcher from University College London. The author has contributed to research in topics: Pulse sequence & Liposome. The author has an hindex of 3, co-authored 7 publications receiving 59 citations.

QUESP and QUEST revisited - fast and accurate quantitative CEST experiments.

Abstract: Purpose Chemical exchange saturation transfer (CEST) NMR or MRI experiments allow detection of low concentrated molecules with enhanced sensitivity via their proton exchange with the abundant water pool. Be it endogenous metabolites or exogenous contrast agents, an exact quantification of the actual exchange rate is required to design optimal pulse sequences and/or specific sensitive agents. Methods Refined analytical expressions allow deeper insight and improvement of accuracy for common quantification techniques. The accuracy of standard quantification methodologies, such as quantification of exchange rate using varying saturation power or varying saturation time, is improved especially for the case of nonequilibrium initial conditions and weak labeling conditions, meaning the saturation amplitude is smaller than the exchange rate (γB1 Results The improved analytical 'quantification of exchange rate using varying saturation power/time' (QUESP/QUEST) equations allow for more accurate exchange rate determination, and provide clear insights on the general principles to execute the experiments and to perform numerical evaluation. The proposed methodology was evaluated on the large-shift regime of paramagnetic chemical-exchange-saturation-transfer agents using simulated data and data of the paramagnetic Eu(III) complex of DOTA-tetraglycineamide. Conclusions The refined formulas yield improved exchange rate estimation. General convergence intervals of the methods that would apply for smaller shift agents are also discussed. Magn Reson Med 79:1708-1721, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Effect of Liposomal Encapsulation on the Chemical Exchange Properties of Diamagnetic CEST Agents.

Abstract: Exogenous chemical exchange saturation transfer (CEST) contrast agents such as glucose or 2-deoxy-d-glucose (2-DG) have shown high sensitivities and significant potential for monitoring glucose uptake in tumors with MRI. Here, we show that liposome encapsulation of such agents can be exploited to enhance the CEST signal by reducing the overall apparent exchange rate. We have developed a concise analytical model to describe the liposomal contrast dependence on several parameters such as pH, temperature, irradiation amplitude, and intraliposomal water content. This is the first study in which a model has been constructed to measure the exchange properties of diamagnetic CEST agents encapsulated inside liposomes. Experimentally measured exchange rates of glucose and 2-DG in the liposomal system were found to be reduced due to the intermembrane exchange between the intra- and extraliposomal compartments because of restrictions in water transfer imposed by the lipid membrane. These new theoretical and experimental findings will benefit applications of diamagnetic liposomes to image biological processes. In addition, combining this analytical model with measurements of the CEST signal enhancement using liposomes as a model membrane system is an important new general technique for studying membrane permeability.

PRO-QUEST: a rapid assessment method based on progressive saturation for quantifying exchange rates using saturation times in CEST.

Abstract: Purpose To develop a new MRI technique to rapidly measure exchange rates in CEST MRI. Methods A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (progressive saturation for quantifying exchange rates using saturation times), has been developed. Using this method, the water magnetization is sampled under non-steady-state conditions, and off-resonance saturation is interleaved with the acquisition of images obtained through a Look-Locker type of acquisition. A complete theoretical framework has been set up, and simple equations to obtain the exchange rates have been derived. Results A reduction of scan time from 58 to 16 minutes has been obtained using PRO-QUEST versus the standard QUEST. Maps of both T1 of water and B1 can simply be obtained by repetition of the sequence without off-resonance saturation pulses. Simulations and calculated exchange rates from experimental data using amino acids such as glutamate, glutamine, taurine, and alanine were compared and found to be in good agreement. The PRO-QUEST sequence was also applied on healthy and infarcted rats after 24 hours, and revealed that imaging specificity to ischemic acidification during stroke was substantially increased relative to standard amide proton transfer-weighted imaging. Conclusion Because of the reduced scan time and insensitivity to nonchemical exchange factors such as direct water saturation, PRO-QUEST can serve as an excellent alternative for researchers and clinicians interested to map pH changes in vivo.

Quantitative magnetic resonance imaging of brain anatomy and in vivo histology

Abstract: Quantitative magnetic resonance imaging (qMRI) goes beyond conventional MRI, which aims primarily at local image contrast. It provides specific physical parameters related to the nuclear spin of protons in water, such as relaxation times. These parameters carry information about the local microstructural environment of the protons (such as myelin in the brain). Non-invasive in vivo histology using MRI (hMRI) aims to use this information to directly characterize biological tissue microstructure, partially replacing or complementing classical invasive histology. The understanding of MRI tissue contrast provided by hMRI is, in turn, crucial for further improvements of qMRI, and they should be considered closely interlinked. We discuss concepts, models and validation approaches, pointing out challenges and the latest advances in this field. Further, we point out links to physics, including computational and analytical approaches and developments in materials science and photonics, that aid in reference data acquisition and model validation. Quantitative magnetic resonance imaging and in vivo histology go beyond standard magnetic resonance imaging, aiming at characterizing tissue microstructure of the living brain. This Technical Review discusses advances in concepts, instrumentation, biophysical models and validation approaches facilitating this rapidly developing field.

Rapid and quantitative chemical exchange saturation transfer (CEST) imaging with magnetic resonance fingerprinting (MRF).

Abstract: PURPOSE To develop a fast magnetic resonance fingerprinting (MRF) method for quantitative chemical exchange saturation transfer (CEST) imaging. METHODS We implemented a CEST-MRF method to quantify the chemical exchange rate and volume fraction of the Nα -amine protons of L-arginine (L-Arg) phantoms and the amide and semi-solid exchangeable protons of in vivo rat brain tissue. L-Arg phantoms were made with different concentrations (25-100 mM) and pH (pH 4-6). The MRF acquisition schedule varied the saturation power randomly for 30 iterations (phantom: 0-6 μT; in vivo: 0-4 μT) with a total acquisition time of ≤2 min. The signal trajectories were pattern-matched to a large dictionary of signal trajectories simulated using the Bloch-McConnell equations for different combinations of exchange rate, exchangeable proton volume fraction, and water T1 and T2 relaxation times. RESULTS The chemical exchange rates of the Nα -amine protons of L-Arg were significantly (P < 0.0001) correlated with the rates measured with the quantitation of exchange using saturation power method. Similarly, the L-Arg concentrations determined using MRF were significantly (P < 0.0001) correlated with the known concentrations. The pH dependence of the exchange rate was well fit (R2 = 0.9186) by a base catalyzed exchange model. The amide proton exchange rate measured in rat brain cortex (34.8 ± 11.7 Hz) was in good agreement with that measured previously with the water exchange spectroscopy method (28.6 ± 7.4 Hz). The semi-solid proton volume fraction was elevated in white (12.2 ± 1.7%) compared to gray (8.1 ± 1.1%) matter brain regions in agreement with previous magnetization transfer studies. CONCLUSION CEST-MRF provides a method for fast, quantitative CEST imaging.

Towards the complex dependence of MTRasym on T1w in amide proton transfer (APT) imaging.

Abstract: Amide proton transfer (APT) imaging is a variation of chemical exchange saturation transfer MRI that has shown promise in diagnosing tumors, ischemic stroke, multiple sclerosis, traumatic brain injury, etc. Specific quantification of the APT effect is crucial for the interpretation of APT contrast in pathologies. Conventionally, magnetization transfer ratio with asymmetric analysis (MTRasym ) has been used to quantify the APT effect. However, some studies indicate that MTRasym is contaminated by water longitudinal relaxation time (T1w ), and thus it is necessary to normalize T1w in MTRasym to obtain specific quantification of the APT effect. So far, whether to use MTRasym or the T1w -normalized MTRasym is still under debate in the field. In this paper, the influence of T1w on the quantification of APT was evaluated through theoretical analysis, numerical simulations, and phantom studies for different experimental conditions. Results indicate that there are two types of T1w effect (T1w recovery and T1w -related saturation), which have inverse influences on the steady-state MTRasym . In situations with no or weak direct water saturation (DS) effect, there is only the T1w recovery effect, and MTRasym linearly depends on T1w . In contrast, in situations with significant DS effects, the dependence of MTRasym on T1w is complex, and is dictated by the competition of these two T1w effects. Therefore, by choosing appropriate irradiation powers, MTRasym could be roughly insensitive to T1w . Moreover, in non-steady-state acquisitions with very short irradiation time, MTRasym is also roughly insensitive to T1w . Therefore, for steady-state APT imaging at high fields or with very low irradiation powers, where there are no significant DS effects, it is necessary to normalize T1w to improve the specificity of MTRasym . However, in clinical MRI systems (usually low fields or non-steady-state acquisitions), T1w normalization may not be necessary when appropriate sequence parameters are chosen.

Review and consensus recommendations on clinical APT‐weighted imaging approaches at 3T: Application to brain tumors

Abstract: Amide proton transfer‐weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed‐on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi‐center trials in larger patient cohorts and, ultimately, routine clinical use.