Radiofrequency Saturation Research Articles

Estimating the synaptic density deficit in Alzheimer's disease using multi-contrast CEST imaging.

In vivo noninvasive imaging of neurometabolites is crucial to improve our understanding of the underlying pathophysiological mechanism in neurodegenerative diseases. Abnormal changes in synaptic organization leading to synaptic degradation and neuronal loss is considered as one of the primary factors driving Alzheimer's disease pathology. Magnetic resonance based molecular imaging techniques such as chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) can provide neurometabolite specific information which may relate to underlying pathological and compensatory mechanisms. In this study, CEST and short echo time single voxel MRS was performed to evaluate the sensitivity of cerebral metabolites to beta-amyloid (Aβ) induced synaptic deficit in the hippocampus of a mouse model of Alzheimer's disease. The CEST based spectra (Z-spectra) were acquired on a 9.4 Tesla small animal MR imaging system with two radiofrequency (RF) saturation amplitudes (1.47 μT and 5.9 μT) to obtain creatine-weighted and glutamate-weighted CEST contrasts, respectively. Multi-pool Lorentzian fitting and quantitative T1 longitudinal relaxation maps were used to obtain metabolic specific apparent exchange-dependent relaxation (AREX) maps. Short echo time (TE = 12 ms) single voxel MRS was acquired to quantify multiple neurometabolites from the right hippocampus region. AREX contrasts and MRS based metabolite concentration levels were examined in the ARTE10 animal model for Alzheimer's disease and their wild type (WT) littermate counterparts (age = 10 months). Using MRS voxel as a region of interest, group-wise analysis showed significant reduction in Glu-AREX and Cr-AREX in ARTE10, compared to WT animals. The MRS based results in the ARTE10 mice showed significant decrease in glutamate (Glu) and glutamate-total creatine (Glu/tCr) ratio, compared to WT animals. The MRS results also showed significant increase in total creatine (tCr), phosphocreatine (PCr) and glutathione (GSH) concentration levels in ARTE10, compared to WT animals. In the same ROI, Glu-AREX and Cr-AREX demonstrated positive associations with Glu/tCr ratio. These results indicate the involvement of neurotransmitter metabolites and energy metabolism in Aβ-mediated synaptic degradation in the hippocampus region. The study also highlights the feasibility of CEST and MRS to identify and track multiple competing and compensatory mechanisms involved in heterogeneous pathophysiology of Alzheimer's disease in vivo.

Evidence of 13 C-lactate oxidation in the human brain from hyperpolarized 13 C-MRI.

To test the hypothesis that lactate oxidation contributes to the C-bicarbonate signal observed in the awake human brain using hyperpolarized C MRI. Healthy human volunteers (N = 6) were scanned twice using hyperpolarized C-MRI, with increased radiofrequency saturation of C-lactate on one set of scans. C-lactate, C-bicarbonate, and C-pyruvate signals for 132 brain regions across each set of scans were compared using a clustered Wilcoxon signed-rank test. Increased C-lactate radiofrequency saturation resulted in a significantly lower C-bicarbonate signal (p = 0.04). These changes were observed across the majority of brain regions. Radiofrequency saturation of C-lactate leads to a decrease in C-bicarbonate signal, demonstrating that the C-lactate generated from the injected C-pyruvate is being converted back to C-pyruvate and oxidized throughout the human brain.

CEST-based detection of labile protons by ultrafast 2D NMR

Chemical exchange saturation transfer (CEST) NMR is widely used for enhancing the sensitivity of low-abundance exchanging sites in general, and for the water-based detection of labile metabolite protons under in vivo conditions in particular. CEST, however, faces a number of limitations when targeting multiple metabolites, including a radiofrequency (RF)-induced broadening of the detected peaks, and relatively long acquisition times deriving from its continuous-wave nature. Methods have been proposed to overcome these limitations, including a Fourier-encoded version of CEST –the Frequency-Labeled EXchange (FLEX) experiment– and the incorporation of background gradients during the RF saturation time. This work explores an alternative avenue, based on spatiotemporally encoded ultrafast (UF) 2D NMR. UF NMR can compress the time-domain indirect-dimension encoding of 2D NMR into a single shot; to exploit these potential time savings, an UF version of the FLEX experiment was taken as starting point, and the multiple t1-incremented amplitude modulation cycles that the FLEX experiment normally requires were replaced by a single-shot spatiotemporal encoding. The ensuing UF 2D FLEX experiment was then used to monitor the spectral signatures of multiple moieties as they exchange with the solvent, by imprinting these onto the water resonance as in the original experiment –but now all within a single shot. Upon incorporating two-scan phase cycling and quadrature detection, the resulting method showed an experimental performance similar to t1-encoded FLEX, while providing significant time savings plus imaging information that could be of further use in in vivo studies. The main advantages, features and drawbacks observed for UF 2D FLEX are briefly discussed.

Demonstration of pH imaging in acute stroke with endogenous ratiometric chemical exchange saturation transfer magnetic resonance imaging at 2ppm.

pH change is often considered a hallmark of metabolic disruption in diseases such as ischemic stroke and cancer. Chemical exchange saturation transfer (CEST) MRI, particularly amide proton transfer (APT), has emerged as a noninvasive pH imaging approach. However, there are changes in multipool CEST effects besides APT MRI. Our study investigated radiofrequency (RF) amplitude-based ratiometric CEST pH imaging in acute stroke. Briefly, adult male Wistar rats underwent CEST MRI under two RF saturation (B1 ) levels of 0.75 and 1.5 μT following middle cerebral artery occlusion. Magnetization transfer (MT), direct water saturation, CEST at 2ppm (CEST@2ppm), amine (2.75 ppm), and APT (3.5ppm) effects were resolved with the multipool Lorentzian fitting approach. The ratiometric analysis was measured in the ischemic lesion and the contralateral normal area, which was also correlated with pH-specific MT and the relaxation normalized APT (MRAPT) index. MT, amine CEST effect, and their respective ratiometric indices did not show significant changes in ischemic regions (p> 0.05), as expected. Whereas APT decreased in the ischemic lesion for B1 of 1.5 μT (p< 0.01), the correlation between the amide ratio with MRAPT index was moderate (r = 0.52, p= 0.02). By comparison, the ischemic tissue showed a significantly increased CEST@2ppm for both saturation levels from the contralateral normal area (p≤0.01). Importantly, the CEST@2ppm ratio decreased in the ischemic lesion (p< 0.01), which highly correlated with the MRAPT index (r = 0.93, p< 0.001). To summarize, our study demonstrated the feasibility of endogenous CEST@2ppm ratiometric imaging of pH upon acute stroke, promising to detect pH changes in metabolic diseases.

Quasi-steady-state amide proton transfer (QUASS APT) MRI enhances pH-weighted imaging of acute stroke.

Chemical exchange saturation transfer (CEST) imaging measurement depends not only on the labile proton concentration and pH-dependent exchange rate but also on experimental conditions, including the relaxation delay and radiofrequency (RF) saturation time. Our study aimed to extend a quasi-steady-state (QUASS) solution to a modified multi-slice CEST MRI sequence and test if it provides enhanced pH imaging after acute stroke. Our study derived the QUASS solution for a modified multislice CEST MRI sequence with an unevenly segmented RF saturation between image readout and signal averaging. Numerical simulation was performed to test if the generalized QUASS solution corrects the impact of insufficiently long relaxation delay, primary and secondary saturation times, and multi-slice readout. In addition, multiparametric MRI scans were obtained after middle cerebral artery occlusion, including relaxation and CEST Z-spectrum, to evaluate the performance of QUASS CEST MRI in a rodent acute stroke model. We also performed Lorentzian fitting to isolate multi-pool CEST contributions. The QUASS analysis enhanced pH-weighted magnetization transfer asymmetry contrast over the routine apparent CEST measurements in both contralateral normal (-3.46% ± 0.62% (apparent) vs. -3.67% ± 0.66% (QUASS), P&lt; 0.05) and ischemic tissue (-5.53% ± 0.68% (apparent) vs. -5.94% ± 0.73% (QUASS), P&lt; 0.05). Lorentzian fitting also showed significant differences between routine and QUASS analysis of ischemia-induced changes in magnetization transfer, amide, amine, guanidyl CEST, and nuclear Overhauser enhancement (-1.6parts per million) effects. Our study demonstrated that generalized QUASS analysis enhanced pH MRI contrast and improved quantification of the underlying CEST contrast mechanism, promising for further in vivo applications.

Saturation-prolongated and inhomogeneity-mitigated chemical exchange saturation transfer imaging with parallel transmission.

Chemical exchange saturation transfer (CEST) imaging benefits from a longer saturation duration and a higher saturation duty cycle. Dielectric shading effects occur when the radiofrequency (RF) wavelength approaches the object size. Here, we proposed a simultaneous parallel transmission-based CEST (pTx-CEST) sequence to prolongate the saturation duration at a 100% duty cycle and improve the RF saturation homogeneity in CEST imaging. The simultaneous pTx-CEST sequence was implemented by switching the CEST saturation module from the non-pTx to pTx mode, using the pTx functionality with both transmit channels being driven simultaneously (instead of time-interleaved). The optimization of amplitude ratio and phase difference settings between RF channels for best B1 homogeneity was performed in phantoms of two different sizes mimicking the human brain and abdomen. The optimal amplitude and phase settings generating the best B1 homogeneity in the phantoms were used in pTx-CEST scans of the human study. The comparison of the maximum achievable saturation duration between the non-pTx-CEST and pTx-CEST sequences was performed in a protein phantom, healthy volunteers, and a metastatic brain tumor patient. The optimal amplitude ratio and phase difference setting between transmit channels manifested circular and elliptical polarization in the head-sized and abdomen-sized phantoms. In the brain, the maximum saturation durations achieved at a 100% duty cycle using the simultaneous pTx-CEST sequence were prolonged to 2240, 3220, and 4200 ms compared with 980 ms using the non-pTx-CEST sequence at repetition times of 3, 4, and 5s, respectively. The longer saturation duration helped improve the image contrast between the tumor and the normal tissue in the patient. The optimized elliptical polarization mode saturation pulses yielded improved uniformity of CEST signals acquired from the human abdomen. The proposed simultaneous pTx-CEST sequence enabled essentially arbitrarily long saturation duration at a 100% duty cycle and helped reduce the dielectric shading effects with the optimized RF setting.

A strategy to reduce the sensitivity of inhomogeneous magnetization transfer (ihMT) imaging to radiofrequency transmit field variations at 3 T.

To minimize the sensitivity of inhomogeneous magnetization transfer gradient-echo (ihMT-GRE) imaging to radiofrequency (RF) transmit field ( ) inhomogeneities at 3 T. The ihMT-GRE sequence was optimized by varying the concentration of the RF saturation energy over time, obtained by increasing the saturation pulse power while extending the sequence repetition time (TR). Different protocols were tested using numerical simulations and human in vivo experiments in the brain white matter (WM) of healthy subjects at 3 T. The sensitivity of the ihMT ratio (ihMTR) to variations was investigated by comparing measurements obtained at nominal transmitter adjustments and following a 20% global drop. The resulting relative variations (δihMTR ) were evaluated voxelwise as a function of the local distribution. The reproducibility of the protocol providing minimal bias was assessed in a test-retest experiment. In line with simulations, ihMT-GRE experiments conducted at high concentration of the RF energy over time demonstrated strong reduction of the inhomogeneity effects in the human WM. Under the optimal conditions of 350-ms TR and 3-µT root mean square (RMS) saturation power, 73% of all WM voxels presented δihMTR below 10%. Reproducibility analysis yielded a close-to-zero systematic bias (ΔihMTR=-0.081%) and a high correlation (ρ²=0.977) between test and retest experiments. Concentrating RF saturation energy in ihMT-GRE sequences mitigates the sensitivity of the ihMTR to variations and allows for clinical-ready ihMT imaging at 3 T. This feature is of particular interest for high and ultra-high field applications.

Germanium Photodiode Arrays on Silicon-On-Insulator With On-Chip Bias Circuit

Foundry-enabled Ge-on-Si waveguide (WG) photodiodes (PDs) with on-chip bias circuit are demonstrated. While a single-element PD has a 52-GHz bandwidth (BW) and a radio frequency (RF) saturation power of -11 dBm at 40 GHz, PD arrays composed of 2 and 4 PDs have RF saturation powers of -6.7 dBm at 40 GHz and -2.3 dBm at 27 GHz, respectively. The bias circuits are analyzed.

A model-based framework for correcting inhomogeneity effects in magnetization transfer saturation and inhomogeneous magnetization transfer saturation maps.

In this work, we propose that Δ -induced errors in magnetization transfer (MT) saturation (MTsat ) maps can be corrected with use of an R1 and map and through numerical simulations of the sequence. One healthy subject was scanned at 3.0T using a partial quantitative MT protocol to estimate the relationship between observed R1 (R1,obs ) and apparent bound pool size ( ) in the brain. MTsat values were simulated for a range of , R1,obs , and . An equation was fit to the simulated MTsat , then a linear relationship between R1,obs and was generated. These results were used to generate correction factor maps for the MTsat acquired from single-point data. The proposed correction was compared to an empirical correction factor with different MT-preparation schemes. was highly correlated with R1,obs (r > 0.96), permitting the use of R1,obs to estimate for correction. All corrected MTsat maps displayed a decreased correlation with compared to uncorrected MTsat and MTsat corrected with an empirical factor in the corpus callosum. There was good agreement between the proposed approach and the empirical correction with radiofrequency saturation at 2 kHz, with larger deviations seen when using saturation pulses further off-resonance and in inhomogeneous (ih) MTsat maps. The proposed correction decreases the dependence of MTsat on inhomogeneities. Furthermore, this flexible framework permits the use of different saturation protocols, making it useful for correcting inhomogeneities in ihMT.

Development of Radiofrequency Saturation Amplitude-independent Quantitative Markers for Magnetization Transfer MRI of Prostate Cancer.

In the United States, prostate cancer has a relatively large impact on men's health. Magnetic resonance imaging (MRI) is useful for the diagnosis and treatment of prostate cancer. The purpose of this study was to develop a quantitative marker for use in prostate cancer magnetization transfer (MT) magnetic resonance imaging (MRI) studies that is independent of radiofrequency (RF) saturation amplitude. Eighteen patients with biopsy-proven prostate cancer were enrolled in this study. MTMRI images were acquired using four RF saturation amplitudes at 33 frequency offsets. ROIs were delineated for the peripheral zone (PZ), central gland (CG), and tumor. Z-spectral data were collected in each region and fit to a three-parameter equation. The three parameters are: the magnitude of the bulk water pool (Aw), the full width at half maximum of the water pool (Gw), and the magnitude of the bound pool (Ab), while, the slopes from the linear regressions of Gw and Ab on RF saturation amplitude (called kAb and kGw) were used as quantitative markers. A pairwise statistically significant difference was found between the PZ and tumor regions for the two saturation amplitude-independent quantitative markers. No pairwise statistically significant differences were found between the CG and tumor regions for any quantitative markers. The significant differences between the values of the two RF saturation amplitudeindependent quantitative markers in the PZ and tumor regions reveal that these markers may be capable of distinguishing healthy PZ tissue from prostate cancer.

Germanium photodetector with distributed absorption regions.

The bandwidth and saturation power of germanium photodetectors are two crucial parameters for implementing analog and microwave photonics circuits. In conventional schemes, it is hard to optimize these two parameters simultaneously, due to different requirements for the size of absorption region. We report the design and demonstration of a high-power and high-speed germanium photodetector with distributed absorption regions. In this distributed-absorption photodetector (DAPD), the junction is formed by a multiple absorption region (n-cell) on a mutual substrate, and the input light is split and fed into the n cells. A comprehensive theoretical model is developed, and the device bandwidth and power loss in aspect of the number of cells is discussed. Experimentally, 2-, 4- and 8-cell DAPDs are investigated, and the 2-cell scheme shows the superior performance with the radio-frequency saturation photocurrent as high as 16.1 mA and the 3 dB bandwidth as high as 50 GHz. Without changing the standard process in the silicon photonic foundry, the DAPD can be seamlessly integrated with other photonics devices, and it is very attractive to applications such as integrated microwave photonics systems.

Quantifying amide proton exchange rate and concentration in chemical exchange saturation transfer imaging of the human brain

Current chemical exchange saturation transfer (CEST) neuroimaging protocols typically acquire CEST-weighted images, and, as such, do not essentially provide quantitative proton-specific exchange rates (or brain pH) and concentrations. We developed a dictionary-free MR fingerprinting (MRF) technique to allow CEST parameter quantification with a reduced data set. This was accomplished by subgrouping proton exchange models (SPEM), taking amide proton transfer (APT) as an example, into two-pool (water and semisolid macromolecules) and three-pool (water, semisolid macromolecules, and amide protons) models. A variable radiofrequency saturation scheme was used to generate unique signal evolutions for different tissues, reflecting their CEST parameters. The proposed MRF-SPEM method was validated using Bloch-McConnell equation-based digital phantoms with known ground-truth, which showed that MRF-SPEM can achieve a high degree of accuracy and precision for absolute CEST parameter quantification and CEST phantoms. For in-vivo studies at 3 T, using the same model as in the simulations, synthetic Z-spectra were generated using rates and concentrations estimated from the MRF-SPEM reconstruction and compared with experimentally measured Z-spectra as the standard for optimization. The MRF-SPEM technique can provide rapid and quantitative human brain CEST mapping.

Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI

The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile proteins at the frequency offsets for the composite protein amide proton (+3.6 ppm) and aliphatic proton (−3.6 ppm) signals. Using a relatively weak radiofrequency (RF) saturation amplitude, contributions due to strong magnetization transfer contrast (MTC) from solid-like macromolecules and direct water saturation (DS) were minimized. For practical measure of the changes in the mobile protein configuration, we defined a saturation transfer difference (ΔST) by subtracting the Z-spectral signals at ±3.6 ppm from a control signal at 8 ppm. Phantom studies of glutamate solution, protein (egg white) and hair conditioner show the capability of the proposed scheme to minimize the contributions from amine protons, DS, and MTC, respectively. The ST signal at ±3.6 ppm of the cross-linked bovine serum albumin (BSA) solutions demonstrated that the ΔST signal can be used to monitor the aggregation process of the mobile proteins. High-resolution ΔST images of AD mouse brains at ±3.6 ppm of mouse brains showed significantly reduced ΔST (-3.6) signal compared to the age-matched wild-type (WT) mice. Thus, this signal has potential to serve as a molecular biomarker for monitoring protein aggregation in AD.

Direct radiofrequency saturation corrected amide proton transfer tumor MRI at 3T.

Amide proton transfer (APT) imaging has been increasingly applied in tumor characterization that complements diffusion and dynamic contrast-enhanced MRI. However, quantification of in vivo APT effect is challenging because of concomitant semisolid magnetization transfer (MT) and nuclear overhauser enhancement effects. A direct saturation corrected (DISC) chemical exchange saturation transfer (CEST) analysis has been recently proposed that simplifies the determination of in vivo CEST effects. Our present study aimed to extend the DISC analysis to pulsed radiofrequency CEST MRI and evaluate it at 3T. Nine adult male Sprague-Dawley rats implanted C6 gliomas underwent multiparametric MRI of T1 , T2 , CEST, and T1 -weighted gadolinium-enhanced imaging 1 day before and 3 days after chemoradiotherapy. The routine MT asymmetry, 3-point method, and the extended DISC analysis were compared in tumor characterization with histology as a reference. Regional variations were assessed by 1-way analysis of variance. T1 , T2 , and MT asymmetry and the DISC CEST effects showed significant alterations in tumor/necrosis with respect to the contralateral reference (P < 0.05). The resolved APT effect revealed a significant difference among the contralateral reference (2.42 ± 0.24%), necrosis (2.86 ± 0.19%), and tumor (3.25 ± 0.15%) regions after chemoradiotherapy (P < 0.05), consistent with histological observations. Conversely, the MT asymmetry did not show tumor regional variation post-treatment (P > 0.05), whereas the 3-point method detected no regional alteration at both time points (P > 0.05). Our study translated DISC CEST MRI to 3T, evaluated it in glioma rat models, and confirmed its advantages in resolving tumor heterogeneity over the routine asymmetry and 3-point analyses.

Whole brain inhomogeneous magnetization transfer (ihMT) imaging: Sensitivity enhancement within a steady‐state gradient echo sequence

To implement, characterize, and optimize an interleaved inhomogeneous magnetization transfer (ihMT) gradient echo sequence allowing for whole-brain imaging within a clinically compatible scan time. A general framework for ihMT modelling was developed based on the Provotorov theory of radiofrequency saturation, which accounts for the dipolar order underpinning the ihMT effect. Experimental studies and numerical simulations were performed to characterize and optimize the ihMT-gradient echo dependency with sequence timings, saturation power, and offset frequency. The protocol was optimized in terms of maximum signal intensity and the reproducibility assessed for a nominal resolution of 1.5 mm isotropic. All experiments were performed on healthy volunteers at 1.5T. An important mechanism driving signal optimization and leading to strong ihMT signal enhancement that relies on the dynamics of radiofrequency energy deposition has been identified. By taking advantage of the delay allowed for readout between ihMT pulse bursts, it was possible to boost the ihMT signal by almost 2-fold compared to previous implementation. Reproducibility of the optimal protocol was very good, with an intra-individual error < 2%. The proposed sensitivity-boosted and time-efficient steady-state ihMT-gradient echo sequence, implemented and optimized at 1.5T, allowed robust high-resolution 3D ihMT imaging of the whole brain within a clinically compatible scan time. Magn Reson Med 79:2607-2619, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Radiofrequency saturation induced bias in aqueductal cerebrospinal fluid flow quantification obtained using two-dimensional cine phase contrast magnetic resonance imaging.

To explore the extent of bias in cerebrospinal fluid flow estimates due to radiofrequency saturation, and its possible impact on the use of two-dimensional cine phase contrast magnetic resonance imaging in the diagnosis and characterization of normal pressure hydrocephalus in patients. Theoretical signal equations were generated to describe saturation dependence on velocity. An experimental set of phase contrast magnetic resonance imaging scans with two different flip angles was used to show bias in flow estimates in a flow phantom, and in six different healthy volunteers. The cerebral aqueduct was targeted as the flow region of interest. Data from a constant flow phantom showed a spatial distribution of voxels with significant bias in flow at the periphery of the flow region. The velocity difference (bias) maps of the cerebral aqueduct correlated with the spatial velocity gradients around peak systole and peak diastole, and high correlation with temporal velocity gradients during transition between systole and diastole. The aqueductal stroke volume for θ = 30° were found to be significantly higher than for θ = 10° using a Wilcoxon signed rank test. This work shows the extent of bias in cerebrospinal fluid flow quantification due to radiofrequency saturation effects. This clinical relevance of this error was presented with respect to shunt responsiveness among normal pressure hydrocephalus patients. Magn Reson Med 79:2067-2076, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Clinical applications of chemical exchange saturation transfer (CEST) MRI

5 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:11-27.

Chemical-exchange-saturation-transfer magnetic resonance imaging to map gamma-aminobutyric acid, glutamate, myoinositol, glycine, and asparagine: Phantom experiments

The physical and technical development of chemical-exchange-saturation-transfer (CEST) magnetic resonance imaging (MRI) using clinical 3 T MRI was explored with the goal of mapping asparagine (Asn), gamma-aminobutyric acid (GABA), glutamate (Glu), glycine (Gly), and myoinositol (MI), which exist in the brain. Phantoms with nine different conditions at concentrations of 10, 30, and 50 mM and pH values of 5.6, 6.2, and 7.4 were prepared for the five target molecules to evaluate the dependence of the CEST effect in the concentration, the pH, and the amplitude of the applied radiofrequency field B1. CEST images in the offset frequency range of ±6 parts per million (ppm) were acquired using a pulsed radio-frequency saturation scheme with a clinical 3 T MRI system. A voxel-based main magnetic field B0 inhomogeneity correction, where B0 is the center frequency offset at zero ppm, was performed by using the spline interpolation method to fit the full Z-spectrum to estimate the center frequency. A voxel-based CEST asymmetry map was calculated to evaluate amide (-NH), amine (-NH2), and hydroxyl (-OH) groups for the five target molecules. The CEST effect for Glu, GABA, and Gly clearly increased with increasing concentrations. The CEST effect for MI was minimal, with no noticeable differences at different concentrations. The CEST effect for Glu and Gly increased with increasing acidity. The highest CEST asymmetry for GABA was observed at pH 6.2. The CEST effect for Glu, GABA, and Gly increased with increasing B1 amplitude. For all target molecules, the CEST effect for the human 3 T MRI system increased with increasing concentration and B1 amplitude, but varied with pH, depending on the characteristics of the molecules. The CEST effect for MI may be not suitable with clinical MRI systems. These results show that CEST imaging in the brain with the amine protons by using 3 T MRI is possible for several neuronal diseases.

Tissue Characterization with Quantitative High-Resolution Magic Angle Spinning Chemical Exchange Saturation Transfer Z-Spectroscopy.

Chemical exchange saturation transfer (CEST) provides sensitive magnetic resonance (MR) contrast for probing dilute compounds via exchangeable protons, serving as an emerging molecular imaging methodology. CEST Z-spectrum is often acquired by sweeping radiofrequency saturation around bulk water resonance, offset by offset, to detect CEST effects at characteristic chemical shift offsets, which requires prolonged acquisition time. Herein, combining high-resolution magic angle spinning (HRMAS) with concurrent application of gradient and rf saturation to achieve fast Z-spectral acquisition, we demonstrated the feasibility of fast quantitative HRMAS CEST Z-spectroscopy. The concept was validated with phantoms, which showed excellent agreement with results obtained from conventional HRMAS MR spectroscopy (MRS). We further utilized the HRMAS Z-spectroscopy for fast ex vivo quantification of ischemic injury with rodent brain tissues after ischemic stroke. This method allows rapid and quantitative CEST characterization of biological tissues and shows potential for a host of biomedical applications.

(15)N Heteronuclear Chemical Exchange Saturation Transfer MRI.

A two-step heteronuclear enhancement approach was combined with chemical exchange saturation transfer (CEST) to magnify (15)N MRI signal of molecules through indirect detection via water protons. Previous CEST studies have been limited to radiofrequency (rf) saturation transfer or excitation transfer employing protons. Here, the signal of (15)N is detected indirectly through the water signal by first inverting selectively protons that are scalar-coupled to (15)N in the urea molecule, followed by chemical exchange of the amide proton to bulk water. In addition to providing a small sensitivity enhancement, this approach can be used to monitor the exchange rates and thus the pH sensitivity of the participating (15)N-bound protons.