Amide Proton Transfer Contrast Research Articles

Unraveling contributions to the Z-spectrum signal at 3.5 ppm of human brain tumors.

To evaluate the influence of the confounding factors, direct water saturation (DWS), and magnetization transfer contrast (MTC) effects on measured Z-spectra and amide proton transfer (APT) contrast in brain tumors. High-grade glioma patients were scanned using an RF saturation-encoded 3D MR fingerprinting (MRF) sequence at 3 T. For MRF reconstruction, a recurrent neural network was designed to learn free water and semisolid macromolecule parameter mappings of the underlying multiple tissue properties from saturation-transfer MRF signals. The DWS spectra and MTC spectra were synthesized by solving Bloch-McConnell equations and evaluated in brain tumors. The dominant contribution to the saturation effect at 3.5 ppm was from DWS and MTC effects, but 25%-33% of the saturated signal in the gadolinium-enhancing tumor (13%-20% for normal tissue) was due to the APT effect. The APT# signal of the gadolinium-enhancing tumor was significantly higher than that of the normal-appearing white matter (10.1% vs. 8.3% at 1 μT and 11.2% vs. 7.8% at 1.5 μT). The RF saturation-encoded MRF allowed us to separate contributions to the saturation signal at 3.5 ppm in the Z-spectrum. Although free water and semisolid MTC are the main contributors, significant APT contrast between tumor and normal tissues was observed.

Amide proton transfer MRI at 9.4 T for differentiating tissue acidosis in a rodent model of ischemic stroke

AbstractPurposeDifferentiating ischemic brain damage is critical for decision making in acute stroke treatment for better outcomes. We examined the sensitivity of amide proton transfer (APT) MRI, a pH‐weighted imaging technique, to achieve this differentiation.MethodsIn a rat stroke model, the ischemic core, oligemia, and the infarct‐growth region (IGR) were identified by tracking the progression of the lesions. APT MRI signals were measured alongside ADC, T1, and T2 maps to evaluate their sensitivity in distinguishing ischemic tissues. Additionally, stroke under hyperglycemic conditions was studied.ResultsThe APT signal in the IGR decreased by about 10% shortly after stroke onset, and further decreased to 35% at 5 h, indicating a progression from mild to severe acidosis as the lesion evolved into infarction. Although ADC, T1, and T2 contrasts can only detect significant differences between the IGR and oligemia for a portion of the stroke duration, APT contrast consistently differentiates between them at all time points. However, the contrast to variation ratio at 1 h is only about 20% of the contrast to variation ratio between the core and normal tissues, indicating limited sensitivity. In the ischemic core, the APT signal decreases to about 45% and 33% of normal tissue level at 1 h for the normoglycemic and hyperglycemic groups, respectively, confirming more severe acidosis under hyperglycemia.ConclusionThe sensitivity of APT MRI is high in detecting severe acidosis of the ischemic core but is much lower in detecting mild acidosis, which may affect the accuracy of differentiation between the IGR and oligemia.

Chemical Exchange Saturation Transfer Magnetic Resonance Imaging for Longitudinal Assessment of Intracerebral Hemorrhage and Deferoxamine Treatment at 3T in a Mouse Model.

Noninvasive imaging of molecular alterations after intracerebral hemorrhage (ICH) could provide valuable information to guide and monitor treatments. Chemical exchange saturation transfer (CEST) magnetic resonance imaging has demonstrated promises in identifying proliferation, necrosis, and changes in cellularity in brain tumors. Here, we applied CEST magnetic resonance imaging to monitor molecular changes in hematoma without and with treatment noninvasively over 2 weeks at 3T using endogenous contrast. CEST contrast related to proteins at 3.5 ppm (amide proton transfer) and proteins/lipids at -3.5 ppm (relayed nuclear overhauser effect [rNOE]) were examined over 14 days in a collagenase-induced ICH mouse model. Imaging findings were validated with immunohistochemistry based on the ICH neuropathology. We also examined iron-containing phantoms that mimicked iron concentrations in hematoma to ensure the iron will not attenuate the CEST contrast during disease progression. Based on the validity of the CEST contrast of hematoma, we further examined related molecular alterations under iron-chelation treatment with deferoxamine. We observed the temporal and spatial differences of CEST contrasts between rNOE at -3.5 ppm and amide proton transfer at 3.5 ppm, in which the core and perihematoma could be identified by rNOE on day 3 and day 14, and amide proton transfer on day 1, day 7, and day 14. Moreover, we observed a 25.7% significant reduction (P<0.05) of rNOE contrast after deferoxamine treatment to the ICH mice on day 3, which was not observable in amide proton transfer contrast. Our histology data indicated that rNOE primarily correlated with the myelin pathology, and amide proton transfer could reflect the cellularity increase at hematoma up to day 7. Significant rNOE changes correlated well with histologic findings, especially myelin lipids, and regional characteristics in hematoma indicate the uniqueness of CEST magnetic resonance imaging in monitoring molecular changes during ICH and treatment.

Two point Dixon-based chemical exchange saturation transfer (CEST) MRI in renal transplant patients on 3 T

PurposeTo assess the performance of two point (2-pt) Dixon-based chemical exchange saturation transfer (CEST) imaging for fat suppression in renal transplant patients. MethodsThe 2-pt Dixon-based CEST MRI was validated in an egg-phantom and in fourteen renal transplant recipients (5 females and 9 males; age range: 23–78 years; mean age: 51 ± 16.8). All CEST experiments were performed on a 3 T clinical MRI scanner using a dual-echo CEST sequence. The 2-pt Dixon technique was applied to generate water-only CEST images at different frequency offsets, which were further used to calculate the z-spectra. The magnetization transfer ratio asymmetry (MTRasym) values in the frequency ranges of hydroxyl, amine and amide protons were estimated in the renal cortex and medulla. ResultsResults of the in vitro experiments suggest that the 2-pt Dixon technique enables effective fat peak removal and does not introduce additional asymmetries to the z-spectrum. Accordingly, our results in vivo show that the fat-corrected amide proton transfer (APT) effect in the kidney is significantly higher compared to that obtained from the CEST data acquired close to the in-phase condition both in the renal cortex (−0.1 [0.7] vs. −0.7 [1.2], P = 0.029) and medulla (0.3 [0.8] vs. 0.01 [1.3], P = 0.049), indicating that the 2-pt Dixon-based CEST method increases the specificity of the APT contrast by correcting the fat-induced artifacts. ConclusionCombination of the dual-echo CEST acquisition with Dixon post-processing provides effective water-fat separation, allowing more accurate quantification of the APT CEST effect in the transplanted kidney.

Whole brain snapshot CEST at 3T using 3D-EPI: Aiming for speed, volume, and homogeneity.

CEST MRI enables imaging of distributions of low-concentrated metabolites as well as proteins and peptides and their alterations in diseases. CEST examinations often suffer from low spatial resolution, long acquisition times, and concomitant motion artifacts. This work aims to maximize both resolution and volume coverage with a 3D-EPI snapshot CEST approach at 3T, allowing for fast and robust whole-brain CEST MRI. Resolution and temporal SNR of 3D-EPI examinations with nonselective excitation were optimized at a clinical 3T MR scanner in five healthy subjects using a clinical head/neck coil. A CEST presaturation module for low power relayed nuclear Overhauser enhancement and amide proton transfer contrast was applied as an example. The suggested postprocessing included motion correction, dynamic B0 correction, denoising, and B1 correction and was compared to an established 3D-gradient echo-based sequence. CEST examinations were performed at 1.8mm nominal isotropic resolution in 4.3s per presaturation offset. In contrast to slab-selective 3D or multislice approaches, the whole brain was covered. Repeated examinations at three different B1 values took 13 minutes for 58 presaturation offsets with temporal SNR around 75. The resulting CEST effects revealed significant gray and white matter contrast and were of similar quality across the whole brain. Coefficient of variation across three healthy subjects was below 9%. The suggested protocol enables whole brain coverage at 1.8mm isotropic resolution and fast acquisition of 4.3s per presaturation offset. For the fitted CEST amplitudes, high reproducibility was proven, increasing the opportunities of quantitative CEST investigations at 3T significantly.

A novel normalization for amide proton transfer CEST MRI to correct for fat signal-induced artifacts: application to human breast cancer imaging.

The application of amide proton transfer (APT) CEST MRI for diagnosis of breast cancer is of emerging interest. However, APT imaging in the human breast is affected by the ubiquitous fat signal preventing a straightforward application of existing acquisition protocols. Although the spectral region of the APT signal does not coincide with fat resonances, the fat signal leads to an incorrect normalization of the Z-spectrum, and therefore to distorted APT effects. In this study, we propose a novel normalization for APT-CEST MRI that corrects for fat signal-induced artifacts in the postprocessing without the need for application of fat saturation schemes or water-fat separation approaches. The novel normalization uses the residual signal at the spectral position of the direct water saturation to estimate the fat contribution. A comprehensive theoretical description of the normalization for an arbitrary phase relation of the water and fat signal is provided. Functionality and applicability of the proposed normalization was demonstrated by in vitro and in vivo experiments. In vitro, an underestimation of the conventional APT contrast of approximately -1.2% per 1% fat fraction was observed. The novel normalization yielded an APT contrast independent of the fat contribution, which was also independent of the water-fat phase relation. This allowed APT imaging in patients with mamma carcinoma corrected for fat signal contribution, field inhomogeneities, spillover dilution, and water relaxation effects. The proposed normalization increases the specificity of APT imaging in tissues with varying fat content and represents a time-efficient and specific absorption rate-efficient alternative to fat saturation and water-fat separation approaches.

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

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.

Improved Differentiation of Low-Grade and High-Grade Gliomas and Detection of Tumor Proliferation Using APT Contrast Fitted from Z-Spectrum.

The purpose of the study is to demonstrate the value of quantitative amide proton transfer (APT) imaging for differentiating glioma grades and detecting tumor proliferation. This study included 32 subjects with 16 low-grade gliomas (LGG) and 16 high-grade gliomas (HGG) confirmed by histopathology. Chemical exchange saturation transfer (CEST) magnetic resonance imaging with APT weighting was performed on a 3T scanner. After B0 correction, Z-spectra were fitted with Lorentzian functions corresponding to the upfield semi-solid magnetization transfer and nuclear overhauser enhancement (MT&NOE) effect, the direct saturation (DS) effect, and the downfield APT effect centered at around - 1.5, 0, and + 3.5ppm, respectively. To compute the Z-spectral fitted APT (fitted_APT) in solid tumor tissue, double-peak histogram fitting of pixel MT&NOE effect from the whole tumor was used to remove necrosis regions. The fitted APT was then compared with the conventional APT based on magnetization transfer ratio asymmetry. Receiver operating characteristic (ROC) analysis was used to compare the performance between Z-spectral fitted contrasts and the con_APT for LGG versus HGG differentiation. Additionally, the correlations between the imaging contrasts (fitted_APT, con_APT, and fitted_MT&NOE) and Ki-67 labeling index for tumor proliferation were also evaluated. Z-spectral fitted_APT shows improved statistical power for differentiating HGG and LGG (7.58 ± 0.99 vs. 6.79 ± 1.05%, p < 0.05) than con_APT (4.34 ± 0.95 vs. 4.05 ± 2.02%, p > 0.05) in solid tumor tissues. Analyses of whole tumor, on the other hand, have less differentiating power for both fitted_APT (p from 0.032 to 0.08) and con_APT (p from 0.696 to 0.809). Similarly, based on ROC analyses, fitted_APT shows larger area under the curve (AUC = 0.723) than con_APT (AUC = 0.543). The combination of fitted APT, DS, and MT&NOE further improved the specificity (75%), diagnostic accuracy (78.2%), and area under the curve (0.758) in differentiating LGG and HGG. Consistently, fitted_APT (r = 0.451, p = 0.018) is better correlated with Ki-67 than con_APT (r = 0.331, p = 0.092). Fitted APT from Z-spectrum improves differentiation of low- and high-grade gliomas and better correlated with tumor proliferation than conventional APT.

Amide proton transfer (APT) imaging of brain tumors at 7 T: The role of tissue water T1 -Relaxation properties.

To provide insight into the effect of water T1 relaxation (T1wat ) on amide proton transfer (APT) contrast in tumors. Three different metrics of APT contrast-magnetization transfer ratio (MTRRex ), relaxation-compensated MTRRex (AREX), and traditional asymmetry (MTRasym )-were compared in normal and tumor tissues in a variety of intracranial tumors at 7 Tesla (T). Six consented intracranial tumor patients were scanned using a low-power, three-dimensional (3D) APT imaging sequence. MTRRex and MTRasym were calculated in the region of 3 to 4 ppm. AREX was calculated by T1wat correction of MTRRex . Tumor tissue masks, which classify different tumor tissues, were drawn by an experienced neuroradiologist. ROI-averaged tumor tissue analysis was done for MTRRex , AREX, and MTRasym . MTRRex and MTRasym were slightly elevated in tumor-associated structures. Both metrics were positively correlated to T1wat . The correlation coefficient (R) was determined to be 0.88 (P < 0.05) and 0.92 (P << 0.05) for MTRRex and MTRasym , respectively. After T1wat correction (R = -0.21, P = 0.69), no difference between normal and tumor tissues was found for AREX. The strong correlation of MTRRex and MTRasym with T1wat and the absence thereof in AREX suggests that much of APT contrast in tumors for the low-power, 3D-acquisition scheme at 7 T originates from the inherent tissue water T1 -relaxation properties. Magn Reson Med 77:1525-1532, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

R1correction in amide proton transfer imaging: indication of the influence of transcytolemmal water exchange on CEST measurements

Amide proton transfer (APT) imaging may potentially detect mobile proteins/peptides non-invasively in vivo, but its specificity may be reduced by contamination from other confounding effects such as asymmetry of non-specific magnetization transfer (MT) effects and spin-lattice relaxation with rate R1 (=1/T1). Previously reported spillover, MT and R1 correction methods were based on a two-pool model, in which the existence of multiple water compartments with heterogeneous relaxation properties in real tissues was ignored. Such simple models may not adequately represent real tissues, and thus such corrections may be unreliable. The current study investigated the effectiveness and accuracy of correcting for R1 in APT imaging via simulations and in vivo experiments using tumor-bearing rats subjected to serial injections of Gd-DTPA that produced different tissue R1 values in regions of blood-brain-barrier breakdown. The results suggest that conventional measurements of APT contrast (such as APT* and MTRasym ) may be significantly contaminated by R1 variations, while the R1 -corrected metric AREX* was found to be relatively unaffected by R1 changes over a broad range (0.4-1 Hz). Our results confirm the importance of correcting for spin-lattice relaxation effects in quantitative APT imaging, and demonstrate the reliability of using the observed tissue R1 for corrections to obtain more specific and accurate measurements of APT contrast in vivo. The results also indicate that, due to relatively fast transcytolemmal water exchange, the influence of intra- and extracellular water compartments on CEST measurements with seconds long saturation time may be ignored in tumors.

Optimization of 7-T chemical exchange saturation transfer parameters for validation of glycosaminoglycan and amide proton transfer of fibroglandular breast tissue.

To (a) implement simulation-optimized chemical exchange saturation transfer (CEST) measurements sensitive to amide proton transfer (APT) and glycosaminoglycan (GAG) hydroxyl proton transfer effects in the human breast at 7 T and (b) determine the reliability of these techniques for evaluation of fibroglandular tissue in the healthy breast as a benchmark for future studies of pathologic findings. All human studies were institutional review board approved, were HIPAA compliant, and included informed consent. The CEST parameters of saturation duration (25 msec) and amplitude (1 μT) were chosen on the basis of simulation-driven optimization for APT contrast enhancement with the CEST effect quantified by using residuals of a Lorentzian fit. Optimized parameters were implemented at 7 T in 10 healthy women in two separate examinations to evaluate the reliability of CEST magnetic resonance (MR) imaging measurements in the breast. CEST z-spectra were acquired over saturation offset frequencies ranging between ±40 ppm by using a quadrature unilateral breast coil. The imaging-repeat imaging reliability was assessed in terms of the intraclass correlation coefficient, which indicates the ratio of between-subject variation to total variation. Simulations were performed of the Bloch equations with chemical exchange-guided selection of optimal values for pulse duration and amplitude, 25 msec and 1 μT, respectively. Reliability was evaluated by using intraclass correlation coefficients (95% confidence intervals), with acceptable results: 0.963 (95% confidence interval: 0.852, 0.991) and 0.903 (95% confidence interval: 0.609, 0.976) for APT and GAG, respectively. Simulations were used to derive optimal CEST preparation parameters to elicit maximal CEST contrast enhancement in healthy fibroglandular breast tissue due to APT at 7 T. By using these parameters, reproducible values were obtained for both the amide and hydroxyl protons from CEST MR imaging at 7 T and are feasible in the human breast.

Assessment of ischemic penumbra in patients with hyperacute stroke using amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI

Chemical exchange saturation transfer (CEST)-derived, pH-weighted, amide proton transfer (APT) MRI has shown promise in animal studies for the prediction of infarction risk in ischemic tissue. Here, APT MRI was translated to patients with acute stroke (1-24 h post-symptom onset), and assessments of APT contrast, perfusion, diffusion, disability and final infarct volume (23-92 days post-stroke) are reported. Healthy volunteers (n = 5) and patients (n = 10) with acute onset of symptoms (0-4 h, n = 7; uncertain onset <24 h, n = 3) were scanned with diffusion- and perfusion-weighted MRI, fluid-attenuated inversion recovery (FLAIR) and CEST. Traditional asymmetry and a Lorentzian-based APT index were calculated in the infarct core, at-risk tissue (time-to-peak, TTP; lengthening) and final infarct volume. On average (mean ± standard deviation), control white matter APT values (asymmetry, 0.019 ± 0.005; Lorentzian, 0.045 ± 0.006) were not significantly different (p > 0.05) from APT values in normal-appearing white matter (NAWM) of patients (asymmetry, 0.022 ± 0.003; Lorentzian, 0.048 ± 0.003); however, ischemic regions in patients showed reduced (p = 0.03) APT effects compared with NAWM. Representative cases are presented, whereby the APT contrast is compared quantitatively with contrast from other imaging modalities. The findings vary between patients; in some patients, a trend for a reduction in the APT signal in the final infarct region compared with at-risk tissue was observed, consistent with tissue acidosis. However, in other patients, no relationship was observed in the infarct core and final infarct volume. Larger clinical studies, in combination with focused efforts on sequence development at clinically available field strengths (e.g. 3.0 T), are necessary to fully understand the potential of APT imaging for guiding the hyperacute management of patients.

Amide proton transfer imaging in grading tumors of the neuroepithelial tissue

Objective To investigate the role of the amide proton transfer (APT) MR sequence in grading tumors of the neuroepithelial tissue,and its application in identifying the different components of the tumors.Methods 33 patients (18 male,15 female,age was from 18 to 71 with mean age of 46 years) were investigated and confirmed to be tumors of neuroepithelial tissue (glioma) by postoperative pathology,in whom 3T MRI with T2-weighted,FLAIR,pre-and post-contrast T1-weighted and APT sequences were performed.For each patient,APT signal intensities of each regions of interest (ROI) was defined and used for grading.Comparisons of APT signal intensities of high grade were done among tumor core,peritumoral edema and the contralateral normal-appearing white matter (CNAWM) and the APT signal intensities of tumor core were also compared between high and low grade glioma.Results 33 patients included 10 grade Ⅱ tumors,11 grade Ⅲ tumors,and 12 grade Ⅳ tumors.The average APT signal intensities were significantly higher in the tumor cores both in high and low grade than the peritumoral edema (P ＜ 0.05)and the contralateral normal-appearing white matter (P ＜ 0.01).Moreover,the APT signal intensities of the tumor cores of high-grade brain tumors were significantly higher than those of low-grade (P ＜ 0.01).Conclusions Amide proton transfer contrast can differentiate the tumor core from peritumoral edema,and combined with routine MRI is of clinical application value in grading of glioma. Key words: Magnetic resonance imaging; Amide proton transfer; Neoplasms, neuroepithelial; Pathology

Quantitative Bayesian model‐based analysis of amide proton transfer MRI

Amide Proton Transfer (APT) reports on contrast derived from the exchange of protons between amide groups and water. Commonly, APT contrast is quantified by asymmetry analysis, providing an ensemble contrast of both amide proton concentration and exchange rate. An alternative is to sample the off-resonant spectrum and fit an exchange model, permitting the APT effect to be quantified, correcting automatically for confounding effects of spillover, field inhomogeneity, and magnetization transfer. Additionally, it should permit amide concentration and exchange rate to be independently quantified. Here, a Bayesian method is applied to this problem allowing pertinent prior information to be specified. A three-pool model was used incorporating water protons, amide protons, and magnetization transfer effect. The method is demonstrated in simulations, creatine phantoms with varying pH and in vivo (n = 7). The Bayesian model-based approach was able to quantify the APT effect accurately (root-mean-square error < 2%) even when subject to confounding field variation and magnetization transfer effect, unlike traditional asymmetry analysis. The in vivo results gave approximate APT concentration (relative to water) and exchange rate values of 3 × 10(-3) and 15 s(-1) . A degree of correlation was observed between these parameter making the latter difficult to quantify with absolute accuracy, suggesting that more optimal sampling strategies might be required.

CEST-imaging: A new contrast in MR-mammography by means of chemical exchange saturation transfer

Chemical exchange saturation transfer (CEST) is a technique in H MR imaging (MRI) that enables visualization of chemical exchange processes between protons bound to solutes and surrounding bulk water molecules [1]. To induce a CEST contrast, the off-resonant solute protons are labeled by a saturation radiofrequency (RF) pulse and the label is then transferred to bulk water by chemical exchange. The magnitude of the subsequent reduction of bulk water signal depends consequently on the dynamics of chemical exchange as well as on the ratio of exchangeable solute protons to bulk water protons. The rate constant of chemical exchange (k) is influenced by the pH value and the temperature within the exchange environment. If the latter two parameters can be assumed to be distributed homogeneously in tissue, the CEST effect will be a surrogate marker of the concentration of a certain solute molecule in tissue. In order for a solute molecule to be considered suitable as an endogenous CEST agent, it must carry labile protons that exchange with bulk water at exchange rates that fulfill the condition k <Dw; where Dw is the resonance offset of the solute protons to the water protons in [s]. The most prominent endogenous CEST contrast is amide proton transfer (APT) imaging [2]. It relies on the exchange between amide protons from the backbone of small intracellular mobile proteins or peptides and bulk water. APT imaging has successfully been applied to imaging of ischemic areas in stroke [3], brain tumors [4] and also radiation necrosis [5] due to its strong dependence on tissue pH value. However, of course, aside from its pH sensitivity, APT contrast

Imaging acute ischemic tissue acidosis with pH-sensitive endogenous amide proton transfer (APT) MRI—Correction of tissue relaxation and concomitant RF irradiation effects toward mapping quantitative cerebral tissue pH

Amide proton transfer (APT) MRI is sensitive to ischemic tissue acidosis and has been increasingly used as a research tool to investigate disrupted tissue metabolism during acute stroke. However, magnetization transfer asymmetry (MTR(asym)) analysis is often used for calculating APT contrast, which only provides pH-weighted images. In addition to pH-dependent APT contrast, in vivo MTR(asym) is subject to a baseline shift (ΔMTR'(asym)) attributable to the slightly asymmetric magnetization transfer (MT) effect. Additionally, APT contrast approximately scales with T(1) relaxation time. Tissue relaxation time may also affect the experimentally obtainable APT contrast via saturation efficiency and RF spillover effects. In this study, we acquired perfusion, diffusion, relaxation and pH-weighted APT MRI data, and spectroscopy (MRS) in an animal model of acute ischemic stroke. We modeled in vivo MTR(asym) as a superposition of pH-dependent APT contrast and a baseline shift ΔMTR'(asym) (i.e., MTR(asym)=APTR(pH)+ΔMTR'(asym)), and quantified tissue pH. We found pH of the contralateral normal tissue to be 7.03±0.05 and the ipsilateral ischemic tissue pH was 6.44±0.24, which correlated with tissue perfusion and diffusion rates. In summary, our study established an endogenous and quantitative pH imaging technique for improved characterization of ischemic tissue acidification and metabolism disruption.

Numerical solutions to the time-dependent Bloch equations revisited

The purpose of this study was to demonstrate a simple and fast method for solving the time-dependent Bloch equations. First, the time-dependent Bloch equations were reduced to a homogeneous linear differential equation, and then a simple equation was derived to solve it using a matrix operation. The validity of this method was investigated by comparing with the analytical solutions in the case of constant radiofrequency irradiation. There was a good agreement between them, indicating the validity of this method. As a further example, this method was applied to the time-dependent Bloch equations in the two-pool exchange model for chemical exchange saturation transfer (CEST) or amide proton transfer (APT) magnetic resonance imaging (MRI), and the Z-spectra and asymmetry spectra were calculated from their solutions. They were also calculated using the fourth/fifth-order Runge-Kutta-Fehlberg (RKF) method for comparison. There was also a good agreement between them, and this method was much faster than the RKF method. In conclusion, this method will be useful for analyzing the complex CEST or APT contrast mechanism and/or investigating the optimal conditions for CEST or APT MRI.

Simplified quantitative description of amide proton transfer (APT) imaging during acute ischemia

Amide proton transfer (APT) imaging employs the chemical exchange saturation transfer (CEST) mechanism to detect mobile endogenous proteins and peptides. It can be used to detect pH reduction during acute ischemia and thus provide complementary information to perfusion-weighted (PWI) and diffusion-weighted (DWI) imaging. However, the APT contrast depends strongly on the choice of imaging parameters, especially the radiofrequency (RF) saturation time and strength, which need to be optimized. In this work it is shown that even though at least three proton pools are present, the description of the APT process during acute ischemia can be greatly simplified by means of a dual two-pool model analysis. With this approach, the experimentally measured RF irradiation power dependence of the effect in the rat brain was well predicted. The results showed an optimal RF strength of 0.75 microT for our particular coil setup, and a maximally obtainable APT ratio difference of 2.9%+/-0.3% between ischemic and normal brain regions.