Magnetization Transfer Effects Research Articles

Ratiometric NOE(-1.6) contrast in brain tumors.

Recently, a new nuclear Overhauser enhancement (NOE)-mediated saturation transfer effect at around -1.6ppm from water, termed NOE(-1.6), was reported to show hypointense signals in brain tumors. Similar to chemical exchange saturation transfer or magnetization transfer (MT) effects, which depend on the solute pool concentration, the exchange/coupling rate, the solute transverse relaxation rate, etc., the NOE(-1.6) effect should also depend on these factors. Since the exchange rate is relevant to tissue pH, and the coupling rate and the solute transverse relaxation rate are relevant to the motional property of the coupled molecules, further studies to quantify the contribution from only the exchange/coupling rate and the solute transverse relaxation rate are always interesting. The purpose of this paper is to apply a ratiometric approach to the NOE(-1.6) effect to obtain a metric that is more specific to the NOE coupling rate and the solute transverse relaxation rate than the NOE(-1.6) signal amplitude. Simulations indicate that the ratiometric approach allows us to rule out nearly all of the non-specific factors including the solute pool concentration, solute and water longitudinal relaxation rates, direct water saturation, and semi-solid MT effects, and provides a more specific NOE coupling rate- and solute transverse relaxation rate-weighted signal. Animal studies show that the ratiometric NOE(-1.6) decreases dramatically in brain tumors, which suggests that the change in the NOE(-1.6) coupling rate and/or the solute transverse relaxation rate are major contributors to the previously observed hypointense NOE(-1.6) signal in tumors.

Fast quantitative MRI using controlled saturation magnetization transfer.

PurposeThis study demonstrates magnetization transfer (MT) effects directly affect relaxometry measurements and develops a framework that allows single‐pool models to be valid in 2‐pool MT systems.MethodsA theoretical framework is developed in which a 2‐pool MT system effectively behaves as a single‐pool if the RMS RF magnetic field (B1rms{\ ext{B}}_{1}^{{{\ ext{rms}}}}) is kept fixed across all measurements. A practical method for achieving controlled saturation magnetization transfer (CSMT) using multiband RF pulses is proposed. Numerical, Phantom, and in vivo validations were performed directly comparing steady state (SS) estimation approaches that under correct single‐pool assumptions would be expected to vary in precision but not accuracy.ResultsNumerical simulations predict single‐pool estimates obtained from MT model generated data are not consistent for different SS estimation methods, and a systematic underestimation of T2 is expected. Neither effect occurs under the proposed CSMT approach. Both phantom and in vivo experiments corroborate the numerical predictions. Experimental data highlights that even when using the same relaxometry method, different estimates are obtained depending on which combination of flip angles (FAs) and TRs are used if the CSMT approach is not used. Using CSMT, stable measurements of both T1 and T2 are obtained. The measured T1 (T1CSMT)) depends on B1rms{\ ext{B}}_{1}^{{{\ ext{rms}}}}, which is therefore an important parameter to specify.ConclusionThis work demonstrates that conventional single pool relaxometry, which is highly efficient for human studies, results in unreliable parameter estimates in biological tissues because of MT effects. The proposed CSMT framework is shown to allow single‐pool assumptions to be valid, enabling reliable and efficient quantitative imaging to be performed.

Low duty-cycle pulsed irradiation reduces magnetization transfer and increases the inhomogeneous magnetization transfer effect

Intense off-resonant RF irradiation can lead to saturation of the macromolecular pool magnetization and enhance bound pool dipolar order responsible for the inhomogeneous magnetization transfer (ihMT) effect, but the intensity of RF power in human imaging studies is limited by safety constraints on RF heating. High RF intensities can still be achieved if applied in short pulses with low duty-cycle. Here we investigate the benefits of low duty-cycle irradiation for MT and ihMT studies with both theoretical and experimental methods.Solutions for pulsed irradiation of a two-pool model including dipolar order effects were implemented. Experiments were conducted at 3 T in the brain and through the calf of healthy human subjects. 2D echo planar images were acquired following a preparation of RF irradiation with a 2 s train of 5 ms pulses repeated from between 10 to 100 ms for duty-cycles (DCs) of 50% to 5%, and at varying offset frequencies, and time averaged RF powers. MT and ihMT data were measured in regions of interest within gray matter, white matter and muscle, and fit to the model.RF irradiation effects on signal intensity were reduced at 5% relative to 50% DCs. This reduced RF effect was much larger for single than dual frequency irradiation. 5% DC irradiation reduced single and dual frequency MT ratios but increased ihMT ratios up to 3 fold in brain tissues. Muscle ihMT increased by an even larger factor, depending on the frequency and applied power. The model predicted these changes with duty-cycle. The model fit the data well and constrained model parameters.Low duty-cycle pulsed irradiation reduces MT effects and markedly increases dipolar order effects. This approach is an attractive method to enhance ihMT signal-to-noise ratio and demonstrates a measurable ihMT effect in muscle tissue at 3 T under acceptable specific absorption rates. The effects of duty-cycle changes demonstrated in a separate MT/ihMT preparation provide a route for new applications in magnetization-prepared MRI sequences.

Chemical exchange saturation transfer fingerprinting for exchange rate quantification.

There is an increased interest to determine the exchange rate using CEST to provide pH information. However, current CEST quantification methods require lengthy scan times and do not address magnetization transfer effects. The purpose of this work was to apply the magnetic resonance fingerprinting (MRF) concept to CEST to achieve more efficient and accurate exchange rate quantification. The proposed CEST fingerprinting method used varying saturation powers and saturation times to create unique signal evolutions for different exchange rates. The acquired signal was matched to a predefined dictionary to determine the exchange rate. The magnetization transfer effects were also addressed in the framework of CEST fingerprinting: The simulated dictionary could predict the signal curves without magnetization transfer effects, and comparing the dictionary to the acquired signals allowed the correction of the magnetization transfer effects. The CEST fingerprinting method was compared with the conventional pulsed quantitative CEST method using omega plots in the creatine phantom study. The CEST fingerprinting method has a significantly reduced scan time (10 minutes versus 50 minutes) while providing more accurate exchange rate quantification using literature values as the reference. In this study, we demonstrate that CEST fingerprinting is more efficient (5 times faster) compared with pulsed quantitative CEST. It is also shown that the results of the proposed CEST fingerprinting technique are much closer to the literature values than pulsed quantitative CEST at 3 T.

CONTRAST-ENHANCED MRI WITH MAGNETIZATION TRANSFER EFFECT IN THE IMAGING OF BRAIN METASTATIC LESIONS

Purpose: to investigate the diagnostic opportunities of contrast magnetic resonance imaging with the effect of magnetization transfer effect in the diagnosis of focal metastatic lesions in the brain.Materials and methods.The material of the study was images of contrast MRI of the brain of 16 patients (mean age 49 ± 18.5 years). Diagnosis of the direction is focal brain lesion. All MRI studies were carried out using the Toshiba Titan Octave with magnetic field of 1.5 T. The contrast agent is “Magnevist” at concentration of 0.2 ml/kg was used. After contrasting process two T1-weighted studies were performed: without T1-SE magnetization transfer with parameters of pulse: TR = 540 ms, TE = 12 ms, DFOV = 24 sm, MX = 320 × 224 and with magnetization transfer – T1-SEMTC with parameters of pulse: ΔF = −210 Hz, FA(МТС) = 600°, TR = 700 ms, TE = 10 ms, DFOV = 23.9 sm, MX = 320 × 224. For each detected metastatic lesion, a contrast-to-brain ratio (CBR) was calculated. Comparative analysis of CBR values was carried out using a non-parametric Wilcoxon test at a significance level p < 0.05. To evaluate the sensitivity and specificity of the techniques in the detection of metastatic foci (T1-SE and T1-SE-MTC), ROC analysis was used. The sample is divided into groups: 1 group is foci ≤5 mm in size, 2 group is foci from 6 to 10 mm, and 3 group is foci >10 mm.Results.Comparative analysis of CBR using non-parametric Wilcoxon test showed that the values of the CBR on T1-weighted images with magnetization transfer are significantly higher (p < 0.001) that on T1-weighted images without magnetization transfer. According to the results of the ROC analysis, sensitivity in detecting metastases (n = 90) in the brain on T1-SE-MTC and T1-SE was 91.7% and 81.6%, specificity was 100% and 97.6%, respectively. The accuracy of the T1-SE-MTC is 10% higher in comparison with the technique without magnetization transfer. Significant differences (p < 0.01) between the size of the foci detected in post-contrast T1-weighted images with magnetization transfer and in post-contrast T1-weighted images without magnetization transfer, in particular for foci ≤5 mm in size, were found.Conclusions.1. Comparative analysis of CBR showed significant (p < 0.001) increase of contrast between metastatic lesion and white matter on T1-SE-MTC in comparison with T1-SE. 2. The sensitivity, specificity and accuracy of the magnetization transfer program (T1-SE-MTC) in detecting foci of metastatic lesions in the brain is significantly higher (p < 0.01), relative to T1-SE. 3. The T1-SE-MTC program allows detecting more foci in comparison with T1-SE, in particular foci of ≤5 mm (96% and 86%, respectively, with p < 0.05).

Evaluation of Glioblastoma Response to Therapy With Chemical Exchange Saturation Transfer

To monitor cellular and metabolic characteristics of glioblastoma (GBM) over the course of standard 6-week chemoradiation treatment with chemical exchange saturation transfer (CEST)-MRI; and to identify the earliest time point CEST could determine subsequent therapeutic response. Nineteen patients with newly diagnosed GBM were recruited, and CEST-MRI was acquired immediately before (Day0), 2weeks (Day14) and 4weeks (Day28) into treatment, and 1month after the end of treatment (Day70). Several CEST metrics, including magnetization transfer ratio and area under the curve of CEST peaks corresponding to nuclear Overhauser effect (NOE) and amide protons (MTRNOE, MTRAmide, CESTNOE, and CESTAmide respectively), magnetization transfer (MT), and direct water effect were investigated. Lack of early progression was determined as no increase in tumor size or worsening of clinical symptoms according to routine post-chemoradiation serial structural MRI. Changes in MTRNOE (nonprogressors=1.35±0.18, progressors=0.97±0.22, P=.006) and MTRAmide (nonprogressors=1.25±0.17, progressors=0.99±0.10, P=.017) between baseline (Day0) and Day14 resulted in the best separation of nonprogressors from progressors. Moreover, the baseline (Day0) MTRNOE (nonprogressors =6.5%±1.6%, progressors=9.1%±2.1%, P=.015), MTRAmide (nonprogressors=6.7%±1.7%, progressors=8.9%±1.9%, P=.028), MT (nonprogressors=3.8%±0.9%, progressors=5.4%±1.4%, P=.019), and CESTNOE (nonprogressors=4.1%ċHz±1.7%ċHz, progressors=6.1%ċHz±1.9%ċHz, P=.044) were able to identify progressors even before the start of the treatment. Chemical exchange saturation transfer (CEST) provides imaging-based biomarkers of GBM response as early as 2weeks into the treatment. Certain CEST metrics can characterize tumor aggressiveness and identify early progressors even before beginning the treatment. Such an early biomarker of response may allow for adjusting the GBM treatment plan for adaptive radiation therapy in early progressors and more confidently continuing standard adjuvant treatment for nonprogressors.

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.

Simulation-based quantification of native T1 and T2 of the myocardium using a modified MOLLI scheme and the importance of Magnetization Transfer

Quantitative cardiovascular Magnetic Resonance Imaging techniques are gaining wide acceptance within the MR community due to their potential to diagnose non-localized disease, guide therapy and improve patient outcome. During the last decade, there has been an increasing interest for developing new techniques that allow for simultaneous quantification of both T1 and T2 maps of myocardium. Newer studies demonstrated that the incorporation of MRI simulations could yield similar results to conventional mapping techniques in the myocardium. However, these simulation-based quantitative MR techniques usually compare the in-vivo T1 estimates against less accurate T1 techniques, whereas they present inconsistencies between simulation studies, phantom and in-vivo measurements. Moreover, these studies do not investigate the effect of Magnetization Transfer on the myocardial T1 and T2 estimates but are usually validated on phantoms where the MT effect is small.The main aim of this study was to perform simultaneous mapping of the native T1 and T2 of the myocardium through the utilization of a modified MOLLI pulse sequence and the incorporation of advanced MR simulations through the SQUAREMR framework. A second aim of this study was to investigate the effect of MT on simulation-based quantitative MR techniques.A conventional MOLLI pulse sequence was modified so as to present combined high T2 sensitivity and low MT effect. The new technique was applied in healthy volunteers and demonstrated an improved T1 accuracy compared to the conventional MOLLI and a T2 accuracy similar to the one provided by the T2prep-bSSFP method. The effect of MT on T1 and T2 estimates was also investigated in the current study. Phantoms with an increasing MT effect as well as phantoms without an MT effect were included in this work whereas several variants of the modified-MOLLI that introduce different amounts of T2 modulation on the MR signal and induce different MT effects were applied on the phantoms.The proposed simulation-based quantitative MR technique for simultaneous T1 and T2 mapping of the myocardium does not require the incorporation of a complicated custom designed pulse sequence and does not require a complicated reconstruction workflow. Moreover, the current study demonstrates for the first time that MT plays an important role in the simulation-based quantitative MR studies and points out the necessity of incorporating the study of MT in future techniques.

Extended phase graph formalism for systems with magnetization transfer and exchange.

PurposeAn extended phase graph framework (EPG‐X) for modeling systems with exchange or magnetization transfer (MT) is proposed.TheoryEPG‐X models coupled two‐compartment systems by describing each compartment with separate phase graphs that exchange during evolution periods. There are two variants: EPG‐X(BM) for systems governed by the Bloch‐McConnell equations, and EPG‐X(MT) for the pulsed MT formalism. For the MT case, the “bound” protons have no transverse components, so their phase graph consists of only longitudinal states.MethodsThe EPG‐X model was validated against steady‐state solutions and isochromat‐based simulation of gradient‐echo sequences. Three additional test cases were investigated: (i) MT effects in multislice turbo spin‐echo; (ii) variable flip angle gradient‐echo imaging of the type used for MR fingerprinting; and (iii) water exchange in multi‐echo spin‐echo T2 relaxometry.ResultsEPG‐X was validated successfully against isochromat based transient simulations and known steady‐state solutions. EPG‐X(MT) simulations matched in‐vivo measurements of signal attenuation in white matter in multislice turbo spin‐echo images. Magnetic resonance fingerprinting–style experiments with a bovine serum albumin (MT) phantom showed that the data were not consistent with a single‐pool model, but EPG‐X(MT) could be used to fit the data well. The EPG‐X(BM) simulations of multi‐echo spin‐echo T2 relaxometry suggest that exchange could lead to an underestimation of the myelin‐water fraction.ConclusionsThe EPG‐X framework can be used for modeling both steady‐state and transient signal response of systems exhibiting exchange or MT. This may be particularly beneficial for relaxometry approaches that rely on characterizing transient rather than steady‐state sequences. Magn Reson Med 80:767–779, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Specific visualization of neuromelanin-iron complex and ferric iron in the human post-mortem substantia nigra using MR relaxometry at 7T

Neuromelanin (NM) is an endogenous iron chelating molecule of pigmented neurons in the human substantia nigra (SN). Along with the increase in iron deposition, the reduction in NM-containing dopaminergic neurons and the variation of iron load on NM are generally considered to be important factors participating to pathogenesis of Parkinson's disease (PD). The aim of this study was to non-invasively delineate the spatial distributions of paramagnetic magnetic susceptibility perturbers, such as NM-iron complex and ferric iron in SN. Multiple quantitative MR parameters of T1, T2, T2*, susceptibility weighted image (SWI), quantitative susceptibility map (QSM), and T1 weighted image with magnetization transfer (MT) effects were acquired for six post-mortem SN samples without a history of neurological disease. Co-registered quantitative histological validations were performed to identify and correlate NM pigments, iron deposits, and myelin distributions with respect to associated MR parameters. The regions with NM pigments and iron deposits showed positive magnetic susceptibility (paramagnetic) values, while myelinated areas showed negative magnetic susceptibility (diamagnetic) values from the QSM. The region of reduced T2 values in SN mostly coincided with high iron deposits, but not necessarily with the NM pigments. The correlations between T2*/T2 (or T2*/T22) values and NM pigments were higher than those between T2* values and NM pigments, due to the effective size differences between NM-iron complex and ferric iron. Consequently, separate segmentations of ferric iron from the T2 map and NM-iron complex from the T2*/T2 map (or T2*/T22 map) were possible with the boundary of the SN determined from the T1 weighted image.

Contrast-Enhanced MRI with Magnetization Transfer Effect in the Imaging of Brain Metastatic Lesions

Purpose: to investigate the diagnostic opportunities of contrast magnetic resonance imaging with the effect of magnetization transfer effect in the diagnosis of focal metastatic lesions in the brain.Materials and methods.Images of contrast MRI of the brain of 16 patients (mean age 49 ± 18.5 years) were analysed. Diagnosis of the direction is focal brain lesion. All MRI studies were carried out using the Toshiba Titan Octave with magnetic field of 1.5 T. The contrast agent is “Magnevist” at concentration of 0.2 ml/kg was used. After contrasting process two T1-weighted studies were performed: without T1-SE magnetization transfer with parameters of pulse: TR = 540 ms, TE = 12 ms, DFOV = 24 sm, MX = 320 × 224 and with magnetization transfer – T1-SE-MTC with parameters of pulse: ΔF = −210 Hz, FA(МТС) = 600°, TR = 700 ms, TE = 10 ms, DFOV = 23.9 sm, MX = 320 x 224. For each detected metastatic lesion, a contrast-to-brain ratio (CBR) was calculated. Comparative analysis of CBR values was carried out using a non-parametric Wilcoxon test at a significance level p &lt; 0.05. To evaluate the sensitivity and specificity of the techniques in the detection of metastatic foci (T1-SE and T1-SE-MTC), ROC analysis was used. The sample is divided into groups: 1 group is foci ≤5 mm in size, 2 group is foci from 6 to 10 mm, and 3 group is foci &gt;10 mm. Results.Comparative analysis of CBR using non-parametric Wilcoxon test showed that the values of the CBR on T1-weighted images with magnetization transfer are significantly higher (p &lt;0.001) that on T1-weighted images without magnetization transfer. According to the results of the ROC analysis, sensitivity in detecting metastases (n = 90) in the brain on T1-SE-MTC and T1-SE was 91.7% and 81.6%, specificity was 100% and 97.6%, respectively. The accuracy of the T1-SE-MTC is 10% higher in comparison with the technique without magnetization transfer. Significant differences (p &lt; 0.01) between the size of the foci detected in post-contrast T1- weighted images with magnetization transfer and in post-contrast T1-weighted images without magnetization transfer, in particular for foci ≤5 mm in size, were found. Conclusions1. Comparative analysis of CBR showed significant (p &lt; 0.001) increase of contrast between metastatic lesion and white matter on T1-SE-MTC in comparison with T1-SE.2. The sensitivity, specificity and accuracy of the magnetization transfer program (T1-SE-MTC) in detecting foci of metastatic lesions in the brain is significantly higher (p &lt; 0.01), relative to T1-SE.3. The T1-SE-MTC program allows detecting more foci in comparison with T1-SE, in particular foci of ≤5 mm (96% and 86%, respectively, with p &lt; 0.05).

A comparison of inhomogeneous magnetization transfer, myelin volume fraction, and diffusion tensor imaging measures in healthy children

Sensitive and specific biomarkers of myelin can help define baseline brain health and development, identify and monitor disease pathology, and evaluate response to treatment where myelin content is affected. Diffusion measures such as radial diffusivity (RD) are commonly used to assess myelin content, but are not specific to myelin. Inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1 and T2 (mcDESPOT) offer quantitative parameters (qihMT and myelin volume fraction/VFm, respectively) which are suggested to have improved sensitivity to myelin. We compared RD, qihMT, and VFm in a cohort of 23 healthy children aged 8–13 years to evaluate the similarities and differences across these measures. All 3 measures were significantly related across brain voxels, but VFm and qihMT were significantly more strongly correlated (qihMT-VFm r = 0.89) than either measure was with RD (RD-qihMT r = −0.66, RD-VFm r = −0.74; all p < 0.001). Mean parameters differed in several regions, especially in subcortical gray matter. These differences can likely be explained by unique sensitivities of each measure to non-myelin factors, such as crossing fiber geometry, axonal packing, fiber orientation, glial density, or magnetization transfer effects in a voxel. We also observed an orientation dependence of qihMT in white matter, such that qihMT decreased as fiber orientation went from parallel to perpendicular to B0. All measures appear to be sensitive to myelin content, though qihMT and VFm appear to be more specific to it than RD. Scan time, noise tolerance, and resolution requirements may inform researchers of the appropriate measure to choose for a specific application.

High-resolution in vivo imaging of human locus coeruleus by magnetization transfer MRI at 3T and 7T

Locus Coeruleus (LC) is a neuromelanin-rich brainstem structure that is the source of noradrenaline in the cortex and is thought to modulate attention and memory. LC imaging in vivo is commonly performed with a 2D T1-weighted Turbo Spin Echo (TSE) MRI sequence, an approach that suffers from several drawbacks at 3T, including long acquisition times and highly anisotropic spatial resolution. In this study, we developed a high-resolution Magnetization Transfer (MT) sequence for LC imaging at both 7T and 3T and compared its performance to a TSE sequence. Results indicate that LC imaging can be achieved with an MT sequence at both 7 and 3T at higher spatial resolution than the 3T TSE. Furthermore, we investigated whether the currently disputed source of contrast in the LC region with a TSE sequence relates to MT effects or shortened T1 and T2* due to increased iron concentration. Our results suggest that the contrast in the LC area relates to MT effects. To conclude, in this study we managed to image the LC, for the first time, at 7T and at an increased resolution compared to the current state-of-the-art. Imaging the LC is highly relevant for clinical diagnostics as structural tissue properties of the LC may hold promise as a biomarker in neurodegenerative diseases.

A dual flip angle 3D bSSFP magnetization transfer-like method to differentiate between recent and old myocardial infarction.

Magnetic resonance imaging (MRI) tissue signal is modulated by magnetization transfer (MT) phenomena, intrinsically induced by balanced steady-state free precession (bSSFP) imaging. To investigate the possible value of such a MT-like bSSFP approach in two clinical settings involving focal myocardial lesions highligthed by late gadolinium enhancement (LGE+): edema induced by recent myocardial infarction (MI) and fibrotic scar related to chronic infarction. Population: 48 LGE + patients were studied: 26 with recent MI, 22 with chronic MI. 20 LGE-normal subjects were considered the control group. Field strength/sequence: Navigator-based short axis 3D-bSSFP sequences with 20° and 90° excitation flip angles were acquired (1.5T). Pixel-wise normalized MT Ratio (nMTR) parametric images were calculated according to: nMTR = 100*(S20 -S90 *k)/S20 , with S20 and S90 signal intensity in 20° and 90° flip angle images and k = Blood20 /Blood90 as a normalization ratio. Statistical tests: analysis of variance (ANOVA), receiver operating characteristic (ROC) analysis. Overall normal myocardial nMTR was 50.2 ± 3.6%. In recent MI, nMTR values were significantly reduced in LGE + regions (-22.3 ± 9.9%, P < 0.0001). In cases of chronic infarct, nMTR was significantly increased in LGE + regions (14.2 ± 11.4%, P < 0.0001). Comparison between observed results and theoretical values obtained with the Freeman-Hill formula showed that most variations observed in MI are related to MT effects instead of relaxation effects. In contrast to LGE imaging, which may show a similar hyperenhancement in recent and old infarctions, nMTR imaging demonstrates an opposite pattern: decreased values for recent infarction and increased values for old infarction, thus allowing to discriminate between these two clinical conditions without gadolinium injection. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:798-808.

Magnetization transfer in a partly deuterated lyotropic liquid crystal by single- and dual-frequency RF irradiations

The mechanism of magnetization transfer (MT) in a lyotropic liquid crystal made of sodium dodecyl sulfate, decanol, and water molecules is investigated by using deuterated molecules and single- and dual-frequency RF irradiations. The resulting Z-spectra suggest that the decanol molecules are mainly responsible for the MT effects in this system, through proton exchange to water. This is further confirmed by monitoring the relaxation of dipolar order, which allows one to estimate the transfer rate of magnetization from decanol to water. The potential benefits of using dual-frequency RF irradiation for inducing MT effects are explored through numerical solutions to a MT model based on Provotorov’s partial saturation theory.

MRI evaluation of regional and longitudinal changes in Z-spectra of injured spinal cord of monkeys.

In principle, MR methods that exploit magnetization transfer (MT) may be used to quantify changes in the molecular composition of tissues after injury. The ability to track such changes in injured spinal cord may allow more precise assessment of the state of neural tissues. Z-Spectra were obtained from the cervical spinal cord before and after a unilateral dorsal column lesion in monkeys at 9.4T. The amplitudes of chemical exchange saturation transfer (CEST) and nuclear Overhauser enhancement (NOE) effects from multiple proton pools, along with nonspecific semisolid MT effects from immobile macromolecules, were quantified using a five-peak Lorenzian fitting of each Z-spectrum. Abnormal tissues/cysts that formed around lesion sites exhibited relatively low correlations between their Z-spectra and that of normal gray matter (GM). Compared with normal GM, cysts showed strong CEST but weak semisolid MT and NOE effects after injury. The abnormal tissues around lesion sites were heterogeneous and showed different regional Z-spectra. Different regional correlations between proton pools were observed. Longitudinally, injured spinal cord tissue exhibited remarkable recovery in all subjects. Characterization of multiple proton pools from Z-spectra permitted noninvasive, regional, quantitative assessments of changes in tissue composition of injured spinal cord over time. Magn Reson Med 79:1070-1082, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Acceleration of ASL-based time-resolved MR angiography by acquisition of control and labeled images in the same shot (ACTRESS).

PurposeNoncontrast 4D‐MR‐angiography (MRA) using arterial spin labeling (ASL) is beneficial because high spatial and temporal resolution can be achieved. However, ASL requires acquisition of labeled and control images for each phase. The purpose of this study is to present a new accelerated 4D‐MRA approach that requires only a single control acquisition, achieving similar image quality in approximately half the scan time.MethodsIn a multi‐phase Look‐Locker sequence, the first phase was used as the control image and the labeling pulse was applied before the second phase. By acquiring the control and labeled images within a single Look‐Locker cycle, 4D‐MRA was generated in nearly half the scan time of conventional ASL. However, this approach potentially could be more sensitive to off‐resonance and magnetization transfer (MT) effects. To counter this, careful optimizations of the labeling pulse were performed by Bloch simulations. In in‐vivo studies arterial visualization was compared between the new and conventional ASL approaches.ResultsOptimization of the labeling pulse successfully minimized off‐resonance effects. Qualitative assessment showed that residual MT effects did not degrade visualization of the peripheral arteries.ConclusionThis study demonstrated that the proposed approach achieved similar image quality as conventional ASL‐MRA approaches in just over half the scan time. Magn Reson Med 79:224–233, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

CEST imaging of fast exchanging amine pools with corrections for competing effects at 9.4T.

Chemical exchange saturation transfer (CEST) imaging of fast exchanging amine protons at 3ppm offset from the water resonant frequency is of practical interest, but quantification of fast exchanging pools by CEST is challenging. To effectively saturate fast exchanging protons, high irradiation powers need to be applied, but these may cause significant direct water saturation as well as non-specific semi-solid magnetization transfer (MT) effects, and thus decrease the specificity of the measured signal. In addition, the CEST signal may depend on the water longitudinal relaxation time (T1w ), which likely varies between tissues and with pathology, further reducing specificity. Previously, an analysis of the asymmetry of saturation effects (MTRasym ) has been commonly used to quantify fast exchanging amine CEST signals. However, our results show that MTRasym is greatly affected by the above factors, as well as asymmetric MT and nuclear Overhauser enhancement (NOE) effects. Here, we instead applied a relatively more specific inverse analysis method, named AREX (apparent exchange-dependent relaxation), that has previously been applied only to slow and intermediate exchanging solutes. Numerical simulations and controlled phantom experiments show that, although MTRasym depends on T1w and semi-solid content, AREX acquired in steady state does not, which suggests that AREX is more specific than MTRasym . By combining with a fitting approach instead of using the asymmetric analysis to obtain reference signals, AREX can also avoid contaminations from asymmetric MT and NOE effects. Animal experiments show that these two quantification methods produce differing contrasts between tumors and contralateral normal tissues in rat brain tumor models, suggesting that conventional MTRasym applied in vivo may be influenced by variations in T1w , semi-solid content, or NOE effect. Thus, the use of MTRasym may lead to misinterpretation, while AREX with corrections for competing effects likely enhances the specificity and accuracy of quantification to fast exchanging pools.

Quantitative chemical exchange saturation transfer (CEST) MRI of glioma using Image Downsampling Expedited Adaptive Least-squares (IDEAL) fitting

Chemical Exchange Saturation Transfer (CEST) MRI is sensitive to dilute metabolites with exchangeable protons, allowing tissue characterization in diseases such as acute stroke and tumor. CEST quantification using multi-pool Lorentzian fitting is challenging due to its strong dependence on image signal-to-noise ratio (SNR), initial values and boundaries. Herein we proposed an Image Downsampling Expedited Adaptive Least-squares (IDEAL) fitting algorithm that quantifies CEST images based on initial values from multi-pool Lorentzian fitting of iteratively less downsampled images until the original resolution. The IDEAL fitting in phantom data with superimposed noise provided smaller coefficient of variation and higher contrast-to-noise ratio at a faster fitting speed compared to conventional fitting. We further applied the IDEAL fitting to quantify CEST MRI in rat gliomas and confirmed its advantage for in vivo CEST quantification. In addition to significant changes in amide proton transfer and semisolid macromolecular magnetization transfer effects, the IDEAL fitting revealed pronounced negative contrasts of tumors in the fitted CEST maps at 2 ppm and −1.6 ppm, likely arising from changes in creatine level and nuclear overhauser effects, which were not found using conventional method. It is anticipated that the proposed method can be generalized to quantify MRI data where SNR is suboptimal.

Contrast-Enhanced Magnetic Resonance Imaging with Magnetic Transfer Effect in Differential Diagnosis of Hemangiomas and Metastases of Liver

Objective: to investigate the operating characteristics of contrast MRI of the liver using magnetization transfer effect in the differential diagnosis of hemangiomas and metastatic lesions in comparison with dynamic contrast.Material and methods. The material of the study were dynamic contrast MRI images of 25 patients with diagnosis of direction of focal liver lesion. Inclusion criteria were detection of typical MR-semiotic for hemangioma (n = 10 to 40% of cases) or multiple liver metastases (n = 15 to 60% of cases).In the group with metastases exclusion criteria was the primary detection of obscure single focal lesions, as well as the diagnosis of other primary tumors, in particular cholangiocellular cancer (n = 1). All MRI studies were performed using MRI Toshiba Titan Octave with of 1.5 Tesla magnetic field. T1-weighted static contrast MRI investigation of liver performed after 3–5 minutes after a series of dynamic contrast MRI with modes: T1-FE-FSat and T1-TSEMTS (Δf = -210 Hz, FA = 600°). The magnevist at a dose of 0.1 mmol/kg was used as a contrast agent. Each focal liver lesion differentiated between hemangiomaand metastasis with the calculation of contrast ratio (CR) for each lesion. Statistical analysis of CR was performed using T-test and T-test Welch. The sensitivity and specificity parameters were compared during the ROC-analysis.Results. In our statistical analysis groups formed not from patients, because we were compared results about focal lesions of a liver referred to metastasis or hemangiomas. All the patients included in a research had focal lesions mostly multiple and in the comparative analysis of contrast ratio in the T1-FE-FSat and T1-TSE-MTC was carried out on 21 (20%) hemangiomas and 84 (80%) metastasises. The significant (p &lt; 10–4) contrast enhancement using T1-TSE-MTS, as in the case of hemangiomas and in metastatic lesions relative to T1-FE-FSat revealed by comparing the CRs. No significant differences were found in the differentiation of hemangiomas and liver metastases in modes T1-FE-FSat and T1-TSE-MTS when paired comparison of ROC-curves (p &gt; 0.18). No significant differences were found when paired comparison of CRs between hemangiomas in T1-FE-FSat mode and metastases in T1-TSEMTSimages (p &gt; 0.8). An additive effect (sensitivity and specificity – 98.8% and 85.7%) occurs when we used to CRcomm=35.7% in T1-FE-FSat modes and T1-TSE-MTS.Conclusions. 1. Contrast MRI using magnetization transfer effect allows significantly increase the contrast of focal liver formations on the type of hemangiomas and metastases. 2. The achieved contrast level in 2D TSE images with magnetization transfer effect of liver metastatic foci corresponds to that of hemangiomas in 2D FE mode. 3. Maximum parameters of sensitivity and specificity in the differential diagnosis of hemangiomas and liver metastases obtained by using 2D-FE-FSat and 2D-TSE-MTC in post contrast phase.