Magnetization Transfer Effects Research Articles

Quantitative description of the asymmetry in magnetization transfer effects around the water resonance in the human brain

Magnetization transfer (MT) imaging provides a unique method of tissue characterization by capitalizing on the interaction between solid-like tissue components and bulk water. We used a continuous-wave (CW) MT pulse sequence with low irradiation power to study healthy human brains in vivo at 3 T and quantified the asymmetry of the MT effects with respect to the water proton frequency. This asymmetry was found to be a difference of approximately a few percent from the water signal intensity, depending on both the RF irradiation power and the frequency offset. The experimental results could be quantitatively described by a modified two-pool MT model extended with a shift contribution for the semisolid pool with respect to water. For white matter, this shift was fitted to be 2.34 +/- 0.17 ppm (N = 5) upfield from the water signal.

Impact of incidental magnetization transfer effects on inversion‐recovery sequences that use a fast spin‐echo readout

Multislice MR images obtained using a fast spin-echo (FSE) readout are strongly affected by magnetization transfer (MT) effects, which will cause a decrease in the observed longitudinal relaxation times for tissues with a large bound water component. This is pertinent for FSE-based inversion-recovery (IR) sequences, as it would be expected to cause a change in the required inversion times. Furthermore, the effect will be greater as the number of slices that are acquired within the repetition time (TR) is increased. A pseudo-3D IR-FSE sequence was used to obtain images of a phantom consisting of thermally crosslinked bovine serum albumin. It was found that increasing the number of slabs acquired per TR period led to a decrease in the inversion time that maximally suppressed the signal from the MT phantom; this was not the case for water. This has important consequences for any IR imaging sequence that uses an FSE readout.

Optimized balanced steady‐state free precession magnetization transfer imaging

Balanced steady-state free precession (bSSFP) suffers from a considerable signal loss in tissues. This apparent signal reduction originates from magnetization transfer (MT) and may be reduced by an increase in repetition time or by a reduction in flip angle. In this work, MT effects in bSSFP are modulated by a modification of the bSSFP sequence scheme. Strong signal attenuations are achieved with short radio frequency (RF) pulses in combination with short repetition times, whereas near full, i.e., MT-free, bSSFP signal is obtained by a considerable prolongation of the RF pulse duration. Similar to standard methods, the MT ratio (MTR) in bSSFP depends on several sequence parameters. Optimized bSSFP protocol settings are derived that can be applied to various tissues yielding maximal sensitivity to MT while minimizing contribution from other impurities, such as off-resonances. Evaluation of MT in human brain using such optimized bSSFP protocols shows high correlation with MTR values from commonly used gradient echo (GRE) sequences. In summary, a novel method to generate MTR maps using bSSFP image acquisitions is presented and factors that optimize and influence this contrast are discussed.

Modeling pulsed magnetization transfer

Modeling the effects of clinical magnetization transfer (MT) scans, which generate contrast using short, shaped radiofrequency (RF) pulses (pulsed MT), is complex and time-consuming. As a result, several studies have proposed approximate methods for a simplified analysis of the experimental data. However, potential differences in the MT parameters estimated by each method may complicate the comparison of reported results. In this study we evaluated three approximate methods currently used in quantitative MT (qMT) studies. In the first part of the investigation, an MT modeling technique that makes minimal approximations, other than the use of a two-pool tissue representation, was developed and validated. Subsequently, this technique served as a standard against which to evaluate the other, more approximate models. Each model was used to fit experimental data from samples of wild-type (WT) and shiverer mouse spinal cord, as well as simulated data generated by our minimal approximation modeling technique. The results of this study demonstrate that the approximations used in pulsed MT modeling are quite robust. In particular, it was shown that the semisolid pool fraction, M(0)(B), which is known to correlate strongly with myelin content, and the transverse relaxation time of macromolecular protons, T(2)(B), could be evaluated with reasonable accuracy regardless of the model used.

Effect of multislice acquisition on T1 and T2 measurements of articular cartilage at 3T

The aim of this study was to investigate the effect of magnetization transfer on multislice T1 and T2 measurements of articular cartilage. A set of phantoms with different concentrations of collagen and contrast agent (Gd-DTPA2-) were used for the in vitro study. A total of 20 healthy knees were used for the in vivo study. T1 and T2 measurements were performed using fast-spin-echo inversion-recovery (FSE-IR) sequence and multi-spin-echo (MSE) sequence, respectively, in both in vitro and in vivo studies. We investigated the difference in T1 and T2 values between that measured by single-slice acquisition and that measured by multislice acquisition. Regarding T1 measurement, a large drop of T1 in all slices and also a large interslice variation in T1 were observed when multislice acquisition was used. Regarding T2 measurement, a substantial drop of T2 in all slices was observed; however, there was no apparent interslice variation when multislice acquisition was used. This study demonstrated that the adaptation of multislice acquisition technique for T1 measurement using FSE-IR methodology is difficult and its use for clinical evaluation is problematic. In contrast, multislice acquisition for T2 measurement using MSE was clinically applicable if inaccuracies caused by multislice acquisition were taken into account.

Effects of formalin fixation and collagen cross‐linking on T2 and magnetization transfer in bovine nasal cartilage

Endogenous collagen cross-links influence cartilage biomechanical properties and resistance to degradation. Formalin fixation modifies collagen residues and forms new cross-links in a dose-dependent manner. We tested the hypothesis that magnetization transfer (MT) effects and T(2) depend on collagen cross-linking in cartilage. These parameters were measured in bovine nasal cartilage (BNC) prior to fixation, after 9 weeks of immersion in formalin solutions ranging in concentration from 0% to 10%, and after NaBH(3)CN reduction and washing. T(2) decreased by 59.4% +/- 1.1% upon fixation in 10% formalin, and was 32.2% +/- 5.2% shorter than initial values after washing. The apparent MT rate increased 25.9% +/- 3.7% and 52.8% +/- 7.1% over baseline under these conditions. Biochemical assays showed no significant differences in water, proteoglycan, natural cross-link, or collagen content between the 0% and 10% formalin-treated samples, while amino acid analysis demonstrated losses in (hydroxy)lysine and tyrosine, and new peaks consistent with methylene cross-links in fixed samples only. We conclude that formalin fixation of cartilage results in significant decreases in T(2) and increases in MT parameters that persist after removal of unreacted formaldehyde. The collagen cross-links thus created are associated with large changes in MT and T(2), indicating that interpretation of T(2) and MT values in terms of cartilage macromolecular content must be made with caution.

Incidental magnetization transfer effects in multislice brain MRI at 3.0T

To evaluate the effect of incidental magnetization transfer (iMT) in multislice brain imaging at 3.0T. The contribution of iMT to multislice brain MRI was evaluated at 3.0T. In 10 normal subjects we obtained multislice fast spin-echo (FSE) MR images using a 16-echo pulse train without an off-resonance MT pulse at 3.0T and 1.5T. We quantified the extent of iMT by calculating the iMT ratio (iMTR). We found that the iMT contrast (iMTC) has a greater effect at 3.0T. As the number of slices increased in multislice FSE imaging, the difference between two field strengths became larger. Compared to WM structures, however, the difference in iMT effect between 1.5T and 3.0T was smaller in the case of GM structures. The iMTC has a greater effect at 3.0T. The strength of the iMT is different for different tissue types and also varies according to the number of slices used.

Magnetization transfer effects on the efficiency of flow-driven adiabatic fast passage inversion of arterial blood.

Continuous arterial spin labeling experiments typically use flow-driven adiabatic fast passage inversion of the arterial blood water protons. In this article, we measure the effect of magnetization transfer in blood and how it affects the inversion label. We use modified Bloch equations to model flow-driven adiabatic inversion in the presence of magnetization transfer in blood flowing at velocities from 1 to 30 cm/s in order to explain our findings. Magnetization transfer results in a reduction of the inversion efficiency at the inversion plane of up to 3.65% in the range of velocities examined, as well as faster relaxation of the arterial label in continuous labeling experiments. The two effects combined can result in inversion efficiency reduction of up to 8.91% in the simulated range of velocities. These effects are strongly dependent on the velocity of the flowing blood, with 10 cm/s yielding the largest loss in efficiency due to magnetization transfer effects. Flowing blood phantom experiments confirmed faster relaxation of the inversion label than that predicted by T(1) decay alone.

In vivo 13C saturation transfer effect of the lactate dehydrogenase reaction

Lactate dehydrogenase (LDH, EC 1.1.1.27) catalyzes an exchange reaction between pyruvate and lactate. It is demonstrated here that this reaction is sufficiently fast to cause a significant magnetization (saturation) transfer effect when the 13C resonance of pyruvate is saturated by a continuous-wave (CW) RF pulse. Infusion of [2-(13)C]glucose was used to allow labeling of pyruvate C2 at 207.9 ppm to determine the pseudo first-order rate constant of the unidirectional lactate-->pyruvate flux in vivo. During systemic administration of GABAA receptor antagonist bicuculline, this pseudo first-order rate constant was determined to be 0.08+/-0.01 s-1 (mean+/-SD, N=4) in halothane-anesthetized adult rat brains. In 9L and C6 rat glioma models, the 13C saturation transfer effect of the LDH reaction was also detected in vivo. Our results demonstrate that the 13C magnetization transfer effect of the LDH reaction may be useful as a novel marker for utilizing noninvasive in vivo MRS to study many physiological and pathological conditions, such as cancer.

Dynamics of paramagnetic agents by off-resonance rotating frame technique in the presence of magnetization transfer effect

The simple method for measuring the rotational correlation time of paramagnetic ion chelates via off-resonance rotating frame technique is challenged in vivo by the magnetization transfer effect. A theoretical model for the spin relaxation of water protons in the presence of paramagnetic ion chelates and magnetization transfer effect is described. This model considers the competitive relaxations of water protons by the paramagnetic relaxation pathway and the magnetization transfer pathway. The influence of magnetization transfer on the total residual z-magnetization has been quantitatively evaluated in the context of the magnetization map and various difference magnetization profiles for the macromolecule conjugated Gd-DTPA in cross-linked protein gels. The numerical simulations and experimental validations confirm that the rotational correlation time for the paramagnetic ion chelates can be measured even in the presence of strong magnetization transfer. This spin relaxation model also provides novel approaches to enhance the detection sensitivity for paramagnetic labeling by suppressing the spin relaxations caused by the magnetization transfer. The inclusion of the magnetization transfer effect allows us to use the magnetization map as a simulation tool to design efficient paramagnetic labeling targeting at specific tissues, to design experiments running at low RF power depositions, and to optimize the sensitivity for detecting paramagnetic labeling. Thus, the presented method will be a very useful tool for the in vivo applications such as molecular imaging via paramagnetic labeling.

Off‐resonance saturation as a means of generating contrast with superparamagnetic nanoparticles

This work demonstrates an alternative approach, termed off-resonance saturation (ORS), for generating contrast that is sensitive to superparamagnetic particles. This method leads to a calculated contrast that increases with superparamagnetic nanoparticle concentration. Experimental data demonstrate that in the presence of superparamagnetic particles, an off-resonance effect exists that is distinct from the magnetization transfer (MT) effect and is highly dependent on diffusion. Data show that the dependence on water diffusion becomes most significant at rates of 0.5 x 10(-9) m(2)/s and slower. We investigated the dependence of the off-resonance effect on off-resonance frequency and particle concentration. The data suggest a useful frequency offset range of 500 Hz < |Deltaomega| < 1500 Hz at 3T. This approach may be especially useful in organs and diseases in which diffusion may be altered by pathologies.

Quantifying exchange rates in chemical exchange saturation transfer agents using the saturation time and saturation power dependencies of the magnetization transfer effect on the magnetic resonance imaging signal (QUEST and QUESP): Ph calibration for poly‐L‐lysine and a starburst dendrimer

The ability to measure proton exchange rates in tissue using MRI would be very useful for quantitative assessment of magnetization transfer properties, both in conventional MT imaging and in the more recent chemical exchange saturation transfer (CEST) approach. CEST is a new MR contrast mechanism that depends on several factors, including the exchange rate of labile protons in the agent in a pH-dependent manner. Two new methods to monitor local exchange rate based on CEST are introduced. The two MRI-compatible approaches to measure exchange are quantifying exchange using saturation time (QUEST) dependence and quantifying exchange using saturation power (QUESP) dependence. These techniques were applied to poly-L-lysine (PLL) and a generation-5 polyamidoamine dendrimer (SPD-5) to measure the pH dependence of amide proton exchange rates in the physiologic range. Data were fit both to an analytical expression and to numerical solutions to the Bloch equations. Results were validated by comparison with exchange rates determined by two established spectroscopic methods. The exchange rates determined using the four methods were pooled for the pH-calibration curve of the agents consisting of contributions from spontaneous (k0) acid catalyzed (ka), and base catalyzed (kb) exchange rate constants. These constants were k0 = 68.9 Hz, ka = 1.21 Hz, kb = 1.92 x 10(9) Hz, and k0 = 106.4 Hz, ka = 25.8 Hz, kb = 5.45 x 10(8) Hz for PLL and SPD-5, respectively, showing the expected predominance of base-catalyzed exchange for these amide protons.

Erratum to: Shen J. In vivo carbon‐13 magnetization transfer effect. Detection of aspartate aminotransferase reaction. Magn Reson Med. 2005; 54:1321–1326

Erratum to: Shen J. In vivo carbon‐13 magnetization transfer effect. Detection of aspartate aminotransferase reaction. Magn Reson Med. 2005; 54:1321–1326

Current Awareness in NMR in Biomedicine

Current Awareness in NMR in Biomedicine

MRI of articular cartilage in OA: novel pulse sequences and compositional/functional markers

Osteoarthritis (OA) is a leading cause of disability worldwide. Magnetic resonance imaging (MRI), with its unique ability to image and characterize soft tissue non-invasively, has proven valuable in assessing cartilage in OA. The development of new, fast imaging methods with high contrast show promise to improve the magnetic resonance (MR) evaluation of this disease. In addition to morphologic MRI methods, MRI contrast mechanisms under development may reveal detailed information about the physiology of cartilage. It is anticipated that these and other MRI techniques will play an increasingly important role in assessing the success or failure of therapies for OA. On December 5 and 6, 2002, OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International) held a workshop in Bethesda, MD aiming at providing a state-of-the-art review of imaging outcome measures for OA of the knee to help guide scientists and pharmaceutical companies in the use of MRI in multi-site studies of OA. Applications of MRI were initially reviewed by a multidisciplinary, international panel of expert scientists and physicians from academia, the pharmaceutical industry and regulatory agencies. The findings of the panel were then presented to a wider group of participants for open discussion. The following report summarizes the results of these discussions with respect to novel MRI pulse sequences for evaluating articular cartilage of the knee in OA and notes any additional advances that have been made since.

In vivo carbon‐13 magnetization transfer effect. Detection of aspartate aminotransferase reaction

One of the most remarkable achievements of in vivo NMR spectroscopy has been the detection of rapid enzyme-catalyzed exchange reactions using phosphorus-31 magnetic resonance spectroscopy-based magnetization transfer experiments. In this paper, we report, for the first time, the in vivo carbon magnetization transfer (CMT) effect and in vivo detection of the CMT effects of the alpha-ketoglutarate <--> glutamate and the oxaloacetate <--> aspartate reactions, both of which are catalyzed by aspartate aminotransferase. By saturating the carbonyl carbon of alpha-ketoglutarate at 206 ppm in alpha-chloralose anesthetized adult rat brain, the unidirectional glutamate --> alpha-ketoglutarate flux was determined to be 78 +/- 9 mumol/g/min (mean +/- SD, n = 11) following i.v. infusion of [1,6-(13)C(2)]D-glucose. Contribution from aspartate aminotransferase-catalyzed partial reactions to the observed CMT effects was emphasized. Because of the large chemical shift separation between the alpha-carbons of the amino acids and the carbonyl carbons of the corresponding cognate keto acids, the spillover of the saturation radiofrequency pulses to the alpha-carbon resonances was negligible. The results indicate that the magnetization transfer effects of aspartate aminotransferase-catalyzed reactions can be used as new biomarkers accessible to non-invasive in vivo magnetic resonance spectroscopy techniques.

Magnetization Transfer Imaging in Multiple Sclerosis

Magnetization transfer (MT) is a relatively new way of generating contrast in magnetic resonance (MR) images that is sensitive to the density of the macromolecules found throughout tissue structures such as membranes, myelin, and organelles. MT imaging (MTI) can provide a quantitative measure of macromolecular density, and therefore of tissue damage, and has been applied in the central nervous system in multiple sclerosis (MS) and other diseases. This article introduces the contrast mechanisms behind MTI and gives some practical guidance about implementing MTI and about quantitative analysis of the MT scans. An overview of MT measurements made in animal studies, in postmortem tissue samples, and in other demyelinating diseases attempts to rationalize the pathological basis of changes in MT contrast in MS. The application of MTI to MS is reviewed, with emphasis on the contribution that MTI has made to the current understanding of the MS disease process, both its natural history and the response to treatment. The pathological basis of abnormal MT contrast is still open to debate, with many conflicting reports; indeed, it is unlikely that a simple measure of MT effect will reveal the details of pathology that is a combination of inflammation, demyelination, remyelination, and axonal loss. There is no doubt, however, that MT measurements have contributed to the current understanding of both disease progression and the response to treatment and will prove to be a valuable tool in the future, particularly if more refined techniques can be applied practically in multicenter studies.

Magnetization transfer effect on human brain metabolites and macromolecules

A pulse sequence was implemented to observe the magnetization transfer (MT) effect on metabolites, water, and macromolecules in human frontal lobes in vivo at 1.5 Tesla. Signals were compared following the application of three hard pulses of 0.745 muT amplitude, applied at frequency offsets of either 2500 Hz or 30 kHz, preceding a conventional point-resolved spectroscopy (PRESS)-localized acquisition with an echo time (TE) of 30 ms and repetition time (TR) of 3 s. This gave an MT effect on water in vivo of 46%, while direct saturation by the MT pulses at 2.5 kHz offset was confirmed to be under 4% for all metabolites. We observed significant MT saturation in vivo for N-acetylated compounds, choline (Cho), myo-inositol, and lactate (Lac); a trend of an effect on glutamate + glutamine (Glx); and the typically observed effect on creatine (Cr). No significant MT effect was seen on the macromolecule signal, which was observed using metabolite nulling.

FAWSETS perfusion measurements in exercising skeletal muscle

Arterial spin labeling (ASL) techniques are now recognized as valid tools for providing accurate measurements of cerebral and cardiac perfusion. The labeling process used with most ASL techniques creates two problems, magnetization transfer (MT) effects and arterial transit time effects, that require compensation. The compensation process limits time resolution and hinders absolute quantification. MT effects are particularly problematic in skeletal muscle because they are large and change rapidly during exercise. The protocol presented here was developed specifically for quantification of perfusion in exercising skeletal muscle. The ASL technique that was implemented, FAWSETS, eliminates MT effects and arterial transit times. Localized, single-voxel perfusion measurements were acquired from rat hind limbs at rest, during ischemia and during three different levels of stimulated exercise. The results demonstrate sufficient sensitivity to determine the time constants for perfusion changes at onset of, and during recovery from, exercise and to distinguish the differences in the amplitude of the perfusion response to different levels of exercise. Additional measurements were conducted to demonstrate insensitivity to MT effects. The exercise protocol is easily adaptable to phosphorous magnetic resonance measurements, allowing the possibility to acquire local measurements of perfusion and metabolism from the same tissue in future experiments.

Quantification of cerebral arterial blood volume and cerebral blood flow using MRI with modulation of tissue and vessel (MOTIVE) signals

Regional cerebral arterial blood volume (CBVa) and blood flow (CBF) can be quantitatively measured by modulation of tissue and vessel (MOTIVE) signals, enabling separation of tissue signal from blood. Tissue signal is selectively modulated using magnetization transfer (MT) effects. Blood signal is changed either by injection of a contrast agent or by arterial spin labeling (ASL). The measured blood volume represents CBVa because the contribution from venous blood was insignificant in our measurements. Both CBVa and CBF were quantified in isoflurane-anesthetized rats at 9.4T. CBVa obtained using a contrast agent was 1.1 +/- 0.5 and 1.3 +/- 0.6 ml/100 g tissue (N = 10) in the cortex and caudate putamen, respectively. The CBVa values determined from ASL data were 1.0 +/- 0.3 ml/100 g (N = 10) in both the cortex and the caudate putamen. The match between CBVa values determined by both methods validates the MOTIVE approach. In ASL measurements, the overestimation in calculated CBF values increased with MT saturation levels due to the decreasing contribution from tissue signals, which was confirmed by the elimination of blood with a contrast agent. Using the MOTIVE approach, accurate CBF values can also be obtained.