Magnetization transfer weighted imaging in the upper cervical spinal cord using cerebrospinal fluid as intersubject normalization reference (MTCSF imaging).

The magnetization transfer ratio (MTR) is a reliable measure of MT effects because it employs an internal standard that allows quantitative comparison between subjects, independent of other contrasts, coil loading, and coil sensitivity profiles. However, at very high spatial resolution in the spinal cord at 1.5 T, the use of MTR quantification has been hampered by low signal-to-noise ratio (SNR) and acute sensitivity to motion. Here, the suitability of cerebrospinal fluid (CSF) as an alternative inter-subject MT signal intensity reference for the spine is evaluated. Contrary to MTR, this so-called MTCSF internal standard does not remove interfering T(1), T(2), and spin density contrast and is not expected to be able to discriminate between myelination and inflammation effects. However, it can detect initial changes in myelination when signal alterations are not yet detectable by conventional MRI. As a first example, this is demonstrated for the noninflammatory spinal cord white matter disease adrenomyeloneuropathy.     

Magnetization transfer (MT) asymmetry around the water resonance in human cervical spinal cord

Purpose

To demonstrate the presence of magnetization transfer (MT) asymmetry in human cervical spinal cord due to the interaction between bulk water and semisolid macromolecules (conventional MT), and the chemical exchange dependent saturation transfer (CEST) effect.

Materials and Methods

MT asymmetry in the cervical spinal cord (C3/C4–C5) was investigated in 14 healthy male subjects with a 3T magnetic resonance (MR) system. Both spin‐echo (SE) and gradient‐echo (GE) echo‐planar imaging (EPI) sequences, with low‐power off‐resonance radiofrequency irradiation at different frequency offsets, were used.

Results

Our results show that the z‐spectrum in gray/white matter (GM/WM) is asymmetrical about the water resonance frequency in both SE‐EPI and GE‐EPI, with a more significant saturation effect at the lower frequencies (negative frequency offset) far away from water and at the higher frequencies (positive offset) close to water. These are attributed mainly to the conventional MT and CEST effects respectively. Furthermore, the amplitude of MT asymmetry is larger in the SE‐EPI sequence than in the GE‐EPI sequence in the frequency range of amide protons.

Conclusion

Our results demonstrate the presence of MT asymmetry in human cervical spinal cord, which is consistent with the ones reported in the brain. J. Magn. Reson. Imaging 2009;29:523–528. © 2009 Wiley‐Liss, Inc.     

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.     

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.     

Quantitative magnetization transfer in in vivo healthy human skeletal muscle at 3 T

The value of quantitative MR methods as potential biomarkers in neuromuscular disease is being increasingly recognized. Previous studies of the magnetization transfer ratio have demonstrated sensitivity to muscle disease. The aim of this work was to investigate quantitative magnetization transfer imaging of skeletal muscle in healthy subjects at 3 T to evaluate its potential use in pathological muscle. The lower limb of 10 subjects was imaged using a 3D fast low‐angle shot acquisition with variable magnetization transfer saturation pulse frequencies and amplitudes. The data were analyzed with an established quantitative two‐pool model of magnetization transfer. T₁ and B₁ amplitude of excitation radiofrequency field maps were acquired and used as inputs to the quantitative magnetization transfer model, allowing properties of the free and restricted proton pools in muscle to be evaluated in seven different muscles in a region of interest analysis. The average restricted pool T₂ relaxation time was found to be 5.9 ± 0.2μs in the soleus muscle and the restricted proton pool fraction was 8 ± 1%. Quantitative magnetization transfer imaging of muscle offers potential new biomarkers in muscle disease within a clinically feasible scan time. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Magnetisation transfer ratio measurement in the cervical spinal cord: a preliminary study in multiple sclerosis

MRI readily detects the lesions of multiple sclerosis (MS) in the brain and spinal cord. Conventional MRI sequences do not, however, permit distinction between the various pathological characteristics (oedema, demyelination, axonal loss and gliosis) of lesions in MS. Magnetisation transfer (MT) imaging may be more specific in distinguishing the pathologies responsible for disability in MS, namely demyelination and axonal loss, and therefore may have a potential role in monitoring treatment. We have applied MT imaging to the cervical spinal cord to see if it is feasible to measure MT ratios (MTR) in this region where pathological changes may result in considerable disability. We studied 12 patients with MS and 12 age- and sex-matched normal controls using a sagittal T2-weighted fast spin-echo sequence with and without an MT pulse. The median value for cervical cord mean MTR measurement in normal controls was 19.30 % units (interquartile range 19.05–19.55), whereas values were significantly lower in MS patients (median = 17.95 % units, interquartile range 17.25–19.00, P = 0.0004). There was a low intrarater variability for repeated mean MTR measurements. We conclude that it is possible to measure MTR in the cervical spinal cord, that a significant reduction occurs in patients with MS, and that there may be a role for this measure in future MS treatment trials. Received: 11 May 1996 Accepted: 24 July 1996     

Selective saturation in magnetization transfer experiments

The concept of magnetic saturation in single and binary spin systems is essential to the understanding of magnetization transfer experiments. This paper outlines the requirements for selective magnetic saturation of either of two spin pools contained in a mixture, both having identical chemical shifts. Following a brief discussion of saturation in a homogeneous sample, simple relationships are derived that predict the maximum degree of selective saturation in a two-spin nonexchanging system. Optimal saturation conditions are described in terms of the intrinsic relaxation parameters as well as the experimental conditions of saturation offset frequency and amplitude. In addition, a novel method is proposed that may be applied to saturate the “free” water as opposed to the “bound” water spins in a magnetization transfer experiment. Saturation in an exchanging system is well approximated by these relationships under some physiologically relevant conditions, examples of which are provided. Application of the relationships presented may be useful in the design of experiments to produce maximum magnetization transfer.     

In vivo quantitative microimaging of rat spinal cord at 7T.

In vivo T(2), ADC, and MT properties of the GM and WM of the rat spinal cord were measured at 7T in the cervical region. The GM T(2), T(2GM) = 43.2 +/- 1.0 msec is significantly reduced compared to the WM T(2), T(2WM) = 57.0 +/- 1.6 msec. Diffusion is anisotropic for both GM and WM, with a larger ADC value along the cord axis (ADC(GM//) = 1.05 +/- 0.09 10(-9) m(2)sec(-1) and ADC(WM//) = 1.85 +/- 0.18 10(-9) m(2)sec(-1)) than perpendicular to this plane (ADC(GM)( perpendicular) approximately 0.50 * 10(-9) m(2)sec(-1) and ADC(WM)( perpendicular) approximately 0.18 * 10(-9) m(2)sec(-1)). The MT properties do not significantly differ between the WM and the GM, but allow one to distinguish the thin CSF layer from the WM. DWI with the sensitizing gradient perpendicular to the cord axis leads to the best contrast between GM and WM in the cervical region.     

In vivo magnetic resonance microscopy of rat spinal cord at 7 T using implantable RF coils.

An inductively coupled implanted coil was designed for high-resolution magnetic resonance (MR) studies of rat spinal cord (SC) in vivo at 7 T. The practical issues involved in implementation of the coil at high fields are discussed, and the adjustment of various parameters for optimizing coil performance are described. The utility of the coil was demonstrated with anatomical, magnetization transfer, diffusion tensor imaging, and proton MR spectroscopy (MRS).     

High b-value q-space diffusion-weighted MRI of the human cervical spinal cord in vivo: feasibility and application to multiple sclerosis.

Q-space analysis is an alternative analysis technique for diffusion-weighted imaging (DWI) data in which the probability density function (PDF) for molecular diffusion is estimated without the need to assume a Gaussian shape. Although used in the human brain, q-space DWI has not yet been applied to study the human spinal cord in vivo. Here we demonstrate the feasibility of performing q-space imaging in the cervical spinal cord of eight healthy volunteers and four patients with multiple sclerosis. The PDF was computed and water displacement and zero-displacement probability maps were calculated from the width and height of the PDF, respectively. In the dorsal column white matter, q-space contrasts showed a significant (P < 0.01) increase in the width and a decrease in the height of the PDF in lesions, the result of increased diffusion. These q-space contrasts, which are sensitive to the slow diffusion component, exhibited improved detection of abnormal diffusion compared to perpendicular apparent diffusion constant measurements. The conspicuity of lesions compared favorably with magnetization transfer (MT)-weighted images and quantitative CSF-normalized MT measurements. Thus, q-space DWI can be used to study water diffusion in the human spinal cord in vivo and is well suited to assess white matter damage.     

Using frequency-labeled exchange transfer to separate out conventional magnetization transfer effects from exchange transfer effects when detecting ParaCEST agents

Paramagnetic chemical exchange saturation transfer agents combine the benefits of a large chemical shift difference and a fast exchange rate for sensitive MRI detection. However, the in vivo detection of these agents is hampered by the need for high B(1) fields to allow sufficiently fast saturation before exchange occurs, thus causing interference of large magnetization transfer effects from semisolid macromolecules. A recently developed approach named frequency-labeled exchange transfer utilizes excitation pulses instead of saturation pulses for detecting the exchanging protons. Using solutions and gel phantoms containing the europium (III) complex of DOTA tetraglycinate (EuDOTA-(gly)(-) (4) ), it is shown that frequency-labeled exchange transfer allows the separation of chemical exchange effects and magnetization transfer (MT) effects in the time domain, therefore allowing the study of the individual resonance of rapidly exchanging water molecules (k(ex) >10(4) s(-1) ) without interference from conventional broad-band MT.     

Quantitative proton magnetic resonance spectroscopy of the human cervical spinal cord at 3 Tesla.

Cervical spinal cord spectroscopy has the potential to add metabolic information to spinal cord MRI and improve the clinical evaluation and research investigation of spinal cord diseases, such as multiple sclerosis (MS) and intraspinal tumors. However, in vivo proton MR spectroscopy ((1)H-MRS) of the spinal cord is difficult to perform due to magnetic field inhomogeneities, physiological movements, and the size of the anatomical region of interest (ROI). For these reasons, few spinal cord (1)H-MRS studies have been undertaken and two preliminary studies on a 3T system were only recently presented as abstracts. In this work we demonstrate the feasibility of cervical spinal cord quantitative (1)H-MRS on a clinical 3T system, propose a study protocol, and report quantification results obtained from healthy volunteers. The main metabolite concentration ratios obtained in 10 healthy subjects, as provided by LCModel, were as follows: total N-acetyl aspartate/creatine (tNAA/Cr) 1.4 +/- 0.3, choline/creatine (Cho/Cr) 0.5 +/- 0.1, and myoinositol/creatine (mI/Cr) 1.7 +/- 0.2. A significant difference was found between spinal cord tNAA, Cr, Cho, and mI concentration ratios and brainstem concentrations previously acquired on the same system.