Evaluation of Magnetization Transfer Contrast Sequences: Application to Monitor Age-Related Differences in Muscle Macromolecular Fraction

To demonstrate the feasibility of whole-body magnetization transfer (MT) contrast imaging. Whole-body MT imaging was performed on eight healthy volunteers and five patients (mean age=40.5+/-17.8 years) with diagnoses of dermatomyositis (N=1), B-symptoms with suspicion of paraneoplastic disease (N=1), metastatic malignant melanoma (N=1), and multiple sclerosis (MS) (N=2). Measurements were carried out on a 1.5-Tesla whole-body MR scanner capable of parallel signal reception. A three-dimensional (3D) gradient-echo sequence (TR=17 msec, TE=4.8 msec, flip angle=10 degrees) was applied in combination with a Gaussian off-resonance MT preparation pulse acting at an off-resonance of 1.500 Hz with a 500 degrees effective flip angle. Whole-body images were constructed from five different body regions. In all subjects, whole-body MT contrast images were obtained within less than 20 minutes of measuring time. The images showed sufficient diagnostic image quality to assess the patients' pathologies. The MT ratios (MTRs, in percent units) for the volunteers were as follows: white matter (WM) 51.1+/-1.0, gray matter (GM) 42.2+/-1.3, skeletal muscle (mean value of four muscle groups) 50.3+/-2.1, liver 39.4+/-3.2, spleen 31.8+/-2.6, renal cortex 30.4+/-1.9, and renal medulla 25.6+/-1.3. The MTRs for the pathologies were as follows: skeletal muscle in dermatomyositis approximately 30, metastases in malignant melanoma 30.7-36.0, uterus myoma 49.3, and MS lesions 30-40. Our preliminary data indicate that MT contrast in whole-body MRI is feasible, and may be useful for rapid whole-body assessment of diseases that exhibit high contrast in MT imaging, such as MS and muscular disorders.

This work combines an n-dimensional fat sat(uration) radiofrequency (RF) pulse with steady-state incoherent (SSI) pulse sequences, e.g., spoiled gradient-echo sequence, to simultaneously produce B0 insensitive fat suppression and magnetization transfer (MT) contrast. This pulse is then referred to as "fat sat and MT contrast pulse." We discuss the features of the fat sat and MT contrast pulse and the MT sensitivities of the SSI sequences when combining with fat sat. Moreover, we also introduce an adapted RF spoiling scheme for SSI sequences with fat sat. Simulations and phantom experiments were conducted to demonstrate the adapted RF spoiling. Fat suppression and MT effects are shown in 3T phantom experiments and in vivo experiments, including brain imaging, cartilage imaging, and angiography. To ensure that the sequence reaches steady state, the adapted RF spoiling is required for fat sat SSI sequences. Fat sat and MT contrast pulse works robustly with field inhomogeneity and also produces MT contrasts. SSI sequences with fat sat and MT contrast pulse and adapted RF spoiling can robustly produce fat suppressed and MT contrast images in the presence of field inhomogeneity.

PurposeThis work proposes a novel RF pulse design for parallel transmit (pTx) systems to obtain uniform saturation of semisolid magnetization for magnetization transfer (MT) contrast in the presence of transmit field B1+ inhomogeneities. The semisolid magnetization is usually modeled as being purely longitudinal, with the applied B1+ field saturating but not rotating its magnetization; thus, standard pTx pulse design methods do not apply.Theory and MethodsPulse design for saturation homogeneity (PUSH) optimizes pTx RF pulses by considering uniformity of root‐mean squared B1+, B1rms, which relates to the rate of semisolid saturation. Here we considered designs consisting of a small number of spatially non‐selective sub‐pulses optimized over either a single 2D plane or 3D. Simulations and in vivo experiments on a 7T Terra system with an 8‐TX Nova head coil in five subjects were carried out to study the homogenization of B1rms and of the MT contrast by acquiring MT ratio maps.ResultsSimulations and in vivo experiments showed up to six and two times more uniform B1rms compared to circular polarized (CP) mode for 2D and 3D optimizations, respectively. This translated into 4 and 1.25 times more uniform MT contrast, consistently for all subjects, where two sub‐pulses were enough for the implementation and coil used.ConclusionThe proposed PUSH method obtains more uniform and higher MT contrast than CP mode within the same specific absorption rate (SAR) budget.

To investigate livers of mice afflicted with Niemann Pick type C (NP-C) disease using magnetization transfer contrast (MTC) imaging and to test the hypothesis that the MT ratio reproducibly changes during disease progression. NP-C is a heritable defect of lipid metabolism that results in the accumulation of unesterified cholesterol and gangliosides in virtually all cells. Symptoms predominate in brain and liver, which have high endogenous rates of lipid turnover. It is fatal to children, usually early in the second decade of life. Previous work has shown that the efficiency of magnetization transfer (MT) can be affected by cholesterol and collagen in tissues. The MT ratio (MTR) was calculated and compared during growth and therapy of diseased and control mice. Significant differences in the MTR were observed between livers of diseased and control mice. These ratios were consistent with collagen deposition associated with fibrosis, and not the accumulation of unesterified cholesterol in this organ. These results indicate that MTC imaging may have clinical potential for monitoring progression and therapy in NP-C disease.

Magnetic resonance imaging with magnetization transfer (MT) contrast recently has been described as a method that may provide additional information about the macromolecular composition of tissue. Magnetization transfer contrast images were compared to conventional gradient-recalled echo images in a variety of pulmonary parenchymal diseases and normal lung. Single-slice gradient echo images were obtained with and without an off-resonance radio frequency pulse on a 0.1T MR scanner. The change in signal intensity between identical regions of interest on non-MT and MT images was determined in 13 patients with known lung disease, five healthy volunteers, and three postmortem atelectatic dog lungs. No significant change in signal intensity (MT effect) was observed in fat, flowing blood, normal lung, atelectatic lung, or in acute pulmonary edema. Chronic parenchymal lung disease showed the greatest MT effect, 37.7% +/- 7.5. Acute infectious lung disease showed an intermediate degree of MT effect, 19.5% +/- 3.0. Magnetization transfer contrast magnetic resonance imaging of pulmonary disease is feasible at low field strength and may be useful in the characterization and differentiation of pulmonary parenchymal abnormalities. Magnetization transfer contrast appears to be proportional to the amount of interstitial fibrosis in lung parenchyma, while acute inflammatory cell infiltration exhibits less MT effect and acute pulmonary edema exhibits very little.

We propose a novel RF pulse providing an adiabatic null passage (ANP) for magnetization transfer preparation with improved insensitivity to and B0 inhomogeneities and mitigated direct saturation and T2 effects. The phase modulation function of a 6-ms time-resampled frequency offset-corrected pulse was modified to achieve zero flip angle at the end of the pulse. The spectral response was simulated, and its insensitivity to B0 and was investigated and compared with a phase-inverted (1 1- 2 ) binomial pulse. The proposed pulse was implemented in a 2D-EPI pulse sequence to generate magnetization transfer (MT) contrast and MT ratio (MTR) maps. In vivo experiments were performed on 3 healthy participants with power-matched settings for ANP and the binomial pulse with the following parameters: 6-ms binomial pulse with a flip angle of 107° (shortest element) and pulse repetition period (PRP) of TRslice = 59 ms, three experiments with 6-ms ANP and constant MT used overdrive factor (OF)/PRP values of 1/TRslice , /2TRslice , and /3TRslice . At gray matter (white matter) in vivo, the MTR decreased from 61% (64%) at OF = 1 to 38% (42%) applying ANP with an OF = and PRP = 3 TRslice , demonstrating the mitigation of T2 /direct effect by 22% (22%). Bloch-McConnell simulations gave similar values. In vivo experiments showed significant improvement in the MTR values for areas with high B0 inhomogeneity. ANP pulse was shown to be advantageous over its binomial counterpart in providing MT contrast by mitigating the T2 effect and direct saturation of the liquid pool as well as reduced sensitivity to and B0 inhomogeneity.

Magnetization transfer contrast imaging provides indirect information on the concentration of "bound" water protons and their interactions with "free" water molecules. The purpose of this study is to analyze location- and age-dependent changes in the magnetization transfer ratio (MTR) of lower extremity nerves. Ten younger (20-32 years) and 5 older (50-63 years) healthy volunteers underwent magnetization transfer contrast imaging at 3 Tesla Two 3-dimensional gradient echo sequences with and without an off-resonance saturation pulse (repetition time: 58 milliseconds; echo time: 2.46 milliseconds; band width: 530 Hz/Px; flip angle: α = 7°) were acquired at 3 different locations covering the proximal thigh to the distal lower leg in the group of younger volunteers and at 2 different locations covering the proximal to distal thigh in the group of older volunteers. Sciatic and tibial nerve regions of interest (ROIs) were manually drawn and additional ROIs were placed in predetermined muscles. Magnetization transfer ratios were extracted from respective ROIs and calculated for each individual and location. In young volunteers, mean values of nerve and muscle MTR were not different between the proximal thigh (nerve: 20.34 ± 0.91; muscle: 31.71 ± 0.29), distal thigh (nerve: 19.90 ± 0.98; P = 0.76; muscle: 31.53 ± 0.69; P = 0.87), and lower leg (nerve: 20.82 ± 1.07; P = 0.73; muscle: 32.44 ± 1.11; P = 0.51). An age-dependent decrease of sciatic nerve MTR was observed in the group of older volunteers (16.95 ± 1.2) compared with the group of younger volunteers (20.12 ± 0.65; P = 0.019). Differences in muscle MTR were not significant between older (31.01 ± 0.49) and younger (31.62 ± 0.37; P = 0.20) volunteers. The MTR of lower extremity nerves shows no proximal-to-distal gradient in young healthy volunteers but decreases with age. For future studies using MTR in peripheral nerve disorders, these findings suggest that referencing magnetization transfer contrast values in terms of age, but not anatomical nerve location is required.

Magnetization transfer (MT)–magnetic resonance imaging (MRI) techniques can provide access to visualizing macromolecular content of tissues, otherwise not assessable using conventional MRI. MT contrast is generated by the interaction between mobile water protons and the protons associated with tissue macromolecules. Given substantial variation between macromolecular compositions of tissues, this interaction differs by tissue type and results in macromolecular-sensitive contrast in MT-weighted images. MT contrast is generated by applying radiofrequency pulses to selectively saturate the macromolecular protons, and this saturation is transferred to the water protons resulting in an observed signal attenuation. The MT effect can be characterized via the MT ratio (MTR) and, more recently, via quantitative MT (qMT) methods. MT-MRI indices may be useful to detect and quantify macromolecular alterations, potentially offering unique opportunities to link pathophysiologic and clinical outcomes in disorders of the central nervous system (CNS), and response to treatments.

Magnetization transfer contrast (MTC) imaging provides insight into interactions between free and bounded water. Newly developed ultrashort echo time (UTE) sequences implemented on whole-body magnetic resonance (MR) scanners allow MTC imaging in tissues with extremely fast signal decay such as tendons. The aim of this study was to develop a technique for the quantification of the MT effect in healthy Achilles tendons in-vivo at 3 Tesla. 16 normal tendons of volunteers with no history of tendinopathy were examined using a 3D-UTE sequence with a rectangular on-resonant excitation pulse and a Fermi-shaped off-resonant MT preparation pulse. The frequency of the MT pulse was varied from 1 to 5 kHz. MT effects were calculated in terms of the MT ratio (MTR) between measurements without and with MT preparation. Direct saturation effects of MT preparation on the signal intensity were evaluated using numerical simulation of Bloch equations. One patient with tendinopathy was examined to exemplarily show changes of MTR under pathologic conditions. Calculation of MTR data was feasible in all examined tendons and showed a decrease from 0.53 ± 0.05 to 0.25 ± 0.03 (1 kHz to 5 kHz) for healthy volunteers. Evaluation of variation with gender and dominance of ankle revealed no significant differences (p > 0.05). In contrast, the patient with confirmed tendinopathy showed MTR values between 0.36 (1 kHz) and 0.19 (5 kHz). MT effects in human Achilles tendons can be reliably assessed in-vivo using a 3D UTE sequence at 3 T. All healthy tendons showed similar MTR values (coefficient of variation 10.0 ± 1.2 %). The examined patient showed a clearly different MT effect revealing a changed microstructure in the case of tendinopathy.

To validate the use of the magnetization transfer ratio (MTR) as a practical imaging marker of demyelination and remyelination in acute multiple sclerosis lesions. Case study. University hospital multiple sclerosis clinic. Patients Six patients with relapsing-remitting multiple sclerosis and acute gadolinium-enhancing lesions were studied serially using a quantitative magnetization transfer examination. Changes in the water content and macromolecular content, a marker of myelin content that, unlike MTR, is not affected by changes in water content (edema) associated with acute inflammation, and changes in MTR of lesions. Both the macromolecular content and MTR were lower than normal in acute lesions and recovered over several months. The decrease in macromolecular content relative to contralateral normal-appearing white matter was greater than the decrease in MTR (0.46 vs 0.75 at the time of gadolinium enhancement), likely because edema in the acute lesion increased the T1 relaxation time of water and attenuated the decrease in MTR. Nevertheless, there was still a strong correlation between changes in the relative MTR and macromolecular content (R(2) = 0.70; P < .001). Our data support the use of MTR as a practical marker of demyelination and remyelination, even in acute lesions where decreases in MTR are attenuated because of the effects of edema.

To evaluate the ability of magnetization transfer (MT) contrast-prepared magnetic resonance (MR) imaging to help distinguish healthy from cirrhotic liver by using a spectrum of MT pulse frequency offsets. This HIPAA-compliant prospective study was approved by the institutional review board. Written informed consent was obtained from all subjects. After optimization of the MT sequence by using agar phantoms with protein concentrations ranging from 0% to 4%, 20 patients with cirrhosis and portal hypertension and 20 healthy volunteers with no known liver disease underwent liver MR imaging that included eight separate breath-hold MT contrast sequences, each performed by using a different MT pulse frequency offset (range, 200-2500 Hz). Regions of interest were then placed to calculate the MT ratio for the liver, fat, and muscle in the volunteer group and for the liver in the cirrhosis group. MT ratio increased with decreasing MT pulse frequency offset for each of the four phantoms and the assessed in vivo tissues, consistent with previous reports. At all frequency offsets, MT ratio increased with increasing phantom protein concentration. In volunteers, at frequency offsets greater than 400 Hz, the MT ratio was significantly greater for muscle (range, 34.4%-54.9%) and significantly lower for subcutaneous fat (range, 10.3%-12.6%), compared with that for the liver (range, 22.8%-46.9%; P < .001 all comparisons). However, the MT ratio was nearly identical between healthy (range, 26.0%-80.0%) and cirrhotic livers (range, 26.7%-81.2%) for all frequency offsets (P = .162-.737), aside from a minimal difference in MT ratio of 1.7% at a frequency offset of 2500 Hz (22.8% in healthy liver vs 24.5% in cirrhotic liver) that was not significant when the Bonferroni correction was applied (P = .015). Findings of this study confirm the ability of the MT contrast-prepared sequence to help distinguish substances of varying protein concentration and suggest that MT imaging is unlikely to be of clinical utility in differentiating healthy and cirrhotic livers.

Concurrent saturation transfer contrast in in vivo brain by a uniform magnetization transfer MRI

Magnetization transfer contrast imaging detects early white matter changes in the APP/PS1 amyloidosis mouse model

To use magnetization transfer (MT) imaging in the visualization of healthy articular cartilage and cartilage repair tissue after different cartilage repair procedures, and to assess global as well as zonal values and compare the results to T2-relaxation. Thirty-four patients (17 after microfracture [MFX] and 17 after matrix-associated autologous cartilage transplantation [MACT]) were examined with 3T MRI. The MT ratio (MTR) was calculated from measurements with and without MT contrast. T2-values were evaluated using a multiecho, spin-echo approach. Global (full thickness of cartilage) and zonal (deep and superficial aspect) region-of-interest assessment of cartilage repair tissue and normal-appearing cartilage was performed. In patients after MFX and MACT, the global MTR of cartilage repair tissue was significantly lower compared to healthy cartilage. In contrast, using T2, cartilage repair tissue showed significantly lower T2 values only after MFX, whereas after MACT, global T2 values were comparable to healthy cartilage. For zonal evaluation, MTR and T2 showed a significant stratification within healthy cartilage, and T2 additionally within cartilage repair tissue after MACT. MT imaging is capable and sensitive in the detection of differences between healthy cartilage and areas of cartilage repair and might be an additional tool in biochemical cartilage imaging. For both MTR and T2 mapping, zonal assessment is desirable.

Magnetization transfer contrast imaging (MTC) exploits the principle of exchange of energy between the bound and free protons and was shown to be pathologically informative. There is, however, controversy as to whether it correlates with axonal loss (AL), demyelination (DM), or both. This study addresses the pathophysiological process that underlies the white matter injury using the metric derivative of MTC, magnetization transfer ratio (MTR), and defines the role of MTR in identifying the different stages of inflammation, that is, edema, DM, and AL, using optic nerve as the model. One hundred and forty-two patients with a single, unilateral episode of optic neuritis (ON) were included in the study. Patients were divided into three groups - those with AL, those with DM, and those who were clinically optic neurites but without any electrophysiological changes suggestive of either AL or DM. MTR and electrophysiological studies were performed in the post-acute stage of ON and the results were compared to those obtained from the unaffected optic nerve. MTR was significantly reduced in the optic nerves of both DM and AL groups when compared to that in normal optic nerves (P < 0.001). The difference in MTR between the AL and DM groups did not reach statistical significance. Patient group with acute ON did not show any change in the MTR values compared to the normal controls. MTR is a sensitive technique to identify neuronal injury, whether it is DM or AL. It, however, cannot differentiate these two pathological processes. MTR is not sensitive to identify acute ON.