Magnetization Transfer Contrast Effect Research Articles

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

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

Evaluation of Improvement of Tissue Contrast and Reduction of Imaging Time by Shortening TR in Brain T<sub>2</sub> FLAIR Using MTC Pulse

T2 fluid-attenuated inversion recovery (FLAIR) using inversion recovery pulse to suppress cerebrospinal fluid signal needs adequate T1 recovery time after data acquisition, otherwise, the T2-weighted contrast in brain tissue will get lower. Over 10000 ms of repetition time (TR) is recommended for the 1.5 T MR scanner, so it is difficult to shorten the imaging time. We verified whether T2 FLAIR combined with the magnetization transfer contrast (MTC) pulse shows better gray-to-white matter (GM/WM) and lesion-to-normal tissue contrasts even when the TR is shortened compared to the conventional T2 FLAIR. Optimal parameters of the MTC pulse were determined with a self-produced phantom, which modeled on cerebral cortical gray and white matters. GM/WM contrasts of the phantom were measured in T2 FLAIR with the MTC pulse while decreasing TR gradually from 10000 ms to 6500 ms. Although GM/WM contrast of the phantom in T2 FLAIR with the MTC pulse gradually decreased as the TR got shortened, the T2 FLAIR with the MTC pulse of 6500 ms of TR still showed 27% higher contrast than the conventional T2 FLAIR (TR 10000 ms). GM/WM contrast in T2 FLAIR with the MTC pulse was improved also in healthy volunteers, but improvement in thalamo-medullary contrast was less than that of cerebral cortico-medullary and putamino-medullary contrasts. It seems to be because thalamus, which is a deep gray matter, shows a higher MTC effect than other gray matters. Thus, it is necessary to note that the tissue contrast might differ between T2 FLAIR with the MTC pulse and the conventional T2 FLAIR. Because general lesions with an elongated T2 value show lower MTC effect compared to the normal brain tissue, a clinical case with thalamic lesion showed that the lesion-to-normal tissue contrast improved in T2 FLAIR with the MTC pulse of 6500 ms of TR. Although it is necessary to note the difference in contrast between some tissues, T2 FLAIR with the MTC pulse improves GM/WM and lesion-to-normal tissue contrasts even when the TR is shortened compared to the conventional T2 FLAIR, and it enables to shorten the imaging time.

CEST MRI of sepsis-induced acute kidney injury.

Sepsis-induced acute kidney injury (SAKI) is a major complication of kidney disease associated with increased mortality and faster progression. Therefore, the development of imaging biomarkers to detect septic AKI is of great clinical interest. In this study, we aimed to characterize the endogenous chemical exchange saturation transfer (CEST) MRI contrast in the lipopolysaccharide (LPS)-induced SAKI mouse model and to investigate the use of CEST MRI for detecting such injury. We used a SAKI mouse model that was generated by i.p. injection of 10mg/kg LPS. The resulting kidney injury was confirmed by the elevation of serum creatinine and histology. MRI assessments were performed 24h after LPS injection, including CEST MRI at different B1 strengths (1, 1.8 and 3 μT), T1 mapping, T2 mapping and conventional magnetization transfer contrast (MTC) MRI. The CEST MRI results were analyzed using Z-spectra, in which the normalized water signal saturation (Ssat /S0 ) is measured as a function of saturation frequency. Substantial decreases in CEST contrast were observed at both 3.5 and-3.5ppm frequency offset from water at all B1 powers, with the most significant difference obtained at a B1 of 1.8 μT. The average Ssat /S0 differences between injured and normal kidneys were 0.07 (0.55±0.04 versus 0.62±0.04, P=0.0028) and 0.07 (0.50±0.04 versus 0.57±0.03, P=0.0008) for 3.5 and-3.5ppm, respectively. In contrast, the T1 and T2 relaxation times and MTC contrast in the injured kidneys did not show a significant change compared with the normal control. Our results showed that CEST MRI is more sensitive to the pathological changes in injured kidneys than the changes in T1 , T2 and MTC effect, indicating its potential clinical utility for molecular imaging of renal diseases.

In vivo imaging of paraCEST agents using frequency labeled exchange transfer MRI

A main obstacle to in vivo applications of paramagnetic chemical exchange saturation transfer (paraCEST) is interference from endogenous tissue magnetization transfer contrast (MTC). The suitability of excitation-based frequency labeled exchange transfer (FLEX) to separate out such MTC effects in vivo was tested. The FLEX sequence measures modulation of the water signal based on the chemical shift evolution of solute proton magnetization as a function of evolution time. Time-domain analysis of this water signal allows identification of different solute components and provides a mechanism to separate out the rapidly decaying MTC components with short effective transverse relaxation time ( T2*) values. FLEX imaging of paraCEST agents was possible in vitro in phantoms and in vivo in mouse kidneys and bladder. The results demonstrated that FLEX is capable of separating out the MTC signal from tissues in vivo while providing a quantitative exchange rate for the rapidly exchanging paraCEST water protons by fitting the FLEX time-domain signal to FLEX theory. The first in vivo FLEX images of a paraCEST agent were acquired, which allowed separation of the tissue MTC components. These results show that FLEX imaging has potential for imaging the distribution of functional paraCEST agents in biological tissues.

Incidental magnetization transfer contrast by fat saturation preparation pulses in multislice look‐locker echo planar imaging

In this study, it is demonstrated that fat saturation (FS) preparation (prep) pulses generate incidental magnetization transfer contrast (MTC) in multislice Look-Locker (LL) imaging. It is shown that frequency-selective FS prep pulses can invoke MTC through the exchange between free and motion-restricted protons. Simulation reveals that the fractional signal loss by these MTC effects is more severe for smaller flip angles (FAs), shorter repetition times (TRs), and greater number of slices (SN). These incidental MTC effects result in a signal attenuation at a steady state (up to 30%) and a T(1) measurement bias (up to 20%) when using inversion recovery (IR) LL echo-planar imaging (EPI) sequences. Furthermore, it is shown that water-selective MRI using binomial pulses has the potential to minimize the signal attenuation and provide unbiased T(1) measurement without fat artifacts in MR images.

Magnetization Transfer Contrast(MTC)効果における基礎的検討 : 自作ファントムによるMTパルスの最適化

Magnetization transfer contrast (MTC) was evaluated by changing the off-set frequency and pulse intensity of MTC with the spoiled gradient echo (SPGR) sequence (T2*-weighted image) using an experimental phantom that included olive oil, protein, fiber, collagen, and pure water. The intensity of pure water reached a constant level just above the off-set frequency (1200 Hz) regardless of MT pulse power. The contrast-to-noise ratio (CNR) in each of the phantom materials was maximal at the MT pulse power of 2500 degrees (equivalent flip angle). The CNR and image noise obtained by body coil were inferior to those obtained with an extremity coil. In clinical application, the MTC effect on chondrosarcoma was higher (MT ratio, ROI-1:0.448, ROI-2:0.382) than those of other cases in this study. Since the image contrast was improved between the malignant fibrous histiocytoma (MFH, MT ratio, ROI-1:0.282, ROI-2:0.289) and peripheral tissues, extraskeletal extension could be observed more easily than without MTC imaging. In conclusion, the effects of MTC might be in providing useful information, in presuming composed tissues, differential diagnoses, and extent to the surrounding structures because of changing the image contrast to surrounding tissues corresponding to the rate of included bound water.

A chronological evaluation of experimental brain infarct by diffusion-mapping and magnetization transfer contrast imaging.

There is a complex system of evolving physiochemical processes in the ischemic brain. The evaluation of this chain of processes is a major challenge of recent stroke studies. Two magnetic resonance imaging techniques: diffusion-weighted (DW) and magnetization transfer contrast (MTC) imaging were introduced in experimental studies and were shown to have sensitivity for different stages of brain infarct. We used a reproducible middle cerebral artery (MCA) occlusion model in rat to examine infarcts of different time courses. Magnetic resonance T2-weighted (T2). DW, and MTC imaging were performed 3 h, 1 d, 3 d, 5 d, 2 w, 3 w, and 4 w after MCA occlusion. Haematoxylin/eosin (HE) stained sections, which revealed sub regions within infarct lesions, were compared to T2, DW, diffusion-mapping and MTC-mapping images. On DW images 3 hours post occlusion lesions were detected as an area with high signal intensity, while T2 imaging does not raise significant contrast of the lesion at this early stage. Three sub regions of the lesion having different ADCs, are discernible on diffusion-mapping images from 1 day to 7 days. The decrease of MTC effect was measured within the infarct lesion from core to marginal zone, from 7 days to 4 weeks. Diffusion-mapping imaging may help to examine brain infarction from 3 hours to 5 days. MTC imaging recognizes infarcts 7 days after the onset. Following this stage, MTC-mapping images may provide a quantitative method to assess infarct size.

Fat tissue: relationship between chemical shift and magnetization transfer.

The middle calves of the legs of 25 volunteers (12 men and 13 women, aged 18-25 years), as well as phantoms, were examined with 1.5-T magnetic resonance imaging. Gradient-recalled technique was combined with magnetization transfer contrast (MTC) and chemical shift imaging. Periodic oscillation of the MTC effect in fat tissue with variation of echo time was identified at the frequency corresponding to the water-fat chemical shift difference.

Multi-slice MRI of rat brain perfusion during amphetamine stimulation using arterial spin labeling.

When a single coil is used to measure perfusion by arterial spin labeling, saturation of macromolecular protons occurs during the labeling period. Induced magnetization transfer contrast (MTC) effects decrease tissue water signal intensity, reducing the sensitivity of the technique. In addition, MTC effects must be properly accounted for in acquiring a control image. This forces the image to a single slice centered between the labeling plane and the control plane. In this work, a two-coil system is presented as a way to avoid saturation of macromolecular spins during arterial spin labeling. The system consists of one small surface coil for labeling the arterial water spins, and a head coil for MRI, actively decoupled from the labeling coil by using PIN diodes. It is shown that no signal loss occurs due to MTC effects when the two-coil system is used for MRI of rat brain perfusion, enabling three-dimensional perfusion imaging. Using the two-coil system, a multi-slice MRI sequence was used to study the regional effects of amphetamine on brain perfusion. Amphetamine causes significant increases in perfusion in many areas of the brain including the cortex, cingulate, and caudate putamen, in agreement with previous results using deoxyglucose uptake to monitor brain activation.

Improved time-of-flight MR angiography of the brain with magnetization transfer contrast.

The authors hypothesized that magnetization transfer contrast (MTC) could be used to improve flow contrast in time-of-flight (TOF) magnetic resonance (MR) angiography. Two- and three-dimensional flow-compensated gradient-echo images were obtained with and without MTC. MTC images were obtained by applying low-power radio-frequency (RF) radiation with a frequency offset from the bulk "free" water resonance frequency before the excitation RF pulse. The signal intensity of stationary tissue decreased as the power applied for the MTC pulse was increased. A smaller decrease occurred in venous signal intensity as measured in the superior sagittal sinus, and less change was seen in the arterial signal intensity as measured in the middle cerebral artery. Cerebrospinal fluid showed no MTC effect. The use of MTC improved small-vessel depiction on maximum-intensity projection images. The authors conclude that use of MTC can substantially enhance the quality of TOF MR angiography of the brain.

Tissue specificity of low‐field‐strength magnetization transfer contrast imaging

The time-dependent saturation transfer technique was used to measure the transfer of magnetization in several rat tissues at 0.1 T. The length of the saturation pulse was varied from 0 to 510 msec. The magnetization transfer contrast effect was characteristic for each type of tissue. A substantial reduction of image intensity was obtained in skeletal muscle (74%), heart (71%), spleen (64%), brain (65%), pancreas (64%), liver (64%), kidneys (62%), and lungs (56%) with the longest saturation pulse available. Much smaller declines occurred in stagnant blood and peritoneal fat. The potential of this imaging technique for clinical conditions is discussed.