온도범위에 따른 비침습적 자기공명 온도측정방법의 최적화

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

To develop an on-resonance variable delay multipulse (VDMP) scheme to image magnetization transfer contrast (MTC) and the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above approximately 1 kHz. A train of high power binomial pulses was applied at the water resonance. The interpulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions as a result of their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T2 components in MTC and separated out using a variable mixing time. Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA), and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method, showing strong gray/white matter contrast for the slowly transferring MTC protons, whereas the TFP map was more uniform across the brain but somewhat higher in gray matter. The new method provides a simple way of imaging fast-exchanging protons and MTC components with a slow transfer rate. Magn Reson Med 77:730-739, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Nuclear Overhauser enhancement (NOE) imaging in the human brain at 7T

Chemical exchange saturation transfer (CEST) imaging is a relatively new magnetic resonance imaging contrast approach in which exogenous or endogenous compounds containing either exchangeable protons or exchangeable molecules are selectively saturated and after transfer of this saturation, detected indirectly through the water signal with enhanced sensitivity. The focus of this review is on basic magnetic resonance principles underlying CEST and similarities to and differences with conventional magnetization transfer contrast. In CEST magnetic resonance imaging, transfer of magnetization is studied in mobile compounds instead of semisolids. Similar to magnetization transfer contrast, CEST has contributions of both chemical exchange and dipolar cross-relaxation, but the latter can often be neglected if exchange is fast. Contrary to magnetization transfer contrast, CEST imaging requires sufficiently slow exchange on the magnetic resonance time scale to allow selective irradiation of the protons of interest. As a consequence, magnetic labeling is not limited to radio-frequency saturation but can be expanded with slower frequency-selective approaches such as inversion, gradient dephasing and frequency labeling. The basic theory, design criteria, and experimental issues for exchange transfer imaging are discussed. A new classification for CEST agents based on exchange type is proposed. The potential of this young field is discussed, especially with respect to in vivo application and translation to humans.

Chemical exchange saturation transfer (CEST) is a technique to indirectly detect pools of exchangeable protons through the water signal. To increase its applicability to human studies, it is needed to develop sensitive pulse sequences for rapidly acquiring whole-organ images while adhering to stringent amplifier duty cycle limitations and specific absorption rate restrictions. In addition, the interfering effects of direct water saturation and conventional magnetization transfer contrast complicate CEST quantification and need to be reduced as much as possible. It is shown that for protons exchanging with rates of less than 50-100 Hz, such as imaged in amide proton transfer experiments, these problems can be addressed by using a three-dimensional steady state pulsed acquisition of limited B(1) strength (≈ 1 μT). Such an approach exploits the fact that the direct water saturation width, magnetization transfer contrast magnitude, and specific absorption rate increase strongly with B(1) , while the size of the CEST effect for such protons depends minimally on B(1) . A short repetition time (65 ms) steady-state sequence consisting of a brief saturation pulse (25 ms) and a segmented echo-planar imaging train allowed acquisition of a three-dimensional whole-brain volume in approximately 11 s per saturation frequency, while remaining well within specific absorption rate and duty cycle limits. Magnetization transfer contrast was strongly reduced, but substantial saturation effects were found at frequencies upfield from water, which still confound the use of magnetization transfer asymmetry analysis. Fortunately, the limited width of the direct water saturation signal could be exploited to fit it with a Lorentzian function allowing CEST quantification. Amide proton transfer effects ranged between 1.5% and 2.5% in selected white and grey matter regions. This power and time-efficient 3D pulsed CEST acquisition scheme should aid endogenous CEST quantification at both high and low fields.

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.

BackgroundClinical treatment of cardiac arrhythmia by radiofrequency ablation (RFA) currently lacks quantitative and precise visualization of lesion formation in the myocardium during the procedure. This study aims at evaluating thermal dose (TD) imaging obtained from real-time magnetic resonance (MR) thermometry on the heart as a relevant indicator of the thermal lesion extent.MethodsMR temperature mapping based on the Proton Resonance Frequency Shift (PRFS) method was performed at 1.5 T on the heart, with 4 to 5 slices acquired per heartbeat. Respiratory motion was compensated using navigator-based slice tracking. Residual in-plane motion and related magnetic susceptibility artifacts were corrected online. The standard deviation of temperature was measured on healthy volunteers (N = 5) in both ventricles. On animals, the MR-compatible catheter was positioned and visualized in the left ventricle (LV) using a bSSFP pulse sequence with active catheter tracking. Twelve MR-guided RFA were performed on three sheep in vivo at various locations in left ventricle (LV). The dimensions of the thermal lesions measured on thermal dose images, on 3D T1-weighted (T1-w) images acquired immediately after the ablation and at gross pathology were correlated.ResultsMR thermometry uncertainty was 1.5 °C on average over more than 96% of the pixels covering the left and right ventricles, on each volunteer. On animals, catheter repositioning in the LV with active slice tracking was successfully performed and each ablation could be monitored in real-time by MR thermometry and thermal dosimetry. Thermal lesion dimensions on TD maps were found to be highly correlated with those observed on post-ablation T1-w images (R = 0.87) that also correlated (R = 0.89) with measurements at gross pathology.ConclusionsQuantitative TD mapping from real-time rapid CMR thermometry during catheter-based RFA is feasible. It provides a direct assessment of the lesion extent in the myocardium with precision in the range of one millimeter. Real-time MR thermometry and thermal dosimetry may improve safety and efficacy of the RFA procedure by offering a reliable indicator of therapy outcome during the procedure.

Proton resonance frequency shift (PRFS) is an MRI-based simple temperature mapping method that exhibits higher spatial and temporal resolution than temperature mapping methods based on T1 relaxation time and diffusion. PRFS temperature measurements are validated against fiber-optic thermal sensors (FOSs). However, the use of FOSs may introduce temperature errors, leading to both underestimation and overestimation of PRFS measurements, primarily due to material susceptibility changes caused by the thermal sensors. In this study, we demonstrated susceptibility-corrected PRFS (scPRFS) with a high frame rate and accuracy for suitably distributed temperatures. A single-echo-based background removal technique was employed for phase variation correction, primarily owing to magnetic susceptibility, which enabled fast temperature mapping. The scPRFS was used to validate the temperature fidelity by comparing the temperatures of fiber-optic sensors and conventional PRFS through phantom-mimicked human and ex vivo experiments. This study demonstrates that scPRFS measurements in agar-gel are in good agreement with the thermal sensor readings, with a root mean square error (RMSE) of 0.33-0.36 °C in the phantom model and 0.12-0.16 °C in the ex vivo experiment. These results highlight the potential of scPRFS for precise thermal monitoring and ablation in both low- and high-temperature non-invasive therapies.

Chemical exchange saturation transfer (CEST) imaging is a new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through their exchangeable protons. A new technique, variable delay multi-pulse CEST (VDMP-CEST), is proposed to eliminate the need for recording full Z-spectra and performing asymmetry analysis to obtain CEST contrast. The VDMP-CEST scheme involves acquiring images with two (or more) delays between radiofrequency saturation pulses in pulsed CEST, producing a series of CEST images sensitive to the speed of saturation transfer. Subtracting two images or fitting a time series produces CEST and relayed-nuclear Overhauser enhancement CEST maps without effects of direct water saturation and, when using low radiofrequency power, minimal magnetization transfer contrast interference. When applied to several model systems (bovine serum albumin, crosslinked bovine serum albumin, l-glutamic acid) and in vivo on healthy rat brain, VDMP-CEST showed sensitivity to slow to intermediate range magnetization transfer processes (rate < 100-150 Hz), such as amide proton transfer and relayed nuclear Overhauser enhancement-CEST. Images for these contrasts could be acquired in short scan times by using a single radiofrequency frequency. VDMP-CEST provides an approach to detect CEST effect by sensitizing saturation experiments to slower exchange processes without interference of direct water saturation and without need to acquire Z-spectra and perform asymmetry analysis.

Non-invasive and depth-free temperature monitoring using MR thermometry in plasmonic photothermal therapy using gold nanorods

There is growing interest in performing hyperthermia treatments with clinical magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) therapy systems designed for tissue ablation. During hyperthermia treatment, however, due to the narrow therapeutic window (41–45 °C), careful evaluation of the accuracy of proton resonant frequency (PRF) shift MR thermometry for these types of exposures is required.Purpose: The purpose of this study was to evaluate the accuracy of MR thermometry using a clinical MR-HIFU system equipped with a hyperthermia treatment algorithm.Methods: Mild heating was performed in a tissue-mimicking phantom with implanted temperature sensors using the clinical MR-HIFU system. The influence of image-acquisition settings and post-acquisition correction algorithms on the accuracy of temperature measurements was investigated. The ability to achieve uniform heating for up to 40 min was evaluated in rabbit experiments.Results: Automatic centre-frequency adjustments prior to image-acquisition corrected the image-shifts in the order of 0.1 mm/min. Zero- and first-order phase variations were observed over time, supporting the use of a combined drift correction algorithm. The temperature accuracy achieved using both centre-frequency adjustment and the combined drift correction algorithm was 0.57° ± 0.58 °C in the heated region and 0.54° ± 0.42 °C in the unheated region.Conclusion: Accurate temperature monitoring of hyperthermia exposures using PRF shift MR thermometry is possible through careful implementation of image-acquisition settings and drift correction algorithms. For the evaluated clinical MR-HIFU system, centre-frequency adjustment eliminated image shifts, and a combined drift correction algorithm achieved temperature measurements with an acceptable accuracy for monitoring and controlling hyperthermia exposures.

BACKGROUND Chemical exchange saturation transfer (CEST) MRI provides chemical-group-specificity (e.g., amide, guanidinium, and aliphatic) to exchangeable protons in dissolved proteins. Magnetization transfer (MT) MRI is sensitive to water bound to macromolecules, e.g., myelin and collagen. The major objective of the study was to identify the chemical exchange saturation transfer- and magnetization transfer-derived magnetic resonance images that have high contrast between orthotopic U87 tumours and normal-appearing brain. MATERIAL AND METHODS U-87 MG glioblastoma cell line-derived xenografts were implanted in RNU nude rats (n=9). Animals were divided into two groups based on the scanning schedule. The rats were imaged using 7 tesla scanner (PharmaScan; Bruker BioSpin) at three time points for all animals: 3-5, 7-9, and 11-13 days after implantation. Single-slice saturation-transfer-weighted CEST (saturation amplitude: 0.5 and 2 µT) and MT (3 and 5 µT) contrast Z-spectra and T1 and T2 maps were acquired. The MT Z-spectra and T1 map were fitted to a two-pool quantitative MT model to estimate the T2 of the free and macromolecular-bound water molecules, the relative macromolecular pool size (M0, MT), and the magnetization exchange rate from the macromolecular pool to the free pool. RESULTS Statistically significant differences, by pairwise Wilcoxon signed-rank tests with Holm-Bonferroni adjustment, were found. The differences between enhancing lesion and contralateral cortex for the magnetization transfer ratio with 2 µT saturation at 3.6 ppm frequency offset (corresponding to the amide chemical group) and M0, MT are both strongly significant (p &amp;lt; 0.001) at all time points. CONCLUSION MT and CEST are a promising method of identifying the earliest time points of glioblastoma development. Such an early image biomarker of neoplasia may allow for improved treatment outcomes leading to reduced recurrence events.

Focal bone tumor treatments include amputation, limb-sparing surgical excision with bone reconstruction, and high-dose external-beam radiation therapy. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is an effective non-invasive thermotherapy for palliative management of bone metastases pain. MR thermometry (MRT) measures the proton resonance frequency shift (PRFS) of water molecules and produces accurate (<1°C) and dynamic (<5s) thermal maps in soft tissues. PRFS-MRT is ineffective in fatty tissues such as yellow bone marrow and, since accurate temperature measurements are required in the bone to ensure adequate thermal dose, MR-HIFU is not indicated for primary bone tumor treatments. Magnetic relaxation times are sensitive to lipid temperature and we hypothesize that bone marrow temperature can be determined accurately by measuring changes in T2, since T2 increases linearly in fat during heating. T2-mapping using dual echo times during a dynamic turbo spin-echo pulse sequence enabled rapid measurement of T2. Calibration of T2-based thermal maps involved heating the marrow in a bovine femur and simultaneously measuring T2 and temperature with a thermocouple. A positive T2 temperature dependence in bone marrow of 20 ms/°C was observed. Dynamic T2-mapping should enable accurate temperature monitoring during MR-HIFU treatment of bone marrow and shows promise for improving the safety and reducing the invasiveness of pediatric bone tumor treatments.

The T1 and T2 temperature dependence of female breast adipose tissue was investigated at 1.5 T in order to evaluate the applicability of relaxation-based MR thermometry in fat for the monitoring of thermal therapies in the breast. Relaxation times T1 , T2 and T2TSE (the apparent T2 measured using a turbo spin echo readout sequence) were measured in seven fresh adipose breast samples for temperatures from 25 to 65 °C. Spectral water suppression was used to reduce the influence of the residual water signal. The temperature dependence of the relaxation times was characterized. The expected maximum temperature measurement errors based on average calibration lines were calculated. In addition, the heating-cooling reversibility was investigated for two samples. The T1 and T2TSE temperature (T) dependence could be fitted well with an exponential function of 1/T. A linear relationship between T2 and temperature was found. The temperature coefficients (mean ± inter-sample standard deviation) of T1 and T2TSE increased from 25 °C (dT1/dT = 5.35 ± 0.08 ms/°C, dT2TSE/dT = 3.82 ± 0.06 ms/°C) to 65 °C (dT1 /dT = 9.50 ± 0.16 ms/°C, dT2TSE/dT = 7.99 ± 0.38 ms/°C). The temperature coefficient of T2 was 0.90 ± 0.03 ms/°C. The temperature-induced changes in the relaxation times were found to be reversible after heating to 65 °C. Given the small inter-sample variation of the temperature coefficients, relaxation-based MR thermometry appears to be feasible in breast adipose tissue, and may be used as an adjunct to proton resonance frequency shift (PRFS) thermometry in aqueous tissue (glandular + tumor).

The purpose of this study is to demonstrate the first work of T 1-based magnetic resonance thermometry using magnetic resonance fingerprinting (dubbed MRFT). We compared temperature estimation of MRFT with proton resonance frequency shift (PRFS) thermometry on ex vivo bovine muscle. We demonstrated MRFT’s feasibility in predicting temperature on ex vivo bovine muscles with deep brain stimulation (DBS) lead. B 0 maps generated from MRFT were compared with gold standard B 0 maps near the DBS lead. MRFT and PRFS estimated temperatures were compared in the presence of motion. All experiments were performed on a 3 Tesla whole-body GE Premier system with a 21-channel receive head coil (GE Healthcare, Milwaukee, WI). Four fluoroptic probes were used to measure the temperature at the center of a cold muscle (probe 1), the room temperature water bottle (probe 2), and the center and periphery of the heated muscle (probes 3 and 4). We selected regions of interest (ROIs) around the location of the probes and used simple linear regression to generate the temperature sensitivity calibration equations that convert T 1 maps and Δs maps to temperature maps. We then repeated the same setup and compared MRFT and PRFS thermometry temperature estimation with gold standard probe measurements. For the MRFT experiment on DBS lead, we taped the probe to the tip of the DBS lead and used a turbo spin echo sequence to induce heating near the lead. We selected ROIs around the tip of the lead to compare MRFT temperature estimation with probe measurements and compared with PRFS temperature estimation. Vendor-supplied B 0 mapping sequence was acquired to compare with MRFT-generated B 0 maps. We found strong linear relationships (R 2 > 0.958) between T 1 and temperature and Δs and temperatures in our temperature sensitivity calibration experiment. MRFT and PRFS thermometry both accurately predict temperature (RMSE < 1.55 °C) compared to probe measurements. MRFT estimated temperature near DBS lead has a similar trend as the probe temperature. Both B 0 maps show inhomogeneities around the lead. MRFT estimated temperature is less sensitive to motion.