Off-resonance Magnetization Transfer Research Articles

Acceleration of neuromelanin-sensitive MRI sequences in the substantia nigra using standard MRI options

PurposeNeuromelanin MRI (NM-MRI) is applied as a proxy measurement of dopaminergic functioning of the substantia nigra pars compacta (SN). To increase its clinical applicability, a fast and easily applicable NM-MRI sequence is needed. This study therefore compared accelerated NM-MRI sequences using standard available MRI options with a validated 2D gradient recalled echo NM-MRI sequence with off-resonance magnetization transfer (MT) pulse (2D-MToffRes).MethodsWe used different combinations of compressed sense (CS) acceleration, repetition times (TR), and MT pulse to accelerate the validated 2D-MToffRes. In addition, we compared a recently introduced 3D sequence with the 2D-MToffRes.ResultsOur results show that the 2D sequences perform best with good to excellent reliability. Only excellent intraclass correlation coefficients were found for the CS factor 2 sequences.ConclusionWe conclude that there are several reliable approaches to accelerate NM-MRI, in particular by using CS.

Contrast-free high-resolution 3D magnetization transfer imaging for simultaneous myocardial scar and cardiac vein visualization

ObjectiveTo develop a three-dimensional (3D) high-resolution free-breathing magnetization transfer ratio (MTR) sequence for contrast-free assessment of myocardial infarct and coronary vein anatomy.Materials and methodsTwo datasets with and without off-resonance magnetization transfer preparation were sequentially acquired to compute MTR. 2D image navigators enabled beat-to-beat translational and bin-to-bin non-rigid motion correction. Two different imaging sequences were explored. MTR scar localization was compared against 3D late gadolinium enhancement (LGE) in a porcine model of myocardial infarction. MTR variability across the left ventricle and vessel sharpness in the coronary veins were evaluated in healthy human subjects.ResultsA decrease in MTR was observed in areas with LGE in all pigs (non-infarct: 25.1 ± 1.7% vs infarct: 16.8 ± 1.9%). The average infarct volume overlap on MTR and LGE was 62.5 ± 19.2%. In humans, mean MTR in myocardium was between 37 and 40%. Spatial variability was between 15 and 20% of the mean value. 3D whole heart MT-prepared datasets enabled coronary vein visualization with up to 8% improved vessel sharpness for non-rigid compared to translational motion correction.DiscussionMTR and LGE showed agreement in infarct detection and localization in a swine model. Free-breathing 3D MTR maps are feasible in humans but high spatial variability was observed. Further clinical studies are warranted.

Lysophosphatidyl Choline Induced Demyelination in Rat Probed by Relaxation along a Fictitious Field in High Rank Rotating Frame.

In this work a new MRI modality entitled Relaxation Along a Fictitious Field in the rotating frame of rank 4 (RAFF4) was evaluated in its ability to detect lower myelin content in lysophosphatidyl choline (LPC)-induced demyelinating lesions. The lesions were induced in two areas of the rat brain with either uniform or complex fiber orientations, i.e., in the corpus callosum (cc) and dorsal tegmental tract (dtg), respectively. RAFF4 showed excellent ability to detect demyelinated lesions and good correlation with myelin content in both brain areas. In comparison, diffusion tensor imaging metrices, fractional anisotropy, mean diffusivity and axonal and radial diffusivity, and magnetization transfer (MT) metrices, longitudinal relaxation during off-resonance irradiation and MT ratio, either failed to detect demyelination in dtg or showed lower correlation with myelin density quantified from gold chloride stained histological sections. Good specifity of RAFF4 to myelin was confirmed by its low correlation with cell density assesed from Nissl stained sections as well as its lack of sensitivity to pH changes in the physiological range as tested in heat denaturated bovine serum albumin phantoms. The excellent ability of RAFF4 to detect myelin content and its insensitivity to fiber orientation distribution, gliosis and pH, together with low specific absorption rate, demonstrates the promise of rotating frame of rank n (RAFFn) as a valuable MRI technique for non-invasive imaging of demyelinating lesions.

Simultaneous multi‐angular relaxometry of tissue with MRI (SMART MRI): Theoretical background and proof of concept

Accurate measurement of tissue-specific relaxation parameters is an ultimate goal of quantitative MRI. The objective of this study is to introduce a new technique, simultaneous multiangular relaxometry of tissue with MRI (SMART MRI), which provides naturally coregistered quantitative spin density, longitudinal and transverse relaxation rate constant maps along with parameters characterizing magnetization transfer (MT) effects. SMART MRI is based on a gradient-recalled echo MRI sequence with multiple flip angles and multiple gradient echoes and a derived theoretical expression for the MR signal generated in this experimental conditions. The theory, based on Bloch-McConnell equations, takes into consideration cross-relaxation between two water pools: "free" and "bound" to macromolecules. It describes the role of cross-relaxation effects in formation of longitudinal and transverse relaxation of "free" water signal, thus providing background for measurements of these effects without using MT pulses. Bayesian analysis is used to optimize SMART MRI sequence parameters. Data obtained on three participants demonstrate feasibility of the proposed approach. SMART MRI provides quantitative measurements of longitudinal and transverse relaxation rate constants of "free" water signal affected by cross-relaxation effects. It also provides information on some essential MT parameters without requiring off-resonance MT pulses. Magn Reson Med 77:1296-1306, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

3D neuromelanin-sensitive magnetic resonance imaging with semi-automated volume measurement of the substantia nigra pars compacta for diagnosis of Parkinson’s disease

Neuromelanin-sensitive MRI has been reported to be used in the diagnosis of Parkinson's disease (PD), which results from loss of dopamine-producing cells in the substantia nigra pars compacta (SNc). In this study, we aimed to apply a 3D turbo field echo (TFE) sequence for neuromelanin-sensitive MRI and to evaluate the diagnostic performance of semi-automated method for measurement of SNc volume in patients with PD. We examined 18 PD patients and 27 healthy volunteers (control subjects). A 3D TFE technique with off-resonance magnetization transfer pulse was used for neuromelanin-sensitive MRI on a 3T scanner. The SNc volume was semi-automatically measured using a region-growing technique at various thresholds (ranging from 1.66 to 2.48), with the signals measured relative to that for the superior cerebellar peduncle. Receiver operating characteristic (ROC) analysis was performed at all thresholds. Intra-rater reproducibility was evaluated by intraclass correlation coefficient (ICC). The average SNc volume in the PD group was significantly smaller than that in the control group at all the thresholds (P < 0.01, student t test). At higher thresholds (>2.0), the area under the curve of ROC (Az) increased (0.88). In addition, we observed balanced sensitivity and specificity (0.83 and 0.85, respectively). At lower thresholds, sensitivity tended to increase but specificity reduced in comparison with that at higher thresholds. ICC was larger than 0.9 when the threshold was over 1.86. Our method can distinguish the PD group from the control group with high sensitivity and specificity, especially for early stage of PD.

Visualization of Neuromelanin in the Substantia Nigra and Locus Ceruleus at 1.5T Using a 3D-gradient Echo Sequence with Magnetization Transfer Contrast

Recent technical advances have enabled the visualization of neuromelanin in the substantia nigra pars compacta (SNc) and locus ceruleus (LC) by 3-tesla (T) magnetic resonance imaging in vivo. In the present study, we successfully detected neuromelanin in the SNc and LC of 6 healthy volunteers at 1.5T using a 3D gradient echo sequence with off-resonance magnetization transfer contrast.

Whole‐body magnetization transfer contrast imaging

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.

Mechanism of magnetization transfer during on-resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids.

The mechanism of magnetization transfer (MT) between water and components of the proton spectrum was studied ex vivo in a perfused cell system and in vivo in the rat brain (n = 5). Water was selectively labeled and spectral buildup consequential to transfer of longitudinal magnetization was followed as a function of time. At short mixing time (T(m)), nitrogen-bound solvent-exchangeable protons were observed, predominantly assigned to amide groups of proteins and peptides. At longer T(m), intramolecular nuclear Overhauser enhancement (NOE) was observed in the aliphatic proton region, leading to a mobile-macromolecule-weighted spectrum that resembles typical protein spectra described in the literature. This effect on the proton spectrum is distinct from that of classical off-resonance MT, which has been shown to be due to the immobile solid-like proton pool. When studying a solution of major brain metabolites under physiological concentrations and conditions (pH), no transfer effects were observed, in line with expectations based on reduced NOE effects in rapidly tumbling molecules and the fast proton exchange rates of amino, amine, SH, and OH groups. The spectral intensities of the amide protons may serve as indicators for pH and cellular levels of mobile proteins and peptides, while the aliphatic components are representative of several types of mobile macromolecules, including proteins, peptides, and lipids.

On the importance of exchangeable NH protons in creatine for the magnetic coupling of creatine methyl protons in skeletal muscle.

The methyl protons of creatine in skeletal muscle exhibit a strong off-resonance magnetization transfer effect. The mechanism of this process is unknown. We previously hypothesized that the exchangeable amide/amino protons of creatine might be involved. To test this the characteristics of the creatine magnetization transfer effect were investigated in excised rat hindleg skeletal muscle that was equilibrated in either H2O or D2O solutions containing creatine. The efficiency of off-resonance magnetization transfer to the protons of mobile creatine in excised muscle was similar to that previously reported in intact muscle in vivo. Equilibrating the isolated muscle in D2O solution had no effect on the magnetic coupling to the immobile protons. It is concluded that exchangeable protons play a negligible role in the magnetic coupling of creatine methyl protons in muscle.

Characterization of experimental spinal cord injury with magnetization transfer ratio histograms

This study was designed to characterize the severity of tissue damage in experimental spinal cord injury using magnetization transfer (MT) histogram analysis. Seven Sprague-Dawley rats were subjected to laminectomy and standard weight-drop injury to the spinal cord (four rats at 15 cm drop-height and three rats at 2.5 cm). Three control animals underwent laminectomy without weight-drop. After sacrifice, the animals were scanned at 1.9 T with a pulsed off-resonance MT technique. Following magnetic resonance (MR) imaging, the cords were embedded in paraffin and sectioned into 5-μm sections for semiquantitative histopathological analysis. Composite histograms were generated using data spanning an axial distance of 3 cm centered on the injury site. MT histogram parameters, such as the amount of tissue with statistical correspondence to normal white matter, were highly predictive of histopathological results, including myelination state and neurofilament damage. Less correlation with edema was observed, suggesting that the technique was most sensitive to true tissue alteration. J. Magn. Reson. Imaging 2000;12:247–254. © 2000 Wiley-Liss, Inc.

1H and 31P magnetization transfer studies of hindleg muscle in wild‐type and creatine kinase‐deficient mice

The authors addressed the hypothesis that interactions with creatine kinase (CK) play a role in the off-resonance magnetization transfer (MT) effect of creatine in skeletal muscle. Toward that aim, 1H MT studies were done on hindleg muscle in wild-type mice and in transgenic mice, lacking cytoplasmic CK and/or mitochondrial CK. The 1H MT effect was essentially identical in wild-type muscle and the two single CK knock-out muscles, while moderately decreased in tissue lacking both CK isoforms. 31P-NMR showed no off-resonance 31P MT effect in skeletal muscle for PCr in any of the mice, while the enzymatic CK reaction flux was circa 0.2–0.3 sec−1 in the wild-type muscle and in muscle deficient in mitochondrial CK. The CK enzyme flux was negligible in the other two CK knock-outs. These data suggest that CK plays a minor role in the 1H MT effect of creatine. Irrespective of the underlying mechanism the creatine MT phenomenon probably has no significant consequences for the thermodynamic availability of total creatine to the CK reaction. Magn Reson Med 43:657–664, 2000. © 2000 Wiley-Liss, Inc.

1H and (31)P magnetization transfer studies of hindleg muscle in wild-type and creatine kinase-deficient mice.

The authors addressed the hypothesis that interactions with creatine kinase (CK) play a role in the off-resonance magnetization transfer (MT) effect of creatine in skeletal muscle. Toward that aim, (1)H MT studies were done on hindleg muscle in wild-type mice and in transgenic mice, lacking cytoplasmic CK and/or mitochondrial CK. The (1)H MT effect was essentially identical in wild-type muscle and the two single CK knock-out muscles, while moderately decreased in tissue lacking both CK isoforms. (31)P-NMR showed no off-resonance (31)P MT effect in skeletal muscle for PCr in any of the mice, while the enzymatic CK reaction flux was circa 0.2-0.3 sec(-1) in the wild-type muscle and in muscle deficient in mitochondrial CK. The CK enzyme flux was negligible in the other two CK knock-outs. These data suggest that CK plays a minor role in the (1)H MT effect of creatine. Irrespective of the underlying mechanism the creatine MT phenomenon probably has no significant consequences for the thermodynamic availability of total creatine to the CK reaction.

Characterization of experimental spinal cord injury with magnetization transfer ratio histograms.

This study was designed to characterize the severity of tissue damage in experimental spinal cord injury using magnetization transfer (MT) histogram analysis. Seven Sprague-Dawley rats were subjected to laminectomy and standard weight-drop injury to the spinal cord (four rats at 15 cm drop-height and three rats at 2.5 cm). Three control animals underwent laminectomy without weight-drop. After sacrifice, the animals were scanned at 1.9 T with a pulsed off-resonance MT technique. Following magnetic resonance (MR) imaging, the cords were embedded in paraffin and sectioned into 5-microm sections for semiquantitative histopathological analysis. Composite histograms were generated using data spanning an axial distance of 3 cm centered on the injury site. MT histogram parameters, such as the amount of tissue with statistical correspondence to normal white matter, were highly predictive of histopathological results, including myelination state and neurofilament damage. Less correlation with edema was observed, suggesting that the technique was most sensitive to true tissue alteration.

The characterization of human brain tumor using magnetization transfer technique in magnetic resonance imaging

The clinical applicabiity of magnetization transfer (MT) technique in magnetic resonance imaging (MRI) for the estimation of the histological and constitutional feature of brain tumors was investigated. MT effect was evaluated by measuring the MT ratio (MTR). The parameters in 1.5-tesla MRI system were as follows: TR, 50 msec; TE, 5 msec; flip angle, 30 degree; offset frequency of off-resonance MT pulse, 1000 Hz. The sequence was performed in 20 normal volunteers and 45 patients with brain tumors which were characterized histologically and surgically. The MTR for brain tumors was significantly lower than that for normal brain tissue (p < 0.05). The MTR for meningioma was higher than that for the other brain tumors (p < 0.05). In the meningiomas, MTR for fibrous type was higher than that for méningothélial type, but there was no statistical significance. Regarding the physical consistency for the brain tumors, as classified by surgery, there was a statistically significant difference in MTR between the soft tumor group (0.22 ± 0.03, n = 6) and the hard tumor group (0.36±0.04, n=10) (p < 0.01). This study suggested that the MT technique for patients with brain tumor may be useful to understand the characteristics of the tumors presurgically, based on the degree of intermolecular interaction of macromolecule such as protein. [Neurol Res 1999; 21: 250-254]

Role of magnetization transfer imaging in bone tumors

The authors evaluated the role of magnetization transfer imaging in differentiation of bone tumors, with special emphasis on cartilaginous tumors. Fifty-one patients with skeletal tumors or tumor-like lesions who had undergone magnetic resonance (MR) imaging were included. The tumors were divided into three groups according to their gross appearance and the origin of tissue: cyst, cartilaginous tumor, and noncartilaginous solid tumor. A gradient-recalled acquisition in the steady state sequence was used for MR imaging, and examinations were performed both with and without off-resonance magnetization transfer pulses. Magnetization transfer ratios were obtained as an indicator of magnetization transfer effect of the lesions and were compared. Then, the magnetization transfer ratios of all tumors in the cartilaginous tumor group were compared. The magnetization transfer ratios of benign and malignant solid tumors were also compared. The mean magnetization transfer ratio for cartilaginous tumors was 0.31 +/- 0.08 (standard deviation), and that of cysts and noncartilaginous solid tumors was 0.07 +/- 0.03 and 0.40 +/- 0.14, respectively. Comparisons between the three groups showed statistically significant intergroup differences in magnetization transfer ratio (P < .05). In the cartilaginous tumor category, enchondroma and low-grade chondrosarcoma had a lower magnetization transfer effect than chondroblastoma and mesenchymal chondrosarcoma. The mean magnetization transfer ratios of benign (n = 28) and malignant (n = 18) tumors were 0.35 +/- 0.11 and 0.39 +/- 0.15, respectively; there was no statistically significant intergroup difference (P = .14). Magnetization transfer imaging could be useful for categorizing bone tumors as cysts, cartilaginous tumors, or noncartilaginous solid tumors.

Pulsed off-resonance magnetization transfer for brain tumor in patients

We investigated the clinical applicability of pulsed off-resonance magnetization transfer (MT) technique in magnetic resonance (MR) imaging for the estimation of the histological feature of brain tumor. The parameters were optimized using bovine serum albumin (BSA) solutions and gels in 1.5-tesla MR system as follows: TR, 50 msec; TEl 5 msec; flip angle, 30 degree; offset frequency, 1000 Hz. MT effect was evaluated by measuring the MT ratio (MTR) and reconstructing calculated MTR color image. The MTRs of the BSA solutions and gels increased with increasing concentrations of protein, while the MTRs of the gels were remarkably higher than those of the solutions. The optimized sequence was performed in 20 healthy volunteers and 30 patients with brain tumors. In normal brains, the MTRs were significantly higher in white matter than in gray matter (p<0.05). The MTR in brain tumor was significantly lower than that in normal brain tissue (p<0.05) and the calculated MTR image produced contrast between brain tumor and normal brain tissue. There was a statistically significant difference in MTR between benign (0.30±0.05, n= 17) and malignant (0.26±0.04, n= 13) tumors (p< 0. 05). The optimized MT technique is quite sensitive for estimating the degree of intermolecular interaction between macromolecules and water within the central nervous system. [Neural Res 1998; 20: 313-319]

Spin lock and magnetization transfer MR imaging of focal liver lesions

The present study was designed to evaluate tissue contrast characteristics obtained with the spin-lock (SL) technique by comparing the results with those generated with a magnetization transfer(MT)-weighted gradient echo [GRE, echo-time (TE) = 40 ms] sequence. Twenty-eight patients with hepatic hemangiomas ( n = 14), or metastatic liver lesions ( n = 14) were imaged at 0.1 T by using identical imaging parameters. Gradient echo, single–slice off-resonance MT, and multiple-slice SL sequences were obtained. SL and MT-effects were measured from the focal liver lesions and from normal liver parenchyma. In addition, tissue contrast values for the liver lesions were determined. Statistically significant difference between the SL-effects of the hemangiomas and metastases, and also between the MT-effects of the lesions was observed ( p < 0.02). Tissue contrast values for the lesions proved to be quite similar between the SL and MT techniques. Our results indicate that at 0.1 T multiple-slice SL imaging provides MT based tissue contrast characteristics in tissues rich in protein with good imaging efficiency and wide anatomical coverage, and with reduced motion and susceptibility artifacts.

Analysis of magnetization transfer effects on T1-weighted spin-echo scans using a simple tissue phantom simulating gadolinium-enhanced brain lesions.

The purpose of this study was to analyze the effect of several magnetization transfer (MT) pulse and T1-weighted spin-echo (SE) sequence parameters on lesion-to-background contrast, using a simple tissue phantom emulating the T1 relaxation and MT properties of gadolinium-enhanced brain lesions. Eggbeaters (Nabisco Inc., East Hanover, NJ) liquid egg product was doped with gadolinium in six concentrations from .0 to 1.0 mmol and cooked. The gadolinium-doped egg phantom and normal volunteer brains were studied using an SE sequence with TE = 20 msec and high power, pulsed, off-resonance MT saturation. The effects of MT pulse frequency offset (1,000-6,000 Hz), sequence repetition time (TR = 500-1,000 msec, with MT power held constant), and slice-select flip angle (60-120 degrees) on the magnetization transfer ratio (MTR) and the simulated lesion-to-background contrast were determined at the different "intralesion" gadolinium concentrations. The MTR and lesion-to-background contrast of all materials were greatest at narrow MT pulse frequency offsets. There was in inverse relationship between gadolinium concentration and MTR and a positive correlation between the gadolinium concentration and lesion-to-background (L/B) contrast, a weak negative correlation between slice-select flip angle and L/B, and a negative correlation between TR and L/B. The relaxation properties and MT behavior of the egg phantom are close to that expected for enhancing brain lesions, allowing a rigorous analysis of several variables affecting lesion-to-background contrast for high MT power, T1-weighted SE sequences.

Dispersion in magnetization transfer contrast at a given specific absorption rate due to variations of RF pulse parameters in the magnetization transfer preparation.

The effects of RF pulse parameters on magnetization transfer contrast (MTC) were investigated using a magnetization prepared segmented fast gradient echo sequence. MTC was found not to be uniquely determined by the specific absorption rate (SAR). RF pulse parameters (RF amplitude, number of RF pulses and RF duration) also affect MTC. There can be 40% variation in MTC due to differences in RF parameters at SAR = 1 W/kg for a 70-kg subject. Increasing the number of RF pulses is a more efficient way to increase MTC than increasing RF amplitude. This phenomenon is likely caused by the fact that the time scale for magnetization transfer between the free and restricted proton pools is on the same order or longer than the duration of the MT pulse. Accordingly, increase in the MT pulse duration by increasing the number of RF pulses in the MT pulse allows more effective magnetization transfer. Such information can be used as a guide to select RF pulse parameters for a magnetization transfer (MT) pulse. An off-resonance MT pulse designed under this guide for coronary MR angiography improved the depiction of distal vessels.

Off‐resonance pulsed magnetization transfer in clinical MR imaging: Optimization by an analysis of transients

Significant degrees of magnetization transfer (MT) have been observed in the magnetic resonance imaging of biological materials by conventional clinical imaging sequences, as well as by sequences specifically designed to enhance MT image contrast. Two aspects of these procedures distinguish them from the classic spectroscopic MT experiments using either so-called "hard" radiofrequency (RF) pulses of short duration and high power, or continuous wave RF irradiation of low power. First, clinical sequences must make exclusive use of "soft" pulses of intermediate length and power. Second, biological materials are modeled by a two-spin system involving magnetization transfer between a narrow and a broad homogeneous spectral component. Such materials are a relatively restricted group within the larger family of materials studied with MT by spectroscopy. The current paper addresses these two issues with a theory that gives a new transient analysis of the off-resonance pulsed MT problem for biological materials. It leads to predictions for optimal magnetization transfer in the context of medical imaging that have been verified by computer modeling.