Off-resonance Saturation Research Articles

Flow‐enhanced off‐resonance saturation for remote detection of iron‐based contrast agents

A switchable contrast mechanism, flow enhanced off-resonance saturation, is presented. This technique combines the effects of flow and off-resonance saturation for remote detection of iron oxide contrast agents incorporated into a vessel wall. Initial results from phantom experiments are presented and show the feasibility of this method. A specific saturation contrast could be observed. This contrast mechanism is highly dependent on field homogeneity and spectral selectivity of the off-resonance saturation pulses. The contrast scales directly with the pulse offset of the used saturation pulses, the flow velocity in the vessel, and the duration of the off-resonance saturation module prior to the imaging sequence. This technique has the potential to detect iron-loaded atherosclerotic plaques in future in vivo applications.

Ultrashort TE imaging with off‐resonance saturation contrast (UTE‐OSC)

Short T(2) species such as the Achilles tendon and cortical bone cannot be imaged with conventional MR sequences. They have a much broader absorption lineshape than long T(2) species, therefore they are more sensitive to an appropriately placed off-resonance irradiation. In this work, a technique termed ultrashort TE (UTE) with off-resonance saturation contrast (UTE-OSC) is proposed to image short T(2) species. A high power saturation pulse was placed +1 to +2 kHz off the water peak to preferentially saturate signals from short T(2) species, leaving long T(2) water and fat signals largely unaffected. The subtraction of UTE images with and without an off-resonance saturation pulse effectively suppresses long T(2) water and fat signals, creating high contrast for short T(2) species. The UTE-OSC technique was validated on a phantom, and applied to bone samples and healthy volunteers on a clinical 3T scanner. High-contrast images of the Achilles tendon and cortical bone were generated with a high contrast-to-noise ratio (CNR) of the order of 12 to 20 between short T(2) and long T(2) species within a total scan time of 4 to 10 min.

Magnetization transfer contrast imaging in bovine and human cortical bone applying an ultrashort echo time sequence at 3 Tesla

Magnetization transfer (MT) contrast imaging reveals interactions between free water molecules and macromolecules in a variety of tissues. The introduction of ultrashort echo time (UTE) sequences to clinical whole-body MR scanners expands the possibility of MT imaging to tissues with extremely fast signal decay such as cortical bone. The aim of this study was to investigate the MT effect of bovine cortical bone in vitro on a 3 Tesla whole-body MR unit. A 3D-UTE sequence with a rectangular-shaped on-resonant excitation pulse and a Gaussian-shaped off-resonant saturation pulse for MT preparation was applied. The flip angle and off-resonance frequency of the MT pulse was systematically varied. Measurements on various samples of bovine cortical bone, agar gel, aqueous manganese chloride solutions, and solid polymeric materials (polyurethane) were performed, followed by preliminary applications on human tibial bone in vivo. Direct on-resonant saturation effects of the MT prepulses were calculated numerically by means of Bloch's equations. Corrected for direct saturation effects dry and fresh bovine cortical bone showed "true" MTR values of 0.26 and 0.21, respectively. In vivo data were obtained from three healthy subjects and showed MTR values of 0.30 +/- 0.08. In vivo studies into MT of cortical bone might have the potential to give new insights in musculoskeletal pathologies.

In vivo Off-Resonance Saturation Magnetic Resonance Imaging of αvβ3-Targeted Superparamagnetic Nanoparticles

Magnetic resonance imaging is a powerful clinical imaging technique that allows for noninvasive tomographic visualization of anatomic structures with high spatial resolution and soft tissue contrast. However, its application in molecular imaging of cancer has been limited by the lack of sensitivity and detection accuracy in depicting the biochemical expression of these diseases. Here, we combine an ultrasensitive design of superparamagnetic polymeric micelles (SPPM) and an off-resonance saturation (ORS) method to enhance the imaging efficacy of tumor biomarkers in vivo. SPPM nanoparticles encoded with cyclic(RGDfK) were able to target the alpha(v)beta(3)-expressing microvasculature in A549 non-small cell lung tumor xenografts in mice. ORS greatly improved tumor detection accuracy over the conventional T(2)*-weighted method by its ability to turn "ON" the contrast of SPPM. This combination of ORS imaging with a tumor vasculature-targeted, ultrasensitive SPPM design offers new opportunities in molecular imaging of cancer.

Improvement in the contrast of CEST MRI via intermolecular double quantum coherences

The tremendous potential of chemical exchange saturation transfer (CEST) agents as an emerging class of magnetic resonance imaging contrast media has been demonstrated in recent years. In a CEST experiment, a high CEST contrast is always welcome. However, when the exchange rate is low, which may happen in exchangeable solute protons of low concentration, it is usually hard to obtain an excellent CEST efficiency. Recently, we noted that the intermolecular multiple quantum coherence signal is more sensitive to the changes of the magnetization magnitude than a conventional single quantum coherence signal. Consequently, it may be easier when used in obtaining a CEST contrast. In this note, a modified COSY (two-dimensional correlated spectroscopy) revamped with an asymmetric Z-gradient echo detection (CRAZED) sequence combined with an off-resonance saturation pulse followed by a standard spin-echo imaging sequence was designed to obtain a better CEST contrast image based on the intermolecular double quantum coherence method. An analytical expression was derived from a dipolar field theory. Experiments were performed on an agar–glucose phantom, and the results demonstrate the feasibility of our method.

Equivalent cross‐relaxation rate imaging of axillary lymph nodes in breast cancer

To determine whether equivalent cross-relaxation rate (ECR) imaging (ECRI) is a feasible method for optimization of axillary lymph node dissection (ALND) and thereby improve quality-of-life (QOL). A total of 50 breast cancer patients underwent ECRI, with off-resonance saturation pulse at frequency offset of 5 ppm. ECR threshold values were determined to evaluate metastases to lymph nodes in the ALND group before examining the relationship between ECR value and cellular density. Metastases to lymph nodes of the sentinel lymph node biopsy (SLNB) group were evaluated based on the results of the ALND group. In the ALND group, regions without metastases showed a higher cellular density and ECR value than those with metastases. The relationship of ECR value to cellular density formed two clusters according to the presence or absence of metastasis; cellular density was related to ECR value for both clusters. In the SLNB group, supposing a threshold ECR value of 80%, sensitivity and specificity were 88.2% and 100%, respectively. ECRI is a potentially useful method for cellular density imaging of axillary lymph nodes. ECRI provides active information that enables ALND to be avoided, thus improving QOL.

Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T 1sat Measurements

Variations in blood-brain barrier (BBB) opening after ischemia have been suggested by some tracer and magnetization transfer studies, although direct in vivo proof is still lacking. Contrast-enhanced magnetic resonance imaging (MRI) is also often used to visualize BBB damage in stroke. We hypothesized that MR contrast agents of different sizes enhance differently when BBB openings vary in size and that magnetization transfer alterations, measured by T(1) in the presence of off-resonance radiofrequency saturation (T(1sat)), in these regions reflect such differences. Male Wistar rats ( approximately 300 g, n=7) were subjected to 3 hours of suture occlusion of the middle cerebral artery followed by reperfusion. Status of the BBB at 24 hours after the ictus was assessed first by Gd-DTPA (554 Da) MRI and then by Gd-bovine serum albumin linked to Evans blue (Gd-BSA-EB; approximately 68 kDa) MRI for contrast enhancement; T(1sat) changes, cerebral blood flow, and blood-to-brain transfer constants (K(i)s) for the 2 contrast agents were measured. After MRI, rats were injected with fluorescent dextran and brains were studied by fluorescence microscopy. The Gd-BSA-EB-enhancing areas were always smaller (147+/-80 pixels) than those for Gd-DTPA (308+/-204 pixels) and were contained within the latter. The difference between the 2 areas was significant (P=0.024). Changes in T(1sat) were larger in Gd-BSA-EB-enhancing areas (ipsilateral to contralateral [I/C]=1.53+/-0.20) than in Gd-DTPA-enhancing areas (I/C=1.40+/-0.24, P=0.005). The differences in cerebral blood flow values between the 2 regions were not significant (P=0.62), but those for the K(i) values of the 2 tracers were different (P=0.01 to 0.02). Excellent agreement between regions of Gd-BSA-EB enhancement and EB fluorescence was also observed. These results substantiate earlier reports of regional differences in BBB opening after stroke and provide the first in vivo evidence for this phenomenon. They also support the possible use of T(1sat) in quantifying stroke-induced graded BBB damage in the absence of contrast-enhanced MRI.

Observation of three-photon absorption and saturation of two-photon absorption in amorphous nanolayered Se/As2S3 thin film structures

We have studied the nonlinear optical properties of nanolayered Se/As2S3 film with a modulation period of 10 nm and a total thickness of 1.15 μm at two [1064 nm (8 ns) and 800 nm (20 ps)] wavelengths using the standard Z-scan technique. Three-photon absorption was observed at off-resonant excitation and saturation of two-photon absorption at quasiresonant excitation. The observation of the saturation of two-photon absorption is because the pulse duration is shorter than the thermalization time of the photocreated carriers in their bands and three-photon absorption is due to high excitation irradiance.

Quantitative magnetization transfer imaging via selective inversion recovery with short repetition times

Quantitative magnetization transfer imaging (qMTI) methods are able to estimate fundamental sample parameters, such as the relative size of the solid-like macromolecular proton pool and the spin exchange rate between this pool and the directly measured free water protons. One such method is selective inversion recovery (SIR), in which the free water protons are selectively inverted and the signal is fit to a biexponential function of the inversion time (TI). SIR uses only low-power pulses and requires no separate RF (B1) or static field (B0) field maps, and the analysis is largely independent of the macromolecular pool lineshape. These are all advantages over steady-state off-resonance saturation qMTI methods. However, up to now, SIR has been implemented only with repetition times TR>>T1. This paper describes a modification of SIR with smaller TR values and a greater signal-to-noise ratio (SNR) efficiency.

Off‐resonance saturation as a means of generating contrast with superparamagnetic nanoparticles

This work demonstrates an alternative approach, termed off-resonance saturation (ORS), for generating contrast that is sensitive to superparamagnetic particles. This method leads to a calculated contrast that increases with superparamagnetic nanoparticle concentration. Experimental data demonstrate that in the presence of superparamagnetic particles, an off-resonance effect exists that is distinct from the magnetization transfer (MT) effect and is highly dependent on diffusion. Data show that the dependence on water diffusion becomes most significant at rates of 0.5 x 10(-9) m(2)/s and slower. We investigated the dependence of the off-resonance effect on off-resonance frequency and particle concentration. The data suggest a useful frequency offset range of 500 Hz < |Deltaomega| < 1500 Hz at 3T. This approach may be especially useful in organs and diseases in which diffusion may be altered by pathologies.

Equivalent cross-relaxation rate imaging of breast cancer.

To determine whether equivalent cross-relaxation rate (ECR) imaging is a feasible method for demonstrating breast cancer. Fifteen breast cancer patients underwent both ECR imaging, with off-resonance saturation pulses at frequency offsets of 7 and 19 ppm (ECR-7 and ECR-19, respectively) from water resonance, and gadolinium (Gd)-enhanced dynamic magnetic resonance imaging (MRI) of the breast. The mean tumor size was 26.5 mm. The tumor outlines defined by their shape and margin on ECR-7 images were compared with the subtraction images produced by the dynamic study, and the distribution of hyperintensity areas and their shapes on ECR-19 images were assessed. All patients had surgery and pathological findings were compared to ECR images. The tumor outline of 13/15 (87%) tumors on ECR-7 images was nearly identical to that on subtraction images; ECR-19 images demonstrated the location and degree of fibrosis. The tumor outline of the other two tumors was less clear on ECR-7 images, and internal hyperintensity on ECR-19 images reflected intratumoral fibrotic foci. ECR-7 and -19 imaging findings allowed identification of four distinct tumor types that reflected the tumor growth patterns and their internal structures associated with fibrosis. ECR imaging is a feasible imaging technique for demonstrating breast cancer.

Equivalent cross-relaxation rate imaging in the synthetic copolymer gels and invasive ductal carcinomas of the breast

The values of equivalent cross-relaxation rate (ECR) correlated well with [i] water conditions in various copolymer gels and [ii] nature of malignant cells with regard to nuclear dysplasia and mitotic potential in breast carcinomas. The synthetic copolymer gels composed of any two or three monomers among 2-hydroxyethyl methacrylate (HEMA), glycidyl methacrylate (GMA), N-vinyl-2-pyrrolidinone (N-VP), methyl methacrylate (MMA) and benzyl methacrylate (BMA). The ECR measurement was performed by using an off-resonance saturation pulse under conventional field-echo imaging at frequency within ± 75 ppm apart from the water resonance frequency. The ECR values were readily to determine and non-time consuming parameter for cross relaxation rate. The ECR values at the frequency offset by 7-ppm (ECR-7) were divided the sample gels two classes, which must correspond to hydrophilic or hydrophobic ones. The sensitivity in the gels was nearly equivalent to the cross-relaxation rate itself. In the breast carcinomas, the ECR-7 correlates with the nature of malignant cells with regard to nuclear dysplasia and mitotic potential. The ECR-7 is better or more accurate than the STR-7 because the SDNRs between carcinoma and glandular tissue increased by approximately 50% on the ECR-7 compared with the STR-7. Thus the ECR values could be a new parameter for malignancy and cell proliferative activity of the breast carcinomas with non-invasive modalities by magnetic resonance imaging.

Magnetization transfer MRI: Application to treatment of middle cerebral artery occlusion in rat

The temporal profiles of MRI parameters which use quantitative estimates of magnetization transfer were measured in 22 male Wistar rats subjected to middle cerebral artery occlusion, with and without therapeutic intervention with an anti-ICAM-1 monoclonal antibody. Two measures were used: the value of a magnetization transfer-related parameter in a predetermined region of interest, and the area of damage, as measured by changes in this parameter. In both groups, the value and area of damage of the inverse of the apparent forward transfer rate for magnetization transfer (1/kfa) significantly increased from the preischemic values (P < 0.05), as did T1 under an off-resonance partial saturation of the macromolecular pool (T1sat), and T1 (P < 0.05). Moreover, the increase in the value and total area of damage, as measured by 1/kfa, T1, and T1sat in the treated group, was smaller compared to that of the untreated group, with significant differences detected between groups at 5, 24, and 48 hours. Our data suggest that a quantitative measure of MT may provide a sensitive and early method to detect the efficacy of therapeutic intervention in experimental stroke. J. Magn. Reson. Imaging 2001;13:178–184. © 2001 Wiley-Liss, Inc.

Magnetization transfer MRI: application to treatment of middle cerebral artery occlusion in rat.

The temporal profiles of MRI parameters which use quantitative estimates of magnetization transfer were measured in 22 male Wistar rats subjected to middle cerebral artery occlusion, with and without therapeutic intervention with an anti-ICAM-1 monoclonal antibody. Two measures were used: the value of a magnetization transfer-related parameter in a predetermined region of interest, and the area of damage, as measured by changes in this parameter. In both groups, the value and area of damage of the inverse of the apparent forward transfer rate for magnetization transfer (1/k(fa)) significantly increased from the preischemic values (P < 0.05), as did T1 under an off-resonance partial saturation of the macromolecular pool (T1sat), and T1 (P < 0.05). Moreover, the increase in the value and total area of damage, as measured by 1/k(fa), T1, and T1sat in the treated group, was smaller compared to that of the untreated group, with significant differences detected between groups at 5, 24, and 48 hours. Our data suggest that a quantitative measure of MT may provide a sensitive and early method to detect the efficacy of therapeutic intervention in experimental stroke.

Saturation Transfer Ratio in Magnetic Resonance Imaging. A Novel Physical Parameter for Evaluation of the Hydrophilicity of Synthetic Copolymer Gels

It was first found that there is good correlation between saturation transfer ratio (STR) values in magnetic resonance imaging (MRI) measurement and the hydrophilicity of various synthetic copolymer gels containing 2-hydroxyethyl methacrylate (HEMA), glycidryl methacrylate (GMA), N-vinyl-2-pyrrolidinone (N-VP), and/or methyl methacrylate (MMA). The hydrophilicity of these copolymer gels was characterized by water contents evaluated by differential scanning calorimeter (DSC) and also the solubility parameter in theoretical sense. The MRI measurement was performed by conventional field-echo imaging as well as under the irradiation of an off-resonance saturation pulse apart by 75, 19, and 4ppm from a resonance point of water. The STR values offset at the 75-ppm correlated well with the total water contents in the samples. The values offset at the 19-ppm divided the samples into two classes corresponding to hydrophilic and hydrophobic gels. In the case of 4-ppm offset, the hydrophilic gels showed significantly higher STR values than the hydrophobic ones and the values among the hydrophilic gels were reflective to the constrained water content in the gel. Moreover the values correlated linearly with the solubility parameter of the samples. Thus the STR values in measurement of MRI could be adopted as a new useful parameter for molecular or material characterization of synthetic copolymers without any invasive processes.

Ethanol in Human Brain by Magnetic Resonance Spectroscopy: Correlation With Blood and Breath Levels, Relaxation, and Magnetization Transfer

Background: Proton magnetic resonance spectroscopy (1H MRS) allows measurement of alcohol in the human brain after alcohol consumption. However, the quantity of alcohol that can be detected in the brain by 1H MRS pulse sequences has been controversial, with values ranging from about 24% to 94% of the temporally concordant blood alcohol concentrations. The quantitation of brain alcohol is critically affected by the kinetics of alcohol uptake and elimination, by the relaxation times of the protons that give rise to the brain alcohol signal, and by the specifics of both pulse sequence timing and radio frequency pulse applications. Methods: We investigated these factors in 20 light-drinking subjects after oral administration of approximately 0.85 g/kg body weight of alcohol by localized 1H MRS and measurements of blood and breath alcohol concentrations obtained at the same time. Specifically, we measured transverse and longitudinal relaxation times of brain alcohol and its signal saturation on application of on- or off-resonance radio frequency pulses. All 1H MRS measurements were performed at a time after brain and blood alcohol concentrations had equilibrated. Results: 1H MRS measures of brain alcohol were correlated highly with both breath and blood alcohol concentrations after equilibration in brain tissue. The measured 1H MRS relaxation times of brain alcohol were shorter than given in previous reports that were limited by smaller subject numbers, improper use of 1H MRS methods, and estimates rather than measurements. The brain alcohol signal decreased by about 30% on application of on- or off-resonance saturation pulses. Conclusions: 1H MRS allows direct measurement of brain alcohol, formerly only possible indirectly through inferences from breath alcohol levels. Quantitation of brain alcohol levels need to take into account measured relaxation times and alcohol signal attenuation due to presence and timing of standard radio frequency MRS pulses. Saturation experiments give evidence for the existence of more than one compartment of brain alcohol characterized by different molecular environments. They suggest that a fraction of brain alcohol is invisible to 1H MRS.

Ethanol in Human Brain by Magnetic Resonance Spectroscopy: Correlation With Blood and Breath Levels, Relaxation, and Magnetization Transfer

Proton magnetic resonance spectroscopy (1H MRS) allows measurement of alcohol in the human brain after alcohol consumption. However, the quantity of alcohol that can be detected in the brain by 1H MRS pulse sequences has been controversial, with values ranging from about 24% to 94% of the temporally concordant blood alcohol concentrations. The quantitation of brain alcohol is critically affected by the kinetics of alcohol uptake and elimination, by the relaxation times of the protons that give rise to the brain alcohol signal, and by the specifics of both pulse sequence timing and radio frequency pulse applications. We investigated these factors in 20 light-drinking subjects after oral administration of approximately 0.85 g/kg body weight of alcohol by localized 1H MRS and measurements of blood and breath alcohol concentrations obtained at the same time. Specifically, we measured transverse and longitudinal relaxation times of brain alcohol and its signal saturation on application of on- or off-resonance radio frequency pulses. All 1H MRS measurements were performed at a time after brain and blood alcohol concentrations had equilibrated. 1H MRS measures of brain alcohol were correlated highly with both breath and blood alcohol concentrations after equilibration in brain tissue. The measured 1H MRS relaxation times of brain alcohol were shorter than given in previous reports that were limited by smaller subject numbers, improper use of 1H MRS methods, and estimates rather than measurements. The brain alcohol signal decreased by about 30% on application of on- or off-resonance saturation pulses. 1H MRS allows direct measurement of brain alcohol, formerly only possible indirectly through inferences from breath alcohol levels. Quantitation of brain alcohol levels need to take into account measured relaxation times and alcohol signal attenuation due to presence and timing of standard radio frequency MRS pulses. Saturation experiments give evidence for the existence of more than one compartment of brain alcohol characterized by different molecular environments. They suggest that a fraction of brain alcohol is invisible to 1H MRS.

Quantitative Interpretation of Magnetization Transfer in Spoiled Gradient Echo MRI Sequences

A method for analyzing general pulsed magnetization transfer (MT) experiments in which off-resonance saturation pulses are interleaved with on-resonance excitation pulses is presented. We apply this method to develop a steady-state signal equation for MT-weighted spoiled gradient echo sequences and consider approximations that facilitate its rapid computation. Using this equation, we assess various experimental designs for quantitatively imaging the fractional size of the restricted pool, cross-relaxation rate, and T(1) and T(2) relaxation times of the two pools in a binary spin bath system. From experiments on agar gel, this method is shown to reliably and accurately estimate the exchange and relaxation properties of a material in an imaging context, suggesting the feasibility of using this technique in vivo.

Saturation transfer ratio imaging in invasive ductal carcinomas of the breast

A prospective study was performed to investigate the correlations between saturation transfer ratio (STR) and histologic parameters of invasive ductal carcinomas in human breast. The histologic parameters investigated were the extent of fibrosis in the intercellular matrix, dysplastic changes of nuclei, and mitotic index. Twenty-seven patients with breast carcinoma were examined using an off-resonance saturation pulse in conjunction with conventional field-echo T1-weighted imaging at frequency offsets of 448 Hz and 1200 Hz from water resonance. The values of STR at frequency offset of 1200 Hz (STR1200) increased from non-scirrhous carcinoma to scirrhous carcinoma. Although STR1200 showed correlation with the extent of fibrosis in the intercellular matrix (p < 0.01, n = 27), they did not correlate with the dysplastic changes of nuclei or mitotic index. On the other hand, the values of STR at frequency offset of 448 Hz (STR448) demonstrated close correlation to dysplastic changes of nuclei and mitotic index (p < 0.01, n = 27). STR1200 correlates with the structural characteristics and STR448 correlates with the nature of malignant cells with regard to nuclear dysplasia and mitotic potential.

Toroid Cavity Detectors for High-Resolution NMR Spectroscopy and Rotating Frame Imaging: Capabilities and Limitations

The capabilities of toroid cavity detectors for simultaneous rotating frame imaging and NMR spectroscopy have been investigated by means of experiments and computer simulations. The following problems are described: (a) magnetic field inhomogeneity and subsequent loss of chemical shift resolution resulting from bulk magnetic susceptibility effects, (b) image distortions resulting from off-resonance excitation and saturation effects, and (c) distortion of lineshapes and images resulting from radiation damping. Also, special features of signal analysis including truncation effects and the propagation of noise are discussed. B0 inhomogeneity resulting from susceptibility mismatch is a serious problem for applications requiring high spectral resolution. Image distortions resulting from off-resonance excitation are not serious within the rather narrow spectral range permitted by the RF pulse lengths required to read out the image. Incomplete relaxation effects are easily recognized and can be avoided. Also, radiation damping produces unexpectedly small effects because of self-cancellation of magnetization and short free induction decay times. The results are encouraging, but with present designs only modest spectral resolution can be achieved.