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QSim, a program for NMR simulations.

We present QSim, a program for simulation of NMR experiments. Pulse sequences are implemented and analyzed in QSim using a mouse driven interface. QSim can handle almost any modern NMR experiment, using multiple channels, shaped pulses, mixing, decoupling, phase-cycling and pulsed field gradients. Any number of spins with any spin quantum number can, in theory, be used in simulations. Relaxation is accounted for during all steps of pulse sequences and relaxation interference effects are supported. Chemical kinetics between any numbers of states can be simulated. Both classical and quantum mechanical calculations can be performed. The result of a simulation can be presented either as magnetization as a function of time or as a processed spectrum.

Computer Graphics↗

Use of magnetic resonance imaging to analyze the performance of hollow-fiber bioreactors.

Preliminary experiments were described that demonstrate that MRI is an effective tool for the noninvasive study of hollow-fiber bioreactors. Flow-compensated velocity-encoding pulse sequences were successively applied to analyze the velocity patterns in a module operated without cells, with an artificially induced flow field perturbation. Diffusion damping pulse sequences were also used to spatially resolve regions of cell growth in a bioreactor. These experiments provide the necessary basis from which future flow and spectroscopic studies can be conducted.

Animals↗

Patellofemoral joint: evaluation during active flexion with ultrafast spoiled GRASS MR imaging.

An ultrafast spoiled gradient-recalled acquisition in the steady state pulse sequence was developed that permits multiple images to be obtained at a temporal resolution suitable for examining the patellofemoral joint during active flexion. This pulse sequence was used to perform kinematic magnetic resonance imaging of patellar alignment and tracking in five healthy subjects and seven patients with a provisional clinical diagnosis of abnormal patellofemoral joints.

Female↗

Squamous cell carcinoma of the oral cavity: MR findings and value of T1-versus T2-weighted fast spin-echo images.

OBJECTIVE: The purposes of this study were to describe the characteristics of squamous cell carcinomas of the oral cavity on unenhanced and contrast-enhanced T1-weighted spin-echo (SE) MR images and unenhanced T2-weighted fast spin-echo (FSE) MR images and to determine which sequences best delineate the margins and extent of the tumors. MATERIALS AND METHODS: Forty-four patients with proved squamous cell carcinoma of the oral cavity (tongue, 24; floor of mouth, seven; buccal mucosa, four; maxillary gingiva, two; and mandibular gingiva, seven) underwent unenhanced axial T2-weighted FSE MR imaging and unenhanced and enhanced axial and coronal T1-weighted SE MR imaging. The appearance, signal characteristics, and extent of the tumors were assessed, and the delineation of tumor margins with each sequence or combination of sequences was evaluated by use of a grading system ranging from 1 (poor) to 3 (excellent). Three patients were excluded because of artifacts on the MR images caused by dental restorations. RESULTS: Tumors in all 41 patients were depicted on unenhanced T1-weighted SE images, but in four patients, tumors were not visible on T2-weighted FSE images. Except for tumors that invaded the maxillary gingiva, the tumors generally had homogeneous, low signal intensity on unenhanced T1-weighted images and nonhomogeneous, high signal intensity on T2-weighted FSE images. All tumors showed enhancement, 76% with a nonhomogeneous appearance. The delineation of tumor margins was excellent (grade 3) in 31 cases and fair (grade 2) in 10 cases. The highest rating was given for unenhanced T1-weighted images in 10 cases, for contrast-enhanced T1-weighted images in 10 cases, for the combination of both unenhanced and contrast-enhanced T1-weighted images in 18 cases, for the combination of unenhanced T1-weighted and T2-weighted FSE images in five cases, and for T2-weighted FSE images in one case. In three cases, the highest rating was given for both combinations of pulse sequences. CONCLUSION: An unenhanced T1-weighted sequence should be used as the basic pulse sequence for MR imaging of tumors of the oral cavity. When tumor margins are not clearly delineated with this sequence, T2-weighted FSE and contrast-enhanced T1-weighted sequences should be added. Although both of these sequences provide supplementary information, the contrast-enhanced T1-weighted sequence is more useful in delineating the margins and extent of tumors than is the T2-weighted FSE sequence.

Adult↗

Three-dimensional T1rho-weighted MRI at 1.5 Tesla.

PURPOSE: To design and implement a magnetic resonance imaging (MRI) pulse sequence capable of performing three-dimensional T(1rho)-weighted MRI on a 1.5-T clinical scanner, and determine the optimal sequence parameters, both theoretically and experimentally, so that the energy deposition by the radiofrequency pulses in the sequence, measured as the specific absorption rate (SAR), does not exceed safety guidelines for imaging human subjects. MATERIALS AND METHODS: A three-pulse cluster was pre-encoded to a three-dimensional gradient-echo imaging sequence to create a three-dimensional, T(1rho)-weighted MRI pulse sequence. Imaging experiments were performed on a GE clinical scanner with a custom-built knee-coil. We validated the performance of this sequence by imaging articular cartilage of a bovine patella and comparing T(1rho) values measured by this sequence to those obtained with a previously tested two-dimensional imaging sequence. Using a previously developed model for SAR calculation, the imaging parameters were adjusted such that the energy deposition by the radiofrequency pulses in the sequence did not exceed safety guidelines for imaging human subjects. The actual temperature increase due to the sequence was measured in a phantom by a MRI-based temperature mapping technique. Following these experiments, the performance of this sequence was demonstrated in vivo by obtaining T(1rho)-weighted images of the knee joint of a healthy individual. RESULTS: Calculated T(1rho) of articular cartilage in the specimen was similar for both and three-dimensional and two-dimensional methods (84 +/- 2 msec and 80 +/- 3 msec, respectively). The temperature increase in the phantom resulting from the sequence was 0.015 degrees C, which is well below the established safety guidelines. Images of the human knee joint in vivo demonstrate a clear delineation of cartilage from surrounding tissues. CONCLUSION: We developed and implemented a three-dimensional T(1rho)-weighted pulse sequence on a 1.5-T clinical scanner.

Adult↗

Method for reduced SAR T1rho-weighted MRI.

A reduced specific absorption rate (SAR) version of the T(1rho)-weighted MR pulse sequence was designed and implemented. The reduced SAR method employs a partial k-space acquisition approach in which a full power spin-lock pulse is applied to only the central phase-encode lines of k-space, while the remainder of k-space receives a low-power spin-lock pulse. Acquisition of high- and low-power phase-encode lines are interspersed chronologically to minimize average power deposition. In this way, the majority of signal energy in the central portion of k-space receives full T(1rho)-weighting, while the average SAR of the overall acquisition can be reduced, thereby lowering the minimum safely allowable TR. The pulse sequence was used to create T(1rho) maps of a phantom, an in vivo mouse brain, and the brain of a human volunteer. In the images of the human brain, SAR was reduced by 40% while the measurements of T(1rho) differed by only 2%. The reduced SAR sequence enables T(1rho)-weighted MRI in a clinical setting, even at high field strengths.

Animals↗

Experiments to detect long-range heteronuclear shift correlations: LR-J-HSMQC.

The utility of the J-HSMQC experiment to detect long-range CH correlations was investigated. Two new long-range J-compensated pulse sequences, LR-J-HSMQC(80,27) and LR-J-HSMQC(27,80), were developed using the (3beta(x))beta(y) composite 90 degrees pulse sequence. These two experiments were shown to be effective for long-range coupling constants, (n)J(CH), that were greater than 3 Hz. Although the overall sensitivities of the long-range J-HSMQC experiments were slightly lower than that of the conventional decoupled HMBC experiment, their 2D maps showed additional cross peaks that could be useful in structure elucidation. LR-J-HSMQC(27,80) was very efficient in yielding two- and four-bond relay correlations. The utility of the new sequences is demonstrated with strychnine as the sample.

Acetic Acid↗

The Wellcome Foundation lecture, 1984. Nuclear magnetic resonance imaging in medicine: medical and biological applications and problems.

From early biological work and the first T1 nuclear magnetic resonance (n.m.r.) animal image in 1974, whole-body patient images, by using a two-dimensional Fourier transform method were achieved in Aberdeen in 1980 with a 0.04 T vertical resistive magnet. Different pulse sequences produce images dependent by different amounts on proton density, T1 and T2, and for clinical work it is advantageous to use more than one pulse sequence to image pathology. The slow improvement of spatial resolution with increasing standing magnetic field strength is discussed and information on the T1 and T2 contrast dependence is reviewed: it suggests that the gains from high fields may be less than believed hitherto. Electrocardiogram gating can be used to produce moving images of the beating heart; blood flow can be imaged and surface radiofrequency coils are used for improved detail. N.m.r. imaging has considerable potential for studying response to therapy; mental states and dementia; tissue generation; discriminating body fat and body fluids. Other nuclei such as 23Na can be imaged and the potential to image fluorine-labelled pharmaceuticals could be very exciting; n.m.r. contrast agents are now being developed. Images formed from T1 values measured for each pixel are very useful for diagnosis, but the numerical values themselves are less valuable for distinctive pathological identification. With 15 companies manufacturing n.m.r. imagers and over 200 in use in hospitals, the technique is rapidly becoming established in diagnostic clinical practice and some typical uses are presented.

Adenocarcinoma↗

Simultaneous and independent rotations with arbitrary flip angles and phases for I, ISalpha, and ISbeta spin systems.

A new pulse sequence element for simultaneous and independent rotations with arbitrary flip angles and phases for isolated I, ISalpha, and ISbeta resonances without the use of selective radiofrequency pulses is introduced and experimentally demonstrated. S is a directly attached heteronucleus either at natural abundance or isotopically enriched. This pulse sequence element, dubbed TIG-BIRD (triselective independent gyrations BIRD), generalizes earlier elements like BIRD, TANGO, BANGO, and BIG-BIRD, the latter of which allows for arbitrary selection of flip angles and phases for I and IS spin systems without discriminating between ISalpha and ISbeta resonances. For ISalpha and ISbeta spin systems it also generalizes the spin-state-selective excitation (S3E) element selectively exciting only one of the ISalpha or ISbeta resonances. TIG-BIRD is a nonselective addition to the NMR toolkit which effects the equivalent of three independent selective rotations for I, ISalpha, and ISbeta resonances.

Hydrocarbons, Iodinated↗

MR imaging of hepatic focal nodular hyperplasia: characterization and distinction from primary malignant hepatic tumors.

Spin-echo MR imaging at 0.35 T was used to image hepatic focal nodular hyperplasia (FNH) and to attempt to distinguish it from primary malignant hepatic tumors. There were six FNH and 10 malignant tumors including seven hepatocellular carcinomas, two cholangiocarcinomas, and one hepatoblastoma. Our results show that FNH has a fairly consistent appearance, dissimilar from that of malignant primary hepatic tumors. Four of six FNH lesions were isointense (except for a central scar in three) and indistinguishable from normal hepatic parenchyma on all pulse sequences, whereas two of six were homogeneous but slightly hyperintense on T2-weighted sequences. Furthermore, a central hyperintense scar was seen in three of six lesions on T2-weighted sequences. In contrast, each of the malignant primary hepatic tumors was hyperintense on T2-weighted sequences and seven of 10 were hypointense on T1-weighted sequences; in nine of 10, heterogeneous areas of intensity were noted. In two fibrolamellar hepatocellular carcinomas a central scar was seen that was hypointense on all pulse sequences. By using quantitative data, the best characterization was obtained by using lesion/normal-liver intensity ratios from a T2-weighted sequence; all FNH had a ratio less than 1.33, while in nine of 10 primary malignant tumors it was greater than 1.41. We conclude that focal nodular hyperplasia may have a consistent appearance on spin-echo MR imaging and probably can be distinguished from primary malignant lesions in most instances.

Adenoma, Bile Duct↗

Recent topics in NMR imaging and MRI.

NMR and NMR imaging (MRI) are finding increasing use not only in the clinical and medical fields, but also in material, physicochemical, biological, geological, industrial and environmental applications. This short review is limited to two topics: (i) new techniques and pulse sequences and their application to non-clinical fields that may have clinical application; and (ii) new trends in MR contrast agents. The former topic addresses pulse sequence and data analysis; dynamics such as diffusion, flow, velocity and velocimetry; chemometrics; pharmacological agents; and chemotherapy; the latter topic addresses contrast agents (CA) sensitive to biochemical activity; CA based on water exchange; molecular interactions and stability of CA; characteristics of emerging CA; superparamagnetic CA; and macromolecular CA.

Contrast Media↗

[Methods of NMR signal spatial localization for in vivo spectroscopy. A metabolic approach to diseases].

State-of-the-art methods for in vivo localized NMR spectroscopy are described. The methods are presented according to the type of pulse sequences implemented and the number of spatial dimensions which are obtained. The advantages and limitations of methods based either on (i) surface coil, (ii) complex radiofrequency pulse sequences with or without gradients, or (iii) double phase encoding (spectroscopic imaging) are discussed. The specific features of 31P and 1H localized spectroscopy are presented with a description of potential clinical applications of this approach which affords precise biochemical and metabolic information on a variety of organs and tissues in a strictly non-invasive manner.

Humans↗

Fast 3D large-angle spin-echo imaging (3D FLASE).

A rapid steady-state 3D spin-echo imaging pulse sequence, based on the principle of nutating the spins by an angle greater than 90 degrees, has been designed and implemented on a clinical 1.5-T whole-body MR scanner. The pulse sequence, denoted fast large-angle spin-echo (FLASE), has been optimized for high-resolution imaging of tissues with short T2 and T2*. Features of FLASE include a minimum-phase Shinnar-Le Roux excitation pulse and distribution of phase- and slice-encoding gradients before and after the 180 degrees refocusing pulse to minimize the critical time delay between inversion and restoration of the residual longitudinal magnetization and for minimizing echo time. A Bloch equation analysis, corroborated by experimental data, shows FLASE signal-to-noise to be superior to its closest analog, 3D rapid spin-echo excitation (RASEE) (Jara et al., Magn Reson Medicine 29, 528 (1993)), and 3D gradient-recalled acquisition in steady state (GRASS). It is demonstrated that with judicious RF phase-cycling and steady state operation, FLASE can produce high-quality microimages free of intravoxel phase dispersion from susceptibility-induced background gradients. The performance of the method is exemplified with ultra high-resolution images of trabecular bone in vitro and in vivo in the human calcaneus and wrist at voxel sizes as low as 98 x 98 x 200 microns3. Finally, the contrast behavior of refocused FLASE can be altered by disrupting the steady state analogous to gradient echo imaging.

Bone and Bones↗

A Pulsed Field Gradient Spin-Echo Method for Diffusion Measurements in the Presence of Internal Gradients.

Over the past decade several pulsed field gradient stimulated-echo methods have been presented for diffusion measurements in heterogeneous media. These methods have reduced or eliminated the coupling between the applied magnetic field gradient and a constant internal magnetic field gradient caused by susceptibility changes throughout the sample. For many research purposes the z-storage delay between the second and third pi/2 RF pulse has been included in order to increase the decay of the echo attenuation to an appropriate level and to increase the signal-to-noise ratio by avoiding T2 relaxation of the magnetization in parts of the pulse sequence. For these reasons a stimulated-echo method has been applied instead of a spin-echo method. When studying systems where it is necessary to keep the duration of the pulse sequence at a minimum, and one is not dependent on using z-storage time to increase the echo attenuation or to study diffusion as a function of observation time, a spin-echo method should be chosen. Here we propose a bipolar pulsed field gradient spin-echo method which is well suited to this purpose, and preliminary diffusion measurements are presented as illustration. Copyright 1999 Academic Press.

Journal Article↗

Differentiation of hepatocellular carcinoma and hepatic metastasis from cysts and hemangiomas with calculated T2 relaxation times and the T1/T2 relaxation times ratio.

PURPOSE: To determine the diagnostic capability of the T1 and T2 relaxation times and the T1/T2 relaxation times ratio generated with the mixed turbo spin echo (mixed-TSE) pulse sequence, in order to discriminate between hepatocellular carcinoma (HCC)/metastases and hemangiomas/cysts. MATERIALS AND METHODS: A retrospective review of 36 MR examinations implementing the mixed-TSE pulse sequence demonstrated 70 focal hepatic lesions. Quantitative MR algorithms were used to generate T1 and T2 relaxation times, and the T1/T2 relaxation times ratio for each lesion. A two-sample t-test compared mean T1 and T2 relaxation times, and the T1/T2 relaxation times ratio, by lesion type: carcinoma/metastases and hemangiomas/cysts. Sensitivity and specificity for discriminating carcinoma/metastases from hemangiomas/cysts with T2 relaxation time thresholds of 112 and 125 msec, as well as a ratio of T1/T2 relaxation times of 5.8, were calculated. RESULTS: Using a T2 relaxation time threshold of 112 msec, 92% sensitivity and 100% specificity discriminating cysts/hemangiomas from HCC/liver metastasis was demonstrated. With a threshold of 125 msec, 96% sensitivity and 98% specificity was demonstrated. There was no correlation between calculated T1 relaxation times and type of lesion. Using a T1/T2 relaxation times ratio of 5.8, 100% sensitivity and specificity were demonstrated. CONCLUSION: Although there is high sensitivity and specificity associated with the use of T2 relaxation times alone to discriminate carcinoma/metastases from hemangiomas/cysts, using the T1/T2 relaxation times ratio threshold of 5.8 allowed proper classification of all lesions.

Algorithms↗

Integrated volume-selective/spectral editing 1H NMR and postdetection signal processing for the sensitive determination of lactate.

A new volume selection/spectral editing pulse sequence (VOSING) is presented. The features specific to the technique are that the volume selection and the editing intervals coincide and that no decoupling is necessary. The pulse sequence can be applied under both homo- and heteronuclear conditions. Phantom experiments with lactate solutions and human serum led to water suppression factors of about 20,000. A postdetection signal processing method has been implemented. The final sensitivity for lactate determinations could thus be improved by a factor of more than 4. Ischemia-induced lactate could easily be detected in serum. At present, the lower detection limit of lactate is 1 mmol/liter for a (1.2 cm)3 voxel and 32 scans in a 4.7-T/40-cm magnet.

Humans↗

An optimal strategy for recovering the deuterium (2H) quadrupolar interaction under magic-angle spinning NMR.

By exploiting the homology in the form of the truncated high-field homonuclear dipole-dipole and quadrupole coupling Hamiltonians, we have previously demonstrated that a simple adaptation of a rotor-synchronized pulse sequence (DRAMA) used for the recovery of dipole-dipole couplings can also be used to resurrect quadrupole couplings (QUADRAMA). In the canonical implementation of these recovery pulse sequences, the couplings are not significantly scaled down from their static sample values. While such minimal scaling is of course desirable in the recovery of typical homonuclear dipolar couplings (< or =2 kHz) and small quadrupole couplings, it is clearly not ideal for the recovery of the much larger quadrupole couplings (20-200 kHz) often encountered in solid-state 2H NMR. In such a case, some prior knowledge of the order of magnitude of the coupling is required to optimize the experimental conditions for QUADRAMA. In order to overcome this drawback, in this study, we have developed a general and optimized strategy for implementing the QUADRAMA technique which does not require any knowledge of the size of the coupling vQ. Experimental tests of the optimized protocol demonstrate that by judicious choices of a combination of scaling factors and recoupling times, 2H quadrupole couplings ranging over an order of magnitude from 3 to 42 kHz can be measured. Since this optimized protocol can reliably be used to recover couplings over a broad range, it expands the range of systems accessible to study by 2H NMR into a realm where static sample NMR and simple MAS NMR may fail.

Journal Article↗

PJNMR: a platform-independent graphical simulation tool for NMR spectroscopy.

A new simulation program for multinuclear NMR is introduced. PJNMR (Pure Java NMR) 2.0, written entirely in the Java programming language, simulates pulse sequences on systems of up to three weakly coupled spins-1/2 with a command-driven, spectrometer-like interface. Users may simulate the effects of pulses, precessions, and pulsed field gradients on the spin system, with a graphical display showing the state of the density matrix (in a novel polar-coordinate representation) as well as the magnetization vectors for each nucleus. Relevant computations and optimizations as implemented in the code are detailed, along with the object-oriented structures used. A description of the simulation environment is given, illustrated with a series of example pulse sequences highlighting the insights gained in the graphical presentation.

Algorithms↗