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HMQC and HSQC experiments with water flip-back optimized for large proteins.

An HMQC experiment is proposed, dubbed FHMQC, where water flip-back is achieved by a single water-selective pulse preceding the basic HMQC pulse sequence. The scheme is demonstrated with a 15N,1H-HMQC spectrum of uniformly 15N/2H-labelled S. aureus DNA gyrase B with a molecular weight of 45 kDa for the unlabelled protein. The sensitivity of the experiment is improved compared to that of an FHSQC spectrum. It is further shown that the original FHSQC experiment can be shortened by the use of bipolar gradients. Relaxation times of different 15N magnetizations and coherences were measured. The new FHMQC scheme is implemented in 3D NOESY-15N-HMQC and 3D 15N-HMQC-NOESY-15N-HMQC pulse sequences which are demonstrated with a 24 kDa fragment of uniformly 15N/13C/2H-labelled S. aureus DNA gyrase B.

Bacterial Proteins↗

A perspective on needle artifacts in MRI: an electromagnetic model for experimentally separating susceptibility effects.

A thorough understanding of artifacts caused by metallic instruments is essential for the guidance of interventional procedures by magnetic resonance imaging (MRI), because the accurate localization of each instrument is mandatory for this. In the past, this problem has been addressed by several groups, using theoretical, as well as experimental approaches. The artifacts associated with MRI are caused by geometry distortion and intravoxel dephasing. Usually, both effects mingle in the image, and depending on the pulse sequences and its parameters used for data acquisition, these effects are reflected in the image with different magnitude. In this paper we shortly present the well-known mathematical background of the two underlying effects. Mathematically, both can be treated separately. Here, we propose a new electromagnetic model which also allows to experimentally separate the effects better than by comparing spin-echo and gradient-echo images of the same object. With this new model, both effects-geometry distortion and intravoxel dephasing-are demonstrated separately using the same gradient-echo pulse sequence for all scans and adjusting the fields of the model properly. Furthermore, as this model allows to adjust both effects independently, it is used to study different weightings of both effects when they appear simultaneously in the image.

Artifacts↗

Optimizing of gadolinium-enhanced MR angiography by manipulation of acquisition and scan delay times.

An optimized protocol for achieving high-quality contrast-enhanced MR angiography (CE MRA) was designed and evaluated. Time-intensity curves of the test bolus and main bolus were compared in 11 volunteers. To identify the acquisition zone sensitive to venous overprojection, sequential filling phantoms which consisted of 12 test tubes were developed and scanned. Using the parameters of the time-intensity curve which were consistent between the test and main boluses and the parameters of the sensitive acquisition zone in the pulse sequences, the protocol for calculation of scan delay time and acquisition time was optimized. The new protocol was verified by comparison of lower extremity CE MRAs acquired by traditional (scan delay time = peak enhancement time minus injection duration/2 + acquisition time/2; n = 12) and new (n = 23) protocols. The arterial and venous enhancing times of the time-intensity curves of the test and main boluses were statistically consistent (p < 0.01). The length of the sensitive acquisition zone was one-half the acquisition duration. With the parameters identified in the time-intensity curve and pulse sequence analyses, a new protocol was developed. For validation, the new protocol was able to study the smaller arteries such as the distal tibial arteries and branches of the femoral and iliac arteries (p < 0.01). Using the optimized protocol, higher-quality images were obtained than those acquired by traditional methods.

Adult↗

Instrumentation for rapid MR image synthesis.

MR image synthesis has previously been developed as a means of retrospectively optimizing contrast of arbitrary materials in MR images. The first step of this process is to form computed N(H), T1, and T2 images from source images acquired at a variety of echo delay and repetition times. The second step is to take these computed images, along with operator-selected timing parameters, and mathematically generate a synthesized image. Computation is carried out pixel by pixel according to the equation describing the chosen pulse sequence. This paper presents a study of design considerations for a digital image processor capable of rapidly performing the second step, the actual synthesis. In this work the computations inherent to image synthesis are identified, and the feasibility of performing them in high-speed hardware examined. An analysis of the imprecision due to bit-limited calculations shows that an error bound of 0.4% is possible with a 16-bit processor design. A method is described which uses a commercially available image processor by which images can be synthesized according to any of the standard pulse sequences in less than 600 ms.

Computers↗

Breath-hold 3D MR angiography of the renal vasculature using a contrast-enhanced multiecho gradient-echo technique.

OBJECTIVE: Significant evolution of contrast-enhanced MR angiography for evaluating vascular diseases in the abdomen has occurred during the past several years. The state-of-the-art gradient-echo imaging technique employs a short echo time (TE) and a short repetition time (TR) for rapid vascular imaging with contrast-enhanced MR angiography. However, because of the short TR (< or = 3-8 msec), the background stationary tissue becomes saturated, with resultant poor contrast resolution of visceral organs. The authors present a new approach to vascular imaging using a multiecho gradient-echo technique with a TR sufficiently long (41 msec) to image the renal vasculature and parenchyma without background tissue suppression. METHODS: Twenty-four partitions (3D slab thickness = 72 mm) with an in-plane resolution of 224 x 256 were obtained in 21 seconds. Three measurements were performed with an interscan delay of 8 seconds. In the pulse sequence, the partition loop is defined as the innermost loop, in which Kz views are acquired centrically for a fixed Ky, followed by Ky views in a conventional linear or sequential order. The partition encodings are segmented to permit multiple encodings in which two TR loops were used to span a total of 24 echoes with 12 along the positive and 12 along the negative direction in k space. A large bandwidth of 650 Hz/pixel was used to keep the echo train length short, with an echo spacing of 1.86 msec. A frequency-selective fat saturation pulse was placed before slab-selective excitation. The other parameters in the pulse sequence were TR/TE/flip = 41/2.2/45; the field of view was 360 to 390 mm. Maximum intensity projections of each 3D contrast-enhanced measurement were performed. The vascular-to-background contrast, bowel-related magnetic susceptibility artifact, and background stationary signals were subjectively graded. The authors examined the utility of this technique in 16 randomly selected patients (3 normal, 13 abnormal) with varied renal vasculature and parenchymal abnormalities. Results were confirmed with conventional x-ray angiography, surgery, or clinical follow-up. RESULTS: Vascular-to-background contrast was graded as very good (grade III/III) in all cases. The bowel-related magnetic susceptibility artifacts were not considered significant. Background visceral organ soft tissue contrast was not suppressed and was graded as good (grade III/III) in all cases. Eight hemodynamically significant (> 50% diameter) stenoses in seven patients were accurately assessed (one with fibromuscular dysplasia). Three patients with renal masses (two with renal cell carcinoma and one with renal lymphoma) were accurately assessed for arterial anatomy and venous extension. Other renal venous abnormalities seen were retroaortic renal vein (n = 1), chronic occlusion (n = 1), and accessories (total of five) (n = 1). CONCLUSIONS: Rapid breath-hold contrast-enhanced MR angiography of the renal vasculature with a multiecho gradient-echo using a long TR depicted the renal vasculature with high vessel-to-background contrast without significant bowel-related susceptibility artifact and without background visceral organ tissue signal suppression, resulting in high background soft tissue contrast resolution.

Artifacts↗

[The tissue characterization of focal liver lesions with magnetic resonance imaging].

This study was aimed at assessing the accuracy of Magnetic Resonance Imaging (MRI) in the characterization of focal liver masses. We prospectively examined 51 patients with focal liver masses: the morphological features were investigated with different pulse sequences and the functional characteristics were studied after the i.v. administration of Gd-DTPA (2 mmol/kg). MR findings were compared with those of gold standard methods, i.e., percutaneous biopsy, surgery or, for hemangiomas, 99mTc-labelled blood cell liver scintigraphy. All hemangiomas presented with typical features: signal intensity was very high on long TE images (> 140 msec) and a globular enhancement pattern, with centripetal progression, was observed after dynamic studies. This signal pattern on T2-weighted images is highly indicative of hemangioma. Five of 7 focal nodular hyperplasias (71%) were isointense with hepatic parenchyma on all pulse sequences; the central scar was observed in 5/7 cases on short TR/TE images and in all cases on long TR/TE images in 16/17 cases (94%). High signal intensity on T1-weighted images was statistically significant for HCC. A pseudocapsule was observed in 12 cases (70%). A mosaic pattern on T2-weighted images was observed in 3 cases. Seventy-four per cent of HCCs exhibited signal enhancement during the arterial phase of the dynamic study. Metastases presented a uniform pattern, i.e., they were hypointense on T1-weighted and hyperintense on T2-weighted images in 12/13 cases (92%). A central hypointense area on T2-weighted images is indicative of coagulative necrosis. A lesion with these morphological features and hypovascular signal is suggestive of metastasis.

Biopsy, Needle↗

CSF-suppressed T2-weighted three-dimensional MP-RAGE MR imaging.

Fluid-attenuated inversion recovery (FLAIR) is a pulse sequence used for acquiring T2-weighted images of the brain and spine in which the normally high signal intensity of CSF is greatly attenuated. The CSF-suppressed T2-weighted contrast of this technique may be more sensitive to a variety of disorders than that of conventional T2-weighted imaging. The primary disadvantage associated with conventional spin-echo implementations of FLAIR is the relatively limited anatomic coverage that can be achieved in a reasonable imaging time. We developed and optimized a three-dimensional magnetization-prepared rapid gradient-echo (3D MP-RAGE) pulse sequence that combines CSF-suppressed T2-weighted contrast similar to existing FLAIR techniques with anatomic coverage characteristic of 3D imaging. A preliminary evaluation of the new sequence was performed by imaging healthy volunteers and patients with multiple sclerosis.

Brain↗

Isointense model for the evaluation of tumor-specific MRI contrast agents.

An isointense model has been developed to evaluate the applicability of putative tumor-specific MRI contrast agents. Data for tissue relaxation measurements in the presence of Mn(III)TPPS4 are used to illustrate the model. The concentration of contrast agent in tumor tissue required for a tumor/normal tissue signal difference-to-noise ratio of 5 (delta SNR = 5) is determined for a T1 weighted pulse sequence and several hypothetical tumor/normal tissue pairs. The impact of various contrast agent characteristics including initial tumor/normal tissue relaxation values, differential uptake of contrast agent, and in vivo relaxivity are considered. Isointense tumor/normal tissue with longer initial relaxation times are shown to be more affected by the presence of contrast agent. In addition those with initially longer relaxation times have less rigorous requirements for tumor specificity. Typically, a normal tissue/tumor uptake ratio of 1:2 increases the concentration required for delta SNR = 5 by a factor of two compared to that of exclusive uptake in tumor. For the T1 weighted pulse sequence employed, the concentration required for delta SNR = 5 is shown to be linear with the inverse of in vivo relaxivity for the hypothetical tissues considered. The isointense model is also extended to predict the field dependence of tumor-specific contrast enhancement by Mn(III)TPPS4.

Contrast Media↗

Heteronuclear two-bond correlation: suppressing heteronuclear three-bond or higher NMR correlations while enhancing two-bond correlations even for vanishing 2J(CH).

A novel two-dimensional NMR pulse sequence, H2BC, for long-range correlation of 1H and 13C nuclei is presented. The experiment has several attractive features compared to the widely used HMBC experiment, for example, (a) typically strong enhancement of correlations over two bonds while suppressing those over more bonds, that is, resolving ambiguities in standard HMBC spectra and showing two-bond correlations not present in HMBC spectra, (b) independence of long-range 1H-13C coupling constants, (c) full homo- and heteronuclear decoupling in the indirect dimension and heteronuclear decoupling in the acquisition dimension, (d) pure 2D absorption peak shapes, and (e) a pulse sequence duration significantly shorter than that of HMBC. The experiment is quite complementary to HMBC and does not effect correlations to quaternary carbons that must be obtained by HMBC.

Carbon Isotopes↗

Techniques for high-resolution echo-planar MR imaging of the pancreas.

Recent technical advances in echo-planar magnetic resonance (MR) imaging prompted an investigation of these new techniques in pancreatic MR imaging and evaluation of bowel lumen enhancement with an aqueous bowel contrast agent. In 42 subjects (36 healthy, six with pancreatic disease), various T1-weighted inversion-recovery and T2-weighted spin-echo fat-suppressed pulse sequences were assessed with an echo-planar technique implemented with a modified clinical MR imager. Single-excitation imaging (echo time, 26 msec) provided a higher (P less than .05) signal-to-noise ratio than did conventional spin-echo and all other echo-planar techniques. In 13 (72%) of 18 healthy subjects who did not undergo administration of the contrast agent, the entire pancreas was distinguished from adjoining bowel. In all 18 subjects who underwent contrast-enhanced imaging, a significantly greater (P less than .05) intraluminal signal intensity was apparent with all echo-planar pulse sequences and the entire pancreas was identified. In six patients with pancreatic disease, lesions could be identified by their difference in signal intensity.

Barium Sulfate↗

Magnetic resonance imaging of neonatal encephalopathy at 4.7 tesla: initial experiences.

OBJECTIVES: The goals were to develop safe 4.7-T MRI examination protocols for newborn infants and to explore the advantages of this field strength in neonatal encephalopathy. METHODS: Nine ventilated newborn infants with moderate or severe encephalopathy were studied at 4.7 T, with ethical approval and informed parental consent. The custom-made, 4.7-T-compatible, neonatal patient management system included acoustic noise protection and physiologic monitoring. An adult head coil was used. Acquisition parameters for T2-weighted fast spin echo MRI and a variety of T1-weighted methods were adapted for MRI of neonatal brain at 4.7 T. The pulse sequences used had a radiofrequency specific absorption rate of <2 W/kg. RESULTS: Physiologic measures were normal throughout each scan. T2-weighted fast spin echo imaging provided better anatomic resolution and gray/white matter contrast than typically obtained at 1.5 T; T1-weighted images were less impressive. CONCLUSIONS: With appropriate safety precautions, MRI of newborn infants undergoing intensive care is as feasible at 4.7 T as it is at 1.5 T; our initial studies produced T2-weighted fast spin echo images with more detail than commonly obtained at 1.5 T. Although T1-weighted images were not adequately informative, additional pulse sequence optimization may be advantageous. A smaller neonatal head coil should also permit greater flexibility in acquisition parameters and even more anatomic resolution and tissue contrast. In neonatal encephalopathy, interpretation of the T2-weighted pathologic detail in combination with comprehensive neurodevelopmental follow-up should improve prognostic accuracy and enable more patient-specific therapeutic interventions. In addition, more precise relationships between structural changes and functional impairment may be defined.

Brain Diseases↗

Radiofrequency power deposition utilizing thermal imaging.

Wavelength effects influence radiofrequency (RF) power deposition distributions and limit magnetic resonance (MR) medical applications at very high magnetic fields. The power depositions in spherical saline gel phantoms were deduced from proton resonance shift thermal maps at both 1.5 T and 3.0 T over a range of conductivities. Phase differences before and after RF heating were measured for both a quadrature head coil and a circular surface coil. A long echo time (TE) pulse sequence with a 3D phase unwrap algorithm provided increased thermal sensitivity. The measured thermal maps agreed with a model of eddy-current heating by circularly polarized oscillating RF fields in a conducting dielectric sphere. At 3.0 T, thermal maps were acquired with a <0.32 degrees C temperature rise at 4 W. Proton resonance shift thermal maps provided a measure of hot spots in very-high-field MR imaging (MRI), in which both the phase sensitivity and signal-to-noise ratio (SNR) were increased. The method provides a means of studying the heat distribution generated by RF coils excited by clinical pulse sequences.

Magnetic Resonance Imaging↗

Primary liver tumors: diagnosis by MR imaging.

MR features of 153 proved primary liver tumors (95 malignant, 58 benign) in 55 patients with hepatocellular carcinoma (21), cholangiocarcinoma (seven), carcinosarcoma (one), hepatoblastoma (one), hemangioma (16), hepatic adenoma (four), focal nodular hyperplasia (three), leiomyoma (one), and hemangioendothelioma (one) were studied retrospectively to determine which techniques are most reliable for lesion detection and which criteria are most useful for differential diagnosis. MR data were correlated with histologic features such as fatty degeneration, fibrosis, and peritumoral edema. Unlike metastatic cancer, hepatocellular carcinoma was best detected (p less than .01) with T2-weighted pulse sequences. The mean tumor-liver T2 difference was 34.4%, while the mean T1 difference was only 21.8%. A tissue-specific diagnosis of hepatocellular carcinoma was possible in 14 of 21 patients by identification of fatty degeneration of the tumor (eight of 17), tumor capsule (five of 21), and/or vascular invasion (six of 21). MR features of peritumoral edema, present in six of 21 patients with hepatocellular carcinoma and in seven of 25 patients with metastases, were exclusively associated with malignant tumors. The large variation in tissue characteristics (relaxation times and proton density) seen in primary liver tumors necessitates the use of multiple pulse sequences to maximize lesion detection. However, the combined use of T1- and T2-weighted spin-echo and T2-weighted phase-contrast images had the advantage of distinguishing benign from malignant primary liver tumors in 48 of 55 patients in this series.

Adenoma↗

Solvent magnetization artifacts in high-field NMR studies of macromolecular hydration.

With the use of high magnetic fields and improved quality factor ratings of the probeheads in modern NMR spectrometers, radiation damping becomes more and more important. In addition, the demagnetizing field effect from protonated solvents gains significance with the increase of the magnetic field strength. During a typical NMR pulse sequence the magnetic fields caused by these effects become time-dependent, which makes the system nonlinear and may, for example, measurably influence the precession frequencies of all nuclei in the sample. Since radiation damping can affect signals that are several kilohertz away from the solvent resonance, the amplitude, phase, and frequency of the desired signals can be disturbed so as to give rise to spectral artifacts. In particular when difference methods are used to obtain the final spectrum, the data sets may be severely deteriorated by such artifacts. This paper investigates effects from the demagnetizing field and from radiation damping with a selection of pulse sequences in use for studies of macromolecular hydration, and strategies are described for the detection and elimination of the ensuing artifacts.

Artifacts↗

Magnetically labeled cells can be detected by MR imaging.

To determine the feasibility of MR imaging of magnetically labeled cells, different cell lines were labeled with monocrystalline iron oxide (MION) particles. Phantoms containing MION labeled cells were then assembled and imaged by MR at 1.5 T using T1-weighted and T2-weighted pulse sequences. MION uptake ranged from 8.5 x 10(4) to 2.9 x 10(5) particles/cell for tumor cells (9L and LX1, respectively) to 1.5 x 10(6) to 4.8 x 10(8) particles/cell for "professional phagocytes" (J774 and peritoneal macrophages, respectively). On the T1-weighted images, cell-internalized MION appeared hyperintense relative to agar and similar to MION in aqueous solution. On T2-weighted images, signal intensity varied according to concentration of MION within cells. Cell-internalized MION caused similar MR signal changes of cells as did free MION; however, at a dose that was an order of magnitude lower, depending on the pulse sequence used. The detectability of MION within cells was approximately 2 ng Fe, which corresponded to 10(5) tumor cells/well or 5 x 10(3) macrophages/well. We conclude that a variety of cells can be efficiently labeled with MION by simple incubation. Intracellular labeling may be used for MR imaging of in vivo cell tracking.

Contrast Media↗

Detection and quantification of free cytosolic inorganic phosphate and other phosphorus metabolites in the beating mouse heart muscle in situ.

The aim of this study was the quantification of inorganic phosphate (Pi) and other phosphorus metabolites by (31)P NMR spectroscopy in the mouse heart muscle in situ, beating at around 600 min(-1). Male adult Quacker-bush mice (mean weight 32 +/- 7 g) were anaesthetized, ventilated and placed in a temperature-controlled animal holder. A purpose-built (31)P NMR surface coil was positioned against the exposed left ventricular myocardium. Partial signal overlap of Pi with 2,3-DPG from chamber blood was minimized using a DEPTH pulse sequence (180 degrees -90 degrees -180 degrees -180 degrees -acq.). Quantification of phosphorus metabolites was performed using an external standard positioned directly above the surface coil. We report for the mouse myocardium in situ an intracellular free [Pi] of <0.4 mM, pH of 7.32 +/- 0.1, free [Mg2+] of 0.41 +/- 0.1 mM, free [ADP] of 13 +/- 1.5 microM, [ATP] of 5 +/- 0.5 mM and [PCr] of 14 +/- 1.5 mM. The phosphorylation ratio (ATP/ADP Pi) was 1005 +/- 200 mM (-1) for a PCr/ATP ratio of 2.7 +/- 0.3. It was concluded that the detection of free [Pi] in the mouse myocardium in situ can be greatly enhanced using a DEPTH pulse sequence. Quantification of compounds using an external standard positioned directly above the surface coil gave comparable results to estimations using internal ATP that was quantified enzymatically. The close agreement between the external and internal methods indicates that ATP is 100% NMR visible in the mouse heart in situ.

Animals↗

Fast-MAS total through-bond correlation spectroscopy using adiabatic pulses.

Pulse sequences consisting of adiabatic pulses for total through-bond correlation spectroscopy (TOBSY) under magic-angle spinning (MAS) are introduced. Above a certain threshold, the polarization transfer achieved with these sequences is largely insensitive to the amplitude and homogeneity of the radiofrequency field employed. An experimental transfer efficiency of up to 76% was achieved in a two-spin system using the sequence WiW9(24)(1) at a MAS frequency of 26.67 kHz. Applications to resonance assignments in the dipeptide L-Val-L-Phe and in the cyclic decapeptide antamanide are demonstrated.

Algorithms↗

Target delineation in radiosurgery for cerebral arteriovenous malformations. Assessment of the value of stereotaxic MR imaging and MR angiography.

A study of 6 selected arteriovenous malformation (AVM) patients was performed to investigate the feasibility of delineating an AVM on MR images and to compare the AVM volume outlined on different images. Conventional stereotaxic angiograms, stereotaxic MR images and MR angiograms using several different pulse sequences were obtained prior to radiosurgery. Treatment plans were made from the conventional stereotaxic angiograms. These plans were then transferred to a separate dose planning computer which displayed the MR images with the superimposed isodose lines. The radiated volumes of AVM and brain tissue were measured from these MR images. Last, an assessment was made of the radiation volume needed for an appropriate treatment of the AVM if the treatment plan was made from the MR images rather than from the conventional stereotaxic angiogram. It was possible to delineate medium and large size AVM nidi on stereotaxic MR images based on an integration of information obtained from various pulse sequences. The estimated volumes of the AVM nidi were found to be larger on the conventional stereotaxic angiograms than on the stereotaxic MR images. Consequently, a dose plan based on a conventional stereotaxic angiogram would result in a higher integral dose to the brain with the same target dose. By using reliable MR information it is expected that the volume of brain exposed to radiation could be decreased and the adverse effects of stereotactic radiosurgery for AVM thereby minimized.

Adult↗