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Biomedical subjects

P Bendel

Publications and source records attributed to P Bendel.

36 records · Page 2Linked to original sources

Snapshot MRI with T2*-weighted magnetization preparation.

A method for encoding T2*-dependent contrasts into the preparation period of magnetization-prepared ultrafast MRI sequences is demonstrated and validated. The preparation block consists of a 90 degrees---tau---90 degrees p sequence, where p is shifted by 90 degrees for successive images. By adding two such successive images in quadrature, a combined image is obtained, in which the pixel intensities depend on the incoherent intravoxel dephasing that occurred during tau in a way that is similar to the dependence of TE in a gradient-echo sequence. The method could therefore be useful for applications that require very short repetition times for good temporal resolution, together with detection of T2*-weighted contrasts, such as functional MRI in the brain.

Brain↗

Quantitation of ventricular size in normal and spontaneously hypertensive rats by magnetic resonance imaging.

Magnetic resonance imaging (MRI) performed at high field (4.7 Tesla), and high spatial resolution (0.6 mm slice thickness, 0.18 mm inplane) enabled noninvasive quantitative measurement of the ventricular vol. in live rats. Comparing the results for 15 male Wistar-Kyoto (WKY) rats, aged 2.5-10 months, with those from 17 spontaneously hypertensive rats (SHR), clearly confirmed the previously reported elevated ventricular vols. in the SHR strain. A significant difference in ventricular vol. between the two strains was detected above the age of 3 months. For mature animals above the age of 6 months the mean vol. in the SHR strain was elevated by about a factor of two compared to the WKY control animals.

Animals↗

Tamoxifen induced changes in MCF7 human breast cancer: in vitro and in vivo studies using nuclear magnetic resonance spectroscopy and imaging.

The effects of 17 beta-estradiol versus tamoxifen on the growth and metabolism of MCF7 human breast cancer cells, in culture and in tumors implanted in nude mice, were studied by 31P and 13C nuclear magnetic resonance spectroscopy and by proton magnetic resonance imaging. In culture, the content of the phosphate metabolites including nucleoside triphosphates (NTP), phosphomonoesters, phosphodiesters and inorganic phosphate (Pi) were not affected by tamoxifen treatment. However, in the presence of estrogen the rate of glucose consumption and lactate production via glycolysis (270 and 280 fmol/cell.h, respectively) were twice that of tamoxifen treated cells. Estrogen rescue of tamoxifen treated cells indicated that glycolysis induction occurs at the early stages of the hormonal response. The in vivo studies included recording of proton images that provided an accurate measure of tumor size and distribution of tumor cells, necrotic regions and stromal tissue. Tamoxifen caused enhanced necrosis extending from the center of the tumor during the first two days of treatment (12 h to 6 days). This was followed by growth of reparative tissue along with tumor regression. Tamoxifen also modified the content of the phosphate metabolites, increasing markedly (P less than 0.0002) the ratio of NTP to Pi from 0.41 before treatment to 1.75 9-19 days after treatment. This change was attributed to the enhanced growth of repair tissue. The results provide new information regarding the response of human breast cancer to hormonal treatment and suggest a mechanism for the induction of tumor regression by tamoxifen.

Animals↗

In vivo boron-11 MRI and MRS using (B24H22S2)4- in the rat.

In vivo boron-11 magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were performed on a rat that had been infused with a potential boron neutron capture therapy agent, Na4B24H22S2, using methods for detecting nuclei with a short T2 relaxation time. MRI and MRS were also performed on a euthanized rat that had been similarly infused in vivo. Boron-11 spectral intensities decreased in the living rat over a 25-h period. The results demonstrate the capability of MRI and MRS to noninvasively monitor the distribution and excretion of boron agents in vivo.

Animals↗

In vivo studies by magnetic resonance imaging and spectroscopy of the response to tamoxifen of MCF7 human breast cancer implanted in nude mice.

Magnetic resonance 1H-imaging and 31P-localized spectroscopy were utilized to monitor, noninvasively, MCF7 human breast cancer tumors implanted in immunodeficient mice. The tumors were followed during estrogen dependent growth and tamoxifen induced remission. Early after tamoxifen administration enhanced necrosis developed, extending to most of the tumor volume. This was followed by growth of repair tissue along with tumor regression. The short-term tamoxifen treatment also modified the content of the phosphate metabolites, increasing the nucleoside triphosphate to inorganic phosphate ratio from 0.41 +/- 0.15 (n = 14) before treatment to 1.10 +/- 0.70 (n = 8, P less than 0.025) and to 1.75 +/- 0.66 (n = 9, P less than 0.0002) 4-7 days and 9-19 days, respectively, after treatment. This change was attributed to the growth of reparative tissue. The results provide new information regarding the response and the mechanism of action of tamoxifen.

Animals↗

Blood flow in the carotid arteries: quantification by using phase-sensitive MR imaging.

The feasibility of MR phase-sensitive imaging for the quantification of blood flow in the carotid arteries was studied in two normal volunteers and six patients with carotid artery and/or cerebrovascular disease. The technique consists of sensitizing the phase of the MR signal to blood flow velocity gated to different times in the cardiac cycle. Flow velocities and volumes were measured by using transverse planes in the common, internal, and external carotid arteries, and flow curves were generated. Measurements made by using flow phantoms correlated well with calculated results. The MR measurements yielded values between 250 and 580 ml/min for the total flow through each of the common carotid arteries in the two normal volunteers. Markedly reduced flow (about 50% below normal) was detected in a patient whose arteriogram showed severe occlusion of the internal carotid artery. In a second patient, who had a large frontal intracranial arteriovenous malformation noted by arteriography, the MR-quantified flow was abnormally high (about 1 liter/min). In the remaining four patients, the findings on phase-sensitive quantification were consistent with those expected from clinical and other laboratory studies (including arteriography and sonography). These preliminary findings suggest that MR phase mapping may be a feasible tool for the noninvasive quantification of carotid blood flow.

Adult↗

An analysis of fast imaging sequences with steady-state transverse magnetization refocusing.

Recently, several groups have proposed and demonstrated the use of rapid imaging methods, using short pulse repetition times and gradient-reversal echoes. Here, we analyze the behavior of the magnetization and the resulting image contrasts in such sequences for the case where the pulse repetition time TR is of the order of, or shorter than, the transverse relaxation time T2, and the transverse magnetization is not destroyed between phase-encoding cycles. Exact analytical expressions describing the signal evolution between the pulses are derived, taking into account the effects of resonance offsets and flip angles, and examining the influence of constant-phase or alternate-phase RF pulse trains. It is shown that for typical imaging sequences two distinct echo signals will develop between pulses, which may have a detrimental effect on image quality if they partially overlap within the sampling window. It is shown that artifact-free images can be obtained only if the two echo signals overlap precisely, which seems technically close to impossible to achieve, or if they are sufficiently separated in time to allow sampling of only one of the signals.

Image Enhancement↗

Boron-11 MRI and MRS of intact animals infused with a boron neutron capture agent.

Boron neutron capture therapy (BNCT) depends on the delivery of boron-containing drugs to a targeted lesion. Currently, the verification and quantification of in vivo boron content is a difficult problem. Boron-11 spectroscopy was utilized to confirm the presence of a dimeric sulfhydryl dodecaborane BNCT agent contained in an intact animal. Spectroscopy experiments revealed that the decay time of transverse magnetization of the boron-11 spins was less than 1 ms which precluded the use of a 2DFT imaging protocol. A back-projection protocol was developed and utilized to generate the first boron-11 image of a BNCT agent in the liver of an intact Fisher 344 rat.

Animals↗

T2-weighted contrasts in rapid low flip-angle imaging.

Expressions for the contrast-to-noise (C/N) behavior in images obtained from rapid low flip-angle excitation pulses are derived, taking into account both T1- and T2-dependent contrasts. It is shown, and demonstrated experimentally, that images with T2-weighted contrasts can be efficiently acquired with such sequences, by a suitable choice of TR, TE, and tip angle.

Head↗

One- and two-dimensional 90.5-MHz 13C-NMR spectroscopy of the N-linked triantennary oligosaccharide units of calf fetuin.

Complete assignments of all anomeric resonances in the proton and carbon spectra of the N-linked oligosaccharide units of fetuin were made using one- and two-dimensional NMR spectroscopy. We are able to confirm the presence of microheterogeneity in the N-acetylneuraminic acid linkages to the galactose residues and the presence of a unique triantennary structure which carries a side chain: NeuAc alpha(1-3)Gal beta(1-3)GlcNac beta(1-4)-. Anomeric carbon chemical shifts changes resulting from long-range conformational effects were observed.

Animals↗

Measurement of the helix opening rate in Z-DNA by 1H nuclear magnetic resonance relaxation spectroscopy.

The exchange rate of the hydrogen-bonded guanine imino protons N(1) in the high-salt form of Poly(dG-dC) was measured by following the non-selective inversion-recovery of their 1H NMR signal at 360 MHz, in the temperature range between 77 degrees C and 90 degrees C. In a 4.5M NaCl solution, Poly(dG-dC) is believed to adapt the left-handed Z-conformation, and the results reported here represent the first quantitative measurements of this rate process for Z-DNA by Nuclear Magnetic Resonance, complementing previous measurements made by tritium exchange at 0 degrees C (Ramstein, J. and Leng, M. (1980) Nature 288, 413-414). The results confirm that this process is much slower in the Z-form, compared to the B-structure, and that this difference in rates results mainly from a large decrease in the entropy of activation for Z-DNA.

DNA↗

Deuterium NMR in the solid-state and in solution of the molecular motion of the bases in poly(I) and poly(I) . poly(C).

To provide information regarding the conformational flexibility of nucleic acids, in particular the rate and amplitude of base motions, we have observed the deuterium NMR from single-stranded and double-stranded polynucleotides. Poly(I) was deuterated at the 8-position of the base, and the deuterium NMR was examined in solution (at 23.0 and 55.4 MHz) and for hydrated and dry fibers (at 23.0 MHz). In the solid state, the deuterium signal of dry poly(I) exhibits a powder pattern with the maximal expected quadrupolar splitting, while the relatively short spin-lattice relaxation time indicates the presence of a rapid internal reorientation of the C-D bond with an amplitude of that motion of at least +/- 2.4 degrees. Hydrating the poly(I) fibers to the extent of eight molecules of water per nucleotide results in the disappearance of the deuterium signal, apparently due to a decreased spin-spin relaxation time shorter than the instrumental dead-time (even using the quadrupolar echo technique); this could occur if conformational fluctuations are occurring at a rate comparable to the deuterium quadrupole interaction strength, i.e., 175 kHz. In solution, a theoretical fit to the measured Lorentzian linewidths and spin-lattice relaxation times necessitates the inclusion of at least two motional correlation times, with a subnanosecond internal motion. Double-stranded poly(I) . poly(C) yielded a solid state spectrum similar to poly(I), albeit with a longer T1, which reduced the lower limit for the amplitude of an internal motion to +/- 1.9 degrees. The 2H signal from the poly(I) . poly(C), hydrated to a degree of approx. eight molecules of water per base pair, retained its solid-state lineshape (with a reduced T1 value, indicating increased internal mobility of the bases with a lower limit on amplitude of +/- 4.7 degrees). In solution, however, the 2H-NMR signal from poly(I) . poly(C) became virtually undetectable, even in solid-echo experiments, when the echo was observed after 52 microseconds. This indicates that the spin-spin relaxation time of the deuterium nucleus must be close to its theoretical minimum of about 9 microseconds, and the correlation time for an isotropic reorientation of the C-D vector can be estimated to be between 0.2 and 200 microseconds.

Magnetic Resonance Spectroscopy↗

Structural and dynamic differences between supercoiled and linear DNA from proton NMR.

Proton NMR experiments on an intact plasmid supercoiled DNA molecule are reported. Spectra of the hydrogen-bonded exchangeable imino protons and nonexchangeable aromatic protons of pIns36 (7,200 base pairs; Mr 5 x 10(6)) were examined at 240 and 360 MHz. In contrast to linear DNA of comparable size in which the signals from these protons are broadened almost beyond detection, the supercoiled DNA exhibits a remarkably well-resolved spectrum in the range 12-15 ppm, with linewidths characteristic of linear DNA molecules with molecular weight nearly two orders of magnitude smaller. These results imply an extraordinary degree of mobility in accord with our earlier discovery of unusually long 31P spin-spin relaxation times in the supercoiled molecule. Alterations in the chemical shift of the imino proton resonance positions in supercoiled DNA compared to linear DNA imply that the structure is modified in the A . T base pairs with at least two distinct structures apparent from the spectrum. However, little or no alteration is evident in the resonances due to the G . C base pairs.

Animals↗

Thin-section MR imaging of rat brain at 4.7 T.

The brains of anesthetized 7-month-old male hooded rats were imaged in coronal, sagittal, and horizontal planes at 4.7 T. Images were obtained with a section thickness of 0.6 mm and in-plane pixel size of 0.18-0.20 mm, resulting in finer combined spatial and contrast resolution than in most previously published reports. This allowed detailed anatomic assignment of many brain structures on the basis of comparison with a histologic brain atlas. T1, apparent T2, and water proton density values of gray matter, white matter, and cerebrospinal fluid (CSF) were derived from saturation-recovery and multi-echo measurements. These values were used to calculate expected contrast-to-noise ratios as a function of TR and TE in spin-echo imaging sequences. The optimal simultaneous contrast between gray and white matter and between CSF and gray matter was obtained on images with moderate T2 weighing, with a TR of 3.6 seconds and a TE of 45 msec. The use of thin sections was found to be essential for resolving many fine structures, and the improved sensitivity provided by the high magnetic field strength was crucial for imaging such thin sections at adequate signal-to-noise ratios.

Animals↗

Correlation of MR imaging and histologic findings in mouse melanoma.

M2R melanoma tumors in male C57 black mice were used to correlate magnetic resonance (MR) images with the corresponding histologic slices and to determine if analysis of the achievable correlation can provide a basis for predicting gross histologic features with MR imaging alone. The MR imaging sections obtained at 4.7 T were each 680 microns thick, with an in-plane resolution of 195 microns. The distribution of melanin within the histologic slices correlated well with the high-signal-intensity regions on the T1-weighted images (T1WIs), while these regions had low signal intensity on the T2-weighted images (T2WIs), providing evidence that melanin or melanin-associated paramagnetic species are responsible for the observed proton relaxation rate enhancement. Viable melanoma cells typically showed intermediate signal intensity on T2WIs, T1WIs, and proton-density images. Necrosis typically had high signal intensity on T2WIs, T1WIs, and proton-density images. Quantitation of the MR imaging results, followed by statistical analysis, demonstrated statistically significant differences between melanin-rich, viable-melanoma, and necrotic regions on MR images.

Animals↗

The effects of simultaneous pulsing in different gradient coils on the nuclear magnetic resonance imaging of oblique slices.

The definition and mapping of oblique planes by magnetic resonance imaging (MRI) requires the simultaneous application of two or three orthogonal gradients to define the desired intermediate direction of the frequency encoding or "readout" gradient. Each of the three main gradient coils produces different patterns of eddy currents. Consequently, the application of dephasing and rephasing lobes of these gradients will produce echoes at slightly different times for each gradient. If two or three gradients are applied simultaneously to create an arbitrary view direction, the resulting echo will therefore be shifted in time and considerably reduced in intensity. In this article, we present an analysis of the behavior of the magnetization in a typical two-dimensional Fourier transform pulse sequence for the imaging of oblique slices. The theoretical displacements in time and reduction in intensity of the echo amplitudes are calculated and compared to the experimental behavior. We show that, in spite of this phenomenon, the final image suffers only marginally in signal-to-noise ratio, provided the slice width is small compared to the field of view. This is due to the fact that there always exists a cycle in the sequence in which the phase-encoding gradient almost completely compensates for the above described effect.

Humans↗