Biomedical subjects

P Bendel

Publications and source records attributed to P Bendel.

At least 19 recordsLinked to original sources

PubMed2006

Subarachnoid hemorrhage is followed by temporomesial volume loss: MRI volumetric study.

OBJECTIVE: To assess whether subarachnoid hemorrhage (SAH) and its treatment is followed by volume loss in temporomesial structures. METHODS: One hundred fifty-five consecutive patients with aneurysmal SAH were randomly assigned to surgical or endovascular treatment. Volumetric MRI was performed in 77 SAH patients with good or moderate clinical outcome 1 year after hemorrhage. A comprehensive neuropsychological test battery was used to evaluate the cognitive performance of the subjects. Thirty healthy individuals were imaged as MRI controls. RESULTS: The normalized hippocampal (HC) volumes were 24.7/23.7 (right/left), and the amygdaloid (AM) volumes were 21.0/20.5 in the matched control population. In SAH patients, the corresponding volumes were smaller, HC 23.2/21.3 (p = 0.072/0.002) and AM 18.4/18.7 (p = 0.012/0.045). In addition, the AM ipsilateral to the ruptured aneurysm was smaller in patients who had undergone surgical treatment (15.7) vs endovascular treatment (20.3; p < 0.001). Treatment modality did not significantly affect the measured HC volumes. The hippocampal but not amygdaloid volumes correlated with the scores of several neuropsychological tests. CONCLUSION: Subarachnoid hemorrhage and its treatment may be followed by atrophy in temporomesial structures. A clear correlation was demonstrated between neuropsychological performance and reduced temporomesial volumes.

Atrophy↗

PubMed2003

Observation of electro-osmotic flow echoes in porous media by nuclear magnetic resonance.

A method for assessing the time reversibility of molecular displacements in fluids is presented. The method utilizes pulsed field gradient NMR experiments, in which the flow driving force is inverted during the magnetization lifetime in each measurement cycle. The method is suitable for opaque three-dimensional systems and short displacements, and provides inherent separation between thermal diffusion and displacements driven by externally controlled forces. This approach was applied to study the time reversibility of an electric-field-driven flow of water in natural sand samples, over time scales of up to 0.4 s and displacement scales of the order of one particle diameter. It is demonstrated that the intensity loss of the NMR signal, caused by flow-induced phase dispersion, is fully refocused upon inversion of the polarity of the applied electric field, resulting in flow echoes.

Journal Article↗

PubMed2001

Significant differences in the retention of the borocaptate monomer (BSH) and dimer (BSSB) in malignant cells.

The (10)B enriched form of Na(2)B(12)H(11)SH (BSH) is used in a binary cancer radiation treatment, known as boron neutron capture therapy (BNCT). The BSH anion can also form a dimer, [B(24)H(22)S(2)](4-) (BSSB), previously used in animal model studies. It is demonstrated here that the retention of BSSB in mouse M2R melanoma and rat C6 glioma cells is significantly longer than that of the monomer BSH. The washout of the BNCT agents from cultured cells was followed using (11)B nuclear magnetic resonance spectroscopy. One hour after switching to boron-free culture medium, the relative amount of BSSB retained in M2R cells was at least about six times higher than that of BSH. The initial washout rate (over the first approximately 4 h) of BSSB was 4x10(-3) min(-1) (t(1/2), approximately 3 h) for M2R cells, and of the same order of magnitude for glioma cells.

Animals↗

PubMed2001

In vivo imaging of the neutron capture therapy agent BSH in mice using (10)B MRI.

Boron neutron capture therapy (BNCT) is an experimental cancer treatment modality requiring the targeting of (10)B-enriched compounds to the tumor, which is then irradiated by low-energy neutrons. One of the boron-containing compounds used for this purpose is the mercaptoborane Na(2)B(12)H(11)SH (BSH). The first in vivo MR images of (10)B-enriched BSH are presented here. BSH, injected into the tail vein of mice with implanted M2R melanoma xenografts, was imaged using 3D gradient echo (10)B MRI. (10)B NMR spectroscopy, localized mainly to the tumor by virtue of the use of a small surface coil, was applied to measure the T(1) (2.9 +/- 0.3 ms) and T(2) (1.75 +/- 0.25 ms) values of the (10)B signal. The MRI experiments detected levels of about 20 ppm (microg boron / g tissue) at 6 x 6 x 6 mm spatial resolution in a total scan time of 16 min. Magn Reson Med 46:13-17, 2001.

Animals↗

PubMed2001

Magnetization transfer and double-quantum filtered imaging as probes for motional restricted water in tulip bulbs.

Parameter sensitive MRI experiments were performed on tulip bulbs before and after storage at two different temperatures, 4 degrees C (chilled), and 20 degrees C (non-chilled). Quantitative measurements of the amount of magnetization transfer (MT) in the storage scales of the bulbs, were compared to the average values of the relaxation rates R(1) and R(2), and the apparent normalized spin density (NSD). At the end of the storage period, bulbs were also scanned using 1H double quantum (DQ) filtered imaging. Both MT and DQ filtered imaging revealed significant differences between chilled and non-chilled bulbs, which were consistent with the differences observed in the average values of NSD, R(1,) and R(2.) The results indicated a smaller fraction of solid protons (e.g., starch, sugars, and possibly bound water), or less contact between these solid protons and (free) water in the storage scales of the chilled bulbs, after 8 weeks of storage at low temperature.

Cold Temperature↗

PubMed2001

Optimal detection of the neutron capture therapy agent borocaptate sodium (BSH): a comparison between 1H and 10B NMR.

Boron Neutron Capture Therapy (BNCT), an experimental binary cancer treatment modality, requires selective targeting of 10B containing compounds to tumors. One of the compounds under evaluation in an EORTC phase I trial, and used in Japan for patient treatments for many years, is borocaptate sodium (BSH, also known as sulfhydril boron hydride). To optimize the clinical applications, a noninvasive method is needed to monitor the distribution of the boron compound, and NMR may offer such a possibility. A comparison between the relative sensitivities for detecting BSH by 10B or 1H NMR was conducted at two magnetic field strengths: 2 and 4.7 T. At each field strength, similar-sized radio frequency (rf) coils were used for both nuclei. Theoretical predictions for the intrinsic signal to noise (S/N) advantage of 1H over 10B detection vary between a factor of 5.4 and a factor of 28.9, depending on whether the effective resistance is dominated by coil losses or sample losses. Our tests, conducted on relatively small aqueous samples, which loaded the coils less than expected for animal or human subjects, resulted nevertheless in advantage factors close to the lower limit of this range. The measured S/N detection advantage factors for 1H were about 5.2 at 4.7 T, using a dedicated 1H coil, and 7.7 at 2 T, where the measurements were conducted with a double-tuned coil. However, when predicting the expected performance for in vivo MRS or MRI, one should bear in mind that proton detection has to be conducted by spectral-editing pulse sequences with an inherent S/N loss by at least a factor of 2, and that the T1 relaxation time for 10B in BSH is about 30 times shorter than the 1HT1 value. In view of these considerations, direct 10B detection could well be the preferred strategy for MRI/MRS of BSH in vivo.

Biophysical Phenomena↗

PubMed2001

Antivascular treatment of solid melanoma tumors with bacteriochlorophyll-serine-based photodynamic therapy.

We describe here a strategy for photodynamic eradication of solid melanoma tumors that is based on photo-induced vascular destruction. The suggested protocol relies on synchronizing illumination with maximal circulating drug concentration in the tumor vasculature attained within the first minute after administrating the sensitizer. This differs from conventional photodynamic therapy (PDT) of tumors where illumination coincides with a maximal concentration differential of sensitizer in favor of the tumor, relative to the normal surrounding tissue. This time window is often achieved after a delay (3-48 h) following sensitizer administration. We used a novel photosensitizer, bacteriochlorophyll-serine (Bchl-Ser), which is water soluble, highly toxic upon illumination in the near-infrared (lambda max 765-780 nm) and clears from the circulation in less than 24 h. Nude CD1 mice bearing malignant M2R melanotic melanoma xenografts (76-212 mm3) received a single complete treatment session. Massive vascular damage was already apparent 1 h after treatment. Changes in vascular permeability were observed in vivo using contrast-enhanced magnetic resonance imaging (MRI), with the contrast reagent Gd-DTPA, by shortening spin-spin relaxation time because of hemorrhage formation and by determination of vascular macromolecular leakage. Twenty-four hours after treatment a complete arrest of vascular perfusion was observed by Gd-DTPA-enhanced MRI. Histopathology performed at the same time confirmed primary vascular damage with occlusive thrombi, hemorrhage and tumor necrosis. The success rate of cure of over 80% with Bchl-Ser indicates the benefits of the short and effective treatment protocol. Combining the sensitizer administration and illumination steps into one treatment session (30 min) suggests a clear advantage for future PDT of solid tumors.

Animals↗

PubMed2000

Developmental changes and water status in tulip bulbs during storage: visualization by NMR imaging.

Magnetic Resonance Imaging (MRI) and light and scanning electron microscopy (SEM) were used to follow time-dependent morphological changes and changes in water status of tulip bulbs (Tulipa gesneriana L., cv. 'Apeldoorn') during bulb storage for 12 weeks at 20 degrees C (non-chilled) or 4 degrees C (chilled) and after planting. MR images reflecting the water content, the relaxation times T1 and T2 (or their reciprocal values, the relaxation rates R1 and R2), and the apparent self-diffusion coefficient of water molecules (ADC), were obtained for intact bulbs. After planting, scape elongation and flowering occurred only in chilled bulbs, while elongation in non-chilled bulbs was retarded. Microscopic observations showed different structural components and high heterogeneity of the bulb tissues. MRI revealed the elongation of the flower bud during storage, which was significantly faster in the chilled bulbs. In addition, MRI demonstrated a redistribution of water between different bulb organs, as well as significant differences in the pattern of this redistribution between the chilled and non-chilled bulbs. Generally, R2 relaxation rates became faster in all bulb organs during storage. At the same time, ADC values remained constant in the chilled bulbs, while exhibiting a significant increase in the non-chilled bulbs.

Magnetic Resonance Imaging↗

PubMed2000

Uptake and washout of borocaptate sodium and borono-phenylalanine in cultured melanoma cells: a multi-nuclear NMR study.

The cellular uptake and washout of the two principal boron neutron capture therapy (BNCT) agents, borocaptate sodium (BSH) and borono-phenylalanine (BPA), were monitored on-line, noninvasively, using nuclear magnetic resonance (NMR) spectroscopy. The uptake and washout of inorganic borate (B(i)) was also followed for comparison. M2R mouse melanoma cells grown on polystyrene microspheres were perfused inside the NMR sample tube. (11)B NMR was used to detect the presence of B(i), BSH and BPA, and (19)F NMR was applied to detect fluorinated BPA ((19)F-BPA). The results revealed chemical modifications of BSH due to spontaneous formation of the borocaptate dimer, BSSB, in the culture medium. BPA readily formed a complex with glucose contained in the culture medium but was also converted in the cells to a yet unidentified compound in a reaction that probably involves the hydrolysis of BPA and the release of B(i). The cellular accumulation ratio for BPA was significantly higher than 1 and was also significantly higher than that for BSH. On the other hand, the cellular retention time observed for BSH was much longer than for BPA, indicating a strong trapping of BSH in cells.

Animals↗

PubMed1999

Line narrowing of I = 12 spins coupled to quadrupolar nuclei in liquids: effects of weak decoupling fields

In this paper an exact description of the observed transverse magnetization of spin 12 nuclei, coupled to quadrupolar spins which are subjected to RF irradiation, is presented. It is shown that for on-resonance CW decoupling at weak to intermediate irradiation levels, the transverse decay of the spin 12 magnetization is modulated with a period of 1/nu(2), where nu(2) is the amplitude of the decoupling irradiation. When the spin 12 signal is created as a spin echo, and the quadrupolar resonance continuously irradiated during the echo evolution, the echo amplitudes experience much stronger modulation with period 2/nu(2). In previous treatments of such spin systems, the regime of weak decoupling power was usually neglected, and approximate analytical expressions seeking to define the "adequate" or "minimal" decoupling power, necessary to achieve the collapse of the spin 12 multiplet into a single narrow line, were derived. It is demonstrated here, both by experiments and by simulations using a full Redfield formalism, that simple analytical predictions for the T(2) decay of the spin 12 magnetization are still possible, even when the scalar relaxation is not in the "fast exchange" limit and the transverse decay is considerably modulated due to insufficient decoupling power. In this case, the expected single exponential decay rate is obtained for the nonmodulated component of the signal. The theoretical solution for spin I = 12 coupled to S = 3 is derived, and results for the proton decay in (10)B-enriched sodium borocaptate in aqueous solution are presented. The effects of irradiation by several composite pulse decoupling sequences are also considered. Copyright 1999 Academic Press.

Journal Article↗

PubMed1998

Altered brain glucose metabolism in transgenic-PFKL mice with elevated L-phosphofructokinase: in vivo NMR studies.

The gene for the liver-type subunit of phosphofructokinase (PFKL) resides on chromosome 21 and is overexpressed in Down syndrome (DS) patients. Transgenic PFKL (Tg-PFKL) mice with elevated levels of PFKL were used to determine whether, as in DS, overexpression of PFKL was also associated with altered sugar metabolism. We found that Tg-PFKL mice had an abnormal glucose metabolism with reduced clearance rate from blood and enhanced metabolic rate in brain. Transgenic-PFKL mice exhibited elevated activity of phosphofructokinase in both blood and brain, as compared to control non-transgenic (ntg) mice. Following glucose infusion, the rate of glucose clearance from the blood of Tg-PFKL mice was significantly slower than that of control ntg mice, although the basal blood glucose levels were similar. However, unlike the slower rate of glucose metabolism in blood, the initial rate of glucose utilization in the brain of the transgenic mice, was 58% faster than in control ntg mice. This was determined by infusion of [1-13C]-glucose followed by in vivo nuclear magnetic resonance (NMR) measurements of brain glucose metabolism. The faster utilization of glucose in Tg-PFKL brain is similar to the increased rate of cerebral glucose metabolism found in the brain of young adult DS patients, which may play a role in the etiology of their cognitive disabilities.

Animals↗

PubMed1998

Boron-11 NMR of borocaptate: relaxation and in vivo detection in melanoma-bearing mice.

Longitudinal and transverse relaxation rates for the 11B resonances in sodium borocaptate (BSH) at varying concentrations were measured in undiluted horse serum in a 4.7 Tesla field. The results could be fit by a model that assumes fast exchange of the BSH molecule between a free and a bound state, using values of 0.77+/-0.7 MHz for the 11B quadrupole coupling constant and (6.3+/-0.9) x 10(-9) s for the rotational correlation time in the bound state. These results were used as a basis for assessing the requirements and limitations of quantitative determination of BSH concentrations in vivo, using 11B NMR. Surface coil 11B NMR spectroscopy was performed on a total of 14 mice injected with BSH. Some of the animals (n=9) had implanted M2R melanoma tumors grown to various sizes in the rear thigh, in which case the surface coil was placed against the tumor, whereas for the other animals (without tumor), the coil was placed against the rear thigh muscle. NMR spectra were acquired under fully relaxed conditions. The spectra were quantitated by peak integration; apparent absolute BSH concentrations were derived by comparison with spectra from a phantom with known BSH concentration, using extrapolation of the time-domain data to zero preacquisition delay. The results indicate significantly higher 11B BSH signal intensities in tumors, compared with muscle tissue, whereas the uptake and clearance kinetics were similar.

Algorithms↗

PubMed1998

Choline metabolism in breast cancer; 2H-, 13C- and 31P-NMR studies of cells and tumors.

Choline metabolism in breast cancer cells and tumors has been investigated by multinuclear NMR in order to provide the biochemical basis for the presence of high phosphocholine in breast carcinoma relative to benign breast tumors and normal breast tissue. Choline was found to be transported into MCF7 human breast cancer cells and rapidly phosphorylated to phosphocholine which was then accumulated in the cells to high concentrations. The increased level of phosphocholine did not affect the rate of synthesis of phosphatidylcholine, indicating tight regulation of this pathway. The incorporation of [1,2-13C]choline (100 microM) into phosphocholine and phosphatidylcholine after 24 h was 69.5 and 36% of the total respective pools. Incorporation of 2H9-choline to tumors implanted in nude mice was achieved by infusing the deuterated choline to the blood circulation. The metabolism of deuterated choline was then monitored by 2H localized MRS. The blood level of choline before the infusion was 58.6 +/- 10.3 microM (measured by 1H-NMR of plasma samples) and increased approximately 5-fold during the infusion (measured by 2H-NMR). This increase in the blood level resulted in a gradual increase of a signal at 3.2 ppm due to deuterated choline metabolites. It appears that the increased availability of choline in the blood circulation leads to accumulation of phosphocholine in the tumors by the same mechanism as in the cells.

Animals↗

PubMed1997

Quantitative diffusion imaging in implanted human breast tumors.

Quantitative diffusion measurements were performed in tumors arising from inoculation of nude mice with two human breast cancer cell lines (MCF7 and T47D) to evaluate the specificity of this technique for characterizing solid tumors. ADC maps were compared to histology and correlated well with gross tumor morphology. Measured ADCs were highly specific for viable and necrotic tumor in the five T47D tumors included in this study (P < 0.02), while only two of the five MCF7 tumors studied developed distinguishable areas of necrosis. No statistically significant difference was observed in ADCs from viable tumor between the different cell lines (P > 0.05).

Animals↗

PubMed1997

Quadrupolar relaxation of spin 3 in the intermediate omega0tauc regime

The equations for the quadrupolar relaxation of spin 3 were derived for the Redfield limit where the molecular reorientation rate is much faster than the size of the quadrupolar interaction. In the extreme narrowing regime (omega0tauc << 1), the results converge to the analytical expressions for the relaxation rates available in the literature. For slower motions, both longitudinal (spin-lattice) and transverse (spin-spin) relaxations are described by a superposition of three exponentials, where both the rates themselves and their relative weights are functions of omega0tauc. Numerical calculations of the relevant relaxation parameters in the intermediate omega0tauc regime are presented. Spin-lattice relaxation is described to very good approximation by a single exponential for all values of omega0tauc, with the weight of the dominant decay mode exceeding 0. 97 for the entire range. The predictions of these simulations were found to be in good agreement with experimentally measured relaxation rates of the 10B resonances in the sodium salt of Na2B12H12S, mercaptoundecahydro-closo-dodecaborane (sodium borocaptate or BSH) dissolved in glycerol, determined at omega0 = 53. 73 MHz, between temperatures of 268 and 323 K. The fit to the experimental results yielded a value of 1.25 MHz for the average 10B quadrupolar coupling constant in this molecule. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

PubMed1997

The role of boron MRI in boron neutron capture therapy.

Boron magnetic resonance imaging (MRI) and spectroscopy (MRS) are being developed for use in boron neutron capture therapy (BNCT). With continued development, boron MRI may be used to locate BNCT agents in vivo, evaluate the pharmacokinetics of BNCT agents, and aid in treatment planning.

Animals↗

PubMed1996

The ontogeny of a neurotoxic lesion in rat brain revealed by combined MRI and histology.

We have used magnetic resonance imaging (MRI) of the living rat brain to longitudinally analyze the ontogenesis of an ibotenic acid lesion targeted at the piriform cortex. The MRI data were systematically compared with data obtained from a battery of histopathological techniques, including Nissl stain, hematoxylin stain, and a stain for cytochrome oxidase activity. Two days after the lesioning, widespread and heterogeneous damage was detected in, around and distant from the toxin-targeted area. Some damage apparently diminished within approximately 10 days, whereas other damage remained throughout the length of this study (60 days). We found that the small-animal MRI technology used by us is useful in determining the initial, transient impact of surgery and neurotoxic lesioning, and in delineating the gross effects of the lesion over time. This is particularly useful for early elimination of animals from the protocol of physiological and behavioral experiments in which the lesion exceeds the target area. Our data also indicate that, in order to avoid confounding effects of transient post-lesioning phenomena, behavioral and physiological tests should be carried out in neurotoxically lesioned animals > 2 weeks after infliction of the lesion.

Animals↗

PubMed1994

In vivo detection of a boron-neutron-capture agent in melanoma by proton observed 1H-10B double resonance.

The Cesium salt of BSSB (Cs4B24H22S2), a common boron-neutron-capture-therapy (BNCT) agent, was injected into M2R mouse melanoma xenografts, and detected in vivo by 1H-observed, 10B-edited NMR spectroscopy. The technique of spin-echo difference spectroscopy, in which a proton spin-echo is detected following the alternating presence and absence of a 10B 180 degrees pulse was used. This method provides much higher sensitivity than direct 10B NMR detection, and should thus be suitable for in vivo detection in patients about to undergo BNCT treatment, where the infused agents are 95% isotopically enriched in 10B.

Animals↗