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Biomedical subjects

B R Persson

Publications and source records attributed to B R Persson.

At least 19 recordsLinked to original sources

Toward clinical application of prompt gamma spectroscopy for in vivo monitoring of boron uptake in boron neutron capture therapy.

In boron neutron capture therapy (BNCT) the absorbed dose to the tumor cells and healthy tissues depends critically on the boron uptake. Pronounced individual variations in the uptake patterns have been observed for two boron compounds currently used in clinical trials. This implies a high uncertainty in the determination of the boron dose component. In the present work a technique known as prompt gamma spectroscopy (PGS) is studied that potentially can be used for in vivo and noninvasive boron concentration determination at the time of the treatment. The technique is based upon measurement of gamma rays promptly emitted in the 10B(n,alpha)7Li and 1H(n,gamma)2D reactions. The aim of this work is to prepare the present setup for clinical application as a monitor of boron uptake in BNCT patients. Therefore, a full calibration and a set of phantom experiments were performed in a clinical setting. Specifically, a nonuniform boron distribution was studied; a skin/ dura, a larger blood vessel, and tumor within a head phantom was simulated. The results show that it is possible to determine a homogeneous boron concentration of 5 microg/g within +/-3% (1 standard deviation). In the nonuniform case, this work shows that the boron concentration can be determined through a multistep measurement procedure, however, with a somewhat higher uncertainty (approximately 10%). The present work forms the basis for a subsequent clinical application of the PGS setup aimed at in vivo monitoring of boron uptake.

Blood Vessels↗

Studies of in vivo electropermeabilization by gamma camera measurements of (99m)Tc-DTPA.

A protocol was developed to study the drug uptake from in vivo electropermeabilization at different settings of parameters influencing the uptake efficiency. Radiolabelled diethylenetriaminepentaacetic acid (DTPA) was used to trace the distribution and internalization of a hydrophilic drug after in vivo electropermeabilization. Skeletal muscle tissue in rat was treated with permeabilizing electric pulses before or after intravenous administration of (99m)Tc-DTPA. The drug accumulation in the treated volume was subsequently evaluated with a scintillation camera. The dependence of uptake on field strength and duration of the applied electric pulses was investigated for exponentially decaying pulses and square wave pulses. Further, the uptake dependence on time interval between injection and pulsation was studied as well as the uptake dependence on the number of pulses applied in a single electropermeabilization treatment. Dynamic gamma camera studies were performed to quantify the time scale of the drug uptake in electropermeabilized tissue.

Animals↗

Simplified treatment planning for interstitial laser thermotherapy by disregarding light transport: a numerical study.

BACKGROUND AND OBJECTIVE: The objective was to investigate the effect of light transport on the temperature distribution and the coagulated volume under conditions relevant to interstitial laser thermotherapy (ILT) of tumors in the human liver. STUDY DESIGN/MATERIALS AND METHODS: Temperature distributions and coagulated volumes produced with a diffusing laser fiber or a conductive heat source, at equal output power, were numerically calculated for tissue with different optical penetration depths. Four irradiation times (5, 10, 20, and 30 min) were studied. A three-dimensional finite-element model was used to calculate the temperature distribution during heating with four conductive heat sources (no light emission). Results were compared with measured temperature distributions during laser irradiation in a gel phantom with known optical properties. RESULTS: Numerical calculations showed that the influence of light transport on the coagulated volume was negligible in tissue with optical penetration depths below 3-4 mm at all studied irradiation times. The phantom experiment indicated good agreement with the calculated temperature distribution, both with a single diffusing laser fiber and with four fibers. CONCLUSION: Light transport influences coagulated volumes only slightly under conditions presented in this work, which is relevant to ILT of tumors in the human liver.

Culture Techniques↗

Feedback interstitial diode laser (805 nm) thermotherapy system: ex vivo evaluation and mathematical modeling with one and four-fibers.

BACKGROUND AND OBJECTIVE: In this study a newly developed microprocessor controlled power regulation and thermometry system integrated with a diode laser (805 nm wavelength) was evaluated with respect to temperature distribution, effectiveness of regulation, and ability to predict temperature distributions by computer simulation. STUDY DESIGN/MATERIALS AND METHODS: Experiments were performed in ground bovine muscle using either a single laser fiber or four-fibers. The target temperature at one (feedback) thermistor, placed 5 mm from one of the laser fibers, was set to 50 degrees C and was maintained by means of stepwise power regulation. The temperature distribution was monitored using multiple thermistor probes. A numerical model based on the bioheat equation was used to calculate the temperature distributions. RESULTS: Temperature regulation was excellent with a tendency towards better regulation in the four-fiber than in the single-fiber experiments. Agreement between calculated and measured temperatures was good. The coagulated (> 55 degrees C) and hyperthermic (> 45 degrees C) volumes were 6 and 10-11 times larger, respectively, with four-fibers than with a single fiber. CONCLUSION: It is concluded that the stepwise power regulation system was efficient in maintaining a stable target temperature. The results indicate that the system can produce lesion volumes adequate for treating a relatively large tumor in a single session and that computer simulation may be useful for predicting temperature distribution.

Animals↗

Thermal conductivity of uterine tissue in vitro.

Thermotherapy of the uterus has emerged as an alternative to hysterectomy in the treatment of menorrhagia, from whence it follows that the thermal properties of uterine tissue have become of importance. This study presents measurements of the thermal conductivity and the water content of uterine tissue in vitro. A steady-state thermal conductivity apparatus, based on the comparison of test samples with a material with known thermal conductivity, is described. Measurements were conducted on tissue samples from eleven patients, directly after hysterectomy. Samples with and without endometrium, as well as coagulated samples, were examined. The thermal conductivity of myometrial tissue was found to be 0.536 +/- 0.012 W m(-1) K(-1) (mean +/- 1 SD) and the corresponding water content was 81.2 +/- 1.5% (mean +/- 1 SD). Measurements on samples with both endometrium and myometrium showed similar thermal conductivity (0.542 +/- 0.008 W m(-1) K(-1), mean +/- 1 SD) and water content (81.6 +/- 0.7%, mean +/- 1 SD). It was also indicated that coagulation causes dehydration, resulting in a lower thermal conductivity.

Body Temperature↗

MRI thermometry in phantoms by use of the proton resonance frequency shift method: application to interstitial laser thermotherapy.

In this work the temperature dependence of the proton resonance frequency was assessed in agarose gel with a high melting temperature (95 degrees C) and in porcine liver in vitro at temperatures relevant to thermotherapy (25-80 degrees C). Furthermore, an optically tissue-like agarose gel phantom was developed and evaluated for use in MRI. The phantom was used to visualize temperature distributions from a diffusing laser fibre by means of the proton resonance frequency shift method. An approximately linear relationship (0.0085 ppm degrees C(-1)) between proton resonance frequency shift and temperature change was found for agarose gel, whereas deviations from a linear relationship were observed for porcine liver. The optically tissue-like agarose gel allowed reliable MRI temperature monitoring, and the MR relaxation times (T1 and T2) and the optical properties were found to be independently alterable. Temperature distributions around a diffusing laser fibre, during irradiation and subsequent cooling, were assessed with high spatial resolution (voxel size = 4.3 mm3) and with random uncertainties ranging from 0.3 degrees C to 1.4 degrees C (1 SD) with a 40 s scan time.

Animals↗

Quantification of low-velocity motion using a navigator-echo supported MR velocity-mapping technique: application to intracranial dynamics in volunteers and patients with brain tumours.

Gradient-echo pulse sequences with velocity-encoding gradients of 22.5-25 mT/m, were used for brain-motion and CSF-flow studies. To reduce motion artifacts, a phase-correction technique based on navigator echoes was evaluated. Three patients with right-sided parietal tumours were investigated; one astrocytoma grade III-IV, one astrocytoma grade I-II and one benign meningioma. In healthy volunteers, a maximal brain-tissue velocity of (0.94 +/- 0.26) mm/s (mean +/- 1SD) was observed, which is consistent with previously presented results. The phase correction was proven useful for reduction of artifacts due to external head movements in modulus and phase images, without loss of phase information related to internal motion. The tissue velocity within the astrocytomas was low during the entire cardiac cycle. An abnormally high rostral velocity component was, however, observed in the brain tissue frontal to the astrocytomas. In all patients, an abnormal CSF flow pattern was observed. The study of brain motion may provide further understanding of the effects of tumours and other pathological conditions in the brain. When considering intracranial motion as a source of error in diffusion/perfusion MRI, the present study suggests that a pathology can alter the properties of brain motion and CSF flow considerably, leading to a more complex impact on diffusion/perfusion images.

Adult↗

Endometrial destruction by hyperthermia--a possible treatment of menorrhagia. An experimental study.

BACKGROUND: Treatment of menorrhagia by heat-destruction of the endometrium, intended to be an alternative to hysterectomy, was investigated in an experimental study. METHOD: A specially designed catheter (CavatermTM) with a silicone balloon containing a self-regulating containing heating element is inserted into the uterus, filled with glycine to a pressure of around 180 mmHg and heated to about 75 degrees C. We investigated the treatment effect in vitro in five extirpated uteri (series A) and in vivo in three patients treated peroperatively just before hysterectomy, temperatures being monitored in the surrounding tissues (series B). In both series we monitored the following variables: heating-power, balloon-pressure, temperature of the heating element (around 85 degrees C) and the temperatures at five locations from top to bottom of the balloon surface. RESULTS: After 30 min in vitro treatment at 75 degrees C, the endometrium was partly destructed, and condensed. Histological examination showed smooth muscle cells to be destroyed to a depth of 2-5 mm close to the endometrium. With in vivo treatment for 30 min at a heating power of about 20 W (resulting in balloon surface temperatures of 58-65 degrees C), the increases in temperature of the surrounding tissue were too small to measure accurately (+/-1 degree C). Histological examination showed destruction of cells in the corpus uteri to a maximum depth of 8 mm. CONCLUSION: Findings in in vitro and in vivo experiments suggest that 30 min heating of the endometrium to 58-65 degrees C with an intrauterine silicone balloon filled with a liquid to a pressure of 180 mmHg exerts therapeutic effects on both endometrium and uterine cavity smooth muscle cells without damage to surrounding tissues.

Catheterization↗

A computer simulation program for MR imaging: application to RF and static magnetic field imperfections.

A computer simulation program capable of demonstrating various artifacts, such as image distortion caused by metallic implants in MR imaging, is presented. The structure of the program allows for the implementation of various imaging situations as long as spins only experience weak interaction, i.e., the Bloch equations are obeyed. The raw data are obtained by repeatedly applying the Bloch equations to the magnetization vector of each point of the simulated object, throughout the pulse sequence. With only a limited number of spins in each voxel, the effects of intravoxel dephasing and rephasing require special attention, and algorithms for this have been implemented.

Algorithms↗

A stochastic model for subcellular dosimetry in boron neutron capture therapy.

The therapeutic effectiveness of boron neutron capture therapy is highly dependent on the microscopic distribution of the administered boron compound. Two boron compounds with different uptake mechanisms in the tumour cells may thus cause effects of different degrees even if the macroscopic boron concentrations in the tumour tissue are the same. This difference is normally expressed quantitatively by the so-called relative local efficiency (RLE). In this work, a stochastic model for the subcellular dosimetry has been developed. This model can be used to calculate the probability for an energy deposition above a certain threshold level in the cell nucleus due to a single neutron capture reaction. If a threshold cell-kill function is assumed, and if the dose is low enough that multiple energy depositions are rare, the model can also be applied to calculations of the survival probability for a cell population. Subcellular boron distributions in rats carrying RG 2 rat gliomas were measured by subcellular fractionation after administration of two different boron compounds: a sulphydryl boron hydride (BSH) and a boronated porphyrin (BOPP). Based on these data, the RLE factors were then calculated for these compounds using the stochastic model.

Animals↗

Performance of sulfhydryl boron hydride in patients with grade III and IV astrocytoma: a basis for boron neutron capture therapy.

This study investigated the rationale of boron neutron capture therapy (BNCT) for the treatment of Grade III and IV astrocytoma. The European Community joint research program on BNCT plans to use sulfhydryl boron hydride (BSH) in clinical trials. The work presented here, examines the performance of BSH in eight patients with Grade III and IV astrocytoma using a measurement technique which precisely correlates the boron uptake with the histology of the tumor and the peritumoral brain. Astrocytomas are exceptionally heterogeneous and spread migrating tumor cells into the surrounding brain. The patients were infused with 50 mg BSH per kilogram of body weight at 12, 18, 24 or 48 hours before surgery. At the time of operation, specimens were obtained of the tumor, skin, muscle, dura, blood, urine, and, when surgically possible, the brain adjacent to tumor. In three patients the intracellular boron distribution was investigated by subcellular fractionation. The blood clearance was biphasic with half-lives of 0.6 and 8.2 hours. After 3 days, approximately 70% of the dose injected was excreted in the urine. The maximum boron concentration in the tumor was 20 ppm, 12 hours after the infusion. The tumor-to-blood ratios ranged between 0.2 and 1.4, with the highest values after 18 to 24 hours. In the brain specimens the boron concentration never exceeded 1 ppm. This work confirms a selective uptake of boron in the tumor compared to the surrounding brain and that boron, to some extent, is incorporated in the tumor cells.

Astrocytoma↗

A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model.

Boron neutron capture therapy is a treatment modality for cancer that depends on the specific uptake of boron by the tumor cells. The infiltrative growth of malignant gliomas requires that boron reach and accumulate in migrating cells outside the margin of the tumor; thus, it is important that the biodistribution of new boron compounds is also studied in the surrounding healthy brain tissue. This study is undertaken in the present work, in which the biodistribution and pharmacokinetics of sulfhydryl boron hydride (BSH) and boronated porphyrin (BOPP) in the RG2 rat glioma model are investigated. This model mimics the characteristics of human glioma with cells migrating into the surrounding brain. The animals were infused intravenously with either BSH (25 micrograms or 175 micrograms of boron per gram of body weight) or BOPP (12 micrograms of boron per gram body weight). For the low dose of BSH, the maximum tumor-boron content was 8 ppm at approximately 9 hours after the infusion with a tumor-to-blood ratio of 0.6. At the higher dose, the corresponding figures were 15 ppm after 12 hours with a tumor-to-blood ratio of 0.5. For BOPP, a tumor-boron concentration of 81 ppm was achieved 24 hours after the infusion and sustained in that range for at least 72 hours. The tumor-to-blood ratio at 24 hours was slightly above 6, but continued to increase as the blood was cleared. These results indicate that both compounds are spread into the normal brain tissue following the same pathways as the migrating tumor cells and in this way can be taken up even in distant tumor cell foci.

Animals↗

Permeability of the blood-brain barrier induced by 915 MHz electromagnetic radiation, continuous wave and modulated at 8, 16, 50, and 200 Hz.

Biological effects of electromagnetic fields (EMF) on the blood-brain barrier (BBB) can be studied in sensitive and specific models. In a previous investigation of the permeability of the blood-brain barrier after exposure to the various EMF-components of proton magnetic resonance imaging (MRI), we found that the exposure to MRI induced leakage of Evans Blue labeled proteins normally not passing the BBB of rats [Salford et al. (1992), in: Resonance Phenomena in Biology, Oxford University Press, pp. 87-91]. In the present investigation we exposed male and female Fischer 344 rats in a transverse electromagnetic transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse-modulated with repetition rates of 8, 16, 50, and 200 s-1. The specific energy absorption rate (SAR) varied between 0.016 and 5 W/kg. The rats were not anesthetized during the 2-hour exposure. All animals were sacrificed by perfusion-fixation of the brains under chloral hydrate anesthesia about 1 hour after the exposure. The brains were perfused with saline for 3-4 minutes, and thereafter fixed in 4% formaldehyde for 5-6 minutes. Central coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 microns. Albumin and fibrinogen were demonstrated immunohistochemically. The results show albumin leakage in 5 of 62 of the controls and in 56 of 184 of the animals exposed to 915 MHz microwaves. Continuous wave resulted in 14 positive findings of 35, which differ significantly from the controls (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

A current injecting device for electrical impedance tomography.

Electrical impedance tomography (EIT) has to be improved in order to become an accepted diagnostic technique in clinical use. The aim of this study is to improve the hardware of this technique and preferably upgrade the current injecting device. Instead of using a constant current generator the idea is to implement a voltage source and measure current accurately, in order to improve the resolution in the image. The performance of such a device is analysed, particularly concerning theoretical and practical limitations. The amplitude and phase accuracy, noise and settling time are measured and presented in diagrams. The results show that improvements are possible to achieve and that such a device will improve the stability of an EIT system and the image quality.

Electric Impedance↗

Enhanced boron uptake in RG 2 rat gliomas by electropermeabilization in vivo--a new possibility in boron neutron capture therapy.

Accumulation of boron in tumor tissue is an indispensable requirement for boron neutron capture therapy and it is important that the uptake is as high as possible. In this work we have studied the influence of electropermeabilization in vivo on the uptake of boron in normal and RG 2 glioma bearing Fischer 344 rats. Two different boron compounds, a sulfhydryl boron hydride (BSH) and a boronated porphyrin (BOPP), have been investigated. The rats were infused intravenously during 5 min with 175 micrograms BSH/g body weight or 12 micrograms BOPP/g body weight. Two electrodes were placed 5 mm apart in the brain and electropermeabilization was performed with eight square 400 V pulses at 4 and 7 min after the end of the infusion. After 6 h the animals were killed, and the boron content in the tumors and the surrounding brain was measured with neutron-activated autoradiography. In electropermeabilized healthy animals the BOPP uptake was low and limited to the electrode lesions, whereas BSH was spread extensively throughout the hemisphere. Rats with gliomas showed doubled (BOPP) to 10-fold (BSH) uptake of boron in the tumor when electropermeabilization was performed as compared with untreated animals. We conclude that electropermeabilization in the future may provide an interesting possibility to increase the uptake of certain boron compounds before neutron capture therapy.

Animals↗

A new brain tumour therapy combining bleomycin with in vivo electropermeabilization.

The potentials of in vivo electropermeabilization in combination with bleomycin in brain tumor treatment have been explored. In the brain of normal Fischer 344 rats, 2 electrodes were placed 5 mm apart. Electropermeabilization was performed with 8 to 12 exponential 400 V pulses with a time constant of 325 microseconds. Some animals were given bleomycin i.v., 1mg/kg b.w., 4 minutes before electric pulses delivery. No adverse effects were recorded during the observation of the animals during the following month. The effect of bleomycin and electropermeabilization upon tumour growth was studied in rats with glioma cells (RG2) implanted in the head of the right caudate nucleus. Treatment was given at different time intervals after the implantation of tumor cells and the effect upon survival was studied. Bleomycin alone did not prolong the survival of the animals. On the contrary, bleomycin plus electropermeabilization on the 10th, 11th or 12th day after inoculation increased the survival time to almost double that of untreated animals. We conclude that this treatment may be of value in brain tumour therapy.

Animals↗

Neutron capture imaging of 10B in tissue specimens.

Boron Neutron Capture Therapy (BNCT) is an attractive concept for radiation treatment of malignant tumours. The patients receive a 10B-carrying compound with selective uptake in tumour cells, after which they are irradiated with epithermal neutrons. Theoretically, the tumour cells are killed by the high-LET particles produces in 10B(n, alpha)7Li reactions inside or close to the cell nucleus, while healthy brain cells with no boron uptake will be spared. In practice, a successful BNCT depends on the actual boron-distribution in the tissue, and consequently a new boron-compound aimed for BNCT must undergo detailed bio-distribution studies before clinical trials. In experimental work there is accordingly a great need for methods for quantitative bio-distribution measurements in tissue samples. In this paper we present an improved technique for neutron activated autoradiography providing quantitative boron images of freeze-sectioned tissue specimens from highly malignant rat brain gliomas. Particular attention has been paid to the correlation with the morphology of the specimens and to the altered self-absorption properties due to freeze-drying. A self-absorption correction factor for tumour tissue has been experimentally determined.

Absorption↗