A versatile plutonium-238 irradiator for radiobiological studies with alpha-particles.

A versatile irradiator has been constructed for in vitro irradiation of mammalian cells with alpha-particles of well-defined energy, LET, direction, dose and dose rate. It is based on approximately 1.2 x 10(9) Bq of 238Pu (on a platinum disc) contained in a He-filled chamber. In a standard configuration, monolayers of cells grown in 10 Hostaphan-based dishes are irradiated with 3.26 +/- 0.22 MeV alpha-particles (LET 121 keV microns-1) at selectable dose rates from approximately 2 Gy min-1 down to less than 10(-4) Gy min-1 (i.e. fluence rates of 1 x 10(7) cm-2 min-1 to 3 x 10(2) cm-2 min-1). Single dishes can be irradiated at dose rates up to 24 Gy min-1 (fluence rate 1 x 10(8) cm-2 min-1). Incident energy and LET can be varied from 0.8 to 4.2 MeV and 266 to 102 keV microns-1, respectively. The irradiator has full incubation and gassing facilities for protracted irradiations. The irradiator is particularly suitable for in vitro analytical studies of the biological effects of alpha-particles of energies and LETs similar to those which cells may receive in vivo from radionuclides such as radon and the actinides. It has been used successfully for investigations of a variety of alpha-particle-induced effects in different cell types irradiated either as attached monolayers or as very thin suspensions.     

Some radiobiological consequences of mycoplasma contamination of mammalian cells in tissue culture

Cells of the mouse Ehrlich ascites carcinoma grown in vitro became contaminated with an arginine-splitting mycoplasma. The slopes of the radiation dose-survival curves of the contaminated cells, assayed by colony-forming ability, were extremely variable; eventually it became impossible to grow colonies at all. Experiments on the feeder cell requirement showed that, whereas for clean cells the maximum plating efficiency was obtained within a range of 5 X 10(4) and 4 X 10(5) feeder cells in a 5 cm dish, contaminated cells would only produce colonies in the presence of between 10(4) and 3 X 10(4) feeder cells. Doubling the concentration of arginine in the medium allowed contaminated cells to grow with maximum plating efficiency within an increased range of 10(4) and 4 X 10(5) feeder cells. The mycoplasmas were apparently behaving as feeders, reducing the requirement for added feeder cells, but also depleting the medium of essential arginine. The cells were eventually decontaminated by passing them through a mouse as an ascites tumour.     

A time encoding method for single-shot imaging

A new 2D single-shot imaging technique is introduced that uses only one dimension of Fourier encoding. The second dimension is encoded in time, rather than using phase encoding. The data is acquired in the form of a closely spaced echo train with each echo produced from a different physical line in the object. A 1D Fourier transform is applied to each echo for image reconstruction. Because only the desired lines are excited, there can be no aliasing in the time encoding direction even when the object is much larger than the field of view. This technique is also very insensitive to motion, as motion-related artifacts do not propagate in the time encoding direction.     

Initial feasibility studies using single-shot EPI for the detection of focal liver lesions

Echo planar MR imaging (EPI) has been developed to completely eliminate motion artifacts and is currently being prepared for implementation into clinical MR systems. Thus, the purpose of this study was to evaluate the clinical utility of EPI in the detection of focal liver lesions and to compare EPI with contrast-enhanced CT. EPI studies were performed on an experimental 1.0 Tesla whole body system using fat-suppressed single-shot spin echo (SE) and inversion recovery (IR) pulse sequences. A total of 26 liver tumors in 12 patients scheduled for liver resection were prospectively examined and correlated with intraoperative ultrasound, surgery, and pathology as the gold standard. Quantitative analysis of EPI was performed by means of liver signal-to-noise and tumorliver contrast-to-noise calculations. Diagnostic performance compared with contrast-enhanced CT was assessed by means of ROC analysis. Lesion-liver contrast was highest with EPI SE at a TE-time of 70 ms and this technique showed best lesion detectability as measured by area under curve (AUC) values. Among EPI techniques, the IR sequence with an inversion time of 300 ms to null the liver signal showed high lesion-liver contrast but all four reviewers reported problems assessing liver anatomy. Improved EPI techniques may prove useful for screening of focal liver lesions.     

A perfusion technique for 13C NMR studies of the metabolism of 13C-labeled substrates by mammalian cells

We describe an improved perfusion system designed for NMR studies with 13C-labeled metabolites. Using this system we have monitored the uptake and metabolism of [13C]acetate and [13C]glucose in pooled human lymphocytes cast in an agarose gel thread.     

An electrocardiograph-respiration gating device for MR studies.

A versatile gating device for magnetic resonance (MR) spectroscopy and imaging is presented. The device uses electrocardiograph (ECG) and respiration signals as input, applies appropriate signal conditioning, and generates control signals for ECG, respiration, or combined gating studies. In the combined ECG and respiration mode, in conjunction with a proper MR pulse program, one can acquire MR data gated by the ECG signal within a selected window of the respiration cycle, while maintaining a steady level of magnetization saturation during the remainder of the respiration cycle, by gating the radio-frequency excitation with the ECG while inhibiting data acquisition.     

The radiobiological and physical basis for radiotherapy with protons and heavier ions

Heavy charged particles exhibit a superior dose distribution compared to all conventionally used beams. The small lateral and range straggling, combined with an increase of the dose deposition with increasing penetration depth enables the production of dose profiles shaped precisely to the contours of the treatment volume. In addition, heavy ion beams exhibit an elevated biological efficiency close to the end of the particle range. Therefore, beams of heavy ions deliver a high physical dose combined with a high biological efficiency to a tumor volume while the surrounding healthy tissue is maximally spared.     

Labelling of mammalian cells for visualisation by MRI

Through labelling of cells with magnetic contrast agents it is possible to follow the fate of transplanted cells in vivo with magnetic resonance imaging (MRI) as has been demonstrated in animal studies as well as in a clinical setting. A large variety of labelling strategies are available that allow for prolonged and sensitive detection of the labelled cells with MRI. The various protocols each harbour specific advantages and disadvantages. In choosing a particular labelling strategy it is also important to ascertain that the labelling procedure does not negatively influence cell functionality, for which a large variety of assays are available. In order to overcome the challenges still faced in fully exploiting the benefits of in vivo cell tracking by MRI a good understanding and standardisation of the procedures and assays used will be crucial.     

A ventilatory assistance device for use with Technegas.

The demand for high-quality ventilation imaging of the lungs has resulted in the advent of Technegas, which has proven its superiority to the more conventional agents in a number of clinical trials. Images of similar diagnostic quality have been difficult to obtain in patients who are uncooperative, intubated or very young. With this problem as the impetus, a ventilatory assistance device (VAD) was designed to exploit the superior imaging qualities of Technegas. The Technegas generator was interposed between the patient and the VAD, allowing the controlled movement of Technegas into the patient from the generator. Utilizing this device, the problems of increased dead space, turbulent gas flow and possible contamination were circumvented. Twenty patients, comprising nine children and eleven adults, were studied for various indications including assessment of pulmonary parenchymal disease, suspected pulmonary embolism and the lung clearance of modified Technegas. In all cases, images of diagnostic quality were obtained with ease, facilitating relevant clinical decision making. We conclude from this preliminary appraisal that the VAD is a simple, safe addition to the Technegas generator for imaging a group of patients in whom images of diagnostic quality have traditionally proven difficult to obtain.     

A partially biodegradable material device for repair and reconstruction of injured tendons. Experimental studies

We assessed the applicability of a partially biodegradable synthetic material composed of polyglycolic acid (PGA) and dacron to repair or replace severely injured tendons. Adult rabbits underwent complete laceration and repair of one Achilles tendon. Group 1 (N = 8) had end to end tenorrhaphy with size 0 braided polyester suture, and Group 2 (N = 16) tendons were similarly repaired with the bicomposite designed PGA-dacron device. Group 3 (N = 16) received laceration and removal of 1 cm of tissue, and the defect was bridged with the same PGA-dacron material. No postoperative immobilization was applied. Evaluation, consisting of biomechanical testing or histologic inspection, was done at 4 and 8 weeks after tenorrhaphy. All tendons healed, and at 8 weeks the mean maximum load at failure of the repaired tendons was 32.2 +/- 3.4 kgf, 40.3 +/- 2.4 kgf, and 31.8 +/- 3.2kgf for Groups 1, 2, and 3, respectively. Values between groups were not significantly different, but all were significantly less (P less than or equal to 0.05) than the strength of the unoperated control tendons (55.8 +/- 7.2 kgf). The most noteworthy finding was the lengthening of the repaired tendons, due to scar elongation at the tenorrhaphy site, that occurred during healing as determined by a landmark placed a fixed distance proximal to the repair site. Group 1 tendons lengthened 22 mm, while Group 2 and 3 tendons increased by 12.5 mm. Histologically, fibrous tissue ingrowth into the residual dacron scaffold occurred, but it was inconsistent and inadequate in quality and quantity to be satisfactory as neotendon. The fibrous tissue did not mature or align in response to load. We concluded that the PGA-dacron material had adequate strength and physical properties to use both for primary tenorrhaphy and to bridge the tendon defect. However, in our experience this material lacks any significant advantage over other materials available or known to be under evaluation to support neotendon formation when an actual soft tissue defect exists.