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Miniature end-plate potentials in rat skeletal muscle poisoned with botulinum toxin.

Spontaneous transmitter release, recorded as miniature end-plate potentials (m.e.p.p.s), was studied in rat extensor digitorum longus (e.d.l.) and soleus muscles partially or completely paralysed by botulinum toxin type A (BoTx). Normal unpoisoned muscles were examined for comparison. Analysis of m.e.p.p.s in both normal and BoTx-poisoned muscles confirmed the presence of two populations of potentials. One population, which comprised about 96% of the m.e.p.p.s recorded at non-poisoned end-plates, was characterized by a uniform time course and a mean time-to-peak of 0.5-0.7 ms. These potentials had a shape and time-to-peak similar to that of quantal end-plate potentials (e.p.p.s) evoked by nerve stimuli. These were designated 'fast m.e.p.p.s'. The other population of m.e.p.p.s was characterized by a slower, more variable rise-time, the time-to-peak exceeding 1.1 ms, and generally a larger amplitude. These were designated 'slow m.e.p.p.s'. In both partial and complete paralysis by BoTx the frequency of fast m.e.p.p.s was reduced by more than 90% and the reduction lasted several weeks. After 6-10 days of poisoning the frequency of slow m.e.p.p.s gradually increased. The highest frequency of slow m.e.p.p.s (0.4 Hz) was recorded in the partially paralysed soleus muscle, the frequency being about ten times that at unpoisoned end-plates. In both partially paralysed muscles slow m.e.p.p. frequency returned towards normal 28 days after poisoning. A significant correlation (r = 0.67) was observed between the quantal content of e.p.p.s and the frequency of fast m.e.p.p.s in partially paralysed e.d.l. muscles. No significant correlation was observed between quantal content of e.p.p.s and the frequency of slow m.e.p.p.s. To further study if muscle activity influenced the appearance of slow m.e.p.p.s, partially paralysed soleus muscles were directly stimulated in vivo during the first 11-13 days following BoTx poisoning, using a stimulation pattern which inhibits nerve terminal sprouting and the appearance of denervation changes. This procedure did not alter the frequency of slow m.e.p.p.s as compared to unstimulated poisoned controls. It is concluded that enhancement of slow m.e.p.p. frequency in muscles poisoned with BoTx is related to the blockade of evoked Ca2+-dependent quantal transmitter release. However, additional factors influence this type of spontaneous and Ca2+-insensitive release of acetylcholine since there is a great variability between fibres and a time lag between the disappearance of fast m.e.p.p.s and the activation of slow m.e.p.p. frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Miniature and evoked inhibitory junctional currents and gamma-aminobutyric acid-activated current noise in locust muscle fibres.

gamma-Aminobutyric acid (GABA) current noise and inhibitory junctional currents (i.j.c.s) have been examined to give properties of the GABA receptor and its associated synaptic channel. Various procedures were used to identify muscle bundles receiving inhibitory innervation. In normal bathing medium the decay time constant of the i.j.c. was tau i.j.c. = 7.6 +/- 0.7 ms (clamp potential, Vm = -80 mV; temperature, T = 21 degrees C). Most muscle fibres were sensitive to ionophoretically applied GABA, irrespective of the presence of inhibitory innervation. GABA current noise obtained at junctional sites gave spectra which were fitted usually with a single Lorentzian component, or occasionally with the sum of two Lorentzians. The conductance of the single inhibitory channel was, gamma (GABA) = 21.6 +/- 0.9 pS (Vm = -80 mV; T = 21 degrees C). The mean 'burst length' of the openings produced by a single receptor activation was tau noise = 4.0 +/- 0.8 ms, at Vm = -80 mV. This decreased exponentially with hyperpolarization. On average tau i.j.c. exceeded tau noise although good agreement was found in some fibres. I.j.c.s were examined in greater detail after excitatory synaptic receptors had been desensitized with 10(-3) M-L-glutamate to abolish all excitatory synaptic activity. Their decay time constant was tau i.j.c. = 7.2 +/- 0.4 ms, and their rise time was 3.3 +/- 0.12 ms, at Vm = -80 mV. An e-fold decrease in tau i.j.c. resulted from a 103 +/- 7.9 mV hyperpolarization; time to peak showed a smaller dependence on Vm. The mean size of the inhibitory quantal event (i.e. response to a single transmitter packet) was estimated from fluctuations in i.j.c. amplitude. Mean quantal content of the i.j.c. was about 30 at normal levels of release. Mean amplitude of the directly measured miniature i.j.c. = 0.65 +/- 0.08 nA at Vm = -80 mV (V eq approximately equal to -40 mV). The amplitude of the quantal event showed a non-linear dependence on Vm. The burst length of the inhibitory channel, produced by a single receptor activation, is longer in duration (at -80 mV) and exhibits greater voltage dependence than the burst length of the excitatory glutamate-activated channel in these fibres. It is estimated that a single quantum of GABA opens about 600-1000 post-synaptic chloride channels.

Animals↗

Changes in miniature end-plate potentials due to moderate hypertonicity at the frog neuromuscular junction.

The effect of an increase in tonicity on the amplitude and frequency of miniature end-plate potentials (m.e.p.p.s) following superfusion of 50 mM- or 100 mM-sucrose-Ringer solution was determined from intracellular recording at end-plates of the frog cutaneous pectoris muscle, in the absence of drugs and using on-line statistical analysis. An immediate decrease in mean amplitude of the order of 20% control was associated with a marked increase in mean frequency. A delayed increase in mean amplitude, independent of frequency, followed the initial response in the majority of end-plates exposed to 100 mM-sucrose-Ringer solution. The net gain was of the order of 34% and was attained over 20-40 min. This was not reversible over at least 20 min. There was an increase in the variability of m.e.p.p. amplitudes associated with the increase of mean amplitude but this was reversible. A moderate increase in tonicity is considered to induce two kinds of presynaptic changes. First, an immediate increase in the probability of release of smaller quantal packets and secondly, an increased loading of transmitter into vesicles within the readily releasable store.

Action Potentials↗

The nature and origin of calcium-insensitive miniature end-plate potentials at rodent neuromuscular junctions.

1. To study the nature and origin of slow-rising, Ca2+-insensitive miniature end-plate potentials (m.e.p.p.s) in mammalian muscle we used intracellular recording techniques and drugs which block acetylcholine (ACh) synthesis or the uptake of ACh into synaptic vesicles. Slow m.e.p.p.s were induced in vivo by paralysing the extensor digitorum longus muscle of the rat with botulinum toxin type A or in vitro by the application of 4-aminoquinoline to the mouse diaphragm nerve-muscle preparation. 2. Hemicholinium-3, which blocks ACh synthesis, reduced the amplitude of all synaptic potentials including slow m.e.p.p.s, but only if the nerve was stimulated. 3. 2(4-phenylpiperidino)cyclohexanol (AH-5183), which blocks the active uptake of ACh into synaptic vesicles, reduced both the frequency and the amplitude of slow m.e.p.p.s and did so without requiring nerve stimulation. 4. No correlation was observed between the molecular leakage of ACh from the motor nerve and the frequency and amplitude of slow m.e.p.p.s. 5. We conclude that slow m.e.p.p.s are caused by the release of ACh from the nerve terminal, possibly from a small pool of synaptic vesicle-like structures.

Acetylcholine↗

Characteristics of spontaneous miniature and subminiature end-plate currents at the mouse neuromuscular junction.

1. Neuromuscular junctions of the mouse diaphragm were voltage clamped with a two-electrode voltage clamp in order to evaluate time characteristics of miniature end-plate currents (MEPCs). 2. The MEPCs fell into two amplitude classes: a larger class with an overall bell-shaped distribution (bell MEPCs) and a smaller class which forms a right-hand skew distribution (skew MEPCs). The mean MEPC amplitudes varied greatly because of the large range in the ratio of skew to bell MEPCs. This variation was greatest in neonate mice. 3. Rise time and time-to-peak were the same for MEPCs of the skew and bell classes. The MEPCs of both classes in neonate and adult mice had the same ratio of area (charge) over amplitude and the same time constant of decay. The absolute values changed with maturation (at 30 degrees C the ratio of area/amplitude was 4.5 +/- 0.8 ms in the newborn and 1.2 +/- 0.05 ms in the adult; the time constant of decay was 5.6 +/- 1.2 ms in the newborn and 0.8 +/- 0.05 ms in the adult). 4. Atypical MEPCs were found at all junctions. These had slow rising and falling phases, notches on the rising phases or a step the size of the sub-MEPC class. The number of atypical MEPCs increased during the experiment. 5. The data suggest that both skew and bell MEPC classes are released from the same presynaptic region and are generated by the same postsynaptic mechanism.

Animals↗

Subunit composition of the spontaneous miniature end-plate currents at the mouse neuromuscular junction.

1. Adult, neonate and young mouse diaphragm muscle fibres were voltage clamped with a two-electrode clamp. Miniature end-plate currents (MEPCs) were recorded on magnetic tape and analysed with a computer. The MEPC amplitude, charge, rise time, time-to-peak, decay time constant and root mean square (r.m.s.) noise level were determined for each MEPC. 2. The MEPC amplitude and charge distributions showed integral peaks starting from zero. Peaks were enhanced by selecting MEPCs with uniform time characteristics, with low noise, with increased sample size, with a curve smoothing routine and/or with a selected bin size. 3. Integral peaks were found in histograms from neonate, young and old mice. The ratio of sub-MEPCs to bell MEPCs decreased during neonatal development. 4. The size of the peak intervals was the same in all preparations of the same developmental stage. The adult modal peak varied between 8 and 12 times the subunit value, but peak intervals were similar (0.44 +/- 0.04 nA). 5. Changes in the holding potential or the bath temperature, or addition of an anticholinesterase agent, changed the peak interval. 6. The number of peaks in the overall MEPC amplitude and area-to-peak (charge) histogram profiles were usually the same. 7. Integral peaks on MEPC amplitude profiles, notches and steps on the MEPC rising phase and changes in the overall MEPC profiles are explained by a subunit composition of the quantum of transmitter release.

Aging↗

Spontaneous release of multiquantal miniature excitatory junction potentials induced by a Drosophila mutant.

1. Intracellular recordings were made from muscle fibre No. 6 of the dorsal longitudinal flight muscle (DLM) of Drosophila melanogaster in both wild-type flies and the temperature-sensitive paralytic mutant, shibirets-1 (shi). 2. Continuous recordings of the miniature excitatory junction potentials (MEJPs) in this fibre were made as the temperature was changed from 19 to 29 degrees C, and back to 19 degrees C. In shi flies, synapses become depleted of vesicles at 29 degrees C due to a temperature-dependent blockage in the recycling process, while transmitter release proceeds normally. When the temperature is lowered to 19 degrees C, recycling is allowed to proceed and recovery of the full complement of synaptic vesicles gradually occurs in about 20 min. 3. It was observed that the MEJP amplitude distribution in shi flies was unimodal at 19 degrees C prior to heating (as was wild-type), but during recovery from 8 min exposure to 29 degrees C became multimodal, with peaks at roughly integral multiples of the original peak prior to heating. This effect was never seen in wild-type flies. 4. Also, during recovery, the MEJP did not occur randomly, but rather occurred in a clustered fashion. 5. It is concluded that during recovery from depletion in shi neuromuscular junctions, a condition exists which causes the synchronization of spontaneous release, causing multiquantal MEJPs or clustering of MEJPs, depending on the degree of synchronization. 6. The possible role of Ca2+ in this phenomenon is discussed.

Action Potentials↗

Giant miniature end-plate potentials at the untreated and emetine-treated frog neuromuscular junction.

1. Intracellular recordings from the cutaneous pectoris muscle fibres of the frog showed that giant miniature end-plate potentials (gMEPPs) occurred in untreated preparations. Emetine (10 microM), after a 15-20 min delay, increased the frequency of gMEPPs. In both cases gMEPPs disappeared in the presence of (+)-tubocurarine. 2. There was no correlation between the frequency of gMEPPs and the frequency of normal MEPPs (nMEPPs) in untreated or emetine-treated fibres. 3. Tetraphenylborate (TPB, 50 microM) applied to muscles pre-treated with emetine caused the frequency and amplitude of both nMEPPs and gMEPPs to decrease gradually. All MEPPs disappeared in about 10 min. 4. Chloride permeability was modified by changing the pH of the Ringer solution. Changing the pH from 7.2 to 8.2 or 6.2, which in both cases caused marked increases in nMEPP frequency, had no significant effect on gMEPP frequency in untreated muscles. 5. Decreasing the pH from 7.2 to 6.2 blocked the ability of emetine to increase gMEPP frequency. Increasing the pH from 7.2 to 8.2 had no significant effect on emetine ability to increase gMEPP frequency. 6. Treatment with the Cl- channel blocker SITS (0.5 mM) had no effect on gMEPPs in untreated muscle or on the ability of emetine to increase the frequency of these potentials. 7. The Ca2+ sensitivity of gMEPPs in untreated or emetine-treated muscles was tested by treatments which are known to alter intracellular Ca2+. Raising extracellular Ca2+ (10 mM), treatment with Mn2+ (10 mM), Mg2+ (10 mM), K+ (7.5 mM), hypotonic solution, ouabain (0.2 mM) or ethanol (0.5 M), although causing profound changes in nMEPP frequency had no significant effect on gMEPP frequency in untreated fibres or on the ability of emetine to increase gMEPP frequency. 8. It is concluded that at the frog neuromuscular junction generation of the normally occurring or emetine-induced gMEPPs is independent of Ca2+ and does not seem to be influenced by changing membrane C1- permeability.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Protein kinase A-mediated enhancement of miniature IPSC frequency by noradrenaline in rat cerebellar stellate cells.

1. Cellular mechanisms underlying the enhancement by noradrenaline (NA) of inhibitory postsynaptic currents (IPSCs) were studied at inhibitory synapses in the molecular layer of the cerebellum. IPSCs were obtained from stellate cells in rat cerebellar slices using tight-seal whole-cell recording. 2. Miniature IPSCs (mIPSCs) were recorded in the presence of tetrodotoxin (TTX; 100 nM). NA (10 microM) markedly increased the frequency of mIPSCs, but did not alter their mean amplitude. Bath application of the inhibitor of adenylyl cyclase 9-(tetrahydro-2'-furyl) adenine (SQ 22,536; 300 microM), of the wide spectrum protein kinase inhibitor staurosporine (1 microM), and of the Rp-diastereomer of adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS; 500 microM), a specific inhibitor of cAMP-dependent protein kinase (PKA), inhibited the mIPSC frequency increase induced by NA. 3. The increase in mIPSC frequency was not attenuated by Cd2+ (100 microM), a blocker of voltage dependent calcium channels. However, after a 12-15 min pre-incubation in Ca(2+)-free saline, the effect of NA on mIPSCs was markedly inhibited. If Ca2+ ions were readmitted in the presence of NA, enhancement of the mIPSC frequency was largely restored. 4. Application of the membrane permeant analogue of cAMP, 8-Br-cAMP (1 mM), together with the inhibitor of cAMP phosphodiesterase, 3-isobutyl-1-methylxanthine (IBMX; 100 microM), caused a frequency increase of mIPSCs. Forskolin also mimicked the stimulatory effect of NA on mIPSC frequency. The effects of both 8-Br-cAMP and forskolin persisted in Ca(2+)-free saline, suggesting that the modulation of transmitter release does not require Ca2+ influx. 5. On the whole, the results indicate that the potentiation of mIPSC frequency by NA is mediated through the sequential activation of adenylyl cyclase and protein kinase A (PKA), and that PKA modulates the vesicle release mechanism rather than Ca2+ influx. The lack of effect of NA after prolonged incubation in Ca(2+)-free solution may be due to an inhibition of adenylyl cyclase by a gradual lowering of the cytosolic presynaptic Ca2+ concentration.

Animals↗

Dosimetric characteristics of the CDC-type miniature cylindrical 137Cs brachytherapy sources.

The low dose rate CDC-type miniature cylindrical 137Cs sources are available, with one or three active beads, for use in source trains in automatic and manual afterloading systems for gynecological brachytherapy. Absolute dose rate distributions in water have been calculated around these sources using the Monte Carlo GEANT3 code and they are presented as conventional two-dimensional Cartesian lookup tables. The AAPM Task Group 43 formalism for dose calculation has been also applied. The dose rate constant obtained for the one bead source is lambda = 1.113 +/- 0.003cGyh(-1) U(-1), and the value for the three bead source is A= 1.103 +/- 0.003cGyh(-1) U(-1). Finally, for the treatment planning systems based on Sievert-type algorithms, the attenuation coefficients that best reproduce Monte Carlo dose rate distribution are given.

Air↗

Assessment of errors in intensity measurements of pulse echo ultrasound using miniature hydrophones.

Total transmitted power and intensity distributions from diagnostic ultrasound systems have been measured with a radiation force balance and with a miniature hydrophone and instrumentation available in many medical centers. In assessing the accuracy of absolute intensity and power determinations from measurements of acoustic pressure with a hydrophone, ultrasonic power was computed from hydrophone measurements. This power value was compared with the power determined by a radiation force technique. On five pulse echo ultrasound systems, the ratio of the power measured with a radiation force balance to the power determined with the hydrophone varied from 0.25 to 5.5. These differences are attributed mainly to the known large variations in hydrophone response as a function of frequency, and possible time, since several other possible sources of error were evaluated and estimated to have a reasonably small net effect of 25%. The errors evaluated were those dealing primarily with measurement procedures.

Ultrasonics↗

A miniature MOSFET radiation dosimeter probe.

Prototype miniature dosimeter probes have been designed, built, and characterized employing a small, radiation sensitive metal oxide semiconductor field effect transistor (MOSFET) chip to measure, in vivo, the total accumulated dose and dose rate as a function of time after internal administration of long range beta particle radiolabeled antibodies and in external high energy photon and electron beams. The MOSFET detector is mounted on a long narrow alumina substrate to facilitate electrical connection. The MOSFET, alumina substrate, and lead wires are inserted into a 16 gauge flexineedle, which, in turn, may be inserted into tissue. The radiation dosimeter probe has overall dimensions of 1.6 mm diam and 3.5 cm length. The MOSFET probe signals are read, stored, and analyzed using an automated data collection and analysis system. Initially, we have characterized the probe's response to long range beta particle emission from 90Y sources in solution and to high energy photon and electron beams from linear accelerators. Since the prototype has a finite substrate thickness, the angular dependence has been studied using beta particle emission from a 90Sr source. Temperature dependence and signal drift have been characterized and may be corrected for. Measurements made in spherical volumes containing 90Y with diameters less than the maximum electron range, to simulate anticipated geometries in animal models, agree well with Berger point kernel and EGS4 Monte Carlo calculations. The results from the prototype probes lead to design requirements for detection of shorter range beta particles used in radioimmunotherapy and lower photon energies used in brachytherapy.

Biophysical Phenomena↗

Monte Carlo simulation of a miniature, radiosurgery x-ray tube using the ITS 3.0 coupled electron-photon transport code.

A miniature, interstitial x-ray generator has recently been developed and is currently undergoing clinical trials for the treatment of brain tumors. The maximum photon energy from this x-ray tube is 50 keV, although most of the initial testing has been carried out at 40 keV. Dose rates of up to 2 Gy/min in a water phantom at a distance of 10 mm from the tube tip are produced. In this paper we describe the modeling and simulation of x-ray production from this device using the ITS 3.0 Monte Carlo code. Verification of the simulation of x-ray production in the device was carried out by comparing predictions of spatial photon distribution, energy spectrum, and dose versus depth in water with experimentally obtained measurements. Agreement between the simulated results and experimental measurements was fairly good when comparing the angular distribution of photons emitted from the x-ray tube and very good when comparing dose rate versus depth in a water phantom. Discrepancies observed when comparing the calculated and measured estimates of characteristic line radiation were reduced by incorporation of a modification to the ITS code. Possible causes of the remaining discrepancy in bremsstrahlung intensity are discussed.

Biophysical Phenomena↗

Anisotropy of an 192iridium high dose rate source measured with a miniature ionization chamber.

The anisotropy of a high dose rate (HDR) 192Ir source was measured in air and in water using a miniature (0.147 cm3) ionization chamber. Measurements were made at a distance of 5 cm from the source center at polar angles from 10 degrees-170 degrees. The anisotropy was found to be less pronounced in water, and the anisotropy is asymmetric about the transverse axis. The results agree with previous ionization chamber and TLD measurements to within +/- 4%. Mean anisotropy factors were determined at each angle from all existing data at 5 cm distance, and compared to published Monte Carlo calculations, and to the values used in the microSelectron HDR brachytherapy planning system (BPS). The Monte Carlo photon transport code appears to systematically underestimate the anisotropy factor by up to 4% in the forward direction and overestimate it by up to 3% in the backward direction. The mean anisotropy factors also indicate that the BPS systematically underestimates the anisotropy factor by up to 3% in the forward direction, and overestimates it by up to 15% in the backward direction. However, the 15% difference occurs at 180 degrees where it is not likely to be clinically significant.

Air↗

A pencil-beam photon dose algorithm for stereotactic radiosurgery using a miniature multileaf collimator.

A computer-controlled miniature multileaf collimator (MMLC) with 4 mm leaf width and a maximum field size of 6 cm X 6 cm has been designed as a tertiary beam-shaping device for linac-based stereotactic radiosurgery. The purpose of this study is to develop an accurate and efficient dose calculation model for use with the MMLC. A pencil-beam based algorithm using a sum of three Gaussian kernels was developed to model the off-axis ratio of MMLC fields. Because the kernel integration over a rectangular field can be solved in closed form, dose to any point from an arbitrary MMLC field can be calculated efficiently by summing dose contribution from a set of rectangular apertures and transmission blocks that model individual leaf openings or leaf transmissions. The model uses an effective rectangular field and equivalent square method for determination of depth dose and dose output. Results showed that the calculated percentage depth dose was within 1% and output factor was within 1.5% of measured data. The parameters of the pencil beam kernels were extracted by fitting measured off-axis profiles for a few field sizes at a few depths. The accuracy of the calculated off-axis ratio was tested by comparison with measured data for a number of MMLC fields. The algorithm was shown to be accurate to within 1.5% or 1 mm for off-axis ratios. The algorithm computes at a speed of 34,600 data points per second on a DEC Alpha server model 2000/433 (Digital Equipment Corp., Maynard, MA), which is about 15 times faster than a Clarkson-type summation method.

Algorithms↗

Physical characteristics of a miniature multileaf collimator.

A preliminary study of the physical characteristics of a miniature multileaf collimator (mMLC) used with 4 MV x rays is reported. The mMLC attached to the accessory mount of a class C or D Varian linear accelerator (Varian Oncology Systems, Palo Alto, CA) with a source to aperture distance of 65 cm. The field penumbra using the small leaves was found to be consistent with the anticipated field penumbra using photon jaws at the same source to aperture distance as the mMLC. The percentage depth dose values of square fields were found to be consistent with the fields collimated with the upper and lower jaws. Output factors for the very small fields were found to vary rapidly. Circular fields could be produced with depth dose characteristics similar to those produced using conical tertiary collimators, commonly used for radiosurgery, but with a broader penumbra.

Dose-Response Relationship, Radiation↗

Dosimetric characteristics of a double-focused miniature multileaf collimator.

The dosimetric characteristics of a double-focused miniature multileaf collimator (mMLC) attached to a Philips SL75/5 linear accelerator (linac) have been investigated. Output factors, percentage depth-dose, penumbra, leaf transmission, and leakage between the leaves were measured for the 6 MV x-ray beam on this accelerator. Because leakage both through and between the leaves is minimal, the linac jaws can be kept fixed while the mMLC leaf configuration is modified for different aperture shapes. This allows for accurate output prediction using the equivalent square formalism. Percent depth-dose measured for fields defined by the mMLC show little deviation from the percent depth-dose measured for fields defined by the machine jaws or Lipowitz metal blocks. Because the mMLC matches beam divergence in both directions, allows minimal beam transmission, and has a large source-to-collimator distance, the penumbra is sharper for fields defined by the mMLC than for fields defined by the linac jaws or Lipowitz metal blocks. Based on these data, dose calculations for mMLC-defined fields can be applied with no change in procedures from those used for fields defined using conventional methods.

Radiotherapy Planning, Computer-Assisted↗

Distance-dose curve for a miniature x-ray tube for stereotactic radiosurgery using an optimized aperture with a parallel-plate ionization chamber.

A recently developed miniature x-ray tube operating at 40 kV has been used in a randomized trial for the treatment of small intracranial lesions. The diameter of these lesions ranges from 10 to 30 mm. A thin window parallel-plate ionization chamber was used to calibrate the output of the x-ray tube, modified by the addition of a thin platinum aperture to reduce the charge collecting area of the chamber. The effect of such an aperture on the measurement of dose versus distance from the x-ray tube in a phantom has been examined as a function of aperture diameter. Aperture diameters were varied between 0 and 5 mm and dose measurements were made for distances between the x-ray source and the front surface of the chamber of 5-30 mm in water. The ratio of doses measured with and without an aperture, when normalized to unity at a distance of 10 mm, differs significantly from unity, for distances between 7.5 and 15 mm, for aperture diameters <1.5 mm and differs from unity, but less significantly, for apertures > or =3 mm. For intermediate diameters, however, this dose dependence is minimized, indicating an aperture diameter that provides a similar distance-dose curve as the measurement taken without an aperture over this range of distances. This diameter was found to be between 2 and 2.5 mm with a dose variation of less than +/- 1%. For distances <7.5 mm, measurements made with a 1.5-mm-diam aperture agree better with those taken with a 1.7-mm-diam chamber compared with a 5.2-mm-diam chamber.

Dose-Response Relationship, Radiation↗