Kenneth A. Wright

Early effects of x-irradiation of the cerebellum in infant rats: Decimation and reconstitution of the external granular layer

Abstract The cerebellum of rats was irradiated daily with 200 r x-ray from the day of birth, with the number of exposures ranging from one to ten. The animals were killed 2 and 24 hours, and 4 days after the last exposure, and at the constant ages of 8 and 10 days. The cell population of the external granular layer was drastically reduced 24 hours after irradiation with a single dose of 200 r, and it was subtotally and maximally destroyed 24 hours after the second exposure. In animals exposed up to 5 × 200 r, recovery of the external granular layer was evident 4 days after the last irradiation; the extent of recovery was inversely related to the number of doses received. The width of the external granular layer was normal or supernormal by 10 days of age in all these groups, though planimetric measurements showed that the total area occupied by this proliferative matrix was subnormal (due to the decreased surface area of the cerebellum) and it was inversely related to the number of doses received. Some evidence was obtained that after some delay the recovered cells differentiated, and led to the development of the molecular and internal granular layers. Several abnormalities were noted in the morphology of the developing cerebellar cortex after exposure to a higher number of x-ray doses, such as abnormal folding of the cerebellar cortex and the massing and disoriented growth of Purkinje cells, and explanations were offered for these effects.

Differential radiosensitivity of stationary and migratory primitive cells in the brains of infant rats

The heads of infant rats were irradiated with 200 r X-ray. In one group the animals were injected with thymidine-3H immediately after irradiation, in the other, 24 hours before irradiation. All were killed at 3 days of age, 6 hours after irradiation and 6 or 30 hours after injection. In autoradiograms from the brains of unirradiated animals killed 6 hours after injection, the proportion of labeled cells, reflecting regional rate of cell poliferation, was determined at several brain sites. The relative reduction in the rate of cell proliferation in irradiated animals was also established. In matched stained sections the proportion of pyknotic cells, reflecting rate of cell death, was determined in the same brain regions. Finally, pyknosis index/labeling index ratios were calculated to relate radiation-induced cell death to rate of cell proliferation at different loci. It was established that migrating cells and prospective migratory cells, whether mitotic or postmitotic, are extremely radiosensitive, with a large proportion of them killed by exposure to 200 r. Relatively few of the stationary proliferating cells were killed with this dose. Stationary differentiating cells, and mature cells were not visibly affected. These results suggest that damage to the cellular mechanisms that enable primitive cells to locomote, rather than damage to DNA, is the principal cause of cell death in the nervous system exposed to low-level radiation. Moreover, the selective effect of this procedure could provide a technique for the identification of migratory cells at different brain sites during different stages of development.

Selective destruction of precursors of microneurons of the cerebellar cortex with fractionated low-dose x-rays.

Abstract The study was undertaken to determine the amount of irradiation needed to selectively destroy certain postnatally-forming neural elements of the brain. The heads of kittens during their first 2 weeks of life were irradiated unilaterally with five repeated doses of x-ray, single doses ranging from 50 to 400r; the animals were killed on the sixteenth day. The effects of radiation were evaluated quantitatively on the irradiated and control sides in the ansiform lobule of the cerebellar cortex. Repeated doses of 50 to 100r reduced the migratory cell population of the external granular layer; 150r produced a subtotal, and 200r a total destruction of the layer. With 150r and higher doses the total area and the cell population of the internal granular layer of the ansiform lobule were appreciably reduced; with 200r and higher doses the cell packing density of the granular layer was also affected. Irradiation with 150r or higher doses reduced the ratio of granule cells to Purkinje cells. Although x-ray irradiation up to 200r had no effect on the control side, effects were produced with 300 and 400r. The Purkinje cells were adversely affected only with 400r. We concluded that 200r is the optimal dose in kittens for selective destruction of the precursors of the postnatally-forming granule cells in circumscribed parts of the cerebellar cortex.

Back‐Scattering of Megavolt Electrons from Thick Targets

Measurements are reported of the number and energy of the electrons which rebound from thick metal targets bombarded at normal incidence by monoenergetic electrons of from 1 to 3 Mev. The ratio of back‐scattered to incident electron current, measured for twelve metal targets, was found to vary from 0.47 for 1‐Mev electrons incident on U to 0.01 for 3‐Mev electrons on Be. The total energy scattered backward from targets of Al, Cu, and Pb bombarded with 1‐ to 3.5‐Mev electrons was determined by calorimetric methods. This energy diminished from 34% of the incident energy for Pb bombarded with 1‐Mev electrons to 1% for Al bombarded with 3.5‐Mev electrons. The dependence of the number and energy of the back‐scattered electrons on the atomic number of the target and on the incident electron energy is discussed.

Single-dose electron beam irradiation in treatment and prevention of keloids and hypertrophic scars

Low megavolt electron beam irradiation was used on 354 sites in 199 patients at the Lahey Clinic either for palliation of symptomatic hypertrophic scars or as post-operative irradiation in an attempt to prevent formation or recurrence of hypertrophic scars. Electron energies used ranged from 1.5 to 3.5 MeV. The median age of the 59 male patients was 22 years and of the 140 female patients, 35 years. All patients had at least one follow-up visit, and the median follow-up was 35 months. Of the 294 sites treated for the first time, 272 (93%) were irradiated with a single fraction with a skin dose ranging from 2 to 20 Gy. Of the 85 sites in 63 patients without excision of symptomatic hypertrophic scars, single-dose electron beam irradiation was of clinically significant value in only 41 sites (48%). No patients have been treated without surgical excision since 1973. Because of a history of formation of hypertrophic scars elsewhere in the body, 13 patients with 19 incisions were treated prophylactically after operation for other diseases. All sites were irradiated with single doses ranging from 8 to 20 Gy, and hypertrophic scars did not subsequently develop in any patient. Altogether, 119 patients with 174 sites were irradiated after surgical excision of hypertrophic scars to prevent recurrence; 168 sites (97%) received single-fraction irradiation, and 161 received a dose of 8 Gy or greater, up to 15 Gy. No statistically significant differences were observed in complete success rates, ranging from 82 to 90% with doses of 9 Gy or greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Gross morphological consequences of irradiation of the cerebellum in infant rats with repeated doses of low-level X-ray

Abstract The cerebellum of rats was irradiated with daily doses of 50–200 r hard X-ray, on successive days following birth, total number of exposures ranging from 1 to 10. The purpose was to design a method of selectively eliminating a specifiable proportion of the postnatally proliferating and migrating precursor cells of cerebellar microneurons. In this study the gross morphological consequences of different irradiation schedules were determined. Mortality rate was not raised by localized cerebellar irradiation, except in rats that received ten successive daily doses, and the animals that survived through infancy, including those that received 10 × 200 r, showed normal body growth. Total brain weight was markedly reduced in the animals receiving more than 2 × 100–200 r; the highest reduction was seen in animals that received 10 × 200 r. The bulk of reduction in total brain weight could be attributed to weight loss in the intended area of irradiation. Areal measurements showed that cerebellar irradiation did not affect appreciably the growth with age in the width and length of the cerebrum, but increase in the length and height of the cerebellum was markedly retarded. With single or multiple doses of 200 r cerebellar length was greatly reduced by day 10. Reduction at 30 and 90 days was not evident with 1–2 × 200 r, but with 4–5 × 200 r cerebellar length was reduced to the level of control animals 10 days of age, and with 10 × 200 r to the level of neonates. The cytological bases of the drastic effects produced by radiation remain to be determined.

Radiotherapy for Kaposi's sarcoma

Between 1954 and 1976, 60 patients with Kaposis sarcoma were treated in the Department of Radiotherapy of the Lahey Clinic Foundation at the High Voltage Research Laboratory of Massachusetts Institute of Technology. Only 2 patients were free of clinical disease in the lower extremities at the time of initial presentation, and 40 patients (69%) had cutaneous lesions involving areas extending above the knees. Eight patients (13%) also presented with mucous membrane involvement in addition to skin disease.

Distribution of Ionization in Materials Irradiated by Two and Three Million‐Volt Cathode Rays

Measurements are reported on the distribution of ionization in depth of aluminum produced by steady beams of two and three million‐volt electrons. The variation of cathode‐ray current density in a plane transverse to the beam, the effect on this transverse distribution of additional aluminum scattering foils, and a practical method of cathode‐ray dosage computation are given.

Synchronous Field Shaping and Protection in 2-Million-Volt Rotational Therapy

This presentation is concerned primarily with certain irradiation technics evolved over the past eleven years of clinical radiotherapeutic experience with the 2-million-volt Van de Graaff electrostatic x-ray generator. Field shaping may be considered to have two objectives: that of conforming the shape of the beam of radiation to the known tumor volume and its possible extension and that of protecting adjacent normal areas by exclusion from the beam. In the absence of motion between patient and beam, the field may be given any desired shape depending upon the clinical problem and the philosophy of the radiotherapist. Accessory protective devices in such stationary-field therapy are usually modifications in the outline or dose distribution of the original field. Applied to 360° rotation of the patient, a fixed field is usually considered as necessarily symmetrical about the axis of rotation. The use of an accessory protective device in this situation requires in general that it also be shaped and rotate. T...

Field Shaping and Selective Protection in Megavolt Radiation Therapy

The availability of intense sources of megavolt radiation makes possible the treatment of regional as well as localized disease with more adequate doses. These new capabilities are often best exploited by the use of large treatment fields, carefully shaped to include known tumor and local extensions and to exclude uninvolved regions. This procedure results in a more uniform dose distribution and reduces the problems of overlap inherent in the multiple field approach. Field shaping, or field outline control, is accomplished by interposing sufficient thickness of absorbing material into the beam cross section. In addition, the beam may be intensity-modulated by filters to adjust for variations in the anatomical thickness. In our megavolt x-ray equipment a light-beam localizer is used to facilitate the placing of such absorbers and filters. Double-exposure radiographs are taken to confirm and record the field location and the position of these absorbers. Fields of typical shape used in both rotational and op...