The meaning of linear dose-response relations, made evident by use of absorbed dose to the cell.

Experimental evidence shows that if the probability of biological response is plotted against the absorbed dose from ionizing radiation, and if both dose and response are determined at the same level of biological organization (e.g., cell or organ-organism) the result appears as a sigmoid, medical-toxicological type of "dose-response" function when plotted using linear coordinates. However, if the biological response expressed at the cellular level is similarly plotted against the average absorbed dose expressed at the organ-organism level, a linearly proportional, "non-threshold" function is obtained. To explain this marked difference in curve shape, the absorbed dose at the organ level in terms of its meaning at the cellular level was examined, and both dose and response were put on the latter level. The result is consistent with the conclusion that absorbed dose at the organ-organism level can be treated, at the cellular level, as the product of two quantities: 1) the mean energy concentration or dose in a cell from a deposition event, i.e., "hit size" (the frequency-averaged specific energy in a reference cell target), and 2) the number of deposition events, or "hits," on the exposed cells. When the mean hit size for a given radiation remains constant, and the number of hits is increased, the total number of responses follows a linearly proportional "hit number response function." However, if the hit number is held constant or normalized to a given value, and the hit size is varied, the resulting probability of cell response again plots as the apparently sigmoid curve mentioned above, which has been termed the "hit size effectiveness function." With decreasing hit size, the probability of a cellular response appears to decrease asymptotically, and become indistinguishable from zero before zero dose is reached. It follows from this inherent relationship between the two kinds of functions that a sufficiently extensive set of data on a population of cells permits either type of function to be produced at will. These findings bear on the interpretation of the "linear, non threshold" hypothesis.

A combined heat clearance method for tissue blood flow measurement.

Tissue Blood Flow is measured by applying a combined procedure of two independent approaches based on heat clearance: the Pulse Decay Method and the Continuous Method. The Pulse Method allows absolute assessment of tissue BF with no need for calibration, and can be applied only if the tissue BF is steady during the period of measurement. On the other hand, the Continuous Method enables the observation of rapid changes in tissue BF, and can be applied under non steady-state conditions. Using the combined method, a continuous quantitative measurement of transient changes in tissue BF can be obtained. For this purpose, we have developed two experimental systems consisting of independent electronic units: a Pulse Unit and a Continuous Unit. A micro-computer with dedicated software controls the operation of the electronic units and calculates tissue BF on-line. In vitro measurements are performed and demonstrate the reliability of the methods. In vivo measurements in rat brain tissue are also performed and include physiological and pharmacological changes of local tissue BF. The results of the two heat clearance methods correlate well with tissue BF values measured by a third independent method, the Hydrogen Clearance Method.

A different perception of the linear, nonthreshold hypothesis for low-dose irradiation.

Two equally useful dosimetric quantities, both of which are called dose, are used in toxicology. With radiation measurement, only one--the energy per unit mass D--is called dose. The other--the total energy in the irradiated system--is here distinguished from D by assigning it the name collective energy, epsilon. The collective energy is a more complete statement of dose because it is the product of the energy concentration D and the mass irradiated m. Especially in radioepidemiology, in which epsilon is the total energy imparted to all persons irradiated, the quantity m must be specified because it is situation specific and thus highly variable. At present, radioepidemiological dose-response curves are given only in terms of the toxicological model--i.e., the fraction (probability) of radiation-attributable cancers occurring as a function of D. Because this relation does not involve the number of persons at each value of D, it fosters the illusion that any dose, no matter how small, can result in cancer. However, we show that if the dose-response relationship is expressed in terms of the absolute number of attributable cancers as a function of epsilon, cancer occurs, on average, only if the collective energy exceeds a relatively large minimum value, the magnitude of which will be estimated. Therefore, we conclude that the nonthreshold aspect of the linear hypothesis is misleading and quite probably invalid. For example, in or around a facility in which exposure of humans to relatively low values of D occurs, attributable cancers are most unlikely to appear unless the epsilon to the irradiated population exceeds this minimum value.

A planning method for 125I implants in cancer therapy.

A method for planning implants of 125I seeds has been developed. The treatment dose prescribed by the physician is delivered to the tumour, as uniformly as possible, by a minimal number of seeds. The number of seeds and their locations are derived by requesting that, at any point in the tumour, the dose will be equal to or higher than the prescribed dose. As a result, the total implanted activity is lower for small volumes and higher for large volumes, relative to other implantation protocols which derive their planning from requests on the minimum peripheral dose. Results obtained from computer simulations performed on different tumour shapes and volumes, show a linear dependence between the total implanted activity and the tumour volume. The total activity does not depend on the shape of the tumour. A description of the algorithm of our procedure and a detailed example of its application are presented.

Bidirectional LDV system for absolute measurement of blood speed in retinal vessels.

A laser Doppler technique which provides a means of obtaining absolute measurements of the speed of red blood cells (RBCs) flowing in individual retinal vessels is described. Doppler-shift frequency spectra of laser light scattered from the RBCs are obtained for two directions of the scattered light. Each spectrum exhibits a cutoff frequency that is directly related to the maximum RBC speed (V(max)). The difference in cutoff frequencies is used to obtain an absolute measure of V(max) that is independent of the exact orientation of the vessel and of the relative direction of the incident and scattered beams with respect to the flow direction. Preliminary measurements obtained using a prototype instrument are presented.