Patent Number: 062018523
Section: summary

BACKGROUND OF THE INVENTION The present invention relates to irradiation systems, generally and, more particularly, but not by way of limitation, to methods and means of variably attenuating radiation. When radionuclides are administered for diagnostic purposes in nuclear medicine, the absorbed doses received by the critical organs and tissues of the target are usually sufficiently low that the biological effects cannot be measured with any reliability. In these instances, reliance solely on calculated absorbed doses may be appropriate and sufficient for risk estimations and comparison of the relative merits of different radiopharmaceuticals. However, when radionuclides are administered for therapeutic purposes, or in cases involving accidental ingestion of high levels of radioactivity, dependence on untested absorbed dose calculations can lead to serious errors in predicting the biological consequence of the radiation exposure. Such concerns are particularly relevant to complex biological systems, such as the bone marrow. For example, computational bone marrow dosimetry techniques used in radioimmunotherapy have failed to yield a reasonable correlation between absorbed dose and biological response of the marrow. The shortcomings and failures of existing techniques may include, among others, the following reasons: the underlying assumptions in the absorbed dose calculations; differences in dose rate patterns; prior treatment history and bone marrow reserve; and nonuniform activity distributions in the marrow compartment. These problems are not unique to bone marrow, but can also exist for other organs and tissue as well. Hence, in view of the limitations inherent in computational dosimetry, a need exists for reliable biological dosimeters to verify the computational methods. It is well known that the biological effect of a given radiation insult is highly dependent on factors such as total absorbed dose, dose rate, linear energy transfer (LET) of the radiations, and radiosensitivity of the tissue. See: ICRP, RBE for Deterministic Effects, Publication 58, International Commission on Radiological Protection, Pergamon, Oxford (1989); and ICRP, 1990 Recommendations, Publication 60, International Commission on Radiological Protections, Pergamon, Oxford (1991); both of which are incorporated by reference herein in their entirety. While the consequences of these variables are well established for acute and constant chronic radiation exposure conditions, little is known about the role of these variables for exposures involving internal radionuclides. Also see: Testa, et al., Biomedicine, 19:183-186 (1973); Wu, et al., Int. J. Radiat. Biol., 27:41-50 (1975); and Thames, et al., Br. J. Cancer, 49, Suppl. VI:263-269 (1984); all of which are incorporated by reference herein in their entirety. Internal radionuclides are unique in that they deliver radiation exposures at dose rates that vary exponentially in time as determined by the effective half-time, which in turn is dictated by the physical half-life of the radionuclide and the biological half-time of the radiochemical. Further complications to the dose rate pattern can emerge when the uptake of the radiochemical by the tissue is slow, followed by a complex multicomponent exponential clearance pattern. Although the total dose delivered to a tissue may be the same, differences in dose rate patterns from one radiochemical to another can have a major impact on the biological response of the tissue. See: Fowler, Int. J Radiat. Oncol. Biol. Phys., 18:1261-1269 (1990); Langmuir, et al., Med. Phys., 20, Pt. 2:601-610 (1993); Rao, et al., J. Nucl. Med., 34:1801-1810 (1993); and Howell, et al., J. Nucl. Med., 35:1861-1869 (1994); all of which are incorporated by reference herein in their entirety. Such differences cannot always be predicted a priori using computational absorbed dose estimates and extrapolations based on the response to acute and chronic exposure at constant dose rates. Therefore it is imperative to develop experimental irradiators that are capable of precisely delivering exposure that simulate the conditions encountered with internal radionuclides and to establish biological endpoints that can serve as "dosimeters" so that the consequence of different dose rate patterns on the biological effect can be investigated. Two endpoints which may serve as biological dosimeters are survival of bone marrow granulocyte-macrophage colony-forming cells (GM-CFC) and induction of micronuclei in peripheral blood reticulocytes. See: Testa, Cell Clones: Manual of Mammalian Cell Techniques, Edinburgh: Churchill-Livingstone, 27-43 (1985); and Lenarczyk, et al., Mutation Res., 335:229-234 (1995); both of which are incorporated by reference herein in their entirety. DESCRIPTION OF THE RELATED ART U.S. Pat. No. 5,148,463 issued to Mulder et al. discloses an X-ray filter which is lens-like and filled with a liquid whereby variations in the thickness of the liquid provides varying amounts of attenuation for image compensation. The filter thickness is adjustable by the supply and the discharge of the liquid. Fluid is supplied to or withdrawn from the filter by a pump until a uniform radiation image is achieved. It should be noted that Mulder et al. fails to disclose selectively metering the attenuation or delivery of radiation, and also fails to disclose adjustment of the radiation achieved by a siphon effect. U.S. Pat. No. 4,481,419 issued to Persyk discloses the attenuation of radiation with a changeable volume of mercury disposed within a reservoir. A radiation transmitting housing includes a fluid chamber and means for selectively adjusting the shape of the fluid chamber as to vary the configuration of the radiation pattern. However, the fluid chamber is wedge-shaped and the adjusting means varies the internal angle of the wedge. A reservoir cavity is incorporated into the fluid chamber, but the reservoir is provided to accommodate changes in the volume of fluid material needed to feed the wedge portion and that due to fluid temperature changes. Radiation is attenuated by thickness of the fluid material. A fluid chamber is preferably filled with mercury, then sealed. However, once adjusted and set, the fluid chamber can not be varied. It should be noted that Persyk fails to disclose selectively metering the attenuation or delivery of radiation, and also fails to disclose adjustment of the radiation achieved by a siphon effect. U.S. Pat. No. 3,755,627 issued to Edholm et al. discloses the use of a mercury attenuator for providing image compensation. The compensating filter device includes a radiation absorbing medium consisting of a liquid enclosed in a thin flat chamber, wherein the radiation absorbing liquid may be mercury or some other liquid metal or solution or stable suspension of a radiation absorbing substance, such as an aqueous solution of cesium acetate. The flat chamber has an upper wall consisting of a resiliently flexible diaphragm whose contour is adjusted by a polarity of wires attached to the diaphragm. The thickness of the liquid layer follows the contour of the flexible diaphragm. It should be noted that Edholm et al. fails to disclose selectively metering the attenuation or delivery of radiation, and also fails to disclose adjustment of the radiation achieved by a siphon effect. U.S. Pat. No. 4,446,570 issued to Guth discloses a radiation collimator which includes internal cavities which are filled with radiation opaque fluid, such as mercury. The fluid fills the spaces between the pins within a toroidal-shaped chamber, thereby providing a vertical multi-channel parallel collimator which serves as a mask for outlining the field of view of the radiation detector. A toroidal recess which forms a raised ring around the periphery of the upper internal surface functions as an expansion chamber to accommodate changes in volume of the mercury due to changes in temperature. Fluid is introduced into the cavities, and the chamber is sealed. The introduction of fluid can be assisted by evacuating the cavities, such as by a vacuum pump. It should be noted that Guth fails to disclose selectively metering the attenuation or delivery of radiation, and also fails to disclose adjustment of the radiation achieved by a siphon effect. U.S. Pat. No. 4,497,062 issued to Mistretta et al. discloses a digitally controlled X-ray attenuator and a method for its use in which a control responsive ink-jet printer prints pixels containing various proportions of attenuation substances in order to form compensation masks for X-ray imaging. It should be noted that Mistretta et al. fails to disclose selectively metering the attenuation or delivery of radiation, and also fails to disclose adjustment of the radiation achieved by a siphon effect. U.S. Pat. No. 5,559,853 issued to Linders et al. discloses an X-ray filter in which electrodes in a matrix are selectively energized in order to distribute X-ray absorption particles, electrophoretically, in a compensation filter. The filter has a number of electrodes and grains or powder particles containing an X-ray absorbing material and suspended in a suspension liquid. When a voltage is applied to the electrodes, the X-ray absorbing material and the suspension will move toward the electrodes due to electrophoresis, and a distribution corresponding to a X-ray absorption profile can be achieved by a suitable voltage pattern. It should be noted that Linders et al. fails to disclose selectively metering the attenuation or delivery of radiation, and also fails to disclose adjustment of the radiation achieved by a siphon effect. OBJECTS AND SUMMARY OF THE INVENTION It is an object of the present invention to provide method and means of attenuating radiation. It is another object of the present invention to provide a method and means of attenuating radiation in a highly controlled or selectively metered manner. It is still another object of the present invention to provide a method and means of delivering radiation according to user defined input or input parameters or pre-selected schedules. It is yet another object of the present invention to provide a method and means capable of attenuating radiation in a temporally variable manner. It is another object of the present invention to provide a method and means for delivering radiation exposures at dose rates that vary exponentially in time. It is yet another object of the present invention to provide a means of delivering radiation exposure. It is a further object of the present invention to provide a means of delivering radiation exposure which simulates conditions encountered with internal radionuclides. It is still another object of the present invention to provide a method and means of attenuating radiation by controlling the level of a radiation-blocking liquid layer by siphon effect. Another object of the present invention is to provide a method and means to investigate the biological response of bone marrow to chronic exponentially decreasing dose rates encountered in therapy with bone-seeking radiochemicals having different effective half-lives, and hence different dose rate patterns. It is another object of the present invention to provide a method and means of verifying absorbed dose calculations. It is yet another object of the present invention to provide a method and means of determining how the biological effects caused by complex dose rate patterns correlate with variables such as initial dose rate, effective half-times, and other factors associated with radiation dosing. It is yet another object of the present invention to provide a method and means of calibrating biological dosimeters. Other objects of the present invention, as well as particular features, elements, and advantages thereof, will be elucidated in, or be apparent from, the following description and the accompanying drawing figures. The present invention achieves the above objects, among others, by providing, a method and means for variably attenuating radiation The present invention provides, in a particular embodiment, a variable attenuation apparatus for use with a radiation-blocking liquid and a radiation source. The apparatus includes an attenuation chamber capable of containing a layer of the radiation-blocking liquid and an adjustment means for selectively metering the thickness of the layer of the radiation-blocking liquid, whereby changes in the thickness of the layer alter the radiation transmitted through the attenuation chamber. The adjustment means may further include a reservoir capable of containing the radiation-blocking liquid and a siphon connection means for allowing the transfer of the radiation-blocking liquid between the reservoir and the attenuation chamber, wherein the thickness of the layer in the attenuation chamber is a function of the difference in elevation between the top of the layer in the attenuation chamber and the top of the liquid in the reservoir, whereby an increase in the thickness of the layer causes a drop in the radiation transmitted through the attenuation chamber. In a particular embodiment, a substantially linear increase in the thickness of the layer in the attenuation chamber yields a substantially exponential drop in the radiation dose rate transmitted through the attenuation chamber. Preferably, the elevation of the attenuation chamber is substantially fixed and the reservoir is vertically moveable, whereby changes in the radiation dose rate transmitted through the attenuation chamber are a function of changes of the elevation of the reservoir. The adjustment means further preferably includes a control means for controlling the movement of the reservoir, thereby providing control of the radiation transmitted through the attenuation chamber. The control means may further preferably include means for maintaining at least a minimum liquid thickness in the reservoir, and means for preventing the level of the liquid in the reservoir from rising above a maximum liquid height. Moreover, the control means may include means for specifying a desired dose rate pattern, such as an exponential dose rate pattern. The adjustment means further preferably includes a movable support means for supporting the reservoir and for adjusting the elevation of the reservoir relative to the attenuation chamber, such as a platform and drive means for vertically moving the platform. The drive means may include a shaft connected to the platform, a stepper motor connected to the shaft, and a stepper motor control means for receiving instructions from the control means and for sending motor control signals to the stepper motor. Preferably, the radiation-blocking liquid is liquid mercury. The apparatus further preferably includes a mutual vent means connecting the attenuation chamber and reservoir above respective maximum liquid levels for allowing an equalization of gas pressure therebetween. Furthermore, the present invention achieves the above objects, among others, by providing, in a particular embodiment, a method for delivering varying temporal radiation dose rates using an adjustable irradiator system, the system comprising a radiation source, a reservoir containing a radiation-blocking liquid, and an attenuation chamber connected to the reservoir by a siphon coupling and disposed in front of the radiation source, the method including selectively adjusting the elevation of the reservoir relative to the attenuation chamber and allowing the radiation-blocking liquid to seek a common level in the attenuation chamber and in the reservoir, thereby selectively adjusting the thickness of the radiation-blocking liquid in the attenuation chamber, whereby changes in the radiation dose rate transmitted through the attenuation chamber are a function of changes in the thickness of the radiation-blocking liquid in the attenuation chamber. The system is thus capable of administering a metered dose of radiation. The method further preferably includes selectively adjusting the elevation of the reservoir to cause an exponential rate of change in the radiation transmitted through the attenuation chamber. Preferably, a substantially constant rate of change in the level of the liquid in the reservoir causes a substantially constant rate of change in the level of the liquid in the attenuation chamber. Moreover, a substantially linear change in the thickness of the layer preferably causes a substantially exponential change in the radiation dose rate transmitted through the attenuation chamber. The method may also include maintaining a minimum liquid thickness in the attenuation chamber. The method may further include preventing the level of the liquid in the attenuation chamber from rising above a maximum liquid level. The present invention comprises a radiation attenuation apparatus and method which allows adjustment of the level of the radiation blocking liquid in finite increments thereby allowing the use of radiation-blocking fluids having the ability to attenuate high levels of radiation at a minimal fluid thickness. Such an apparatus and method allow for the attenuation means to be used in environments where a small-sized attenuator means is required. Furthermore, the present invention achieves the above objects, among others, by providing, in a particular embodiment, an adjustable irradiator system for use with a radiation-blocking liquid, the system including a radiation source and a variable attenuator means for intercepting at least a portion of the radiation emitted from the radiation source and for selectively blocking at least a part of the intercepted radiation with the radiation-blocking liquid, wherein the variable attenuator means is capable of transmitting at least another part of the intercepted radiation. The system is preferably capable of delivering exponentially varying temporal radiation dose rates. The variable attenuator means further preferably includes an attenuation chamber containing a layer of the radiation-blocking liquid and an adjustment means for adjusting the thickness of the layer, whereby changes in the thickness of the layer alter the radiation transmitted through the attenuation chamber. The system is thus capable of administering a metered dose of radiation. The system may also include a target means having at least one target station capable of receiving radiation transmitted through the attenuation chamber. The distance between the target station and the attenuation chamber may be adjustable. Furthermore, the target means may include a plurality of spaced apart target stations, wherein each station is disposed a different respective distance away from the attenuation chamber, whereby the target stations are capable of simultaneously receiving different respective radiation rates from the attenuation chamber.