X-ray or gamma ray systems or devices – Beam control – Filter
Reexamination Certificate
1997-04-11
2001-03-13
Church, Craig E. (Department: 2876)
X-ray or gamma ray systems or devices
Beam control
Filter
C378S156000
Reexamination Certificate
active
06201852
ABSTRACT:
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
Goddu Sreekrishna Murty
Howell Roger W.
Rao Dandamudi V.
Church Craig E.
Klauber & Jackson
University of Medicine & Denistry of New Jersey
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