US6226352B1
Expired / Lapsed
US
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System and method for radiographic imaging of tissue
Assignee: Veritas Pharmaceuticals Inc
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Filing: 1998-09-08
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Granted: 2001-05-01
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Expires: 2018-09-08
Abstract
Abstract System and method for radiographic imaging of tissue using a non-radioactive, radio-opaque imaging agent that accumulates intracellularly in tissue in proportion to its functional, or physiological, activity. In one embodiment, the imaging agent is a cell-membrane permeable, radio-opaque, high affinity ligand for the intracellular enzyme hexokinase. The imaging agent is administered to a patient, and after an accumulation interval, radiographic images are acquired. The imaging agent preferentially accumulates in malignant tissue and increases its radio-opacity because of its elevated glucose metabolic rate relative to benign and normal tissue. The tissue being examined is transilluminated by X-ray beams with preselected different mean energy spectra, and a separate radiographic image is acquired during transillumination by each beam. An image processing system performs a weighted combination of the acquired images to produce a single displayed image. The image processing procedure isolates the radiographic density contributed solely by differential accumulation of the imaging agent in malignant, benign, and normal tissue. The system and method thus provides a functional image displayed with the anatomical detail and spatial resolution of a radiographic image. The viewer may interactively control the relative proportion of radiographic density contributed by imaging agent, soft tissue, and bone to the displayed image, allowing the display of functional and anatomical information in complete registration, and facilitating localization of malignant tissue in relation to nearby anatomical structures. In other embodiments, the system and method may be used to detect enzymes, nucleic acids, coenzymes, fatty acids, and other cellular targets in diagnostic imaging applications.
Inventors
- 👤 Jesse Salb
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 21:42
CPC Classifications
A; A61; A61B; A61B6/00; A61B6/48; A61B6/482; A61B6/40; A61B6/4035; A61B6/4042; A61B6/42; A61B6/4208; A61B6/4241; A61B6/02; A61B6/03; A61B6/032; A61B6/4064; A61B6/4092
Claims Analysis
Total Claims: 84
Claim 1
Independent Claim
79 words
A system for radiographic imaging of body tissue comprising: a) a cell membrane-permeable, radio-opaque imaging agent; b) means for administering said imaging agent to a patient; c) means for generating a plurality of X-ray beams with predetermined different energy spectra; d) means for acquiring radiographic images disposed on the side of said patient opposite said X-ray beam generating means; and e) means for performing a weighted combination of a plurality of said radiographic images to produce a single image.
Claim 2
Independent Claim
79 words
A system for radiographic imaging of body tissue comprising: a) a cell membrane-permeable, radio-opaque imaging agent; b) means for administering said imaging agent to a patient; c) means for generating a plurality of X-ray beams with predetermined different energy spectra; d) means for acquiring radiographic images disposed on the side of said patient opposite said X-ray beam generating means; and e) means for performing a weighted combination of a plurality of said radiographic images to produce a single image.
Claim 3
Dependent Claim
12 words
The system of claim 1 wherein said plurality of beams are quasi-monoenergetic.
Claim 4
Dependent Claim
12 words
The system of claim 1 wherein said plurality of beams are monoenergetic.
Claim 5
Dependent Claim
10 words
The system of claim 1 wherein 2 beams are generated.
Claim 6
Dependent Claim
12 words
The system of claim 1 wherein more than 2 beams are generated.
Claim 7
Dependent Claim
29 words
The system of claim 1 , further including means for displaying variable proportions of radiographic density contributed by said imaging agent, soft tissue, and bone to said single image.
Claim 8
Dependent Claim
18 words
The system of claim 1 wherein said cell membrane-permeable, radio-opaque imaging agent selectively binds to a cellular target.
Claim 9
Dependent Claim
13 words
The system of claim 7 wherein said cellular target is a cellular structure.
Claim 10
Dependent Claim
12 words
The system of claim 7 wherein said cellular target is a molecule.
Claim 11
Dependent Claim
21 words
The system of claim 7 wherein said cellular target is selected from the group of proteins, nucleic acids, coenzymes, and lipids.
Claim 12
Dependent Claim
12 words
The system of claim 7 wherein said cellular target is an enzyme.
Claim 13
Dependent Claim
11 words
The system of claim 7 wherein said cellular target is hexokinase.
Claim 14
Dependent Claim
21 words
The system of claim 1 wherein said imaging agent accumulates in malignant tissue at a different rate than in non-malignant tissue.
Claim 15
Dependent Claim
23 words
The system of claim 1 wherein said imaging agent accumulates in abnormal myocardial tissue at a different rate than in normal myocardial tissue.
Claim 16
Dependent Claim
15 words
The system of claim 1 wherein said imaging agent has a logP of above 0.0.
Claim 17
Independent Claim
69 words
A system for radiographic imaging of body tissue comprising: a) a radio-opaque imaging agent which is capable of entering a cell through passive diffusion and which selectively binds to a cellular target; b) means for administering said imaging agent to a patient; c) means for generating an X-ray beam; and d) means for acquiring radiographic images disposed on the side of said patient opposite said X-ray beam generating means.
Claim 18
Independent Claim
69 words
A system for radiographic imaging of body tissue comprising: a) a radio-opaque imaging agent which is capable of entering a cell through passive diffusion and which selectively binds to a cellular target; b) means for administering said imaging agent to a patient; c) means for generating an X-ray beam; and d) means for acquiring radiographic images disposed on the side of said patient opposite said X-ray beam generating means.
Claim 19
Dependent Claim
49 words
The system according to claim 16 , wherein the means for generating said X-ray beam is capable of generating a plurality of beams with predetermined different energy spectra and further comprising means for performing a weighted combination of a plurality of said radiographic images to produce a single image.
Claim 20
Dependent Claim
12 words
The system of claim 17 wherein said plurality of beams are quasi-monoenergetic.
Claim 21
Dependent Claim
12 words
The system of claim 17 wherein said plurality of beams are monoenergetic.
Claim 22
Dependent Claim
10 words
The system of claim 17 wherein 2 beams are generated.
Claim 23
Dependent Claim
12 words
The system of claim 17 wherein more than 2 beams are generated.
Claim 24
Dependent Claim
32 words
The system of claim 17 wherein said means for generating said plurality of beams with predetermined different energy spectra is disposed between said means for generating an X-ray beam and said patient.
Claim 25
Dependent Claim
31 words
The system of claim 17 wherein said means for generating said plurality of beams with predetermined different energy spectra is disposed between said patient and said means for acquiring radiographic images.
Claim 26
Dependent Claim
29 words
The system of claim 17 , further including means for displaying variable proportions of radiographic density contributed by said imaging agent, soft tissue, and bone to said single image.
Claim 27
Dependent Claim
13 words
The system of claim 16 wherein said cellular target is a cellular structure.
Claim 28
Dependent Claim
12 words
The system of claim 16 wherein said cellular target is a molecule.
Claim 29
Dependent Claim
21 words
The system of claim 16 wherein said cellular target is selected from the group of proteins, nucleic acids, coenzymes, and lipids.
Claim 30
Dependent Claim
12 words
The system of claim 16 wherein said cellular target is an enzyme.
Claim 31
Dependent Claim
11 words
The system of claim 16 wherein said cellular target is hexokinase.
Claim 32
Dependent Claim
21 words
The system of claim 16 wherein said imaging agent accumulates in malignant tissue at a different rate than in non-malignant tissue.
Claim 33
Dependent Claim
23 words
The system of claim 16 wherein said imaging agent accumulates in abnormal myocardial tissue at a different rate than in normal myocardial tissue.
Claim 34
Dependent Claim
15 words
The system of claim 16 wherein said imaging agent has a logP of above 0.0.
Claim 35
Independent Claim
48 words
A method for radiographic imaging of body tissue comprising: a) administering to a live organism containing tissue a bidirectionally cell membrane-permeable, radio-opaque imaging agent, b) generating an X-ray beam; c) illuminating said tissue with said X-ray beam; and d) acquiring a radiographic image of said tissue during illumination.
Claim 36
Independent Claim
48 words
A method for radiographic imaging of body tissue comprising: a) administering to a live organism containing tissue a bidirectionally cell membrane-permeable, radio-opaque imaging agent, b) generating an X-ray beam; c) illuminating said tissue with said X-ray beam; and d) acquiring a radiographic image of said tissue during illumination.
Claim 37
Dependent Claim
66 words
The method of claim 33 , further including: a) generating a plurality of X-ray beams with predetermined different energy spectra; b) illuminating said tissue with each of said plurality of beams; c) acquiring a radiographic image of said tissue during illumination by each of said plurality of beams; and d) performing a weighted combination of a plurality of said radiographic images to produce a single image.
Claim 38
Dependent Claim
12 words
The method of claim 34 wherein said plurality of beams are monoenergetic.
Claim 39
Dependent Claim
12 words
The method of claim 34 wherein said plurality of beams are quasi-monoenergetic.
Claim 40
Dependent Claim
10 words
The system of claim 34 wherein 2 beams are generated.
Claim 41
Dependent Claim
12 words
The system of claim 34 wherein more than 2 beams are generated.
Claim 42
Dependent Claim
26 words
The method of claim 34 , further displaying variable proportions of radiographic density contributed by said imaging agent, soft tissue, and bone to said single image.
Claim 43
Dependent Claim
18 words
The method of claim 33 wherein said cell membrane-permeable, radio-opaque imaging agent selectively binds to a cellular target.
Claim 44
Dependent Claim
13 words
The method of claim 40 wherein said cellular target is a cellular structure.
Claim 45
Dependent Claim
12 words
The method of claim 40 wherein said cellular target is a molecule.
Claim 46
Dependent Claim
21 words
The method of claim 40 wherein said cellular target is selected from the group of proteins, nucleic acids, coenzymes, and lipids.
Claim 47
Dependent Claim
12 words
The method of claim 40 wherein said cellular target is an enzyme.
Claim 48
Dependent Claim
11 words
The method of claim 40 wherein said cellular target is hexokinase.
Claim 49
Dependent Claim
21 words
The method of claim 33 wherein said imaging agent accumulates in malignant tissue at a different rate than in non-malignant tissue.
Claim 50
Dependent Claim
15 words
The method of claim 33 wherein said imaging agent has a logP of above 0.0.
Claim 51
Independent Claim
57 words
A method for radiographic imaging of body tissue comprising: a) administering to a live organism containing tissue a cell membrane-permeable, radio-opaque imaging agent which selectively binds to an intracellular target in the organism; b) generating an X-ray beam; c) illuminating said tissue with said X-ray beam; and d) acquiring a radiographic image of said tissue during illumination.
Claim 52
Independent Claim
57 words
A method for radiographic imaging of body tissue comprising: a) administering to a live organism containing tissue a cell membrane-permeable, radio-opaque imaging agent which selectively binds to an intracellular target in the organism; b) generating an X-ray beam; c) illuminating said tissue with said X-ray beam; and d) acquiring a radiographic image of said tissue during illumination.
Claim 53
Dependent Claim
66 words
The method of claim 48 , further including: a) generating a plurality of X-ray beams with predetermined different energy spectra; b) illuminating said tissue with each of said plurality of beams; c) acquiring a radiographic image of said tissue during illumination by each of said plurality of beams; and d) performing a weighted combination of a plurality of said radiographic images to produce a single image.
Claim 54
Dependent Claim
12 words
The method of claim 49 wherein said plurality of beams are monoenergetic.
Claim 55
Dependent Claim
12 words
The method of claim 49 wherein said plurality of beams are quasi-monoenergetic.
Claim 56
Dependent Claim
10 words
The system of claim 49 wherein 2 beams are generated.
Claim 57
Dependent Claim
12 words
The system of claim 49 wherein more than 2 beams are generated.
Claim 58
Dependent Claim
26 words
The method of claim 49 , further displaying variable proportions of radiographic density contributed by said imaging agent, soft tissue, and bone to said single image.
Claim 59
Dependent Claim
13 words
The method of claim 48 wherein said intracellular target is a cellular structure.
Claim 60
Dependent Claim
12 words
The method of claim 48 wherein said intracellular target is a molecule.
Claim 61
Dependent Claim
22 words
The method of claim 48 wherein said intracellular target is selected from the group consisting of proteins, nucleic acids, coenzymes, and lipids.
Claim 62
Dependent Claim
12 words
The method of claim 48 wherein said intracellular target is an enzyme.
Claim 63
Dependent Claim
11 words
The method of claim 48 wherein said intracellular target is hexokinase.
Claim 64
Dependent Claim
21 words
The method of claim 48 wherein said imaging agent accumulates in malignant tissue at a different rate than in non-malignant tissue.
Claim 65
Dependent Claim
23 words
The system of claim 48 wherein said imaging agent accumulates in abnormal myocardial tissue at a different rate than in normal myocardial tissue.
Claim 66
Dependent Claim
15 words
The method of claim 48 wherein said imaging agent has a logP of above 0.0.
Claim 67
Independent Claim
82 words
A method for generating a functional image and an anatomical image of live tissue in registration comprising: a) administering to a live organism a radio-opaque imaging agent; b) generating a plurality of X-ray beams with predetermined different energy spectra; c) illuminating said live tissue with each of said plurality of beams; d) acquiring a radiographic image of said live tissue during illumination by each of said plurality of beams; e) generating said functional image from at least two of said radiographic images.
Claim 68
Independent Claim
82 words
A method for generating a functional image and an anatomical image of live tissue in registration comprising: a) administering to a live organism a radio-opaque imaging agent; b) generating a plurality of X-ray beams with predetermined different energy spectra; c) illuminating said live tissue with each of said plurality of beams; d) acquiring a radiographic image of said live tissue during illumination by each of said plurality of beams; e) generating said functional image from at least two of said radiographic images.
Claim 69
Dependent Claim
58 words
The method of claim 63 wherein said radio-opaque imaging agent comprises a composition having a general formula S-L-X, wherein said composition is cell membrane-permeable and wherein: S is a binding moiety which selectively binds to a cellular molecule; X is a radio-opaque moiety; and L is a linking moiety which links the S moiety to the X moiety.
Claim 70
Dependent Claim
86 words
A computer-readable storage medium containing executable computer instructions which, when executed by an image processing system, cause said image processing system to perform a method comprising: a) acquiring a plurality of radiographic images, wherein each of said radiographic images is acquired during transillumination of live tissue in a living organism by one of a plurality of X-ray beams with a predetermined unique energy spectrum, said living organism having been administered a radio-opaque imaging agent; and b) generating a functional image from said plurality of radiographic images.
Claim 71
Dependent Claim
86 words
A computer-readable storage medium containing executable computer instructions which, when executed by an image processing system, cause said image processing system to perform a method comprising: a) acquiring a plurality of radiographic images, wherein each of said radiographic images is acquired during transillumination of live tissue in a living organism by one of a plurality of X-ray beams with a predetermined unique energy spectrum, said living organism having been administered a radio-opaque imaging agent; and b) generating a functional image from said plurality of radiographic images.
Claim 72
Dependent Claim
33 words
A computer-readable storage medium as in claim 65 wherein said method further comprises: a) displaying said functional image; and b) displaying one of said plurality of radiographic images which is an anatomical image.
Claim 73
Dependent Claim
23 words
A computer-readable storage medium as in claim 66 wherein said functional image and said anatomical image are displayed simultaneously and in aligned registration.
Claim 74
Dependent Claim
19 words
A computer-readable storage medium as in claim 66 wherein said functional image and said anatomical image are displayed separately.
Claim 75
Dependent Claim
92 words
A computer-readable storage medium containing executable computer program instructions which, when executed by a image processing system, cause said image processing system to perform a method comprising: a) acquiring at least one radiographic image obtained by irradiating tissue in a living organism with a radiation source which is capable of being attenuated by a composition which is administered to said living organism, wherein said composition is bidirectionally cell membrane-permeable and radio-opaque and capable of binding to a cellular target; and b) generating an image from at least one of said radiographic images.
Claim 76
Dependent Claim
92 words
A computer-readable storage medium containing executable computer program instructions which, when executed by a image processing system, cause said image processing system to perform a method comprising: a) acquiring at least one radiographic image obtained by irradiating tissue in a living organism with a radiation source which is capable of being attenuated by a composition which is administered to said living organism, wherein said composition is bidirectionally cell membrane-permeable and radio-opaque and capable of binding to a cellular target; and b) generating an image from at least one of said radiographic images.
Claim 77
Dependent Claim
21 words
A computer-readable storage medium as in claim 69 wherein said method further comprises displaying said image which is a functional image.
Claim 78
Dependent Claim
31 words
A computer-readable storage medium as in claim 69 wherein said method further comprises displaying a radiographic image which is an anatomical image and which is in registration with a functional image.
Claim 79
Dependent Claim
20 words
A medium as in claim 65 , wherein said functional image indicates the presence or absence of a molecular target.
Claim 80
Dependent Claim
20 words
A medium as in claim 65 , wherein said functional image indicates the presence or absence of a cellular target.
Claim 81
Dependent Claim
18 words
A medium as in claim 65 , wherein said functional image indicates the concentration of a cellular target.
Claim 82
Dependent Claim
20 words
A method as in claim 63 , wherein said functional image indicates the presence or absence of a molecular target.
Claim 83
Dependent Claim
20 words
A method as in claim 63 , wherein said functional image indicates the presence or absence of a cellular target.
Claim 84
Dependent Claim
18 words
A method as in claim 63 , wherein said functional image indicates the concentration of a cellular target.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 2004-04-30 | 2004-10-30 | 2005-05-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2008-04-30 | 2008-10-30 | 2009-05-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2012-04-30 | 2012-10-30 | 2013-05-01 | $7700.00 | Window Closed / Lapsed |