WO2004049001A1 - Gamma camera with dynamic threshold - Google Patents
Gamma camera with dynamic threshold Download PDFInfo
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- WO2004049001A1 WO2004049001A1 PCT/IB2003/005123 IB0305123W WO2004049001A1 WO 2004049001 A1 WO2004049001 A1 WO 2004049001A1 IB 0305123 W IB0305123 W IB 0305123W WO 2004049001 A1 WO2004049001 A1 WO 2004049001A1
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- 239000011159 matrix material Substances 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 33
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- 238000002591 computed tomography Methods 0.000 claims abstract description 12
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01T—MEASUREMENT OF NUCLEAR OR X-RADIATION
- G01T1/00—Measuring X-radiation, gamma radiation, corpuscular radiation, or cosmic radiation
- G01T1/16—Measuring radiation intensity
- G01T1/161—Applications in the field of nuclear medicine, e.g. in vivo counting
- G01T1/1615—Applications in the field of nuclear medicine, e.g. in vivo counting using both transmission and emission sources simultaneously
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
- A61B6/02—Arrangements for diagnosis sequentially in different planes; Stereoscopic radiation diagnosis
- A61B6/03—Computed tomography [CT]
- A61B6/037—Emission tomography
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01T—MEASUREMENT OF NUCLEAR OR X-RADIATION
- G01T1/00—Measuring X-radiation, gamma radiation, corpuscular radiation, or cosmic radiation
- G01T1/16—Measuring radiation intensity
- G01T1/161—Applications in the field of nuclear medicine, e.g. in vivo counting
- G01T1/164—Scintigraphy
- G01T1/1641—Static instruments for imaging the distribution of radioactivity in one or two dimensions using one or several scintillating elements; Radio-isotope cameras
- G01T1/1642—Static instruments for imaging the distribution of radioactivity in one or two dimensions using one or several scintillating elements; Radio-isotope cameras using a scintillation crystal and position sensing photodetector arrays, e.g. ANGER cameras
Definitions
- the present invention relates to the art of nuclear medical imaging. It finds particular application in conjunction with gamma cameras, and will be described with particular reference thereto. It is usable in connection with emission computed tomography ("ECT"), including positron emission tomography (“PET”) and single photon emission computed tomography (“SPECT”); whole body nuclear scans; transmission imaging; etc. Those skilled in the art will appreciate that the present invention is also amenable to other like applications and diagnostic imaging modes.
- ECT emission computed tomography
- PET positron emission tomography
- SPECT single photon emission computed tomography
- Diagnostic nuclear imaging or ECT is directed to a qualitative and quantitative examination of a distribution of radiotracers, typically, injection into the subject of the examination, e.g., a patient.
- ECT scanners usually have one or more radiation detectors or gamma cameras that are mounted on a movable gantry to view an examination region which receives the subject therein.
- one or more radionuclides or radiopharmaceuticals that generate detectable radiation are introduced into the subject.
- the radiopharmaceuticals preferably travel to an organ or organs of interest whose image is to beproduced.
- the detectors scan the subject along a selected path or scanning trajectory and radiation events are detected on each gamma camera.
- the detector has a scintillator made up of a large scintillation crystal or matrix of smaller scintillation crystals. In either case, the scintillator is viewed by a matrix of sensors.
- a commonly employed sensor is a photomultiplier tube ("PMT").
- PMT photomultiplier tube
- a coUimator which includes a grid- or honeycomb-like array of radiation absorbent material may be located between the scintillator and the subj ect being examined to limit the angle of acceptance of radiation which impinges on the scintillator.
- the relative outputs of the PMTs are processed and corrected to generate a signal indicative of the position and energy of detected radiation events.
- the radiation data is then reconstructed into an image representation of a region of interest.
- Each radiation event impinging on the scintillator generates a corresponding flash of light (scintillation) that is seen by the PMTs.
- An individual PMT's proximity to the flash's origin affects the degree to which the light is seen by that PMT.
- Each PMT that sees an event generates a corresponding electrical pulse.
- the respective amplitudes of the electrical pulses are generally proportional to the distance of each PMT from the flash.
- the gamma camera maps radiation events, i.e., it determines the energy and position of radiation rays impinging the scintillator.
- a conventional method for event positioning is known as the Anger method, which sums and weights signals output by PMTs after the occurrence of an event.
- the Anger method for event positioning is based on a simple first moment calculation. More specifically, the energy is typically measured as the sum of all the PMT signals, and the position is typically measured as the "center of mass" or centroid of all the PMT signals.
- centroid calculation Several methods have been used for implementing the centroid calculation. With fully analog cameras, all such calculations (e.g., summing, weighting, dividing) are done using analog circuits. With hybrid analog/digital cameras, the summing and weighting are done using analog circuits, but the summed values are digitized and the final calculation of position is done digitally.
- the PMT output signals will be digitized individually. Regardless of the aforementioned camera type employed, the quality and/or accuracy of the images ultimately reconstructed is dependant on accurately measuring or otherwise determining the location or position of an event so as to match the actual event location or position.
- a scintillation light flash is mostly contained within a small subset of the PMTs. For example, out of a total number of PMTs, typically on the order of 50 or 60, over 90% of a total signal is often detected in the seven (7) PMTs closest to a scintillation flash.
- light from the scintillator undesirably straying to more remote PMTs, noise in the PMT outputs, and the like can effect the centroid calculation in the traditional Anger method because all the PMT outputs are used in the positioning calculation. Accordingly, this may give rise to an artificial shifting of event location measurements. Stray signals also tend to arise at high-counting rates due to events occurring nearly simultaneously in the scintillator. When two events occur substantially simultaneously, their "center-of-mass" is midway between the two ⁇ where no event actually occurred. Again, events can be mis- positioned as a result.
- the stray or otherwise undesirable signals are typically characterized by lower PMT signal amplitudes as compared to PMT signals associated with and/or corresponding to actual observed events.
- PMT signal amplitudes as compared to PMT signals associated with and/or corresponding to actual observed events.
- techniques have been developed to address the mis-positioning problem associated with stray signals. In particular ways, these techniques aim to selectively limit the number of PMTs used in the centroid calculation and/or limited the contribution thereto from selected PMTs.
- One option is to set an arbitrary threshold, and omit from the centroid calculation for an event PMT outputs with amplitudes that due not meet the threshold.
- the PMT output amplitudes may be reduced by the threshold amount thereby effectively eliminating any contributions from PMT outputs below the threshold.
- This technique is undesirably inflexible and can at times eliminate or omit PTM outputs that would otherwise be wanted in the centroid calculation or still include PTM outputs that would otherwise not be wanted in the centroid calculation (e.g., from PMTs that are significantly remote from the event).
- FIGURE 8 is an exemplary illustration of event data generated using the 7-PMT cluster technique. The hexagonal artifact clearly evident is an indication of event mis- positioning.
- FIGURE 9 is an exemplary illustration of event data generated using a combined thresholding and 7-PMT cluster technique.
- the 7-PMT cluster is selected in the same way, however, a threshold is set, and for each event, those PMT outputs with amplitudes less than the threshold are omitted from the centroid calculation for that event.
- the PMT output amplitudes may be reduced by the threshold amount thereby effectively eliminating any contributions from PMT outputs below the threshold.
- the PMT output amplitudes from all the PMTs are summed up or otherwise totaled together, and the threshold is set as a percentage (e.g., 3%) of this total.
- FIGURE 11 which shows a close hexagonal packed 7-PMT cluster 300 including a center PMT 310 and six (6) surrounding PMTs 312a-312f, an exemplary double point being indicated generally by point 320 and an exemplary triple point being indicated generally by point 322.
- the tliree (3) other PMTs namely, PMTs 312c, 312d and 312e
- PMTs 312c, 312d and 312e can have a significant impact on the determined location of the event, and while they see the double point event relatively more weakly, it can still be sigmficant enough to overcome the "percentage of total" threshold.
- the outputs of the three other PMTs 312c, 312d and 312e may be more largely based on individual gain variations, random noise, and other such factors which are not suitably reliable for positioning the event, rather than on the degree to which the scintillator light is seen. Near the triple point 322, the analogous problem occurs.
- the present invention contemplates a new and improved gamma camera and technique therefor which overcomes the above- referenced problems and others.
- a method of locating an event with a gamma camera of an emission computed tomography (ECT) scanner includes a matrix of sensors situated to view the event.
- the sensors have respective outputs that are responsive to the event.
- the method includes: identifying a first sensor in the matrix that has in response to the event a highest output relative to the other sensors in the matrix; identifying a number of second sensors in the matrix that are closest neighbors to the first sensor; combining into a total output a number of outputs from the identified sensors, the number of outputs being at least one (1) and less than the number of all the identified sensors; and, determining a threshold value which is a percentage of the total output.
- a gamma camera for locating a radiation event in an emission computed tomography (ECT) scanner.
- the gamma camera includes: a matrix of sensors situated to view the event, the sensors having respective outputs that are responsive to the event; means for identifying a first sensor in the matrix that has in response to the event a highest output relative to the other sensors in the matrix; means for identifying a number of second sensors in the matrix that are closest neighbors to the first sensor; means for combining into a total output a number of outputs from the identified sensors, the number of outputs being at least one (1) and less than the number of all the identified sensors; and, means for determining a threshold value which is a percentage of the total output.
- an emission computed tomography (ECT) scanner includes an examination region in which a subject being examined is situated, the subject containing a distribution of radionuclides.
- a detector has a matrix of sensors situated to view a radiation event emanating from the examination region, the sensors having respective outputs that are responsive to the event.
- a processor (i) identifies a first sensor in the matrix that has in response to the event a highest output relative to the other sensors in the matrix; (ii) identifies a number of second sensors in the matrix that are closest neighbors to the first sensor; (iii) combines into a total output a number of outputs from the identified sensors, said number of outputs being at least one (1) and less than the number of all the identified sensors; and, (iv) determines a threshold value which is a percentage of the total output.
- a method of emission computed tomography includes : approximating a location of a detected event with respect to a matrix of sensors that view the event, and determining if the approximated location of the detected event is substantially within effective boundaries of a sensor in the matrix. If it is determined that the approximated location of the detected event is substantially within effective boundaries of a sensor in the matrix, then a first number of sensors nearest the approximated location are sampled. Otherwise, if it is determined that the approximated location of the detected event is not substantially within effective boundaries of a sensor in the matrix, then a second number of sensors nearest the approximated location are sampled, the second number being less than the first number. A position for the detected event is generated from the sampled sensors.
- One advantage of the present invention is the ability to improve image quality resulting from better spatial resolution and event positioning.
- Another advantage of the present invention is the ability to reduce hexagon artifacts in images obtained from gamma cameras.
- the invention may take form in various components and arrangements of components, and in various steps and arrangements of steps.
- the drawings are only for purposes of illustrating preferred embodiments and are not to be construed as limiting the invention. The drawings are not to scale.
- FIGURE 1 is a diagrammatic illustration of an exemplary ECT scanner in accordance with aspects of the present invention.
- FIGURE 2 is an overview flow chart showing an exemplary method in accordance with aspects of the present invention.
- FIGURE 3 is a flow chart showing exemplary sub-steps for carrying out a step shown in the flow chart of FIGURE 2.
- FIGURE 4 is a flow chart showing exemplary sub-steps for carrying out a step shown in the flow chart of FIGURE 2.
- FIGURE 5 is a diagrammatic illustration showing an exemplary spread of light from a scintillation event to a close packed hexagonal arrangement of sensors in accordance with aspects of the present invention.
- FIGURE 6 is a flow chart showing an exemplary method in accordance with aspects of the present invention.
- FIGURE 7 is an illustration showing event data obtained in accordance with practicing aspects of the present invention.
- FIGURE 8 is an illustration showing event data obtained in accordance with practicing a prior art approach.
- FIGURE 9 is an illustration showing event data obtained in accordance with practicing a prior art approach.
- FIGURE 10 is a diagrammatic illustration of another exemplary ECT scanner in accordance with aspects of the present invention.
- FIGURE 11 is a diagrammatic illustration showing exemplary locations of double and triple points in a close packed hexagonal 7-PMT cluster.
- an ECT scanner 10 includes a plurality of detectors heads (“detectors”) or gamma cameras 12 facing and mounted for movement around a subject 14 (preferably containing a radionuclide distribution) located in an examination region 16.
- Each of the detectors 12 includes a scintillator 20 that converts a radiation event (e.g., a ray of radiation from the radionuclide distribution that impinges on the scintillator 20) into a flash of light or scintillation.
- a matrix of sensors 22, e.g., 59 sensors, is situated to view or receive the light flashes from the scintillator 20.
- the matrix of sensors is a close hexagonal packed arrangement of PMTs. However, other sensors and packing arrangements are also contemplated.
- Each of the sensors 22 generates a respective output signal, e.g., an analog electrical pulse, in response to a received light flash, the output signal being proportional to that of the received light flash.
- each of the sensors 22 is optionally electrically connected to analog-to-digital (A/D) converters 24 that convert the respective analog outputs to digital signals. While “fully digital " cameras 12 are shown, “fully analog” or “hybrid analog/digital” cameras may also be suitably employed.
- a processor 26 measures or otherwise determines the location and/or energy of respective scintillation events that occur. The location of an event on the scintillator 20 is resolved and or determined in a two dimensional (2D) Cartesian coordinate system with nominally termed x and y coordinates. However, other coordinate systems are contemplated.
- radiation is detected and converted into sensor output signal, which are transmitted to the processor 26 in a step A.
- the processor 26 detects that an event occurs and identifies and/or selects sensor outputs that will be used and/or sampled to determine the position and or energy of the event.
- the processor regulates the extent to which particular sensor outputs will contribute to the determination or calculation of an event's position and/or energy.
- the processor 26 calculates or otherwise determines the position and/or energy of the event.
- an image is reconstructed from the located events, the image being representative of the radionuclide distribution within the subject 14.
- each of the steps A and B includes a plurality of respective sub-steps, which are discussed below.
- each of the sub- steps is identified with a reference numeral specifying both the step (see FIGURE 2) and the sub-step (see FIGURES 3 and 4).
- each radiation event is detected within the matrix of sensors 22 in a sub-step Al.
- the radiation produces gamma quanta that arise in the disintegration of radioisotopes.
- the disintegration quanta strike the scintillator 20, which preferably includes doped sodium iodide (Nal), causing a scintillation. Light from the scintillation is distributed over a number of the sensors 22.
- Nal doped sodium iodide
- an exemplary scintillation which is created by a radiation event, is centered at an arbitrary position 28.
- the amount of light from a particular scintillation that a given sensor 22 sees or receives tends to progressively diminish with the sensor's distance from the event (indicated by reference numerals dl-dl9).
- reference numerals dl-dl9 indicate that only a partial portion of the matrix of the sensors 22 is shown in FIGURE 5.
- the energy of the absorbed gamma quantum is converted, or transformed, into the flash of light at the position 28 by the scintillator 20 in a sub-step A2.
- the sensors 22 detect (receive) the scintillation light in a sub-step A3.
- the sensors 22 produce their respective output signals in a sub-step A4.
- the relative the sensor output signals are proportional to the respective amounts of the scintillation light received by the sensors 22 in the sub-step A3.
- the A/D converters 24 convert analog output signals to respective digital output in a sub-step A5.
- the digital outputs are then transmitted to the processor 26 in a sub-step A6.
- the output value of each sensor 22 is optionally determined by: integration of the sensor's output signal response to the event (i.e., finding the area or some portion thereof under a curve plotting amplitude or intensity vs.
- the processor 26 detects that an event occurs (starts) in a sub-step Bl by analyzing the output values for each of the sensors. In a preferred embodiment, the processor 26 triggers (detects) that an event occurs when a sensor output value surpasses a trigger amplitude. hi a sub-step B2, the sensor 22 having the highest output value relative to all the other sensors 22 is identified, and a number of closest neighboring sensors 22 thereto are also identified in sub-step B3.
- the number closest neighboring sensors 22 identified is six (6), thereby defining a 7-PMT cluster, with the center sensor 22 being the identified one having the highest output value and the six (6) closest neighboring sensors 22 surrounding the same.
- a threshold is dynamically determined for each detected event.
- the threshold is preferably not based on or a percentage of the total sum of output values from all the sensors 22 identified in sub-steps B2 and B3 (collectively referred to as the identified sensors). Rather, the threshold is based on or a percentage of an output value from one of the identified sensors, or alternately the threshold is based on or a percentage of the total sum of output values from multiple, but less than all, of the identified sensors (e.g., in a 7-PMT cluster, from 2 to 6 of the identified sensors).
- the threshold is calculated or otherwise determined as a percentage (e.g., 30%) of the output value from the identified sensor having the third highest output value.
- FIGURE 7 illustrates exemplary event data obtained in accordance with such an embodiment.
- other percentages are also contemplated, and it is contemplated to also base the percentage on the output value of an identified sensor having a relative output value ranked other than the third highest.
- step C the position of a particular event is determined using only output values obtained from the identified subset of sensors determined in sub-step B5, i.e., without factoring in output values from sensors that are not members of the identified subset.
- the position is preferably calculated as the centroid of the output values obtained from the identified subset of sensors, e.g., using an Anger sum that omits output values from sensors that are not members of the identified subset.
- the output values from all the identified sensors may be reduced by the determined threshold amount thereby effectively eliminating any contributions from identified sensors having output values below the threshold in a subsequent position determination that uses the so modified output values from all the identified sensors. More specifically, in sub-step B5, the determined threshold value from sub-step B4 is subtracted from the output values of all the identified sensors from sub-steps B2 and B3, with negative results being given a zero (0) value. Then, at step C, the position of a particular event is determined using the resulting output values (as reduced in sub-step B5) from all the identified sensors.
- the result is a relative reduction in mis-positioning events as evidenced by the significant (in fact, the nearly complete) elimination of the hexagonal artifact.
- the threshold is set to be approximately 30% of the output value obtained from the PMT with the third highest- ranked output value in accordance with the technique proposed herein.
- an approximation of an event location is determined at a step 100. Then, it is determined at a decision step 102, if the approximate location is at or near a boundary of a sensor 22 or is between sensors 22.
- a first number of sensors nearest the approximate location are sampled to generate the final position determination in a step 106, e.g., employing an Anger sum. Otherwise, if the approximate location is determined in step 102 to be at or near a boundary of a sensor or is between sensors, then at step 104 a second number (less than the first number) of sensors nearest the approximate location are sampled to generate the final position determination in step 106.
- the scanner 10 illustrated in FIGURE 1 is selectively operable as desired in either a SPECT mode or a PET mode, h the SPECT mode, the cameras 12 have collimators attached thereto which limit acceptance of radiation to particular directions, i.e., along known rays.
- the determined location on the scintillator 20 at which radiation is detected and the angular position of the camera 12 define the ray along which each radiation event occurred.
- These ray trajectories and camera angular positions (e.g., obtained from an angular position resolver 60) are conveyed to a reconstruction processor 62 which backproj ects or otherwise reconstructs the rays into a volumetric image representation in an image memory 64.
- the collimators are removed.
- the location of a single scintillation event does not define a ray.
- the radionuclides used in PET scanning undergo an annihilation event in which two photons of radiation are emitted simultaneously in diametrically opposed directions, i.e., 180 degrees apart.
- a coincidence detector 66 detects when scintillations on two cameras 12 occur simultaneously.
- the locations of the two simultaneous scintillations define the end points of a ray through the annihilation event.
- a ray or traj ectory calculator 68 calculates the corresponding ray through the subj ect 14 from each pair of simultaneously received scintillation events.
- the ray trajectories form the ray calculator 68 are conveyed to the reconstruction processor 60 for reconstruction into a volumetric image representation.
- a video processor 70 processes and/or formats the image representation data for display on a monitor 72.
- a scanner in accordance with another embodiment of the present invention is illustrated. For ease of understanding this embodiment, like components are designated by like reference numerals and previously unreferenced components are designated by new numerals.
- the scanner 10 includes three (3) detectors or cameras 12 mounted for movement around the subject 14 situated in an examination region 16, the subj ect being inj ected with a radionuclide that emits emission radiation.
- Each of the detectors 12 includes a scintillator 20 for converting radiation events from the injected radionuclide into a flash of light energy or scintillation.
- a radiation source 202 produces a fan of transmission radiation of a different energy than the emission radiation.
- Collimators 204 on the detectors 20 limit and define the paths or rays along which each detector 20 accepts emission and transmission radiation. The location of a resulting scintillation and the position of the receiving detector 20 uniquely determine the ray. That is to say, the processor 26 determines the energy and the location of each scintillation on the face of the detectors 20, hence the ray along which the radiation originated.
- the reconstruction processor 60 reconstructs an image representation from the emission data, which is distinguished via the determined energy associated with the data.
- transmission data (similarly identified via the energy associated with the data) is used to correct the emission data for an improved image, e.g., by generating an attenuation map or the like of the subject 14.
- the image representation is stored in the image memory 62, and accessing the same, the video processor 70 processes the image representation data for display on the monitor 72.
- the scanner 10 can be used without collimators 204 in a PET mode.
- a switch or other suitable control 206 is optionally provided for mode selection. It is to be appreciated that while shown arranged on one of the cameras 20, the radiation source 202 is optionally disposed elsewhere.
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Abstract
Description
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Priority Applications (4)
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US10/536,061 US7262416B2 (en) | 2002-11-27 | 2003-11-12 | Gamma camera with dynamic threshold |
EP03769812A EP1579246A1 (en) | 2002-11-27 | 2003-11-12 | Gamma camera with dynamic threshold |
AU2003278513A AU2003278513A1 (en) | 2002-11-27 | 2003-11-12 | Gamma camera with dynamic threshold |
JP2004554773A JP4429915B2 (en) | 2002-11-27 | 2003-11-12 | Gamma camera with dynamic threshold |
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US42950402P | 2002-11-27 | 2002-11-27 | |
US60/429,504 | 2002-11-27 |
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WO2004049001A1 true WO2004049001A1 (en) | 2004-06-10 |
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EP (1) | EP1579246A1 (en) |
JP (1) | JP4429915B2 (en) |
AU (1) | AU2003278513A1 (en) |
WO (1) | WO2004049001A1 (en) |
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WO2012025858A3 (en) * | 2010-08-26 | 2012-06-14 | Koninklijke Philips Electronics N.V. | Pixellated detector device |
DE102011075520A1 (en) * | 2011-05-09 | 2012-11-15 | Siemens Aktiengesellschaft | Method for detecting X-ray quantum generated in X-ray unit used in medical field, involves evaluating measurement signals which is produced for approximating specific position at which X-ray quantum interacts with X-ray detector |
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- 2003-11-12 AU AU2003278513A patent/AU2003278513A1/en not_active Abandoned
- 2003-11-12 WO PCT/IB2003/005123 patent/WO2004049001A1/en active Application Filing
- 2003-11-12 EP EP03769812A patent/EP1579246A1/en not_active Withdrawn
- 2003-11-12 JP JP2004554773A patent/JP4429915B2/en not_active Expired - Fee Related
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US5508524A (en) * | 1994-10-03 | 1996-04-16 | Adac Laboratories, Inc. | Spatially variant PMT cluster constitution and spatially variant PMT weights |
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DE102004048962A1 (en) * | 2004-10-07 | 2006-04-20 | Siemens Ag | Digital x-ray imaging device or method for recording x-ray images in a digital x-ray imaging device |
DE102004048962B4 (en) * | 2004-10-07 | 2006-09-21 | Siemens Ag | Digital x-ray imaging device or method for recording x-ray images in a digital x-ray imaging device |
US7473902B2 (en) | 2004-10-07 | 2009-01-06 | Siemens Aktiengesellschaft | Digital radiographic unit and a method for taking radiographs in a digital radiographic unit |
WO2012025858A3 (en) * | 2010-08-26 | 2012-06-14 | Koninklijke Philips Electronics N.V. | Pixellated detector device |
US9110174B2 (en) | 2010-08-26 | 2015-08-18 | Koninklijke Philips N.V. | Pixellated detector device |
DE102011075520A1 (en) * | 2011-05-09 | 2012-11-15 | Siemens Aktiengesellschaft | Method for detecting X-ray quantum generated in X-ray unit used in medical field, involves evaluating measurement signals which is produced for approximating specific position at which X-ray quantum interacts with X-ray detector |
Also Published As
Publication number | Publication date |
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US20060163486A1 (en) | 2006-07-27 |
US7262416B2 (en) | 2007-08-28 |
EP1579246A1 (en) | 2005-09-28 |
JP2006508344A (en) | 2006-03-09 |
AU2003278513A1 (en) | 2004-06-18 |
JP4429915B2 (en) | 2010-03-10 |
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