The present invention is directed to the field of detectors for blood flow and chromatography. More specifically, the present invention relates to a low background beta radiation detector.
The art knows that the basis for detection of a beta emitting nuclei is a nucleus emitting a beta particle (electron or positron) with some kinetic energy. The beta particle will “bounce” around the electric charges in the matter, and will share its kinetic energy mainly interacting with electrons. In the case of emitted positrons, the probability that the positron, which is the anti-matter to an electron, will be annihilated when coming close to an electron increases as the positron's kinetic energy goes down, and at some point the positron and an electron will annihilate and their mass will be converted to two gamma photons each of 511 keV energy. The distance that a positron travels from the nucleus to the point of annihilation may vary, but is described by a typical range which is of the order of a millimeter.
Positron Emission Tomography (PET) is a technique where the distribution of positron emitting nuclei in a body is detected by measuring the pair of annihilation gamma photons, typically in a ring shaped detector configuration, and reconstructing the pair-wise detected events using tomographic techniques. See, Timothy G. Turkington, J Nucl Med Technol, 29 (2001) 4-11. Prior to, or during the PET scan, a patient or animal is injected by a radioactively labeled molecule. This causes the patient to be the highest radiation source in the room, which will cause difficulties for the signal quality in the below mentioned devices.
Detection of radioactivity in blood is useful so that modeling of a patient's or animal's response to (radioactively labeled) injected molecules can be performed. Modeling is typically performed by assuming a number of different compartments, with unknown rate constants going in and out of each compartment. Intensity distributions from the images of a PET study may, via modeling, be translated to such characteristics as transport rates, metabolic rates, receptor occupancy etc. Since molecules are transported in the blood system, the blood system acts as the input to a response model, and is thus necessary to measure.
Often, the plasma concentration is the interesting input function, whereas continuous blood measuring systems only measure the whole-blood radioactivity. Therefore a number of discrete samples are taken and centrifuged to measure both the whole-blood and plasma concentrations. Moreover, if the molecule is metabolized by the patient, chromatographic separations must also be performed on the discrete samples, before measuring the radio-activity of chromatographic fractions. These discrete measures are then combined with the continuously-measured whole-blood activity to yield a continuous plasma input function.
Discrete samples are analyzed by putting an extracted sample in a well crystal counter. The counter is formed from one or more scintillating crystals forming a cylindrical detector, each crystal connected to a photo-multiplier tube. The scintillating material (typically NaI, BGO, LSO) lights up when a gamma ray strikes and the photo-multiplier tube converts the light to an electric pulse which can be counted. Counting is typically performed “in coincidence” with the pulses from two detectors, so that an event is only registered if both detectors give a pulse within a very short time window (ranging, e.g., from nanoseconds to a microsecond). Coincidence counting is used to discriminate background events. The setup normally uses two half-moon shaped cylinder halves, where each half feeds light to one photo-multiplier tube.
Continuous blood sampling typically involves (a) continuously tapping arterial or venous blood through a catheter from a patient or animal at a controlled flow rate of the order of 5 ml/min, employing a syringe pump or peristaltic pump; (b) positioning the catheter in a detector configuration designed so that collection of radiation from the catheter is maximized and collection of radiation from outside the catheter is minimized; and (c) using the detector and electronic system to analyze the radiation to minimize the detection of radiation from outside the catheter (typically single 511 keV gamma photons) while maximizing the detection of events from inside the catheter (typically the simultaneous absorption of two 511 keV gamma photons).
It is desirable to measure the radio-activity in the continuous blood with a catheter length being as short as possible, to minimize dispersion of the signal, especially in the initial state following injection of radioactivity to the subject patient/animal.
Several known principles, or methods for detection, will now be examined, referring to Table 1.
The first principles described in Table 1, in rows a-d, employ a detector principle where a scintillating crystal, such as for instance BGO, LSO, NaI, converts the gamma photon to a large number of photons. The process follows the steps:
More specifically, the prior art represented in Table 1 may be described as follows (using the annotation of Table 1x, where x denotes the row of Table 1 being described):
All detection systems discussed in Table 1 employ a threshold technique, in which all signals that are below a set threshold level are discarded.
Several problems are known to exist with the prior art. Most of the techniques require shielding, employing a high density material such as lead, which ideally has to be fitted around the detector in all directions. The implementation of so much shielding causes the system to weigh of the order of 50-100 kg. Accidents involving dropping of the detector can easily happen, causing serious injuries to the operator or patient. One solution is to use lead only in one direction, but this renders the system susceptible to false counts such as from somebody passing by with radioactivity on the wrong side, or a faulty alignment of the detector relative the patient or due to bad positioning of the radioactive waste blood. The added weight thus requires centering the detector on a steady cart with a wide base, thereby frustrating the need to place the heavy detector close to the patient. The alternative approach to measure activity within the artery using a minute scintillator is indeed a light-weight approach, but suffers from limited signal to noise ratio, due to the sensitivity to noise from the high flux of gamma photons in the near vicinity of the patient.
Thus, there is a need in the art for a light-weight detector which can be placed very close to the patient and which efficiently can remove false counts from background activity. All the above-identified shortcomings of prior art are addressed by the present invention.
In view of the needs of the prior art, the present invention provides a detection device for beta radiation having first and second adjacent detectors and a coincidence counter unit. Each of the first and second detectors are coupled to the coincidence counter unit.
The present invention takes the approach of directly detecting parts of the positron kinetic energy following its passing of two detectors summed at a coincidence counter. Desirably, the detectors are in the form of thin planar silicon diodes. Thin diodes have a low probability of detecting gamma photons due to gamma radiation's comparatively low probability of interacting with matter, but are almost certain to detect the deposited kinetic energy from the positron due to beta particles high probability of interaction. The two signals from the diode detectors are fed through a coincidence unit to discard signals detected in only one of the detectors, thus diminishing the risk of detecting the low probability gamma photons. Desirably, the detector should be sufficiently thin to allow a large fraction of the positron's energy to be retained while passing through each detector, and to allow a high probability for passing without annihilation.
Alternatively, the detector can be made of a thin scintillating crystal optically coupled to a light-sensitive device such as a photo-multiplier, or a semi-conducting diode. The range for positrons is for many isotopes of the order of a millimeter, which is compatible with, for instance, the 0.3 mm thickness of the Hamamatsu S3588-09 large area diode. With this diode, only 1% of gamma photons above 150 keV are detected (see, e.g., Ramsey, http://www.carroll-ramsey.com/detect.htm quoting Silicon Photodiodes and Charge Sensitive Amplifiers for Scintillation Counting and High Energy Physics Hamamatsu Photonics K.K., Solid State Division, Catalog #KOTH0002E02, June, 1993). For other beta emitting isotopes, the detector thickness must be thinner.
The present invention contemplates a flow-through cell incorporating two thin solid state (thickness in the order of 0.01-2 millimeters) detectors. The detectors are desirably in the form of semi-conducting diodes or transistors. It will be appreciated that the diodes may be formed from silicon, although any suitable semi-conducting material may be used. Alternatively, the detectors may include pieces of scintillating material (thickness in the order of 0.01-2 millimeters) attached to the semi-conducting detectors so that the detectors are sandwiched together, thus minimizing unnecessary path length for the beta particle. It is not necessary that the two detectors are in an abutting relationship as there may be some air or low-density material provided therebetween. Geometrical considerations, however, suggest the desirability of placing each of the detectors in close proximate overlying registry. A catheter can be attached to this flow-through cell and to the patient/animal.
Obviously, the detector of the present invention is also useful as a detector for a much wider application field, e.g., for chromatographic applications.
To make the detector as sensitive as possible, it could be incorporated into the wall of a flow-through cell so that unnecessary passage through catheter walls is removed.
It is further contemplated by the present invention that the detection of a positron may be combined with the detection of one or both of the annihilation gamma photons. In this setup, either one or several passages of a single positron can be detected in coincidence with one or two gamma photons, where gamma photons are detected through one or more additional gamma photon detectors, such as for instance a scintillator or a thick semi-conducting device known for detecting gamma photons, which is also connected to the coincidence counter 15.
The description will focus on positron detection, which is a more difficult problem than electron detection since annihilation photons from background in patient or animal may be present in large quantities.
Two or more detectors are placed adjacent to each other in a design that allows a fraction of the kinetic energy of a positron to be deposited in each detector. Keeping the detector thickness small lowers the probability for gamma detection, while still a sizeable fraction of the positron's kinetic energy will be detected.
The following demonstrates the capacity of the present invention to discriminate background events:
σN1N2=1·0−6·310·310=0.1 counts/s
Several factors can be used to reduce the random events further:
Thus, the capacity of this invention to discriminate noise is tremendous even without any shielding.
We have experimentally verified that with two Hamamatsu S3588-09 large area diodes on top of each other, positrons from Gallium 68 decay do reach the second diode through the first diode.
In summary, using the conventions of Table 1, Table 2 shows how the following principles are covered in the different implementations of the present invention:
Detector 301 includes an annular scintillator 350 extending about diodes 12 and 14 of detector 10 and conduit 302. Scintillator 350 is optically coupled to a light-sensitive device 360 such as a photo-multiplier or a semi-conducting diode. Light-sensitive device 360 converts the optical signal from scintillator 350 into an electrical signal which may be detected by a coincidence unit 370. Coincidence unit 370 is also connected to the output of detector 10 so that it can detect the thresholded outputs of detector 10 and device 360 within a time window so as to provide an output signal indicating the beta-beta output of detector 10 and the gamma signal from device 360. Scintillator 350 may alternatively be provided about only a portion of conduit 302.
Detector 401 includes first and second semi-annular scintillators 450 and 455 extending fully about diodes 12 and 14 of detector 10 and conduit 402. Scintillators 450 and 455 are optically coupled to light-sensitive devices 460 and 465, respectively. Devices 460 and 465 are desirably formed from a photo-multiplier or a semi-conducting diode. Light-sensitive devices 460 and 465 convert the optical signal from scintillators 450 and 455, respectively, into first and second electrical signals which may be detected by a coincidence unit 470. The output of coincidence unit 470, indicating a gamma signal has been received from each of scintillators 450 and 455 within a predetermined time window, is provided to a coincidence unit 480. Coincidence unit 480 is also connected to the output of detector 10 so that it can detect the thresholded outputs of detector 10 and devices 460 and 465 within a time window so as to provide an output signal indicating the beta-beta output of detector 10 and the gamma-gamma signal from device 470. Scintillators 450 and 455 may alternatively be provided about only a portion of conduit 302.
Detector 501 includes an annular scintillator 550 extending about diode 514 and conduit 502. Scintillator 550 is optically coupled to a light-sensitive device 560 such as a photo-multiplier or a semi-conducting diode. Light-sensitive device 560 converts the optical signal from scintillator 550 into an electrical signal which may be detected by a coincidence unit 570. Coincidence unit 570 is also connected to the output of diode 514 so that it can detect the outputs of diode 514 and device 560 within a time window so as to provide an output signal indicating the beta output of diode 514 and the gamma signal from device 560. Scintillator 550 may alternatively be provided about only a portion of conduit 502.
Detector 601 includes first and second semi-annular scintillators 650 and 655 extending fully about diode 614 and conduit 602. Scintillators 650 and 655 are optically coupled to light-sensitive devices 660 and 665, respectively. Devices 660 and 665 are desirably formed from a photo-multiplier or a semi-conducting diode. Light-sensitive devices 660 and 665 convert the optical signal from scintillators 650 and 655, respectively, into first and second electrical signals which may be detected by a coincidence unit 670. The output of coincidence unit 670 is provided to a coincidence unit 680. Coincidence unit 680 is also connected to the output of diode 614 so that it can detect the output of diode 614 and coincidence unit 670 within a time window so as to provide an output signal indicating the beta output of diode 614 and the gamma-gamma signal from device 670. Scintillators 650 and 655 may alternatively be provided about only a portion of conduit 602.
In
While each of the positron detectors of the present invention have been shown to extend about a relatively small portion of the conduit to which it is adjacent, it is further that each of the detectors may cover larger such radials of the conduit. For example, the positron detectors could extend to be fully annular about the conduit. Alternatively, multiple positron detectors may be provided to cover more of the conduit circumference, such detectors also being coupled in parallel.
While the particular embodiment of the present invention has been shown and described, it will be obvious to those skilled in the art that changes and modifications may be made without departing from the teachings of the invention. The matter set forth in the foregoing description and accompanying drawings is offered by way of illustration only and not as a limitation. The actual scope of the invention is intended to be defined in the following claims when viewed in their proper perspective based on the prior art.
Filing Document | Filing Date | Country | Kind | 371c Date |
---|---|---|---|---|
PCT/IB07/00401 | 2/19/2007 | WO | 00 | 4/2/2009 |
Number | Date | Country | |
---|---|---|---|
60774340 | Feb 2006 | US |