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1. (WO2010085139) TIME-OF-FLIGHT POSITRON EMISSION TOMOGRAPHY USING CERENKOV RADIATION
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Title: Time-of-flight positron emission tomography using Cerenkov radiation

FIELD

The invention relates to a time-of-flight positron emission tomography, operating using Cerenkov radiation. More in particular, the invention relates to a method of time-of-flight detection using Cerenkov radiation. Still more in particular, the invention relates to a positron emission tomography apparatus enabling a time-of-flight detection using Cerenkov radiation. Still more in particular, the invention relates to a computer program for enabling a time-of-flight positron emission tomography using Cerenkov radiation.

BACKGROUND

Positron emission tomography (PET) is known per se. Currently, clinical use of PET is rapidly advancing. PET becomes one of the key medical modalities for diagnosis of cancerous and cardiovascular abnormalities, which constitute two major death causes in the developed countries. Because of its high sensitivity and selectivity, PET has emerged as one of the imaging modalities of choice for the diagnosis, staging, therapy monitoring and recurrence assessment of cancer. Presently, oncology accounts for about 90% of all clinical PET examinations, the remaining 10% being distributed between cardiology and neurology.

PET is a functional imaging modality: it is capable of imaging a specific physiological function. To do so, the patient is administered a substance which distributes in the body such that it correlates with the function of interest; a so-called tracer. In case of PET, the tracer is labelled with a positron-emitting radionuclide. Once the radiotracer is distributed in the body, preferably in a target region thereof, imaging may be commenced for localizing the positron emitters and concentration distribution thereof.

The principle of PET is based on the following. After emission, the free positron is decelerated in the body and finally it annihilates with an electron, which is followed by emission of two annihilation photons of equal and well- determined energy (511 keV), which travel in opposed directions. In order to detect the coincident photons, i.e. those resulting from the same annihilation event, a PET scanner may use a multi-ring detector configuration which is substantially concentrically arranged with respect to the target region in the patient. If two gamma photons with the correct energy (i.e. δllkeV) are detected in coincidence, the positron annihilation must have occurred on a geometric line connecting the two detectors. Such a line is often referred to as a line of response (LOR). From a large number of such LOR's a tomographic image representing the distribution of the radiotracer in the body can be reconstructed.

Time- of- flight (TOF) detectors used in a PET scanner provide an improvement in image quality. The principle of operation of the TOF detectors is based on the insight that the time of flight difference of two annihilation photons detected by opposite detectors identifies a position of the annihilation event along the LOR.

In order to convert energy of the 511 keV photons impinging on the detector elements of a PET scanner, the detector elements are implemented as scintillators. It is believed that a minimum technically achievable time resolution of a PET scanner based on scintillator crystals is about 100 ps. However, given the range of a positron in a detector material of about 1 mm, a corresponding theoretically possible time resolution of a time-of-flight acquisition may be as low as 10 ps, which is an order of magnitude lower than the conceivably obtainable time resolution using scintillation light of 100 ps. Therefore, it is desirable to reduce the time resolution compared to conventional scintillator crystals.

SUMMARY OF THE INVENTION

It is an object of the invention to provide a method of time-of- flight PET acquisition, having a time resolution lower than 100 ps. To this end the method according to the invention of time- of- flight positron emission tomography of an object comprising a positron emitter located in a target region spatially surrounded by an array of detector elements, comprises the steps of:

- using for the detector elements a material capable of generating a first event and a second event pursuant to a passage of a 511 keV photoelectron therein;

- detecting in the detector element the first event for timing the time- of- flight measurement;

- detecting in the detector element the second event for carrying out energy measurement.

An aspect of the invention is based on the insight that instead of deriving energy and timing information from a single detector response, like for example, scintillation light, an improved performance may be obtained by decoupling timing information and energy information by generating two response events in the detector material and by using a first, relatively fast, response for timing and a second, relatively slower response, for energy measurement.

According to the invention the spatial resolution following from the TOF difference may be improved. In particular, when the improved spatial resolution is smaller than the size of the target region, image noise may be reduced and image quality may be improved. It will be appreciated that advantage of TOF PET with respect to a non-TOF PET lies in improved contrast of the image, due to narrowing down the position of annihilation on the LOR with a resolution smaller than the size of the object.

However, in accordance with the invention it may be possible to obtain spatial resolution better than 2-6 mm. This, however, may require a time resolution of 13-40 ps.

Preferably, the first event relates to a Cerenkov photon generated in the detector element and the second event relates to a corresponding scintillation photon.

It is found that Cerenkov radiation is created much faster in the detector material than the scintillation light. Therefore, by timing the TOF measurement based on the Cerenkov light a considerable improvement of temporal uncertainty of the detector element may be obtained. As a result, the corresponding spatial uncertainty is improved. It is found that in accordance with the invention temporal uncertainty of about 70 ps is achievable, and even lower falling into the interval of 10—40 ps, which constitutes a factor of about 6 improvement with respect to the prior art, wherein timing resolution of about 400 - 600 ps are used. Preferably, the material of the detector element is substantially transparent to blue light and/or to UV light as the Cerenkov radiation intensity increases with decreasing wavelength in a quadratic way. In general, transmission of the material of the detector element in the range of [200-600] nm may be at least 50%. According to the invention, obtainable timing resolution of the detector element may be less than 200 ps, preferably less than 100 ps, more preferably less than 70 ps. It will be appreciated that the quoted data relates to FWHM of respective peaks.

It is noted that an embodiment of a time-of- flight measurement using Cerenkov light is known from M. Myata et al'Development of TOF-PET using Cerenkov radiation", Journal of Nuclear Science and Technology, vol. 34, pp. 339-343, 2006. However, Myata et al suggest using Cerenkov light for both the timing and for energy measurement. However, in this approach it is not possible to discriminate between a full energy effect and Compton scattering as Cerenkov light does not carry any information about energy absorption in the detector material.

According to the invention, on the other hand, Cerenkov light, being emitted substantially at the same instance when energy is absorbed by the detector element is used as a trigger for timing purposes. Factual energy absorption, however, manifests itself in emission of scintillation light, which is a relatively slow process having a temporal delay. By timing the TOF measurements using the fast process, i.e. Cerenkov radiation, and by performing energy measurement using the scintillation light, a due discrimination between the full energy effect and Compton scattering is performed, next to improving temporal and spatial resolution of the detector elements.

In an embodiment of a method according to the invention an energy threshold is set for the energy measurement for suppressing undesired events.

It will be appreciated that a threshold may be implemented by different means. Preferably, the threshold is set electronically in order to cut-off low energy events, corresponding to Compton scattering. As a result an improvement of discrimination between the full-energy event and Compton scattering is achieved.

According to a further aspect of the invention the material of the detector elements is selected from a group of materials having high efficiency for 511 keV photons, high scintillation yield and high Cerenkov radiation yield. For example, a suitable material for a detector element should have at least 30% efficiency of detecting the full energy of an incoming 511 keV photon. In addition, the material for the detector element should have a scintillation yield of not less than 10 000 photons per event. Finally, the material of the detector element should have a Cerenkov yield for the full absorption of a 511 keV photon of at least 10 photons. Suitable detector material meeting the above criteria may be BGO. However, other materials like CsI(Tl) and LaBr3 may also be suitable. It will be appreciated that these examples of suitable detector materials meeting the above criteria are not exhaustive.

It is found that these detector materials are particularly suitable for carrying out the invention, as they have relatively high yield of Cerenkov radiation and scintillation light. However, it is found that in terms of stopping power for 511 keV photons and detection efficiency ratio for full energy versus Compton photons, BGO may be preferable.

In a further embodiment of the method according to the invention, it further comprises the step of reconstructing an image of the target region based on data related to the first event and data related to the second event.

A positron-emission tomography unit according to the invention for generating images of an object comprising a positron emitter located in a target region, comprises:

- an array of detector elements that spatially surrounds the target region;

- the detector elements comprising a material capable of generating a first event and a second event pursuant to a passage of a 511 keV photoelectron therein;

- a timing unit for generating a timing signal pursuant to detection of the first event in the detector element;

- a measurement unit for generating a data signal pursuant to detecting the second event in the detector element.

A computer program product according to the invention comprises instructions for causing a processor for carrying out a time- of- flight positron emission tomography of an object comprising a positron emitter located in a target region, said target region being spatially surrounded by an array of detector elements, wherein the detector elements comprise a material capable of generating a first event and a second event pursuant to a passage of a 511 keV photoelectron therein; the computer program comprising instructions for:

- detecting in the detector element the first event for timing the time -of- flight measurement;

- detecting in the detector element the second event for carrying out energy measurement.

The computer program may further comprise an instruction for reconstructing an image of the target region based on data related to the first event and data related to the second event, wherein the first event may relate to Cerenkov radiation and the second event may relate to scintillation light. These and other aspects of the invention will be discussed in more detail with reference to drawings, wherein like reference numerals refer to like elements. It will be appreciated that the drawings are presented for illustrative purposes and may not be used for limiting the scope of the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 depicts in a schematic way a set-up for a TOF measurement triggered by Cerenkov radiation.

Figure 2 presents in a schematic way an embodiment of a detector signal as may be measured in a detector element in a temporal sequence. Figure 3 presents in a schematic way an embodiment of a PET apparatus according to an aspect of the invention.

DETAILED DESCRIPTION OF THE DRAWINGS Figure 1 depicts in a schematic way a set-up for a TOF measurement triggered by Cerenkov radiation. A detector element 10 may comprise a scintillator crystal 2 suitably coupled to a photosensor 4, for example a photomultiplier tube. In case when an annihilation photon P impinges on a material of the detector element 10 two substantially simultaneous effects may take place. First, Cerenkov radiation C may be generated and, secondly scintillation light S may be generated. It will be appreciated that not all scintillator crystals are capable of generating two named events, however, it lies within the general skill of the artisan to select a suitable scintillator capable of generating two distinct events (i.e., for example, Cerenkov radiation and scintillator light) pursuant to a passage of a 511 keV photon and a corresponding 511 keV photoelectron in its volume. It will be appreciated that the term '511 keV photoelectron' should be construed as an electron emitted pursuant to absorption of a 511 keV photon, which itself may have a lower energy.

It is found that photons of Cerenkov radiation are promptly emitted by moving photoelectrons, however, the number of such photons is considerably smaller than the number of scintillation photons S. In addition, Cerenkov radiation is emitted in a forward direction with respect to a direction of propagation of the electron, whereby scintillation light is radiated substantially in 3D. Due to the fact that Cerenkov radiation is promptly delivered to the photosensor 4, timing for the TOF measurement, carried out by a TDC module 8 may be advantageously carried out based on Cerenkov photons. Suitable electronic signal is provided by a data line D from the photosensor 4 towards the TDC module 8. Accordingly, by using a high speed and high efficiency photosensor and by setting a discriminator threshold as low as possible Cerenkov photons may be detected. When the Cerenkov photon is detected for purposes of TOF measurement, energy measurement may be enabled by detecting slower scintillator photons which arrive later. Figure 2 presents a schematic view of the expected detector 10 signal, depicted in a temporal sequence.

As is seen from Figure 2 Cerenkov photons C arrive much earlier at the photosensor 4, shown in Figure 1, than the scintillation photons S. Therefore, triggering the TOF measurement on the Cerenkov photons C is more accurate. Due to the fact that the Cerenkov light does not carry accurate information about the energy of the photoelectron, energy measurements have to be carried out using scintillating photons S, preferably above a pre-set threshold T.

Figure 3 presents in a schematic way an embodiment of a PET apparatus according to an aspect of the invention. The PET apparatus 30, schematically shown in a simplified cross-section, may comprise a ring incorporating detector elements Dl, D2, D3,..rDn. It will be appreciated that respective dimensions are not in proportion for simplicity and comprehension purposes. The ring of detector elements is arranged to provide a three-dimensional shell around a target area T of a patient Pat, for enabling detection of annihilation photons Pl, P2 in coincidence, for example the PET apparatus may comprise a number of detector rings, resulting in a cylindrical detector array around the patient. The length of the cylinder may be about 15-20 cm. As is briefly explained earlier, the annihilation photons Pl, P2 are generated when a positron emitted by a suitable radioactive nucleus, like C-Il, for example, interacts with an electron by means of an annihilation event A. As is explained earlier, the patient Pat is provided with a radioactively labelled tracer for studying a specific function, for example metabolism in a specific area or region. It is, therefore, expected that the tracer will be accumulated in such organ or region. By examining distribution of the tracer in the organ or region, suitable medical conclusions may be enabled. In order to accurately determine the distribution of the tracer in a target region it is important to accurately determine the origin of annihilation events A. For this purpose the annihilation photons Pl, P2 are detected in coincidence. Secondly, a time-of-flight measurement is carried out to more specifically determine the position of the annihilation event A along the line running through vectors Pl, P2. In accordance with an aspect of the invention, the PET apparatus 30 is provided with a detector capable of generating two distinct and different events pursuant to a passage of a 511 keV photoelectron in its volume. In particular, the detector element is capable of generating Cerenkov light and scintillation light pursuant to such passage.

The PET apparatus according to the invention is arranged to detect Cerenkov light for timing the time-of-flight measurements and to detect scintillation light for purposes of energy measurement. Accordingly, the apparatus 30 may comprise a data line D which may comprise one or more sub-lines, for example, for enabling dedicated data acquisition, wherein signals corresponding to Cerenkov photons are recorded and suitably processed for TOF experiment and signals corresponding to scintillation light are recorded and suitably processed for purposes of energy measurement. The data line D may terminate at a suitable data acquisition and processing hardware block 31. The hardware block 31 may comprise a data acquisition system 32 wherein a timing unit and an energy measurement unit are provided. Alternatively, the timing unit and the energy measurement unit may be integrated, for example, they may be implemented as a suitable computer program. The PET apparatus may further comprise a processor 33 arranged for conducting the TOF and energy measurement. For example, the PET apparatus may further comprise a computer program product 34, which may comprise suitable instructions for causing the processor 33 to carry out the steps enabling detecting in the detector element the first event for timing the time-of-flight measurement; enabling detecting in the detector element the second event for carrying out energy measurement. The computer program product 34 may further comprise suitable instructions for carrying out TOF data analysis based on the detected signal corresponding to the first event as well as further instructions for carrying out energy measurement based on data provided by the detector elements corresponding to the second events. Additionally, the computer program 34 may comprise instructions for reconstructing an image based on the TOF and the energy measurements. It will be appreciated that the above functioning of the Cerenkov TOF PET scanner presents an embodiment from a great variety of possibilities wherein suitable hardware component interact with software. Therefore, such exemplary embodiment may not limit the scope of the appended claims.

It will be appreciated that the computer program product 34 may be run internally or externally with respect to the PET apparatus 30. For example, the computer program product 34 may be run on a suitable data reconstruction station (not shown), which may be arranged as a suitable periphery of the PET apparatus 30.

Finally, results of image reconstruction may be displayed on a suitable display 35 showing an image I corresponding to a distribution of the tracer in the target region.

It will be appreciated that while specific embodiments of the invention have been described above, that the invention may be practiced otherwise than as described. In addition, isolated features discussed with reference to different figures may be combined.