Computer-implemented method and apparatus for non-invasively and extracorporeally determining intra-arterial concentrations of radiopharmaceuticals, particularly radiotracers, in organs of the animal and / or human body

Abstract

The presently disclosed computer-implementable method for non-invasively and extracorporeally determining the arterial concentration of a radiopharmaceutical, e.g., a radiotracer, in an organ of an animal and / or human body includes the steps of: i) receiving electromagnetic radiation emitted by the radiopharmaceutical over time, starting from the time a dose of the radiopharmaceutical is administered to the animal and / or human body, by one or more radiation sensors positioned near or at a measurement location on the organ; ii) converting the received electromagnetic radiation into a time series of radiation signals; iii) generating one or more time-frequency representations of the radiation signals by a time-frequency transformation; and iv) analyzing the time-frequency representations to determine the intraarterial concentration of the radiopharmaceutical.

Description

[Technical Field]

[0001] The present disclosure relates to techniques for non-invasively and extracorporeally measuring intra-arterial concentrations of radiopharmaceuticals, particularly radiotracers, administered to an animal and / or human body or subject using radiation detectors / sensors. [Background technology]

[0002] Current ( 18 Clinical quantification of F-FDG (PET) images is based on the evaluation of radiotracer uptake at specific time points after radiotracer administration using the standardized uptake value (SUV). Although SUV is the most commonly used PET metric in clinical practice, it suffers from several important drawbacks. In addition to the radiotracer uptake time, the measured SUV depends on the total cumulative radiotracer concentration in arterial blood over time. Prior art studies have demonstrated that these drawbacks may lead to erroneous conclusions regarding the therapeutic response of tumor patients using SUV.

[0003] Alternatively, if the time-dependent arterial blood radiotracer concentration is known, the SUV can be corrected for radiotracer availability to determine the true metabolic activity of the tissue. 18 This adds value to the clinical value of F-FDG PET imaging. Besides the correction of SUV, arterial radiotracer concentrations over time are also required for pharmacokinetic modeling, which is commonly used in research applications of various (new) PET radiotracers. Summary of the Invention [Problem to be solved by the invention]

[0004] Known measurement techniques for assessing intraarterial radiotracer concentrations require the placement of an arterial line in the patient / subject. Arterial line placement is invasive, time-consuming, and not without risk. Therefore, this technique is not used clinically. Another known technique, known as image-derived input function (IDIF), requires a long dynamic PET acquisition, typically 30–60 minutes, after administration of the radiotracer into the blood vessels. The arterial radiotracer concentration is then determined from the reconstructed PET images at various time points. Because this technique requires a long PET scan time, the number of patients who can be scanned is significantly reduced. Therefore, this technique cannot be applied to current clinical PET scans, which involve a short static (whole-body) PET scan after a specific acquisition time.

[0005] Alternatively, another known approach is based on population studies, where longitudinal data are used to construct population-based input functions. 18 The general shape of the F-FDG radiotracer concentration was determined. Using one or more venous blood samples, this population-based input function can be scaled for individual patients. However, this technique suffers from inter- and intra-patient variability in time-dependent arterial radiotracer concentrations.

[0006] It is therefore an object of the present disclosure to provide improved methods and apparatus for non-invasively and extracorporeally determining the intra-arterial concentration of a radiopharmaceutical in an organ of an animal and / or human body. The radiopharmaceutical used may be a radiotracer, more particularly a positron emission tomography (PET) radiotracer. [Means for solving the problem]

[0007] A first embodiment of the present disclosure proposes a computer-implemented method for non-invasively and extracorporeally determining the intra-arterial concentration of a radiopharmaceutical, e.g., a radiotracer, in an organ of an animal and / or human body, the computer-implemented method comprising the following steps: i) receiving electromagnetic radiation emitted by the radiopharmaceutical over time from the time a certain amount of the radiopharmaceutical is administered to the animal and / or human body by one or more radiation sensors positioned near or at a measurement location on the organ; ii) converting the received electromagnetic radiation into a time sequence of radiation signals; iii) generating one or more time-frequency representations of the radiation signal by time-frequency transformation; iv) analyzing the time-frequency representation to determine the intra-arterial concentration of the radiopharmaceutical.

[0008] By directly measuring the time-dependent radiopharmaceutical or radiotracer concentration after administration of the radiopharmaceutical (radiotracer) in the blood vessels of an animal or human body, a direct and accurate correction of SUV is achieved without the need to apply invasive arterial blood sampling or lengthy / costly data acquisition, e.g., PET acquisition. Therefore, this direct and accurate correction of SUV can be achieved, e.g., ( 18 This adds value to the clinical value of F-FDG PET imaging. Besides the correction of SUV, the radiopharmaceutical concentration over time in the arterial blood perfusing the organ is also required to perform pharmacokinetic modeling, which is commonly used in research applications of various (new) radiotracers, such as PET radiotracers.

[0009] In advantageous embodiments of the present disclosure, the time-frequency transformation is exemplified by, but not limited to, a short-time Fourier transform, a wavelet transform, a filter bank, or a discrete cosine transform. This results in an analysis in the time-frequency domain and the calculation of a correct measurement of the time-dependent radiotracer concentration in an organ, e.g., the heart or an artery. Although the concentration is not measured directly from the signal acquired by the radiation sensor, the acquired signal can be used to obtain the actual measurement, e.g., based on a PET / SPECT scan or based on a venous blood sample acquired at a later stage.

[0010] In a further elaboration of the present disclosure, step i) comprises receiving electromagnetic radiation over time using two radiation sensors placed on opposite sides of the measurement location on the organ, thereby obtaining a more accurate measurement using the so-called coincidence radiation emission principle.

[0011] To further improve the accuracy of the measurement of the time-dependent radiotracer concentration, step i) further comprises collimating the electromagnetic radiation emitted by the radiopharmaceutical prior to reception by the one or more radiation sensors, thereby ensuring radiation safety and ensuring that only electromagnetic radiation emanating from the measurement location in the organ is detected and analyzed for measurement.

[0012] The present disclosure also relates to an apparatus for non-invasively and extracorporeally determining the concentration of a radiopharmaceutical, in particular a radiotracer administered intravascularly in an animal and / or human body. Preferably, the apparatus is configured to implement a computer-executable method. In a preferred embodiment, the apparatus may comprise one or more radiation sensors positioned near or on a measurement location in an organ of the animal and / or human body and configured to receive electromagnetic radiation emitted by the radiopharmaceutical over time. The apparatus may also include a transformation unit configured to transform the received electromagnetic radiation into a time sequence of radiation signals, and at least one processing unit configured to generate one or more time-frequency representations of the time sequence of radiation signals by a time-frequency transformation and to determine the concentration of the radiopharmaceutical.

[0013] This configuration provides a non-invasive, extracorporeal measurement device for determining the arterial concentration of a radiopharmaceutical in an organ (e.g., heart or artery) of an animal and / or human body. Thus, due to its non-invasive nature, the device limits the burden on the animal and / or human body and can be easily implemented in less stringent medical situations using simple detection equipment.

[0014] In particular, an output unit is used which is adapted to output the measured concentration of the radiopharmaceutical, for example via a display.

[0015] To obtain measurement results quickly and efficiently in terms of computation time, the time-frequency transformation is exemplified by, but not limited to, short-time Fourier transform, wavelet transform, filter bank or discrete cosine transform.

[0016] In a preferred embodiment of the device according to the present disclosure, two radiation sensors are placed on opposite sides of the measurement location on the organ. In this particular embodiment, the device may comprise a coincidence processing unit for detecting simultaneous detections of electromagnetic radiation by the two radiation sensors placed on opposite sides of the measurement location on the organ. This allows for a more accurate measurement of the concentration of the radiopharmaceutical and achieves a direct and accurate correction of the SUV. Thus, a direct and accurate correction of the SUV can be achieved, e.g. 18 This adds value to the clinical value of F-FDG PET imaging. Besides the correction of SUV, radiopharmaceutical concentrations over time are also required to perform pharmacokinetic modeling, which is commonly used in research applications of various (new) radiopharmaceuticals, e.g., PET radiopharmaceuticals.

[0017] In a further embodiment, the device may comprise a housing for accommodating at least one or more radiation sensors and radiation collimating means arranged around each of the one or more radiation sensors, which facilitates handling or operation of the device according to the present disclosure and also improves radiation safety as only electromagnetic radiation emanating from the measurement location on the organ is detected and analyzed for measurement.

[0018] In a preferred embodiment, the device is configured as a wearable device, e.g., having a structure for attachment around limbs and on or near measurement locations on organs of an animal and / or human body. Thus, due to their non-invasive nature, the device limits the burden on animal and / or human subjects and can be easily implemented in less stringent medical situations using simple sensing equipment.

[0019] for example,( 18In an advantageous embodiment that allows for simple yet straightforward implementation during F-FDG PET image acquisition, the device is configured to be placed on, adjacent to, or integrated into a hospital chair, hospital bed, or patient table.

[0020] In another advantageous embodiment, the methods of the present disclosure may be embodied in a computer program or product that includes computer coded instructions that, when the computer program or product program is executed by a computer, such as a laptop or computer, cause the computer to perform the steps of the computer-implemented methods disclosed herein.

[0021] In a particular embodiment, a computer-readable storage medium is proposed that includes computer-coded instructions stored therein, which, when executed by a computer, cause the computer to perform the steps of the computer-implemented method disclosed herein. Such a computer-readable storage medium may be a (solid-state) hard drive, a USB drive, or a (digital) optical disk. [Brief explanation of the drawings]

[0022] The present invention will now be described with reference to the accompanying drawings. [Figure 1] 1 is a schematic example of an apparatus for carrying out an example method according to the present disclosure. [Figure 2] 1 is a more detailed example of an apparatus for carrying out an example method according to the present disclosure. [Figure 3] 1 is a detailed example of a radiation sensor for use in a device according to the present disclosure. [Figure 4] 1 is a further example of an apparatus for carrying out an example method according to the present disclosure. [Figure 5] 1 is a detail of signals acquired and processed in an example method according to the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0023] For a proper understanding of the present disclosure, in the following detailed description, corresponding elements or portions of the present disclosure are designated with the same reference numerals in the drawings.

[0024] Figure 1 shows a first schematic example of a computer-implemented method for non-invasively and extracorporeally determining the intraarterial concentration of a radiopharmaceutical in an organ of an animal and / or human body in accordance with the present disclosure. It should be noted that any radiopharmaceutical may be used, particularly a radiotracer. The present method and apparatus are equally applicable to radiopharmaceuticals used in radionuclide therapy, where obtaining similar measurement signals can more accurately predict the effectiveness of the treatment.

[0025] This non-invasive computer-implemented method can be implemented, for example, as follows: 18 This paper proposes an improved alternative to current clinical quantification of F-FDG (PET) imaging, which is based on the evaluation of radiopharmaceutical uptake at specific time points after radiopharmaceutical administration using standardized uptake values ​​(SUVs). As outlined at the beginning of this application, SUVs are the most commonly used PET metric in clinical practice, but they suffer from several important drawbacks. In addition to the radiotracer uptake time, the measured SUVs depend on the total cumulative radiotracer concentration in arterial blood over time. Prior art studies have demonstrated that these drawbacks can lead to erroneous conclusions regarding the treatment response of tumor patients using SUVs.

[0026] Therefore, in FIG. 1 , an improved method for non-invasively and extracorporeally determining arterial blood concentrations of radiopharmaceuticals, particularly radiotracers, and more particularly arterial blood concentrations of positron emission tomography (PET) radiotracers in organs of the animal and / or human body is described below.

[0027] The computer-implemented method is preferably implemented in an apparatus for non-invasively and extracorporeally determining the intra-arterial concentration of a radiopharmaceutical, particularly a radiotracer, injected into the blood vessels of an animal and / or human body. In Figure 1, the apparatus is designated by the reference numeral 100 and is outlined in further detail in the detailed description.

[0028] In Figure 1, the computer-implemented method is organized along four steps. The first step involves a patient positioned or lying in a treatment area 101, indicated by the box with reference numeral 101, on a hospital chair, hospital bed or patient table, which may be part of the device 100. The patient, which may be an animal or a human, is administered a quantity of a radiopharmaceutical, for example injected into the bloodstream, for example intravascularly. The radiopharmaceutical may be any type of radiopharmaceutical, for example selected from the group of radiotracers, in particular 18 F]Fluorodeoxyglucose, also known as Fluorodeoxyglucose F18 18 F-FDG may also be used. 18 F]FDG, 2-[ 18 [F]FDG or FDG) is a radiopharmaceutical, particularly a radioactive tracer, used in the medical imaging modality positron emission tomography. However, other types of known radiopharmaceuticals can also be used in the methods and devices according to the present disclosure.

[0029] The computer-implemented method of the present disclosure particularly focuses on its first step i), in which, immediately or from the moment of administration of a certain amount of radiopharmaceutical into the bloodstream of the animal and / or human body, electromagnetic radiation emitted by the injected radiopharmaceutical is received over time by one or more radiation sensors placed near or at a measurement location in the organ of interest. This is depicted in box 102 of Figure 1 and in more detail in Figure 5B, both of which show how the electromagnetic radiation emitted by the radiopharmaceutical is received (detected) over time.

[0030] The organ may be the heart of an animal or human, or any other part of the body that is well perfused with blood. The target organ may also be a limb, such as a hand or foot, or part of a limb, such as an ankle or wrist, so long as the radiation sensor or sensors can be placed in close proximity to a blood vessel, but most preferably in a blood artery that perfuses the respective target organ, e.g., a wrist or ankle artery.

[0031] In a next step ii) of the computer-implemented method according to the present disclosure, the received electromagnetic radiation is transformed into a time sequence of radiation signals, as depicted diagrammatically by boxes 103 and 104. Preferably, the time-frequency transformation is a short-time Fourier transform, although it should be noted that the time-frequency transformation implemented by the computer-implemented method according to the present disclosure is not limited to the Fourier transform. Other time-frequency transformations may also be used, for example selected from the group exemplified by, but not limited to, the wavelet transform, the filter bank, or the discrete cosine transform.

[0032] Therefore, performing a time-frequency transform on the time series of the radiation signal results in an analysis in the time-frequency domain, and this step iv) of analyzing the time-frequency representation results in an accurate determination of the concentration of the radiopharmaceutical and the calculation of a correct measurement of the time-dependent radiotracer concentration in an organ, e.g., the heart or an artery, as indicated by the peak in box 104 and depicted in more detail in Figure 5B.

[0033] The concentration is not measured directly from the signal acquired with the radiation sensor, but the acquired signal can be used to obtain the actual measurement, for example based on a PET / SPECT scan or based on a venous blood sample taken at a later stage.

[0034] By directly measuring the time-dependent radiopharmaceutical or radiotracer concentration after administration of the radiopharmaceutical (radiotracer) into the blood vessels of an animal or human body, a direct and accurate correction of SUV is achieved without the need to apply invasive arterial blood sampling or lengthy / costly data acquisition, e.g., PET acquisition. Thus, this direct and accurate correction of SUV can be achieved, e.g., ( 18 This adds value to the clinical value of F-FDG PET imaging. Besides the correction of SUV, the time-dependent evolution of radiopharmaceutical concentrations in organs is also required to perform pharmacokinetic modeling, which is commonly used in research applications of various (new) radiotracers such as PET radiotracers. When a radiopharmaceutical or radiotracer undergoes radioactive decay, positrons are formed, which combine with electrons to produce electromagnetic radiation in the form of gamma rays. These gamma rays are detected by radiation sensors.

[0035] As outlined above, one or more radiation sensors are placed in close proximity to a blood vessel or artery that perfuses the organ of interest. For example, if the organ of interest is a hand or a foot, more accurate measurements can be obtained by using the so-called coincidence radiation emission principle. According to this principle, step i) is further detailed, as it may include receiving electromagnetic radiation over time using two or more radiation sensors operating in coincidence detection mode, positioned on opposite sides of the measurement location on the organ of interest.

[0036] Further improvement in the measurement accuracy of the time-dependent radiotracer concentration can be achieved if step i) further comprises a step of collimating the electromagnetic radiation emitted by the radiopharmaceutical before reception by one or more radiation sensors. This ensures radiation safety and also ensures measurement accuracy, since only electromagnetic radiation emitted from the measurement location of the organ is detected and analyzed for measurement. It should be noted that the step of collimating the electromagnetic radiation does not necessarily apply when the so-called coincidence radiation emission principle is implemented.

[0037] An example of an apparatus for implementing the computer-implemented method of the present disclosure to non-invasively and extracorporeally determine the intra-arterial concentration of a radiopharmaceutical, particularly a radiotracer, administered into the blood vessels of an animal and / or human body is shown in FIG. 2, and details of the apparatus are shown in FIGS. 3 and 4A and 4B.

[0038] The apparatus is designated by reference numeral 100 and may be implemented or incorporated into a treatment area 101, such as an operating room or treatment room. Reference numeral 101a denotes a hospital chair, hospital bed, or patient table, e.g., a patient scanner table. In the example of a patient table 101a, it may comprise a mattress 101b on which a subject to be examined may be placed. The subject may be an animal or a human. For ease of explanation, the apparatus 100 according to the present disclosure will be described as being implemented on a human patient 10.

[0039] A patient 10 (animal or human) is administered a dose of a radiopharmaceutical, e.g., by injection into the bloodstream, e.g., a blood vessel. Alternatively, multiple radiation sensors 110 are placed near or on a measurement location of an organ of interest 11 in the animal and / or human body 10. In this particular application of the device according to the present disclosure, the device 100 implements one radiation sensor 110 directed toward the organ of interest, here the heart 11. The organ of interest 11 can be any body part of the animal and / or human body 10; it is essential for both the method and device according to the present disclosure that the body part be sufficiently perfused with blood. The organ of interest can be a limb, such as a hand or foot, as long as one or more radiation sensors can be placed in close proximity to a blood artery, preferably one that perfuses the organ of interest 11. In particular, the method and device according to the present disclosure can be used on or near the heart, or on / around the ankle or wrist, with one or more radiation sensors measuring electromagnetic radiation emitted by the radiopharmaceutical passing through the cardiac artery or the ankle or wrist artery.

[0040] One radiation sensor 110, such as that used in the embodiment of Figure 2, has an outer surface 110b (see Figure 3) facing the organ of interest 11 and is configured to receive electromagnetic radiation 111 over time, which radiation 111 is emitted by a radiopharmaceutical injected during perfusion of the organ of interest 11.

[0041] Referring to Figure 3, an example of such a radiation sensor 110 is shown. The radiation sensor 110 may consist of a radiation-sensing region or radiation-sensing element 110d housed within a housing 110a. The housing 110a incorporates an outer sensing surface 110b as well as radiation-collimating means 110c disposed around the radiation-detecting element 110d. The outer sensing surface 110b serves to receive the electromagnetic radiation 111, while the radiation-collimating means 110c serves to collimate and direct only the electromagnetic radiation 111 emitted by the radiopharmaceutical in the bloodstream passing through or perfusing the measurement location in the organ of interest 11 toward the radiation-sensing element 110d. The radiation-collimating means 110c may be configured as a small bore in the sensing surface 110b of the housing 110a, which may be oriented to converge toward the radiation-sensing element 110d.

[0042] The housing 110a may be made of a radiation-shielding material or may include radiation-shielding elements to prevent stray radiation from being detected by the radiation detection elements 110d that is not emanating from the measurement location of the organ of interest 11. Thus, the radiation collimating means / bore 110c, and optionally the radiation-shielding housing 110a, ensures that only electromagnetic radiation 111 emanating from the measurement location of the organ of interest 11 is detected for measurement, thus improving its accuracy.

[0043] Thus, the radiation sensor 110, which is comprised of a housing 110a incorporating the components necessary to detect electromagnetic radiation 111 for measurement, makes the device of the present disclosure easier to handle or operate, and this configuration improves radiation safety.

[0044] The device 100 can incorporate multiple radiation sensors 110-1, 110-2, 110-3, ..., 110-n, where n is a positive integer of 1, 2 or more. An embodiment of the device implementing one radiation sensor 110 is depicted in Figure 2, its detailed configuration is shown in Figure 3 and a schematic diagram of such a single sensor application is depicted in Figure 4B. In this embodiment 1002 of the device according to the present disclosure (shown in Figures 2 and 4B), one radiation sensor 110 is implemented which receives, via a detection surface 110b and via radiation collimating means 110c (see Figure 3), electromagnetic radiation 111 emitted by a radiopharmaceutical in the bloodstream passing through or perfusing the measurement location in the organ of interest 11.

[0045] The collimated electromagnetic radiation 111 is received by the radiation detection element 110d, and the detected radiation is converted into a corresponding electronic signal by the conversion unit 110e. For example, if the radiation sensor is configured as a scintillation detector, the absorbed radiation energy is first converted into a (visible) light signal by a scintillation crystal (reference numeral 110d), and then the light signal is converted into an electrical signal by a photomultiplier tube (or APD, SiPM) (reference numeral 110e). In examples where the radiation sensor is a semiconductor, direct conversion to an electrical signal may also be performed.

[0046] In this particular example, the conversion unit 110e is part of the radiation sensor 110. However, it should be noted that the conversion unit 110e does not necessarily have to be part of the radiation sensor 110, but can be implemented as a separate component 110e of the device 100.

[0047] The conversion unit 110e can convert, in a known manner, the electromagnetic radiation 111 detected over time by the radiation detection elements 110d into a suitable time-dependent electronic signal 102. Such a time-dependent electronic signal 102 can have a form as depicted in Figure 5A, with a typical periodic shape due to the pulsating nature of the arterial blood flow passing through / perfusing the measurement location of the organ of interest 11 due to the heart rate of the animal / human 10.

[0048] Reference numeral 103 indicates another relevant component of the apparatus 100 according to the present disclosure, which is incorporated as at least one processing unit 103 configured to generate one or more time-frequency representations of the time sequence of the radiation signal 102 by time-frequency conversion.

[0049] An example of a time-frequency representation of a time sequence of radiation signal 102 is designated by reference numeral 104 and is shown in detail, for example, in FIG. 5B. A time-to-frequency transform of the time sequence of radiation signal 102 decomposes the time sequence of radiation signal 102 into its frequency components, which are represented by the output of the transform as a function of frequency, as shown in FIG. 5B. In this illustrative example of the time-to-frequency transform of FIG. 5B, two frequency peaks are resolved from the time sequence of radiation signal 102. One frequency peak may correspond to the respiratory rhythm of subject 10, and the other frequency peak may correspond to the pulsation of blood circulation in subject 10.

[0050] The frequency output of the conversion can be processed to ultimately provide the concentration or amount of radiopharmaceutical in the bloodstream perfused through the measurement location in the organ of interest 11 .

[0051] Thus, a non-invasive, extracorporeal measurement of the arterial concentration / amount of the radiopharmaceutical is obtained in an organ (e.g., heart or artery) of the animal and / or human body 10. Thus, due to its non-invasive nature, the device 100 limits the burden on the animal and / or human body 10 and can be easily implemented in less stringent medical situations with simple detection equipment.

[0052] For practical use, an output unit 105 may be used, which is configured to output the thus determined intra-arterial concentration of the radiopharmaceutical, for example via a monitor or display. Other output means may also be implemented, such as a printing unit for suitable reporting on paper.

[0053] In order to obtain measurement results quickly and efficiently in terms of computation time, the time-frequency transformation performed by at least the processing unit 103 is preferably a short-time Fourier transform. However, as mentioned above, the time-frequency transformation as performed by at least the processing unit 103 is not limited to a Fourier transform. Other time-frequency transformations can also be used, for example selected from the group exemplified by, but not limited to, a wavelet transform, a filter bank, or a discrete cosine transform.

[0054] Furthermore, it should be noted that although only one processing unit 103 is used in the illustrated example, the apparatus 100 according to the present disclosure may implement multiple processing units 103, denoted 103-1, 103-2, ... 103-n, etc. Each processing unit 103-n may be assigned to each radiation sensor 110-n and thus used to perform a time-to-frequency transformation of the time sequence of the radiation signals 102 generated by the respective radiation sensor 110-n.

[0055] Another embodiment of a device 1001 according to the present disclosure is shown in FIG. 4A. This embodiment 1001 implements two radiation sensors 110-1 and 110-2 positioned on opposite sides of a measurement location in an organ of interest 11. For example, the organ of interest 11 may be a wrist artery or an ankle artery, and accordingly, the device 1001 may be configured as a wearable device having a structure for wearing around a limb (wrist or ankle) of an animal and / or human body 10 and on or near the measurement location in the organ of interest 11 (e.g., a wrist artery or ankle artery). Furthermore, due to the non-invasive nature of this particular embodiment 1001 of a device according to the present disclosure, the device 1001 limits the burden on the animal and / or human body 10 and can be easily implemented in less stringent medical situations using simple sensing equipment.

[0056] 4A, the two radiation sensors 110-1 and 110-2 are positioned on opposite sides of the measurement position on the organ of interest 11. The apparatus 1001 further implements a coincidence processing unit 106 configured to detect coincident detection of electromagnetic radiation 1111 by a first radiation sensor 110-1 and electromagnetic radiation 1112 by another radiation sensor 110-2 positioned on the opposite side of the first radiation sensor 110-1 and on either side of the measurement position on the organ 11.

[0057] In particular, the coincidence processing unit 106 can be implemented when a radiopharmaceutical or radioactive tracer is used, which undergoes radioactive decay to form a positron. This positron annihilates with an electron, thereby emitting two anti-collinear high-energy photons (gamma rays). These two high-energy photons 111-1 and 111-2, each with 511 keV, propagate in opposite directions, and are therefore simultaneously detected by two radiation sensors 110-1 and 110-2 located on opposite sides of the organ 11.

[0058] The coincidence detection by the radiation sensors 110-1 and 110-2 results in so-called trigger signals 107-1 and 107-2, which are processed by the coincidence processing unit 106 to finally obtain a time series of the radiation signal 102. This configuration therefore allows a more accurate measurement of the concentration (amount) of the radiopharmaceutical in the bloodstream perfusing the organ of interest 11, and a direct and accurate correction of the SUV is achieved. Thus, a direct and accurate correction of the SUV can be achieved, e.g. 18 It adds value to the clinical value of F-FDG PET imaging. Besides the correction of SUV, arterial radiopharmaceutical concentrations over time are also required to perform pharmacokinetic modeling, which is commonly used in research applications of various (new) radiopharmaceuticals, e.g., PET radiopharmaceuticals.

[0059] Similarly, in this particular embodiment, both radiation sensors 110-1 and 110-2 may be implemented without radiation collimating means 110c as used in the single radiation sensor embodiment of apparatus 1001 of FIG. 4B (and FIG. 3).

[0060] By implementing coincidence detection, the positions of the simultaneously detected high-energy photons 111-1 and 111-2 on the detectors can be used to identify, based on early measurements immediately after administration of the radiopharmaceutical, whether connecting lines between opposing detectors (so-called reaction lines) pass through or intersect with (arterial) blood vessels perfusing the organ 11. Because these connecting lines do not change during the measurement, the data obtained in this way can be used to examine only these reaction lines and eliminate the rest. This is an important way to further reduce background signal, especially in measurements at later time points when arterial concentrations are very low and background signal from surrounding tissues may be high.

[0061] In other advantageous embodiments, the methods of the present disclosure may be embodied in a computer program or product that includes computer coded instructions that, when the computer program or product program is executed by a computer, such as a laptop or computer, cause the computer to perform the steps of the computer-implemented methods disclosed herein.

[0062] In a particular embodiment, a computer-readable storage medium is proposed comprising computer-coded instructions stored therein, which, when executed by a computer, cause the computer to perform the steps of the computer-implemented method disclosed herein. Such a computer-readable storage medium may be a (solid-state) hard drive, or a USB drive, or a (digital) optical disk.

[0063] An embodiment 1001 of the device according to the present disclosure as shown in FIG. 4A implements two radiation sensors 110-1 and 110-2 and can be configured as a so-called synchronized arterial PET scanning device.

[0064] Contrary to known PET systems that derive arterial radiotracer concentration using image-derived methods, both embodiments 1001 (FIG. 4A) and 1002 (FIG. 4B) of the device according to the present disclosure can be constructed as miniature arterial PET scanning systems that can evaluate arterial radiotracer concentration in the bloodstream from periodic fluctuations in the measured radiation signal resulting from ventricular contractions or arterial vascular pulsations.

[0065] This technique avoids the need to create 3D tomographic images of the radiotracer distribution within the patient, allows the use of relatively standard, low-cost radiation detectors, and enables accurate and personalized measurement of arterial radiotracer concentrations in a non-invasive manner without the need for invasive arterial blood sampling, image-derived techniques, or population-based generic input functions. [Explanation of symbols]

[0066] 10 Moving body, human body, patient, 11 Measurement position, measurement target point / area, organ, 100, 1001, 1002 Non-invasive in vitro determination device (first, second, and third embodiments of the present disclosure), 101 treatment area, 101a Hospital Bed, 101b mattress, 102 Radiation signal time series, 103 processing equipment, 104 Time-frequency representation of radiation signals, 105 output units, 106 Coincidence processing unit, 1071, 1072 simultaneous detection radiation signals, 110, 110-n radiation sensors, 110a Housing / Radiation Shielding, 110b entrance surface of the housing; 110c radiation collimating means; 110d detection surface, detection area, 110e conversion unit, 111, 1111, 1112 Electromagnetic radiation.

Claims

1. 1. A computer-implementable method for non-invasively and extracorporeally determining arterial concentrations of a radiopharmaceutical, e.g., a radiotracer, in an organ of an animal and / or human body, comprising: i) receiving, over time, electromagnetic radiation emitted by said radiopharmaceutical by one or more radiation sensors placed near or at a measurement location on an organ, starting from the time when a certain amount of said radiopharmaceutical is administered to the animal and / or human body; ii) converting the received electromagnetic radiation into a time sequence of radiation signals; iii) generating one or more time-frequency representations of said radiation signal by a time-frequency transformation; iv) analyzing the time-frequency representation to determine the intra-arterial concentration of the radiopharmaceutical; A method comprising:

2. 2. The method of claim 1, wherein the time-frequency transform is a short-time Fourier transform, a wavelet transform, a filter bank, or a discrete cosine transform.

3. 3. The method of claim 1, wherein the step of receiving electromagnetic radiation over time includes receiving electromagnetic radiation over time using two radiation sensors positioned on opposite sides of the arterial measurement location.

4. 4. The method of claim 1, wherein the step of receiving the electromagnetic radiation over time further comprises the step of collimating the electromagnetic radiation emitted by the radiopharmaceutical prior to reception by one or more radiation sensors.

5. 1. A device for non-invasively and extracorporeally determining the intra-arterial concentration of a radiopharmaceutical, in particular a radioactive tracer, administered to an organ in an animal and / or human body, comprising: - one or more radiation sensors placed near or on the measurement location of an organ in the animal and / or human body, receiving the electromagnetic radiation emitted by the radiopharmaceutical over time; a conversion unit that converts said electromagnetic radiation received over time into a time series of radiation signals; a processing unit for generating one or more time-frequency representations of the time sequence of radiation signals by time-frequency transformation and for determining the arterial concentration of said radiopharmaceutical; An apparatus comprising:

6. 6. The apparatus of claim 5, further comprising an output unit for outputting the determined concentration of the radiopharmaceutical.

7. 7. The device according to claim 5, wherein the time-frequency transformation is a short-time Fourier transform, a wavelet transform, a filter bank or a discrete cosine transform.

8. 8. The device according to claim 5, wherein two or more radiation sensors are arranged on opposite sides of the organ to be measured.

9. The apparatus according to claim 8, further comprising a coincidence counting processing unit for detecting simultaneous detection values ​​of electromagnetic radiation by two or more radiation sensors arranged on opposite sides of the measurement position of the organ.

10. a housing containing at least one radiation sensor; radiation collimating means disposed around each of the one or more radiation sensors; 10. The apparatus according to claim 5, further comprising:

11. 11. A device according to any one of claims 5 to 10, characterized in that it is configured for attachment around a limb of an animal and / or human body.

12. 11. The device according to any one of claims 5 to 10, characterized in that it has a structure that is incorporated into a hospital chair, a hospital bed, or a patient table in the vicinity of the hospital chair, a hospital bed, or a patient table.

13. A computer program comprising instructions which, when executed by a computer, cause the computer to carry out the method according to any one of claims 1 to 4.

14. A computer-readable storage medium having stored thereon a computer program comprising instructions that, when executed by a computer, cause the computer to carry out the method according to any one of claims 1 to 4.

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