WO2018150348A1 - Non-invasive system for measuring the arterial input function for pet imaging - Google Patents

Abstract

It is developed a non-invasive system for the determination of the arterial input function (AIF) for Positron Emission Tomography (PET) image quantification. The system is based on a distributed set of transducers (A) attached to a patient's body that non-invasively measure, in distinct blood arteries, the concentration of the radiotracer used in PET scans. The measured data are then combined to calculate the AIF. The transducers (A) composing the system have a scintillator material (B) that interacts with the gamma photons emitted by the radiotracer and converts them into ultraviolet or visible light. This light is subsequently collected by a light sensor (C) creating an electric signal which is amplified (D) and pre-processed (E). The system is controlled remotely by an external processing device enabling its customization to each situation.

Description

DESCRIPTION

"Non-invasive system for measuring the arterial input function for PET imaging"

Technical field

This application relates to a non-invasive system for measuring the arterial input function for PET imaging.

Background art

Positron Emission Tomography (PET) technology has the ability of depicting the distribution of a biological molecule labelled with a positron emitter. This capacity, generally associated to static acquisition, has medical meaning and is relevant both in the clinical and in the research setting. However, PET data holds a much more valuable power, which is the capacity of providing quantitative information about biochemical, physiological and pharmacokinetics processes which are targeted by different radiotracers. In order to quantify the parameters related to the biological behaviour, for each radiotracer dynamic acquisitions are required as well as performing a mathematical treatment of the collected data. Only then PET data is translated into quantities amenable to statistical analysis. There is a plethora of methods for calculating parametric images that are generally classified either as data-driven or model-driven methods. Data-driven methods make no assumptions about the data structure whereas model- driven methods start from a model that constraint data.

Graphical analysis, such as Patlak and Logan plots are well known examples of data-driven methods where parameters are estimated using a fairly unrestricted description of the biological process. In the graphical analysis the dynamic PET data is transformed into a linear plot from which the binding parameters of the radioligands are easily calculated. The graph is obtaining by plotting the normalized tracer concentration in the Region Of Interest (ROI) at each instant against the accumulated activity in the plasma normalized to the plasma concentration at each instant. At the right conditions, the plot becomes linear and the slope and intercept can be related to the binding and transport characteristics of the radiotracer. Nevertheless, it has been pointed that the linearity of the plot could be biased by statistical noise, hindering the retrieval of the correct parameters .

Another data-driven method is spectral analysis, in which the tissue time activity curve is modelled as a convolution of the plasma input with exponential terms. The system is described by its impulse response function expressed as a positive sum of exponentials. The technique provides information on the number of compartments underlying the kinetics of the system.

Model-driven methods assume PET data as a mixture of several components originated by different pools of tracer, labelled as compartments. In order to isolate the part of signal of interest a mathematical framework was developed and is known as compartment analysis. A typical four compartments model has one compartment of arterial blood (Cp) , one of free radiotracer (Ct) , one compartment of specific binding (Cb) and one of non-specific binding (Cn) . Depending on the characteristics of each radiotracer other models, simpler or even more complex, can be devised. All the above methods require the knowledge of the plasma time activity curve. However, arterial blood sampling is very invasive and technically demanding. Therefore, there have been several attempts to obtain the necessary information by other forms, namely the image-derived input function (IDIF) . If large pools of the blood are within the PET field-of-view it is possible to derived the arterial input function from the PET image. IDIF is well-established for the heart, aortic segments and the femoral arteries. Nonetheless brain imaging presents difficulties to derive the input function from the carotids arteries due to the partial volume effect caused by the limited spatial resolution of PET cameras. Clinical scanners have a spatial resolution of about 6 mm whereas the typical diameter of carotids is about 5 mm which naturally causes an error on the evaluation of the input function. Many approaches have been suggested to handle this source of error. Whilst IDIF may be an elegant technique some nuisances persist, namely: the requirement for blood sampling is not complete overcome, the validation for a specific tracer and machine may not be correct for a different experimental setting and the accuracy of the image input might dependent on the radiometabolite fraction .

An alternative to blood sampling are the tissue reference methods (TRM) that are based on compartmental analysis. In these methods, a region without specific binding of the radioligand to its target is used as a reference to describe the time-activity curve of a region of interest. The inaccuracies arise in these methods especially because of failures on the assumption of absence of binding in the reference region. On other hand, for some radiotracers the identification of a region of reference that lies in the field-of-view could be problematic.

Summary

The present application describes a non-invasive system for measuring the arterial input function for PET imaging comprising :

— at least two transducers attached to a patient's body;

Wherein each transducer is encapsulated in a box and is comprised by:

at least one scintillator material encapsulated in a radioactive shielding;

at least one light sensor;

an amplification module;

a control and communication module comprising processing and wireless communication means; a power module; and

— an external processing device comprising processing means configured to process data sent by the at least two transducers, and communication means configured to remotely program the control and communication module with a set of measuring parameters.

In one embodiment of the system, the measuring parameters are an integration period of the signal generated by each transducer (A) and a lower and upper bounds of a gamma photons radiation energy range.

In another embodiment of the system, the scintillator material is configured to collect and transform gamma photons emitted by a radiotracer used in PET scan into ultraviolet or visible light photons.

In another embodiment of the system, the scintillator material is of a regular prism with rectangular or square base .

Yet in another embodiment of the system, the scintillator material is a scintillator crystal.

Yet in another embodiment of the system, the radioactive shielding is lead.

Yet in another embodiment of the system, the shielding material involves all the faces of the scintillator material that are not facing towards the patient's body.

Yet in another embodiment of the system, the light sensor is a photodiode.

Yet in another embodiment of the system, the processing means of the control and communication module (E) are configured to determine, during the integration period, the number of effective events representing gamma photons whose radiation energy sensed by the scintillator material (B) is within a specific range of energy, defined by the lower and upper bounds .

Yet in another embodiment of the system, the box is made of a metal such as copper or iron. Description

The present application is related to a radioactive sensor system capable of continuously measuring the concentration of a radiotracer within the blood flow of a patient who undergoes a Positron Emission Tomography (PET) scan (A) .

Based on that, a non-invasive system for measuring the arterial input function is developed. Said system comprising at least two transducers, distributed along the body of a patient, being each transducer comprised by:

- one or more scintillator materials encapsulated in a radioactive shield;

- one or more light sensors;

- an amplification module;

- a control and communication module;

- a power module.

Each transducer is encapsulated in a metal box, that shield all the transducer components against exterior electronic noise providing also mechanical robustness.

An advantage of the present non-invasive solution is the small dimension of each transducer used, which allows its temporarily attachment to the patient's body who can move freely without hindering the AIF determination. In fact, with this approach the AIF is measured attaching at least two transducers (A) , before the administration of the radiotracer, to the patient's body in different locations and having them remain attached during the PET scan.

Therefore it is possible to achieve a distributed measuring, non-invasive, redundant measuring, adaptable to each patient, independent of the radiotracer used in PET scans, which is tolerant to the patient motion and remotely controllable and programmable. In fact, the process of measuring the AIF is adapted according to the patient's characteristics, choice of radiotracer and PET acquisition protocol, with the information on these three conditions being remotely indicated via wireless communication to the control and communication module before beginning the process of measuring.

Said control and communication module (E) is configured to adjust the measured data by selecting only the events that are most likely to be real gamma photon interactions, before sending it via wireless communication to external processing devices .

Brief description of drawings

For easier understanding of this application, figures are attached in the annex that represent the preferred forms of implementation which nevertheless are not intended to limit the technique disclosed herein.

Figure 1 illustrate a particular embodiment of the system wherein four transducers are temporarily attached to a patient's body, in which the reference signs represent:

A - transducer;

I - external processing device.

Figure 2 is a 2D depiction of a single transducer and its components, in which the reference signs represent:

B - scintillator material;

C - light sensor; D - amplification module;

E - control and communication module;

F - power module;

G - radioactive shielding;

H - box .

Figure 3 is a 3D depiction of a single transducer and its components, in which the reference signs represent:

B - scintillator material;

C - light sensor;

D - amplification module;

E - control and communication module;

F - power module;

G - radioactive shielding;

H - box .

Figure 4 is a 3D depiction of a single transducer and its components, in which the reference signs represent:

B - scintillator material;

G - radioactive shielding.

H - box .

Detailed Description

Now, preferred embodiments of the present application will be described in detail with reference to the annexed drawings. However, they are not intended to limit the scope of this application.

The present application relates to non-invasive system for the determination of the arterial input function (AIF) for Positron Emission Tomography image quantification (PET) . The AIF is fundamental to the gold standard procedure employed for the quantification of images obtained by this clinical imaging technology.

The system now developed is composed by several, at least two, transducers (A) that are configured to detect gamma photons emitted from radiotracers used in PET scans. For that purpose, each transducer (A) is comprised by one or more scintillator materials (B) encapsulated in a radioactive shielding (G) , one or more light sensors (C) , an amplification module (D) , a control and communication module (E) and a power module (F) . All this components are contained in the transducer box (H) .

The said scintillator material (B) , such as a scintillator crystal, is of a regular prism with a rectangular or square base. It transforms the gamma photons emitted by the radiotracer used in the PET scan into ultraviolet or visible light photons. The scintillator material (B) is encapsulated in a radioactive shielding material (G) , such as lead, that shields the crystal limiting the directions of the photons reaching the said scintillator material (B) . The said radioactive shielding material (G) surrounds only the faces of the said scintillator material (B) that do not contribute for measuring the AIF, in order to reduce the noisy radiation from other parts of the patient's body. In other words, the shielding material involves the scintillator materials (B) in all the faces of the scintillator material (B) except the one that faces towards the patient's body when a transducer (A) is attached to the body.

The light originated in the said scintillator material (B) is collected by one or more light sensors (C) , such as photodiodes, that transforms it into an electric signal. The amplification module (D) is responsible for the integration and amplification of the signal coming from the light sensor, which is then processed and transmitted to external devices

(I) by the control and communication module (E) . Module (E) is provided with processing means configured to process the integrated signal coming from the module (D) in order to determine, in a predefined time period, the number of effective events representing gamma photons whose radiation energy sensed by the scintillator material (B) is within a specific range of values. Said control and communication module (E) is also provided with wireless communication capabilities, which allows for remote programming. Based on that, it is possible to configure the processing stage at module (E) to measure the AIF for each radiotracer, each patient and each protocol acquisition, according to a set of measuring parameters . Such measuring parameters are the integration period of the signal generated by each transducer

(A) , and the configuration of the lower and upper bounds of the gamma photons radiation energy range values used to count the number of effective events.

To power all the different modules of the transducer, a power module (F) such as a battery, is used. The transducer box (H) , encapsulating all the transducer components is made of a metal such as copper, iron or any other metal that has the capacity of reducing electrical noise.

The transducers (A) are placed at different locations on the body, receiving the signal corresponding to the AIF at slightly different instants. The preferential locations to place the said transducers (A) are near blood arteries, such as the aorta, the carotid, the radial, the brachial or the femoral artery. Each transducer (A) collects different signal components that are related not only to the arterial blood's radiopharmaceutical element, which is responsible for the AIF calculation, but also to the signals from the surrounding tissues' radiopharmaceutical elements. Therefore, each transducer (A) is responsible for the integration of these distinct signal components and its respective processing stage according to the set of parameters programmed at module (E) , prior to sending the information to an external processing device.

This remote processing device is provided with processing means adapted to combine the distinct components carried by the signals sent by the set of transducers (A) , in order to determine the AIF that is used to PET quantification.

This description is of course not in any way restricted to the forms of implementation presented herein and any person with an average knowledge of the area can provide many possibilities for modification thereof without departing from the general idea as defined by the claims. The preferred forms of implementation described above can obviously be combined with each other. The following claims further define the preferred forms of implementation.

Claims

1. Non-invasive system for measuring the arterial input function for PET imaging comprising:

— at least two transducers (A) attached to a patient's body;

Wherein each transducer (A) is encapsulated in a box (H) and is comprised by:

at least one scintillator material (B) encapsulated in a radioactive shielding (G) ;

at least one light sensor (C) ;

an amplification module (D) ;

a control and communication module (E) comprising processing and wireless communication means; a power module (F) ; and

— an external processing device (I) comprising processing means configured to process data sent by the at least two transducers (A) , and communication means configured to remotely program the control and communication module (E) with a set of measuring parameters.

2. System according to claim 1, wherein the measuring parameters are the integration period of the signal generated by each transducer (A) and a lower and upper bounds of a gamma photons radiation energy range.

3. System according to any of the previous claims, wherein the scintillator material (B) is configured to collect and transform gamma photons emitted by a radiotracer used in PET scan into ultraviolet or visible light photons.

4. System according to claim 3, wherein the scintillator material is of a regular prism with rectangular or square base .

5. System according to claims 3 or 4, wherein the scintillator material is a scintillator crystal.

6. System according to any of the previous claims, wherein the radioactive shielding (G) is lead.

7. System according to any of the previous claims, wherein the shielding material (G) involves all the faces of the scintillator material (B) that are not facing towards the patient's body.

8. System according to claim 1, wherein the light sensor (C) is a photodiode.

9. System according to any of the previous claims, wherein the processing means of the control and communication module (E) are configured to determine, during the integration period, the number of effective events representing gamma photons whose radiation energy sensed by the scintillator material (B) is within a specific range of energy values, defined by the lower and upper bounds.

10. System according to claim 1, wherein the box is made of a metal such as copper or iron.