阅读说明：本技术 淀粉样蛋白筛查的方法和装置 (Method and device for screening amyloid ) 是由 A·安德烈耶夫 D·B·麦克奈特 N·塞拉菲诺 D·匹托克 白传勇 C-H·董 于 2019-08-13 设计创作，主要内容包括：一种用于执行淀粉样蛋白评估的设备(10)包括辐射探测器组件(12),所述辐射探测器组件包括至少一个辐射探测器(14)。至少一个电子处理器(20)被编程为：在数据采集时间间隔内使用所述辐射探测器组件来探测辐射计数；根据探测到的辐射计数来计算至少一个当前计数度量；将与当前测试日期相关联的所述至少一个当前计数度量存储在非瞬态存储介质(26)中；并且基于所述至少一个当前计数度量与在所述非瞬态存储介质中存储的与较早测试日期相关联的计数度量的比较来确定淀粉样蛋白度量。(An apparatus (10) for performing amyloid assessments includes a radiation detector assembly (12) including at least one radiation detector (14). At least one electronic processor (20) is programmed to: detecting radiation counts using the radiation detector assembly over a data acquisition time interval; calculating at least one current count metric from the detected radiation counts; storing the at least one current count metric associated with a current test date in a non-transitory storage medium (26); and determining an amyloid metric based on a comparison of the at least one current count metric to a count metric stored in the non-transitory storage medium associated with an earlier test date.)

1. An apparatus (10) for performing amyloid assessment, the apparatus comprising:

a radiation detector assembly (12) including at least one radiation detector (14); and

at least one electronic processor (20) programmed to:

detecting radiation counts using the radiation detector assembly over a data acquisition time interval;

calculating at least one current count metric from the detected radiation counts;

storing the at least one current count metric associated with a current test date in a non-transitory storage medium (26); and is

Determining an amyloid metric based on a comparison of the at least one current count metric to count metrics stored in the non-transitory storage medium associated with earlier test dates.

2. The apparatus (10) according to claim 1, wherein the radiation detector assembly (12) further includes:

a radiation shielding collar (36) comprising a radiation absorbing material and shaped and dimensioned to be disposed around the neck.

3. The device (10) according to any one of claims 1-2, wherein the radiation detector assembly (12) includes:

a rear radiation detector (30); and

two side radiation detectors (32);

wherein the rear radiation detector and the two side radiation detectors are arranged to define a chamber (C) dimensioned to accommodate a head, wherein the rear radiation detector is arranged to view a rear side of the head disposed in the chamber and the two side radiation detectors are arranged to view left and right sides of the head disposed in the chamber.

4. The apparatus (10) according to claim 3, wherein the radiation detector assembly (12) further includes:

a crown radiation detector (34) arranged to further define the chamber (C), wherein the crown radiation detector is arranged to view a crown of the head disposed in the chamber.

5. The device (10) according to any one of claims 1-4, wherein:

the radiation detector assembly (12) does not include a radiation collimator; and is

The apparatus does not include a time stamp circuit for assigning a time stamp to a count of radiation detected using the radiation detector assembly; and is

Calculating the at least one current count metric as a function of the detected radiation counts does not include performing image reconstruction on the detected radiation counts.

6. The device (10) according to any one of claims 1-4, wherein:

the radiation detector assembly (12) includes at least one of (i) at least one radiation collimator (40) or (ii) coincidence detection circuitry (42) for acquiring the radiation counts as radiation coincidence counts;

the at least one electronic processor (20) is further programmed to reconstruct the detected radiation counts into an image.

7. The device (10) according to any one of claims 1-4, wherein:

the radiation detector assembly (12) includes at least one slat radiation collimator (40); and is

The at least one electronic processor (20) is further programmed to reconstruct the detected radiation counts into a one-dimensional image.

8. The device (10) according to any one of claims 1-7, wherein:

the radiation detector assembly (12) does not include a robotic actuator configured for moving the at least one radiation detector during the data acquisition time interval during which radiation counts are detected using the radiation detector assembly.

9. The device (10) according to any one of claims 1-8, wherein:

the at least one current count metric comprises at least one of a count rate and a total count detected within the data acquisition time interval; and is

Calculating the at least one current count metric includes scaling the at least one current count metric by one or more of patient weight, patient age, patient gender, and patient ethnicity.

10. The device (10) according to any one of claims 1-9, wherein the radiation detector assembly (12) is configured to detect a count of radiation emitted from at least half of a brain monitored by the radiation detector assembly.

11. A radiation detector assembly (12) comprising:

a rear radiation detector (30); and

two side radiation detectors (32);

wherein the rear radiation detector and the two side radiation detectors are arranged to define a chamber (C) sized to accommodate a head, wherein the rear radiation detector is arranged to view a rear side of the head disposed in the chamber and the two side radiation detectors are arranged to view left and right sides of the head disposed in the chamber.

12. The radiation detector assembly (12) according to claim 11, further comprising:

a crown radiation detector (34) arranged to further define the chamber (C), wherein the crown radiation detector is arranged to view a crown of the head disposed in the chamber.

13. The radiation detector assembly (12) according to any one of claims 11-12, further including:

an adjustable support (38) arranged to position the two side radiation detectors at an adjustable distance from the chamber.

14. The radiation detector assembly (12) according to any one of claims 11-13, wherein the rear radiation detector (30) and the two side radiation detectors (32) have curved radiation detection surfaces shaped to conform to the head disposed in the chamber.

15. The radiation detector assembly (12) according to any one of claims 11-14, wherein the rear radiation detector (30) and the two side radiation detectors (32) each have a planar radiation detection surface.

16. The radiation detector assembly (12) according to claim 15, further comprising:

a radiation collimator panel (40), wherein each of the rear radiation detector (30) and the two side radiation detectors (32) has collimator mounting hardware (44) via which one of the radiation collimator panels is mountable to the planar radiation detection surface.

17. The radiation detector assembly (12) according to any one of claims 11-15, wherein the radiation detector assembly does not include a radiation collimator and is not configured to detect coincidence radiation counts.

18. The radiation detector assembly (12) according to any one of claims 11-17, further including:

a radiation shielding collar (36) comprising a radiation absorbing material and shaped and sized to be disposed around a neck connected to the head disposed in the chamber.

19. The radiation detector assembly (12) according to any one of claims 11-18, wherein the radiation detector assembly is configured to detect a count of radiation emitted from at least half of a brain contained by the head disposed in the chamber.

20. A method (100) for performing a clinical assessment, the method comprising:

obtaining imaging data using a radiation detector assembly (12) including at least one radiation detector (14) mounted in or on a patient support on which the patient is positioned to view the positioned patient's head;

detecting radiation counts from a radiotracer that binds to a target protein administered to the patient over a data acquisition time interval;

calculating at least one current count metric from the detected radiation counts; and is

Determining a metric of deposition of the target protein in the head of the located patient based on a comparison of the at least one current count metric and a previous count metric.

21. The method of claim 20, further comprising:

performing follow-up assessment on the patient using the determined measure of deposition.

22. The method according to either one of claims 20 and 21, further including:

generating a one-dimensional (1D) count profile from the measured total counts or count rates; and is

Controlling a display (24) to display the generated count profile having peaks in its outer region and valleys in its central portion.

23. The method according to either one of claims 20 and 21, wherein the detecting includes: continuously detecting a monomer radiation count from at least half of the brain of the located patient over the data acquisition time interval.

24. The method of claim 23, wherein the monomer radiation counts are detected without collimating the radiation.

25. The method of any one of claims 20-24, wherein the target protein comprises amyloid beta.

Technical Field

The following generally relates to the field of image acquisition, the field of brain images, the field of amyloid beta imaging, and related fields.

Background

The elevation of beta amyloid deposition in the human brain is relevant for the ultimate diagnosis of alzheimer's disease. Timely detection of amyloid deposition can provide the necessary prophylactic procedure to better control this destructive disorder. Recently, new Positron Emission Tomography (PET) radiotracers have been developed to detect increases in amyloid plaque deposition. Other types of chronic neurological diseases are also associated with characteristic amyloid accumulation, e.g., parkinson's disease is associated with amyloid alpha-synuclein accumulation, while other types of protein deposition are also associated with other neurological diseases, e.g., tau accumulation is associated with Chronic Traumatic Encephalopathy (CTE).

Although effective in diagnosing amyloid plaques, conventional PET/Computed Tomography (CT) systems are not routinely used in the general population to monitor and detect the disease at its early stages. This includes even those individuals who have known high risk factors (e.g., genetic susceptibility to alzheimer's disease diagnosis). The main obstacles are cost issues (which may require about thousands of dollars (see, e.g., https:// www.alzforum.org/news/community-news/100 m-idea-cms-texts-term-evaluation-analog-nucleic-scans-clinical-practice)) and the relatively high radiation dose (at least about 5mSV) associated with such PET/CT scans.

The following discloses a new and improved system and method that overcomes these problems.

Disclosure of Invention

In one disclosed aspect, an apparatus for performing amyloid assessment includes a radiation detector assembly including at least one radiation detector. At least one electronic processor is programmed to: detecting radiation counts using the radiation detector assembly over a data acquisition time interval; calculating at least one current count metric from the detected radiation counts; storing the at least one current count metric associated with a current test date in a non-transitory storage medium; and determining an amyloid metric based on a comparison of the at least one current count metric to a count metric stored in the non-transitory storage medium associated with an earlier test date.

In another disclosed aspect, a radiation detector assembly includes a rear radiation detector and two side radiation detectors. The rear radiation detector and the two side radiation detectors are arranged to define a chamber sized to accommodate a head, wherein the rear radiation detector is arranged to view a rear side of the head disposed in the chamber and the two side radiation detectors are arranged to view left and right sides of the head disposed in the chamber.

In another disclosed aspect, a method for performing a clinical assessment includes: obtaining imaging data using a radiation detector assembly comprising at least one radiation detector mounted in or on a patient support on which the patient is positioned to view a head of the positioned patient; detecting radiation counts from a radiotracer that binds to a target protein administered to the patient over a data acquisition time interval; calculating at least one current count metric from the detected radiation counts; and determining a metric of deposition of the target protein in the head of the located patient based on a comparison of the at least one current count metric and a previous count metric.

One advantage resides in providing a low cost device for assessing the accumulation of beta amyloid or another amyloid or other target protein in the brain.

Another advantage resides in providing an imaging device in which a reduced radiopharmaceutical dose is ingested by a patient being imaged.

Another advantage resides in providing an apparatus for early detection of gradual accumulation of amyloid deposits.

A given embodiment may provide none, one, two, more, or all of the aforementioned advantages, and/or may provide other advantages as will become apparent to those skilled in the art upon reading and understanding the present disclosure.

Drawings

The disclosure may take form in various components and arrangements of components, and in various steps and arrangements of steps. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the disclosure.

Fig. 1 schematically illustrates an apparatus for performing amyloid beta assessment according to one aspect;

2A-2C schematically illustrate a radiation detector assembly of the apparatus of FIG. 1;

FIG. 3 illustrates exemplary flowchart operations of the apparatus of FIG. 1; and is

Fig. 4 shows a count contour plot of data collected by the apparatus of fig. 1.

Detailed Description

Amyloid beta (a β) deposits in brain tissue are associated with certain neurodegenerative diseases, such as alzheimer's disease. Other types of amyloid deposits are associated with other neurological diseases (e.g., alpha-synuclein is associated with parkinson's disease), and even more commonly, various types of protein deposits are associated with various neurological diseases (e.g., tau protein deposits are associated with Chronic Traumatic Encephalopathy (CTE)). PET or Single Photon Emission Computed Tomography (SPECT) imaging can be used in conjunction with radiotracers that preferentially bind a β to image amyloid beta deposits in the brain, providing a screening tool for detecting and monitoring these diseases. However, PET or SPECT are not ideal options for screening patients. This technique is expensive to perform and requires the delivery of a relatively high radioactive dose to the patient.

It is recognized herein that: some of these drawbacks of PET or SPECT can be mitigated by eliminating imaging aspects, or to a lesser extent, by employing lower resolution and/or reduced dimension imaging (e.g., acquiring 2D or 1D maps). In order to perform imaging, sufficient radiotracer must be administered so that the concentration of the radiotracer in each voxel of the image (or at least in those voxels with large amounts of target protein) is at a detectable level. In contrast, if other measures of deposition of the target protein in the patient's head are used (e.g., total counts from the entire head), the minimum necessary dose of the radiotracer can be significantly reduced (e.g., by an order of magnitude or more in some embodiments).

However, with such methods, sensitivity may become diminished because the amount of information is reduced due to the loss of spatial resolution provided by the imaging and the signal-to-noise ratio is reduced due to the reduction of the radiotracer dose. In some embodiments disclosed herein, the metric of deposition of the target protein in the head is based on a comparison of a current count metric to a previous count metric (e.g., obtained in an earlier test date). This will automatically normalize the various factors and focus the metric on changes over time, which is more likely to be clinically meaningful than a metric that references nominally similar measurements in a nominally similar patient cohort.

In the embodiments disclosed herein, low cost instrumentation is employed and a reduced radiotracer dose is administered to the patient. In some embodiments, a low cost radiation detector is integrated into the head region of the patient couch, together with a radiation shielding collar arranged to fit around the neck of the patient to reduce detection of stray radiation from the torso region. The objective is to measure the total counts (or equivalently the count rate) over a fixed acquisition time measured after delivery of a radiotracer that targets amyloid or other target protein deposits. In some embodiments, costs are further reduced by detecting monomers rather than coincidence and/or omitting or simplifying image generation and/or omitting conventional coincidence detection circuitry and/or radiation collimators (thus losing imaging capability). Low dose is achieved in part by measuring the counts of most or all of the brain; rather than using a local radiation probe or by effectively dividing the detected counts into image voxel values by image reconstruction.

In other embodiments, a plurality of radiation detectors are disposed around part or all of the head, thereby further maximizing the detected counts and allowing for further reduction of the radiotracer dose. Various implementations can be implemented, for example, a three or four probe plate design, where the rear side plate is embedded in the table, two side plates are arranged on the left and right sides of the head, and an optional crown plate is positioned above the crown of the "head". The side and crown plates can be mounted on rails and can slide into contact with the sides and crown of the head, thereby also stabilizing the head and inhibiting movement. A radiation shielding collar fitted around the patient's neck may further stabilize the head and may also block stray counts from radiotracer concentrations in the torso or other body parts "under" the head. An additional detector plate may be placed in front of the patient's face, but it may potentially induce claustrophobia, which will be a factor in deciding whether to include (or use) such an additional detector plate.

Note that the term "patient" as used herein broadly refers to a human that receives a clinical assessment of beta amyloid (or other target protein) deposits in the brain (i.e., head). The patient may be a patient diagnosed with early-onset alzheimer's disease or another chronic neurological disease whose clinical progression is being monitored, or the patient may be a healthy individual who is screened for amyloid beta deposits only. Indeed, the disclosed methods have the advantage that their low cost and reduced radiotracer dose make these methods well suited for screening healthy patients, which can be done on an outpatient basis or during routine medical examinations (e.g., during an annual physical examination of a patient).

It is recognized herein that: providing a fair comparison for screening is a formidable challenge. In an illustrative example, the external baseline is not relied upon (e.g., derived from similar measurements of a cohort of similar patients or derived from measurements taken from "normal" portions of the patient's body); rather, the test is designed to be performed on a given patient on successive test days in order to detect an increase in counts over time, which may indicate an increase in a β deposits in the patient's brain.

Other aspects disclosed herein relate to data quantization, for which various metrics may be used alone or in combination. The count at a fixed time after administration of the radiopharmaceutical (i.e., the radiotracer) may be a suitable metric, but depends on the precise timing of the measurement, and may be susceptible to differences in the radiotracer dose and uptake between courses due to metabolic differences, etc. Another approach is to measure a count versus time curve from which various metrics can be extracted, e.g., number of peaks, FWHM of uptake curve, ramp-up slope, elution decay constant, area under curve, etc. Here, the desire for high time resolution in the count versus time curve may be balanced with the need for sufficient count statistics in each time bin. In any case, the metric may be adjusted or normalized for the amount of radiotracer injected, the patient's body weight or Body Mass Index (BMI), age (to account for the natural accumulation of a β due to aging), and/or other variables (e.g., gender or ethnicity).

In some embodiments disclosed herein, no imaging is performed. This may save costs, for example, eliminating the use of time stamp circuitry and coincidence detection and/or radiation collimators (e.g., honeycomb collimators mounted in front of the radiation detectors), the use of radiation detectors with coarse resolution or even single large area detectors (which may also be facilitated by the use of low radioactive tracer doses and thus reduced likelihood of count stacking), eliminating scatter correction, and enabling the use of fixed detectors that do not completely encircle the patient's head. It is also recognized that: the energy window for monomer detection can be expanded towards the low energy end to deliberately account for elastic scattering events, again enabling further dose reduction. Scatter events can present problems for imaging because the source radioactive decay events generally do not lie on the "line of response" defined by the coincidence or radiation collimator, and scatter events are largely removed by employing an energy window that filters out scatter detection that loses energy during (inelastic) scattering. However, if imaging is not performed, as with certain protein deposit assessment methods disclosed herein, these scattering events can be preserved by extending the energy window on the low energy side, thereby increasing the overall count. With such a strategy, it is estimated that the dose can be reduced to 1/1000 at most, compared to the effect that can be achieved with conventional PET, thereby making the a β screening dose comparable to that of conventional dental X-ray.

In other embodiments disclosed herein, imaging is performed. In this case, a radiation detector is provided that provides multiple viewpoints, for example, the design described above with a backside detector, a side detector, and optionally a crown detector. Since the clinical result is derived from the total or average count, the low resolution image is sufficient to provide the clinician with some visual background. In the PET embodiment, coincidence detection is used to spatially encode the counts. In a SPECT embodiment, a radiation collimator (e.g., a honeycomb collimator) provides spatial encoding of the counts. Advantageously, since the radiation detector is stationary (possibly in addition to the pre-acquisition positioning of the detector plate relative to the patient's head), the collimator can be provided as a set of slats or grid inserted into receiving slots of the radiation detector, or as a mounting of the radiation detector when imaging is required. In one embodiment, "imaging" is a one-dimensional (1D) counting profile. As has been observed, a β deposits tend to accumulate in the outer regions of the brain, so the resulting contours are expected to peak at the outer regions and sink in the center, and this shape and possible extracted quantification (e.g., peak-to-valley ratio) can be used to provide a visual representation to the clinician, and optionally also quantitative data.

Referring to fig. 1, an illustrative device or system 10 for performing amyloid beta assessment is shown. In the following, amyloid beta assessments are described, which are useful for assessing whether a patient has an associated chronic neurological disease (e.g., alzheimer's disease). In other embodiments, deposits of different targeted amyloid proteins or more generally different target proteins may be assessed; this is accomplished by selecting a radiotracer to be administered to the patient that preferentially binds to a particular targeted amyloid protein or, more generally, preferentially binds to a particular target protein). As shown in FIG. 1, the system 10 includes a radiation detector assembly 12 having at least one radiation detector 14. In the illustrative example of fig. 1, the radiation detector assembly 12 includes a single radiation detector panel 14 embedded in a head region of a patient support 16; in other embodiments described herein, the radiation detector assembly may include two or more detector plates, e.g., additional plates disposed at the left and right sides of the head, and optionally also additional plates disposed at the crown of the head. It should also be noted that each such detector panel may be configured as two or more operationally independent detector tiles, e.g., a 2 x 2 array of detector tiles may constitute a single radiation detector panel as shown in fig. 1. The radiation detector assembly 12 can be integrated with a patient support 16 on which the patient P is lying or otherwise attached to the patient support 16. The radiation detector assembly 12 is sized and configured to receive a portion of a patient (i.e., the head H) when the patient is lying on the patient support 16.

The device 10 may also include or otherwise be connected to a workstation 18, the workstation 18 including a computer or other electronic data processing device having typical components, such as at least one electronic processor 20, at least one user input device (e.g., a mouse, keyboard, trackball, etc.) 22, and a display device 24. It should be noted that these components can be variously distributed. For example, the electronic processor 20 may include a local processor of a workstation terminal and a processor of a server computer accessed by the workstation terminal. In some embodiments, the display device 24 can be a separate component from the computer 18. The workstation 18 can also include one or more databases or non-transitory storage media 26. The various non-transitory storage media 26 may include, by way of non-limiting illustrative examples, one or more of the following: a disk, RAID, or other magnetic storage medium; a solid state drive, flash drive, Electrically Erasable Read Only Memory (EEROM), or other electronic memory; optical disks or other optical storage devices; various combinations thereof, and the like. They may also be variously combined, for example, a single server RAID storage device. The display device 24 is configured to display a Graphical User Interface (GUI)28, the GUI 28 including one or more fields to receive user input from the user input device 22.

In particular, the workstation 18 is operatively connected with the radiation detector assembly 12 to receive counts of radiation detection events from the at least one radiation detector 14. These counts may be processed in various ways by the workstation 18 and/or pre-processed by the electronics of the radiation detector assembly 12 (such electronics not shown in fig. 1) to perform various filtering, etc. on the acquired count data. For example, energy filtering can be applied to filter out counts whose energies lie outside a defined energy window that is positioned to contain the energy or energy range of the radioactive particles emitted by the radioactive tracer. For example, positron-emitting PET radiotracers emit oppositely directed 511keV gamma rays emanating from each positron-electron annihilation event; thus, in this case, the energy window suitably comprises 511 keV. As previously mentioned, for non-imaging embodiments, it is contemplated that the energy window is designed to extend to substantially lower energies to capture inelastically scattered gamma rays that lose energy due to scattering and are therefore detected at particle energies below 511 keV. Some radiotracers emit gamma rays, beta particles, alpha particles and/or other radio emissions over a range of energies, in which case the energy window preferably extends over the range. It is also contemplated that the energy window is a configurable parameter to tune to a particular type of radiotracer for a particular patient assessment, thereby increasing the flexibility of the device.

Figures 2A-2C illustrate another exemplary embodiment of the radiation detector assembly 12. Figure 2A shows a "rear" view of the radiation detector assembly. As shown in fig. 2A, the radiation detector assembly 12 includes several radiation detectors 14, for example, a rear radiation detector 30 (e.g., positioned at the same location as the single radiation detector 14 shown in fig. 1) and two side radiation detectors 32. The rear radiation detector 30 and the two side radiation detectors 32 are arranged or otherwise configured to define a chamber C sized to receive the head H of the patient. A rear radiation detector 30 is arranged to view the rear side of the head disposed in the chamber C, and two side radiation detectors 32 are arranged to view the left and right sides of the head disposed in the chamber. In one example, the rear radiation detector 30 and the two side radiation detectors 32 each have a planar radiation detection surface (as shown). In another example, the rear radiation detector 30 and the two side radiation detectors 32 have curved radiation detection surfaces (not shown) that are shaped to conform to the shape of the head disposed in the chamber C. The side detector 32 (if provided) generates additional counts to enable further reduction in the radiopharmaceutical dose administered. In some embodiments, a crown radiation detector 34 (shown by dashed lines) is included to further define the chamber C and provide more counts, and the crown radiation detector 34 is arranged to view the crown (i.e., top) of the head H disposed in the chamber. In some embodiments, the radiation detector assembly 12 further includes a radiation shielding collar 36 (see fig. 1), the radiation shielding collar 36 including a radiation absorbing material (e.g., a high atomic weight material (e.g., lead) or a composite or other matrix containing high atomic weight elements (e.g., leaded glass)) shaped and sized to be disposed around a portion of the patient (i.e., the neck). The optional radiation shielding collar 36 blocks stray radiation from the torso and/or other parts of the body from reaching the detector(s) 14 surrounding the head H and may also serve to mechanically stabilize the head H.

In some embodiments, the radiation detector assembly 12 does not include a robotic actuator configured to move the radiation detector 14 during a data acquisition time interval during which radiation counts are detected using the radiation detector assembly. In other embodiments, an adjustable support 38 is attached to the side radiation detector 32 and the patient support 14 to move and position the side radiation detector at an adjustable distance from the chamber C.

As shown in fig. 2A, the radiation detector assembly 12 does not include a radiation collimator, nor does the apparatus 10 include time stamp circuitry for assigning time stamps to radiation counts detected using the radiation detector assembly. (Note, however, that the collected count data set may be assigned a test date as opposed to time stamping individual counts). In other embodiments, the radiation detector assembly 12 includes at least one radiation collimator panel 40 (see fig. 2B) or coincidence detection circuitry 42 (see fig. 2C) to collimate the radiation detected by the radiation detector 14. (more specifically, the collimator panel 40 passes only radiation traveling along a straight line or narrow angle cone to the coupled radiation detector, thereby collimating the detected radiation). Each of the rear radiation detector 30 and the two side radiation detectors 32 has collimator mounting hardware 44 via which one of the radiation collimator panels can be mounted to a planar radiation detection surface. In some examples, the radiation collimator panel 40 can comprise a slat or honeycomb radiation collimator panel, and the collimator mounting hardware 44 comprises corresponding slits configured to receive and retain the slat or honeycomb collimator panel. With such collimation, at least one electronic processor 20 can be programmed to reconstruct the detected radiation counts into an image (e.g., a one-dimensional image in the case of a slat collimator, or a two-dimensional or three-dimensional image in the case of a honeycomb collimator). Such image reconstruction can employ any suitable image reconstruction technique, such as those typically employed in reconstructing SPECT imaging data. In another embodiment, if the radiotracer is a PET radiotracer that emits positrons that attenuate to opposite directions 511keV gamma rays, coincidence detection can be employed in which coincident 511keV detection events are detected using an appropriate time window, one count for each pair of 511keV detections. In this case, the counts can be reconstructed into an image using any conventional PET reconstruction technique. In some examples, the radiation detector assembly 12 is configured to detect radiation counts emanating from at least half of the tissue of the brain monitored by the radiation detector assembly.

Referring back to fig. 1, system 10 is configured to perform a method or process 100 for performing beta amyloid (or other targeted amyloid or protein) assessment. To this end, the non-transitory storage medium 26 stores instructions that are readable and executable by at least one electronic processor 20 of the workstation 18 to perform the disclosed operations, including performing the method or process 100 for performing amyloid beta assessment. In some examples, method 100 may be performed at least in part by cloud processing.

Referring to fig. 3, an illustrative embodiment of a method 100 for performing an assessment of amyloid beta is schematically shown in flow chart form. To begin the method 100, a patient is positioned (e.g., laid down) on the patient support 16. The radiotracer is then administered to the patient while the patient is positioned on the patient support 16. (alternatively, the radiotracer may be administered prior to placing the patient on the patient support; however, at 102, the at least one electronic processor 20 is programmed to control (or in some embodiments only read) the detectors 14 of the radiation detector assemblies 12 to detect radiation counts over data acquisition time intervals, the detecting including continuously detecting monomer radiation counts from at least half of the brain of the located patient over data acquisition time intervals (in some preferred embodiments, although monitoring of smaller portions of the brain is also contemplated). The individual radiation counts are detected without collimating the radiation and without determining a time stamp and assigning the time stamp to the individual counts.

At 104, the at least one electronic processor 20 is programmed to calculate at least one current count metric based on the detected radiation counts. In some examples, the at least one current count metric includes at least one of a count rate and a total count detected within the data acquisition time interval. In this example, calculating the at least one current count metric includes scaling the at least one current count metric by one or more of patient weight, patient age, patient gender, and patient ethnicity. The scaling may be determined empirically, for example using a look-up table that applies a scaling factor based on the patient's age or proportional to the patient's weight, etc. As another contemplated adjustment, the radioactivity of the radiotracer may be measured prior to or during administration of the radiotracer to the patient (e.g., using a geiger counter to monitor the radioactivity of a fluid tube that intravenously feeds a radiotracer solution into a patient's blood vessel). The count metric may be scaled in proportion to the actually measured radioactivity of the radiotracer. The adjustment takes into account daily variations in the dose of the injected radiotracer.

At 106, the at least one electronic processor 20 is programmed to store the at least one current count metric associated with the current test date in the non-transitory storage medium 26. As such, it may optionally have a relatively low time resolution, such as storing calendar dates, but not times of day.

At 108, the at least one electronic processor 20 is programmed to determine an amyloid-beta metric based on a comparison of the at least one current count metric to a count metric stored in the non-transitory storage medium 26 associated with an earlier test date. For example, the amyloid-beta metric (or more generally, an amyloid metric, or even more generally, a metric of deposition of the target protein in the head H of the patient P) may be a percentage change between the current count metric and the count metric of an earlier test date.

At 110, with certain imaging embodiments, the at least one electronic processor 20 is programmed to generate a one-dimensional (1D) count profile from the measured total count or count rate based on an image reconstructed from the spatial localization of events provided by collimator in SPECT type imaging or PET type coincidence detection.

At 112, the at least one electronic processor 20 is programmed to control the display 24 to display the amyloid-beta metric and, if generated, a generated count profile having peaks in its outer regions and valleys in its central portion. Other information may be displayed, such as the current count metric and the count metric of the earlier test date. If two or more past tests are stored in the non-transitory storage medium 26, one or more trendlines can optionally be plotted, for example, plotting the count metric for each test as a function of the test date. The display of such a trend line allows the clinician to immediately visually perceive whether the counting metric (and by inference the amyloid-beta deposits) is increasing and at what rate in the case of an increase. These various metrics may also have associated uncertainty or statistical significance values based on empirical analysis of how much the multiple test count metric should reach before clinical significance is obtained. It should also be noted that the amyloid-beta metric and any other displayed metrics (e.g., the trend line of the counting metric in multiple tests) are merely clinical information to consider, in conjunction with which a clinician may ask the patient for a reported symptom (e.g., mental memory level, etc.), for example, in assessing whether the patient P should be diagnosed as having alzheimer's disease (or other disease associated with accumulation of target amyloid or protein in the brain).

The amyloid beta metric (generated at 108) and/or the count profile (generated at 110) may additionally or alternatively be used for follow-up treatment of the patient. For example, if a drug is administered to inhibit amyloid deposition, the patient may be monitored during drug treatment (e.g., using amyloid beta assessment method 100) to determine the effectiveness of the drug regimen. Advantageously, the low radiopharmaceutical dose and use of the system 10 (rather than using a complete PET imaging system with its attendant high cost and requisite higher radiopharmaceutical dose) allows for more frequent monitoring of patients.

Although the illustrative example employs a dedicated system 10, it should be noted that in alternative embodiments, the count contours obtained by the system 10 can be acquired using a conventional PET imaging system (e.g., including coincidence detection circuitry and configured to perform image reconstruction).

Fig. 4 shows a hypothetical example of a generated count profile (i.e., trend) line. As schematically shown in fig. 4, the amount of amyloid tracer uptake (e.g. measured by a counting metric such as count rate or total count) can be compared over the time of consecutive test dates (e.g. the test may be performed every two years, e.g. in 2018, 2020, 2022, 2024 and 2026 in the hypothetical example of fig. 4). If the current tests indicate a statistically significant increase in intake (e.g., the test at 2026 in the hypothetical fig. 4 shows a relatively greater increase in outcome than the test at 2024 and years ago), the patient may be referred to for further testing, particularly if he is an at-risk population classified based on age, occupation, or family history. After a certain period of time, another test may be performed using the apparatus of fig. 1 to confirm the trend. At least two repeated scans (e.g., at certain intervals in time) can be considered clinically meaningful in order to facilitate (along with other factors (e.g., patient reported mental acuity) amyloidosis risk assessment.

It may be noted that the foregoing method assumes that there are one or more past tests, resulting in past count metric(s), and compares the count metric of the current test with the past count metric. The first time a given patient is tested, there will be no past results to compare with, and it is therefore difficult or impossible to derive clinically useful information from this first test alone. In some embodiments, it is contemplated to compare the first test result to typical values for the cohort of similar patients — if the count rate (or other count metric) of the current patient is much higher than those of these similar patients, the clinician may draw a conclusion, particularly in support of forgetfulness or other evidence of alzheimer's disease onset reported by the patient. However, as highlighted herein, it is expected that clinical conclusions drawn from trends in test results over the years are more likely to yield clinically meaningful information.

Examples of the invention

Apparatus 10 is configured to provide a low-cost amyloid screening tool that can screen for risk of amyloid accumulation on a large scale (e.g., population level). The patient is injected with a microdose of an amyloid-specific radiotracer and after the uptake time, the number of monomer hits collected is counted using, for example, a gamma camera to assess the increase in radioactivity in the head of the patient. The scan is repeated each year or according to the clinician's specifications and the obtained monomer count rate (and/or other count metrics) of the current test is compared to the count rates of past tests to determine the potential amyloid plaque accumulation trend. If the trend becomes positive (increased uptake in recent tests), the patient may be referred for further testing. Such proposed screening is affordable because inexpensive detectors can be used to measure the monomer rate, and because there is no need to create tomographic images, only micro-curie radioactivity can be used.

The device 10 is configured to improve patient throughput and reduce the radiation burden on the patient compared to other routine examinations, such as dental and chest X-ray examinations (0.1-0.005mSv), to make amyloid screening as feasible, and even much lower than in the case of low dose CT pulmonary screening (1.5 mSv).

It is contemplated that by utilizing such a device, patients belonging to a group having an elevated risk of developing alzheimer's disease, or even patients belonging to the general population, will be examined annually (or at other clinically determined rates) using the device 10. Patient examination begins with the injection of a small controlled amount of a radiotracer (e.g., florbetapir or flutemetamol) that binds to amyloid plaques. After a certain uptake time, the patient's head will be scanned on a nuclear medicine camera operating in monomer detection mode without collimation. Only the monomer rate (or total number of monomers) needs to be recorded.

The detector 14 may optionally surround the patient's head with additional radiation sensitive blocks, such as described with reference to fig. 2A-2C. Scanning in a sitting or standing position is also envisaged. It is also advantageous to shield the detector components from radioactivity entering from the rest of the body as much as possible, for example by using an illustrative radiation shielding collar 36 and/or by placing a lead shirt on the patient during the examination, etc.

The scans are repeated each year (or at other clinically determined rates). It is advantageous to scale the counts obtained for the corresponding implant dose (i.e. according to the radioactivity of the administered radiotracer) and to ensure that the uptake period and acquisition time for each test are the same and that the same type of tracer is used (or conversion factors are employed) to allow direct comparison of the scan series. Alternatively, if these factors cannot be made constant (e.g., if the radiotracer used in the previous test becomes unavailable), the count metric(s) may be appropriately scaled based on empirical information.

Normal aging may also lead to increased plaque deposition, possibly leading to false positives, and this may optionally be accounted for again by scaling the count metric(s). It is also beneficial to begin the test as early as possible to provide a baseline for the counting metric(s) during the healthy uptake period before amyloid deposits begin to accumulate in brain tissue. It would be particularly beneficial to start such tracking and track patients in certain professions more frequently (e.g., professional football players) because the increased deposition of beta amyloid plaques is also associated with CTE.

Machine learning techniques can optionally be employed to determine and empirically quantify the impact of factors and variables (e.g., age, gender, race, etc.) that may affect the quantification of the screening in order to reduce the risk of false positives. For example, any change in patient Body Mass Index (BMI) over the years may affect the relative uptake rate.

It may be beneficial to perform each screening test using the same camera or detector 14. If this is not possible, another camera may be used, but it is preferable to apply a sensitivity conversion factor between the two cameras to ensure reproducibility and consistency of the measurements.

Device 10 may use low cost radiation detection electronics with sufficient stopping power, and in one example, a Bismuth Germanate (BGO) detector may be used for this purpose. No coincidence mode is required unless PET imaging is desired as an option, and therefore, increased sensitivity is contemplated due to the single-body detection mode and close positioning of the object to the detector 14. In addition, as is the case with conventional PET or SPECT systems, in embodiments where no imaging is performed, there is no requirement such as "minimum detection count per image voxel". Since the attenuation in the brain remains almost constant throughout the patient's life, there is also no need for a CT acquisition or other source for the attenuation map. Rather, attenuation effects in the head H of the patient P are automatically considered by generating an amyloid metric based on a comparison of the current count metric(s) to past count metric(s) from past tests performed on the same patient P.

If even 100000 cell counts are detected during acquisition, the resulting signal noise (in terms of poisson processes) will only constitute less than 0.5% of the signal. This means that only a micro-curie dose level of amyloid tracer injection is required, the dose is reduced to below 1/1000 compared to conventional PET, the scan is comparable to a dental X-ray examination in terms of radiation burden.

The present disclosure has been described with reference to the preferred embodiments. Modifications and alterations will occur to others upon reading and understanding the preceding detailed description. It is intended that the invention be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.