NL2026116B1 - Method for obtaining quantifiable information from an imaging modality - Google Patents

Abstract

The present invention relates to a method for obtaining quantifiable information from an imaging modality (such as MRI), comprising the steps of: a) Providing a carrier with a number of biomarkers with (known concentration and/or) known imaging values (such as a number of known T2 or T2* values or fat concentrations); b) Imaging the carrier with an imaging machine and determine imaging values of the biomarkers of the carrier; 0) Comparing the determined imaging values of the biomarkers with the known imaging values of the biomarkers, in order to provide a report on the quality of the imaging device and/or advice on possible changes to enhance precision of diagnosis.

Description

Method for obtaining quantifiable information from an imaging modality The present invention relates to a method for obtaining quantifiable information from an imaging modality, in particular an imaging manufactured independent method for obtaining standardized and accurate quantifiable information from an imaging modality.

Tracking tissue biomarkers is useful to assess various diseases and monitor treatment response in human. For instance, either fat and iron status biomarkers may be related to different diseases status. For instance thalassemia or sickle cell diseases may be relate to iron excess or deficiency in the human body. Accumulation of iron in the heart can result in heart failure. In addition to iron, fat may for instance also accumulate in the liver as in Non-Alcoholic Fatty Liver diseases (NAFLD), estimated 20% of normal population and 80% of obese, 35% of NAFLD develop Non-alcoholic steatohepatitis (NASH), potentially resulting in cirrhosis. Accurate tracking of iron and fat in these organs may thus serve to predict or assess whether or not patients are, or could be, at risk for these serious underlying conditions. it has however been proven difficult to measure exact concentrations of certain biomarkers like iron concentrations. Serum ferritin can be used to assess iron, however its value may fluctuate in response to inflammation and abnormal liver function, another way of measuring iron or fat concentration in for instance the liver is to take a liver biopsy, and measure the liver iron or fat concentrations of that biopsy. However, biopsy suffers from sampling errors and it is an invasive and painful process with potential serious complications. Moreover, and this holds for other concentration measurements (e.g. ferritin level measurement) as well, measurements typically differ largely from one laboratory to the other, or even from one measurement to the other due for instance, the biopsy sampling error and to the lack of strict standardization between sites.

There is no existing commercial solution today to standardize or check the quality of quantitative mapping (e.g. T2 mapping). it is therefore a goal of the present invention to provide an improved and standardized method of determining biomarker presence non-invasively among different clinical institutions. This also allow the analysis of the (MRI) data to be done in-house.

The present invention thereto provides a method for obtaining quantifiable information from an imaging modality (such as MRI), comprising the steps of: a) Providing a carrier with a number of biomarkers with (known concentration and/or) known imaging values (such as a number of known T1, T2 or T2* values or fat concentrations); b) Imaging the carrier with an imaging machine and determine imaging values of the biomarkers of the carrier; c} Comparing the determined imaging values of the biomarkers with the known imaging values of the biomarkers.

The carrier for instance is a reference-carrier. The known imaging values are for instance known quantitative imaging values The determination of the imaging values of the biomarkers of the carrier is preferably performed via a post-processing algorithm or post-processing software, or via an automatic detection of the biomarkers of the carrier.

The method thus aims to standardize and provide quantifiable information from imaging modalities, such as MRI. MRI is known to provide high resolution images, with tuneable contrast between different tissues in human body for instance. Basically, a magnetic field is applied, and hydrogen particles align with the magnetic field. The way these particles react or respond when aligned in the magnetic field differs from tissue to tissue, creating the contrast in MR imaging. In this way relative behaviour or relative contrast can be obtained. However, it is difficult to quantity, in absolute terms, imaging values in MR imaging. Although this information is obtained with imaging (T1, T2 or T2* times for instance in MRI), these values could well differ between scans, for instance due to different sequence settings, of between scanners even though using the same sequence setting. The preferred imaging modality is an NMR modality, such as MRI. Although the present invention is very useful in MR imaging, it is imaginable that the invention may be applied to other forms or modalities of imaging as well.

In step a) of the invention, a carrier is provided with a number of biomarkers with (known concentration and/or) known imaging values (such as a number of known T1, T2 or T2* values or fat concentrations). Such carrier is often also referred to as a phantom. By providing a carrier with biomarkers with known imaging values, or set imaging values, an expected outcome of imaging the carrier can be provided.

When the imaging outcome is known, the quality of each individual scanner or scan can be determined as well. By providing a number, or a range, of biomarkers the quality can be determined either over a range of different materials and/or over a range of different area’s of the imaging spectrum. In step b), the carrier is imaged with an imaging machine and imaging values of the biomarkers are determined.

This determination may for instance occur by a dedicated autodetection algorithm or post-processing software or algorithms. In step c) the determined imaging values of the biomarkers are compared with the known imaging values of the biomarkers. Since the known imaging values should in theory match the measured imaging values, a quantification or determination of the quality of the imaging modality can be performed and a report could be produced on the quality of the machine vs. imaged biomarkers.

When there is no match between the values, or the match is not close enough, action may be taken to improve imaging or to transform the measured values to more closely resemble the actual values, this step can be performed by reporting on the quality of the imaging machine; proposing changing setting of the imaging machine; or determining a transformation to transform the determined imaging values to the known imaging values, to correct the determined imaging values.

When the measured and known imaging values are within a predetermined bandwidth, the method may provide a report indicating that the imaging is presently able to provide accurate imaging values. If not within the predetermined bandwidth, a report failing the present imaging may be provided. Alternatively, or additionally, the method may provide a report indicating suggested improvements, for instance changes to the imaging sequence, to improve imaging to more closely resemble the known imaging values in the end. Alternatively, or additionally, the method may provide a transformation, to transform measured imaging values to (closely resemble) the known imaging values and thus correct for any imaging errors or mistakes made by the imaging machine.

A further option the present invention provides is to control or check post- processing or visualization software typically used to asses the images or image information. As example, typically regions of interest are placed, to determine imaging values from specific locations, which regions of interest could be placed in wrong positions resulting in wrong values. The same may happen with post-

processing software used to process the imaging values before visualization for instance. This post-processing, if wrongly tuned, might cause the post-processed image values to be wrong as well. The present invention provides a control or check, which takes all these elements into account.

In a preferred embodiment of the present invention, in step b) an object to be imaged is imaged together with the carrier, wherein for instance the imaging values of the object are corrected based on the comparison of the determined imaging values of the biomarkers with the known imaging values of the biomarkers.

Typically it is not the carrier that one aims to image or measure the imaging values of. Instead, typically objects or patients are imaged, to image say organs or other soft tissues. It is possible that the imaged objects or patients themselves to alter or influence the magnetic field or other imaging parameters of the imaging machine, which might lead to inaccurate result. To be able to correct for these changes or alternations it is thus beneficial if the objects or patients are imaged together with the carrier, such that corrections that potentially have to be made to the imaging values can already include the alterations caused by the presence of the object in the imaging machine.

Itis further preferred if the object and the carrier are attached, or at least in close vicinity, during imaging. When for instance MR imaging is used to determine fat concentration in the liver, the carrier may be located close to the location of the liver (so on the abdomen of the patient). This way any changes caused locally to the imaging machine, or to the magnetic field, at the location of interest, in this case the liver, may be corrected to in the most accurate way. Preferably the carrier is strapped to the object, to keep the carrier close to the object, and more particularly close to the area of interest of the object, to be imaged.

The carrier provided in step a) may for instance be provided with at least three biomarkers with different known imaging values, wherein preferably the carrier comprises a set of at least two of each different biomarker. With three biomarkers it is possible to focus measurement, imaging or control around a particular biomarker or biomarker concentration, including two points (slightly) outside or around. it allows for providing an indication of control over a larger spectrum of substances.

When providing sets of biomarkers it is possible to further improve the quality of the measurement, as each known value is present at least twice, such that averaging of measurements can be applied.

Step b) of the present invention may comprise the steps of selecting or identifying a 5 region-of-interest (ROI) and determining imaging values in said region-of-interest, wherein preferably the region-of-interest is selected or identified automatically by an analyzing algorithm.

Preferably the region of interest is a symmetrical one.

The biomarkers are typically present in a predetermined location or volume within or on the carrier.

To present providing measurement values from outside the location or volume, a ROI may be determined, to focus on the location of which the known value is relatively certain.

The carrier to be used may be selected based on the parameter of interest of the object to be imaged.

For example, when one would like to determine fat concentration in the liver, or determine iron content in the liver, a different carrier may be appropriate.

In particular the type of biomarker in the carrier and/or the concentration of the biomarker(s) in the carrier may be tuned depending on the type of measurement or imaging that is to be performed.

The carrier may be arranged to measure fat or iron content or concentration, and the biomarkers for instance comprise fat or iron at different concentrations.

The carrier may for instance be arranged on the object relatively close or adjacent the location where fat or iron content is to be determined.

In step b) the carrier may be imaged with various different imaging parameters, for example repetition time or echo time.

The choice of these parameters can influence the accuracy of the result.

The ability to accurately determine the imaging values (which basically comply with the known imaging values) may be different for different imaging parameters.

Potentially a scanner or imaging device is able to accurately determine imaging values only within certain imaging parameters, and for instance requires modification or transformation at parameters outside these boundaries.

The present invention further relates to a carrier, in particular one to be used in a method according to any of the preceding claims, comprising a number of biomarkers with (known concentration and/or) known imaging values (such as a number of known, T1, T2 or T2* values, iron concentrations or fat concentrations). The carrier may for instance shaped according to the object or location to be imaged. In case liver concentrations of fat or iron are determined, the carrier may for instance be shaped like a liver. This simplifies choices to be made when for instance a large array of different carriers are available. When knowing which object or location is to be focused on with the imaging, an operator can simply select the carrier with corresponding shape.

The invention will be elucidated on the basis of non-limitative exemplary embodiments shown in the following figures. Herein: - Figure 1 schematically shows a MRI scanner with a carrier according to the present invention; - Figure 2 schematically shows a carrier according to the present invention, in an opened view; - Figure 3 schematically shows an MRI image of a carrier according to the present invention; and - Figure 4 schematically shows a number of different carriers according to the present invention. Figure 1 schematically shows an MRI-scanner (1), into which a carrier (2) according to the invention is to be placed. The carrier (2) is schematically shown to include four biomarkers (3), indicated as black dots in the figure. In figure 1, the carrier (2) is substantially liver-shaped. Figure 2 schematically shows a carrier (2) according to the present invention, in an opened view. The carrier (2) is shown in a view wherein the carrier (2) is basically split into two, wherein a base (4) and a lid (5) may be identified. The base (4) in figure 2 is provided with a number of biomarkers (3), in this case ten, shown as spheres. These spheres are for instance arranged into recesses (not shown) in the base (4) of the carrier (2), and the lid (5) may for instance also be provided with recesses (6) to house the spheres or keep the spheres in predetermined location in the carrier (2).

Figure 3 schematically shows an image, in this case an MR image, of a carrier (2) as shown in figure 2. The ten biomarkers are clearly identifiable in the image, and are numbered 3A-3J in figure 3, with 3A in the bottom left, 3C on the top left, 31 on the bottom right and 3J on the top right. In the image of figure 3, regions of interest (7) are indicated with areas (7) within biomarkers 3A, 3C, 3G and 31. The identification of such regions of interest may for instance be performed manually, but is typically performed by an automated image analysis algorithm or software program. In particular when the shape or form of the biomarker housing, in case of the carrier (2) imaged in figure 3 a spherical one, is known, locating regions of interest is relatively straight forward.

Using the regions of interest (7) of the image, imaging values can be determined in a known way. For instance, T2* values can be determined from these images, or at least from the regions of interest, which provides a T2* value for the biomarker (that contains the region of interest (7) of choice). A problem or drawback of this determination is that the determined T2* value of a given region of interest of the carrier (2) may well differ when imaged with different MRI scanners, while the biomarker for which the T2 value is determined is exactly the same.

The present invention provides a carrier (2) with biomarkers (3) of which the imaging values are known. So, of the biomarkers (3) the T2* value is for instance known. By determining the T2* value of the biomarkers with the MRI scanner used and the imaging software that is used with that MRI scanner, and comparing the T2* that is determined with the known T2* value, a comparison can be made between the expected outcome (the known T2* value) and the measured value {the determined T2* value with the MRI scanner and the imaging software). This allows the preparation of a report for instance that indicates to what extent the measured value match the expected value. Based on the assumption that the known values are the correct values, an indication on the quality of the measurement can be provided.

The indication of the quality, or the correctness of the measurement, may for instance differ depending on certain measurement parameters. For example in MR imaging, repetition and echo times may be such parameters. The indication of quality of measurement may provide the insight that for shorter echo times the MR scanner operates as expected and provides the expected outcome, but at longer echo times does not. Figure 4 schematically shows a number of carriers (2) according to the present invention, numbered from left to right as 2A, 2B, 2C, 2D, and 2E. On the left a spherical carrier (2A) is shown, which is a relatively generic form. In the sphere (2A) one or more biomarkers (3) may be present, for instance in smaller spheres (3). Next to that a belt shaped carrier (2B) is shown, which may be provided at or around the abdomen of a patient for instance. In the belt (2B) one or more biomarkers (3) may be present, for instance in smaller spheres (3). Such belt (2B) can be conveniently attached or arranged on a patient. Next a capsule (2C) is shown. In the capsule (2C) one or more biomarkers (3) may be present, for instance in smaller spheres (3). The capsule (2C) is relatively similar to the sphere (2A). Next a liver shaped carrier (2D) is shown, comprising biomarkers (3). The liver shaped carrier (2D) is similar to the one shown in figures 1 and 2. On the right a substantially heart-shaped carrier (2E) is shown. In the heart (2k) one or more biomarkers (3) may be present, for instance in smaller spheres (3). Similarly to the carrier (2) shown in figure 2, the carriers 2C, 2D and 2E are shown with a base (4) and a lid (5), together housing the biomarkers (3). it will be apparent that the invention is not limited to the working examples shown and described herein, but that numerous variants are possible within the scope of the attached claims that will be obvious to a person skilled in the art.

The above-described inventive concepts are illustrated by several illustrative embodiments. It is conceivable that individual inventive concepts may be applied without, in so doing, also applying other details of the described example. It is not necessary to elaborate on examples of all conceivable combinations of the above- described inventive concepts, as a person skilled in the art will understand numerous inventive concepts can be (re)combined in order to arrive at a specific application.

The verb “comprise” and conjugations thereof used in this patent publication are understood to mean not only “comprise”, but are also understood to mean the phrases “contain”, “substantially consist of”, “formed by” and conjugations thereof.

Claims (14)

Conclusions A method of obtaining quantifiable information from an imaging modality (such as MRI), comprising the steps of: a. Providing a carrier with a plurality of biomarkers of {known concentration and/or} known quantitative imaging values (such as a number of known T1 or T2 values or fat concentrations) b. Imaging the support with an imaging machine and determining imaging values of the biomarkers c. Compare the determined imaging values of the biomarkers with the known imaging values of the biomarkers. A method according to claim 1, wherein in step b) an object to be imaged is imaged together with the support, wherein for example: a. The imaging values of the object are corrected based on the comparison of the determined imaging values of the biomarkers with the known imaging values of the biomarkers The method of claim 2, wherein the object and carriers are connected, or at least in close proximity, during imaging. A method according to any one of the preceding claims, wherein the imaging modality is an NMR modality, such as MRL A method according to any one of the preceding claims, wherein the support provided in step a) is provided with at least three biomarkers with different known imaging values, preferably the support is provided with a set of at least two of each different biomarker. A method according to any preceding claim, further comprising the steps of either: a. Reporting the quality of the imaging machine; b. Suggest changing the settings of the imaging machine; or c. Determining a transformation to transform the determined imaging values to the known imaging values, to correct the determined imaging values. A method according to any one of the preceding claims, wherein step b) comprises the step of selecting or identifying a region-of-interest and determining imaging values in that region of interest, the region of interest being preferably automatically selected or identified by an analyzing algorithm. A method according to any one of the preceding claims, wherein the carrier used is selected based on the relevant parameter of the object being imaged. A method according to any one of the preceding claims, wherein the carrier is adapted to measure fat or iron content or concentration, and wherein the biomarkers comprise, for example, fat or iron at different concentrations. A method according to claim 9, wherein the carrier is applied to the object relatively close to or adjacent to the location where the fat or iron content is to be determined. A method according to any one of the preceding claims, wherein during step b) the carrier is imaged with different mapping parameters, such as, for example, repetition time or echo time. A carrier, in particular one for use in a method according to any one of the preceding claims, comprising a number of biomarkers with, preferably different, (known concentrations and/or) known quantitative imaging values (such as a number of known T1 or T2 values or fat concentrations). The support of claim 12, wherein the support is formed according to the object or location to be imaged. The carrier of claim 12 or 13, comprising at least two biomarkers of any number of biomarkers with known quantitative imaging values such that at least one set of biomarkers is present for each known value.