Characterization of lesions in the liver using dynamic contrast-enhanced magnetic resonance imaging

Abstract

The present invention relates to the technical field of characterizing liver lesions using dynamic contrast-enhanced magnetic resonance imaging.

Description

[Technical field]

[0001] The present invention deals with the technical field of characterization of lesions in the liver by dynamic contrast-enhanced magnetic resonance imaging. [Background technology]

[0002] The liver can be affected by multiple benign tumors, which may appear as cystic or solid focal lesions within the hepatic parenchyma. However, the liver is also vulnerable to malignant tumors, including extrahepatic types of cancer and metastases of primary types of cancer originating in the liver itself. Globally, the two most common types of malignant liver tumors are metastases, especially colorectal cancer metastases, and hepatocellular carcinoma (HCC). Nearly 20% of colorectal cancer patients have liver metastases at the time of diagnosis, and more than 50% of colorectal cancer patients will develop liver metastases during the course of their disease. Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is also the sixth most common cancer worldwide and the fourth most common cause of cancer-related deaths.

[0003] Accurate and reliable detection and characterization of focal liver lesions at early disease stages is of great clinical importance, especially for patients at risk of liver metastases or primary liver cancer, as they are of fundamental importance for appropriate treatment planning and determine the suitability of candidate treatment options.

[0004] Magnetic resonance imaging (MRI) is of particular importance for the radiological examination of liver lesions: it distinguishes itself by its excellent soft-tissue contrast and high spatial resolution, without exposing the patient to ionizing radiation or iodized contrast agents.

[0005] The most commonly used contrast agents in MRI are gadolinium-based paramagnetic contrast agents. These agents are administered by intravenous (iv) bolus injection. Their contrast effect is mediated by the central gadolinium ion (Gd-III) in a chelate complex. When T1-weighted (w) scan sequences are used in MRI, the spin-lattice relaxation time (T1) of excited nuclei is shortened by the gadolinium ion, thus increasing the signal intensity and therefore the image contrast of the examined tissue.

[0006] Based on their pattern of spread within tissue, gadolinium-based contrast agents can be broadly divided into extracellular and intracellular contrast agents.

[0007] Extracellular contrast agents refer to low molecular weight, water-soluble compounds that spread into blood vessels and interstitial spaces after intravenous administration. After a certain relatively short period of circulation in the blood circulation system, they are excreted via the kidneys. Examples of extracellular MRI contrast agents include gadolinium chelates gadobutrol (Gadovist®), gadoteridol (Prohance®), gadoteric acid (Dotarem®), gadopentetic acid (Magnevist®) and gadodiamide (Omnican®).

[0008] Intracellular contrast agents are taken up to some extent by the cells of tissues and then excreted. For example, intracellular MRI contrast agents of the gadoxetic acid family are distinguished by being taken up proportionately and specifically by liver cells, i.e., hepatocytes, accumulating in functional tissue (parenchyma), enhancing contrast in healthy liver tissue, and then being excreted in stool through the gallbladder. Examples of such contrast agents of the gadoxetic acid family are described in US 6,039,931A, and they are commercially available, for example, under the trade names Primovist® and Eovist®. Another MRI contrast agent with lower hepatocyte uptake is gadobenate dimeglumine (Multihance®).

[0009] Gadoxetate disodium (GD, Primovist®) belongs to the group of intracellular contrast agents. It has been approved for use in MRI of the liver to detect and characterize lesions in patients with known or suspected focal liver disease. GD, which has a lipophilic ethoxybenzyl unit, exhibits a two-stage diffusion, first diffusing into the intravascular and interstitial spaces after bolus injection, followed by selective uptake by hepatocytes. GD is excreted unchanged from the body in approximately equal amounts via the renal and hepatobiliary pathways (50:50 dual excretion mechanism). Due to its selective accumulation in healthy liver tissue, GD is also called hepatobiliary contrast agent.

[0010] GD is approved at a dose of 0.1 mL / kg body weight (BW) (0.025 mmol / kg BWGd). The recommended administration of GD involves an undiluted intravenous bolus injection at a flow rate of approximately 2 mL / s, followed by flushing of the venous cannula with saline. The standard protocol for liver imaging using GD consists of multiple planning and precontrast sequences. After an intravenous bolus injection of contrast agent, dynamic images are usually acquired in the arterial phase (approximately 30 s after injection), the portal venous phase (approximately 60 s after injection), and the transitional phase (approximately 2–5 min after injection). Typically, a certain increase in liver signal intensity is seen already in the transitional phase due to the initial uptake of the agent into hepatocytes. Additional T2-weighted and diffusion-weighted (DWI) images can be obtained after the dynamic phase and before the late hepatobiliary phase.

[0011] Contrast-enhanced dynamic images from arterial, portal and transitional phases provide important information about the patterns of lesion enhancement (angiogenesis) that change over time and contribute to the characterization of specific liver lesions. Hepatocellular carcinoma, with typical arterial phase hyperenhancement (APHE) and contrast washout in the venous phase, can be diagnosed solely on the basis of the distinctive angiogenesis pattern observed during dynamic phase imaging, and patients are consequently spared from invasive and possibly high-risk liver biopsies.

[0012] Other lesions can also be characterized by dynamic contrast-enhanced MRI.

[0013] The advantage of hepatobiliary contrast agents over extracellular agents in diagnosing liver lesions is their higher sensitivity and therefore better detection of especially small carinomas (see, e.g., RF Hanna et al.: Comparative 13-year meta-analysis of the sensitivity and positive predictive value of ultrasound, CT, and MRI for detecting hepatocellular carcinoma, Abdom Radiol 2016, 41, 71-90; YJ Lee et al.: Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis, Radiology 2015, 275, 97-109; DK Owens et al.: High-value, cost-conscious health care: concepts for clinicians to evaluate the benefits, harms, and costs of medical interventions, Ann Intern Med 2011, 154, 174-180). [Prior art documents] [Patent documents]

[0014] [Patent Document 1] US6,039,931A [Non-patent literature]

[0015] [Non-Patent Document 1] RF Hanna et al.: Comparative 13-year meta-analysis of the sensitivity and positive predictive value of ultrasound, CT, and MRI for detecting hepatocellular carcinoma, Abdom Radiol 2016, 41, 71-90. [Non-Patent Document 2] YJ Lee et al.: Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis, Radiology 2015, 275, 97-109. [Non-Patent Document 3] DK Owens et al.: High-value, cost-conscious health care: concepts for adherents to evaluate the benefits, harms, and costs of medical interventions, Ann Intern Med 2011, 154, 174-180. Summary of the Invention

[0016] The problem is that the dynamic increase and / or decrease in contrast in liver lesions is typically assessed by visual inspection by the radiologist (subjective assessment of the relative change in contrast between liver tissue and liver lesions), which may result in erroneous interpretation.

[0017] For macroscopic evaluation, differences arise whether extracellular or intracellular contrast agents are used: for example, when using hepatobiliary contrast agents, an increase in signal in healthy liver tissue may be misinterpreted as washout of contrast agent from adjacent liver lesions (relative increase in contrast between liver tissue and liver lesions).

[0018] Therefore, the European Association for the Study of the Liver, in its guidelines (EASL Clinical Practice Guidelines: Management of hepatocellular carconima), specified different features for identifying hepatocellular carcinoma depending on the contrast agent used (see Journal of Hepatology, 2018, Vol. 69, pages 182-236).

[0019] · When using extracellular contrast agents: combination of hypervascularization in the late arterial phase and washout in the portal venous and / or delayed phases.

[0020] When using hepatobiliary contrast agents: combination of hypervascularity in the late arterial phase and washout in the portal venous phase.

[0021] Thus, the use of extracellular contrast agents to detect hepatocellular carcinoma requires the use of both the portal venous phase and a subsequent delayed phase, whereas the use of hepatobiliary contrast agents requires the use of only the portal venous phase to detect washout and only the portal venous phase to detect washout and no phases following the portal venous phase.

[0022] As already explained, the reason is that hepatic cholangiographic contrast agents (as opposed to extracellular contrast agents) are taken up by liver cells, where they accumulate and are then excreted in the feces via the gallbladder. Thus, when using hepatic cholangiographic agents, there is an initial relatively rapid vascular contrast enhancement in the arterial phase followed by a more slowly and continuously increasing contrast enhancement in healthy liver tissue. When a radiologist visually compares the contrast enhancement of a lesion with that of healthy liver tissue, the continuously increasing contrast enhancement in healthy liver tissue may be misinterpreted as a washout of the contrast agent from the lesion.

[0023] Therefore, the European Association for the Study of the Liver explicitly recommends that when hepatobiliary contrast agents are used, analysis of MRI images for confirmation of HCC should be limited to the arteries and portal vein (maximum 60 seconds after intravenous administration of the contrast agent).

[0024] The problem, however, is that some lesions can only be clearly characterized by their dynamic behavior in later phases.

[0025] In some hepatocellular carcinomas, washout is, for example, only evident after the portal venous phase (see, for example, CJ Zech et al.: Consensus report from the 8th International Forum for Liver Magnetic Resonance Imaging, European Radiology 2020, 30, 370-382).

[0026] If the period after the portal venous phase is not taken into account for the detection of washout, as recommended by the European Association for the Study of the Liver, for example, hepatocellular carcinoma, where washout becomes detectable, will remain undetected. As a result, more biopsies may need to be performed to confirm whether the lesion is benign or malignant (see in particular Figure 2 in Journal of Hepatology, 2018, Vol. 69, page 194). Biopsies are not just additional effort for medical professionals. They also represent a risk for patients.

[0027] It would be desirable to reduce the number of such biopsies.When using hepatobiliary contrast agents, it would be desirable to be able to reliably identify and characterize liver lesions without running the risk of increased signal in healthy liver tissue being misinterpreted as washout of the contrast agent from liver lesions.

[0028] This is accomplished by the present invention.

[0029] The present invention in a first aspect provides a computer-implemented method for identifying washout of a thickening agent from a region of a patient's liver during a dynamic contrast-enhanced magnetic resonance imaging examination, comprising the steps of: - receiving a plurality of images, The plurality of images are ■ the liver of the patient or a part of the liver of the patient, and ■ Reference tissue of the patient represents During the portal venous phase of the dynamic contrast-enhanced magnetic resonance imaging study, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents At least one image of the plurality of images during a transition phase of the dynamic contrast-enhanced magnetic resonance imaging study ■ The liver or a part of the liver, and ■ Reference Organization The stage representing - one or more regions of the liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, the reference tissue not containing hepatocytes, and / or the absolute value of the gradient of the decreasing contrast enhancement in the portal phase and / or the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue; identifying one or more regions in the liver; - outputting an image of the liver or part of the liver, in which the identified region or a number of the identified regions are highlighted in the image. The present invention provides a method comprising:

[0030] The present invention further comprises: ● Receiving unit, ●Control and calculation unit and Output unit A computer system comprising: - the control and computing unit is configured to cause the receiving unit to receive a plurality of images; The plurality of images are ■ the liver of a patient or a part of the liver of said patient, and ■ Reference tissue of the patient represents During the portal venous phase of a dynamic contrast-enhanced magnetic resonance imaging study, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents At least one image of the plurality of images during a transition phase of a dynamic contrast-enhanced magnetic resonance imaging study, ■ The liver or a part of the liver, and ■ Reference Organization represents - the control and computing unit is arranged to detect one or more regions of the liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, the reference tissue not containing hepatocytes, and / or the absolute value of the gradient of the decreasing contrast enhancement in the portal phase and / or the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue; configured to identify one or more regions in the liver; the control and computing unit is configured to cause the output unit to output an image of the liver or a part of the liver, in which the identified region is highlighted or a plurality of the identified regions are highlighted in the image; A computer system is provided.

[0031] The present invention further provides a computer program product comprising a computer program loadable into the memory of a computer, the program causing said computer to perform the following steps: - receiving a plurality of images, The plurality of images are ■ the liver of a patient or a part of the liver of said patient, and ■ Reference tissue of the patient represents During the portal venous phase of a dynamic contrast-enhanced magnetic resonance imaging study, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents At least one image of the plurality of images during a transition phase of a dynamic contrast-enhanced magnetic resonance imaging study, ■ The liver or a part of the liver, and ■ Reference Organization Stage representing - one or more regions of the liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, the reference tissue not containing hepatocytes, and / or the absolute value of the gradient of the decreasing contrast enhancement in the portal phase and / or the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue; identifying one or more regions in the liver - outputting an image of the liver or part of the liver, in which the identified region or a number of the identified regions are highlighted in the image. The present invention provides a computer program product for causing the

[0032] The present invention further relates to the use of a contrast agent in a dynamic magnetic resonance imaging method comprising the steps of: - administering said contrast agent; generating a plurality of images, The plurality of images are ■ the liver of a patient or a part of the liver of said patient, and ■ Reference tissue of the patient represents During the portal vein phase of the examination method, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents At least one image of the plurality of images during a transition phase of the inspection method ■ The liver or a part of the liver, and ■ Reference Organization Stage representing - one or more regions of the liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, the reference tissue not containing hepatocytes, and / or the absolute value of the gradient of the decreasing contrast enhancement in the portal phase and / or the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue; identifying one or more regions in the liver - outputting an image of the liver or part of the liver, in which the identified region or a number of the identified regions are highlighted in the image. The present invention provides uses including:

[0033] The present invention further comprises a contrast agent for use in a method for dynamic contrast enhanced magnetic resonance imaging, comprising the steps of: - administering said contrast agent; generating a plurality of images, The plurality of images are ■ the liver of a patient or a part of the liver of said patient, and ■ Reference tissue of the patient represents During the portal vein phase of the examination method, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents At least one image of the plurality of images during a transition phase of the inspection method ■ The liver or a part of the liver, and ■ Reference Organization Stage representing - one or more regions of the liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, the reference tissue not containing hepatocytes, and / or the absolute value of the gradient of the decreasing contrast enhancement in the portal phase and / or the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue; identifying one or more regions in the liver - outputting an image of the liver or part of the liver, in which the identified region or a number of the identified regions are highlighted in the image. The present invention provides a contrast agent comprising:

[0034] The present invention further provides a kit comprising an imaging agent according to the present invention and a computer program product. [Brief description of the drawings]

[0035] [Figure 1] FIG. 1 shows a schematic diagram of the temporal profile (t=time) of signal intensity I induced by a hepatic biliary contrast agent in the hepatic artery (A), hepatic vein (V), and healthy liver cells (L) during dynamic contrast MRI examination. [Diagram 2] FIG. 13 is a graphical illustration of the terms high and low enhancement. [Diagram 3] FIG. 1 shows, by way of example and schematic, the liver of a patient. [Figure 4] FIG. 3(a), 3(b), 3(c), 3(d), and 3(e) are redrawn on a smaller scale. [Diagram 5] 1 illustrates, diagrammatically and by way of example, one embodiment of a computer system according to the present invention; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] Further subject matters and preferred embodiments of the invention are found in the dependent claims, the description and the drawings.

[0037] In the following, the invention will be described in more detail without distinguishing between the subject matter of the invention (method, computer system, computer program product, use, imaging agent for use, kit). Instead, the following description is intended to apply equally to all subject matter of the invention, regardless of the context (method, computer system, computer program product, use, imaging agent for use, kit) in which it occurs.

[0038] The present invention provides a means for automatically identifying washout of contrast agent from regions of a patient's liver during a dynamic contrast-enhanced magnetic resonance imaging study, in other words, the present invention allows for the automatic identification of a region or regions within the liver that are characterized by washout of contrast agent.

[0039] Washout refers to the finding that contrast enhancement in regions of the liver during the portal and / or transition phases of dynamic contrast-enhanced magnetic resonance imaging decreases more rapidly than the surrounding (healthy) liver tissue.

[0040] Such washout is often used as a characteristic feature to identify liver lesions (see, for example, YI Liu et al.: Quantitatively Defining Washout in Hepatocellular Carcinoma, American Journal of Roentgenology 2013 200:1, 84-89; Journal of Hepatology, 2018, Vol. 69, pages 182-236).

[0041] Magnetic resonance imaging, or MRI for short, is an imaging technique used especially in medical diagnostics to depict the structure and function of tissues and organs within the human or animal body.

[0042] In MRI, the magnetic moments of protons in the examined object are aligned in a basic magnetic field, resulting in macroscopic magnetization along the longitudinal direction, which is then deflected from its rest position by irradiation with a radio frequency pulse (excitation).The return from the excited state to the rest position (relaxation) or magnetization dynamics is then detected as a relaxation signal by one or more radio frequency receiver coils.

[0043] For spatial encoding, a fast switching magnetic gradient field is superimposed on the basic magnetic field. The captured relaxation signals, i.e. the detected and spatially resolved MRI data, initially exist as raw data in spatial frequency space and can be transformed into real space (image space) by a subsequent Fourier transformation.

[0044] In the case of native MRI, tissue contrast is created by different relaxation times (T1 and T2) and proton densities.

[0045] The T1 relaxation describes the transition of the longitudinal magnetization to the equilibrium state, T1 is the time it takes to reach 63.21% of the equilibrium magnetization before resonant excitation, which is also called the longitudinal relaxation time or spin-lattice relaxation time.

[0046] T2 relaxation similarly describes the transition of the transverse magnetization to an equilibrium state.

[0047] The first step in a dynamic contrast-enhanced magnetic resonance imaging study is to administer an MRI contrast agent to the subject.

[0048] A "test subject" is usually a living organism, preferably a mammal, and very particularly preferably a human. The term "patient" is also used herein.

[0049] The imaging agent can be an extracellular or an intracellular imaging agent. Preferred is a hepatobiliary imaging agent.

[0050] A hepatobiliary contrast agent is understood to mean a contrast agent which is specifically taken up by healthy liver cells, ie hepatocytes.

[0051] Examples of hepatobiliary contrast agents are gadoxetic acid-based contrast agents, which are described, for example, in US Pat. No. 6,039,931A. They are commercially available, for example, under the trade names Primovist® or Eovist®.

[0052] The contrast effect of Primovist® / Eovist® is mediated by the stable gadolinium complex Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid). DTPA forms a complex with the paramagnetic gadolinium ion that has very high thermodynamic stability. The ethoxybenzyl (EOB) radical is the mediator of hepatobiliary uptake of the contrast agent.

[0053] In a particularly preferred embodiment, the contrast agent used is a substance or mixture of substances which has gadoxetic acid or a gadoxetate salt as contrast active substance. Very particular preference is given to the disodium salt of gadoxetic acid (disodium Gd-EOB-DTPA).

[0054] After intravenous administration of a hepatobiliary contrast agent in the form of a bolus into a vein in the arm, the agent first reaches the liver via the arteries, which are visualized with contrast enhancement in the corresponding MRI images. The phase in which the hepatic arteries are visualized with contrast enhancement in the MRI images is called the "arterial phase."

[0055] The contrast agent then reaches the liver via the hepatic veins. The contrast in the hepatic veins reaches a maximum value, whereas the contrast in the hepatic artery is already reduced. The phase in which the hepatic veins are visualized with enhanced contrast in the MRI image is called the "portal venous phase". This phase can already start during the arterial phase and can overlap with it.

[0056] The portal venous phase is followed by a "transitional phase" in which contrast in the hepatic artery is further reduced, as is contrast in the hepatic vein. If a hepatobiliary contrast agent is used, contrast in healthy liver tissue gradually increases during the transitional phase.

[0057] The arterial, portal, and transitional phases are collectively referred to as the "dynamic phases."

[0058] At 10-20 minutes after injection, the hepatobiliary contrast agent produces a clear signal enhancement in healthy liver parenchyma. This phase is called the "hepatobiliary phase." Because the contrast agent is only slowly excreted from liver cells, the hepatobiliary phase can last for 2 hours or more.

[0059] The described phases are described in more detail, for example, in the following publications: J. Magn. Reson. Imaging, 2012, 35(3): 492-511, doi:10.1002 / jmri.22833; Clujul Medical, 2015, Vol. 88 no. 4: 438-448, DOI: 10.15386 / cjmed-414; Journal of Hepatology, 2019, Vol. 71: 534-542, http: / / dx.doi.org / 10.1016 / j.jhep.2019.05.005).

[0060] FIG. 1 shows a schematic representation of the temporal profile (t=time) of the signal intensity I induced by a hepatobiliary contrast agent in the hepatic artery (A), hepatic vein (V) and healthy liver cells (L) in a dynamic contrast-enhanced MRI study. The signal intensity I is positively correlated with the contrast agent concentration in a given region. After an intravenous bolus injection, the contrast agent concentration first increases in the hepatic artery (A) (dashed curve). The concentration exceeds a maximum value and then decreases. The concentration in the hepatic vein (V) increases more slowly and reaches a maximum value later than in the hepatic artery (dashed curve). The contrast agent concentration in the liver cells (L) increases slowly (solid curve) and reaches a maximum value much later (the maximum value is not depicted in FIG. 1). Several characteristic time points can be defined: at time point TP0, the contrast agent is administered intravenously as a bolus. Since the administration of the contrast agent itself takes a certain period of time, the time TP0 preferably defines the time when the administration is completed, i.e. when the contrast agent is completely introduced into the examination subject. At the time TP1, the signal intensity of the contrast agent in the hepatic artery (A) reaches a maximum value. At the time TP2, the signal intensity curve for the hepatic artery (A) and the signal intensity curve for the hepatic vein (V) intersect. At the time TP3, the signal intensity of the contrast agent in the hepatic vein (V) passes through a maximum value. At the time TP4, the signal intensity curve for the hepatic artery (A) intersects with the signal intensity curve for healthy liver cells (L). At the time T5, the concentration in the hepatic artery (A) and the hepatic vein (V) has decreased to a level that no longer causes measurable contrast enhancement.

[0061] During a contrast magnetic resonance imaging examination, multiple magnetic resonance images of the patient's liver or a portion of the patient's liver are generated. Such magnetic resonance images are referred to herein as images. They represent the patient's liver or a portion of the liver before and / or after administration of a contrast agent. The images may be images in real space or images in frequency space.

[0062] In magnetic resonance imaging, due to the measurement method, raw data is usually generated as so-called k-space data. Said k-space data is a representation (image) of the examination area in frequency space. Such k-space data can be transformed into an image in real space by an inverse Fourier transformation. Conversely, an image in real space can be transformed into an image in frequency space (also called spatial-frequency space, or Fourier space, or frequency domain, or Fourier image) by a Fourier transformation.

[0063] The operations described herein are preferably performed on images in real space.

[0064] An image of an area of ​​interest (such as the liver) in real space is the image that is more familiar to humans. It is easier for humans to grasp (understand). For such real space images, the term "image" is also commonly used.

[0065] An image in the context of the present invention can be a two-dimensional, three-dimensional or higher dimensional image. Usually there is a two-dimensional tomogram (slice image) or there are multiple two-dimensional tomograms (slice images).

[0066] Images are usually present in digital form. The term "digital" means that the image can be processed by a machine, typically a computer system. "Processing" is understood to mean known Electronic Data Processing (EDP) methods. One example of a common format for digital images is the DICOM format (Digital Imaging and Communications in Medicine), which is an open standard for the storage and exchange of information in medical image data management.

[0067] For ease of explanation, in some places in this specification the present invention is described based on the existence of two-dimensional images, but it is not intended to limit the present invention to two-dimensional images. It is clear to those skilled in the art how the described contents can be applied to multiple two-dimensional images, three-dimensional images, or images in frequency space, respectively (see, for example, M. Reisler, W. Semmler: Magnetresonanztomographie [Magnetic resonance imaging], Springer Verlag, 3rd edition, 2002, ISBN: 978-3-642-63076-7).

[0068] Digital images can exist in various formats. For example, digital images can be coded as raster graphics. Raster graphics consist of a grid arrangement of so-called picture elements (pixels) or volume elements (voxels), which in each case are assigned a color or gray value. The main characteristics of 2D raster graphics are the image size (width and height measured in pixels, also informally called image resolution) and the color depth. Colors are usually assigned to picture elements in a digital image file. The color coding used for a picture element is specified, among other things, in terms of a color space and a color depth. The simplest case is a binary image, where black and white values ​​are stored in the picture element. In the case of an image whose colors are specified in terms of the so-called RGB color space (RGB stands for the primary colors red, green and blue), each picture element consists of three subpixels: one for the red color, one for the green color and one for the blue color. The color of a picture element is generated by superposition (additive mixing) of the color values ​​of the subpixels. The color values ​​of the subpixels can be divided, for example, into 256 color tones, called tone values, usually ranging from 0 to 255. Tone "0" in each color channel is the darkest. If all three channels have a tone value of 0, the corresponding picture element appears black, and if all three channels have a tone value of 255, the corresponding picture element appears white. When implementing the present invention, the digital image is subjected to a given operation. In this context, the operation mainly affects the tone values ​​of the picture elements or individual picture elements (pixels or voxels). There are many different possible digital image formats and color codings. For simplicity, it is assumed herein that the image is a grayscale raster graphic with a certain number of picture elements, each of which is assigned a tone value that indicates the gray value of the image. However, this assumption should not be understood as limiting in any way.It will be clear to one skilled in the art of image processing how the teachings of this description can be applied to image files existing in other image formats and / or to image files in which the color values ​​are coded differently.

[0069] During a contrast-enhanced magnetic resonance imaging examination, multiple images of a patient's liver or portions of the liver are generated.

[0070] The plurality of images includes at least one image representing the liver or a portion of the liver during a portal venous phase and at least one image representing the liver or a portion of the liver during a transition phase.

[0071] It is preferred to further generate at least one image of the liver or part of the liver before administration of a hepatic biliary contrast agent (pre-TP0) (native image) and / or at least one image of the liver or part of the liver in the arterial phase.

[0072] In a preferred embodiment, at least the following images are generated:

[0073] at least one first image, which represents the liver or a part of the liver during the time period TP1 to TP3;

[0074] - at least one second image, which represents the liver or a part of the liver during the period from TP3 to TP5.

[0075] Here, time point TP0 is shown in FIG. 1 and explained in the description associated with FIG.

[0076] In a further preferred embodiment, at least the following images are generated:

[0077] - at least one first image, the at least one first image representing the liver or a part of the liver of the patient in the time period from TP0 to TP3.

[0078] - at least a second image, said at least one second image representing the liver or a part of the liver of the patient in the time period from TP2 to TP5.

[0079] - at least a third image, said at least one third image being representative of the liver or a portion of the liver of the patient during the period from TP4 to 5 minutes after TP0.

[0080] Here, time TP0 is shown in FIG. 1 and explained in the description associated with FIG.

[0081] In a particularly preferred embodiment, at least the following images are generated:

[0082] - at least one first image, the at least one first image representing the liver or a part of the liver of the patient during a time range from TP0 to TP1.

[0083] - at least one second image, which represents the liver or a part of the liver of the patient during the time range from TP1 to TP2.

[0084] - at least one third image, the at least one third image representing the liver or a portion of the liver of the patient during the time period from TP2 to TP3.

[0085] at least one fourth image, wherein the at least one fourth image represents the liver or a portion of the liver of the patient during the time period from TP3 to TP4.

[0086] at least one fifth image, wherein the at least one fifth image represents the liver or a portion of the liver of the patient during the period from TP0 to TP4 seconds after TP5 seconds; and / or at least one sixth image, wherein the at least one sixth image represents the liver or a portion of the liver of the patient during the time range from TP5 to 5 minutes after TP0.

[0087] Here, time TP0 is shown in FIG. 1 and explained in the description associated with FIG.

[0088] The generated image is sent to a computer system according to the invention, which is configured to automatically analyze the image.

[0089] The term "automatically" means without the need for human assistance.

[0090] This analysis identifies the region or regions of the patient's liver in which there is washout of contrast agent during the portal and / or transition phase.

[0091] Washout can be confirmed in a variety of ways.

[0092] In one embodiment, the area identified is one in the liver where the contrast agent provides lower contrast enhancement in portal phase and / or transition phase than in the reference tissue. Lower contrast enhancement in portal phase and / or transition phase is also referred to as hypoenhancement. Hypoenhancement is a lower signal intensity compared to the reference tissue. In this embodiment, the reference tissue used is preferably a tissue that does not contain liver cells. A suitable reference tissue is, for example, muscle tissue. Extracellular contrast agents or hepatic cholangiographic agents can be used for contrast enhancement. It is preferred to use hepatic cholangiographic agents.

[0093] In a further embodiment, the region in the liver where the contrast enhancement in the portal venous phase and / or transition phase falls off more rapidly than in the reference tissue is identified. In this embodiment, the reference tissue used is preferably a tissue that does not contain liver cells. A suitable reference tissue is, for example, muscle tissue. The time gradient of the signal intensity is identified, and the region where the time gradient of the signal intensity is negative (signal intensity decreases over time) and the absolute value of the time gradient is greater than the absolute value of the negative time gradient of the signal intensity in the reference tissue is identified. The contrast agent used can be an extracellular contrast agent or a hepatic cholangiographic agent. It is preferable to use a hepatic cholangiographic agent.

[0094] In a further embodiment, the region in the liver is identified where the absolute value of the gradient of the contrast enhancement decrease in the portal venous phase and / or transition phase is greater than the gradient of the contrast enhancement increase in healthy liver tissue. In this embodiment, the reference tissue used is healthy liver tissue. The contrast agent used is preferably a hepatobiliary contrast agent, which is selectively taken up by healthy liver tissue and gradually increases the signal intensity in the portal venous phase and / or transition phase. Thus, what is present in healthy liver tissue is a positive time gradient of the signal intensity in the portal venous phase and / or transition phase. The region that is identified is where the signal intensity decreases in the portal venous phase and / or transition phase, and the absolute value of the decrease (absolute rate of decrease) is greater than the absolute value of the signal intensity increase in healthy liver tissue.

[0095] It is conceivable to combine the described embodiments with each other. It is conceivable that an identification is made of regions in the liver in which the contrast agent leads to a lower contrast enhancement in the portal venous phase and / or transition phase than in a first reference tissue, and in which the contrast enhancement in the portal venous phase and / or transition phase falls off more rapidly than in a second reference region and / or the absolute value of the gradient of the contrast enhancement fall off in the portal venous phase and / or transition phase is greater than the gradient of the contrast enhancement rise in healthy liver tissue. The first and / or second reference tissue can be, for example, muscle tissue or healthy liver tissue.

[0096] In a particularly preferred embodiment, the present invention is used to identify hepatocellular carcinoma, in which an area or areas that show both high enhancement in the arterial phase and washout in the portal venous and / or transitional phase are identified.

[0097] Hyperenhancement is present when a region shows higher signal intensity compared to a reference tissue (e.g., M. Kim et al.: Identification of Arterial Hyperenhancement in CT and MRI in Patients with Hepatocellular Carcinoma: Value of Unenhanced Images, Korean Journal of Radiology 2019, 20(2), 236-245). The reference tissue used to detect hyperenhancement in the arterial phase is preferably healthy liver tissue. The contrast agent used may be an extracellular contrast agent or a hepatic cholangiographic contrast agent. It is preferred to use a hepatic cholangiographic contrast agent. Preferably, an embodiment for identifying hepatocellular carcinoma comprises the following steps:

[0098] - receiving a plurality of images of a liver or a portion of a liver of a patient, the image is the result of a contrast-enhanced magnetic resonance imaging study of the liver or a part of the liver, at least one first image represents the liver or a part of the liver during the arterial phase, at least one second image represents the liver or a part of the liver during the portal venous phase, and at least one third image represents the liver or a part of the liver during the transition phase, - analyzing at least one of the first, second and third images to identify a region or regions of the liver in which the contrast agent provides a higher contrast enhancement than a first reference tissue in the arterial phase and in which the contrast agent provides a lower contrast enhancement than a second reference tissue in the portal venous phase and / or transition phase; - outputting an image of the liver or part of the liver, in which the identified region or the identified regions are highlighted.

[0099] As already explained, the first reference tissue is preferably healthy liver tissue and the second reference tissue is preferably muscle tissue.

[0100] In a further preferred embodiment, the method for identifying hepatocellular carcinoma comprises: - receiving a plurality of images of a liver or a portion of a liver of a patient, the image is the result of a contrast-enhanced magnetic resonance imaging study of the liver or a part of the liver, at least one first image represents the liver or a part of the liver during the arterial phase, at least one second image represents the liver or a part of the liver during the portal venous phase, and at least one third image represents the liver or a part of the liver during the transition phase, - analyzing the received image, said image having the following characteristics: the contrast agent produces a greater signal increase in the arterial phase than in a first reference tissue, and the contrast enhancement in the portal venous phase and / or the transition phase decreases more rapidly than in a second reference tissue, and the second reference tissue does not contain hepatocytes; and / or The absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue. identifying one or more regions of the liver characterized by Includes.

[0101] The first reference tissue is preferably healthy liver tissue and the second reference tissue is preferably muscle tissue.

[0102] In Fig. 2(a) and Fig. 2(b), the terms hyperenhancement and hypoenhancement are explained using graphs. In Fig. 2(a) and Fig. 2(b), the signal intensity I of two different regions of a patient's liver measured during an MRI examination is plotted as a function of time t. The solid curves with reference HCC respectively show the dynamic profile of the intensity I of hepatocellular carcinoma; the dashed curves with reference L show the dynamic profile of the intensity I of healthy liver tissue. The references AP, PVP and TP show the arterial phase (AP), the portal venous phase (PVP) and the transitional phase (TP). The time TP0 shows the time of completion of the administration of the hepatic biliary contrast agent in each case. After administration, the intensity of the MRI signal due to hepatocellular carcinoma increases sharply. The intensity of the MRI signal due to healthy liver tissue increases as well, although less sharply. In the arterial phase AP, there is hyperenhancement in the case of HCC tissue compared to healthy liver tissue.

[0103] After passing the maximum, the intensity of the MRI signal due to the hepatocellular carcinoma tissue decreases, more rapidly for the curve in Fig. 2(a) than for the curve in Fig. 2(b). The intensity of the MRI signal due to the healthy liver tissue increases further even after the end of the arterial phase AP, but more slowly than the arterial phase, indicating the uptake of the contrast agent in the hepatocytes.

[0104] In Figure 2(a), the solid curve (HCC) falls below the dotted curve (L) in the portal venous phase PVP, and the signal enhancement in HCC is lower than that in healthy liver tissue. In the portal venous phase, the enhancement is lower in HCC tissue compared to healthy liver tissue.

[0105] In the case of hepatocellular carcinoma in Figure 2(b), hypoenhancement does not occur until later. It is only after the end of the portal venous phase that the solid line in Figure 2(b) falls below the dashed line in Figure 2(b). Hypoenhancement does not occur until later.

[0106] According to the present invention, the presence of hepatocellular carcinoma is indicated when there is high enhancement in the lesion compared to a first reference tissue in the arterial phase and when there is low enhancement in the lesion compared to a second reference tissue in the portal venous phase or transitional phase, or when the contrast enhancement in the portal venous phase and / or transitional phase decreases more rapidly than in a second reference tissue, which does not contain hepatocytes, and / or when the absolute value of the slope of the decrease in decreasing contrast enhancement in the portal venous phase and / or transitional phase is greater than the slope of the increasing contrast enhancement in healthy liver tissue.

[0107] The grey values ​​of pixels or voxels of real space images (2D or 3D images) of the lesion and reference tissues can be analysed to assess whether hyperenhancement and / or hypoenhancement is present.

[0108] In order to be able to describe a region as to whether it shows hyperenhancement in one time period and hypoenhancement in another, the region must be clearly identified and obtained in images representative of the region at various time periods. In other words, the assessment as to whether hyperenhancement is present in a region is based on at least one first image representative of the region after administration of a contrast agent in the arterial phase; the assessment as to whether hypoenhancement is present in a region is based on at least one second image representative of the region after administration of a contrast agent in the portal venous phase and / or transition phase. Thus, the region must be clearly determinable in both the first and second images, and the region in the at least one first image and the at least one second image must be the same.

[0109] To this end, the generated images can be image registered. Image registration (also called "co-registration") is a process in digital image processing that serves to match two or more images of the same or at least similar scenes with each other in the best possible way. One of the images is defined as the reference image, the other image is called the object image. A compensation transformation is calculated to optimally match said object image with the reference image. The images to be registered differ from each other because they were acquired at different positions, at different times, or with different sensors.

[0110] In the case of our images, they are taken at different times.

[0111] The goal of image registration is therefore to find a transformation that matches a given object image with a reference image in the best possible way, such that, if possible, each pixel / voxel in an image represents the same region inside the patient's body as the pixel / voxel in a different (co-registered) image with the same coordinates.

[0112] Methods for image registration have been described in the prior art (see, for example, EH Seeley et al.: Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease, Bone 2014, 61, 208-216; C. Bhushan et al.: Co-registration and distortion correction of diffusion and anatomical images based on inverse contrast normalization, Neuroimage 2015, 15, 115: 269-80; US20200214619; US20090135191; EP3639272A).

[0113] Co-registration can be performed for the entire image (the entire image including all anatomical features captured therein), or it is also possible to restrict co-registration to lesions, i.e., to alter the individual images by a transformation such that at least lesions in the individual images are represented by corresponding pixels / voxels (where corresponding pixels / voxels have the same coordinates).

[0114] It is further contemplated that each image may be subjected to a segmentation method that detects lesions within the image and marks them as such.

[0115] Methods for detecting and segmenting lesions are described in the prior art (see, for example, C. Krishnamurthy et al.: Snake-based liver lesion segmentation, 6th IEEE Southwest Symposium on Image Analysis and Interpretation 2004 pp. 187-191, doi: 10.1109 / IAI.2004.1300971; F.-A. Maayan et al.: GAN-based synthetic medical image augmentation for increased CNN performance in liver lesion classification, Neurocomputing 2018, 321, 321-331; WO2005 / 106773; EP3629898A; WO2012 / 040410).

[0116] The region or regions in the image representing the reference tissue may be defined / determined by a radiologist or automatically.

[0117] It is therefore conceivable that a radiologist may mark one or more regions in an image of the liver or part of the liver to serve as reference regions.

[0118] To automatically determine one or more reference regions, segmentation methods (see, for example, WO2020 / 144134) can also be used to detect muscle tissue and / or liver tissue in an image and define reference regions representing muscle tissue and / or liver tissue.

[0119] According to the teachings of the present invention, hyperenhancement is present in a region (lesion) if the grey values ​​of the pixels / voxels representing the region in the arterial phase are significantly higher than the grey values ​​of the pixels / voxels representing the reference tissue.

[0120] Hypoenhancement is present in a region (lesion) if the grey value of the pixels / voxels representing the region in the arterial phase is significantly higher than the grey value of the pixels / voxels representing the reference tissue.

[0121] The term "significantly" means that higher or lower grey values ​​are measurements that are beyond the error limits of the measurement system.

[0122] Basically, to detect high enhancement, it is sufficient to compare the gray value of the pixels / voxels representing the region with the gray value of the pixels / voxels representing the reference tissue. If the gray value of the pixels / voxels of the region is greater than the gray value of the pixels / voxels of the reference region (higher signal enhancement), high enhancement is present, otherwise it is absent. Similarly, basically, to detect low enhancement, it is sufficient to compare the gray value of the pixels / voxels representing the region with the gray value of the pixels / voxels representing the reference tissue. If the gray value of the pixels / voxels of the region is less than the gray value of the pixels / voxels of the reference region (lower signal enhancement), low enhancement is present, otherwise it is absent.

[0123] It is preferred to evaluate multiple pixels / voxels of the region and the reference region. Preferably, multiple pixels / voxels define a contiguous region in one image or multiple images. In other words, multiple pixels / voxels preferably represent a contiguous region in the patient's body. When multiple pixels / voxels are used, the average of the gray values ​​(or some other value indicating the signal intensity) can be calculated (e.g., arithmetic mean). A comparison between a region and the reference region is then made based on the respective averages. Instead of or in addition to the averaging of multiple locally adjacent pixels / voxels, it is also possible to perform an averaging of multiple pixels / voxels from images that follow each other in time.

[0124] In a preferred embodiment, in addition to the signal intensity, the gradient of the signal intensity is also ascertained.

[0125] In the case of a region, such a gradient can be obtained, for example, from two images representing the region at a time interval from each other. The time interval can be, for example, in the range of 1 second to 30 seconds. The shorter the time interval, the more accurately the change in signal intensity (gradient) can be determined. Preferably, the gradient within a phase is determined by generating 2 to 5 images representing the liver or a part of the liver during that phase (arterial phase, portal venous phase, transition phase). If the signal intensity of the region increases in time from one image to the next, the gradient is positive. In contrast, if the signal intensity decreases, the gradient is negative. The magnitude of the gradient provides information about how strong (rapid) the increase in signal intensity or the decrease in signal intensity is. By determining one or more gradients following the arterial phase, it is possible, for example, to ascertain how fast the washout of the contrast agent in the portal venous phase and / or transition phase is in a region. This information can be used, for example, to define one or more time points for acquiring one or more second (or further) images.

[0126] FIG. 3 shows, by way of example and diagrammatically, the liver of a patient. In FIGS. 3(a), 3(b), 3(c), 3(d), 3(e) and 3(f), the same cross-section through the liver is always drawn at different times. In addition to the liver, a reference tissue (R) is also drawn, which can be, for example, muscle tissue. The reference numbers entered in FIGS. 3(a) and 3(f) apply to all of FIGS. 3(a), 3(b), 3(c), 3(d), 3(e) and 3(f). For the sake of clarity only, they are entered each only once.

[0127] Figure 3(a) shows a cross section through the liver before intravenous administration of hepatic biliary contrast agent (raw image). At a time point between the time points depicted by Figures 3(a) and 3(b), the hepatic biliary contrast agent was administered intravenously (e.g., into an arm vein) as a bolus. It reaches the liver through the hepatic artery (A) in Figure 3(b). The hepatic artery (A) is therefore depicted with signal enhancement (arterial phase). Lesions that are primarily supplied with blood via arteries similarly stand out as brighter (signal enhanced) areas from the healthy liver tissue (L) and reference tissue (R). At the time point depicted in Figure 3(c), the contrast agent reaches the liver via a vein (V). In Figure 3(d), the venous vessels (V) stand out as bright (signal enhanced) areas (portal venous phase) from the liver tissue (L) and reference tissue (R). At the same time, the signal intensity of healthy liver cells (L), which are mainly supplied with contrast agent via the veins, increases continuously (Figure 3(c) → 3(d) → 3(e) → 3(f)). In the hepatobiliary phase depicted in Figure 3(f), liver cells (L) are depicted with enhanced signal, while blood vessels, reference tissues, and lesions are depicted dark because of the absence of contrast agent.

[0128] The question arises as to whether the lesion in Figure 3 (HCC) is hepatocellular carcinoma.

[0129] In Figure 4, the images shown in Figures 3(a), 3(b), 3(c), 3(d), and 3(e) are redrawn on a smaller scale and are labeled with reference characters (a), (b), (c), (d), and (e).

[0130] Signal strength SB can be identified for areas in the image that represent lesions. What can be identified is the signal intensity S B (a) , signal intensity S of image (b) B (b) , signal intensity S of image (c) B (c) , signal intensity S of image (d) B (d) , and the signal intensity S of image (e). B (e) The signal intensity can be, for example, the grey value or color value of a pixel / voxel representing the region.

[0131] Similarly, the signal strength S R can be ascertained for the area in the image representing the reference tissue. What can be ascertained is the signal intensity S R (a) , signal intensity S of image (b) R (b) , signal intensity S of image (c) R (c) , signal intensity S of image (d) R (d) and the signal intensity S of image (e). R (e) The signal intensity can be, for example, the grey value or color value of a pixel / voxel representing the region.

[0132] To resolve the question of whether a lesion is hepatocellular carcinoma or not, the signal intensity of the region representing the lesion is compared with the signal image of the region representing the reference tissue, specifically for at least one image during the arterial phase AP, and for at least one image during the portal venous phase PVP and / or for at least one image during the transition phase TP. B (b) where S is the signal intensity in the region representing the reference tissue R (b)A check is made as to whether the signal intensity is greater than 100x or not. If so, there is a first indication that the lesion is hepatocellular carcinoma. If not, there is no need to check the signal intensity further and hepatocellular carcinoma can be ruled out.

[0133] Image (d) shows the portal venous phase PVP. The signal intensity of the area showing the lesion, S B (d) where S is the signal intensity in the region representing the reference tissue. R (d) If so, there is a second indication that the lesion is hepatocellular carcinoma. If the first and second indications are present, then according to the present invention, the lesion is shown to be hepatocellular carcinoma. If only the first indication is present and the second indication is not present, then look at the transitional phase TP. Image (e) represents the transitional phase TP. The signal intensity S of the region representing the lesion B (e) where S is the signal intensity in the region representing the reference tissue R (e) Check if it is less than S B (e) S R (e) If it is smaller and the first signs are also present, then the present invention indicates that the lesion is hepatocellular carcinoma.

[0134] If the lesion is confirmed to be hepatocellular carcinoma according to the invention, a message may be output that indicators of hepatocellular carcinoma are present. A preferred output is an image of the patient's liver or part of the liver, with the lesions that are indicators of hepatocellular carcinoma marked. For example, the relevant lesions may be marked with a color.

[0135] The present invention can be implemented using a computer system.

[0136] A "computer system" is an electronic data processing system that processes data by means of programmable computational rules. Such a system typically includes a "computer", which is a unit that contains a processor for performing logical operations, and also peripheral devices.

[0137] In computer technology, a "peripheral" refers to any device connected to a computer and used to control the computer and / or used as an input / output device. Examples are monitors (screens), printers, scanners, mice, keyboards, drives, cameras, microphones, speakers, etc. Internal ports and expansion cards are also considered peripherals in computer technology.

[0138] Today's computer systems are generally subdivided into desktop PCs, portable PCs, laptops, notebooks, netbooks and tablet PCs, and so-called handhelds (e.g., smartphones), and all such systems can be used in the practice of the present invention.

[0139] Input to the computer system is accomplished via input means such as, for example, a keyboard, mouse, microphone, touch-sensitive display, and / or the like.

[0140] The output may be accomplished on a monitor, a printer, or a data storage medium.

[0141] 5 shows, diagrammatically and by way of example, an embodiment of a computer system according to the invention. The computer system (10) comprises a receiving unit (11), a control and calculation unit (12) and an output unit (13).

[0142] A computer system (10) according to the present invention is configured to receive an image of a patient's liver or a portion of the liver and identify one or more regions within the image indicative of hepatocellular carcinoma.

[0143] The control and calculation unit (12) serves to control the receiving unit (11) and the output unit (13), to coordinate the data and signal flow between the various units, to process the images and to check the signal strength comparison. There may be several control and calculation units.

[0144] The receiving unit (11) serves the function of receiving an image. The image can for example be transmitted from a magnetic resonance imaging system or read from a data storage medium. The magnetic resonance imaging system can be a component of the computer system according to the invention. However, it is also conceivable that the computer system according to the invention is a component of the magnetic resonance imaging system. The image can be transmitted via a network connection or a direct connection. The image can be transmitted via wireless communication (WLAN, Bluetooth, mobile communication and / or the like) and / or via a cable. It is conceivable that there are several receiving units. The data storage medium can also be a component of the computer system according to the invention and can be connected to the computer system for example via a network. It is conceivable that there are several data storage media.

[0145] Possible further data of the image (e.g. information about the examination object, image acquisition parameters, etc.) are received by the receiving unit and transmitted to the control and calculation unit.

[0146] The control and computing unit is configured to identify regions indicative of hepatocellular carcinoma based on the received data.

[0147] Via an output unit (13), the results of the analysis can be displayed (eg on a monitor), output (eg via a printer) or stored on a data storage medium. It is conceivable that there are several output units.

[0148] Further embodiments of the invention are as follows.

[0149] 1. - receiving a plurality of images of a liver or a portion of a liver of a patient undergoing a contrast-enhanced magnetic resonance imaging study, at least one image representing the liver or a portion of the liver of the patient during a portal venous phase and at least one image representing the liver or a portion of the liver during a transition phase; - identifying one or more regions in the liver in which the contrast agent provides lower contrast enhancement in the portal venous phase and / or in the transition phase than in a reference tissue, and / or in which the contrast enhancement in the portal venous phase and / or in the transition phase falls off more rapidly than in the reference tissue, which reference tissue does not contain hepatocytes, and / or in which the absolute value of the gradient of the falling contrast enhancement in the portal venous phase and / or in the transition phase is greater than the absolute value of the gradient of the rising contrast enhancement in healthy liver tissue, - outputting an image of the liver or a part of the liver, the identified region being highlighted or the identified regions being highlighted. 4. A computer-implemented method comprising:

[0150] 2. The method according to embodiment 1, wherein said imaging agent is a hepatobiliary imaging agent, preferably the disodium salt of gadoxetic acid.

[0151] 3. The method according to any of embodiments 1 and 2, wherein said reference tissue is muscle tissue.

[0152] 4. - receiving said plurality of images of the patient's liver or portion of the liver, at least two images representing the liver or portion of the liver during a portal venous phase and at least two images representing the liver or portion of the liver during a transition phase; - analyzing said plurality of received images and, in so doing, identifying a region or regions in the liver in which contrast enhancement in the portal venous phase and / or transition phase falls off more rapidly than in reference tissue, the reference tissue not containing hepatocytes and / or in which the absolute value of the gradient of the falling contrast enhancement in the portal venous phase and / or transition phase is greater than the absolute value of the gradient of the rising contrast enhancement in healthy liver tissue, - outputting an image of the liver or a part of the liver, the identified region being highlighted or the identified regions being highlighted. The method according to any one of embodiments 1 to 3, comprising:

[0153] 5. receiving at least one image of the liver or part of the liver representative of the liver or part of the liver during an arterial phase, - identifying one or more regions in the liver, said region / regions having the following characteristics: the contrast agent provides a higher contrast enhancement in the arterial phase than a first reference tissue, said first reference tissue being healthy liver tissue or muscle tissue; and the contrast agent provides lower contrast enhancement in the portal venous phase and / or the transition phase than a second reference tissue, said second reference tissue being muscle tissue; and / or o contrast enhancement in the portal venous phase and / or transition phase decreases more rapidly than in the second reference tissue, and / or The absolute value of the gradient of decreasing contrast enhancement during the portal venous phase and / or transition phase is greater than the absolute value of the gradient of increasing contrast enhancement in healthy liver tissue. A step characterized by - outputting an image of the liver or a part of the liver, the identified region being highlighted or the identified regions being highlighted. The method according to any one of embodiments 1 to 4, further comprising:

[0154] 6. ● Receiving unit, ●Control and calculation unit and Output unit A computer system comprising: - the control and computing unit is configured to cause the receiving unit to receive a plurality of images of the patient's liver or a portion of a liver, at least one image representing the liver or a portion of a liver during a portal venous phase and at least one image representing the liver or a portion of a liver during a transition phase; - the control and computing unit is configured to identify one or more regions in the liver in which the contrast agent provides a lower contrast enhancement in the portal venous phase and / or in the transition phase than in a reference tissue, and / or in which the contrast enhancement in the portal venous phase and / or in the transition phase decreases more rapidly than in the reference tissue, the reference tissue not containing hepatocytes, and / or in which the absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase and / or in the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue, - a computer system, wherein the control and computing unit is configured to cause the output unit to output an image of the liver or a part of the liver, wherein the identified area is highlighted, or wherein the identified areas are highlighted.

[0155] 7. A computer program product comprising a computer program loadable into the memory of a computer, the program causing said computer to perform the following steps: - receiving a plurality of images of a patient's liver or a portion of a liver, at least one image representing the liver or a portion of the liver during a portal venous phase and at least one image representing the liver or a portion of the liver during a transition phase; - identifying one or more regions in the liver in which the contrast agent provides lower contrast enhancement in the portal venous phase and / or in the transition phase than in a reference tissue, and / or in which the contrast enhancement in the portal venous phase and / or in the transition phase decreases more rapidly than in a reference tissue, the reference tissue not containing hepatocytes, and / or in which the absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase and / or in the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue, - outputting an image of the liver or a part of the liver, the identified region being highlighted or the identified regions being highlighted. A computer program product that causes the execution of

[0156] 8. Use of a contrast agent in a radiological examination method, said radiological examination method comprising the steps of: administering a contrast agent; - generating a plurality of images of a patient's liver or a portion of a liver, at least one image representing the liver or a portion of the liver during a portal venous phase and at least one image representing the liver or a portion of the liver during a transition phase; - identifying one or more regions in the liver in which the contrast agent provides lower contrast enhancement in the portal venous phase and / or in the transition phase than in a reference tissue, and / or in which the contrast enhancement in the portal venous phase and / or in the transition phase decreases more rapidly than in a reference tissue, the reference tissue not containing hepatocytes, and / or in which the absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase and / or in the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue, - outputting an image of the liver or a part of the liver, the identified region being highlighted or the identified regions being highlighted. Use including.

[0157] 9. A contrast agent for use in a radiological examination method, said radiological examination method comprising the steps of: administering a contrast agent; - generating a plurality of images of a patient's liver or a portion of a liver, at least one image representing the liver or a portion of the liver during a portal venous phase and at least one image representing the liver or a portion of the liver during a transition phase; - identifying one or more regions in the liver in which the contrast agent provides lower contrast enhancement in the portal venous phase and / or in the transition phase than in a reference tissue, and / or in which the contrast enhancement in the portal venous phase and / or in the transition phase decreases more rapidly than in a reference tissue, the reference tissue not containing hepatocytes, and / or in which the absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase and / or in the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue, - outputting an image of the liver or a part of the liver, the identified region being highlighted or the identified regions being highlighted. A contrast agent comprising:

[0158] 10. A kit comprising an imaging agent and the computer program product of claim 7.

[0159] 11. The kit according to embodiment 10, wherein said imaging agent is the disodium salt of gadoxetic acid.

Claims

1. 1. A computer-implemented method comprising: - receiving a plurality of images, The plurality of images are ■ the liver of a patient or a part of the liver of said patient, and ■ Reference tissue of the patient represents During the portal venous phase of a dynamic contrast-enhanced magnetic resonance imaging study, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents During a transition phase of the dynamic contrast-enhanced magnetic resonance imaging study, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization The stage representing - one or more regions of the liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, the reference tissue not containing hepatocytes, and / or the absolute value of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the absolute value of the gradient of increasing contrast enhancement in healthy liver tissue; identifying one or more regions in the liver; - outputting an image of the liver or part of the liver, in which the identified region or a number of identified regions are highlighted in the image; 4. A computer-implemented method comprising:

2. 2. The method of claim 1, wherein the contrast agent is a hepatobiliary contrast agent, preferably the disodium salt of gadoxetic acid.

3. The method of claim 1 , wherein the reference tissue is muscle tissue.

4. - receiving said plurality of images, At least two of the plurality of images are taken during the portal vein phase. ■ The liver or a part of the liver, and ■ Reference Organization represents At least two of the plurality of images are ■ The liver or a part of the liver, and ■ Reference Organization The stage representing - analyzing said plurality of received images, and in so doing the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, and the reference tissue does not contain hepatocytes, and / or the absolute value of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the absolute value of the gradient of increasing contrast enhancement in healthy liver tissue; identifying a region or regions in the liver; - outputting an image of the liver or part of the liver, in which the identified region or a number of identified regions are highlighted; The method of claim 1 , comprising:

5. - receiving at least one image, The at least one image is obtained during the arterial phase of the dynamic contrast-enhanced magnetic resonance imaging study. ■ The liver or a part of the liver, and ■ First and / or second reference entity The stage representing - identifying one or more regions in said liver, said region / regions having the following characteristics: the contrast agent provides a higher contrast enhancement in the arterial phase than a first reference tissue, the first reference tissue being a healthy liver tissue or a muscle tissue; and the contrast agent provides lower contrast enhancement in said portal phase and / or said transition phase than a second reference tissue, said second reference tissue being muscle tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the second reference tissue, and / or The absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue. A step characterized by - outputting an image of the liver or part of the liver, in which the identified region or a number of identified regions are highlighted in the image; The method of any one of claims 1 to 4, further comprising:

6. ● Receiving unit, ●Control and calculation unit and Output unit A computer system comprising: - said control and calculation unit is configured to cause said receiving unit to receive a plurality of images; The plurality of images are ■ the liver of a patient or a part of the liver of said patient, and ■ Reference tissue of the patient represents During the portal venous phase of a dynamic contrast-enhanced magnetic resonance imaging study, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents During a transition phase of the dynamic contrast-enhanced magnetic resonance imaging study, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents - said control and computing unit being in one or more regions of said liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or The contrast enhancement in the portal phase and / or the transition phase is greater than that in the reference tissue. rapidly decreases, the reference tissue does not contain hepatocytes, and / or the absolute value of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the absolute value of the gradient of increasing contrast enhancement in healthy liver tissue; configured to identify one or more regions in the liver; - A computer system, wherein the control and calculation unit is configured to cause the output unit to output an image of the liver or a part of the liver, in which the identified area is highlighted or a number of identified areas are highlighted in the image.

7. A computer program product comprising a computer program loadable into the memory of a computer, the program causing said computer to perform the following steps: - receiving a plurality of images, The plurality of images are ■ the liver of a patient or a part of the liver of said patient, and ■ Reference tissue of the patient represents During the portal venous phase of a dynamic contrast-enhanced magnetic resonance imaging study, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents During a transition phase of the dynamic contrast-enhanced magnetic resonance imaging study, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization The stage representing - one or more regions of the liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, and the reference tissue does not contain hepatocytes, and / or the absolute value of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the absolute value of the gradient of increasing contrast enhancement in healthy liver tissue; identifying one or more regions in the liver; - outputting an image of the liver or a part of the liver, in which the identified area or a number of identified areas are highlighted in the image.

8. Use of a contrast agent in the manufacture of a medicament for a dynamic contrast-enhanced magnetic resonance imaging examination method, said examination method comprising the steps of: - administering said contrast agent, - generating a plurality of images, The plurality of images are ■ the liver of a patient or a part of the liver of said patient, and ■ Reference tissue of the patient represents During the portal vein phase of the examination method, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents During a transition phase of the inspection method, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization The stage representing - one or more regions of the liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, and the reference tissue does not contain hepatocytes, and / or the absolute value of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the absolute value of the gradient of increasing contrast enhancement in healthy liver tissue; identifying one or more regions in the liver; - outputting an image of the liver or part of the liver, in which the identified region or a number of identified regions are highlighted in the image; Use including.

9. A contrast agent for use in a dynamic contrast enhanced magnetic resonance imaging method, said method comprising the steps of: - administering said contrast agent, - generating a plurality of images, The plurality of images are ■ the liver of a patient or a part of the liver of said patient, and ■ Reference tissue of the patient represents During the portal vein phase of the examination method, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization represents During a transition phase of the inspection method, at least one image of the plurality of images ■ The liver or a part of the liver, and ■ Reference Organization The stage representing - one or more regions of the liver, the contrast agent provides lower contrast enhancement in the portal phase and / or in the transition phase than in the reference tissue, and / or the contrast enhancement in the portal phase and / or the transition phase decreases more rapidly than in the reference tissue, and the reference tissue does not contain hepatocytes, and / or the absolute value of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the absolute value of the gradient of increasing contrast enhancement in healthy liver tissue; identifying one or more regions in the liver; - outputting an image of the liver or part of the liver, in which the identified region or a number of identified regions are highlighted in the image; A contrast agent comprising:

10. A kit comprising an imaging agent and the computer program product of claim 7.

11. The kit of claim 10, wherein the imaging agent is a hepatobiliary imaging agent.

12. The kit of claim 10, wherein the imaging agent is the disodium salt of gadoxetic acid.

Images