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

Description

[0001] The present invention relates to the technical field of characterizing lesions in the liver using dynamic contrast-enhanced magnetic resonance imaging.

[0002] The liver can be affected by several benign tumors, which may present as cystic or solid focal lesions within the liver parenchyma. However, the liver is also susceptible to malignant tumors, such as metastases from extrahepatic cancers or from primary cancers originating in the liver itself. Worldwide, the two most common types of malignant liver tumors are metastases—particularly colorectal cancer metastases—and hepatocellular carcinoma (HCC). Nearly 20% of patients with colorectal cancer have liver metastases at the time of diagnosis, and more than 50% of colorectal cancer patients 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 leading cause of cancer-related deaths.

[0003] The accurate and reliable detection and characterization of focal liver lesions in early stages of disease is of high clinical relevance, especially in patients at risk for liver metastases or primary liver cancer, as it is fundamental for appropriate treatment planning and determines suitability for potentially curative treatment options.

[0004] Magnetic resonance imaging (MRI) is of particular importance for the radiological examination of liver lesions. It is characterized by excellent soft tissue contrast and high spatial resolution, without exposing the patient to ionizing radiation or iodinated contrast agents.

[0005] The most commonly used contrast agents in MRI are paramagnetic gadolinium-based contrast agents. These agents are administered via an intravenous (IV) bolus injection. Their contrast-enhancing effect is mediated by the central gadolinium ion (Gd-III) in the chelate complex. When T1-weighted (w) scanning sequences are used in MRI, the gadolinium-induced shortening of the spin-lattice relaxation time (T1) of excited atomic nuclei leads to an increase in signal intensity and thus to an increase in the image contrast of the examined tissue.

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

[0007] Extracellular contrast agents are low-molecular-weight, water-soluble compounds that, after intravenous administration, distribute themselves in the blood vessels and interstitial space. They are excreted via the kidneys after a relatively short period of circulation in the bloodstream. Examples of extracellular MRI contrast agents include the gadolinium chelates gadobutrol (Gadovist®), gadoteridol (Prohance®), gadoteric acid (Dotarem®), gadopentetic acid (Magnevist®), and gadodiamide (Omnican®).

[0008] Intracellular contrast agents are partially absorbed into tissue cells and subsequently excreted. For example, gadoxetic acid-based intracellular MRI contrast agents are characterized by their partial uptake specifically by liver cells (hepatocytes), accumulation in functional tissue (parenchyma), and enhancement of contrast in healthy liver tissue before being excreted via bile into the feces. Examples of such gadoxetic acid-based contrast agents are described in US 6,039,931A; they are commercially available under brand names such as 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 is approved for use in MRI of the liver to detect and characterize lesions in patients with known or suspected focal liver disease. GD, with its lipophilic ethoxybenzyl moiety, exhibits a biphasic distribution: first, distribution in 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 kidneys and the hepatobiliary pathway (50:50 dual excretion mechanism). Due to its selective accumulation in healthy liver tissue, GD is also referred to as a hepatobiliary contrast agent.

[0010] GD is approved at a dose of 0.1 ml / kg body weight (BW) (0.025 mmol / kg BW Gd). The recommended administration of GD involves an undiluted intravenous bolus injection at a flow rate of approximately 2 ml / second, followed by flushing the IV cannula with physiological saline. A standard protocol for liver imaging using GD consists of several planning and pre-contrast sequences. Following IV bolus injection of the contrast agent, dynamic images are typically acquired during the arterial (approximately 30 seconds post-injection, pi), portal venous (approximately 60 seconds pi), and transition phases (approximately 2–5 minutes pi). The transition phase typically already shows some increase in liver signal intensity due to the incipient uptake of the agent by hepatocytes.Additional T2-weighted and diffusion-weighted (DWI) images can be acquired after the dynamic phase and before the late hepatobiliary phase.

[0011] Contrast-enhanced dynamic images from the arterial, portal venous, and transition phases provide crucial information about the time-varying patterns of lesion enhancement (vascularization), which contribute to the characterization of the specific liver lesion. Hepatocellular carcinoma, with its typical arterial phase hyperenhancement (APHE) and washout (i.e., washout ) of the contrast in the venous phase, can be diagnosed solely based on its unique vascularization pattern observed during dynamic phase imaging, thus sparing patients from an invasive and potentially risky liver biopsy.

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

[0013] In the diagnosis of liver lesions, a hepatobiliary contrast agent has the advantage over an extracellular contrast agent of having higher sensitivity and thus allowing for better detection of smaller carcinomas in particular (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).

[0014] The problem is that the dynamic increase and / or decrease in contrast in liver lesions is often assessed by radiologists visually (subjective assessment of the relative contrast change between liver tissue and liver lesion), and misinterpretations can occur as a result.

[0015] Visual assessment makes a difference whether an extracellular or intracellular contrast agent is used. For example, when using a hepatobiliary contrast agent, an increase in signal intensity in healthy liver tissue can be misinterpreted as a washout of contrast agent from adjacent liver lesions (relative contrast increase between liver tissue and liver lesion).

[0016] Therefore, the European Association for the Study of Liver in their guidelines ( EASL Clinical Practice Guidelines: Management of hepatocellular carconima ), depending on the contrast agent used, different characteristics for the identification of hepatocellular carcinoma have been specified: (see Journal of Hepatology, 2018, Vol. 69, pages 182-236): When using an extracellular contrast agent: combination of hypervascularity in the late arterial phase and washout in the portal venous and / or delayed phase; when using a hepatobiliary contrast agent: combination of hypervascularity in the late arterial phase and washout in the portal venous phase.

[0017] Thus, while when using an extracellular contrast agent to detect hepatocellular carcinomas, both the portal venous and the subsequent delayed phases are used, when using a hepatobiliary contrast agent, only the portal venous phase is used to detect washout, and no phase following the portal venous phase.

[0018] The reason for this, as previously described, is that a hepatobiliary contrast agent (unlike an extracellular contrast agent) is taken up by the liver cells and accumulates there before being excreted into the feces via bile. Therefore, when using a hepatobiliary contrast agent, following an initial, relatively rapid increase in vascular contrast during the arterial phase, there is a slowly and continuously increasing contrast enhancement in healthy liver tissue. If a radiologist visually compares the contrast enhancement in a lesion with the contrast enhancement in healthy liver tissue, the continuously increasing contrast enhancement in healthy liver tissue can be misinterpreted as a washout of contrast agent from lesions.

[0019] The European Association for the Study of Liver It therefore explicitly recommends that, when using a hepatobiliary contrast agent, the analysis of MRI scans for the identification of hepatocellular carcinoma should be limited to the arterial and portal venous lines (up to 60 seconds after intravenous administration of the contrast agent).

[0020] The problem, however, is that some lesions can only be clearly characterized by their dynamic behavior in a later phase.

[0021] In some hepatocellular carcinomas, for example, washout is only evident after the portal venous phase (see e.g. CJ Zech et al.: Consensus report from the 8th International Forum for Liver Magnetic Resonance Imaging, European Radiology 2020, 30, 370-382).

[0022] Is the time interval after the portal venous phase, as described by the European Association for the Study of Liver If the recommended procedure is not taken into account for the detection of washout, for example, hepatocellular carcinomas where washout only becomes apparent after the portal venous phase remain undetected. The consequence may be that more biopsies need to be performed to determine whether a lesion is benign or malignant (see in particular Fig. 2 (in Journal of Hepatology, 2018, Vol. 69, page 194). A biopsy is not only an additional burden for medical staff; it also poses a risk to the patient.

[0023] It would be desirable to be able to reduce the number of such biopsies. It would also be desirable to be able to reliably identify and characterize liver lesions without the risk of misinterpreting a signal increase from healthy liver tissue as contrast medium washout from liver lesions when using a hepatobiliary contrast agent.

[0024] This is achieved by the present invention.

[0025] A first object of the present invention is a computer-implemented method for identifying washout of contrast medium from an area of ​​a patient's liver during a dynamic contrast-enhanced magnetic resonance imaging examination, comprising the steps of: Receiving a plurality of representations, wherein the plurality of representations represent the patient's liver or a part of the patient's liver, and patient's reference tissue, wherein at least one representation of the plurality of representations represents the liver or the part of the liver, and the reference tissue during a portal venous phase of the dynamic contrast-enhanced magnetic resonance imaging examination, and wherein at least one representation of the plurality of representations represents the liver or the part of the liver, and the reference tissue during a transition phase of the dynamic contrast-enhanced magnetic resonance imaging examination, wherein the contrast agent is a hepatobiliary contrast agent, and wherein the reference tissue is muscle tissue, analyzing the representations and identifying one or more areas in the liver.• where the contrast agent results in lower contrast enhancement in the portal venous phase and / or the transition phase than in the reference tissue, and / or • where the contrast enhancement in the portal venous phase and / or the transition phase decreases more rapidly than in the reference tissue, wherein the reference tissue does not include hepatocytes, and / or • where the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue, outputting a representation of the liver or part of the liver, wherein the identified area(s) are highlighted in the representation.

[0026] Another object of the present invention is a computer system comprising a receiving unit, a control and processing unit, and an output unit, wherein the control and processing unit is configured to cause the receiving unit to receive a plurality of representations, wherein the plurality of representations represent a patient's liver or part of the patient's liver, and patient's reference tissue, wherein at least one representation of the plurality of representations represents the liver or part of the liver, and the reference tissue during a portal venous phase of a dynamic contrast-enhanced magnetic resonance imaging (MRI) examination, and wherein at least one representation of the plurality of representations represents the liver or part of the liver, and the reference tissue during a transition phase of the dynamic contrast-enhanced MRI examination, wherein the contrast agent is a hepatobiliary contrast agent.wherein the reference tissue is muscle tissue, wherein the control and processing unit is configured to analyze the representations and identify one or more areas in the liver, where: ∘ contrast agent results in lower contrast enhancement in the portal venous phase and / or the transition phase than in the reference tissue, and / or ∘ the contrast enhancement decreases more rapidly in the portal venous phase and / or the transition phase than in the reference tissue, wherein the reference tissue does not include hepatocytes, and / or ∘ the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue, wherein the control and processing unit is configured to cause the output unit to output a representation of the liver or part of the liver.where the identified area(s) are highlighted in the representation.

[0027] Another object of the present invention is a computer program product comprising a computer program that can be loaded into a computer's main memory and causes the computer to perform the following steps: Receiving a plurality of representations, wherein the plurality of representations represent a patient's liver or part of the patient's liver, and patient's reference tissue, wherein at least one representation of the plurality of representations represents the liver or part of the liver, and the reference tissue during a portal venous phase of a dynamic contrast-enhanced magnetic resonance imaging (MRI) examination, and wherein at least one representation of the plurality of representations represents the liver or part of the liver, and the reference tissue during a transition phase of the dynamic contrast-enhanced MRI examination, wherein the contrast agent is a hepatobiliary contrast agent, and wherein the reference tissue is muscle tissue, analyzing the representations and identifying one or more areas in the liver.• where the contrast agent results in lower contrast enhancement in the portal venous phase and / or the transition phase than in the reference tissue, and / or • where the contrast enhancement in the portal venous phase and / or the transition phase decreases more rapidly than in the reference tissue, wherein the reference tissue does not include hepatocytes, and / or • where the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue, outputting a representation of the liver or part of the liver, wherein the identified area(s) are highlighted in the representation.

[0028] Another object of the present invention is the use of a hepatobiliary contrast agent in a dynamic magnetic resonance imaging examination procedure, wherein the examination procedure comprises the following steps: Applying the contrast medium into a vein of a patient distant from an artery, generating a plurality of representations, wherein the plurality of representations represent a patient's liver or part of a patient's liver, and patient's reference tissue, wherein at least one representation of the plurality of representations represents the liver or part of the liver, and the reference tissue during a portal venous phase of the examination procedure, and wherein at least one representation of the plurality of representations represents the liver or part of the liver, and the reference tissue during a transition phase of the examination procedure, the reference tissue being muscle tissue, analyzing the representations and identifying one or more areas in the liver.• where the contrast agent results in lower contrast enhancement in the portal venous phase and / or the transition phase than in the reference tissue, and / or • where the contrast enhancement in the portal venous phase and / or the transition phase decreases more rapidly than in the reference tissue, wherein the reference tissue does not include hepatocytes, and / or • where the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue, outputting a representation of the liver or part of the liver, wherein the identified area(s) are highlighted in the representation.

[0029] Another object of the present invention is a kit comprising a contrast agent and the computer program product according to the invention.

[0030] Preferred embodiments of the invention can be found in the dependent claims, the present description and the drawings.

[0031] The invention is explained in more detail below, without distinguishing between the subject matter of the invention (method, computer system, computer program product, use, kit). Rather, the following explanations are intended to apply analogously to all subject matter of the invention, regardless of the context in which they are made (method, computer system, computer program product, use, kit).

[0032] The present invention provides means for the automated identification of a washout (English: washout ) of contrast medium from a region of a patient's liver during a dynamic contrast-enhanced magnetic resonance imaging examination. In other words, with the aid of the present invention, one or more regions within the liver can be automatically identified that are characterized by contrast medium washout.

[0033] As washing out / leaching (English: washout ) refers to the observation that the contrast enhancement in an area of ​​the liver decreases more rapidly in the portal venous phase and / or the transition phase of a dynamic contrast-enhanced magnetic resonance imaging examination than in the surrounding (healthy) liver tissue.

[0034] Such washout is often used as a characteristic feature to specify liver lesions (see e.g.: 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).

[0035] Magnetic resonance imaging, abbreviated MRI (English: MRI: Magnetic Resonance Imaging ) , is an imaging technique used primarily in medical diagnostics to depict the structure and function of tissues and organs in the human or animal body.

[0036] In MRI imaging, the magnetic moments of protons in a sample are aligned in a baseline magnetic field, resulting in macroscopic magnetization along a longitudinal axis. This magnetization is then displaced from its resting position by the application of high-frequency pulses (excitation). The return of the excited states to their resting positions (relaxation), or the magnetization dynamics, is subsequently detected as relaxation signals using one or more high-frequency receiver coils.

[0037] For spatial encoding, rapidly switched magnetic gradient fields are superimposed on the fundamental magnetic field. The acquired relaxation signals, or the detected and spatially resolved MR data, initially exist as raw data in a spatial frequency domain and can be transformed into spatial space (image space) by subsequent Fourier transformation.

[0038] In native MRI, tissue contrasts are generated by the different relaxation times (T1 and T2) and the proton density.

[0039] The T1 relaxation time describes the transition of the longitudinal magnetization to its equilibrium state, where T1 is the time required to reach 63.21% of the equilibrium magnetization prior to resonance excitation. It is also called the longitudinal relaxation time or spin-lattice relaxation time.

[0040] T2 relaxation describes, in an analogous way, the transition of the transverse magnetization to its equilibrium state.

[0041] In the first step of a dynamic contrast-enhanced magnetic resonance imaging examination, an MRI contrast agent is administered to the subject.

[0042] The "subject of study" is usually a living being, preferably a mammal, and most preferably a human. The term "patient" is also used in this description.

[0043] According to the invention, the contrast agent is a hepatobiliary contrast agent.

[0044] A hepatobiliary contrast agent is a contrast agent that is specifically absorbed by healthy liver cells, the hepatocytes.

[0045] Examples of hepatobiliary contrast agents include gadoxetic acid-based contrast agents. These are described, for example, in US 6,039,931A. They are commercially available, for example, under the brand names Primovist® or Eovist®.

[0046] The contrast-enhancing effect of Primovist® / Eovist® is mediated by the stable gadolinium complex Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid). DTPA forms a complex with the paramagnetic gadolinium ion, exhibiting extremely high thermodynamic stability. The ethoxybenzyl group (EOB) mediates the hepatobiliary uptake of the contrast agent.

[0047] In a particularly preferred embodiment, the contrast agent used is a substance or a mixture of substances comprising gadoxetic acid or a salt of gadoxetic acid as the contrast-enhancing agent. Most preferably, this is the disodium salt of gadoxetic acid (Gd-EOB-DTPA disodium).

[0048] Following intravenous administration of the hepatobiliary contrast agent as a bolus into an arm vein, the contrast agent initially reaches the liver via the arteries. These are shown with contrast enhancement in the corresponding MRI scans. The phase in which the hepatic arteries appear with contrast enhancement in MRI scans is referred to as the "arterial phase."

[0049] The contrast agent then reaches the liver via the hepatic veins. While the contrast in the hepatic arteries is already decreasing, it reaches its maximum in the hepatic veins. The phase in which the hepatic veins appear contrast-enhanced in MRI scans is called the "portal venous phase." This phase can begin during the arterial phase and overlap with it.

[0050] The portal venous phase is followed by the "transition phase" (English: transition phase). transitional phase ) in which the contrast in the hepatic arteries continues to decrease, and the contrast in the hepatic veins also decreases. When using a hepatobiliary contrast agent, the contrast in healthy liver cells gradually increases during the transition phase.

[0051] The arterial phase, the portal venous phase and the transition phase are collectively referred to as the "dynamic phase".

[0052] Ten to twenty minutes after injection, a hepatobiliary contrast agent leads to a marked increase in signal intensity in healthy liver parenchyma. This phase is called the "hepatobiliary phase." The contrast agent is eliminated from the liver cells only slowly; accordingly, the hepatobiliary phase can last two hours or more.

[0053] The phases mentioned are described in more detail in the following publications, for example: 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).

[0054] Figur 1 schematically shows the time course ( t ( = time) of signal intensities I, which are caused by a hepatobiliary contrast agent in hepatic arteries (A), hepatic veins (V), and healthy liver cells (L) during a dynamic contrast-enhanced MRI examination. The signal intensity IThis correlates positively with the contrast agent concentration in the aforementioned areas. Following an intravenous bolus injection, the contrast agent concentration in the hepatic arteries (A) rises first (dashed curve). The concentration reaches a maximum and then decreases. The concentration in the hepatic veins (V) rises more slowly than in the hepatic arteries and reaches its maximum later (dotted curve). The contrast agent concentration in the liver cells (L) rises slowly (solid curve) and reaches its maximum only at a much later time (in the Figur 1 (not shown). Several characteristic time points can be defined: At time point TP0, contrast medium is administered intravenously as a bolus. Since the administration of a contrast medium itself takes a certain amount of time, time point TP0 preferably defines the time at which the administration is complete, i.e., when the contrast medium has been completely introduced into the subject of the examination. At time point TP1, the signal intensity of the contrast medium reaches its maximum in the hepatic arteries (A). At time point TP2, the signal intensity curves of the hepatic arteries (A) and the hepatic veins (V) intersect. At time point TP3, the signal intensity of the contrast medium reaches its maximum in the hepatic veins (V). At time point TP4, the signal intensity curves of the hepatic arteries (A) and the healthy liver cells (L) intersect.At time TP5, the concentrations in the hepatic arteries (A) and hepatic veins (V) have decreased to a level at which they no longer cause measurable contrast enhancement.

[0055] During contrast-enhanced magnetic resonance imaging (MRI), multiple MRI images of the patient's liver or a portion thereof are acquired. These MRI images are referred to as representations in this description. They represent the liver or a portion thereof before and / or after the administration of a contrast agent. These representations can be spatial or frequency-domain.

[0056] In magnetic resonance imaging (MRI), the raw data are typically generated as so-called k-space data due to the measurement method. This k-space data represents a region of investigation in the frequency domain. Such k-space data can be transformed into a spatial representation using an inverse Fourier transform. Conversely, spatial representations can be transformed into a frequency-domain representation (also known as spatial frequency domain, Fourier space, frequency domain, or Fourier representation) using a Fourier transform.

[0057] The actions described in this description are preferably carried out with representations in the local area.

[0058] A representation of an area of ​​investigation (e.g., the liver) in spatial space is the more familiar representation for a person; it is easier for a person to grasp (understand). The term "image" (English: ) is also commonly used for such a representation in spatial space. image ) used.

[0059] A representation within the meaning of the present invention can be a two-dimensional, three-dimensional, or higher-dimensional representation. Typically, two-dimensional tomograms (layer images) are available, or a stack of two-dimensional tomograms (layer images) is available.

[0060] Representations are usually in digital form. The term "digital" means that the representations can be processed by a machine, typically a computer system. "Processing" refers to the known methods of electronic data processing (EDP). An example of a common format for a digital representation is the DICOM format (DICOM: Digital Imaging and Communications in Medicine ) - an open standard for storing and exchanging information in medical image data management.

[0061] For the sake of simplicity, the invention is explained in some places in this description using the example of two-dimensional images, without, however, limiting the invention to two-dimensional images. It is clear to those skilled in the art how what is described can be applied to stacks of two-dimensional images, to 3D recordings, or to representations in the frequency domain (see, for example, M. Reisler, W. Semmler: Magnetresonanztomographie [Magnetic Resonance Tomography], Springer Verlag, 3rd edition, 2002, ISBN: 978-3-642-63076-7).

[0062] Digital images can exist in various formats. For example, digital images can be encoded as raster graphics. Raster graphics consist of a grid-like arrangement of so-called picture elements (pixels) or volume elements (voxels), each assigned a color or a grayscale value. The main characteristics of a 2D raster graphic are therefore the image size (width and height measured in pixels, also commonly called image resolution) and the color depth. A pixel in a digital image file is typically assigned a color. The color encoding used for a pixel is defined, among other things, by the color space and the color depth. The simplest case is a binary image, in which a pixel stores a black and white value.In an image whose color is defined by the so-called RGB color space (RGB stands for the primary colors red, green, and blue), each pixel consists of three subpixels: one subpixel for red, one subpixel for green, and one subpixel for blue. The color of a pixel results from the superposition (additive mixing) of the color values ​​of the subpixels. The color value of a subpixel can, for example, be divided into 256 color shades, called tonal values, which typically range from 0 to 255. The color shade "0" of each color channel is the darkest. If all three channels have a tonal value of 0, the corresponding pixel appears black; if all three channels have a tonal value of 255, the corresponding pixel appears white. In the embodiment of the present invention, digital images are subjected to certain operations. These operations primarily concern the pixels, or rather...The tonal values ​​of the individual image points (pixels or voxels). There are numerous possible digital image formats and color encodings. For the sake of simplicity, this description assumes that the images in question are grayscale raster graphics with a specific number of image points, where each image point is assigned a tonal value that indicates the gray value of the image. However, this assumption should in no way be considered limiting. Those skilled in image processing will understand how to apply the principles of this description to image files that are in other image formats and / or where the color values ​​are encoded differently.

[0063] During contrast-enhanced magnetic resonance imaging, multiple representations of the liver or part of the liver of a patient are generated.

[0064] The majority of representations includes at least one representation representing the liver or part of the liver during the portal venous phase, and at least one representation representing the liver or part of the liver during the transition phase.

[0065] Preferably, at least one representation of the liver or part of the liver is generated before the application of the hepatobiliary contrast medium (before TP0) (native image) and / or at least one representation of the liver or part of the liver is generated in the arterial phase.

[0066] In a preferred embodiment, at least the following recordings are produced: at least one first representation, wherein the at least one first representation represents the liver or part of the liver during the time period from TP1 to TP3, at least one second representation, wherein the at least one second representation represents the liver or part of the liver during the time period from TP3 to TP5, where the time points TP0 in Fig. 1 depicted and described in the description of Fig. 1 are explained.

[0067] In a further preferred embodiment, at least the following recordings are produced: at least one first representation, wherein the at least one first representation represents the liver or part of the liver of a patient during the time period from TP0 to TP3, at least one second representation, wherein the at least one second representation represents the liver or part of the liver of the patient during the time period from TP2 to TP5, at least one third representation, wherein the at least one third representation represents the liver or part of the liver of the patient during the time period from TP4 to 5 minutes after TP0, where the time points TP0 in Fig. 1 depicted and described in the description of Fig. 1 are explained.

[0068] In a particularly preferred embodiment, at least the following recordings are produced: at least one first representation, wherein the at least one first representation represents the liver or part of the liver of a patient during the time interval from TP0 to TP1, and at least one second representation, wherein the at least one second representation represents the liver or part of the liver of a patient during the time interval from TP1 to TP2, and at least one third representation, wherein the at least one third representation represents the liver or part of the liver of a patient during the time interval from TP2 to TP3, and at least one fourth representation, wherein the at least one fourth representation represents the liver or part of the liver of a patient during the time interval from TP3 to TP4, and at least one fifth representation, wherein the at least one fifth representation represents the liver or part of the liver of the patient during the time interval TP4 to TP5 seconds after TP0,and / or at least one sixth representation, wherein the at least one sixth representation represents the patient's liver or part of the liver during the time interval TP5 to 5 minutes after TP0, , where the time points TP0 in Fig. 1 depicted and described in the description of Fig. 1 are explained.

[0069] The generated representations are fed to the computer system according to the invention, which is configured to automatically analyze the representations.

[0070] The term "automated" means without human intervention.

[0071] The analysis identifies one or more areas in the patient's liver where contrast medium washout occurs during the portal venous phase and / or the transition phase.

[0072] Washout can be identified in various ways: In one embodiment, those areas in the liver are identified where contrast medium results in lower contrast enhancement in the portal venous phase and / or the transition phase than in a reference tissue. The lower contrast enhancement in the portal venous and / or transition phase is also referred to as hypoenhancement. Hypoenhancement is the lower signal intensity compared to a reference tissue. In this embodiment, the reference tissue used is a tissue that does not include hepatocytes. According to the invention, muscle tissue is used as the reference tissue.

[0073] According to the invention, a hepatobiliary contrast agent is used. In a further embodiment, those areas in the liver are identified where the contrast enhancement decreases more rapidly in the portal venous phase and / or the transition phase than in the reference tissue. In this embodiment as well, tissue that does not include hepatocytes is used as the reference tissue. According to the invention, muscle tissue is used as the reference tissue.

[0074] The temporal gradient of the signal intensity is determined, and those areas are identified where the temporal gradient of the signal intensity is negative (decrease in signal intensity with increasing time) and where the magnitude of the temporal gradient is greater than the magnitude of the negative temporal gradient of the signal intensity in the reference tissue.

[0075] According to the invention, a hepatobiliary contrast agent is used.

[0076] In a further embodiment, those areas in the liver are identified where the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the gradient of increasing contrast enhancement in healthy liver tissue. In this embodiment, healthy liver tissue is used as the reference tissue. According to the invention, a hepatobiliary contrast agent is used, which is selectively taken up by healthy liver tissue and leads to a gradually increasing signal intensity in the portal venous phase and / or the transition phase. Thus, a positive temporal gradient of signal intensity is present in the healthy liver tissue in the portal venous phase and / or the transition phase.Areas are identified where the signal intensity decreases in the portal venous phase and / or the transition phase, with the amount of decrease (the absolute rate of decrease) being greater than the amount of increase in signal intensity in healthy liver tissue.

[0077] It is conceivable to combine the aforementioned embodiments. It is conceivable to identify those areas in the liver where contrast medium results in lower contrast enhancement in the portal venous phase and / or the transition phase than in a first reference tissue, and where the contrast enhancement in the portal venous phase and / or the transition phase decreases more rapidly than in a second reference tissue, and / or where the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the gradient of increasing contrast enhancement in healthy liver tissue. The first and / or second reference tissue could, for example, be muscle tissue or healthy liver tissue.

[0078] In a particularly preferred embodiment, the present invention is used to identify hepatocellular carcinomas. In this embodiment, one or more areas are identified that show both hyperenhancement in the arterial phase and washout in the protalvenous phase and / or the transition phase.

[0079] Hyperenhancement is present when an area exhibits a higher signal intensity compared to a reference tissue (see, 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). Healthy liver tissue is preferably used as the reference tissue for detecting hyperenhancement in the arterial phase. According to the invention, a hepatobiliary contrast agent is used. Preferably, the embodiment for identifying hepatocellular carcinoma comprises the following steps: Receiving multiple representations of the liver or part of the liver of a patient, wherein the representations are the result of a contrast-enhanced magnetic resonance imaging examination of the liver or part of the liver, wherein at least one first representation represents the liver or part of the liver during an arterial phase, wherein at least one second representation represents the liver or part of the liver during a portal venous phase, and wherein at least one third representation represents the liver or part of the liver during a transition phase; analyzing the at least one first, second, and third representation to identify one or more areas of the liver.where contrast medium in the arterial phase results in higher contrast enhancement than in a first reference tissue and where contrast medium in the portal venous and / or transition phase results in lower contrast enhancement than in a second reference tissue, output of a representation of the liver or part of the liver, wherein the identified area(s) are highlighted in the representation.

[0080] As already described, the first reference tissue is preferably healthy liver tissue and the second reference tissue is muscle tissue according to the invention.

[0081] In another preferred embodiment, the method for identifying a hepatocellular carcinoma comprises the following steps: Receiving multiple representations of the liver or part of the liver of a patient, wherein the representations are the result of a contrast-enhanced magnetic resonance imaging examination of the liver or part of the liver, wherein at least one first representation represents the liver or part of the liver during an arterial phase, wherein at least one second representation represents the liver or part of the liver during a portal venous phase, and wherein at least one third representation represents the liver or part of the liver during a transition phase; analyzing the received representation, identifying one or more areas of the liver characterized by the following features: contrast medium leads to 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, where the second reference tissue does not include hepatocytes, and / or ∘ the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue.

[0082] The first reference tissue is preferably healthy liver tissue and the second reference tissue is muscle tissue according to the invention.

[0083] In Fig. 2 (a) und Fig. 2 (b) The terms hyperenhancement and hypoenhancement are graphically illustrated. Fig 2 (a) und Fig 2 (b) is the intensity I of the signal measured during the MRI examination for two different areas in the liver of a patient as a function of time tThe solid curves, labeled with the reference symbol HCC, show the dynamic course of the intensity. I of a hepatocellular carcinoma; the dashed curves, labeled with the reference symbol L, show the dynamic course of the intensity. I of healthy liver tissue. The reference markers AP, PVP, and TP indicate the arterial phase (AP), the portal venous phase (PVP), and the transition phase (TP). The time point TP0 indicates the completion of the hepatobiliary contrast agent administration. After administration, the intensities of the MRI signals attributable to hepatocellular carcinomas increase sharply. The intensities of the MRI signals attributable to healthy liver tissue also increase, but less sharply: hyperenhancement of the HCC tissue compared to healthy liver tissue is present in the arterial phase AP.

[0084] After passing through a maximum, the intensities of the MRI signals attributable to the hepatocellular carcinoma tissue decrease again; in the case of the curve in Fig. 2 (a) faster than in the case of the curve in Fig. 2 (b) The intensities of the MRI signals attributable to healthy liver tissue continue to increase even after the arterial AP phase has ended; however, more slowly than in the arterial phase: this indicates the uptake of contrast agent in the liver cells.

[0085] The solid curve (HCC) decreases in Fig. 2 (a) In the portal venous phase, PVP is below the dashed curve (L): signal enhancement in hepatocellular carcinoma is lower than signal enhancement in healthy liver tissue. Hypoenhancement is present in HCC tissue compared to healthy liver tissue in the portal venous phase.

[0086] In the case of hepatocellular carcinoma in Fig. 2 (b) The hypoenhancement only kicks in later. The solid line in Fig. 2 (b) It only falls below the dashed line after the portal venous phase has ended. Fig. 2 (b) Hypoenhancement occurs only after the portal venous phase has ended.

[0087] According to the invention, the presence of a hepatocellular carcinoma is indicated if the lesion shows hyperenhancement compared to a first reference tissue in the arterial phase, and if the lesion shows hypoenhancement compared to a second reference tissue in the portal venous phase or in the transition phase, or if the contrast enhancement in the portal venous phase and / or the transition phase decreases more rapidly than in a second reference tissue, wherein the second reference tissue does not include hepatocytes, and / or the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and / or the transition phase is greater than the gradient of increasing contrast enhancement in healthy liver tissue.

[0088] To assess whether hyperenhancement and / or hypoenhancement is present, the gray values ​​of the pixels or voxels of the spatial representations (of the 2D images or 3D images) of lesions and reference tissue(s) can be analyzed.

[0089] In order to make a statement about whether a region exhibits hyperenhancement in one time period and hypoenhancement in another, the region must be uniquely identified and located in the representations that represent the region in the different time periods.In other words, the assessment of whether hyperenhancement is present in a region is based on at least one first representation that represents the region after administration of a contrast agent in the arterial phase; the assessment of whether hypoenhancement is present in a region is based on at least one second representation that represents the region after administration of a contrast agent in the portal venous phase and / or the transition phase; the region must therefore be clearly identifiable in both the first and second representations, and it must be the same region in both the first and second representations.

[0090] The generated representations can then be subjected to image registration. Image registration (also called "co-registration") is a process in digital image processing used to align two or more images of the same scene, or at least similar scenes, as closely as possible. One of the images is designated as the reference image, while the others are called object images. To optimally align these object images with the reference image, a compensating transformation is calculated. The images to be registered differ from each other because they were taken from different positions, at different times, or with different sensors.

[0091] In the case of the representations of the present invention, they were taken at different times.

[0092] The goal of image registration is therefore to find the transformation that best aligns a given object image with the reference image. The aim is that, as far as possible, each pixel / voxel of an image represents the same area in a patient's body as the pixel / voxel of another (co-registered) image with the same coordinates.

[0093] Methods for image registration are described in the state of the art (see e.g.: 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).

[0094] Co-registration can be performed for each entire representation (the whole image with all anatomical features captured in the image). It is also conceivable to restrict co-registration to the lesions, i.e., to modify the individual representations through transformation so that at least the lesions in each representation are represented by the corresponding pixel / voxel (where corresponding pixels / voxels have the same coordinates).

[0095] It is also conceivable to subject each representation to a segmentation procedure that detects lesions in the representations and marks them as such.

[0096] Methods for the detection and segmentation of lesions are described in the prior art (see, e.g., 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).

[0097] The area or areas in a representation that represent the reference tissue(s) can be determined by a radiologist or automatically.

[0098] It is therefore conceivable that a radiologist might mark one or more areas in the representations of the liver or part of the liver to serve as reference area(s).

[0099] Segmentation methods can also be used for the automated determination of one or more reference ranges (see e.g. WO2020 / 144134), which, for example, detect muscle tissue and / or liver tissue in the representations and define a reference range that represents the muscle tissue and / or liver tissue.

[0100] According to the teaching of the present invention, hyperenhancement for an area (a lesion) is present when the gray values ​​of the pixels / voxels representing the area are significantly above the gray values ​​of the pixels / voxels representing reference tissue within the arterial phase.

[0101] Hypoenhancement is present for an area (a lesion) when the gray values ​​of the pixels / voxels representing the area are significantly higher than the gray values ​​of the pixels / voxels representing the reference tissue during the arterial phase.

[0102] The term "significant" means that a higher or lower gray value is a measurement result that lies outside the error limits of the measurement system.

[0103] In principle, to detect hyperenhancement, it is sufficient to compare the gray value of a pixel / voxel representing the area with the gray value of a pixel / voxel representing a reference tissue. If the gray value of the pixel / voxel in the area is higher than the gray value of the pixel / voxel in the reference area (higher signal gain), hyperenhancement is present; otherwise, it is not. Similarly, to detect hypoenhancement, it is sufficient to compare the gray value of a pixel / voxel representing the area with the gray value of a pixel / voxel representing a reference tissue. If the gray value of the pixel / voxel in the area is lower than the gray value of the pixel / voxel in the reference area (lower signal gain), hypoenhancement is present; otherwise, it is not.

[0104] Preferably, multiple pixels / voxels of both the area and the reference area are evaluated. Preferably, the multiple pixels / voxels define a contiguous area in one or more representations; in other words, preferably the multiple pixels / voxels represent a contiguous area within the patient's body. If multiple pixels / voxels are used, a mean value of the grayscale value (or another value indicating signal intensity) can be calculated (e.g., the arithmetic mean). The comparison between an area and a reference area is then based on the respective mean values. Instead of or in addition to averaging over multiple spatially adjacent pixels / voxels, averaging over multiple pixels / voxels from temporally successive representations can also be performed.

[0105] In a preferred embodiment, signal intensities are determined along with their gradients. Such a gradient can be obtained for a region, for example, from two representations that represent the region at a time interval. This time interval can range from 1 second to 30 seconds. The shorter the time interval, the higher the accuracy with which changes (gradients) in signal intensity can be determined. Preferably, to determine gradients in a phase, 2 to 5 representations are generated that represent the liver or a part of the liver during that phase (arterial phase, portal venous phase, transition phase). If the signal intensity for a region increases from one representation to the next, the gradient is positive; conversely, if the signal intensity decreases, it is negative.The magnitude of the gradient indicates how rapid the increase or decrease in signal intensity is. For example, by determining one or more gradients following the arterial phase, it is possible to ascertain the rate of contrast agent washout in the portal venous and / or transition phase for a given area. This information can then be used, for instance, to define one or more time points for acquiring one or more secondary (or subsequent) representations.

[0106] Figur 3 This shows exemplary and schematic representations of a patient's liver. In the Figuren 3 (a), 3 (b), 3 (c), 3 (d), 3 (e) und 3 (f) The same cross-section of the liver is always shown at different times. In addition to the liver, reference tissue (R) is also shown; this could be, for example, muscle tissue. The information in the Figuren 3 (a) und 3 (f) The reference symbols shown apply to all Figuren 3 (a), 3 (b), 3 (c), 3 (d), 3 (e) and3 (f) They are only shown once each for the sake of clarity.

[0107] Fig. 3 (a) shows the cross-section through the liver before the intravenous administration of a hepatobiliary contrast agent (native representation). At a time point between the time points indicated by the Figuren 3 (a) und 3 (b) To visualize the contrast medium, a hepatobiliary contrast agent was administered intravenously (e.g., into an arm vein) as a bolus. This reached the target area in the bloodstream. Fig. 3 (b) The liver is supplied via the hepatic artery (A). Accordingly, the hepatic artery (A) is shown with increased signal intensity (arterial phase). A lesion that is primarily supplied with blood via arteries also stands out as a brighter (increased signal) area against the healthy liver tissue (L) and the reference tissue (R). At the time that in Figur 3 (c) As shown, the contrast agent reaches the liver via the veins (V). Figur 3 (d) The venous blood vessels (V) stand out as bright (signal-enhanced) areas from the liver tissue (L) and the reference tissue (R) (portal venous phase). Simultaneously, the signal intensity in the healthy liver cells (L), which are primarily supplied with contrast medium via the veins, increases continuously ( Fig. 3 (c) → 3 (d) → 3 (e) → 3 (f)). In the hepatobiliary phase, which in Fig. 3 (f) As shown, the liver cells (L) are displayed with enhanced signal; the blood vessels, the reference tissue and the lesion no longer contain any contrast agent and are accordingly shown in dark colors.

[0108] The question arises whether the lesion (HCC) in Fig. 3 it is a hepatocellular carcinoma.

[0109] In Fig. 4 are the representations that are in Fig. 3 (a), 3 (b), 3 (c), 3 (d) und 3 (e) The figures shown are presented again in a reduced size. They are labeled (a), (b), (c), (d) and (e).

[0110] For the area in the representations that represents the lesion, a signal intensity SB can be determined; for representation (a) the signal intensity SB (a)< , for representation (b) the signal intensity SB (b)< , for representation (c) the signal intensity SB (c)< , for representation (d) the signal intensity SB (d)< , and for representation (e) the signal intensity SB (e)< . The signal intensities can be, for example, the grayscale or color values ​​of pixels / voxels that represent the area.

[0111] Similarly, a signal intensity SR can be determined for the area in the representations that represents the reference tissue; for representation (a) the signal intensity SR (a)< , for representation (b) the signal intensity SR (b)< , for representation (c) the signal intensity SR (c)< , for representation (d) the signal intensity SR (d)< , and for representation (e) the signal intensity SR (e)< . The signal intensities can be, for example, the grayscale or color values ​​of pixels / voxels that represent the area.

[0112] To determine whether the lesion is a hepatocellular carcinoma, signal intensities in the area representing the lesion are compared with signal intensities in the area representing the reference tissue, for at least one representation during the arterial phase (AP), at least one representation during the portal venous phase (PVP), and / or at least one representation during the transition phase (TP). Representation (b) represents the arterial phase (AP). It is checked whether the signal intensity SB (b)< in the area representing the lesion is greater than the signal intensity SR (b)< in the area representing the reference tissue. If so, this provides initial evidence that the lesion is a hepatocellular carcinoma. If not, no further signal intensities need to be checked; a hepatocellular carcinoma can be ruled out.

[0113] Representation (d) represents the portal venous phase (PVP). It is checked whether the signal intensity SB(d)< in the area representing the lesion is lower than the signal intensity SR(d)< in the area representing the reference tissue. If so, this provides a second indication that the lesion is a hepatocellular carcinoma. If both the first and second indications are present, the lesion is reported as a hepatocellular carcinoma according to the invention. If only the first but not the second indication is present, the transition phase (TP) is considered. Representation (e) represents the transition phase (TP). It is checked whether the signal intensity SB(e)< in the area representing the lesion is lower than the signal intensity SR(e)< in the area representing the reference tissue.If SB (e)< is less than SR (e)< and the first indication is also present, it is indicated according to the invention that the lesion is a hepatocellular carcinoma.

[0114] If, according to the invention, a lesion is determined to be a hepatocellular carcinoma, a notification can be issued indicating that there is evidence of hepatocellular carcinoma. Preferably, a representation of the patient's liver or a part of the liver is displayed, in which the lesion showing evidence of hepatocellular carcinoma is identified. The corresponding lesion can, for example, be color-coded.

[0115] The invention can be implemented using a computer system.

[0116] A "computer system" is a system for electronic data processing that processes data using programmable instructions. Such a system typically comprises a "computer," the unit containing a processor for performing logical operations, as well as peripherals.

[0117] In computer technology, "peripherals" refers to all devices connected to a computer that are used to control the computer and / or as input and output devices. Examples include monitors (screens), printers, scanners, mice, keyboards, drives, cameras, microphones, speakers, etc. Internal ports and expansion cards are also considered peripherals in computer technology.

[0118] Today's computer systems are often divided into desktop PCs, portable PCs, laptops, notebooks, netbooks and tablet PCs, and so-called handhelds (e.g., smartphones); all these systems can be used to carry out the invention.

[0119] Input into the computer system is made via input devices such as a keyboard, a mouse, a microphone, a touch-sensitive display and / or the like.

[0120] Output can be displayed on a monitor, a printer, or a data storage device.

[0121] Figur 5 Figure 10 schematically and exemplarily shows an embodiment of the computer system according to the invention. The computer system (10) comprises a receiving unit (11), a control and processing unit (12), and an output unit (13).

[0122] The computer system (10) according to the invention is configured to receive representations of a liver or part of a patient's liver and to identify one or more areas in the representations that are indicative of hepatocellular carcinoma.

[0123] The control and processing unit (12) serves to control the receiving unit (11) and the output unit (13), to coordinate the data and signal flows between the different units, to process representations, and to determine and compare signal intensities. It is conceivable that several control and processing units are present.

[0124] The receiving unit (11) serves to receive the representations. The representations can, for example, be transmitted from a magnetic resonance imaging (MRI) scanner or read from a data storage device. The MRI scanner 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 a MRI scanner. The transmission of representations can take place via a network connection or a direct connection. The transmission of representations can take place via a wireless connection (WLAN, Bluetooth, mobile network, and / or the like) and / or via a cable. It is conceivable that several receiving units are present. The data storage device can also be a component of the computer system according to the invention or be connected to it, for example, via a network. It is conceivable that several data storage devices are present.

[0125] The receiving unit receives the representations and possibly further data (such as information about the object under investigation, recording parameters and / or the like) and transmits them to the control and computing unit.

[0126] The control and computing unit is configured to identify areas that may indicate hepatocellular carcinoma based on the received data.

[0127] The output unit (13) can display the results of the analysis (for example, on a monitor), output them (e.g., via a printer), or store them in a data storage device. It is conceivable that multiple output units are present.

Claims

1. Computer-implemented method comprising the steps of: - receiving a plurality of representations, ∘ wherein the plurality of representations represents ▪ a liver of a patient or part of the liver of the patient, and ▪ reference tissue (R) of the patient, ∘ wherein at least one representation of the plurality of representations represents ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during a portal venous phase (PVP) of a dynamic contrast-enhanced magnetic resonance imaging examination, and ∘ wherein at least one representation of the plurality of representations represents ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during a transitional phase (TP) of the dynamic contrast-enhanced magnetic resonance imaging examination, wherein the contrast agent is a hepatobiliary contrast agent, wherein the reference tissue (R) is muscle tissue, - analysing the representations and, in doing so, identifying one or more regions in the liver ∘ in which contrast agent leads in the portal venous phase (PVP) and / or the transitional phase (TP) to a lower contrast enhancement than in the reference tissue (R), and / or ∘ in which the contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) drops more rapidly than in the reference tissue (R), wherein the reference tissue does not comprise hepatocytes (R), and / or ∘ in which the absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue (L), - outputting a representation of the liver or the part of the liver, wherein in the representation the identified region is highlighted or the identified regions are highlighted.

2. Method according to Claim 1, wherein the hepatobiliary contrast agent is the disodium salt of gadoxetic acid.

3. Method according to any of Claims 1 to 2, comprising the steps of: - receiving the plurality of representations, ∘ wherein at least two representations of the plurality of representations represent ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during the portal venous phase (PVP), and ∘ wherein at least two representations of the plurality of representations represent ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during the transitional phase (TP), - analysing the plurality of received representations and, in doing so, identifying the one region or the multiple regions in the liver ∘ in which the contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) drops more rapidly than in the reference tissue (R), wherein the reference tissue (R) does not comprise hepatocytes, and / or ∘ in which the absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue (L), - outputting the representation of the liver or the part of the liver, wherein in the representation the identified region is highlighted or the identified regions are highlighted.

4. Method according to any of Claims 1 to 3, further comprising the steps of: - receiving at least one representation, ∘ wherein the at least one representation represents ▪ the liver or the part of the liver, and ▪ a first and / or second reference tissue during an arterial phase (AP) of the dynamic contrast-enhanced magnetic resonance imaging examination, - identifying one or more regions in the liver, wherein the region / regions is / are characterized by the following features: ∘ contrast agent leads in the arterial phase (AP) to a higher contrast enhancement than in the first reference tissue, wherein the first reference tissue is healthy liver tissue (L) or muscle tissue, and ∘ contrast agent leads in the portal venous phase (PVP) and / or transitional phase (TP) to a lower contrast enhancement than in the second reference tissue, wherein the second reference tissue is muscle tissue, and / or ∘ the contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) drops 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 (PVP) and / or the transitional phase (TP) is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue (L), - outputting a representation of the liver or the part of the liver, wherein in the representation the identified region is highlighted or the identified regions are highlighted.

5. Computer system (10) comprising • a receiving unit (11), • a control and calculation unit (12) and • an output unit (13), - wherein the control and calculation unit (12) is configured to cause the receiving unit (10) to receive a plurality of representations ∘ wherein the plurality of representations represents ▪ a liver of a patient or part of the liver of the patient, and ▪ reference tissue (R) of the patient, o wherein at least one representation of the plurality of representations represents ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during a portal venous phase (PVP) of a dynamic contrast-enhanced magnetic resonance imaging examination, and ∘ wherein at least one representation of the plurality of representations represents ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during a transitional phase (TP) of the dynamic contrast-enhanced magnetic resonance imaging examination, wherein the contrast agent is a hepatobiliary contrast agent, wherein the reference tissue (R) is muscle tissue, - wherein the control and calculation unit (12) is configured to analyse the representations and, in doing so, identify one or more regions in the liver ∘ in which contrast agent leads in the portal venous phase (PVP) and / or the transitional phase (TP) to a lower contrast enhancement than in the reference tissue (R), and / or ∘ in which the contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) drops more rapidly than in the reference tissue (R), wherein the reference tissue (R) does not comprise hepatocytes, and / or ∘ in which the absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue (L), - wherein the control and calculation unit (12) is configured to cause the output unit (13) to output a representation of the liver or the part of the liver, wherein in the representation the identified region is highlighted or the identified regions are highlighted.

6. Computer program product comprising a computer program which can be loaded into a working memory of a computer, where it causes the computer to execute the following steps: - receiving a plurality of representations ∘ wherein the plurality of representations represents ▪ a liver of a patient or part of the liver of the patient, and ▪ reference tissue (R) of the patient, o wherein at least one representation of the plurality of representations represents ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during a portal venous phase (PVP) of a dynamic contrast-enhanced magnetic resonance imaging examination, and ∘ wherein at least one representation of the plurality of representations represents ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during a transitional phase (TP) of the dynamic contrast-enhanced magnetic resonance imaging examination, wherein the contrast agent is a hepatobiliary contrast agent, wherein the reference tissue (R) is muscle tissue, - analysing the representations and, in doing so, identifying one or more regions in the liver ∘ in which contrast agent leads in the portal venous phase (PVP) and / or the transitional phase (TP) to a lower contrast enhancement than in the reference tissue (R), and / or ∘ in which the contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) drops more rapidly than in the reference tissue (R), wherein the reference tissue (R) does not comprise hepatocytes, and / or ∘ in which the absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue (L), - outputting a representation of the liver or the part of the liver, wherein in the representation the identified region is highlighted or the identified regions are highlighted.

7. Use of a hepatobiliary contrast agent in a dynamic contrast-enhanced magnetic resonance imaging examination method, wherein the examination method comprises the following steps: - administering the contrast agent into a vein of a patient remote from an artery, - generating a plurality of representations ∘ wherein the plurality of representations represents ▪ the liver of the patient or part of the liver of the patient, and ▪ reference tissue (R) of the patient, ∘ wherein at least one representation of the plurality of representations represents ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during a portal venous phase (PVP) of the examination method, and ∘ wherein at least one representation of the plurality of representations represents ▪ the liver or the part of the liver, and ▪ the reference tissue (R) during a transitional phase (TP) of the examination method, wherein the reference tissue (R) is muscle tissue, - analysing the representations and, in doing so, identifying one or more regions in the liver ∘ in which contrast agent leads in the portal venous phase (PVP) and / or the transitional phase (TP) to a lower contrast enhancement than in the reference tissue (R), and / or ∘ in which the contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) drops more rapidly than in the reference tissue (R), wherein the reference tissue (R) does not comprise hepatocytes, and / or ∘ in which the absolute value of the gradient of the decreasing contrast enhancement in the portal venous phase (PVP) and / or the transitional phase (TP) is greater than the absolute value of the gradient of the increasing contrast enhancement in healthy liver tissue (L), - outputting a representation of the liver or the part of the liver, wherein in the representation the identified region is highlighted or the identified regions are highlighted.

8. Kit comprising a contrast agent and a computer program product according to Claim 6.

9. Kit according to Claim 8, wherein the contrast agent is the disodium salt of gadoxetic acid.