EP4041057A1

EP4041057A1 - Acceleration of mri examinations

Info

Publication number: EP4041057A1
Application number: EP20785507.3A
Authority: EP
Inventors: Gesine KNOBLOCH; Christian LIENERTH
Original assignee: Bayer AG
Current assignee: Bayer AG
Priority date: 2019-10-11
Filing date: 2020-10-05
Publication date: 2022-08-17
Also published as: AU2020362909A1; WO2021069343A1; EP4241672A3; CA3157469A1; EP4241672A2; JP2022552484A; CN114502069A; US20230120273A1

Abstract

The invention relates to the acceleration of MRI examinations, particularly during the detection and differential diagnosis of focal liver lesions by way of dynamic contrast-enhanced magnetic resonance imaging (MRI). The invention also relates to a method, a system and a computer program product for generating MRI images, particularly of the liver.

Description

Speed up MRI exams

The present invention is concerned with the acceleration of MRT examinations, in particular in the detection and differential diagnosis of focal liver lesions by means of dynamic contrast-enhancing magnetic resonance tomography (MRT). The present invention relates in particular to a method, a system and a computer program product for generating MRT images, in particular of the liver.

Magnetic resonance imaging, abbreviated as MRT or MR (MRT Magnetic Resonance Imaging), is an imaging method that is used primarily in medical diagnostics to display the structure and function of tissues and organs in the human or animal body.

In MR imaging, the magnetic moments of protons in an examination subject are aligned in a basic magnetic field, so that macroscopic magnetization occurs along a longitudinal direction. This is then deflected from the rest position by the radiation of high frequency (HF) pulses (excitation). The return of the excited states to the rest position (relaxation) or the magnetization dynamics is then detected as relaxation signals by means of one or more RF receiving coils.

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

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

The TI relaxation describes the transition of the longitudinal magnetization to its equilibrium state, where TI is the time that is required to reach 63.21% of the equilibrium magnetization before the resonance excitation. It is also called the longitudinal relaxation time or the spin-lattice relaxation time.

The T2 relaxation describes in an analogous way the transition of the transverse magnetization to its equilibrium state.

MR contrast media develop their effect by changing the relaxation times of the structures that absorb the contrast media. A distinction can be made between two groups of substances: paramagnetic and superparamagnetic substances. Both groups of substances have unpaired electrons that induce a magnetic field around the individual atoms or molecules.

Superparamagnetic contrast media lead to a predominant T2 shortening, while paramagnetic contrast media mainly lead to a T1 shortening. A shortening of the Tl time leads to an increase in the signal intensity in TI -weighted MRI images, a shortening of the T2 time leads to a decrease in the signal intensity in T2 -weighted MRI images.

The effect of this contrast agent is indirect, since the contrast agent itself does not emit a signal, but only influences the signal intensity of the hydrogen protons in its environment.

An example of a superparamagnetic contrast agent are iron oxide nanoparticles (SPIO, English: superparamagnetic iron oxide).

Examples of paramagnetic contrast media are gadolinium chelates such as gadopentetate dimeglumine (trade name: Magnevist ^®, etc.), gadobenate dimeglumine (trade name: Multihance ^® ), gadoteric acid (Dotarem ^® , Dotagita ^® , Cyclolux ^® ), gadodiamide (Omniscan ^® ), gadoteridol (ProHance ^® ) and gadobutrol (Gadovist ^® ).

Extracellular, intracellular and intravascular contrast media can be differentiated according to their distribution pattern in the tissue.

Contrast media based on gadoxetic acid are characterized by the fact that they are specifically absorbed by liver cells, the hepatocytes, accumulate in the functional tissue (parenchyma) and the contrasts in healthy liver tissue increase. The cells of cysts, metastases and most hepatocellular carcinomas no longer work like normal liver cells, do not or hardly absorb the contrast medium, are not shown intensified and can thus be identified and localized.

Examples of contrast media based on gadoxetic acid are described in US Pat. No. 6,039,931A; they are commercially available, for example under the brand names Primovist ^® or Eovist ^®.

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, which has an extremely high thermodynamic stability. The ethoxybenzyl residue (EOB) is the mediator of the hepatobiliary uptake of the contrast agent.

Primovist ^® can be used to detect tumors in the liver. The blood supply to healthy liver tissue is primarily via the portal vein (Vena portae), while the liver artery (Arteria hepatica) supplies most of the primary tumors. Accordingly, after an intravenous bolus injection of a contrast agent, a time delay can be observed between the signal increase in the healthy liver parenchyma and the tumor.

In addition to malignant tumors, benign lesions such as cysts, hemangiomas and focal nodular hyperplasias (FNH) are often found in the liver. For proper therapy planning, these must be differentiated from the malignant tumors. Primovist ^® can be used to detect benign and malignant focal liver lesions. It provides information about the character of these lesions using TI-weighted MRI. The differentiation uses the different blood supply to the liver and tumor and the time course of the contrast enhancement.

The contrast enhancement achieved with Primovist ^® can be divided into at least two phases: a dynamic phase (including the so-called arterial phase, portal venous phase and late phase) and the hepatobiliary phase, in which a significant uptake of Primovist ^® in the hepatocytes has already taken place .

The temporal tracking of the distribution of the contrast medium over the dynamic phase and the hepatobiliary phase offers on the one hand a good possibility for the detection and differential diagnosis of focal liver lesions; on the other hand, however, the investigation extends over a comparatively long period of time. During this period of time, movements of the patient should be avoided in order to minimize movement artifacts in the MRT image. The long-term restriction of movement can be uncomfortable for a patient.

Based on the state of the art described, the technical task was to reduce the time span of the MRT examination.

This object is achieved by the subjects of the independent claims. Preferred embodiments of the present invention can be found in the dependent claims, in this description and in the drawings. A first object of the present invention is a method comprising the steps

Receiving a first MRT recording of an examination subject, the first MRT recording showing a liver or part of a liver of the examination subject at a first point in time after application of a first contrast agent, with healthy liver cells at the first point in time as a result of the application of the first contrast agent in of the first MRI image are displayed with enhanced contrast,

Receiving a second MRT image of the same examination subject, the second MRT image showing the same liver or the same part of the liver at a second point in time after the application of a second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRT recording are shown with a high contrast, and blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRT recording are shown with a high contrast,

Generating a first MRT image from the first MRT recording and the second MRT recording, the first MRT image showing the same liver or the same part of the liver at the second point in time, the contrast between healthy liver cells and blood vessels in the first MRT Image is enlarged compared to the second MRI image,

Displaying and / or outputting the first MRT image and / or storing the first MRT image in a data memory.

Another object of the present invention is a system comprising

• a receiving unit,

• a control and computing unit and

An output unit, the control and computing unit being configured to cause the receiving unit to receive a first MRT image of an examination subject, the first MRT image of a liver or part of a liver of the examination subject at a first point in time after an application shows healthy liver cells at the first point in time as a result of the application of the first contrast agent in the first MRI image with a higher contrast, the control and computing unit being configured to cause the receiving unit to assign a second MRI image to an examination subject received, wherein the second MRT image shows the same liver or the same part of the liver at a second point in time after application of a second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRI image with increased contrast are, and wherein blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRT image are shown with enhanced contrast, the control and computing unit being configured to generate a first MRT image from the first MRI image and the second MRI image. Generate image, the first MRI image being the same Shows the liver or the same part of the liver at the second point in time, the contrast between healthy liver cells and blood vessels in the first MRT image being increased compared to the second MRT recording, the control and arithmetic unit being configured to cause the output unit to do the display, output or save the first MRT image in a data memory.

Another object of the present invention is a computer program product comprising a computer program that can be loaded into a main memory of a computer system and there causes the computer system to carry out the following steps:

Receiving a second MRI image of the same examination subject, the second MRI image showing the same liver or the same part of the liver at a second point in time after the application of a second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRT recording are shown with a high contrast, and blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRT recording are shown with a high contrast,

Another object of the present invention is the use of a first and a second contrast agent in an MRT method, the MRT method comprising the following steps:

Application of the first contrast agent,

Generating a first MRT recording, the first MRT recording showing a liver or part of a liver at a first point in time after the application of the first contrast agent, with healthy liver cells at the first point in time as a result of the application of the first contrast agent in the first MRT Recording are shown with enhanced contrast,

Application of the second contrast agent at a point in time after the first MRT image has been generated, Generating a second MRI image, the second MRI image showing the same liver or the same part of the liver at a second point in time after the application of the second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRI Recordings are shown with increased contrast, and blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRT image are shown with increased contrast,

Another subject matter is a first and a second contrast agent for use in an MRT method, the MRT method comprising the following steps:

Application of the first contrast agent,

Generating a first MRT recording, the first MRT recording showing a liver or part of a liver at a first point in time after the application of the first contrast medium, with healthy liver cells at the first point in time as a result of the application of the first contrast medium in the first MRT Recording are shown with enhanced contrast,

Application of the second contrast agent at a point in time after the first MRT image has been generated,

Generating a second MRI image, the second MRI image showing the same liver or the same part of the liver at a second point in time after the application of the second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRI Recordings are shown with increased contrast, and blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRT image are shown with increased contrast,

Another subject matter is a kit comprising a contrast agent and a computer program product according to the invention. The invention is explained in more detail below without distinguishing between the subjects of the invention (method, system, computer program product, use, contrast agent for use, kit). Rather, the following explanations should apply analogously to all subjects of the invention, regardless of the context (method, system, computer program product, use, contrast agent for use, kit) in which they are made.

In a classic MRT examination of the liver or part of the liver of an examination subject, a hepatobiliary contrast agent is applied in the form of a single bolus. A series of MRI images are then generated showing the liver or part of the liver during the arterial phase, the portal venous phase, the late phase and the hepatobiliary phase. The examination subject is usually already in the nuclear spin tomograph when the contrast agent is applied. Since the contrast agent is distributed comparatively slowly in the examination area after intravenous administration as a bolus, the MRT examination extends over a comparatively long period of time. It is usually around ten to twenty minutes.

According to the invention, this examination period is shortened in that contrast agent is applied in the form of two boluses, the examination subject not yet being in the magnetic resonance tomograph at the time of the first application.

A first contrast agent is applied as a bolus while the examination subject is not yet in the magnetic resonance tomograph and a second contrast agent is applied as a bolus when the examination subject is in the magnetic resonance tomograph. The first contrast agent is a hepatobiliary contrast agent; the second contrast agent can be the same contrast agent as the first contrast agent; however, the second contrast agent can also be a different one, in particular an extracellular contrast agent.

The MRT examination only begins at a point in time in a (first) hepatobiliary phase at which the first contrast agent already leads to a contrast enhancement of healthy liver tissue. At this point in time, which is also referred to as the first point in time in this description, a first MRT image is generated. Only at this point in time does the examination object have to be in the nuclear spin tomograph. At this first point in time, the arterial phase, the portal venous phase and the late phase as a result of the application of the first contrast agent have already passed; therefore, no MRT images could be generated which show the liver or part of the liver during this arterial phase, this portal venous phase and / or this late phase. In order to still receive MRT recordings of these phases, a second contrast agent is administered and the spread of the second contrast agent via the blood vessels is tracked by means of MRI. In the MRT recordings that are generated after the application of the second contrast agent, the first contrast agent is still in the healthy liver cells, so that the contrast between the blood vessels and the healthy liver cells is low. In order to increase the contrast between the healthy liver cells and the blood vessels, artificial MRI images are made from the MRI images after the application of the second contrast agent using one or more MRI images before the application of the second contrast agent but after the application of the first contrast agent generated with an increased contrast. In one embodiment, this is done by subtracting an MRI image that was generated during the hepatobiliary phase after the application of the first contrast agent and before the application of the second contrast agent, from one or more MRI images that were generated during the dynamic phase (ie during the arterial, portal venous and / or the late phase) has / have been generated after the application of the second contrast agent. In a further embodiment, artificial MRT images are generated with the aid of an artificial neural network. In both embodiments, artificial MRT images can be generated that give the impression that no first contrast agent had been administered, but only the second contrast agent had been applied.

The “object to be examined” is usually a living being, preferably a mammal, very particularly preferably a human.

A part of the examination subject is subjected to a contrast-enhanced magnetic resonance tomography examination. The “examination area”, also called the recording volume (field of view, FOV), represents in particular a volume that is mapped in the magnetic resonance recordings. The examination area is typically determined by a radiologist, for example on a localizer. Of course, the examination area can alternatively or additionally also be determined automatically, for example on the basis of a selected protocol. The examination area comprises at least part of the liver of the examination subject.

A first contrast agent, which is distributed in the examination area, is administered to the examination subject. The first contrast agent is preferably administered intravenously as a bolus, weight-adapted (e.g. into a vein in the arm).

A “contrast medium” is understood to mean a substance or mixture of substances, the presence of which leads to a changed signal in a magnetic resonance measurement. The first contrast agent preferably leads to a shortening of the TI relaxation time and / or the T2 relaxation time.

The first contrast agent is a hepatobiliary contrast agent such as Gd-EOB-DTPA or Gd-BOPTA.

In a particularly preferred embodiment, the first contrast agent is a substance or a mixture of substances with gadoxetic acid or a salt of gadoxetic acid as the contrast-enhancing active ingredient. It is very particularly preferably the disodium salt of gadoxetic acid (Gd-EOB-DTPA disodium).

After intravenous administration of the hepatobiliary contrast agent in the form of a bolus into a vein in the arm, the contrast agent first reaches the liver via the arteries. These are shown with enhanced contrast in the corresponding MRI images. The phase in which the hepatic arteries are shown with enhanced contrast in MRI images is known as the "arterial phase". This phase begins immediately after the application of the contrast agent and usually lasts 15 to 60 seconds.

The contrast agent then reaches the liver via the hepatic veins. While the contrast in the hepatic arteries is already decreasing, the contrast in the hepatic veins reaches a maximum. The phase in which the hepatic veins are shown with enhanced contrast in MRI images is referred to as the "portal venous phase". This phase can begin during the arterial phase and overlap with it. This phase usually starts 60 to 70 seconds after intravenous administration and usually lasts 50 to 70 seconds.

The "late phase" follows the portal venous 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 the healthy liver cells gradually increases in the late phase. This phase usually begins 100 to 140 seconds after the application of the contrast agent and usually lasts 50 to 70 seconds.

The arterial phase, the portal venous phase and the late phase are collectively referred to as the “dynamic phase”. 10-20 minutes after its injection, a hepatobiliary contrast agent leads to a clear signal amplification in the healthy liver parenchyma. This phase is known as the "hepatobiliary phase". The contrast agent is only slowly excreted from the liver cells; accordingly, the hepatobiliary phase can last two hours or more.

The phases mentioned 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/jjhep.2019.05.005).

An extracellular contrast agent is not absorbed by the liver cells and does not accumulate in healthy liver tissue. An extracellular contrast medium therefore only shows a dynamic phase (comprising an arterial phase, a portal venous phase and a late phase).

According to the invention, contrast agent is administered in the form of two boluses. The first application takes place at a point in time at which the examination subject is not yet in the nuclear spin tomograph. The first contrast agent is administered during the first application.

After the application of the first contrast agent, a period of time can be waited before the examination object is introduced into the nuclear spin tomograph and a first MRT image is generated at a first point in time. The period of time between the first application and the generation of the first MRT image is preferably in the range from 5 minutes to 1 hour, even more preferably in the range from 10 minutes to 30 minutes, most preferably in the range from 8 minutes to 25 minutes.

The first MRT image shows the liver or part of the liver of the examination subject during the hepatobiliary phase after the application of the first contrast agent. Healthy liver cells as a result of the application of the first contrast agent are shown with increased contrast in the first MRI image.

The hepatobiliary phase in which the first MRT image is generated is also referred to in this description as the first hepatobiliary phase. The first contrast agent has reached the healthy liver cells and leads to a contrast enhancement, in the case of a paramagnetic contrast agent to a signal amplification of the healthy liver cells. During the arterial phase, the portal venous phase and the late phase that occur after the application of the first contrast agent, no MRT images are generated. The arterial phase, the portal venous phase and the late phase that occur after the application of the first contrast agent are also referred to in this description as the first arterial phase, the first portal venous phase and the first late phase.

It is conceivable that several MRT images are generated during the first hepatobiliary phase.

After one or more first MRT images have been generated during the first hepatobiliary phase, contrast agent is applied a second time. The second time, a second contrast agent is applied. The second contrast agent can be the same contrast agent as the first contrast agent; however, the second contrast agent can also be another, preferably an extracellular, contrast agent. The second contrast agent is also preferably administered intravenously as a bolus, weight-adapted (e.g. into a vein in the arm).

The application of the first contrast agent is also referred to as the first application in this description; the application of the second contrast agent is also referred to as the second application in this description. If the first contrast agent and the second contrast agent are the same, a first application of a hepatobiliary contrast agent takes place and a second application of the hepatobiliary contrast agent takes place at a later point in time. Are the first contrast agent and the second Contrast media different, a first application of a first contrast agent takes place, the first contrast agent being a hepatobiliary contrast agent, and a second application of a second (different) contrast agent takes place at a later point in time.

At the time of the second application (or at the time of the application of the second contrast agent) the examination subject is preferably already in the nuclear spin tomograph. After the application of the second contrast agent, an arterial phase, a portal venous phase and a late phase are passed through again. This arterial phase, portal venous phase and late phase are also referred to in this description as the second arterial phase, second portal venous phase and second late phase. In the second arterial phase and / or in the second portal venous phase and / or in the second late phase, an MRT image or several MRT images are generated. These MRI images are referred to as second, third, fourth, and so on in the order they were taken.

In a preferred embodiment, a second MRT recording is generated during the second arterial phase, a third MRT recording is generated during the second portal venous phase and a fourth MRT recording is generated during the second late phase. Such a second MRT image shows, in particular, arteries with enhanced contrast; Such a third MRI image shows veins in particular with enhanced contrast.

It is also conceivable that more than one MRT image is generated during the phases mentioned.

The measured MRT recordings can be present as two-dimensional image recordings which show a cutting plane through the examination subject. The measured MRT recordings can be present as a stack of two-dimensional image recordings, with each individual image record of the stack showing a different cutting plane. The measured MRT images can be available as three-dimensional images (3D images). For the sake of simplicity of illustration, the invention is explained at some points in the present description on the basis of the presence of two-dimensional MRT images, without, however, wishing to restrict the invention to two-dimensional MRT images. It is clear to the person skilled in the art how what is described in each case can be transferred to stacks of two-dimensional image recordings and to 3D recordings (see, for example, M. Reisler, W. Semmler: Magnetetresonanztomographie, Springer Verlag, 3rd edition, 2002, ISBN: 978-3- 642-63076-7).

The measured MRT images are usually available as digital image files. The term “digital” means that the MRT images can be processed by a machine, usually a computer system. “Processing” is understood to mean the known procedures for electronic data processing (EDP).

Digital image files can be in a variety of formats. For example, digital image files can be encoded as raster graphics. Raster graphics consist of a raster-shaped arrangement of so-called image points (pixels) or volume elements (voxels), each of which is assigned a color or a gray value. The main characteristics of a 2D raster graphic are therefore the image size (width and height measured in pixels, colloquially also called image resolution) and the color depth. A color is usually assigned to a pixel in a digital image file. The color coding 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 saves a black and white value. In an image whose color is defined via the so-called RGB color space (RGB stands for the basic colors red, green and blue), each pixel consists of three subpixels, one subpixel for the color red, one subpixel for the color green and one Subpixels for the color blue. The color of an image point results from the superimposition (additive mixing) of the color values of the subpixels. The color value of a subpixel is divided into 256 color nuances, which are called tone values and usually range from 0 to 255. The color shade "0" of each color channel is the darkest. If all three channels have the tone value 0, the corresponding pixel appears black; if all three channels have the tone value 255, the corresponding pixel appears white. In carrying out the present invention, digital image files (MRI recordings) are subjected to certain operations. The operations mainly concern the pixels or the tonal values of the individual pixels. There are a variety of possible digital image formats and color codings. For the sake of simplicity, it is assumed in this description that the present images are grayscale raster graphics with a specific number of image points, with each image point being assigned a tone value which indicates the gray value of the image. However, this assumption should in no way be understood as limiting. It is clear to the person skilled in the art of image processing how he can transfer the teaching of this description to image files which exist in other image formats and / or in which the color values are coded differently.

In a next step, MRT images are generated from the MRT images that were generated during one or more phases after the application of the first and the second contrast agent.

The term “MRT image” is a language creation. The term was created in order to be able to better distinguish the various MRT images generated and used within the scope of the invention. While a first, second, third and fourth MRT image in the sense of the present invention is an image generated by measurement technology, an MRT image is understood to be an artificial representation that is the result of calculations. An MRT image itself is therefore not generated by measurement technology, but rather it is calculated from at least two measurement technology generated MRT images. MRT images are preferably in the same form as the MRT images from which they are generated (e.g. in the form of digital image files).

An MRT image is calculated from each MRT image generated during one or more phases after the application of the second contrast agent, preferably using the first MRT image: from the second MRT image and preferably from the first MRI image a first MRT image is calculated; if available, a second MRT image is calculated from the third MRT image and preferably the first MRT image; if available, a third MRT image is calculated from the fourth MRT recording and preferably the first MRT recording; and so on.

The aim of generating MRI images from the MRI images is to increase the contrast between healthy liver tissue and other areas. When using a hepatobiliary paramagnetic contrast medium as the first contrast medium, the signal intensity of healthy liver tissue is still increased during the second arterial phase, the second portal venous phase and the second late phase as a result of the application of the first contrast medium. The second contrast agent, which spreads in said second phases, also leads to an increased signal in the tissue in which it spreads. This means that there is only a slight contrast in the MRT images between the healthy liver tissue and the rest of the tissue that has been contrast-enhanced by a (second) contrast agent. In order to increase this contrast, in a preferred embodiment the first MRT image is subtracted from the second MRT image. If available, the first MRT image can also be subtracted from the third MRT image. If available, the first MRI image can also be subtracted from the fourth MRI image. And so on.

With such a subtraction, the tone values of corresponding pixels or voxels are usually subtracted from one another. Two pixels or voxels then correspond to one another if they show the same examination area. It is conceivable that the MRT images that are subjected to a subtraction are subjected to a movement correction beforehand. Such a movement correction ensures that a pixel or voxel of the first MRT recording shows the same examination area as the corresponding pixel or voxel of the second MRT recording, the third MRT recording, the fourth MRT recording and so on. Motion correction methods are described in the prior art (see for example: EP3118644, EP3322997, US20080317315, US20170269182, US20140062481, EP2626718).

By subtracting MRT images, in particular the signal intensity in the healthy liver tissue is reduced.

The MRT images that are generated by subtracting the first MRT exposure from the second MRT exposure and from the third MRT exposure and from the fourth MRT exposure and so on show the distribution of contrast agent in the tissue approximately as follows what it would be like if only contrast agent had been applied in the form of a single bolus - with the difference that the MRT examination is shortened, since the examination subject has to spend a shorter period of time in the magnetic resonance tomograph.

In a further embodiment, one or more MRT images are calculated with the aid of an artificial neural network that is trained to generate an MRT image from a first MRT recording and a second MRT recording. The first MRI image shows a liver or part of a liver of an examination subject in a first hepatobiliary phase, ie at a first point in time after application of a hepatobiliary contrast agent, with healthy liver cells at the first point in time as a result of application of the first contrast agent in the first MRI -The recording is shown with enhanced contrast. The second MRT image shows the same liver or the same part of the liver at a second point in time after the application of a second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent being shown in the second MRI image with increased contrast, and with blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRT image are shown in a contrast-enhanced manner. The MRI image shows the same liver or the same part of the liver as it would look if only the second contrast agent had been applied: the blood vessels are contrast-enhanced as a result of the application of the second contrast agent, but healthy liver cells are not as a result of the application of one first contrast agent shown with enhanced contrast. In other words, an MRT image is generated that looks like the second MRT image, with the difference that the contrast enhancement of the healthy liver cells, which was caused by the application of the first contrast agent, comes from the second MRT image is deducted (eliminated).

Such an artificial neural network comprises at least three layers of processing elements: a first layer with input neurons (nodes), an N-th layer with at least one output neuron (node) and N-2 inner layers, where N is a natural number and greater than 2 .

The input neurons are used to receive digital MRT recordings as input values, for example a first MRT recording and a second MRT recording. There is usually an input neuron for each pixel or voxel in a digital MRI image. Additional input neurons can be used for additional input values (e.g. information on the examination area, on the examination subject, on conditions that prevailed when the MRT recordings were generated, and / or information on the times or periods of time at which the MRT recordings were generated) to be available. In such a network, the output neurons are used to output an MRT image.

The processing elements of the layers between the input neurons and the output neurons are connected to one another in a predetermined pattern with predetermined connection weights.

The artificial neural network is preferably a so-called convolutional neural network (CNN for short).

A convolutional neural network is able to process input data in the form of a matrix. This makes it possible to use digital MRT images (e.g. width x height x color channels) displayed as a matrix as input data. A normal neural network, for example in the form of a multi-layer perceptron (MLP), on the other hand, requires a vector as input, ie to use an MRI image as an input, the pixels or voxels of the MRI image would have to be rolled out in a long chain . As a result, normal neural networks are not able, for example, to recognize objects in an MRI image regardless of the position of the object in the MRI image. The same object at a different position in the MRI image would have a completely different input vector.

A CNN essentially consists of filters (convolutional layer) and aggregation layers (pooling layer), which are alternately repeated, and at the end of one or more layers of "normal" completely connected neurons (dense / fully connected layer).

Details can be found in the state of the art (see e.g. S. Khan et al .: A Guide to Convolutional Neural Networks for Computer Vision, Morgan & Claypool Publishers 2018, ISBN 1681730227, 9781681730226, WO2018 / 183044A1, WO2018 / 200493, WO2019 / 074938A1, WO2019 / 204406A1, WO2019 / 241659A1).

The training of the neural network can take place in a monitored machine learning with a training data set. The training data set comprises a multiplicity of first reference MRT recordings, second reference MRT recordings and third reference MRT recordings.

Such a first reference MRT recording corresponds to a first MRT recording: it shows a liver or part of a liver of an examination subject at a first point in time after application of a first contrast agent, with healthy liver cells at the first point in time as a result of application of the first contrast agent are shown with enhanced contrast in the first MRI image.

Such a second reference MRI image corresponds to a second MRI image: it shows the same liver or the same part of the liver at a second point in time after the application of a second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in of the second MRT image are shown with increased contrast, and blood vessels at the second point in time as a result of the application of the second contrast agent are shown with increased contrast in the second MRT image. The blood vessels can be arteries and / or veins.

Such a third reference MRI image shows the same liver or the same part of the liver at a second point in time after application of a second contrast agent without a first contrast agent having been applied before the second point in time: only blood vessels are present at the second point in time as a result of the application of the second contrast agent shown in the second MRI image with enhanced contrast. In machine learning, a statistical model is generated that is based on the training data. This means that the examples are not simply learned by heart, but the model “recognizes” patterns and regularities in the training data. In this way, the model can also assess unknown data. Validation data can be used to check the quality of the assessment of unknown data.

The model is usually trained by means of supervised learning, ie the model is presented with first and second reference MRT recordings and it is informed which third reference MRT recordings with the respective first and second reference -MRT receptacles are connected. The algorithm then learns a relationship between the reference MRT recordings in order to predict (calculate) third MRT images for unknown first and second MRT recordings.

Self-learning algorithms that are trained by means of supervised learning are described in many ways in the prior art (see e.g. C. Perez: Machine Learning Techniques: Supervised Learning and Classification, Amazon Digital Services LLC - Kdp Print Us, 2019, ISBN 1096996545, 9781096996545, WO2018 / 183044A1, WO2018 / 200493, WO2019 / 074938A1, W02019 / 204406A1, WO2019 / 241659A1).

The training of the neural network can be carried out, for example, by means of a backpropagation method. The most reliable possible mapping of given input data to given output data is sought for the network. The quality of the image is described by an error function. The goal is to minimize the error function. In the backpropagation method, an artificial neural network is incorporated by changing the connection weights.

In the trained state, the connection weights between the processing elements contain information relating to the relationship between the first and second reference MRT recordings and the third reference MRT recordings, which can be used to determine the corresponding MRT recordings for new first and second MRT recordings. Predict images.

A cross-validation method can be used to split the data into training and validation records. The training data set is used in backpropagation training of the network weights. The validation data set is used to check the predictive accuracy with which the trained network can be applied to unknown MRT images.

As already described, further information on the examination subject, the examination area, the examination conditions and / or the measured MRT recordings can also be used for training, validation and predictions.

Examples of information on the examination subject are: gender, age, weight, height, anamnesis, type and duration and amount of medication already taken, blood pressure, central venous pressure, respiratory rate, serum albumin, total bilirubin, blood sugar, iron content, respiratory capacity and the like. These can also be used, for example, in a database or an electronic patient file.

Examples of information about the examination area are: previous illnesses, operations, partial resection, liver transplantation, iron liver, fatty liver and the like.

It is conceivable that MRT recordings are subjected to a movement correction before they are fed to the prediction model. Such a motion correction ensures that a pixel or Voxel of a first MRT recording shows the same examination area as the corresponding pixel or voxel of a second MRT recording. Motion correction methods are described in the prior art (see for example: EP3118644, EP3322997, US20080317315, US20170269182, US20140062481, EP2626718).

The present invention relates to a system with which the method according to the invention can be carried out.

Such a system has a receiving unit, a control and computing unit and an output unit.

It is conceivable that the units mentioned are part of a single computer system; however, it is also conceivable that the units mentioned are part of several separate computer systems that are connected to one another via a network in order to transmit data and / or control signals from one unit to another unit.

A "computer system" is a system for electronic data processing that processes data using programmable arithmetic rules. Such a system usually comprises a "computer", that unit which comprises a processor for performing logical operations, and peripherals.

In computer technology, "peripherals" are all devices that are connected to the computer and are used to control the computer and / or as input and output devices. Examples of this are monitors (screens), printers, scanners, mice, keyboards, drives, cameras, microphones, loudspeakers, etc. Internal connections and expansion cards are also considered peripherals in computer technology.

Today's computer systems are often divided into desktop PCs, portable PCs, laptops, notebooks, netbooks and tablet PCs and so-called handheids (e.g. smartphones); any of these systems can be used to practice the invention.

Inputs into the computer system are made via input means such as a keyboard, a mouse, a microphone, a touch-sensitive display and / or the like.

The system according to the invention is configured to generate an MRT image from two MRT images. This is preferably done by subtracting the tone values of corresponding image points of the two MRT images. It is conceivable that the absolute difference is formed in order to avoid negative tonal values. It is also conceivable that a negative tone value is set to the tone value zero in order to avoid negative tone values.

The receiving unit is used to receive MRT images. The MRT recordings can, for example, be transmitted by a magnetic resonance system or read out from a data memory. The magnetic resonance system can be a component of the system according to the invention. However, it is also conceivable that the system according to the invention is a component of a magnetic resonance system.

At least the first MRT recording and the second MRT recording are transmitted from the receiving unit to the control and computing unit. If available, the third, fourth and so on MRT recordings can also be transmitted.

The control and computing unit is used to calculate MRT images from the received MRT images. The control and processing unit is also used to control the receiving unit and to coordinate the data and signal flows between different units. It is conceivable that there are several control and computing units. The calculated MRT images can be displayed (for example on a monitor), output (for example via a printer) or stored in a data memory via the output unit.

Further embodiments of the invention are:

1. A method comprising the steps

Receiving a first MRT image of an examination subject, the first MRT image showing a liver or part of a liver of the examination subject at a first point in time after a first application of a contrast agent, with healthy liver cells at the first point in time as a result of the first application of the contrast agent in of the first MRI image are displayed with enhanced contrast,

Receiving a second MRT image of the same examination subject, the second MRT image showing the same liver or the same part of the liver at a second point in time after a second application of the contrast agent, with healthy liver cells at the second point in time as a result of the first application of the contrast agent in the second MRT recording are shown with a high contrast, and blood vessels at the second point in time as a result of the second application of the contrast agent in the second MRT recording are shown with a high contrast,

2. The method according to embodiment 1, comprising the steps

Receiving the first MRT recording of the examination subject, the first MRT recording showing the liver or part of a liver of the examination subject at the first point in time after the first application of the contrast agent during a first hepatobiliary phase,

Receiving the second MRT image of the same examination subject, the second MRI image showing the same liver or the same part of the liver at the second point in time after the second application of the contrast medium during a second arterial phase,

Receiving a third MRT image of the same examination subject, the third MRT image showing the same liver or the same part of the liver at a third point in time after the second application of the contrast medium during a second portal venous phase,

Receiving a fourth MRT image of the same examination subject, the fourth MRT image showing the same liver or the same part of the liver at a fourth point in time after the second application of the contrast medium during a second late phase, Generating MRT images from the received MRT images, the first MRT image being calculated by subtracting the first MRT image from the second MRT image, a second MRT image being calculated by subtracting the first MRT image from the third MRT recording is calculated, a third MRT image being calculated by subtracting the first MRT recording from the third MRT recording,

Displaying and / or outputting one or more of the generated MRT images and / or storing one or more of the generated MRT images in a data memory.

3. The method according to one of embodiments 1 or 2, wherein the MRT images are TI -weighted images of the liver or part of the liver after application of a hepatobiliary, paramagnetic contrast agent.

4. The method according to one of embodiments 1 to 3, wherein the contrast agent is a substance or a mixture of substances with gadoxetic acid or a salt of gadoxetic acid as a contrast-enhancing active ingredient, preferably the disodium salt of gadoxetic acid.

5. The method according to one of embodiments 1 to 4, wherein the object to be examined is a mammal, preferably a human.

6. One system encompassing

• a receiving unit,

• a control and computing unit and

An output unit, the control and computing unit being configured to cause the receiving unit to receive a first MRT image of an examination subject, the first MRT image of a liver or part of a liver of the examination subject at a first point in time after a first Application of a contrast agent shows, with healthy liver cells being shown with increased contrast at the first point in time as a result of the first application of the contrast agent in the first MRT recording, the control and computing unit being configured to cause the receiving unit to assign a second MRT recording of an examination subject received, wherein the second MRT image shows the same liver or the same part of the liver at a second point in time after a second application of the contrast agent, healthy liver cells at the second point in time as a result of the first application of the contrast agent in the second MRI image with increased contrast ind, and wherein blood vessels are shown with enhanced contrast at the second point in time as a result of the second application of the contrast agent in the second MRT recording, the control and computing unit being configured to generate a first MRT recording from the first MRT recording and the second MRT recording. Generate image, the first MRT image showing the same liver or the same part of the liver at the second point in time, the contrast between healthy liver cells and blood vessels in the first MRT image being increased compared to the second MRT recording, the control and the arithmetic unit is configured to cause the output unit to display, output or store the first MRT image in a data memory. 7. The computer system according to embodiment 6, wherein the control and arithmetic unit is configured to cause the receiving unit to receive a first MRT recording, a second MRT recording, a third MRT recording and a fourth MRT recording, wherein the first MRI image shows the liver or part of the liver of the examination subject at the first point in time after the first application of the contrast agent during a first hepatobiliary phase, the second MRI image showing the same liver or the same part of the liver at a second point in time after the shows the second application of the contrast agent during a second arterial phase, the third MRI image showing the same liver or the same part of the liver at a third point in time after the second application of the contrast agent during a second portal venous phase, the fourth MRI image showing the same liver or the same part of the liver at a fourth point in time after the second application s shows contrast agent during a second late phase, the control and computing unit being configured to calculate MRT images from the received MRT images, a first MRT image being calculated by subtracting the first MRT image from the second MRT image , wherein a second MRT image is calculated by subtracting the first MRT recording from the third MRT recording, a third MRT image being calculated by subtracting the first MRT recording from the third MRT recording, the control and Computing unit is configured to cause the output unit to display one or more of the calculated MRT images on a screen and / or to output them on a printer and / or to store them in a data memory.

8. A computer program product comprising a computer program that can be loaded into a main memory of a computer and there causes the computer to carry out the following steps:

Receiving a second MRI image, the second MRI image showing the same liver or the same part of the liver at a second point in time after a second application of the contrast medium, with healthy liver cells at the second point in time as a result of the first application of the contrast medium in the second MRI Recordings are shown with increased contrast, and blood vessels at the second point in time as a result of the second application of the contrast agent in the second MRT image are shown with increased contrast, Generating a first MRT image from the first MRT recording and the second MRT recording, the first MRT image showing the same liver or the same part of the liver at the second point in time, the contrast between healthy liver cells and blood vessels in the first MRT Image is enlarged compared to the second MRI image,

9. The computer program product according to embodiment 8, wherein the computer program causes the computer to perform the following steps:

Receiving the first MRT image of the examination subject, the first MRT image showing the liver or part of the liver of the examination subject at the first point in time after the first application of the contrast agent during a first hepatobiliary phase,

Receiving the second MRI image, the second MRI image showing the same liver or the same part of the liver at the second point in time after the second application of the contrast medium during a second arterial phase,

Receiving a third MRI image, the third MRI image showing the same liver or the same part of the liver at a third point in time after the second application of the contrast medium during a second portal venous phase,

Receiving a fourth MRI image, the fourth MRI image showing the same liver or the same part of the liver at a fourth point in time after the second application of the contrast medium during a second late phase,

Generating MRT images from the received MRT images, the first MRT image being calculated by subtracting the first MRT image from the second MRT image, a second MRT image being calculated by subtracting the first MRT image from the third MRT recording is calculated, a third MRT image being calculated by subtracting the first MRT recording from the third MRT recording,

10. The computer program product according to embodiment 9, wherein the computer program causes the computer to carry out one or more of the steps listed in claims 1 to 5.

11. Use of a contrast agent in an MRT method, the MRT method comprising the following steps: first application of the contrast agent,

Generating a first MRT image, the first MRT image showing a liver or part of a liver at a first point in time after the first application of the contrast agent shows, with healthy liver cells at the first point in time as a result of the first application of the contrast medium in the first MRI image being shown with enhanced contrast, second application of the contrast medium at a point in time after the first MRI image has been generated,

Generating a second MRI image, the second MRI image showing the same liver or the same part of the liver at a second point in time after the second application of the contrast medium, with healthy liver cells at the second point in time as a result of the first application of the contrast medium in the second MRI Recordings are shown with increased contrast, and blood vessels at the second point in time as a result of the second application of the contrast agent in the second MRT image are shown with increased contrast,

Displaying and / or outputting one or more of the generated MRT images and / or storing one or more of the generated MRT images in a data memory. Use according to embodiment 11, comprising the steps: first application of the contrast agent,

Generating the first MRT recording, the first MRT recording showing the liver or part of the liver of the examination subject at the first point in time after the first application of the contrast agent during a first hepatobiliary phase, the second application of the contrast agent at a point in time after the generation of the first MRI scan,

Generating the second MRT image, the second MRT image showing the same liver or the same part of the liver at the second point in time after the second application of the contrast medium during a second arterial phase,

Generating a third MRI image, the third MRI image showing the same liver or the same part of the liver at a third point in time after the second application of the contrast medium during a second portal venous phase,

Generating a fourth MRI image, the fourth MRI image showing the same liver or the same part of the liver at a fourth point in time after the second application of the contrast medium during a second late phase,

13. A contrast agent for use in an MRT method, the MRT method comprising the following steps: first application of the contrast agent,

Generating a first MRT recording, the first MRT recording showing a liver or part of a liver at a first point in time after the first application of the contrast medium, with healthy liver cells at the first point in time as a result of the first application of the contrast medium in the first MRT Images are shown with enhanced contrast, second application of the contrast agent at a point in time after the first MRT image has been generated,

Generating a second MRT recording, the second MRT recording showing the same liver or the same part of the liver at a second point in time after the second application of the contrast medium, with healthy liver cells at the second point in time as a result of the first application of the contrast medium in the second MRT Recordings are shown in a contrast-enhanced manner, and blood vessels at the second point in time as a result of the second application of the contrast agent are shown in a contrast-enhanced manner in the second MRT picture,

14. A contrast agent for use according to embodiment 13, the MRT method comprising the following steps: first application of the contrast agent,

Generating the second MRT recording, the second MRT recording showing the same liver or the same part of the liver at the second point in time after the second application of the contrast medium during a second arterial phase, Generating a third MRI image, the third MRI image showing the same liver or the same part of the liver at a third point in time after the second application of the contrast medium during a second portal venous phase,

15. A contrast agent for use according to one of the embodiments 13 or 14, the contrast agent being a substance or a mixture of substances with gadoxetic acid or a salt of gadoxetic acid as a contrast-enhancing active ingredient, preferably the disodium salt of gadoxetic acid.

16. A kit comprising a contrast agent according to one of the embodiments 13 or 14 and a computer program product according to one of the embodiments 8, 9 or 10.

The invention is explained in more detail below with reference to figures, without wishing to restrict the invention to the features or combinations of features shown in the figures.

Show it:

FIG. 1 shows schematically the time course of the concentration of contrast medium in the liver arteries (A), the liver veins (P) and the liver cells (L). The concentrations are shown in the form of the signal intensities I in the areas mentioned (liver arteries, liver veins, liver cells) in the magnetic resonance measurement as a function of time t. In the case of an intravenous bolus injection, the concentration of the contrast agent in the hepatic arteries (A) is the first to increase (dashed curve). The concentration goes through a maximum and then decreases. The concentration in the hepatic veins (P) increases more slowly than in the hepatic arteries and reaches its maximum later (dotted curve). The concentration of the contrast agent in the liver cells increases slowly (solid curve) and only reaches its maximum at a very much later point in time (not shown in FIG. 1). A number of characteristic points in time can be defined: At the point in time TPO, contrast medium is administered intravenously as a bolus. At the point in time TP1, the concentration (the signal intensity) of the contrast agent in the hepatic arteries reaches its maximum. At time TP2, the curves of the signal intensities intersect in the hepatic arteries and the hepatic veins. At the point in time TP3, the concentration (the signal intensity) of the contrast agent in the hepatic veins passes through its maximum. At time TP4, the curves of the signal intensities intersect in the hepatic arteries and the liver cells. At time T5, the concentrations in the hepatic arteries and hepatic veins have dropped to a level at which they no longer cause any measurable enhancement of contrast. According to the invention, contrast agent is administered in the form of two boluses. A first bolus with a first contrast agent is administered at time TR0, a second bolus with a second contrast agent at a time after time TP3, preferably after time TP4, even more preferably after time TP5. A first MRT recording is preferably generated after time TP4, even more preferably after time TP5. After the application of the second contrast agent, at least the arterial phase and the portal venous phase are run through a second time. These phases are characterized by an analogous concentration curve of contrast medium in the arteries and the hepatic veins; ie the times TP1 (maximum contrast enhancement of the arteries), TP2 (equal contrast enhancement of arteries and veins) and TP3 (maximum contrast enhancement of the veins) occur a second time; they can be referred to as times TRG, TP2 'and TP3'. Preferably, a second MRT recording and possibly a third MRT recording and possibly further MRT recordings are generated in a time span between the point in time of the application of the second contrast agent and the point in time TP3 '.

FIG. 2 schematically shows an example of a shortened MRT examination according to the invention. Here, a first contrast agent is initially applied in the form of a first bolus (1). After a certain waiting period (2), e.g. 8 to 20 minutes, the examination subject is fed to the MRI. The MRT process is then started and a first MRT image is generated (3) showing the liver of the examination subject or part of it in the hepatobiliary phase. A second contrast agent is then administered intravenously to the examination subject in the form of a bolus injection (4) and one or more further MRT images of the liver or a part thereof are then generated in the dynamic phase.

FIG. 3 schematically shows a preferred embodiment of the system according to the invention. The system (10) comprises a receiving unit (11), a control and computing unit (12) and an output unit (13).

The control and computing unit (12) is configured to cause the receiving unit (11) to receive a first MRT image of an examination subject, the first MRT image of a liver or part of a liver of the examination subject at a first point in time after a Application of a first contrast agent shows, with healthy liver cells at the first point in time as a result of the application of the first contrast agent in the first MRT image being shown with increased contrast.

The control and computing unit (12) is also configured to cause the receiving unit (11) to receive a second MRT image of an examination subject, the second MRT image of the same liver or the same part of the liver at a second point in time after an application of a second contrast agent, with healthy liver cells being shown with increased contrast at the second point in time due to the application of the first contrast agent in the second MRI image, and blood vessels being shown with higher contrast at the second time as a result of the application of the second contrast agent in the second MRI image .

The control and computing unit (12) is further configured to generate a first MRT image from the first MRT image and the second MRT image, the first MRT image showing the same liver or the same part of the liver at the second point in time , the contrast between healthy liver cells and blood vessels in the first MRI image being increased compared to the second MRI image,

The control and computing unit (12) is also configured to cause the output unit (13) to display the first MRT image, to output it or to store it in a data memory. FIG. 4 shows schematically and by way of example an embodiment of the method according to the invention. The method (100) comprises the steps:

(110) Receiving a first MRT image of an examination subject, the first MRT image showing a liver or part of a liver of the examination subject at a first point in time after application of a first contrast agent, with healthy liver cells at the first point in time as a result of the application of the the first contrast agent in the first MRI image are shown with enhanced contrast,

(120) Receiving a second MRT image of the same examination subject, the second MRT image showing the same liver or the same part of the liver at a second point in time after application of a second contrast agent, with healthy liver cells at the second point in time as a result of application of the first contrast agent are shown in the second MRI image with increased contrast, and blood vessels at the second point in time as a result of the application of the second contrast agent are shown in the second MRI image with increased contrast,

(130) Generating a first MRT image from the first MRT recording and the second MRT recording, the first MRT image showing the same liver or the same part of the liver at the second point in time, the contrast between healthy liver cells and blood vessels in the first MRI image is enlarged compared to the second MRI image,

(140) displaying and / or outputting the first MRT image and / or storing the first MRT image in a data memory.

FIG. 5 shows MRT images of a liver during the dynamic and the hepatobiliary phase. In FIGS. 5 (a), 5 (b), 5 (c), 5 (d), 5 (e) and 5 (f), the same cross-section through the liver is always shown at different times. The reference symbols drawn in FIGS. 5 (a), 5 (b), 5 (d) and 5 (f) apply to all FIGS. 5 (a), 5 (b), 5 (c), 5 (d), 5 (e) and 5 (f); they are only shown once for the sake of clarity.

5 (a) shows the cross section through the liver (L) before the intravenous application of a (hepatobiliary) contrast medium. A hepatobiliary contrast agent was administered intravenously as a bolus at a point in time between the points in time represented by Figures 5 (a) and 5 (b). This reaches the liver in FIG. 5 (b) via the hepatic artery (A). Correspondingly, the hepatic artery is shown with an enhanced signal (arterial phase). A tumor (T), which is mainly supplied with blood via arteries, also stands out as a lighter (signal-enhanced) area in front of the liver cell tissue. At the point in time shown in Figure 5 (c), the hepatobiliary contrast agent reaches the liver via the veins. In FIG. 5 (d), the venous blood vessels (V) stand out as bright (signal-enhanced) areas from the liver tissue (portal venous phase). At the same time, the signal intensity in the healthy liver cells, which are mainly supplied with contrast medium via the veins, increases continuously (FIG. 5 (c) 5 (d) 5 (e) 5 (f)). In the hepatobiliary phase, which is shown in FIG. 5 (f), the liver cells (P) are shown with an enhanced signal; the blood vessels and the tumor no longer have any contrast agent and are accordingly darkened.

According to the invention, a first MRT image is generated at a first point in time during the hepatobiliary phase. This can be, for example, the recording shown in FIG. 5 (f).

FIG. 6 shows the same liver (L) that is already shown in FIG. The state shown in Fig. 6 (g) temporally follows the state shown in Fig. 5 (f). The liver is still due to the Application of the hepatobiliary contrast agent shown with enhanced signal. At the point in time shown in FIG. 6 (g), contrast medium is administered intravenously a second time in the form of a bolus. The phases already described in connection with FIG. 5 are run through again: the arterial phase (FIG. 6 (h)), the portal venous phase (FIG. 6 j)) and the late phase (FIG. 6 (k)). If the second contrast agent is also a hepatobiliary contrast agent, a second hepatobiliary phase is also run through (FIG. 6 (1)), with the difference that the healthy liver cells still contain the first contrast agent from the first application and signal-amplified over all phases are shown. Accordingly, the contrast between blood vessels and the healthy liver cells, in particular in the recordings shown in FIGS. 6 (i) and 6 (j), is lower than in the recordings shown in FIGS. 5 (c) and 5 (d).

In order to increase this contrast, recordings are made for one or more of the recordings shown in FIGS. 6 (g), 6 (h), 6 (i), 6 (j) and 6 (k) MRI images generated. This is shown by way of example in FIG. 7.

Fig. 7 shows schematically and by way of example the generation of three MRT images 6 (h) ‘, 6 (i)‘ and 6 j) ‘. The MRT image 6 (h) ‘is generated by subtracting the MRT image from FIG. 5 (f) from the MRT image from FIG. 6 (h). The MRT image 6 (i) ‘is generated by subtracting the MRT image from FIG. 5 (f) from the MRT image from FIG. 6 (i). The MRT image 6 j) ‘is generated by subtracting the MRT image from FIG. 5 (f) from the MRT image from FIG. 6 (j). The subtraction takes place in each case for the tone values of the individual pixels of the MRT images. MRT image 6 (h) ‘corresponds to the MRT image shown in FIG. 5 (b); MRT image 6 (i) ‘corresponds to the MRT image shown in FIG. 5 (c); MRT image 6 (j) ‘corresponds to the MRT image shown in FIG. 5 (d).

FIG. 8 shows, by way of example and schematically in the form of a flow chart, a preferred embodiment of the method according to the invention. The method (200) comprises the steps:

(210) receiving a first MRT image of an examination subject, the first MRT image showing a liver or part of a liver of the examination subject at a first point in time after application of a first contrast agent during a first hepatobiliary phase,

(220) receiving a second MRT image of the same examination subject, the second MRT image showing the same liver or the same part of the liver at a second point in time after application of a second contrast agent during a second arterial phase,

(230) receiving a third MRT image of the same examination subject, the third MRT image showing the same liver or the same part of the liver at a third point in time after the application of the second contrast agent during a second portal venous phase,

(240) Receiving a fourth MRT image of the same examination subject, the fourth MRT image showing the same liver or the same part of the liver at a fourth point in time after the application of the second contrast agent during a second late phase,

(250) generating MRT images from the received MRT images, wherein a first MRT image is calculated by subtracting the first MRT image from the second MRT image, wherein a second MRT image is calculated by subtracting the first MRT image is calculated from the third MRT recording, a third MRT image being calculated by subtracting the first MRT recording from the third MRT recording, (260) display and / or output one or more of the generated MRT images and / or storage of one or more of the generated MRT images in a data memory.

5

Claims

1. Computer-implemented method comprising the steps

Receiving a second MRT image of the same examination subject, the second MRT image showing the same liver or the same part of the liver at a second point in time after the application of a second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRT recording are shown with enhanced contrast, and blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRT recording are shown with high contrast,

2. The method according to claim 1, comprising the steps

Receiving the first MRT recording of the examination subject, the first MRT recording showing the liver or part of the liver of the examination subject at the first point in time after the application of the first contrast agent, with healthy liver cells at the first point in time as a result of the application of the first contrast agent in of the first MRI image are shown with enhanced contrast,

Receiving the second MRI image of the same examination subject, the second MRI image showing the same liver or the same part of the liver at the second point in time after the application of the second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRT recording are shown in a contrast-enhanced manner, and blood vessels at the second point in time as a result of the application of the second contrast agent are shown in a contrast-enhanced manner in the second MRT recording,

Generating the first MRT image from the first MRT recording and the second MRT recording, the first MRT image showing the same liver or the same part of the liver after the application of the second contrast agent, the contrast enhancement of healthy liver cells caused by the first contrast agent is eliminated, Displaying and / or outputting the first MRT image and / or storing the first MRT image in a data memory.

3. The method according to any one of claims 1 or 2, comprising the steps

Receiving the first MRT recording of the examination subject, the first MRT recording showing the liver or part of a liver of the examination subject at the first point in time after the application of the first contrast agent during a first hepatobiliary phase,

Receiving the second MRT image of the same examination subject, the second MRT image showing the same liver or the same part of the liver at the second point in time after the application of the second contrast agent during a second arterial phase, optionally receiving a third MRT image of the same examination subject, with the third MRI image shows the same liver or the same part of the liver at a third point in time after the application of the second contrast medium during a second portal venous phase, optional reception of a fourth MRI image of the same examination subject, the fourth MRI image showing the same liver or the same part shows the liver at a fourth point in time after the application of the second contrast agent during a second late phase,

Generating MRT images from the received MRT images, the first MRT image being calculated by subtracting the first MRT image from the second MRT image, optionally with a second MRT image by subtracting the first MRT image from the third MRT recording is calculated, with a third MRT image optionally being calculated by subtracting the first MRT recording from the third MRT recording,

4. The method according to any one of claims 1 or 2, comprising the steps

Receiving the second MRI image of the same examination subject, the second MRI image showing the same liver or the same part of the liver at the second point in time after the application of the second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRI recordings are shown with increased contrast, and with blood vessels at the second point in time as a result of the Application of the second contrast agent are shown in the second MRI image with a higher contrast,

Supplying the first MRT recording and the second MRT recording to an artificial neural network, the artificial neural network having been trained in a monitored learning process, from first reference MRT recordings and second reference MRT recordings, third reference MRT recordings each first reference MRT image showing a liver or part of a liver of the examination subject at a first point in time after application of a first contrast agent, with healthy liver cells at the first point in time as a result of the application of the first contrast agent in the first reference MRT recording are shown in a contrast-enhanced manner, with every second reference MRT recording showing the same liver or the same part of the liver at a second point in time after application of a second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRI image shown with enhanced contrast si nd, and wherein blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRI image are shown with increased contrast, and wherein every third reference MRI image is the same liver or the same part of the liver at the second point in time after the application of the second Shows contrast agent, with only blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRI image being shown with enhanced contrast, with healthy liver cells not being shown with high-contrast,

5. The method according to any one of claims 1 or 2, wherein the first contrast agent is a hepatobiliary contrast agent, preferably a substance or a mixture of substances with gadoxetic acid or a salt of gadoxetic acid as a contrast-enhancing agent, and the second contrast agent is either is the same contrast agent as the first contrast agent or the second contrast agent is an extracellular contrast agent, preferably a substance or a mixture of substances with gadobutrol, gadoteridol, gadoteric acid, gadopentetic acid or gadodiamide as a contrast-enhancing agent.

6. System comprehensive

• a receiving unit,

• a control and computing unit and

An output unit, the control and computing unit being configured to cause the receiving unit to receive a first MRT image of an examination subject, the first MRT image of a liver or part of a liver of the examination subject at a first point in time after an application shows a first contrast agent, with healthy liver cells at the first point in time as a result of the application of the first contrast agent in the first MRI image being shown with increased contrast, wherein the control and computing unit is configured to cause the receiving unit to receive a second MRT image of an examination subject, the second MRT image showing the same liver or the same part of the liver at a second point in time after an application of a second contrast agent, wherein healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRI image are shown with increased contrast, and blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRI image are shown with increased contrast, the control and Computing unit is configured to generate a first MRT image from the first MRT recording and the second MRT recording, the first MRT image showing the same liver or the same part of the liver at the second point in time, the contrast between healthy liver cells and Blood vessels in the first MRI image versus the second en MRT recording is enlarged, the control and computing unit being configured to cause the output unit to display the first MRT image, to output it or to store it in a data memory.

7. The computer system according to claim 6, wherein the control and arithmetic unit is configured to cause the receiving unit to receive a first MRT recording, a second MRT recording, a third MRT recording and a fourth MRT recording, the first MRI image shows the liver or part of the liver of the examination subject at the first point in time after the application of the first contrast agent during a first hepatobiliary phase, the second MRI image showing the same liver or the same part of the liver at a second point in time after application of the shows the second contrast agent during a second arterial phase, the third MRI image showing the same liver or the same part of the liver at a third point in time after the application of the second contrast agent during a second portal venous phase, the fourth MRI image showing the same liver or the same part the liver at a fourth point in time after the application of the second contrast center Is shown during a second late phase, the control and computing unit being configured to calculate MRT images from the received MRT images, a first MRT image being calculated by subtracting the first MRT image from the second MRT image, wherein a second MRT image is calculated by subtracting the first MRT recording from the third MRT recording, a third MRT image being calculated by subtracting the first MRT recording from the third MRT recording, wherein the control and computing unit is configured to cause the output unit to display one or more of the calculated MRT images on a screen and / or to output them on a printer and / or to store them in a data memory.

8. Computer program product comprising a computer program that can be loaded into a main memory of a computer system and there causes the computer system to carry out the following steps:

Receiving a second MRI image, the second MRI image showing the same liver or the same part of the liver at a second point in time after application of a second contrast agent, with healthy liver cells at the second point in time as a result of the application of the first contrast agent in the second MRI Recordings are shown with increased contrast, and blood vessels at the second point in time as a result of the application of the second contrast agent in the second MRT image are shown with increased contrast,

9. Computer program product according to claim 8, wherein the computer program causes the computer system to carry out the following steps:

Receiving the first MRT image of the examination subject, the first MRT image showing the liver or part of the liver of the examination subject at the first point in time after the application of the first contrast agent during a first hepatobiliary phase,

Receiving the second MRI image, the second MRI image showing the same liver or the same part of the liver at the second point in time after the application of the contrast agent during a second arterial phase,

Receiving a third MRI image, the third MRI image showing the same liver or the same part of the liver at a third point in time after the application of the second contrast agent during a second portal venous phase, Receiving a fourth MRI image, the fourth MRI image showing the same liver or the same part of the liver at a fourth point in time after the application of the second contrast agent during a second late phase,

10. Computer program product according to claim 9, wherein the computer program causes the computer system to carry out one or more of the steps listed in claims 1 to 5.

11. Use of a first and a second contrast agent in an MRI method, the MRT method comprising the following steps:

Application of the first contrast agent,

12. Use according to claim 11, comprising the steps:

Application of the first contrast agent,

Generating the first MRT recording, the first MRT recording showing the liver or part of the liver of the examination subject at the first point in time after the application of the first contrast agent during a first hepatobiliary phase,

Generating the second MRT image, the second MRT image showing the same liver or the same part of the liver at the second point in time after the application of the second contrast agent during a second arterial phase,

Generating a third MRI image, the third MRI image showing the same liver or the same part of the liver at a third point in time after the application of the second contrast medium during a second portal venous phase,

Generating a fourth MRT image, the fourth MRT image showing the same liver or the same part of the liver at a fourth point in time after the application of the second contrast agent during a second late phase,

13. A first and a second contrast agent for use in an MRI method, the MRT method comprising the following steps:

Application of the first contrast agent,

14. Contrast agent for use according to claim 13, wherein the first contrast agent is a hepatobiliary contrast agent, preferably a substance or a mixture of substances with gadoxetic acid or a salt of gadoxetic acid as a contrast-enhancing agent, and the second contrast agent is either the same Contrast agent is like the first contrast agent or the second contrast agent is an extracellular contrast agent, preferably a substance or a mixture of substances with gadobutrol, gadoteridol, gadoteric acid, gadopentetic acid or gadodiamide as a contrast-enhancing active ingredient.

15. Kit comprising a contrast agent according to claim 13 and a computer program product according to one of claims 8, 9 or 10.