Generate artificial contrast-enhanced radiographic images

Abstract

The present invention relates to the technical field of generating artificially contrast-enhanced radiological images.

Description

Technical Field

[0001] The present disclosure relates to the technical field of generating artificially contrast-enhanced radiological images. Background Art

[0002] WO 2019 / 074938 A1 discloses a method for reducing the amount of contrast agent when generating radiological images using an artificial neural network.

[0003] In the disclosed method, in a first step, a training dataset is generated. For a plurality of individuals, the training dataset includes each individual's i) original radiographic image (zero-contrast image), ii) radiographic image after administration of a low amount of contrast agent (low-contrast image), and iii) radiographic image after administration of a standard amount of contrast agent (full-contrast image).

[0004] In the second step, an artificial neural network was trained based on the original images and images after administration of a low dose of contrast agent to predict, for each person in the training dataset, an artificial radiographic image showing the acquisition region after administration of a standard dose of contrast agent. In each case, the radiographic image measured after administration of a standard dose of contrast agent served as the reference (ground truth) for training.

[0005] In a third step, the trained artificial neural network can be used to predict an artificial radiographic image for a new person based on the original image and the radiographic image after administration of a low amount of contrast agent, the artificial radiographic image showing the acquisition region as after administration of a standard amount of contrast agent.

[0006] The method disclosed in WO 2019 / 074938 A1 has several disadvantages.

[0007] For example, training an artificial neural network requires training data. A large number of radiology examinations on a large number of people need to be performed, and the training data needs to be generated in order to be able to train the network.

[0008] The artificial neural network disclosed in WO2019 / 074938A1 was trained to predict radiographic images after administration of a standard dose of contrast agent. The artificial neural network was not configured and trained to predict radiographic images after administration of a contrast agent in a dose lower than or higher than the standard dose. The method described in WO2019 / 074938A1 could, in principle, be trained to predict radiographic images after administration of a contrast agent in a dose other than the standard dose, but this would require additional training data and further training. Summary of the Invention

[0009] It is desirable to be able to generate radiographic images with variable contrast enhancement without the need to generate training data for each individual contrast enhancement and without the need to train an artificial neural network. Furthermore, it is desirable to be able to generate radiographic images with variable contrast enhancement using a traceable deterministic method to generate variable contrast enhancement. This would facilitate the approval and use of appropriate medical procedures while minimizing false negative and false positive results. Machine learning methods employ statistical models that have limited generalizability because they are typically based on a selection of limited training data. Furthermore, it is desirable to be able to generate radiographic images with variable contrast enhancement using a variety of contrast agents. Furthermore, it is desirable to be able to generate radiographic images with variable contrast enhancement using the methods described using a variety of different contrast agents, regardless of their physical, chemical, physiological or other properties.

[0010] These and other objects are achieved by the subject-matter of the independent claims.Preferred embodiments of the disclosure are to be found in the dependent claims, the description and the drawings.

[0011] Thus, the present invention provides in a first aspect a computer-implemented method for generating a synthetic contrast-enhanced radiological image, comprising the following steps:

[0012] - receiving or generating a first representation, wherein the first representation represents an examination region of the examination object in frequency space or in real space without administration of a contrast agent or after administration of a first amount of a contrast agent,

[0013] - receiving or generating a second representation, wherein the second representation represents the examination region of the examination object in frequency space or in real space after administration of a second amount of contrast agent,

[0014] - generating a third representation based on the first representation and the second representation, wherein generating the third representation comprises subtracting the first representation from the second representation,

[0015] - optionally: generating a weighted third representation, wherein the generating of the weighted third representation comprises a frequency-dependent weighting of the third representation,

[0016] - generating a fourth representation, wherein said generating the fourth representation comprises adding α-times the optionally weighted third representation to the first representation or the second representation, wherein α is a positive or negative real number,

[0017] - if the fourth representation represents the examination region in frequency space: transforming the fourth representation into a fourth representation of the examination region in real space,

[0018] - outputting and / or storing a fourth representation of the examination region in real space and / or transmitting the fourth representation of the examination region in real space to a separate computer system.

[0019] The present disclosure also provides a computer system comprising:

[0020] processor; and

[0021] A memory storing an application program, the application program being configured to perform operations when executed by the processor, the operations comprising:

[0022] - receiving or generating a first representation, wherein the first representation represents an examination region of the examination object in frequency space or in real space without administration of a contrast agent or after administration of a first amount of a contrast agent,

[0023] - receiving or generating a second representation, wherein the second representation represents the examination region of the examination object in frequency space or in real space after administration of a second amount of contrast agent,

[0024] - generating a third representation based on the first representation and the second representation, wherein generating the third representation comprises subtracting the first representation from the second representation,

[0025] - optionally: generating a weighted third representation, wherein the generating of the weighted third representation comprises a frequency-dependent weighting of the third representation,

[0026] - generating a fourth representation, wherein generating the fourth representation comprises adding α-times the optionally weighted third representation to the first representation or the second representation, wherein α is a positive or negative real number,

[0027] - if the fourth representation represents the examination region in frequency space: transforming the fourth representation into a fourth representation of the examination region in real space,

[0028] Outputting and / or storing a fourth representation of the examination region in real space and / or transmitting the fourth representation of the examination region in real space to a separate computer system.

[0029] The present disclosure also provides a computer program that can be loaded into a working memory of a computer system, wherein the computer program causes the computer system to perform the following steps:

[0030] - receiving or generating a first representation, wherein the first representation represents an examination region of the examination object in frequency space or in real space without administration of a contrast agent or after administration of a first amount of a contrast agent,

[0031] - receiving or generating a second representation, wherein the second representation represents the examination region of the examination object in frequency space or in real space after administration of a second amount of contrast agent,

[0032] - generating a third representation based on the first representation and the second representation, wherein generating the third representation comprises subtracting the first representation from the second representation,

[0033] - optionally: generating a weighted third representation, wherein the generating of the weighted third representation comprises a frequency-dependent weighting of the third representation,

[0034] - generating a fourth representation, wherein said generating the fourth representation comprises adding α-times the optionally weighted third representation to the first representation or the second representation, wherein α is a positive or negative real number,

[0035] - if the fourth representation represents the examination region in frequency space: transforming the fourth representation into a fourth representation of the examination region in real space,

[0036] Outputting and / or storing a fourth representation of the examination region in real space and / or transmitting the fourth representation of the examination region in real space to a separate computer system.

[0037] The present disclosure also provides use of a contrast agent in a radiological examination method, the method comprising:

[0038] - receiving or generating a first representation, wherein the first representation represents an examination region of the examination object in frequency space or in real space without administration of a contrast agent or after administration of a first amount of a contrast agent,

[0039] - receiving or generating a second representation, wherein the second representation represents the examination region of the examination object in frequency space or in real space after administration of a second amount of contrast agent,

[0040] - generating a third representation based on the first representation and the second representation, wherein generating the third representation comprises subtracting the first representation from the second representation,

[0041] - optionally: generating a weighted third representation, wherein the generating of the weighted third representation comprises a frequency-dependent weighting of the third representation,

[0042] - generating a fourth representation, wherein said generating the fourth representation comprises adding α-times the optionally weighted third representation to the first representation or the second representation, wherein α is a positive or negative real number,

[0043] - if the fourth representation represents the examination region in frequency space: transforming the fourth representation into a fourth representation of the examination region in real space,

[0044] Outputting and / or storing a fourth representation of the examination region in real space and / or transmitting the fourth representation of the examination region in real space to a separate computer system.

[0045] The present disclosure also provides a contrast agent for use in a radiological examination method, the method comprising:

[0046] - receiving or generating a first representation, wherein the first representation represents an examination region of the examination object in frequency space or in real space without administration of a contrast agent or after administration of a first amount of a contrast agent,

[0047] - receiving or generating a second representation, wherein the second representation represents the examination region of the examination object in frequency space or in real space after administration of a second amount of contrast agent,

[0048] - generating a third representation based on the first representation and the second representation, wherein generating the third representation comprises subtracting the first representation from the second representation,

[0049] - optionally: generating a weighted third representation, wherein the generating of the weighted third representation comprises a frequency-dependent weighting of the third representation,

[0050] - generating a fourth representation, wherein said generating the fourth representation comprises adding α-times the optionally weighted third representation to the first representation or the second representation, wherein α is a positive or negative real number,

[0051] - if the fourth representation represents the examination region in frequency space: transforming the fourth representation into a fourth representation of the examination region in real space,

[0052] Outputting and / or storing a fourth representation of the examination region in real space and / or transmitting the fourth representation of the examination region in real space to a separate computer system.

[0053] The present disclosure also provides a kit comprising a computer program product and a contrast agent, wherein the computer program product comprises a computer program that can be loaded into a working memory of a computer system, wherein the computer program causes the computer system to perform the following steps:

[0054] - receiving or generating a first representation, wherein the first representation represents an examination region of the examination object in frequency space or in real space without administration of a contrast agent or after administration of a first amount of a contrast agent,

[0055] - receiving or generating a second representation, wherein the second representation represents the examination region of the examination object in frequency space or in real space after administration of a second amount of contrast agent,

[0056] - generating a third representation based on the first representation and the second representation, wherein generating the third representation comprises subtracting the first representation from the second representation,

[0057] - optionally: generating a weighted third representation, wherein the generating of the weighted third representation comprises a frequency-dependent weighting of the third representation,

[0058] - generating a fourth representation, wherein said generating the fourth representation comprises adding α-times the optionally weighted third representation to the first representation or the second representation, wherein α is a positive or negative real number,

[0059] - if the fourth representation represents the examination region in frequency space: transforming the fourth representation into a fourth representation of the examination region in real space,

[0060] Outputting and / or storing a fourth representation of the examination region in real space and / or transmitting the fourth representation of the examination region in real space to a separate computer system. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Figure 1 An embodiment of generating a third representation based on a first representation and a second representation is exemplarily and schematically shown.

[0062] Figure 2 The generation of the weighted third representation R3 is shown exemplarily and schematically. F,w .

[0063] Figure 3 An embodiment of a frequency-dependent weighting function that may be used to weight the third representation is shown. Figure 3 (a) shows that Figure 2 The weight function WF is shown in FIG. In this weight function, the weight factor may decrease from the center in an exponential form as the frequency increases, for example. Figure 3 (b) shows a weighting function where the weighting factor decreases linearly from the center as the frequency increases. Figure 3 (c) shows a weighting function in which the weighting factor decreases from the center in the form of an inverse parabola as the frequency increases. Figure 3 (d) shows a weighting function where the weighting factor is constant within a defined range near the center and then decreases exponentially from the threshold frequency. Figure 3 (e) shows a weight function where the weight factors have a cosine function form near the center. Figure 3 (f) shows a weight function where the weight factors have a step function form near the center. Figure 3 (g) shows a weight function where the weight factors have a Gaussian distribution function form near the center. Figure 3 (h) shows a weight function where the weight factors have the form of a Hann function near the center.

[0064] Figure 4An embodiment of generating the fourth representation is shown exemplarily and schematically.

[0065] Figure 5 It is shown exemplarily and schematically how to Figure 1 The inverse transform operation T described -1 from Figure 4 The fourth representation R4 of the examination region in frequency space has already been shown in F Generate a fourth representation R4 of the inspection area in real space I .

[0066] Figure 6 Exemplarily and schematically shown in Figure 1 、 Figure 2 、 Figure 4 and Figure 5 The entire method is partially shown in FIG.

[0067] Figure 7 Various representations of an examination region of an examination object in real space are shown by way of example and schematically.

[0068] Figure 8 A preferred embodiment of outputting an artificial contrast-enhanced radiographic image of an examination region by a computer system / computer program is shown.

[0069] Figure 9 A first representation R1 of the examination region of the examination object is shown I and the second characterization R2 I .

[0070] Figure 10 A computer system according to the present disclosure is shown exemplarily and schematically.

[0071] Figure 11 Another embodiment of a computer system is shown illustratively and schematically.

[0072] Figure 12 Embodiments of the computer-implemented method are exemplarily and schematically shown in flowchart form. DETAILED DESCRIPTION

[0073] The present invention will be explained in more detail below without distinguishing between the subject matter of the present invention (method, computer system, computer program (product), use, contrast agent used, kit). On the contrary, the following explanation is intended to apply analogously to all subject matters of the present invention, regardless of the context in which they appear (method, computer system, computer program (product), use, contrast agent used, kit).

[0074] If steps are stated in a sequence in this specification or claims, this does not necessarily mean that the present disclosure is limited to the stated sequence. Rather, it is contemplated that the steps may be performed in a different sequence or in parallel with one another, unless one step builds upon another, necessitating the subsequent execution of the step that builds upon it (however, this will be clear in individual cases). Therefore, the stated sequence constitutes a preferred embodiment.

[0075] The present invention will be described in greater detail in certain places with reference to the accompanying drawings. The drawings show specific embodiments with specified features and combinations of features, which are primarily intended for illustrative purposes; the present invention should not be construed as being limited to the features and combinations of features shown in the drawings. Furthermore, statements regarding features and combinations of features in the descriptions of the drawings are intended to apply generally, that is, also to other embodiments, and are not limited to the embodiments shown.

[0076] The present disclosure describes a method for generating one or more artificial radiographic images based on at least two representations representing an examination region of an examination object after adding / administering / using different amounts of contrast agent, wherein the contrast between regions with contrast agent and regions without contrast agent can be varied.

[0077] The "inspection subject" is usually a living organism, preferably a mammal, and most preferably a human.

[0078] The “examination region” is a portion of the examination object, such as an organ, a portion of an organ or multiple organs, or another portion of the examination object.

[0079] For example, the examination region may be the liver, kidney, heart, lung, brain, stomach, bladder, prostate, intestine, or a portion thereof, or another part of the mammalian (eg, human) body.

[0080] In one embodiment, the examination region includes the liver or a portion of the liver, or the examination region is the liver or a portion of the liver of a mammal, preferably a human.

[0081] In a further embodiment, the examination region comprises the brain or a portion of the brain, or the examination region is the brain or a portion of the brain of a mammal, preferably a human.

[0082] In a further embodiment, the examination region comprises the heart or a portion of the heart, or the examination region is the heart or a portion of the heart of a mammal, preferably a human.

[0083] In a further embodiment, the examination region comprises the thorax or a portion of the thorax, or the examination region is the thorax or a portion of the thorax of a mammal, preferably a human.

[0084] In a further embodiment, the examination region comprises the stomach or a portion of the stomach, or the examination region is the stomach or a portion of the stomach of a mammal, preferably a human.

[0085] In a further embodiment, the examination region comprises the pancreas or a portion of the pancreas, or the examination region is the pancreas or a portion of the pancreas of a mammal, preferably a human.

[0086] In a further embodiment, the examination region comprises a kidney or a portion of a kidney, or the examination region is a kidney or a portion of a kidney of a mammal, preferably a human.

[0087] In a further embodiment, the examination region comprises one or both lungs or a portion of a lung of a mammal, preferably a human.

[0088] In a further embodiment, the examination area comprises a breast or a portion of a breast, or the examination area is a breast or a portion of a breast of a female mammal, preferably a female human.

[0089] In a further embodiment, the examination region comprises the prostate or a portion of the prostate, or the examination region is the prostate or a portion of the prostate of a male mammal, preferably a male human.

[0090] The examination region (field of view, FOV) is, in particular, the volume imaged in a radiological image. The examination region is typically defined by the radiologist, for example, on a localizer image. Alternatively or additionally, the examination region can, of course, also be defined automatically, for example based on a selected protocol.

[0091] Perform a radiographic examination of the examined area.

[0092] "Radiology" is a branch of medicine that deals with the use of electromagnetic radiation and mechanical waves (including, for example, ultrasound diagnosis) for diagnostic, therapeutic and / or scientific purposes. In addition to X-rays, other ionizing radiations are also used, such as gamma radiation or electrons. Imaging is a major application, and other imaging methods such as ultrasonography and magnetic resonance imaging (MRI) are also considered radiology, even though these methods do not use ionizing radiation. Therefore, the term "radiology" in the context of the present disclosure specifically covers the following examination methods: computed tomography, magnetic resonance imaging, ultrasonography.

[0093] In one embodiment of the present disclosure, the radiological examination is a magnetic resonance imaging examination.

[0094] In a further embodiment, the radiological examination is a computed tomography examination.

[0095] In a further embodiment, the radiological examination is an ultrasound examination.

[0096] In radiological examinations, contrast agents are often used to enhance contrast.

[0097] A "contrast medium" is a substance or mixture of substances that improves the depiction of body structure and function during radiological examinations.

[0098] In computed tomography, iodine-containing solutions are typically used as contrast agents. In magnetic resonance imaging (MRT), superparamagnetic substances (e.g., iron oxide nanoparticles, superparamagnetic iron platinum particles (SIPPs)) or paramagnetic substances (e.g., gadolinium chelates, manganese chelates) are typically used as contrast agents. In ultrasound contrast imaging, a liquid containing gas-filled microbubbles is typically administered intravenously. Examples of contrast agents can be found in the literature (see, for example, ASL Jascinth et al.: Contrast Agents in computed tomography: A Review, Journal of Applied Dental and Medical Sciences, 2016, Vol. 2, No. 2, 143-149; H. Lusic et al.: X-ray-Computed Tomography Contrast Agents, Chem. Rev, 2013, 113, 3, 1641-166; https: / / www.radiology.wisc.edu / wp-content /

[0099] uploads / 2017 / 10 / contrast-agents-tutorial.pdf, M.R. Nough et al.: Radiographic and magnetic resonances contrast agents: Essentials and tips for safe practices, World J Radiol, Sep 28, 2017, 9(9): 339-349; L.C. Abonyi et al.: Intravascular Contrast Media in Radiography: Historical Development & Review of Risk Factors for Adverse Reactions, South American Journal of Clinical Research, 2016, Vol. 3, No. 1, 1-10; ACR Manual on Contrast Media, 2020, ISBN: 978-1-55903-012-0; A. Ignee et al.: Ultrasound contrast agents, Endosc Ultrasound, Nov-Dec 2016, 5(6), 355-362).

[0100] MRT contrast agents act by changing the relaxation time of the structure that takes up the contrast agent. A distinction can be made between two groups of substances: paramagnetic substances and superparamagnetic substances. Both groups of substances have unpaired electrons, which induce magnetic fields around individual atoms or molecules. Superparamagnetic contrast agents mainly cause T2 shortening, while paramagnetic contrast agents mainly cause T1 shortening. The effect of the contrast agent is indirect, because the contrast agent itself does not emit a signal, but instead only affects the signal intensity in its vicinity. An example of a superparamagnetic contrast agent is iron oxide nanoparticles (SPIO, in English: superparamagneticiron oxide (superparamagnetic iron oxide)). An example of a paramagnetic contrast agent is a gadolinium chelate, such as gadopentetate dimeglumine (trade name: etc.), gadoteric acid Gadolinium Gadoteridol Gadobutrol gadopiclenol (Elucirem, Vueway) and gadoxetate

[0101] In one embodiment, the radiological examination is an MRT examination using an MRT contrast agent.

[0102] In another embodiment, the radiological examination is a CT examination using a CT contrast agent.

[0103] In another embodiment, the radiological examination is a CT examination using an MRT contrast agent.

[0104] Generating an artificial radiological image with variable contrast enhancement is based on at least two representations of the examination region: a first representation and a second representation.

[0105] The first representation and the second representation are the results of a radiological examination. The first representation and the second representation are preferably measured radiological images or generated based on the measured radiological images. The first representation and / or the second representation can be an MRT image, a CT image, an ultrasound image and / or other radiological images, respectively.

[0106] The first representation represents the examination region without administration of contrast agent or after administration of a first amount of contrast agent. Preferably, the first representation represents the examination region without administration of contrast agent.

[0107] The second representation represents the examination region after administration of a second amount of contrast agent. The second amount is greater than the first amount (as described, the first amount may also be zero). The expression "after administration of the second amount of contrast agent" should not be understood to mean that the first amount and the second amount are added together in the examination region (unless the first amount is zero). Thus, the expression "the representation represents the examination region after administration of the (first or second) amount" should be understood as "the representation represents the examination region having the (first or second) amount" or "the representation represents the examination region including the (first or second) amount."

[0108] In one embodiment, the first amount and the second amount of contrast agent are both less than a standard amount.

[0109] In another embodiment, the second amount of contrast agent corresponds to a standard amount.

[0110] In another embodiment, the first amount of contrast agent is equal to zero and the second amount of contrast agent is less than a standard amount.

[0111] In a further embodiment, the first amount of contrast agent is equal to zero and the second amount of contrast agent corresponds to a standard amount.

[0112] The standard amount is typically the amount recommended by the contrast agent manufacturer and / or distributor and / or the amount authorized by the regulatory agency and / or the amount specified in the contrast agent package insert.

[0113] For example The standard amount is 0.025 mmol Gd-EOB-DTP disodium / kg body weight.

[0114] In one embodiment of the present disclosure, the contrast agent is an agent comprising gadolinium(III) 2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]acetate (also known as gadolinium-DOTA or gadoteric acid).

[0115] In a further embodiment, the contrast agent is an agent comprising gadolinium (III) ethoxybenzyldiethylenetriaminepentaacetate (Gd-EOB-DTPA); preferably, the contrast agent comprises the disodium salt of gadolinium (III) ethoxybenzyldiethylenetriaminepentaacetate (also known as gadoxetic acid).

[0116] In one embodiment of the present disclosure, the contrast agent is an agent comprising 2-[3,9-bis[1-carboxylate-4-(2,3-dihydroxypropylamino)-4-oxobutyl]-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-trien-6-yl]-5-(2,3-dihydroxypropylamino)-5-oxopentanoate gadolinium(III) (also known as Gadopiclenol) (see, for example, WO2007 / 042504 and WO2020 / 030618 and / or WO2022 / 013454).

[0117] In one embodiment of the present disclosure, the contrast agent is a 5-hydroxy-2-oxa-5,8,11-tris(carboxymethyl)-1-phenyl-2-oxa-5,8,11-triazatridecane-13-ato (5-)] gadolinium salt (2-), also known as gadobenic acid ( bezeichnet)) reagents.

[0118] In one embodiment of the present disclosure, the contrast agent is an agent comprising [4,10-bis(carboxylatemethyl)-7-{3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatemethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[({2-[4,7,10-tris-(carboxylatemethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propionyl}amino)acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]tetragadinium acetate (also known as Gadoquatrane bezeichnet) (see, e.g., J. Lohrke et al.: Preclinical Profile of Gadoquatrane: A Novel Tetrameric, Macrocyclic High Relaxivity Gadolinium-Based Contrast Agent. Invest Radiol., 2022, 1, 57(10): 629-638; WO2016193190).

[0119] In one embodiment of the present disclosure, the contrast agent is an agent comprising a Gd-containing compound of formula (I) 3+ complex or a stereoisomer, tautomer, hydrate, solvate or salt thereof, or a mixture thereof,

[0120]

[0121] in

[0122] Ar is a group selected from the following

[0123]

[0124] Where # is the connection key with X,

[0125] X is a group selected from the following

[0126] CH2, (CH2)2, (CH2)3, (CH2)4 and *-(CH2)2-O-CH2- # ,

[0127] Wherein * is the bond to Ar, and # represents the bond to the acetic acid residue,

[0128] R 1 、R 2 and R 3are each independently a hydrogen atom or a group selected from C1-C3 alkyl, -CH2OH, -(CH2)2OH and -CH2OCH3,

[0129] R 4 is a group selected from the group consisting of C2-C4 alkoxy, (H3C-CH2)-O-(CH2)2-O-, (H3C-CH2)-O-(CH2)2-O-(CH2)2-O- and (H3C-CH2)-O-(CH2)2-O-(CH2)2-O-(CH2)2-O-,

[0130] R 5 is a hydrogen atom,

[0131] and

[0132] R 6 A hydrogen atom.

[0133] In one embodiment of the present disclosure, wherein the contrast agent is an agent comprising a Gd 3+ complex or a stereoisomer, tautomer, hydrate, solvate or salt thereof, or a mixture thereof,

[0134]

[0135] in

[0136] Ar is a group selected from the following

[0137]

[0138] Where # is the connection key with X,

[0139] X is selected from CH2, (CH2)2, (CH2)3, (CH2)4 and *-(CH2)2-O-CH2- # wherein * is a bond to Ar, and # is a bond to an acetic acid residue,

[0140] R 7 is a hydrogen atom or a group selected from C1-C3 alkyl, -CH2OH, -(CH2)2OH and -CH2OCH3;

[0141] R 8 is a group selected from the group consisting of C2-C4 alkoxy, (H3C-CH2O)-(CH2)2-O-, (H3C-CH2O)-(CH2)2-O-(CH2)2-O- and (H3C-CH2O ) -(CH2)2-O-(CH2)2-O-(CH2)2-O-;

[0142] R9 and R 10 are each independently a hydrogen atom.

[0143] The term "C1-C3 alkyl" refers to a linear or branched saturated monovalent hydrocarbon group having 1, 2 or 3 carbon atoms, such as methyl, ethyl, n-propyl or isopropyl. The term "C2-C4 alkyl" refers to a linear or branched saturated monovalent hydrocarbon group having 2, 3 or 4 carbon atoms.

[0144] The term "C2-C4alkoxy" denotes a straight or branched saturated monovalent group of formula (C2-C4alkyl)-O-, wherein the term "C2-C4alkyl" is as defined above, for example methoxy, ethoxy, n-propoxy or isopropoxy.

[0145] In one embodiment of the present disclosure, the contrast agent is an agent comprising 2,2′,2″-(10-{1-carboxy-2-[2-(4-ethoxyphenyl)ethoxy]ethyl}-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)gadolinium triacetate (see, e.g., WO 2022 / 194777, Example 1).

[0146] In one embodiment of the present disclosure, the contrast agent is an agent comprising 2,2′,2″-{10-[1-carboxy-2-{4-[2-(2-ethoxyethoxy)ethoxy]phenyl}ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triyl}gadolinium triacetate (see, e.g., WO 2022 / 194777, Example 2).

[0147] In one embodiment of the present disclosure, the contrast agent is an agent comprising 2,2′,2″-{10-[(1R)-1-carboxy-2-{4-[2-(2-ethoxyethoxy)ethoxy]phenyl}ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triyl}gadolinium triacetate (see, e.g., WO2022 / 194777, Example 4).

[0148] In one embodiment of the present disclosure, the contrast agent is an agent comprising (2S,2'S,2"S)-2,2',2"-{10-[(1S)-1-carboxy-4-{4-[2-(2-ethoxyethoxy)ethoxy]phenyl}butyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triyl}tris(3-hydroxypropionate)gadolinium (see, e.g., WO2022 / 194777, Example 15).

[0149] In one embodiment of the present disclosure, the contrast agent is an agent comprising 2,2′,2″-{10-[(1S)-4-(4-butoxyphenyl)-1-carboxybutyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triyl}gadolinium triacetate (see, e.g., WO2022 / 194777, Example 31).

[0150] In one embodiment of the present disclosure, the contrast agent is an agent comprising 2,2',2"-{(2S)-10-(carboxymethyl)-2-[4-(2-ethoxyethoxy)benzyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triyl}gadolinium triacetate.

[0151] In one embodiment of the present disclosure, the contrast agent is an agent comprising 2,2',2"-[10-(carboxymethyl)-2-(4-ethoxybenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl]gadolinium triacetate.

[0152] In one embodiment of the present disclosure, the contrast agent is an agent comprising gadolinium (III) 5,8-bis(carboxylatemethyl)-2-[2-(methylamino)-2-oxoethyl]-10-oxo-2,5,8,11-tetraazadodecane-1-carboxylate hydrate (also known as gadodiamide).

[0153] In one embodiment of the present disclosure, the contrast agent is an agent comprising 2-[4-(2-hydroxypropyl)-7,10-bis(2-oxo-2-oxoethyl)-1,4,7,10-tetraazacyclododec-1-yl]gadolinium(III) acetate (also known as gadoteridol).

[0154] In one embodiment of the present disclosure, the contrast agent is an agent comprising 2,2′,2″-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)gadolinium(III) triacetate (also known as gadobutrol or Gd-DO3A-Butrol).

[0155] In a first step, a first representation and a second representation are received or generated.

[0156] The term "receiving" includes both retrieving a representation and accepting a representation for transmission to, for example, a computer system of the present disclosure. The representation may be received from a computed tomography system, a magnetic resonance imaging system, or an ultrasound scanner. Radiological images may be read from one or more data stores and / or transmitted from a separate computer system.

[0157] The term "generating" preferably means generating a representation based on another (e.g., received) representation or based on multiple other (e.g., received) representations. For example, the received representation can be a representation of the examination region of the examination object in real space. Based on this real space representation, a representation of the examination region of the examination object in frequency space can be generated, for example, by a transform operation (e.g., a Fourier transform). Other ways of generating a representation based on one or more other representations are described in this specification.

[0158] The first representation and the second representation represent the examination region in real space or frequency space.

[0159] Radiological images produced by radiological examinations are usually obtained in the form of representations in real space (also called image space).

[0160] “Real space” is ordinary three-dimensional Euclidean space, which corresponds to the space that we humans experience with our senses and that we move around in. Therefore, representations in real space are familiar representations.

[0161] In a representation in real space (also referred to in this specification as a real space depiction or real space representation), the examination region is typically represented by a large number of image elements (pixels or voxels), which can be arranged, for example, in a raster pattern, in which case each image element represents a portion of the examination region and can be assigned a color or grayscale value. A format widely used in radiology for storing and processing real space representations is the DICOM format. DICOM (Digital Imaging and Communications in Medicine) is an open standard for storing and exchanging information in medical image data management.

[0162] "Frequency space" is a domain in which a signal is considered as the sum of its individual frequency components.

[0163] In the representation in frequency space (also referred to in this specification as frequency space depiction or frequency space representation), the examination region is represented by a superposition of elementary oscillations. For example, the examination region can be represented by the sum of sine and / or cosine functions with different amplitudes, frequencies, and phases. These amplitudes and phases can be plotted as a function of frequency, for example, in a two-dimensional or three-dimensional representation. Typically, the lowest frequency (the origin) is located in the center. The farther from this center, the higher the frequency. Each frequency can be assigned an amplitude (representing the frequency in the frequency space depiction) and a phase (representing the degree to which the corresponding oscillation is offset from the sine or cosine oscillation).

[0164] Raw data obtained in a magnetic resonance imaging examination (so-called k-space data) is an example of a representation in frequency space. Such raw data (k-space data) from a magnetic resonance imaging examination can be used directly as the first and / or second representation in the present disclosure.

[0165] The representation in the real space can be converted (transformed) into the representation in the frequency space, for example, by a Fourier transform operation. Conversely, the representation in the frequency space can be converted (transformed) into the representation in the real space, for example, by an inverse Fourier transform.

[0166] Detailed information on real-space and frequency-space representations and their respective conversions to each other is described in many publications, see for example https: / / see.stanford.edu / materials / lsoftaee261 / book-fall-07.pdf.

[0167] Before converting the real-space representation into a frequency-space depiction, the real-space representations can be co-registered. Co-registration (also known as image registration in the prior art) is used to make two or more real-space depictions of the same examination region as consistent as possible. One of the real-space depictions is defined as the reference image, the other as the target image. To optimally match the target image to the reference image, a compensating transformation is calculated.

[0168] It is also possible to co-register representations in frequency space; it should be noted here that a translation in real space corresponds to an additive linear phase ramp in frequency space. On the other hand, scaling and rotation are preserved in the Fourier transform and inverse Fourier transform—scaling and rotation in frequency space are also scaling and rotation in real space (e.g., see S. Skare: Rigid Body Image Realignment in Image Space vs. k-Space, ISMRM SCIENTIFIC WORKSHOP on Motion Correction, 2014, https: / / cds.ismrm.org / protected / Motion_14 / Program / Syllabus / Skare.pdf).

[0169] It should be noted that the co-registration in frequency space does not have to be very precise, as the frequency filter attenuates the high frequencies of the mapped image details, thereby reducing inaccuracies in the registration. This is an advantage of the method described in this disclosure over methods that perform operations in real space.

[0170] Based on the first representation and the second representation, a third representation is generated.

[0171] The third representation represents the examination region in real space or frequency space.

[0172] The third characterization represents the signal enhancement in the examination region caused by the second amount of contrast agent (contrast agent signal characterization). In other words, the third characterization comprises the difference between the second characterization caused by the second amount of contrast agent and the first characterization.

[0173] In a preferred embodiment, the generation of the third representation comprises subtracting the first representation from the second representation. In other words, in a preferred embodiment, the third representation is the difference between the first representation and the second representation.

[0174] The subtraction can be performed in real space or frequency space.

[0175] If the first representation and the second representation represent the examination region in real space, then the subtraction of the first representation from the second representation is preferably performed in real space; the result is a third representation in real space (contrast agent signal representation).

[0176] If the first representation and the second representation represent the examination region in frequency space, the subtraction of the first representation from the second representation is preferably performed in frequency space; the result is a third representation in frequency space (contrast agent signal representation).

[0177] However, it is also possible to first convert the first representation in real space and the second representation in real space into a first representation in frequency space and a second representation in frequency space, and then generate a third representation in frequency space by subtracting the first frequency space representation from the second frequency space representation.

[0178] Similarly, the first representation in frequency space and the second representation in frequency space can be first converted into a first representation in real space and a second representation in real space, and then the third representation in real space can be generated by subtracting the first real space representation from the second real space representation.

[0179] Preferably, a third representation in frequency space is generated based on the first representation in frequency space and the second representation in frequency space. In this third frequency space representation, each frequency is represented by an amplitude value, wherein the more strongly a frequency is affected by the second amount of contrast agent, the higher the value.

[0180] Figure 1 An embodiment of generating a third representation based on a first representation and a second representation is exemplarily and schematically shown.

[0181] Figure 1 The examination region of the examination object is shown in various representations.

[0182] First characterization R1 I represents the examination region in real space before administration of contrast agent or after administration of a first amount of contrast agent. Figure 1 The examination area shown in FIG includes the pig's liver. First Characterization R1 I It is a magnetic resonance image.

[0183] Through the transformation operation T (such as Fourier transform), the first real space representation R1 can be I Converted to a first representation R1 of the examined region in frequency space F The first frequency space representation R1 F Representation and the first real space representation R1 I The same examination area of ​​the same examination subject is also examined before or after administration of a first amount of contrast agent.

[0184] The first frequency space representation R1 F The inverse transformation operation T -1 is converted into the first real space representation R1 I . Inverse transformation operation T -1 is the inverse transformation of the transformation operation T.

[0185] Second characterization R2 I Representation and the first representation R1 in real space I Same inspection area of ​​the same inspection object. Second real space representation R2 I The second characterization R1 represents the examination region after the second amount of contrast agent is administered. The second amount is greater than the first amount (as mentioned, the first amount may also be zero). I Also an MRI image. Figure 1 The contrast agent used in the embodiment shown is a hepatobiliary MRI contrast agent. Hepatobiliary contrast agents have the characteristics of being specifically taken up by liver cells (hepatocytes), accumulating in functional tissue (parenchyma), and enhancing contrast in healthy liver tissue. An example of a hepatobiliary contrast agent is gadoxetate disodium salt (Gd-EOB-DTPA disodium), which is described in U.S. Patent No. 6,039,931A and is marketed under the trade name and Commercially available. In addition, other hepatobiliary contrast agents are also described in WO2022 / 194777.

[0186] Representation R2 in the second real space I In the image, the contrast between the liver tissue and the surrounding tissue is enhanced due to the second amount of contrast agent.

[0187] The second real space can be represented by R2 through the transformation operation T I Converted to a second representation R2 of the examination region in frequency space FThe second frequency space representation R2 F Representation and second real space representation R2 I The same examination area of ​​the same examination subject is also administered after a second amount of contrast agent.

[0188] The second frequency space representation R2 F The inverse transformation operation T -1 Convert to the second real space representation R2 I .

[0189] Based on the first frequency space representation R1 F and the second frequency space representation R2 F , generate the third frequency space representation R3 F .exist Figure 1 In the embodiment shown, the third frequency space representation R3 F The second frequency space representation R2F With the first frequency space representation R1 F The difference (R3 F =R2 F -R1 F ).

[0190] The third frequency space can be represented by R3 F Normalization is performed, that is, the amplitude values ​​may be multiplied by a factor so that the amplitude with the highest value is represented by the hue "white" for example, and the amplitude with the lowest value is represented by the hue "black" for example.

[0191] In this normalization process, negative values ​​that may appear when the first representation is subtracted from the second representation may also be set to zero (or another value) to avoid negative values.

[0192] The third frequency space representation R3 F represents the contrast enhancement caused by the second amount of contrast agent in the examination region.

[0193] In a further step, a weighted third representation can be generated based on the third representation. This weighting of the third representation allows frequencies that contribute more to the contrast to be given a higher weight than frequencies that contribute less to the contrast. The expression "contrast" refers to a real-space depiction that corresponds to the frequency-space depiction. Contrast information is represented in the frequency-space depiction by low frequencies, while higher frequencies represent information about fine structures. Image noise is typically evenly distributed in the frequency depiction. Therefore, a weighted third representation can be generated by applying a frequency-dependent weighting function to the third representation, wherein low frequencies are given a higher weight relative to higher frequencies. The frequency-dependent weighting function has the effect of a filter. The filter increases the signal-to-noise ratio by reducing the spectral noise density at high frequencies.

[0194] The weighting of the third representation (ie, generating a weighted third representation) is performed in the frequency space. If the third representation is a real space representation, it can be transformed into a third representation in the frequency space by a Fourier transform operation.

[0195] Weighting the third representation in frequency space can be accomplished by multiplying the third representation in frequency space by a frequency-dependent weighting function. In this frequency-dependent weighting function, each frequency is assigned a weighting factor. If the weighting factor for a particular frequency is, for example, zero, then when the third representation in frequency space is multiplied by the frequency-dependent weighting function, the amplitude of the corresponding frequency in the third representation will be set to zero, i.e., the frequency will be eliminated. If the weighting factor for a particular frequency is, for example, 1, then when the third representation in frequency space is multiplied by the frequency-dependent weighting function, the amplitude of the corresponding frequency in the third representation will remain unchanged, i.e., the frequency will remain unchanged. If the weighting factor for a particular frequency is, for example, 0.5, then when the third representation in frequency space is multiplied by the frequency-dependent weighting function, the amplitude of the corresponding frequency will be reduced to half its value, i.e., the corresponding frequency will be attenuated in the third representation in frequency space. If the weighting factor for a particular frequency is, for example, 2, then when the third representation in frequency space is multiplied by the frequency-dependent weighting function, the amplitude of the corresponding frequency will be doubled, i.e., the corresponding frequency will be enhanced in the third representation in frequency space.

[0196] In the frequency-dependent weighting of the third characterization, the amplitudes of lower frequencies are preferably multiplied by a higher weighting factor than the amplitudes of higher frequencies. In a preferred embodiment, the higher the frequency, the lower the weighting factor by which the frequency amplitude is multiplied.

[0197] Figure 3 An embodiment of a frequency-dependent weighting function is shown.

[0198] Figure 2 The generation of the weighted third representation R3 is shown exemplarily and schematically. F,w . Figure 2 Shown Figure 1 The third frequency space representation R3 has been shown in F The third frequency space representation R3 F The amplitude value is multiplied by the weight factor. The weight factor is related to the frequency, that is, the weight factor is a function of the frequency. For the sake of convenience, the weight function WF is Figure 2 The weight function WF shows the weight factor wf as a function of the frequency f along one dimension (along the dashed line). In the same image plane, along the dimension perpendicular to the dashed line, the weight function has the same shape; it is just compressed because the representation R3 in this embodiment F It's a rectangle, not a square.

[0199] Compared to the higher frequency amplitudes (which are further away from the characterization R3F The WF weighting function reduces the low frequency amplitude (in the embodiment shown, the frequency from the center of the characterization R3 F The weight factor is multiplied by a higher weighting factor; that is, a higher weight is given to low frequencies than to higher frequencies. This can be seen in the weighted representation R3 F,w It is identified in the figure, where the gray value towards the edge of the representation is greater than that in the representation R3 F The case is darker, and the overall brightness from the center outward is better than that in the characterization R3 F decreases faster in the case of .

[0200] The weighted representation R3 F,w Normalization is performed, that is, the amplitude values ​​may be multiplied by a factor so that the amplitude with the highest value is represented by, for example, the hue "white" and the amplitude with the lowest value is represented by, for example, the hue "black".

[0201] Figure 3 An embodiment of a frequency dependent weighting function that can be used to weight the third representation is shown.For simplicity, the weighting function is represented as a two-dimensional graph, where the weighting factor wf (ordinate) is plotted as a function of the frequency f (abscissa).

[0202] Figure 3 (a) shows that Figure 2 The weight function WF is shown in FIG. In this weight function, the weight factor may decrease from the center in an exponential form as the frequency increases, for example.

[0203] Figure 3 (b) shows a weighting function where the weighting factor decreases linearly from the center as the frequency increases.

[0204] Figure 3 (c) shows a weighting function in which the weighting factor decreases from the center in the form of an inverse parabola as the frequency increases.

[0205] Figure 3 (d) shows a weighting function where the weight factor is constant within a defined range near the center and then decreases exponentially from the threshold frequency.

[0206] Figure 3 (e) shows a weight function where the weight factors have a cosine function form near the center.

[0207] Figure 3 (f) shows a weight function where the weight factors have a step function form near the center.

[0208] Figure 3(g) shows a weight function where the weight factors have a Gaussian distribution function form near the center.

[0209] Figure 3 (h) shows a weight function where the weight factors have the form of a Hann function near the center.

[0210] Combinations of the weight functions shown with further / other weight functions are possible. Examples of other weight functions can be found, for example, at https: / / de.wikipedia.org / wiki / Fensterfunktion#Beispiele_von_Fensterfunktionen; FJ Harris et al.: On the Use of Windows for Harmonic Analysis with the Discrete Fourier Transform, Proceedings of the IEEE, Vol. 66, No. 1, 1978; https: / / docs.scipy.org / doc / scipy / reference / signal.windows.html; KMMPrabhu: Window Functions and Their Applications in Signal Processing, CRC Press, 2014, 978-1-4665-1583-3.

[0211] The weight functions that can be used are also called window functions in the literature.

[0212] The k-space data in MRT imaging and spectroscopy are preferably weighted using weighting functions of proven utility, such as the Hann function (also known as the Hann window, see, for example, the Hanning window, see, for example, R. Pohmann et al.: Accurate phosphorus metabolite images of the human heart by 3D acquisition-weighted CSI, Magnetic Resonance in Medicine: An Official Journal of the International Society for Magnetic Resonance in Medicine 45.5 (2001): 817-826).

[0213] Another preferred weighting function is the Poisson function (Poisson window).

[0214] In a further step, a fourth representation is generated by combining the first representation with the optionally weighted third representation.This combination transfers information about the contrast enhancement brought about by the second amount of contrast agent in the examination region to the first representation.

[0215] For example, the combination may be or comprise the addition of the first representation and an optionally weighted third representation.However, multiplicative or non-linear combination is also possible.

[0216] The generation of the fourth representation based on the optionally weighted third representation can be performed in real space or in frequency space, that is, the optionally weighted third frequency space representation can be combined with the first frequency space representation (for example, by adding the optionally weighted third frequency space representation to the first frequency space representation by a factor of α), or the optionally weighted third real space representation can be combined with the first real space representation (for example, by adding the optionally weighted third real space representation to the first real space representation by a factor of α).

[0217] In principle, a fourth representation (in real space or frequency space) can also be generated by combining the optionally weighted third representation with the second representation (eg by adding the optionally weighted third representation to the second representation by a factor of α).

[0218] Figure 4 An embodiment of generating a fourth representation is shown exemplarily and schematically. Figure 4 By putting Figure 1 The first frequency-space representation R1 has been shown F With Figure 2 The weighted representation R3 already shown in F,w Combined, a fourth representation R4 of the inspection area of ​​the inspection object in the frequency space is generated F The combination in the embodiment is completed by addition. The fourth characterization R4 can be F Perform normalization processing.

[0219] If the fourth representation is a representation in frequency space (such as Figure 4 ), the fourth frequency-space representation is converted into a fourth real-space representation in a further step by a transformation operation (e.g., an inverse Fourier transform). If the fourth representation is a representation in real space (e.g., because it is generated by combining the first real-space representation with an optionally weighted third real-space representation), such a transformation operation into real space is not required.

[0220] The fourth real-space depiction of the examination region may be output (eg, displayed on a screen or printed using a printer), stored in a data storage device, and / or transmitted to a separate computer system.

[0221] Figure 5 It is shown exemplarily and schematically how to Figure 1 The inverse transform operation T described -1 from Figure 4 The fourth representation R4 of the examination region in frequency space has already been shown in F Generate a fourth representation R4 of the inspection area in real space I .

[0222] Figure 6 Exemplarily and schematically shown in Figure 1 、 Figure 2 、 Figure 4 and Figure 5 The entire method is partially shown in FIG.

[0223] When the third representation is generated by subtracting the first representation from the second representation, adding the (unweighted) third representation to the first representation will again produce the second representation.

[0224] Adding the weighted third representation to the first representation produces a representation that is different from the second representation.

[0225] The weighting brings the contrast information into focus, ie features in the resulting fourth representation are emphasized due to the contrast increase brought about by the second amount of contrast agent.

[0226] The optionally weighted third representation may be added multiple times to the first representation to achieve further contrast enhancement without amplifying interference and / or noise to the same extent as the contrast.

[0227] Therefore, the optionally weighted third characterization can be multiplied by a gain factor α and added to the first characterization, where the gain factor α represents the degree of contrast enhancement in the fourth characterization. An enhancement of less than 1 can also be selected here, that is, the contrast between the area with contrast agent and the area without contrast agent is lower in the fourth characterization than in the second characterization. It is also possible to achieve a greater enhancement than the contrast enhancement brought about by a standard amount of contrast agent. Using the method described in WO2019 / 074938A1, it is not possible to achieve such a contrast enhancement without administering to people an amount of contrast agent higher than the standard amount (therefore beyond the range approved by the regulatory agency) to generate training data.

[0228] The gain factor α may be selected by the user, ie it may be variable or predefined, ie predetermined.

[0229] Figure 7Various representations of the examination area of ​​the examination object in real space are shown exemplarily and schematically. These representations differ in the gain factor α. In this embodiment, it is assumed that the gain factor α can have values ​​of 0, 1, 2, 3 and 4.

[0230] A gain factor α=0 means that no contrast enhancement is performed in the first representation. Hence, the representation shows the original first representation in real space.

[0231] A gain factor α=1 means that the optionally weighted third representation is added once to the first representation (either in frequency space or in real space). The contrast enhancement is similar to that in the second representation, but the weighting performed (eg low frequency weighting) makes it less noisy / interfering.

[0232] A gain factor α = 2, 3 or 4 means that the optionally weighted third representation is added to the first representation two, three or four times (in frequency space or in real space).The contrast enhancement increases with increasing gain factor.

[0233] exist Figure 7 In the illustrated embodiment, an integer multiple of the optionally weighted third representation is added to the first representation in all cases. Of course, non-integer ratios of the optionally weighted third representation can also be added to the first representation (e.g., α = 1.5 or α = 3.7 or α = 4.159). This means that the enhancement can be increased in a continuous manner.

[0234] Negative α values ​​are also possible, which can be chosen, for example, such that regions of the examination area which experience a contrast agent-induced signal enhancement in the representation generated by the measurement appear completely dark (black) in the artificially generated representation.

[0235] The gain factor α is a positive or negative real number.

[0236] The gain factor α can also be determined in an automated manner. "Automatically" means without manual assistance. For example, at least one area in the real-space depiction of the first and / or second representation can be defined and / or selected by the user, and the gain factor α can be set so that the grayscale values ​​in the real-space depiction (or in the case of a depiction other than a grayscale value depiction, different tonal values) take a defined value and / or are above or below a threshold value, and / or so that two grayscale values ​​in two different selected or defined areas have a defined distance from each other and / or a distance between each other that is above or below a threshold value. Other criteria can also be used in the automatic determination of the gain factor α. The automatic determination criterion for the gain factor α can, for example, be based on a histogram of the real-space depiction of the first, second, third, weighted third and / or fourth representation. Such a histogram can show the number of image elements with defined tonal values ​​or grayscale values.

[0237] Figure 8 A preferred embodiment of outputting an artificial contrast-enhanced radiographic image of an examination region by a computer system / computer program is shown. The output is provided to a user of the computer system and / or computer program of the present disclosure.

[0238] A first real-space representation R1 of the examination area of ​​the examination object I , a second real space representation R2 of the inspection area of ​​the inspection object I and a fourth real space representation R4 of the examination area of ​​the examination object I Displayed to the user (e.g., on a monitor).

[0239] First characterization R1 I It represents the examination region before administration of contrast agent or after administration of a first amount of contrast agent.

[0240] Second characterization R2 I The examination region is shown after administration of a second amount of contrast agent. The second amount is greater than the first amount.

[0241] Fourth Characterization R4 I The contrast between the region without contrast agent and the region with contrast agent is shown in the fourth characterization R4. I In the second case, the ratio is R2 I The case is bigger.

[0242] Fourth Characterization R4 I was generated as described in this disclosure (see in particular with Figures 1 to 7 Related description).

[0243] All displayed representations are of the inspection area in real space. Figure 8 In the embodiment shown, the frequency-space representation is not displayed to the user. This is generally not envisaged, as many users are not familiar with frequency-space representations.

[0244] In the characterization shown R1 I 、R2 I and R4 I Below the graph, a histogram of the representation is displayed to the user in an overlay manner.

[0245] In the characterization shown R1 I 、R2 I and R4 I Above the , three virtual sliders are provided for users to adjust. The first slider α allows users to freely select the gain factor α in the range of 1 to 10. The slider indicates that the gain factor can be continuously increased from 1 to 10.

[0246] The second slider, β, and the third slider, γ, allow the user to change the parameters of the weighting function. For example, these parameters can determine how strongly the weighting factor decreases as the frequency increases.

[0247] Figure 8 The output shown is preferably configured so that when the user makes a change via one of the sliders, the fourth representation R4 I The display is updated immediately. The user can then, for example, change the gain factor α and immediately see how the change in gain factor α affects the characteristic R4 I This allows the user to identify those fourth representations R4 that lead to an area of ​​inspection for the user. I For the best setting.

[0248] Any change in one of the parameters α, β and / or γ will cause the computer system to recalculate the fourth representation R4 each time based on the changed parameters. I And display it in the background. The same applies to the fourth representation R4 I Histogram of .

[0249] So far, the contrast enhancement according to the present disclosure may bring about a contrast enhancement that is not desired by the user. This will be explained using an embodiment. The embodiment is in Figure 9 is schematically shown in FIG.

[0250] Figure 9 A first representation R1 of the examination region of the examination object is shown I and the second characterization R2 I The examination area includes the pig's liver L and gallbladder B. First characterization R1 I The second representation R2 represents the examination region in real space without contrast agent administration or after administration of a first amount of contrast agent. I represents the examination region after the second amount of contrast agent is administered in real space. The second amount is greater than the first amount. In the second representation R2 I In the image, it can be seen that the gallbladder has been partially filled with a fluid containing a contrast agent or other fluid, resulting in high contrast between the partially filled gallbladder and the surrounding area.

[0251] The contrast enhancement described in the present disclosure results in an artificially contrast-enhanced radiographic image R4 of the examination region. I The contrast between the partially filled gallbladder and other areas is further enhanced. However, it is conceivable that the user may be interested in contrast enhancement of the liver instead.

[0252] In a preferred embodiment, the computer system and computer program of the present disclosure are configured to receive user input. In the input, the user can specify one or more areas that they do not want contrast enhancement. The user can use, for example, a mouse or other input method to draw such areas in the first, second, and / or fourth representations in real space. For example, Figure 9 In the embodiment shown, the user can first characterize R1 I , the second characterization R2 I and / or fourth characterization R4 I The gallbladder is selected and / or highlighted in the image. The computer system or computer program may be configured to set the hue value or grayscale value of all image elements (pixels, voxels) representing the (highlighted) gallbladder to zero. The result is a representation of R2 I* , where the gallbladder is represented by a black image element. If the representation R1 described in the present disclosure is I and R2 I* (or based on their corresponding frequency-space representations) to perform contrast enhancement, an artificial contrast-enhanced radiographic image R4 will be produced. I* , whereby there is now in particular an increased contrast between the liver L and other areas, but the partially filled gallbladder is no longer shown with increased contrast.

[0253] In a preferred embodiment, the regions not to be (or to be) contrast enhanced are determined in an automatic manner. Preferably, a first real space representation R1 is determined I and the second real space representation R2 I The quotient of the hue values ​​of all corresponding pairs of image elements (i.e., with the same coordinates):

[0254] Q = g2(x,y,z) / g1(x,y,z)

[0255] Where Q is the quotient of the hue value, g2(x,y,z) is the second representation R2 I The hue value of the image element with coordinates x, y, z in the first representation R1 I The quotient Q of the tonal values ​​is a measure of the brightness of the image element with coordinates x, y, z depicted in the second representation compared to the corresponding image element in the first representation. It specifies the contrast enhancement brought about by the second amount of contrast agent in the examination region represented by the image element with coordinates x, y, z.

[0256] The computer system and computer program may be configured to compare the quotient of the tonal values ​​of all image elements with a predetermined threshold value. The predetermined threshold value specifies the maximum contrast enhancement expected due to the contrast agent.

[0257] If the quotient of the hue values ​​of the corresponding image element is greater than a predetermined threshold, the hue value of the corresponding image element may be set to zero.

[0258] Figure 10 A computer system according to the present disclosure is shown exemplarily and schematically.

[0259] A "computer system" is an electronic data processing system that processes data by means of programmable computational rules. Such a system typically includes a "computer," which is a unit including a processor for performing logical operations, and peripheral devices.

[0260] In computer technology, the term "peripheral device" refers to any device that is connected to a computer and is used to control it and / or serve as an input and output device. Examples of peripheral devices are monitors (screens), printers, scanners, mice, keyboards, drives, cameras, microphones, speakers, etc. Internal ports and expansion cards are also considered peripheral devices in computer technology.

[0261] Figure 10 The computer system (1) shown in the figure comprises a receiving unit (10), a control and calculation unit (20) and an output unit (30).

[0262] The control and calculation unit (20) is used to control the computer system (1), coordinate the data flow between the various units of the computer system (1) and perform calculations.

[0263] The control and computing unit (20) is configured to:

[0264] - generating a first representation or causing a receiving unit (10) to receive the first representation, wherein the first representation represents the examination region of the examination object in real space or in frequency space without administration of a contrast agent or after administration of a first amount of a contrast agent,

[0265] - generating a second representation or causing a receiving unit (10) to receive the second representation, wherein the second representation represents the examination region of the examination object in real space or in frequency space after administration of the second amount of contrast agent,

[0266] - generating a third representation based on the first representation and the second representation, wherein the generating of the third representation comprises subtracting the first representation from the second representation, wherein the third representation represents the examination region in real space or in frequency space,

[0267] - optionally, generating a weighted third representation based on the third representation, wherein generating the weighted third representation comprises performing a frequency-dependent weighting of the third representation in frequency space,

[0268] - generating a fourth representation based on the optionally weighted third representation and the first representation or the second representation, wherein generating the fourth representation comprises adding α times the optional third representation to the first representation or the second representation, wherein α is a positive or negative real number,

[0269] - if the fourth representation represents the examination region in frequency space, transforming the fourth representation into a representation of the examination region in real space,

[0270] - causing the output unit (30) to output the fourth representation of the examination region in real space and / or to store it and / or to transmit it to a separate computer system.

[0271] Figure 11 Another embodiment of a computer system is shown exemplarily and schematically. The computer system (1) comprises a processing unit (21) connected to a memory (22). The processing unit (21) and the memory (22) form a control and calculation unit, such as Figure 10 As shown in .

[0272] The processing unit (21) may comprise one or more processors, either alone or in combination with one or more memories. The processing unit (21) may be conventional computer hardware capable of processing information such as digital images, computer programs and / or other digital information. The processing unit (21) typically consists of an arrangement of electronic circuits, some of which may be designed as an integrated circuit or as a plurality of interconnected integrated circuits (integrated circuits are sometimes also referred to as "chips"). The processing unit (21) may be configured to execute a computer program, which may be stored in a working memory of the processing unit (21) or in a memory (22) of the same or a different computer system.

[0273] The memory (22) may be conventional computer hardware capable of temporarily and / or permanently storing information such as digital images (e.g., representations of the examination area), data, computer programs, and / or other digital information. The memory (22) may include volatile and / or non-volatile memory and may be non-removable or removable. Examples of suitable memory are RAM (random access memory), ROM (read-only memory), hard disk, flash memory, interchangeable computer disks, optical disks, magnetic tape, or combinations thereof. Optical disks may include compact disks with read-only memory (CD-ROM), compact disks with read / write capabilities (CD-R / W), DVDs, Blu-ray discs, and the like.

[0274] The processing unit (21) can be connected not only to the memory (22), but also to one or more interfaces (11, 12, 31, 32, 33) for displaying, transmitting and / or receiving information. The interface may include one or more communication interfaces (11, 32, 33) and / or one or more user interfaces (12, 31). The one or more communication interfaces may be configured to send and / or receive information, for example, to an MRT scanner, a CT scanner, an ultrasound camera, other computer systems, a network, a data storage device, etc. The one or more communication interfaces may be configured to transmit and / or receive information via a physical (wired) and / or wireless communication connection. The one or more communication interfaces may include one or more interfaces for connecting to a network, for example, using technologies such as mobile phones, Wi-Fi, satellite, cable, DSL, fiber optics, etc. In some embodiments, the one or more communication interfaces may include one or more short-range communication interfaces, which are configured to connect devices having short-range communication technologies such as NFC, RFID, Bluetooth, Bluetooth LE, ZigBee, infrared (e.g., IrDA), etc.

[0275] The user interface may include a display (31). The display (31) may be configured to display information to a user. Suitable examples thereof are a liquid crystal display (LCD), a light emitting diode display (LED), a plasma display panel (PDP), etc. The user input interface (11, 12) may be wired or wireless and may be configured to receive information from a user in the computer system (1), for example for processing, storage and / or display. Suitable examples of user input interfaces are a microphone, an image or video recording device (e.g., a camera), a keyboard or keypad, a joystick, a touch-sensitive interface (separate from or integrated into the touch screen), etc. In some embodiments, the user interface may include automatic identification and data capture technology (AIDC) for machine-readable information. This may include bar codes, radio frequency identification (RFID), magnetic strips, optical character recognition (OCR), integrated circuit cards (ICC), etc. The user interface may also include one or more interfaces for communicating with peripheral devices such as printers.

[0276] One or more computer programs (40) may be stored in the memory (22) and executed by the processing unit (21), thereby programming the processing unit (21) to perform the functions described in this specification. Retrieval, loading, and execution of the instructions of the computer program (40) may be performed sequentially, thereby retrieving, loading, and executing the instructions, respectively. However, retrieval, loading, and / or execution may also be performed in parallel.

[0277] The computer system of the present disclosure may be designed as a laptop, notebook, netbook and / or tablet PC; it may also be a component of an MRT scanner, a CT scanner or an ultrasound diagnostic device.

[0278] Figure 12 Embodiments of the computer-implemented method are exemplarily and schematically shown in flowchart form.

[0279] The method (100) comprises the following steps:

[0280] (110) receiving or generating a first representation, wherein the first representation represents an examination region of the examination subject in real space or in frequency space without administration of a contrast agent or after administration of a first amount of a contrast agent,

[0281] (120) receiving or generating a second representation, wherein the second representation represents the examination region of the examination subject in real space or in frequency space after administration of a second amount of contrast agent,

[0282] (130) generating a third representation based on the first representation and the second representation, wherein generating the third representation comprises subtracting the first representation from the second representation,

[0283] (140) Optionally, generating a weighted third representation by applying a frequency-dependent weight function to the third representation in frequency space,

[0284] (150) generating a fourth representation, wherein generating the fourth representation comprises adding α-times the optionally weighted third representation to the first representation or the second representation, wherein α is a positive or negative real number,

[0285] (160) If the fourth representation represents the examination region in frequency space: transforming the fourth representation into a fourth representation of the examination region in real space,

[0286] (170) Outputting and / or storing a fourth representation of the examination region in real space and / or transmitting the fourth representation of the examination region in real space to a separate computer system.

[0287] The present invention can be used for various applications. Some application examples are described below, but the present invention is not intended to be limited to these application examples.

[0288] A first example of a use involves magnetic resonance imaging (MRI) examinations for differentiating intraaxial tumors, such as brain metastases and malignant gliomas. The infiltrative growth of these tumors makes it difficult to accurately distinguish between tumor and healthy tissue. However, determining the extent of the tumor is crucial for surgical resection. Administration of an extracellular contrast agent makes it easier to distinguish between tumor and healthy tissue; intraaxial tumors can be more easily distinguished after intravenous administration of a standard dose of 0.1 mmol / kg body weight of the extracellular MRI contrast agent gadobutrol. At higher doses, the contrast between lesions and healthy brain tissue is further enhanced; the detection rate of brain metastases increases linearly with contrast agent dose (see, e.g., M. Hartmann et al.: Does the administration of a high dose of a paramagnetic contrast medium (Gadovist) improve the diagnostic value of magnetic resonance tomography in glioblastomas? doi: 10.1055 / s-2007-1015623).

[0289] Here a single triple dose or a second subsequent dose may be administered, up to a total dose of 0.3 mmol / kg body weight. This would expose the patient and the environment to additional gadolinium and would incur other additional costs in performing the second scan.

[0290] The present invention can be used to avoid exceeding the standard dose of contrast agent. A first MRT image can be generated without administering contrast agent or with an amount less than the standard dose, and a second MRT image can be generated with the standard dose. Based on these generated MRT images, a composite MRT image can be generated as described herein, in which the contrast between lesions and healthy tissue can be varied within wide limits by varying the gain factor α. This enables the achievement of contrast that, with other methods, can only be achieved by administering a larger-than-standard amount of contrast agent.

[0291] Another example of use relates to reducing the amount of MRI contrast agent used in magnetic resonance imaging examinations. Gadolinium-containing contrast agents (such as gadobutrol) are used in a variety of examinations. They are used to enhance contrast during skull examinations, spinal examinations, breast examinations, and other examinations. In the central nervous system, gadobutrol highlights areas with impaired blood-brain barriers and / or vascular abnormalities. In breast tissue, gadobutrol can visualize the presence and extent of malignant breast disease. Gadobutrol is also used in contrast-enhanced magnetic resonance angiography for diagnosing stroke, monitoring tumor blood perfusion, and detecting focal cerebral ischemia.

[0292] Due to the increasing impact on the environment, the cost burden on the healthcare system, and concerns about acute side effects and possible long-term health risks, especially in cases of repeated and prolonged exposure, it is desirable to reduce the dose of gadolinium-containing contrast agents. This can be achieved through the present invention.

[0293] A first MRT image can be generated without contrast agent administration, and a second MRT image can be generated after administration of a less-than-standard amount of contrast agent. Based on these generated MRT images, a composite MRT image can be generated as described herein, wherein the contrast can be varied within wide limits by varying the gain factor α. This allows the use of less-than-standard amounts of contrast agent to achieve the same contrast as that achieved after administration of the standard amount.

[0294] Another example of use is the use of hepatobiliary contrast agents (e.g. ) detect, identify and / or characterize lesions in the liver.

[0295] It is administered intravenously (iv) at a standard dose of 0.025 mmol / kg body weight. This standard dose is lower than the standard dose of 0.1 mmol / kg body weight in the case of extracellular MRT contrast agents. Unlike contrast-enhanced MRT using extracellular gadolinium-containing contrast agents, allows dynamic multiphasic T1w imaging. However, The lower dose and the observation that transient motion artifacts may appear shortly after intravenous administration mean that radiologists perceive that the use of The contrast enhancement of hepatic lesions is poorer than that achieved with extracellular MRI contrast agents. However, assessment of contrast enhancement during the arterial phase and the vascularity of focal hepatic lesions is crucial for accurate lesion characterization.

[0296] By means of the present invention, the contrast can be enhanced, in particular in the arterial phase, without having to administer higher doses.

[0297] A first MRT image without contrast agent administration and a second MRT image in the arterial phase after administration of a standard amount of contrast agent can be generated. Based on these generated MRT images, a composite MRT image can be generated as described herein, wherein the contrast in the arterial phase can be varied within wide limits by varying the gain factor α. This enables the achievement of contrast that, with other methods, can only be achieved by administering a larger-than-standard amount of contrast agent.

[0298] Another example of use relates to the use of MRT contrast agents in computed tomography examinations.

[0299] In CT examinations, MRT contrast agents generally have a lower contrast enhancement effect than CT contrast agents. However, it would be advantageous to apply MRT contrast agents to CT examinations. One embodiment is to perform minimally invasive intervention on the patient's liver, wherein the surgeon monitors the operation via a CT scanner. Compared to magnetic resonance imaging, the advantage of computed tomography (CT) is that more major surgical interventions can be performed in the examination area while generating a CT image of the examination area of ​​the object being examined. On the other hand, only a few surgical instruments and surgical equipment are compatible with MRT. In addition, the magnets used in MRT limit contact with the patient. Therefore, when performing surgery in the examination area, the surgeon will be able to visualize the examination area via CT and can track the surgery on a monitor.

[0300] For example, if a surgeon wishes to perform surgery on a patient's liver, for example to biopsy a liver lesion or remove a tumor, the contrast between the liver lesion or tumor and healthy liver tissue will not be as evident in a CT image of the liver as it would be in an MRT image after administration of a hepatobiliary contrast agent. Currently, there are no known and / or licensed CT-specific hepatobiliary contrast agents. Therefore, the use of MRT contrast agents (more particularly hepatobiliary MRT contrast agents) in computed tomography combines the ability to distinguish healthy from diseased liver tissue with the ability to visualize the liver while undergoing surgery.

[0301] By means of the present invention, the relatively low contrast enhancement achieved by MRT contrast agents can be increased without the need to administer a higher than standard dose.

[0302] A first CT image can be generated without administering an MRT contrast agent, and a second CT image can be generated after administering a standard amount of MRT contrast agent. Based on these generated CT images, a synthetic CT image can be generated as described herein, wherein the contrast produced by the MRT contrast agent can be varied within wide limits by varying the gain factor α. This enables the achievement of contrast that can otherwise only be achieved by administering an MRT contrast agent in amounts greater than the standard.

Claims

1. A computer-implemented method comprising the following steps: - receiving or generating a first representation (R1 F ), wherein the first characterization (R1 F ) represents an examination region of the examination object in frequency space without administration of a contrast agent or after administration of a first amount of a contrast agent, - receiving or generating a second representation (R2 F ), wherein the second characterization (R2 F ) denotes an examination region of the examination object after administration of the second amount of contrast agent in the frequency space, -Based on the first characterization (R1 F ) and the second characterization (R2 F ) to generate the third representation (R3 F ), wherein the third characterization (R3 F ) represents the signal amplification caused by the second amount of contrast agent in the examination region in frequency space, - by applying a frequency-dependent weighting function (WF) to the third representation (R3 F ) to generate the weighted third representation (R3 F,w ), - By first characterizing (R1 F ) and the weighted third representation (R3 F,w ) to generate the fourth representation (R4 F ), - The fourth representation (R4 F ) is transformed into a representation of the inspection area in real space (R4 I ), - Output and / or storage of a representation of the inspection area in real space (R4 I ) and / or representation of the inspection area in real space (R4 I ) to a separate computer system; The method further comprises: - receiving a first real space representation (R1 I ), where the first real space representation (R1 I ) represents an examination region of the examination object in real space without administration of a contrast agent or after administration of a first amount of a contrast agent, - The first real space representation (R1 I ) is transformed into a first representation (R1) of the inspection region of the inspection object in the frequency space F ), - Receive a second real space representation (R2 I ), wherein the second real space representation (R2 I ) denotes an examination region of the examination object after administration of the second amount of contrast agent in real space, - Represent the second real space (R2 I ) is transformed into a second representation (R2) of the inspection region of the inspection object in the frequency space F ). The method according to claim 1 , wherein the inspection object is a living organism.

3. The method according to claim 1 or 2, wherein the examination region is the liver, kidney, heart, lung, brain, stomach, bladder, prostate, intestine or a part thereof or another part of the human body.

4. The method according to claim 1 or 2, wherein based on the first characterization (R1 F ) and the second characterization (R2 F ) to generate the third representation (R3 F )include: From the second characterization (R2 F ) minus the first representation (R1 F ).

5. The method according to claim 1 or 2, wherein the first characterization (R1 F ) and the weighted third representation (R3 F,w ) combination includes: Add the first characterization (R1 F ) and the weighted third representation (R3 F,w ).

6. The method according to claim 1 or 2, wherein the frequency-dependent weighting function (WF) is applied to the third representation (R3 F ), the amplitude values ​​with low frequencies are multiplied by a larger weight factor than the amplitude values ​​with high frequencies.

7. The method according to claim 1 or 2, wherein when applying a frequency-dependent weighting function (WF) to the third representation (R3 F ), the amplitude value is multiplied by a window function, wherein the window function is a Gaussian distribution function or a Hann function.

8. The method according to claim 1 or 2, wherein the first characterization (R1 F ) and the weighted third representation (R3 F,w ) combination includes: The α-fold weighted third representation (R3 F,w ) is added to the first representation (R1 F ), where α is a negative or positive real number.

9. The method according to claim 8, further comprising: - Receive one or more alpha values ​​from the user.

10. The method according to claim 8, further comprising: - receiving a first real space representation (R1 I ) or the second real space representation (R2 I ), a first hue value of a first image element of - receiving a first real space representation (R1 I ) or the second real space representation (R2 I ), a second hue value of a second image element of - determining the value of α so that the difference between the first hue value and the second hue value takes a predetermined value or is above or below a predetermined threshold.

11. The method according to claim 1 or 2, further comprising: - receiving a second real space representation (R2 I ), - set the hue value of said area to zero, - Generate a second representation (R2) based on the real space representation F ).

12. The method according to claim 1 or 2, further comprising: -For the first real space representation (R1 I ) all coordinates: determine the first hue value, -For the second real space representation (R2 I ) all coordinates: determine the second hue value, -For the first real space representation (R1 I ) and the second real space representation (R2 I ) all coordinates: determine the quotient of the second hue value and the first hue value, - Represent the second real space (R2 I ) whose quotient is greater than a predetermined threshold is set to zero, -According to the second real space representation (R2 I ) to generate the second representation (R2 F ). The method according to claim 1 , wherein the subject to be examined is a mammal.

14. The method of claim 1, wherein the subject under examination is a human.

15. Computer system (1), including a receiving unit (10), a control and computing unit (20), and Output unit (30), wherein the control and calculation unit (20) is configured to - causing the receiving unit (10) to receive the first representation (R1 F ), wherein the first characterization (R1 F ) represents an examination region of an examination object in frequency space without administering a contrast agent or after administering a first amount of a contrast agent, or causes a receiving unit (10) to receive a first real space representation (R1 I ), wherein the first real space representation (R1 I ) represents an examination region of the examination object in real space without administration of a contrast agent or after administration of a first amount of a contrast agent, - In the first real space representation (R1 I ) has been received by the receiving unit (10): the first real space representation (R1 I ) is transformed into a first representation (R1) of the inspection region of the inspection object in the frequency space F ), - causing the receiving unit (10) to receive the second representation (R2 F ), wherein the second characterization (R2 F ) represents the examination region of the examination object after administration of the second amount of contrast agent in the frequency space, or causes the receiving unit (10) to receive the second real space representation (R2 I ), wherein the second real space representation (R2 I ) denotes an examination region of the examination object after administration of the second amount of contrast agent in real space, - Representation in the second real space (R2 I ) has been received by the receiving unit (10): the second real space representation (R2 I ) is transformed into a second representation (R2) of the inspection region of the inspection object in the frequency space F ), -Based on the first characterization (R1 F ) and the second characterization (R2 F ) to generate the third representation (R3 F ), wherein the third characterization (R3 F ) represents the signal amplification caused by the second amount of contrast agent in the examination region in frequency space, - by applying a frequency-dependent weighting function (WF) to the third representation (R3 F ) to generate the weighted third representation (R3 F,w ), - By first characterizing (R1 F ) and the weighted third representation (R3 F,w ) to generate the fourth representation (R4 F ), - The fourth representation (R4 F ) is transformed into a representation of the inspection area in real space (R4 I ), - causing the output unit (30) to output a representation of the inspection area in real space (R4 I ) and / or store it and / or transmit it to a separate computer system; The control and calculation unit (20) is further configured to: - receiving a first real space representation (R1 I ), where the first real space representation (R1 I ) represents an examination region of the examination object in real space without administration of a contrast agent or after administration of a first amount of a contrast agent, - The first real space representation (R1 I ) is transformed into a first representation (R1) of the inspection region of the inspection object in the frequency space F ), - Receive a second real space representation (R2 I ), wherein the second real space representation (R2 I ) denotes an examination region of the examination object after administration of the second amount of contrast agent in real space, - Represent the second real space (R2 I ) is transformed into a second representation (R2) of the inspection region of the inspection object in the frequency space F ).

16. Computer program product comprising a data carrier, wherein a computer program (40) is stored on the data carrier, wherein the computer program (40) can be loaded into a working memory (22) of a computer system (1), wherein the computer program causes the computer system (1) to execute the following steps: - receiving or generating a first representation (R1 F ), wherein the first characterization (R1 F ) represents an examination region of the examination object in frequency space without administration of a contrast agent or after administration of a first amount of a contrast agent, - receiving or generating a second representation (R2 F ), wherein the second characterization (R2 F ) denotes an examination region of the examination object after administration of the second amount of contrast agent in the frequency space, -Based on the first characterization (R1 F ) and the second characterization (R2 F ) to generate the third representation (R3 F ), wherein the third characterization (R3 F ) represents the signal amplification caused by the second amount of contrast agent in the examination region in frequency space, - by applying a frequency-dependent weighting function (WF) to the third representation (R3 F ) to generate the weighted third representation (R3 F,w ), - By first characterizing (R1 F ) and the weighted third representation (R3 F,w ) to generate the fourth representation (R4 F ), - The fourth representation (R4 F ) is transformed into a representation of the inspection area in real space (R4 I ), - Output and / or storage of a representation of the inspection area in real space (R4 I ) and / or representation of the inspection area in real space (R4 I ) to a separate computer system; The computer program causes the computer system (1) to further perform the following steps: - receiving a first real space representation (R1 I ), where the first real space representation (R1 I ) represents an examination region of the examination object in real space without administration of a contrast agent or after administration of a first amount of a contrast agent, - The first real space representation (R1 I ) is transformed into a first representation (R1) of the inspection region of the inspection object in the frequency space F ), - Receive a second real space representation (R2 I ), wherein the second real space representation (R2 I ) denotes an examination region of the examination object after administration of the second amount of contrast agent in real space, - Represent the second real space (R2 I ) is transformed into a second representation (R2) of the inspection region of the inspection object in the frequency space F ).

17. A kit comprising the computer program product according to claim 16 and a contrast agent.

Images