Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/0033—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room
  • A61B5/004—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
  • G01R33/48—NMR imaging systems
  • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
  • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
  • G01R33/5601—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
  • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
  • A61B5/4222—Evaluating particular parts, e.g. particular organs
  • A61B5/4244—Evaluating particular parts, e.g. particular organs liver
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
  • G01R33/48—NMR imaging systems
  • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
  • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
  • G01R33/5602—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution by filtering or weighting based on different relaxation times within the sample, e.g. T1 weighting using an inversion pulse
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
  • G01R33/48—NMR imaging systems
  • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
  • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
  • G01R33/5608—Data processing and visualization specially adapted for MR, e.g. for feature analysis and pattern recognition on the basis of measured MR data, segmentation of measured MR data, edge contour detection on the basis of measured MR data, for enhancing measured MR data in terms of signal-to-noise ratio by means of noise filtering or apodization, for enhancing measured MR data in terms of resolution by means for deblurring, windowing, zero filling, or generation of gray-scaled images, colour-coded images or images displaying vectors instead of pixels
• • G—PHYSICS
  • G06—COMPUTING OR CALCULATING; COUNTING
  • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
  • G06T7/00—Image analysis
  • G06T7/0002—Inspection of images, e.g. flaw detection
  • G06T7/0012—Biomedical image inspection
  • G06T7/0014—Biomedical image inspection using an image reference approach
  • G06T7/0016—Biomedical image inspection using an image reference approach involving temporal comparison
• • G—PHYSICS
  • G06—COMPUTING OR CALCULATING; COUNTING
  • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
  • G06T7/00—Image analysis
  • G06T7/30—Determination of transform parameters for the alignment of images, i.e. image registration
  • G06T7/33—Determination of transform parameters for the alignment of images, i.e. image registration using feature-based methods
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K49/00—Preparations for testing in vivo
  • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
  • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
  • A61K49/10—Organic compounds
  • A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
  • A61K49/103—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA
• • G—PHYSICS
  • G06—COMPUTING OR CALCULATING; COUNTING
  • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
  • G06T2207/00—Indexing scheme for image analysis or image enhancement
  • G06T2207/10—Image acquisition modality
  • G06T2207/10072—Tomographic images
  • G06T2207/10088—Magnetic resonance imaging [MRI]
  • G06T2207/10096—Dynamic contrast-enhanced magnetic resonance imaging [DCE-MRI]
• • G—PHYSICS
  • G06—COMPUTING OR CALCULATING; COUNTING
  • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
  • G06T2207/00—Indexing scheme for image analysis or image enhancement
  • G06T2207/30—Subject of image; Context of image processing
  • G06T2207/30004—Biomedical image processing
  • G06T2207/30056—Liver; Hepatic
• • G—PHYSICS
  • G06—COMPUTING OR CALCULATING; COUNTING
  • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
  • G06T2207/00—Indexing scheme for image analysis or image enhancement
  • G06T2207/30—Subject of image; Context of image processing
  • G06T2207/30004—Biomedical image processing
  • G06T2207/30096—Tumor; Lesion

Definitions

• the present invention deals with the technical field of characterizing lesions in the liver using dynamic contrast-enhanced magnetic resonance imaging.
• the liver can be affected by multiple benign tumors that can appear as cystic or solid focal lesions in the liver parenchyma.
• the liver is also susceptible to malignancies such as metastases from extrahepatic cancers or from primary cancers originating in the liver itself.
• malignancies such as metastases from extrahepatic cancers or from primary cancers originating in the liver itself.
• the two most common types of malignant liver tumors are metastases - particularly colon cancer metastases - and hepatocellular carcinoma (HCC).
• HCC hepatocellular carcinoma
• HCC Hepatocellular carcinoma
• HCC is the most common primary liver cancer. It is also the sixth most common cancer worldwide and the fourth leading cause of cancer-related deaths.
• the accurate and reliable detection and characterization of focal liver lesions in early disease stages is of high clinical relevance, especially in patients at risk for liver metastases or primary liver cancer, as it is fundamental for appropriate treatment planning and determine suitability for potentially curative treatment options.
• Magnetic resonance imaging is of particular importance for the radiological examination of liver lesions. It features excellent soft-tissue contrast and high spatial resolution without exposing the patient to ionizing radiation or iodinated contrast media.
• the most commonly used contrast agents in MRI are gadolinium-based paramagnetic contrast agents. These agents are administered via an intravenous (IV) bolus injection. Their contrast-enhancing effect is mediated by the central gadolinium ion (Gd - III) in the chelate complex.
• Gd - III central gadolinium ion
• TI-weighted (w) scan sequences are used in MRI, the gadolinium ion-induced shortening of the spin-lattice relaxation time (TI) of excited atomic nuclei leads to an increase in signal intensity and thus to an increase in image contrast of the examined tissue.
• gadolinium-based contrast agents can be roughly divided into extracellular and intracellular contrast agents.
• extracellular contrast agents Low-molecular, water-soluble compounds are referred to as extracellular contrast agents, which are distributed in the blood vessels and in the interstitial space after intravenous administration. They are eliminated via the kidneys after a certain, comparatively short period of circulation in the bloodstream.
• the extracellular MRI contrast agents include, for example, the gadolinium chelates gadobutrol (Gadovist ® ), gadoteridol (Prohance ® ), gadoteric acid (Dotarem ® ), gadopentetic acid (Magnevist ® ) and gadodiamide (Omnican ® ).
• Intracellular MRI contrast agents based on gadoxetic acid are characterized, for example, by the fact that they are specifically absorbed by liver cells, the hepatocytes, accumulate in the functional tissue (parenchyma) and enhance the contrasts in healthy liver tissue before they are then transported via bile to the faeces are excreted.
• Examples of such contrast media based on gadoxetic acid are described in US Pat. No. 6,039,931A; they are commercially available, for example, under the trade names Primovist® and Eovist® available.
• Another MRI contrast agent with a lower uptake in the hepatocytes is gadobenate dimeglumine (Multihance®).
• Gadoxetate disodium belongs to the group of intracellular contrast agents. It is approved for use in MRI of the liver to detect and characterize lesions in patients with known or suspected focal liver disease.
• GD with its lipophilic ethoxybenzyl moiety, exhibits a biphasic distribution: first distribution in the intravascular and interstitial spaces after bolus injection, followed by selective uptake by elepatocytes.
• GD is eliminated unchanged from the body via the kidneys and the hepatobiliary route (50:50 dual elimination mechanism) in approximately equal amounts. Due to its selective accumulation in healthy liver tissue, GD is also referred to as a hepatobiliary contrast agent.
• GD is approved at a dose of 0.1 mL/kg body weight (BW) (0.025 mmol/kg BW Gd).
• BW body weight
• the recommended administration of GD involves an undiluted bolus intravenous injection at a flow rate of approximately 2 mL/second, followed by flushing of the i.v. Cannula with a physiological saline solution.
• a standard protocol for liver imaging using GD consists of several planning and precontrast sequences. After IV After bolus injection of contrast agent, dynamic images are commonly taken during the arterial (approximately 30 seconds post-injection, pi), portal venous (approximately 60 seconds pi), and transition phase (approximately 2-5 minutes pi).
• the transitional phase typically already shows some increase in liver signal intensity due to the incipient uptake of the agent in elepatocytes.
• Additional T2-weighted and diffusion-weighted (DWI) images can be generated after the dynamic phase and before the late hepatobiliary phase.
• the contrast-enhanced dynamic images from the arterial, portal venous and the transition phase provide crucial information about the time-varying pattern of lesion enhancement (vascularization) that contribute to the characterization of the specific liver lesion.
• vascularization vascularization
• Hepatocellular carcinoma, with its typical arterial phase hyperenhancement (APHE) and contrast washout in the venous phase, can be diagnosed solely by its unique vascularization pattern observed during dynamic phase imaging, thereby protecting patients from invasive and potentially risky liver biopsy.
• APHE arterial phase hyperenhancement
• a hepatobiliary contrast agent In the diagnosis of liver lesions, a hepatobiliary contrast agent has the advantage over an extracellular contrast agent that it has a higher sensitivity and is therefore better able to detect smaller carcinomas in particular (see e.g.: R.F. Hanna et al.: Comparative 13-year meta-analysis of the sensitivity and positive predictive value of ultrasound CT, and MRI for detecting hepatocellular carcinoma, Abdom Radiol 2016, 41, 71-90 Lee YJ et al.: Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis , Radiology 2015, 275, 97-109 DK Owens et al.: High-value, cost-conscious health care: concepts for clinicians to evaluate the benefits, harms, and costs of medical interventions, Ann Intern Med 2011, 154, 174 -180).
• the problem is that the dynamic increase and/or decrease in contrast in liver lesions is often assessed visually by radiologists (subjective assessment of the relative contrast change between liver tissue and liver lesion) and misinterpretations can occur. In an apparent assessment, it makes a difference whether an extracellular or an intracellular contrast agent is used.
• a hepatobiliary contrast agent for example, an increase in signal in healthy liver tissue can be misinterpreted as a washout of contrast agent from adjacent liver lesions (relative increase in contrast between liver tissue and liver lesion).
• both the portal venous phase and the subsequent delayed phase are used to detect hepatocellular carcinoma when using an extracellular contrast agent
• only the portal venous phase is used to detect washout when using a hepatobiliary contrast agent and not a phase subsequent to the portal venous phase.
• a hepatobiliary contrast agent in contrast to an extracellular contrast agent
• a hepatobiliary contrast medium is used following a first comparatively rapid vascular contrast enhancement in the arterial phase, there is a slowly, continuously increasing contrast enhancement in healthy liver tissue.
• a radiologist visually compares the contrast enhancement in a lesion with the contrast enhancement in healthy liver tissue, the continuously increasing contrast enhancement in healthy liver tissue can be misinterpreted as a washout of contrast agent from lesions.
• the European Association for the Study of Liver therefore explicitly recommends that when using a hepatobiliary contrast agent, the analysis of the MRI images for the identification of a hepatocellular carcinoma is limited to the arterial and the portal venous (up to 60 seconds after the intravenous administration of the contrast agent).
• a first object of the present invention is a computer-implemented method for identifying a washout of contrast agent from a region of a patient's liver during a dynamic contrast-enhanced magnetic resonance imaging examination, comprising the steps:
• ⁇ represents reference tissue of the patient, o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a portal venous phase of the dynamic contrast-enhanced magnetic resonance imaging examination, and o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a transition phase of dynamic contrast-enhanced magnetic resonance imaging examination
• a further object of the present invention is a computer system comprising
• control and computing unit is configured to cause the receiving unit to receive a plurality of representations, o the plurality of representations
• ⁇ represents reference tissue of the patient, o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a portal venous phase of a dynamic contrast-enhanced magnetic resonance imaging examination, and o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a transitional phase of a dynamic contrast-enhanced magnetic resonance imaging examination
• the control and computing unit being configured to identify one or more areas in the liver, o in which the contrast agent(s) is/are in the portal venous phase and/or the transitional phase to a lesser one Contrast enhancement than in the reference tissue leads, and/or o in which the contrast enhancement in the portal venous phase and/or the transitional phase decreases faster than in the reference tissue, wherein the reference tissue does not include hepatocytes, and/or o in which the amount of the gradient of decreasing contrast enhancement in the portal venous phase and/or the transitional phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue, wherein the control and computing unit is configured to cause the output unit to display a representation of the liver or part of the Liver output with the identified region or regions highlighted in the representation.
• Another subject matter of the present invention is a computer program product comprising a computer program that can be loaded into a working memory of a computer and causes the computer there to carry out the following steps:
• ⁇ a patient's liver or part of the patient's liver, and represents reference tissue of the patient, o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a portal venous phase of a dynamic contrast-enhanced magnetic resonance imaging examination, and o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a transition phase of a dynamic contrast-enhanced magnetic resonance imaging examination
• Another object of the present invention is the use of a contrast agent in a dynamic magnetic resonance tomographic examination method, wherein the
• investigation procedure includes the following steps:
• ⁇ represents reference tissue of the patient, o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a portal venous phase of the examination procedure, and o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a transition phase of the examination procedure
• Another object of the present invention is a contrast agent for use in a dynamic contrast-enhanced magnetic resonance imaging examination method, the examination method comprising the following steps:
• ⁇ represents reference tissue of the patient, o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a portal venous phase of the examination method, and o wherein at least one representation of the plurality of representations
• ⁇ represents the reference tissue during a transition phase of the examination procedure
• a further object of the present invention is a kit comprising a contrast agent and the computer program product according to the invention.
• the present invention provides means for automated identification of a washout of contrast agent from a region of a patient's liver during a dynamic contrast-enhanced magnetic resonance imaging examination.
• a washout of contrast agent from a region of a patient's liver during a dynamic contrast-enhanced magnetic resonance imaging examination.
• one or more areas within the liver that are characterized by contrast agent washout can be automatically identified.
• Washout refers to the observation that the contrast enhancement in an area of a liver in the portal venous phase and/or the transitional phase of a dynamic contrast-enhanced magnetic resonance imaging examination decreases more rapidly than in the surrounding (healthy) liver tissue.
• washout is often used as a characteristic feature for specifying liver lesions (see e.g.: Y.I. Liu et al.: Quantitatively Defining Washout in Hepatocellular Carcinoma, American Journal of Roentgenology 2013 200:1, 84-89; Journal of Hepatology, 2018, Vol. 69, pages 182-236).
• Magnetic resonance tomography is an imaging method that is used primarily in medical diagnostics to display the structure and function of tissues and organs in the human or animal body.
• the magnetic moments of protons in an examination object are aligned in a basic magnetic field, so that macroscopic magnetization occurs along a longitudinal direction. This is then deflected from the resting position (excitation) by the irradiation of high-frequency pulses. The return of the excited states to the rest position (relaxation) or the magnetization dynamics is then detected as relaxation signals by means of one or more high-frequency receiver coils. Rapidly switched magnetic gradient fields are superimposed on the basic magnetic field for spatial coding. The recorded relaxation signals or the detected and spatially resolved MR data are initially available as raw data in a spatial frequency space and can be transformed into the spatial space (image space) by subsequent Fourier transformation.
• the tissue contrasts are generated by the different relaxation times (TI and T2) and the proton density.
• the TI relaxation describes the transition of the longitudinal magnetization (longitudinal magnetization) to its equilibrium state, where TI is the time required to reach 63.21% of the equilibrium magnetization before resonance excitation. It is also called longitudinal relaxation time or spin lattice relaxation time.
• the T2 relaxation describes the transition of the transverse magnetization to its equilibrium state in an analogous manner.
• an MRT contrast agent is administered to an examination object.
• the "object under examination” is usually a living being, preferably a mammal, very particularly preferably a human being.
• the term patient is also used in this description.
• the contrast agent can be an extracellular or an intracellular contrast agent. It is preferably a hepatobiliary contrast medium.
• a hepatobiliary contrast agent is understood to be a contrast agent that is specifically taken up by healthy liver cells, the hepatocytes.
• hepatobiliary contrast media are contrast media based on gadoxetic acid. They are described, for example, in US Pat. No. 6,039,931A. They are commercially available, for example, under the brand names Primovist® or Eovist® .
• the contrast-enhancing effect of Primovist®/Eovist® is mediated by the stable gadolinium complex Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid).
• Gd-EOB-DTPA gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid
• DTPA forms a complex with the paramagnetic gadolinium ion that exhibits extremely high thermodynamic stability.
• the ethoxybenzyl residue (EOB) mediates the hepatobiliary uptake of the contrast medium.
• the contrast agent used is a substance or a mixture of substances containing gadoxetic acid or a salt of gadoxetic acid as the contrast-enhancing active ingredient. It is very particularly preferably the disodium salt of gadoxetic acid (Gd-EOB-DTPA disodium).
• the contrast medium After the intravenous application of the hepatobiliary contrast medium in the form of a bolus into a vein in the arm, the contrast medium first reaches the liver via the arteries. These are shown with enhanced contrast in the corresponding MRI images.
• the phase in which the hepatic arteries are displayed with enhanced contrast in MRI images is referred to as the "arterial phase".
• the contrast medium then reaches the liver via the hepatic veins. While the contrast in the hepatic arteries is already decreasing, the contrast in the hepatic veins reaches a maximum.
• the phase in which the hepatic veins are displayed with enhanced contrast in MRI images is referred to as the "portal venous phase". This phase can already begin during the arterial phase and overlap with it.
• the portal venous phase is followed by the "transitional phase", in which the contrast in the hepatic arteries continues to decrease and the contrast in the hepatic veins also decreases.
• the contrast in the healthy liver cells gradually increases in the transition phase.
• the arterial phase, the portal venous phase and the transitional phase are collectively referred to as the "dynamic phase".
• hepatobiliary phase a hepatobiliary contrast medium leads to a significant signal amplification in the healthy liver parenchyma. This phase is called the "hepatobiliary phase".
• the contrast medium is only slowly cleared from the liver cells; accordingly, the hepatobiliary phase can last two hours or more.
• the signal intensity I correlates positively with the concentration of the contrast agent in the areas mentioned.
• concentration of the contrast medium in the hepatic arteries (A) increases first (dashed curve). The concentration goes through a maximum and then decreases.
• the concentration in the hepatic veins (V) increases more slowly than in the hepatic arteries and reaches its maximum later (dotted curve).
• the concentration of the contrast agent in the liver cells (L) increases slowly (continuous curve) and only reaches its maximum at a much later point in time (not shown in FIG. 1).
• Some characteristic points in time can be defined: At the point in time TR0, contrast medium is administered intravenously as a bolus. Since the application of a contrast medium itself takes a certain amount of time, the point in time TR0 preferably defines the point in time at which the application is complete, that is to say the contrast medium has been completely introduced into the examination subject.
• the signal intensity of the contrast agent in the hepatic arteries (A) reaches its maximum.
• the signal intensity curves intersect at the hepatic arteries (A) and hepatic veins (V).
• the signal intensity of the contrast agent in the hepatic veins (V) passes through its maximum.
• the signal intensity curves in the hepatic arteries (A) and the healthy liver cells (L) intersect.
• the concentrations in the hepatic arteries (A) and hepatic veins (V) have decreased to a level where they no longer cause measurable contrast enhancement.
• multiple magnetic resonance imaging recordings of the patient's liver or of a part of the patient's liver are generated.
• Such magnetic resonance imaging recordings are referred to as representations in this description. They represent the liver or a part of the liver of the patient before and/or after the application of a contrast agent. This can involve representations in the spatial domain or representations in the frequency domain.
• the raw data usually occurs as so-called k-space data due to the measurement method.
• This k-space data is a display (representation) of an examination area in frequency space.
• Such k-space data can be converted into a representation in position space by means of inverse Fourier transformation.
• Representations in spatial space can be converted into a representation in frequency space (also referred to as spatial frequency space or Fourier space or frequency domain or Fourier representation) by means of Fourier transformation.
• a representation of an area of interest (e.g., the liver) in position space is the representation more familiar to a human; it is easier for people to grasp (understand).
• image is also commonly used for such a representation in the local space.
• a representation within the meaning of the present invention can be a two-dimensional, three-dimensional or higher-dimensional representation.
• Two-dimensional tomograms (slice recordings) or a stack of two-dimensional tomograms (slice recordings) are usually available.
• the representations are usually in digital form.
• digital means that the representations can be processed by a machine, usually a computer system.
• Processing means the known procedures for electronic data processing (EDP).
• EDP electronic data processing
• An example of a common format for a digital representation is the DICOM format (DICOM: Digital Imaging and Communications in Medicine) - an open standard for storing and exchanging information in medical image data management.
• Digital images can come in a variety of formats.
• digital images may be encoded as raster graphics.
• Raster graphics consist of a raster arrangement of so-called image points (pixels) or volume elements (voxels), each of which is assigned a color or gray value.
• the main features of a 2D raster graphic are therefore the image size (width and fles measured in pixels, colloquially also called image resolution) and the color depth.
• a color is usually assigned to a pixel of a digital image file.
• the color coding used for a pixel is defined, among other things, by the color space and the color depth. The simplest case is a binary image where a pixel stores a black and white value.
• each pixel In an image whose color is defined by the so-called RGB color space (RGB stands for the primary colors red, green and blue), each pixel consists of three subpixels, one subpixel for the color red, one subpixel for the color green and one Subpixels for the color blue.
• the color of a pixel results from the superimposition (additive mixing) of the color values of the subpixels.
• the color value of a sub-pixel can be broken down into 256 shades of color called tone values, typically ranging from 0 to 255.
• the "0" hue of each color channel is the darkest. If all three channels have the tonal value 0, the corresponding pixel appears black; if all three channels have the tonal value 255, the corresponding pixel appears white.
• digital images are subjected to certain operations.
• the operations predominantly relate to the pixels or the tonal values of the individual pixels (pixels or voxels).
• the present images are greyscale raster graphics with a specific number of pixels, with each pixel being assigned a tonal value which indicates the gray value of the image.
• this assumption should not be understood as limiting in any way. It is clear to a person skilled in the art of image processing how to transfer the teaching of this description to image files which are present in other image formats and/or in which the color values are encoded differently.
• a plurality of representations of the liver or a part of the liver of a patient are generated.
• the plurality of representations includes at least one representation representing the liver or part of the liver during the portal venous phase and at least one representation representing the liver or part of the liver during the transition phase.
• At least one representation of the liver or part of the liver is preferably generated before application of the hepatobiliary contrast agent (before TR0) (native image) and/or at least one representation of the liver or part of the liver in the arterial phase.
• At least the following recordings are generated: at least one first representation, with the at least one first representation representing the liver or part of the liver during the time period from TP 1 to TP3, at least one second representation, with the at least one second representation represents the liver or part of the liver during the period from TP3 to TP5, the times TR0 being shown in FIG. 1 and explained in the description of FIG.
• At least the following recordings are generated: at least one first representation, wherein the at least one first representation represents the liver or part of the liver of a patient during the time period from TR0 to TP3, at least one second representation, wherein the at least one second representation representing the patient's liver or part of the liver during the time period from TP2 to TP5, at least one third representation, wherein the at least one third representation represents the patient's liver or part of the liver during the time period TP4 to 5 minutes after TR0 , the points in time TR0 being shown in FIG. 1 and explained in the description of FIG.
• At least the following recordings are generated: at least one first representation, wherein the at least one first representation represents the liver or part of the liver of a patient during the period from TR0 to TP 1, and at least one second representation, wherein the at least one second representation representing the liver or part of the liver of a patient during the time period from TP1 to TP2, and at least one third representation, wherein the at least one third representation represents the liver or part of the liver of a patient during the time period from TP2 to TP3 represented, and at least one fourth representation, wherein the at least one fourth representation represents the liver or part of the liver of a patient during the time period from TP3 to TP4, and at least one fifth representation, wherein the at least one fifth representation represents the liver or part of the liver of the patient during the time period TP4 to TP5 seconds after TR0, and/or at least one sixth representation, wherein the at least one sixth representation represents the liver or part of the liver of the patient during the time period TP5 to 5 minutes after TPO, the
• the representations generated are supplied to the computer system according to the invention, which is configured to analyze the representations in an automated manner.
• the analysis identifies an area or areas in the patient's liver that is experiencing contrast washout in the portal venous phase and/or transitional phase.
• Washout can be identified in a number of ways:
• those areas in the liver are identified in which contrast agent in the portal venous phase and/or the transitional phase leads to a lower contrast enhancement than in a reference tissue.
• the lower contrast enhancement in the portal venous and/or transition phase is also referred to as hypoenhancement.
• Hypoenhancement is the lower signal intensity compared to a reference tissue.
• a tissue that does not include any hepatocytes is preferably used as the reference tissue.
• a suitable reference tissue is muscle tissue, for example.
• An extracellular or a hepatobiliary contrast agent can be used for contrast enhancement.
• a hepatobiliary contrast agent is used.
• those areas in the liver are identified in which the contrast enhancement in the portal venous phase and/or the transitional phase decreases faster than in the reference tissue.
• a tissue that does not include any hepatocytes is preferably used as the reference tissue.
• a suitable reference tissue is muscle tissue, for example.
• the time gradient of the signal intensity is determined and those areas are identified in which the time gradient of the signal intensity is negative (decrease in signal intensity with increasing time) and in which the amount of the time gradient is greater than the amount of the negative time gradient of the Signal intensity in the reference tissue.
• An extracellular or a hepatobiliary contrast agent can be used as the contrast agent.
• a hepatobiliary contrast agent is used.
• those areas in the liver are identified where the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and/or the transitional phase is greater than the gradient of increasing contrast enhancement in healthy liver tissue.
• the healthy liver tissue is used as the reference tissue.
• a hepatobiliary contrast medium is preferably used as the contrast medium, which is selectively taken up by healthy liver tissue and leads to a gradually increasing signal intensity there in the portal venous and/or the transition phase. So it lies in the healthy Liver tissue exhibits a positive temporal gradient in signal intensity in the portal venous phase and/or the transitional phase.
• Those areas are identified where the signal intensity decreases in the portal venous phase and/or the transitional phase, where the magnitude of the decrease (the absolute rate of decrease) is greater than the magnitude of the increase in signal intensity in healthy liver tissue.
• contrast medium in the portal venous phase and/or the transition phase leads to less contrast enhancement than in a first reference tissue and in which the contrast enhancement in the portal venous phase and/or the transition phase is faster decreases than in a second reference tissue and/or where the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and/or the transitional phase is greater than the gradient of increasing contrast enhancement in healthy liver tissue.
• the first and/or the second reference tissue can be muscle tissue or healthy liver tissue, for example.
• the present invention is used to identify hepatocellular carcinoma.
• an area or areas are identified that exhibit both hyperenhancement in the arterial phase and washout in the protalvenous phase and/or transitional phase.
• Hyperenhancement is present when an area shows higher signal intensity compared to a reference tissue (see e.g. M. Kim et al.: Identification of Arterial Hyperenhancement in CT and MRI in Patients with Hepatocellular Carcinoma: Value of Unenhanced Images, Korean Journal of Radiology 2019 , 20(2), 236-245). Healthy liver tissue is preferably used as reference tissue for detecting hyperenhancement in the arterial phase.
• An extracellular or a hepatobiliary contrast agent can be used as the contrast agent.
• a hepatobiliary contrast agent is used.
• the embodiment for identifying a hepatocellular carcinoma preferably comprises the following steps:
• a plurality of representations of the liver or part of the liver of a patient Receiving a plurality of representations of the liver or part of the liver of a patient, o wherein the representations are the result of a contrast-enhanced magnetic resonance imaging examination of the liver or part of the liver, o wherein at least a first representation is the liver or part of the liver during a arterial phase, with at least a second representation representing the liver or part of the liver during a portal venous phase, with at least a third representation representing the liver or part of the liver during a transitional phase,
• Analyzing the at least one first, second and third representation identifying an area or areas of the liver where contrast agent in the arterial phase leads to a higher contrast enhancement than in a first reference tissue and where contrast agent in the portal venous and/or transitional phase leads to a lower contrast enhancement than in a second reference tissue,
• the first reference tissue is preferably healthy liver tissue and the second reference tissue is preferably muscle tissue.
• the method for identifying a hepatocellular carcinoma comprises the steps:
• a plurality of representations of the liver or part of the liver of a patient Receiving a plurality of representations of the liver or part of the liver of a patient, o wherein the representations are the result of a contrast-enhanced magnetic resonance imaging examination of the liver or part of the liver, o wherein at least a first representation is the liver or part of the liver during an arterial phase, with at least a second representation representing the liver or part of the liver during a portal venous phase, with at least a third representation representing the liver or part of the liver during a transitional phase,
• o contrast agent leads to a greater signal increase in the arterial phase than in a first reference tissue
• o the contrast enhancement in the portal venous phase and/ or the transitional phase decreases faster than in a second reference tissue, wherein the second reference tissue does not include hepatocytes
• o the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and/or the transitional phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue.
• the first reference tissue is preferably healthy liver tissue and the second reference tissue is preferably muscle tissue.
• FIG. 2 (a) and FIG. 2 (b) The terms hyperenhancement and hypoenhancement are illustrated graphically in FIG. 2 (a) and FIG. 2 (b).
• FIG. 2 (a) and FIG. 2 (b) the intensity I of the signal measured during the MRT examination for two different areas in the liver of a patient is shown as a function of time t.
• the reference characters AP, PVP and TP indicate the arterial phase (AP), the portal venous phase (PVP) and the transitional phase (TP).
• the time TR0 indicates the time at which the application of a hepatobiliary contrast medium was completed.
• the intensities of the MRI signals which can be attributed to the hepatocellular carcinomas, increase sharply.
• the intensities of the MRI signals, which can be traced back to healthy liver tissue, also increase - but to a lesser extent: there is hyperenhancement in the HCC tissue compared to the healthy liver tissue in the arterial phase AP.
• the intensities of the MRI signals decrease again; faster in the case of the curve in Fig. 2(a) than in the case of the curve in Fig. 2(b).
• the intensities of the MRI signals, which can be traced back to healthy liver tissue continue to increase even after the end of the arterial phase AP; but slower than in the arterial phase: this indicates the uptake of contrast medium in the liver cells.
• the solid curve (HCC) descends below the dashed curve (L) in the portal venous phase PVP in Fig. 2(a): the signal enhancement in hepatocellular carcinoma is less than the signal enhancement in healthy liver tissue. There is hypoenhancement in HCC tissue relative to healthy liver tissue in the portal venous phase.
• the presence of a hepatocellular carcinoma is indicated when the lesion shows hyperenhancement compared to a first reference tissue in the arterial phase, and when the lesion shows hypoenhancement compared to a second reference tissue in the portal venous phase or in the transitional phase, or when the contrast enhancement is in the portal venous phase and/or the transition phase decreases faster than in a second reference tissue, the second reference tissue not comprising hepatocytes, and/or the magnitude of the gradient of the decreasing contrast enhancement in the portal venous phase and/or the transition phase is greater than the gradient of the increasing one Contrast enhancement in healthy liver tissue.
• the gray values of the pixels or voxels of the spatial representations (of the 2D images or 3D images) of lesions and reference tissue(s) can be analyzed.
• the area In order to be able to make a statement about an area, whether that area exhibits hyperenhancement in one time period and hypoenhancement in another time period, the area must be uniquely identified and retrieved from the representations that represent the area in the different time periods.
• the assessment of whether hyperenhancement is present in an area is based on at least one first representation, which represents the area after the application of a contrast agent in the arterial phase;
• the assessment of whether hypoenhancement is present in an area is based on at least one second representation, which represents the area after the application of a contrast agent in the portal venous phase and/or the transitional phase; the area must therefore be unambiguously determinable both in the first and in the second representation and it must be the same area in the at least one first and in the at least one second representation.
• Image registration also called “co-registration”
• co-registration is a process in digital image processing and is used to match two or more images of the same scene, or at least similar scenes, as best as possible.
• One of the images is defined as the reference image, the others are called object images.
• a compensating transformation is calculated in order to optimally adapt these object images to the reference image.
• the images to be registered differ from each other because they were taken from different positions, at different times or with different sensors.
• the aim of image registration is therefore to find the transformation that best matches a given object image with the reference image.
• the goal is that, whenever possible, each pixel/voxel of one image represents the same area in a patient's body as the pixel/voxel of another (co-registered) image with the same coordinates.
• Methods for image registration are described in the prior art (see e.g.: EH Seeley et al.: Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease, Bone 2014, 61, 208-216; C.
• Co-registration can be done for each entire representation (the entire image with all anatomical features captured in the image). It is also conceivable to limit the co-registration to the lesions, i.e. to change the individual representations by transformation in such a way that at least the lesions in the individual representations are represented by the corresponding pixels/voxels (whereby corresponding pixels/voxels have the same coordinates ).
• the region or regions in a representation representing reference tissues can be determined/determined by a radiologist or in an automated manner.
• a radiologist marks one or more areas in the representations of the liver or a part of the liver, which act as reference area(s).
• segmentation methods can also be used (see e.g. WO2020/144134), which, for example, recognize muscle tissue and/or liver tissue in the representations and define a reference area that represents the muscle tissue and/or liver tissue.
• hyperenhancement for an area is present if the gray values of the pixels/voxels representing the area are significantly above the gray values of the pixels/voxels representing reference tissue within the arterial phase.
• hypoenhancement is present for an area (a lesion) if the gray values of the pixels/voxels representing the area are significantly above the gray values of the pixels/voxels representing the reference tissue within the arterial phase.
• the gray value of a pixel/voxel that represents the region is smaller than the gray value of the pixel/voxel of the reference area (lower signal amplification), hypoenhancement is present; otherwise not.
• a number of pixels/voxels of the area and of the reference area are preferably evaluated.
• the multiple pixels/voxels define a contiguous region in one or more representations; in other words: preferably the plurality of pixels/voxels represent a contiguous region in the patient's body.
• an average value of the gray value (or another value that indicates the signal intensity) can be calculated (eg the arithmetic mean).
• the comparison between a range and a reference range is then based on the respective mean values.
• an averaging over a number of pixels/voxels located next to each other in terms of location an averaging over a number of pixels/voxels of temporally successive representations can also be undertaken.
• gradients of the signal intensities are also determined in addition to the signal intensities.
• a gradient can be obtained for an area, for example, from two representations that represent the area at a time distance from one another.
• the time interval can be in the range from 1 second to 30 seconds, for example. The shorter the time interval, the higher the accuracy with which changes (gradients) in the signal intensity can be determined.
• a number of 2 to 5 representations are preferably generated which represent the liver or a part of the liver during the phase (arterial phase, portal venous phase, transition phase). If the signal intensity for a region increases from one representation to the subsequent representation, then the gradient is positive; if the signal intensity decreases, on the other hand, it is negative.
• the size of the gradient provides information about how strong (fast) the signal intensity increase or the signal intensity decrease is.
• it can be determined, for example, how quickly contrast agent is washed out in the portal venous phase and/or the transitional phase for an area. This information can be used, for example, to determine one or more points in time for the acquisition of one or more second (or further) representations.
• FIG. 3 shows, by way of example and diagrammatically, representations of the liver of a patient.
• FIGS. 3(a), 3(b), 3(c), 3(d), 3(e) and 3(f) the same cross section through the liver is always shown at different points in time.
• reference tissue (R) is also shown; this can be muscle tissue, for example.
• the reference numerals drawn in Figures 3(a) and 3(f) apply to all Figures 3(a), 3(b), 3(c), 3(d), 3(e) and 3(f); they are only drawn in once for the sake of a better overview.
• FIG. 3 (a) shows the cross section through the liver before the intravenous administration of a hepatobiliary contrast agent (native representation).
• a hepatobiliary contrast agent was administered intravenously (eg, into an arm vein) as a bolus.
• This reaches the liver in FIG. 3 (b) via the hepatic artery (A).
• the hepatic artery (A) is shown with enhanced signal (arterial phase).
• a lesion that is primarily blood-supplied by arteries also stands out as a brighter (signal-enhanced) area against healthy hepatocyte tissue (L) and reference tissue (R).
• the contrast medium reaches the liver via the veins (V).
• the venous blood vessels (V) stand out as bright (signal-enhanced) areas from the liver tissue (L) and the reference tissue (R) (portal venous phase).
• the signal intensity in the healthy liver cells (L) increases continuously (Fig. 3(c) 3(d) 3(e) 3(f)).
• the liver cells (L) are shown enhanced; the blood vessels, the reference tissue and the lesion no longer have any contrast medium and are displayed accordingly dark.
• the question arises whether the lesion (HCC) in FIG. 3 is a hepatocellular carcinoma.
• FIG. 4 the representations shown in FIGS. 3(a), 3(b), 3(c), 3(d) and 3(e) are shown again on a smaller scale. They bear the reference symbols (a), (b), (c), (d) and (e).
• a signal intensity S B can be determined for the region in the representations that represents the lesion; for representation (a) the signal intensity S B ®, for representation (b) the signal intensity S B (b) , for representation (c) the signal intensity S B (c) , for representation (d) the signal intensity S B ® and for representation (e) the signal intensity S B ®.
• the signal intensities can be, for example, the gray values or color values of pixels/voxels that represent the area.
• a signal intensity S R can be determined for the area in the representations that represents the reference tissue; for representation (a) the signal intensity S R ®, for representation (b) the signal intensity S R ®, for representation (c) the signal intensity S R ®, for representation (d) the signal intensity S R ® and for the Representation (e) the signal intensity S R ®.
• the signal intensities can be, for example, the gray values or color values of pixels/voxels that represent the area.
• signal intensities in the area representing the lesion are compared with signal intensities in the area representing the reference tissue for at least one representation during the arterial phase AP and at least one representation during the portal venous phase PVP and/or at least one representation during the transitional phase TP.
• Representation (b) represents the arterial phase AP. It is checked whether the signal intensity S B ® in the area that represents the lesion is greater than the signal intensity S R ® in the area that represents the reference tissue. If so, there is a first indication that the lesion is a hepatocellular carcinoma. If no, no further signal intensities need to be checked; a hepatocellular carcinoma can be excluded.
• Representation (d) represents the portal venous phase PVP. It is checked whether the signal intensity S B ® in the area that represents the lesion is smaller than the signal intensity S R ® in the area that represents the reference tissue. If so, there is a second indication that the lesion is a hepatocellular carcinoma. If the first and the second indication are present, the lesion is indicated according to the invention as a hepatocellular carcinoma. If only the first but not the second indication is present, the transition phase TP is considered.
• Representation (e) represents the transition phase TP. It is checked whether the signal intensity S B ® in the area that represents the lesion is smaller than the signal intensity S R ® in the area that represents the reference tissue. If S B ® is smaller than S R ® and the first indication is also present, it is indicated according to the invention that the lesion is a hepatocellular carcinoma.
• a message can be issued that there are indications of a hepatocellular carcinoma.
• a representation of the patient's liver or portion of the liver is output in which the lesion is identified that has evidence of hepatocellular carcinoma.
• the corresponding lesion can be marked in color, for example.
• the invention can be implemented using a computer system.
• a “computer system” is an electronic data processing system that processes data using programmable calculation rules. Such a system usually includes a “computer”, the unit that includes a processor for performing logical operations, and peripherals.
• peripherals are all devices that are connected to the computer and are used to control the computer and/or as input and output devices. Examples of this are monitors (screens), printers, scanners, mice, keyboards, drives, cameras, microphones, loudspeakers, etc. Internal connections and expansion cards are also considered peripherals in computer technology.
• Today's computer systems are often divided into desktop PCs, portable PCs, laptops, notebooks, netbooks and tablet PCs and so-called elandheroes (e.g. smartphones); all of these systems can be used to practice the invention.
• Inputs into the computer system are made via input means such as a keyboard, a mouse, a microphone, a touch-sensitive display and/or the like.
• Output can be on a monitor, on a printer or on a data storage device.
• FIG. 5 shows, schematically and by way of example, an embodiment of the computer system according to the invention.
• the computer system (10) comprises a receiving unit (11), a control and processing unit (12) and an output unit (13).
• the computer system (10) is configured to receive representations of a liver or part of a patient's liver and to identify one or more areas in the representations that are indicative of a hepatocellular carcinoma.
• the control and computing unit (12) is used to control the receiving unit (11) and the output unit (13), coordinate the data and signal flows between the various units, process representations and determine the comparison of signal intensities. It is conceivable that several control and computing units are present.
• the receiving unit (11) serves to receive the representations.
• the representations can be transmitted by a magnetic resonance tomograph, for example, or can be read out from a data memory.
• the magnetic resonance tomograph can be a component of the computer system according to the invention.
• the computer system according to the invention is a component of a magnetic resonance tomograph.
• the delivery of representations can be done over a network connection or a direct connection.
• Representations can be transmitted via a radio connection (WLAN, Bluetooth, mobile radio and/or the like) and/or by cable. It is conceivable that several receiving units are present.
• the data memory can also be a component of the computer system according to the invention or can be connected to it, for example, via a network. It is conceivable that several data stores are present.
• the representations possibly further data (such as information about the examination object, recording parameters and/or the like) are received by the receiving unit and transmitted to the control and processing unit.
• the control and processing unit is configured to use the received data to identify areas that indicate a hepatocellular carcinoma.
• results of the analysis can be displayed (for example on a monitor) via the output unit (13), output (for example via a printer) or stored in a data memory. It is conceivable that several output units are present. Further embodiments of the present invention are:
• the contrast agent is a hepatobiliary contrast agent, preferably the disodium salt of gadoxetic acid.
• the contrast enhancement decreases faster in the portal venous phase and/or the transitional phase than in the reference tissue, the reference tissue not including hepatocytes, and/ or in which the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and/or the transitional phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue,
• Identifying one or more areas in the liver where the area(s) are characterized by the following characteristics: o Contrast agent leads to a higher contrast enhancement in the arterial phase than in a first reference tissue, the first reference tissue being healthy liver tissue or muscle tissue acts, and o Contrast agent results in less contrast enhancement in the portal venous and/or transition phase than in a second reference tissue, where the second reference tissue is muscle tissue, and/or o contrast enhancement in the portal venous phase and/or the transition phase decreases faster than in the second reference tissue, and/or o the magnitude of the gradient of decreasing contrast enhancement in the portal venous phase and/or the transitional phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue,
• control and computing unit is configured to cause the receiving unit to receive a plurality of representations of a liver or a part of the liver of a patient, wherein at least one representation represents the liver or the part of the liver during a portal venous phase and at least one representation represents the liver or the part of the liver during a transition phase, wherein the control and computing unit is configured to identify one or more areas in the liver in which contrast agent(s) is/are in the portal venous phase and/or the transition phase less contrast enhancement than in a reference tissue, and/or the contrast enhancement in the portal venous phase and/or the transitional phase decreases more rapidly than in the reference tissue, the reference tissue not comprising elepatocytes, and/or the magnitude of the gradient of the decreasing contrast enhancement in the portal venous Pha se and/or the transition phase is greater than the magnitude of the gradient of increasing contrast enhancement in healthy liver tissue, wherein the control and computing unit is configured to cause the output unit to display a representation of the liver or the part of the liver in which
• a computer program product comprising a computer program that can be loaded into the main memory of a computer and causes the computer there to perform the following steps:
• the radiological examination procedure comprising the following steps:
• generating a plurality of representations of a liver or part of the liver of a patient wherein at least one representation represents the liver or part of the liver during a portal venous phase and at least one representation represents the liver or part of the liver during a transition phase,
• a contrast medium for use in a radiological examination procedure comprising the following steps:
• generating a plurality of representations of a liver or part of the liver of a patient wherein at least one representation represents the liver or part of the liver during a portal venous phase and at least one representation represents the liver or part of the liver during a transition phase,
• kits comprising a contrast agent and a computer program product according to claim? .

Landscapes

• Health & Medical Sciences (AREA)
• Physics & Mathematics (AREA)
• Engineering & Computer Science (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Radiology & Medical Imaging (AREA)
• High Energy & Nuclear Physics (AREA)
• General Physics & Mathematics (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Animal Behavior & Ethology (AREA)
• Medical Informatics (AREA)
• Signal Processing (AREA)
• Condensed Matter Physics & Semiconductors (AREA)
• Biophysics (AREA)
• Pathology (AREA)
• Biomedical Technology (AREA)
• Heart & Thoracic Surgery (AREA)
• Molecular Biology (AREA)
• Surgery (AREA)
• Computer Vision & Pattern Recognition (AREA)
• Gastroenterology & Hepatology (AREA)
• Artificial Intelligence (AREA)
• Theoretical Computer Science (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Epidemiology (AREA)
• Endocrinology (AREA)
• Physiology (AREA)
• Quality & Reliability (AREA)
• Magnetic Resonance Imaging Apparatus (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Priority Applications (5)

Applications Claiming Priority (2)

Publications (1)

Family

ID=75870425

Family Applications (1)

Country Status (6)

Families Citing this family (2)

Citations (8)

Family Cites Families (6)

• 2022
  • 2022-04-28 CN CN202280032200.8A patent/CN117242362A/zh active Pending
  • 2022-04-28 JP JP2023567939A patent/JP2024517820A/ja active Pending
  • 2022-04-28 EP EP22724112.2A patent/EP4334733B1/de active Active
  • 2022-04-28 US US18/559,323 patent/US20240225448A1/en active Pending
  • 2022-04-28 WO PCT/EP2022/061289 patent/WO2022233689A1/de not_active Ceased
  • 2022-04-28 CA CA3219070A patent/CA3219070A1/en active Pending

Patent Citations (9)

Non-Patent Citations (15)

Also Published As

Similar Documents

Legal Events