Patent Application
20190365344
This invention relates to systems for characterizing liver perfusion of contrast agent flow and, in particular, to systems which processes contrast-enhanced ultrasound image data. Contrast-enhanced ultrasound imaging is known to be able to assist the clinicians to identify and characterize lesions such as liver tumors.
Hepatitis B and hepatitis C patients have been found to be at an increased risk of developing primary liver cancer, hepatocellular carcinoma (HCC). Due to the discovery that hepatitis C was being contracted by patients through blood transfusions in the early 1980's, there remain a significant number of hepatitis C patients who need to be examined regularly for the onset of HCC, as the lesions are best treated in their early stages. The usual progression of the disease is from hepatitis to liver cirrhosis to HCC. An easy-to-use monitoring technique for liver disease progression would have widespread application in assisting in the early detection of this serious disease.
There are a number of lesions in addition to HCC which can develop in the liver. The paper “Ultrasound Contrast Imaging Research” by M. Averkiou et al., published in Ultrasound Quarterly, vol. 19, no. 1 at pp 27 et seq. (2003) discusses four primary liver lesions: hepatocellular carcinoma (HCC), metastasis from a primary tumor at some other location, hemangioma, and focal nodal hyperplasia. The former two are malignant and the latter two are benign. A technique for identifying lesions in the liver should be able to detect all four of these lesions so that more detailed diagnosis can identify and distinguish between all lesions found in the liver. The papger “Hepatic Perfusion Imaging Using Factor Analysis of Contrast Enhanced Ultrasound” by G. J. Lueck et al., published in IEEE TRANSACTIONS ON MEDICAL IMAGING, vol. 27, no. 10 at pp 1449 et seq. (2008) presents a method of using factor analysis for visual separation of two different phases of contrast-enhancement from the independent feeding vessels, namely thehepatic artery and the portal vein. WO2011/041244 A1 discloses a method for assessing a liver comprising steps of identifying the location of the main hepatic artery (MHA) and the location of the main portal vein (MPV) in at least one contrast-enhanced ultrasound image of the liver, obtaining time-intensity information corresponding to perfusion of contrast agent in the MHA and MOV, and determining a biomarker index value.
Since liver lesions, like other cancers, are most effectively treated when detected early, high-risk patients should be monitored frequently for signs of these diseases. But in their early stages liver lesions are often difficult to detect through conventional diagnostic imaging due to their small size. Thus, clinicians often conduct their diagnoses to look for other signs that a lesion is developing. One of these signs is changes in the blood flow to the liver. The liver has a unique blood supply network. A primary source of fresh blood to the liver is the arterial inflow from the hepatic artery. But the liver has a secondary blood supply, the portal vein in the abdomen. Being both arterial and venous, these sources of supply function differently. The pulsatile flow of blood from the hepatic artery occurs shortly after systole, like other arterial vessels. The inflow of blood from the portal vein occurs later in the heart cycle. The relative timing and amount of blood flow from these two sources has been related to the onset of lesions in the liver. Thus, it is desirable to be able to analyze the characteristics of blood flow in the liver from these two sources.
However, the flow of blood in the liver parenchyma is a combination of blood flows from these two sources. It is not possible to discern separately the amount of blood arriving in regions of interest in the liver from these separate sources. It is desirable to be able to separate the flow of blood in different regions of interest in the liver as it relates to the hepatic arterial and portal venous flows.
In accordance with the principles of the present invention a system and method are described for identifying the sources of blood flow in regions of interest in the liver as being arterial or venous. The present inventors have noted that the combined blood flow in the liver is linearly related to inflows from both the hepatic artery and the portal vein. The time-intensity curve (TIC) of blood flow in the hepatic artery, or additionally the TIC of blood flow in the portal vein are used as references for these separate sources of blood supply. A time-intensity curve of the perfusion of blood in a region of interest (ROI) in the liver parenchyma. A scaled replica of the hepatic artery TIC is subtracted from the TIC of the ROI to separate the TIC into two curves, one relating to hepatic arterial inflow and the other relating to portal vein inflow.
Moreover, the present inventors have noted that he initial portion of the TIC of the ROI, when inflow is only from the hepatic artery, is mostly related to the hepatic artery time-intensity curve. Hence, in accordance with some embodiments of the present invention, the whole time-intensity curve of contrast agent flow in the hepatic artery is scaled in amplitude such that the initial position of the time-intensity curve of contrast agent flow in the hepatic artery matches the time-intensity in the ROI. The initial portion can be a region or a part of the region when inflow is substantially only from the hepatic artery, which can be, for example, demarcated by time interval from the arrival of contrast from the hepatic artery to the later time of arrival of contrast from a portal vein of the liver. The arrival of contrast from the hepatic artery in the ROI can be estimated as equal to the arrival of contrast in the ROI. The arrival time of contrast from the portal vein in the ROI can be presumably estimated as being later than the arrival of the contrast in the ROI by a predetermined time interval. Additionally or alternatively, the arrival time of contrast from the portal vein in the ROI can be estimated on basis of a time-intensity curve of contrast agent flow in the portal vein.
In accordance with some further embodiments, the time-intensity curve of contrast agent flow in the hepatic artery can be further scaled in time. For example, the scaling in time can be implemented as a time shift.
The time-intensity curves (TICs) of contrast agent flow in the hepatic artery, the portal vein and in the ROI can be provided in various ways. In some example, there is a source for contrast-enhanced ultrasound (CEUS) image data of the liver, and the TICs are produced from the contrast-enhanced ultrasound image data using known or future technologies. The source of such CEUS image data can be a local or a remote storage medium. The source of such CEUS image data can be an ultrasound probe. In some other example, there is a source for directly providing the TICs, which can be a local or remote storage medium, or can be a time-intensity curve processor.
In accordance with some further embodiments, an output unit is provided for outputting one or more of the time-intensity curve data representative of arterial flow in the ROI and the time-intensity curve data representative of venous flow in the ROI. The time-intensity curve data can be one or more characteristics of the time-intensity curves of any one or both sources of blood flow in the liver. The output unit can comprise a user interface, such as a display. Additionally or alternatively, the output unit can comprise a data communication unit for sending out the time-intensity curve data via any kind of communication link. In this way, a separate user interface can receive the time-intensity curve data and then present the data to the users.
The time-intensity curve data can be presented in various ways. In some embodiments, one or more characteristics parameters of the TICs of one or more ROIs can be presented in texture, graphical, or audio format. In some embodiments, a parameter map representing a parameter for each imaging point in an imaging region can be produced and displayed. For an example, a parametric map of the time-intensity curve data representative of arterial flow in the liver or the time-intensity curve data representative of venous flow in the liver can be produced. Additionally, the parametric map can be overlaid on a B-mode image of the liver.
In accordance with some further embodiments, a user control can be provided to select an ROI in a liver image. Additionally, the user control is further configured to apply the spatial location of an ROI in a liver image to the time-intensity curve processor.
In accordance with an embodiment of a first aspect of the invention, there is provided a systems for characterizing liver perfusion of contrast agent flow on basis of ultrasound data acquired from a liver in the presence of contrast agent flow. The system comprises: a first source of time-intensity curves of contrast agent flow in a hepatic artery, a portal vein, and in at least one region of interest, i.e. ROI, in liver parenchyma of the liver, the time-intensity curves being produced from the ultrasound data; and the system is characterized by a time-intensity curve scalar and subtractor, which is configured to produce, for an ROI of the at least one ROI, time-intensity curve data representative of arterial flow in the ROI by scaling the time-intensity curve of contrast agent flow in the hepatic artery to the time-intensity curve of contrast agent flow in the ROI, and to produce time-intensity curve data representative of venous flow in the ROI by subtracting the time-intensity curve data representative of arterial flow in the ROI from the time-intensity curve of contrast agent flow in the ROI.
In some embodiments, the first source comprises: a second source of ultrasound liver image data acquired in the presence of contrast agent flow; a nonlinear signal separator, coupled to receive the ultrasound liver image data, and configured to produce harmonic echo signal data from contrast agent flow; and a time-intensity curve processor, responsive to the harmonic echo signal data, which is configured to produce the time-intensity curves of contrast agent flow in the hepatic artery, and in the at least one ROI.
In accordance with an embodiment of a second aspect of the invention, there is provided a method of characterizing liver perfusion of contrast agent flow on basis of ultrasound liver image data acquired from a liver in the presence of contrast agent flow. The method comprises steps of acquiring a time-intensity curve of contrast agent flow in a hepatic artery location, and a time-intensity curve of contrast agent flow in each of at least one region of interest, i.e. ROI, in the liver parenchyma of the liver, wherein the time-intensity curves are produced from the ultrasound liver image data. The method is characterized by steps of, for a ROI of the at least one ROI, producing time-intensity curve data representative of arterial flow in the ROI by scaling the time-intensity curve of contrast agent flow in the hepatic artery location to match the time-intensity curve of contrast agent flow in the ROI, and producing time-intensity curve data representative of venous flow in the ROI by subtracting the time-intensity curve data representative of arterial flow in the ROI from the time-intensity curve of contrast agent flow in the ROI.
In accordance with an embodiment of a third aspect of the invention, there is provided a computer program product comprising instructions which, when the computer program product is executed by a computer, cause the computer to carry out the method.
In accordance with an embodiment, there is provided a computer-readable storage medium for storing computer executable instructions, which, when being executed by a processor, cause the processor to carry out the method.
In the drawings:
The hepatic artery 12 is outlined in both images. The hepatic artery 12 is easier to locate in the left contrast image due to its cyclical brightening with each heartbeat as contrast perfused blood is pumped through the vessel. Showing both the contrast and tissue images at the same time assists the sonographer in stabilizing the probe during image acquisition. The right tissue image, in which contrast flow is suppressed, should be relatively static and helps the sonographer maintain the probe constantly aligned with the same scan plane, while the pulsatile flow in the more dynamic contrast image assists in spotting the hepatic artery from its cyclical blood flow.
Accordingly, the first time-intensity curve 302 correspond to the varying intensity of a first group of pixels of contrast flow in the first ROI drawn over the hepatic artery 12 in
The flow of contrast in the capillary structure of the liver parenchyma from these two sources of flow is a combination of both, as shown in
Referring now to
Echoes from the transmitted ultrasonic energy are received by the transducers of the array 102, which generate echo signals that are coupled through the T/R switch 22 and digitized by the analog to digital converters when the system uses a digital beamformer. Analog beamformers may alternatively be used. The A/D converters sample the received echo signals at a sampling frequency controlled by a signal fs generated by a system controller 28. The desired sampling rate dictated by sampling theory is at least twice the highest frequency of the received passband, and might be on the order of 30-40 MHz. Sampling rates higher than the minimum requirement are also desirable. Control of the ultrasound system and of various control setting for imaging such as probe selection and ROI delineation is effected by user manipulation of the controls of a user control panel 20 which is coupled to and applies its control through the system controller 28.
The echo signal samples from the individual transducers of the array 14 are delayed and summed by the beamformer 30 to form coherent echo signals along scanline directions for an image. The digital coherent echo signals may then be filtered by a digital filter and undergo noise reduction as by spatial or frequency compounding. The digital filter can also shift the frequency band to a lower or baseband frequency range. The digital filter could be a filter of the type disclosed in U.S. Pat. No. 5,833,613 (Averkiou et al.), for example. When phase information is needed as is the case for Doppler processing, quadrature (I and Q) demodulation may also be performed on the echo signals. In this implementation, the transmit frequency fo and the receiver frequency are individually controlled so that the beamformer 32 is free to receive a band of frequencies which is different from that of the transmitted band such as a harmonic frequency band around frequency 2fo.
The beamformed coherent echo signals are coupled to a nonlinear signal separator 32. The nonlinear signal separator 32 preferably separates harmonic frequency echoes returned from harmonic contrast agents by the pulse inversion technique, in which echo signals resulting from the transmission of multiple, differently phased (inverted) pulses to an image location are additively combined to cancel fundamental signal components and enhance harmonic components, thus producing echo signals in a harmonic band 2fo. The same echo signals are subtractively combined to produce echo signals in a fundamental frequency band fo. A preferred pulse inversion technique is described in U.S. Pat. No. 6,186,950 (Averkiou et al.) and in U.S. Pat. No. 5,706,819 (Hwang et al.) for instance.
Harmonic echo signals from a contrast agent, such as microbubbles, are coupled to a contrast image processor 38. Contrast agents are often used to more clearly delineate blood vessels, or to perform perfusion studies of the microvasculature of tissue as described in U.S. Pat. No. 6,692,438 (Skyba et al.) for example. In the implementation shown in
The fundamental frequency echo signals are coupled to a B mode processor 36 which produces a standard B mode tissue image. The B mode processor performs in the same manner as the contrast image processor, but operates on fundamental frequency echoes. The echo signals are amplitude (envelope) detected and scan converted to produce a spatially delineated image of tissue such as the B mode images shown on the right side of
In accordance with the principles of the present invention the harmonic echo signals are coupled to a TIC processor 50. The TIC processor processes echo signals from a contrast agent received over time from a region of interest (ROI) to produce a time-intensity curve such as those shown in
A time-intensity curve is generally computed by measuring the intensity of signals returned from the contrast agent as it flows into and out of blood vessels and the microvasculature of the tissue. These measurements of the rise and fall of the amount of contrast agent are then fitted to a curve such as that defined by the Gamma-variate curve model
A*(x−t0)*exp(−ρ*(x−t0))+C,
where A is the curve peak, to is the time of initiation of the increase of contrast agent, ρ is the slope of the rise of the curve, and x is the instantaneous measurement of the amount of the contrast agent. These time and intensity representations provide an indication to a trained clinician of the manner in which the tissue is perfused.
In an implementation of the present invention a time-intensity curve is formed from the contrast wash-in and wash-out in an ROI located over the hepatic artery 12 as shown in
Theoritically, the arrival of contrast agent flow from the hepatic artery in different ROIs varies from each other depending on the location of the ROIs, e.g. earlier in ROIs nearer to the hepatic artery. Practically, due to the fast perfusion of the contrast agent flow, such differences can be neglected especially in cases when the differences are not significant. In some other embodiments, the hepatic artery TIC may be further scaled in time, by time shifting the curve for example. Particularly, time delay may be introduced because the arrival of contrast agent flow in liver parenchyma is theoritically later than the arrival of contrast agent flow in the hepatic artery. The amount of the time shift can be determined by comparing the hepatic artery TIC and the TIC in the ROI. For example, the arrival time of contrast in each of the two curves can be determined as the time when the amplitude exceeds a predetermined threshold. In an embodiment, the predetermined threshold can be set as an absolute value. As the amplitude of the hepatic artery TIC is much greater than the amplitude of the TIC in the ROI, the predetermined threshold for determining the arrival of contrast in the hepatic artery is set as being different from that for determining the arrival of contrast in the ROI. In another embodiment, the predetermined threshold for determining the arrival of contrast can be set as a relative value to the peak of the corresponding TIC.
Since the combined flow in the liver ROI is linearly related to the flow of blood from both sources, the scaled hepatic artery TIC is then subtracted from TIC from the liver ROI, which, for instance, is the combination of curves 72 and 74′ in
One or more characteristics of these estimated curves are coupled to a graphics processor 56 which displays them to the clinician for diagnostic purposes. A simple display is to display the data of the two estimated curves of arterial and venous perfusion for a selected ROI on the display screen, which will appear similar to the curves shown in
The steps of an exemplary method in accordance with the present invention is shown in
It should be noted that the ultrasound system which acquires contrast data from flow in the hepatic artery, portal vein, and liver and produces estimates of flow in the liver due to the individual sources of blood flow as shown in
As used herein, the term “computer” or “module” or “processor” may include any processor-based or microprocessor-based system including systems using microcontrollers, reduced instruction set computers (RISC), ASICs, logic circuits, and any other circuit or processor capable of executing the functions described herein. The above examples are exemplary only, and are thus not intended to limit in any way the definition and/or meaning of these terms.
The computer or processor executes a set of instructions that are stored in one or more storage elements, in order to process input data. The storage elements may also store data or other information as desired or needed. The storage element may be in the form of an information source or a physical memory element within a processing machine.
The set of instructions of an ultrasound system including the acquisition of contrast data and the calculation of time-intensity curves and parameters described above may include various commands that instruct a computer or processor as a processing machine to perform specific operations such as the methods and processes of the various embodiments of the invention. The set of instructions may be in the form of a software program. The software may be in various forms such as system software or application software and which may be embodied as a tangible and non-transitory computer readable medium. Further, the software may be in the form of a collection of separate programs or modules, a program module within a larger program or a portion of a program module. For example, the equations calculated by the time-intensity data processors of
Furthermore, the limitations of the following claims are not written in means-plus-function format and are not intended to be interpreted based on 35 U.S.C. 112, sixth paragraph, unless and until such claim limitations expressly use the phrase “means for” followed by a statement of function devoid of further structure.
| Number | Date | Country | Kind |
|---|---|---|---|
| PCT/CN2016/105682 | Nov 2016 | CN | national |
| 17161867.1 | Mar 2017 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2017/078690 | 11/9/2017 | WO | 00 |
