Patent Application
20160125597
The present invention relates to a novel magnetic resonance imaging technique for imaging and evaluating collateral circulation.
Cerebral infarction is one of the leading causes of death worldwide, and shows a high outcome of disability and the highest death rate, as a single disease, among the causes of death in Korea. A cerebral infarction is a symptom in which the supply of blood to brain tissues is blocked due to cerebrovascular occlusion, resulting in the infarction of the brain tissues. The only way for cerebral infarction therapy is to early recanalize the occluded blood vessel, thereby restoring the cerebral blood flow before the brain tissues reach a complete infarction. The cerebral blood flow is maintained by the collateral circulation supplied from surrounding blood vessels until the occluded brain blood vessel is recanalized. Therefore, the collateral status before recanalization therapy is an important determinant of tissue fate with respect to cerebral infarction [Bang O Y et al., J Neurol Neurosurg Psychiatry, 2008; 79:625]. In addition, collateral circulation has a profound effect on the recanalization rates of the occluded blood vessel and hemorrhagic change of brain tissues [Bang O Y et al., Stroke, 2011; 42:693; Bang O Y et al., Stroke, 2011; 42: 2235]. In other words, it is very important to assess the collateral status at the early stage in making therapeutic decisions and predicting the outcomes in patients with cerebral infarction. Since the cerebral infarction has various causes and therapeutic responses, it is very important to develop image biomarkers using various magnetic resonance imaging techniques. Representative research techniques of cerebral infarction using magnetic resonance imaging are diffusion and perfusion-weighted imaging, fluid attenuation inversion recovery (FLAIR), and the like, and these images and maps made through image post-processing are actively used as image biomarkers in clinical trials. Although these various techniques have been developed, the method of directly imaging collateral circulation using magnetic resonance imaging and evaluating the collateral status has not yet developed.
Generally, digital subtraction angiography (DSA) is currently used as the gold standard for the imaging of collateral circulation and evaluation of collateral status in clinical diagnosis. However, DSA technique is invasive, takes a relatively long time for the implementation, requires expertise, and has a risk of thrombotic complications. Moreover, when the collateral status is evaluated using DSA, the evaluation is not sufficiently implemented until the late venous phase or the evaluation on the contralesional blood vessel is omitted, and thus the collateral evaluation may be restricted. Therefore, novel techniques need to be developed that are non-invasive to the human body and can grasp the collateral status easily and objectively for a shorter time.
Throughout the entire specification, many papers and patent documents are referenced and their citations are represented. The disclosure of cited papers and patent documents is entirely incorporated by reference into the present specification, and the level of the technical field within which the present invention falls and details of the present invention are explained more clearly.
The present inventors have endeavored to solve the above-mentioned problems, and as a result, the present inventors have developed a novel method for visualizing collateral circulation and evaluating the collateral status using magnetic resonance imaging, and have completed the present invention.
Accordingly, an aspect of the present invention is to provide a method for imaging collateral circulation in the body.
Another aspect of the present invention is to provide a computer-readable recording medium storing a program for imaging collateral circulation.
Other purposes and advantages of the present disclosure will become more obvious with the following detailed description of the invention, claims, and drawings.
In accordance with an aspect of the present invention, there is provided a method for imaging collateral circulation in the body, the method including: (a) image post-processing source data of dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) as magnetic resonance imaging in the body; and (b) comparing images obtained through the image post-processing in step (a) with digital subtraction angiography (DSA) images to image collateral circulation.
As used herein, the term “collateral circulation” refers to a situation where the blood flow detours to other blood vessels when a normal blood flow is blocked due to stricture or occlusion of the blood vessel. Cerebral blood flows are composed of anterior circulation by carotid arteries at both sides and posterior circulation by the vertebrobasilar artery at the back side, and theses anastomose in the skull base to form the circle of Willis, and diverge into the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery. These blood vessels are ultimately in charge of the supply of blood to a predetermined region of the brain, but the anastomosis between these blood vessels occurs in some sites to make collateral circulation when a lesion occurs on one blood vessel.
According to a preferable embodiment of the present invention, the collateral circulation of the present invention includes ones at the regions of the brain, heart, leg and arm terminals, and intestine, and more preferably, the collateral circulation of the present invention includes ones occurring at the time of cerebral infarction or myocardial infarction.
As used herein, the term “cerebral infarction” refers to a disease in which the blood vessel of the brain becomes occluded and thus a portion of the brain dies. The cerebral infarction is caused by cerebrovascular occlusion due to blood clots resulting from cerebrovascular arteriosclerosis and emboli derived from the heart.
As used herein, the term “magnetic resonance imaging” refers to a diagnostic technique that provides pictures of the body's internal structures using a magnetic field. The machine that is used for the magnetic resonance imaging forms a very strong magnetic field in the body using magnetic pulses, and images the body's internal structures using signals made during the formation and destruction of such a magnetic field.
As used herein, the term “dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI)” refers to one technique of the magnetic resonance imaging that detects the change in the magnetic field, caused by the increase in susceptibility. In general, DSC-PWI is a technique in which gadolinium diethylene triamine penta acetic acid (GD-DTPA) as a paramagnetic contrast agent is intravenously injected into the arm of patient to observe the signal change over time through consecutive photographing, and then images various cerebral blood flow-derived maps, such as cerebral blood flow, cerebral blood flow amount, and mean travel time of the contrast agent, through the detection of the signal change.
As used herein, the term “image post-processing” is a collective term for a series of operations in which, after the acquisition of an image, multiple pieces of information of the image, as source data, are corrected and reconstructed to output a new image. Generally, the medical image may be defined by 3-D function, f(x, y, z), and here, x, y, and z mean spatial coordinates, and the magnitude of f at the coordinates is called the signal intensity of the image. The medical image is composed of finite components since it is a digital image. Each component has a particular location and value, and is called a voxel. The signal intensity values of the respective voxels are corrected and reconstructed through an image post-processing procedure, and output as an image composed of new pieces of information.
As used herein, the term “digital subtraction angiography (DSA)” refers to one technique of angiography. Specifically, first, a simple X-ray is performed on a site that is to be subjected to angiography, and then a contrast agent, which is observable by an X-ray, is injected to the blood vessel, and then an X-ray is performed thereon. These two kinds of scan information are input to a computer to subtract first scan information from second scan information. Through this procedure, an image in which only the blood vessels are clearly contrasted but the other area is eliminated can be obtained. The technique that obtains an image of the blood vessel more clearly through this manner is called a digital subtraction angiography.
According to a preferable embodiment of the present invention, the image post-processing of the DSC-PWI source data in step (a) comprises step (a)-1 of subtracting a signal of an image obtained before the injection of a contrast agent from signals of images obtained after the injection of the contrast agent to obtain sequential images over time.
As described above, by subtracting the signal of the image obtained before the injection of the contrast agent from the signals of the sequential images over time obtained after the injection of the contrast agent, signals from anatomical structures are eliminated and only signals from the contrast agent are left, and thus the tissue to be imaged can be sequentially visualized. The sequential DSC-PWI images over time mean sequential images having a predetermined time interval, and the predetermined time interval is preferably 0.1-10 seconds, more preferably 0.5-5 seconds, still more preferably 1.0-3 seconds, and most preferably 1.5-2 seconds.
According to another preferable embodiment of the present invention, the image post-processing of DSC-PWI source data in step (a) comprises step (a)-2 of merging adjacent consecutive image cuts in the sequential images obtained in step (a)-1.
Herein, by merging the adjacent consecutive image cuts in the sequential DSC-PWI images, the spatial resolution of the image is improved and the signal intensity change over time is maximized. The number of consecutive image cuts that are merged may be appropriately selected within the range in which the spatial resolution can be improved and the signal intensity change over time can be maximized. For example, the merging of the adjacent consecutive image cuts may be performed by merging two to ten, preferably two to seven, more preferably two to five, still more preferably two to three, and the most preferably two adjacent consecutive image cuts.
According to another preferable embodiment of the present invention, the comparing of the post-processed DSC-PWI images in step (b) and the DSA images is performed on images corresponding to an arterial, capillary, venous, or late venous phase.
As used herein, the term “arterial phase” refers to a phase in which contrast staining starts from the insular region of the cerebral parenchyma of the normal hemisphere; the term “capillary phase” refers to a phase in which the whole cerebral parenchyma of the normal hemisphere is stained at the maximal signal intensity; the term “venous phase” refers to a phase in which the contrast agent is washed out in the cerebral parenchyma of the normal hemisphere; and the term “late venous phase” refers to a phase in which the contrast agent is washed out in the cerebral parenchyma of the normal hemisphere but the remaining contrast is shown in the cerebral parenchyma of the lesional hemisphere.
According to another preferable embodiment of the present invention, the DSC-PWI images in the arterial, capillary, venous, and late venous phases are composed of consecutive “images, each of which is obtained by merging adjacent consecutive image cuts” described as above. More preferably, the DSC-PWI images in the arterial, venous, and late venous phases are composed of two consecutive images, “each of which is obtained by merging adjacent consecutive image cuts” described as above, and the DSC-PWI images in the capillary phase are composed of three consecutive images, “each of which is obtained by merging adjacent consecutive image cuts” described as above.
According to another preferable embodiment of the present invention, the DSC-PWI images in the arterial phase are merged to construct an early-phase image of collateral circulation, the DSC-PWI images in the capillary phase are merged to construct a mid-phase image of collateral circulation, and the DSC-PWI images in the venous and late venous phases are merged to construct a late-phase image of collateral circulation.
In accordance with another aspect of the present invention, there is provided a method for creating a collateral circulation image, the method including:
R
2*(t)=−1/TE log [S(t)/So]
In accordance with still another aspect of the present invention, there is provided a computer readable recording medium storing a program for creating a collateral circulation image, comprising the following steps:
R
2*(t)=−1/TE log [S(t)/So]
The step of merging adjacent images to create collateral circulation images in step (d)′ and (d)″ is the same as the method described in the method for imaging collateral circulation in the body according to another aspect of the present invention, and thus the descriptions thereof are omitted.
Based on collateral grades observed on the collateral circulation images obtained by the method of the present invention, outcomes after blood vessel recanalization in patients with cerebral infarction can be predicted (see example 6).
Features and advantages of the present invention are summarized as follows.
The present invention is directed to a novel magnetic resonance imaging technique for visualizing collateral circulation in the body. In the present invention, the collateral circulation is visualized by image post-processing source data of dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI), and then comparing the images obtained through the post-processing with digital subtraction angiography (DSA) images. According to the method of the present invention, the collateral circulation can be non-invasively visualized and evaluated easily and promptly, thereby providing information that is important in understanding, making therapeutic decision, and predicting outcomes, of diseases caused by stricture or occlusion of the blood vessel.
Hereinafter, the present invention will be described in detail with reference to examples. These examples are only for illustrating the present invention more specifically, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples.
As a first step for visualizing collateral circulation, contrast staining and washout in the brain parenchyma was sequentially visualized using DSC-PWI source data (
As a second step for imaging collateral circulation, the images obtained from DSC-PWI were sequentially merged stage by stage, and then a comparison of temporal and spatial resolution was performed (
As the last step for visualizing collateral circulation, the two-cut merged images determined in example 2 were matched to images obtained by digital subtraction angiography (
Collateral circulation images were automatically generated using the same logic algorithm as in the method of obtaining collateral circulation images described in example 3. This automatic software was named a fast analysis system for collaterals (FAST-COLL). The overall flow for generating collateral circulation images using FAST-COLL is shown in
where S(t) is the magnetic resonance signal intensity at the corresponding time; So is the baseline magnetic resonance signal intensity; and TE is the echo time. For the creation of collateral circulation images, all R2* values at every voxel on each cut are summed, and the change in the summated R2* value over time was plotted on a graph (
After the collateral circulation images were generated, the collateral status was determined from the generated images. The collateral status may be largely classified into no collateral circulation, slow collateral circulation, and fast collateral circulation. No collateral circulation indicates that contrast staining is completely non-visible until the late phase; slow collateral circulation indicates that contrast staining is non-visible in the mid-phase but is visible in the late phase; and fast collateral circulation indicates that contrast staining is visible in the mid-phase in the lesional hemisphere, similarly to the normal hemisphere. Based on this matter, the collateral circulation may be evaluated. As shown in collateral circulation images in the
The outcomes deepening on the recanalization or not of blood vessels can be predicted according to the collateral grade obtained from collateral circulation images in patients with acute cerebral infarction after blood vessel recanalization therapy. As shown in
Although the present invention has been described in detail with reference to the specific features, it will be apparent to those skilled in the art that this description is only for a preferred embodiment and does not limit the scope of the present invention. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10-2013-0063423 | Jun 2013 | KR | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/KR2014/003346 | 4/17/2014 | WO | 00 |
