KR102097044B1 - Information offering method for parkinson's disease diagnosis - Google Patents

Abstract

A method of providing information for diagnosing Parkinson's disease according to the present invention includes: a first step of obtaining an image of a multi-echo size and phase image from an MRI of an image acquisition unit's brain; A second step in which the image processing unit post-processes to observe only the black matter and the nigrosome 1 region presented as an image biomarker of Parkinson's disease in the acquired image; A third step in which the image analysis unit analyzes the post-processed image to classify an image containing the nigrosome 1 region, and detects the nigrosome 1 region from the classified image; And a fourth step of determining whether or not the patient has Parkinson's disease, wherein the image analysis unit provides information on the detected region of the nigrosome 1 to the diagnosis unit. It may include.

Description

Information on how to diagnose Parkinson's disease {INFORMATION OFFERING METHOD FOR PARKINSON'S DISEASE DIAGNOSIS}

The present invention relates to a method for providing information for diagnosing Parkinson's disease, and more particularly, to a Parkinson disease diagnosis apparatus and method for diagnosing Parkinson's disease by analyzing magnetic resonance imaging (hereinafter referred to as 'MRI') will be.

Neurodegenerative disease refers to a disease that causes brain dysfunction as nerve cells disappear by some cause.

Typical neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, and rarely Lou Gehrig's disease.

Among neurodegenerative diseases, Parkinson's disease is a representative neurodegenerative disease in which nerve cells are destroyed, and the body hardens, the hands and feet tremble, and the symptoms of inability to walk are accompanied by depression and anxiety, which greatly reduces the quality of life.

As a method of diagnosing such a neurodegenerative disease, it is diagnosed by contact with mucous membranes, skin destruction, or a non-invasive method for diagnosis without internal body cavity other than natural or artificial body structures.

For example, Patent Document 1 and Patent Document 2 below disclose techniques for diagnosing neurodegenerative diseases according to the prior art.

Republic of Korea Patent Registration No. 10-1754291 (announced on July 6, 2017) Republic of Korea Patent Publication No. 10-2016-0058812 (released on May 25, 2016)

 Sung-Min Gho et al., "Susceptibility Map-Weighted Imaging (SMWI) for Neuroimaging", Magnetic Resonance in Medicine 72: 337-346 (2014)  Yoonho Nam et al., "Imaging of Nigrosome 1 in Substantia Nigra at 3T Using Multiecho Susceptibility Map-Weighted Imaging (SMWI)", J. MAGN. RESON. IMAGING 2017; 46: 528-536  Christian Langkammer et al., "Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study", Neuroimage. 2012 Sep; 62 (3): 1593-9. doi: 10.1016 / j.neuroimage. 2012.05.049. Epub 2012 May 24.

[18F] FP-CIT positron emission tomography (PET) using isotopes is the most objective method for diagnosing Parkinson's disease and differential diagnosis of drug-induced Parkinsonism.

However, the [18F] FP-CIT PET is a very expensive test method and there is a risk of radioactive exposure.

Therefore, there is a need to develop a technique for diagnosing Parkinson's disease by observing the region of nigrosome 1 using MRI.

An object of the present invention is to solve the problems as described above, to provide an apparatus and method for diagnosing Parkinson's disease by analyzing MRI to diagnose Parkinson's disease.

Another object of the present invention is to provide an apparatus and method for diagnosing Parkinson's disease by analyzing a region of nigrosome 1 presented as an image biomarker of Parkinson's disease.

In order to achieve the above object, a method for providing information for diagnosing Parkinson's disease according to the present invention includes: a first step of obtaining an image of a multi-echo size and phase image from an MRI of a patient's brain; A second step in which the image processing unit post-processes to observe only the black matter and the nigrosome 1 region presented as an image biomarker of Parkinson's disease in the acquired image; A third step in which the image analysis unit analyzes the post-processed image to classify an image containing the nigrosome 1 region, and detects the nigrosome 1 region from the classified image; And a fourth step of determining whether or not the patient has Parkinson's disease, wherein the image analysis unit provides information on the detected region of the nigrosome 1 to the diagnosis unit. It may include.

In addition, in the second step, the image processing unit may apply a quantitative susceptibility map mask to the image obtained in the first step using a quantitative susceptibility mapping algorithm to post-process the susceptibility map through weighted imaging.

In addition, in the third step, the image analysis unit classifies an image including a region containing a region of nigrosome 1 and an image not included in the entire MRI through machine learning, and to the image containing the classified region of region 1 of nigrosome. The position of the nigrosome 1 region can be designated to detect the nigrosome 1 region.

As described above, according to the information providing method for diagnosing Parkinson's disease according to the present invention, only the image containing the region of nigrosome 1 in MRI is classified, and the region of parkedson's disease is analyzed by analyzing the region of nigrosome 1 in the classified image. The effect that can be diagnosed is obtained.

And according to the present invention, by applying a susceptibility map weighted imaging protocol and a quantitative susceptibility mapping algorithm to improve the visibility of the nigrosome 1 region, and diagnosed Parkinson's disease using a visualized image of the black matter structure, universally supplied Parkinson's disease can be accurately diagnosed using MRI equipment, and the effect of improving the accuracy of the diagnosis results is obtained.

1 is a view illustrating an MRI including the black matter and the nigrosome 1 region,
Figure 2 is a block diagram of a Parkinson's disease diagnosis apparatus according to a preferred embodiment of the present invention,
3 is a view for explaining the operation of the image acquisition unit and the image processing unit,
4 and 5 are views for explaining the operation of the image analysis unit,
6 is a view for explaining the operation of the diagnostic unit,
7 is a view showing a state in which a diagnosis result is applied to an input image,
8 is a process step-by-step illustrating a method for diagnosing Parkinson's disease according to a preferred embodiment of the present invention.

Hereinafter, an apparatus and method for diagnosing Parkinson's disease according to a preferred embodiment of the present invention will be described in detail with reference to the accompanying drawings.

First, referring to FIG. 1, the criteria for diagnosing Parkinson's disease by observing the region of nigrosome 1 in the black matter will be described.

1 is a view illustrating an MRI including the black matter and the nigrosome 1 region.

FIG. 1 (a) shows an imaging slab, and FIG. 1 (b) shows images of a normal person's black matter (substantia nigra) and the nigrosome 1 region, and FIG. 1 (c) ) Shows images of the black matter and the nigrosome 1 region of Parkinson's disease patients.

The region of nigrosome 1 in the black matter of normal people is black as shown in FIG. 1 (b), and the region of nigrosome 1 in patients with Parkinson's disease is relatively gray as shown in FIG. 1 (c). Is displayed closely.

Therefore, the present invention can diagnose the presence or absence of Parkinson's disease by observing the shadow of the region of the Nigrosome 1 presented as an image biomarker of Parkinson's disease in MRI.

For example, the present invention applies the susceptibility map weighted imaging (hereinafter referred to as 'SMWI') protocol and an internal quantitative susceptibility mapping (hereinafter referred to as 'QSM') algorithm in 3T MRI. Parkinson's disease is diagnosed by analyzing the normality of the nigrosome 1 region by improving the visibility of the grosome 1 region.

The substantia nigra pars compacta is a midbrain structure that contains a dense population of dopamine neurons. These neurons gradually disappear in idiopathic Parkinson's disease (IPD), leading to disability. This area shows an increase in iron concentration in IPD patients compared to healthy controls.

Recently, as a result of visualizing a small portion of the dense part of the black matter known as nigrosome 1 in a high-resolution susceptibility contrast image of a healthy subject, the contrast between the nigrosome 1 and its surrounding substantia nigra regions was compared to the difference in iron concentration. As a result, the difference in susceptibility between the two sites was significantly decreased in patients with IPD.

The reduction in the susceptibility difference between these two sites is being used as an imaging biomarker for IPD.

Therefore, the Nigrosome 1 structure has been successfully described in 7T MRI using high resolution (eg 0.3mm planar resolution) T2-weighted imaging or susceptibility weighted imaging (SWI).

However, in a low magnetic field strength, such as 3T MRI, due to limited spatial resolution and signal / contrast-to-noise ratio (SNR / CNR), in 3D high-resolution T2-weighted imaging, a contrast, a structure in which contrast is significantly reduced, is observed.

This limitation hindered the reliability and applicability of nigrosome 1 imaging in 3T MRI, despite several successful studies demonstrating the usefulness of the approach.

Recently, a new method for providing an improved magnetic susceptibility contrast has been proposed to solve the above problems.

One of them is to use multi-echo gradient recall echo (hereinafter referred to as 'multi-echo GRE') size image instead of using a single echo image to improve SNR. By combining, it shows a relatively high accuracy in diagnosing IPD in 3T MRI.

An alternative to the size image is susceptibility-weighted imaging (SWI), which uses phase information as a weight mask to increase susceptibility contrast, or artifacts due to blooming of phase imaging. ).

Other susceptibility contrast related approaches are GRE phase (or frequency) images and quantitative susceptibility mapping (QSM), both of which have good susceptibility to susceptibility and have been widely applied in recent years.

In addition, a new method using a susceptibility weighting mask derived from QSM for a size image has been proposed.

This approach is similar to SWI, but it can solve SWI's blooming artifacts and potentially improve visualization of susceptibility changes.

QSM mask weighted imaging has proven useful in visualizing the structure of the Nigrosome 1.

The non-patent document 1 discloses an SMWI technology for neuroimaging, and the non-patent document 2 discloses an imaging technique of nigrosome 1 in black matter using multi-echo SMWI in 3T MRI, and the ratio Patent Document 3 discloses a QSM technology for brain iron measurement.

Therefore, the present invention diagnoses Parkinson's disease based on the change in the region of nigrosome 1 due to Parkinson's disease according to the correlation between brain iron concentration and susceptibility.

2 is a block diagram of a Parkinson's disease diagnosis apparatus according to a preferred embodiment of the present invention.

Parkinson's disease diagnosis apparatus 10 according to a preferred embodiment of the present invention, as shown in Figure 2, an image acquisition unit 20 for acquiring a multi-echo size and phase image from the MRI of the patient's brain, obtained In the image, the image processing unit 30 that post-processes the black matter and the nigrosome 1 region presented as the image biomarker of Parkinson's disease to be observed, analyzes the processed image, classifies and classifies the image containing the nigrosome 1 region. It includes an image analysis unit 40 for detecting a region of nigrosome 1 in an image and a diagnosis unit 50 for diagnosing Parkinson's disease by determining whether the region of nigrosome 1 is normal in each classified image.

The configuration of the image stroke feature and the image processor will be described in detail with reference to FIG. 3.

3 is a view for explaining the operation of the image acquisition unit and the image processing unit. FIG. 3 shows a process of generating an SMWI image for a structure of a nigrosome 1 from a multi-echo synthetic GRE image.

As shown in FIG. 3, the image acquisition unit 20 is communicatively connected to a MRI equipment 21 or a database (not shown) that stores and manages the MRI photographed by the MRI equipment 21 to prevent Parkinson's disease. Obtain the MRI of the patient to be diagnosed.

As shown in FIG. 3, the image processing unit 30 uses a multi-echo sized image and a multi-echo phase image using a QSM algorithm to visualize the structure of the Nigrosome 1 structure. Creates a SMWI video.

For example, the image processor 30 generates a channel-sized size image from the multi-channel composite image by the square root of the sum of squares of the multi-channel size image, and the phase image is a complex average after correcting the global phase offset of each channel. Combined (step 1).

Then, the image processing unit 30 combines six echo images into a single image by the square root of the sum of the image squares (step 2).

The image processor 30 calculates phase images of different TEs using a Laplacian unwrapping algorithm, and calculates a combined frequency w in each voxel (step 3).

The image processing unit 30 removes a background region from harmonic background phase removal using a Laplacian operator method in a frequency image (step 4).

Here, the QSM can be reconstructed using an improved sparse linear equation and least-squares (iLSQR) method.

For example, the error tolerance in the reconstruction parameters of iLSQR = 0.01, the threshold D ₂ for an incomplete k-region mask, _{and thres} = 0.1.

Subsequently, the image processing unit 30 additionally processes the resulting QSM to generate a QSM mask (S _mask ) for weighting compared to the susceptibility (step 5).

The mask may be generated using Equation (1).

[Equation 1]

Here, X is a quantitative susceptibility value (in ppm) calculated in step 4, and X _th is a paramagnetic threshold. The threshold can later be determined using Nigrosome 1 imaging data for optimal CNR.

Finally, the image processing unit 30 may generate an SMWI image by multiplying a multi-echo-combined sized image by a QSM mask using Equation 2 below.

[Equation 2]

Here, m is the number of multiplications for the susceptibility weight, and mag is the multi-echo magnitude combined image of the two steps.

Next, the operation of the image analysis unit will be described in detail with reference to FIGS. 4 and 5.

4 and 5 are views for explaining the operation of the image analysis unit. 4 shows a process of classifying an image containing a region of nigrosome 1, and FIG. 5 shows a process of detecting a region of nigrosome 1 in the classified image.

As illustrated in FIG. 4 through the post-processing process of the image processing unit 30, a plurality of SWMI images may be acquired.

In general, MRI photographed for diagnosis of Parkinson's disease is about 40 to 70 per patient, and among these, images containing a region of Nigrosome 1 used for diagnosing Parkinson's disease are within about 3 to 6 images.

As illustrated in FIG. 4, the image analysis unit 40 analyzes an image containing a region of nigrosome 1 among all MRIs through machine learning and includes an image containing a region of nigrosome 1 and not included. You can classify images.

For example, the image analysis unit 40 uses a region-convolutional neural network (hereinafter, referred to as 'RCNN') among the methods using a machine learning deep learning neural network. A region including one region can be classified.

That is, the image analysis unit 40 detects a feature map using the obtained image using a convolutional neural network (hereinafter referred to as 'CNN'), and a Region Proposal Network (hereinafter referred to as “Region Proposal Network”). About 2,000 regions of interest (RoI) are selected from the feature map detected using 'RPN'), and after resizing the selected regions of interest to the same size, interest input to the CNN In order to increase the accuracy of the location of the region, a CNN is performed for each region of interest using a support vector machine (SVM) composed of neural networks, and classification loss and a bounding box are classified for the classification result. By processing the regression loss (bounding-box regression loss), it can be minimized by only the image containing the region of the nigrosome 1 finally.

In addition, as shown in FIG. 5, the image analysis unit 40 designates a location where the region of the region of nigrosome 1 exists in each image including the region of nigrosome 1 classified through machine learning, and the designated nigrosome 1 The area can be detected.

Next, the operation of the diagnostic unit will be described with reference to FIGS. 6 and 7.

6 is a diagram illustrating the operation of the diagnostic unit, and FIG. 7 is a diagram showing a state in which a diagnostic result is applied to an input image.

As illustrated in FIG. 6, the diagnostic unit 50 may diagnose whether Parkinson's disease is present or not by analyzing normality of the region of nigrosome 1 detected by the image analysis unit 40 through machine learning.

For example, as shown in (e) to (h) of FIG. 7 according to the diagnosis result of Parkinson's disease in the input images of (a) to (d) of FIG. 7, a diagnosis result may be applied.

Next, a method of diagnosing Parkinson's disease according to a preferred embodiment of the present invention will be described in detail with reference to FIG. 8.

8 is a process chart for explaining the Parkinson's disease diagnosis method step by step according to a preferred embodiment of the present invention.

In step S10 of FIG. 8, the image acquisition unit 20 acquires a number of MRIs of patients who want to diagnose Parkinson's disease through communication with the MRI equipment 21 or a database.

Here, the image acquisition unit 20 may acquire a multi-echo GRE composite image in which a multi-echo size image and a multi-echo phase image are combined in 3T MRI.

In step S12, the image processing unit 30 post-processes a multi-echo GRE composite image in which a multi-echo size image and a multi-echo phase image are combined using a QSM algorithm to visualize the structure of the Nigrosome 1 SMWI. Create an image.

In step S14, the image analysis unit 40 analyzes an image containing a region of nigrosome 1 among all MRIs through machine learning to classify an image containing a region of nigrosome 1 and an image that does not include (classification). )do.

In addition, the image analysis unit 40 designates a location where the region of the region of nigrosome 1 exists in each image including the region of nigrosome 1 classified through machine learning, and detects the designated region of nigrosome 1 (S16).

Finally, the diagnosis unit 50 diagnoses the presence or absence of Parkinson's disease by determining whether or not the detected region of the nigrosome 1 region is normal in each image classified as an image including the nigrosome 1 region in the image analysis unit 40.

Through the above-described process, the present invention classifies only the image containing the region of nigrosome 1 in MRI, and analyzes the region of nigrosome 1 in the classified image to diagnose the presence or absence of Parkinson's disease.

Although the invention made by the present inventors has been described in detail according to the above-described embodiments, the present invention is not limited to the above-described embodiments, and it is needless to say that the invention can be changed in various ways without departing from the gist thereof.

The present invention is applied to an apparatus and method for diagnosing Parkinson's disease by diagnosing Parkinson's disease by classifying only the image containing the Nigrosome 1 region in MRI and analyzing the Nigrosome 1 region in the classified image.

10: Parkinson's disease diagnosis device
20: image acquisition unit
21: MRI equipment
30: image processing unit
40: image analysis unit
50: diagnostic unit

Claims (3)

A first step of acquiring a multi-echo magnitude and phase image from an MRI of an image acquisition unit imaging a patient's brain;
A second step in which the image processing unit post-processes to observe only the black matter and the nigrosome 1 region presented as an image biomarker of Parkinson's disease in the acquired image;
A third step in which the image analysis unit analyzes the post-processed image to classify an image containing the nigrosome 1 region, and detects the nigrosome 1 region from the classified image; And
A fourth step of determining whether or not the patient has Parkinson's disease, wherein the image analysis unit provides information on the detected region of the nigrosome 1 to the diagnosis unit; Method for providing information for diagnosing Parkinson's disease, including.
According to claim 1,
In the second step, the image processing unit,
A method of providing information for diagnosing Parkinson's disease, characterized in that a quantitative susceptibility map mask is applied to the image obtained in the first step using a quantitative susceptibility mapping algorithm to post-process through susceptibility map weighted imaging.
According to claim 1,
In the third step, the image analysis unit,
Through machine learning, an image containing a region containing a region of nigrosome 1 and an image not containing a region among all MRIs are classified, and a location of the region of nigrosome 1 is designated in the image containing the classified region of nigrosome 1 to generate the nigro. A method of providing information for diagnosing Parkinson's disease, characterized by detecting a region 1.

Images