CN103854284B - Based on graphics search serous pigmentary epithelial pull-up from retina dividing method - Google Patents
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Abstract
本发明公开了一种基于三维图搜索浆液性色素上皮层脱离的视网膜分割方法,包括:(1)基于视网膜上界面分割的块速B扫描图像对齐方法;(2)按分界面显著程度顺序、以已分割界面为约束条件的多分辨率图搜分割方法;(3)用不同的约束条件进行图搜算法得到有隆起区域的色素上皮层下界面和平滑的视网膜底部分界面的方法;(4)基于色素上皮层下界面和视网膜底部分界面位置差别,并结合区域大小和亮度信息的浆液性色素上皮层脱离的分割方法;(5)将图像平坦化后进行外层视网膜层次分割和校正的方法。本发明分割结果具有较高的准确性,能够替代手动分割,对于临床相关眼科疾病的诊断与治疗能起到重要的辅助作用。
The invention discloses a retinal segmentation method for searching for serous pigment epithelial layer detachment based on a three-dimensional image, including: (1) a block-speed B-scan image alignment method based on interface segmentation on the retina; A multi-resolution image search segmentation method with the segmented interface as a constraint; (3) A method of image search algorithm with different constraints to obtain the lower interface of the pigment epithelium with raised areas and the smooth sub-retinal interface; (4) Segmentation method of serous pigment epithelial layer detachment based on the position difference between the lower interface of the pigment epithelium and the interface of the bottom part of the retina, combined with the area size and brightness information; (5) The method of segmenting and correcting the outer retinal layer after flattening the image . The segmentation result of the invention has high accuracy, can replace manual segmentation, and can play an important auxiliary role in the diagnosis and treatment of clinically relevant ophthalmic diseases.
Description
技术领域technical field
本发明属于视网膜图像分割方法,尤其是对SD-OCT(频域光学相干断层成像)的视网膜图像中的组织层次和病变区域的分割方法。The invention belongs to a method for segmenting retinal images, in particular to a method for segmenting tissue levels and lesion regions in retinal images of SD-OCT (frequency-domain optical coherence tomography).
背景技术Background technique
视网膜是脑部神经组织的延伸,具有复杂的多层次组织结构。SD-OCT技术已经成为无损评估视网膜疾病的一种强有力的工具,它能提供快速的、高分辨率的、显示视网膜内部分层的三维图像,为临床眼科医生对疾病的诊断和治疗提供了帮助。视网膜OCT图像的分割对临床实践具有重要意义:病变区域的分割及对其形状、大小、位置的定量分析对疾病诊断和治疗有关键作用;视网膜组织层次的分割及对各类组织形态、亮度的定量分析对于发现早期病变、观测病程和研究病理都起到重要作用。然而目前大部分眼科医生采用手动方式对OCT显示的视网膜病变进行定量分析,主观性强,无法保证准确性和一致性,而且难以全面分析三维扫描带来的大量数据。The retina is an extension of the neural tissue of the brain and has a complex multi-layered organizational structure. SD-OCT technology has become a powerful tool for non-destructive evaluation of retinal diseases. It can provide fast, high-resolution, three-dimensional images showing the internal layers of the retina, and provide clinical ophthalmologists with a great tool for diagnosis and treatment of diseases. help. The segmentation of retinal OCT images is of great significance to clinical practice: the segmentation of lesion areas and the quantitative analysis of their shape, size, and location play a key role in the diagnosis and treatment of diseases; the segmentation of retinal tissue levels and the analysis of various tissue shapes and brightness Quantitative analysis plays an important role in discovering early lesions, observing disease course and studying pathology. However, at present, most ophthalmologists use manual methods to conduct quantitative analysis of retinopathy displayed by OCT, which is highly subjective, cannot guarantee accuracy and consistency, and is difficult to comprehensively analyze the large amount of data brought by 3D scanning.
目前的视网膜OCT图像自动分割算法存在以下的缺陷:(1)大部分算法都是二维算法,即在每个切片图像(x-z平面图像,称为B扫描图像)中独立进行分割,这类方法没有充分利用三维的上下文信息,较容易受到图像噪声或伪影的影响,导致分割错误。(2)大部分已有的视网膜组织层次分割算法都是针对正常视网膜设计的,当视网膜组织由于病变产生较大的形变时,这些算法将失效。The current automatic retinal OCT image segmentation algorithm has the following defects: (1) Most of the algorithms are two-dimensional algorithms, that is, they are segmented independently in each slice image (x-z plane image, called B-scan image). The three-dimensional context information is not fully utilized, and it is more susceptible to image noise or artifacts, resulting in segmentation errors. (2) Most of the existing retinal tissue hierarchical segmentation algorithms are designed for the normal retina, and these algorithms will fail when the retinal tissue is greatly deformed due to lesions.
浆液性色素上皮层脱离可能由多种脉络膜/视网膜疾病引起,如年龄相关性黄斑变性、息肉状脉络膜血管病变、中心性浆液性脉络膜视网膜病变、葡萄膜炎等。目前为止,还没有针对浆液性色素上皮层脱离的视网膜OCT图像中所有可分辨的组织层次及病变区域的系统的三维自动分割方法的相关报道。Serous pigment epithelial detachment may be caused by a variety of choroidal/retinal diseases, such as age-related macular degeneration, polypoidal choroidal vasculopathy, central serous chorioretinopathy, uveitis, etc. So far, there is no report on a systematic three-dimensional automatic segmentation method for all resolvable tissue layers and lesion regions in retinal OCT images of serous pigment epithelial detachment.
发明内容Contents of the invention
本发明提供了一种解决上述问题的方案,首次提供了一种具有可行性和有效性的针对浆液性色素上皮层脱离的视网膜OCT图像中所有可分辨的组织层次及病变区域的系统的三维自动分割方法。其中组织层次包括10层:神经纤维层(NFL)、神经节细胞层(GCL)、内丛状层(IPL)、内核层(INL)、外丛状层(OPL)、外核层(ONL)+内节层(ISL)、连接纤毛(CL),外节层(OSL)、维尔赫夫膜(VM)、色素上皮层(RPE),共有11各分界面。再加上由于色素上皮层和视网膜底部脱离,视网膜底部形成一个单独的界面,因此本发明共可检测12个分界面。The present invention provides a solution to the above problems. For the first time, it provides a feasible and effective three-dimensional automatic system for all resolvable tissue layers and lesion areas in retinal OCT images of serous pigment epithelial detachment. split method. The organizational hierarchy includes 10 layers: nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) +Inner segment layer (ISL), connecting cilia (CL), outer segment layer (OSL), Verhoff membrane (VM), pigment epithelium (RPE), a total of 11 interfaces. In addition, due to the detachment of the pigment epithelium and the retinal base, the retinal base forms a separate interface, so the present invention can detect 12 interfaces in total.
本发明提供了一种基于三维图搜索浆液性色素上皮层脱离的视网膜分割方法,该方法主要包括5个步骤:The present invention provides a retinal segmentation method for searching for serous pigment epithelial detachment based on a three-dimensional image. The method mainly includes five steps:
步骤S01,图像预处理:主要进行OCT去噪和B扫描图像间的对齐;Step S01, image preprocessing: mainly perform OCT denoising and alignment between B-scan images;
步骤S02,内层视网膜各层次的分割:采用多分辨率图搜算法,依据分界面对比度从高到低的顺序依次分割,得到神经纤维层(NFL)、神经节细胞层(GCL)、内丛状层(IPL)、内核层(INL)、外丛状层(OPL),外核层(ONL)+内节层(ISL)的分界面;Step S02, segmentation of each layer of the inner retina: using a multi-resolution image search algorithm, sequentially segmenting according to the order of interface contrast from high to low, to obtain the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexus Inner layer (IPL), inner core layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) + inner segmental layer (ISL) interface;
步骤S03,色素上皮层分割及视网膜底部估计:在外层视网膜区域,用不同的约束条件进行图搜算法得到有隆起区域的色素上皮层下界面和平滑的视网膜底部分界面;Step S03, segmentation of the pigment epithelium and estimation of the retinal base: in the outer retinal area, use different constraints to perform a graph search algorithm to obtain the lower interface of the pigment epithelium with raised areas and the smooth interface of the retinal base;
步骤S04,色素上皮层脱离区域分割:色素上皮层下界面和平滑的视网膜底部分界面之间的区域为色素上皮层脱离区域,并根据区域大小或亮度信息去除误检区域;Step S04, segmentation of the pigment epithelium detachment area: the area between the lower interface of the pigment epithelium and the smooth sub-retinal interface is the detachment area of the pigment epithelium, and the false detection area is removed according to the size of the area or the brightness information;
步骤S05,外层视网膜各层次的分割:根据色素上皮层下界面将图像平坦化后用图搜算法检测外层视网膜各层次,得到连接纤毛(CL),外节层(OSL)、维尔赫夫膜(VM)、色素上皮层(RPE)之间分界面。Step S05, segmentation of each layer of the outer retina: flatten the image according to the lower interface of the pigment epithelium, and then use the image search algorithm to detect each layer of the outer retina, and obtain connecting cilia (CL), outer segment layer (OSL), Verhoff The interface between membrane (VM) and pigment epithelium (RPE).
上述5个步骤具体描述如下,The above five steps are described in detail as follows:
(1)图像预处理(1) Image preprocessing
图像预处理主要包括以下两个步骤:去噪和B扫描图像对齐。Image preprocessing mainly includes the following two steps: denoising and B-scan image alignment.
(a)OCT图像去噪(a) OCT image denoising
OCT眼部成像仪获取的三维图像含有较多的散斑噪声。为保证后续分割的效果,必须在有效去除噪声的同时尽可能保留图像中的边缘信息。本发明采用一种快速双边滤波器对每个B扫描图像进行去噪。双边滤波结果为:The 3D images obtained by the OCT eye imager contain more speckle noise. In order to ensure the effect of subsequent segmentation, the edge information in the image must be preserved as much as possible while effectively removing noise. The present invention uses a fast bilateral filter to denoise each B-scan image. The result of bilateral filtering is:
其中 in
这里p为当前处理的像素点,q为p的邻域S中的像素点,Ip和Iq分别为p和q的灰度值,为滤波结果的灰度值,为归一化系数,和是标准差分别为σs和σr的高斯函数,σs和σr这两个参数分别根据图像尺寸大小和边缘对比度大小进行取值。Here p is the currently processed pixel, q is the pixel in the neighborhood S of p, I p and I q are the gray values of p and q respectively, is the gray value of the filtering result, is the normalization coefficient, and It is a Gaussian function whose standard deviation is σ s and σ r respectively, and the two parameters of σ s and σ r are valued according to the image size and edge contrast respectively.
(b)B扫描图像对齐(b) B-scan image alignment
成像过程中眼部的运动可造成连续B扫描图像中视网膜位置上下波动,即图像在切片方向(y-方向)上不连续。这会给三维分割造成困难。本发明基于对视网膜上界面的分割结果进行B扫描图像对齐,因为这个界面在所有层次分界面中对比度最高,即使在错位的图像上也能正确分割。用多分辨率图搜算法分割的过程如下:对去噪后的三维图像在竖直方向(z-方向)上进行下采样使该方向像素点个数变为一半,重复一次该过程,得到三个不同分辨率的图像,按分辨率从低到高表示为尺度1、2、3。分割首先在最低分辨率的尺度1上进行,在所得结果的基础上,在尺度2上附近区域内进行进一步的精确分割,依次类推,最终得到原图像上的分割结果。分割过程为寻找代价最小的分割面的过程,由图搜算法完成。神经纤维层上界面的代价函数用索贝尔算子计算得到,在由暗到亮的边缘位置代价函数较小。为了与内外层分界面即连接纤毛上界面相区别,在尺度1上,代价函数加入了另一个分量,该分量为各图像点上方若干像素点的亮度之和。这样,由于神经纤维层上界面上方为较暗的背景区域,它对应的代价就小于连接纤毛上界面位置的代价,能够被正确检测。神经纤维层上界面分割完成后,在每张B扫描图像上计算其平均高度,即平均z值。计算过程中排除图像中间位置的点,因为这些点受中央凹或病变的影响有较大的位移。根据每张B扫描中得到的神经纤维层上界面平均高度上移或下移该图像,使得结果中神经纤维层上界面平均高度为一常数,就起到了对齐各图像的作用The movement of the eye during the imaging process can cause the position of the retina to fluctuate up and down in the continuous B-scan image, that is, the image is discontinuous in the slice direction (y-direction). This can cause difficulties in 3D segmentation. The present invention is based on the B-scan image alignment of the segmentation results of the supraretinal interface, because this interface has the highest contrast among all layered interfaces, and can be correctly segmented even on misaligned images. The process of segmentation using the multi-resolution image search algorithm is as follows: the denoised 3D image is down-sampled in the vertical direction (z-direction) so that the number of pixels in this direction is reduced to half, and the process is repeated once to obtain three Images with different resolutions are expressed as scales 1, 2, and 3 from low to high resolution. Segmentation is first performed on scale 1 of the lowest resolution, and based on the obtained results, further accurate segmentation is performed in the vicinity of scale 2, and so on, and finally the segmentation result on the original image is obtained. The segmentation process is the process of finding the segmentation plane with the least cost, which is completed by the graph search algorithm. The cost function of the interface on the nerve fiber layer is calculated by the Sobel operator, and the cost function is smaller at the edge position from dark to bright. In order to distinguish it from the interface between the inner and outer layers, that is, the upper interface connecting the cilia, on scale 1, another component is added to the cost function, which is the sum of the brightness of several pixels above each image point. In this way, since the upper interface of the nerve fiber layer is a darker background area, its corresponding cost is less than the cost of connecting the position of the interface on the cilium, and can be correctly detected. After the upper interface segmentation of the nerve fiber layer is completed, its average height, that is, the average z value, is calculated on each B-scan image. Points in the middle of the image are excluded from the calculation because these points have a large displacement due to the fovea or lesion. Move the image up or down according to the average height of the upper interface of the nerve fiber layer obtained in each B-scan, so that the average height of the upper interface of the nerve fiber layer in the result is a constant, which plays a role in aligning the images
(2)内层视网膜各层次的分割(2) Segmentation of each layer of the inner retina
内层视网膜受病变的影响较小,因此先进行分割。其分割方法为与步骤(1)中类似的多分辨率图搜方法。首先检测连接纤毛上界面,即内外层的分界面作为约束条件。分割在神经纤维层上界面下方的子图中进行,由于病变导致视网膜内积液,视网膜外层的部分组织在OCT图像中不显影,因此检测出的内外层分界面实际为连接纤毛上界面和色素上皮层下表面合并而成的,将之定义为连接纤毛色素上皮层合并界面。然后,按照各分界面边缘对比度顺序,以分割出的界面为约束条件,分割神经节细胞层(GCL)、内丛状层(IPL)、内核层(INL)、外丛状层(OPL),外核层(ONL)+内节层(ISL)的分界面。边界对比度较低的界面可能在低尺度上无法有效分割,因此需从较高的分辨率开始分割。为消除噪声的影响,对得到的结果在x方向上进行均值滤波,以得到平滑的分割界面。The inner retina is less affected by the lesion, so it is segmented first. The segmentation method is a multi-resolution image search method similar to that in step (1). First, the upper interface connecting the cilia, that is, the interface between the inner and outer layers is detected as a constraint. Segmentation is carried out in the sub-image below the upper interface of the nerve fiber layer. Because the lesion causes fluid in the retina, some tissues of the outer layer of the retina are not visualized in the OCT image, so the detected interface between the inner and outer layers is actually connecting the upper interface of cilia and The lower surface of the pigment epithelium was merged, which was defined as the merged interface connecting the ciliated pigment epithelium. Then, according to the order of the edge contrast of each interface, using the segmented interface as a constraint, segment the ganglion cell layer (GCL), inner plexiform layer (IPL), inner inner layer (INL), outer plexiform layer (OPL), The interface of the outer nuclear layer (ONL) + inner segmental layer (ISL). Interfaces with low border contrast may not be segmentable at low scales, so start segmentation at a higher resolution. In order to eliminate the influence of noise, mean filtering is performed on the obtained results in the x direction to obtain a smooth segmentation interface.
(3)色素上皮层分割及视网膜底部估计(3) Pigment epithelium segmentation and retinal base estimation
在浆液性色素上皮层脱离的视网膜OCT图像中,色素上皮层在脱离区域呈光滑的隆起,在前后B扫描图像中的变化较大。而下方为较暗的积液区域,其底部界面可能不显影。本发明在基于图搜算法检测这两个界面时,采用相同的代价函数和不同的界面平滑度约束条件。当平滑度约束参数较大时,,一般当平滑度约束参数取5~10时,分割结果为有局部隆起的色素上皮层下界面。当参数取值较小时,平滑度约束参数取1~4,时,分割结果为平滑的视网膜底部分界面。In retinal OCT images of serous pigment epithelial detachment, the pigment epithelium appears as a smooth bulge in the detachment area, with large changes in the anterior and posterior B-scan images. Below is a darker area of effusion, the bottom interface of which may not be visualized. The present invention uses the same cost function and different interface smoothness constraint conditions when detecting the two interfaces based on the graph search algorithm. When the smoothness constraint parameter is large, generally when the smoothness constraint parameter is 5-10, the segmentation result is the lower interface of the pigment epithelium with local bulges. When the value of the parameter is small and the smoothness constraint parameter is 1-4, the segmentation result is a smooth retinal bottom part interface.
(4)脱离区域分割(4) Breakaway region segmentation
步骤(3)分割得到的色素上皮层下界面和视网膜底部分界面之间的区域为色素上皮层脱离区域。但由于噪声的影响导致界面分割局部的误差,可能会出现误检的情况。首先将色素上皮层下界面和视网膜底部分界面之间的所有像素点构成若干个三维连通区域,分别计算这些区域的体积和平均亮度。当体积小于某一预定值或平均亮度大于某一预定值时,认为这个区域是误检的脱离区域予以去除。The area between the lower interface of the pigment epithelium and the interface at the bottom of the retina obtained from the segmentation in step (3) is the detachment area of the pigment epithelium. However, due to the influence of noise, local errors in interface segmentation may occur, and false detection may occur. First, all the pixel points between the lower interface of the pigment epithelium and the lower interface of the retina form several three-dimensional connected areas, and the volume and average brightness of these areas are calculated respectively. When the volume is smaller than a certain predetermined value or the average brightness is greater than a certain predetermined value, this region is considered to be a falsely detected detachment region and removed.
在得到三维的脱离区域的同时,也能够得到脱离区域在x-y方向上的二维分布图。这将用于下一步中对外层视网膜分割结果的校正。While obtaining the three-dimensional detachment area, a two-dimensional distribution diagram of the detachment area in the x-y direction can also be obtained. This will be used for the correction of the outer retinal segmentation results in the next step.
(5)外层视网膜各层次的分割(5) Segmentation of each layer of the outer retina
外层视网膜各组织在正常视网膜中呈较平坦的形状。当存在色素上皮层脱离时,这些组织也随着色素上皮层的隆起而隆起,而且在隆起区域上方可能不显影,因此在OCT图像中,这些组织不连续,因此必须加上一定的约束条件以保证分割的正确性。本发明中,基于色素上皮层下界面分割的结果,将视网膜图像平坦化,即将图像中各列上下移动,使得色素上皮层下界面变为一个平面。这样就将色素上皮层隆起部分恢复成平坦的形状,也就能近似恢复外层视网膜在正常情况下的平坦形状。在平坦化之后的图像上,首先基于步骤(2)中分割得到的连接纤毛色素上皮层合并界面,根据步骤(4)结果,在色素上皮层脱离区域用二阶多项式进行插值校正以得到连接纤毛上界面。然后用图搜算法分割外节层(OSL)、维尔赫夫膜(VM)、色素上皮层(RPE)的界面,对外节层(OSL)、维尔赫夫膜(VM)的分界面,在色素上皮层脱离区域也需用二阶多项式进行插值校正。将本步骤中得到的连接纤毛(CL)、外节层(OSL)、维尔赫夫膜(VM)、色素上皮层(RPE)的分界面重新映射回原图像上得到最终分割结果。The tissues of the outer retina have a relatively flat shape in the normal retina. When there is detachment of the pigment epithelium, these tissues also rise with the uplift of the pigment epithelium, and may not be developed above the raised area, so in the OCT image, these tissues are discontinuous, so certain constraints must be added to Ensure the correctness of segmentation. In the present invention, based on the segmentation result of the lower interface of the pigment epithelium, the retinal image is flattened, that is, each column in the image is moved up and down, so that the lower interface of the pigment epithelium becomes a plane. This restores the raised part of the pigment epithelium to a flat shape, which approximates the normal flat shape of the outer retina. On the image after flattening, firstly, based on the merging interface of the connecting cilium pigment epithelium obtained in step (2), according to the result of step (4), the second-order polynomial is used for interpolation correction in the detachment area of the pigment epithelium to obtain the connecting cilium upper interface. Then use the graph search algorithm to segment the interface of the outer segment layer (OSL), Verhoff's membrane (VM), and pigment epithelium (RPE), and the interface between the outer segment layer (OSL) and Verhoff's membrane (VM). Regions of epithelial detachment were also corrected for by interpolation using a second-order polynomial. Remap the interface connecting cilia (CL), outer segment layer (OSL), Verhoff membrane (VM), and pigment epithelium (RPE) obtained in this step back to the original image to obtain the final segmentation result.
本发明融合了双边滤波去噪、B扫描对齐、三维图割技术、连通区域分割、图像平坦化、分割结果校正等步骤,分割结果具有较高的准确性,能够替代手动分割,对于临床相关眼科疾病的诊断与治疗能起到重要的辅助作用。The invention integrates steps such as bilateral filter denoising, B-scan alignment, three-dimensional graph cutting technology, connected region segmentation, image flattening, and segmentation result correction. The segmentation result has high accuracy and can replace manual segmentation. Disease diagnosis and treatment can play an important auxiliary role.
附图说明Description of drawings
图1为本发明结构示意图;Fig. 1 is a structural representation of the present invention;
图2为视网膜组织层次图像,图2(a)为原B扫描图像,图2(b)为正常视网膜的10层组织和11个分界面;Figure 2 is an image of the retinal tissue hierarchy, Figure 2(a) is the original B-scan image, and Figure 2(b) is the 10-layer tissue and 11 interfaces of the normal retina;
图3为双边滤波器去噪结果,图3(a)为原图像,图3(b)为去噪后图像;Figure 3 is the denoising result of the bilateral filter, Figure 3(a) is the original image, and Figure 3(b) is the image after denoising;
图4为B扫描对齐结果x-y平面图,图4(a)原图像,图4(b)对齐后图像;Figure 4 is the x-y plane view of the B-scan alignment result, Figure 4(a) the original image, and Figure 4(b) the aligned image;
图5为连接纤毛(CL)、外节层(OSL)、维尔赫夫膜(VM)、色素上皮层(RPE)的界面分割结果,图5(a)为色素上皮层下界面和视网膜底部分界面分割结果,图5(b)为根据色素上皮层下界面平坦化后的图像,图5(c)为在图5(b)中对界面7-10的分割结果,图5(d)为映射回原图像后连接纤毛(CL)、外节层(OSL)、维尔赫夫膜(VM)、色素上皮层(RPE)的界面的结果(其中维尔赫夫膜(VM)、色素上皮层(RPE)的界面在此图像中基本重叠);Figure 5 shows the interface segmentation results of connecting cilia (CL), outer segment layer (OSL), Verhoff's membrane (VM), and pigment epithelium (RPE). Figure 5(a) shows the lower interface of the pigment epithelium and the bottom part of the retina The results of interface segmentation, Figure 5(b) is the image after flattening the interface under the pigment epithelium, Figure 5(c) is the segmentation result of interface 7-10 in Figure 5(b), and Figure 5(d) is After mapping back to the original image, the results of the interface connecting cilia (CL), outer segment layer (OSL), Verhoff’s membrane (VM), and pigment epithelium (RPE) (wherein Verhoff’s membrane (VM), pigment epithelium ( RPE) interfaces substantially overlap in this image);
图6为浆液性色素上皮脱离OCT图像分割结果,图6(a)为分层结果的二维显示,自上至下为12个分界面,图6(b)为神经纤维层上界面、连接纤毛上界面、色素上皮层下界面、视网膜底部分界面分割结果的三维显示,图6(c)为脱离区域分割的二维显示,图6(d)为脱离区域分割的三维显示。Figure 6 is the OCT image segmentation results of serous pigment epithelium detachment, Figure 6(a) is a two-dimensional display of the layered results, with 12 interfaces from top to bottom, and Figure 6(b) is the upper interface and connections of the nerve fiber layer The three-dimensional display of the segmentation results of the upper interface of the cilia, the lower interface of the pigment epithelium, and the interface at the bottom of the retina. Figure 6(c) is a two-dimensional display of the detachment area segmentation, and Figure 6(d) is a three-dimensional display of the detachment area segmentation.
图2中,附图标记如下,1神经纤维层(NFL)、2神经节细胞层(GCL)、3内丛状层(IPL)、4内核层(INL)、5外丛状层(OPL)、6外核层(ONL)+内节层(ISL)、7连接纤毛(CL),8外节层(OSL)、9维尔赫夫膜(VM)、10色素上皮层(RPE)。In Fig. 2, the reference signs are as follows, 1 nerve fiber layer (NFL), 2 ganglion cell layer (GCL), 3 inner plexiform layer (IPL), 4 inner inner plexiform layer (INL), 5 outer plexiform layer (OPL) , 6 outer nuclear layer (ONL) + inner segment layer (ISL), 7 connecting cilia (CL), 8 outer segment layer (OSL), 9 Verhoff membrane (VM), 10 pigment epithelium (RPE).
具体实施方式detailed description
下面结合具体实施方式,进一步阐述本发明。The present invention will be further described below in combination with specific embodiments.
参见图1所示,本方法主要包括5个步骤:图像预处理、内层视网膜各层次的分割、色素上皮层分割及视网膜底部估计、脱离区域分割、外层视网膜各层次的分割。As shown in Figure 1, this method mainly includes five steps: image preprocessing, segmentation of each layer of the inner retina, segmentation of the pigment epithelium and estimation of the retinal base, segmentation of the detachment region, and segmentation of each layer of the outer retina.
如图2所示,视网膜组织层次包括10层:神经纤维层(NFL)1、神经节细胞层(GCL)2、内丛状层(IPL)3、内核层(INL)4、外丛状层(OPL)5、外核层(ONL)+内节层(ISL)6、连接纤毛(CL)7,外节层(OSL)8、维尔赫夫膜(VM)9、色素上皮层(RPE)10,共有11个分界面。As shown in Figure 2, the retinal tissue hierarchy includes 10 layers: nerve fiber layer (NFL) 1, ganglion cell layer (GCL) 2, inner plexiform layer (IPL) 3, inner inner layer (INL) 4, outer plexiform layer (OPL) 5, outer nuclear layer (ONL) + inner segment layer (ISL) 6, connecting cilia (CL) 7, outer segment layer (OSL) 8, Verhoff membrane (VM) 9, pigment epithelium (RPE) 10. There are 11 interfaces in total.
本发明一种基于三维图搜索浆液性色素上皮层脱离的视网膜分割方法,具体描述如下,The present invention is a retinal segmentation method based on a three-dimensional map search for serous pigment epithelial layer detachment, specifically described as follows,
(1)图像预处理(1) Image preprocessing
图像预处理主要包括以下两个步骤:去噪和B扫描图像对齐。Image preprocessing mainly includes the following two steps: denoising and B-scan image alignment.
(a)OCT图像去噪(a) OCT image denoising
OCT眼部成像仪获取的三维图像含有较多的散斑噪声。为保证后续分割的效果,必须在有效去除噪声的同时尽可能保留图像中的边缘信息。本发明采用一种快速双边滤波器对每个B扫描图像进行去噪。双边滤波结果为:The 3D images obtained by the OCT eye imager contain more speckle noise. In order to ensure the effect of subsequent segmentation, the edge information in the image must be preserved as much as possible while effectively removing noise. The present invention uses a fast bilateral filter to denoise each B-scan image. The result of bilateral filtering is:
其中 in
这里p为当前处理的像素点,q为p的邻域S中的像素点。Ip和Iq分别为p和q的灰度值。为滤波结果的灰度值,为归一化系数。和是标准差分别为σs和σr的高斯函数。σs和σr这两个参数分别根据图像尺寸大小和边缘对比度大小进行取值。去噪结果如图3所示。Here p is the currently processed pixel, and q is the pixel in the neighborhood S of p. I p and I q are the gray values of p and q, respectively. is the gray value of the filtering result, is the normalization coefficient. and are Gaussian functions with standard deviations σ s and σ r respectively. The two parameters σ s and σ r take values according to the image size and edge contrast respectively. The denoising results are shown in Figure 3.
(b)B扫描图像对齐(b) B-scan image alignment
成像过程中眼部的运动可造成连续B扫描图像中视网膜位置上下波动,即图像在切片方向(y-方向)上不连续。这会给三维分割造成困难。本发明基于对神经纤维层1上界面,即视网膜上界面的分割结果进行B扫描图像对齐,因为这个界面在所有层次分界面中对比度最高,即使在错位的图像上也能正确分割。用多分辨率图搜算法分割神经纤维层1上界面的过程如下:对去噪后的三维图像在竖直方向(z-方向)上进行下采样使该方向像素点个数变为一半,重复一次该过程,得到三个不同分辨率的图像,按分辨率从低到高表示为尺度1、尺度2和尺度3。分割首先在最低分辨率的尺度1上进行,在所得结果的基础上,在尺度2上附近区域内进行进一步的精确分割,依次类推,最终得到原图像上的分割结果。The movement of the eye during the imaging process can cause the position of the retina to fluctuate up and down in the continuous B-scan image, that is, the image is discontinuous in the slice direction (y-direction). This can cause difficulties in 3D segmentation. The present invention is based on B-scan image alignment of the segmentation results of the upper interface of the nerve fiber layer 1, that is, the upper interface of the retina, because this interface has the highest contrast among all layer interfaces, and can be correctly segmented even on misplaced images. The process of segmenting the upper interface of the nerve fiber layer 1 with the multi-resolution image search algorithm is as follows: the denoised three-dimensional image is down-sampled in the vertical direction (z-direction) so that the number of pixels in this direction becomes half, repeat Once this process is performed, three images with different resolutions are obtained, which are represented as scale 1, scale 2, and scale 3 in order of resolution from low to high. Segmentation is first performed on scale 1 of the lowest resolution, and based on the obtained results, further accurate segmentation is performed in the vicinity of scale 2, and so on, and finally the segmentation result on the original image is obtained.
分割过程为寻找代价最小的分割面的过程,由图搜算法完成。神经纤维层1上界面的代价函数用索贝尔算子计算得到,在由暗到亮的边缘位置代价函数较小。为了与内外层分界面即连接纤毛7上界面相区别,在尺度1上,代价函数加入了另一个分量,该分量为各图像点上方若干像素点的亮度之和。这样,由于神经纤维层1上界面上方为较暗的背景区域,它对应的代价就小于连接纤毛7上界面位置的代价,能够被正确检测。神经纤维层1上界面分割完成后,在每张B扫描图像上计算其平均高度,即平均z值。计算过程中排除图像中间位置的点,因为这些点受中央凹或病变的影响有较大的位移。根据每张B扫描中得到的神经纤维层1上界面平均高度上移或下移该图像,使得结果中神经纤维层1上界面平均高度为一常数,就起到了对齐各图像的作用。对齐后的图像效果可以从x-y方向看出,如图4所示。The segmentation process is the process of finding the segmentation plane with the least cost, which is completed by the graph search algorithm. The cost function of the upper interface of the nerve fiber layer 1 is calculated by the Sobel operator, and the cost function is smaller at the edge from dark to bright. In order to distinguish it from the interface between the inner and outer layers, that is, the upper interface connecting cilia 7, on scale 1, another component is added to the cost function, which is the sum of the brightness of several pixel points above each image point. In this way, since there is a darker background area above the upper interface of the nerve fiber layer 1, its corresponding cost is less than the cost of connecting the position of the upper interface of the cilium 7, and can be correctly detected. After the segmentation of the upper interface of the nerve fiber layer 1 is completed, its average height, that is, the average z value, is calculated on each B-scan image. Points in the middle of the image are excluded from the calculation because these points have a large displacement due to the fovea or lesion. According to the average height of the upper interface of the nerve fiber layer 1 obtained in each B-scan, the image is moved up or down, so that the average height of the upper interface of the nerve fiber layer 1 in the result is a constant, which plays a role in aligning the images. The image effect after alignment can be seen from the x-y direction, as shown in Figure 4.
(2)内层视网膜各层次的分割(2) Segmentation of each layer of the inner retina
内层视网膜受病变的影响较小,因此先进行分割。其分割方法为与步骤(1)中类似的多分辨率图搜方法。The inner retina is less affected by the lesion, so it is segmented first. The segmentation method is a multi-resolution image search method similar to that in step (1).
首先检测连接纤毛7上界面,即内外层的分界面作为约束条件。分割在神经纤维层1上界面下方的子图中进行,由于病变导致视网膜内积液,视网膜外层的部分组织在OCT图像中不显影,因此检测出的内外层分界面实际为连接纤毛7上界面和色素上皮层10上分界面合并而成的,将之定义为连接纤毛色素上皮层合并界面。First, the upper interface connecting the cilia 7, that is, the interface between the inner and outer layers is detected as a constraint condition. Segmentation is carried out in the sub-image below the upper interface of the nerve fiber layer 1. Because the lesion causes fluid accumulation in the retina, some tissues of the outer layer of the retina are not visualized in the OCT image, so the interface detected between the inner and outer layers is actually connected to the cilia 7 The interface formed by merging with the interface on the pigment epithelium 10 is defined as the merging interface connecting the ciliated pigment epithelium.
然后,按照各分界面边缘对比度顺序,以分割出的界面为约束条件,分割神经节细胞层(GCL)2、内丛状层(IPL)3、内核层(INL)4、外丛状层(OPL)5,外核层(ONL)+内节层(ISL)6的界面。边界对比度较低的界面可能在低尺度上无法有效分割,因此需从较高的分辨率开始分割。具体分割顺序、上下约束面、对应的边界变化及多分辨率分割的起始尺度如表1所示。为消除噪声的影响,对得到的结果在x方向上进行均值滤波,以得到平滑的分割界面。Then, according to the order of the edge contrast of each interface, with the segmented interface as a constraint condition, the ganglion cell layer (GCL) 2, inner plexiform layer (IPL) 3, inner inner plexiform layer (INL) 4, outer plexiform layer ( OPL)5, the interface of outer nuclear layer (ONL) + inner segment layer (ISL)6. Interfaces with low border contrast may not be segmentable at low scales, so start segmentation at a higher resolution. The specific segmentation sequence, upper and lower constraint surfaces, corresponding boundary changes, and the starting scale of multi-resolution segmentation are shown in Table 1. In order to eliminate the influence of noise, mean filtering is performed on the obtained results in the x direction to obtain a smooth segmentation interface.
(3)色素上皮层分割及视网膜底部估计(3) Pigment epithelium segmentation and retinal base estimation
在浆液性色素上皮层脱离的视网膜OCT图像中,色素上皮层在脱离区域呈光滑的隆起,在前后B扫描图像中的变化较大。而下方为较暗的积液区域,其底部界面可能不显影。本发明在基于图搜算法检测这两个界面时,采用相同的代价函数和不同的界面平滑度约束条件。当平滑度约束参数取5~10时,分割结果为有局部隆起的色素上皮层下界面。当平滑度约束参数取1~4时时,分割结果为平滑的视网膜底部分界面。In retinal OCT images of serous pigment epithelial detachment, the pigment epithelium appears as a smooth bulge in the detachment area, with large changes in the anterior and posterior B-scan images. Below is a darker area of effusion, the bottom interface of which may not be visualized. The present invention uses the same cost function and different interface smoothness constraint conditions when detecting the two interfaces based on the graph search algorithm. When the smoothness constraint parameter is 5-10, the segmentation result is the lower interface of the pigment epithelium with local uplift. When the smoothness constraint parameter is 1 to 4, the segmentation result is a smooth retinal bottom part interface.
(4)脱离区域分割(4) Breakaway area segmentation
步骤(3)分割得到的色素上皮层10下界面和视网膜底部分界面之间的区域为色素上皮层脱离区域。但由于噪声的影响导致界面分割局部的误差,可能会出现误检的情况。首先将色素上皮层10下界面和视网膜底部分界面之间的所有像素点构成若干个三维连通区域,分别计算这些区域的体积和平均亮度。当体积小于某一预定值或平均亮度大于某一预定值时,认为这个区域是误检的脱离区域予以去除。The area between the lower interface of the pigment epithelium layer 10 and the interface at the bottom of the retina obtained by the segmentation in step (3) is the area of pigment epithelial layer detachment. However, due to the influence of noise, local errors in interface segmentation may occur, and false detection may occur. First, all the pixels between the lower interface of the pigment epithelium 10 and the interface at the bottom of the retina form several three-dimensional connected areas, and the volume and average brightness of these areas are calculated respectively. When the volume is smaller than a certain predetermined value or the average brightness is greater than a certain predetermined value, this region is considered to be a falsely detected detachment region and removed.
在得到三维的脱离区域的同时,也能够得到脱离区域在x-y方向上的二维分布图。这将用于下一步中对外层视网膜分割结果的校正。While obtaining the three-dimensional detachment area, a two-dimensional distribution diagram of the detachment area in the x-y direction can also be obtained. This will be used for the correction of the outer retinal segmentation results in the next step.
(5)外层视网膜各层次的分割(5) Segmentation of each layer of the outer retina
外层视网膜各组织在正常视网膜中呈较平坦的形状。当存在色素上皮层脱离时,这些组织也随着色素上皮层的隆起而隆起,而且在隆起区域上方可能不显影,因此在OCT图像中,这些组织不连续,因此必须加上一定的约束条件以保证分割的正确性。The tissues of the outer retina have a relatively flat shape in the normal retina. When there is detachment of the pigment epithelium, these tissues also rise with the uplift of the pigment epithelium, and may not be developed above the raised area, so in the OCT image, these tissues are discontinuous, so certain constraints must be added to Ensure the correctness of segmentation.
本发明中,基于色素上皮层10下界面分割的结果,将视网膜图像平坦化,即将图像中各列上下移动,使得色素上皮层10下界面变为一个平面。这样就将色素上皮层隆起部分恢复成平坦的形状,也就能近似恢复外层视网膜在正常情况下的平坦形状。在平坦化之后的图像上,首先基于步骤(2)中分割得到的连接纤毛色素上皮层合并界面,In the present invention, based on the segmentation result of the lower interface of the pigment epithelium 10, the retinal image is flattened, that is, each column in the image is moved up and down, so that the lower interface of the pigment epithelium 10 becomes a plane. This restores the raised part of the pigment epithelium to a flat shape, which approximates the normal flat shape of the outer retina. On the image after flattening, firstly, based on the merging interface of connecting ciliated pigment epithelium obtained in step (2),
根据步骤(4)结果,在色素上皮层脱离区域用二阶多项式进行插值校正以得到连接纤毛7上界面。然后用图搜算法分割外节层(OSL)8、维尔赫夫膜(VM)9、色素上皮层(RPE)10的分界面,分割顺序和约束条件等同样见表1。对分割外节层(OSL)8、维尔赫夫膜(VM)9的分界面,在色素上皮层脱离区域也需用二阶多项式进行插值校正。将本步骤中得到的连接纤毛(CL)7、外节层(OSL)8、维尔赫夫膜(VM)9、色素上皮层(RPE)10的界面重新映射回原图像上得到最终分割结果。According to the result of step (4), the second-order polynomial is used for interpolation correction in the detachment area of the pigment epithelium to obtain the upper interface of the connecting cilium 7 . Then, the graph search algorithm was used to segment the interfaces of the outer segment layer (OSL)8, Verhoff's membrane (VM)9, and pigment epithelium (RPE)10. The segmentation sequence and constraints are also shown in Table 1. For the interface that separates the outer segment layer (OSL)8 and Verhoff's membrane (VM)9, the second-order polynomial should also be used for interpolation correction in the detachment area of the pigment epithelium. Remap the interface of connecting cilia (CL)7, outer segment layer (OSL)8, Verhoff membrane (VM)9, and pigment epithelium (RPE)10 obtained in this step back to the original image to obtain the final segmentation result.
本步骤结果如图5所示。The result of this step is shown in Figure 5.
表1视网膜各层次分界面分割方法Table 1 Segmentation method of each layer of retina
(6)实验结果(6) Experimental results
部分实验结果如图6所示。Some experimental results are shown in Figure 6.
对层次分割,以两个专家独立手动分割结果的平均值为金标准。自动分割结果和金标准分割界面z值之差的绝对值为分割误差。两个专家分割结果z值之差的绝对值代表观察者间差异。在20个样本上的实验结果显示,本发明分割平均误差为2.25±0.96像素(7.87±3.36微米),与观察者间差异2.23±0.73像素(7.81±2.56微米)相比,无明显统计差异,可认为基本相同。因此本方法能够替代手动分割方法。For hierarchical segmentation, the average of the results of two independent manual segmentations by two experts was used as the gold standard. The absolute value of the difference between the automatic segmentation result and the z value of the gold standard segmentation interface is the segmentation error. The absolute value of the difference between the z-scores of the two expert segmentation results represents the inter-observer difference. The experimental results on 20 samples show that the average segmentation error of the present invention is 2.25 ± 0.96 pixels (7.87 ± 3.36 microns), compared with the inter-observer difference of 2.23 ± 0.73 pixels (7.81 ± 2.56 microns), there is no significant statistical difference, can be considered basically the same. Therefore, this method can replace the manual segmentation method.
对色素上皮层脱离区域分割,以一个专家手动分割结果作为金标准,采用真阳性率TPVF和假阳性率FPVF作为评估方法的客观指标,计算如下:For the segmentation of pigment epithelial layer detachment, an expert's manual segmentation result was used as the gold standard, and the true positive rate TPVF and false positive rate FPVF were used as the objective indicators of the evaluation method, calculated as follows:
其中|·|表示体积,CTP表示真阳性点集,CFP表示假阳性点集,CGT表示金标准中脱离区域点集,V表示整个视网膜区域所有像素点集合。实验结果表明,本方法平均真阳性率为87.9%,平均假阳性率为0.36%。Where |·| represents the volume, C TP represents the true positive point set, C FP represents the false positive point set, C GT represents the detachment area point set in the gold standard, and V represents the set of all pixels in the entire retinal region. The experimental results show that the average true positive rate of this method is 87.9%, and the average false positive rate is 0.36%.
至此,一种适用于浆液性色素上皮层脱离的视网膜SD-OCT图像的自动分割方法已经实现并进行了验证。本发明融合了双边滤波去噪、B扫描对齐、三维图割技术、连通区域分割、图像平坦化、分割结果校正等步骤,分割结果具有较高的准确性,能够替代手动分割,对于临床相关眼科疾病的诊断与治疗能起到重要的辅助作用。So far, an automatic segmentation method for retinal SD-OCT images of serous pigment epithelial detachment has been implemented and validated. The invention integrates steps such as bilateral filter denoising, B-scan alignment, three-dimensional graph cutting technology, connected region segmentation, image flattening, and segmentation result correction. The segmentation result has high accuracy and can replace manual segmentation. Disease diagnosis and treatment can play an important auxiliary role.
以上描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的只是说明本发明的原理,在不脱离本发明精神和范围的前提下,本发明还会有各种变化和改进,这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。The basic principles, main features and advantages of the present invention have been described above. Those skilled in the industry should understand that the present invention is not limited by the above-mentioned embodiments, and what described in the above-mentioned embodiments and the description only illustrates the principles of the present invention, and the present invention will also have other functions without departing from the spirit and scope of the present invention. Variations and improvements are possible, which fall within the scope of the claimed invention. The protection scope of the present invention is defined by the appended claims and their equivalents.
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