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Automatic Histogram Specification for Glioma Grading Using Multicenter Data

Automatic Histogram Specification for Glioma Grading Using Multicenter Data Hindawi Journal of Healthcare Engineering Volume 2019, Article ID 9414937, 12 pages https://doi.org/10.1155/2019/9414937 Research Article Automatic Histogram Specification for Glioma Grading Using Multicenter Data 1,2 3 2 3 2 4 Xi Chen, Yaping Wu, Guohua Zhao, Meiyun Wang , Wenyi Gao, Qian Zhang, 1,2 and Yusong Lin School of Software, Zhengzhou University, Zhengzhou, Henan 450002, China Collaborative Innovation Center for Internet Healthcare, Zhengzhou University, Zhengzhou, Henan 450052, China Department of Radiology, Henan Provincial People’s Hospital, Zhengzhou, Henan 450003, China School of Computer Science, Zhongyuan University of Technology, Zhengzhou 450000, China Correspondence should be addressed to Yusong Lin; yslin@ha.edu.cn Received 22 July 2019; Revised 6 November 2019; Accepted 23 November 2019; Published 19 December 2019 Academic Editor: Emiliano Schena Copyright©2019XiChenetal.)isisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Multicenter sharing is an effective method to increase the data size for glioma research, but the data inconsistency among different institutions hindered the efficiency. )is paper proposes a histogram specification with automatic selection of reference frames for magnetic resonance images to alleviate this problem (HSASR). )e selection of reference frames is automatically performed by an optimized grid search strategy with coarse and fine search. )e search range is firstly narrowed by coarse search of intraglioma samples, and then the suitable reference frame in histogram is selected by fine search within the sample selected by coarse search. Validation experiments are conducted on two datasets GliomaHPPH2018 and BraTS2017 to perform glioma grading. )e results demonstrate the high performance of the proposed method. On the mixed dataset, the average AUC, accuracy, sensitivity, and specificity are 0.9786, 94.13%, 94.64%, and 93.00%, respectively. It is about 15% higher on all indicators compared with those without HSASR and has a slight advantage over the result of a manually selected reference frame by radiologists. Results show that our methods can effectively alleviate multicenter data inconsistencies and lift the performance of the prediction model. accurately display the location and size, and it correlates well 1. Introduction with histological characteristics. In medical research, high quality data is difficult to obtain in a single institution, so it Glioma is a prevalent fatal brain disease and the most malignant, which accounts for approximately 24.7% of all needs to be shared through multicenter. However, the primary brain and other central nervous system tumors and difference of multicentre data is a serious challenge. 74.6% of malignant tumors [1]. )e World Health Orga- In the acquisitionof multicenter gliomaMRI data,due to nization’s guidelines for glioma diagnosis and treatment are differences in acquisition equipment and parameters result divided into four levels, namely, I–II and III–IV for low- significant differences in data samples in terms of specifi- grade glioma (LGG) and high-grade glioma (HGG) [2]. In cation, size, contrast, and brightness. Differences among the clinical applications, biological behavior, treatment options, data lead to deviations in the grading effect of glioma [4]. and prognoses of patients with glioma of different grades are Figure 1 shows the differences among multicenter data. clearly different. )erefore, the accurate preoperation Figure 1(a) shows that some of the data contain skulls and grading of Glioma is important. Magnetic Resonance Im- the others do not contain. Figure 1(b) shows that these data aging (MRI) is characterized by multidirectional tomogra- have different scales and number of slices. A previous study phy and multiparameter high-resolution soft-tissue imaging indicated that pixel size and slice thickness remarkably affect and is widely used to evaluate the tumor heterogeneity [3]. space and strength characteristics of the calculation [5, 6]. MRI is commonly used in glioma grading because it can )erefore, voxel size must be unified to reduce the error in 2 Journal of Healthcare Engineering )e main contributions of this study are as follows: (1) )is paper proposes a histogram specification with automatic selection of reference frames (HSASR). (a) )is method can automatically select the suitable reference frame of histogram instead of radiologists during image enhancement, so as to enhance the consistency of brain tumors image contrast. (2) )is paper proposes a set of image standardization (b) algorithms to make the preprocessed multicenter data have better consistency, improve the adapt- 512 × 512 × 18 320 × 320 × 18 240 × 240 × 155 ability of data, and improve the accuracy of the glioma prediction model. 2. Related Works C1 C2 C3 (c) In recent years, researchers have gradually adopted multi- center data to replace single institution in clinical medical research. However, multicenter data also faced many C4 C5 C6 challenges. Berenguer et al. [14] carried out a test-retest phantom study of individual image acquisition parameters. Figure 1: Multicenter data. (a) Space of dataset is uneven. (b) )e impact of image parameters on the image cannot be Volume pixel of data element is not uniform. (c) Dataset contrast analyzed because of the difference of the model or machine brightness is not uniform, and C1–C6 are randomly selected data manufacturer. )erefore, variations because of the use of samples. images were eliminated by exclusively scanning phantoms. In addition, Hugo et al. [15] indicated that multicenter structure MRI studies have stronger statistical efficacy than calculating characteristics. Figure 1(c) presents six images with different contrasts. )ese differences are due to de- single-institution studies. However, central differences in viation in acquisition equipment and parameters. contrast sensitivity and spatial uniformity lead to differences In order to alleviate the inconsistency of contrast of in tissue classification or image registration that may reduce multicenter data, it is necessary to enhance the image data or completely offset the enhanced statistical efficacy of appropriately. Histogram correction is a commonly used multicenter data. )erefore, maintaining data in a standard technique in image enhancement [7]. Among them, histo- environment is important. Nyul et al. [16] mentioned some gram equalization (HE) and normalization techniques [8, 9] problems in the original MRI scale preprocessing method are often used to adjust the overall brightness of images. )is and attempted to use the median value and other percentile type of methods mainly expands the range of gray value in numerical methods, such as landmark, to solve these the histogram without adjusting its intensity. )ese methods problems; they obtained robust results after preprocessing. )e validity of the standardized new landmark was also only enhance the overall image and improve its brightness, but the contrast between tumors and other tissues is not mentioned in the study, after which the image brightness considerably enhanced [10, 11]. Histogram specification level and contrast consistency were significantly improved. (HS) can change the frequency of grayscale values and Bakas et al. [17, 18] focused on the data preprocessing enhance any local brightness [12, 13], but it mainly adjusts method, which has a certain enlightening effect on the the local brightness according to the reference frame. In preprocessing method of this study. general, the reference frame is selected by a radiologist. In preprocessing, contrast enhancement of multicenter However, this process consumes a considerable amount of data image is an important challenge. It was shown that a time and the final reference frame may not be the best high-contrast medical image could lead to a better in- choice. )erefore, it is an urgent problem to automatically terpretation of the different adjacent tissues in the imaged search for the best reference frame of histogram instead of body part [19, 20]. Accordingly, the resulting enhanced searching by a radiologist. image, which is in terms of signal intensities of different )is paper presents a histogram specification with au- tissues, can facilitate the automated segmentation, feature tomatic selection of reference frames for magnetic resonance extraction, and classification of these tissues. Existing image images, called HSASR, specifically used to replace radiolo- enhancement techniques (empirical or heuristic) are re- gists manually selecting reference frames. )is method can markably related to a particular image and usually aimed at enhance the consistency of tumor intensity in the whole improving image contrast. However, no unified standard is medical image. In this work, we apply HSASR to the pre- available to measure the quality effect of image enhancement processing of multicenter glioma data, and the effectiveness [21–24]. of this method is proved by Glioma grading experiment. )e Image enhancement can be divided into two categories: results showed that this method had certain practical value spatial domain method and frequency domain method. in glioma grading research. Image enhancement in spatial domain usually corrects Journal of Healthcare Engineering 3 histogram. Histogram equalization is a commonly used N (1) P (l) � , ∀l ∈ L, global grayscale image enhancement technique, and the grayscale value is uniformly redistributed based on the where N � H × W and N is the number of pixels with a gray cumulative density function of the histogram [25]. However, level. )e cumulative distribution function (CDF) of P is equalization fails to consider the intensity of the grayscale r presented as follows: value. )e average brightness of the image can make the x x regions with large original intensity fade, whereas dark areas N s (x) � 􏽘 P (j) � 􏽘 , ∀x ∈ L. (2) r r will brighten after image equalization. Sengee et al. [26] j�0 j�0 suggested an extension method of BBHE based on the neighbourhood metric. )is method involved a few steps: Similarly, if the specified reference image is z, then the first, a large histogram was divided into the subregion using gray cumulative distribution function is the neighbourhood metric and process independently. )is method results in boundary noise and possibly uneven v (y) � 􏽘 P (i) � 􏽘 , ∀y ∈ L, (3) z z histogram brightness in two parts. In addition, MedGA [24] M i�0 i�0 wasan enhancementmethodthatHEcombinedwithgenetic algorithm to directly improve the histogram frequency of where Mand N arethe numberofpixelswith graylevel L.HS attempts to obtain transformation function y � F(x) and images and has achieved obvious results. However, this method could only be limited to the presence of two maps gray level x in the original image to gray level y, such that the transformed image can have a histogram similar to grayscale regional tissues and not enhance complex brain tumors. the reference histogram. To preserve the inherent in- formation of the original image, function F should be a monotonically increasing function. )is function can be 3. Materials and Methods obtained by using the following equation: 3.1. Data Collection. Glioma data used in the study were v (y) � s (x). (4) z r obtained from two separate sources, BraTS2017 and Glio- )erefore, the gray level of the map can be obtained by maHPPH2018 datasets. )e BraTS2017 dataset came from a variety of scanning instruments from 19 medical in- using stitutions. BraTS2017 dataset includes 210 HGG data and 75 − 1 (5) y � v 􏼂s (x)􏼃, z r LGG data; the data was already segmented when it was − 1 acquired. GliomaHPPH2018 dataset was obtained from where v is the inverse of v . multiple equipment of different models from multiple In the discrete case, the inverse function usually does not manufacturers, including 4 Siemens equipment (1 1.5t exist. )e inverse function is usually replaced by the best equipment, 3 3T equipment) and 4GE equipment (2 1.5t objective function to approximate the y of a particular gray equipment, 2 3T equipment), as shown in Table 1. )e level x as follows: 􏼌 􏼌 magnetic resonance data collected on these devices are 􏼌 􏼌 􏼌 􏼌 y � argmin 􏼌 s (x) − v (k)􏼌. r z (6) different from each other. After data inspection, there are up to 186 default inspection protocols for the devices, and Equation (6) represents the absolute value of the dif- contrast-enhanced T1-weighted imaging (CET1) was used in ference between the original image’s cumulative histogram this study, including 35 CET1 sequences (see Table 2), layer and gray level functions of the specified reference histogram, thickness of 5mm to 6.5mm, repetition time of 220– and then the minimum value is selected as the y value. With 1970ms, echo time of 2.46–28.60ms, and resolution of this transformation rule, each gray level x can be mapped to 256 ×256 ×18, 320 ×290 ×18, 320 ×320 ×18, 384 ×384 ×18, y. )erefore, the mapped image will be similar to the desired 448 ×408 ×18, and 512 ×512 ×18. )e GliomaHPPH2018 histogram. dataset includes 161HGG data and 77 LGG data. A three- )e reference frame in the histogram is usually selected dimensional region of interest (ROI) for all the tumors in by the doctor. However, the selected reference image may GliomaHPPH2018 was depicted by two senior radiologists not be suitable, thereby consuming a considerable amount of in Henan provincial people’s hospital. )e ROIs were seg- the radiologist’s time. To solve this problem, an optimized mented slice-by-slice on the axial plane using the CET1 grid search strategy with coarse and fine search is proposed sequences. After discussion between the two radiologists, the to select the suitable reference frame automatically. final decision is made to select the optimal segmentation file. 3.3. HSASR. In this study, an improved grid search method 3.2. Histogram Specification. HS, an effective image en- is proposed to solve the problem of selecting a specified hancement technique, is an extension of histogram equal- reference image. )e grid search is generally used to divide ization that can effectively alleviate the problems of grids of the same length in a certain spatial range based on histogram equalization. Let r � 􏽮r 􏽯be an H × W discrete ij the proposed coordinate system. Each coordinate point input digital image with L gray levels, and let L �{0, 1, . . ., represents a parameter, and these searched parameters are L − 1}. )e histogram or gray level probability density of an calculated and analysed based on the step size. Finally, image is defined as follows: 4 Journal of Healthcare Engineering Table 1: GliomaHPPH2018MR acquisition equipment list. Number Manufacturer Model Magnetic field strength Amount 1 GE OPTIMA MR360 1.5T 1 2 GE Signa HDxt 1.5T 1 3 GE DISCOVERY MR750 3T 2 4 SIEMENS Sempra 1.5T 1 5 SIEMENS Prisma 3T 1 6 SIEMENS TrioTim 3T 1 7 SIEMENS Verio 3T 1 Note: amount is for number of machines. Table 2: CET1 sequence collection parameter statistics. Number Manufacturer Magnetic field Model D-spacing Layer thickness Resolution Voxel size 1 GE 1.5 OPTIMA MR360 6.5 5.5 512 ×512 ×18 0.4688\0.4688 2 GE 1.5 OPTIMA MR360 7 6 512 ×512 ×18 0.4688\0.4688 3 GE 1.5 OPTIMA MR360 7.5 6 256 ×256 ×18 0.9375\0.9375 4 GE 1.5 OPTIMA MR360 7.5 6 512 ×512 ×18 0.4688\0.4688 5 GE 1.5 OPTIMA MR360 8 6 512 ×512 ×18 0.4688\0.4688 6 GE 1.5 Signa HDxt 7 6 512 ×512 ×18 0.4688\0.4688 7 GE 1.5 Signa HDxt 7 6 512 ×512 ×18 0.5273\0.5273 8 GE 1.5 Signa HDxt 7.5 6 512 ×512 ×18 0.4688\0.4688 9 GE 1.5 Signa HDxt 7.5 6.5 512 ×512 ×18 0.4688\0.4688 10 GE 1.5 Signa HDxt 8 6 512 ×512 ×18 0.4688\0.4688 11 GE 3 DISCOVERY MR750 6.5 5 512 ×512 ×18 0.4688\0.4688 12 GE 3 DISCOVERY MR750 7 6 512 ×512 ×18 0.4688\0.4688 13 GE 3 DISCOVERY MR750 7.5 6 512 ×512 ×18 0.4688\0.4688 14 SIEMENS 1.5 Sempra 7.2 6 448 ×408 ×18 0.5134\0.5134 15 SIEMENS 3 Prisma 7.2 6 320 ×320 ×18 0.7188\0.7188 16 SIEMENS 3 Prisma 7.2 6 384 ×384 ×18 0.5989\0.5989 17 SIEMENS 3 Prisma 7.8 6 320 ×320 ×18 0.7188\0.7188 18 SIEMENS 3 TrioTim 6.6 6 320 ×320 ×18 0.7188\0.7188 19 SIEMENS 3 TrioTim 6.6 6 320 ×320 ×18 0.75\0.75 20 SIEMENS 3 TrioTim 7.2 6 256 ×256 ×18 0.8984\0.8984 21 SIEMENS 3 TrioTim 7.2 6 256 ×256 ×18 0.9375\0.9375 22 SIEMENS 3 TrioTim 7.2 6 320 ×290 ×18 0.7188\0.7188 23 SIEMENS 3 TrioTim 7.2 6 320 ×320 ×18 0.7188\0.7188 24 SIEMENS 3 TrioTim 7.2 6 320 ×320 ×18 0.75\0.75 optimal parameters are considered the output. Given that randomly selected for histogram specification (the this method must traverse all the corresponding points in same sample is selected each time), and then the the grid, many unnecessary invalid calculations are gener- performance of data after histogram specification is tested. ated, resulting in an exponential increase in time. To reduce time consumption, this study improves the (3) Select the sets of all the best area under the curve directional grid optimization search based on data charac- (AUC) values according to threshold Tand perform teristics. On the basis of the characteristics of glioma itself, the next fine search. the method is improved by using coarse segmentation and (4) Fine search: in the optimal cluster, the search is subdivision. Horizontal and vertical searches are used for initiated from the middle section (two pointers are coarse segmentation and subdivision, respectively. )e set to point to the middle section), and pointer 1 specific steps of the improved method are as follows: searches upward successively. If reference frames (1) )e number of clusters N and the number of slices K do not contain tumors, then the search is stopped. of each tumor are determined. Each cluster is set to i, If the difference between the current and previous and the initialization step size is K/2. A 2D grid is values is greater than T, then the search is stopped, established by using N and K, and the grid nodes are and the optimal value is selected. At the same time, the corresponding reference slices of N and K. similar to the previous step, pointer 2 is searched downward. (2) In the coarse search, each time it searched by step size from the beginning of each set(horizontally), the (5) )e optimal reference slice map is the final output. If median slice in each cluster was selected as the multiple optimal values exist, then selection is made reference frame. )en, 30% of data in all datasets are based on accuracy and specificity indicators. If Journal of Healthcare Engineering 5 (i) Input: Mixed dataset F, data sample number N, number of each sample slice K (ii) Output: Optimal reference slice F (1) Step1: Coarse search (2) Function HSBM (n, F1, l )//Histogram specification based on brain MRI (3) { (4) F1 �Random (range (0, N), F∗30%)//Random selection of 30% of dataset (5) For each n ∈ F do (6) For each n1 ∈ F1 do (7) cdf � hist · cumsum( ) F F 1 n1 n (8) cdf � hist · cumsum( ) F F n n k/2 min (9) Calculate: hist � arg |(cdf /shape(F )) − ((cdf /shape(F ))(m))| F n Fn1 n1 n k/2 k/2 (10) End for (11) Calculate: Auc(n ) � roc auc score(Lable − Lable ) K/2 original predict (12) End for (13) } (14) F2 � Sort max(Auc ) k/2 (15) F2 �Max(F2) (16) For each c ∈ F2 do (17) if |F2 − Auc(c)|≤ T then (18) Select c ⟶ F3 (19) end (20) End for (21) Select the optimal set F3 (22) Step 2 Fine search (23) Initializes Pointers l , l 1 2 (24) For each n ∈ F3//Search both ends (25) l � k/2 (26) For l ≤ kandexit(tumor ); l + +do 1 l ++ 1 (27) HSBM (n, F1, l ) (28) End for (29) End for (30) For each n ∈ F3 (31) l � k/2 (32) For l ≤ kandexit(tumor ); l + +do 2 l ++ 2 (33) HSBM (n, F1, l ) (34) End for (35) End for (36) Output: select the first optimal slice F ALGORITHM 1: HSASR algorithm pseudocode description. several optimal reference frames existed, then the 3.4. Experiments. Figure 3 shows the overall process of first optimal reference frame is selected as the final multicenter data grading prediction. First, data are im- reference frame. ported, data preprocessing is performed, features are extracted by using the feature calculation method, features Algorithm 1 describes the HSASR algorithm. )e pa- are selected, and model training is finally conducted. rameter T in Step 1 prevents the collection of additional Contribution points of this study are in the preprocessing optimal values from being missed. )e T in Step 2 saves stage. )e HSASR method proposed is the most important search time. Figure 2 presents the 2D diagram of the im- part of preprocessing. proved optimization grid search. In this study, N represents the number of data samples, K denotes the number of slices of each sample, and K/2 is the middle slice of the sample. 3.5. Preprocessing. Storage formats of multicenter data are First, a horizontal coarse search is performed. )e pale blue often inconsistent. Data formats of this study include NIfTI circles indicate the performance values of intermediate slices and DICOM format files. )erefore, to standardize multi- in each cluster. )e optimal clusters are selected for lon- center data formats, this study adopts the format conversion gitudinal fine search, the middle slice is considered the initial method based on the Convert3D tool to unify all data sample value, and both ends are searched simultaneously. )e formats into the NIfTI format. )e majority of patients in vertical circles and dark blue squares represent the perfor- the GliomaHPPH2018 dataset have 18 DICOM files with mance values in the optimal set and the selected final ref- CET1 sequence, and a small number of patients have 36 files. erence frame, respectively. After format conversion, all slices of each patient’s CET1 6 Journal of Healthcare Engineering k/2 Intermediate slice as reference Optimal slice as reference Single sample slice as reference Figure 2: Diagram of the optimized grid search (note: k/2 represents the middle slice of the cluster). Multicenter standardization Feature engineering Feature calculation Feature selection Grading prediction Preprocessing Raw data BraTS2017 Feature Set1 Format conversion Feature selection diagram PCA Brain tissues extraction Pyradiomics Feature Set2 Feature samples Resampling x x GliomaHPPH2018 Selection feature Predictive analysis Figure 3: Flowchart of multicenter data grading prediction. sequence are converted into the NIfTI format file, thereby In addition, spatial consistency of the data image is maintained.Multiple voxelrangesoccur inboth datasets.On providing convenience in subsequently unifying data processing. the basis of Convert3D, we adopt the shortest distance in- Furthermore, to unify the multicenter data in pre- terpolation resampling technology to carry out scale processing, maintaining the consistency of brain tissue resampling in each data sample. )e size of each data sample structureis alsoimportant.)e GliomaHPPH2018 datasetin is unified to 240 ×240 ×155, and the label sample is also this study contained skull images, which are removed at the converted into a file of the same size. In addition, the dis- time of acquisitionin the BraTS2017dataset. )issituation is tance between unified slices is 1mm, and the original po- not only a certain impact on HS but also introduced diffi- sition was [0, − 239, 0]. culties in combining the two datasets due to the gap between To solve the problem of inconsistent brightness and them. In this study, the FSL tool is firstly used in location contrast of multicenter data, this paper proposes a histogram registration, and then the skulls are removed based on the specification withautomatic selection ofreferenceframes for bet script. In this study, 238 data skulls are removed, and magnetic resonance images. On the basis of the character- brain tissues and regions of interest are relatively intact. istics of glioma itself, this paper puts forward an optimized Journal of Healthcare Engineering 7 MRI without HSASR MRI with HSASR L1 L2 L3 L1 L2 L3 L4 L5 L6 L4 L5 L6 H1 H2 H3 H1 H2 H3 H4 H5 H6 H4 H5 H6 Figure 4: MRI comparison map before and after HSASR. Table 3: Results of the first three glioma grading experiments. Without HSASR With HSASR Training Testing AUC ACC (%) SEN (%) SPE (%) AUC ACC (%) SEN (%) SPE (%) GH BT 0.6850 59.93 58.45 64.00 0.9507 90.88 90.18 82.67 BT GH 0.7605 72.68 81.98 53.25 0.9146 85.90 89.87 77.63 (80%) (GH+BT)+(20%) 0.8252 78.17 85.42 61.67 0.9786 94.13 94.64 93.00 (GH+BT) (80%)GH+(20%)GH 0.8394 81.25 82.06 76.32 0.9556 89.36 87.20 94.71 (80%)BT+(20%)BT 0.8512 79.12 80.19 74.99 0.9934 95.61 97.35 92.65 Note: GH is for GliomaHPPH2018, and BTstands for BraTS2017. BTrepresents 80% of the data as training and 20% as testing. GH alone represents 80% of GH data as training and 20% of GH as testing. BT alone represents 80% of BT dataset as training and 20% of BT as testing. grid search strategy with coarse and fine search. First, in search, the step size is changed to 1, data are searched from coarse search, all data samples are selected as the object of the middle number upward and downward, and the search is reference selection in this study. Each file is considered a over according to the end condition. collection, and the step size is set to the middle number of the collection (78), starting from the beginning of every collection each time. )e middle slice (78) of each collection 3.6. Feature Engineering. All the data being processed are imported into feature calculation. For each region of in- is used as the reference slice of HS, 30% of image samples are randomly selected from all data, and image enhancement is terest, 557 radiomics features are calculated through Pyr- adiomics (Pyradiomics is a tool for the computational carried out via HS and subsequently imported into the model verification process of this study. T is set to 1%, and characteristics of medical images). In this study, 9 spatial geometric features are included, which are only calculated in the set with the highest AUC value and AUC value error less the original space. Eighteen first-order statistical features than 1% is selected. Furthermore, the study carries out fine 8 Journal of Healthcare Engineering Receiver operating characteristic curve Receiver operating characteristic curve 1.0 1.0 0.8 0.8 0.6 0.6 0.4 0.4 0.2 0.2 0.0 0.0 0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0 False positive rate False positive rate Train ROC AUC = 0.98571 Train ROC AUC = 0.95225 Test ROC AUC = 0.91456 Test ROC AUC = 0.95073 (a) (b) Figure 5: ROC plot. Table 4: Results of the contrast experiment. Training Testing Method AUC ACC (%) SEN (%) SPE (%) (80%) (GH+BT)+(20%) (GH+BT) HE 0.9176 86.19 90.44 76.05 (80%) (GH+BT)+(20%) (GH+BT) Handpicked 0.9447 89.90 90.35 88.88 (80%) (GH+BT)+(20%) (GH+BT) Our method 0.9786 94.13 94.64 93.00 Note: GH is for GliomaHPPH2018, and BT is for BraTS2017. GH+BT represents 80% of the data as training and 20% as testing. and 43 texture features are calculated in the original data and 3.7. Experimental Comparison Designs. To verify the effec- eight wavelet decomposition spaces, respectively. For all tiveness of processed multicenter data, this study proposed image histological features, model training is conducted the following process designs: directly after the processing of missing values. (1) Take the processed GliomaHPPH2018 and )e calculated features are imported into the model BraTS2017 datasets as the training and testing sets, scriptof this studyfor prediction.)e modelscript isdivided respectively. )en, use the two unpreprocessed into two parts, namely, feature selection and classifier. Five datasets as contrast experiments. selection methods and nine classifiers are combined to set up (2) Mix together 521 data samples from Glio- the classifier, and the training and testing sets are imported maHPPH2018 and BraTS2017, preprocess the data, into the model for prediction. For the designs of experiment carry out feature selection and model training, and 2 and 3 in the next section, 80% and 20% of data are selected analyze the results. from the data table as training and testing sets, respectively. )e prediction is then repeated 10 times. )e average value (3) Use single sequences from the processed and un- of final results is obtained, and the classifier and selection processed GliomaHPPH2018 and BraTS2017 as methods with the best results are finally selected with the comparison experiment. rating device. )e selection methods used in the study are (4) Make comparisonexperiments between this research SelectKBest (f_classif) for classifying the tag features be- method and common image enhancement methods tween tasks for ANOVA f values, principal component on the mixed dataset. Finally, compare these results analysis (PCA), kernel principal component analysis with the untreated data. In addition, to verify the (KPCA), independent component correlation algorithm effectiveness of HSASR, compare the research results (ICA), and factor analysis (FA). )e classifiers used in this with the reference diagram results selected by study are decision tree (DT), random forest (RF), bagging radiologists. (BAG), binary search tree (BSA), naive Bayes (NB), mul- tilayer perception (MLP), support vector machine (SVM), 4. Results and Discussion logistic (LR), and k-nearest neighbour (KNN). For the two separate datasets in experiment 1, the stable training model 4.1. Analysis of Image Enhancement. )e purpose of weak- is selected by using a tenfold cross-validation scheme, and ening the multicenter data is to relieve the differences between then the grading prediction is finally performed. groups and retain individual characteristics. )at is to say, True positive rate True positive rate Journal of Healthcare Engineering 9 Table 5: Performance comparison with similar works. Author and reference Architecture/method Output class Data Maximum ACC (%) Khawaldeh et al. [27] AlexNet+Preprocessing 3 130 91.16 Chen et al. [28] CAD+Preprocessing 2 274 91.27 Our method HSASR 2 523 94.13 80 80 22 9 2 26 60 15 3 58 73 LGG HGG LGG HGG Predicted lable Predicted lable (a) (b) Figure 6: Confusion matrix of mixed dataset. 0.84 0.83 0.77 0.82 FILT 0.72 0.82 0.82 0.81 0.77 0.79 0.80 PCA 0.81 0.81 0.71 0.83 0.77 0.78 0.69 0.8 0.8 0.76 KPCA 0.67 0.78 0.76 0.81 0.81 0.73 0.84 0.74 0.81 0.72 ICA 0.69 0.8 0.79 0.82 0.69 0.79 0.76 0.75 0.8 FA 0.79 0.79 0.81 0.72 0.81 0.69 0.83 0.76 0.8 0.68 DT RF BAG BST NB MLP SVM LR KNN Classifier Figure 7: Heat map without HSASR. Feature reduction True lable HGG LGG True lable HGG LGG AUC score 10 Journal of Healthcare Engineering FILT 0.9 0.97 0.97 0.97 0.95 0.98 0.98 0.96 0.97 0.96 0.85 0.94 0.9 0.98 0.95 0.97 PCA 0.96 0.97 0.95 0.93 0.87 0.96 0.93 0.97 0.97 0.96 0.97 KPCA 0.94 0.96 0.90 ICA 0.84 0.96 0.95 0.96 0.9 0.97 0.97 0.96 0.96 0.87 FA 0.85 0.95 0.94 0.96 0.88 0.97 0.96 0.97 0.95 0.84 DT RF BAG BST NB MLP SVM LR KNN Classifier Figure 8: Heat map with HSASR. Experiment 1 in Table 3 presents the results of Glio- under the premise of retaining tumor morphological char- acteristics,theimagedataofdifferentmedicalinstitutionshave maHPPH2018and BraTS2017 datasets as the training and similar contrast and brightness. In this study, contrast and testing set, respectively. )e results show that the data with brightness of multicenter glioma data images are significantly HSASR is better predicted, and the indexes are significantly improved after image enhancement in preprocessing. Figure 4 improved compared with the unprocessed data, as shown in shows the MRI results of the CET1 sequence in 12 patients. Figure 5. Figure 5(a) shows the ROC curve in which )eleft-handsideofFigure4presents thatthe firstandsecond BraTS2017 is a training set and GliomaHPPH2018 is a rows are LGG without HSASR, and the third and fourth rows testing set, and Figure 5(b) shows the ROC curve in which are HGG without HSASR. All processed glioma data are the testing set and the training set interchange. It can be shown on the right side of the figure. )e examples show on observed from the figure that when testing set and training the left and right sides had a one-to-one correspondence. set swap, the better results can also be obtained. )e results show that the data processed by the HRASR method have From the perspective of image, the range of contrast and brightness of data without HSASR in Figure 4 are relatively good adaptability and can alleviate the difference among complex and the tumor area is fuzzy and difficult to distin- multicenter data images. guish. )e data after HSASR are consistent in contrast and Experiment 2 in Table 3 presents the results of the mixed brightness, the tumor area is significantly enhanced, and basic dataset. )e calculated characteristics are imported into the features (tumor morphology and lesion range) of the original proposed grading model for 10 iterations of random pre- image can be retained. diction, and the average value is subsequently obtained. Finally, the model with the best average performance is selected as the final model. )e results show that AUC after 4.2. Performance of Glioma Grading. )ispaperaimstoreflect processing generally increased by more than 15%, and other the effectiveness of these methods indirectly by using model indicators also improve significantly. Experiment 3 in Ta- prediction indicators. To validate the effect of the processed ble 3 shows that the data processed by HSASR on a single multicenterdatafurther,thissectionconductstheverificationof dataset also achieve a good grading effect. grading results based on the following indicators: AUC, ac- Experiment 4 in Table 4 shows the comparison exper- curacy (ACC), sensitivity (SEN), and specificity (SPE). iment conducted by three different methods on the mixed Feature reduction AUC score Journal of Healthcare Engineering 11 Coarse search 0.980 Fine search 0.98 0.978 0.96 0.976 0.94 0.92 0.974 0.90 0.972 0.88 0.970 0.86 6(78) 12(78) 18(78) 24(78) 30(78) 36(78) 42(78) 48(78) 69(10) 71(10) 73(10) 75(10) 77(10) 79(10) 81(10) N K (a) (b) Figure 9: Diagram of the proposed method (note: the red circle and blue square represent the AUC of machine and manually selected reference images, respectively. )e black square represents optimal reference frame). dataset. )ese methods include the HE method, reference Figure 9 illustrates the experimental results of the grid frame method of manual selection by radiologists, and the search in this study. In this study, five reference slices with the method proposed in this paper. )e results show that highest performance indexes were selected from two datasets via rough search, and the reference slices with the best per- compared withthe othertwo methods, the methodproposed in this paper significantly improves the grading effect of formance were screened out. )e N axis, K, circle, and square denoted the number of samples, the number of slices in each glioma. )e reference frame selected by radiologists based on experience shows significant improvement in glioma sampleset,the valueof AUCof thereferenceimageselectedby grading, but it can be seen from the results that the per- the HSASR, and the predicted performance value of the formance of the selected reference frame is worser than that reference image selected by the doctor, respectively. )e ob- of the automatically selected. tained performance of the reference frame selected by the Table 5 gives the performance comparison of similar method is both low and high, indicating that the difference in work in the references using glioma dataset. In [27], after reference objects had a significant impact on the result of data preprocessing, they used a modified version of AlexNet grading. )e proposed method can replace radiologists in for classifying MR brain images into three classes like choosing the best reference frame and save a considerable amount of time. Hence, the proposed method has certain healthy brain, LGG, and HGG. However, the amount of data of this work is so small that cannot verify the robustness of application value in clinical trials. the proposed method. Reference [28] also involved data preprocessing, but our data is twice as large, and the result 5. Conclusions verified by the grading model is better than this method. Figure 6 is the confusion matrix corresponding to the Inconsistencies among data prevent multicenter data from final model of mixed glioma data in experiment 2, and playing to its shared advantage. )is paper proposes a LGG and HGG represent the low-level label and high-level histogram specification method with automatic selection of label, respectively. Figure 6(a) shows the confusion matrix reference frames for magnetic resonance images to alleviate before processing, and Figure 6(b) shows the predicted the problem of contrast inconsistencies among multicenter data distribution after processing. Figure 6 shows a sig- data. )e core of histogram specification is to change the nificant decrease in the number of glioma predicted in- local brightness of the image according to the reference correctly after preprocessing. Meanwhile, in order to frame, but the reference frame of traditional histogram intuitively evaluate the performance differences of the specification is usually manually selected by radiologists. model before and after preprocessing, Figures 7 and 8 list )is method not only increases the workload of radiologists, the performance heat maps of grading prediction before but also cannot guarantee the optimal reference frame. In and after preprocessing, respectively. )e horizontal and the method of this paper, the search range is firstly narrowed vertical coordinates and corresponding results represent by coarse search intraglioma samples, then the suitable the classifier, feature selection or dimension reduction reference frame in histogram is selected by fine search within method, and the maximum average AUC value, re- sample selected by coarse search. Finally, the effectiveness spectively. )ese data indicate that the overall perfor- and feasibility of the proposed method are verified by a mance of the data after preprocessing is about 15% higher grading experiment based on two datasets. )e results show than that without HSASR processing. that multicenter data processed by this method have good AUC AUC 12 Journal of Healthcare Engineering International Journal of Pattern Recognition and Artificial adaptability, which improves the grading results and has Intelligence, vol. 31, no. 4, Article ID 1754006, 2017. certain practical value for clinical prediction. [13] M. F. A. Hassan, A. S. A. Ghani, D. Ramachandram, A. Radman, and S. A. Suandi, “Enhancement of under-ex- Data Availability posed image for object tracking algorithm through homo- morphic filtering and mean histogram matching,” Advanced )e datasets used in this paper are public dataset Science Letters, vol. 23, no. 11, pp. 11257–11261, 2017. (BraTS2017) and Henan Provincial People’s Hospital [14] R. Berenguer, P. J. Mdr, z. J. Canales-Vazquez ´ et al., (GliomaHPPH2018) dataset; BraTS2017 can be obtained “Radiomics of CT features may be nonreproducible and re- through the following URL: https://www.med.upenn.edu/ dundant: influence of CTacquisition parameters,” Radiology, sbia/brats2017/data.html. vol. 288, no. 2, Article ID 172361, 2018. [15] H. Schnack, N. van Haren, M. Picchioni et al., “A multicenter mri schizophrenia study: reliability of voxel-based mor- Conflicts of Interest phometry,” Schizophrenia Research, vol. 102, no. 1–3, p. 75, )e authors declare that they have no conflicts of interest. [16] L. G. Nyul, J. K. Udupa, and X. Xuan Zhang, “New variants of a method of MRI scale standardization,” IEEE Transactions on Acknowledgments Medical Imaging, vol. 19, no. 2, pp. 143–150, 2000. [17] S. Bakas, H. Akbari, A. 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Automatic Histogram Specification for Glioma Grading Using Multicenter Data

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Hindawi Publishing Corporation
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Copyright © 2019 Xi Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2040-2295
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2040-2309
DOI
10.1155/2019/9414937
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Abstract

Hindawi Journal of Healthcare Engineering Volume 2019, Article ID 9414937, 12 pages https://doi.org/10.1155/2019/9414937 Research Article Automatic Histogram Specification for Glioma Grading Using Multicenter Data 1,2 3 2 3 2 4 Xi Chen, Yaping Wu, Guohua Zhao, Meiyun Wang , Wenyi Gao, Qian Zhang, 1,2 and Yusong Lin School of Software, Zhengzhou University, Zhengzhou, Henan 450002, China Collaborative Innovation Center for Internet Healthcare, Zhengzhou University, Zhengzhou, Henan 450052, China Department of Radiology, Henan Provincial People’s Hospital, Zhengzhou, Henan 450003, China School of Computer Science, Zhongyuan University of Technology, Zhengzhou 450000, China Correspondence should be addressed to Yusong Lin; yslin@ha.edu.cn Received 22 July 2019; Revised 6 November 2019; Accepted 23 November 2019; Published 19 December 2019 Academic Editor: Emiliano Schena Copyright©2019XiChenetal.)isisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Multicenter sharing is an effective method to increase the data size for glioma research, but the data inconsistency among different institutions hindered the efficiency. )is paper proposes a histogram specification with automatic selection of reference frames for magnetic resonance images to alleviate this problem (HSASR). )e selection of reference frames is automatically performed by an optimized grid search strategy with coarse and fine search. )e search range is firstly narrowed by coarse search of intraglioma samples, and then the suitable reference frame in histogram is selected by fine search within the sample selected by coarse search. Validation experiments are conducted on two datasets GliomaHPPH2018 and BraTS2017 to perform glioma grading. )e results demonstrate the high performance of the proposed method. On the mixed dataset, the average AUC, accuracy, sensitivity, and specificity are 0.9786, 94.13%, 94.64%, and 93.00%, respectively. It is about 15% higher on all indicators compared with those without HSASR and has a slight advantage over the result of a manually selected reference frame by radiologists. Results show that our methods can effectively alleviate multicenter data inconsistencies and lift the performance of the prediction model. accurately display the location and size, and it correlates well 1. Introduction with histological characteristics. In medical research, high quality data is difficult to obtain in a single institution, so it Glioma is a prevalent fatal brain disease and the most malignant, which accounts for approximately 24.7% of all needs to be shared through multicenter. However, the primary brain and other central nervous system tumors and difference of multicentre data is a serious challenge. 74.6% of malignant tumors [1]. )e World Health Orga- In the acquisitionof multicenter gliomaMRI data,due to nization’s guidelines for glioma diagnosis and treatment are differences in acquisition equipment and parameters result divided into four levels, namely, I–II and III–IV for low- significant differences in data samples in terms of specifi- grade glioma (LGG) and high-grade glioma (HGG) [2]. In cation, size, contrast, and brightness. Differences among the clinical applications, biological behavior, treatment options, data lead to deviations in the grading effect of glioma [4]. and prognoses of patients with glioma of different grades are Figure 1 shows the differences among multicenter data. clearly different. )erefore, the accurate preoperation Figure 1(a) shows that some of the data contain skulls and grading of Glioma is important. Magnetic Resonance Im- the others do not contain. Figure 1(b) shows that these data aging (MRI) is characterized by multidirectional tomogra- have different scales and number of slices. A previous study phy and multiparameter high-resolution soft-tissue imaging indicated that pixel size and slice thickness remarkably affect and is widely used to evaluate the tumor heterogeneity [3]. space and strength characteristics of the calculation [5, 6]. MRI is commonly used in glioma grading because it can )erefore, voxel size must be unified to reduce the error in 2 Journal of Healthcare Engineering )e main contributions of this study are as follows: (1) )is paper proposes a histogram specification with automatic selection of reference frames (HSASR). (a) )is method can automatically select the suitable reference frame of histogram instead of radiologists during image enhancement, so as to enhance the consistency of brain tumors image contrast. (2) )is paper proposes a set of image standardization (b) algorithms to make the preprocessed multicenter data have better consistency, improve the adapt- 512 × 512 × 18 320 × 320 × 18 240 × 240 × 155 ability of data, and improve the accuracy of the glioma prediction model. 2. Related Works C1 C2 C3 (c) In recent years, researchers have gradually adopted multi- center data to replace single institution in clinical medical research. However, multicenter data also faced many C4 C5 C6 challenges. Berenguer et al. [14] carried out a test-retest phantom study of individual image acquisition parameters. Figure 1: Multicenter data. (a) Space of dataset is uneven. (b) )e impact of image parameters on the image cannot be Volume pixel of data element is not uniform. (c) Dataset contrast analyzed because of the difference of the model or machine brightness is not uniform, and C1–C6 are randomly selected data manufacturer. )erefore, variations because of the use of samples. images were eliminated by exclusively scanning phantoms. In addition, Hugo et al. [15] indicated that multicenter structure MRI studies have stronger statistical efficacy than calculating characteristics. Figure 1(c) presents six images with different contrasts. )ese differences are due to de- single-institution studies. However, central differences in viation in acquisition equipment and parameters. contrast sensitivity and spatial uniformity lead to differences In order to alleviate the inconsistency of contrast of in tissue classification or image registration that may reduce multicenter data, it is necessary to enhance the image data or completely offset the enhanced statistical efficacy of appropriately. Histogram correction is a commonly used multicenter data. )erefore, maintaining data in a standard technique in image enhancement [7]. Among them, histo- environment is important. Nyul et al. [16] mentioned some gram equalization (HE) and normalization techniques [8, 9] problems in the original MRI scale preprocessing method are often used to adjust the overall brightness of images. )is and attempted to use the median value and other percentile type of methods mainly expands the range of gray value in numerical methods, such as landmark, to solve these the histogram without adjusting its intensity. )ese methods problems; they obtained robust results after preprocessing. )e validity of the standardized new landmark was also only enhance the overall image and improve its brightness, but the contrast between tumors and other tissues is not mentioned in the study, after which the image brightness considerably enhanced [10, 11]. Histogram specification level and contrast consistency were significantly improved. (HS) can change the frequency of grayscale values and Bakas et al. [17, 18] focused on the data preprocessing enhance any local brightness [12, 13], but it mainly adjusts method, which has a certain enlightening effect on the the local brightness according to the reference frame. In preprocessing method of this study. general, the reference frame is selected by a radiologist. In preprocessing, contrast enhancement of multicenter However, this process consumes a considerable amount of data image is an important challenge. It was shown that a time and the final reference frame may not be the best high-contrast medical image could lead to a better in- choice. )erefore, it is an urgent problem to automatically terpretation of the different adjacent tissues in the imaged search for the best reference frame of histogram instead of body part [19, 20]. Accordingly, the resulting enhanced searching by a radiologist. image, which is in terms of signal intensities of different )is paper presents a histogram specification with au- tissues, can facilitate the automated segmentation, feature tomatic selection of reference frames for magnetic resonance extraction, and classification of these tissues. Existing image images, called HSASR, specifically used to replace radiolo- enhancement techniques (empirical or heuristic) are re- gists manually selecting reference frames. )is method can markably related to a particular image and usually aimed at enhance the consistency of tumor intensity in the whole improving image contrast. However, no unified standard is medical image. In this work, we apply HSASR to the pre- available to measure the quality effect of image enhancement processing of multicenter glioma data, and the effectiveness [21–24]. of this method is proved by Glioma grading experiment. )e Image enhancement can be divided into two categories: results showed that this method had certain practical value spatial domain method and frequency domain method. in glioma grading research. Image enhancement in spatial domain usually corrects Journal of Healthcare Engineering 3 histogram. Histogram equalization is a commonly used N (1) P (l) � , ∀l ∈ L, global grayscale image enhancement technique, and the grayscale value is uniformly redistributed based on the where N � H × W and N is the number of pixels with a gray cumulative density function of the histogram [25]. However, level. )e cumulative distribution function (CDF) of P is equalization fails to consider the intensity of the grayscale r presented as follows: value. )e average brightness of the image can make the x x regions with large original intensity fade, whereas dark areas N s (x) � 􏽘 P (j) � 􏽘 , ∀x ∈ L. (2) r r will brighten after image equalization. Sengee et al. [26] j�0 j�0 suggested an extension method of BBHE based on the neighbourhood metric. )is method involved a few steps: Similarly, if the specified reference image is z, then the first, a large histogram was divided into the subregion using gray cumulative distribution function is the neighbourhood metric and process independently. )is method results in boundary noise and possibly uneven v (y) � 􏽘 P (i) � 􏽘 , ∀y ∈ L, (3) z z histogram brightness in two parts. In addition, MedGA [24] M i�0 i�0 wasan enhancementmethodthatHEcombinedwithgenetic algorithm to directly improve the histogram frequency of where Mand N arethe numberofpixelswith graylevel L.HS attempts to obtain transformation function y � F(x) and images and has achieved obvious results. However, this method could only be limited to the presence of two maps gray level x in the original image to gray level y, such that the transformed image can have a histogram similar to grayscale regional tissues and not enhance complex brain tumors. the reference histogram. To preserve the inherent in- formation of the original image, function F should be a monotonically increasing function. )is function can be 3. Materials and Methods obtained by using the following equation: 3.1. Data Collection. Glioma data used in the study were v (y) � s (x). (4) z r obtained from two separate sources, BraTS2017 and Glio- )erefore, the gray level of the map can be obtained by maHPPH2018 datasets. )e BraTS2017 dataset came from a variety of scanning instruments from 19 medical in- using stitutions. BraTS2017 dataset includes 210 HGG data and 75 − 1 (5) y � v 􏼂s (x)􏼃, z r LGG data; the data was already segmented when it was − 1 acquired. GliomaHPPH2018 dataset was obtained from where v is the inverse of v . multiple equipment of different models from multiple In the discrete case, the inverse function usually does not manufacturers, including 4 Siemens equipment (1 1.5t exist. )e inverse function is usually replaced by the best equipment, 3 3T equipment) and 4GE equipment (2 1.5t objective function to approximate the y of a particular gray equipment, 2 3T equipment), as shown in Table 1. )e level x as follows: 􏼌 􏼌 magnetic resonance data collected on these devices are 􏼌 􏼌 􏼌 􏼌 y � argmin 􏼌 s (x) − v (k)􏼌. r z (6) different from each other. After data inspection, there are up to 186 default inspection protocols for the devices, and Equation (6) represents the absolute value of the dif- contrast-enhanced T1-weighted imaging (CET1) was used in ference between the original image’s cumulative histogram this study, including 35 CET1 sequences (see Table 2), layer and gray level functions of the specified reference histogram, thickness of 5mm to 6.5mm, repetition time of 220– and then the minimum value is selected as the y value. With 1970ms, echo time of 2.46–28.60ms, and resolution of this transformation rule, each gray level x can be mapped to 256 ×256 ×18, 320 ×290 ×18, 320 ×320 ×18, 384 ×384 ×18, y. )erefore, the mapped image will be similar to the desired 448 ×408 ×18, and 512 ×512 ×18. )e GliomaHPPH2018 histogram. dataset includes 161HGG data and 77 LGG data. A three- )e reference frame in the histogram is usually selected dimensional region of interest (ROI) for all the tumors in by the doctor. However, the selected reference image may GliomaHPPH2018 was depicted by two senior radiologists not be suitable, thereby consuming a considerable amount of in Henan provincial people’s hospital. )e ROIs were seg- the radiologist’s time. To solve this problem, an optimized mented slice-by-slice on the axial plane using the CET1 grid search strategy with coarse and fine search is proposed sequences. After discussion between the two radiologists, the to select the suitable reference frame automatically. final decision is made to select the optimal segmentation file. 3.3. HSASR. In this study, an improved grid search method 3.2. Histogram Specification. HS, an effective image en- is proposed to solve the problem of selecting a specified hancement technique, is an extension of histogram equal- reference image. )e grid search is generally used to divide ization that can effectively alleviate the problems of grids of the same length in a certain spatial range based on histogram equalization. Let r � 􏽮r 􏽯be an H × W discrete ij the proposed coordinate system. Each coordinate point input digital image with L gray levels, and let L �{0, 1, . . ., represents a parameter, and these searched parameters are L − 1}. )e histogram or gray level probability density of an calculated and analysed based on the step size. Finally, image is defined as follows: 4 Journal of Healthcare Engineering Table 1: GliomaHPPH2018MR acquisition equipment list. Number Manufacturer Model Magnetic field strength Amount 1 GE OPTIMA MR360 1.5T 1 2 GE Signa HDxt 1.5T 1 3 GE DISCOVERY MR750 3T 2 4 SIEMENS Sempra 1.5T 1 5 SIEMENS Prisma 3T 1 6 SIEMENS TrioTim 3T 1 7 SIEMENS Verio 3T 1 Note: amount is for number of machines. Table 2: CET1 sequence collection parameter statistics. Number Manufacturer Magnetic field Model D-spacing Layer thickness Resolution Voxel size 1 GE 1.5 OPTIMA MR360 6.5 5.5 512 ×512 ×18 0.4688\0.4688 2 GE 1.5 OPTIMA MR360 7 6 512 ×512 ×18 0.4688\0.4688 3 GE 1.5 OPTIMA MR360 7.5 6 256 ×256 ×18 0.9375\0.9375 4 GE 1.5 OPTIMA MR360 7.5 6 512 ×512 ×18 0.4688\0.4688 5 GE 1.5 OPTIMA MR360 8 6 512 ×512 ×18 0.4688\0.4688 6 GE 1.5 Signa HDxt 7 6 512 ×512 ×18 0.4688\0.4688 7 GE 1.5 Signa HDxt 7 6 512 ×512 ×18 0.5273\0.5273 8 GE 1.5 Signa HDxt 7.5 6 512 ×512 ×18 0.4688\0.4688 9 GE 1.5 Signa HDxt 7.5 6.5 512 ×512 ×18 0.4688\0.4688 10 GE 1.5 Signa HDxt 8 6 512 ×512 ×18 0.4688\0.4688 11 GE 3 DISCOVERY MR750 6.5 5 512 ×512 ×18 0.4688\0.4688 12 GE 3 DISCOVERY MR750 7 6 512 ×512 ×18 0.4688\0.4688 13 GE 3 DISCOVERY MR750 7.5 6 512 ×512 ×18 0.4688\0.4688 14 SIEMENS 1.5 Sempra 7.2 6 448 ×408 ×18 0.5134\0.5134 15 SIEMENS 3 Prisma 7.2 6 320 ×320 ×18 0.7188\0.7188 16 SIEMENS 3 Prisma 7.2 6 384 ×384 ×18 0.5989\0.5989 17 SIEMENS 3 Prisma 7.8 6 320 ×320 ×18 0.7188\0.7188 18 SIEMENS 3 TrioTim 6.6 6 320 ×320 ×18 0.7188\0.7188 19 SIEMENS 3 TrioTim 6.6 6 320 ×320 ×18 0.75\0.75 20 SIEMENS 3 TrioTim 7.2 6 256 ×256 ×18 0.8984\0.8984 21 SIEMENS 3 TrioTim 7.2 6 256 ×256 ×18 0.9375\0.9375 22 SIEMENS 3 TrioTim 7.2 6 320 ×290 ×18 0.7188\0.7188 23 SIEMENS 3 TrioTim 7.2 6 320 ×320 ×18 0.7188\0.7188 24 SIEMENS 3 TrioTim 7.2 6 320 ×320 ×18 0.75\0.75 optimal parameters are considered the output. Given that randomly selected for histogram specification (the this method must traverse all the corresponding points in same sample is selected each time), and then the the grid, many unnecessary invalid calculations are gener- performance of data after histogram specification is tested. ated, resulting in an exponential increase in time. To reduce time consumption, this study improves the (3) Select the sets of all the best area under the curve directional grid optimization search based on data charac- (AUC) values according to threshold Tand perform teristics. On the basis of the characteristics of glioma itself, the next fine search. the method is improved by using coarse segmentation and (4) Fine search: in the optimal cluster, the search is subdivision. Horizontal and vertical searches are used for initiated from the middle section (two pointers are coarse segmentation and subdivision, respectively. )e set to point to the middle section), and pointer 1 specific steps of the improved method are as follows: searches upward successively. If reference frames (1) )e number of clusters N and the number of slices K do not contain tumors, then the search is stopped. of each tumor are determined. Each cluster is set to i, If the difference between the current and previous and the initialization step size is K/2. A 2D grid is values is greater than T, then the search is stopped, established by using N and K, and the grid nodes are and the optimal value is selected. At the same time, the corresponding reference slices of N and K. similar to the previous step, pointer 2 is searched downward. (2) In the coarse search, each time it searched by step size from the beginning of each set(horizontally), the (5) )e optimal reference slice map is the final output. If median slice in each cluster was selected as the multiple optimal values exist, then selection is made reference frame. )en, 30% of data in all datasets are based on accuracy and specificity indicators. If Journal of Healthcare Engineering 5 (i) Input: Mixed dataset F, data sample number N, number of each sample slice K (ii) Output: Optimal reference slice F (1) Step1: Coarse search (2) Function HSBM (n, F1, l )//Histogram specification based on brain MRI (3) { (4) F1 �Random (range (0, N), F∗30%)//Random selection of 30% of dataset (5) For each n ∈ F do (6) For each n1 ∈ F1 do (7) cdf � hist · cumsum( ) F F 1 n1 n (8) cdf � hist · cumsum( ) F F n n k/2 min (9) Calculate: hist � arg |(cdf /shape(F )) − ((cdf /shape(F ))(m))| F n Fn1 n1 n k/2 k/2 (10) End for (11) Calculate: Auc(n ) � roc auc score(Lable − Lable ) K/2 original predict (12) End for (13) } (14) F2 � Sort max(Auc ) k/2 (15) F2 �Max(F2) (16) For each c ∈ F2 do (17) if |F2 − Auc(c)|≤ T then (18) Select c ⟶ F3 (19) end (20) End for (21) Select the optimal set F3 (22) Step 2 Fine search (23) Initializes Pointers l , l 1 2 (24) For each n ∈ F3//Search both ends (25) l � k/2 (26) For l ≤ kandexit(tumor ); l + +do 1 l ++ 1 (27) HSBM (n, F1, l ) (28) End for (29) End for (30) For each n ∈ F3 (31) l � k/2 (32) For l ≤ kandexit(tumor ); l + +do 2 l ++ 2 (33) HSBM (n, F1, l ) (34) End for (35) End for (36) Output: select the first optimal slice F ALGORITHM 1: HSASR algorithm pseudocode description. several optimal reference frames existed, then the 3.4. Experiments. Figure 3 shows the overall process of first optimal reference frame is selected as the final multicenter data grading prediction. First, data are im- reference frame. ported, data preprocessing is performed, features are extracted by using the feature calculation method, features Algorithm 1 describes the HSASR algorithm. )e pa- are selected, and model training is finally conducted. rameter T in Step 1 prevents the collection of additional Contribution points of this study are in the preprocessing optimal values from being missed. )e T in Step 2 saves stage. )e HSASR method proposed is the most important search time. Figure 2 presents the 2D diagram of the im- part of preprocessing. proved optimization grid search. In this study, N represents the number of data samples, K denotes the number of slices of each sample, and K/2 is the middle slice of the sample. 3.5. Preprocessing. Storage formats of multicenter data are First, a horizontal coarse search is performed. )e pale blue often inconsistent. Data formats of this study include NIfTI circles indicate the performance values of intermediate slices and DICOM format files. )erefore, to standardize multi- in each cluster. )e optimal clusters are selected for lon- center data formats, this study adopts the format conversion gitudinal fine search, the middle slice is considered the initial method based on the Convert3D tool to unify all data sample value, and both ends are searched simultaneously. )e formats into the NIfTI format. )e majority of patients in vertical circles and dark blue squares represent the perfor- the GliomaHPPH2018 dataset have 18 DICOM files with mance values in the optimal set and the selected final ref- CET1 sequence, and a small number of patients have 36 files. erence frame, respectively. After format conversion, all slices of each patient’s CET1 6 Journal of Healthcare Engineering k/2 Intermediate slice as reference Optimal slice as reference Single sample slice as reference Figure 2: Diagram of the optimized grid search (note: k/2 represents the middle slice of the cluster). Multicenter standardization Feature engineering Feature calculation Feature selection Grading prediction Preprocessing Raw data BraTS2017 Feature Set1 Format conversion Feature selection diagram PCA Brain tissues extraction Pyradiomics Feature Set2 Feature samples Resampling x x GliomaHPPH2018 Selection feature Predictive analysis Figure 3: Flowchart of multicenter data grading prediction. sequence are converted into the NIfTI format file, thereby In addition, spatial consistency of the data image is maintained.Multiple voxelrangesoccur inboth datasets.On providing convenience in subsequently unifying data processing. the basis of Convert3D, we adopt the shortest distance in- Furthermore, to unify the multicenter data in pre- terpolation resampling technology to carry out scale processing, maintaining the consistency of brain tissue resampling in each data sample. )e size of each data sample structureis alsoimportant.)e GliomaHPPH2018 datasetin is unified to 240 ×240 ×155, and the label sample is also this study contained skull images, which are removed at the converted into a file of the same size. In addition, the dis- time of acquisitionin the BraTS2017dataset. )issituation is tance between unified slices is 1mm, and the original po- not only a certain impact on HS but also introduced diffi- sition was [0, − 239, 0]. culties in combining the two datasets due to the gap between To solve the problem of inconsistent brightness and them. In this study, the FSL tool is firstly used in location contrast of multicenter data, this paper proposes a histogram registration, and then the skulls are removed based on the specification withautomatic selection ofreferenceframes for bet script. In this study, 238 data skulls are removed, and magnetic resonance images. On the basis of the character- brain tissues and regions of interest are relatively intact. istics of glioma itself, this paper puts forward an optimized Journal of Healthcare Engineering 7 MRI without HSASR MRI with HSASR L1 L2 L3 L1 L2 L3 L4 L5 L6 L4 L5 L6 H1 H2 H3 H1 H2 H3 H4 H5 H6 H4 H5 H6 Figure 4: MRI comparison map before and after HSASR. Table 3: Results of the first three glioma grading experiments. Without HSASR With HSASR Training Testing AUC ACC (%) SEN (%) SPE (%) AUC ACC (%) SEN (%) SPE (%) GH BT 0.6850 59.93 58.45 64.00 0.9507 90.88 90.18 82.67 BT GH 0.7605 72.68 81.98 53.25 0.9146 85.90 89.87 77.63 (80%) (GH+BT)+(20%) 0.8252 78.17 85.42 61.67 0.9786 94.13 94.64 93.00 (GH+BT) (80%)GH+(20%)GH 0.8394 81.25 82.06 76.32 0.9556 89.36 87.20 94.71 (80%)BT+(20%)BT 0.8512 79.12 80.19 74.99 0.9934 95.61 97.35 92.65 Note: GH is for GliomaHPPH2018, and BTstands for BraTS2017. BTrepresents 80% of the data as training and 20% as testing. GH alone represents 80% of GH data as training and 20% of GH as testing. BT alone represents 80% of BT dataset as training and 20% of BT as testing. grid search strategy with coarse and fine search. First, in search, the step size is changed to 1, data are searched from coarse search, all data samples are selected as the object of the middle number upward and downward, and the search is reference selection in this study. Each file is considered a over according to the end condition. collection, and the step size is set to the middle number of the collection (78), starting from the beginning of every collection each time. )e middle slice (78) of each collection 3.6. Feature Engineering. All the data being processed are imported into feature calculation. For each region of in- is used as the reference slice of HS, 30% of image samples are randomly selected from all data, and image enhancement is terest, 557 radiomics features are calculated through Pyr- adiomics (Pyradiomics is a tool for the computational carried out via HS and subsequently imported into the model verification process of this study. T is set to 1%, and characteristics of medical images). In this study, 9 spatial geometric features are included, which are only calculated in the set with the highest AUC value and AUC value error less the original space. Eighteen first-order statistical features than 1% is selected. Furthermore, the study carries out fine 8 Journal of Healthcare Engineering Receiver operating characteristic curve Receiver operating characteristic curve 1.0 1.0 0.8 0.8 0.6 0.6 0.4 0.4 0.2 0.2 0.0 0.0 0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0 False positive rate False positive rate Train ROC AUC = 0.98571 Train ROC AUC = 0.95225 Test ROC AUC = 0.91456 Test ROC AUC = 0.95073 (a) (b) Figure 5: ROC plot. Table 4: Results of the contrast experiment. Training Testing Method AUC ACC (%) SEN (%) SPE (%) (80%) (GH+BT)+(20%) (GH+BT) HE 0.9176 86.19 90.44 76.05 (80%) (GH+BT)+(20%) (GH+BT) Handpicked 0.9447 89.90 90.35 88.88 (80%) (GH+BT)+(20%) (GH+BT) Our method 0.9786 94.13 94.64 93.00 Note: GH is for GliomaHPPH2018, and BT is for BraTS2017. GH+BT represents 80% of the data as training and 20% as testing. and 43 texture features are calculated in the original data and 3.7. Experimental Comparison Designs. To verify the effec- eight wavelet decomposition spaces, respectively. For all tiveness of processed multicenter data, this study proposed image histological features, model training is conducted the following process designs: directly after the processing of missing values. (1) Take the processed GliomaHPPH2018 and )e calculated features are imported into the model BraTS2017 datasets as the training and testing sets, scriptof this studyfor prediction.)e modelscript isdivided respectively. )en, use the two unpreprocessed into two parts, namely, feature selection and classifier. Five datasets as contrast experiments. selection methods and nine classifiers are combined to set up (2) Mix together 521 data samples from Glio- the classifier, and the training and testing sets are imported maHPPH2018 and BraTS2017, preprocess the data, into the model for prediction. For the designs of experiment carry out feature selection and model training, and 2 and 3 in the next section, 80% and 20% of data are selected analyze the results. from the data table as training and testing sets, respectively. )e prediction is then repeated 10 times. )e average value (3) Use single sequences from the processed and un- of final results is obtained, and the classifier and selection processed GliomaHPPH2018 and BraTS2017 as methods with the best results are finally selected with the comparison experiment. rating device. )e selection methods used in the study are (4) Make comparisonexperiments between this research SelectKBest (f_classif) for classifying the tag features be- method and common image enhancement methods tween tasks for ANOVA f values, principal component on the mixed dataset. Finally, compare these results analysis (PCA), kernel principal component analysis with the untreated data. In addition, to verify the (KPCA), independent component correlation algorithm effectiveness of HSASR, compare the research results (ICA), and factor analysis (FA). )e classifiers used in this with the reference diagram results selected by study are decision tree (DT), random forest (RF), bagging radiologists. (BAG), binary search tree (BSA), naive Bayes (NB), mul- tilayer perception (MLP), support vector machine (SVM), 4. Results and Discussion logistic (LR), and k-nearest neighbour (KNN). For the two separate datasets in experiment 1, the stable training model 4.1. Analysis of Image Enhancement. )e purpose of weak- is selected by using a tenfold cross-validation scheme, and ening the multicenter data is to relieve the differences between then the grading prediction is finally performed. groups and retain individual characteristics. )at is to say, True positive rate True positive rate Journal of Healthcare Engineering 9 Table 5: Performance comparison with similar works. Author and reference Architecture/method Output class Data Maximum ACC (%) Khawaldeh et al. [27] AlexNet+Preprocessing 3 130 91.16 Chen et al. [28] CAD+Preprocessing 2 274 91.27 Our method HSASR 2 523 94.13 80 80 22 9 2 26 60 15 3 58 73 LGG HGG LGG HGG Predicted lable Predicted lable (a) (b) Figure 6: Confusion matrix of mixed dataset. 0.84 0.83 0.77 0.82 FILT 0.72 0.82 0.82 0.81 0.77 0.79 0.80 PCA 0.81 0.81 0.71 0.83 0.77 0.78 0.69 0.8 0.8 0.76 KPCA 0.67 0.78 0.76 0.81 0.81 0.73 0.84 0.74 0.81 0.72 ICA 0.69 0.8 0.79 0.82 0.69 0.79 0.76 0.75 0.8 FA 0.79 0.79 0.81 0.72 0.81 0.69 0.83 0.76 0.8 0.68 DT RF BAG BST NB MLP SVM LR KNN Classifier Figure 7: Heat map without HSASR. Feature reduction True lable HGG LGG True lable HGG LGG AUC score 10 Journal of Healthcare Engineering FILT 0.9 0.97 0.97 0.97 0.95 0.98 0.98 0.96 0.97 0.96 0.85 0.94 0.9 0.98 0.95 0.97 PCA 0.96 0.97 0.95 0.93 0.87 0.96 0.93 0.97 0.97 0.96 0.97 KPCA 0.94 0.96 0.90 ICA 0.84 0.96 0.95 0.96 0.9 0.97 0.97 0.96 0.96 0.87 FA 0.85 0.95 0.94 0.96 0.88 0.97 0.96 0.97 0.95 0.84 DT RF BAG BST NB MLP SVM LR KNN Classifier Figure 8: Heat map with HSASR. Experiment 1 in Table 3 presents the results of Glio- under the premise of retaining tumor morphological char- acteristics,theimagedataofdifferentmedicalinstitutionshave maHPPH2018and BraTS2017 datasets as the training and similar contrast and brightness. In this study, contrast and testing set, respectively. )e results show that the data with brightness of multicenter glioma data images are significantly HSASR is better predicted, and the indexes are significantly improved after image enhancement in preprocessing. Figure 4 improved compared with the unprocessed data, as shown in shows the MRI results of the CET1 sequence in 12 patients. Figure 5. Figure 5(a) shows the ROC curve in which )eleft-handsideofFigure4presents thatthe firstandsecond BraTS2017 is a training set and GliomaHPPH2018 is a rows are LGG without HSASR, and the third and fourth rows testing set, and Figure 5(b) shows the ROC curve in which are HGG without HSASR. All processed glioma data are the testing set and the training set interchange. It can be shown on the right side of the figure. )e examples show on observed from the figure that when testing set and training the left and right sides had a one-to-one correspondence. set swap, the better results can also be obtained. )e results show that the data processed by the HRASR method have From the perspective of image, the range of contrast and brightness of data without HSASR in Figure 4 are relatively good adaptability and can alleviate the difference among complex and the tumor area is fuzzy and difficult to distin- multicenter data images. guish. )e data after HSASR are consistent in contrast and Experiment 2 in Table 3 presents the results of the mixed brightness, the tumor area is significantly enhanced, and basic dataset. )e calculated characteristics are imported into the features (tumor morphology and lesion range) of the original proposed grading model for 10 iterations of random pre- image can be retained. diction, and the average value is subsequently obtained. Finally, the model with the best average performance is selected as the final model. )e results show that AUC after 4.2. Performance of Glioma Grading. )ispaperaimstoreflect processing generally increased by more than 15%, and other the effectiveness of these methods indirectly by using model indicators also improve significantly. Experiment 3 in Ta- prediction indicators. To validate the effect of the processed ble 3 shows that the data processed by HSASR on a single multicenterdatafurther,thissectionconductstheverificationof dataset also achieve a good grading effect. grading results based on the following indicators: AUC, ac- Experiment 4 in Table 4 shows the comparison exper- curacy (ACC), sensitivity (SEN), and specificity (SPE). iment conducted by three different methods on the mixed Feature reduction AUC score Journal of Healthcare Engineering 11 Coarse search 0.980 Fine search 0.98 0.978 0.96 0.976 0.94 0.92 0.974 0.90 0.972 0.88 0.970 0.86 6(78) 12(78) 18(78) 24(78) 30(78) 36(78) 42(78) 48(78) 69(10) 71(10) 73(10) 75(10) 77(10) 79(10) 81(10) N K (a) (b) Figure 9: Diagram of the proposed method (note: the red circle and blue square represent the AUC of machine and manually selected reference images, respectively. )e black square represents optimal reference frame). dataset. )ese methods include the HE method, reference Figure 9 illustrates the experimental results of the grid frame method of manual selection by radiologists, and the search in this study. In this study, five reference slices with the method proposed in this paper. )e results show that highest performance indexes were selected from two datasets via rough search, and the reference slices with the best per- compared withthe othertwo methods, the methodproposed in this paper significantly improves the grading effect of formance were screened out. )e N axis, K, circle, and square denoted the number of samples, the number of slices in each glioma. )e reference frame selected by radiologists based on experience shows significant improvement in glioma sampleset,the valueof AUCof thereferenceimageselectedby grading, but it can be seen from the results that the per- the HSASR, and the predicted performance value of the formance of the selected reference frame is worser than that reference image selected by the doctor, respectively. )e ob- of the automatically selected. tained performance of the reference frame selected by the Table 5 gives the performance comparison of similar method is both low and high, indicating that the difference in work in the references using glioma dataset. In [27], after reference objects had a significant impact on the result of data preprocessing, they used a modified version of AlexNet grading. )e proposed method can replace radiologists in for classifying MR brain images into three classes like choosing the best reference frame and save a considerable amount of time. Hence, the proposed method has certain healthy brain, LGG, and HGG. However, the amount of data of this work is so small that cannot verify the robustness of application value in clinical trials. the proposed method. Reference [28] also involved data preprocessing, but our data is twice as large, and the result 5. Conclusions verified by the grading model is better than this method. Figure 6 is the confusion matrix corresponding to the Inconsistencies among data prevent multicenter data from final model of mixed glioma data in experiment 2, and playing to its shared advantage. )is paper proposes a LGG and HGG represent the low-level label and high-level histogram specification method with automatic selection of label, respectively. Figure 6(a) shows the confusion matrix reference frames for magnetic resonance images to alleviate before processing, and Figure 6(b) shows the predicted the problem of contrast inconsistencies among multicenter data distribution after processing. Figure 6 shows a sig- data. )e core of histogram specification is to change the nificant decrease in the number of glioma predicted in- local brightness of the image according to the reference correctly after preprocessing. Meanwhile, in order to frame, but the reference frame of traditional histogram intuitively evaluate the performance differences of the specification is usually manually selected by radiologists. model before and after preprocessing, Figures 7 and 8 list )is method not only increases the workload of radiologists, the performance heat maps of grading prediction before but also cannot guarantee the optimal reference frame. In and after preprocessing, respectively. )e horizontal and the method of this paper, the search range is firstly narrowed vertical coordinates and corresponding results represent by coarse search intraglioma samples, then the suitable the classifier, feature selection or dimension reduction reference frame in histogram is selected by fine search within method, and the maximum average AUC value, re- sample selected by coarse search. Finally, the effectiveness spectively. )ese data indicate that the overall perfor- and feasibility of the proposed method are verified by a mance of the data after preprocessing is about 15% higher grading experiment based on two datasets. )e results show than that without HSASR processing. that multicenter data processed by this method have good AUC AUC 12 Journal of Healthcare Engineering International Journal of Pattern Recognition and Artificial adaptability, which improves the grading results and has Intelligence, vol. 31, no. 4, Article ID 1754006, 2017. certain practical value for clinical prediction. [13] M. F. A. Hassan, A. S. A. Ghani, D. Ramachandram, A. Radman, and S. A. Suandi, “Enhancement of under-ex- Data Availability posed image for object tracking algorithm through homo- morphic filtering and mean histogram matching,” Advanced )e datasets used in this paper are public dataset Science Letters, vol. 23, no. 11, pp. 11257–11261, 2017. 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Journal

Journal of Healthcare EngineeringHindawi Publishing Corporation

Published: Dec 19, 2019

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