cvpr cvpr2013 cvpr2013-83 knowledge-graph by maker-knowledge-mining

83 cvpr-2013-Classification of Tumor Histology via Morphometric Context


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Author: Hang Chang, Alexander Borowsky, Paul Spellman, Bahram Parvin

Abstract: Image-based classification oftissue histology, in terms of different components (e.g., normal signature, categories of aberrant signatures), provides a series of indices for tumor composition. Subsequently, aggregation of these indices in each whole slide image (WSI) from a large cohort can provide predictive models of clinical outcome. However, the performance of the existing techniques is hindered as a result of large technical and biological variations that are always present in a large cohort. In this paper, we propose two algorithms for classification of tissue histology based on robust representations of morphometric context, which are built upon nuclear level morphometric features at various locations and scales within the spatial pyramid matching (SPM) framework. These methods have been evaluated on two distinct datasets of different tumor types collected from The Cancer Genome Atlas (TCGA), and the experimental results indicate that our methods are (i) extensible to different tumor types; (ii) robust in the presence of wide technical and biological variations; (iii) invariant to different nuclear segmentation strategies; and (iv) scalable with varying training sample size. In addition, our experiments suggest that enforcing sparsity, during the construction of morphometric context, further improves the performance of the system.

Reference: text


Summary: the most important sentenses genereted by tfidf model

sentIndex sentText sentNum sentScore

1 , normal signature, categories of aberrant signatures), provides a series of indices for tumor composition. [sent-13, score-0.194]

2 Subsequently, aggregation of these indices in each whole slide image (WSI) from a large cohort can provide predictive models of clinical outcome. [sent-14, score-0.156]

3 However, the performance of the existing techniques is hindered as a result of large technical and biological variations that are always present in a large cohort. [sent-15, score-0.107]

4 In this paper, we propose two algorithms for classification of tissue histology based on robust representations of morphometric context, which are built upon nuclear level morphometric features at various locations and scales within the spatial pyramid matching (SPM) framework. [sent-16, score-1.778]

5 In addition, our experiments suggest that enforcing sparsity, during the construction of morphometric context, further improves the performance of the system. [sent-18, score-0.563]

6 Introduction Histology sections provide a wealth of information about the tissue architecture that contains multiple cell types at different states of cell cycles. [sent-20, score-0.281]

7 These sections are often ∗This work was supported by NIH U24 CA1437991 carried out at Lawrence Berkeley National Laboratory under Contract No. [sent-21, score-0.044]

8 stained with hematoxylin and eosin (H&E;) stains, which label DNA (e. [sent-23, score-0.051]

9 Abberations in the histology architecture often lead to disease progression. [sent-26, score-0.175]

10 It is desirable to quantify indices associated with these abberations since they can be tested against the clinical outcome, e. [sent-27, score-0.061]

11 Even though there are inter- and intra- observer variations [7], a trained pathologist always uses rich content (e. [sent-30, score-0.051]

12 , various cell types, cellular organization, cell state and health), in context, to characterize tumor architecture. [sent-32, score-0.308]

13 Due to the effectiveness of our representations, our methods achieve excellent performance even with small number of training samples across different segmentation strategies and independent datasets of tumors. [sent-34, score-0.097]

14 These characteristics dramatically improve the (i) effectiveness of our techniques when applied to a large cohort, and (ii) extensibility to other cell-based assays. [sent-36, score-0.062]

15 Related Work For the analysis of the H&E; stained sections, several excellent reviews can be found in [13, 8]. [sent-41, score-0.051]

16 Fundamentally, the trend has been based either on nuclear segmentation and corresponding morphometric representaion, or patch-based 222222000311 Figure 1. [sent-42, score-0.865]

17 Computational workflows: (a) Morphometric nonlinear kernel SPM; (b) Sparse Morphometric linear SPM. [sent-43, score-0.056]

18 In both approaches, the nuclear segmentation could be based on any of the existing methods. [sent-44, score-0.302]

19 representation of the histology sections that aids in clinical association. [sent-45, score-0.23]

20 For example, a recent study indicates that detailed segmentation and multivariate representation of nuclear features from H&E; stained sections can predict DCIS recurrence [1] in patients with more than one nuclear grade. [sent-46, score-0.678]

21 The major challenge for tissue classification is the large amounts of technical and biological variations in the data, which typically results in techniques that are tumor type specific. [sent-47, score-0.425]

22 In the context of image categorization research, the traditional bag of features (BoF) model has been widely studied and improved through different variations, e. [sent-49, score-0.038]

23 , modeling of co-occurrence of descriptors based on generative methods [4, 3, 20, 24], improving dictionary construction through discriminative learning [9, 22], modeling the spatial layout of local descriptors based on spatial pyramid matching kernel (SPM) [18]. [sent-51, score-0.197]

24 At the same time, SPM partially captures context because of its hierarchical nature. [sent-54, score-0.038]

25 Motivated by the works of [18, 28], we encode morphometric signatures, at different locations and scales, within the SPM framework. [sent-55, score-0.563]

26 The end results are highly robust and effective systems across multiple tumor types with limited number of training samples. [sent-56, score-0.237]

27 Approaches The computational workflows for the proposed methods are shown in Figure 1, where the nuclear segmentation can be based on any of the existing methods for delineating nuclei from background. [sent-58, score-0.397]

28 For some tissue images and their corresponding nuclear segmentation, let: 1. [sent-59, score-0.382]

29 N be the number of morphometric descriptors extracted from each segmented nucleus, e. [sent-61, score-0.563]

30 X be the set of morphometric descriptors for all segmented nuclei, where X = [x1, . [sent-64, score-0.563]

31 Morphometric SPM) nonlinear kernel SPM (MK- In this approach, we utilize the nuclear morphometric information within the SPM framework to construct the morphometric context at various locations and scales for tissue image representation and classification. [sent-72, score-1.648]

32 are the K nuclear morphometric types to be learned by the following optimization: ? [sent-78, score-0.846]

33 =1||xm− zmD||2 (1) subject to card(zm) = 1, |zm | = 1, zm ? [sent-80, score-0.088]

34 indicates the assignment of the nuclear morphometric type, card(zm) is a cardinality constraint enforcing only one nonzero element of zm, zm ? [sent-85, score-0.909]

35 Construct spatial histogram as the descriptor for the morphometric context for SPM [18]. [sent-89, score-0.62]

36 This is done by repeatedly subdividing an image and computing the histograms of different nuclear morphometric types over the resulting subregions. [sent-90, score-0.846]

37 As a result, the spatial histogram, H, is formed by concatenating the appropriately weighted histograms of all nuclear morphometric types at all resolutions. [sent-91, score-0.865]

38 In practice, the intersection kernel and χ2 kernel have been found to be the most suitable for histogram representations [28]. [sent-99, score-0.094]

39 are the K nuclear morphmetric types to be learned by the following sparse coding optimization: ? [sent-115, score-0.351]

40 Construct spatial pyramid representation as the descriptor of morphometric context for the linear SPM [28]. [sent-120, score-0.67]

41 Let Z be the sparse codes calculated through Equation 3 for a descriptor set X. [sent-121, score-0.058]

42 Based on pre-learned and fixed dictionary D, the image descriptor is computed based on a pre-determined pooling function as follows, f = P(Z) (4) In our implementation, P is selected to be the max pooling function on the absolute sparse codes fj = max{ |z1j | , |z2j |, . [sent-122, score-0.369]

43 , |zMj |} (5) where fj is the j-th element of f, zij is the matrix element at i-th row and j-th column of Z, and M is the number of nuclei in the region. [sent-125, score-0.14]

44 The choice of max pooling procedure is justified by biophysical evidence in the visual cortex [25], algorithms in image categorization [28], and our experimental comparison with other common pooling strategies (see Table 7). [sent-126, score-0.219]

45 Similar to the construction of SPM, the pooled features from various locations and scales are then concatenated to form a spatial pyramid representation ofthe image, and a linear SPM kernel is applied as follows, κ(fi,fj) = fi? [sent-127, score-0.131]

46 1 (6) where fi and fj are spatial pyramid representations for image Ii and Ij, respectively, ? [sent-141, score-0.144]

47 fj, and fil (s, t) and fjl (s,, ,t )r are cthtiev max pooling st fatistics of the sparse codes in the (s, t)-th segment of image Ii and Ij in the scale level l, respectively. [sent-144, score-0.184]

48 SMLSPM: the linear SPM that uses linear kernel on spatial-pyramid pooling of morphometric sparse codes; 2. [sent-151, score-0.713]

49 MKSPM: the nonlinear kernel SPM that uses spatialpyramid histograms of morphometric features and χ2 kernels; 3. [sent-152, score-0.647]

50 ScSPM [28]: the linear SPM that uses linear kernel on spatial-pyramid pooling of SIFT sparse codes; 4. [sent-153, score-0.15]

51 KSPM [18]: the nonlinear kernel SPM that uses spatial-pyramid histograms of SIFT features and χ2 kernels; 5. [sent-154, score-0.056]

52 Comparison of average segmentation performance among MRGC [6], SRCD [5], and OTGR. [sent-162, score-0.044]

53 MRGC [6]: A multi-reference graph cut approach for nuclear segmentation in histology tissue sections; 2. [sent-165, score-0.582]

54 SRCD [5]: A single-reference color decomposition approach for nuclear segmentation in histology tissue sections; 3. [sent-166, score-0.582]

55 OTGR: A simple Otsu thresholding [23] approach nuclear segmentation in histology tissue sections. [sent-167, score-0.582]

56 our implementation, nuclear mask was generated applying Otsu thresholding on gray-scale image, refined by geometric reasoning [27]. [sent-168, score-0.258]

57 for In by and reap- A comparison of the segmentation performance, for the above methods, is quoted from [6], and listed in Table 1, and the computed morphometric features are listed in Table 2. [sent-170, score-0.676]

58 Additionally, for all five methods, we fixed the level of pyramid to be 3, and used linear SVM for classification. [sent-177, score-0.05]

59 GBM Dataset The GBM dataset contains 3 classes: Tumor, Necrosis, and Transition to Necrosis, which were curated from whole MRGCSRCDOTGR SMLSPM92. [sent-182, score-0.059]

60 Performance of SMLSPM and MKSPM on the GBM dataset based on three different segmentation approaches, where the number of training images per category was fixed to be 160, and the dictionary sizes for SMLSPM and MKSPM were fixed to be 1024 and 512, respectively, to achieve optimal performance. [sent-207, score-0.179]

61 Performance of SMLSPM and MKSPM on the KIRC dataset based on three different segmentation approaches, where the number of training images per category was fixed to be 280, and the dictionary sizes for both SMLSPM and MKSPM were fixed to be 512, to achieve the optimal performance. [sent-233, score-0.179]

62 slide images (WSI) scanned with a 20X objective (0. [sent-234, score-0.062]

63 The number of images per category are 628, 428 and 324, respectively. [sent-237, score-0.045]

64 In this experiment, we torsatin imeda on 4 a0r,e 8 100 a00nd× 11600 images per category and tested on the rest, with three different dictionary sizes: 256, 512 and 1024. [sent-239, score-0.117]

65 For SMLSPM and MKSPM, we also evaluated the performance based on three different segmentation strategies: MRGC, SRCD and OTGR. [sent-241, score-0.044]

66 KIRC Dataset The KIRC dataset contains 3 classes: Tumor, Normal, and Stromal, which were curated from whole slide images (WSI) scanned with a 40X objective (0. [sent-245, score-0.121]

67 The number of images per category are 568, 796 and 784, respectively. [sent-248, score-0.045]

68 In this experiment, we tirmaaingeeds on e7 10,0 10400 × ×an 1d0 20800 p images per category and tested on the rest, with three different dictionary sizes: 256, 5 12 and 1024. [sent-250, score-0.117]

69 For SMLSPM and MKSPM, we also evaluated the performance based on three different segmentation strategies: MRGC, SRCD and OTGR. [sent-252, score-0.044]

70 , train222222000644 background is defined to be outside the nuclear region, but inside the bounding box of nuclear boundary. [sent-257, score-0.516]

71 Comparison of performance for SMLSPM using different pooling strategies on the GBM and KIRC datasets. [sent-286, score-0.117]

72 For GBM, the number of training images per category was fixed to be 160, and the dictionary size was fixed to be 1024; for KIRC, the number of training images per category was fixed to be 280, and the dictionary size was fixed to be 512. [sent-287, score-0.27]

73 Since GBM and KIRC are two vastly different tumor types with significantly different signatures, we suggest that the consistency in performance assures extensibility to different tumor types. [sent-291, score-0.452]

74 Robustness in the presence of large amounts of technical and biological variations. [sent-292, score-0.087]

75 Performance of different methods on the GBM dataset, where SMLSPM and MKSPM were evaluated based on the segmentation method: MRGC [6]. [sent-473, score-0.044]

76 With respect to the KIRC dataset, shown in Table 5, the performance of our methods, based on 70 training samples per category, is comparable to the performance of ScSPM, KSPM and CTSPM based on 280 training samples per category. [sent-478, score-0.074]

77 Given the fact that TCGA datasets contain large amount of technical and biological variations [17, 19], these results clearly indicate the robustness of our morphometric context representation, which dramatically improved the reliability of our approaches. [sent-479, score-0.731]

78 Ta- × bles 4 and 6 indicate that the performance of our approaches are almost invariant to different segmentation algorithms, given the fact that the segmentation performance itself varies a lot, as shown in Table 1. [sent-482, score-0.088]

79 More importantly, even with the simplest segmentation strategy OTGR, SMLSPM outperforms the methods in [28, 18] on both datasets, and MRSPM outperforms the methods in [28, 18] on the GBM dataset, while generating comparable results on the KIRC dataset. [sent-483, score-0.044]

80 Given the fact that, in a lot of studies, both nuclear segmentation and tissue classification are necessary components, the MethodDictionarySize=256DictionarySize=512DictionarySize=1024 280 trainingSMLSPM98. [sent-484, score-0.426]

81 Performance of different methods on the KIRC dataset, where SMLSPM and MKSPM were evaluated based on the segmentation mehtod: MRGC [6]. [sent-664, score-0.044]

82 use of pre-computed morphometric features dramatically improve the efficiency by avoiding extra feature extraction steps. [sent-665, score-0.606]

83 Our experiments show that the morphometric context representation in SMLSPM works well with linear SVMs, which dramatically improves the scalability of training and the speed of testing. [sent-671, score-0.642]

84 This is very important for the analyzing large cohort of whole slide images. [sent-672, score-0.126]

85 To study the impact of pooling strategies on the SMLSPM method, we also provide an experimental comparison among max pooling and two other common pooling methods, which are defined as follows, Sqrt Abs :fj=? [sent-673, score-0.301]

86 As shown in Table 7, the max pooling strategy outperforms the other two, which is probably due to its robustness to local translations. [sent-680, score-0.102]

87 Conclusion and Future Work In this paper, we proposed two spatial pyramid matching approaches based on morphometric features and morphometric sparse code, respectively, for tissue image classification. [sent-683, score-1.35]

88 By modeling the context of the morphometric information, these methods outperform traditional ones which were typically based on pixel- or patch-level features. [sent-684, score-0.601]

89 Due to i) the effectiveness of our morphometric context representations; and ii) the important role of cellular context for the study of different cell assays, proposed methods are suggested to be extendable to image classification tasks for different cell assays. [sent-686, score-0.753]

90 Future work will be focused on accelerating the sparse coding through the sparse auto encoder [15], utilizing supervised dictionary learning [21] for possible improvement, and further validating our methods on other tissue types and other cell assays. [sent-687, score-0.364]

91 Effect of quantitative 222222000977 [2] [3] [4] [5] nuclear features on recurrence of ductal carcinoma in situ (dcis) of breast. [sent-697, score-0.312]

92 Automatic identification and delineation of germ layer components in h&e; stained images of teratomas derived from human and nonhuman primate embryonic stem cells. [sent-707, score-0.051]

93 Automated cancer diagnosis based on histopathological images: A systematic survey, 2009. [sent-754, score-0.116]

94 Image denoising via sparse and redundant representations over learned dictionaries. [sent-758, score-0.051]

95 The pyramid match kernel: discriminative classification with sets of image features. [sent-790, score-0.05]

96 Time efficient sparse analysis of histopathological whole slide images. [sent-807, score-0.173]

97 Fast infer– [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] ence in sparse coding algorithms with applications to object recognition. [sent-813, score-0.068]

98 Biological interpretation of morphological patterns in histopathological whole slide images. [sent-829, score-0.142]

99 Beyond bags of features: Spatial pyramid matching for recognizing natural scene categories. [sent-835, score-0.05]

100 Linear spatial pyramid matching using sparse coding for image classification. [sent-904, score-0.137]


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