Rupsa Bhattacharjee1,2, Rakesh Kumar Gupta3, Rana Patir4, Sandeep Vaishya4, Sunita Ahlawat4, and Anup Singh1,5
1Center for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India, 2Philips Health Systems, Philips India Limited, Gurugram, India, 3Department of Radiology, Fortis Memorial Research Institute, Gurugram, India, 4Department of Neurosurgery, Fortis Memorial research Institute, Gurugram, India, 5Department of Biomedical Engineering, All India Institute of Medical Sciences, New Delhi, India
Synopsis
No standalone method is yet reported
to differentiate PCNSL and grade-IV glioma with highest accuracy and diagnostic
confidence. Imaging based differentiation between these two types has been a
challenging problem. Objective of this study is to evaluate performance of
texture-based features of SWI in improved differentiation of PCNSL from
grade-IV gliomas. Proposed approach
based upon texture feature-extraction from segmented SWI lesion, enabled
automatic classification of tumors into primary central nervous system lymphoma
and grade-IV glioma cases. One of the texture feature, Contrast, provided
highest AUC along with high sensitivity and specificity. This classification
might improve diagnosis and grading of tumors.
Introduction:
Primary central nervous system
lymphoma (PCNSL) is a common type of malignant tumor, which is different from
glioma in terms of tumor biology as well as treatment planning. Mostly PCNSL
treatment involves chemo and/or radio-therapy [1-2], whereas surgical resection
is the most common practice in case of grade IV gliomas for survival
improvement. Imaging based differentiation between these two types has been a
challenging problem. ADC, T1-post contrast, FLAIR, DTI, DCE-perfusion MR
sequences have been shown to differentiate up to certain accuracy [3]. No
standalone method is yet reported to differentiate PCNSL and grade-IV glioma
with highest accuracy and diagnostic confidence. Ding et.al have reported use
of susceptibility weighted imaging (SWI) in classifying lymphoma based on the
lower incidence of hemorrhages and vessels compared to glioma and metastases,
with an accuracy better than conventional T1-post contrast or DWI imaging
methods alone [4]. Texture based feature extraction methods are also being
employed as one of the ways for differentiation. Leon et.al and few other
studies have already reported that texture features of T1-post contrast
sequence differs in lymphoma compared to GBM [5]. Objective of this study is to
evaluate performance of texture-based features of SWI in improved differentiation
of PCNSL from grade-IV gliomas. Material and Methods
This
retrospective study, approved by IRB, included total 38 patients (15 PCNSL and 23
grade IV glioma confirmed histologically as per WHO-2016-criteria). These
patients underwent brain MRI on a 3.0T scanner (Ingenia, Philips Healthcare,
The Netherlands). SWI data were acquired with 4 echoes at 5.6, 11.8, 18, 24.2ms
(TR=31ms; flip-angle=17°, slice-thickness=1.0mm, acquisition-matrix=384×384,
FOV=240×240mm2). The SW-Magnitude images were obtained from scanner
by multiplying fast-field-echo (FFE)-M image with a phase-mask derived from
PADRE (Phase-Difference-Enhanced-imaging) filtering process. The structural T2, FLAIR and DWI weighted
images were also obtained and used to define the tumor boundary manually and
were co-registered with the SWI magnitude images. For each tumor, polygonal
ROIs were manually marked on registered FLAIR hyper-intense regions visible in
all the tumor-containing slices and the ROIs were copied to subsequent SWI
images. ROI were marked by PhD student and verified by experienced radiologist.
Lesion area was segmented by MATLAB-based in-house developed algorithm. The
segmented lesion intensities were normalized with average intensity in the contralateral
normal area. In this study we computed second-order texture features from multidimensional
histograms: the mean of the 13 Haralick features computed from the gray-scale
co-occurrence matrix (GLCM). The GLCM functions characterize the texture of an
image by calculating how often pairs of pixel with specific values and in a
specified spatial relationship occur in an image, creating a GLCM, and then
extracting statistical measures from this matrix. GLCM considers the spatial
relationship of the pixels taken over all 13 neighbor orientations: Correlation,
Energy, Contrast, Sum of squares variance, Entropy, Homogeneity, Sum average,
Sum entropy, Sum variance, Difference entropy, Difference variance, Information measure of correlation1, and
Information measure of correlation2. Statistical unpaired-t-test was
performed to check whether there is any significant difference of GLCM based
metrics between PCNSL and grade-IV glioma. ROC curve analysis was used to evaluate
the performance of GLCM based texture feature between pCNSL and grade-IV glioma
by comparing the AUC. The highest sum of sensitivity and specificity was used
to establish the cutoff values in differentiating pCNSL and grade-IV glioma. All
statistical analysis were performed using MedCalc [6]. p ≤ 0.05 indicated a
statistically significant difference.Results and Discussion
Figure 1 shows sample case of each lymphoma and Glioma grade-IV.
Unpaired-t-test of 13 features
provided significant p value (p<0.05) only for GLCM texture feature
“Contrast”. Figure-1 summarizes the GLCM: contrast parameter for PCNSL and
Glioma grade-IV. Figure 2 demonstrates the results of the ROC curve analysis where
the AUC is proportional to the diagnostic accuracy. GLCM: contrast parameter showed
an AUC of 0.925, for the discrimination of pCNSL and grade-IV glioma. The best
cut-off value of Contrast texture feature obtained from the ROC analysis is >393862. This cut-off
can differentiate between pCNSL
and grade-IV glioma with a 82.61% and specificity of 92.33%. This study
demonstrate GLCM-Contrast values were much higher in Grade-IV compared to
primary lymphoma. This feature defers the calculation of the intensity contrast-linking
pixel and its neighbor over the whole Lesion area/region. Contrast is a measure
of the local variations present in an image.
In
grade-IV glioma, lesion-segmented region in SWI has a large amount of variation
compared to lymphoma, due to higher amount of hemorrhage and vessels presence
inherently. Thus Contrast texture feature captured this information and
provided differentiation between these two types of lesions. This approach, is
more objective and quantitatively differentiates lymphoma from grade-IV glioma.
Further studies on more number of patients and use of additional features for
improving accuracy of differentiation. In the current study, SWI image
intensities were normalized with values in the contralateral tissue. This normalization
takes care of any intensity-scaling bias that could be present in the datasets.Conclusion
Proposed
approach based upon texture feature extraction from segmented SWI lesion,
enabled automatic classification of tumors into primary central nervous system
lymphoma and grade-IV glioma cases. One of the texture feature, Contrast,
provided highest AUC along with high sensitivity and specificity. This
classification might improve diagnosis and grading of tumors.Acknowledgements
No acknowledgement found.References
[1] Shiels
MS, Pfeiffer RM, Besson C, et al.: Trends in primary central nervous system
lymphoma incidence and survival in the U.S. Br J Haematol 2016; 174: 417–24.
[2] Kuker
W, Nagele T, Korfel A, et al.: Primary central nervous system lymphomas
(PCNSL): MRI features at presentation in 100 patients. J Neurooncol 2005; 72:
169–77.
[3] Zacharia
TT, Law M, Naidich TP, Leeds NE:Central nervous systemlymphoma characterization
by diffusion-weighted imaging and MRspectroscopy.J Neuroimaging2008,18:411–17.
[4] Y. Ding,
Z. Xing, B. Liu, et al., Differentiation of primary central nervous system
lymphoma from high-grade glioma and brain metastases using susceptibility
weighted
imaging, Brain Behav. 4 (2014)
841–849.
[5] Alcaide-Leon
P, Dufort P, Geraldo AF, et al. Differentiation of Enhancing Glioma and Primary
Central Nervous System Lymphoma by Texture-Based Machine Learning. AJNR Am J
Neuroradiol 2017;38:1145-50.
[6] MedCalc Statistical Software Version 14.8.1
(2014) MedCalc Software, Ostend, Belgium.