Jinbo Qi1, Xiaoyue Ma1, Peipei Wang1, Eryuan Gao1, Guohua Zhao1, Kai Zhao1, Yang Song2, Huiting Zhang3, Ankang Gao1, Jie Bai1, Yong Zhang1, and Jingliang Cheng1
1Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, 2Magnetic Resonance Scientific Marketing, Siemens Healthineers Ltd., Shanghai, China, 3Magnetic Resonance Scientific Marketing, Siemens Healthineers Ltd., Wuhan, China
Synopsis
Keywords: Tumors, Diffusion/other diffusion imaging techniques, Neurite orientation dispersion and density imaging
We
aim to explore the value of neurite orientation dispersion and density imaging (NODDI)
maximum abnormal signal area histogram analysis for differentiation between
glioblastoma Multiforme (GBM) and solitary brain metastasis (SBM). 50 patients
with GBM and 50 patients with SBM confirmed by surgical pathology were enrolled
and underwent MR examination. Result showed that multiple histogram parameters can
significantly distinguish GBM from SBM, and the performance of logistic regression
model is better than that of optimal single parameter.
Introduction
Glioblastoma
multiforme (GBM) and solitary brain metastasis (SBM) are
common malignant brain tumors that may have similar imaging appearances to make
differential diagnosis challenging. Neurite
orientation dispersion and density imaging (NODDI) is a multi-sphere shell
diffusion model based on the differences in diffusion of water molecules inside
and out-side the cell1. NODDI can be used to quantize specific
microstructure characteristics directly related to neuron morphology, and the
new MRI technique is expected to provide more specific data on the
microstructure changes of dendrites and axons than diffusion tensor imaging
(DTI) and diffusion kurtosis imaging (DKI) analysis2,3. Kadota et al4 and Mao et al5 reported
that NODDI has potential for distinguish GBM from SBM, however, the sample size
was small and only mean value was analyzed, results in relatively low diagnostic
performance. In previous studies, the regions of interests (ROIs) were
usually placed on maximum cross-section or all-slice of tumor
contrast-enhanced area or peritumoral edema area, and then the mean values
were calculated4,6. Such a method is
only a simple average of the tumor local characteristic values, which cannot specifically
reflect the heterogeneity of tumor cells in the ROI region. Moreover, tumor local
contrast-enhanced area or peritumoral edema area cannot reflect the overall
heterogeneity of the tumor well, and may reduce tumor heterogeneity. Therefore,
this study aimed to evaluate the value
of histogram analysis based on NODDI maximum abnormal signal area (MASA,
included the whole tumor area and peritumoral edema area) in differentiating
between GBM and SBM.Methods
This
study included 100 patients with GBM (n=50) or SBM (n=50) diagnosed by surgical
histopathology who underwent MR examination within 7 days before surgery on a
3T system (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany), which
included axial T2-dark-fluid sequence and NODDI. The NODDI parameters were TR/TE
= 2500/71ms; FOV = 220×220 mm; scan matrix = 100×100; 100 slices; five b values
(500, 1000, 1500, 2000 and 2500 s/mm2) with 30 diffusion-encoding directions for each b value, and one b value of 0
s/mm2. An open source Amico tool (https://github.com/daducci/AMICO/) was used to fit NODDI
parameter, and the parametric maps of isotropic volume fraction (ISOVF),
intra-cellular volume fraction (ICVF) and orientation dispersion index (ODI)
were obtained. The ROI was placed on MASA (Fig. 1). The histogram
parameters (10 percentile (10th), 25 percentiles (25th), 50 percentiles (50th),
75 percentiles (75th), 90 percentiles (90th), mean, maximum (max), minimum (min),
variance, skewness, and kurtosis) were extracted by MATLAB (version. R2017b;
MathWorks, Natick, MA, USA). The gender distribution of patients was compared using the chi-square
test. The differences of the NODDI histogram parameters and age distribution
were compared using Mann–Whitney U test. Furthermore, the combination of these
parameters was also studied by logistic regression analysis to discriminate GBM from SBM more accurately. Receiver operating characteristic
(ROC) analyses and DeLong’s test were used to evaluate and compare the
diagnosis performances of significant univariate parameters and logistic
regression model, respectively. SPSS 26.0 (SPSS Inc., Chicago, IL, USA) and
MedCalc 20.010 (MedCalc Software Ltd, Ostend, Belgium) were used for statistical
analysis. Statistical significance was set at P < 0.05.Result
No
significant difference in gender (p=0.655) or age distribution (p=0.647)
between GBM and SBM. Significant differences were noted for differentiation
between GBM and SBM in ISOVF10th, ISOVF25th, ISOVF50th,
ISOVF75th, ISOVFmean, ISOVFskewness, ISOVFkurtosis,
ICVFmin, ICVFmax, ICVFkurtosis, ODI10th,
ODI25th, ODI50th, ODImin, and ODIskewness. Among them, the ISOVFskewness, ISOVFkurtosis,
ICVFmin, ICVFmax, ICVFkurtosis, ODI10th,
ODI25th, ODI50th, and ODImin of GBM are higher
than SBM, and the other parameters are lower than SBM (Fig. 2). In univariate analysis,
the ISOVF25th obtained the highest diagnostic performance, with AUC,
sensitivity and specificity of 0.731, 74.00% and 68.00%, respectively. The ICVFmax,
ICVFkurtosis, ISOVF25th, ISOVFskewness, and
ODImin were finally incorporated into the regression equation to
build logistic regression model. The AUC, sensitivity and specificity of logistic
regression model were 0.884, 78.00% and 86.00%, respectively (Fig. 3). DeLong’s test revealed that the AUC of ISOVF25th was
significantly different from that of logistic regression model (p=0.028). Finally,
the logistic regression model is visualized by nomogram (Fig. 4).Discussion
This
study evaluated the value of histogram analysis based on NODDI-MASA to
distinguish GBM from SBM. Results showed that multiple histogram parameters can
distinguish GBM from SBM, and the performance is better than previous studies. This
may be because histogram parameter extraction based on MASA of the tumor may
reflect the tumor heterogeneity more accurately and reliably and can also
avoid or reduce the sampling error caused by delineating local ROI as much as
possible7. In univariate
analysis, the ISOVF25th had the highest differential performance, reflecting isotropic
diffusion within the tissue, which was closely related to the pathogenesis of
the two tumors8. However, the univariate analysis may have some
limitations and cannot be analyzed comprehensively. A logistic regression model
was constructed, which greatly improved the differential performance of the two
tumors. Meanwhile, the prediction model can be visualized by nomogram to transform
the abstract mathematical model into quantitative score evaluation and provide
objective identification basis for clinical diagnosis.Conclusion
NODDI-MASA histogram analysis is
helpful in differentiating GBM from SBM, in which the logistic regression model
has the best diagnostic performance.Acknowledgements
We are deeply grateful to our participants and their families for their generous support for our study.References
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