Victor Fritz1, Martin Schwartz1,2, Jens Kübler3, Simon Böke4, Jonas Habrich5, Daniel Zips4, Daniela Thorwarth5, Konstantin Nikolaou3, and Fritz Schick1
1Department of Diagnostic and Interventional Radiology, University of Tuebingen, Section on Experimental Radiology, Tuebingen, Germany, 2University of Stuttgart, Institute of Signal Processing and System Theory, Stuttgart, Germany, 3Department of Diagnostic and Interventional Radiology, University of Tuebingen, University Hospital Tuebingen, Tuebingen, Germany, 4Department of Radiation Oncology, University of Tuebingen, University Hospital and Medical Faculty, Tuebingen, Germany, 5Department of Radiation Oncology, University of Tuebingen, Section for Biomedical Physics, Tuebingen, Germany
Synopsis
The aim of this work was to identify potential texture features as imaging biomarkers for monitoring treatment response in head and neck cancer (HNC). For this purpose, a total number of 93 texture features were extracted on segmented calculated ADC maps and compared at baseline and in the early treatment phase of radiation therapy (RT). Fifteen texture features showed a statistically difference in the course of RT. In particular, features suggesting that ADC-based HNC texture became finer but more heterogeneous changed significantly. Presented preliminary results offer initial findings that will be systematically investigated in upcoming studies.
Introduction
There is an
increasing interest in the identification of magnetic resonance imaging (MRI)
biomarkers to rapidly and accurately predict the response of a tumor to
therapy. In particular, the apparent diffusion coefficient (ADC-value) and
radiomic texture features are considered promising biomarkers for monitoring
treatment response in oncology1-10. Various publications have
already shown that the ADC-value, as determined from diffusion weighted MRI
(DWI), increases with a decrease of tumor cell density caused by the
application of radiation therapy (RT)11,12. Further features changing
significantly between baseline (pre-RT) and the early treatment phase can
create synergies and thus enable an optimized prediction of tumor response.
Texture analysis provides a promising tool for discovering new imaging
biomarkers to identify changes in tumor during the course of therapy. The
texture analysis technique uses mathematical methods to extract features in the
image that contain information about the spatial distribution of image
intensity-levels and their dependence to one another13,14.
The overall
purpose of this work was to identify potential texture features as imaging
biomarkers for monitoring treatment response in head and neck cancer (HNC). For
this, texture features were extracted on segmented calculated ADC maps and
compared at baseline and in the early treatment phase. In addition, differences
in significant features were compared with the change in the ADC-value over the
course of therapy.Materials and Methods
Patient and image acquisition
The
study included eight patients with locally advanced HNC who underwent RT. DWI
was performed on a clinical, whole-body 3.0T MR-scanner (MAGNETOM Vida,Siemens
Healthcare,Erlangen,Germany) at baseline (examination 1) and during the second
week of RT (examination 2). ADC maps derived from DWI were used for the texture
analysis described below. The parameterization of the imaging protocol is shown
in Table 1.
Segmentation and feature extraction
Tumor
segmentation was carried out by an experienced radiologist using an open source
medical image computing software (3D slicer15,https://www.slicer.org/).
For each patient and each examination, the entire tumor volume was manually segmented
on calculated ADC maps (Figure1). T2-weighted (T2w) and T1-weighted (T1w)
dynamic contrast enhanced images were used as a reference for visual
co-registration.
Textural
feature extraction was performed using the open source python package
PyRadiomics16 as a plugin in 3D slicer. A total number of 93 texture
features (first order (18), Gray Level Cooccurrence Matrix-(GLCM) (24), Gray
Level Run Length Matrix-(GLRLM) (16), Gray Level Size Zone Matrix-(GLSZM) (16),
Neighbouring Gray Tone Difference Matrix-(NGTDM) (5), Gray Level Dependence
Matrix-(GLDM) (14)) were extracted from each segmented tumor. All features were
computed on the original non-normalized ADC maps using a bin width of 25. The
definition and mathematical calculation of the texture features can be found on
the PyRadiomics documentation site (https://pyradiomics.readthedocs.io/en/latest/features.html).
Statistical analysis
To check
whether and to what extent certain texture features change in the course of RT,
relative differences in texture between the first and the second examination
were calculated using the following formula: Δ(%) = ((feature2,mean - feature1,mean)/feature1,mean) *100%,
the indices
(1,2) stand for examination 1 (before RT) and examination 2 (second week of
RT), respectively. For each feature and each
examination, the mean value across all eight patients was considered.
Test on
statistically significant differences was applied by using a two-sided Wilcoxon
signed-rank test with a significance level of α = 0.05. The same procedure was
carried out for the ADC-values of both examinations. All statistical analysis
was performed in MATLAB (The MathWorks,Inc.,Natick,MA).Results and Discussion
Fifteen texture
features in HNC showed a statistically significant difference in the course of RT.
Table 2 and Figure 2 illustrate the mean values of each feature and their percentage
differences between the two examinations. In addition, the mean ADC-value of
both examinations and their percentage difference is given.
The ADC-value
averaged over all patients increased during RT. There was a mean increase of
about 20.75 % (p=0.0078). The First Order texture feature “mean” revealed
similar values indicating proper texture analysis settings.
The most
pronounced changes were found for two texture features from the group of the GLSZM:
LargeAreaEmphasis(GLSZM)
(-48,1 %;p=0.0234) and ZoneVariance(GLSZM)
(-59.5 %;p=0.0156). Since smaller values of these two texture features indicate
more fine textures, the significant decrease in the values of both features
suggests that texture in HNC became finer over the course of RT. In addition,
the texture of HNC seems to become more heterogeneous due to the influence of
RT, as highlighted by a decrease of LargeDependenceEmphasis(GLDM) (-21.3 %;p=0.0234),
DependenceVariance(GLDM)
(-27.9 %;p=0.0234) and JointEnergy(GLCM)
(-17.6 %;p=0.0391). Lower values of these texture features indicate less
homogeneous patterns in the masked tissue and thus a lower homogeneity of the
HNC texture.
Other
significant texture features, such as GLRLM features, were not analyzed further
due to their small differences (Δ(%) < 3%) between
the two examinations.Conclusion
Preliminary
results in this work showed that ADC-based HNC texture became finer but more heterogeneous
over the course of RT. Percentage changes in the corresponding texture features
were comparable to or significantly greater than the change in the ADC-value.
Due to the small number of patients, the strength of the preliminary results is
limited. Nevertheless, presented results are promising and offer initial
findings that will be systematically investigated in upcoming studies with a
larger cohort of patients.Acknowledgements
This work was supported and funded by the German Research Foundation (DFG) under Grants SCHI 498/14-1| TH 1528/6-1| NI 707/7-1 (Package No. 997/1).References
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