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Research Article

Impact of slice thickness on reproducibility of CT radiomic features of lung tumors

[version 1; peer review: 1 approved with reservations]
PUBLISHED 12 Oct 2023
Author details Author details
OPEN PEER REVIEW
REVIEWER STATUS

This article is included in the Manipal Academy of Higher Education gateway.

Abstract

Background: Radiomics, a field of research, relies on the theory that quantified characteristics from radiographic images would reflect underlying pathophysiology. Lung cancer continues to stand as one of the prevalent and well-known forms of cancer, causing mortality. The slice thickness (ST) of computed tomography (CT) images would be key concern regarding generalizability of radiomic features (RF) results in oncology. There is scarcity of research that has delved into how ST affects variability of RF in lung tumors. Hence, aim of the study is to evaluate influence of ST on reproducibility of CT-RF for lung tumors.
Methods: This is a prospective study, 32 patients with confirmed histopathological diagnosis of lung tumors were included. Contrast Enhanced CT (CECT) thorax was performed using a 128- Incisive CT (Philips Health Care). The image acquisition was performed with 5-mm and 2 mm ST, and was reconstructed retrospectively. RF were extracted from the CECT thorax images of 5-mm and 2-mm ST. We conducted a paired t-test to evaluate the disparity in RF between the two thicknesses. Lin’s Concordance Correlation Coefficient (CCC) was performed to identify the reproducibility of RF between the two thicknesses.
Results: Out of 107 RF extracted, 66 (61.6%) exhibited a statistically significant distinction (p<0.05) when comparing two slice thicknesses and while 41 (38.3%) RF did not show significant distinction (p>0.05) between the two ST measurements. 29 features (CCC ≥ 0.90) showed excellent to moderate reproducibility, and 78 features (CCC ≤ 0.90) showed poor reproducibility. Among the 7 RF categories, the shape-based features (57.1%) showed the maximum reproducibility whereas NGTDM-based features showed negligible reproducibility.
Conclusions: The slice thickness had a notable impact on the majority of CT-RF of lung tumors. Shape based features (57.1%). First order (44.4%) features showed highest reproducibility compared to other RF categories.

Keywords

Lung Cancer, Radiomics, Computed Tomography, Slice Thickness, CT Parameters

Introduction

Radiomics is a new field that seeks to improve the physician’s visual perception of medical images with addition of more quantitative objectivity. The quantitative attributes from radiographic images are utilized to characterize spatial and textural patterns of lesions which can provide information about the heterogeneity associated with biological processes. Radiomics is a rapidly evolving field particularly in oncology to improve patient care, aid in treatment decision making, characterization, response to therapy and prognosis.15

Lung cancer/carcinoma (LC) remains one among the most prevalent and familiar types of cancer that results in mortality notwithstanding recent improvements in healthcare. As, most detected LC are in the middle to late phase of the disease progression and have few management options left, hence, people with lung cancer have a 10-20% survival rate at 5 years following the diagnosis in most of the developed nations.67 Radiomics and Machine learning methods have been used for classification of histological subtypes of LC, prediction of LC staging and outcome, response to treatment, prognosis of lung cancer.811

Radiomics, a rapidly evolving field, employs quantitative attributes from medical images to enhance physician’s interpretation, particularly in oncology. Radiomics and machine learning models developed based on radiomic features play crucial roles in classifying histological subtypes lung cancer. Evaluating the variability of radiomic features (RF) is important as diagnosis and treatment decision made using these quantitative should be precise and reproducible. Recent studies have shown that the CT technical parameters such as exposure factors, slice thickness (ST) and image reconstruction algorithms (IRA) can significantly affect the values of RF. Experts have recommended that for training predictive models using radiomics based machine learning models, only reproducible RF should be considered.1214 The reproducibility of texture analysis of lung tumors is unclear and there is scarcity of research that has delved into how ST affects variability of RF in lung tumors. Hence, aim of the study is to evaluate the influence of ST on reproducibility of CT -RF for lung tumors.

Methods

This is a prospective study. The study was commenced upon approval from the Institutional Ethical committee of Kasturba Medical College and Hospital, Manipal, India on 12th August 2022 (IEC:193/2022) followed by the enrolment of the first subject after registration in the Clinical Trial Registry – India (CTRI) registration (CTRI/2022/09/045554) on 15th September 2022, and continued till 30th April 2023.

Eligibility criteria

Patients with histopathological diagnosis of lung cancer types such as Non-Small Cell Lung Carcinoma (NSCLC) and Small Cell Lung Carcinoma (SCLC) were included. We excluded patients with ground glass nodules (GGN), lesions measuring less than 4mm, scans with motion artifacts and patients that did not consent to take part in the study. Written informed consent to participate was obtained from each patient.

CT scanning procedure

The study was conducted at the Department of Radiodiagnosis, Kasturba Medical College and Hospital, Manipal, India. Both Kasturba Medical College and Hospital (KMC) and Manipal College of Health Professions (MCHP) are constituent colleges of Manipal Academy of Higher Education (MAHE). A total of thirty-two (32) patients with confirmed histopathological diagnosis of lung cancer (NSCLC- 71.8% & SCLC-28.1%) between September 2022 to April 2023 were included and all patients consented. The study population's demographic characteristics are outlined in (Table 1).

Table 1. Demographic characteristics of study population.

CharacteristicsData
Age (Mean ± SD)53.16 ± 10.25
Gender (%)
Male (M)18 (56.25 %)
Female (F)14 (43.75%)
Tumor size, mm (Mean ± SD)17.20 ± 15.77
Pathology (%)Ca Lung/Pulmonary tumors

  • NSCLC-71.8%

  • SCLC-28.1%

Location (Lung)
Right10 (31.2%)
Left7 (21.8 %)
Bilateral15 (46.8%)

All patients underwent Contrast Enhanced CT (CECT) Thorax examination using 128 Slice Incisive CT (Philips Medical Systems). The protocol used for the CECT Thorax examination of the study population is detailed in Table 2. Retrospective reconstruction of the CT images was carried out utilizing CECT images from a standard protocol of 5mm to produce a ST of 2 mm. Contrast scans were performed using Iohexol 300 mgI/ml (General Electric Health care, Wisconsin, USA) as the contrast agent. The contrast media was administered using Dual Head CT Pressure injector, OptiVantage (Guerbet, France, UK).

Table 2. Technical parameters of CECT Thorax Protocol.

ProtocolChest helical
Patient positionSupine - feet first
ScanogramPA – 180 degree
Area coverageApex of lungs to the domes of diaphragm
Scan orientationCraniocaudal
Acquiring Slice thickness5mm
Slice increment5mm
Kilovoltage (kVp)120
Milliampere second (mAs)360
Collimation64 x 0.625
Rotation time0.75 seconds
Field of view (FOV)350 mm
Matrix size512 x 512
Pitch1.08
ContrastOmnipaque – Iohexol (300 mgI/ml)
Volume (60 ml)

Segmentation

The Digital Imaging and Communication in Medicine (DICOM) CECT sections of two different slice thickness (2 mm and 5 mm) of the same patient were loaded into 3D slicer (version 4.10.2) and a radiologist (Bharath J L) with over 10 years of experience manually delineated the tumours (see Figure 1 for an example). The segmentation was performed using lung window (Window Width (WW): 1500 HU and Window Level (WL): -600 HU). All pulmonary nodules/lesions present in the right, left, and bilateral lungs were segmented rather than solely selecting the largest or most prominent nodule/lesion. The segmentation of the nodule was performed while excluding the airways, blood vessels, or bronchi. We extracted RF from the segmented regions of the lung nodules using both 2-mm and 5-mm ST.

fd39077d-7e38-4cc3-a6ae-3fee2dcbbe70_figure1.gif

Figure 1. An axial CT image of a 52-year-old male with adenocarcinoma showing manual segmentation of tumour using 3D Slicer at (a) 2mm and (b) 5mm slice thickness.

Statistical analysis

Statistical analysis was done using SPSS version 20.0. A Paired t-test was performed to identify the significant difference in RF between the two slice thickness (2 mm and 5 mm) groups. Lin’s Concordance Correlation Coefficient (CCC) was calculated to assess the reproducibility of RF between two groups (2 and 5 mm). Concordance Correlation Coefficient of > 0.99 suggests excellent reproducibility, > 0.95 to 0.99 suggests good reproducibility, >0.90 to 0.95 suggests moderate reproducibility, ≤ 0.90 suggests weak reproducibility. p-value (<0.05) was considered.

Results

A total of 32 cases (18 males and 14 females) with LC [Non-Small Cell Lung Cancer (NSCLC) – 71.8%, Small Cell Lung Cancer (SCLC) – 28.1%)] with mean age of were included 53.16 ± 10.25.

A total of 3424 RF measurements (107 RF per study) were extracted. Among them 66 (61.6%) RF exhibited significant difference between two the slice thickness measurements, while 41 (38.3%) RF did not show significant difference between the two slice thickness measurements. (Figure 2; Table 3).

fd39077d-7e38-4cc3-a6ae-3fee2dcbbe70_figure2.gif

Figure 2. Number of significant (p<0.05) and non-significant (p>0.05) features in each RF category between 2-mm and 5-mm slice thickness.

Table 3. Percentage of significant and non-significant RF between 2-mm and 5-mm ST for each category.

RF CategoryFeatures with p<0.05 [n(%)]Features with p>0.05 [n(%)]
Shape (n=14)4 (28.75%)10 (71.42%)
GLDM (n=14)9 (64.28%)5 (35.71%)
GLCM (n=24)20 (83.33%)4 (16.66%)
First order (n=18)12 (66.66%)6 (33.33%)
GLRLM (n=16)9 (56.25%)7 (43.75%)
GLSZM (n=16)9 (56.25%)7 (43.75%)
NGTDM (n=5)3 (60.00%)2 (40.00%)

Reproducibility of RF

It was found that out of 14 shape-based features 8 (57.1%), out of 14 Gray Level Dependence Matrix (GLDM) RF 5 (35.71%), out of 24 for Gray Level Co-occurrence Matrix (GLCM) RF 3 (12.5%), out of 18 first order RF 8 (44.4%), out of 16 Gray level run length matrix (GLRLM) RF 4 (25%), out of 16 Gray level size zone matrix (GLSZM) RF 1 (6.25%) were found to be reproducible. All 5 neighboring gray tone difference matrix (NGTDM) RF were found to be not reproducible. Among the seven features categories, the shape-based features (57.1%) showed the maximum reproducibility whereas NGTDM based features showed negligible reproducibility (Table 4). The mean CCC of RF categories were shown in (Figure 3).

Table 4. Percentage of reproducibility of RF between 2-mm and 5-mm ST for each category.

RF CategoryExcellent n(%)Good n(%)Moderate n(%)Weak n(%)
Shape (n=14)2 (14.2%)3 (21.4%)3 (21.4%)6 (42.8%)
GLDM (n=14)--5 (35.7%)9 (64.2 %)
GLCM (n=24)--3 (12.5%)21 (87.5%)
First order (n=18)-1 (5.5%)7 (38.8%)10 (55.5%)
GLRLM (n=16)-1 (6.25 %)3 (18.75 %)12 (75 %)
GLSZM (n=16)--1 (6.25%)15 (93.75%)
NGTDM (n=5)---5 (100%)
fd39077d-7e38-4cc3-a6ae-3fee2dcbbe70_figure3.gif

Figure 3. Mean concordance correlation coefficient (CCC) of each radiomic feature category between 2-mm and 5-mm slice thickness.

Shape-based category

In shape-based category, features such as Voxel volume (0.997) and Mesh volume (0.997) showed excellent reproducibility. Major (0.973) and minor axis length (0.959), maximum 2D-diameter (0.976) had good reproducibility. Maximum 3D-diameter (0.944), maximum 2D-diameter slice (0.926) and maximum 2D-diameter row (0.903) had moderate reproducibility and rest of the six features showed poor reproducibility between 2- and 5-mm slice thickness.

GLDM category

In GLDM category, features such as high gray level emphasis [HGLE] (0.918), dependence entropy [DE] (0.929), small dependence emphasis [SDE] (0.935), dependence non uniformity normalized [DNU] (0.935) and large dependence high gray level emphasis [LDHGLE] (0.903) showed moderate reproducibility and rest of the nine features showed poor reproducibility between 2- and 5-mm slice thickness.

GLCM category

In GLCM category, features such as Idm (0.930), Id (0.922) and Sum squares (0.908) showed moderate reproducibility and rest of the twenty-one features showed poor reproducibility between 2- and 5-mm slice thickness.

First order category

In first order category, features such as 10th percentile (0.961) showed good reproducibility, Skewness (0.948), Uniformity (0.947), Median (0.921), Total energy (0.920), Root mean squared (0.945), Entropy (0.943) and Mean (0.943) showed moderate reproducibility and rest of the ten features showed poor reproducibility between 2- and 5-mm slice thickness.

GLRLM category

In GLRLM category, features such as Gray level non uniformity normalized (0.952) showed good reproducibility, Short run emphasis (0.949), Run percentage (0.936) and Run length non uniformity normalized (0.943) showed moderate reproducibility and rest of the twelve features showed poor reproducibility between 2- and 5-mm slice thickness.

GLSZM category

In GLSZM category, feature such as Zone percentage (0.906) showed moderate reproducibility and rest of the fifteen features showed poor reproducibility between two slice thicknesses.

NGTDM category

In the NGTDM category, all the five features showed poor reproducibility between 2- and 5-mm slice thickness.

Discussion

In the present study, we assessed the impact of slice thickness on the reproducibility of CT radiomic features (RF) for lung tumors. Few previous studies had addressed the influence of exposure parameters such as tube voltage (kVP), tube current (mA), image reconstruction algorithms (IRA), CT Scanner vendors on RF in CT for conditions like liver fibrosis, metastatic liver lesions, pancreatic neuroendocrine neoplasm.1518 Variability of acquisition parameters could affect the diagnostic performance of radiomic signatures in oncologic patients.1819 Limited studies had investigated the impact of ST on reproducibility of CT-RF in lung tumors.

In this study, the category of shape-based RF (57.1%) exhibited the highest reproducibility compared to other RF categories. These shape based features demonstrated robustness due to presence of low-frequency components and the reliance on segmented boundaries resulting in consistent reproducibility across changes in ST. Findings by Erdal et al.20 & Lu et al.21 supported this, revealing that RF describing tumor dimension, shape of boundaries, low-order density frequencies, and rough features were less sensitive to image setting parameters, in contrast to features characterizing sharpness of boundaries, high-order density frequencies and smooth features. Both studies analyzed the combination of ST with IRA (lung and standard) and noted that shape-based features were less effected by change in slice thickness and reconstruction algorithm. They also observed that the thinner slices with sharper reconstructions had fewer reproducible features compared to thicker slices with smoother reconstructions.

The GLDM category features in our study, such as HGLE, DE, SDE, DNU, LDHGLE demonstrated moderate reproducibility. A study by Emaminejad et al.22 in non-contrast chest CT (NCCT) identified that GLDM DE, DNU, GLNU were reproducible against the dose and kernel variations with varying slice thickness. Unlike our study, none of the previous research mentioned the reproducibility of GLDM features concerning slice thickness alone.

Within the GLCM category in our study, only two features showed reproducibility with variations in slice thickness. Similar results were documented by Erdal et al.20 & Kim et al.23 indicating that GLCM category (19.4 % & 25 %) had lower reproducibility compared to other RF categories. We observed that first-order features (44.4%) had the second highest reproducibility. Studies by Erdal et al.,20 Park s et al.,24 Choe J et al.25 reported that first-order features exhibited the most reproducibility across various imaging parameters. Park s et al.24 and Choe J et al.25 reported that convolution network-based super resolution (SR) algorithms and kernel-converted images had reduced effects on the reproducibility of RF with variations in slice thickness and reconstruction kernels. Yang et al.26 employed a resampling technique to standardize the voxel measurement of both thick and thin section CT images to 1x1x1 mm3 using linear interpolation and observed that, following resampling of thicker images, 202 RF (66.2%, 202/305) exhibited a noteworthy reduction in variability of RF compared to the original non-resampled data (Table 5).

Table 5. Comparison of reproducibility of radiomic features with CT technical parameters and Slice thickness combinations in lung cancer between current study and other recent studies.

Author name (year)Our study (2023)Lu et al.21 (2016)Erdal et al.20 (2020)Yang et al.26 (2020)Emaminejad et al.22 (2021)
Pathology studiedLung tumors (SCLC, NSCLCL)Lung cancerLung nodulesSolid pulmonary nodulesLung cancer
Study ProcedureCECTNCCTNCCTCECTNCCT
Technical parametersST (2 and 5- mm)IRA (Lung and standard)
ST
Dose levels (4)
Kernels (10)
Thicknesses (8)
ST (1.25 mm and 5 mm)Dose levels (100 %, 50%, 25% and 10 %)
ST (0.6, 1 and 2 mm)
Reconstruction kernel (smooth, medium, sharp)
RF extracted1078928396226
Features extractedShape, GLDM, GLCM
First order, GLRLM
GLSZM, NGTDM
Tumor size, Shape, Boundary shape, Sharpness, Density distributions with and without spatial informationHistogram, GLCM, RLM, NGDLM,NGTDMHistogram, Geometry
Texture features
First-order, Wavelet Features, GLDM, GLRLM, GLCM, GLSZM, NGTDM
Reproducibility of RFShape based features (57.1%), First order (44.4%) features showed highest reproducibility compared to other RF categoriesEight of the feature groups associated with dimensions, form, and rough texture exhibited consistent reproducibility across all combinationsDensity feature was robust against dose changes, Skewness was robust for kernel and ST, Deviation was weakest feature for all cases. GLCM category was least reproducibleIn non-resampled data, 239 features were shown significant differences between thin and thick slice. 66 RF were reproducible.
In resampled data, 202 features exhibited significant differences between two thicknesses. 103 features were reproducible.
Seventeen and Eighteen features were reproducible with respect to dose and kernel changes. Only one to five features were reproducible with changes in slice thickness

For the GLRLM and GLSZM categories, reproducibility rates were 25% and 6.25 %, respectively, in the current study. A Study by Emaminejad et al.22 similarly found that GLRLM Run length non uniformity (1 of 9 features) and GLSZM (1 of 10 features) displayed very limited reproducibility against the dose and kernel variations with varying slice thickness. Contrary to the study reported by Liu J et al.27 which demonstrated that NGTDM exhibited good reproducibility, we did not observe any reproducible features in NGTDM. The reason for this disparity is attributed to differences in technical parameters, specifically in terms of dose variation, rather than slice thickness.

The study has few limitations. Firstly, the sample size was relatively small, as it is time bound study with prospective data collection of patients who underwent CT scan with histopathological proven cases of lung cancer. A larger sample size is required to confirm the reproducibility of RF with slice thickness. Secondly, we did not analyze whether a thinner slice thickness would result in better performance of radiomic models for predicting lung cancer. Thirdly, a single image acquisition variable such as slice thickness was examined to determine how it affects the reproducibility of radiomic features.

Conclusion

Radiomics has the potential to transform lung cancer diagnosis, follow-up, and therapy planning by enabling individualised management in a non-invasive and an economical manner. Our study found that ST is the main parameter impacting the reproducibility of CT-RF for lung tumours. The study also increases awareness regarding the significance of accurately configuring imaging acquisition parameters in the context of radiomic/radio genomic approaches. Standardization of technical parameters and protocols is necessary when conducting multicentre studies, as these factors can impact the diagnostic performance of Machine Learning (ML) models developed using radiomic features.

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Gupta S, Nayak K and Pendem S. Impact of slice thickness on reproducibility of CT radiomic features of lung tumors [version 1; peer review: 1 approved with reservations]. F1000Research 2023, 12:1319 (https://doi.org/10.12688/f1000research.141148.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Current Reviewer Status: ?
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ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
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Reviewer Report 26 Oct 2023
Mubarak Taiwo Mustapha, Near East University, TRNC Mersin, Nicosia, Turkey 
Approved with Reservations
VIEWS 23
Major comments
  1. The abstract could benefit from a more explicit mention of the study's original contribution to the field.
     
  2. Directly state the main research question that the study addresses.
... Continue reading
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HOW TO CITE THIS REPORT
Mustapha MT. Reviewer Report For: Impact of slice thickness on reproducibility of CT radiomic features of lung tumors [version 1; peer review: 1 approved with reservations]. F1000Research 2023, 12:1319 (https://doi.org/10.5256/f1000research.154563.r214642)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 01 Dec 2023
    Saikiran Pendem, Manipal College of Health Professions, Department of Medical Imaging Technology, Manipal Academy of Higher Education, Manipal, 576104, India
    01 Dec 2023
    Author Response
    Major Comments
    1. The abstract could benefit from a more explicit mention of the study's original contribution to the field.
    Response: The present study helps in identifying the specific Radiomic Feature ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 01 Dec 2023
    Saikiran Pendem, Manipal College of Health Professions, Department of Medical Imaging Technology, Manipal Academy of Higher Education, Manipal, 576104, India
    01 Dec 2023
    Author Response
    Major Comments
    1. The abstract could benefit from a more explicit mention of the study's original contribution to the field.
    Response: The present study helps in identifying the specific Radiomic Feature ... Continue reading

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Version 2
VERSION 2 PUBLISHED 12 Oct 2023
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Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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