Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical lymph nodes: A Comparative Analysis Based on DLSCT

Varalee Mingkwansook; Urusaya Wangprasertkul; Warit Tarathipmon; Arvemas Watcharakorn

doi:10.12688/f1000research.146149.2

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Research Article

Revised

Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical lymph nodes: A Comparative Analysis Based on DLSCT

[version 2; peer review: 2 approved]

Previous title: Iodine density of lymphoma, metastatic SCCA, and normal cervical lymph nodes: Based on DLSCT

Varalee Mingkwansook ¹, Urusaya Wangprasertkul¹, Warit Tarathipmon¹, Arvemas Watcharakorn¹

PUBLISHED 02 Jan 2025

Author details Author details

¹ Radiology, Thammasat University, meung, pathumtani, 12000, Thailand

Varalee Mingkwansook
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Urusaya Wangprasertkul
Roles: Data Curation, Project Administration

Warit Tarathipmon
Roles: Formal Analysis

Arvemas Watcharakorn
Roles: Methodology

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the Faculty of Medicine – Thammasat University collection.

Abstract

Objective

To compare iodine density (ID) and contrast-enhanced attenuation value (CEAV) from dual-layer spectral computed tomography (DLSCT) scans of lymphomatous, metastatic squamous cell carcinoma (SCCA), and normal cervical lymph nodes.

Methods

Data including ID and CEAV were retrospectively collected from patients who underwent DLSCT of the neck between January 2020 and August 2023. Results from each group (lymphomatous, metastatic SCCA, and normal) were compared and analyzed using one-way ANOVA and receiver operating characteristic curve.

Results

129 cervical lymph nodes were collected from patients who met the inclusion criteria (50, 41, and 38 nodes from the lymphomatous, metastatic SCCA, and normal group, respectively). The mean ID of lymphomatous, metastatic SCCA, and normal nodes was 1.01±0.27, 1.36±0.28, and 1.45±0.29 mg/mL, respectively. Comparing lymphomatous nodes with metastatic SCCA nodes, the lymphomatous nodes had significantly lower values of ID (p<0.002) and CEAV (p<0.001). Similarly, when comparing lymphomatous nodes with normal nodes, the lymphomatous nodes had significantly lower values of ID (p<0.001) and CEAV (p<0.001). The optimal ID cut-off value for distinguishing between lymphomatous and metastatic SCCA nodes was 1.175 mg/ml (specificity of 84.2%, sensitivity 77.8%, AUC 0.788, P = 0.003). The optimal CEAV cut-off value was 77.5 HU (specificity 88.9%, sensitivity 78.9%, AUC 0.851, P<0.001).

Conclusions

The ID and CEAV measurements from DLSCT were significantly different between lymphomatous, metastatic SCCA, and normal lymph nodes. These findings indicate that DLSCT can be used to distinguish between these conditions in the diagnosis of cervical lymph nodes.

Keywords

Iodine density, contrast-enhanced attenuation value, cervical lymph node, lymphoma, squamous cell cancer, dual-layer spectral computed tomography

Corresponding author: Varalee Mingkwansook

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2025 Mingkwansook V et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Mingkwansook V, Wangprasertkul U, Tarathipmon W and Watcharakorn A. Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical lymph nodes: A Comparative Analysis Based on DLSCT [version 2; peer review: 2 approved]. F1000Research 2025, 13:498 (https://doi.org/10.12688/f1000research.146149.2) First published: 17 May 2024, 13:498 (https://doi.org/10.12688/f1000research.146149.1) Latest published: 02 Jan 2025, 13:498 (https://doi.org/10.12688/f1000research.146149.2)

Revised Amendments from Version 1

- The phrase 'A Comparative Analysis' was incorporated into the title following the recommendation.
- Detailed information regarding the ROI placement was included in the methods section.
- The topic of inter-reader variability was addressed in the discussion section.

See the authors' detailed response to the review by Siriwan Piyapittayanan
See the authors' detailed response to the review by Jarunee Intrapiromkul

Background

Cervical lymphadenopathy is a common problem, and the malignancy rate of lymph nodes in the neck exceeds 50%.¹^–⁵ The most prevalent etiologies in adults are lymphoma and metastatic squamous cell carcinoma (SCCA).² These conditions may present with enlarged cervical nodes and upper aerodigestive tract masses which might overlap and be misdiagnosed on a conventional CT⁶^–⁸ Dual-layer spectral CT (DLSCT), a subgroup of dual-energy CT (DECT), can generate additional data, including iodine density (ID).⁹^,¹⁰ This study compares ID and contrast-enhanced attenuation value (CEAV) between lymphomatous, metastatic SCCA, and normal cervical lymph node groups.

Methods

Study population

The study was approved by the Human Research Ethics Committee of Thammasat University (Medicine) (ref. No. MTU-EC-RA-0-222/66). Patients who underwent DLSCT of the neck with iodinated contrast media between Jan 2020 and Aug 2023 at Thammasat Hospital were retrospectively examined. The inclusion criteria for each group were 1) Metastatic SCCA patients who had primary SCCA of head and neck with pathologically proven metastatic nodes and pre-treatment DLSCT of neck, 2) Lymphoma patients with a final diagnosis of lymphoma involving a neck node with pre-treatment DLSCT of the neck, 3) Normal node patients with DLSCT of the neck for any reason except malignancy, lymphoma, and inflammatory disease. The exclusion criteria were 1) Patients with coexisting primary malignancies (head and neck or another region), and 2) Patients with suboptimal DLSCT, e.g., severe motion or metallic artifact.

Imaging acquisition

A dual-layer spectral CT scanner, DLSCT (Spectral CT7500 and Philips IQon Spectral CT, Philips Healthcare, Eindhoven, Netherlands), was used to scan all patients using the same standard CT neck protocol of the institute. CT parameters were as follows: 1.4:1 helical pitch, 0.4-second rotation time, and 120 kVp tube voltage with a reconstructed FOV of 512 mm2. Automated mAS and beam collimation were registered and differed depending on body habitus. The detector configurations were 128×0.625 mm for Spectral CT7500 and 64×0.625 mm for Philips IQon Spectral CT.

CT neck was performed along the skull base to the aortic arch in the craniocaudal fashion. Intravenous injection of non-ionic iodinated contrast agent (Ultravist 300 mg/ml, Bayer Vital GmbH, Leverkusen, Germany, catalogue numbers: 064-18-27492-00) with 30-mL saline chaser (0.9% sodium chloride, Thai Nakorn Patana, Nonthaburi, Thailand, catalogue numbers: F-013-13035) was administered at the rate of 2.5 mL/sec using a dual syringe injection system (Stellant, MEDRAD, Indianola, Pennsylvania). The non-ionic iodinated contrast agent dosage varied according to body weight (1.5 mL/kg). Enhanced images were obtained 70 seconds after contrast agent injection.

Imaging post-processing

Spectral post-processing workstation (IntelliSpace Portal v11, Philips Healthcare, Netherlands) was used togenerateID and contrast-enhanced images ( Figures 1, 2, and 3).

Figure 1. Measurement of ID and CEAV in lymphomatous node.

An Axial CT image of a patient with lymphoma shows CEAV measurement (70.9 HU) of the enlarged lymph node at left cervical level IIA (A). An ID measurement (1.14 mg/ml) of this lymph node at the same CT level (B).

Figure 2. Measurement of ID and CEAV in metastatic SCCA node.

An Axial CT image of a patient with SCCA at gum shows CEAV measurement (110.4 HU) of the enlarged lymph node at left cervical level IB (A). An ID measurement (2.23 mg/ml) of this lymph node at the same CT level (B).

Figure 3. Measurement of ID and CEAV in normal node.

An Axial CT image of a patient with normal lymph nodes shows CEAV measurement (80.5 HU) of a right cervical level IB node (A). An ID measurement (1.41 mg/ml) of this lymph node at the same CT level (B).

Image assessment

ID and CEAV were measured by placing rounded or oval-shaped regions of interest (ROI) on axial images in which lymph nodes appeared the largest ( Figures 1, 2, and 3). Regions of interest (ROIs) for each lymph node were delineated to encompass the largest possible area within the solid portion of the node, ensuring that each ROI had a minimum size of 6 mm². Areas of necrosis, cysts, calcifications, and fat were systematically excluded from the ROI placement. In instances where the solid portion exhibited heterogeneous enhancement, the largest feasible ROI was selected to ensure accurate and reliable measurements. The mean Hounsfield unit (HU) of each ROI was used as the representative value for the lymph node. ROIs were placed on axial images where the lymph nodes displayed the most prominent enhancement, with a maximum of three nodes selected for analysis. When the lymph node showed consistent enhancement across multiple slices, the slice displaying the largest cross-sectional area was chosen to obtain the most representative ROI. All lymph nodes were evaluated by a radiologist with 15 years of experience in head and neck imaging. The average ID and CEAV values of each patient were recorded.

The selected lymphomatous and metastatic SCCA nodes had to be enlarged (>8 mm in the short axis) or have other radiologic characteristics of pathologic nodes.

To achieve reliable ROI, normal nodes had to be <8 mm and >5 mm in the short axis without other radiologic signs of pathologic nodes.

ID and CEAV of the sternocleidomastoid muscle (SCM) and internal jugular vein (IJV) were obtained from every patient using circular or ellipsoid ROIs.

Standard of reference

Lymphomatous nodes were selected from patients with histopathologically proven lymphoma from cervical nodes or other head and neck areas. The selected lymphomatous nodes showed evidence of post-treatment regression on follow-up imaging. Metastatic SCCA nodes selected on CT had to correlate with the operative report and pathological results regarding side, nodal station, and size. Normal cervical lymph nodes were included in patients who were free from malignancy or inflammation in the neck.

Statistics

ID and CEAV were interpreted in terms of mean, standard deviation (SD), median, and interquartile range (IQR). One-way ANOVA was used to compare mean ID and CEAV between the 3 groups. ROC curve was used to estimate the area under the curve (AUC) with 95%CI for differential diagnosis between lymphomatous and metastatic SCCA nodes. Descriptive statistics was used to evaluate lymph node diameter.

Results

Study population

There was a total of 129 cervical nodes from 55 patients. The number of lymphomatous, metastatic SCCA, and normal cervical nodes was 50, 41, and 38, respectively. Baseline demographic, lymph node diameter, level of lymph nodes, and site of primary lesion of SCCA, including histopathologic subtypes of lymphoma, are described in Table 1.

Table 1. Clinical data of lymphomatous, metastatic SCCA and normal groups.

	Lymphoma	Metastatic SCCA	Normal
Age (Mean±SD)	59.10±16.95	61.59±13.89	48.50±17.40
Gender
	9 female	3 female	10 female
	11 male	14 male	8 male
Number of lymph nodes	50	41	38
Level of lymph nodes	1a (n=2) 1b (n=8) 2a (n=14) 2b (n=3) 3 (n=10) 4 (n=10) 5a (n=3) 5b (n=0) 6 (n=0)	1a (n=2) 1b (n=7) 2a (n=21) 2b (n=7) 3 (n=2) 4 (n=1) 5a (n=0) 5b (n=0) 6 (n=1)	1a (n=1) 1b (n=13) 2a (n=19) 2b (n=2) 3 (n=2) 4 (n=0) 5a (n=1) 5b (n=0) 6 (n=0)
Average diameter of lymph nodes	14.16 (10.15-17.63)	10.64 (9.55-19.10)	5.82 (5.41-6.32)
Note	Histologic subtypes - Hodgkin lymphoma (n=6) - Non Hodgkin lymphoma (n=38) - Diffuse large B cell (n=10) - Follicular cell (n=12) - NLPHL (n=2) - T cell (n=8) - Marginal zone (n=3) - Round cell (n=3)	Site of primary CA - Nasopharynx (n=11) - Nasal septum (n=2) - Tongue (n=3) - Floor of mouth (n=6) - Gum (n=5) - Retromolar trigone (n=2) - Tonsil (n=2) - Pyriform sinus (n=3) - Supraglottis (n=7)	-

Iodine density (ID) and contrast-enhanced attenuation value (CEAV)

The mean (±SD) ID and CEAV of lymphomatous, metastatic SCCA, and normal cervical nodes are summarized in Table 2 and Figure 4. There were significant differences of ID (p<0.001) and CEAV (p<0.001) between the three groups.

Table 2. Comparison of parameters between lymphomatous, metastatic SCCA and normal nodes.

Patient group	Lymphoma	SCCA	Normal	p-value
ID of lymph nodes (mg/ml)	1.01±0.27	1.36±0.28	1.45±0.29	<0.001*
ID of SCM (mg/ml)	0.45±0.19	0.44±0.24	0.42±0.18	0.928
ID of IJV (mg/ml)	3.67±0.76	3.30±0.62	3.25±0.72	0.140
CEAV of lymph nodes (HU)	72.91±10.69	86.84±8.95	95.90±9.67	<0.001*
CEAV of SCM (HU)	68.27±7.31	67.27±9.74	68.27±5.51	0.848
CEAV of IJV (HU)	150.94±23.56	144.38±19.61	149.58±20.10	0.635

* Statistically significant at p-value<0.05 determined by One-way ANOVA.

Figure 4. Box and whiskers plots of ID (A) & CEAV (B) of lymphoma, metastatic SCCA and normal nodes.

Subgroup analysis showed that the ID of lymphomatous nodes (1.01±0.27 mg/ml) was significantly lower than the ID of metastatic SCCA (1.36±0.28 mg/ml), p=0.002, and it was also lower than the ID of normal nodes (1.45±0.29 mg/ml), p<0.0001.

CEAV of lymphomatous nodes (72.91±10.69 HU) was significantly lower than the CEAV of metastatic SCCA (86.84±8.95 HU), p<0.0001, and it was lower than the CEAV of normal nodes (95.90±9.67 HU), p<0.0001. Comparative results of ID and CEAV between subgroups are summarized in Table 3.

Table 3. Pairwise comparison of iodine density and contrast enhanced attenuation value between each group.

	Mean difference	Std. Error	p-value
ID
Normal – Lymphoma	0.44	0.09	<0.001*
Normal – SCCA	0.09	0.09	0.640
Lymphoma – SCCA	-0.35	0.09	0.002*
CEAV
Normal – Lymphoma	22.98	3.20	<0.001*
Normal – SCCA	9.06	3.33	0.032*
Lymphoma – SCCA	-13.93	3.25	<0.001*

* Statistically significant at p-value<0.05 determined by post-hoc test (Scheffe).

There was no significant difference in ID or CEAV of the internal jugular vein (IJV) or sternocleidomastoid muscles (SCM) between the three groups, p≥0.05 ( Table 2).

Receiver operating characteristic curve

The ROC curve for ID and CEAV in differentiation between lymphoma and SCCA showed good diagnostic performance with the area under the curve at 0.788 (95% CI=0.632-0.944) and 0.851 (95% CI=0.721-0.982), respectively ( Figure 5).

Figure 5. ROC curves for ID and CEAV as test to diagnose lymphomatous or metastatic SCCA nodes.

Both curves show high diagnostic performance.

The optimal cut-off value of ID to differentiate lymphomatous nodes from metastatic SCCA, as derived from the ROC curve, was 1.175 mg/ml with a sensitivity of 85% and specificity of 87.5 %. The CEAV at 77.5 HU could also differentiate between these entities, with a specificity of 88.9% and a sensitivity of 78.9%.

Discussion

This is the first study to use DLSCT to compare ID between lymphomatous, metastatic SCCA, and normal cervical lymph nodes. We found lymphomatous nodes had significantly lower ID and CEAV than metastatic SCCA and normal nodes. Our data suggested that a cut-off value of ID at 1.175 mg/ml may enable discrimination between lymphomatous and SCCA nodes with specificity of 84.2% and sensitivity of 77.8%.

Some literature reported ID of cervical nodes studied on dual-sources or rapid-switch technique DECT. Prior studies rated ID and CEAV highest in normal nodes, followed by metastatic and then lymphomatous nodes, similar to our findings.²^,¹¹^,¹² A study by Yang et al. also found lower ID of lymphomatous nodes than of metastatic SCCA nodes, but they did not show a statistical difference between these two diseases.² They performed the study using a rapid switch kVp machine (Gemstone spectral imaging) with acquisition time at 30 seconds after contrast administration, which might explain why their results differ from ours.

The results from this study differ from results of previous studies performed in the abdominal area, which showed higher ID in lymphomatous nodes than in metastatic nodes.¹³ Many studies demonstrated different IDs among various types of tumors.¹⁴^–¹⁶ Differences of histopathological types and vascular supply between neck and abdominal structures could explain these different ID results.

Our results showed a lower ID of metastatic SCCA nodes than of normal neck nodes, which was similar to prior studies.¹⁷^–¹⁹ This might relate to HU distribution, which is highest at the center of normal nodes, whereas it is evenly distributed in metastatic nodes.²⁰ As normal nodes must be less than 8 mm in diameter, the ROI for ID measurement was inevitably placed at their center, resulting in a relatively higher ID. Greater vessel density in normal nodes than in metastatic lymph nodes with possible micronecrosis might explain this result.¹⁹^,²¹

The ID of metastatic SCCA nodes in this study (1.36±0.28 mg/ml) was lower than the ID in a study by Tawfik et al. (2.34±0.45 mg/ml) but higher than in the studies reported by Foust et al. (0.96±0.28 mg/ml) and Luo et al. (0.98±0.42 mg/ml).¹⁷^,¹⁹^,²² Their studies were performed by dual-source DECT (Somatom; Siemens Healthcare, Erlangen, Germany) with different iodine concentrations of contrast media (350-400 iodine/ml). These could result in different ID values of the cervical lymph nodes with the same pathologic type.

This study also showed a relatively lower ID in normal nodes (1.45±0.29 mg/ml) compared to a prior result from Sauter AP et al. (2.09±0.09 mg/ml), which also used a DLSCT machine (iQon, Philips Healthcare, Cleveland, OH, USA).²³ In contrast to this study, they used a higher iodine concentration of contrast media (Imeron 400) with a larger contrast volume (150 ml) on their CT neck protocol. These resulted in higher total iodine load and could have caused the higher ID values in their study.

We also compared the CEAV of lymph nodes between each group. This approach is more practical for routine interpretation because it can be directly measured on PACS. The results corresponded to the ID results, with lowest values in lymphomatous, metastatic SCCA, and normal nodes, respectively. CEAV was notably significantly different between the three groups (p-value<0.001).

As bolus tracking was not included in our routine CT neck protocol, we measured ID and CEAV of the sternocleidomastoid muscle (SCM) and internal jugular vein (IJV) to compare iodine content among the three groups. The results showed no significant difference in ID and CEAV of these two structures between the three patient groups (p-value>0.05).

This study has several limitations. First, it was conducted retrospectively with small patient groups. Iodine qualification data were unavailable for some patients because they were referred to our health care center after having undergone conventional CT. Second, we did not compare ID and CEAV between each lymph node level because some nodes were too small, and we did not have nodes in levels III-VI in the normal group. Comparison between normal and diseased nodes in these cervical levels might affect the results. A larger-scale study including each cervical level might address this limitation. Third, considering prior studies which showed different ID between different types of tumors,¹⁴^–¹⁶ we hypothesized that ID might be affected by the histologic subtype of lymphoma. Study of ID in various lymphomatous subtypes might improve subtype differentiation. Fourth, not all lymph nodes in the lymphomatous group were confirmed because lymph node dissection was not standard treatment for this disease. Fifth, the ROI placement in this study was performed by a single reader, which precludes the evaluation of inter-reader variability. However, efforts were made to standardize the process and ensure consistency throughout the analysis. Incorporating multiple readers in future studies could provide additional insights into the reproducibility and reliability of the findings.

Conclusion

The results of our study indicate that ID and CEAV findings from DLSCT differed significantly between lymphomatous, metastatic SCCA, and normal cervical nodes. This knowledge improves differentiation of these conditions.

Statements and declarations

Ethical approval and consent to participate

The Human Research Ethics Committee of Thammasat Univerity (Medicine) approved conducting this research with the certificate project number MTU-EC-RA-0-222/66, and approved on December 20, 2023. The inform-consent was waived requirement due to the retrospective nature of the study.

Author contributions

MV made contributions in literatures search, study design, data interpretation, draft writing, critical revision and final approval of the final version for submitted. WU made contributions in literatures search, data collection, data analysis and interpretation, and TW and WA made contributions in draft writing, critical revision and also faculty collaborations.

Data availability

Underlying data

Zenodo: Iodine density of lymphoma, metastatic SCCA, and normal cervical lymph nodes: Based on DLSCT. https://doi.org/10.5281/zenodo.11120918.²⁴

This project contains the following underlying data:

Patients demographic data, iodine density and contrast attenuation value of neck nodes for Final data_18 Mar 2024_Final.xlsx.

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Extended data

Reporting guidlines

Zenodo: STARD checklist. https://doi.org/10.5281/zenodo.11120918.²⁴

Acknowledgement

We want to thank Assoc. Prof. Dr. Amonpon Kanlerd, Faculty of Medicine, Thammasat University, for helping us with language editing and submitting this manuscript.

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¹ Radiology, Thammasat University, meung, pathumtani, 12000, Thailand

Urusaya Wangprasertkul
Roles: Data Curation, Project Administration

Warit Tarathipmon
Roles: Formal Analysis

Arvemas Watcharakorn
Roles: Methodology

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

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© 2025 Mingkwansook V et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Mingkwansook V, Wangprasertkul U, Tarathipmon W and Watcharakorn A. Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical lymph nodes: A Comparative Analysis Based on DLSCT [version 2; peer review: 2 approved]. F1000Research 2025, 13:498 (https://doi.org/10.12688/f1000research.146149.2)

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https://doi.org/10.5256/f1000research.160196.r344815

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1. Study design; generally, metastatic cervical lymph nodes are not only SCCA. This study has not include another cell type of metastatic lymph node such as thyroid carcinoma, salivary gland carcinoma or metastatic node from organ outside head and neck such as breast and lung cancer. Explain the reason that why this study include only SCCA nodal metastasis.
2. Heading; may put some word in the heading such as comparative, can iodine density differentiate between, to increasingly interest.

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Yes
Are sufficient details of methods and analysis provided to allow replication by others?

Yes
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

Yes

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Neuroradiology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

CITE

Report a concern

Author Response 23 Dec 2024

Varalee Mingkwansook, Radiology, Thammasat University, meung, 12000, Thailand

23 Dec 2024

Author Response

Thank you for your valuable comment.
1. The decision to focus solely on metastatic SCCA in cervical lymph nodes was made to ensure a more controlled and focused analysis. SCCA ... Continue reading Thank you for your valuable comment.
1. The decision to focus solely on metastatic SCCA in cervical lymph nodes was made to ensure a more controlled and focused analysis. SCCA is one of the most common causes of metastatic cervical lymphadenopathy, particularly in head and neck cancers. By concentrating on SCCA, we aimed to investigate its specific iodine density patterns in relation to lymphoma. Including other types of metastatic lymph nodes, such as those from thyroid carcinoma, salivary gland carcinoma, or cancers from distant organs like the breast or lung, would introduce significant variability due to differences in tumor biology, vascularity, and iodine uptake. This variability could complicate the analysis and make it difficult to draw clear comparisons between the two malignancies. Focusing on SCCA allowed for a more homogenous study sample, providing clearer insights into iodine density patterns specific to SCCA and lymphoma, which is the primary goal of this research. We plan to explore a broader comparison in future studies.
2. The heading will be modified to "Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical Lymph Nodes: A Comparative Analysis Using DLSCT"
Thank you for your valuable comment.
1. The decision to focus solely on metastatic SCCA in cervical lymph nodes was made to ensure a more controlled and focused analysis. SCCA is one of the most common causes of metastatic cervical lymphadenopathy, particularly in head and neck cancers. By concentrating on SCCA, we aimed to investigate its specific iodine density patterns in relation to lymphoma. Including other types of metastatic lymph nodes, such as those from thyroid carcinoma, salivary gland carcinoma, or cancers from distant organs like the breast or lung, would introduce significant variability due to differences in tumor biology, vascularity, and iodine uptake. This variability could complicate the analysis and make it difficult to draw clear comparisons between the two malignancies. Focusing on SCCA allowed for a more homogenous study sample, providing clearer insights into iodine density patterns specific to SCCA and lymphoma, which is the primary goal of this research. We plan to explore a broader comparison in future studies.
2. The heading will be modified to "Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical Lymph Nodes: A Comparative Analysis Using DLSCT"
Competing Interests: The authors declare no competing interests Close
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Author Response 23 Dec 2024

Varalee Mingkwansook, Radiology, Thammasat University, meung, 12000, Thailand

23 Dec 2024

Author Response

Thank you for your valuable comment.
1. The decision to focus solely on metastatic SCCA in cervical lymph nodes was made to ensure a more controlled and focused analysis. SCCA ... Continue reading Thank you for your valuable comment.
1. The decision to focus solely on metastatic SCCA in cervical lymph nodes was made to ensure a more controlled and focused analysis. SCCA is one of the most common causes of metastatic cervical lymphadenopathy, particularly in head and neck cancers. By concentrating on SCCA, we aimed to investigate its specific iodine density patterns in relation to lymphoma. Including other types of metastatic lymph nodes, such as those from thyroid carcinoma, salivary gland carcinoma, or cancers from distant organs like the breast or lung, would introduce significant variability due to differences in tumor biology, vascularity, and iodine uptake. This variability could complicate the analysis and make it difficult to draw clear comparisons between the two malignancies. Focusing on SCCA allowed for a more homogenous study sample, providing clearer insights into iodine density patterns specific to SCCA and lymphoma, which is the primary goal of this research. We plan to explore a broader comparison in future studies.
2. The heading will be modified to "Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical Lymph Nodes: A Comparative Analysis Using DLSCT"
Thank you for your valuable comment.
1. The decision to focus solely on metastatic SCCA in cervical lymph nodes was made to ensure a more controlled and focused analysis. SCCA is one of the most common causes of metastatic cervical lymphadenopathy, particularly in head and neck cancers. By concentrating on SCCA, we aimed to investigate its specific iodine density patterns in relation to lymphoma. Including other types of metastatic lymph nodes, such as those from thyroid carcinoma, salivary gland carcinoma, or cancers from distant organs like the breast or lung, would introduce significant variability due to differences in tumor biology, vascularity, and iodine uptake. This variability could complicate the analysis and make it difficult to draw clear comparisons between the two malignancies. Focusing on SCCA allowed for a more homogenous study sample, providing clearer insights into iodine density patterns specific to SCCA and lymphoma, which is the primary goal of this research. We plan to explore a broader comparison in future studies.
2. The heading will be modified to "Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical Lymph Nodes: A Comparative Analysis Using DLSCT"
Competing Interests: The authors declare no competing interests Close
Report a concern

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Reviewer Report 08 Aug 2024

Jarunee Intrapiromkul, Neuroradiology Radiology, Nuclear Medicine, Pediatric Radiology, West Virginia University, Johns Hopkins University, Morgantown, Baltimore, USA

Approved with Reservations

https://doi.org/10.5256/f1000research.160196.r282853

For ROI measurement, there is no clear description on how to place the ROI in the lymph nodes. Is the size of ROI the same in all cases? Is it placed on the solid portion? For lymph nodes with heterogeneous enhancement, do you place it on the most enhanced portion or cover all lymph nodes. The details of ROI placement should be described in more detail so that the study can be reproduce. Also, having a second reader placing the ROI is a great way to ensure the study reproducibility by evaluating the inter-reader variability. The mean value from 2 readers can then be used for analysis.
The proposed cut-off ID value may depend on the contrast concentration and dosage, which are varied on each imaging centers.

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Partly
Are the conclusions drawn adequately supported by the results?

Yes

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Head and neck imaging, perfusion imaging

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

CITE

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Author Response 22 Aug 2024

Varalee Mingkwansook, Radiology, Thammasat University, meung, 12000, Thailand

22 Aug 2024

Author Response

For ROI measurement, there is no clear description on how to place the ROI in the lymph nodes.
- Is the size of ROI the same in all cases? ... Continue reading For ROI measurement, there is no clear description on how to place the ROI in the lymph nodes.
- Is the size of ROI the same in all cases?
- ROI placement for each lymph node was drawn in the largest area as much as possible in the solid portion. The size must be at least 6 mm².
- Is it placed on the solid portion?
            - Yes. ROIs were placed on the solid enhancing portion. Areas of necrosis, cyst, calcification or fat were carefully avoided.
- For lymph nodes with heterogeneous enhancement, do you place it on the most enhanced portion or cover all lymph nodes.
           - If the solid portion (excluding necrosis, cystic area, fat and calcification) was heterogenously enhanced, we drawn the largest ROI as much as possible to acheive the reliable ROI. The mean HU of each ROI was used as a representative for each lymph node.
- The details of ROI placement should be described in more detail so that the study can be reproduce.
            - ROIs were placed on axial images in which lymph nodes appeared the most prominent enhancement (3 nodes maximum). If the lymph node had similar degree of enhancement on each axial view, the slice which lymph node appeared to be largest was selected in order to achieve the largest ROI. ROI must be at least 6 mm² in size. We drew largest ROI for each lymph node as much as possible, avoiding areas of necrosis, cyst, calcification or fat.
- Also, having a second reader placing the ROI is a great way to ensure the study reproducibility by evaluating the inter-reader variability. The mean value from 2 readers can then be used for analysis.
            - We will conduct the new article with more subjects and providing inter-reader variability in the future.
- The proposed cut-off ID value may depend on the contrast concentration and dosage, which are varied on each imaging centers
            - The authors agree with this issue which already mentioned in discussion section.
For ROI measurement, there is no clear description on how to place the ROI in the lymph nodes.
- Is the size of ROI the same in all cases?
- ROI placement for each lymph node was drawn in the largest area as much as possible in the solid portion. The size must be at least 6 mm².
- Is it placed on the solid portion?
            - Yes. ROIs were placed on the solid enhancing portion. Areas of necrosis, cyst, calcification or fat were carefully avoided.
- For lymph nodes with heterogeneous enhancement, do you place it on the most enhanced portion or cover all lymph nodes.
           - If the solid portion (excluding necrosis, cystic area, fat and calcification) was heterogenously enhanced, we drawn the largest ROI as much as possible to acheive the reliable ROI. The mean HU of each ROI was used as a representative for each lymph node.
- The details of ROI placement should be described in more detail so that the study can be reproduce.
            - ROIs were placed on axial images in which lymph nodes appeared the most prominent enhancement (3 nodes maximum). If the lymph node had similar degree of enhancement on each axial view, the slice which lymph node appeared to be largest was selected in order to achieve the largest ROI. ROI must be at least 6 mm² in size. We drew largest ROI for each lymph node as much as possible, avoiding areas of necrosis, cyst, calcification or fat.
- Also, having a second reader placing the ROI is a great way to ensure the study reproducibility by evaluating the inter-reader variability. The mean value from 2 readers can then be used for analysis.
            - We will conduct the new article with more subjects and providing inter-reader variability in the future.
- The proposed cut-off ID value may depend on the contrast concentration and dosage, which are varied on each imaging centers
            - The authors agree with this issue which already mentioned in discussion section.
Competing Interests: No competing interests were disclosed. Close
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COMMENTS ON THIS REPORT

Author Response 22 Aug 2024

Varalee Mingkwansook, Radiology, Thammasat University, meung, 12000, Thailand

22 Aug 2024

Author Response

For ROI measurement, there is no clear description on how to place the ROI in the lymph nodes.
- Is the size of ROI the same in all cases? ... Continue reading For ROI measurement, there is no clear description on how to place the ROI in the lymph nodes.
- Is the size of ROI the same in all cases?
- ROI placement for each lymph node was drawn in the largest area as much as possible in the solid portion. The size must be at least 6 mm².
- Is it placed on the solid portion?
            - Yes. ROIs were placed on the solid enhancing portion. Areas of necrosis, cyst, calcification or fat were carefully avoided.
- For lymph nodes with heterogeneous enhancement, do you place it on the most enhanced portion or cover all lymph nodes.
           - If the solid portion (excluding necrosis, cystic area, fat and calcification) was heterogenously enhanced, we drawn the largest ROI as much as possible to acheive the reliable ROI. The mean HU of each ROI was used as a representative for each lymph node.
- The details of ROI placement should be described in more detail so that the study can be reproduce.
            - ROIs were placed on axial images in which lymph nodes appeared the most prominent enhancement (3 nodes maximum). If the lymph node had similar degree of enhancement on each axial view, the slice which lymph node appeared to be largest was selected in order to achieve the largest ROI. ROI must be at least 6 mm² in size. We drew largest ROI for each lymph node as much as possible, avoiding areas of necrosis, cyst, calcification or fat.
- Also, having a second reader placing the ROI is a great way to ensure the study reproducibility by evaluating the inter-reader variability. The mean value from 2 readers can then be used for analysis.
            - We will conduct the new article with more subjects and providing inter-reader variability in the future.
- The proposed cut-off ID value may depend on the contrast concentration and dosage, which are varied on each imaging centers
            - The authors agree with this issue which already mentioned in discussion section.
For ROI measurement, there is no clear description on how to place the ROI in the lymph nodes.
- Is the size of ROI the same in all cases?
- ROI placement for each lymph node was drawn in the largest area as much as possible in the solid portion. The size must be at least 6 mm².
- Is it placed on the solid portion?
            - Yes. ROIs were placed on the solid enhancing portion. Areas of necrosis, cyst, calcification or fat were carefully avoided.
- For lymph nodes with heterogeneous enhancement, do you place it on the most enhanced portion or cover all lymph nodes.
           - If the solid portion (excluding necrosis, cystic area, fat and calcification) was heterogenously enhanced, we drawn the largest ROI as much as possible to acheive the reliable ROI. The mean HU of each ROI was used as a representative for each lymph node.
- The details of ROI placement should be described in more detail so that the study can be reproduce.
            - ROIs were placed on axial images in which lymph nodes appeared the most prominent enhancement (3 nodes maximum). If the lymph node had similar degree of enhancement on each axial view, the slice which lymph node appeared to be largest was selected in order to achieve the largest ROI. ROI must be at least 6 mm² in size. We drew largest ROI for each lymph node as much as possible, avoiding areas of necrosis, cyst, calcification or fat.
- Also, having a second reader placing the ROI is a great way to ensure the study reproducibility by evaluating the inter-reader variability. The mean value from 2 readers can then be used for analysis.
            - We will conduct the new article with more subjects and providing inter-reader variability in the future.
- The proposed cut-off ID value may depend on the contrast concentration and dosage, which are varied on each imaging centers
            - The authors agree with this issue which already mentioned in discussion section.
Competing Interests: No competing interests were disclosed. Close
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VERSION 2 PUBLISHED 17 May 2024

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Jarunee Intrapiromkul, West Virginia University, Johns Hopkins University, Morgantown, Baltimore, USA
Siriwan Piyapittayanan, Siriraj Hospital, Mahidol University, Bangkok, Thailand

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15 Jan 2025 | for Version 2

Siriwan Piyapittayanan, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

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Approved

No new commment

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03 Jan 2025 | for Version 2

Jarunee Intrapiromkul, Neuroradiology Radiology, Nuclear Medicine, Pediatric Radiology, West Virginia University, Johns Hopkins University, Morgantown, Baltimore, USA

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Approved

No additional comment.

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Head and neck imaging, perfusion imaging

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

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20 Dec 2024 | for Version 1

Siriwan Piyapittayanan, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

8 Views Cite this report Responses(1)

Approved

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Yes
Are sufficient details of methods and analysis provided to allow replication by others?

Yes
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

Yes

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Neuroradiology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (1)

Author Response

23 Dec 2024

Varalee Mingkwansook, Radiology, Thammasat University, meung, 12000, Thailand

Thank you for your valuable comment.
1. The decision to focus solely on metastatic SCCA in cervical lymph nodes was made to ensure a more controlled and focused analysis. SCCA is one of the most common causes of metastatic cervical lymphadenopathy, particularly in head and neck cancers. By concentrating on SCCA, we aimed to investigate its specific iodine density patterns in relation to lymphoma. Including other types of metastatic lymph nodes, such as those from thyroid carcinoma, salivary gland carcinoma, or cancers from distant organs like the breast or lung, would introduce significant variability due to differences in tumor biology, vascularity, and iodine uptake. This variability could complicate the analysis and make it difficult to draw clear comparisons between the two malignancies. Focusing on SCCA allowed for a more homogenous study sample, providing clearer insights into iodine density patterns specific to SCCA and lymphoma, which is the primary goal of this research. We plan to explore a broader comparison in future studies.
2. The heading will be modified to "Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical Lymph Nodes: A Comparative Analysis Using DLSCT"

View more View less

Competing Interests

The authors declare no competing interests

Back to all reports

Reviewer Report

46 Views

08 Aug 2024 | for Version 1

Jarunee Intrapiromkul, Neuroradiology Radiology, Nuclear Medicine, Pediatric Radiology, West Virginia University, Johns Hopkins University, Morgantown, Baltimore, USA

46 Views Cite this report Responses(1)

Approved With Reservations

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Partly
Are the conclusions drawn adequately supported by the results?

Yes

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Head and neck imaging, perfusion imaging

Respond to this report

Responses (1)

Author Response

22 Aug 2024

Varalee Mingkwansook, Radiology, Thammasat University, meung, 12000, Thailand

For ROI measurement, there is no clear description on how to place the ROI in the lymph nodes.
- Is the size of ROI the same in all cases?
- ROI placement for each lymph node was drawn in the largest area as much as possible in the solid portion. The size must be at least 6 mm².
- Is it placed on the solid portion?
            - Yes. ROIs were placed on the solid enhancing portion. Areas of necrosis, cyst, calcification or fat were carefully avoided.
- For lymph nodes with heterogeneous enhancement, do you place it on the most enhanced portion or cover all lymph nodes.
           - If the solid portion (excluding necrosis, cystic area, fat and calcification) was heterogenously enhanced, we drawn the largest ROI as much as possible to acheive the reliable ROI. The mean HU of each ROI was used as a representative for each lymph node.
- The details of ROI placement should be described in more detail so that the study can be reproduce.
            - ROIs were placed on axial images in which lymph nodes appeared the most prominent enhancement (3 nodes maximum). If the lymph node had similar degree of enhancement on each axial view, the slice which lymph node appeared to be largest was selected in order to achieve the largest ROI. ROI must be at least 6 mm² in size. We drew largest ROI for each lymph node as much as possible, avoiding areas of necrosis, cyst, calcification or fat.
- Also, having a second reader placing the ROI is a great way to ensure the study reproducibility by evaluating the inter-reader variability. The mean value from 2 readers can then be used for analysis.
            - We will conduct the new article with more subjects and providing inter-reader variability in the future.
- The proposed cut-off ID value may depend on the contrast concentration and dosage, which are varied on each imaging centers
            - The authors agree with this issue which already mentioned in discussion section.

View more View less

Competing Interests

No competing interests were disclosed.

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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Iodine Density of Lymphoma, Metastatic SCCA, and Normal Cervical lymph nodes: A Comparative Analysis Based on DLSCT

Abstract

Objective

Methods

Results

Conclusions

Keywords

Revised Amendments from Version 1

Background

Methods

Study population

Imaging acquisition

Imaging post-processing

Figure 1. Measurement of ID and CEAV in lymphomatous node.

Figure 2. Measurement of ID and CEAV in metastatic SCCA node.

Figure 3. Measurement of ID and CEAV in normal node.

Image assessment

Standard of reference

Statistics

Results

Study population

Table 1. Clinical data of lymphomatous, metastatic SCCA and normal groups.

Iodine density (ID) and contrast-enhanced attenuation value (CEAV)

Table 2. Comparison of parameters between lymphomatous, metastatic SCCA and normal nodes.

Figure 4. Box and whiskers plots of ID (A) & CEAV (B) of lymphoma, metastatic SCCA and normal nodes.

Table 3. Pairwise comparison of iodine density and contrast enhanced attenuation value between each group.

Receiver operating characteristic curve

Figure 5. ROC curves for ID and CEAV as test to diagnose lymphomatous or metastatic SCCA nodes.

Discussion

Conclusion

Statements and declarations

Author contributions

Data availability

Underlying data

Extended data

Acknowledgement

References

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