bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.06.13.658854

Mapping 3D Heterogeneity of Thyroid Tumors Using Micro-CTbased Radiomics

Abstract

Tumor heterogeneity plays a central role in treatment resistance, disease progression, and diagnostic uncertainty. However, it may be overlooked by traditional 2D histology. Accurate 3D assessment of tumor microarchitecture is therefore essential for capturing its spatial complexity. Micro-CT, an emerging imaging modality that offers high-resolution 3D virtual histology of soft tissues, provides a promising alternative. Combined with radiomics--a computational approach for interpretable quantification of tissue phenotypes--this technique enables a deeper understanding of tumor biology beyond visual inspection. In this study, we analyzed a large cohort of thyroid tumors (418 patients) using micro-CT imaging of next-generation tissue microarrays, from which we extracted radiomics features. We achieved robust classification of (i) neoplastic versus non-neoplastic thyroid tissues, (ii) papillary versus follicular thyroid carcinoma, and (iii) BRAF V600E mutation status. Feature interpretation using Shapley additive explanations revealed key visual traits driving these classification decisions. Preliminary results also indicated radiomic patterns associated with TERT promoter mutations, suggesting the existence of potential surrogate imaging biomarkers. Overall, micro-CT radiomics shows strong potential as a complementary tool for improving diagnostic and prognostic accuracy in thyroid cancer and offers a novel platform for quantitative pathology into the 3D spatial complexity of neoplastic tissues.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Tajbakhsh, K., Stanowska, O., Buljan, M., Neels, A., Perren, A., Zboray, R.. 2025-06-14. Mapping 3D Heterogeneity of Thyroid Tumors Using Micro-CTbased Radiomics. https://doi.org/10.1101/2025.06.13.658854

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗

Angiotensin II Induces Abdominal Aortic Branch Aneurysms in Fibrillin-1C1041G/+ Mice

BackgroundMice harboring a missense variant (C1041G) of fibrillin-1 (Fbn1) have been used extensively for aortopathy research, but do not mimic all facets of the human disease. The role of increased angiotensin II (AngII) or blood pressure in determining the arterial phenotype of these mice remains incompletely defined. The purpose of this study was to determine whether AngII, either directly or indirectly through increased blood pressure, promotes pathology in the proximal thoracic aorta and beyond. MethodsFbn1+/+ and Fbn1C1041G/+ littermates were infused with either AngII or norepinephrine (NE) via subcutaneously implanted osmotic pumps. Micro computed tomography (microCT) was used to visualize vascular pathologies. Maximal arterial dimensions were measured using in situ or microCT images. ResultsAngII infusion dramatically augmented aortopathy in Fbn1C1041G/+ mice. Aortic dissection was visible within 3 days of AngII infusion. Over 50% of male Fbn1C1041G/+ mice died during AngII infusion, primarily due to aortic rupture in either the thoracic or abdominal regions. Surviving males had increased ascending and suprarenal aortic diameters and developed pathological lesions at the celiac and superior mesenteric branches of the abdominal aorta. Female mice had a much lower incidence of death but had increased ascending aortic and branch diameters. Although NE infusion also increased systolic blood pressure, it did not affect mortality or enlarge aortic or branch diameters in Fbn1C1041G/+ mice. MicroCT identified novel pathological changes during AngII infusion, including development of aortic branch aneurysms in the celiac and superior mesenteric arteries; however, the maximal diameters of the adjacent suprarenal aorta showed only modest increases in male Fbn1C1041G/+ mice. ConclusionAngII exacerbated aortic pathology in Fbn1C1041G/+ mice. It also promoted development of pathologies at aortic branch points, including the celiac and superior mesenteric arteries.

pathology↗

Anatomical Research on the Anterior Cruciate Ligament of the Knee

ObjectiveThe Ribbon Theory challenges the traditional perspective that the anterior cruciate ligament (ACL) consists of a two-bundle structure, specifically the anterior inner bundle and the posterior outer bundle. Consequently, there is a pressing need to conduct further anatomical studies of the ACL to furnish a more precise anatomical foundation for ACL reconstruction procedures. Materials and MethodsA total of 30 fresh knee specimens, sourced from donor cadavers utilized for educational purposes, were dissected. The morphology of the ACL was observed, and its length, insertion position, and surface area were systematically measured.In males, the mean length of the right ACL was 34.52 mm, while the left ACL measured an average of 34.87 mm. In females, the mean length of the right ACL was 30.8 mm, and the left ACL averaged 30.53 mm. The average femoral footprint area on the right side was 143 mm2 {+/-} 16 for males and 124 mm2 {+/-} 21 for females, whereas on the left side, it was 145 mm2 {+/-} 22 for males and 123 mm2 {+/-} 17 for females. In conclusion, the majority of ACLs are characterized by a single flat band extending from the femoral origin to the midpoint, with no distinct separation observed at the midpoint. This discovery has significantly influenced the techniques used in ACL reconstruction, advancing the development of the anatomical single-bundle ACL reconstruction method.

pathology↗