Benign nature of incidental orbital uptake on bone scintigraphy: insights from multi- modality imaging and follow-up

Benign nature of incidental orbital uptake on bone scintigraphy: insights from multi- modality imaging and follow-up | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Benign nature of incidental orbital uptake on bone scintigraphy: insights from multi- modality imaging and follow-up Le Song, Na Guo, Weifang Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7472182/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Objective To characterize incidental orbital radionuclide uptake on bone scintigraphy using multi-modal imaging and follow-up. Methods This retrospective study included 66 patients with focal orbital uptake on whole-body bone scintigraphy (2019–2022). Subsets underwent follow-up bone scintigraphy (n = 27 patients, median interval 23.0 months), MRI (n = 31 patients, within 14 days of bone scintigraphy), and CT or fluorine-18 fluorodeoxyglucose (FDG) PET/CT (n = 21 patients, median interval from bone scan 8 months). Serial changes in the target-to-nontarget (T/NT) ratio on bone scans were analyzed, while MRI signal/ bone reporting and data system (Bone-RADS)classification, CT morphology/Bone-RADS classification, and metabolic activity (maximum standardized uptake value, SUVmax) were assessed. Results Seventy-six orbital foci were evaluated, predominantly localized to the superior/lateral walls (61/76, 80.3%) with round morphology (72/76, 94.7%). Extra-orbital findings included metastasis (5 patients), degenerative changes (34 patients), and benign lesions (17 patients). Follow-up bone scintigraphy showed non-significant T/NT ratio decrease (median 4.9 to 3.7; P = 0.301), with visual stability in 25/28 lesions (metastatic: 4/5 patients; non-metastatic: 21/23 patients). MRI detected abnormal orbital lesions in 16 patients (16 lesions; mean size 9.0 ± 2.4 mm), involving the frontal bone (n=10) and zygomatic bone (n=6); Bone-RADS categories: 12 category 2/3, 4 category 4. Follow-up MRI (11 lesions) showed stable size; two lesions had signal evolution. CT identified abnormal orbital findings in 20 patients (21 foci), including one osteolytic sphenoid lesion (cortical destruction, Bone-RADS 4, SUVmax 5.1) suggested metastasis. The remaining 20 foci demonstrated benign CT features: 18 Bone-RADS 1 lesions (ground-glass opacities: 16) and 2 Bone-RADS 2/3 lucent lesions. These lesions showed minimal FDG uptake (median SUVmax 1.4) on PET/CT. Conclusions: Incidental focal orbital uptake on bone scintigraphy typically localizes to superior/lateral walls with rounded morphology. Multi-modality imaging, particularly CT demonstrating characteristic benign features (predominantly ground-glass opacities) combined with low FDG avidity and longitudinal stability, confirms benign etiology in most cases. CT provides superior osseous characterization versus MRI. Individualized imaging surveillance is appropriate. Bone scintigraphy Orbital bone lesions Fibrous dysplasia Incidental findings Multimodal imaging Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Bone metastasis remains a significant clinical challenge in oncology, often leading to debilitating complications such as pathological fractures and intractable pain that profoundly impact patient quality of life. Whole-body bone scintigraphy serves as the primary imaging modality for detecting skeletal metastases, which typically present as multifocal asymmetric radiotracer uptake in the axial skeleton. In contrast, focal orbital uptake represents a diagnostically complex entity with distinct characteristics across different populations. In pediatric patients, orbital uptake may be associated with neuroblastoma metastases, classically manifesting as bilateral symmetric uptake with periorbital ecchymosis – the "Raccoon Eyes" sign [ 1 ]. Adult presentations differ substantially, where orbital metastases are exceptionally rare events. Documented cases include prostate carcinoma causing the "Eyebrow Sign" through supraorbital involvement [ 2 ], and renal cell carcinoma invading orbito-sinus regions with neurological sequelae [ 3 ]. Crucially, non-malignant etiologies constitute the majority of differential considerations, encompassing physiological variants like frontozygomatic suture uptake [ 4 ], lacrimal gland disorders, and benign osseous conditions [ 5 – 9 ]. This etiological heterogeneity creates substantial diagnostic uncertainty in clinical practice. Current literature lacks comprehensive analyses quantifying prevalence or establishing evidence-based management pathways for incidental orbital uptake. To address these critical knowledge gaps, we conducted a retrospective multi-modality investigation integrating bone scintigraphy with structural and metabolic imaging (CT, MRI, PET-CT) complemented by longitudinal follow-up. The study was designed to determine the incidence and topographic features of orbital uptake, verify underlying etiologies through imaging correlation, and derive clinically applicable evaluation algorithms. Methods Study Population The patient selection process is schematically illustrated in Fig. 1 . This retrospective study was approved by the institutional review board, with a waiver of informed consent. Among 6,723 patients who underwent whole-body bone scintigraphy at our institution between January 2019 and December 2022, a PACS database search using the keyword 'orbit' identified 73 potential subjects. Inclusion criteria comprised: (1) focal radionuclide uptake localized to the orbital wall on whole-body bone scintigraphy, and (2) age > 18 years. Exclusion criteria were history of orbital fracture, or prior orbital surgery. After screening, 66 patients were ultimately included, comprising 46 males and 20 females, with a median age of 63.5 (range: 29–83) years. Among the 66 patients, 60 had malignancies (lung: 33; prostate: 13; breast: 11; rectal: 1; lymphoma: 1; osteosarcoma: 1), and 6 had benign conditions (pulmonary hamartoma: 1; hypercalcemia: 1; elevated M protein: 1; fever: 1; rib lesion: 1; arthritis: 1). ​​No patients reported orbital discomfort during bone scintigraphy or the follow-up period. Bone Scintigraphy Protocol Bone scintigraphy was performed using Siemens Symbia Intevo SPECT/CT or Philips Skylight SPECT systems equipped with low-energy high-resolution collimators. Patients received intravenous administration of Tc-99m Methylene Diphosphonate (MDP, 740 MBq; radiochemical purity > 95%). Whole-body anterior and posterior planar images were acquired 4 hours post-injection at a scanning speed of 15 cm/min (energy window: 140 keV ± 20%; matrix: 512×1024). MRI Acquisition Protocols Brain MRI was conducted using 1.5T or 3.0T scanners (Siemens Prisma, GE Signa HDxt, GE Optima MR360, or UIH uMR 770). Standard sequences included: T1-weighted imaging (T1WI): TR = 300–800 ms, TE 2000 ms, TE = 80–130 ms. FLAIR T2WI: TR = 8000-10,000 ms, TE = 80–130 ms. All scans utilized a slice thickness of 5 mm, interslice gap of 6 mm, and FOV of 200–240 mm. PET/CT Protocol PET/CT imaging was performed using a Siemens Biograph 64 scanner. Patients fasted for ≥ 6 hours before intravenous injection of fluorine-18 fluorodeoxyglucose (FDG) (3.7–5.5 MBq/kg). Trunk and cranial imaging commenced 60 minutes post-injection. Cranial CT parameters included: 120 kV, 250 mA, pitch 0.9, slice thickness 3 mm. Cranial PET data were reconstructed using True X software (4 iterations, 16 subsets; Gaussian filter: 4.0 mm FWHM). Image Analysis Two senior nuclear medicine physicians independently reviewed all imaging studies, ​​with discrepancies resolved through consensus.​ ​​Multimodal imaging (bone scintigraphy, CT, and MRI) was evaluated via the Centricity RIS CE V3.0 platform (GE healthcare, USA).​ The location (superior, lateral, medial, and inferior walls) and morphology of orbital radiotracer uptake foci were meticulously documented through bone scintigraphy. For follow-up patients, 1) the grayscale of the bone scintigraphy images was calibrated to ensure consistency in the degree of radiotracer uptake in the skull across imaging sessions. Changes in the radiotracer uptake of orbital lesions were systematically observed, with attention to increases, decreases, or no significant alterations. 2) Quantitative analysis was performed by drawing regions of interest (ROI) to calculate the target-to-nontarget (T/NT), with the nontarget ROI placed within the contralateral orbit, avoiding the orbital wall, and selecting the maximum value. 3) Additionally, the assessment of the entire skeletal system was conducted to determine the presence of any new bone metastases and to evaluate the changes in existing bone metastases. On cranial CT or MRI images, orbital lesions were systematically evaluated using the bone reporting and data system (Bone-RADS) criteria [ 10 ]. Both modalities assessed lesion location, size, and aggressive features—including cortical destruction, soft tissue extension, pathologic fracture, and aggressive periosteal reaction. CT specifically classified density patterns: lucent lesions were defined as > 90% volume exhibiting lower attenuation than normal trabecular bone, while lesions with higher attenuation were categorized as sclerotic or mixed density. MRI evaluations focused on signal intensity characteristics: T1 hyperintense (> skeletal muscle), T1 iso/hypointense (≤ skeletal muscle); T2 hyperintense (fluid-equivalent), T2 hypointense (air/cortical bone-equivalent), and intermediate T2 (between fluid and muscle). For patients who underwent PET/CT imaging, the maximum standardized uptake value (SUVmax) of each orbital lesion was quantified on a Medex workstation (Medix Technology Co., Ltd., Beijing, China). Statistical Analysis Analyses were conducted using SPSS v27.0 (IBM Corp.). Continuous variables were assessed for normality using the Shapiro-Wilk test. Normally distributed data are expressed as mean ± standard deviation; non-normally distributed variables are expressed as median with interquartile range (IQR; P25-P75). Categorical variables expressed as percentages. Wilcoxon signed-rank test was used to evaluate changes in T/NT values during follow-up. A p-value < 0.05 was considered statistically significant. Results Bone Scan Findings Among the 66 patients, 58 presented with solitary orbital lesions, while 8 patients exhibited multiple orbital lesions. A total of 76 foci of increased radioactivity were detected in the orbits, including 44 in the superior orbital wall (Fig. 2 ), 17 in the lateral wall (Fig. 3 , 4 ), 6 in the medial wall, and 9 in the inferior wall. Seventy-two lesions were round in shape, while four showed stripe-shaped increased radioactivity. Five patients demonstrated multifocal radiotracer uptake in the spine, ribs, and sternum, consistent with typical metastatic disease. One patient exhibited sacral radiotracer uptake representing a primary osteosarcoma lesion. One arthritis patient showed multifocal hypermetabolic foci involving the spine and joints. Thirty-four patients demonstrated degenerative changes in the spine and/or joints, while 17 patients exhibited other benign foci of increased radiotracer uptake, including fractures, dental disease, and sinusitis. In 13 patients, the whole-body bone scan revealed no abnormal radiotracer uptake outside the orbits. Twenty-seven patients (including 5 with bone metastasis) with 28 orbital radiotracer uptake foci underwent repeat bone scintigraphy at a median interval of 23.0 months (range: 11.0–34.0 months) after the initial scan. The median T/NT ratio of orbital lesions decreased from 4.9 (IQR 3.7–6.3) to 3.7 (IQR 3.1–5.8), though this reduction was not statistically significant (Z = -1.034, P = 0.301). Among the five patients with bone metastasis: one demonstrated decreased metabolism in both the orbital lesion and sternal metastatic foci; the remaining four exhibited stable orbital radiotracer uptake, while their osseous metastases showed divergent evolution—progression in two patients (new lesions), decreased metabolic activity in one, and stable disease in one. Regarding the 22 non-metastatic patients with 23 orbital foci: 21 lesions showed no significant interval changes versus baseline imaging (Fig. 2 ), whereas two demonstrated decreased radiotracer intensity (Fig. 3 ). Whole-body evaluation in these patients revealed new extra-orbital uptake suggestive of metastasis in one individual, with no new foci detected in the remaining 21. MRI Findings Thirty-one patients underwent MRI within 14 days of bone scintigraphy. As shown in Table 1 , the results revealed no abnormal signals in orbital bones for 15 patients (48.4%), while 16 patients (51.6%) exhibited 16 lesions with abnormal signals localized to the frontal bone (n = 10) and zygomatic bone (n = 6). The mean long-axis diameter of the lesions was 9.0 ± 2.4 mm. On T1-weighted imaging, 13 lesions demonstrated low signal intensity (Fig. 2 , 3 ), one isointensity, and two slight hyperintensity; T2-weighted sequences showed low signal in 10 lesions (Fig. 2 ), isointensity in four (Fig. 3 ), and high signal in two. Bone-RADS classification assigned category 2 or 3 to 12 lesions and category 4 to four lesions. Eleven lesions underwent MRI follow-up (median interval 16 months; range 11.0–50.0 months), demonstrating stable size in all cases. Signal evolution occurred in two lesions: one T2-hyperintense to isointense, and one T2-isointense to hypointense (Fig. 3 ), while nine maintained stable signal intensity (Fig. 2 ). Table 1 MRI characteristics of orbital uptake in 16 patients detected by bone scintigraphy No. Age Gender Primary Lesion Location on MRI T1 signal T2 Signal MRI Bone-RADS Longest Diameter (mm) follow-up MRI (months) MRI signal changes 1 54 Male Pulmonary Hamartoma Frontal Bone Slightly high Isointense 2 9.0 - - 2 59 Male Rectal Cancer Frontal Bone Low Isointense 4 6.6 44 - 3 63 Male Lung Cancer Zygomatic Bone Low Low 2 or 3 7.6 12 - 4 75 Female Lung Cancer Zygomatic Bone Low Isointense 4 7.3 25 T2 low 5 71 Female Lung Cancer Frontal Bone Slightly high High 2 11.0 102 - 6 64 Male Lung Cancer Zygomatic Bone Low Low 2 or 3 8.6 - - 7 53 Male PVFT Frontal Bone Low High 4 9.8 50 T2 isointense 8 60 Female Lung Cancer Frontal Bone Low Isointense 4 7.3 11 - 9 61 Female Lung Cancer Frontal Bone Low Low 2 or 3 9.1 12 - 10 70 Female Lung Cancer Frontal Bone Low Low 2 or 3 7.3 60 - 11 80 Male Lung Cancer Zygomatic Bone Low Low 2 or 3 5.0 - - 12 59 Male Lung Cancer Frontal Bone Low Low 2 or 3 10.5 16 - 13 73 Male Lung Cancer Zygomatic Bone Isointense Low 2 or 3 10.0 - - 14 67 Male Lung Cancer Frontal Bone Low Low 2 or 3 15.7 11 - 15 70 Female Lung Cancer Frontal Bone Low Low 2 or 3 10.5 13 - 16 66 Male Lung Cancer Zygomatic Bone Low Low 2 or 3 7.9 - - Bone-RADS, bone reporting and data system; PVFT, Pulmonary vascular fibrohistiocytic tumor CT and PET/CT Findings Twenty-one patients with 25 orbital radiotracer uptake foci underwent CT (n = 6) or FDG PET/CT (n = 15) at median 8 months (range, 1 day-86 months) from bone scintigraphy. CT detected abnormal orbital findings in 20 patients (21 foci). One malignant osteolytic lesion with cortical destruction was identified (right sphenoid greater wing; Bone-RADS 4). It showed hypermetabolism (SUVmax 5.1) on PET/CT. Post-therapy imaging confirmed metastasis with osseous remodeling and reduced uptake. The remaining 20 foci demonstrated benign features without aggressive characteristics. These included: 18 Bone-RADS 1 lesions (ground-glass opacities: homogeneous n = 9, heterogeneous n = 7; Fig. 4 ), one benign hypodense focus, and one osteoma; plus 2 Bone-RADS 2/3 lucent lesions. Beyond the previously identified metastatic foci, PET/CT showed minimal or no FDG uptake in other lesions (median SUVmax 1.4, IQR 1.1–1.9). Discussion Our study provides novel insights into the clinical significance of incidentally detected focal orbital uptake on bone scintigraphy, a finding with limited prior characterization. We established a baseline incidence of approximately 0.9% (66/6723 studies), with lesions demonstrating predominant localization to the superior/lateral orbital walls (80.3%, 61/76) and frequent rounded configuration (94.7%, 72/76). Crucially, through a comprehensive multi-modality approach integrating longitudinal follow-up, CT, MRI, and PET/CT, we demonstrated that the overwhelming majority of these lesions are benign. This robust evidence stems from multiple angles: metabolic stability over time (median ΔT/NT = -1.2, P = 0.301), visual stability in 89.3% (25/28) of followed lesions across both metastatic and non-metastatic patient groups, and the absence of aggressive imaging features in all but a single case with morphological studies. The study innovatively applies the Bone-RADS framework to characterize incidental orbital abnormalities on both MRI and CT in the context of focal bone scintigraphy uptake, providing novel etiological insights. Among the 31 patients who underwent brain MRI within 2 weeks of bone scintigraphy, 48.4% (15/31) exhibited no abnormal signals in the orbital bones; in these cases, the focal radiotracer uptake on bone scan may represent physiological uptake at common sites such as the frontozygomatic suture [ 4 ]. Crucially, for the 16 patients exhibiting MRI signal abnormalities within the orbital bones (mean long-axis diameter 9.0 ± 2.4 mm), systematic Bone-RADS classification yielded actionable results: 12 lesions were categorized as Bone-RADS 2 or 3 (benign or probably benign), while 4 lesions were classified as Bone-RADS 4 (suspicious, warranting biopsy or specialist consultation) [ 10 ]. The pivotal finding emerged from longitudinal follow-up (median 16 months) of 11 patients (including all 4 Bone-RADS 4 lesions): Lesion size remained stable in all 11 patients, and signal intensity remained unchanged in 9/11 patients. The signal changes observed in the other two lesions (one T2-hyperintense to isointense, one T2-isointense to hypointense) were not indicative of malignant progression. This compelling stability observed even in initially suspicious (Bone-RADS 4) lesions underscores a critical clinical implication: For focal orbital uptake on bone scan with concomitant MRI signal abnormality, follow-up imaging surveillance is a rational and often preferable strategy over immediate additional or invasive diagnostic procedures. Complementary CT and PET/CT evaluations elucidated orbital uptake foci in 21 patients (25 lesions). CT detected abnormal orbital densities in 21 foci (20 patients), which were subsequently classified using Bone-RADS. One sphenoid greater wing lesion was classified as Bone-RADS category 4 with increased FDG uptake (SUVmax 5.1), consistent with clinically and radiologically diagnosed metastasis. The other 20 lesions demonstrated benign or intermediate features: 18 categorized as Bone-RADS 1 and 2 as Bone-RADS 2 or 3. The predominant subgroup (16 lesions) exhibited characteristic CT ground-glass density—a hallmark of fibrous dysplasia [ 11 – 13 ]. One lesion demonstrated osseous-like hyperdensity compatible with osteoma [ 14 ]. FDG PET/CT revealed predominantly mild metabolic activity (median SUVmax 1.4), consistent with benign entities [ 15 – 17 ]. Collectively, CT findings establish fibrous dysplasia as the principal pathological etiology for incidental orbital uptake. Notably, CT outperformed MRI in abnormality detection (95.2% [20/21] vs 51.6% [16/31]). The principal value of this work lies in its practical guidance for clinicians. By demonstrating the high prevalence of benign etiologies through multi-modality correlation and follow-up, we provide strong evidence supporting conservative management—primarily imaging surveillance—for the vast majority of incidentally detected focal orbital uptake on bone scintigraphy, particularly when solitary and located in the superior/lateral orbit. This approach minimizes the burden of unnecessary invasive procedures for patients. While acknowledging the limitations inherent in our retrospective design, the lack of histopathological confirmation, the unavailability of SPECT/CT fusion, and the fact that some CT or PET/CT examinations were performed at substantially different time points from the bone scintigraphy, the convergence of evidence from diverse imaging modalities and stability over time offers a robust foundation for this clinical recommendation. Future prospective studies incorporating dedicated orbital SPECT/CT could further refine localization and diagnostic accuracy. Conclusions Incidental focal orbital uptake on bone scintigraphy is a relatively uncommon finding, demonstrating characteristic localization to superior/lateral walls with predominantly rounded morphology. Multi-modality correlation, particularly CT-based identification of fibrous dysplasia as the predominant etiology combined with low metabolic profiles and longitudinal stability, establishes a benign origin for the vast majority of cases. CT provides superior structural characterization versus MRI. Individualized imaging surveillance represents an appropriate management approach. Abbreviations FDG fluorodeoxyglucose T/NT target-to-nontarget Bone-RADS bone reporting and data system SUVmax maximum standardized uptake value Declarations Acknowledgements Not applicable. Authors' contributions LS: conceptualisation, data-curation, writing-original draft, formal analysis, writing-original draft, writing-review, and editing. NG: methodology, formal analysis, editing. WFZ: supervision, conceptualisation, data-curation, formal analysis, editing. Funding This work was supported by the National Key R&D Program of China (2023YFC3404600 to LS), Key Clinical Project of Peking University Third Hospital (BYSYZD2024005 to WZ) Data availability The analysed and/or used datasets in this study can be obtained on reasonable request to the corresponding author. Ethics approval and consent to participate This study was conducted as per the Declaration of Helsinki. The approval to the protocol was done by the Ethics Committee of Peking University Third Hospital and each regulation was followed. The requirement for informed consent was waived by the board due to the retrospective nature of the study. Consent for publication  Not Applicable. Competing interests The authors declare that they have no competing interests. References Johnston DL, Story E, Matzinger MA, Halton J. Periorbital ecchymosis ("raccoon eyes") on a bone scan. J Pediatr. 2014; 1271. Gyetvai EJ, Stadalnik RC. Scintigraphic 'eyebrow sign' on bone scan. Clin Nucl Med. 1997; 419. Evgeniou E, Menon KR, Jones GL, Whittet H, Williams W. Renal cell carcinoma metastasis to the paranasal sinuses and orbit. BMJ Case Rep. 2012; Thang SP, Tan AE, Goh AS. Bone Scan "Hot Spot" at the Superior Lateral Orbital Margin Fronto-zygomatic Suture Uptake Characterized with Tc-99m MDP SPECT/CT. World J Nucl Med. 2011; 139-40. Swiętaszczyk C, Pilecki SE. Enhanced accumulation of bone seekers at superior lateral orbital margin: potential origin. World J Nucl Med. 2014; 3-5. Wakankar R, Dharmashaktu Y, Venugopal A, Kumar R. Malignant phyllodes tumor with sphenoid bone metastasis detected on 99mTc-MDP SPECT/CT and 18F-FDG PET/CT. Clin Nucl Med. 2024; Bonnet SE, Palko JR. False-positive technetium-99m methylene diphosphonate bone scan activity in the orbit in a patient with a history of breast carcinoma. World J Nucl Med. 2018; 299-301. Kothekar E, Seraj SM, Kaghazchi F, Werner TJ, Alavi A. 18F-NaF uptake in ocular prosthesis (Implant). Clin Nucl Med. 2020; e59-e60. Wakefield MJ, Ross AH, Damato EM, Salvi SM, Baker GR. Review of lateral orbital wall ossifying fibroma. Orbit. 2010; 317-20. Chang CY, Garner HW, Ahlawat S, Amini B, Bucknor MD, Flug JA, et al. Society of Skeletal Radiology- white paper. Guidelines for the diagnostic management of incidental solitary bone lesions on CT and MRI in adults: bone reporting and data system (Bone-RADS). Skeletal Radiol. 2022; 1743-64. Bedell M, Naous R. Primary osseous tumors of the orbit. Virchows Archiv. 2024; Gerrie SK, Navarro OM, Lyons CJ, Marie E, Rajani H, Frayn CS, et al. Pediatric orbital lesions: bony and traumatic lesions. Pediatr Radiol. 2024; 897-909. Kushchayeva YS, Kushchayev SV, Glushko TY, Tella SH, Teytelboym OM, Collins MT, et al. Fibrous dysplasia for radiologists: beyond ground glass bone matrix. Insights Imaging. 2018; 1035-56. Xing Y, Zhao J, Wang T. A case of paranasal sinuses osteoma detected on bone SPECT/CT. Clin Nucl Med. 2011; 224-6. Muheremu A, Niu X. Positron emission tomography/computed tomography for bone tumors (Review). Oncol Lett. 2015; 522-6. Dimitrakopoulou-Strauss A, Strauss LG, Heichel T, Wu H, Burger C, Bernd L, et al. The role of quantitative (18)F-FDG PET studies for the differentiation of malignant and benign bone lesions. J Nucl Med. 2002; 510-8. Cheung H, Yechoor A, Behnia F, Abadi AB, Khodarahmi I, Soltanolkotabi M, et al. Common Skeletal Neoplasms and Nonneoplastic Lesions at 18F-FDG PET/CT. RadioGraphics. 2022; 250-67. Additional Declarations No competing interests reported. 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02:13:10","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":124204,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7472182/v1/9cb61161f4af2fe1d52314a1.png"},{"id":93728847,"identity":"2e382492-c8ee-4aa6-a9e3-730ef00ae622","added_by":"auto","created_at":"2025-10-17 02:13:10","extension":"xml","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":68844,"visible":true,"origin":"","legend":"","description":"","filename":"cd64401277d34c9caef079699e2be5931structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7472182/v1/39d72928df156cc2dfac064b.xml"},{"id":93730586,"identity":"7d1f1f7b-d825-47b8-ace0-54fe7b07f376","added_by":"auto","created_at":"2025-10-17 02:21:10","extension":"html","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":74020,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7472182/v1/7556fa1e520cc9c3daf9bb8b.html"},{"id":93730582,"identity":"49ea1e5a-a0e2-4584-8d16-56e8601b9a16","added_by":"auto","created_at":"2025-10-17 02:21:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":794977,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study protocol.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7472182/v1/dabd7ff7fe24a4346d32c74c.png"},{"id":93728836,"identity":"ff0ef19c-6f03-476e-b28f-62a0602b9dc3","added_by":"auto","created_at":"2025-10-17 02:13:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1584764,"visible":true,"origin":"","legend":"\u003cp\u003eImaging findings of a patient with lung cancer. Bone scintigraphy (\u003cstrong\u003eA\u003c/strong\u003e) revealed a focal radiotracer uptake in the superior wall of the right orbit (arrow). Concurrent MRI demonstrated an abnormal signal in the right frontal bone, with low signal intensity on both T1-weighted (\u003cstrong\u003eB\u003c/strong\u003e) and T2-weighted (\u003cstrong\u003eC\u003c/strong\u003e) images (arrows, Bone-RADS 2 or 3). Follow-up bone scintigraphy (\u003cstrong\u003eD\u003c/strong\u003e) and MRI 12 months later showed no significant changes in the right orbital radiotracer uptake or signal intensity on T1-weighted (\u003cstrong\u003eE\u003c/strong\u003e) and T2-weighted (\u003cstrong\u003eF\u003c/strong\u003e) images (arrows). Bone-RADS, bone reporting and data system.\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7472182/v1/fb6d052c539b99a0938b6031.png"},{"id":93730583,"identity":"61d1ff0c-5130-4a1f-a8ef-dccfcb588dd5","added_by":"auto","created_at":"2025-10-17 02:21:09","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1606352,"visible":true,"origin":"","legend":"\u003cp\u003eImaging findings of a patient with a left lung nodule. Bone scintigraphy (\u003cstrong\u003eA\u003c/strong\u003e) revealed a focal area of increased radiotracer uptake in the lateral wall of the left orbit (arrow). MRI (\u003cstrong\u003eB\u003c/strong\u003e, \u003cstrong\u003eC\u003c/strong\u003e) demonstrated a hypointense lesion in the left zygomatic bone on T1-weighted image and isointense signal on T2-weighted image (arrow, Bone-RADS 4). Post-surgical histopathology of the lung nodule confirmed adenocarcinoma. The patient was treated with gefitinib but showed mediastinal lymph node progression on chest CT after 25 months. Follow-up bone scintigraphy (\u003cstrong\u003eD\u003c/strong\u003e) indicated a decrease in radiotracer uptake in the left orbital lesion (arrow). MRI showed that the lesion in the left zygomatic bone exhibited hypointense signals on both T1-weighted (\u003cstrong\u003eE\u003c/strong\u003e) and T2-weighted (\u003cstrong\u003eF\u003c/strong\u003e) images (arrow). Bone-RADS, bone reporting and data system.\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7472182/v1/5bca541d09e954a83fd24eb1.png"},{"id":93728837,"identity":"a5ce9abc-23a4-4c3c-8c24-a6b688b7212b","added_by":"auto","created_at":"2025-10-17 02:13:09","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1155148,"visible":true,"origin":"","legend":"\u003cp\u003eImaging findings of a patient with a history of renal failure and hypercalcemia. Bone scintigraphy (\u003cstrong\u003eA\u003c/strong\u003e) revealed a focal area of increased radiotracer uptake in the lateral wall of the right orbit (arrow). She had undergone PET/CT (\u003cstrong\u003eB\u003c/strong\u003e, \u003cstrong\u003eC\u003c/strong\u003e) 16 months earlier for evaluation of a pulmonary nodule, which demonstrated a ground-glass opacity in the right zygomatic bone with a lower density area within (Bone-RADS 1) and mild fluorodeoxyglucose uptake (arrow). Eighty-four months prior, a brain CT (\u003cstrong\u003eD\u003c/strong\u003e) performed due to trauma showed an inhomogeneous ground-glass opacity in the right zygomatic bone (arrow), similar to the findings on PET/CT. Bone-RADS, bone reporting and data system.\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7472182/v1/6be32902553bfab6545a4bf3.png"},{"id":93730617,"identity":"44c3fb62-10a2-4053-9ac1-4b4c621d8e0d","added_by":"auto","created_at":"2025-10-17 02:21:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":9159718,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7472182/v1/cd8f0047-3918-467c-8a23-e9dc734c4abf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Benign nature of incidental orbital uptake on bone scintigraphy: insights from multi- modality imaging and follow-up","fulltext":[{"header":"Background","content":"\u003cp\u003eBone metastasis remains a significant clinical challenge in oncology, often leading to debilitating complications such as pathological fractures and intractable pain that profoundly impact patient quality of life. Whole-body bone scintigraphy serves as the primary imaging modality for detecting skeletal metastases, which typically present as multifocal asymmetric radiotracer uptake in the axial skeleton. In contrast, focal orbital uptake represents a diagnostically complex entity with distinct characteristics across different populations.\u003c/p\u003e\u003cp\u003eIn pediatric patients, orbital uptake may be associated with neuroblastoma metastases, classically manifesting as bilateral symmetric uptake with periorbital ecchymosis \u0026ndash; the \"Raccoon Eyes\" sign [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Adult presentations differ substantially, where orbital metastases are exceptionally rare events. Documented cases include prostate carcinoma causing the \"Eyebrow Sign\" through supraorbital involvement [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], and renal cell carcinoma invading orbito-sinus regions with neurological sequelae [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Crucially, non-malignant etiologies constitute the majority of differential considerations, encompassing physiological variants like frontozygomatic suture uptake [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], lacrimal gland disorders, and benign osseous conditions [\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis etiological heterogeneity creates substantial diagnostic uncertainty in clinical practice. Current literature lacks comprehensive analyses quantifying prevalence or establishing evidence-based management pathways for incidental orbital uptake. To address these critical knowledge gaps, we conducted a retrospective multi-modality investigation integrating bone scintigraphy with structural and metabolic imaging (CT, MRI, PET-CT) complemented by longitudinal follow-up. The study was designed to determine the incidence and topographic features of orbital uptake, verify underlying etiologies through imaging correlation, and derive clinically applicable evaluation algorithms.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Population\u003c/h2\u003e\u003cp\u003eThe patient selection process is schematically illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. This retrospective study was approved by the institutional review board, with a waiver of informed consent. Among 6,723 patients who underwent whole-body bone scintigraphy at our institution between January 2019 and December 2022, a PACS database search using the keyword 'orbit' identified 73 potential subjects. Inclusion criteria comprised: (1) focal radionuclide uptake localized to the orbital wall on whole-body bone scintigraphy, and (2) age\u0026thinsp;\u0026gt;\u0026thinsp;18 years. Exclusion criteria were history of orbital fracture, or prior orbital surgery. After screening, 66 patients were ultimately included, comprising 46 males and 20 females, with a median age of 63.5 (range: 29\u0026ndash;83) years. Among the 66 patients, 60 had malignancies (lung: 33; prostate: 13; breast: 11; rectal: 1; lymphoma: 1; osteosarcoma: 1), and 6 had benign conditions (pulmonary hamartoma: 1; hypercalcemia: 1; elevated M protein: 1; fever: 1; rib lesion: 1; arthritis: 1). ​​No patients reported orbital discomfort during bone scintigraphy or the follow-up period.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eBone Scintigraphy Protocol\u003c/h3\u003e\n\u003cp\u003eBone scintigraphy was performed using Siemens Symbia Intevo SPECT/CT or Philips Skylight SPECT systems equipped with low-energy high-resolution collimators. Patients received intravenous administration of Tc-99m Methylene Diphosphonate (MDP, 740 MBq; radiochemical purity\u0026thinsp;\u0026gt;\u0026thinsp;95%). Whole-body anterior and posterior planar images were acquired 4 hours post-injection at a scanning speed of 15 cm/min (energy window: 140 keV\u0026thinsp;\u0026plusmn;\u0026thinsp;20%; matrix: 512\u0026times;1024).\u003c/p\u003e\n\u003ch3\u003eMRI Acquisition Protocols\u003c/h3\u003e\n\u003cp\u003eBrain MRI was conducted using 1.5T or 3.0T scanners (Siemens Prisma, GE Signa HDxt, GE Optima MR360, or UIH uMR 770). Standard sequences included: T1-weighted imaging (T1WI): TR\u0026thinsp;=\u0026thinsp;300\u0026ndash;800 ms, TE\u0026thinsp;\u0026lt;\u0026thinsp;30 ms. T2-weighted imaging (T2WI): TR\u0026thinsp;\u0026gt;\u0026thinsp;2000 ms, TE\u0026thinsp;=\u0026thinsp;80\u0026ndash;130 ms. FLAIR T2WI: TR\u0026thinsp;=\u0026thinsp;8000-10,000 ms, TE\u0026thinsp;=\u0026thinsp;80\u0026ndash;130 ms. All scans utilized a slice thickness of 5 mm, interslice gap of 6 mm, and FOV of 200\u0026ndash;240 mm.\u003c/p\u003e\n\u003ch3\u003ePET/CT Protocol\u003c/h3\u003e\n\u003cp\u003ePET/CT imaging was performed using a Siemens Biograph 64 scanner. Patients fasted for \u0026ge;\u0026thinsp;6 hours before intravenous injection of fluorine-18 fluorodeoxyglucose (FDG) (3.7\u0026ndash;5.5 MBq/kg). Trunk and cranial imaging commenced 60 minutes post-injection. Cranial CT parameters included: 120 kV, 250 mA, pitch 0.9, slice thickness 3 mm. Cranial PET data were reconstructed using True X software (4 iterations, 16 subsets; Gaussian filter: 4.0 mm FWHM).\u003c/p\u003e\n\u003ch3\u003eImage Analysis\u003c/h3\u003e\n\u003cp\u003eTwo senior nuclear medicine physicians independently reviewed all imaging studies, ​​with discrepancies resolved through consensus.​ ​​Multimodal imaging (bone scintigraphy, CT, and MRI) was evaluated via the Centricity RIS CE V3.0 platform (GE healthcare, USA).​ The location (superior, lateral, medial, and inferior walls) and morphology of orbital radiotracer uptake foci were meticulously documented through bone scintigraphy. For follow-up patients, 1) the grayscale of the bone scintigraphy images was calibrated to ensure consistency in the degree of radiotracer uptake in the skull across imaging sessions. Changes in the radiotracer uptake of orbital lesions were systematically observed, with attention to increases, decreases, or no significant alterations. 2) Quantitative analysis was performed by drawing regions of interest (ROI) to calculate the target-to-nontarget (T/NT), with the nontarget ROI placed within the contralateral orbit, avoiding the orbital wall, and selecting the maximum value. 3) Additionally, the assessment of the entire skeletal system was conducted to determine the presence of any new bone metastases and to evaluate the changes in existing bone metastases.\u003c/p\u003e\u003cp\u003eOn cranial CT or MRI images, orbital lesions were systematically evaluated using the bone reporting and data system (Bone-RADS) criteria [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Both modalities assessed lesion location, size, and aggressive features\u0026mdash;including cortical destruction, soft tissue extension, pathologic fracture, and aggressive periosteal reaction. CT specifically classified density patterns: lucent lesions were defined as \u0026gt;\u0026thinsp;90% volume exhibiting lower attenuation than normal trabecular bone, while lesions with higher attenuation were categorized as sclerotic or mixed density. MRI evaluations focused on signal intensity characteristics: T1 hyperintense (\u0026gt;\u0026thinsp;skeletal muscle), T1 iso/hypointense (\u0026le;\u0026thinsp;skeletal muscle); T2 hyperintense (fluid-equivalent), T2 hypointense (air/cortical bone-equivalent), and intermediate T2 (between fluid and muscle).\u003c/p\u003e\u003cp\u003eFor patients who underwent PET/CT imaging, the maximum standardized uptake value (SUVmax) of each orbital lesion was quantified on a Medex workstation (Medix Technology Co., Ltd., Beijing, China).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eAnalyses were conducted using SPSS v27.0 (IBM Corp.). Continuous variables were assessed for normality using the Shapiro-Wilk test. Normally distributed data are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; non-normally distributed variables are expressed as median with interquartile range (IQR; P25-P75). Categorical variables expressed as percentages. Wilcoxon signed-rank test was used to evaluate changes in T/NT values during follow-up. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eBone Scan Findings\u003c/h2\u003e\u003cp\u003eAmong the 66 patients, 58 presented with solitary orbital lesions, while 8 patients exhibited multiple orbital lesions. A total of 76 foci of increased radioactivity were detected in the orbits, including 44 in the superior orbital wall (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), 17 in the lateral wall (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), 6 in the medial wall, and 9 in the inferior wall. Seventy-two lesions were round in shape, while four showed stripe-shaped increased radioactivity.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFive patients demonstrated multifocal radiotracer uptake in the spine, ribs, and sternum, consistent with typical metastatic disease. One patient exhibited sacral radiotracer uptake representing a primary osteosarcoma lesion. One arthritis patient showed multifocal hypermetabolic foci involving the spine and joints. Thirty-four patients demonstrated degenerative changes in the spine and/or joints, while 17 patients exhibited other benign foci of increased radiotracer uptake, including fractures, dental disease, and sinusitis. In 13 patients, the whole-body bone scan revealed no abnormal radiotracer uptake outside the orbits.\u003c/p\u003e\u003cp\u003eTwenty-seven patients (including 5 with bone metastasis) with 28 orbital radiotracer uptake foci underwent repeat bone scintigraphy at a median interval of 23.0 months (range: 11.0\u0026ndash;34.0 months) after the initial scan. The median T/NT ratio of orbital lesions decreased from 4.9 (IQR 3.7\u0026ndash;6.3) to 3.7 (IQR 3.1\u0026ndash;5.8), though this reduction was not statistically significant (Z = -1.034, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.301). Among the five patients with bone metastasis: one demonstrated decreased metabolism in both the orbital lesion and sternal metastatic foci; the remaining four exhibited stable orbital radiotracer uptake, while their osseous metastases showed divergent evolution\u0026mdash;progression in two patients (new lesions), decreased metabolic activity in one, and stable disease in one. Regarding the 22 non-metastatic patients with 23 orbital foci: 21 lesions showed no significant interval changes versus baseline imaging (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), whereas two demonstrated decreased radiotracer intensity (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Whole-body evaluation in these patients revealed new extra-orbital uptake suggestive of metastasis in one individual, with no new foci detected in the remaining 21.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eMRI Findings\u003c/h2\u003e\u003cp\u003eThirty-one patients underwent MRI within 14 days of bone scintigraphy. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the results revealed no abnormal signals in orbital bones for 15 patients (48.4%), while 16 patients (51.6%) exhibited 16 lesions with abnormal signals localized to the frontal bone (n\u0026thinsp;=\u0026thinsp;10) and zygomatic bone (n\u0026thinsp;=\u0026thinsp;6). The mean long-axis diameter of the lesions was 9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 mm. On T1-weighted imaging, 13 lesions demonstrated low signal intensity (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), one isointensity, and two slight hyperintensity; T2-weighted sequences showed low signal in 10 lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), isointensity in four (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), and high signal in two. Bone-RADS classification assigned category 2 or 3 to 12 lesions and category 4 to four lesions. Eleven lesions underwent MRI follow-up (median interval 16 months; range 11.0\u0026ndash;50.0 months), demonstrating stable size in all cases. Signal evolution occurred in two lesions: one T2-hyperintense to isointense, and one T2-isointense to hypointense (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), while nine maintained stable signal intensity (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMRI characteristics of orbital uptake in 16 patients detected by bone scintigraphy\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo.\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePrimary Lesion\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eLocation on MRI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eT1 signal\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eT2 Signal\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eMRI Bone-RADS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eLongest Diameter (mm)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003efollow-up MRI (months)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eMRI signal changes\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePulmonary Hamartoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSlightly high\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIsointense\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e9.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRectal Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIsointense\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e6.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eZygomatic Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e7.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eZygomatic Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIsointense\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eT2 low\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSlightly high\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHigh\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e11.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e102\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eZygomatic Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e8.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePVFT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHigh\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e9.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eT2 isointense\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIsointense\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e9.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eZygomatic Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e5.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e10.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eZygomatic Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eIsointense\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e15.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrontal Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e10.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLung Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eZygomatic Bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 or 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e7.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"11\"\u003eBone-RADS, bone reporting and data system; PVFT, Pulmonary vascular fibrohistiocytic tumor\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eCT and PET/CT Findings\u003c/h2\u003e\u003cp\u003eTwenty-one patients with 25 orbital radiotracer uptake foci underwent CT (n\u0026thinsp;=\u0026thinsp;6) or FDG PET/CT (n\u0026thinsp;=\u0026thinsp;15) at median 8 months (range, 1 day-86 months) from bone scintigraphy. CT detected abnormal orbital findings in 20 patients (21 foci). One malignant osteolytic lesion with cortical destruction was identified (right sphenoid greater wing; Bone-RADS 4). It showed hypermetabolism (SUVmax 5.1) on PET/CT. Post-therapy imaging confirmed metastasis with osseous remodeling and reduced uptake. The remaining 20 foci demonstrated benign features without aggressive characteristics. These included: 18 Bone-RADS 1 lesions (ground-glass opacities: homogeneous n\u0026thinsp;=\u0026thinsp;9, heterogeneous n\u0026thinsp;=\u0026thinsp;7; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), one benign hypodense focus, and one osteoma; plus 2 Bone-RADS 2/3 lucent lesions. Beyond the previously identified metastatic foci, PET/CT showed minimal or no FDG uptake in other lesions (median SUVmax 1.4, IQR 1.1\u0026ndash;1.9).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study provides novel insights into the clinical significance of incidentally detected focal orbital uptake on bone scintigraphy, a finding with limited prior characterization. We established a baseline incidence of approximately 0.9% (66/6723 studies), with lesions demonstrating predominant localization to the superior/lateral orbital walls (80.3%, 61/76) and frequent rounded configuration (94.7%, 72/76). Crucially, through a comprehensive multi-modality approach integrating longitudinal follow-up, CT, MRI, and PET/CT, we demonstrated that the overwhelming majority of these lesions are benign. This robust evidence stems from multiple angles: metabolic stability over time (median ΔT/NT = -1.2, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.301), visual stability in 89.3% (25/28) of followed lesions across both metastatic and non-metastatic patient groups, and the absence of aggressive imaging features in all but a single case with morphological studies.\u003c/p\u003e\u003cp\u003eThe study innovatively applies the Bone-RADS framework to characterize incidental orbital abnormalities on both MRI and CT in the context of focal bone scintigraphy uptake, providing novel etiological insights. Among the 31 patients who underwent brain MRI within 2 weeks of bone scintigraphy, 48.4% (15/31) exhibited no abnormal signals in the orbital bones; in these cases, the focal radiotracer uptake on bone scan may represent physiological uptake at common sites such as the frontozygomatic suture [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Crucially, for the 16 patients exhibiting MRI signal abnormalities within the orbital bones (mean long-axis diameter 9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 mm), systematic Bone-RADS classification yielded actionable results: 12 lesions were categorized as Bone-RADS 2 or 3 (benign or probably benign), while 4 lesions were classified as Bone-RADS 4 (suspicious, warranting biopsy or specialist consultation) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The pivotal finding emerged from longitudinal follow-up (median 16 months) of 11 patients (including all 4 Bone-RADS 4 lesions): Lesion size remained stable in all 11 patients, and signal intensity remained unchanged in 9/11 patients. The signal changes observed in the other two lesions (one T2-hyperintense to isointense, one T2-isointense to hypointense) were not indicative of malignant progression. This compelling stability observed even in initially suspicious (Bone-RADS 4) lesions underscores a critical clinical implication: For focal orbital uptake on bone scan with concomitant MRI signal abnormality, follow-up imaging surveillance is a rational and often preferable strategy over immediate additional or invasive diagnostic procedures.\u003c/p\u003e\u003cp\u003eComplementary CT and PET/CT evaluations elucidated orbital uptake foci in 21 patients (25 lesions). CT detected abnormal orbital densities in 21 foci (20 patients), which were subsequently classified using Bone-RADS. One sphenoid greater wing lesion was classified as Bone-RADS category 4 with increased FDG uptake (SUVmax 5.1), consistent with clinically and radiologically diagnosed metastasis. The other 20 lesions demonstrated benign or intermediate features: 18 categorized as Bone-RADS 1 and 2 as Bone-RADS 2 or 3. The predominant subgroup (16 lesions) exhibited characteristic CT ground-glass density\u0026mdash;a hallmark of fibrous dysplasia [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. One lesion demonstrated osseous-like hyperdensity compatible with osteoma [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. FDG PET/CT revealed predominantly mild metabolic activity (median SUVmax 1.4), consistent with benign entities [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Collectively, CT findings establish fibrous dysplasia as the principal pathological etiology for incidental orbital uptake. Notably, CT outperformed MRI in abnormality detection (95.2% [20/21] vs 51.6% [16/31]).\u003c/p\u003e\u003cp\u003eThe principal value of this work lies in its practical guidance for clinicians. By demonstrating the high prevalence of benign etiologies through multi-modality correlation and follow-up, we provide strong evidence supporting conservative management\u0026mdash;primarily imaging surveillance\u0026mdash;for the vast majority of incidentally detected focal orbital uptake on bone scintigraphy, particularly when solitary and located in the superior/lateral orbit. This approach minimizes the burden of unnecessary invasive procedures for patients. While acknowledging the limitations inherent in our retrospective design, the lack of histopathological confirmation, the unavailability of SPECT/CT fusion, and the fact that some CT or PET/CT examinations were performed at substantially different time points from the bone scintigraphy, the convergence of evidence from diverse imaging modalities and stability over time offers a robust foundation for this clinical recommendation. Future prospective studies incorporating dedicated orbital SPECT/CT could further refine localization and diagnostic accuracy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIncidental focal orbital uptake on bone scintigraphy is a relatively uncommon finding, demonstrating characteristic localization to superior/lateral walls with predominantly rounded morphology. Multi-modality correlation, particularly CT-based identification of fibrous dysplasia as the predominant etiology combined with low metabolic profiles and longitudinal stability, establishes a benign origin for the vast majority of cases. CT provides superior structural characterization versus MRI. Individualized imaging surveillance represents an appropriate management approach.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFDG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003efluorodeoxyglucose\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eT/NT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003etarget-to-nontarget\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBone-RADS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ebone reporting and data system\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSUVmax\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emaximum standardized uptake value\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLS: conceptualisation, data-curation, writing-original draft, formal analysis, writing-original draft, writing-review, and editing. NG: methodology, formal analysis, editing. WFZ: supervision, conceptualisation, data-curation, formal analysis, editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Key R\u0026amp;D Program of China (2023YFC3404600 to LS), Key Clinical Project of Peking University Third Hospital (BYSYZD2024005 to WZ)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe analysed and/or used datasets in this study can be obtained on reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted as per the Declaration of Helsinki. The approval to the protocol was done by the Ethics Committee of Peking University Third Hospital and each regulation was followed. The requirement for informed consent was waived by the board due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Not Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJohnston DL, Story E, Matzinger MA, Halton J. Periorbital ecchymosis (\u0026quot;raccoon eyes\u0026quot;) on a bone scan. J Pediatr. 2014; 1271.\u003c/li\u003e\n\u003cli\u003eGyetvai EJ, Stadalnik RC. Scintigraphic \u0026apos;eyebrow sign\u0026apos; on bone scan. Clin Nucl Med. 1997; 419.\u003c/li\u003e\n\u003cli\u003eEvgeniou E, Menon KR, Jones GL, Whittet H, Williams W. Renal cell carcinoma metastasis to the paranasal sinuses and orbit. BMJ Case Rep. 2012; \u003c/li\u003e\n\u003cli\u003eThang SP, Tan AE, Goh AS. Bone Scan \u0026quot;Hot Spot\u0026quot; at the Superior Lateral Orbital Margin Fronto-zygomatic Suture Uptake Characterized with Tc-99m MDP SPECT/CT. World J Nucl Med. 2011; 139-40.\u003c/li\u003e\n\u003cli\u003eSwiętaszczyk C, Pilecki SE. Enhanced accumulation of bone seekers at superior lateral orbital margin: potential origin. World J Nucl Med. 2014; 3-5.\u003c/li\u003e\n\u003cli\u003eWakankar R, Dharmashaktu Y, Venugopal A, Kumar R. Malignant phyllodes tumor with sphenoid bone metastasis detected on 99mTc-MDP SPECT/CT and 18F-FDG PET/CT. Clin Nucl Med. 2024; \u003c/li\u003e\n\u003cli\u003eBonnet SE, Palko JR. False-positive technetium-99m methylene diphosphonate bone scan activity in the orbit in a patient with a history of breast carcinoma. World J Nucl Med. 2018; 299-301.\u003c/li\u003e\n\u003cli\u003eKothekar E, Seraj SM, Kaghazchi F, Werner TJ, Alavi A. 18F-NaF uptake in ocular prosthesis (Implant). Clin Nucl Med. 2020; e59-e60.\u003c/li\u003e\n\u003cli\u003eWakefield MJ, Ross AH, Damato EM, Salvi SM, Baker GR. Review of lateral orbital wall ossifying fibroma. Orbit. 2010; 317-20.\u003c/li\u003e\n\u003cli\u003eChang CY, Garner HW, Ahlawat S, Amini B, Bucknor MD, Flug JA, et al. Society of Skeletal Radiology- white paper. Guidelines for the diagnostic management of incidental solitary bone lesions on CT and MRI in adults: bone reporting and data system (Bone-RADS). Skeletal Radiol. 2022; 1743-64.\u003c/li\u003e\n\u003cli\u003eBedell M, Naous R. Primary osseous tumors of the orbit. Virchows Archiv. 2024; \u003c/li\u003e\n\u003cli\u003eGerrie SK, Navarro OM, Lyons CJ, Marie E, Rajani H, Frayn CS, et al. Pediatric orbital lesions: bony and traumatic lesions. Pediatr Radiol. 2024; 897-909.\u003c/li\u003e\n\u003cli\u003eKushchayeva YS, Kushchayev SV, Glushko TY, Tella SH, Teytelboym OM, Collins MT, et al. Fibrous dysplasia for radiologists: beyond ground glass bone matrix. Insights Imaging. 2018; 1035-56.\u003c/li\u003e\n\u003cli\u003eXing Y, Zhao J, Wang T. A case of paranasal sinuses osteoma detected on bone SPECT/CT. Clin Nucl Med. 2011; 224-6.\u003c/li\u003e\n\u003cli\u003eMuheremu A, Niu X. Positron emission tomography/computed tomography for bone tumors (Review). Oncol Lett. 2015; 522-6.\u003c/li\u003e\n\u003cli\u003eDimitrakopoulou-Strauss A, Strauss LG, Heichel T, Wu H, Burger C, Bernd L, et al. The role of quantitative (18)F-FDG PET studies for the differentiation of malignant and benign bone lesions. J Nucl Med. 2002; 510-8.\u003c/li\u003e\n\u003cli\u003eCheung H, Yechoor A, Behnia F, Abadi AB, Khodarahmi I, Soltanolkotabi M, et al. Common Skeletal Neoplasms and Nonneoplastic Lesions at 18F-FDG PET/CT. RadioGraphics. 2022; 250-67.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bone scintigraphy, Orbital bone lesions, Fibrous dysplasia, Incidental findings, Multimodal imaging","lastPublishedDoi":"10.21203/rs.3.rs-7472182/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7472182/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective \u003c/strong\u003eTo characterize incidental orbital radionuclide uptake on bone scintigraphy using multi-modal imaging and follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eThis retrospective study included 66 patients with focal orbital uptake on whole-body bone scintigraphy (2019–2022). Subsets underwent follow-up bone scintigraphy (n = 27 patients, median interval 23.0 months), MRI (n = 31 patients, within 14 days of bone scintigraphy), and CT or fluorine-18 fluorodeoxyglucose (FDG) PET/CT (n = 21 patients, median interval from bone scan 8 months). Serial changes in the target-to-nontarget (T/NT) ratio on bone scans were analyzed, while MRI signal/ bone reporting and data system (Bone-RADS)classification, CT morphology/Bone-RADS classification, and metabolic activity (maximum standardized uptake value, SUVmax) were assessed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eSeventy-six orbital foci were evaluated, predominantly localized to the superior/lateral walls (61/76, 80.3%) with round morphology (72/76, 94.7%). Extra-orbital findings included metastasis (5 patients), degenerative changes (34 patients), and benign lesions (17 patients). Follow-up bone scintigraphy showed non-significant T/NT ratio decrease (median 4.9 to 3.7; \u003cem\u003eP\u003c/em\u003e = 0.301), with visual stability in 25/28 lesions (metastatic: 4/5 patients; non-metastatic: 21/23 patients). MRI detected abnormal orbital lesions in 16 patients (16 lesions; mean size 9.0 ± 2.4 mm), involving the frontal bone (n=10) and zygomatic bone (n=6); Bone-RADS categories: 12 category 2/3, 4 category 4. Follow-up MRI (11 lesions) showed stable size; two lesions had signal evolution. CT identified abnormal orbital findings in 20 patients (21 foci), including one osteolytic sphenoid lesion (cortical destruction, Bone-RADS 4, SUVmax 5.1) suggested metastasis. The remaining 20 foci demonstrated benign CT features: 18 Bone-RADS 1 lesions (ground-glass opacities: 16) and 2 Bone-RADS 2/3 lucent lesions. These lesions showed minimal FDG uptake (median SUVmax 1.4) on PET/CT.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eIncidental focal orbital uptake on bone scintigraphy typically localizes to superior/lateral walls with rounded morphology. Multi-modality imaging, particularly CT demonstrating characteristic benign features (predominantly ground-glass opacities) combined with low FDG avidity and longitudinal stability, confirms benign etiology in most cases. CT provides superior osseous characterization versus MRI. Individualized imaging surveillance is appropriate.\u003c/p\u003e","manuscriptTitle":"Benign nature of incidental orbital uptake on bone scintigraphy: insights from multi- modality imaging and follow-up","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 02:13:04","doi":"10.21203/rs.3.rs-7472182/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-03T12:16:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-15T00:32:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-12T08:10:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-09T08:25:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"59150193710137347558289017709635320522","date":"2025-10-06T02:44:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"244416863483558812449193974343881302713","date":"2025-10-05T13:36:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"55811594964343169526889377758674409826","date":"2025-10-04T05:43:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-03T13:15:41+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-02T11:40:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-02T11:38:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-30T02:17:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medical Imaging","date":"2025-08-30T02:14:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6d447a91-c792-4033-b3e5-8134720b075c","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-01T13:23:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-17 02:13:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7472182","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7472182","identity":"rs-7472182","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}