Hexagonal Enhancement Pattern on Hepatobiliary Phase MRI: A New Diagnostic Marker for Budd-Chiari Syndrome

Hexagonal Enhancement Pattern on Hepatobiliary Phase MRI: A New Diagnostic Marker for Budd-Chiari Syndrome | 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 Hexagonal Enhancement Pattern on Hepatobiliary Phase MRI: A New Diagnostic Marker for Budd-Chiari Syndrome Bilal Egemen Cifci, Yusuf Öztürk, Derya Arı, Dilara Turan Gökçe, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6895733/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The aim of our study is to identify the hexagonal-shaped specific enhancement pattern observed in the hepatobiliary phase images obtained using hepatocyte-specific contrast agents in patients who developed chronic hepatic parenchymal disease due to Budd-Chiari Syndrome. Methods Our study included 56 patients with chronic parenchymal disease due to Budd-Chiari Syndrome and two control groups comprising 100 patients with chronic parenchymal disease due to other causes. Hepatocyte-specific contrast agents (5–10 ml) were administered during MRI, and late-phase images were obtained at the 20th and 40th minutes. These images were independently evaluated by three radiologists. The presence of specific imaging findings and hepatic venous variations, if any, were recorded in both groups. Results Among the 56 patients with chronic parenchymal disease caused by Budd-Chiari Syndrome, 46 exhibited a hexagonal-shaped focal enhancement pattern. However, this specific finding was not observed in the two control groups, each consisting of 50 patients with chronic liver parenchymal disease of different etiologies. In the target group, 10 patients without the enhancement pattern were found to have an enlarged right inferior hepatic vein. Conclusion The hexagonal-shaped enhancement pattern observed in the 20th and 40th-minute late-phase MRI images using hepatocyte-specific contrast agents appears to be a specific finding for chronic hepatic parenchymal disease due to Budd-Chiari Syndrome. Budd-Chiari syndrome magnetic resonance imaging hepatic venous outflow obstruction gadoxetic acid Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Budd-Chiari Syndrome (BCS) involves hepatic venous outflow obstruction, affecting any level from the hepatic sinusoids to the inferior vena cava (IVC)–right atrium junction, excluding right heart failure or pericarditis [ 1 , 2 ]. Primary BCS is commonly caused by hypercoagulable states, while membranous webs in hepatic veins or IVC may also lead to thrombosis [ 3 , 4 ]. Secondary BCS usually results from external compression or tumor invasion of hepatic veins [ 5 ]. BCS is classified by venous occlusion level: Type 1 involves IVC ± hepatic veins; Type 2, major hepatic veins; and Type 3, small centrilobular venules (now termed Sinusoidal Obstruction Syndrome) [ 6 , 7 ]. Clinically, it is categorized as acute, subacute, or chronic based on progression. Pathologically, venous congestion raises sinusoidal pressure, causing hepatocyte necrosis. Portal hypertension develops due to venous insufficiency. Preserved drainage areas experience compensatory hepatic arterial hyperperfusion, stimulating regeneration [ 5 ]. Untreated, fibrosis progresses to cirrhosis. Colour Doppler Ultrasound (CDU) is often sufficient for acute-phase diagnosis, detecting hepatic vein/IVC obstruction when supported by clinical and lab findings [ 6 , 7 ]. If inconclusive, CT or MRI is essential for confirmation, assessing disease extent, and guiding treatment [ 8 , 9 ]. Both modalities identify venous occlusion, ascites, splenomegaly, collaterals, portal vein thrombosis, and cirrhosis. Characteristic enhancement patterns (e.g., "Flip-Flop Sign" [ 10 ], "Zonal Contrast Enhancement" [ 11 ], "Mosaic Attenuation" [ 12 ]) aid diagnosis. MRI excels in detecting regenerative nodules, HCC, and chronic changes like parenchymal atrophy and thrombosed veins. Imaging plays a critical role in the diagnosis and monitoring of BCS. This study investigates the association between BCS and focal, hexagonal, sharply demarcated hepatobiliary-phase enhancement (20.–40. minutes post-Primovist) in chronic BCS-related liver disease. This rare finding, reported only once before in only one prior case [ 13 ]. We propose that this contrast enhancement pattern serves as a significant diagnostic marker for BCS, potentially aiding in its diagnosis, and warrants further recognition and inclusion in the medical literature. Material and methods This study was approved by the Human Research Ethics Committee of … Hospital (Approval Date: May 11, 2024; Approval Number: I5-366-21). Written informed consent was waived due to the retrospective nature of the study. Patient Selection This retrospective study compared the radiological imaging findings of patients diagnosed with Budd-Chiari Syndrome (BCS) and non-BCS cirrhosis who underwent dynamic magnetic resonance imaging (MRI) between 2019 and 2024. The study cohort included 56 patients (24 males, 32 females; mean age 49.8 ± 13.6 years) with chronic parenchymal liver disease secondary to Budd-Chiari Syndrome, all of whom underwent MRI with hepatobiliary phase imaging and met the predefined quality standards. Additionally, a control group of 92 patients (44 males, 48 females; mean age 53.3 ± 15.3 years) with chronic parenchymal liver disease due to etiologies such as steatotic liver disease, viral hepatitis, Wilson disease, primary sclerosing cholangitis, primary biliary cholangitis, and cholestatic liver diseases was included for comparison. Exclusion criteria comprised patients with hepatocellular carcinoma (HCC), ascites, or suboptimal imaging quality, ensuring a homogeneous study population. Flow chart of this study is given in Fig. 1 . All dynamic MRI examinations were performed using gadoxetic acid (Primovist, Bayer Healthcare, Leverkusen, Germany) as the intravenous contrast agent, with imaging analysis conducted during the hepatobiliary phase at 20 and 40 minutes post-injection. The contrast agent was administered at a standardized dose of 0.025 mmol/kg and delivered at a rate of 4 mL/s using an automated injector. Imaging was performed using a Signa Pioneer 3T MRI scanner (General Electric), with detailed acquisition parameters provided in Table 1 . Table 1 Detailed T1-weighted sequence parameters following intravenous Gd-EOB-DTPA. Sequence TE TR Matrix FOV Slice thickness Spacing Axial C + T1 2,6 4,9 260x262 40 2 mm 0,5 mm Radiological Evaluation In the Budd-Chiari Syndrome (BCS) group, clinical and radiological characteristics were systematically analyzed to assess the prevalence of specific imaging features and the interobserver consistency in detecting a hexagonal pattern. All radiological images were independently and blindly evaluated by three radiologists with varying expertise (SO: senior [10 years], EO: expert [30 + years], and JO: junior [final-year resident]). Before the study, the senior observer trained the junior observer using 10 BCS cases. Assessors analyzed imaging features like ascites, splenomegaly, collateral veins, portal vein thrombosis, and cirrhosis signs. They also evaluated contrast enhancement patterns ("Flip-Flop Sign," "Zonal Contrast Enhancement," "Mosaic Attenuation") and used MRI to detect regenerative nodules, HCC, and thrombosed hepatic veins. Evaluations were conducted independently without patient details or peer input to ensure objectivity. Statistical Analysis Statistical analyses were performed using Jamovi, a user-friendly and robust statistical analysis software. Cohen’s Kappa was used to evaluate inter-rater agreement between the three observers, focusing on the reliability of hexagonal pattern detection. To assess diagnostic performance, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each observer, with the most experienced radiologist’s findings serving as the gold standard. Univariate and multivariate logistic regression analyses were conducted to explore potential associations between the hexagonal pattern and clinical factors. Odds ratios, p-values, and confidence intervals were calculated for each variable to determine statistical significance. Descriptive statistics, including frequencies, percentages, means, and standard deviations, were also generated to summarize the data. Results Detection of Hexagonal Pattern The EO and the SO, each identified the hexagonal imaging pattern in 79% of cases (44 out of 56 patients), demonstrating a high level of consistency in their assessments. The JO detected the pattern in 73% of cases (41 out of 56 patients). While there was strong agreement between the EO and SO, the JO exhibited a slightly lower detection rate, indicating moderate consistency across all observers (Table 2 ). Table 2 The detection rate of the hexagonal pattern in patients with BCS Expert observer Senior observer Junior observer The the hexagonal pattern, n (%) 44/56 (79%) 44/56 (79%) 41/56 (73%) These findings underscore both the clinical profile of patients with Budd-Chiari Syndrome (BCS) and the reliability of the hexagonal pattern as a diagnostic imaging feature, with particularly strong alignment between the expert and senior observer in pattern identification. Cohen’s Kappa analysis was employed to evaluate interobserver agreement in identifying the hexagonal MRI pattern. The results revealed the following: SO vs JO : The Kappa value was 0.71, indicating moderate to substantial agreement. This level of consistency suggests that the SO and JO largely concurred, with minor discrepancies in their assessments. SO vs EO : The Kappa value was 0.93, reflecting almost perfect agreement. This high Kappa score demonstrates that the SO’s findings closely aligned with those of the EO, establishing the SO as a highly reliable assessor. JO vs EO : The Kappa value was 0.64, indicating moderate agreement. While the JO showed reasonable alignment with the expert, the lower Kappa score reflects reduced reliability compared to the senior observer. These Kappa values highlight the highest level of agreement between the SO and EO, visually reinforcing the conclusion that the senior observer’s assessments most closely align with the expert’s standards. The SO showed near-perfect agreement with the expert EO, with sensitivity = 0.97, specificity = 1.0, PPV = 1.0, and NPV = 0.9. The JO had lower accuracy (sensitivity = 0.85, specificity = 0.89, PPV = 0.97, NPV = 0.62). The hexagonal pattern appeared in 79% of BCS cases (44/56) but was absent in all 92 controls, confirming its diagnostic specificity for BCS (Table 2 – 3 ). Table 3 Clinical features of patients with Budd-Chiari Syndrome (BCS) and non- BCS. Variable BCS(56) Non-BCS (92) p-value Sex, (female), n(%) 32 (57,1%) 28 (25,1%) 0.012 Age, years(mean ± SD) 49.8 ± 13.6 53.3 ± 15.3 0.178 The sensitivity of the hexagonal pattern for diagnosing BCS was calculated to be 78.6% (95% CI: 66.2% − 87.3%), while the specificity was 100% (95% CI: 96.0% − 100%). The positive predictive value (PPV) was 100% (95% CI: 91.9% − 100%), indicating that all patients exhibiting the pattern were correctly diagnosed with BCS. The negative predictive value (NPV) was 82.4% (95% CI: 80.9% − 93.3%), reflecting the ability of the absence of the pattern to exclude the diagnosis in the majority of cases (Fig. 4 ). Additional Findings of BCS Population Of the 56 patients with BCS, 57.1% were female (32 patients). The mean age was 49.8 years, with a standard deviation of 13.6 years, reflecting a varied age distribution within the group. Radiological assessment showed that 17.8% of patients had involvement of the right inferior hepatic vein (RIHV), while 5.7% had undergone Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement. Portal vein thrombosis was observed in 13.1% of patients, with total thrombosis present in 7.4% and partial thrombosis in 5.7%. The occlusion levels were predominantly within the hepatic segment (57.1%), followed by hepatic junction (33.9%) and suprahepatic level (8.9%) (Table 4). Univariate logistic regression analysis demonstrated that no significant associations were observed for age, gender, the level of occlusion or portal vein thrombosis (Table 5). None of the 10 patients with RIHV exhibited the specific finding we defined (Fig. 5 ). Therefore, these patients were not included in the multivariate statistical analysis. Table 5 Associations of Clinical and Imaging Variables with the Hexagonal Imaging Pattern in Budd-Chiari Syndrome Discussion Our study revealed that patients with chronic parenchymal disease secondary to Budd-Chiari Syndrome (BCS) exhibit partially well-demarcated hexagonal areas of contrast enhancement on hepatobiliary phase imaging using hepatocyte-specific contrast agents. This distinctive imaging feature was absent in all patients within the control group. The sensitivity of this finding for diagnosing BCS was 78.6%, with a specificity of 100%, underscoring its diagnostic significance. Computed tomography (CT) is key for diagnosing Budd-Chiari syndrome (BCS), showing distinct patterns in acute and chronic phases. In acute BCS, hepatic vein occlusion causes sinusoidal congestion and parenchymal injury, while preserved drainage areas show compensatory arterial hyperperfusion. On CT, this appears as strong central enhancement with weak peripheral enhancement early, reversing in late-phase imaging—known as the "flip-flop sign" or "zonal enhancement" [ 14 – 16 ]. In the chronic phase of BCS, CT imaging often demonstrates "mosaic perfusion," characterized by heterogeneous and, in some cases, intensely nodular enhancement on portal phase images following contrast administration. During this phase, the hallmark CT findings include hepatic fibrosis and morphologically altered hepatic veins, which appear as non-enhancing, thin, web-like, or tubular structures within the liver parenchyma [ 17 ]. These imaging features collectively contribute to the comprehensive diagnostic evaluation of BCS across its disease spectrum. MRI findings in BCS correlate well with CT and provide reliable non-invasive diagnosis, showing high sensitivity and specificity (> 90%). Advanced techniques like MR elastography, T1/T2 mapping, and DWI further enhance evaluation of congestive, necrotic, and fibrotic liver changes [ 18 ].MRI offers superior diagnostic performance for hepatic pathologies, including BCS, and is the only imaging modality that can use hepatocyte-specific contrast agents like gadoxetic acid (Gd-EOB-DTPA). After injection, the contrast initially circulates in vascular and extravascular spaces, then enters hepatocytes via OATP1 receptors and is excreted into bile via MRP receptors during the hepatobiliary phase [ 19 , 20 ]. This enhances MRI's ability to detect hepatic abnormalities in BCS. In chronic BCS, perisinusoidal fibrosis develops around central venules, though this is nonspecific. Thrombotic vein fibrosis also causes parenchymal retraction [ 21 ]. On hepatobiliary-phase MRI (20–40 min post Gd-EOB-DTPA), sharply demarcated, hyperintense hexagonal enhancing islands appear, bordered by hypointense lines—likely due to parenchymal fibrosis and occluded hepatic veins. No signal differences were seen on pre-contrast or dynamic phases. To reduce confounders, we excluded patients with focal lesions (e.g., FNH-like nodules, HCC, hemangiomas) or classic perfusion anomalies (e.g., mosaic pattern, wedge-shaped changes) seen in acute/subacute BCS [ 22 ]. Few studies describe the hepatobiliary-phase enhancement pattern seen in our BCS cases. Kitajima et al. reported similar patchy enhancement with hypointense borders in a BCS cirrhosis patient, attributing it to hepatocyte necrosis from sinusoidal congestion [ 13 ]. Nakajima et al. (2020) observed a comparable "frog spawn" pattern in Fontan-associated liver disease (FALD), featuring ovoid enhanced islands surrounded by thin hypointense lines [ 23 ]. While similar, morphological differences suggest distinct pathophysiological mechanisms between BCS and FALD. Following Fontan surgery, elevated central venous pressure results in increased pressures within the inferior vena cava (IVC) and hepatic veins, initiating a pathological process analogous to Budd-Chiari Syndrome (BCS). This process begins with hepatic sinusoidal congestion, progresses to hepatocyte necrosis, and ultimately culminates in fibrosis and cirrhosis [ 24 ]. These findings underscore the shared pathophysiological mechanisms between BCS and Fontan-associated liver disease, which are reflected in their imaging characteristics. The characteristic enhancement pattern was absent in 10 patients with a variant right inferior hepatic vein (RIHV), who showed milder lobulation, less portal hypertension, and minimal ascites. We suggest that preserved venous drainage through the RIHV—either directly or via bridging veins—may reduce parenchymal damage, preventing this pattern. Its specificity for BCS is reinforced by its absence in cirrhotic controls (viral/non-viral hepatitis). Hepatic vein occlusion, portal vein thrombosis, and Child/MELD-Na scores did not influence the finding. A limitation of this study is a single centre study, and needs supportive studies for generalizability. The relatively lower diagnostic accuracy observed with the junior radiologist compared to the senior and expert observers. Nevertheless, the strong interobserver agreement between the senior and expert observers supports the statistical reliability of the findings. To our knowledge this study—the largest MRI-based analysis of BCS to date—identifies a unique hepatobiliary-phase finding in chronic BCS: partially demarcated, hexagonal enhancing areas (78.6% sensitivity, 100% specificity). Absent in controls, this pattern likely reflects parenchymal fibrosis and hepatic venous occlusion, serving as a specific imaging biomarker for BCS. This distinctive imaging pattern enhances BCS diagnosis, particularly in chronic cases where findings may overlap with other liver diseases. Its absence in patients with a preserved RIHV underscores its specificity, suggesting intact venous drainage prevents parenchymal damage. Despite limitations from the small cohort and observer variability, strong agreement among senior radiologists supports its reliability. This feature improves diagnostic accuracy and could refine clinical decision-making in BCS. Abbreviations BCS: Budd-Chiari Syndrome CDU: Colour Doppler Ultrasound CT: Computed Tomography EO: Expert observer FALD: Fontan-associated liver disease Gd-EOB-DTPA: gadoxetic acid HCC: Hepatocellular carcinoma IVC: Inferior vena cava JO: Junior observer MRI: Magnetic Resonance Imaging NPV: Negative predictive value PPV: Positive predictive value RIHV: Right inferior hepatic vein SO: Senior observer TIPS: Transjugular Intrahepatic Portosystemic Shunt Declarations Statements and Declarations: All authors of this manuscript disclose no financial or non-financial interests that are directly or indirectly related to the work submitted for publication. Author Contribution BEC (First Author): Conceptualized and designed the study, collected and analyzed the data, contributed significantly to the interpretation of results, and was a major contributor in writing and revising the manuscript. YÖ: Assisted in data collection, contributed to the study design, and participated in drafting and editing the manuscript. DTG and DA: Conducted statistical analyses, contributed to data interpretation, and provided critical feedback on methodological rigor. RSÖ and MA: Played key roles in drafting the manuscript, critically reviewing the content for intellectual depth, and ensuring the accuracy and coherence of the final work. All authors (BEC, YÖ, DTG, DA, RSÖ, MA) reviewed the manuscript critically for important intellectual content, approved the final version to be published, and agreed to be accountable for all aspects of the work. References Janssen HL, Garcia-Pagan JC, Elias E et al (2003) Budd-Chiari syndrome: a review by an expert panel. J Hepatol 38:364–371. https://doi.org/10.1016/S0168-8278(02)00434-8 Valla DC (2003) The diagnosis and management of the Budd-Chiari syndrome: consensus and controversies. Hepatology 38:793–803. https://doi.org/10.1053/jhep.2003.50415 Shrestha SM (2015) Liver cirrhosis in hepatic vena cava syndrome (or membranous obstruction of inferior vena cava). World J Hepatol 7:874–881. https://doi.org/10.4254/wjh.v7.i6.874 Aydinli M (2007) Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. World J Gastroenterol 13:2693–2696. https://doi.org/10.3748/wjg.v13.i19.2693 Cazals-Hatem D (2003) Arterial and portal circulation and parenchymal changes in Budd-Chiari syndrome: a study in 17 explanted livers. Hepatology 37:510–519. https://doi.org/10.1053/jhep.2003.50076 Ludwig J, Hashimoto E, McGill DB, van Heerden JA (1990) Classification of hepatic venous outflow obstruction: ambiguous terminology of the Budd-Chiari syndrome. Mayo Clin Proc 65(1):51–55. https://doi.org/10.1016/s0025-6196(12)62109-0 Loomes DE, Chang A, Webber D, Scudamore CH, Yoshida EM (2011) Acute Budd-Chiari syndrome. Can J Gastroenterol 25:302–303. https://doi.org/10.1155/2011/756425 Van Wettere M, Bruno O, Rautou PE, Vilgrain V, Ronot M (2018) Diagnosis of Budd-Chiari syndrome. Abdom Radiol 43:1896–1907. https://doi.org/10.1007/s00261-017-1447-2 Mamone G, Carollo V, Di Piazza A, Cortis K, Degiorgio S, Miraglia R (2019) Budd-Chiari syndrome and hepatic regenerative nodules: magnetic resonance findings with emphasis of hepatobiliary phase. Eur J Radiol 117:15–25. https://doi.org/10.1016/j.ejrad.2019.05.015 Shukla A, Shreshtha A, Mukund A et al (2021) Budd-Chiari syndrome: consensus guidance of the Asian Pacific Association for the Study of the Liver (APASL). Hepatol Int 15:531–567. https://doi.org/10.1007/s12072-021-10189-4 Madhusudhan KS, Sharma S (2020) Ultrasonography in pediatric Budd-Chiari syndrome. Pediatr Radiol 50:1768–1780. https://doi.org/10.1007/s00247-020-04753-7 Mamone G, Miraglia R (2019) The “mosaic pattern” in hepatic sinusoidal dilatation. Abdom Radiol 44:2949–2950. https://doi.org/10.1007/s00261-019-02057-5 Kitajima K et al (2011) A case of Budd-Chiari syndrome: Gd-EOB-DTPA-enhanced MR findings. Magn Reson Imaging 29:579–583. https://doi.org/10.1016/j.mri.2010.10.013 Brancatelli G, Vilgrain V, Federle MP et al (2007) Budd-Chiari syndrome: spectrum of imaging findings. AJR Am J Roentgenol 188:W168–W176. https://doi.org/10.2214/ajr.05.0168 Bargalló X, Gilabert R, Nicolau C et al (2006) Sonography of Budd-Chiari syndrome. AJR Am J Roentgenol 187:W33–W41. https://doi.org/10.2214/ajr.04.0918 Mathieu D, Vasile N, Menu Y et al (1987) Budd-Chiari syndrome: dynamic CT. Radiology 165:409–413. https://doi.org/10.1148/radiology.165.2.3659365 Noone TC, Semelka RC, Siegelman ES et al (2000) Budd-Chiari syndrome: spectrum of appearances of acute, subacute, and chronic disease with magnetic resonance imaging. J Magn Reson Imaging 11:44–50. https://doi.org/10.1002/(sici)1522-2586 (200001)11:1%3C44::aid-jmri6%3E3.0.co;2-o Erden A, Öz DK, Adıguzel M, Ateş FSÖ (2023) Quantitative liver magnetic resonance imaging: correlation between conventional magnetic resonance imaging, laboratory values, and prognostic indices in Budd–Chiari syndrome. Diagn Interv Radiol 29(3):428–436. DOI: 10.4274/dir.2022.221462 Ringe KI, Husarik DB, Sirlin CB, Merkle EM (2010) Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. AJR Am J Roentgenol 195(1):13–28. https://doi.org/10.2214/ajr.10.4392 Cruite I, Schroeder M, Merkle EM, Sirlin CB (2010) Gadoxetate disodium-enhanced MRI of the liver: part 2, protocol optimization and lesion appearance in the cirrhotic liver. AJR Am J Roentgenol 195(1):29–41. https://doi.org/10.2214/ajr.10.4538 Rizzetto F, Rutanni D, Carnonaro LA, Vanzulli A (2023) Focal Liver Lesions in Budd-Chiari Syndrome: Spectrum of Imaging Findings. Diagnostics 13(14):2346. doi: 10.3390/diagnostics13142346 . Saxena R (2011) Practical hepatic pathology: a diagnostic approach. 1st ed. Elsevier Saunders, Philadelphia, PA, USA Nakajima K, Seki M, Hatakeyama S et al (2020) Visual liver assessment using Gd-EOB-DTPA–enhanced magnetic resonance imaging of patients in the early post-Fontan period. Sci Rep 10:4909. https://doi.org/10.1038/s41598-020-61618-7 Wu FM et al (2011) Liver disease in the patient with Fontan circulation. Congenit Heart Dis 6:190–201. https://doi.org/10.1111/j.1747-0803.2011.00504.x Tables Table 4 is not available with this version. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6895733","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":473321834,"identity":"55d6deb4-918d-44bd-9798-6e47172aa7e5","order_by":0,"name":"Bilal Egemen Cifci","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYDCCA0CcYMPAww/iJBQQrSWNgUeyAcQwIFYLQxoDgwGYQYwWvtuHD354kGAnY3x+deKHBwYM8vxiB/BrkTyXliyRkJDMY3bj7WYJoMMMZ85OwK/F4AyPGUPijwNALWc3gLQkGNwmqIX/G0NCwgEe4xlnN/8gUgsPG1iLAX/vNuJskTzDZgz2i8QN3m0WCQYShP3Cd4b54ccfCXb2/P1nN9/8UWEjzy9NQAsCSIBVShCrHAT4D5CiehSMglEwCkYSAABzekNrwvtdxAAAAABJRU5ErkJggg==","orcid":"","institution":"Ankara Bilkent City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Bilal","middleName":"Egemen","lastName":"Cifci","suffix":""},{"id":473321835,"identity":"cedd1caf-963d-4d00-9a14-516be1204226","order_by":1,"name":"Yusuf Öztürk","email":"","orcid":"","institution":"Ankara Bilkent City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yusuf","middleName":"","lastName":"Öztürk","suffix":""},{"id":473321836,"identity":"f20798c1-dad1-478a-b714-361d27a21631","order_by":2,"name":"Derya Arı","email":"","orcid":"","institution":"Ankara Bilkent City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Derya","middleName":"","lastName":"Arı","suffix":""},{"id":473321837,"identity":"0f8084e9-3c3f-49db-84b0-64d205fc2d37","order_by":3,"name":"Dilara Turan Gökçe","email":"","orcid":"","institution":"Ankara Sincan Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dilara","middleName":"Turan","lastName":"Gökçe","suffix":""},{"id":473321838,"identity":"eb5b4ea7-2cc4-4e8f-be32-1b9ff8eeedfd","order_by":4,"name":"Meral Akdoğan","email":"","orcid":"","institution":"Ankara Bilkent City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Meral","middleName":"","lastName":"Akdoğan","suffix":""},{"id":473321839,"identity":"83bf10a9-b3d1-4ed7-b636-1d1fc157ac30","order_by":5,"name":"Rıza Sarper Ökten","email":"","orcid":"","institution":"Ankara Bilkent City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Rıza","middleName":"Sarper","lastName":"Ökten","suffix":""}],"badges":[],"createdAt":"2025-06-14 21:53:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6895733/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6895733/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85615263,"identity":"54a53013-871c-4d9a-a590-71464d73f16a","added_by":"auto","created_at":"2025-06-29 14:23:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":261034,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow chart of the study.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6895733/v1/0c618327fc01e17828c0cfed.png"},{"id":85615260,"identity":"5b75f8b8-91e8-49c3-a409-4e6b593b33de","added_by":"auto","created_at":"2025-06-29 14:23:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":287555,"visible":true,"origin":"","legend":"\u003cp\u003eAxial hepatobiliary phase image following intravenous Gd-EOB-DTPA administration demonstrates predominantly hexagonal-shaped enhancing foci surrounded by hypointense borders, indicated by black arrows (A). The same section is shown with the boundaries of the contrast-enhancing areas marked by black dots (B).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6895733/v1/8f122ddf6e98a3cbc745dd8f.png"},{"id":85615254,"identity":"c6cf1e12-880f-4d13-b976-745507d6b772","added_by":"auto","created_at":"2025-06-29 14:23:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":182517,"visible":true,"origin":"","legend":"\u003cp\u003eCoronal hepatobiliary phase image following intravenous Gd-EOB-DTPA administration reveals predominantly hexagonal-shaped enhancing foci surrounded by hypointense borders, indicated by black arrows (A). The same section is shown with the boundaries of the contrast-enhancing areas marked by black dots (B).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6895733/v1/1a579cea2b067e6e3cee5117.png"},{"id":85615261,"identity":"43c8cba3-df1f-49a4-bb29-70a7a0ec0b62","added_by":"auto","created_at":"2025-06-29 14:23:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":53572,"visible":true,"origin":"","legend":"\u003cp\u003eDiagnostic metrics of hexagonal imaging pattern.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6895733/v1/2c84ff87f37ca45156c4ee5b.png"},{"id":85615232,"identity":"fd389423-a6d0-4c89-be1d-580b8e7a03ad","added_by":"auto","created_at":"2025-06-29 14:23:40","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":266923,"visible":true,"origin":"","legend":"\u003cp\u003eVenous phase images following intravenous Gd-EOB-DTPA administration demonstrate a patent right inferior hepatic vein (black arrow, A). Axial (B) and coronal (C) hepatobiliary phase images show no evidence of hexagonal contrast-enhanced nodules.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-6895733/v1/847bd9ff9827e2f599e38662.png"},{"id":85709023,"identity":"34fbef90-87d2-49df-bbdd-28aa3a00f968","added_by":"auto","created_at":"2025-07-01 02:01:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1724624,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6895733/v1/ebd914aa-80ae-4652-abf5-92618059d46b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Hexagonal Enhancement Pattern on Hepatobiliary Phase MRI: A New Diagnostic Marker for Budd-Chiari Syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBudd-Chiari Syndrome (BCS) involves hepatic venous outflow obstruction, affecting any level from the hepatic sinusoids to the inferior vena cava (IVC)\u0026ndash;right atrium junction, excluding right heart failure or pericarditis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Primary BCS is commonly caused by hypercoagulable states, while membranous webs in hepatic veins or IVC may also lead to thrombosis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Secondary BCS usually results from external compression or tumor invasion of hepatic veins [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBCS is classified by venous occlusion level: Type 1 involves IVC\u0026thinsp;\u0026plusmn;\u0026thinsp;hepatic veins; Type 2, major hepatic veins; and Type 3, small centrilobular venules (now termed Sinusoidal Obstruction Syndrome) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Clinically, it is categorized as acute, subacute, or chronic based on progression.\u003c/p\u003e \u003cp\u003ePathologically, venous congestion raises sinusoidal pressure, causing hepatocyte necrosis. Portal hypertension develops due to venous insufficiency. Preserved drainage areas experience compensatory hepatic arterial hyperperfusion, stimulating regeneration [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Untreated, fibrosis progresses to cirrhosis.\u003c/p\u003e \u003cp\u003eColour Doppler Ultrasound (CDU) is often sufficient for acute-phase diagnosis, detecting hepatic vein/IVC obstruction when supported by clinical and lab findings [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. If inconclusive, CT or MRI is essential for confirmation, assessing disease extent, and guiding treatment [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Both modalities identify venous occlusion, ascites, splenomegaly, collaterals, portal vein thrombosis, and cirrhosis. Characteristic enhancement patterns (e.g., \"Flip-Flop Sign\" [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], \"Zonal Contrast Enhancement\" [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], \"Mosaic Attenuation\" [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]) aid diagnosis. MRI excels in detecting regenerative nodules, HCC, and chronic changes like parenchymal atrophy and thrombosed veins.\u003c/p\u003e \u003cp\u003eImaging plays a critical role in the diagnosis and monitoring of BCS.\u003c/p\u003e \u003cp\u003eThis study investigates the association between BCS and focal, hexagonal, sharply demarcated hepatobiliary-phase enhancement (20.\u0026ndash;40. minutes post-Primovist) in chronic BCS-related liver disease. This rare finding, reported only once before in only one prior case [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. We propose that this contrast enhancement pattern serves as a significant diagnostic marker for BCS, potentially aiding in its diagnosis, and warrants further recognition and inclusion in the medical literature.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003eThis study was approved by the Human Research Ethics Committee of \u0026hellip; Hospital (Approval Date: May 11, 2024; Approval Number: I5-366-21). Written informed consent was waived due to the retrospective nature of the study.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Selection\u003c/h2\u003e \u003cp\u003eThis retrospective study compared the radiological imaging findings of patients diagnosed with Budd-Chiari Syndrome (BCS) and non-BCS cirrhosis who underwent dynamic magnetic resonance imaging (MRI) between 2019 and 2024. The study cohort included 56 patients (24 males, 32 females; mean age 49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 years) with chronic parenchymal liver disease secondary to Budd-Chiari Syndrome, all of whom underwent MRI with hepatobiliary phase imaging and met the predefined quality standards. Additionally, a control group of 92 patients (44 males, 48 females; mean age 53.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3 years) with chronic parenchymal liver disease due to etiologies such as steatotic liver disease, viral hepatitis, Wilson disease, primary sclerosing cholangitis, primary biliary cholangitis, and cholestatic liver diseases was included for comparison. Exclusion criteria comprised patients with hepatocellular carcinoma (HCC), ascites, or suboptimal imaging quality, ensuring a homogeneous study population. Flow chart of this study is given in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAll dynamic MRI examinations were performed using gadoxetic acid (Primovist, Bayer Healthcare, Leverkusen, Germany) as the intravenous contrast agent, with imaging analysis conducted during the hepatobiliary phase at 20 and 40 minutes post-injection. The contrast agent was administered at a standardized dose of 0.025 mmol/kg and delivered at a rate of 4 mL/s using an automated injector. Imaging was performed using a Signa Pioneer 3T MRI scanner (General Electric), with detailed acquisition parameters provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\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\u003eDetailed T1-weighted sequence parameters following intravenous Gd-EOB-DTPA.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSequence\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMatrix\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFOV\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSlice thickness\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSpacing\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAxial C\u0026thinsp;+\u0026thinsp;T1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e260x262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0,5 mm\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRadiological Evaluation\u003c/h3\u003e\n\u003cp\u003eIn the Budd-Chiari Syndrome (BCS) group, clinical and radiological characteristics were systematically analyzed to assess the prevalence of specific imaging features and the interobserver consistency in detecting a hexagonal pattern.\u003c/p\u003e \u003cp\u003eAll radiological images were independently and blindly evaluated by three radiologists with varying expertise (SO: senior [10 years], EO: expert [30\u0026thinsp;+\u0026thinsp;years], and JO: junior [final-year resident]). Before the study, the senior observer trained the junior observer using 10 BCS cases.\u003c/p\u003e \u003cp\u003eAssessors analyzed imaging features like ascites, splenomegaly, collateral veins, portal vein thrombosis, and cirrhosis signs. They also evaluated contrast enhancement patterns (\"Flip-Flop Sign,\" \"Zonal Contrast Enhancement,\" \"Mosaic Attenuation\") and used MRI to detect regenerative nodules, HCC, and thrombosed hepatic veins. Evaluations were conducted independently without patient details or peer input to ensure objectivity.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using Jamovi, a user-friendly and robust statistical analysis software. Cohen\u0026rsquo;s Kappa was used to evaluate inter-rater agreement between the three observers, focusing on the reliability of hexagonal pattern detection.\u003c/p\u003e \u003cp\u003eTo assess diagnostic performance, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each observer, with the most experienced radiologist\u0026rsquo;s findings serving as the gold standard.\u003c/p\u003e \u003cp\u003eUnivariate and multivariate logistic regression analyses were conducted to explore potential associations between the hexagonal pattern and clinical factors. Odds ratios, p-values, and confidence intervals were calculated for each variable to determine statistical significance. Descriptive statistics, including frequencies, percentages, means, and standard deviations, were also generated to summarize the data.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDetection of Hexagonal Pattern\u003c/h2\u003e \u003cp\u003eThe EO and the SO, each identified the hexagonal imaging pattern in 79% of cases (44 out of 56 patients), demonstrating a high level of consistency in their assessments. The JO detected the pattern in 73% of cases (41 out of 56 patients). While there was strong agreement between the EO and SO, the JO exhibited a slightly lower detection rate, indicating moderate consistency across all observers (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe detection rate of the hexagonal pattern in patients with BCS\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExpert observer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSenior observer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eJunior observer\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe the hexagonal pattern, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44/56 (79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44/56 (79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41/56 (73%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThese findings underscore both the clinical profile of patients with Budd-Chiari Syndrome (BCS) and the reliability of the hexagonal pattern as a diagnostic imaging feature, with particularly strong alignment between the expert and senior observer in pattern identification.\u003c/p\u003e \u003cp\u003eCohen\u0026rsquo;s Kappa analysis was employed to evaluate interobserver agreement in identifying the hexagonal MRI pattern. The results revealed the following:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSO vs JO\u003c/b\u003e: The Kappa value was 0.71, indicating moderate to substantial agreement. This level of consistency suggests that the SO and JO largely concurred, with minor discrepancies in their assessments.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSO vs EO\u003c/b\u003e: The Kappa value was 0.93, reflecting almost perfect agreement. This high Kappa score demonstrates that the SO\u0026rsquo;s findings closely aligned with those of the EO, establishing the SO as a highly reliable assessor.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eJO vs EO\u003c/b\u003e: The Kappa value was 0.64, indicating moderate agreement. While the JO showed reasonable alignment with the expert, the lower Kappa score reflects reduced reliability compared to the senior observer.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThese Kappa values highlight the highest level of agreement between the SO and EO, visually reinforcing the conclusion that the senior observer\u0026rsquo;s assessments most closely align with the expert\u0026rsquo;s standards.\u003c/p\u003e \u003cp\u003eThe SO showed near-perfect agreement with the expert EO, with sensitivity\u0026thinsp;=\u0026thinsp;0.97, specificity\u0026thinsp;=\u0026thinsp;1.0, PPV\u0026thinsp;=\u0026thinsp;1.0, and NPV\u0026thinsp;=\u0026thinsp;0.9. The JO had lower accuracy (sensitivity\u0026thinsp;=\u0026thinsp;0.85, specificity\u0026thinsp;=\u0026thinsp;0.89, PPV\u0026thinsp;=\u0026thinsp;0.97, NPV\u0026thinsp;=\u0026thinsp;0.62). The hexagonal pattern appeared in 79% of BCS cases (44/56) but was absent in all 92 controls, confirming its diagnostic specificity for BCS (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical features of patients with Budd-Chiari Syndrome (BCS) and non- BCS.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCS(56)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-BCS (92)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, (female), n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (57,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (25,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe sensitivity of the hexagonal pattern for diagnosing BCS was calculated to be 78.6% (95% CI: 66.2% \u0026minus;\u0026thinsp;87.3%), while the specificity was 100% (95% CI: 96.0% \u0026minus;\u0026thinsp;100%). The positive predictive value (PPV) was 100% (95% CI: 91.9% \u0026minus;\u0026thinsp;100%), indicating that all patients exhibiting the pattern were correctly diagnosed with BCS. The negative predictive value (NPV) was 82.4% (95% CI: 80.9% \u0026minus;\u0026thinsp;93.3%), reflecting the ability of the absence of the pattern to exclude the diagnosis in the majority of cases (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAdditional Findings of BCS Population\u003c/h2\u003e \u003cp\u003eOf the 56 patients with BCS, 57.1% were female (32 patients). The mean age was 49.8 years, with a standard deviation of 13.6 years, reflecting a varied age distribution within the group. Radiological assessment showed that 17.8% of patients had involvement of the right inferior hepatic vein (RIHV), while 5.7% had undergone Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement. Portal vein thrombosis was observed in 13.1% of patients, with total thrombosis present in 7.4% and partial thrombosis in 5.7%. The occlusion levels were predominantly within the hepatic segment (57.1%), followed by hepatic junction (33.9%) and suprahepatic level (8.9%) (Table\u0026nbsp;4).\u003c/p\u003e \u003cp\u003eUnivariate logistic regression analysis demonstrated that no significant associations were observed for age, gender, the level of occlusion or portal vein thrombosis (Table\u0026nbsp;5). None of the 10 patients with RIHV exhibited the specific finding we defined (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Therefore, these patients were not included in the multivariate statistical analysis.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eTable\u0026nbsp;5\u003c/strong\u003e Associations of Clinical and Imaging Variables with the Hexagonal Imaging Pattern in Budd-Chiari Syndrome\u003c/p\u003e \u003c/p\u003e\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img1750832759.png\"\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study revealed that patients with chronic parenchymal disease secondary to Budd-Chiari Syndrome (BCS) exhibit partially well-demarcated hexagonal areas of contrast enhancement on hepatobiliary phase imaging using hepatocyte-specific contrast agents. This distinctive imaging feature was absent in all patients within the control group. The sensitivity of this finding for diagnosing BCS was 78.6%, with a specificity of 100%, underscoring its diagnostic significance.\u003c/p\u003e \u003cp\u003eComputed tomography (CT) is key for diagnosing Budd-Chiari syndrome (BCS), showing distinct patterns in acute and chronic phases. In acute BCS, hepatic vein occlusion causes sinusoidal congestion and parenchymal injury, while preserved drainage areas show compensatory arterial hyperperfusion. On CT, this appears as strong central enhancement with weak peripheral enhancement early, reversing in late-phase imaging\u0026mdash;known as the \"flip-flop sign\" or \"zonal enhancement\" [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the chronic phase of BCS, CT imaging often demonstrates \"mosaic perfusion,\" characterized by heterogeneous and, in some cases, intensely nodular enhancement on portal phase images following contrast administration. During this phase, the hallmark CT findings include hepatic fibrosis and morphologically altered hepatic veins, which appear as non-enhancing, thin, web-like, or tubular structures within the liver parenchyma [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. These imaging features collectively contribute to the comprehensive diagnostic evaluation of BCS across its disease spectrum.\u003c/p\u003e \u003cp\u003eMRI findings in BCS correlate well with CT and provide reliable non-invasive diagnosis, showing high sensitivity and specificity (\u0026gt;\u0026thinsp;90%). Advanced techniques like MR elastography, T1/T2 mapping, and DWI further enhance evaluation of congestive, necrotic, and fibrotic liver changes [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].MRI offers superior diagnostic performance for hepatic pathologies, including BCS, and is the only imaging modality that can use hepatocyte-specific contrast agents like gadoxetic acid (Gd-EOB-DTPA). After injection, the contrast initially circulates in vascular and extravascular spaces, then enters hepatocytes via OATP1 receptors and is excreted into bile via MRP receptors during the hepatobiliary phase [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This enhances MRI's ability to detect hepatic abnormalities in BCS.\u003c/p\u003e \u003cp\u003eIn chronic BCS, perisinusoidal fibrosis develops around central venules, though this is nonspecific. Thrombotic vein fibrosis also causes parenchymal retraction [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. On hepatobiliary-phase MRI (20\u0026ndash;40 min post Gd-EOB-DTPA), sharply demarcated, hyperintense hexagonal enhancing islands appear, bordered by hypointense lines\u0026mdash;likely due to parenchymal fibrosis and occluded hepatic veins. No signal differences were seen on pre-contrast or dynamic phases. To reduce confounders, we excluded patients with focal lesions (e.g., FNH-like nodules, HCC, hemangiomas) or classic perfusion anomalies (e.g., mosaic pattern, wedge-shaped changes) seen in acute/subacute BCS [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFew studies describe the hepatobiliary-phase enhancement pattern seen in our BCS cases. Kitajima et al. reported similar patchy enhancement with hypointense borders in a BCS cirrhosis patient, attributing it to hepatocyte necrosis from sinusoidal congestion [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Nakajima et al. (2020) observed a comparable \"frog spawn\" pattern in Fontan-associated liver disease (FALD), featuring ovoid enhanced islands surrounded by thin hypointense lines [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. While similar, morphological differences suggest distinct pathophysiological mechanisms between BCS and FALD.\u003c/p\u003e \u003cp\u003eFollowing Fontan surgery, elevated central venous pressure results in increased pressures within the inferior vena cava (IVC) and hepatic veins, initiating a pathological process analogous to Budd-Chiari Syndrome (BCS). This process begins with hepatic sinusoidal congestion, progresses to hepatocyte necrosis, and ultimately culminates in fibrosis and cirrhosis [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These findings underscore the shared pathophysiological mechanisms between BCS and Fontan-associated liver disease, which are reflected in their imaging characteristics.\u003c/p\u003e \u003cp\u003eThe characteristic enhancement pattern was absent in 10 patients with a variant right inferior hepatic vein (RIHV), who showed milder lobulation, less portal hypertension, and minimal ascites. We suggest that preserved venous drainage through the RIHV\u0026mdash;either directly or via bridging veins\u0026mdash;may reduce parenchymal damage, preventing this pattern. Its specificity for BCS is reinforced by its absence in cirrhotic controls (viral/non-viral hepatitis). Hepatic vein occlusion, portal vein thrombosis, and Child/MELD-Na scores did not influence the finding.\u003c/p\u003e \u003cp\u003eA limitation of this study is a single centre study, and needs supportive studies for generalizability. The relatively lower diagnostic accuracy observed with the junior radiologist compared to the senior and expert observers. Nevertheless, the strong interobserver agreement between the senior and expert observers supports the statistical reliability of the findings.\u003c/p\u003e \u003cp\u003eTo our knowledge this study\u0026mdash;the largest MRI-based analysis of BCS to date\u0026mdash;identifies a unique hepatobiliary-phase finding in chronic BCS: partially demarcated, hexagonal enhancing areas (78.6% sensitivity, 100% specificity). Absent in controls, this pattern likely reflects parenchymal fibrosis and hepatic venous occlusion, serving as a specific imaging biomarker for BCS.\u003c/p\u003e \u003cp\u003eThis distinctive imaging pattern enhances BCS diagnosis, particularly in chronic cases where findings may overlap with other liver diseases. Its absence in patients with a preserved RIHV underscores its specificity, suggesting intact venous drainage prevents parenchymal damage. Despite limitations from the small cohort and observer variability, strong agreement among senior radiologists supports its reliability. This feature improves diagnostic accuracy and could refine clinical decision-making in BCS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eBCS:\u003c/strong\u003e Budd-Chiari Syndrome\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCDU:\u003c/strong\u003e Colour Doppler Ultrasound\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCT:\u003c/strong\u003e Computed Tomography\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEO:\u003c/strong\u003e Expert observer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFALD:\u003c/strong\u003e Fontan-associated liver disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGd-EOB-DTPA:\u003c/strong\u003e gadoxetic acid\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHCC:\u003c/strong\u003e Hepatocellular carcinoma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIVC:\u003c/strong\u003e Inferior vena cava\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eJO:\u003c/strong\u003e Junior observer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRI:\u003c/strong\u003e Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNPV:\u003c/strong\u003e Negative predictive value\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePPV:\u003c/strong\u003e Positive predictive value\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRIHV:\u003c/strong\u003e Right inferior hepatic vein\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSO:\u003c/strong\u003e Senior observer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTIPS:\u003c/strong\u003e Transjugular Intrahepatic Portosystemic Shunt\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatements and Declarations:\u0026nbsp;\u003c/strong\u003eAll authors of this manuscript disclose no financial or non-financial interests that are directly or indirectly related to the work submitted for publication.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eBEC (First Author): Conceptualized and designed the study, collected and analyzed the data, contributed significantly to the interpretation of results, and was a major contributor in writing and revising the manuscript. Y\u0026Ouml;: Assisted in data collection, contributed to the study design, and participated in drafting and editing the manuscript. DTG and DA: Conducted statistical analyses, contributed to data interpretation, and provided critical feedback on methodological rigor. RS\u0026Ouml; and MA: Played key roles in drafting the manuscript, critically reviewing the content for intellectual depth, and ensuring the accuracy and coherence of the final work. All authors (BEC, Y\u0026Ouml;, DTG, DA, RS\u0026Ouml;, MA) reviewed the manuscript critically for important intellectual content, approved the final version to be published, and agreed to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJanssen HL, Garcia-Pagan JC, Elias E et al (2003) Budd-Chiari syndrome: a review by an expert panel. J Hepatol 38:364\u0026ndash;371. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0168-8278(02)00434-8\u003c/span\u003e\u003cspan address=\"10.1016/S0168-8278(02)00434-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValla DC (2003) The diagnosis and management of the Budd-Chiari syndrome: consensus and controversies. Hepatology 38:793\u0026ndash;803. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1053/jhep.2003.50415\u003c/span\u003e\u003cspan address=\"10.1053/jhep.2003.50415\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShrestha SM (2015) Liver cirrhosis in hepatic vena cava syndrome (or membranous obstruction of inferior vena cava). World J Hepatol 7:874\u0026ndash;881. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4254/wjh.v7.i6.874\u003c/span\u003e\u003cspan address=\"10.4254/wjh.v7.i6.874\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAydinli M (2007) Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. World J Gastroenterol 13:2693\u0026ndash;2696. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3748/wjg.v13.i19.2693\u003c/span\u003e\u003cspan address=\"10.3748/wjg.v13.i19.2693\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCazals-Hatem D (2003) Arterial and portal circulation and parenchymal changes in Budd-Chiari syndrome: a study in 17 explanted livers. Hepatology 37:510\u0026ndash;519. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1053/jhep.2003.50076\u003c/span\u003e\u003cspan address=\"10.1053/jhep.2003.50076\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLudwig J, Hashimoto E, McGill DB, van Heerden JA (1990) Classification of hepatic venous outflow obstruction: ambiguous terminology of the Budd-Chiari syndrome. Mayo Clin Proc 65(1):51\u0026ndash;55. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0025-6196(12)62109-0\u003c/span\u003e\u003cspan address=\"10.1016/s0025-6196(12)62109-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoomes DE, Chang A, Webber D, Scudamore CH, Yoshida EM (2011) Acute Budd-Chiari syndrome. Can J Gastroenterol 25:302\u0026ndash;303. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2011/756425\u003c/span\u003e\u003cspan address=\"10.1155/2011/756425\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Wettere M, Bruno O, Rautou PE, Vilgrain V, Ronot M (2018) Diagnosis of Budd-Chiari syndrome. Abdom Radiol 43:1896\u0026ndash;1907. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00261-017-1447-2\u003c/span\u003e\u003cspan address=\"10.1007/s00261-017-1447-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMamone G, Carollo V, Di Piazza A, Cortis K, Degiorgio S, Miraglia R (2019) Budd-Chiari syndrome and hepatic regenerative nodules: magnetic resonance findings with emphasis of hepatobiliary phase. Eur J Radiol 117:15\u0026ndash;25. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ejrad.2019.05.015\u003c/span\u003e\u003cspan address=\"10.1016/j.ejrad.2019.05.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShukla A, Shreshtha A, Mukund A et al (2021) Budd-Chiari syndrome: consensus guidance of the Asian Pacific Association for the Study of the Liver (APASL). Hepatol Int 15:531\u0026ndash;567. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12072-021-10189-4\u003c/span\u003e\u003cspan address=\"10.1007/s12072-021-10189-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadhusudhan KS, Sharma S (2020) Ultrasonography in pediatric Budd-Chiari syndrome. Pediatr Radiol 50:1768\u0026ndash;1780. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00247-020-04753-7\u003c/span\u003e\u003cspan address=\"10.1007/s00247-020-04753-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMamone G, Miraglia R (2019) The \u0026ldquo;mosaic pattern\u0026rdquo; in hepatic sinusoidal dilatation. Abdom Radiol 44:2949\u0026ndash;2950. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00261-019-02057-5\u003c/span\u003e\u003cspan address=\"10.1007/s00261-019-02057-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitajima K et al (2011) A case of Budd-Chiari syndrome: Gd-EOB-DTPA-enhanced MR findings. Magn Reson Imaging 29:579\u0026ndash;583. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.mri.2010.10.013\u003c/span\u003e\u003cspan address=\"10.1016/j.mri.2010.10.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrancatelli G, Vilgrain V, Federle MP et al (2007) Budd-Chiari syndrome: spectrum of imaging findings. AJR Am J Roentgenol 188:W168\u0026ndash;W176. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2214/ajr.05.0168\u003c/span\u003e\u003cspan address=\"10.2214/ajr.05.0168\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBargall\u0026oacute; X, Gilabert R, Nicolau C et al (2006) Sonography of Budd-Chiari syndrome. AJR Am J Roentgenol 187:W33\u0026ndash;W41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2214/ajr.04.0918\u003c/span\u003e\u003cspan address=\"10.2214/ajr.04.0918\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMathieu D, Vasile N, Menu Y et al (1987) Budd-Chiari syndrome: dynamic CT. Radiology 165:409\u0026ndash;413. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1148/radiology.165.2.3659365\u003c/span\u003e\u003cspan address=\"10.1148/radiology.165.2.3659365\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoone TC, Semelka RC, Siegelman ES et al (2000) Budd-Chiari syndrome: spectrum of appearances of acute, subacute, and chronic disease with magnetic resonance imaging. J Magn Reson Imaging 11:44\u0026ndash;50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/(sici)1522-2586\u003c/span\u003e\u003cspan address=\"10.1002/(sici)1522-2586\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e(200001)11:1%3C44::aid-jmri6%3E3.0.co;2-o\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErden A, \u0026Ouml;z DK, Adıguzel M, Ateş FS\u0026Ouml; (2023) Quantitative liver magnetic resonance imaging: correlation between conventional magnetic resonance imaging, laboratory values, and prognostic indices in Budd\u0026ndash;Chiari syndrome. Diagn Interv Radiol 29(3):428\u0026ndash;436. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4274/dir.2022.221462\u003c/span\u003e\u003cspan address=\"10.4274/dir.2022.221462\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRinge KI, Husarik DB, Sirlin CB, Merkle EM (2010) Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. AJR Am J Roentgenol 195(1):13\u0026ndash;28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2214/ajr.10.4392\u003c/span\u003e\u003cspan address=\"10.2214/ajr.10.4392\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCruite I, Schroeder M, Merkle EM, Sirlin CB (2010) Gadoxetate disodium-enhanced MRI of the liver: part 2, protocol optimization and lesion appearance in the cirrhotic liver. AJR Am J Roentgenol 195(1):29\u0026ndash;41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2214/ajr.10.4538\u003c/span\u003e\u003cspan address=\"10.2214/ajr.10.4538\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRizzetto F, Rutanni D, Carnonaro LA, Vanzulli A (2023) Focal Liver Lesions in Budd-Chiari Syndrome: Spectrum of Imaging Findings. Diagnostics 13(14):2346. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/diagnostics13142346\u003c/span\u003e\u003cspan address=\"10.3390/diagnostics13142346\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaxena R (2011) Practical hepatic pathology: a diagnostic approach. 1st ed. Elsevier Saunders, Philadelphia, PA, USA\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakajima K, Seki M, Hatakeyama S et al (2020) Visual liver assessment using Gd-EOB-DTPA\u0026ndash;enhanced magnetic resonance imaging of patients in the early post-Fontan period. Sci Rep 10:4909. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41598-020-61618-7\u003c/span\u003e\u003cspan address=\"10.1038/s41598-020-61618-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu FM et al (2011) Liver disease in the patient with Fontan circulation. Congenit Heart Dis 6:190\u0026ndash;201. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1747-0803.2011.00504.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1747-0803.2011.00504.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 4 is not available with this version.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Budd-Chiari syndrome, magnetic resonance imaging, hepatic venous outflow obstruction, gadoxetic acid","lastPublishedDoi":"10.21203/rs.3.rs-6895733/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6895733/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe aim of our study is to identify the hexagonal-shaped specific enhancement pattern observed in the hepatobiliary phase images obtained using hepatocyte-specific contrast agents in patients who developed chronic hepatic parenchymal disease due to Budd-Chiari Syndrome.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eOur study included 56 patients with chronic parenchymal disease due to Budd-Chiari Syndrome and two control groups comprising 100 patients with chronic parenchymal disease due to other causes. Hepatocyte-specific contrast agents (5\u0026ndash;10 ml) were administered during MRI, and late-phase images were obtained at the 20th and 40th minutes. These images were independently evaluated by three radiologists. The presence of specific imaging findings and hepatic venous variations, if any, were recorded in both groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 56 patients with chronic parenchymal disease caused by Budd-Chiari Syndrome, 46 exhibited a hexagonal-shaped focal enhancement pattern. However, this specific finding was not observed in the two control groups, each consisting of 50 patients with chronic liver parenchymal disease of different etiologies. In the target group, 10 patients without the enhancement pattern were found to have an enlarged right inferior hepatic vein.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe hexagonal-shaped enhancement pattern observed in the 20th and 40th-minute late-phase MRI images using hepatocyte-specific contrast agents appears to be a specific finding for chronic hepatic parenchymal disease due to Budd-Chiari Syndrome.\u003c/p\u003e","manuscriptTitle":"Hexagonal Enhancement Pattern on Hepatobiliary Phase MRI: A New Diagnostic Marker for Budd-Chiari Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-29 14:23:11","doi":"10.21203/rs.3.rs-6895733/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4ec09d78-ecf1-4d25-9e7b-f7ac7562602f","owner":[],"postedDate":"June 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-01T01:53:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-29 14:23:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6895733","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6895733","identity":"rs-6895733","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}