18F-FDG PET/CT in the evaluation of femoral head osteonecrosis in patients with lymphoma

18F-FDG PET/CT in the evaluation of femoral head osteonecrosis in patients with lymphoma | 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 18F-FDG PET/CT in the evaluation of femoral head osteonecrosis in patients with lymphoma Le Song, Hui Li, Anhui Zhu, Weifang Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5855164/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Objective To describe the imaging features of osteonecrosis of the femoral head (ONFH) on fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and explore the value of PET/CT in assessing ONFH in patients with lymphoma. Methods A retrospective analysis was conducted on the clinical data, PET/CT, and MRI manifestations of 17 patients with ONFH and lymphoma. The FDG uptake of ONFH was recorded, and the maximum standardized uptake value (SUV max ) of ONFH was measured. The staging and extent of ONFH, and other bone involvements, were visually assessed. Results A total of 31 femoral heads were involved, including 2 in stage 1, 24 in stage 2, 4 in stage 3, and 1 in stage 4. The median SUV max of ONFH in stage 3–4 (5.27) was higher than that in stage 1–2 (1.37) ( P = 0.002). In stage 1 lesions, both density and FDG uptake were normal. For stage 2 lesions, 11 showed increased FDG uptake along the peripheral linear high-density and/or within the necrotic region, 5 had peripheral increased uptake with internal decreased uptake, 2 exhibited decreased uptake, and 6 showed normal uptake. All lesions in stages 3–4 demonstrated increased FDG uptake along the peripheral linear high-density and/or at the osteolytic area. Thirteen stage 2 lesions were confined above the epiphyseal line, while 11 stage 2 lesions and 5 stage 3–4 lesions extended below the epiphyseal line. The extent of 20 stage 2 lesions and 5 stage 3–4 lesions observed on CT matched that seen on MRI. Nine patients had osteonecrosis in other bones. The humeral heads were involved in 9 patients, with 4 showing increased FDG uptake along the linear high-densities. Bilateral ilia were involved in 6 patients, with 5 demonstrating peripheral linear high densities and internal decreased FDG uptake. One patient had multiple involvements of the vertebrae, ribs, and scapulae. Conclusions In patients with lymphoma, ONFH exhibits variable degrees of FDG uptake and may be accompanied by involvement of other bones. PET/CT is helpful in diagnosing ONFH and detecting multiple bone involvements while assessing lymphoma. Femoral head Osteonecrosis Lymphoma Positron emission tomography-computed tomography Magnetic resonance imaging Figures Figure 1 Figure 2 Figure 3 Background Osteonecrosis of the femoral head (ONFH) is a common disease of the hip joint and characterized by death of the osteocytes and the bone marrow. The main etiological factors for non-traumatic ONFH include the application of corticosteroids, chronic alcohol overconsumption, decompression sickness, haemoglobin diseases, autoimmune diseases, etc. [1, 2]. Patients treated with lymphoma are at high risk of developing ONFH, with an incidence rate of approximately 15% [3]. Early diagnosis is essential for optimal therapeutic management. It is recommended that for patients who complain of hip pain during or after the treatment of lymphoma, a hip MRI examination is suggested to diagnose ONFH [3]. Nevertheless, Ratcliffe et al reported that 40% of patients with ONFH were asymptomatic [3]. Whether asymptomatic patients at risk should be screened, is still not clarified. Asymptomatic osteonecrosis has a high prevalence (59%) of progression to symptomatic disease and femoral head collapse [4]. It seems impractical to perform hip X-rays or even MRIs for all asymptomatic patients with lymphoma. It is also difficult to determine the timing and frequency of the screening examinations. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT has been an important imaging modality for the staging and therapeutic evaluation of lymphoma [5, 6]. We speculate that 18 F-FDG PET/CT also has a role in the evaluation of ONFH for patients with lymphoma. Studies about the value of 18 F-FDG PET/CT for osteonecrosis are limited to a few case reports [7–10]. This retrospective study aims to describe the imaging features of ONFH on 18 F-FDG PET/CT and explore the value of PET/CT in the assessment of ONFH in patients with lymphoma. Methods Study population This was a retrospective study and was approved by the institutional review board of Peking University Third Hospital. The PET/CT image database was searched with the keywords “femoral head” and “osteonecrosis” in patients with lymphoma. All of the retrieved patients underwent magnetic resonance imaging (MRI) scan of the hip and were diagnosed as ONFH. Patients with previously known ONFH before the diagnosis of lymphoma or incomplete clinical data were excluded. A total of 17 patients with ONFH were recruited at Peking University Third Hospital between September 2014 and June 2024. We recorded the symptoms such as aches around the hip joint or at the buttocks. PET/CT examination A Siemens Biograph 64 PET/CT scanner was applied for image acquisition. 18 F-FDG was provided by Beijing Atomic High Technology Co. Patients fasted for longer than 6 hours, and blood glucose levels were monitored (below 11.1 mmol/L) before an injection of 18 F-FDG (5.55 MBq per kilogram of body weight). About 60 minutes after injection, the PET/CT was performed from the tip of the skull to the mid-thigh. CT scan parameters: tube voltage 120 kV, effective tube current 100 mAs, pitch 0.9. PET scans have the same extent as CT, 2 minutes per bed, True X reconstruction, 3 iterations, subset 21, Gaussian filtering, half-peak width 5.0. Image analysis The PET/CT images were transferred to the SIEMENS syngoMMWP VE40A workstation. Two nuclear medicine physicians, both with over 10 years of experience in PET/CT, jointly assessed the PET/CT images. In cases where their opinions diverged, a more senior physician was consulted to make the final decision. The ONFH was staged according to the modified 2019 version of the Association Research Circulation Osseous international classification of osteonecrosis staging system [1]: stage 1, a band lesion of low signal intensity around the necrotic area is seen on MRI, but no changes are seen on CT; stage 2, osteosclerosis or cystic changes are seen in the femoral head without evidence of subchondral fracture, fracture in the necrotic portion or flattening of the femoral head on CT; stage 3, subchondral fracture, fracture in the necrotic portion and/or flattening of the femoral head on CT; stage 4, osteoarthritis of the hip joint with joint space narrowing, acetabular changes and destruction. The FDG uptake of ONFH was compared with that of the surrounding unaffected femoral head. For the semi-quantitative assessment of ONFH, regions of interest (ROIs) were manually delineated on the PET/CT fused images. The maximum standardized uptake value (SUV max ) is calculated as ROI activity (mCi/mL) multiplied by body weight (g), divided by the injected dose (mCi). The extent of ONFH on CT was visually evaluated and compared with that on MRI. Additionally, other bones within the scope of the PET/CT scan were examined for any signs of osteonecrosis. For patients who underwent multiple PET/CT examinations, the FDG metabolism and CT features of ONFH at different time points were analyzed. Statistical Analysis Statistical analyses were conducted using SPSS Statistics software (IBM Corp., Chicago). The Shapiro-Wilk test was employed to assess the normality of data distribution. Data were presented as mean ± standard deviation if they followed a normal distribution; otherwise, they were expressed as median (quartile 1, quartile 3). The Mann-Whitney U test was utilized to compare the SUV max of ONFH at different stages. A P value less than 0.05 was considered to indicate statistical significance. Results Clinical characteristics A total of 17 patients with ONFH (14 men and 3 women; median age 40 years) were enrolled in this retrospective study. All patients had non-Hodgkin lymphoma. At the time of the MRI examination, 6 patients complained of hip or thigh discomfort, such as intermittent or persistent pain and soreness, while the remaining patients did not report local discomfort. The clinical characteristics and PET/CT findings are summarized in Table 1 . Table 1 Clinical characteristics of enrolled patients and PET/CT findings of osteonecrosis of the femoral head No. Gender Age (years) Type of lymphoma Osteonecrosis of the femoral head Other bone involvement Right Left SUV max ARCO stage SUV max ARCO stage 1 Male 43 Diffuse large B-cell lymphoma 4.27 2 6.03 2 Bilateral ilia, humeral heads 2 Male 40 Diffuse large B-cell lymphoma 1.42 2 8.06 3 Left humeral head 3 Male 32 High-grade B-cell lymphoma 1.31 2 1.06 2 No 4 Female 25 High-grade B-cell lymphoma 1.82 1 2.71 2 Bilateral ilia, humeral heads 5 Male 32 T-cell lymphoblastic lymphoma 0.88 2 0.98 2 Bilateral ilia, humeral heads, ribs, scapulae and vertebrae 6 Male 64 Diffuse large B-cell lymphoma 0.55 1 - - No 7 Male 25 T-cell lymphoblastic lymphoma 1.53 2 2.02 2 Bilateral ilia, humeral heads 8 Male 42 Diffuse large B-cell lymphoma 1.14 2 1.00 2 No 9 Male 33 T-cell lymphoblastic lymphoma 5.45 3 1.30 2 Bilateral ilia, humeral heads 10 Male 52 Diffuse large B-cell lymphoma 0.72 2 0.85 2 Bilateral humeral heads 11 Male 44 Mantle cell lymphoma 4.41 3 2.23 2 No 12 Female 73 High-grade B-cell lymphoma 1.65 2 2.12 2 No 13 Female 22 Diffuse large B-cell lymphoma 1.59 2 2.64 3 Bilateral ilia, humeral heads 14 Male 20 T-cell lymphoblastic lymphoma 0.56 2 0.45 2 Bilateral humeral heads 15 Male 67 Mantle cell lymphoma 5.27 4 - - No 16 Male 27 T-cell lymphoblastic lymphoma 1.82 2 1.28 2 No 17 Male 52 Diffuse large B-cell lymphoma 1.63 2 - - No ARCO Association Research Circulation Osseous, SUV max maximum standardized uptake value PET/CT findings PET/CT was performed before or after MRI with a median time interval of 3 days (range, 0–98 days). A total of 31 femoral heads were involved (14 bilateral, 3 unilateral), comprising 2 in stage 1, 24 in stage 2, 4 in stage 3, and 1 in stage 4. The median SUV max value was 1.37 (0.96, 1.87) for stage 1–2 lesions and 5.27 (3.53, 6.76) for stage 3–4 lesions. The SUV max of ONFH in stage 3–4 was significantly higher than that in stage 1–2 ( P = 0.002). On maximum intensity projection (MIP) images, increased FDG uptake was observed in 8 femoral heads, including 3 in stage 2 (12.5%, 3/24) and 5 in stage 3–4 (100.0%). On tomographic images, increased FDG uptake was detected in 21 femoral head lesions, comprising 16 in stage 2 and 5 in stages 3–4. In stage 1 femoral head lesions, both density and FDG uptake were normal (Fig. 1 ). For all stage 2 lesions, linear high density was observed at the edge of osteonecrosis on CT. Among these stage 2 lesions, 11 exhibited increased FDG uptake along the peripheral linear high-density and/or within the necrotic region, 5 showed peripheral increased uptake with internal decreased uptake (Fig. 2 ), 2 demonstrated decreased FDG uptake, and 6 had normal FDG uptake. All 5 lesions in stages 3 and 4 displayed increased FDG uptake along the peripheral linear high-density and/or at the osteolytic area (Fig. 3 ). Among the 24 lesions in stage 2, 13 were confined above the epiphyseal line, while 11 extended below the epiphyseal line on MRI. The extent of 20 lesions in stage 2 observed on CT matched that seen on MRI. All 5 lesions in stages 3–4 extended below the epiphyseal line, and the extent of these 5 lesions in stages 3–4 as seen on CT was consistent with that on MRI. Twelve patients had previous PET/CT scans. On these previous PET/CT examinations, which were conducted a median of 27 months (range, 2–63 months) before MRI, linear high-densities were observed in the bilateral femoral heads of 11 patients, with 4 of them showing bilateral increased FDG uptake in the corresponding high-density areas. Five patients had follow-up PET/CT scans 4–46 months after MRI and 8 femoral head lesions were involved. One lesion progressed from stage 2 to stage 3. A stage 1 lesion exhibited a new linear high density (Fig. 1 ). The other 6 lesions showed no significant changes. Nine patients exhibited osteonecrosis in bones other than the femoral head. The humeral heads were affected in 9 patients (8 bilateral, 1 unilateral), showing linear high densities on CT, with 4 of them demonstrating increased FDG uptake along these linear high densities. MRI revealed geographic abnormal signals in the bilateral ilia of 6 patients, characterized by peripheral low signal intensity and internal high signal intensity on T1-weighted images. On PET/CT, the iliac lesions showed peripheral linear high densities and internal decreased FDG uptake in 5 patients (Fig. 2 ), and isodensity with isometabolism in one patient. Additionally, one patient had multiple involvements of the vertebrae, ribs, and scapulae. Discussion This study demonstrated that FDG metabolism varies across different stages of ONFH. Specifically, increased FDG uptake was observed in 100.0% (5/5) of stage 3–4 lesions and 66.7% (16/24) of stage 2 ONFH. The median SUV max of lesions in stage 3–4 was higher than that in stage 1–2. In the early stages of ONFH, the blood supply to the epiphysis is typically blocked, leading to trabecular bone and marrow necrosis. Theoretically, FDG uptake in the necrotic region should decrease. However, detecting this reduction can be challenging due to the low level of FDG metabolism in a normal adult femoral head [11]. Adult femoral heads are primarily composed of yellow bone marrow, which has limited vasculature and consists of approximately 95% adipocytes [12]. As the disease progresses, new bone forms around the necrotic area, appearing as linear high-density regions on CT and potentially increasing FDG uptake on PET. This characteristic was evident in most stage 2 lesions in this study. Subchondral fractures, granulation tissue, and osteoarthritis may contribute to the increased FDG uptake in stage 3–4 lesions. Furthermore, in patients with lymphoma, bone marrow FDG uptake is influenced by various factors, including tumour infiltration, anaemia, and colony-stimulating factors [13]. Against the backdrop of increased skeletal marrow metabolism, focal decreased FDG uptake may be observed in the necrotic area. Karimova et al. [14] conducted a retrospective analysis of the clinical data and MRI images from 80 children and adolescents with haematological diseases and ONFH. They found that lesion size was the best prognostic factor for ONFH. Specifically, patients with lesions exceeding 30% of the femoral head were more likely to experience disease progression and require joint replacement surgery. In the present study, the epiphyseal line of the femoral head was used as a reference to assess the extent of the lesions. It was observed that all stage 3–4 ONFH lesions extended below the epiphyseal line, while 51.1% (13/24) of stage 2 lesions were confined above the epiphyseal line. The proportion of large lesions (those extending beyond the epiphyseal line) was higher in stage 3–4 compared to stage 1–2. HU et al. [15] reported that for patients with stage 3 or higher ONFH, CT and MRI showed a high degree of consistency in accurately depicting the location, shape, and spatial structure of the lesion. In this study, the extent of most ONFH lesions in stages 2–4 shown on CT was consistent with that on MRI, despite the relatively low-dose scan parameters used for the CT portion of PET/CT. Therefore, PET/CT may prove to be a valuable tool in assessing the extent of ONFH. Osteonecrosis involving three or more separate anatomic sites of the skeleton concurrently or consecutively is defined as multifocal osteonecrosis [16]. Multifocal osteonecrosis has been reported in 3–11% of patients diagnosed with osteonecrosis [17, 18]. In this study, patients with bilateral ONFH accounted for 82.4% (14/17). Additionally, nine patients exhibited osteonecrosis in other bones, including the humeral heads (9 patients, 8 bilateral) and the bilateral ilia (6 patients). Consequently, more than half (9/17) of the patients had multifocal osteonecrosis. We speculate that lymphoma-associated ONFH may represent a localized manifestation of systemic osteonecrosis [16, 19, 20]. Therefore, it is crucial to evaluate the entire skeleton in patients with lymphoma-associated ONFH. Although MRI is considered the optimal method for diagnosing osteonecrosis, screening for multifocal osteonecrosis using MRI can be time-consuming and costly. Bone scintigraphy may offer a useful alternative for diagnosing multifocal osteonecrosis [17, 18]. The present study suggests that PET/CT may play a significant role in detecting multiple skeletal lesions in patients with lymphoma-associated ONFH. In 11 patients, PET/CT scans conducted a median of 27 months (range 2–63 months) prior to the MRI diagnosis of ONFH revealed abnormal imaging features in the femoral heads. Regrettably, these abnormal features were overlooked in the initial PET/CT interpretation for 9 of these patients. Similar findings were reported by Barille et al. [21], who noted that the diagnosis of femoral head avascular necrosis was frequently missed (89%) on pelvic CT performed for alternative primary indications. Therefore, when interpreting PET/CT scans for lymphoma evaluation, it is crucial to routinely assess for signs of osteonecrosis to prevent delays in diagnosis and treatment. Lesions with low FDG uptake may be easily missed on PET scans. In this study, while only 12.5% (3/24) of stage 2 ONFH lesions showed increased uptake on the MIP images, a significantly higher proportion, 66.7% (16/24), demonstrated increased uptake on the tomographic images. Consequently, greater emphasis should be placed on examining the tomographic PET and CT images to identify features of ONFH. The present study had several limitations. Firstly, the retrospective nature of the study and the relatively small sample size may have influenced the results. Secondly, the diagnosis of ONFH was based solely on MRI findings and lacked histological confirmation. Additionally, we did not establish a specific threshold for SUV max in diagnosing ONFH, due to the variable degree of FDG uptake observed in the lesions. Given these considerations, we recommend that greater attention be given to CT features when diagnosing ONFH, as they can provide valuable supplementary information. Future studies with larger sample sizes and incorporating histological verification are needed to further validate our findings and establish more definitive diagnostic criteria. Conclusions In patients with lymphoma, osteonecrosis of the femoral head exhibits variable degrees of FDG uptake, which is related to different pathological stages. Additionally, it may be accompanied by involvement of other bones, such as the humeral heads and ilia. PET/CT proves to be a valuable tool in diagnosing ONFH and detecting multiple bone involvements while assessing lymphoma. Abbreviations FDG: Fluorodeoxyglucose MIP: Maximum intensity projection ONFH: Osteonecrosis of the femoral head SUV max : Maximum Standardized uptake value Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki. Approval for the study protocol was obtained from our institutional Research Ethics Committee, and all regulations were strictly adhered to. Due to the retrospective nature of the study, the requirement for informed consent was waived by the ethics board. Consent for publication All the authors gave a signed consent to publish. Availability of data and material The analysed and/or used datasets in this study can be obtained on reasonable request to the corresponding author. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the special fund of the Beijing Clinical Key Specialty Construction Program, P. R. China (2022), the National Key R&D Program of China (2023YFC3404600), the Key Clinical Projects of Peking University Third Hospital (BYSY2022060). Authors' contributions LS: conceptualisation, data-curation, writing-original draft, formal analysis, writing-original draft, writing-review, and editing. HL: methodology, formal analysis, editing. WFZ: supervision, conceptualisation, data-curation, formal analysis, editing. AHZ: conceptualisation, data-curation, editing. All authors read and approved the final manuscript. Acknowledgements Not applicable. References Zhao D, Zhang F, Wang B, Liu B, Li L, Kim SY, et al. Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version). J Orthop Translat. 2020; 100-10. Liu LH, Zhang QY, Sun W, Li ZR, Gao FQ. Corticosteroid-induced osteonecrosis of the femoral head: detection, diagnosis, and treatment in earlier stages. Chin Med J (Engl). 2017; 2601-7. Ratcliffe MA, Gilbert FJ, Dawson AA, Bennett B. Diagnosis of avascular necrosis of the femoral head in patients treated for lymphoma. Hematol Oncol. 1995; 131-7. Mont MA, Zywiel MG, Marker DR, McGrath MS, Delanois RE. The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review. J Bone Joint Surg Am. 2010; 2165-70. Ricard F, Cheson B, Barrington S, Trotman J, Schmid A, Brueggenwerth G, et al. Application of the Lugano Classification for initial evaluation, staging, and response assessment of hodgkin and non-hodgkin lymphoma: The PRoLoG Consensus Initiative (Part 1-Clinical). J Nucl Med. 2023; 102-8. Liu Y. The role of 18F-FDG PET/CT in staging and restaging primary bone lymphoma. Nucl Med Commun. 2017; 319-24. Choi KH, Oh JK, Kim SH, Yoo ID, Choi EK, Han EJ. Osteonecrosis mimicking bone metastasis in femoral head on (18)F-FDG PET/CT: a case report. Nucl Med Mol Imaging. 2011; 68-71. Chaudhary K, Ngai S. Vertebral body osteonecrosis mimicking malignant disease on 18F-FDG PET. Clin Nucl Med. 2023; e115-e7. Song L, Li H, Zhang W. Process of hard palate osteonecrosis demonstrated on serial 18F-FDG PET/CT scans. Clin Nucl Med. 2023; e44-e5. Öztürk AE, Şahin R, Ergül N, Çermik TF, Arslan E. A comparison of 18 F-FDG PET/CT and 68 Ga-PSMA PET/CT in detecting osteonecrosis of the jaw in a patient with prostate cancer. Clin Nucl Med. 2024; e68-e9. Aras M, Dede F, Ones T, Inanır S, Erdıl TY, Turoglu HT. Evaluation of physiological FDG uptake in the skeleton in adults: Is it uniformly distributed? Revista Española de Medicina Nuclear e Imagen Molecular. 2014; 286-9. Guillerman RP. Marrow: red, yellow and bad. Pediatr Radiol. 2013; S181-92. Adams HJ, de Klerk JM, Fijnheer R, Heggelman BG, Dubois SV, Nievelstein RA, Kwee TC. Variety in bone marrow 18F-FDG uptake in Hodgkin lymphoma patients without lymphomatous bone marrow involvement: does it have an explanation? Nucl Med Commun. 2016; 23-9. Karimova EJ, Rai SN, Howard SC, Neel M, Britton L, Pui CH, Kaste SC. Femoral head osteonecrosis in pediatric and young adult patients with leukemia or lymphoma. J Clin Oncol. 2007; 1525-31. Hu LB, Huang ZG, Wei HY, Wang W, Ren A, Xu YY. Osteonecrosis of the femoral head: using CT, MRI and gross specimen to characterize the location, shape and size of the lesion. Br J Radiol. 2015; 20140508. Sun W, Shi Z, Gao F, Wang B, Li Z. The pathogenesis of multifocal osteonecrosis. Sci Rep. 2016; 29576. Cajiao K, Setoain FJ, Peris P. Multifocal osteonecrosis: the usefulness of bone scintigraphy. J Clin Rheumatol. 2021; e196-e7. An YS, Park S, Jung JY, Suh CH, Kim HA. Clinical characteristics and role of whole-body bone scan in multifocal osteonecrosis. BMC Musculoskelet Disord. 2019; 23. Terao T, Matsue K. Bone marrow necrosis in acute monoblastic leukemia. N Engl J Med. 2021; 650. Song L, Li H, Zhang W. Bone marrow necrosis with underlying skeletal lymphoma evaluated by (18)F-FDG PET/CT and MRI. Mol Imaging Radionucl Ther. 2024; 203-5. Barille MF, Wu JS, McMahon CJ. Femoral head avascular necrosis: a frequently missed incidental finding on multidetector CT. Clin Radiol. 2014; 280-5. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 03 Feb, 2025 Editor assigned by journal 22 Jan, 2025 Submission checks completed at journal 22 Jan, 2025 First submitted to journal 18 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-5855164","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":405616399,"identity":"3fb3bff6-8101-4e7e-a326-a79bc8ab9869","order_by":0,"name":"Le Song","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Le","middleName":"","lastName":"Song","suffix":""},{"id":405616400,"identity":"bbcce53f-95b6-453a-9740-4b9d4648e502","order_by":1,"name":"Hui Li","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Li","suffix":""},{"id":405616401,"identity":"e21eaf7e-f214-4a63-a66d-3bc54349e8a9","order_by":2,"name":"Anhui Zhu","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Anhui","middleName":"","lastName":"Zhu","suffix":""},{"id":405616402,"identity":"4d4b0a8e-1712-4ec0-abdd-ee178402088e","order_by":3,"name":"Weifang Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYJCCAx8q/suxsTcfIE45DwMD48EZZ5iN+XiOJRCthfkwbxtz4jyJHAXitNjznzEAamFLb2PIYWD4UbGNCFskcgwOzjnHk9vGcPYAY8+Z28Ro4TE48KZMIreNsS+BmbGNGC1Ahx3gYTNIZ2PmMSBSCwPQYTxtCQlsbERruZFWAAzkA4ZtPGwJB4nyC3v/4c0fPlQckJef//jggx8VRGhhYOAwgDMPEKMeZM8DIhWOglEwCkbBiAUAFBY891ZtRO4AAAAASUVORK5CYII=","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":true,"prefix":"","firstName":"Weifang","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-01-18 12:53:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5855164/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5855164/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74691459,"identity":"dff041c3-c4e7-4df5-8e5c-26c21a18121e","added_by":"auto","created_at":"2025-01-24 18:38:51","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":750074,"visible":true,"origin":"","legend":"\u003cp\u003eOsteonecrosis of the femoral head. PET/CT and MRI images from a 64-year-old male (patient 6) with diffuse large B-cell lymphoma after 4 cycles of chemotherapy. No abnormal signs were detected in the bilateral femoral heads on CT (\u003cstrong\u003ea\u003c/strong\u003e) and PET/CT fused image (\u003cstrong\u003eb\u003c/strong\u003e). However, an MRI scan performed on the same day as the PET/CT revealed an adipose-like high signal surrounded by linear hypointensity (arrow) at the right femoral head on the T2-weighted (\u003cstrong\u003ec\u003c/strong\u003e) and T1-weighted (\u003cstrong\u003ed\u003c/strong\u003e) images. According to the modified 2019 version of the Association Research Circulation Osseous international classification of osteonecrosis staging system, the osteonecrotic lesion of the right femoral head was classified as stage 1. A follow-up PET/CT was performed 46 months later and demonstrated a linear hyperdensity lesion (arrows) at the right femoral head on CT (\u003cstrong\u003ee\u003c/strong\u003e) and PET/CT fused image (\u003cstrong\u003ef\u003c/strong\u003e).\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5855164/v1/db474e003889d21fbbe57f96.jpg"},{"id":74691830,"identity":"a8fd2d4e-d354-4a26-8a51-bb03d467b478","added_by":"auto","created_at":"2025-01-24 18:46:51","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":510149,"visible":true,"origin":"","legend":"\u003cp\u003eOsteonecrosis of the femoral heads and ilia. PET/CT and MRI images from a 25-year-old male (patient 7) with T-lymphoblastic lymphoma after allogeneic hematopoietic stem cell transplantation. The CT image (\u003cstrong\u003ea\u003c/strong\u003e) shows multiple linear hyperdensity lesions (yellow arrows) in the bilateral femoral heads and ilia. PET/CT fused image (\u003cstrong\u003eb\u003c/strong\u003e) reveals decreased FDG uptake (green arrows) with peripheral increased uptake (yellow arrow). An MRI scan performed the day after the PET/CT shows multiple geographic abnormal signals (red arrows) at the bilateral femoral heads and ilia on the T1-weighted image (\u003cstrong\u003ec\u003c/strong\u003e). According to the modified 2019 version of the Association Research Circulation Osseous international classification of osteonecrosis staging system, the osteonecrotic lesions of the bilateral femoral head are classified as stage 2.\u003c/p\u003e","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5855164/v1/09afdf7bcaf48f97d43f285e.jpg"},{"id":74691466,"identity":"95e437bf-de78-40d3-894c-9d28bc5e47aa","added_by":"auto","created_at":"2025-01-24 18:38:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":513491,"visible":true,"origin":"","legend":"\u003cp\u003eOsteonecrosis of the femoral head. PET/CT and MRI images from a 44-year-old male (patient 11) with mantle cell lymphoma. The maximum intensity projection image of PET (\u003cstrong\u003ea\u003c/strong\u003e) shows increased FDG uptake (black arrows) in the regions of the bilateral femoral heads. The CT image (\u003cstrong\u003eb\u003c/strong\u003e) demonstrates osteolytic area with internal sequestrum, peripheral osteosclerosis, and subchondral fracture at the right femoral head (yellow arrow), as well as high density at the left femoral head (white arrow). The PET/CT fused image (\u003cstrong\u003ec\u003c/strong\u003e) shows increased FDG uptake at the bilateral femoral heads with SUV\u003csub\u003emax\u003c/sub\u003e 4.41 (yellow arrow) and 2.23 (white arrow), respectively. An MRI scan performed three days after the PET/CT shows geographic abnormal signals at the bilateral femoral heads on the fat-saturated proton density-weighted image (red arrows in\u003cstrong\u003e d\u003c/strong\u003e). According to the modified 2019 version of the Association Research Circulation Osseous international classification of osteonecrosis staging system, the osteonecrosis in the right femoral head is classified as stage 3.\u003c/p\u003e","description":"","filename":"figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5855164/v1/e8432e56d1d996863df305bb.jpg"},{"id":74692378,"identity":"773154c8-4fde-4b35-aeb9-64372caaf5be","added_by":"auto","created_at":"2025-01-24 18:54:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2440840,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5855164/v1/8ca369d3-b07c-4e04-8b9c-fb79fa8255e9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"18F-FDG PET/CT in the evaluation of femoral head osteonecrosis in patients with lymphoma","fulltext":[{"header":"Background","content":"\u003cp\u003eOsteonecrosis of the femoral head (ONFH) is a common disease of the hip joint and characterized by death of the osteocytes and the bone marrow. The main etiological factors for non-traumatic ONFH include the application of corticosteroids, chronic alcohol overconsumption, decompression sickness, haemoglobin diseases, autoimmune diseases, etc. [1, 2]. Patients treated with lymphoma are at high risk of developing ONFH, with an incidence rate of approximately 15% [3]. Early diagnosis is essential for optimal therapeutic management. It is recommended that for patients who complain of hip pain during or after the treatment of lymphoma, a hip MRI examination is suggested to diagnose ONFH [3]. Nevertheless, Ratcliffe et al reported that 40% of patients with ONFH were asymptomatic [3]. Whether asymptomatic patients at risk should be screened, is still not clarified. Asymptomatic osteonecrosis has a high prevalence (59%) of progression to symptomatic disease and femoral head collapse [4]. It seems impractical to perform hip X-rays or even MRIs for all asymptomatic patients with lymphoma. It is also difficult to determine the timing and frequency of the screening examinations.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e18\u003c/sup\u003eF-fluorodeoxyglucose (\u003csup\u003e18\u003c/sup\u003eF-FDG) positron emission tomography (PET)/CT has been an important imaging modality for the staging and therapeutic evaluation of lymphoma [5, 6]. We speculate that \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT also has a role in the evaluation of ONFH for patients with lymphoma. Studies about the value of \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT for osteonecrosis are limited to a few case reports [7\u0026ndash;10]. This retrospective study aims to describe the imaging features of ONFH on \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT and explore the value of PET/CT in the assessment of ONFH in patients with lymphoma.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003e This was a retrospective study and was approved by the institutional review board of Peking University Third Hospital. The PET/CT image database was searched with the keywords \u0026ldquo;femoral head\u0026rdquo; and \u0026ldquo;osteonecrosis\u0026rdquo; in patients with lymphoma. All of the retrieved patients underwent magnetic resonance imaging (MRI) scan of the hip and were diagnosed as ONFH. Patients with previously known ONFH before the diagnosis of lymphoma or incomplete clinical data were excluded. A total of 17 patients with ONFH were recruited at Peking University Third Hospital between September 2014 and June 2024. We recorded the symptoms such as aches around the hip joint or at the buttocks.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePET/CT examination\u003c/h3\u003e\n\u003cp\u003eA Siemens Biograph 64 PET/CT scanner was applied for image acquisition. \u003csup\u003e18\u003c/sup\u003eF-FDG was provided by Beijing Atomic High Technology Co. Patients fasted for longer than 6 hours, and blood glucose levels were monitored (below 11.1 mmol/L) before an injection of \u003csup\u003e18\u003c/sup\u003eF-FDG (5.55 MBq per kilogram of body weight). About 60 minutes after injection, the PET/CT was performed from the tip of the skull to the mid-thigh. CT scan parameters: tube voltage 120 kV, effective tube current 100 mAs, pitch 0.9. PET scans have the same extent as CT, 2 minutes per bed, True X reconstruction, 3 iterations, subset 21, Gaussian filtering, half-peak width 5.0.\u003c/p\u003e\n\u003ch3\u003eImage analysis\u003c/h3\u003e\n\u003cp\u003eThe PET/CT images were transferred to the SIEMENS syngoMMWP VE40A workstation. Two nuclear medicine physicians, both with over 10 years of experience in PET/CT, jointly assessed the PET/CT images. In cases where their opinions diverged, a more senior physician was consulted to make the final decision. The ONFH was staged according to the modified 2019 version of the Association Research Circulation Osseous international classification of osteonecrosis staging system [1]: stage 1, a band lesion of low signal intensity around the necrotic area is seen on MRI, but no changes are seen on CT; stage 2, osteosclerosis or cystic changes are seen in the femoral head without evidence of subchondral fracture, fracture in the necrotic portion or flattening of the femoral head on CT; stage 3, subchondral fracture, fracture in the necrotic portion and/or flattening of the femoral head on CT; stage 4, osteoarthritis of the hip joint with joint space narrowing, acetabular changes and destruction. The FDG uptake of ONFH was compared with that of the surrounding unaffected femoral head. For the semi-quantitative assessment of ONFH, regions of interest (ROIs) were manually delineated on the PET/CT fused images. The maximum standardized uptake value (SUV\u003csub\u003emax\u003c/sub\u003e) is calculated as ROI activity (mCi/mL) multiplied by body weight (g), divided by the injected dose (mCi). The extent of ONFH on CT was visually evaluated and compared with that on MRI. Additionally, other bones within the scope of the PET/CT scan were examined for any signs of osteonecrosis. For patients who underwent multiple PET/CT examinations, the FDG metabolism and CT features of ONFH at different time points were analyzed.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were conducted using SPSS Statistics software (IBM Corp., Chicago). The Shapiro-Wilk test was employed to assess the normality of data distribution. Data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation if they followed a normal distribution; otherwise, they were expressed as median (quartile 1, quartile 3). The Mann-Whitney U test was utilized to compare the SUV\u003csub\u003emax\u003c/sub\u003e of ONFH at different stages. A \u003cem\u003eP\u003c/em\u003e value less than 0.05 was considered to indicate statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eClinical characteristics\u003c/h2\u003e \u003cp\u003eA total of 17 patients with ONFH (14 men and 3 women; median age 40 years) were enrolled in this retrospective study. All patients had non-Hodgkin lymphoma. At the time of the MRI examination, 6 patients complained of hip or thigh discomfort, such as intermittent or persistent pain and soreness, while the remaining patients did not report local discomfort. The clinical characteristics and PET/CT findings are summarized 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\u003eClinical characteristics of enrolled patients and PET/CT findings of osteonecrosis of the femoral head\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\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=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eType of lymphoma\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c8\" namest=\"c5\"\u003e \u003cp\u003eOsteonecrosis of the femoral head\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOther bone involvement\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eARCO stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eARCO stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiffuse large B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBilateral ilia, humeral heads\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiffuse large B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLeft humeral head\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh-grade B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh-grade B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBilateral ilia, humeral heads\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT-cell lymphoblastic lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBilateral ilia, humeral heads, ribs, scapulae and vertebrae\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiffuse large B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT-cell lymphoblastic lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBilateral ilia, humeral heads\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiffuse large B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT-cell lymphoblastic lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBilateral ilia, humeral heads\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiffuse large B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBilateral humeral heads\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMantle cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh-grade B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiffuse large B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBilateral ilia, humeral heads\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT-cell lymphoblastic lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBilateral humeral heads\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMantle cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT-cell lymphoblastic lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiffuse large B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cem\u003eARCO\u003c/em\u003e Association Research Circulation Osseous, \u003cem\u003eSUV\u003c/em\u003e\u003csub\u003e\u003cem\u003emax\u003c/em\u003e\u003c/sub\u003e maximum standardized uptake value\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePET/CT findings\u003c/h3\u003e\n\u003cp\u003ePET/CT was performed before or after MRI with a median time interval of 3 days (range, 0\u0026ndash;98 days). A total of 31 femoral heads were involved (14 bilateral, 3 unilateral), comprising 2 in stage 1, 24 in stage 2, 4 in stage 3, and 1 in stage 4. The median SUV\u003csub\u003emax\u003c/sub\u003e value was 1.37 (0.96, 1.87) for stage 1\u0026ndash;2 lesions and 5.27 (3.53, 6.76) for stage 3\u0026ndash;4 lesions. The SUV\u003csub\u003emax\u003c/sub\u003e of ONFH in stage 3\u0026ndash;4 was significantly higher than that in stage 1\u0026ndash;2 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). On maximum intensity projection (MIP) images, increased FDG uptake was observed in 8 femoral heads, including 3 in stage 2 (12.5%, 3/24) and 5 in stage 3\u0026ndash;4 (100.0%). On tomographic images, increased FDG uptake was detected in 21 femoral head lesions, comprising 16 in stage 2 and 5 in stages 3\u0026ndash;4.\u003c/p\u003e \u003cp\u003eIn stage 1 femoral head lesions, both density and FDG uptake were normal (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). For all stage 2 lesions, linear high density was observed at the edge of osteonecrosis on CT. Among these stage 2 lesions, 11 exhibited increased FDG uptake along the peripheral linear high-density and/or within the necrotic region, 5 showed peripheral increased uptake with internal decreased uptake (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), 2 demonstrated decreased FDG uptake, and 6 had normal FDG uptake. All 5 lesions in stages 3 and 4 displayed increased FDG uptake along the peripheral linear high-density and/or at the osteolytic area (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong the 24 lesions in stage 2, 13 were confined above the epiphyseal line, while 11 extended below the epiphyseal line on MRI. The extent of 20 lesions in stage 2 observed on CT matched that seen on MRI. All 5 lesions in stages 3\u0026ndash;4 extended below the epiphyseal line, and the extent of these 5 lesions in stages 3\u0026ndash;4 as seen on CT was consistent with that on MRI.\u003c/p\u003e \u003cp\u003eTwelve patients had previous PET/CT scans. On these previous PET/CT examinations, which were conducted a median of 27 months (range, 2\u0026ndash;63 months) before MRI, linear high-densities were observed in the bilateral femoral heads of 11 patients, with 4 of them showing bilateral increased FDG uptake in the corresponding high-density areas. Five patients had follow-up PET/CT scans 4\u0026ndash;46 months after MRI and 8 femoral head lesions were involved. One lesion progressed from stage 2 to stage 3. A stage 1 lesion exhibited a new linear high density (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The other 6 lesions showed no significant changes.\u003c/p\u003e \u003cp\u003eNine patients exhibited osteonecrosis in bones other than the femoral head. The humeral heads were affected in 9 patients (8 bilateral, 1 unilateral), showing linear high densities on CT, with 4 of them demonstrating increased FDG uptake along these linear high densities. MRI revealed geographic abnormal signals in the bilateral ilia of 6 patients, characterized by peripheral low signal intensity and internal high signal intensity on T1-weighted images. On PET/CT, the iliac lesions showed peripheral linear high densities and internal decreased FDG uptake in 5 patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), and isodensity with isometabolism in one patient. Additionally, one patient had multiple involvements of the vertebrae, ribs, and scapulae.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that FDG metabolism varies across different stages of ONFH. Specifically, increased FDG uptake was observed in 100.0% (5/5) of stage 3\u0026ndash;4 lesions and 66.7% (16/24) of stage 2 ONFH. The median SUV\u003csub\u003emax\u003c/sub\u003e of lesions in stage 3\u0026ndash;4 was higher than that in stage 1\u0026ndash;2. In the early stages of ONFH, the blood supply to the epiphysis is typically blocked, leading to trabecular bone and marrow necrosis. Theoretically, FDG uptake in the necrotic region should decrease. However, detecting this reduction can be challenging due to the low level of FDG metabolism in a normal adult femoral head [11]. Adult femoral heads are primarily composed of yellow bone marrow, which has limited vasculature and consists of approximately 95% adipocytes [12]. As the disease progresses, new bone forms around the necrotic area, appearing as linear high-density regions on CT and potentially increasing FDG uptake on PET. This characteristic was evident in most stage 2 lesions in this study. Subchondral fractures, granulation tissue, and osteoarthritis may contribute to the increased FDG uptake in stage 3\u0026ndash;4 lesions. Furthermore, in patients with lymphoma, bone marrow FDG uptake is influenced by various factors, including tumour infiltration, anaemia, and colony-stimulating factors [13]. Against the backdrop of increased skeletal marrow metabolism, focal decreased FDG uptake may be observed in the necrotic area.\u003c/p\u003e \u003cp\u003eKarimova et al. [14] conducted a retrospective analysis of the clinical data and MRI images from 80 children and adolescents with haematological diseases and ONFH. They found that lesion size was the best prognostic factor for ONFH. Specifically, patients with lesions exceeding 30% of the femoral head were more likely to experience disease progression and require joint replacement surgery. In the present study, the epiphyseal line of the femoral head was used as a reference to assess the extent of the lesions. It was observed that all stage 3\u0026ndash;4 ONFH lesions extended below the epiphyseal line, while 51.1% (13/24) of stage 2 lesions were confined above the epiphyseal line. The proportion of large lesions (those extending beyond the epiphyseal line) was higher in stage 3\u0026ndash;4 compared to stage 1\u0026ndash;2. HU et al. [15] reported that for patients with stage 3 or higher ONFH, CT and MRI showed a high degree of consistency in accurately depicting the location, shape, and spatial structure of the lesion. In this study, the extent of most ONFH lesions in stages 2\u0026ndash;4 shown on CT was consistent with that on MRI, despite the relatively low-dose scan parameters used for the CT portion of PET/CT. Therefore, PET/CT may prove to be a valuable tool in assessing the extent of ONFH.\u003c/p\u003e \u003cp\u003eOsteonecrosis involving three or more separate anatomic sites of the skeleton concurrently or consecutively is defined as multifocal osteonecrosis [16]. Multifocal osteonecrosis has been reported in 3\u0026ndash;11% of patients diagnosed with osteonecrosis [17, 18]. In this study, patients with bilateral ONFH accounted for 82.4% (14/17). Additionally, nine patients exhibited osteonecrosis in other bones, including the humeral heads (9 patients, 8 bilateral) and the bilateral ilia (6 patients). Consequently, more than half (9/17) of the patients had multifocal osteonecrosis. We speculate that lymphoma-associated ONFH may represent a localized manifestation of systemic osteonecrosis [16, 19, 20]. Therefore, it is crucial to evaluate the entire skeleton in patients with lymphoma-associated ONFH. Although MRI is considered the optimal method for diagnosing osteonecrosis, screening for multifocal osteonecrosis using MRI can be time-consuming and costly. Bone scintigraphy may offer a useful alternative for diagnosing multifocal osteonecrosis [17, 18]. The present study suggests that PET/CT may play a significant role in detecting multiple skeletal lesions in patients with lymphoma-associated ONFH.\u003c/p\u003e \u003cp\u003eIn 11 patients, PET/CT scans conducted a median of 27 months (range 2\u0026ndash;63 months) prior to the MRI diagnosis of ONFH revealed abnormal imaging features in the femoral heads. Regrettably, these abnormal features were overlooked in the initial PET/CT interpretation for 9 of these patients. Similar findings were reported by Barille et al. [21], who noted that the diagnosis of femoral head avascular necrosis was frequently missed (89%) on pelvic CT performed for alternative primary indications. Therefore, when interpreting PET/CT scans for lymphoma evaluation, it is crucial to routinely assess for signs of osteonecrosis to prevent delays in diagnosis and treatment. Lesions with low FDG uptake may be easily missed on PET scans. In this study, while only 12.5% (3/24) of stage 2 ONFH lesions showed increased uptake on the MIP images, a significantly higher proportion, 66.7% (16/24), demonstrated increased uptake on the tomographic images. Consequently, greater emphasis should be placed on examining the tomographic PET and CT images to identify features of ONFH.\u003c/p\u003e \u003cp\u003eThe present study had several limitations. Firstly, the retrospective nature of the study and the relatively small sample size may have influenced the results. Secondly, the diagnosis of ONFH was based solely on MRI findings and lacked histological confirmation. Additionally, we did not establish a specific threshold for SUV\u003csub\u003emax\u003c/sub\u003e in diagnosing ONFH, due to the variable degree of FDG uptake observed in the lesions. Given these considerations, we recommend that greater attention be given to CT features when diagnosing ONFH, as they can provide valuable supplementary information. Future studies with larger sample sizes and incorporating histological verification are needed to further validate our findings and establish more definitive diagnostic criteria.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn patients with lymphoma, osteonecrosis of the femoral head exhibits variable degrees of FDG uptake, which is related to different pathological stages. Additionally, it may be accompanied by involvement of other bones, such as the humeral heads and ilia. PET/CT proves to be a valuable tool in diagnosing ONFH and detecting multiple bone involvements while assessing lymphoma.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eFDG: Fluorodeoxyglucose\u003c/p\u003e\n\u003cp\u003eMIP: Maximum intensity projection\u003c/p\u003e\n\u003cp\u003eONFH: Osteonecrosis of the femoral head\u003c/p\u003e\n\u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e: Maximum Standardized uptake value\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. Approval for the study protocol was obtained from our institutional Research Ethics Committee, and all regulations were strictly adhered to. Due to the retrospective nature of the study, the requirement for informed consent was waived by the ethics board.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors gave a signed consent to publish.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\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\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the special fund of the Beijing Clinical Key Specialty Construction Program, P. R. China (2022), the National Key R\u0026amp;D Program of China (2023YFC3404600), the Key Clinical Projects of Peking University Third Hospital (BYSY2022060).\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. HL: methodology, formal analysis, editing. WFZ: supervision, conceptualisation, data-curation, formal analysis, editing. AHZ: conceptualisation, data-curation, editing. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZhao D, Zhang F, Wang B, Liu B, Li L, Kim SY, et al. Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version). J Orthop Translat. 2020; 100-10.\u003c/li\u003e\n\u003cli\u003eLiu LH, Zhang QY, Sun W, Li ZR, Gao FQ. Corticosteroid-induced osteonecrosis of the femoral head: detection, diagnosis, and treatment in earlier stages. Chin Med J (Engl). 2017; 2601-7.\u003c/li\u003e\n\u003cli\u003eRatcliffe MA, Gilbert FJ, Dawson AA, Bennett B. Diagnosis of avascular necrosis of the femoral head in patients treated for lymphoma. Hematol Oncol. 1995; 131-7.\u003c/li\u003e\n\u003cli\u003eMont MA, Zywiel MG, Marker DR, McGrath MS, Delanois RE. The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review. J Bone Joint Surg Am. 2010; 2165-70.\u003c/li\u003e\n\u003cli\u003eRicard F, Cheson B, Barrington S, Trotman J, Schmid A, Brueggenwerth G, et al. Application of the Lugano Classification for initial evaluation, staging, and response assessment of hodgkin and non-hodgkin lymphoma: The PRoLoG Consensus Initiative (Part 1-Clinical). J Nucl Med. 2023; 102-8.\u003c/li\u003e\n\u003cli\u003eLiu Y. The role of 18F-FDG PET/CT in staging and restaging primary bone lymphoma. Nucl Med Commun. 2017; 319-24.\u003c/li\u003e\n\u003cli\u003eChoi KH, Oh JK, Kim SH, Yoo ID, Choi EK, Han EJ. Osteonecrosis mimicking bone metastasis in femoral head on (18)F-FDG PET/CT: a case report. Nucl Med Mol Imaging. 2011; 68-71.\u003c/li\u003e\n\u003cli\u003eChaudhary K, Ngai S. Vertebral body osteonecrosis mimicking malignant disease on 18F-FDG PET. Clin Nucl Med. 2023; e115-e7.\u003c/li\u003e\n\u003cli\u003eSong L, Li H, Zhang W. Process of hard palate osteonecrosis demonstrated on serial 18F-FDG PET/CT scans. Clin Nucl Med. 2023; e44-e5.\u003c/li\u003e\n\u003cli\u003e\u0026Ouml;zt\u0026uuml;rk AE, Şahin R, Erg\u0026uuml;l N, \u0026Ccedil;ermik TF, Arslan E. A comparison of 18 F-FDG PET/CT and 68 Ga-PSMA PET/CT in detecting osteonecrosis of the jaw in a patient with prostate cancer. Clin Nucl Med. 2024; e68-e9.\u003c/li\u003e\n\u003cli\u003eAras M, Dede F, Ones T, Inanır S, Erdıl TY, Turoglu HT. Evaluation of physiological FDG uptake in the skeleton in adults: Is it uniformly distributed? Revista Espa\u0026ntilde;ola de Medicina Nuclear e Imagen Molecular. 2014; 286-9.\u003c/li\u003e\n\u003cli\u003eGuillerman RP. Marrow: red, yellow and bad. Pediatr Radiol. 2013; S181-92.\u003c/li\u003e\n\u003cli\u003eAdams HJ, de Klerk JM, Fijnheer R, Heggelman BG, Dubois SV, Nievelstein RA, Kwee TC. Variety in bone marrow 18F-FDG uptake in Hodgkin lymphoma patients without lymphomatous bone marrow involvement: does it have an explanation? Nucl Med Commun. 2016; 23-9.\u003c/li\u003e\n\u003cli\u003eKarimova EJ, Rai SN, Howard SC, Neel M, Britton L, Pui CH, Kaste SC. 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N Engl J Med. 2021; 650.\u003c/li\u003e\n\u003cli\u003eSong L, Li H, Zhang W. Bone marrow necrosis with underlying skeletal lymphoma evaluated by (18)F-FDG PET/CT and MRI. Mol Imaging Radionucl Ther. 2024; 203-5.\u003c/li\u003e\n\u003cli\u003eBarille MF, Wu JS, McMahon CJ. Femoral head avascular necrosis: a frequently missed incidental finding on multidetector CT. Clin Radiol. 2014; 280-5.\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":"Femoral head, Osteonecrosis, Lymphoma, Positron emission tomography-computed tomography, Magnetic resonance imaging","lastPublishedDoi":"10.21203/rs.3.rs-5855164/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5855164/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eObjective\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo describe the imaging features of osteonecrosis of the femoral head (ONFH) on fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and explore the value of PET/CT in assessing ONFH in patients with lymphoma.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA retrospective analysis was conducted on the clinical data, PET/CT, and MRI manifestations of 17 patients with ONFH and lymphoma. The FDG uptake of ONFH was recorded, and the maximum standardized uptake value (SUV\u003csub\u003emax\u003c/sub\u003e) of ONFH was measured. The staging and extent of ONFH, and other bone involvements, were visually assessed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA total of 31 femoral heads were involved, including 2 in stage 1, 24 in stage 2, 4 in stage 3, and 1 in stage 4. The median SUV\u003csub\u003emax\u003c/sub\u003e of ONFH in stage 3\u0026ndash;4 (5.27) was higher than that in stage 1\u0026ndash;2 (1.37) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). In stage 1 lesions, both density and FDG uptake were normal. For stage 2 lesions, 11 showed increased FDG uptake along the peripheral linear high-density and/or within the necrotic region, 5 had peripheral increased uptake with internal decreased uptake, 2 exhibited decreased uptake, and 6 showed normal uptake. All lesions in stages 3\u0026ndash;4 demonstrated increased FDG uptake along the peripheral linear high-density and/or at the osteolytic area. Thirteen stage 2 lesions were confined above the epiphyseal line, while 11 stage 2 lesions and 5 stage 3\u0026ndash;4 lesions extended below the epiphyseal line. The extent of 20 stage 2 lesions and 5 stage 3\u0026ndash;4 lesions observed on CT matched that seen on MRI. Nine patients had osteonecrosis in other bones. The humeral heads were involved in 9 patients, with 4 showing increased FDG uptake along the linear high-densities. Bilateral ilia were involved in 6 patients, with 5 demonstrating peripheral linear high densities and internal decreased FDG uptake. One patient had multiple involvements of the vertebrae, ribs, and scapulae.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn patients with lymphoma, ONFH exhibits variable degrees of FDG uptake and may be accompanied by involvement of other bones. PET/CT is helpful in diagnosing ONFH and detecting multiple bone involvements while assessing lymphoma.\u003c/p\u003e","manuscriptTitle":"18F-FDG PET/CT in the evaluation of femoral head osteonecrosis in patients with lymphoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-24 18:38:46","doi":"10.21203/rs.3.rs-5855164/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-02-03T10:53:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-22T12:34:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-22T12:30:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medical Imaging","date":"2025-01-18T12:42:18+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":"January 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T15:23:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-24 18:38:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5855164","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5855164","identity":"rs-5855164","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}