FAPI PET Missed Widespread Bone Marrow Metastases From Follicular Thyroid Cancer That Were Detected by FDG PET.

ABSTRACT: A 62-year-old woman with follicular thyroid cancer who had received total thyroidectomy and multiple rounds of radioactive iodine therapy underwent both 18 F-FDG and 18 F-FAPI PET/CT. 18 F-FAPI PET failed to reveal widespread bone marrow metastases that were clear visualized on 18 F-FDG PET. This case highlights that FAPI PET may not be used to describe bone metastases in detail in follicular thyroid cancer patients, as it is not a sensitive method to detect bone marrow metastases.

Whole-body three-dimensional short tau inversion recovery and T1-weighted in/opposed phase MRI in the detection of neuroblastoma bone marrow metastasis: comparative study with PET/CT utilising bone marrow biopsy as the reference standard.

AIM: To evaluate the diagnostic accuracy of whole-body (WB) magnetic resonance imaging (MRI) utilising three-dimensional (3D) short tau inversion recovery (STIR) and T1-weighted in/opposed-phase MRI in the detection of neuroblastoma bone marrow metastasis compared to 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT). MATERIALS AND METHODS: A prospective study of 20 consecutive histopathologically proven neuroblastoma patients enrolled in this study from January 2021 to August 2022. WB MRI and FDG-PET/CT were performed for all cases. Bone marrow biopsy served as the standard of reference. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were calculated. In addition, lesion-by-lesion analysis was performed and the number of bone marrow metastatic lesions in different body segments using both imaging methods was recorded and compared. RESULTS: WB MRI correctly identified true positives and true negatives in all cases with a sensitivity and specificity of 100%. In contrast, FDG-PET/CT showed two false-negative cases that resulted in a sensitivity, specificity, PPV, NPV, and accuracy of 86.7%, 100%, 100%, 71.4%, and 92%, respectively. In the lesion-by-lesion analysis, WB MRI detected more (24.3%) bone marrow metastatic lesions than FDG-PET/CT. CONCLUSION: Whole-body MRI can reliably identify neuroblastoma bone marrow infiltration, and could be an alternative to PET/CT in that regard.

Detection of bone marrow metastases in children and young adults with solid cancers with diffusion-weighted MRI.

OBJECTIVE: To compare the diagnostic accuracy of diffusion-weighted (DW)-MRI with b-values of 50 s/mm2 and 800 s/mm2 for the detection of bone marrow metastases in children and young adults with solid malignancies. METHODS: In an institutional review board-approved prospective study, we performed 51 whole-body DW-MRI scans in 19 children and young adults (14 males, 5 females; age range: 1-25 years) with metastasized cancers before (n = 19 scans) and after (n = 32 scans) chemotherapy. Two readers determined the presence of focal bone marrow lesions in 10 anatomical areas. A third reader measured ADC and SNR of focal lesions and normal marrow. Simultaneously acquired 18F-FDG-PET scans served as the standard of reference. Data of b = 50 s/mm2 and 800 s/mm2 images were compared with the Wilcoxon signed-rank test. Inter-reader agreement was evaluated with weighted kappa statistics. RESULTS: The SNR of bone marrow metastases was significantly higher compared to normal bone marrow on b = 50 s/mm2 (mean ± SD: 978.436 ± 1239.436 vs. 108.881 ± 109.813, p < 0.001) and b = 800 s/mm2 DW-MRI (499.638 ± 612.721 vs. 86.280 ± 89.120; p < 0.001). On 30 out of 32 post-treatment DW-MRI scans, reconverted marrow demonstrated low signal with low ADC values (0.385 × 10-3 ± 0.168 × 10-3mm2/s). The same number of metastases (556/588; 94.6%; p > 0.99) was detected on b = 50 s/mm2 and 800 s/mm2 images. However, both normal marrow and metastases exhibited low signals on ADC maps, limiting the ability to delineate metastases. The inter-reader agreement was substantial, with a weighted kappa of 0.783 and 0.778, respectively. CONCLUSION: Bone marrow metastases in children and young adults can be equally well detected on b = 50 s/mm2 and 800 s/mm2 images, but ADC values can be misleading.

Staging of newly diagnosed Ewing sarcoma: Results of bone marrow aspiration and biopsy versus (18)FDG-PET/CT imaging for bone marrow involvement.

BACKGROUND: Ewing sarcoma (ES) is an aggressive bone or extraosseous tumour with an unfavourable prognosis when bone marrow metastases are present at diagnosis. The gold standard diagnosis for bone marrow (BM) involvement is cytological and pathological analysis through bone marrow aspiration and biopsy (BMAB). Several recent studies suggest that these invasive and painful procedures could be replaced by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)FDG-PET/CT), as this nuclear imaging technique is highly sensitive at detecting bone and extraosseous metastases of ES. METHODS: In order to study the precision of (18)FDG-PET/CT in the evaluation of bone marrow metastases at diagnosis, we compared the imaging results with cytological/histological analyses performed on BM samples. We retrospectively studied 180 patients with ES recorded at the Léon Bérard Centre over the past 10 years, who were evaluated by (18)FDG-PET/CT and BMAB at diagnosis. RESULTS: Of the 180 patients, 13 displayed marrow metastases by cytological/histological examination, and only one of these did not have (18)FDG-PET/CT signs of bone marrow involvement, whereas the 167 remaining patients without marrow metastasis all had a negative (18)FDG-PET/CT, except for one. Hence, the sensitivity and specificity of (18)FDG-PET/CT in these patients was 92.3% and 99.4%, respectively. The overall survival at five years of all patients was 67.4% but decrease to 38.5% in the group with bone marrow metastases. CONCLUSION: Given the results presented herein the bone sarcoma group of the French Sarcoma Group suggests that invasive BMAB no longer be systematically performed for the staging at the diagnosis of ES.

Diagnostic Accuracy of 2-[18F]FDG-PET and whole-body DW-MRI for the detection of bone marrow metastases in children and young adults.

OBJECTIVES: To compare the diagnostic accuracy of 2-[18F]fluoro-2-deoxy-D-glucose-enhanced positron emission tomography (2-[18F]FDG-PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection of bone marrow metastases in children and young adults with solid malignancies. METHODS: In this cross-sectional single-center institutional review board-approved study, we investigated twenty-three children and young adults (mean age, 16.8 years ± 5.1 [standard deviation]; age range, 7-25 years; 16 males, 7 females) with 925 bone marrow metastases who underwent 66 simultaneous 2-[18F]FDG-PET and DW-MRI scans including 23 baseline scans and 43 follow-up scans after chemotherapy between May 2015 and July 2020. Four reviewers evaluated all foci of bone marrow metastasis on 2-[18F]FDG-PET and DW-MRI to assess concordance and measured the tumor-to-bone marrow contrast. Results were assessed with a one-sample Wilcoxon test and generalized estimation equation. Bone marrow biopsies and follow-up imaging served as the standard of reference. RESULTS: The reviewers detected 884 (884/925, 95.5%) bone marrow metastases on 2-[18F]FDG-PET and 893 (893/925, 96.5%) bone marrow metastases on DW-MRI. We found different "blind spots" for 2-[18F]FDG-PET and MRI: 2-[18F]FDG-PET missed subcentimeter lesions while DW-MRI missed lesions in small bones. Sensitivity and specificity were 91.0% and 100% for 18F-FDG-PET, 89.1% and 100.0% for DW-MRI, and 100.0% and 100.0% for combined modalities, respectively. The diagnostic accuracy of combined 2-[18F]FDG-PET/MRI (100.0%) was significantly higher compared to either 2-[18F]FDG-PET (96.9%, p < 0.001) or DW-MRI (96.3%, p < 0.001). CONCLUSIONS: Both 2-[18F]FDG-PET and DW-MRI can miss bone marrow metastases. The combination of both imaging techniques detected significantly more lesions than either technique alone. KEY POINTS: • DW-MRI and 2-[18F]FDG-PET have different strengths and limitations for the detection of bone marrow metastases in children and young adults with solid tumors. • Both modalities can miss bone marrow metastases, although the "blind spot" of each modality is different. • A combined PET/MR imaging approach will achieve maximum sensitivity and specificity for the detection of bone marrow metastases in children with solid tumors.

Diagnostic Accuracy and Prognostic Relevance of Immunoglobulin Heavy Chain Rearrangement and 18F-FDG-PET/CT Compared With Unilateral Bone Marrow Trephination for Detecting Bone Marrow Involvement in Patients With Diffuse Large B-Cell Lymphoma.

BACKGROUND: In diffuse large B-cell lymphoma (DLBCL), bone marrow involvement (BMI) has an important clinical implication as a component of staging and International Prognostic Index. This study aimed to determine whether molecular analysis of immunoglobulin heavy chain (IgH) genes and positron emission tomography-computed tomography (PET/CT) could overcome the limitation of defining morphologic BMI by trephination biopsy and could increase the diagnostic accuracy or prognostic prediction. METHODS: A total of 94 de novo patients with DLBCL underwent PET/CT, polymerase chain reaction (PCR) test for detection of IgH gene rearrangement, and unilateral bone marrow (BM) trephination at diagnosis. RESULTS: A total of 9 patients (9.6%) were confirmed to present morphologic BMI (mBMI) based on trephination biopsy. On the other hand, 21 patients (22.3%) were confirmed to have IgH clonality (IgH BMI), while 16 (17.0%) were classified with BMI based on the assessment of PET/CT (PET BMI). Each IgH rearrangement PCR and PET/CT showed the high negative predictive value of detecting the BMI. However, the combined assessment of IgH rearrangement and PET/CT could increase the diagnostic accuracy and specificity with 87.2% and 97.0%, respectively. The survival outcome of patients with double positive PET BMI and IgH BMI was significantly worse than that with either single positive PET BMI or IgH BMI, and even less than patients with neither PET BMI nor IgH BMI (3-year PFS: 50.0% vs. 75.4% vs. 97.9%, P = 0.007, 3-year OS: 50.0% vs. 75.6% vs. 80.1%, P = 0.035, respectively). CONCLUSION: This study suggests that the combined evaluation of PET/CT and IgH rearrangement could give additional information for predicting therapeutic outcomes in patients with negative morphologic BMI as an important part of the prognosis.

Role of in-phase and out-of-phase chemical shift MRI in differentiation of non-neoplastic versus neoplastic benign and malignant marrow lesions.

OBJECTIVE: To determine its ability of in-phase (IP) and out-of-phase (OOP) chemical shift imaging (CSI) to distinguish non-neoplastic marrow lesions, benign bone tumours and malignant bone tumours. METHODS: CSI was introduced into our musculoskeletal tumour protocol in May 2018 to aid in characterisation of suspected bone tumours. The % signal intensity (SI) drop between IP and OOP sequences was calculated and compared to the final lesion diagnosis, which was classified as non-neoplastic (NN), benign neoplastic (BN) or malignant neoplastic (MN). RESULTS: The study included 174 patients (84 males; 90 females: mean age 44.2 years, range 2-87 years). Based on either imaging features (n = 105) or histology (n = 69), 44 lesions (25.3%) were classified as NN, 66 (37.9%) as BN and 64 (36.8%) as MN. Mean % SI drop on OOP for NN lesions was 36.6%, for BN 3.19% and for MN 3.24% (p < 0.001). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of CSI for differentiating NN from neoplastic lesions were 65.9%, 94.6%, 80.6%, 89.1%% and 87.4% respectively, and for differentiating BN from MN were 9.1%, 98.4%, 85.7%, 51.2 and 53.1% respectively. CONCLUSION: CSI is accurate for differentiating non-neoplastic and neoplastic marrow lesions, but is of no value in differentiating malignant bone tumours from non-fat containing benign bone tumours. ADVANCES IN KNOWLEDGE: CSI is of value for differentiating non-neoplastic marrow lesions from neoplastic lesions, but not for differentiating benign bone tumours from malignant bone tumours as has been previously reported.

Magnetic resonance imaging for assessing treatment response in bone marrow metastases.

Cancer metastasis to bone is a frequent observation in malignancy that may result in complications such as pathological fractures and spinal cord compression. Monitoring treatment effects is the main concern in oncology; however, the evaluation of treatment response in bone is particularly challenging as it lacks well-established criteria. In addition, bone metastases have traditionally been considered non-measurable manifestations of cancer. Magnetic resonance imaging (MRI) is one of the most specific and sensitive methods for imaging skeletal metastases. The aim of this article is to highlight the diagnostic performance of MRI in the treatment monitoring of bone metastases, to review the current literature, and to provide an overview of recommendations for the evaluation of treatment response in bone.

Pearls and Pitfalls in Imaging Bone Marrow in Pediatric Patients.

Magnetic resonance is a noninvasive, nonionizing modality used in the detection and evaluation of marrow lesions, as well as surgical planning and treatment follow-up. Since the distribution of red and yellow marrow occurs in a predictable sequence according to age, understanding this sequence is essential in establishing an accurate and timely diagnosis. This article provides an overview of the normal appearance of bone marrow in healthy children as well as focal and diffuse marrow abnormalities. Imaging pitfalls unique to children and solutions to use in difficult cases will be described.

Pictorial review of whole body MRI in myeloma: emphasis on diffusion-weighted imaging.

There have been major advances in myeloma imaging over the past few years with focal lesions on imaging now forming part of the disease defining criteria. Whole body diffusion-weighted MRI (WB-MRI) is considered the most sensitive technique for the detection of focal active lesions. This pictorial review will focus on imaging the spectrum of myelomatous disorders on WB-MRI including diffusion and Dixon sequences. The typical imaging patterns of disease are demonstrated including in the contexts of staging, presumed solitary plasmacytoma, smouldering myeloma and examples of paramedullary and extramedullary disease. The utility of diffusion-weighted imaging in response assessment is a major advantage and this will be exemplified here.

Prominent Bone Marrow Metastases Without Concurrent Intra-Chest Metastasis in a Case of Cardiac Angiosarcoma.

Primary cardiac angiosarcoma is rare and often advances by dissemination. Lungs are the most common metastatic sites, especially when the tumor originates in the right side of the heart. Bone metastases from cardiac angiosarcoma very rarely occur without concurrent pulmonary metastases. We report a case of cardiac angiosarcoma having prominent bone metastases without concurrent pulmonary lesions, as demonstrated by FDG PET/CT scan.

Diagnostic performance of 18F-2-fluoro-2-deoxy-D-glucose PET/computerized tomography in identifying bone marrow infiltration in new patients with diffuse large B-cell lymphoma and Hodgkin lymphoma.

OBJECTIVE: To compare between F-2-fluoro-2-deoxy-D-glucose PET/computerized tomography (F-FDG PET/CT) and routine iliac bone marrow biopsy (BMB) in assessment of bone marrow infiltration (BMI) in Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) patients at initial presentation. PATIENTS AND METHODS: A retrospective analysis of 138 patients (50 Hodgkin lymphomas, 88 DLBCLs). The study included 70 males and 68 females with median age of 43 years. All patients underwent F-FDG PET/CT and iliac crest BMB before treatment. Any focal or patchy FDG uptake in the bone marrow, superior-to hepatic uptake was interpreted as abnormal with or without corresponding CT changes. Treatment response was evaluated clinically with each cycle of chemotherapy, radiologically after three cycles and at the end of treatment. RESULTS: The overall diagnostic performance showed significant higher sensitivity of F-FDG PET/CT than that of BMB (73.9 versus 62.5%, P = 0.046), while the specificity was higher in BMB than in F-FDG PET/CT (100% in BMB versus 93.5% in F-FDG PET/CT). In Hodgkin lymphoma, sensitivity, negative predictive value (NPV) and accuracy were significantly higher in F-FDG PET/CT compared with BMB, being 87.5, 94.4 and 96% versus 50, 81 and 84% (P = 0.02, 0.03, 0.04, respectively). However, for DLBCL patients, almost comparable results were found between both tests in terms of sensitivity, NPV and accuracy (66.7, 83.9 and 81.8% versus 68.8, 84.9 and 88.6%, respectively). After PET/CT scan, 12 patients (8.6%) were upstaged to stage IV, eight of them were negative by BMB. CONCLUSION: F-FDG PET/CT seemed to be an excellent diagnostic test in assessment of BMI at initial assessment and staging of Hodgkin lymphoma and DLBCL patients.

Advanced MR imaging of bone marrow: quantification of signal alterations on T1-weighted Dixon and T2-weighted Dixon sequences in red marrow, yellow marrow, and pathologic marrow lesions.

OBJECTIVES: To quantify and compare signal intensity (SI) changes on T1-weighted (W) and T2W Dixon imaging in yellow marrow, red marrow, and bone marrow lesions. MATERIALS AND METHODS: A total of 141 patients (77 controls, 64 lesions-33 benign, 31 malignant) between January 2016 and December 2017 were retrospectively identified. For the control group, fixed 2-cm2 region of interests (ROI) were drawn at L5, bilateral ilium and femurs on in-phase and opposed-phase T1W and T2W Dixon images. For the lesion group, ROIs of best fit were drawn around each lesion on in-phase and opposed-phase T2W Dixon images. SI changes between in-phase and opposed phase maps for each group were compared. Inter-reader analysis was performed. RESULTS: Yellow marrow exhibited smaller SI changes as compared to red marrow on both T1W and T2W Dixon imaging at all locations (p < 0.0001) except at L5 on T2W Dixon imaging (p = 0.206). Both benign and malignant lesions showed significantly smaller SI changes as compared to both yellow (p = 0.0087, p < 0.0001) and red marrow (p = 0.0004, p < 0.0001) on T2W Dixon imaging. Malignant lesions exhibited smaller SI change as compared to benign lesions on T2W Dixon imaging (p = 0.0005). Signal intensity loss on both red and yellow marrow were smaller on T1W Dixon as compared to T2W Dixon (0.49-0.64, 0.27-0.31 vs. 0.70-0.74, 0.48-0.71). Inter-reader agreements were excellent (0.91-0.97). CONCLUSIONS: SI change calculated from T2-weighted Dixon imaging can adequately differentiate between yellow marrow, red marrow, and osseous lesions, both benign and malignant.

FDG-PET/CT Demonstrates Splenic Angiosarcoma Bone Marrow Metastasis.

Some patients with splenic angiosarcoma initially manifest thrombocytopenia owing to hypersplenism or tumor-related bone marrow fibrosis. The diagnosis of bone marrow metastasis in patients with splenic angiosarcoma is challenging, as the presentation mimics idiopathic thrombocytopenic purpura or primary myelofibrosis. Our case showed diffuse FDG uptake in the vertebral bodies, sacroiliac bone, humerus, femur, and clavicles. It was pathologically diagnosed as bone marrow metastasis of splenic angiosarcoma. We believe that the heterogeneous FDG accumulation in the bone marrow, although nonspecific, can be useful for the diagnosis of the bone marrow metastasis in patients with splenic angiosarcoma.

The new international neuroblastoma response criteria.

Over recent years significant advances in histopathology and functional imaging techniques for the diagnosis and restaging of children with neuroblastoma have led to better quantification of disease and assessment of disease response, allowing for better treatment stratification. In this review we summarise recent changes to the International Neuroblastoma Response Criteria including the use of RECIST (Response Evaluation Criteria in Solid Tumours) guidance for measurable soft-tissue disease, replacement of technetium-99 m-methylene diphosphonate (MDP) bone scans with metaiodobenzylguanidine (MIBG) scan or [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT scanning, and a new category of minimal residual bone marrow disease.

Myeloproliferative Neoplasms: A Primer for Radiologists.

The myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Knowledge of the radiological and clinical features of MPNs and their associated complications is critical for interpreting radiologists. The purpose of this article is to provide a primer to radiologists summarizing the modern understanding of MPNs from an imaging-based perspective, including common disease-related findings and complications related to hematopoietic cell transplant.

The Value of 18F-FDG PET/CT in Detecting Bone Marrow Involvement in Childhood Cancers.

BACKGROUND: The aim of this study was to assess the utility of F-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in the initial staging of pediatric patients with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), Ewing sarcoma (ES), and neuroblastoma (NB). PROCEDURE: A total of 94 patients (57 boys, 37 girls, median age 7 y, range 1 to 18 y) with newly diagnosed NHL, HL, ES, and NB between July 2014 and December 2017, who underwent BMB and F-FDG PET/CT before chemotherapy were included in this study. There were 36 patients with NHL, 27 HL, 16 ES, and 15 NB. F-FDG PET/CT and BMB results were reviewed and compared retrospectively. FINDINGS: Retrospective analysis of data from 94 pediatric patients (57 boys, 37 girls, median age 7 y, range 1 to 18 y) was performed. Of the 94 patients, 29 had BMI on F-FDG PET/CT. BMB was positive in 14, negative in 13, and insufficient in 2 of these 29 patients. In 65 patients negative on F-FDG PET/CT, BMB was also negative in 54 and insufficient in 7. For the whole group, sensitivity, specificity, and positive and negative predictive values of F-FDG PET/CT in detecting bone marrow metastasis at the time of diagnosis were 90.6%, 100%, 100%, and 95.4% and those of BMB were 53.1%, 87.1%, 94.4%, and 80.6%, respectively. CONCLUSION: Our study demonstrates that F-FDG PET/CT predicts BMI better than BMB. F-FDG PET/CT may be used at initial staging of pediatric patients with NHL, HL, ES, and NB.