Original article
Diagnostic value of 99mTc-MDP SPECT/spiral CT combined with three-phase bone scintigraphy in assessing suspected bone tumors in patients with no malignant history Yiqiu Zhanga,b,c, Hongcheng Shia,b,c, Beilei Lia,b,c, Yan Xiua,b,c, Liang Caia,b,c, Yushen Gua,b,c and Shuguang Chena,b,c Introduction Three-phase bone scintigraphy using technetium-99m-methylene diphosphonate is used to diagnose skeletal lesions, whereas single-photon emission computed tomography/computed tomography (SPECT/CT) improves the diagnostic accuracy of bone disease. We investigated the usefulness of SPECT/CT combined with three-phase bone scintigraphy over three-phase bone scintigraphy alone in assessing suspected bone tumors in patients with no malignant history. Materials and methods Forty-eight patients (30 men and 18 women; mean age, 43.3 ± 20.1 years; age range, 11–82 years) with suspected bone tumors who underwent technetium-99m-methylene diphosphonate three-phase bone scintigraphy and SPECT/CT between July 2008 and August 2013 were retrospectively reviewed. The lesion from each patient was resected or biopsied for pathological confirmation of the diagnosis within 3 weeks of the bone scan. All images were interpreted by two experienced nuclear medicine physicians who had not been involved in the selection of data for the present study. The reviewers were aware of the patient’s sex, age, and the lesion’s site but were unaware of the results of other imaging modalities, such as radiography, MRI, and laboratory tests. In cases of discrepancy regarding the interpretations, a consensus was reached after mutual discussion. The diagnostic ability of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy was compared with pathological results using the χ2-test, with P-values less than 0.05 indicating significant differences. Agreement between three-phase bone scintigraphy alone or SPECT/CT combined with three-phase bone scintigraphy with pathological results was evaluated using κ scores. Results Pathological results from the 48 lesions of all patients revealed 32 malignant bone tumors and 16 benign
Introduction Three-phase bone scintigraphy using technetium-99mlabeled diphosphonate (99mTc-MDP) has long been well accepted and widely performed as an imaging modality to detect suspected inflammatory osseous conditions, diabetic foot, complex regional pain syndrome, and bone tumors [1–4]. Three-phase bone scanning involves targeted imaging of the area of interest in the angiographic (flow, immediately after injection), soft-tissue (pool,
lesions. On using three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy for the differential diagnosis of bone lesions, we found sensitivities to be 96.9 and 100%, specificities to be 31.2 and 81.3%, positive predictive values to be 73.8 and 91.4%, and negative predictive values to be 83.3 and 100%, respectively. The diagnostic accuracies of three-phase bone scintigraphy alone and SPECT/CT combined with threephase bone scintigraphy were 75.0 and 93.8%, respectively (χ2 = 5.057; P = 0.025). κ scores for the agreement of threephase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy with pathological results were 0.333 (P = 0.005) and 0.850 (P < 0.0001), respectively. Conclusion Compared with three-phase bone scintigraphy, the diagnostic accuracy of SPECT/CT combined with three-phase bone scintigraphy was higher. SPECT/CT combined with three-phase bone scintigraphy is beneficial over three-phase bone scintigraphy for the differential diagnosis of suspected bone tumors in patients with no malignant history. Nucl Med Commun 36:686–694 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Nuclear Medicine Communications 2015, 36:686–694 Keywords: benign, diagnosis, malignant, single-photon emission computed tomography/computed tomography, three-phase bone scintigraphy a Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, bNuclear Medicine Institute of Fudan University and cShanghai Institute of Medical Imaging, Shanghai, China
Correspondence to Hongcheng Shi, MD, PhD, Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China Tel: + 86 216 404 1990 x2064; fax: + 86 216 403 8472; e-mail: [email protected] Received 8 November 2014 Revised 25 January 2015 Accepted 25 January 2015
2–10 min after injection), and delayed (2–4 h after injection) phases [5]. It is routine practice to perform a delayed whole-body examination as part of a focused three-phase bone scanning at our institution to provide additional information without increasing the radiation dose to the patient. Three-phase bone scanning is well known to be a sensitive but nonspecific examination in the differential diagnosis of benign or malignant lesions in patients with suspected bone tumors. The specific
0143-3636 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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DOI: 10.1097/MNM.0000000000000299
SPECT/CT with three-phase bone scan Zhang et al. 687
diagnosis of a bone tumor is based on the location, matrix change, and appearance of soft-tissue around the bone lesion, all of which can be obtained from diagnostic computed tomography (CT) scans. Hybrid single-photon emission computed tomography (SPECT)/spiral CT offers the opportunity to obtain diagnostic-quality CT and SPECT images, combining the diagnostic power of morphological changes with that of abnormal metabolism within lesions and improving the diagnostic accuracy of bone disease imaging [6–10].
∼ 1110 MBq (30 mCi) 99mTc-MDP. Scintigraphic images of the lesion of the suspected bone tumor were acquired in angiographic (128 × 128 matrix, 3 s/frame, 40 frames), soft-tissue (256 × 256 matrix, 500k count, one frame), and delayed planar whole-body scintigraphy (256 × 1024 matrix) phases as part of a focused three-phase bone scanning performed after 3–6 h. These images were analyzed immediately after acquisition by an experienced nuclear medicine physician who determined the field of view of SPECT/CT.
We aimed to investigate the benefit of SPECT/CT combined with three-phase bone scintigraphy over threephase bone scintigraphy alone in the differential diagnosis of suspected bone tumor in patients with no history of malignancy.
The SPECT raw data were reconstructed into transaxial, coronal, and sagittal slices using reconstruction software (Astonish; Philips, San Jose, California, USA). Immediately after SPECT, CT scans were performed with the patient in the same position. The CT scan parameters were as follows: 120 kV, 160 mA, 400 mm view, 5 mm scan, and 3 mm reconstruction. Both SPECT and CT were performed with the patients lying supine and breathing shallowly. For all fused images, the accuracy of the matching of internal anatomic landmarks visible on both CT and SPECT was checked. No misregistration exceeding 2 mm was found.
Materials and methods Patient selection
The study was retrospective, and patients were selected if they fulfilled the following criteria: (a) they had no history of extraskeletal malignancies; (b) they had no surgical history for the lesion; and (c) they had undergone histological verification of the lesion as part of their clinical management. A total of 48 patients (30 men and 18 women; mean age, 43.3 ± 20.1 years; age range, 11–82 years) with suspected bone tumors underwent 99mTc-MDP three-phase bone scintigraphy and SPECT/CT between July 2008 and August 2013. The locations of the bone lesions are listed in Table 1. The lesion from each patient was resected or biopsied for pathological confirmation of the diagnosis within 3 weeks from the bone scan. The study was approved by the institutional review board of Zhongshan Hospital affiliated with Fudan University, and all patients gave their written informed consent. Three-phase bone scintigraphy
Images were obtained using Philips Precedence with a 16-slice diagnostic CT scanner (Philips Medical Systems, Bothell, Wisconsin, USA). The camera heads were equipped with a low-energy, high-resolution, parallelhole collimator, with counts from the 20% energy windows at 140 keV. Three-phase bone scans of adult patients were obtained after intravenous injection of
Table 1
Location of bone lesions in 48 patients
Location of bone lesions Clavicle Scapula Humerus Radius Lumbar vertebra Sacrum Innominatum Femur Scutum Tibia
Number of patients 2 3 4 1 1 5 8 18 1 5
Image analyses
All images were interpreted by two experienced nuclear medicine physicians who had not been involved in the selection of data for the present study. The reviewers were aware of the patient’s sex, age, and the lesion’s site but were unaware of the results of other imaging modalities, such as radiography, MRI, and laboratory tests. To minimize recall bias, the reviewers read three-phase bone scintigraphy images first and interpreted SPECT/CT combined images with three-phase bone scintigraphy images 3 weeks later. Each lesion was scored as benign or malignant. In cases of discrepancy regarding the interpretations, a consensus was reached after mutual discussion. For analyzing the results of three-phase bone scanning alone, the reviewers were trained and tested to assess the images using the following reference standards: malignant bone tumors often manifested as increased blood supply, with the area of increased uptake in all flow, pool, and delayed phases; however, primary benign bone tumors were usually not associated with increased blood supply, with the area of increased uptake commonly found only in the delayed phase [11,12]; for SPECT/spiral CT fusion imaging analysis, if CT showed osteolytic changes (bone erosion, edge irregularity, no osteosclerosis, or a soft-tissue mass) or osteoblastic changes (high bone density without a soft-tissue mass) in areas of abnormal radioactivity uptake, a diagnosis of malignancy was made. The area of abnormal uptake was considered benign when the regions corresponded to benign findings on CT, such as osteomyelitis, bone cyst, or other primary benign bone tumors [13,14]. Characterization of the bone tumors was based on the
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location, calcification, and ossification of the tumor and on the patient’s age at the time of diagnosis [15].
Table 3 Comparison of pathology results and lesion grades from both reviewers after review of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy Pathology results
Statistical analysis
Compared with the pathological diagnosis, the diagnostic ability of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy was compared using the χ2-test, with P-values less than 0.05 indicating significant differences. SPSS 10.0 software (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. The agreement between the interpretations of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy with pathological results was evaluated using κ scores, ranging from − 1 (complete disagreement) to + 1 (perfect agreement). κ scores were classified as follows: 0, chance agreement; less than 0.20, poor agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement; 0.61–0.80, substantial agreement; 0.81–1.00, almost perfect agreement [16].
Results Pathological results from the 48 lesions of all patients revealed a final diagnosis of 32 malignant bone tumors and 16 benign lesions. The distribution of the pathological results in the 48 examined lesions is shown in Table 2. Among the malignant bone tumors, five metastasized from hepatocellular carcinoma (n = 2), squamous cell carcinoma of the lung (n = 1), seminoma (n = 1), and cancerous goiter (n = 1). The comparison of pathology results and lesion grades from both reviewers after review of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy is shown in Table 3. On using threephase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy for the differential diagnosis of bone lesions, we found sensitivities to be 96.9
Table 2
Distribution of the pathology results in the 48 examined
lesions Malignant (n = 32)
Pathological type Osteosarcoma
Benign (n = 16) Number of patients 13
Chondrosarcoma Adamantinoma
6 1
Malignant schwannoma Rhabdomyosarcoma
1 1
Inflammatory myofibroblastic sarcoma Lymphoma Plasmacytoma Synovial sarcoma Malignant epithelioid hemangioendothelioma Bone metastatic tumor
1 1 1 1 1 5
Pathological type Giant cell tumor of the bone Osteochondroma Aneurysmal bone cyst Cyst with infection Osteofibrous dysplasia Langerhans cell histiocytosis Myelolipoma Necrosis of the bone Osteoarthritis Granulomatous inflammation Osteomyelitis
Number of patients 5 2 1 1 1 1 1 1 1 1 1
Malignancy Three-phase bone scintigraphy Malignancy 31 Benign 1 SPECT/CT combined with three-phase bone scintigraphy Malignancy 32 Benign 0
Benign 11 5 3 13
SPECT/CT, single-photon emission computed tomography/computed tomography.
and 100%, specificities to be 31.2 and 81.3%, positive predictive values to be 73.8 and 91.4%, and negative predictive values to be 83.3 and 100%, respectively. The diagnostic accuracies of three-phase bone scintigraphy alone and SPECT/CT combined with three-phase bone scintigraphy were 75.0 and 93.8%, respectively (χ2 = 5.057; P = 0.025). κ scores for the agreement of the interpretations of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy with pathological results were 0.333 (P = 0.005) and 0.850 (P < 0.0001), respectively. As listed in Table 4, 12 lesions (Nos. 1–12) were misdiagnosed on the basis of three-phase bone scintigraphy images alone, and three lesions (Nos. 10–12) were misdiagnosed on the basis of SPECT/CT combined with three-phase bone scintigraphy images. There were no cases correctly diagnosed by three-phase bone scintigraphy but misdiagnosed according to SPECT/CT combined with three-phase bone scintigraphy images in our study. Of the 12 lesions misdiagnosed according to three-phase bone scintigraphy images alone, nine (Nos. 1–9) were diagnosed correctly on the basis of SPECT/CT combined with three-phase bone scintigraphy images. One case of knee osteoarthritis, one case (No. 1) of granulomatous inflammation of the femur (No. 2; Fig. 1), one case of osteomyelitis of the clavicle (No. 3), and one case of necrosis of the tibia (No. 4) were misdiagnosed as malignant lesions on the basis of three-phase bone scintigraphy images because of enhanced blood flow, softtissue hyperemia, and increased uptake in the delayed phase; however, they were correctly diagnosed as benign lesions on the basis of SPECT/CT combined with threephase bone scintigraphy. Because of enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase displayed in three-phase bone scintigraphy, four cases (Nos. 5–8; Fig. 2) of giant cell tumors were misdiagnosed as malignant lesions; however, SPECT/CT showed a clear boundary expansion of bone destruction, accompanied by abnormal uptake of radioactivity, and thus they were finally diagnosed as benign lesions. One case (No. 9; Fig. 3) of a lumbar vertebra metastatic tumor from seminoma was misdiagnosed as a
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Misdiagnoses based on three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy from both reviewers
Table 4
Case no.
Sex/Age (years)
Location of bone lesions
Three-phase bone scintigraphy
SPECT/CT combined with three-phase bone scintigraphy
1 2 3 4 5 6 7 8 9
M/21 M/38 F/55 F/58 F/46 F/22 M/33 M/56 M/37
Knee Femur Clavicle Tibia Tibia Tibia Tibia Femur Lumbar vertebra
Malignant Malignant Malignant Malignant Malignant Malignant Malignant Malignant Benign
Benign Benign Benign Benign Benign Benign Benign Benign Malignant
10 11 12
M/17 M/17 F/53
Innominatum Femur Sacrum
Malignant Malignant Malignant
Malignant Benign Malignant
Pathology results Osteoarthritis Granulomatous inflammation Osteomyelitis Necrosis of the bone Giant cell tumor of the bone Giant cell tumor of the bone Giant cell tumor of bone Giant cell tumor of the bone Bone metastatic tumor from seminoma Langerhans cell histiocytosis Osteofibrous dysplasia Giant cell tumor of the bone
SPECT/CT, single-photon emission computed tomography/computed tomography.
benign lesion on the basis of three-phase bone scintigraphy images because of no flow phase or pool phase uptake changes, and decreased uptake only in the delayed phase. However, SPECT/CT images revealed the lesion to show decreased radioactive uptake in the mild osteolytic bone destruction and in a surrounding soft-tissue mass, and thus the lesion was diagnosed as being malignant. Three cases were misdiagnosed on the basis of both three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy, and all lesions that were misdiagnosed as malignant were, in fact, benign. Among them, a case of Langerhans cell histiocytosis of the left innominatum (No. 10; Fig. 4) showed enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging and bone destruction with increased radioactivity on SPECT/CT imaging. Another case of right femur bone fibrous dysplasia (No. 11) showed enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging and mixed-density intramedullary violation of the cortical bone with increased radioactivity on SPECT/CT. Finally, another case of giant cell tumor of the sacrum (No. 12) showed enhanced blood flow, softtissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging and radioactivity concentration located in the peripheral part of a wide range of osteolytic bone destruction on SPECT/CT.
Discussion Bone scintigraphy using 99mTc-MDP is one of the most frequently performed radionuclide procedures. Its excellent sensitivity makes it useful in screening for generalized bone abnormalities, but it is not specific [17]. Hotspots in a whole-body bone scan can result from various common disorders, including bone metastases, osteoarthritis, trauma, inflammation, and other malignant or benign bone diseases [18,19]. Three-phase bone scintigraphy has received considerable attention predominantly in the investigation of patients
with bone-related diseases such as osteomyelitis, bone tumors, and sympathetic dystrophy, as blood supply and soft-tissue vascularity may be assessed in addition to any associated bone changes [20,21]. Three-phase bone scintigraphy can evaluate blood vessels and tissue perfusion in solid organs and soft tissues and detect bone abnormalities. Various bone lesions have hemodynamic characteristics. Three-phase bone scintigraphy images during the arterial, tissue perfusion, and blood pool phases also provide insight into the underlying physiologic and pathologic processes. There is considerable malignant bone tumor capillary proliferation and capillary network formation, which increase the blood supply and may be accompanied by the formation of a soft-tissue mass. Thus, three-phase bone scintigraphy plays an important role in the differential diagnosis of benign and malignant bone tumors. Hybrid SPECT/spiral CT offers the opportunity to obtain diagnostic-quality CT and SPECT images. SPECT/spiral CT has been used clinically, and many investigations have been published that have explored its diagnostic value [6 –10]. SPECT/spiral CT provides a clear view of the anatomic sites of any lesion with abnormal radioactivity concentrations. In addition, SPECT/spiral CT combines the diagnostic power of the morphological changes of the lesions. The specific diagnosis of benign and malignant bone tumors is based on the location, matrix appearance, and growth rate of a lesion, all of which can be obtained from diagnostic CT scans. On the basis of improved access to the lesion site of the blood supply and bone salt metabolic characteristics, combined with characteristic CT signs of benign and malignant bone tumors, we can state that the accuracy of the diagnosis of bone disease has effectively improved. In 32 cases of malignant lesions in the present study, 31 cases showed enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging. Only one case of a lumbar vertebra metastatic tumor from seminoma was misdiagnosed as a benign lesion because of no flow or pool
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Fig. 1
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A 38-year-old male patient with no history of malignancy who showed symptoms of right hip pain for 3 months. Three-phase bone scintigraphy images showed enhanced blood flow (a), soft-tissue hyperemia (b), and increased uptake in the delayed phase (c) of the right proximal femur (misdiagnosed as being malignant). SPECT/CT images (d) revealed low-density lesions with peripheral atherosclerosis and cortical bone fuzziness with increased radioactive uptake (correctly diagnosed as being benign). Pathological diagnosis of the lesion was granulomatous inflammation. SPECT/CT, singlephoton emission computed tomography/computed tomography.
phase uptake changes, and because of decreased uptake in the delayed phase on three-phase bone scintigraphy imaging. However, SPECT/CT images revealed that the lesion showed decreased radioactive uptake in the osteolytic bone destruction with a surrounding soft-tissue mass, and thus the lesion was diagnosed correctly as malignant. In that case, the misdiagnosis of three-phase bone scintigraphy may be due to the lack of blood supply to the metastatic seminoma itself, or because the metastatic bone lesions were in the pathological stages of osteolytic change and necrosis, leading to reduced blood flow and bone salt metabolism. In 16 cases of benign lesions, one case of a cyst with infection and two cases of
osteochondroma showed no flow phase or pool phase uptake changes, with increased uptake only in the delayed phase; one case of an aneurysmal bone cyst and one case of myelolipoma that showed no uptake changes in the three phases were diagnosed as benign lesions, and were then definitely diagnosed when three-phase bone scintigraphy was combined with SPECT/CT. One case of osteoarthritis, one case of bone granulomatous inflammation, one case of osteomyelitis, one case of bone necrosis, five cases of giant cell tumors, one case of Langerhans cell histiocytosis, and one case of osteofibrous dysplasia showed enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging and were
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SPECT/CT with three-phase bone scan Zhang et al. 691
Fig. 2
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A 33-year-old male patient with no history of malignancy who showed symptoms of left knee pain for 3 months. Three-phase bone scintigraphy images showed enhanced blood flow (a), soft-tissue hyperemia (b), and increased uptake (c) in the delayed phase of the left proximal tibia (misdiagnosed as being malignant). SPECT/CT images (d) revealed a lesion with increased radioactive uptake in well-defined expansion bone destruction with a nonsclerotic margin (correctly diagnosed as being benign). Pathological diagnosis of the lesion was a giant cell tumor of the bone. SPECT/CT, singlephoton emission computed tomography/computed tomography.
misdiagnosed as malignant lesions; however, three cases of inflammation, one case of necrosis, and four cases of giant cell tumors were further definitely diagnosed as benign lesions when three-phase bone scintigraphy was combined with SPECT/CT. Our study results showed that the diagnostic accuracy of three-phase bone scintigraphy alone was 75.0%, which improved to 93.8% when combined with SPECT/CT (χ2 = 5.057; P = 0.025). Thus, SPECT/CT combined with three-phase bone scintigraphy can effectively overcome the limitations of three-phase bone scintigraphy alone. In particular, for some inflammatory lesions with enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase, SPECT/CT imaging is helpful
to obtain a definitive diagnosis. In addition to detecting extraskeletal lesions, three-phase bone scintigraphy helps to improve the specificity by allowing the vascularity of skeletal lesions and surrounding soft tissues to be visualized. Furthermore, SPECT/CT images can clearly show whether the surrounding soft-tissue tumors involve bone lesions. The diagnosis and differential diagnosis of suspected bone lesions based on blood flow and bone salt metabolism in nuclear medicine images and on morphological changes of CT images can raise diagnostic confidence remarkably. In addition, at our institution, it is routine practice to perform delayed whole-body examination as part of a focused three-
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Fig. 3 Flow
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A 37-year-old male patient with no history of malignancy who showed symptoms of low back pain for 1 month. Three-phase bone scintigraphy images showed no flow phase (a) or pool phase (b) uptake changes, and decreased uptake in the delayed phase (c) of the second lumbar vertebra (misdiagnosed as being benign). SPECT/CT imaging (d) revealed a lesion with decreased radioactive uptake in mild osteolytic bone destruction with a surrounding soft-tissue mass (correctly diagnosed as being malignant). Pathological diagnosis of the lesion was bone metastatic tumor from seminoma. SPECT/CT, single-photon emission computed tomography/computed tomography.
phase study to provide free additional information because no additional radiation dose is used to examine the rest of the body. Furthermore, the whole-body skeletal screen could show the existence of bone metastases in patients with malignant tumors, as well as other bone lesions. If the diagnosis of distant lesions remains unclear, it is feasible to perform an additional SPECT/CT scan. However, the present study revealed that not all suspected bone lesions could be definitively diagnosed by SPECT/CT combined with three-phase bone scintigraphy because there were still three misdiagnosed cases of iliac Langerhans cell histiocytosis, sacral giant cell
tumors, and femur bone fibrous dysplasia. Although these lesions showed a benign pathology, they have a rich blood supply at the lesion site and a malignant growth pattern, with CT showing various degrees of bone destruction. When morphological features of these lesions are not typical according to CT findings, these lesions can be easily misdiagnosed as malignant lesions, and their differential diagnosis remains difficult, which depends to a large extent on the experience of the reading physicians. The current study has a few limitations. First, the generalizability of the results is limited by the retrospective and very selective nature of the patient population; we
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Fig. 4
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A 17-year-old male patient with no history of malignancy who showed symptoms of left hip pain for 20 days. Three-phase bone scintigraphy images showed enhanced blood flow (a), soft-tissue hyperemia (b), and increased uptake in the delayed phase (c) of the left innominatum (misdiagnosed as being malignant). SPECT/CT images (d) revealed a lesion with increased radioactive uptake in osteolytic bone destruction with cortical discontinuity (misdiagnosed as being malignant). Pathological diagnosis of the lesion was Langerhans cell histiocytosis. SPECT/CT, single-photon emission computed tomography/computed tomography.
selected only cases with a pathological diagnosis for inclusion in the present study. Second, the number of cases in the study was relatively small.
Conclusion Compared with three-phase bone scintigraphy alone, the diagnostic accuracy of SPECT/CT combined with threephase bone scintigraphy was significantly higher. SPECT/CT combined with three-phase bone scintigraphy provides a benefit over three-phase bone scintigraphy for differential diagnosis of suspected bone tumors in patients with no malignant history.
Acknowledgements This study is in part supported by Advanced and Suitable Technology Promotion Projects of Health System of Shanghai (Grant No. 2013SY008). Conflicts of interest
There are no conflicts of interest.
References 1 2
Baqer MM, Loutfi I. Optimal imaging positions for 3-phase bone scanning of patients with bony pathology of the feet. J Nucl Med Technol 2010; 38:69–75. Wüppenhorst N, Maier C, Frettlöh J, Pennekamp W, Nicolas V. Sensitivity and specificity of 3-phase bone scintigraphy in the diagnosis of complex regional pain syndrome of the upper extremity. Clin J Pain 2010; 26:182–189.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
694
3
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Sella EJ, Grosser DM. Imaging modalities of the diabetic foot. Clin Podiatr Med Surg 2003; 20:729–740. 4 Villani MF, Falappa P, Pizzoferro M, Toniolo RM, Lembo A, Chiapparelli S, Garganese MC. Role of three-phase bone scintigraphy in paediatric osteoid osteoma eligible for radiofrequency ablation. Nucl Med Commun 2013; 34:638–644. 5 Davenport MS, Brown RK, Frey KA. Utility of delayed whole-body bone scintigraphy after directed three-phase scintigraphy. Am J Roentgenol 2009; 193:338–342. 6 Zhao Z, Li L, Li F, Zhao L. Single photon emission computed tomography/spiral computed tomography fusion imaging for the diagnosis of bone metastasis in patients with known cancer. Skeletal Radiol 2010; 39:147–153. 7 Helyar V, Mohan HK, Barwick T, Livieratos L, Gnanasegaran G, Clarke SE, Fogelman I. The added value of multislice SPECT/CT in patients with equivocal bony metastasis from carcinoma of the prostate. Eur J Nucl Med Mol Imaging 2010; 37:706–713. 8 Zhang Y, Shi H, Gu Y, Xiu Y, Li B, Zhu W, et al. Differential diagnostic value of single-photon emission computed tomography/spiral computed tomography with Tc-99m-methylene diphosphonate in patients with spinal lesions. Nucl Med Commun 2011; 32:1194–1200. 9 Sharma P, Singh H, Kumar R, Bal C, Thulkar S, Seenu V, Malhotra A. Bone scintigraphy in breast cancer: added value of hybrid SPECT-CT and its impact on patient management. Nucl Med Commun 2012; 33:139–147. 10 Zhang Y, Shi H, Cheng D, Jiang L, Xiu Y, Li B, et al. Added value of SPECT/spiral CT versus SPECT in diagnosing solitary spinal lesions in patients with extraskeletal malignancies. Nucl Med Commun 2013; 34:451–458.
11 12 13 14
15 16
17 18 19
20 21
Focacci C, Lattanzi R, Iadeluca ML, Campioni P. Nuclear medicine in primary bone tumors. Eur J Radiol 1998; 27: (Suppl 1):S123–S131. Yang DC, Ratani RS, Mittal PK, Chua RS, Pate SM. Radionuclide threephase whole-body bone imaging. Clin Nucl Med 2002; 27:419–426. Theodorou DJ, Theodorou SJ, Sartoris DJ. An imaging overview of primary tumors of the spine: part 1. Benign tumors. Clin Imaging 2008; 32:196–203. Theodorou DJ, Theodorou SJ, Sartoris DJ. An imaging overview of primary tumors of the spine: part 2. Malignant tumors. Clin Imaging 2008; 32:204–211. Erlemann R. Imaging and differential diagnosis of primary bone tumors and tumor-like lesions of the spine. Eur J Radiol 2006; 58:48–67. Utsunomiya D, Shiraishi S, Imuta M, Tomiguchi S, Kawanaka K, Morishita S, et al. Added value of SPECT/CT fusion in assessing suspected bone metastasis: comparison with scintigraphy alone and nonfused scintigraphy and CT. Radiology 2006; 238:264–271. Love C, Din AS, Tomas MB, Kalapparambath TP, Palestro CJ. Radionuclide bone imaging: an illustrative review. Radiographics 2003; 23:341–358. Rybak LD, Rosenthal DI. Radiological imaging for the diagnosis of bone metastases. Q J Nucl Med 2001; 45:53–64. Savelli G, Maffioli L, Maccauro M, De Deckere E, Bombardieri E. Bone scintigraphy and the added value of SPECT (single photon emission tomography) in detecting skeletal lesions. Q J Nucl Med 2001; 45:27–37. McLean RG, Murray IP. Three-phase skeletal scintigraphy for suspected bone tumors. Clin Nucl Med 1984; 9:378–382. Kozin F, Soin JS, Ryan LM, Carrera GF, Wortmann RL. Bone scintigraphy in the reflex sympathetic dystrophy syndrome. Radiology 1981; 138:437–443.
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Diagnostic value of 99mTc-MDP SPECT/spiral CT combined with three-phase bone scintigraphy in assessing suspected bone tumors in patients with no malignant history Yiqiu Zhanga,b,c, Hongcheng Shia,b,c, Beilei Lia,b,c, Yan Xiua,b,c, Liang Caia,b,c, Yushen Gua,b,c and Shuguang Chena,b,c Introduction Three-phase bone scintigraphy using technetium-99m-methylene diphosphonate is used to diagnose skeletal lesions, whereas single-photon emission computed tomography/computed tomography (SPECT/CT) improves the diagnostic accuracy of bone disease. We investigated the usefulness of SPECT/CT combined with three-phase bone scintigraphy over three-phase bone scintigraphy alone in assessing suspected bone tumors in patients with no malignant history. Materials and methods Forty-eight patients (30 men and 18 women; mean age, 43.3 ± 20.1 years; age range, 11–82 years) with suspected bone tumors who underwent technetium-99m-methylene diphosphonate three-phase bone scintigraphy and SPECT/CT between July 2008 and August 2013 were retrospectively reviewed. The lesion from each patient was resected or biopsied for pathological confirmation of the diagnosis within 3 weeks of the bone scan. All images were interpreted by two experienced nuclear medicine physicians who had not been involved in the selection of data for the present study. The reviewers were aware of the patient’s sex, age, and the lesion’s site but were unaware of the results of other imaging modalities, such as radiography, MRI, and laboratory tests. In cases of discrepancy regarding the interpretations, a consensus was reached after mutual discussion. The diagnostic ability of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy was compared with pathological results using the χ2-test, with P-values less than 0.05 indicating significant differences. Agreement between three-phase bone scintigraphy alone or SPECT/CT combined with three-phase bone scintigraphy with pathological results was evaluated using κ scores. Results Pathological results from the 48 lesions of all patients revealed 32 malignant bone tumors and 16 benign
Introduction Three-phase bone scintigraphy using technetium-99mlabeled diphosphonate (99mTc-MDP) has long been well accepted and widely performed as an imaging modality to detect suspected inflammatory osseous conditions, diabetic foot, complex regional pain syndrome, and bone tumors [1–4]. Three-phase bone scanning involves targeted imaging of the area of interest in the angiographic (flow, immediately after injection), soft-tissue (pool,
lesions. On using three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy for the differential diagnosis of bone lesions, we found sensitivities to be 96.9 and 100%, specificities to be 31.2 and 81.3%, positive predictive values to be 73.8 and 91.4%, and negative predictive values to be 83.3 and 100%, respectively. The diagnostic accuracies of three-phase bone scintigraphy alone and SPECT/CT combined with threephase bone scintigraphy were 75.0 and 93.8%, respectively (χ2 = 5.057; P = 0.025). κ scores for the agreement of threephase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy with pathological results were 0.333 (P = 0.005) and 0.850 (P < 0.0001), respectively. Conclusion Compared with three-phase bone scintigraphy, the diagnostic accuracy of SPECT/CT combined with three-phase bone scintigraphy was higher. SPECT/CT combined with three-phase bone scintigraphy is beneficial over three-phase bone scintigraphy for the differential diagnosis of suspected bone tumors in patients with no malignant history. Nucl Med Commun 36:686–694 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Nuclear Medicine Communications 2015, 36:686–694 Keywords: benign, diagnosis, malignant, single-photon emission computed tomography/computed tomography, three-phase bone scintigraphy a Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, bNuclear Medicine Institute of Fudan University and cShanghai Institute of Medical Imaging, Shanghai, China
Correspondence to Hongcheng Shi, MD, PhD, Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China Tel: + 86 216 404 1990 x2064; fax: + 86 216 403 8472; e-mail: [email protected] Received 8 November 2014 Revised 25 January 2015 Accepted 25 January 2015
2–10 min after injection), and delayed (2–4 h after injection) phases [5]. It is routine practice to perform a delayed whole-body examination as part of a focused three-phase bone scanning at our institution to provide additional information without increasing the radiation dose to the patient. Three-phase bone scanning is well known to be a sensitive but nonspecific examination in the differential diagnosis of benign or malignant lesions in patients with suspected bone tumors. The specific
0143-3636 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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DOI: 10.1097/MNM.0000000000000299
SPECT/CT with three-phase bone scan Zhang et al. 687
diagnosis of a bone tumor is based on the location, matrix change, and appearance of soft-tissue around the bone lesion, all of which can be obtained from diagnostic computed tomography (CT) scans. Hybrid single-photon emission computed tomography (SPECT)/spiral CT offers the opportunity to obtain diagnostic-quality CT and SPECT images, combining the diagnostic power of morphological changes with that of abnormal metabolism within lesions and improving the diagnostic accuracy of bone disease imaging [6–10].
∼ 1110 MBq (30 mCi) 99mTc-MDP. Scintigraphic images of the lesion of the suspected bone tumor were acquired in angiographic (128 × 128 matrix, 3 s/frame, 40 frames), soft-tissue (256 × 256 matrix, 500k count, one frame), and delayed planar whole-body scintigraphy (256 × 1024 matrix) phases as part of a focused three-phase bone scanning performed after 3–6 h. These images were analyzed immediately after acquisition by an experienced nuclear medicine physician who determined the field of view of SPECT/CT.
We aimed to investigate the benefit of SPECT/CT combined with three-phase bone scintigraphy over threephase bone scintigraphy alone in the differential diagnosis of suspected bone tumor in patients with no history of malignancy.
The SPECT raw data were reconstructed into transaxial, coronal, and sagittal slices using reconstruction software (Astonish; Philips, San Jose, California, USA). Immediately after SPECT, CT scans were performed with the patient in the same position. The CT scan parameters were as follows: 120 kV, 160 mA, 400 mm view, 5 mm scan, and 3 mm reconstruction. Both SPECT and CT were performed with the patients lying supine and breathing shallowly. For all fused images, the accuracy of the matching of internal anatomic landmarks visible on both CT and SPECT was checked. No misregistration exceeding 2 mm was found.
Materials and methods Patient selection
The study was retrospective, and patients were selected if they fulfilled the following criteria: (a) they had no history of extraskeletal malignancies; (b) they had no surgical history for the lesion; and (c) they had undergone histological verification of the lesion as part of their clinical management. A total of 48 patients (30 men and 18 women; mean age, 43.3 ± 20.1 years; age range, 11–82 years) with suspected bone tumors underwent 99mTc-MDP three-phase bone scintigraphy and SPECT/CT between July 2008 and August 2013. The locations of the bone lesions are listed in Table 1. The lesion from each patient was resected or biopsied for pathological confirmation of the diagnosis within 3 weeks from the bone scan. The study was approved by the institutional review board of Zhongshan Hospital affiliated with Fudan University, and all patients gave their written informed consent. Three-phase bone scintigraphy
Images were obtained using Philips Precedence with a 16-slice diagnostic CT scanner (Philips Medical Systems, Bothell, Wisconsin, USA). The camera heads were equipped with a low-energy, high-resolution, parallelhole collimator, with counts from the 20% energy windows at 140 keV. Three-phase bone scans of adult patients were obtained after intravenous injection of
Table 1
Location of bone lesions in 48 patients
Location of bone lesions Clavicle Scapula Humerus Radius Lumbar vertebra Sacrum Innominatum Femur Scutum Tibia
Number of patients 2 3 4 1 1 5 8 18 1 5
Image analyses
All images were interpreted by two experienced nuclear medicine physicians who had not been involved in the selection of data for the present study. The reviewers were aware of the patient’s sex, age, and the lesion’s site but were unaware of the results of other imaging modalities, such as radiography, MRI, and laboratory tests. To minimize recall bias, the reviewers read three-phase bone scintigraphy images first and interpreted SPECT/CT combined images with three-phase bone scintigraphy images 3 weeks later. Each lesion was scored as benign or malignant. In cases of discrepancy regarding the interpretations, a consensus was reached after mutual discussion. For analyzing the results of three-phase bone scanning alone, the reviewers were trained and tested to assess the images using the following reference standards: malignant bone tumors often manifested as increased blood supply, with the area of increased uptake in all flow, pool, and delayed phases; however, primary benign bone tumors were usually not associated with increased blood supply, with the area of increased uptake commonly found only in the delayed phase [11,12]; for SPECT/spiral CT fusion imaging analysis, if CT showed osteolytic changes (bone erosion, edge irregularity, no osteosclerosis, or a soft-tissue mass) or osteoblastic changes (high bone density without a soft-tissue mass) in areas of abnormal radioactivity uptake, a diagnosis of malignancy was made. The area of abnormal uptake was considered benign when the regions corresponded to benign findings on CT, such as osteomyelitis, bone cyst, or other primary benign bone tumors [13,14]. Characterization of the bone tumors was based on the
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location, calcification, and ossification of the tumor and on the patient’s age at the time of diagnosis [15].
Table 3 Comparison of pathology results and lesion grades from both reviewers after review of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy Pathology results
Statistical analysis
Compared with the pathological diagnosis, the diagnostic ability of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy was compared using the χ2-test, with P-values less than 0.05 indicating significant differences. SPSS 10.0 software (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. The agreement between the interpretations of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy with pathological results was evaluated using κ scores, ranging from − 1 (complete disagreement) to + 1 (perfect agreement). κ scores were classified as follows: 0, chance agreement; less than 0.20, poor agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement; 0.61–0.80, substantial agreement; 0.81–1.00, almost perfect agreement [16].
Results Pathological results from the 48 lesions of all patients revealed a final diagnosis of 32 malignant bone tumors and 16 benign lesions. The distribution of the pathological results in the 48 examined lesions is shown in Table 2. Among the malignant bone tumors, five metastasized from hepatocellular carcinoma (n = 2), squamous cell carcinoma of the lung (n = 1), seminoma (n = 1), and cancerous goiter (n = 1). The comparison of pathology results and lesion grades from both reviewers after review of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy is shown in Table 3. On using threephase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy for the differential diagnosis of bone lesions, we found sensitivities to be 96.9
Table 2
Distribution of the pathology results in the 48 examined
lesions Malignant (n = 32)
Pathological type Osteosarcoma
Benign (n = 16) Number of patients 13
Chondrosarcoma Adamantinoma
6 1
Malignant schwannoma Rhabdomyosarcoma
1 1
Inflammatory myofibroblastic sarcoma Lymphoma Plasmacytoma Synovial sarcoma Malignant epithelioid hemangioendothelioma Bone metastatic tumor
1 1 1 1 1 5
Pathological type Giant cell tumor of the bone Osteochondroma Aneurysmal bone cyst Cyst with infection Osteofibrous dysplasia Langerhans cell histiocytosis Myelolipoma Necrosis of the bone Osteoarthritis Granulomatous inflammation Osteomyelitis
Number of patients 5 2 1 1 1 1 1 1 1 1 1
Malignancy Three-phase bone scintigraphy Malignancy 31 Benign 1 SPECT/CT combined with three-phase bone scintigraphy Malignancy 32 Benign 0
Benign 11 5 3 13
SPECT/CT, single-photon emission computed tomography/computed tomography.
and 100%, specificities to be 31.2 and 81.3%, positive predictive values to be 73.8 and 91.4%, and negative predictive values to be 83.3 and 100%, respectively. The diagnostic accuracies of three-phase bone scintigraphy alone and SPECT/CT combined with three-phase bone scintigraphy were 75.0 and 93.8%, respectively (χ2 = 5.057; P = 0.025). κ scores for the agreement of the interpretations of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy with pathological results were 0.333 (P = 0.005) and 0.850 (P < 0.0001), respectively. As listed in Table 4, 12 lesions (Nos. 1–12) were misdiagnosed on the basis of three-phase bone scintigraphy images alone, and three lesions (Nos. 10–12) were misdiagnosed on the basis of SPECT/CT combined with three-phase bone scintigraphy images. There were no cases correctly diagnosed by three-phase bone scintigraphy but misdiagnosed according to SPECT/CT combined with three-phase bone scintigraphy images in our study. Of the 12 lesions misdiagnosed according to three-phase bone scintigraphy images alone, nine (Nos. 1–9) were diagnosed correctly on the basis of SPECT/CT combined with three-phase bone scintigraphy images. One case of knee osteoarthritis, one case (No. 1) of granulomatous inflammation of the femur (No. 2; Fig. 1), one case of osteomyelitis of the clavicle (No. 3), and one case of necrosis of the tibia (No. 4) were misdiagnosed as malignant lesions on the basis of three-phase bone scintigraphy images because of enhanced blood flow, softtissue hyperemia, and increased uptake in the delayed phase; however, they were correctly diagnosed as benign lesions on the basis of SPECT/CT combined with threephase bone scintigraphy. Because of enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase displayed in three-phase bone scintigraphy, four cases (Nos. 5–8; Fig. 2) of giant cell tumors were misdiagnosed as malignant lesions; however, SPECT/CT showed a clear boundary expansion of bone destruction, accompanied by abnormal uptake of radioactivity, and thus they were finally diagnosed as benign lesions. One case (No. 9; Fig. 3) of a lumbar vertebra metastatic tumor from seminoma was misdiagnosed as a
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Misdiagnoses based on three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy from both reviewers
Table 4
Case no.
Sex/Age (years)
Location of bone lesions
Three-phase bone scintigraphy
SPECT/CT combined with three-phase bone scintigraphy
1 2 3 4 5 6 7 8 9
M/21 M/38 F/55 F/58 F/46 F/22 M/33 M/56 M/37
Knee Femur Clavicle Tibia Tibia Tibia Tibia Femur Lumbar vertebra
Malignant Malignant Malignant Malignant Malignant Malignant Malignant Malignant Benign
Benign Benign Benign Benign Benign Benign Benign Benign Malignant
10 11 12
M/17 M/17 F/53
Innominatum Femur Sacrum
Malignant Malignant Malignant
Malignant Benign Malignant
Pathology results Osteoarthritis Granulomatous inflammation Osteomyelitis Necrosis of the bone Giant cell tumor of the bone Giant cell tumor of the bone Giant cell tumor of bone Giant cell tumor of the bone Bone metastatic tumor from seminoma Langerhans cell histiocytosis Osteofibrous dysplasia Giant cell tumor of the bone
SPECT/CT, single-photon emission computed tomography/computed tomography.
benign lesion on the basis of three-phase bone scintigraphy images because of no flow phase or pool phase uptake changes, and decreased uptake only in the delayed phase. However, SPECT/CT images revealed the lesion to show decreased radioactive uptake in the mild osteolytic bone destruction and in a surrounding soft-tissue mass, and thus the lesion was diagnosed as being malignant. Three cases were misdiagnosed on the basis of both three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy, and all lesions that were misdiagnosed as malignant were, in fact, benign. Among them, a case of Langerhans cell histiocytosis of the left innominatum (No. 10; Fig. 4) showed enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging and bone destruction with increased radioactivity on SPECT/CT imaging. Another case of right femur bone fibrous dysplasia (No. 11) showed enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging and mixed-density intramedullary violation of the cortical bone with increased radioactivity on SPECT/CT. Finally, another case of giant cell tumor of the sacrum (No. 12) showed enhanced blood flow, softtissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging and radioactivity concentration located in the peripheral part of a wide range of osteolytic bone destruction on SPECT/CT.
Discussion Bone scintigraphy using 99mTc-MDP is one of the most frequently performed radionuclide procedures. Its excellent sensitivity makes it useful in screening for generalized bone abnormalities, but it is not specific [17]. Hotspots in a whole-body bone scan can result from various common disorders, including bone metastases, osteoarthritis, trauma, inflammation, and other malignant or benign bone diseases [18,19]. Three-phase bone scintigraphy has received considerable attention predominantly in the investigation of patients
with bone-related diseases such as osteomyelitis, bone tumors, and sympathetic dystrophy, as blood supply and soft-tissue vascularity may be assessed in addition to any associated bone changes [20,21]. Three-phase bone scintigraphy can evaluate blood vessels and tissue perfusion in solid organs and soft tissues and detect bone abnormalities. Various bone lesions have hemodynamic characteristics. Three-phase bone scintigraphy images during the arterial, tissue perfusion, and blood pool phases also provide insight into the underlying physiologic and pathologic processes. There is considerable malignant bone tumor capillary proliferation and capillary network formation, which increase the blood supply and may be accompanied by the formation of a soft-tissue mass. Thus, three-phase bone scintigraphy plays an important role in the differential diagnosis of benign and malignant bone tumors. Hybrid SPECT/spiral CT offers the opportunity to obtain diagnostic-quality CT and SPECT images. SPECT/spiral CT has been used clinically, and many investigations have been published that have explored its diagnostic value [6 –10]. SPECT/spiral CT provides a clear view of the anatomic sites of any lesion with abnormal radioactivity concentrations. In addition, SPECT/spiral CT combines the diagnostic power of the morphological changes of the lesions. The specific diagnosis of benign and malignant bone tumors is based on the location, matrix appearance, and growth rate of a lesion, all of which can be obtained from diagnostic CT scans. On the basis of improved access to the lesion site of the blood supply and bone salt metabolic characteristics, combined with characteristic CT signs of benign and malignant bone tumors, we can state that the accuracy of the diagnosis of bone disease has effectively improved. In 32 cases of malignant lesions in the present study, 31 cases showed enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging. Only one case of a lumbar vertebra metastatic tumor from seminoma was misdiagnosed as a benign lesion because of no flow or pool
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Fig. 1
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A 38-year-old male patient with no history of malignancy who showed symptoms of right hip pain for 3 months. Three-phase bone scintigraphy images showed enhanced blood flow (a), soft-tissue hyperemia (b), and increased uptake in the delayed phase (c) of the right proximal femur (misdiagnosed as being malignant). SPECT/CT images (d) revealed low-density lesions with peripheral atherosclerosis and cortical bone fuzziness with increased radioactive uptake (correctly diagnosed as being benign). Pathological diagnosis of the lesion was granulomatous inflammation. SPECT/CT, singlephoton emission computed tomography/computed tomography.
phase uptake changes, and because of decreased uptake in the delayed phase on three-phase bone scintigraphy imaging. However, SPECT/CT images revealed that the lesion showed decreased radioactive uptake in the osteolytic bone destruction with a surrounding soft-tissue mass, and thus the lesion was diagnosed correctly as malignant. In that case, the misdiagnosis of three-phase bone scintigraphy may be due to the lack of blood supply to the metastatic seminoma itself, or because the metastatic bone lesions were in the pathological stages of osteolytic change and necrosis, leading to reduced blood flow and bone salt metabolism. In 16 cases of benign lesions, one case of a cyst with infection and two cases of
osteochondroma showed no flow phase or pool phase uptake changes, with increased uptake only in the delayed phase; one case of an aneurysmal bone cyst and one case of myelolipoma that showed no uptake changes in the three phases were diagnosed as benign lesions, and were then definitely diagnosed when three-phase bone scintigraphy was combined with SPECT/CT. One case of osteoarthritis, one case of bone granulomatous inflammation, one case of osteomyelitis, one case of bone necrosis, five cases of giant cell tumors, one case of Langerhans cell histiocytosis, and one case of osteofibrous dysplasia showed enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase on three-phase bone imaging and were
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Fig. 2
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A 33-year-old male patient with no history of malignancy who showed symptoms of left knee pain for 3 months. Three-phase bone scintigraphy images showed enhanced blood flow (a), soft-tissue hyperemia (b), and increased uptake (c) in the delayed phase of the left proximal tibia (misdiagnosed as being malignant). SPECT/CT images (d) revealed a lesion with increased radioactive uptake in well-defined expansion bone destruction with a nonsclerotic margin (correctly diagnosed as being benign). Pathological diagnosis of the lesion was a giant cell tumor of the bone. SPECT/CT, singlephoton emission computed tomography/computed tomography.
misdiagnosed as malignant lesions; however, three cases of inflammation, one case of necrosis, and four cases of giant cell tumors were further definitely diagnosed as benign lesions when three-phase bone scintigraphy was combined with SPECT/CT. Our study results showed that the diagnostic accuracy of three-phase bone scintigraphy alone was 75.0%, which improved to 93.8% when combined with SPECT/CT (χ2 = 5.057; P = 0.025). Thus, SPECT/CT combined with three-phase bone scintigraphy can effectively overcome the limitations of three-phase bone scintigraphy alone. In particular, for some inflammatory lesions with enhanced blood flow, soft-tissue hyperemia, and increased uptake in the delayed phase, SPECT/CT imaging is helpful
to obtain a definitive diagnosis. In addition to detecting extraskeletal lesions, three-phase bone scintigraphy helps to improve the specificity by allowing the vascularity of skeletal lesions and surrounding soft tissues to be visualized. Furthermore, SPECT/CT images can clearly show whether the surrounding soft-tissue tumors involve bone lesions. The diagnosis and differential diagnosis of suspected bone lesions based on blood flow and bone salt metabolism in nuclear medicine images and on morphological changes of CT images can raise diagnostic confidence remarkably. In addition, at our institution, it is routine practice to perform delayed whole-body examination as part of a focused three-
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Fig. 3 Flow
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A 37-year-old male patient with no history of malignancy who showed symptoms of low back pain for 1 month. Three-phase bone scintigraphy images showed no flow phase (a) or pool phase (b) uptake changes, and decreased uptake in the delayed phase (c) of the second lumbar vertebra (misdiagnosed as being benign). SPECT/CT imaging (d) revealed a lesion with decreased radioactive uptake in mild osteolytic bone destruction with a surrounding soft-tissue mass (correctly diagnosed as being malignant). Pathological diagnosis of the lesion was bone metastatic tumor from seminoma. SPECT/CT, single-photon emission computed tomography/computed tomography.
phase study to provide free additional information because no additional radiation dose is used to examine the rest of the body. Furthermore, the whole-body skeletal screen could show the existence of bone metastases in patients with malignant tumors, as well as other bone lesions. If the diagnosis of distant lesions remains unclear, it is feasible to perform an additional SPECT/CT scan. However, the present study revealed that not all suspected bone lesions could be definitively diagnosed by SPECT/CT combined with three-phase bone scintigraphy because there were still three misdiagnosed cases of iliac Langerhans cell histiocytosis, sacral giant cell
tumors, and femur bone fibrous dysplasia. Although these lesions showed a benign pathology, they have a rich blood supply at the lesion site and a malignant growth pattern, with CT showing various degrees of bone destruction. When morphological features of these lesions are not typical according to CT findings, these lesions can be easily misdiagnosed as malignant lesions, and their differential diagnosis remains difficult, which depends to a large extent on the experience of the reading physicians. The current study has a few limitations. First, the generalizability of the results is limited by the retrospective and very selective nature of the patient population; we
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Fig. 4
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A 17-year-old male patient with no history of malignancy who showed symptoms of left hip pain for 20 days. Three-phase bone scintigraphy images showed enhanced blood flow (a), soft-tissue hyperemia (b), and increased uptake in the delayed phase (c) of the left innominatum (misdiagnosed as being malignant). SPECT/CT images (d) revealed a lesion with increased radioactive uptake in osteolytic bone destruction with cortical discontinuity (misdiagnosed as being malignant). Pathological diagnosis of the lesion was Langerhans cell histiocytosis. SPECT/CT, single-photon emission computed tomography/computed tomography.
selected only cases with a pathological diagnosis for inclusion in the present study. Second, the number of cases in the study was relatively small.
Conclusion Compared with three-phase bone scintigraphy alone, the diagnostic accuracy of SPECT/CT combined with threephase bone scintigraphy was significantly higher. SPECT/CT combined with three-phase bone scintigraphy provides a benefit over three-phase bone scintigraphy for differential diagnosis of suspected bone tumors in patients with no malignant history.
Acknowledgements This study is in part supported by Advanced and Suitable Technology Promotion Projects of Health System of Shanghai (Grant No. 2013SY008). Conflicts of interest
There are no conflicts of interest.
References 1 2
Baqer MM, Loutfi I. Optimal imaging positions for 3-phase bone scanning of patients with bony pathology of the feet. J Nucl Med Technol 2010; 38:69–75. Wüppenhorst N, Maier C, Frettlöh J, Pennekamp W, Nicolas V. Sensitivity and specificity of 3-phase bone scintigraphy in the diagnosis of complex regional pain syndrome of the upper extremity. Clin J Pain 2010; 26:182–189.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
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3
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Sella EJ, Grosser DM. Imaging modalities of the diabetic foot. Clin Podiatr Med Surg 2003; 20:729–740. 4 Villani MF, Falappa P, Pizzoferro M, Toniolo RM, Lembo A, Chiapparelli S, Garganese MC. Role of three-phase bone scintigraphy in paediatric osteoid osteoma eligible for radiofrequency ablation. Nucl Med Commun 2013; 34:638–644. 5 Davenport MS, Brown RK, Frey KA. Utility of delayed whole-body bone scintigraphy after directed three-phase scintigraphy. Am J Roentgenol 2009; 193:338–342. 6 Zhao Z, Li L, Li F, Zhao L. Single photon emission computed tomography/spiral computed tomography fusion imaging for the diagnosis of bone metastasis in patients with known cancer. Skeletal Radiol 2010; 39:147–153. 7 Helyar V, Mohan HK, Barwick T, Livieratos L, Gnanasegaran G, Clarke SE, Fogelman I. The added value of multislice SPECT/CT in patients with equivocal bony metastasis from carcinoma of the prostate. Eur J Nucl Med Mol Imaging 2010; 37:706–713. 8 Zhang Y, Shi H, Gu Y, Xiu Y, Li B, Zhu W, et al. Differential diagnostic value of single-photon emission computed tomography/spiral computed tomography with Tc-99m-methylene diphosphonate in patients with spinal lesions. Nucl Med Commun 2011; 32:1194–1200. 9 Sharma P, Singh H, Kumar R, Bal C, Thulkar S, Seenu V, Malhotra A. Bone scintigraphy in breast cancer: added value of hybrid SPECT-CT and its impact on patient management. Nucl Med Commun 2012; 33:139–147. 10 Zhang Y, Shi H, Cheng D, Jiang L, Xiu Y, Li B, et al. Added value of SPECT/spiral CT versus SPECT in diagnosing solitary spinal lesions in patients with extraskeletal malignancies. Nucl Med Commun 2013; 34:451–458.
11 12 13 14
15 16
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Focacci C, Lattanzi R, Iadeluca ML, Campioni P. Nuclear medicine in primary bone tumors. Eur J Radiol 1998; 27: (Suppl 1):S123–S131. Yang DC, Ratani RS, Mittal PK, Chua RS, Pate SM. Radionuclide threephase whole-body bone imaging. Clin Nucl Med 2002; 27:419–426. Theodorou DJ, Theodorou SJ, Sartoris DJ. An imaging overview of primary tumors of the spine: part 1. Benign tumors. Clin Imaging 2008; 32:196–203. Theodorou DJ, Theodorou SJ, Sartoris DJ. An imaging overview of primary tumors of the spine: part 2. Malignant tumors. Clin Imaging 2008; 32:204–211. Erlemann R. Imaging and differential diagnosis of primary bone tumors and tumor-like lesions of the spine. Eur J Radiol 2006; 58:48–67. Utsunomiya D, Shiraishi S, Imuta M, Tomiguchi S, Kawanaka K, Morishita S, et al. Added value of SPECT/CT fusion in assessing suspected bone metastasis: comparison with scintigraphy alone and nonfused scintigraphy and CT. Radiology 2006; 238:264–271. Love C, Din AS, Tomas MB, Kalapparambath TP, Palestro CJ. Radionuclide bone imaging: an illustrative review. Radiographics 2003; 23:341–358. Rybak LD, Rosenthal DI. Radiological imaging for the diagnosis of bone metastases. Q J Nucl Med 2001; 45:53–64. Savelli G, Maffioli L, Maccauro M, De Deckere E, Bombardieri E. Bone scintigraphy and the added value of SPECT (single photon emission tomography) in detecting skeletal lesions. Q J Nucl Med 2001; 45:27–37. McLean RG, Murray IP. Three-phase skeletal scintigraphy for suspected bone tumors. Clin Nucl Med 1984; 9:378–382. Kozin F, Soin JS, Ryan LM, Carrera GF, Wortmann RL. Bone scintigraphy in the reflex sympathetic dystrophy syndrome. Radiology 1981; 138:437–443.
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