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Value of SPET/CT Image Fusion in the Assessment of Neuroendocrine Tumours with 111In-Pentetreotide Scintigraphy
Valor de la fusión de imágenes de SPET/TAC en la evaluación de tumores neuroendocrinos con gammagrafia con 111In-Pentatreotido
A Paula Moreiraa, L. Hugo Duartea, F. Vieiraa, F. Joãoa, J. Pedroso de Limaa
a Serviço de Medicina Nuclear. Hospitais da Universidade de Coimbra. Portugal.
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          "en" => "--Patient with hepatic lesions and a primitive pancreatic NET &#40;marked&#41;&#46; A&#41; Low-dose CT images&#59; B&#41; SPET images&#59; C&#41; Fusion images&#46;"
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">Neuroendocrine tumours &#40;NET&#41; are rare neoplasms corresponding to a very heterogeneous group&#44; which differ in histology&#44; hormone production and clinical behaviour<span class="elsevierStyleSup">1</span>&#46; Nuclear Medicine plays an important role in the management of patients with NET&#46; The outcome of patients with NET is significantly affected by accurate tumour localization and precise determination of the extent of disease&#46; Management of these patients is primarily based on surgical removal of the primary lesion and single metastases&#44; as these slow growing tumours are only minimally responsive to systemic chemotherapy&#46; In cases of evidence of multifocal metastatic spread&#44; the differentiated tumour may benefit from treatment with therapeutic doses of cold or radiolabelled ligand<span class="elsevierStyleSup">2</span>&#46; Recent studies indicate that somatostatin receptor scintigraphy &#40;SRS&#41; is more sensitive than sonography&#44; CT&#44; MRI and angiography&#44; for identifying these tumours and their metastases<span class="elsevierStyleSup">3&#44;4</span>&#46; However&#44; the shortcomings of SRS in providing precise anatomical localisation of lesions often necessitate correlation with high-resolution anatomical imaging modalities<span class="elsevierStyleSup">1&#44;2</span>&#46;</p><p class="elsevierStylePara">SRS is a functional imaging modality based on preferential binding of <span class="elsevierStyleSup"> 111</span>In-pentetreotide to somatostatin receptors subtypes II and V<span class="elsevierStyleSup">4&#44;6</span>&#46; It has the potential to define the extent of metastatic disease&#44; to localize the primary occult tumour site&#44; and to identify the receptor status of metastases for potential octreotide treatment<span class="elsevierStyleSup">4&#44;6</span>&#46; However&#44; the detection of NET remains challenging&#44; due to their usually reduced dimensions and poorly defined anatomic localization&#46; Its specificity may also be affected by tracer uptake at physiological sites or benign conditions&#46; Because of these limitations&#44; SRS may benefit from co-registration with CT&#44; with acquisition of nuclear medicine and CT data during a single imaging session<span class="elsevierStyleSup">2-5</span>&#46; The implementation of these SPET&#47;CT imaging systems has the advantages of minimizing the errors described with co-registration of independently performed studies and optimizing anatomic localization of foci of increased single photon emitting tracer uptake&#44; in addition to a significant improvement in attenuation correction&#46;</p><p class="elsevierStylePara">The purpose of this study was to evaluate the contribution of hybrid SPET&#47;CT imaging to scintigraphic evaluation&#44; assessing as well fusion related changes and the clinical impact in patients with NET&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHODS</span></p><p class="elsevierStylePara">Twelve patients with proven or clinical suspicion of NET were referred for SRS between February 2003 and January 2004&#46; The patient population included 8 females and 4 males&#44; aged from 32 to 74 years &#40;mean 57 &#177; 13 years&#41;&#46;</p><p class="elsevierStylePara">Seven patients came for staging&#47;follow-up and five came for primary tumour localization with staging &#40;table I&#41;&#46;</p><p class="elsevierStylePara"><img src="125v24n01-13070352tab01.gif"></img></p><p class="elsevierStylePara">Scintigraphy was performed after i&#46;v&#46; administration of 111-222 MBq of <span class="elsevierStyleSup"> 111</span>In-Pentetreotide &#40;Octreoscan&#174;&#44; Mallinckrodt Medical&#41;&#46; Planar views and SPET&#47;CT were obtained using a dual head&#44; variable angle gamma camera equipped with a medium energy collimator and a low-dose X-ray CT transmission system&#44; mounted on the same slip-ring gantry &#40;Discovery VH&#44; with CoDe VC &#38; Hawkeye options&#44; GE Medical Systems&#41;&#46; The combined system that provides hybrid functional &#40;SRS&#41; and anatomic &#40;low-dose CT&#41; images allows for acquisition of both procedures in the same setting&#44; without changing the patient&#39;s positioning&#46; Planar views were recorded for 15 minutes or up to 500 Kcts from skull to mid-thigh at 2 h and 24 h after injection&#46; SPET&#47;CT of abdomen and&#47;or chest and&#47;or pelvis was performed at 24 h after injection&#46;</p><p class="elsevierStylePara">For the CT component of the study&#44; a cross-sectional anatomic transmission map was acquired as the system rotated around the patient&#44; with a rotation speed of 2&#44;6 r&#46;p&#46;m&#46;&#46; Each slice acquisition&#44; termed &#34;half-scan&#34; was performed over 240&#176;&#44; taking 16 sec&#46; acquisition time for each transaxial slice&#46; The x-ray tube is operated at 140 KVp&#44; 2&#44;5 mA&#46; Multiple slices were obtained by moving the table by a slice step &#40;10 mm&#41; before acquiring the next slice&#46; The full field-of-view&#44; consisting of 40 slices&#44; was completed in 10 minutes&#46; The transmission data were reconstructed using filtered back-projection to produce cross-sectional attenuation images in which each pixel represents the estimated attenuation of the imaged tissue&#46; Radiation exposure of the patient following a transmission scan&#44; calculated on the basis of phantom studies&#44; ranged from 1&#44;3-3&#44;5 mGy at the centre to 5 mGy at the surface &#40;CTDIw &#61; 3&#44;54 mGy&#41;&#46;</p><p class="elsevierStylePara">Following transmission&#44; the emission part of the study was acquired&#46; Acquisition parameters included a 360&#176; rotation&#44; 128 x  128 matrix&#44; 6&#176; angle step and acquisition time of 45 sec&#46; per frame for a total 33 min and 45 sec&#46; per study&#46; Reconstruction was performed using the ordered subsets expectation maximization &#40;OSEM&#41; technique &#40;2 iterations&#41;&#44; to avoid the artefacts seen with filtered back projection in areas adjacent to intense tracer activity&#46; The resultant emission images were inherently registered to the anatomical maps&#46; These matching pairs of X&#173;ray and nuclear medicine images were fused using the eNTEGRA workstation software &#40;General Electric Medical Systems&#41; and images of overlying transmission &#40;CT&#41; and emission &#40;SPET&#41; data were generated&#46; Data acquired during SPET&#47;CT were used for anatomic localization of the scintigraphic findings&#46;</p><p class="elsevierStylePara">SRS&#44; including planar and SPET study were interpreted independently of SPET&#47;CT images by a team of nuclear medicine physicians&#46; Subsequently&#44; data obtained from SPET&#47;CT images analysis were compared to the reports of SRS from the independent analyses&#46; SPET&#47;CT data were confirmed with pathological findings&#44; when available&#44; or with clinical and radiological follow-up&#44; during a 4 to 12 month period&#46; SPET&#47;CT was considered to improve image interpretation once it provided a better localization of sites of increased tracer uptake&#44; or when it excluded disease in sites of physiological or benign tracer uptake&#46; Any change or adjustment in the patient management&#44; whether diagnostic or therapeutic&#44; due to the additional information provided by SPET&#47;CT was recorded&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">Six patients had a negative SRS study&#44; and six had receptor-positive findings&#46;</p><p class="elsevierStylePara">Among the 6 patients with negative SRS&#44; no further evidence of disease was documented&#46; They included 1 patient with bronchopulmonary NET&#44; 1 patient with rectal NET &#40;excised&#41; and 2 patients with pancreatic NET&#44; who came for staging&#47;follow-up&#46; Two patients with suspected carcinoid came for primary tumour localization and staging&#46; SPET&#47;CT provided no added value to image interpretation and to clinical decision making in all 6 patients with negative SRS&#46;</p><p class="elsevierStylePara">Among the 6 patients with positive SRS&#44; disease was confirmed pathologically in 2 patients &#40;1 by surgery and 1 by bronchoalveolar lavage analysis&#41;&#44; radiologically in 5 patients &#40;CT or MRI&#41; and by clinical follow-up in one patient &#40;suspected for insulinoma&#41;&#46;</p><p class="elsevierStylePara">SPET&#47;CT improved the image interpretation in all 6 SRS positive patients &#40;100 &#37; of patients with abnormal SRS&#44; and 50 &#37; of the whole group&#41;&#46; Of these&#44; SPET&#47;CT contributed to a better anatomic localization in 3 patients&#44; referred for detection of primary tumour and 3 patients who came for staging&#47;follow-up&#46; SPET&#47;CT detected bronchopulmonary tracer uptake &#40;1 patient&#41; and precisely confined tracer uptake in pancreas &#40;2 patients&#41; of 3 patients referred for primary tumour detection&#46; SPET&#47;CT also identified unsuspected bone extension in 2 patients&#44; during follow-up&#46;</p><p class="elsevierStylePara">SPET&#47;CT results affected patient management in 3 patients&#44; 25 &#37; of the total population and 50 &#37; of the cases where SPET&#47;CT improved image interpretation&#46; It led to a surgical therapeutic approach with chemotherapy in one patient with hepatic lesions in whom was detected a primitive pancreatic NET &#40;fig&#46; 1&#41;&#46; In one patient&#44; referred for follow-up after surgery and chemotherapy&#44; SRS-SPET&#47;CT detected bone metastases&#44; which were no responsive to chemotherapy&#44; and was submitted to cold octreotide first in mensal administrations&#44; then weekly and finally in continued infusion due to worsening of the general condition &#40;fig&#46; 2&#41;&#46; This patient died at 4 months follow-up&#46; In another patient with hepatic lesions referred for primary tumour localization&#44; SPET&#47;CT detected a bronchopulmonary carcinoid &#40;confirmed by bronchoalveolar lavage analysis&#41;&#46; This patient was considered not suitable for surgery and was submitted to chemotherapy&#46;</p><p class="elsevierStylePara"><img src="125v24n01-13070352fig02.jpg"></img></p><p class="elsevierStylePara"> Fig&#46; 1&#46;--<span class="elsevierStyleItalic">Patient with hepatic lesions and a primitive pancreatic NET &#40;marked&#41;&#46; A&#41; Low-dose CT images&#59; B&#41; SPET images&#59; C&#41; Fusion images&#46;</span></p><p class="elsevierStylePara"><img src="125v24n01-13070352fig03.jpg"></img></p><p class="elsevierStylePara">Fig&#46; 2&#46;--<span class="elsevierStyleItalic">SRS-SPET&#47;CT detected new bone metastases&#44; in a patient who was no responsive to chemotherapy&#44; and was submitted to cold octreotide&#46; A lesion in the right femur is shown&#46; A&#41; Low-dose CT images&#59; B&#41; SPET images&#59; C&#41; Fusion images&#46;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">Somatostatin receptors are present on almost all neuroendocrine cells&#46; As a consequence&#44; <span class="elsevierStyleSup">111</span>In-Pentetreotide scintigraphy has shown a high sensitivity for the diagnosis of both primary and metastatic tumour lesions<span class="elsevierStyleSup">6&#44;7</span>&#46; Although peptide receptor scintigraphy may be useful as a tumour localizing technique in a variety of diseases where it may detect tumour localizations prior to or in addition to conventional imaging&#44; it will never be competitive with&#44; for instance&#44; CT or MRI in anatomic delineation of these disease sites<span class="elsevierStyleSup">8</span>&#46; The incidence of multiple organ involvement in patients with NET is high&#46; The knowledge of the precise extent of disease plays a major role in determining the appropriate treatment option and choice of treatment procedures such as chemotherapy&#44; cytoreductive surgery&#44; embolization&#44; or liver transplantation<span class="elsevierStyleSup">3</span>&#46; Diagnosis of bone metastasis is of prognostic significance&#44; indicating short survival and patients may also be spared unnecessary surgery&#46;</p><p class="elsevierStylePara">In the present study&#44; fusion of functional and anatomic images obtained sequentially on the same imaging device showed an additional value in the diagnostic capacities of SRS-SPET and CT&#46; SPET&#47;CT improved SRS image interpretation in 6 of the 12 study group patients &#40;50 &#37;&#41;&#44; not only due to a more accurate localization of tumour sites but also due to the x-ray based attenuation correction&#44; which results in improved image quality for SPET images&#46; Among these 12 patients&#44; 6 patients were referred for detection of primary tumour and staging and 6 patients were evaluated for extent of disease and for follow-up&#46; The primary tumour was detected in 3 patients &#40;2 pancreatic NET and 1 bronchopulmonary carcinoid&#41; and bone involvement in 3&#46; SRS-SPET&#47;CT guided the therapeutic approach in 3 cases &#40;25 &#37;&#41;&#46; The results of our study&#44; evaluating combined SPET&#47;CT in patients with NET are in agreement with the published data&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSION</span></p><p class="elsevierStylePara">The results of this study indicate that the introduction of dual-head gamma camera with an integrated x-ray transmission system &#40;low dose CT&#41; for attenuation correction&#44; anatomical mapping and image fusion&#44; improves image interpretation and provides correct anatomic localization of SRS findings in patients with NET&#46; Hybrid imaging is an accurate&#44; simply achieved method of registration of functional and anatomic data which enhances the already unique role of SRS in the assessment of these tumours&#46; It improves guidance of invasive diagnostic and therapeutic procedures and may help in monitoring therapeutic outcomes&#46;</p>"
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        "resumen" => "Summary&#46;--Objective&#58; The purpose of this study was to evaluate the impact and clinical value of anatomical-functional image fusion in the study interpretation and clinical management of patients with neuroendocrine tumours &#40;NET&#41; using somatostatin receptor scintigraphy &#40;SRS&#41; and combined transmission and emission tomography &#173; single-photon emission tomography&#47;CT &#40;SPET&#47;CT&#41; &#46; Material and methods&#58; Twelve patients &#40;8 female and 4 male&#59; age range 32-74 y&#44; mean 56 y&#41; with proven or clinically suspected NET were studied with routine planar SRS and SPET&#47;CT at 2 and 24 hours after injection of 111-222 MBq 111In-Pentetreotide&#46; Seven patients came for staging&#47;follow-up and 5 patients for primary tumour localization with staging&#46; Analysis of fused images &#40;SPET&#47;CT&#41; was done on a patient basis&#44; with separated evaluation of SPET&#44; low-dose CT images and fusion images&#46; The gold standard for presence or absence of malignancy was pathology or clinical and imaging follow-up data&#46; Results&#58; SRS was negative in 6 patients and positive in 6&#46; SPET&#47;CT provided no additional information in 6 patients&#44; including all 6 negative studies&#46; SPET&#47;CT improved localization of SPET detected lesions in 6 positive studies&#46; It defined the extent of the disease and showed bone involvement in 3 of the 6 positive studies&#46; SPET&#47;CT affected the diagnostic interpretation in 6 patients &#40;50 &#37;&#41; and induced changes of management in 3 &#40;25 &#37;&#41;&#46; Conclusion&#58; The results of this study indicate that combined anatomical-functional imaging with SPET&#47;CT significantly improves tumour localization and characterization&#44; contributing to a better therapeutic management of patients with NET&#46;"
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        "resumen" => "Resumen&#46;--El objetivo de este estudio fue la evaluaci&#243;n del impacto cl&#237;nico de la imagen de fusi&#243;n anatomo-funcional en la interpretaci&#243;n gammagr&#225;fica y el manejo cl&#237;nico de pacientes con tumores neuroendocrinos &#40;TNE&#41;&#44; utilizando gammagraf&#237;a de receptores de la somatostatina &#40;GRS&#41; y tomografia de emisi&#243;n-transmisi&#243;n &#40;SPET&#47;TAC&#41;&#46; Material y m&#233;todo&#58; 12 pacientes &#40;8 mujeres y 4 hombres&#59; edad 32-74 a&#241;os&#44; media 56 a&#241;os&#41; con TNE diagnosticado o cl&#237;nicamente sospechado&#44; fueron estudiados con GRS planar y SPET&#47;TAC a las 2 y 24 horas despu&#233;s de la inyecci&#243;n i&#46;v&#46; de 111-222 MBq de 111In-Pentatre&#243;tido&#46; Siete pacientes fueron valorados para estadificaci&#243;n&#47;seguimiento y 5 pacientes para localizaci&#243;n del tumor primario con estadificaci&#243;n&#46; El an&#225;lisis de las im&#225;genes de fusi&#243;n &#40;SPET&#47;TAC&#41; se realiz&#243; mediante la evaluaci&#243;n de las im&#225;genes de SPET&#44; im&#225;genes TAC de baja dosis e im&#225;genes de fusi&#243;n&#46; Como referencia para la presencia o ausencia de malignidad se utilizan los datos de la histopatolog&#237;a o la evoluci&#243;n cl&#237;nica&#46; Resultados&#58; La GRS fue negativa en 6 pacientes y patol&#243;gica en 6&#46; SPET&#47;TAC no aport&#243; informaci&#243;n adicional en los 6 pacientes GRS negativos&#46; SPET&#47;TAC facilit&#243; la localizaci&#243;n de las lesiones detectadas con SPET en los estudios patol&#243;gicos&#44; aport&#243; mayor informaci&#243;n sobre la extensi&#243;n de la enfermedad y mostr&#243; afectaci&#243;n &#243;sea en 3 de los 6 estudios positivos&#46; La SPET&#47;TAC modific&#243; la interpretaci&#243;n diagnostica en 6 pacientes &#40;50 &#37;&#41; y ha inducido cambios en la decisi&#243;n cl&#237;nica y terap&#233;utica en 3 &#40;25 &#37;&#41;&#46; Conclusi&#243;n&#58; Los resultados de este trabajo inicial indican que la combinaci&#243;n de las im&#225;genes anat&#243;mico-funcionales con SPET&#47;TAC mejoran substancialmente la localizaci&#243;n del tumor y su caracterizaci&#243;n&#44; contribuyendo a un mejor manejo cl&#237;nico en pacientes con TNE&#46;"
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