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Usefulness of SPECT/CT fusion in the verification of lesions detected in somatostatin receptor scintigraphy and in the evaluation of therapy efficiency in patients with gastroenteropancreatic neuroendocrine tumors

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Usefulness of SPECT/CT fusion in the verification of lesions detected in somatostatin receptor scintigraphy and in the evaluation of therapy efficiency in patients with gastroenteropancreatic neuroendocrine tumors

Robert Chrzan

1

, Anna Sowa-Staszczak

2

, Monika Tomaszuk

2

, Andrzej Urbanik

1

, Monika Buziak-Bereza

2

, Wioletta Lenda-Tracz

2

, Bogusław Głowa

2

, Alicja Hubalewska-Dydejczyk

2

1

Radiology Department, Jagiellonian University, Collegium Medicum, Cracow, Poland

2

Laboratory of Nuclear Medicine, Department and Clinic of Endocrinology, Jagiellonian University, Collegium Medicum, Cracow, Poland

Author’s address: Robert Chrzan, Radiology Department, Jagiellonian University, Collegium Medicum, Kopernika 19 Str., 31-501 Cracow, Poland, e-mail: rchrzan@mp.pl

Summary

Background:

Somatostatin receptor scintigraphy (SRS) is one of the most important studies in the diagnostics of patients with gastroenteropancreatic neuroendocrine tumors (GEP NET), but Single Photon Emission Computed Tomography (SPECT) study does not provide sufficient information about location of lesions. Computed Tomography (CT) combined with SPECT may solve this problem by adding morphological information to functional data.

The aim of the study was to determine the usefulness of SPECT/CT fusion on GEP NET diagnostics and therapy.

Material/Methods:

77 patients with GEP NET were analyzed using SPECT/CT software fusion: • in 12 patients the anatomical location of primary tumor was assessed; • in 14 patients clinically suspicious for NET, the presence of lesions was verified in CT, causing an increased accumulation of tracer found in SRS; • in 41 patients with proved NET, an increased local accumulation of the tracer, seen in SRS, was verified;• in 10 patients, the response to somatostatin analogue therapy was verified.

SPECT was performed 3–4 h after injection of 740MBq 99mTc-EDDA/HYNIC-octreotate.

CT was performed using multidetector CT scanner and standard protocols. SPECT/CT fusion was performed on SyngoMI (Siemens) workstation.

Results:

In the first subgroup of 12 patients, the primary tumor was localized in 11 cases (91.7%); • in the second subgroup of 14 patients, NET was confirmed in CT in 10 cases (71.4%), and not confirmed (a false positive scintigraphy) in 4 cases (28.6%), affecting therapy; • in the third subgroup of 41 patients, pathological accumulation of the tracer was confirmed in 10 cases (24.4%), in 23 (56.1%) the local accumulation of tracer was evaluated in fusion as the false positive scintigraphy (retention of tracer in intestines), and in 8 (19,5%) was verified as accumulation in normal adrenal glands; • in the fourth subgroup of 10 patients in all cases SPECT/CT fusion confirmed response to therapy, with SRS and CT compliance.

Conclusions:

SPECT/CT fusion, by combining assessment of morphological and functional imaging, may be a useful tool both in the initial diagnostics of GEP NET improving specificity of lesions detected by SRS alone and in the monitoring of therapy effects.

Key words: SPECT • CT • fusion • GEP NET

PDF fi le: http://www.polradiol.com/fulltxt.php?ICID=900370

Received: 2009.07.17

Accepted: 2009.11.04

O R I G I N A L A R T I C L E

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phase of neoplastic dissemination.

Imaging diagnostics of GEP NET involves both struc- tural imaging (US, CT, MRI), as well as functional imaging (SPECT, PET).

Treatment may be multidirectional and may involve: sur- gery, biotherapy with ‘cold’ long-acting analogues of soma- tostatin or alpha interferon, as well as chemotherapy, and, first of all, radioisotope therapy with labelled somatosta- tin analogues. The somatostatin receptor scintigraphy (SRS) is one of the most important studies in the diagnos- tics of patients with gastroenteropancreatic neuroendo- crine tumors (GEP NET). However, in many cases, even the Single Photon Emission Tomography (SPECT) study does not provide us with sufficient information about the loca- tion of the examined lesion. Computed Tomography (CT) combined with SPECT may solve this problem by adding morphological information to functional data.

The fusion of images obtained with SPECT and CT may be performed with the use of a highly specialized software, i.e.

software fusion [3–5]. However, even if the time interval between the two examinations in not long, a precise superim- position of both images requires application of an advanced mathematical apparatus in the program, and experience of the attendant, especially when the examination concerns other body structures than the brain. Different positioning of the patient and involuntary movements of internal organs require application of complex data processing models.

An alternative for the software fusion is the hardware fusion, which is a combination of two imaging meth- ods with the use of one hybrid scanner [6,7]. In this case, it is possible to obtain different images simultaneously or sequentially, without transferring the patient. Such a solu- tion was presented as early as at the beginning of 1990’s (Hasegawa from the University in San Francisco). It was supposed to be a tandem of a CT scanner and a gamma camera, i.e. the first SPECT/CT system. Nowadays, 90%

of the SPECT/CT systems installed all over the world are based on this primary solution.

Despite many disadvantages connected with the technical aspect of the software fusion (differences in patient’s posi- tion, involuntary movements of the internal organs), this method is becoming more frequent in clinical practice in the centers that are not in possession of hybrid systems.

The aim of the work was to assess the usefulness of the SPECT/CT software fusion in the diagnostics and evalua- tion of the treatment efficiency in patients with GEP NET.

Hospital in Cracow, with the use of a two-headed gamma camera E.CAM by Siemens, 3–4 hours after the injection of 740 MBq 99mTc-EDDA/HYNIC-octreotate.

CT was carried out in the I CT Laboratory of the Imaging Diagnostics Department of the University Hospital in Cracow, with the use of a spiral, multi-row CT scanner Somatom Sensation 16 (Siemens) and a standard protocol for abdomen and pelvis examination (configuration of the detectors 16×0.75 mm, slice thickness and increment of 2 mm, reconstruction kernel B31f, phases before and after i.v. contrast enhancement with the use of non-ionic con- trast medium in the dose of 1ml/kg, with the flow of 2.5 ml/s, arterial phase after 30 seconds and portocaval phase after 60 seconds from the onset of contrast administration).

SPECT/CT fusion was performed on SyngoMI (Siemens) workstation by a medical physicist, according to the instructions of a physician radiologist and a nuclear medi- cine physician, until the agreement on the right position.

After the initial automatic adjustment, the attendants performed manual corrections: reciprocal movements of the images in three dimensions and their rotations. This allowed for a better adjustment of the images in case of any shifts within the structures visualized in different exami- nations, resulting from different positions and respiratory movements. The reference points for the manual correction included kidney outlines (well visible in both examinations and subject to relatively insignificant changes of position).

Movements and rotations of the series of images were per- formed until the kidney outlines in SPECT and in CT exam- ination were precisely superimposed (Figure 1).

We analyzed the results of the software fusion of SPECT and CT images (Figures 1–4) in order to:

• define the anatomical location of the primary tumor in 12 patients,

• verify with CT the presence of lesions causing an increased accumulation of tracer found in SRS in 14 patients clinically suspicious for NET,

• verify an increased local accumulation of the tracer in SRS in 41 patients with a diagnosed NET,

• verify the response to somatostatin analogue therapy in 10 patients.

Results

• in the first subgroup of 12 patients, the tumor was local- ized (Figures 1, 2) and verified histopathologically in 11 cases (91.7%) – 8 cases of NETWD type (neuroendocrine tumor – well differentiated) and 3 cases of NECLM type

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(neuroendocrine carcinoma low malignancy / well differ- entiated endocrine carcinoma),

• in the second subgroup, NET was confirmed with CT in 14 cases and verified histopathologically in 10 cases (71.4%) as a tumor of NETWD type. There was no veri- fication (false positive scintigraphy – not confirmed by CT) in 4 cases (28.6%) (Figure 3) – the fusion influenced further treatment.,

• in the third subgroup of 41 patients, only 10 cases of tracer accumulation were defined as pathological, for further verification (24.4%) – mostly in pancreas and left adrenal gland. In 23 cases (56.1%), the local accumulation of the isotope was defined as unspecific (retention) accu- mulation in the intestines, and in 8 cases we revealed tracer accumulation in normal adrenal glands (19.5%),

• in the fourth subgroup of 10 patients, the SPECT/CT con- firmed the accordance of treatment response with the SRS (intensity of tracer accumulation process) and CT (changes in the lesions’ size according to RECIST) results in all 10 cases (Figure 4).

Discussion

In patients with gastroenteropancreatic neuroendocrine tumors (GEP NET), the somatostatin receptor scintigra- phy (SRS) reveals a significantly higher specificity in lesion detection than the CT [8]. The CT examination is neces- sary for the evaluation of therapy efficiency (according to RECIST) and verification of the anatomical location of the lesions found in SRS, which is particularly important

in the elimination of false positive results connected with unspecific tracer accumulation within the GI track.

So far, a standard procedure involved independent evalua- tions of SPECT and CT results. However, this is the SPECT/

CT fusion that allows for a simultaneous and joint, func- tional and morphological evaluation enabling the inter- pretation of scintigraphic results by the radiologist and of radiological images by the nuclear medicine physician.

Castaldi [9] concluded that SPECT/CT fusion reveals higher diagnostic accuracy than the SPECT alone and thus it is possi- ble to locate the lesions precisely and to reduce the number of false positive results. In 54 patients involved in his study, the fusion affected the interpretation of SPECT results in 23 (43%) cases because it could locate the tumor or exclude its pres- ence. In 14 cases (26%) this method led to changes within the treatment process, including the type of therapy in 6 cases (11%). Pfannenberg [10] showed that the specificity of SPECT/

CT fusion in neuroendocrine tumor location is significantly higher as compared to CT alone and slightly higher in com- parison to SPECT alone. The application of the fusion meth- od influenced the change of therapy in 14 cases (28%) out of 50: the tumor was excluded in 5 cases, the attending physi- cians resigned from surgery in 3 cases after localizing the foci of dissemination, in 4 patients it was decided to change the access route due to a precise tumor localization, and in 2 cases the physicians resigned from the radioisotopic therapy.

Similarly, Krausz [11] confirmed the influence of SPECT/CT fusion on interpretation of the scintigraphic results in 32%

Figure 1. Borders of kidneys correctly superimposed in fusion, additionally NET of pancreas head visible: (A) CT, (B) SPECT, (C) SPECT/CT fusion.

A B C

Figure 2. Two NET lesions of pancreas tail visible in SPECT and CT: (A) CT, (B) SPECT, (C) SPECT/CT fusion.

A B C

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of the studied patients and on changes in patient manage- ment in 14% of cases with neuroendocrine tumors.

Ingi [12] recommends a routine use of SPECT/CT fusion, due to its significant influence on the changes of the thera- peutical management – fusion application in his material led to changes of diagnosis in 4 patients out of 11 (36%).

Amthauer [13], localizing NET, compared the diagnostic accuracy of: independent SPECT and CT evaluations, soft- ware fusion, and of hardware fusion in the hybrid SPECT/

CT scanner and with the use of a low-dosage CT protocol.

The accuracy of the software fusion (88%) and the hard- ware fusion (76%) was significantly higher than the one of independent evaluations (60%). The shift in location of the structures found in SPECT and CT followed from differenc- es in patient’s position and from respiratory movements.

This may lead to difficulties in obtaining technically satis- factory fusion images [14]. Attempts at solving this problem

involve modifications of registration method and of auto- matic image adjustment [15,16], including application of external markers visible in both techniques [17].

However, some authors believe that only the use of the hybrid SPECT/CT scanner produces fusion images of high quality [18].

Advantages of SPECT/CT fusion will make it a method available in highly specialized clinical centers in Poland as well [8,16,18,19].

Conclusions

SPECT/CT fusion, by combining the assessment of morpho- logical and functional imaging, may be a useful tool both in the initial diagnostics of GEP NET, improving specificity of evaluations of lesions detected by SRS, and in the monitor- ing of the therapeutical outcomes.

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gastroenteropancreatic neuroendocrine pathology. Arch Pathol Lab Med, 2008; 132: 1285–89

3. Izrael O, Keidar Z, Iosilevsky G et al: The fusion of anatomic and physiologic imaging in the management of patients with cancer. Sem Nucl Med, 2001; 31: 191–205

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7. Townsend DW: Dual-modality imaging: combining anatomy and function. J Nucl Med, 2008; 49: 938–55

Figure 3. Focus of tracer accumulation visible in SPECT in midgastrium in the median plane, corresponding to intestine retention in CT: (A) CT, (B) SPECT, (C) SPECT/CT fusion.

A B C

Figure 4. Numerous NET metastatic foci in liver visible in SPECT and CT: (A) CT, (B) SPECT, (C) SPECT/CT fusion.

A B C

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8. Ćwikła JB, Nasierowska-Guttmejer A, Jeziorski KG et al: Diagnostic imaging approach to gastro-entero-pancreatic carcinomas of neuroendocrine origin – single NET center experience in Poland.

Neuro Endocrinol Lett, 2007; 28: 789–800

9. Castaldi P, Rufini V, Treglia G et al: Impact of 111In-DTPA-octreotide SPECT/CT fusion images in the management of neuroendocrine tumours. Radiol Med, 2008; 113: 1056–67

10. Pfannenberg AC, Eschmann SM, Horger M et al: Benefit of anatomical-functional image fusion in the diagnostic work-up of neuroendocrine neoplasms. Eur J Nucl Med Mol Imaging, 2003; 30:

835–43

11. Krausz Y, Keidar Z, Kogan I et al: SPECT/CT hybrid imaging with 111In-pentetreotide in assessment of neuroendocrine tumours. Clin Endocrinol (Oxf), 2003; 59: 565–73

12. Ingui CJ, Shah NP, Oates ME: Endocrine neoplasm scintigraphy:

added value of fusing SPECT/CT images compared with traditional side-by-side analysis. Clin Nucl Med, 2006; 31: 665–72

13. Amthauer H, Denecke T, Rohlfing T et al: Value of image fusion using single photon emission computed tomography with integrated low dose computed tomography in comparison with a retrospective voxel-based method in neuroendocrine tumours. Eur Radiol, 2005;

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14. Lemke AJ, Niehues SM, Amthauer H et al: Clinical use of digital retrospective image fusion of CT, MRI, FDG-PET and SPECT – fields of indications and results. Rofo, 2004; 176: 1811–18

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17. Gabriel M, Hausler F, Bale R et al: Image fusion analysis of (99m) Tc-HYNIC-Tyr(3)-octreotide SPECT and diagnostic CT using an immobilisation device with external markers in patients with endocrine tumours. Eur J Nucl Med Mol Imaging, 2005; 32: 1440–51 18. Kunikowska J, Królicki L, Pacho R et al: Fusion of scintigraphic

images and CT in diagnosis of neuroendocrine tumors. Pol Przegl Radiol, 2007; 72(Suppl.1): 77–78

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