Article Text

Download PDFPDF

Hybrid SPECT/CT: the end of “unclear” medicine
  1. C N Patel,
  2. F U Chowdhury,
  3. A F Scarsbrook
  1. Department of Radiology, St James’s University Hospital, Leeds, UK
  1. Correspondence to Dr A F Scarsbrook, Department of Radiology, St James’s University Hospital, Beckett Street, Leeds LS9 7TF, UK; andrew.scarsbrook{at}leedsth.nhs.uk

Abstract

The emergence of hybrid imaging, combining anatomical computed tomography (CT) and functional scintigraphic imaging has increased the armoury of techniques available to image disease. Single photon emission computed tomography/CT (SPECT/CT) is a dual modality technique which increases the sensitivity and specificity of existing radionuclide imaging and helps characterise equivocal lesions detected by other imaging methods. In addition to the many established clinical applications for SPECT/CT, there are new clinical uses emerging in a spectrum of benign and malignant diseases. In this article, we will discuss the established and emerging uses of hybrid SPECT/CT and illustrate the incremental value of the technique in a variety of clinical applications.

  • SPECT/CT
  • hybrid imaging
  • computed tomography
  • single photon emission computed tomography

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Nuclear medicine (or radionuclide) studies have an important role in diagnostic imaging, providing functional information about disease processes. However, the inherent poor spatial resolution of radionuclide imaging and the absence of accurate anatomical correlation can often limit the usefulness of these techniques. Hybrid imaging, combining anatomical and functional information, has the potential to overcome these limitations and has helped to put an end to the old adage of “unclear medicine”. Positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT (SPECT/CT) are both dual modality techniques which co-register anatomical CT and functional PET or SPECT datasets in a single examination.

The integration of CT with the well established nuclear medicine techniques of PET and SPECT imaging has led to a resurgence of interest in these techniques over the last decade.1 The co-registered CT dataset allows more accurate attenuation correction of the emission data and accurate anatomical correlation. Certainly, PET/CT has had a major impact in oncology and has been incorporated into the imaging pathways of several cancers for accurate staging of disease, assessment of treatment response and detecting disease recurrence. While overshadowed by PET/CT, hybrid imaging with SPECT/CT has an equally useful role in the imaging of a range of benign and malignant diseases.2 As a result, the major manufacturers have produced a range of dual modality SPECT/CT machines in recent years making this technology accessible to most radiology or nuclear medicine departments.

This pictorial review will illustrate the clinical utility of SPECT/CT in a spectrum of benign and malignant diseases and highlight the specific incremental value of the technique. In addition, it will discuss the established clinical uses of SPECT/CT and emerging/novel applications including radionuclide therapy dosimetry.

Technique

SPECT imaging has been in clinical use for many decades within general nuclear medicine and nuclear cardiology to provide three dimensional imaging. With hybrid SPECT/CT imaging, the SPECT data are acquired by a dual headed gamma camera, followed by a separate CT acquisition. The sequential acquisition of SPECT and CT datasets provides inherent co-registration and overcomes many of the problems associated with previously attempted software based fusion methods.

The CT images are used for both anatomical localisation and generation of attenuation maps for correction of the SPECT data. Potential sources of error with this technique include misregistration between the SPECT and CT datasets due to cardiac or respiratory motion, table sagging or patient movement. This can lead to inaccurate attenuation correction and subsequent artefacts on the attenuation corrected SPECT images. Co-registration software and routine quality control methods are employed to ensure correct alignment of the datasets. Other sources of error include truncation artefact due to the smaller CT field of view and beam hardening artefact, both of which may result in inaccurate attenuation correction and erroneous activity on the attenuation corrected SPECT images. Newer generation SPECT/CT machines have been designed to reduce these sources of error and many incorporate multidetector CT technology (up to 64 slice) to acquire diagnostic quality CT images during the SPECT/CT acquisition.3

Incremental value of SPECT/CT

SPECT/CT combines the strengths of anatomical and functional imaging to increase the sensitivity and specificity of radionuclide imaging. This in turn improves confidence in interpretation which has a direct impact on patient management.4 Accurate localisation of sites of tracer activity can increase sensitivity by detecting additional lesions and specificity by excluding sites of physiological tracer uptake. SPECT/CT can also help characterise the functional significance of equivocal lesions detected on anatomical imaging studies such as CT or magnetic resonance imaging (MRI). The incremental value of SPECT/CT can be illustrated in a range of clinical scenarios.

Improved localisation

The hybridisation of SPECT and CT images addresses the inherent limitation of radionuclide imaging by providing an anatomical map. Areas of tracer uptake can be defined more accurately rather than correlating scintigraphic findings with separately acquired cross-sectional imaging, which can have potentially erroneous results. Accurate localisation frequently leads to improved patient management as a result of changes in treatment or surgical approach (figs 1 and 2).

Figure 1

Ectopic parathyroid adenoma. Multi-planar fused single photon emission CT/CT images from technetium 99m-sestamibi scintigraphy in a patient with primary hyperparathyroidism localises tracer activity seen on the maximum intensity projection (MIP) image (bottom right, arrow) to an ectopic parathyroid adenoma in the anterior mediastinum (crosshairs). This was confirmed at surgery.

Figure 2

Metastatic differentiated thyroid carcinoma. Anterior planar image (A) from a radioiodine (iodine-131) scan in a patient with previously treated differentiated thyroid carcinoma (DTC) and a rising thyroglobulin level demonstrates a focal area of tracer uptake in the right upper thorax suspicious for a metastasis (arrow). Multi-planar fused single photon emission CT/CT images (B) accurately localise uptake to a right superior mediastinal node (crosshairs). The nodal metastasis was confirmed following surgical resection.

Detection of additional lesions

Accurate localisation of tracer uptake also helps to define the significance of activity at sites distant from the primary tumour that may otherwise be missed on planar or cross-sectional imaging. The detection of additional lesions improves the sensitivity of imaging and, in oncology, the accuracy of disease staging (fig 3). The presence of metastatic disease often changes clinical management and helps guide optimal treatment.

Figure 3

Metastatic neuroendocrine tumour. Coronal image from a contrast enhanced CT (A) shows a large polypoid duodenal mass (arrow) which was confirmed to be a neuroendocrine carcinoma following endoscopic guided biopsy. Indium111-octreotide scintigraphy was performed for staging and the corresponding coronal fused single photon emission CT/CT image (B) demonstrates avid tracer uptake in the primary tumour (arrow) and a further focus in the liver (crosshairs), in keeping with an occult metastasis not visible on the diagnostic CT. Further sites of octreotide-avid metastatic disease were demonstrated (not shown) and the patient was referred for consideration of octreotide labelled radionuclide therapy.

Exclusion of physiological uptake

The exclusion of physiological tracer uptake improves specificity by reducing false positive sites of disease. This can be a particular problem for disease adjacent to organs which demonstrate normal physiological uptake—often liver, spleen, and kidneys (fig 4). Increased specificity improves diagnostic confidence and alters patient management by preventing erroneous upstaging of disease and/or preventing unnecessary treatment in this setting.

Figure 4

Physiological tracer uptake mimicking tumour recurrence. Coronal image (A) from indium111-octreotide scintigraphy in a patient with previously resected mid gut carcinoid carcinoma and elevated tumour markers demonstrates two foci of tracer uptake in the left upper quadrant (short arrow) and right lobe of liver (long arrow) suspicious for metastases. Corresponding axial fused single photon emission CT/CT images (B,C) localise uptake to a solitary liver metastasis in the left lobe (short arrow) and physiological uptake within the gallbladder (long arrow).

Characterisation of equivocal lesions

SPECT/CT is a useful problem solving tool that can be utilised selectively to assess the anatomical significance of equivocal areas of tracer uptake on radionuclide studies (fig 5) or define the functional significance of indeterminate abnormalities detected on cross-sectional imaging (fig 6). SPECT/CT is particularly useful for problem solving indeterminate bone lesions. Conventional bone scintigraphy with Tc99m-methylene diphosphonate (MDP) is sensitive but not specific and often correlation with plain films or cross-sectional imaging is required. SPECT/CT can help confidently characterise indeterminate lesions in patients with known malignancy (fig 7).5

Figure 5

Indeterminate uptake on bone scintigraphy. Anterior and posterior planar images (A) from Tc99m-MDP bone scintigraphy in a patient with previously treated thyroid cancer and new onset low back pain demonstrates focal tracer uptake in the lower lumber spine (arrow) which could represent degenerative changes or a solitary bone metastasis. Multi-planar single photon emission CT/CT images (B) localise the uptake to the L3 vertebral body with abnormal activity extending into the posterior elements (arrows) allowing a confident diagnosis of metastatic disease.

Figure 6

Indeterminate lesion detected on MRI. Axial T2 weighted MR image (A) in a patient with newly diagnosed prostate cancer undergoing staging shows a small indeterminate bony lesion in the left iliac bone adjacent to the sacroiliac joint (arrow) which was suspicious for a bone metastasis. The patient was referred for staging bone scintigraphy which showed no abnormal tracer activity. Axial fused single photon emission CT/CT image (B) following Tc99m-methylene diphosphonate (MDP) bone scintigraphy shows no focal tracer uptake at the site of the MR abnormality (crosshairs) and the corresponding axial low dose CT (bone window) image (C) confirms no bony destruction (crosshairs) providing additional confidence in the interpretation.

Figure 7

Accurate characterisation of an indeterminate lesion. Anterior planar image (A) from Tc99m-MDP bone scintigraphy in a patient with a past history of breast carcinoma and recent onset low back pain demonstrates an indeterminate focus of tracer activity in the right lower lumbar spine (arrow). Axial single photon emission CT/CT images (B) localise tracer activity to a prominent anterior osteophyte at the L5 vertebral body (crosshairs) thereby excluding the presence of a bone metastasis.

Clinical applications of hybrid SPECT/CT

A key factor in the emerging success of SPECT/CT is the application of the technique to radionuclide studies using established radiotracers. The incremental role of SPECT/CT has been established in an increasing number of clinical applications for a range of benign and malignant diseases, although oncology applications for SPECT/CT have been most numerous to date.

Clinical applications in benign disease

SPECT/CT increases the sensitivity and specificity of conventional radionuclide studies. One such application is the accurate preoperative localisation of parathyroid adenoma in patients with primary hyperparathyroidism with Tc99m-sestimbi scintigraphy and SPECT/CT to facilitate minimally invasive surgery. While SPECT imaging is more sensitive than planar scintigraphy in localising parathyroid adenoma, the addition of SPECT/CT has further incremental value in the localisation of ectopic and multiple adenomas and in patients with altered anatomy from prior neck surgery (fig 1).6 7

A number of other radionuclide studies benefit from more accurate localisation of tracer activity with SPECT/CT, including imaging of infection and inflammation with white cell scintigraphy using 99mTc hexamethylpropylene amine oxime (HMPAO) labelled leucocytes, thereby allowing accurate localisation of sites of occult infection or identifying active sites of inflammatory bowel disease (fig 8). The exclusion of false positive physiological sites of activity is equally important. Similarly, red cell scintigraphy can be used to localise accurately sites of occult gastrointestinal haemorrhage which may have evaded detection with cross-sectional imaging or endoscopy (fig 9). In addition, the postoperative appearances following hepatobiliary surgery may be complex, and accurate localisation of tracer activity using bile salt analogue IDA (imino-diacetic acid) scintigraphy can be helpful in demonstrating biliary leaks (fig 10).

Figure 8

Inflammatory bowel disease. Anterior planar image (A) from 99mTc hexamethylpropylene amine oxime (HMPAO) white cell scintigraphy in a patient who had previously undergone a small bowel resection for Crohn’s disease and presented with rising inflammatory markers demonstrates abnormal tracer uptake in the right iliac fossa (arrow). Axial single photon emission CT/CT images (B) accurately localise tracer uptake to the neo-terminal ileum as the site of active disease (arrow).

Figure 9

Gastrointestinal bleeding. Anterior planar image (A) from red cell scintigraphy in a patient previously treated with surgery and pelvic radiotherapy for ovarian carcinoma and presenting with transfusion dependent lower gastrointestinal bleeding. Colonoscopy was unremarkable. There is a linear area of abnormal tracer activity in the midline of the lower abdomen (arrow) and further activity on the right side of the abdomen extending across the midline in a colonic configuration (arrowheads), highly suggestive of active gastrointestinal haemorrhage. Axial fused single photon emission CT/CT images (B) localise tracer activity in the lower abdomen to a loop of distal small bowel (crosshairs). Axial image (C) from a contemporaneous contrast enhanced CT confirms abnormal thickening of this loop of small bowel (arrowheads) which was thought to represent radiation ileitis. The patient underwent surgical resection of the affected loop which cured her bleeding.

Figure 10

Postoperative biliary leak. Static images (A) obtained over 1 h from Tc99m-HIDA scintigraphy in a patient who had recently had resection of colorectal liver metastases and a clinical suspicion of postoperative biliary leak. The images demonstrate prompt tracer uptake in the liver and excretion into small bowel. There is pooling of tracer adjacent to the Roux loop at the cut edge of the liver (arrow) which is suspicious but not definite of a contained leak at this site. Axial fused single photon emission CT/CT images (B) localise this activity to a collection adjacent to the cut surface of the liver (crosshairs) in keeping with a postoperative biliary leak. Corresponding axial contrast enhanced CT images (C) following CT guided drainage confirms a collection adjacent to the liver surface (note drainage catheter in situ).

Clinical applications in nuclear cardiology

Myocardial perfusion scintigraphy with SPECT is a well established method of evaluating myocardial ischaemia and defining the functional significance of coronary artery disease. While controversial, the additional value of cardiac SPECT/CT is in the more accurate attenuation correction of the SPECT data which helps avoid common attenuation artefacts, particularly from breast and diaphragm, thereby increasing the specificity of the study.8 The combination of multidetector 64 slice CT with SPECT allows combined myocardial perfusion imaging and CT angiography to be performed in a single examination allowing structural and functional assessment of coronary artery disease.

Clinical applications in neurology

The use of 99mTc- HMPAO SPECT for brain imaging is predominantly used for the evaluation of patients with suspected dementia. Similarly to cardiac imaging, more accurate attenuation correction with SPECT/CT may help differentiate attenuation artefacts from true pathology. In addition, the CT component has been demonstrated to detect additional abnormalities in up to 25% of patients.9

Clinical applications in oncology

Hybrid imaging has established an important role in oncology, for diagnosis of primary tumours, staging of disease, monitoring response to therapy, and/or the detection of recurrent disease. While SPECT/CT has been largely overshadowed by the impact of PET/CT in oncology, both modalities have unique and often complementary clinical applications. Some tumours cannot be imaged adequately using fluorine18-fluorodeoxyglucouse (FDG) PET/CT, and until non-FDG tracers become more widely available, SPECT/CT using conventional radiotracers has a valuable role in the assessment of some patients with malignant disease.10

Endocrine tumours

The incremental value of SPECT/CT has been most widely evaluated for endocrine tumours which are often diagnosed, staged and followed-up with scintigraphy.11 Neuroendocrine tumours encompass a wide range of tumours including neuroendocrine carcinoma (previously known as carcinoid tumour), phaeochromocytoma, and paraganglioma. These tumour types can be imaged using somatostatin receptor scintigraphy (for example, indium111-octreotide) or meta-iodobenzylguanidine (mIBG) scintigraphy. The use of SPECT/CT increases sensitivity for the detection of additional sites of disease (fig 3) and specificity by excluding physiological sites of tracer activity (fig 4). In addition, the degree of tracer uptake allows the suitability for radionuclide therapy to be assessed.12 Similarly, the use of SPECT/CT with radioiodine scintigraphy (fig 2) can have a major impact on patient management which has been reported to alter management by up to 57% in some studies.13 14

Sentinel node lymphoscintigraphy

Accurate lymph node mapping is essential for the management of several cancers including melanoma, breast carcinoma, and head and neck cancers. SPECT/CT improves the accuracy of anatomical localisation of the sentinel node(s), especially if close to the injection site, and allows detection of nodal disease not seen on planar imaging.15 16

Evaluating indeterminate lesions on bone scintigraphy

Perhaps one of the most useful applications of SPECT/CT, especially with multidetector CT, is the evaluation of indeterminate lesions detected on bone scintigraphy in patients with known malignancy. Tc99m-MDP bone scintigraphy is highly sensitive but often non-specific, with up to 25% of patients with known malignancy requiring further imaging evaluation.17 SPECT/CT allows accurate localisation of tracer activity and evaluation of morphological changes on the CT component to allow confident diagnoses to be made in over 85% of indeterminate lesions found on bone scintigraphy.5 18 In addition, there are further non-oncological applications for SPECT/CT in bone imaging such as localising bone infections or joint inflammation and the imaging of suspected spondylosis and bone trauma.18

Future applications in oncology

The role of SPECT/CT has been evaluated in a number of malignancies including lung cancer, lymphoma, and the assessment of solitary pulmonary nodules, but FDG-PET/CT has now become established in the assessment of these cancers. An emerging use of SPECT/CT in prostate cancer involves radioimmunoscintigraphy using labelled monoclonal antibodies (indium111 capromab pendetide), which improves the detection of nodal involvement in patients at high risk of extra-prostatic disease. SPECT/CT may have a valuable role in the staging of disease, guiding therapy and monitoring response to treatment.19

SPECT/CT may also be of benefit in improving the accuracy of characterising brain lesions as cross-sectional imaging is often poor at differentiating tumour infiltration from surrounding oedema or tumour recurrence from post-therapy changes.20 Brain tumour imaging using radiotracers such as Tc99m-tetrofosmin may have a valuable future role, especially with the introduction of multidetector SPECT/CT machines providing diagnostic quality CT images.21 This may overcome some of the limitations of FDG-PET in the evaluation of brain lesions.

Main messages

  • Hybrid single photon emission computed tomography (SPECT)/CT imaging combines anatomical CT and functional scintigraphic imaging.

  • SPECT/CT can be utilised with established nuclear medicine techniques to increase the sensitivity and specificity of these studies.

  • There are many clinical applications for SPECT/CT in both benign and malignant disease.

  • New clinical applications are emerging with the development of novel radiopharmaceuticals and multidetector SPECT/CT.

  • SPECT/CT can have a role in accurate radionuclide therapy planning and post-treatment monitoring.

Current research questions

  • What are the optimal clinical applications of multidetector single photon emission computed tomography (SPECT)/CT?

  • Does multidetector SPECT/CT provide additional clinical benefit over and above standard SPECT/CT?

  • Is multidetector SPECT/CT cost effective?

SPECT/CT in radionuclide therapy

The aim of radionuclide therapy is to deliver a radiation dose to the target tissue and minimise damage to normal tissues. Accurate dosimetry is essential to minimise end organ toxicity and optimise therapy to individual patients. Hybrid SPECT/CT allows three dimensional quantification of radionuclide therapy dose with more accuracy than planar imaging.22 Both renal and bone marrow radiation exposure can be estimated as well as quantification of tumoral uptake, which allows more accurate dosimetry planning for subsequent therapies.

Key references

  • Schillaci O, Danieli R, Manni C, et al. Is SPECT/CT with a hybrid camera useful to improve scintigraphic imaging interpretation? Nucl Med Commun 2004;7:705–10.

  • Roach PJ, Schembri GP, Ho Shon IA, et al. SPECT/CT imaging using a spiral CT scanner for anatomical localization: Impact on diagnostic accuracy and reporter confidence in clinical practice. Nucl Med Commun 2006;27:977–87.

  • Chowdhury FU, Scarsbrook AF. The Role of Hybrid SPECT-CT in oncology: Current and emerging clinical applications. Clin Radiol 2008;63:241–51.

  • Patel CN, Chowdhury FU, Scarsbrook AF. Clinical utility of hybrid SPECT-CT in endocrine neoplasia. Am J Roentgenol 2008;190:815–24.

  • Horger M, Bares R. The role of single-photon emission computed tomography/computed tomography in benign and malignant bone disease. Semin Nucl Med 2006;36:286–94.

SPECT/CT can be useful in the pre- and post-therapy imaging of novel techniques such as selective internal radiation therapy (SIRT). One application of this is the use of yttrium90 microspheres for the treatment of non-resectable liver tumours.23 Macroaggregated albumin (MAA) particles are of comparable size to microspheres and can be used to predict the distribution of administered microsphere therapy. Following preoperative hepatic angiography and embolisation of collateral vessels to foregut structures, Tc99m labelled MAA is used to ensure the adequacy of embolisation and exclude any arteriovenous shunting which would result in radiation injury to upper abdominal structures and/or the lungs. SPECT/CT can be used for accurate pre-therapy assessment with MAA and post-therapy imaging to confirm tumoral uptake of yttrium90 microspheres (fig 11).

Figure 11

Selective internal radiation therapy (SIRT) for liver metastases. Axial contrast enhanced CT image (A) in a patient with inoperable metastatic liver disease demonstrates multiple liver metastases, the largest lesion in segment 6 (arrow). Corresponding axial single photon emission CT/CT images (B) following yttrium90 microsphere therapy demonstrates β-radiation (Bremsstrahlung) activity throughout the liver, with more intense activity at the site of the large metastasis in segment 6 (crosshairs).

Conclusion

Hybrid imaging with SPECT/CT has a wide variety of clinical applications in benign and malignant disease. The incremental value of SPECT/CT lies in the ability to localise sites of disease accurately, detect additional lesions, exclude physiological sites of tracer uptake, and define the functional significance of equivocal lesions. The resultant increase in sensitivity and specificity of radionuclide imaging improves diagnostic confidence and has a direct impact on patient management. Improving hardware technology and image processing together with the emergence of new clinical applications ensures a bright future for the technique.

Multiple choice questions (true/false; answers after the references)

  1. SPECT/CT combines functional imaging with SPECT using established radiotracers and anatomical imaging with CT.

  2. The CT dataset allows more accurate attenuation correction of the SPECT acquired transmission data.

  3. CT artefacts such as beam hardening and truncation artefact can lead to erroneous activity on the attenuation corrected SPECT images.

  4. The incremental value of SPECT/CT in nuclear cardiology and neurology is predominantly due to the accurate localisation of tracer activity rather than accurate attenuation correction.

  5. SPECT/CT is useful to evaluate indeterminate lesions on bone scintigraphy with Tc99m-MDP and allows confident diagnoses to be made in 85% of these indeterminate lesions.

Answers

  1. True—SPECT/CT imaging can be utilised with established radiotracers and nuclear medicine studies to increase the sensitivity and specificity of imaging. PET/CT imaging requires positron-emitting radiotracers such as 18fluorine-fluorodeoxyglucose (18F-FDG) which is produced in a cyclotron.

  2. False—The CT dataset allows more accurate correction of the emission data acquired with SPECT replacing the separate transmission source previously required to allow attenuation correction.

  3. True—CT artefacts can lead to inaccurate attenuation correction and erroneous activity on the attenuation corrected SPECT images but will not be present on the non-attenuation corrected images.

  4. False—The incremental value of SPECT/CT in nuclear cardiology and neurology is predominantly due to accurate attenuation correction which can help differentiate attenuation related artefacts from true pathology. The CT component may detect additional abnormalities.

  5. True—SPECT/CT allows accurate localisation of tracer activity detected in bone scintigraphy and correlation with morphological changes on the CT component.

REFERENCES

View Abstract

Footnotes

  • Competing interests None.

  • Provenance and Peer review Commissioned; externally peer reviewed.