DOI:10.2214/AJR.08.1218
AJR 2008; 191:1785-1794
© American Roentgen Ray Society
Incremental Value of Diagnostic 131I SPECT/CT Fusion Imaging in the Evaluation of Differentiated Thyroid Carcinoma
Ka Kit Wong1,
Natalia Zarzhevsky1,
John M. Cahill1,
Kirk A. Frey1 and
Anca M. Avram1
1 All authors: Division of Nuclear Medicine, Department of Radiology, University
of Michigan Medical Center, B1G505G University Hospital, 1500 E Medical Center
Dr., Ann Arbor, MI 48109-0028.
Received May 12, 2008;
accepted after revision June 30, 2008.
Presented at the 2007 annual meeting of the European Association of Nuclear
Medicine, Copenhagen, Denmark. 8109-0028.
Address correspondence to A. M. Avram
(ancaa{at}med.umich.edu).
Abstract
OBJECTIVE. The purpose of this study was to determine the
incremental value of 131I SPECT/CT over traditional planar imaging
of patients with differentiated thyroid carcinoma.
MATERIALS AND METHODS. Fifty-six planar and SPECT/CT scans were
obtained for 53 patients. Forty-eight scans were diagnostic 131I
studies before first radioiodine therapy, four were diagnostic 131I
studies with recombinant human thyroid-stimulating hormone stimulation, and
four scans were posttherapy 131I studies. Two nuclear physicians
interpreted central neck and distant activity on planar scans and reviewed
SPECT/CT images to assess the incremental diagnostic value with respect to
localization and characterization of focal activity and to evaluate reader
confidence. One of the readers was unblinded and had access to clinical,
imaging, histologic, and biochemical information.
RESULTS. Planar scans depicted 130 neck foci and 17 distant foci. At
SPECT/CT these foci were further characterized as thyroglossal duct and
thyroid bed remnant (n = 98), cervical nodal metastasis or local
residual disease (n = 26), physiologic activity (n = 11),
and distant metastasis (n = 12). Interobserver disagreement occurred
on eight of 147 foci (5%). Because of superior lesion localization and
additional anatomic information derived from the low-dose CT component,
incremental diagnostic value with SPECT/CT over planar imaging was found for
70 of 147 foci (47.6%), including 53 of 130 neck foci (40.8%) and all 17
(100%) distant foci. Reader confidence increased regarding 104 of 147 foci
(70.7%).
CONCLUSION. Iodine-131 SPECT/CT is useful for accurate evaluation of
regional and distant activity in characterization of foci as residual thyroid
tissue or nodal, pulmonary, or osseous metastasis. Suspected physiologic
mimics of disease can be confirmed with increased reader confidence.
Keywords: differentiated thyroid carcinoma • radioiodine therapy • SPECT/CT
Introduction
Differentiated thyroid carcinoma (DTC) is the most common endocrine cancer
among adults (1% of cancer diagnoses per annum)
[1]. The increasing incidence
in the last three decades has been partially attributed to earlier detection
of small papillary thyroid tumors
[1]. The prognosis for DTC is
favorable. Patients defined as being at low risk have a cancer-specific
mortality of less than 1% 20 years after tumor diagnosis, but this value
increases to 25–45% among patients at high risk (stages III and IV)
[2]. Long-standing controversy
continues regarding the use of radioiodine therapy in the treatment of
patients at low risk. There is no statistical evidence, to our knowledge, that
such therapy decreases the risk of recurrence or improves long-term survival
[3–5].
Some authors [6] see no role
for radioiodine administration to patients at low risk. Others
[7–9]
advocate radioiodine prescription after total thyroidectomy to ablate residual
thyroid tissue and improve surveillance with whole-body iodine scans or
stimulated thyroglobulin measurements. There is agreement, however, that
accurate staging of DTC is needed to rationalize treatment decisions.
We routinely perform diagnostic 131I studies to complete
postoperative staging of disease and to guide selection of radioiodine
therapy. Physicians at many centers omit the diagnostic 131I study
and proceed directly to fixed-dose radioiodine therapy, typically at a dose of
3.7–5.5 GBq (100–150 mCi). Inherent in this protocol, however, is
the inability to complete staging until after the patient has received the
therapeutic dose of radioiodine. Since the first description, in 2001, of the
usefulness of hybrid SPECT/CT technology for the investigation of a mixed
group of endocrine neoplasms
[10], several studies
[11–13]
have shown incremental diagnostic value of 131I SPECT/CT in
posttherapy scanning. Our interest was to ascertain whether hybrid SPECT/CT
technology, compared with planar imaging, would facilitate characterization of
residual thyroid tissue, enabling informed decisions on treatment. The aim of
this study was to investigate the value of 131I SPECT/CT fusion
imaging in the evaluation of central neck and distant foci of radionuclide
activity in a group of images predominately composed of diagnostic
131I scans.
Materials and Methods
Clinical Protocol
At our institution, all patients who undergo total thyroidectomy routinely
undergo diagnostic 131I scanning 5–6 weeks after the
operation to complete staging before the first dose of radioiodine therapy is
administered. Based on staging information incorporating clinical,
histopathologic, and imaging data and whole-body dosimetric calculations, the
131I therapy dose is adjusted according to the patient's risk
classi fication. Our protocol typically involves administration of a low-dose
radioiodine (1.1 GBq [30 mCi]) for thyroid remnant ablation, medium dose
(3.7–5.5 GBq [100–150 mCi]) for regional nodal disease, and high
dose (7.4–11.1 GBq [200–300 mCi]) for distant metastasis.
Whole-body and static neck and chest images with additional neck pinhole
images as required are obtained 24 and 48 hours after administration of a
diagnostic 37-MBq (1 mCi) 131I dose under thyroid hormone
withdrawal (hypothyroid 131I scan protocol) or a 150-MBq (4 mCi)
dose with recombinant human thyroid-stimulating hormone (thyrotropin alfa,
Thyrogen, Genzyme) stimulation. In a selected patient group, SPECT/CT images
are acquired 48 hours after 131I administration for further
evaluation of activity foci seen on planar images. We have found that SPECT/CT
provides useful information for the following indications: characterization of
equivocal central neck activity, identification of regional lymph node
metastasis, anatomic localization of distant metastatic foci, evaluation of
suspected physiologic mimics of disease, and assessment of discrepancies
between 131I planar imaging and histopathologic or biochemical
data. Forty-eight hours after administration of a therapeutic 131I
dose, a posttherapy scan is obtained to assess for additional foci of activity
compared with the diagnostic scan.
Patient Selection Criteria
Fifty-six studies of 53 patients (41 women, 12 men; mean age, 47.3 years;
range, 17–83 years) with DTC referred to the clinic between February
2005 and March 2007 who underwent 131I planar imaging and SPECT/CT
were included in this retrospective study. This group included 48 diagnostic
131I studies before first radioiodine therapy, four diagnostic
131I studies with recombinant human thyroid-stimulating hormone
stimulation, and four posttherapy 131I studies. The histologic
types were papillary thyroid carcinoma (n = 48), follicular carcinoma
(n = 3), and Hürthle cell carcinoma (n = 2). One
patient was excluded from the study because SPECT/CT data were not retrievable
from the archive. This patient had regional lymph node metastasis confirmed at
SPECT/CT. All patients with diagnostic 131I studies also underwent
posttherapy planar imaging. However, posttherapy SPECT/CT was not performed in
most cases because additional foci were rarely identified. Two patients
underwent both diagnostic and posttherapy SPECT/CT, and two patients underwent
only posttherapy SPECT/CT for evaluation of differences between radioiodine
distribution on the diagnostic and posttherapy planar images.
Equipment Characteristics
Iodine-131 whole-body planar and static neck and chest images were acquired
in the anterior and posterior projections with a dual-head gamma camera (ECAM,
Siemens Medical Solutions) with parallel-hole high-energy collimators and a
20% energy window set at 364 keV ± 15%. The table speed for the
whole-body images was 9 cm/s. The static image acquisition time was 10 minutes
to 500 K counts (matrix size, 256 x 256). The field of view for static
planar images was 59.1 x 44.5 cm.
SPECT/CT images were obtained with a dualhead hybrid gamma camera with
inline CT capability (Symbia T6, Siemens Medical Solutions). SPECT images were
accquired with 64 steps (20 s/stop), noncircular orbit over 360°, and a
128 x 128 matrix. Standard reconstruction technique entailed 3D ordered
subset expectation maximization iterative reconstruction with eight iterations
and four subsets and a CT-based attenuation-corrected algorithm applied to the
SPECT images. Filtered back-projection was used in a small number of
reconstructions. Low-dose CT parameters consisted of 130 kV and 100 mAs.
Reconstruction was performed at 5-mm slice thickness on a 512 x 512
matrix and a field of view of 53.3 x 38.7 cm. Patients were imaged with
their arms down; immobilizers were not used.
Study Design and Image Interpretation
The incremental value of 131I SPECT/CT over planar imaging was
determined with focus-based analysis of all discrete 131I activity
identified on planar and SPECT/CT images. The 131I scans were
viewed by two nuclear medicine physicians designated reader 1 and reader 2.
Reader 1 was blinded to clinical and biochemical data to avoid bias in lesion
classification with the intent that interpretation be based solely on imaging
properties. Reader 2, the nuclear endocrinologist, was unblinded and highly
familiar with all patients and provided an independent reading with full
access to clinical, biochemical, and histopathologic results.
Reader 1 interpreted planar 131I images and classified foci as
central neck (thyroid bed or neck) or distant and further evaluated lesions
according to intensity, location, nature, and reader confidence. Pinhole
images were available in 10 cases. The superior resolution of pinhole images
allowed resolution of intense 131I activity into several discrete
foci or confirmation of the presence of very faint planar 131I
uptake. All foci were reinterpreted after review of 131I SPECT/CT
images with software (MedImage, MedView) that allowed display of side-by-side
coregistered images and fused images. Incremental diagnostic information from
SPECT/CT and limitations of SPECT/CT technique, including misregistration and
poor image quality, were recorded.
Interpretations by reader 1 were compared with a reference standard
prepared by reader 2. This standard included comprehensive interpretation of
histopathologic reports, biochemical data, clinical details, and
131I planar and SPECT/CT findings. All patients had histologic
records on the surgical specimen that included information regarding tumor
size, surgical margins, and extrathyroidal tumor spread. Thirty patients
underwent central neck compartment dissection and had histologic records on
the presence or absence of nodal metastasis. This reference standard was
verified with clinical and imaging follow-up findings. Imaging follow-up
included neck sonography or diagnostic CT 2 months after radioiodine therapy
and repeated 131I scintigraphy 6–12 months after therapy.
Biochemical markers were evaluated 2 and 6 months after therapy.
Results
Planar scans including pinhole images depicted 147 foci of 131I
activity classified as 130 neck foci and 17 distant foci. At SPECT/CT these
foci were further characterized as 98 thyroglossal duct and thyroid bed
remnants (Figs. 1A,
1B,
1C,
1D, and
1E), 26 cervical nodal
metastatic lesions (Figs. 2A,
2B,
2C,
2D, and
2E), and local residual
disease, 11 cases due to physiologic activity and 12 to distant
metastasis.
View larger version (84K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1A —47-year-old woman with residual thyroid tissue after total
thyroidectomy for papillary carcinoma of the thyroid. Planar 37-MBq
131I image at 24 hours shows two foci (arrows) of central
neck activity.
|
|
View larger version (91K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1B —47-year-old woman with residual thyroid tissue after total
thyroidectomy for papillary carcinoma of the thyroid. Axial CT (B) and
fused SPECT/CT (C) images obtained 48 hours after 131I
administration show superior focus (arrow, B) localized
immediately anterior in relation to tip of hyoid bone, consistent with
thyroglossal duct remnant. Normal thyroid tissue is present along track of
thyroid embryologic descent.
|
|
View larger version (83K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1C —47-year-old woman with residual thyroid tissue after total
thyroidectomy for papillary carcinoma of the thyroid. Axial CT (B) and
fused SPECT/CT (C) images obtained 48 hours after 131I
administration show superior focus (arrow, B) localized
immediately anterior in relation to tip of hyoid bone, consistent with
thyroglossal duct remnant. Normal thyroid tissue is present along track of
thyroid embryologic descent.
|
|
View larger version (99K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1D —47-year-old woman with residual thyroid tissue after total
thyroidectomy for papillary carcinoma of the thyroid. Axial CT (D) and
fused SPECT/CT (E) images (field of view, 53.3 x 38.7 cm) show
inferior focus (arrow, D) localized to soft tissue in left
thyroid bed consistent with thyroid bed residue.
|
|
View larger version (82K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1E —47-year-old woman with residual thyroid tissue after total
thyroidectomy for papillary carcinoma of the thyroid. Axial CT (D) and
fused SPECT/CT (E) images (field of view, 53.3 x 38.7 cm) show
inferior focus (arrow, D) localized to soft tissue in left
thyroid bed consistent with thyroid bed residue.
|
|
View larger version (62K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2A —30-year-old woman with residual thyroid tissue and
periclavicular nodal metastasis of papillary thyroid carcinoma. Planar 37-MBq
131I image obtained 24 hours after 131I administration
shows two foci of activity (arrows) in central portion of neck.
|
|
View larger version (84K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2B —30-year-old woman with residual thyroid tissue and
periclavicular nodal metastasis of papillary thyroid carcinoma. Axial CT
(B) and fused SPECT/CT (C) images obtained 48 hours after
131I administration show superior focus (arrow, B)
localized to soft tissue in right thyroid bed consistent with thyroid bed
residue.
|
|
View larger version (66K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2C —30-year-old woman with residual thyroid tissue and
periclavicular nodal metastasis of papillary thyroid carcinoma. Axial CT
(B) and fused SPECT/CT (C) images obtained 48 hours after
131I administration show superior focus (arrow, B)
localized to soft tissue in right thyroid bed consistent with thyroid bed
residue.
|
|
View larger version (81K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2D —30-year-old woman with residual thyroid tissue and
periclavicular nodal metastasis of papillary thyroid carcinoma. Axial CT
(D) and fused SPECT/CT (field of view, 53.3 x 38.7 cm) (E)
images show inferior focus localized to normal-size cervical lymph node
(arrow, D) consistent with nodal metastasis.
|
|
View larger version (53K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2E —30-year-old woman with residual thyroid tissue and
periclavicular nodal metastasis of papillary thyroid carcinoma. Axial CT
(D) and fused SPECT/CT (field of view, 53.3 x 38.7 cm) (E)
images show inferior focus localized to normal-size cervical lymph node
(arrow, D) consistent with nodal metastasis.
|
|
For the 130 central neck lesions, the final SPECT/CT diagnoses by reader 1
and reader 2 disagreed on eight foci, for an interobserver variability of 6%
(Fig. 3). Reader 2 interpreted
four foci as lymphnode activity, called equivocal or thyroid remnant by reader
1, and one focus as thyroid remnant, called lymph node activity by reader 1.
Disagreement on these foci appeared related to misregistration of the SPECT/CT
data, which caused misalignment of focal uptake and small lymph nodes. In
addition, three cases of local residual disease were not appreciated by the
blinded reader, probably because the clinical diagnosis by reader 2 was
heavily influenced by histopathologic evidence of positive surgical resection
margins and extrathyroidal tumor extension. One focus interpreted as local
invasive disease by reader 2 had thyroid cartilage erosion evident on the CT
component that was not recognized by reader 1. Although consensus
interpretation with reader 1 unblinded agreed with the final clinical
diagnosis of these eight foci, these foci were excluded from the analysis of
incremental SPECT/CT value because the true nature of the foci could not be
determined with certainty after radioiodine therapy.
View larger version (14K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 3 —Flow chart shows incremental diagnostic value of
131I SPECT/CT for evaluation of central and distant activity foci.
aInterobserver agreement between reader 1, who knew only age, sex,
and thyroglobulin level, and reader 2, who had full access to clinical,
biochemical, histopathologic, and imaging information. bPlanar and
SPECT/CT interpretation of central neck activity were same.
cSPECT/CT was accurate for change of characterization of central
neck activity as thyroid residue from nodal metastasis (n = 2) or
from equivocal source (n = 24). dSPECT/CT was accurate for
change of characterization of central neck activity as nodal metastasis from
thyroid residue (n = 4) or from equivocal source (n = 7).
eSPECT/CT findings led to reclassification of 10 foci as
thyroglossal duct remnant from thyroid bed remnant, both considered thyroid
residue.
|
|
Of the 122 lesions on which there was interobserver agreement, incremental
diagnostic value was found in 53 of 122 foci, defined as a change in focus
classification (Table 1).
SPECT/CT findings led to correct downstaging of 26 of 53 foci from equivocal
or cervical lymph node to thyroid remnant and correct upstaging of 11 of 53
foci from equivocal or thyroid remnant to cervical lymph node. An additional
six of 53 foci were reclassified as physiologic dental or salivary activity.
In the other 10 of 53 foci, on the basis of SPECT/CT findings a planar imaging
diagnosis of thyroid remnant was changed to thyroglossal duct remnant because
additional anatomic information was derived from low-dose CT.
There was no change in focus classification between planar and SPECT/CT
interpretation in 69 of 122 of central neck foci. In the cases of six of the
69 foci, SPECT/CT was deemed nondiagnostic by reader 1 owing to poor quality
of CT images. Therefore, SPECT/CT had no incremental value.
The two readers had complete agreement (100%) on the 17 distant foci. The
final classification was four bone metastatic lesions (Figs.
4A,
4B, and
4C), eight lung metastatic
lesions (in six patients) (Figs.
5A,
5B,
5C,
5D, and
5E), and five physiologic
disease mimics (Figs. 6A,
6B, and
6C). For analytic purposes,
multiple bilateral lung metastatic lesions were counted as a single focus.
SPECT/CT enabled superior anatomic localization of activity in cases of bone
metastasis, allowing exclusion of skin contamination with certainty. For
evaluation of thoracic foci, SPECT/CT showed additional mediastinal nodal
disease in one patient, unsuspected micronodular disease with normal chest
radiographic findings in another, and a decrease in pulmonary lesion size
after therapy in a third patient. In all cases of distant metastasis, although
there was no change in focus classification, SPECT/CT improved lesion
localization, provided additional anatomic information, and increased reader
confidence (Table 2).
Therefore, incremental value of SPECT/CT compared with planar imaging was
found for 53 of 130 central neck lesions (40.8%) and 17 of 17 distant foci
(100%) for a total of 70 of 147 131I foci (47.6%).
View larger version (130K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4A —79-year-old man with papillary thyroid carcinoma has residual
thyroid tissue in neck and osseous metastasis. Planar 37-MBq 131I
image obtained 24 hours after 131I administration shows faint
activity (arrow) overlying right side of thorax.
|
|
View larger version (88K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4B —79-year-old man with papillary thyroid carcinoma has residual
thyroid tissue in neck and osseous metastasis. Axial CT (B) and fused
SPECT/CT (field of view, 53.3 x 38.7 cm) (C) images obtained 48
hours after 131I administration show thoracic activity localized to
anterior rib lesion (arrow, B) with central 131I
activity consistent with bone metastasis. SPECT/CT allows superior
localization and accurate characterization of this distant focus, which on
planar images was speculated to represent bone or lung disease or even skin
contamination.
|
|
View larger version (70K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4C —79-year-old man with papillary thyroid carcinoma has residual
thyroid tissue in neck and osseous metastasis. Axial CT (B) and fused
SPECT/CT (field of view, 53.3 x 38.7 cm) (C) images obtained 48
hours after 131I administration show thoracic activity localized to
anterior rib lesion (arrow, B) with central 131I
activity consistent with bone metastasis. SPECT/CT allows superior
localization and accurate characterization of this distant focus, which on
planar images was speculated to represent bone or lung disease or even skin
contamination.
|
|
View larger version (102K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5A —49-year-old woman with papillary thyroid carcinoma has nodal
metastasis in neck and pulmonary metastasis. Planar 37-MBq 131I
image obtained 24 hours after 131I administration shows two foci
(arrowheads) overlying right side of thorax.
|
|
View larger version (120K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5B —49-year-old woman with papillary thyroid carcinoma has nodal
metastasis in neck and pulmonary metastasis. Axial CT (B and D)
and axial fused SPECT/CT (field of view, 53.3 x 38.7 cm) (C and
E) images obtained 48 hours after 131I administration show
thoracic foci localized to small pulmonary nodules (arrow, B
and D) in right upper lobe, consistent with lung metastasis not
detected on preoperative chest radiograph. SPECT/CT did not improve
interpretation of distant thoracic activity, correct diagnosis being made with
planar images. SPECT/CT findings, however, did increase reader confidence.
Diagnostic chest CT was not required owing to use of SPECT/CT.
|
|
View larger version (78K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5C —49-year-old woman with papillary thyroid carcinoma has nodal
metastasis in neck and pulmonary metastasis. Axial CT (B and D)
and axial fused SPECT/CT (field of view, 53.3 x 38.7 cm) (C and
E) images obtained 48 hours after 131I administration show
thoracic foci localized to small pulmonary nodules (arrow, B
and D) in right upper lobe, consistent with lung metastasis not
detected on preoperative chest radiograph. SPECT/CT did not improve
interpretation of distant thoracic activity, correct diagnosis being made with
planar images. SPECT/CT findings, however, did increase reader confidence.
Diagnostic chest CT was not required owing to use of SPECT/CT.
|
|
View larger version (121K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5D —49-year-old woman with papillary thyroid carcinoma has nodal
metastasis in neck and pulmonary metastasis. Axial CT (B and D)
and axial fused SPECT/CT (field of view, 53.3 x 38.7 cm) (C and
E) images obtained 48 hours after 131I administration show
thoracic foci localized to small pulmonary nodules (arrow, B
and D) in right upper lobe, consistent with lung metastasis not
detected on preoperative chest radiograph. SPECT/CT did not improve
interpretation of distant thoracic activity, correct diagnosis being made with
planar images. SPECT/CT findings, however, did increase reader confidence.
Diagnostic chest CT was not required owing to use of SPECT/CT.
|
|
View larger version (72K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5E —49-year-old woman with papillary thyroid carcinoma has nodal
metastasis in neck and pulmonary metastasis. Axial CT (B and D)
and axial fused SPECT/CT (field of view, 53.3 x 38.7 cm) (C and
E) images obtained 48 hours after 131I administration show
thoracic foci localized to small pulmonary nodules (arrow, B
and D) in right upper lobe, consistent with lung metastasis not
detected on preoperative chest radiograph. SPECT/CT did not improve
interpretation of distant thoracic activity, correct diagnosis being made with
planar images. SPECT/CT findings, however, did increase reader confidence.
Diagnostic chest CT was not required owing to use of SPECT/CT.
|
|
View larger version (117K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 6A —17-year-old girl with Hürthle cell thyroid cancer has
residual thyroid tissue in neck and physiologic uptake in breast tissue.
Planar 150-MBq 131I image obtained 24 hours after 131I
administration under recombinant human thyroid-stimulating hormone stimulation
shows faint activity (arrow) overlying right thorax.
|
|
View larger version (88K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 6B —17-year-old girl with Hürthle cell thyroid cancer has
residual thyroid tissue in neck and physiologic uptake in breast tissue. Axial
CT (B) and fused SPECT/CT (field of view, 53.3 x 38.7 cm)
(C) images obtained 48 hours after 131I administration shows
activity (arrow, B) localized to right breast parenchymal
tissue with asymmetry of glandular tissue representing normal variant.
SPECT/CT did not improve interpretation of distant thoracic activity. Correct
diagnosis was made with planar images, but SPECT/CT findings increased reader
confidence.
|
|
View larger version (85K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 6C —17-year-old girl with Hürthle cell thyroid cancer has
residual thyroid tissue in neck and physiologic uptake in breast tissue. Axial
CT (B) and fused SPECT/CT (field of view, 53.3 x 38.7 cm)
(C) images obtained 48 hours after 131I administration shows
activity (arrow, B) localized to right breast parenchymal
tissue with asymmetry of glandular tissue representing normal variant.
SPECT/CT did not improve interpretation of distant thoracic activity. Correct
diagnosis was made with planar images, but SPECT/CT findings increased reader
confidence.
|
|
Reader Confidence
Evaluation of reader confidence was based on a subjective 5-point scale (1,
no confidence; 2, equivocal; 3, possible; 4, probable; 5, certain). Reader 1
reported increased reader confidence with SPECT/CT compared with planar
imaging in the diagnosis of 104 of the 147 foci; confidence did not change
regarding 32 foci and decreased regarding 11 foci on the basis of suboptimal
SPECT/CT images. Of the 17 distant foci, there was no change in reader
confidence regarding eight foci, but reader confidence increased regarding
nine foci owing to superior anatomic localization and additional findings on
CT.
Clinical Follow-Up
Two months after radioiodine therapy, 47 patients underwent sonography of
the neck or diagnostic CT including the neck region. Iodine-131 scintigraphy
was performed on 42 patients 6–12 months after therapy. The group of 11
patients without follow-up 131I scans included six patients who
underwent clinical follow-up with no evidence of recurrent disease to prompt
further imaging, including the four patients imaged with the recombinant human
thyroid-stimulating hormone protocol. A further four patients underwent
2-month follow-up imaging after which they relocated out of area. One patient
with regional disease detected on SPECT/CT did not undergo follow-up. Clinical
follow-up is summarized in Table
3.
Twenty-nine of 53 patients had the SPECT/CT finding of thyroid remnant.
Twenty-eight of these patients had no evidence of residual functioning thyroid
tissue after radioiodine therapy, either normal findings at sonography of the
neck and 131I scanning and normal thyroglobulin levels (n
= 19) or normal findings at clinical examination and normal thyroglobulin
levels (n = 9). This follow-up finding strongly indicates that
SPECT/CT information is correct in assignment of 131I foci as
thyroid bed or thyroglossal duct remnant, especially in view of the low-risk
histologic surgical specimens (small tumors with negative surgical resection
margins) in most of these patients. One patient with SPECT/CT findings of
thyroid remnant had evidence of recurrent neck disease. This patient had
received medium-dose 131I therapy because the presence of positive
lymph nodes was documented in the postsurgical histopathology report. The
SPECT/CT findings may have been normal because of limited spatial resolution
or the presence of non-iodine-avid disease.
Fifteen of 53 patients had the SPECT/CT diagnosis of regional disease.
Clinical follow-up of six of the 15 patients revealed stable or progressive
regional disease after radioiodine treatment. The other eight patients who
underwent follow-up had normal imaging findings and thyroglobulin levels and
were considered to have controlled nodal metastasis. Despite lack of biopsy
confirmation, the presence of 131I-avid lymph nodes on SPECT/CT was
convincing evidence of the diagnosis. Distant metastatic lesions were found in
nine of 53 patients, including five patients with pulmonary metastasis, two
patients with bone metastasis, and two patients with both lung and bone
metastasis. Iodine-131 scanning and CT follow-up showed stable pulmonary
disease in three patients, an interval decrease in size of lung nodules in one
patient, and complete resolution of lung disease in one patient after
131I therapy. Two patients with bone metastasis had complete
resolution of disease according to 131I scanning and CT findings,
and the two patients with lung and bone metastasis had progressive disease
according to imaging and biochemical data.
Discussion
Benefits of Fusion 131I SPECT/CT
The availability of 131I SPECT/CT has had great impact on our
nuclear therapy clinical practice. Planar 131I imaging has
traditionally suffered from low resolution, and a paucity of anatomic
information along with a long list of physiologic variants makes image
interpretation challenging. The use of multiple maneuvers to aid in
differentiation of physiologic from pathologic foci of activity, including
swallowing water, separate-day imaging, oblique and lateral imaging, washing
the patient's skin, removing and scanning clothing, correlating with other
imaging techniques, and remaining vigilant for pitfalls such as dentures,
handkerchiefs, and other sources of contamination, is essential for accurate
diagnosis. In our experience, 131I SPECT/CT has facilitated rapid,
accurate, and confident assessment of radioiodine activity outside the
expected biodistribution. On SPECT/CT images, central neck activity is
characterized as thyroid remnant or locoregional disease, and the number of
equivocal foci on planar assessment is reduced. In the detection of distant
metastatic disease, the superior lesion localization and additional CT-derived
anatomic information obtained with SPECT/CT increase reader confidence,
assisting clinical management decisions.
The utility of 131I SPECT/CT for investigation of DTC has been
evaluated in studies in which the patient groups underwent predominately or
only posttherapy iodine studies. In early studies, SPECT and CT scans were
compared with software-fused SPECT/CT
[11] and SPECT was compared
with SPECT/CT [12]. Although
it is not routine clinical practice to use SPECT with 131I studies,
both groups of investigators found SPECT/CT had incremental diagnostic value
due to improved lesion localization and characterization. Tharp and colleagues
[13] reported their experience
with 131I SPECT/CT in a mixed group comprising 17 patients who
received a diagnostic dose (eight before ablation) and 54 patients who
underwent therapeutic-dose scanning. Those investigators evaluated the
incremental value in SPECT/CT over planar imaging, which is the usual clinical
imaging method, and found additional value for 57% (41 of 71) of patients,
with a substantial impact on clinical management. SPECT/CT improved
localization and characterization of foci inside and outside the neck,
including equivocal foci on planar 131I images. The SPECT/CT
findings led to a change in treatment approach (dose of radioiodine therapy or
direction of surgical management). Our study confirmed these findings of
incremental value with diagnostic 131I SPECT/CT. The high
interobserver agreement between the blinded reader and the unblinded reader
who provided the reference standard suggests that 131I SPECT/CT is
accurate for characterization of activity foci identified on planar images and
when applied to a diagnostic 131I study allows completion of TNM
staging and risk stratification based on the patient's disease burden.
Limitations of Fusion 131I SPECT/CT
Despite the benefits of 131I SPECT/CT, we encountered technical
difficulties and challenges early in our experience when applying this
technology to diagnostic radioiodine scintigraphy. The low intrinsic activity
of diagnostic 131I scans may be poorly sampled with SPECT and
unresolved after tomographic reconstruction owing to inadequate count
statistics. This problem occurred both regionally and distantly in a small
proportion (< 5%) of our patients with 3D ordered subset expectation
maximization iterative reconstruction technique and might be overcome with the
use of filtered back-projection reconstruction. We are exploring different
parameters, such as matrix size, number of steps, and number of seconds per
step position, with the goal of optimizing SPECT acquisition for
131I imaging with general trade-offs among spatial resolution,
adequate count activity per pixel, and patient movement with longer
acquisition times.
Considerable misregistration of functional and anatomic data was
encountered in only one case. In general, integrated SPECT/CT cameras image
patients in the same bed position during the same session to achieve image
fusion without the use of external fiducial markers. In practice, however,
patient movement on the bed continues to occur and may be reduced with
immobilizers. The difficulty with 131I SPECT/CT, unlike
18F-FDG PET/CT, is the lack of background tissue activity on
functional images, which facilitates recognition of misregistration on FDG
imaging. We use salivary gland activity as a check for registration by
ensuring alignment of activity to the correct anatomic location of the glands.
Misregistration may also be related to the fusion software used and may arise
from the use of different header information on tomographic data from
different vendors.
We have found planar images, including pinhole collimation, very useful for
interpretation of SPECT/CT images. Problems encountered with SPECT of
low-level 131I activity included limited spatial resolution that
blurred two adjacent foci seen distinctly on planar images, reconstruction of
septal penetration activity into discrete foci with iterative reconstruction,
streak artifact related to filtered back-projection reconstruction of intense
131I activity, and attenuation of central neck activity by the
shoulders of patients with non-attenuation-corrected filtered back-projection
images. We therefore support the view that SPECT/CT images should be
interpreted in conjunction with planar images and not in isolation.
Study Limitations
Our study of 131I SPECT/CT was conducted with a selected group
of patients. Therefore, incremental diagnostic value might be expected to
occur in a higher proportion of cases than if SPECT/CT had been used for every
patient. However, that 131I SPECT/CT allows more accurate risk
stratification of patients with DTC may favor its routine use. SPECT/CT test
performance parameters such as sensitivity, specificity, and accuracy could
not be calculated directly owing to the lack of a histologic reference
standard for assessing 131I-avid lesions. After 131I
therapy, thyroid remnant, local residual disease, and regional lymph node
metastasis in the central part of the neck may resolve; therefore, the true
nature of lesions can be inferred with follow-up but not confirmed. The
reference standard included SPECT/CT as a major component in determining the
nature of physiologic and pathologic activity. This limitation is inherent to
most other studies in which an attempt is made to determine the incremental
value of SPECT/CT over planar imaging.
Conclusion
Iodine-131 SPECT/CT provides incremental diagnostic information compared
with that obtained at planar imaging. This information can be used for
accurate characterization of central neck activity, superior localization of
distant metastatic lesions, evaluation and rapid confirmation of suspected
physiologic mimics of disease, and increasing reader confidence.
Acknowledgments
We thank James C. Sisson for valuable insight and advice regarding the
manuscript.
References
- Davies L, Welch HG. Increasing incidence of thyroid cancer in the
United States, 1973–2002. JAMA2006; 295:2164
-2167[Abstract/Free Full Text]
- Jonklaas J, Sarlis NJ, Litofsky D, et al. Outcomes of patients with
differentiated thyroid carcinoma following initial therapy.
Thyroid 2006; 16:1229
-1242[CrossRef][Medline]
- Hay ID, Thompson GB, Grant CS, et al. Papillary thyroid carcinoma
managed at the Mayo Clinic during six decades (1940–1999): temporal
trends in initial therapy and long-term outcome in 2444 consecutively treated
patients. World J Surg 2002;26
: 879-885[CrossRef][Medline]
- Hay ID, McConahey WM, Goellner JR. Managing patients with papillary
thyroid carcinoma: insights gained from the Mayo Clinic's experience of
treating 2,512 consecutive patients during 1940 through 2000. Trans
Am Clin Climatol Assoc 2002;113
: 241-260[Medline]
- Brierley J, Tsang T, Panzarella T, Bana N. Prognostic factors and
the effect of treatment with radioactive iodine and external beam radiation on
patients with differentiated thyroid cancer seen at a single institution over
40 years. Clin Endocrinol 2005;63
: 418-427[CrossRef][Medline]
- Hay ID. Management of patients with low-risk papillary thyroid
carcinoma. Endocr Pract 2007;13
: 521-533[Medline]
- Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for
patients with thyroid nodules and differentiated thyroid cancer.
Thyroid 2006; 16:109
-142[Medline]
- Kloos RT. Papillary thyroid cancer: medical management and
follow-up. Curr Treat Options Oncol 2005;6
: 323-338[Medline]
- Mazzaferri EL. Management of low-risk differentiated thyroid
cancer. Endocr Pract 2007;13
: 498-512[Medline]
- Even-Sapir E, Keidar Z, Sachs J, et al. The new technology of
combined transmission and emission tomography in evaluation of endocrine
neoplasms. J Nucl Med 2001;42
: 998-1004[Abstract/Free Full Text]
- Yamamoto Y, Nishiyama Y, Monden T, Matsumura M, Satoh K, Ohkawa M.
Clinical usefulness of fusion of I-131 SPECT and CT images in patients with
differentiated thyroid carcinoma. J Nucl Med2003; 44:1905
-1910[Abstract/Free Full Text]
- Ruf J, Lehmkuhl L, Bertram H, et al. Impact of SPECT and integrated
low-dose CT after radioiodine therapy on the management of patients with
thyroid carcinoma. Nucl Med Commun 2004;25
: 1177-1182[CrossRef][Medline]
- Tharp K, Israel O, Hausmann J, et al. Impact of I-131 SPECT/CT
images obtained with an integrated system in the follow-up of patients with
thyroid carcinoma. Eur J Nucl Med Mol Imaging2004; 31:1435
-1442[Medline]
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K K WONG, N ZARZHEVSKY, J M CAHILL, K A FREY, and A M AVRAM
Hybrid SPECT-CT and PET-CT imaging of differentiated thyroid carcinoma
Br. J. Radiol.,
October 1, 2009;
82(982):
860 - 876.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
