Material and Methods

ASNR 2015 Scientific Paper (Electronic Poster)
Hirofumi Kuno, MD, PhD1; Kotaro Sekiya, DDS, PhD1; Satoshi Fujii, MD, PhD2; Hiroaki Onaya,
MD, PhD3; Katharina Otani, PhD4; Mitsuo Satake, MD, PhD1; Masahiko Kusumoto MD, PhD1
1. Department of Diagnostic Radiology, 2. Pathology,
National Cancer Center Hospital East, Kashiwa, Chiba, Japan
3. Department of Diagnostic Radiology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan
4. Imaging & Therapy Systems Division, Siemens Japan K.K., Shinagawa-ku, Tokyo, Japan
• Kuno H, Sekiya K, Fujii S, Onaya H, Satake M,
Kusumoto M
– None
• Otani K
– Employee, Siemens Japan K.K.
• The treatment of laryngeal and hypopharyngeal
squamous cell carcinoma (SCC) depends on the
presence or absence of cartilage invasion.
• When the tumor extends through
the cartilage into the soft tissue of
the neck, the patient often requires
aggressive treatment such as total
• Both computed tomography (CT) and magnetic
resonance imaging (MRI) are routinely used for
the detection of subtle cartilage invasion,
although the modality that can most accurately
detect cartilage invasion remains controversial4-10.
Furthermore, both modalities have shortcomings.
• Recently, dual-energy CT was shown to have
higher diagnostic performance than conventional
CT 11,12, although its efficiency has not been
compared with that of MRI.
• To compare the effectiveness of dual-energy CT
and MRI in the detection of cartilage invasion
by laryngeal and hypopharyngeal SCC.
Study design
– Retrospective cross-sectional study with
institutional review board approval.
Study population
– Between September 2010 and September
2014, 605 consecutive patients diagnosed
with laryngeal or hypopharyngeal SCC
were scheduled for a contrast-enhanced
CT examination for cancer staging using
128 slice dual-source CT.
– Among these, 115 underwent 3T-MRI
– Eight (7%) patients were excluded
because of the below mentioned reasons:
Poor general condition
Non contrast MRI study
MR images showed severe artifacts that rendered
the image non-diagnostic
– Eventually, 107 patients (98 men, 9
women; 45 – 82 years; median age, 66
years) were enrolled in the final analysis.
• Dual-energy CT protocol and postprocessing
– 128-slice Dual-Source CT (SOMATOM Definition Flash, Siemens)
• Dual-energy mode (100 kV, 140 kV), 200/200 mAs, 32 × 0.6 mm, 0.33 s, p0.6, 1-mm thickness,
0.7-mm increments, D30f.
• Contrast medium, Ioverin300, 2. 5mL/s; scan start, 70 s.
– Three-material-decomposition analysis (Syngo Dual Energy, Brain Hemorrhage; Siemens
• Weighted-average (WA) images were generated by fusing datasets acquired with different tube
voltages. These appear similar to 120-kV CT images.
• Iodine overlay (IO) images were generated by fusing virtual noncontrast images and iodine images.
• MR protocol and sequences
– All studies were performed using a 3T MRI system (Ingenia 3.0T or Achieva 3.0T TX, Philips
Medical Systems, Best, Netherlands).
• Two-dimensional sequences [T2-weighted (T2W), T1-weighted (T2W), and contrast-enhanced fatsaturated T1W), parallel and vertical to the vocal cords, were obtained with a slice thickness of 3
mm and a 1-mm intersection gap.
• Three-dimensional sequences (T2W, unenhanced T1W, and enhanced T1W) were additionally
performed in regions of interest that included the laryngeal component from 1.0 cm above the
hyoid bone to the inferior margin of the cricoid cartilage.
• Image interpretation
– Two radiologists blinded to the clinical history and the image obtained
using the other modality independently analysed the MRI and dualenergy CT images.
– The images were presented in random order in two sessions, one with
only MR images and one with only dual-energy CT images.
– The invasion of each laryngeal were evaluated
according to diagnostic criteria and five-point
scale (cut off: score 3)
Score 1, definitely negative;
Score 2, probably negative;
Score 3, possibly positive (erosion);
Score 4, probably positive (lysis);
score 5, definitely positive (extra).
– The final diagnosis was determined by consensus and
was used to compare the CT findings with the
pathologic results.
• Diagnostic criteria
– On MRI, cartilage invasion was considered present when the cartilage
displayed a signal intensity similar to that of the adjacent tumor on
T1W, T2W, and contrast-enhanced T1W images.
– With regard to dual-energy CT, combined weighted-average (WA) and
iodine overlay (IO) images were used for the evaluation of cartilage
invasion, as described in previous reports 11. Diagnostic readings
always began with the WA image, followed by additional reading of
the IO image when appropriate. The WA image allows the evaluation
of the cartilage shape, while the enhancement pattern on the IO
image enables the identification of uptake due to the blood vessels of
the cancer tissue, as opposed to the avascular cartilage.
• Histologic evaluation
– Surgical specimens, including all cartilages around the tumor, were
fixed in formalin, decalcified in advance, and cut into 3.0–4.0-mmthick slices in the frontal direction, similar to the cross-sectional MR
and CT images, and evaluated by a pathologist.
• Statistical Analysis
– Fifty five of the 107 patients (51%) underwent surgery, and findings
from histopathological examination were used as the standard of
reference for evaluating the diagnostic performance in terms of
sensitivity and specificity using receiver operating characteristic
(ROC) curve analysis. Sensitivity and specificity were evaluated using
McNemar’s test.
– All statistical tests were performed using commercial software
(STATA ver. 12).
– P-value of <.05 was considered statistically significant.
Table 1
Diagnostic Performance for Evaluation of Cartilage Invasion and Extralaryngeal Spreading
Sensitivity (%)
Thyroid cartilage (n=55)
100 (19/19)
Dual-energy CT
89 (17/19)
Cricoid cartilage (n=55)
100 (8/8)
Dual-energy CT
75 (6/8)
Right Arytenoid cartilage (n=55)
83 (5/6)
Dual-energy CT
67 (4/6)
Left Arytenoid cartilage (n=55)
100 (3/3)
Dual-energy CT
67 (2/3)
Extralaryngeal spread (n=55)
94 (32/34)
Dual-energy CT
94 (32/34)
Specificity (%) PPV (%)
NPV (%)
64 (23/36)
100 (23/23)*
59 (19/32) 100 (23/23)
100 (17/17) 95 (36/38)
87 (41/47)
98 (46/47)
57 (8/14)
86 (6/7)
100 (41/41)
96 (46/48)
88 (43/49)
96 (47/49)
45 (5/11)
67 (4/6)
98 (43/44)
96 (47/49)
92 (48/52)
98 (51/52)
43 (3/7)
67 (2/3)
100 (48/48)
98 (51/52)
81 (17/21)
81 (17/21)
89 (32/36)
89 (32/36)
89 (17/19)
89 (17/19)
Note.-Numbers in parentheses were used to calculate the percentages. TP = true positive, TN = true negative, FP = false positive, FN = false negative, PPV =
Positive Predictive Value, NPV = Negative Predictive Value,
p=0.00009 for comparison between MRI and DECT
The specificity of dual-energy CT was superior to that of MRI (100% vs 64%, respectively; P < .0001) for the
evaluation of thyroid cartilage, but no evidence indicated that the sensitivity of dual-energy CT differed from
that of MRI (89% vs 100%, respectively; P = .50).
DECT_Th ROC area: 0.9518
MRI_Th ROC area: 0.9379
• No evidence indicated differences in the average areas
under the ROC curves between dual-energy CT and MRI
(0.952 vs 0.938, respectively; P = .70).
Case 1: False-positive findings for thyroid cartilage invasion on MRI
False-positive findings for thyroid cartilage invasion on magnetic
resonance imaging (MRI) in a 59-year-old man with hypopharyngeal
(A) T2-weighted, T1-weighted, and fat-suppressed contrast-enhanced
T1-weighted MR images show a tumor mass (T) arising from the right
piriform sinus. The adjacent thyroid cartilage has a signal intensity
similar to that of the tumor (arrow).
(B) A weighted-average (WA) image does not show erosion or lysis at
the same level, and an iodine overlay (IO) image is not used for
diagnosis. (C) A corresponding axial slice from the surgical specimen at
the same level shows that the right thyroid lamina has not been
invaded by the tumor (arrow). The posterior part of the right thyroid
lamina with enhancement shows moderate infiltration of lymphocytes
into the medullary space, accompanied by fibrosis and aggregation of
macrophages (shown on click; square).
(hematoxylin–eosin stain; original magnification, 200×)
Case 2: False-negative findings for thyroid cartilage invasion on DECT
False-negative findings for thyroid cartilage
invasion on dual-energy CT (DECT) in a 67-year-old
man with laryngeal cancer
(A) T2-weighted, T1-weighted, and fat-suppressed
contrast-enhanced T1-weighted MR images show the
signal intensity similar to that of the tumor in thyroid
cartilage has a (arrow).
(B) A weighted-average (WA) image shows focal erosion
on the left thyroid cartilage (arrows). However, iodine
overlay (IO) image shows no corresponding enhancement
in the region indicated in the WA image (arrow).
(C) The minor invasion of tumor cells into an ossified-right
wing of the thyroid cartilage with an extent of 5mmdiameter is observed in the histopathological findings
(arrow). Thyroid lamina with extensively enhancement on
MRI reflect the moderate infiltration of lymphocytes into
the medullary space, accompanied with desmoplastic
reaction according to destruction of normal tissue by
tumor cell invasion (shown on click; square).
(Hematoxylin–eosin stain; original magnification.).
• In the current study, we compared the diagnostic performance
of dual-energy CT with that of MRI with regard to the
evaluation of tumor invasion by laryngeal and hypopharyngeal
• The specificity of dual-energy CT was superior to that of MRI
for the evaluation of thyroid cartilage, but no evidence
indicated that the sensitivity of dual-energy CT differed from
that of MRI.
• High specificity could be achieved because the WA and IO
images depicted a precise shape of ossified cartilages and
iodine distribution in nonossified cartilages, thus preventing
the overestimation of invasion that occurred during diagnoses
with MRI.
• MRI shows great potential for detecting cartilage invasion because of
high contrast resolution for images without motion artifacts. However,
inflammatory changes in cartilage sometimes resemble cartilage
invasion, and high false-positive rates remain an issue. The previously
reported specificity of MRI for the detection of thyroid cartilage
invasion is only 56%–65% 4,12.
• Peritumoral inflammatory changes were shown in both the invaded
and noninvaded laryngeal cartilages surrounding the actual tumor
borders, and changes were easily observed in many ossified cartilages,
particularly in the fatty marrow infiltrated with calcified areas 4,11,12.
MRI cannot identify cortical bone, which has no MR signal. Therefore,
MRI may be inferior for the evaluation of cortical bone changes, while
it can depict fatty marrow changes.
• In addition, for advanced laryngeal and hypopharyngeal SCC in
particular, MRI seems to be prone to motion artifacts because of the
relatively long scan times12.
• Dual-energy CT can provide WA images, which are similar to
conventional 120-kV images, and IO images with high spatial
resolution 13-16. Iodine-enhanced tumors and non-ossified cartilages
can be distinguished using IO images, because iodine enhancement
is evident in tumor tissue, but not in cartilage11,12.
• A preliminary report suggests that the specificity of combined WA
and IO image analysis is significantly superior to that of WA image
analysis alone (96% vs. 70%), with no compromise on sensitivity
(86% vs. 86%)11.
• Furthermore, combined WA and IO images can evaluate the erosion
or loss of ossified cartilages and judge the iodine distribution in the
corresponding area at the same time. When the WA image does
not show cartilage destruction, regardless of inflammatory changes
in the fatty marrow, cartilage invasion is considered absent.
• The specificity of dual-energy CT is higher than
that of MRI for the evaluation of thyroid
cartilage invasion by SCC, and it may be as
useful as MRI during treatment decisionmaking for laryngeal and hypopharyngeal SCC.
1. Hartl DM, Landry G, Hans S, Marandas P, Brasnu DF. Organ preservation surgery for laryngeal squamous cell carcinoma: low incidence of thyroid
cartilage invasion. Laryngoscope 2010;120(6):1173-1176.
2. Pfister DG, Laurie SA, Weinstein GS, et al. American Society of Clinical Oncology clinical practice guideline for the use of larynx-preservation
strategies in the treatment of laryngeal cancer. J Clin Oncol 2006;24(22):3693-3704.
3. Rodriguez CP, Adelstein DJ, Rybicki LA, et al. Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy. Head
Neck 2008;30(12):1535-1542.
4. Becker M, Zbaren P, Casselman JW, Kohler R, Dulguerov P, Becker CD. Neoplastic invasion of laryngeal cartilage: reassessment of criteria for
diagnosis at MR imaging. Radiology 2008;249(2):551-559.
5. Li B, Bobinski M, Gandour-Edwards R, Farwell DG, Chen AM. Overstaging of cartilage invasion by multidetector CT scan for laryngeal cancer and
its potential effect on the use of organ preservation with chemoradiation. Br J Radiol 2011;84(997):64-69.
6. Castelijns JA, Becker M, Hermans R. Impact of cartilage invasion on treatment and prognosis of laryngeal cancer. Eur Radiol 1996;6(2):156-169.
7. Beitler JJ, Muller S, Grist WJ, et al. Prognostic Accuracy of Computed Tomography Findings for Patients With Laryngeal Cancer Undergoing
Laryngectomy. J Clin Oncol 2010;28(14):2318-2322.
8. Becker M, Zbaren P, Delavelle J, et al. Neoplastic invasion of the laryngeal cartilage: reassessment of criteria for diagnosis at CT. Radiology
9. Zbaren P, Becker M, Lang H. Pretherapeutic staging of laryngeal carcinoma. Clinical findings, computed tomography, and magnetic resonance
imaging compared with histopathology. Cancer. 1996;77:1263-1273
10. Becker M, Zbaren P, Laeng H, Stoupis C, Porcellini B, Vock P. Neoplastic invasion of the laryngeal cartilage: comparison of MR imaging and CT
with histopathologic correlation. Radiology 1995;194(3):661-669.
11. Kuno H, Onaya H, Iwata R, Kobayashi T, Fujii S, Hayashi R, Otani K, Ojiri H, Yamanaka T, Satake M. Evaluation of cartilage invasion by laryngeal
and hypopharyngeal squamous cell carcinoma with dual-energy CT. Radiology. 2012;265(2):488-96
12. Kuno H, Onaya H, Fujii S, Ojiri H, Otani K, Satake M. Primary staging of laryngeal and hypopharyngeal cancer: CT, MR imaging and dual-energy CT.
Eur J Radiol. 2014 Jan;83(1):e23-35
13. Graser A, Johnson TR, Hecht EM, et al. Dual-energy CT in patients suspected of having renal masses: can virtual nonenhanced images replace
true nonenhanced images? Radiology 2009;252(2):433-440.
14. Gupta R, Phan CM, Leidecker C, et al. Evaluation of Dual-Energy CT for Differentiating Intracerebral Hemorrhage from Iodinated Contrast
Material Staining. Radiology 2010;257(1):205-211.
15. Johnson TR, Krauss B, Sedlmair M, et al. Material differentiation by dual energy CT: initial experience. Eur Radiol 2007;17(6):1510-1517.
16. Krauss B, Schmidt B, Flohr TG. Dual Source CT. In: Johnson TRC, Fink C, Schönberg SO, Reiser MF, eds. Dual Energy CT in Clinical Practice. 1st ed.
Heidelberg, Dordrecht, London, New York, Springer, 2011; 11-20.