Neuroradiolog y/Head and Neck Imaging • Original Research Park et al. Acoustic Structure Quantification for Diagnosing Thyroiditis
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Neuroradiology/Head and Neck Imaging Original Research
Investigation of Acoustic Structure Quantification in the Diagnosis of Thyroiditis Jisang Park1 Hyun Sook Hong1 Chul-Hee Kim 2 Eun Hye Lee1 Sun Hye Jeong1 A. Leum Lee1 Heon Lee1 Park J, Hong HS, Kim CH, et al.
Keywords: acoustic structure quantification, hypothyroidism, thyroid gland, thyroiditis, ultrasonography DOI:10.2214/AJR.15.14586 Received February 24, 2015; accepted after revision July 6, 2015. 1 Department of Radiology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-767, Korea. Address correspondence to H. S. Hong ([email protected]). 2 Division of Endocrinology and Metabolism, epartment of Internal Medicine, Soonchunhyang D University Bucheon Hospital, Bucheon-si, Gyeonggi-do, Korea.
AJR 2016; 206:601–608 0361–803X/16/2063–601 © American Roentgen Ray Society
OBJECTIVE. The objective of this study was to evaluate the ability of acoustic structure quantification (ASQ) to diagnose thyroiditis. MATERIALS AND METHODS. The echogenicity of 439 thyroid lobes, as determined using ASQ, was quantified and analyzed retrospectively. Thyroiditis was categorized into five subgroups. The results were presented in a modified chi-square histogram as the mode, average, ratio, blue mode, and blue average. We determined the cutoff values of ASQ from ROC analysis to detect and differentiate thyroiditis from a normal thyroid gland. We obtained data on the sensitivity and specificity of the cutoff values to distinguish between euthyroid patients with thyroiditis and patients with a normal thyroid gland. RESULTS. The mean ASQ values for patients with thyroiditis were statistically significantly greater than those for patients with a normal thyroid gland (p 130.7) were successful in distinguishing patients with thy-
TABLE 2: Performance of Acoustic Structure Quantification Values and AUCs in the Diagnostic Differentiation of Thyroiditis From Normal Thyroid Gland Parameter Mode
AUC
Criterion (Maximal AUC to Diagnose as Thyroiditis)
Sensitivity (%), Mean (95% CI)
Specificity (%), Mean (95% CI)
0.872
> 115.3
76.22 (71.1–80.9)
85.59 (77.9–91.4)
Average
0.912
> 116.7
85.34 (80.9–89.1)
83.05 (75.0–89.3)
Ratio
0.937
> 0.27
84.04 (79.5–88.0)
96.61 (91.5–99.1)
Blue average
0.905
> 130.7
79.15 (74.2–83.6)
93.22 (87.1–97.0)
Blue mode
0.872
> 128
68.73 (63.2–73.9)
88.98 (81.9–94.0)
SD
0.833
> 13.3
72.27 (67.0–77.1)
79.66 (71.3–86.5)
TABLE 3: Acoustic Structure Quantification Values, According to Patient Hormonal Status, for 437 Lobes From 234 Patients Parameter
No. of Lobes
Mean ± SD
95% CI
87
123.736 ± 11.5249
121.279–126.192
1b
55
116.919 ± 6.8883
115.057–118.781
2
185
114.243 ± 7.2774
113.187–115.299
3
110
122.596 ± 7.4314
121.192–124.000
All
437
118.572 ± 9.2701
117.701–119.444
Mode 1a
0.000
Average
0.000
1a
87
126.620 ± 10.3932
124.405–128.835
1b
55
120.415 ± 7.2188
118.463–122.366
2
185
116.785 ± 7.5347
115.692–117.877
3
110
125.181 ± 7.0707
123.844–126.517
All
437
121.313 ± 9.0783
120.459–122.166
87
1.1085 ± 0.87850
0.9213–1.2957
FD ratio 1a
0.000
1b
55
0.5935 ± 0.67784
0.4103–0.7768
2
185
0.3378 ± 0.52637
0.2614–0.4141
3
110
0.8406 ± 0.63763
0.7201–0.9611
All
437
0.6500 ± 0.72151
0.5821–0.7178
87
138.397 ± 14.3099
135.347–141.447
Blue mode 1a
p
0.000
1b
55
131.252 ± 13.0266
127.730–134.773
2
185
124.910 ± 11.7929
123.200–126.621
3
110
134.068 ± 10.2805
132.125–136.010
All
437
130.698 ± 13.2464
129.453–131.944
Blue average
0.000
1a
87
145.127 ± 17.9959
141.291–148.962
1b
55
137.307 ± 13.1324
133.757–140.857
2
185
128.704 ± 13.4934
126.747–130.662
3
110
139.137 ± 16.4026
136.038–142.237
All
437
135.683 ± 16.4664
134.135–137.231
Note—Two thyroid lobes affected by Hashimoto thyroiditis were diagnosed during surgery and were excluded from the statistical analysis because patient hormonal status was unavailable near the time of surgery. The mean values for each patient group were compared using one-way ANOVA, with the Tukey honestly significant difference test with multiple comparisons used as the post hoc test. 1a = overt hypothyroidism, 1b = subclinical hypothyroidism, 2 = euthyroid, 3 = hyperthyroid, FD = focal disturbance.
AJR:206, March 2016 605
A
B
108 Occurrence
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Park et al.
90 72 54 36 18 0
C
0
100 200 300 Modified Chi-Square Value (%)
D
Fig. 5—59-year-old woman with Hashimoto thyroiditis and euthyroid status. A–D, Ultrasound images of thyroid show diffuse low echogenicity with coarse heterogeneous echotexture (A and B). Parametric image (C) with ROI (yellow rectangle) shows numerous small red areas. Modified chi-square histogram (D) shows large blue curve, which represents large focal inhomogeneity. Thus, focal disturbance ratio is increased to 3.0.
roiditis from those without thyroiditis, with likelihood ratios of 24.7 for the ratio, 5.0 for the average, and 11.6 for the blue average. The ASQ values according to patient hormonal status are shown in Table 3. When the suggested cutoff values were used, the sensitivity and specificity for distinguishing patients with thyroiditis from euthyroid patients without thyroiditis were as follows: 77.05% and 94.92% for the ratio, 85.25% and 82.20% for the average, and 77.05% and 92.37% for the blue average, respectively. The intraclass correlation coefficient for obtaining ASQ values between two observers was very good (Cronbach α value: 0.921 for the mode, 0.972 for the average, 0.816 for the SD, 0.951 for the ratio, 0.845 for the blue mode, 0.915 for the blue average, and 0.767 for the blue SD). Discussion Thyroiditis is a generic term that describes a group of several common inflam-
606
matory conditions of the thyroid gland and is characterized by lymphocytic infiltration of the gland, leading to parenchymal destruction [3, 4]. Sonography is not generally required for the diagnosis of thyroiditis. However, HT is primarily a subclinical disease, and sonography can detect the subset of patients with HT before clinical signs are noted, when typical sonographic findings are present [18]. In addition, sonography plays a role in excluding focal thyroid disease and in assessing the size of the thyroid. Sonography is also used for the differentiation or characterization of thyroiditis or for the detection of a diffuse-infiltrating tumor. The conventional sonographic features of thyroiditis include decreased or increased diffuse heterogeneous parenchymal echogenicity, a coarse echotexture, micronodulation, and scattered microcalcifications [2, 6, 13, 14, 16]. Hypoechogenicity in the thyroid parenchyma is commonly reported in association with
HT [19, 20]. In addition, hypoechogenicity is also associated with overt hypothyroidism or subclinical hypothyroidism [19–21]. Hypoechogenicity with the elevation of the thyroid-stimulating hormone level could perhaps be observed as an early sign of thyroid failure [1, 19, 21]. The hypoechogenicity of micronodules results from massive infiltration by an exudate of lymphocytes and plasma cells [5]. Formation of fibrous strands around the lobules causes a hyperechoic ring around each micronodule, which increases the detectability of micronodules by sonography. Micronodulation is highly predictive of HT. Rosário et al. analyzed 117 patients with subclinical hypothyroidism (SCH) and reported that both diffuse hypoechogenicity on sonography and the presence of TPOAbs increased the risk of SCH developing into overt hypothyroidism [22]. The presence of chronic thyroiditis, as observed on sonographic images, increases the evolution of
AJR:206, March 2016
SCH to overt hypothyroidism or more severe SCH, necessitating treatment with levothyroxine. Sonographic findings are important in determining the prognosis of mild SCH. However, hypoechogenicity is a subjective finding and may be determined differently, depending on the operator or machine [1, 3, 23, 24]. ASQ provides a modified chi-square histogram, which represents the homogeneity within a selected ROI. In the present study, most of the ASQ values for patients with thyroiditis were significantly greater than those for patients with a normal thyroid gland. With the use of suggested cutoff values, ASQ could be used in our study as an objective measure with which to diagnose thyroiditis. ASQ can distinguish euthyroid patients with thyroiditis from patients with a normal thyroid gland and also shows high sensitivity and specificity. Greater ASQ values may reflect the histologic findings of thyroiditis, which are presented in the following subsections. Fibrosis Recent studies [9, 10] have shown that modified high chi-square values have a strong correlation with the grade of fibrosis in the liver. Fibrosis enhances both global and focal inhomogeneity of the liver. In the thyroid gland, fibrosis is the major pathologic finding of HT or Riedel thyroiditis [3, 25]. In the present study, thyroiditis was characterized by high modified chi-square values [9, 10, 14], which can reflect the histologic findings. In the liver, the degree of fibrosis is a good indicator of chronic hepatitis. Fibrosis increases heterogeneity of the liver parenchyma, and the peak chi-square value is also increased [9]. ASQ results are also significantly correlated with hepatic steatosis [8, 11]. Heterogeneous Hypoechogenic Areas Autoimmune thyroiditis is an organ-specific autoimmune disorder characterized by infiltration of the thyroid gland by lymphocytic inflammatory cells; it is often followed by hypothyroidism that results from the destruction and replacement of the follicular tissue [26]. The pathologic criteria associated with HT included a progressive loss of thyroid follicular cells, a concomitant replacement of the gland by lymphocytes, and the formation of germinal centers associated with fibrosis [26]. The mechanism underlying autoimmune destruction of the thyroid probably involves both cellular and humoral immunity [3]. Hayashi et al. [27] proposed that HT could be divided into two groups, group A (hy-
Fig. 6—Diagnostic performance of acoustic structure quantification values and AUC for differentiation of thyroiditis from normal thyroid gland. AUCs were as follows: 0.93 for ratio, 0.91 for average, 0.90 for blue average, 0.87 for mode, and 0.87 for blue mode, in descending order. Pairwise comparisons of ROC curves show statistically significant differences between ratio and average (p = 0.0580) and between ratio and blue average (p = 0.0437), whereas differences between average and blue average were not statistically significant (p = 0.6535).
100
80
Sensitivity (%)
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Acoustic Structure Quantification for Diagnosing Thyroiditis
60
40 Mode Average Ratio Blue average Blue mode SD
20
0 0
20
poechoic or isoechoic HT) and group B (echogenic HT), by comparing the echogenicity of the thyroid with that of the adjacent muscles. Histopathologically, most cases in group A showed severe degeneration and the disappearance of thyroid follicles, whereas normal-sized follicles were observed in most cases in group B. Hayashi and colleagues indicated that hypoechogenicity of the thyroid may suggest severe follicular degeneration. Sostre and Reyes [28] described and graded four distinct sonography patterns. Their grading system revealed a strong correlation between the degree of thyroid destruction and dysfunction, and grade 4 in their system may overlap with group A in the study by Hayashi and colleagues. Sonography can provide valuable information about the course of SCH and is also being used in the evaluation of thyroiditis in patients with thyroid functional abnormality, with the use of thyroid autoantibodies such as TPOAb and TgAb [5, 15, 18]. Lymphocytic parenchymal infiltration and follicular destruction result in fewer sound reflectors, accounting for the characteristic decreased echogenicity of the thyroid noted on sonography [27]. Finally, the thyroid gland appears to have inhomogeneous parenchyma due to multifocal heterogeneously distributed hypoechoic focuses. This results in an increased FD ratio. Increased Differences in the Echogenicity Between Affected Hypoechoic Parenchyma and Normal Hyperechoic Structures Even if all parts of the thyroid parenchyma become hypoechoic areas, an inhomo-
40 60 100 – Specificity (%)
80
100
geneous echotexture is still evident because there are many hyperechoic structures in the thyroid gland, such as the walls of the vessels or densely fibrotic septa. These normal persistent echogenic structures, regardless of thyroiditis, can contribute to high modified chi-square values. Our study had several limitations. For most patients included in the present study, diagnosis was based on the results of serologic tests. Therefore, the pathologic correlation of thyroiditis with ASQ values could not be evaluated. However, if thyroiditis was suspected clinically, testing for the presence of thyroid autoantibodies and assessment of serum levels of free thyroxine and thyroidstimulating hormone were usually sufficient to confirm the diagnosis. We did not compare the ASQ results with diagnosis of thyroiditis made on the basis of sonographic patterns. Our preliminary study showed a difference of approximately 9% between conventional ultrasound and ASQ in the diagnosis of thyroiditis. Patients were enrolled prospectively, and data were analyzed retrospectively. One radiologist with 24 years of experience in thyroid imaging performed all the examinations. Therefore, the rate of discrepancy between the ASQ results and the sonographic diagnosis of thyroiditis was small, and it may differ between operators. Further studies are required to perform comparisons between the two methods. In addition, the current study was a retrospective analysis of the reproducibility of ASQ imaging. Finally, patients who had previ-
AJR:206, March 2016 607
Park et al.
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ously received thyroid hormone replacement therapy were included. Conclusion ASQ can provide objective and quantitative noninvasive analyses of thyroid echogenicity. The results can be used as an objective guide to the differentiation of thyroiditis from a normal thyroid gland. ROC analysis showed that an FD ratio greater than 0.27 can differentiate between thyroiditis and a normal gland with a sensitivity of 84.0% and a specificity of 96.6%. ASQ is a promising and powerful tool that facilitates quantitative and qualitative noninvasive analyses of thyroiditis. References
1. Pedersen OM, Aardal NP, Larssen TB, Varhaug JE, Myking O, Vik-Mo H. The value of ultrasonography in predicting autoimmune thyroid disease. Thyroid 2000; 10:251–259 2. Vejbjerg P, Knudsen N, Perrild H, et al. The association between hypoechogenicity or irregular echo pattern at thyroid ultrasonography and thyroid function in the general population. Eur J Endocrinol 2006; 155:547–552 3. Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003; 348:2646–2655 4. Sholosh B, Borhani AA. Thyroid ultrasound. Part 1. Technique and diffuse disease. Radiol Clin North Am 2011; 49:391–416 5. Yeh HC, Futterweit W, Gilbert P. Micronodulation: ultrasonographic sign of Hashimoto thyroiditis. J Ultrasound Med 1996; 15:813–819 6. Kim I, Kim EK, Yoon JH, et al. Diagnostic role of conventional ultrasonography and shearwave elastography in asymptomatic patients with diffuse thyroid disease: initial experience with 57 patients. Yonsei Med J 2014; 55:247–253 7. Wakita Y, Nagasaki T, Nagata Y, et al. Thyroid heterogeneity, as indicated by the CV of ultrasonographic intensities, correlates with anti-thyroid
608
peroxidase antibodies in euthyroid Hashimoto’s thyroiditis. Thyroid Res 2013; 6:5 8. Kuroda H, Kakisaka K, Kamiyama N, et al. Non-invasive determination of hepatic steatosis by acoustic structure quantification from ultrasound echo amplitude. World J Gastroenterol 2012; 18:3889–3895 9. Toyoda H, Kumada T, Kamiyama N, et al. B-mode ultrasound with algorithm based on statistical analysis of signals: evaluation of liver fibrosis in patients with chronic hepatitis C. AJR 2009; 193:1037–1043 10. Ricci P, Marigliano C, Cantisani V, et al. Ultrasound evaluation of liver fibrosis: preliminary experience with acoustic structure quantification (ASQ) software. Radiol Med 2013; 118:995–1010 11. Onodera M. The new non-invasive quantification of hepatic steatosis with morbid obesity by acoustic structure quantification (ASQ) from ultrasound echo amplitude. Ultrasound Med Biol 2013; 39:S2 12. Zandieh S, Bernt R, Zwerina J, et al. Acoustic structure quantification analysis of the thyroid in patients with diffuse autoimmune thyroid disease. Ultrason Imaging 2015; 8:1–11 13. Tuthill TA, Sperry RH, Parker KJ. Deviations from Rayleigh statistics in ultrasonic speckle. Ultrason Imaging 1988; 10:81–89 14. Yamada H, Ebara M, Yamaguchi T, et al. A pilot approach for quantitative assessment of liver fibrosis using ultrasound: preliminary results in 79 cases. J Hepatol 2006; 44:68–75 15. Burckhardt CB. Speckle in ultrasound B-mode scans. IEEE Transactions on Sonics and Ultrasonics 1978; 25:1–6 16. Yamaguchi T, Hachiya H, Kamiyama N, Ikeda K, Moriyasu N. Estimation of characteristics of echo envelope using RF echo signal from the liver. Jpn J Appl Phys 2001; 40:3900–3904 17. Yamaguchi T, Hachiya H, Kamiyama N, Moriyasu F. Examination of the spatial correlation of statistics information in the ultrasonic echo from diseased liver. Jpn J Appl Phys 2002; 41:3585–3589 18. Rapoport B. Pathophysiology of Hashimoto’s thy-
roiditis and hypothyroidism. Annu Rev Med 1991; 42:91–96 19. Loy M, Cianchetti ME, Cardia F, Melis A, Boi F, Mariotti S. Correlation of computerized grayscale sonographic findings with thyroid function and thyroid autoimmune activity in patients with Hashimoto’s thyroiditis. J Clin Ultrasound 2004; 32:136–140 20. Marcocci C, Vitti P, Cetani F, Catalano F, Concetti R, Pinchera A. Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism. J Clin Endocrinol Metab 1991; 72:209–213 21. Schiemann U, Avenhaus W, Konturek JW, Gellner R, Hengst K, Gross M. Relationship of clinical features and laboratory parameters to thyroid echogenicity measured by standardized grey scale ultrasonography in patients with Hashimoto’s thyroiditis. Med Sci Monit 2003; 9:MT13–MT17 22. Rosário PW, Bessa B, Valadão MM, Purisch S. Natural history of mild subclinical hypothyroidism: prognostic value of ultrasound. Thyroid 2009; 19:9–12 23. Lai SM, Chang TC, Chang CC, Kuo SH, Chen FW. Sonographic presentation in autoimmune thyroiditis. J Formos Med Assoc 1990; 89:1057–1062 24. Nordmeyer JP, Shafeh TA, Heckmann C. Thyroid sonography in autoimmune thyroiditis: a prospective study on 123 patients. Acta Endocrinol (Copenh) 1990; 122:391–395 25. Harach HR, Williams ED. Fibrous thyroiditis: an immunopathological study. Histopathology 1983; 7:739–751 26. Burek CL. Autoimmune thyroiditis research at Johns Hopkins University. Immunol Res 2010; 47:207–215 27. Hayashi N, Tamaki N, Konishi J, et al. Sonography of Hashimoto’s thyroiditis. J Clin U ltrasound 1986; 14:123–126 28. Sostre S, Reyes MM. Sonographic diagnosis and grading of Hashimoto’s thyroiditis. J Endocrinol Invest 1991; 14:115–121
AJR:206, March 2016
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Neuroradiology/Head and Neck Imaging Original Research
Investigation of Acoustic Structure Quantification in the Diagnosis of Thyroiditis Jisang Park1 Hyun Sook Hong1 Chul-Hee Kim 2 Eun Hye Lee1 Sun Hye Jeong1 A. Leum Lee1 Heon Lee1 Park J, Hong HS, Kim CH, et al.
Keywords: acoustic structure quantification, hypothyroidism, thyroid gland, thyroiditis, ultrasonography DOI:10.2214/AJR.15.14586 Received February 24, 2015; accepted after revision July 6, 2015. 1 Department of Radiology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-767, Korea. Address correspondence to H. S. Hong ([email protected]). 2 Division of Endocrinology and Metabolism, epartment of Internal Medicine, Soonchunhyang D University Bucheon Hospital, Bucheon-si, Gyeonggi-do, Korea.
AJR 2016; 206:601–608 0361–803X/16/2063–601 © American Roentgen Ray Society
OBJECTIVE. The objective of this study was to evaluate the ability of acoustic structure quantification (ASQ) to diagnose thyroiditis. MATERIALS AND METHODS. The echogenicity of 439 thyroid lobes, as determined using ASQ, was quantified and analyzed retrospectively. Thyroiditis was categorized into five subgroups. The results were presented in a modified chi-square histogram as the mode, average, ratio, blue mode, and blue average. We determined the cutoff values of ASQ from ROC analysis to detect and differentiate thyroiditis from a normal thyroid gland. We obtained data on the sensitivity and specificity of the cutoff values to distinguish between euthyroid patients with thyroiditis and patients with a normal thyroid gland. RESULTS. The mean ASQ values for patients with thyroiditis were statistically significantly greater than those for patients with a normal thyroid gland (p 130.7) were successful in distinguishing patients with thy-
TABLE 2: Performance of Acoustic Structure Quantification Values and AUCs in the Diagnostic Differentiation of Thyroiditis From Normal Thyroid Gland Parameter Mode
AUC
Criterion (Maximal AUC to Diagnose as Thyroiditis)
Sensitivity (%), Mean (95% CI)
Specificity (%), Mean (95% CI)
0.872
> 115.3
76.22 (71.1–80.9)
85.59 (77.9–91.4)
Average
0.912
> 116.7
85.34 (80.9–89.1)
83.05 (75.0–89.3)
Ratio
0.937
> 0.27
84.04 (79.5–88.0)
96.61 (91.5–99.1)
Blue average
0.905
> 130.7
79.15 (74.2–83.6)
93.22 (87.1–97.0)
Blue mode
0.872
> 128
68.73 (63.2–73.9)
88.98 (81.9–94.0)
SD
0.833
> 13.3
72.27 (67.0–77.1)
79.66 (71.3–86.5)
TABLE 3: Acoustic Structure Quantification Values, According to Patient Hormonal Status, for 437 Lobes From 234 Patients Parameter
No. of Lobes
Mean ± SD
95% CI
87
123.736 ± 11.5249
121.279–126.192
1b
55
116.919 ± 6.8883
115.057–118.781
2
185
114.243 ± 7.2774
113.187–115.299
3
110
122.596 ± 7.4314
121.192–124.000
All
437
118.572 ± 9.2701
117.701–119.444
Mode 1a
0.000
Average
0.000
1a
87
126.620 ± 10.3932
124.405–128.835
1b
55
120.415 ± 7.2188
118.463–122.366
2
185
116.785 ± 7.5347
115.692–117.877
3
110
125.181 ± 7.0707
123.844–126.517
All
437
121.313 ± 9.0783
120.459–122.166
87
1.1085 ± 0.87850
0.9213–1.2957
FD ratio 1a
0.000
1b
55
0.5935 ± 0.67784
0.4103–0.7768
2
185
0.3378 ± 0.52637
0.2614–0.4141
3
110
0.8406 ± 0.63763
0.7201–0.9611
All
437
0.6500 ± 0.72151
0.5821–0.7178
87
138.397 ± 14.3099
135.347–141.447
Blue mode 1a
p
0.000
1b
55
131.252 ± 13.0266
127.730–134.773
2
185
124.910 ± 11.7929
123.200–126.621
3
110
134.068 ± 10.2805
132.125–136.010
All
437
130.698 ± 13.2464
129.453–131.944
Blue average
0.000
1a
87
145.127 ± 17.9959
141.291–148.962
1b
55
137.307 ± 13.1324
133.757–140.857
2
185
128.704 ± 13.4934
126.747–130.662
3
110
139.137 ± 16.4026
136.038–142.237
All
437
135.683 ± 16.4664
134.135–137.231
Note—Two thyroid lobes affected by Hashimoto thyroiditis were diagnosed during surgery and were excluded from the statistical analysis because patient hormonal status was unavailable near the time of surgery. The mean values for each patient group were compared using one-way ANOVA, with the Tukey honestly significant difference test with multiple comparisons used as the post hoc test. 1a = overt hypothyroidism, 1b = subclinical hypothyroidism, 2 = euthyroid, 3 = hyperthyroid, FD = focal disturbance.
AJR:206, March 2016 605
A
B
108 Occurrence
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Park et al.
90 72 54 36 18 0
C
0
100 200 300 Modified Chi-Square Value (%)
D
Fig. 5—59-year-old woman with Hashimoto thyroiditis and euthyroid status. A–D, Ultrasound images of thyroid show diffuse low echogenicity with coarse heterogeneous echotexture (A and B). Parametric image (C) with ROI (yellow rectangle) shows numerous small red areas. Modified chi-square histogram (D) shows large blue curve, which represents large focal inhomogeneity. Thus, focal disturbance ratio is increased to 3.0.
roiditis from those without thyroiditis, with likelihood ratios of 24.7 for the ratio, 5.0 for the average, and 11.6 for the blue average. The ASQ values according to patient hormonal status are shown in Table 3. When the suggested cutoff values were used, the sensitivity and specificity for distinguishing patients with thyroiditis from euthyroid patients without thyroiditis were as follows: 77.05% and 94.92% for the ratio, 85.25% and 82.20% for the average, and 77.05% and 92.37% for the blue average, respectively. The intraclass correlation coefficient for obtaining ASQ values between two observers was very good (Cronbach α value: 0.921 for the mode, 0.972 for the average, 0.816 for the SD, 0.951 for the ratio, 0.845 for the blue mode, 0.915 for the blue average, and 0.767 for the blue SD). Discussion Thyroiditis is a generic term that describes a group of several common inflam-
606
matory conditions of the thyroid gland and is characterized by lymphocytic infiltration of the gland, leading to parenchymal destruction [3, 4]. Sonography is not generally required for the diagnosis of thyroiditis. However, HT is primarily a subclinical disease, and sonography can detect the subset of patients with HT before clinical signs are noted, when typical sonographic findings are present [18]. In addition, sonography plays a role in excluding focal thyroid disease and in assessing the size of the thyroid. Sonography is also used for the differentiation or characterization of thyroiditis or for the detection of a diffuse-infiltrating tumor. The conventional sonographic features of thyroiditis include decreased or increased diffuse heterogeneous parenchymal echogenicity, a coarse echotexture, micronodulation, and scattered microcalcifications [2, 6, 13, 14, 16]. Hypoechogenicity in the thyroid parenchyma is commonly reported in association with
HT [19, 20]. In addition, hypoechogenicity is also associated with overt hypothyroidism or subclinical hypothyroidism [19–21]. Hypoechogenicity with the elevation of the thyroid-stimulating hormone level could perhaps be observed as an early sign of thyroid failure [1, 19, 21]. The hypoechogenicity of micronodules results from massive infiltration by an exudate of lymphocytes and plasma cells [5]. Formation of fibrous strands around the lobules causes a hyperechoic ring around each micronodule, which increases the detectability of micronodules by sonography. Micronodulation is highly predictive of HT. Rosário et al. analyzed 117 patients with subclinical hypothyroidism (SCH) and reported that both diffuse hypoechogenicity on sonography and the presence of TPOAbs increased the risk of SCH developing into overt hypothyroidism [22]. The presence of chronic thyroiditis, as observed on sonographic images, increases the evolution of
AJR:206, March 2016
SCH to overt hypothyroidism or more severe SCH, necessitating treatment with levothyroxine. Sonographic findings are important in determining the prognosis of mild SCH. However, hypoechogenicity is a subjective finding and may be determined differently, depending on the operator or machine [1, 3, 23, 24]. ASQ provides a modified chi-square histogram, which represents the homogeneity within a selected ROI. In the present study, most of the ASQ values for patients with thyroiditis were significantly greater than those for patients with a normal thyroid gland. With the use of suggested cutoff values, ASQ could be used in our study as an objective measure with which to diagnose thyroiditis. ASQ can distinguish euthyroid patients with thyroiditis from patients with a normal thyroid gland and also shows high sensitivity and specificity. Greater ASQ values may reflect the histologic findings of thyroiditis, which are presented in the following subsections. Fibrosis Recent studies [9, 10] have shown that modified high chi-square values have a strong correlation with the grade of fibrosis in the liver. Fibrosis enhances both global and focal inhomogeneity of the liver. In the thyroid gland, fibrosis is the major pathologic finding of HT or Riedel thyroiditis [3, 25]. In the present study, thyroiditis was characterized by high modified chi-square values [9, 10, 14], which can reflect the histologic findings. In the liver, the degree of fibrosis is a good indicator of chronic hepatitis. Fibrosis increases heterogeneity of the liver parenchyma, and the peak chi-square value is also increased [9]. ASQ results are also significantly correlated with hepatic steatosis [8, 11]. Heterogeneous Hypoechogenic Areas Autoimmune thyroiditis is an organ-specific autoimmune disorder characterized by infiltration of the thyroid gland by lymphocytic inflammatory cells; it is often followed by hypothyroidism that results from the destruction and replacement of the follicular tissue [26]. The pathologic criteria associated with HT included a progressive loss of thyroid follicular cells, a concomitant replacement of the gland by lymphocytes, and the formation of germinal centers associated with fibrosis [26]. The mechanism underlying autoimmune destruction of the thyroid probably involves both cellular and humoral immunity [3]. Hayashi et al. [27] proposed that HT could be divided into two groups, group A (hy-
Fig. 6—Diagnostic performance of acoustic structure quantification values and AUC for differentiation of thyroiditis from normal thyroid gland. AUCs were as follows: 0.93 for ratio, 0.91 for average, 0.90 for blue average, 0.87 for mode, and 0.87 for blue mode, in descending order. Pairwise comparisons of ROC curves show statistically significant differences between ratio and average (p = 0.0580) and between ratio and blue average (p = 0.0437), whereas differences between average and blue average were not statistically significant (p = 0.6535).
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Acoustic Structure Quantification for Diagnosing Thyroiditis
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40 Mode Average Ratio Blue average Blue mode SD
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poechoic or isoechoic HT) and group B (echogenic HT), by comparing the echogenicity of the thyroid with that of the adjacent muscles. Histopathologically, most cases in group A showed severe degeneration and the disappearance of thyroid follicles, whereas normal-sized follicles were observed in most cases in group B. Hayashi and colleagues indicated that hypoechogenicity of the thyroid may suggest severe follicular degeneration. Sostre and Reyes [28] described and graded four distinct sonography patterns. Their grading system revealed a strong correlation between the degree of thyroid destruction and dysfunction, and grade 4 in their system may overlap with group A in the study by Hayashi and colleagues. Sonography can provide valuable information about the course of SCH and is also being used in the evaluation of thyroiditis in patients with thyroid functional abnormality, with the use of thyroid autoantibodies such as TPOAb and TgAb [5, 15, 18]. Lymphocytic parenchymal infiltration and follicular destruction result in fewer sound reflectors, accounting for the characteristic decreased echogenicity of the thyroid noted on sonography [27]. Finally, the thyroid gland appears to have inhomogeneous parenchyma due to multifocal heterogeneously distributed hypoechoic focuses. This results in an increased FD ratio. Increased Differences in the Echogenicity Between Affected Hypoechoic Parenchyma and Normal Hyperechoic Structures Even if all parts of the thyroid parenchyma become hypoechoic areas, an inhomo-
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geneous echotexture is still evident because there are many hyperechoic structures in the thyroid gland, such as the walls of the vessels or densely fibrotic septa. These normal persistent echogenic structures, regardless of thyroiditis, can contribute to high modified chi-square values. Our study had several limitations. For most patients included in the present study, diagnosis was based on the results of serologic tests. Therefore, the pathologic correlation of thyroiditis with ASQ values could not be evaluated. However, if thyroiditis was suspected clinically, testing for the presence of thyroid autoantibodies and assessment of serum levels of free thyroxine and thyroidstimulating hormone were usually sufficient to confirm the diagnosis. We did not compare the ASQ results with diagnosis of thyroiditis made on the basis of sonographic patterns. Our preliminary study showed a difference of approximately 9% between conventional ultrasound and ASQ in the diagnosis of thyroiditis. Patients were enrolled prospectively, and data were analyzed retrospectively. One radiologist with 24 years of experience in thyroid imaging performed all the examinations. Therefore, the rate of discrepancy between the ASQ results and the sonographic diagnosis of thyroiditis was small, and it may differ between operators. Further studies are required to perform comparisons between the two methods. In addition, the current study was a retrospective analysis of the reproducibility of ASQ imaging. Finally, patients who had previ-
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ously received thyroid hormone replacement therapy were included. Conclusion ASQ can provide objective and quantitative noninvasive analyses of thyroid echogenicity. The results can be used as an objective guide to the differentiation of thyroiditis from a normal thyroid gland. ROC analysis showed that an FD ratio greater than 0.27 can differentiate between thyroiditis and a normal gland with a sensitivity of 84.0% and a specificity of 96.6%. ASQ is a promising and powerful tool that facilitates quantitative and qualitative noninvasive analyses of thyroiditis. References
1. Pedersen OM, Aardal NP, Larssen TB, Varhaug JE, Myking O, Vik-Mo H. The value of ultrasonography in predicting autoimmune thyroid disease. Thyroid 2000; 10:251–259 2. Vejbjerg P, Knudsen N, Perrild H, et al. The association between hypoechogenicity or irregular echo pattern at thyroid ultrasonography and thyroid function in the general population. Eur J Endocrinol 2006; 155:547–552 3. Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003; 348:2646–2655 4. Sholosh B, Borhani AA. Thyroid ultrasound. Part 1. Technique and diffuse disease. Radiol Clin North Am 2011; 49:391–416 5. Yeh HC, Futterweit W, Gilbert P. Micronodulation: ultrasonographic sign of Hashimoto thyroiditis. J Ultrasound Med 1996; 15:813–819 6. Kim I, Kim EK, Yoon JH, et al. Diagnostic role of conventional ultrasonography and shearwave elastography in asymptomatic patients with diffuse thyroid disease: initial experience with 57 patients. Yonsei Med J 2014; 55:247–253 7. Wakita Y, Nagasaki T, Nagata Y, et al. Thyroid heterogeneity, as indicated by the CV of ultrasonographic intensities, correlates with anti-thyroid
608
peroxidase antibodies in euthyroid Hashimoto’s thyroiditis. Thyroid Res 2013; 6:5 8. Kuroda H, Kakisaka K, Kamiyama N, et al. Non-invasive determination of hepatic steatosis by acoustic structure quantification from ultrasound echo amplitude. World J Gastroenterol 2012; 18:3889–3895 9. Toyoda H, Kumada T, Kamiyama N, et al. B-mode ultrasound with algorithm based on statistical analysis of signals: evaluation of liver fibrosis in patients with chronic hepatitis C. AJR 2009; 193:1037–1043 10. Ricci P, Marigliano C, Cantisani V, et al. Ultrasound evaluation of liver fibrosis: preliminary experience with acoustic structure quantification (ASQ) software. Radiol Med 2013; 118:995–1010 11. Onodera M. The new non-invasive quantification of hepatic steatosis with morbid obesity by acoustic structure quantification (ASQ) from ultrasound echo amplitude. Ultrasound Med Biol 2013; 39:S2 12. Zandieh S, Bernt R, Zwerina J, et al. Acoustic structure quantification analysis of the thyroid in patients with diffuse autoimmune thyroid disease. Ultrason Imaging 2015; 8:1–11 13. Tuthill TA, Sperry RH, Parker KJ. Deviations from Rayleigh statistics in ultrasonic speckle. Ultrason Imaging 1988; 10:81–89 14. Yamada H, Ebara M, Yamaguchi T, et al. A pilot approach for quantitative assessment of liver fibrosis using ultrasound: preliminary results in 79 cases. J Hepatol 2006; 44:68–75 15. Burckhardt CB. Speckle in ultrasound B-mode scans. IEEE Transactions on Sonics and Ultrasonics 1978; 25:1–6 16. Yamaguchi T, Hachiya H, Kamiyama N, Ikeda K, Moriyasu N. Estimation of characteristics of echo envelope using RF echo signal from the liver. Jpn J Appl Phys 2001; 40:3900–3904 17. Yamaguchi T, Hachiya H, Kamiyama N, Moriyasu F. Examination of the spatial correlation of statistics information in the ultrasonic echo from diseased liver. Jpn J Appl Phys 2002; 41:3585–3589 18. Rapoport B. Pathophysiology of Hashimoto’s thy-
roiditis and hypothyroidism. Annu Rev Med 1991; 42:91–96 19. Loy M, Cianchetti ME, Cardia F, Melis A, Boi F, Mariotti S. Correlation of computerized grayscale sonographic findings with thyroid function and thyroid autoimmune activity in patients with Hashimoto’s thyroiditis. J Clin Ultrasound 2004; 32:136–140 20. Marcocci C, Vitti P, Cetani F, Catalano F, Concetti R, Pinchera A. Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism. J Clin Endocrinol Metab 1991; 72:209–213 21. Schiemann U, Avenhaus W, Konturek JW, Gellner R, Hengst K, Gross M. Relationship of clinical features and laboratory parameters to thyroid echogenicity measured by standardized grey scale ultrasonography in patients with Hashimoto’s thyroiditis. Med Sci Monit 2003; 9:MT13–MT17 22. Rosário PW, Bessa B, Valadão MM, Purisch S. Natural history of mild subclinical hypothyroidism: prognostic value of ultrasound. Thyroid 2009; 19:9–12 23. Lai SM, Chang TC, Chang CC, Kuo SH, Chen FW. Sonographic presentation in autoimmune thyroiditis. J Formos Med Assoc 1990; 89:1057–1062 24. Nordmeyer JP, Shafeh TA, Heckmann C. Thyroid sonography in autoimmune thyroiditis: a prospective study on 123 patients. Acta Endocrinol (Copenh) 1990; 122:391–395 25. Harach HR, Williams ED. Fibrous thyroiditis: an immunopathological study. Histopathology 1983; 7:739–751 26. Burek CL. Autoimmune thyroiditis research at Johns Hopkins University. Immunol Res 2010; 47:207–215 27. Hayashi N, Tamaki N, Konishi J, et al. Sonography of Hashimoto’s thyroiditis. J Clin U ltrasound 1986; 14:123–126 28. Sostre S, Reyes MM. Sonographic diagnosis and grading of Hashimoto’s thyroiditis. J Endocrinol Invest 1991; 14:115–121
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