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Thymic Measurements in Pathologically Proven Normal Thymus and Thymic Hyperplasia

Rationale and Objectives

To determine the intraobserver and interobserver variabilities of thymic measurements on computed tomography (CT) in patients with pathologic diagnosis of thymic hyperplasia or normal thymus.

Materials and Methods

Thirty-three patients with pathologic diagnosis of thymic hyperplasia ( n = 25) or normal thymus ( n = 8) who had identifiable thymus gland on CT were retrospectively studied. Two radiologists independently measured thymic size and CT attenuation. Concordance correlation coefficients (CCCs) and Bland–Altman plots were used to assess intraobserver and interobserver agreements.

Results

The intraobserver and interobserver agreements of thymic diameters and the lobe length were moderate, with CCCs ranging from 0.73 to 0.89 and from 0.72 to 0.81, respectively. Higher agreement was noted among patients whose measurements were performed on the same CT image in two independent measurements, with intraobserver CCC ≥ 0.95 for diameters and length. After providing readers with an instruction for consistent selection of CT image for measurements, the intraobserver and interobserver agreements improved, resulting in CCCs ranging from 0.81 to 0.92 and from 0.77 to 0.85 for diameters and length, respectively. Thymic lobe thickness had the least agreement. CT attenuation measurements were highly reproducible, with CCCs ranging from 0.88 to 0.97. In patients with thymic CT attenuation >30 HU (Hounsfield unit), the attenuation measurements were more reproducible with narrower 95% limits of agreement.

Conclusions

Thymic size measurements had moderate-to-high intraobserver and interobserver agreements, when the instruction for consistent selection of images was provided to the readers. CT attenuation was highly reproducible, with higher reproducibility for thymic glands with >30 HU. Awareness of thymic measurement variability is necessary when interpreting measured values of normal thymus and thymic pathology on CT.

Thymus demonstrates unique morphologic transition according to age, reaching its maximum weight at puberty and subsequently undergoing “involution”, which is defined as a decrease in size and weight with advancing age . The assessment of thymic size on imaging in relation to patient’s age is an important component of radiologic interpretation of thymus glands and thymic pathology. Measurements of normal and abnormal thymus glands using computed tomography (CT) were extensively studied in early 1980s . Baron et al. studied 154 patients without clinical basis to suspect thymic abnormality, who underwent chest CT, and described width, thickness, and attenuation of the normal thymus in different age groups ranging from 6 to >50 years. Francis et al. revisited the age-related changes of thymic size in 309 patients without clinical evidence of thymic abnormality and 23 patients with thymic abnormalities and described transverse and anterior–posterior (AP) diameters, craniocaudal extent, and thickness of thymus gland in each age group. As demonstrated by these earlier studies, given the unique feature of involution over time, thymic measurements should be interpreted relative to the “normal” measurement values in the corresponding age group of patients.

Ackman et al. recently studied the AP diameter, lobe thickness, CT attenuation, and morphologic features of thymus in subjects who were aged 20–30 years and have presumably normal thymus and reported that the thymus gland had significantly higher attenuation and more commonly had quadrilateral shape in women compared to men. In our previous study of 31 patients with pathologically proven thymic hyperplasia, the size of the thymic gland with hyperplasia was significantly larger compared to the age-matched mean values of normal thymus . The study also demonstrated that the thymic CT attenuation >41.2 HU (Hounsfield unit) on contrast-enhanced CT is suggestive of lymphoid hyperplasia rather than true hyperplasia. The size and the CT attenuation of thymic gland are important factors to define “normal” thymus and to diagnose thymic pathology .

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Materials and methods

Subjects

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Initial Sets of Thymic Measurements

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Figure 1, Thymic size measurements including length, thickness, and transverse and anterior–posterior (AP) diameters. With modification from Reference 10 (Araki T, Sholl LM, Gerbaudo VH, Hatabu H, Nishino M. Imaging characteristics of pathologically proven thymic hyperplasia: identifying features that can differentiate true from lymphoid hyperplasia. AJR American Journal of Roentgenology 2014; 202:471-478).

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Second Sets of Measurements after Providing the Instruction for CT Image Selection

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Statistical Analysis

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Results

Intraobserver and Interobserver Variabilities of the Initial Sets of Measurements

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Table 1

Intraobserver Variability of Thymic Measurements: The First Set of Measurements

Thymic Measurements Intraobserver CCC (95% CI) Mean Relative Difference (mm) 95% Limits of Agreement (mm) Transverse diameter 0.73 (0.53–0.85) −2.6 −19.4 to 14.1 AP diameter 0.80 (0.63–0.89) −0.3 −20.5 to 19.9 Right lobe length 0.89 (0.79–0.94) −1.8 −12.7 to 9.1 Left lobe length 0.76 (0.57–0.87) −1.9 −23.1 to 19.2 Right lobe thickness 0.61 (0.35–0.78) 0.7 −11.2 to 12.6 Left lobe thickness 0.65 (0.41–0.81) 0.2 −9.0 to 9.3 CT attenuation 0.91 (0.82–0.95) 4.5 (HU) −24.5 to 33.4 (HU)

AP, anterior–posterior; CCC, concordance correlation coefficient; CI, confidence interval; CT, computed tomography; HU, Hounsfield unit.

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Table 2

Interobserver Variability of Thymic Measurements: The Second Sets of Measurements

Thymic Measurements Interobserver CCC (95% CI) Mean Relative Difference (mm) 95% Limits of Agreement (mm) Transverse diameter 0.81 (0.66–0.90) −1.2 −14.6 to 12.2 AP diameter 0.72 (0.52–0.85) −1.3 −24.8 to 22.2 Right lobe length 0.80 (0.66–0.89) −5.9 −17.0 to 5.1 Left lobe length 0.73 (0.53–0.85) 0.2 −21.9 to 22.4 Right lobe thickness 0.56 (0.29–0.75) −2.8 −16.6 to 11.0 Left lobe thickness 0.59 (0.34–0.76) −2.1 −12.6 to 8.4 CT attenuation 0.90 (0.80–0.95) 0.1 (HU) −31.7 to 31.8 (HU)

AP, anterior–posterior; CCC, concordance correlation coefficient; CI, confidence interval; CT, computed tomography; HU, Hounsfield unit.

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Variability and the Selection of Representative CT Image for Measurement

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Table 3

Intraobserver Variability of Thymic Measurements in Matched and Unmatched CT Image Slice for Measurements

Thymic Measurements Sixteen Patients Measured on the Same Image Seventeen Patients Measured on the Different Images Interobserver CCC (95% CI) Mean Relative Difference (mm) 95% Limits of Agreement (mm) Interobserver CCC (95% CI) Mean Relative Difference (mm) 95% Limits of Agreement (mm) Transverse diameter 0.95 (0.87–0.98) −1.5 −8.8 to 5.8 0.52 (0.14–0.76) −3.7 −26.1 to 18.7 AP diameter 0.99 (0.96–1.00) −0.9 −6.3 to 4.4 0.47 (0.07–0.74) 0.3 −27.8 to 28.4 Right lobe length 0.96 (0.90–0.99) −1.4 −7.7 to 4.8 0.80 (0.54–0.92) −2.1 −16.4 to 12.2 Left lobe length 0.97 (0.93–0.99) −2.8 −8.1 to 2.5 0.47 (0.04–0.76) −1.1 −30.5 to 28.3 Right lobe thickness 0.76 (0.48–0.90) −0.2 −10.7 to 10.3 0.36 (−0.11 to 0.70) 1.6 −11.7 to 14.9 Left lobe thickness 0.80 (0.53–0.93) −0.8 −8.1 to 6.6 0.48 (0.04–0.76) 1.1 −9.4 to 11.6 CT attenuation 0.99 (0.98–1.00) 0.6 (HU) −6.9 to 8.1 (HU) 0.86 (0.66–0.94) 8.1 (HU) −30.7 to 46.9 (HU)

AP, anterior–posterior; CCC, concordance correlation coefficient; CI, confidence interval; CT, computed tomography; HU, Hounsfield unit.

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Intraobserver and Interobserver Variabilities of the Second Sets of Measurements

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Table 4

Intraobserver Variability of Thymic Measurements: The Second Set of Measurements

Thymic Measurements Intraobserver CCC (95% CI) Mean Relative Difference (mm) 95% Limits of Agreement (mm) Transverse diameter 0.81 (0.66–0.90) 0.2 −14.5 to 15.0 AP diameter 0.85 (0.72–0.92) 2.6 −12.6 to 17.8 Right lobe length 0.92 (0.84–0.96) −0.2 −10.7 to 10.2 Left lobe length 0.92 (0.85–0.96) 1.6 −9.7 to 12.9 Right lobe thickness 0.91 (0.82–0.95) −0.2 −5.3 to 4.9 Left lobe thickness 0.83 (0.70–0.91) 0.2 −6.3 to 6.7 CT attenuation 0.97 (0.94–0.99) 0.9 (HU) −16.1 to 18.0 (HU)

AP, anterior–posterior; CCC, concordance correlation coefficient; CI, confidence interval; CT, computed tomography; HU, Hounsfield unit.

Table 5

Interobserver Variability of Thymic Measurements: The Second Set of Measurements

Thymic Measurements Interobserver CCC (95% CI) Mean Relative Difference (mm) 95% Limits of Agreement (mm) Transverse diameter 0.78 (0.61–0.89) 0.2 −17.0 to 17.4 AP diameter 0.77 (0.58–0.88) 2.8 −17.7 to 23.2 Right lobe length 0.85 (0.72–0.92) −0.2 −14.5 to 14.2 Left lobe length 0.82 (0.68–0.91) 0.7 −18.7 to 20.0 Right lobe thickness 0.80 (0.64–0.89) −1.2 −9.2 to 6.9 Left lobe thickness 0.57 (0.29–0.76) 0.1 −11.0 to 11.2 CT attenuation 0.88 (0.78–0.94) −2.9 (HU) −38.4 to 32.5 (HU)

AP, anterior–posterior; CCC, concordance correlation coefficient; CI, confidence interval; CT, computed tomography; HU, Hounsfield unit.

Figure 2 (a-g), Bland–Altman plots demonstrating intraobserver variability of the second set of thymic measurements after providing the instruction for computed tomographic image selection. (Measurements of right lobe length and thickness (c, e) were performed in 32 cases, excluding one patient with round thymus gland located in the left side of the anterior mediastinum, which was considered to represent the left lobe.)

Figure 3 (a-g), Bland–Altman plots demonstrating interobserver variability of the second set of thymic measurements after providing the instruction for computed tomographic image selection. (Measurements of right lobe length and thickness (c, e) were performed in 32 cases, excluding one patient with round thymus gland located in the left side of the anterior mediastinum, which was considered to represent the left lobe.)

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Discussion

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