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Volume-Doubling Time of Pulmonary Nodules with Ground Glass Opacity at Multide tector CT

Rationale and Objectives

To investigate the volume-doubling time (VDT) of histologically proved pulmonary nodules showing ground glass opacity (GGO) at multidetector CT (MDCT) using computer-aided three-dimensional volumetry.

Materials and Methods

We retrospectively evaluated 47 GGO nodules (mixed n = 28, pure n = 19) that had been examined by thin-section helical CT more than once. They were histologically confirmed as atypical adenomatous hyperplasia (AAH, n = 13), bronchioloalveolar carcinoma (BAC, n = 22), and adenocarcinoma (AC, n = 12). Using computer-aided three-dimensional volumetry software, two radiologists independently performed volumetry of GGO nodules and calculated the VDT using data acquired from the initial and final CT study. We compared VDT among the three pathologies and also compared the VDT of mixed and pure GGO nodules.

Results

The mean VDT of all GGO nodules was 486.4 ± 368.6 days (range 89.0–1583.0 days). The mean VDT for AAH, BAC, and AC was 859.2 ± 428.9, 421.2 ± 228.4, and 202.1 ± 84.3 days, respectively; there were statistically significant differences for all comparative combinations of AAH, BAC, and AC (Steel-Dwass test, P < .01). The mean VDT for pure and mixed GGO nodules was 628.5 ± 404.2 and 276.9 ± 155.9 days, respectively; it was significantly shorter for mixed than pure GGO nodules (Mann-Whitney U-test, P < .01).

Conclusion

The evaluation of VDT using computer-aided volumetry may be helpful in assessing the histological entities of GGO nodules.

The introduction of computed tomography (CT) lung cancer screening has increased the number of detected ground glass opacity (GGO) nodules. Henschke et al reported that 44 (19%) of 233 positive results were lesions with GGO nodules; 15 (34%) of the 44 lesions were malignant. Among lesions with a solid component (mixed GGO nodules), 63% were malignant, nodules without solid components (pure GGO nodules) had a lower malignancy rate (18%). GGO nodules may be attributable to focal inflammation, focal interstitial fibrosis , atypical adenomatous hyperplasia (AAH) , bronchioloalveolar carcinoma (BAC) , or adenocarcinoma (AC) . Although the differentiation of BAC and AC, which are malignant, from other diseases is important, it can be difficult on a single CT study . Many inflammatory lesions resolve spontaneously or with antibiotic treatment , on the other hand, the size of GGO nodules attributable to BAC or AC gradually increases . As focal interstitial fibrosis and AAH with pure GGO tend to remain stable in size for months or years , monitoring the nodule size for several months by high-resolution CT (HRCT) can help in obtaining a differential diagnosis. The reported average doubling time of BAC, calculated from the maximal tumor diameter with the Schwartz equation , is very long (457–813 days on average) , therefore, visual evaluation of the growth rate on axial CT image may be unreliable.

Accurate three-dimensional (3D) computer-aided volumetry (CAV) software to assess pulmonary nodules with volumetric data obtained at multidetector CT (MDCT) is available . However, most of the software used in earlier studies only evaluated solid pulmonary nodules and CAV of GGO nodules can be difficult . We developed enhanced CAV software to measure not only the volume of solid and of GGO nodules; it yielded sufficiently accurate and reproducible volume measurements .

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Materials and methods

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Patients and Nodule Selection

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Table 1

Clinical and Pathologic Characteristics of All 47 GGO Nodules

AAH BAC AC Nodules (patients) 13 (9) 22 (20) 12 (10) Patient sex Male 6 6 3 Female 7 16 9 Mean age (year) 58.8 ± 13.1 63.9 ± 9.0 67.4 ± 6.1 GGO subtype Pure-GGO 13 14 1 Mixed-GGO 0 8 11 Mean maximum diameter (mm) 10.1 ± 3.2 13.3 ± 5.6 13.4 ± 4.6 Mean CT attenuation (HU) −614.5 ± 98.4 −611.4 ± 123.0 −323.3 ± 210.7 Mean interval between two CT scans (days) 331.6 ± 436.9 123.9 ± 118.5 85.9 ± 39.8

AAH, atypical adenomatous hyperplasia; BAC, bronchioloalveolar carcinoma; AC, adenocarcinoma.

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Image Acquisition

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Computerized Volumetry of Pulmonary Nodules

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Figure 1, Example of nodule volumetry on thin-section helical computed tomography (CT) images. (a) Target ground glass opacity (GGO) nodule on high-resolution CT. (b) Radiologists manually specify the target GGO nodule and place a region of interest (ROI). (c) The software automatically analyzes the density of the nodule and surrounding lung parenchyma and estimates the nodule border. Occasionally, structures such as vessels, remain around the nodule ( arrow ). (d) Using the concept of mathematical morphology, radiologists subjectively modify the nodule border with a semi-automatic edit tool. Last, the software automatically calculates the nodule volume.

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Evaluation of Volume Doubling Time

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VDT=[log2×t]/[log(V2/V1)], VDT

=

[

log

2

×

t

]

/

[

log

(

V

2

/

V

1

)

]

,

where V 1 and V 2 are the initial and final nodule volume and t is the interval between the two CT scans. The software calculates the VDT automatically by comparing the nodule volume on the two scans ( Fig 2 ). The average value of the two radiologists’ measurements of VDT was adopted.

Figure 2, VDT measurements of ground glass opacity (GGO) nodule with three-dimensional computer-aided volumetry software. Adenocarcinoma with a GGO nodule in a 63-year-old woman. The initial and final computed tomography (CT) images are displayed on the left and right, respectively. The interval between the two CT scans was 270 days. The software automatically calculates the volume-doubling time (VDT) by comparing both scans. In this case, the VDT was 163 days.

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Statistical Analysis

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Results

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Figure 3, Graph showing the mean volume-doubling time (VDT) for atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and adenocarcinoma (AC). There were statistically significant differences in the mean VDT for all combinations of AAH, BAC, and AC (Steel-Dwass test). The upper ( lower ) end of vertical lines, upper ( lower ) margin of boxes, horizontal lines in boxes, and circular symbols represent upper ( lower ) extremes, upper ( lower ) quartiles, medians, and outliers of data, respectively. ∗ P < .01.

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Figure 4, Graph showing the mean volume-doubling time (VDT) for pure- and mixed ground glass opacity (GGO) nodules. VDT was significantly shorter for mixed- than pure GGO nodules (Mann-Whitney U-test). See Figure 3 for explanation of symbols. ∗ P < .01.

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Figure 5, Graph showing the correlation between the volume-doubling time (VDT) and the maximum diameter of ground glass opacity (GGO) nodules on the initial computed tomography scan. No correlation was found ( r = -0.19, P = .19).

Figure 6, Graph showing the correlation between the volume-doubling time (VDT) and the mean internal density of ground glass opacity (GGO) nodules on the initial computed tomography scan. There was a statistically significant correlation ( r = -0.57, P < .01).

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Discussion

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