On the Utility of Quantitative Diffusion-Weighted MR Imaging as a Tool in Differentiation between Malignant and Benign Thyroid Nodules

Rationale and Objectives

To evaluate the ability of diffusion-weighted magnetic resonance imaging (DWI) in differentiating malignant thyroid nodules from benign lesions with a meta-analysis.

Materials and Methods

Articles in English and Chinese language relating to the accuracy of DWI for this utility were retrieved. Pooled estimation and subgroup analysis data were obtained by statistical analysis.

Results

A total of seven studies (17 subsets) with 358 patients, who fulfilled all of the inclusion criteria, were considered for the analysis. No publication bias was found (bias = 7.03, P > .05). Methodological quality was relatively high. DWI sensitivity was 0.91 (95% confidence interval [CI], 0.87–0.94) and specificity was 0.93 (95% CI, 0.86–0.96). Overall, positive likelihood ratio was 12.24 (95% CI, 6.47–23.20) and negative likelihood ratio was 0.99 (95% CI, 0.06–0.15). Diagnostic odds ratio was 123.78 (95% CI, 56.85–269.48). The area under the curve of the summary receiver operating characteristic was 0.94 (95% CI, 0.92–0.96). In patients with high pretest probabilities, DWI enabled confirmation of malignant thyroid lesion; in patients with low pretest probabilities, DWI enabled exclusion of malignant thyroid lesion. Worst-case-scenario (pretest probability, 50%) posttest probabilities were 92% and 9% for positive and negative DWI results, respectively.

Conclusions

A limited number of small studies suggests that quantitative DWI is a reliable diagnostic method for differentiation between benign and malignant thyroid lesions.

Thyroid nodules are commonly encountered in routine medical care. Almost 20% of the population has a palpable thyroid nodule, and approximately 70% has a nodule that can be detected by ultrasound . Most nodules are asymptomatic, with less than 5% of palpable thyroid nodules being malignant .

Magnetic resonance imaging (MRI) has gained importance in the diagnosis of thyroid cancer . The application of diffusion-weighted MRI (DWI) is an important diagnostic tool for assessing in vivo tumor characterization . Several studies have shown that DWI has the potential to differentiate benign from malignant nodules in the thyroid . Structural changes of malignancies or benign thyroid tissue can be evaluated with the apparent diffusion coefficient (ADC), which is an objective parameter of the tissue-specific diffusion capacity of a biologic tissue .

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Materials and methods

Literature Search

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Inclusion and Exclusion Criteria

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Data Extraction and Quality Assessment

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Statistical Analysis

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Results

Literature Search and Selection of Studies

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Table 1

The Principal Characteristics Eligible Studies

Study ID First Author Year Country No. of Patients No. of Total Lesions No. of Benign Lesions No. of Malignant Lesions Design Average Age, Years (range) M/F Patients Enrollment Coil Blind Field Strength Population Selection Reference Standard The Time Interval between MRI Examination and Reference Standard 1. Mutlu 2012 Turkey 44 51 46 (90.2%) 5 (9.8%) Prospective 49 (33–77) 27/17 ND Superficial neck coil ND 1.5 T Ultrasonography selection FNAB + histopathologic analysis Within 1 d 2.Nakahira 2011 Japan 38 42 23 19 Retrospective 55.5 (23–79) 13/29 ND Neck array coil Blind 1.5 T Routine neck MRI Histopathologic analysis ND 3.Schueller-Weidekamm 2010 Austria 27 27 11 16 Prospective 55.2 (25–82) ND ND Head and neck coil Unblind 1.0 T Radionuclide scintigraphy FNAB + histopathologic analysis Within 1 d 4.Ren 2010 China 60 60 30 30 Retrospective 49 (26–68) 20/40 Consecutive Head and neck coil ND 1.5 T Routine neck MRI Histopathologic analysis ND 5.Li 2009 China 50 50 36 14 Retrospective 50 (26–68) 9/41 ND Head and neck coil Blind 1.5 T ND Histopathologic analysis ND 6.Bozgeyik 2009 Turkey 76 93 88 5 Prospective 44.1 ± 13.1 ND Consecutive ND Blind 1.5 T Ultrasonography selection FNAB ND 7.Razek 2008 Egypt 63 63 7 56 Prospective 47 (20–72) ND Consecutive Superficial neck coil ND 1.5 T Ultrasonography selection Histopathologic analysis 7 and 13 d.

FNAB, ultrasound-guided fine-needle aspiration biopsy; M/F, male/female; ND, not documented.

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Study Description

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Table 2

The ADC Measurement of Included Studies (×10 −3 mm 2 /s) ( X¯¯¯ Χ

¯ ± SD)

First Author_b_ Value (s/mm 2 ) Mean ADC of Benign Mean ADC of Malignant Mean ADC of Normal Threshold Mutlu 0, 50, 400, 1000 1.6 ± 0.1 0.8 ± 0.2 0.98 ± 0.28 1.0 Nakahira ) 0, 1000 1.93 ± 0.37 1.20 ± 0.25 1.41 ± 0.14 1.60 Schueller-Weidekamm 0, 800 3.46 ± 0.40 2.73 ± 0.65 ND 2.25 Ren 100 3.0 ± 0.5 2.0 ± 0.5 ND 2.56 200 2.6 ± 0.4 1.7 ± 0.5 ND 2.17 300 2.2 ± 0.4 1.3 ± 0.4 ND 1.81 400 2.3 ± 0.3 1.0 ± 0.4 ND 1.48 Li 150 2.56 ± 0.56 1.75 ± 0.43 ND 1.992 300 1.99 ± 0.51 1.40 ± 0.31 ND 1.582 500 1.68 ± 0.54 1. 24 ± 0.30 ND 1.410 Bozgeyik 100 3.06 ± 0.71 0.96 ± 0.65 2.98 ± 0.67 1.45 200 1.80 ± 0.60 0.56 ± 0.43 1.73 ± 0.58 0.65 300 1.15 ± 0.43 0.30 ± 0.20 1.17 ± 0.46 0.36 Razek 0, 250, 500 1.8 ± 0.27 0.73 ± 0.19 ND 0.98

ADC, apparent diffusion coefficient; ND, not documented; SD, standard deviation.

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Assessment of Study Quality and Publication Bias

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Table 3

Evaluation of Quality of Included Studies Using the QUADAS Tool

Mutlu Nakahira Schueller-Weidekamm Ren Li Bozgeyik Razek Representative spectrum of patients ∗ Yes Yes Yes Yes Yes Yes Yes Selection criteria Yes Yes Yes Yes Yes Yes Yes Reference standard reliable Yes Yes Yes Yes Yes Yes Yes Time interval between MRI and pathology † Yes (within 1 d) Unclear Yes (within 1 d) Unclear Unclear Unclear Yes (7 and 13 d) Whole or random sample received verification Yes Yes Yes Yes Yes Yes Yes Same reference standard No Yes Yes Yes Yes Yes Yes Reference standard independent of the index test Yes Yes Yes Yes Yes Yes Yes Description execution of MRI Yes Yes Yes Yes Yes Yes Yes Description execution of pathology Yes Yes Yes Yes Yes Yes Yes Interpretation of MRI blinded from reference Unclear Yes No Unclear Yes Yes Unclear Interpretation of reference blinded from MRI Unclear Unclear Unclear Unclear Unclear Unclear Unclear Same clinical data available Yes Yes Yes Yes Yes Yes Yes Uninterruptable test results reported Yes Yes Yes Yes Yes Yes Yes Withdrawals explained Yes Yes Yes Yes Yes Yes Yes

MRI, magnetic resonance imaging; QUADAS, a quality assessment tool specifically developed for systematic reviews of diagnostic accuracy studies.

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Diagnostic Accuracy of DWI

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Evaluation of Clinical Utility

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Subgroup Analysis

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Table 4

Subgroup and Meta-regression Analysis

Study Characteristics Summary Sensitivity, % (95% CI)P Summary Specificity, % (95% CI)P χ 2 ( P ) I 2 Total ∗ 0.91 (0.86–0.94) - 0.92 (0.84–0.97) .61 13.91 (.00) 86 No. of patients_n_ > 50 0.91 (0.87–0.95) .17 0.91 (0.84–0.97) .61 0.82 (.66) 0n < 50 0.88 (0.78–0.98) 0.96 (0.88–1.00) Design Prospective 0.93 (0.88–0.98) .09 0.98 (0.95–1.00) .12 9.00 (.01) 78 Retrospective 0.90 (0.85–0.95) 0.85 (0.74–0.96) Patients enrollment Consecutive 0.92 (0.88–0.96) .05 0.95 (0.90–1.00) .73 4.52 (.10) 56 Unconsecutive or unknown 0.87 (0.80–0.94) 0.86 (0.74–0.99) Blind Yes 0.90 (0.83–0.96) .00 0.90 (0.86–0.92) .04 0.69 (.71) 0 Unblind or unknown 0.91 (0.87–0.95) 0.94 (0.88–0.96)

CI, confidence interval.

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Heterogeneity Assessing and Meta-regression Analysis

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Discussion

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