Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Radiol. Apr 28, 2012; 4(4): 174-178
Published online Apr 28, 2012. doi: 10.4329/wjr.v4.i4.174
ARFI elastography for the evaluation of diffuse thyroid gland pathology: Preliminary results
Ioan Sporea, Roxana Sirli, Simona Bota, Mihaela Vlad, Alina Popescu, Ioana Zosin
Ioan Sporea, Roxana Sirli, Simona Bota, Alina Popescu, Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara, 300736 Timisoara, Romania
Mihaela Vlad, Ioana Zosin, Department of Endocrinology, University of Medicine and Pharmacy Timisoara, 300736 Timisoara, Romania
Author contributions: Sporea I designed, supervised and revised the manuscript; Sirli R and Bota S wrote the manuscript draft; Bota S, Sirli R, Popescu A, Vlad M and Zosin I performed the research; Bota S analyzed the data; Sporea I, Vlad M, Popescu A and Zosin I revised the manuscript draft; all authors approved the final version of the manuscript.
Correspondence to: Dr. Ioan Sporea, Professor, Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara, 13, Snagov Street, 300482 Timisoara, Romania. isporea@umft.ro
Telephone: +40-256-309455 Fax: +40-256-488003
Received: October 7, 2011
Revised: March 17, 2012
Accepted: March 24, 2012
Published online: April 28, 2012

Abstract

AIM: To assess whether acoustic radiation force impulse (ARFI) elastography can differentiate normal from pathological thyroid parenchyma.

METHODS: We evaluated 136 subjects (mean age 45.8 ± 15.6 years, 106 women and 30 men): 44 (32.3%) without thyroid pathology, 48 (35.3%) with Basedow-Graves’ disease (GD), 37 (27.2%) with chronic autoimmune thyroiditis (CAT; diagnosed by specific tests), 4 (2.9%) with diffuse thyroid goiter and 3 (2.2%) cases with thyroid pathology induced by amiodarone. In all patients, 10 elastographic measurements were made in the right thyroid lobe and 10 in the left thyroid lobe, using a 1-4.5 MHZ convex probe and a 4-9 MHz linear probe, respectively. Median values were calculated for thyroid stiffness and expressed in meters/second (m/s).

RESULTS: Thyroid stiffness (TS) assessed by means of ARFI in healthy subjects (2 ± 0.40 m/s) was significantly lower than in GD (2.67 ± 0.53 m/s) (P < 0.0001) and CAT patients (2.43 ± 0.58 m/s) (P = 0.0002), but the differences were not significant between GD vs CAT patients (P = 0.053). The optimal cut-off value for the prediction of diffuse thyroid pathology was 2.36 m/s. For this cut-off value, TS had 62.5% sensitivity, 79.5% specificity, 87.6% predictive positive value, 55.5% negative predictive value and 72.7% accuracy for the presence of diffuse thyroid gland pathology (AUROC = 0.804). There were no significant differences between the TS values obtained with linear vs convex probes and when 5 vs 10 measurements were taken in each lobe (median values).

CONCLUSION: ARFI seems to be a useful method for the assessment of diffuse thyroid gland pathology.

Key Words: Acoustic radiation force impulse elastography, Thyroid stiffness, Thyroid pathology



INTRODUCTION

Clinical evaluation through thyroid palpation is the classical method for assessing this superficial gland. In the last years, elastography has been developed as a new dynamic technique that uses ultrasound waves for the evaluation of tissue stiffness. The principle of ultrasound elastography is that compression of the examined tissue induces less strain in hard tissues than in soft ones. The ultrasound probe manually or automatically produces an acoustic “push” pulse that generates shear-waves which propagate into the tissue. The propagation speed increases with fibrosis[1,2].

Recently, several studies have assessed the value of different types of elastography (transient elastography, real time elastography or acoustic radiation force impulse elastography) for the evaluation of liver stiffness in an attempt to replace liver biopsy. Elastographic methods are also used for the assessment of focal lesions or of diffuse pathologies (especially chronic hepatopathies)[3-8]. Many studies have proved these methods to be valuable, especially for the diagnosis of advanced fibrosis in diffuse liver diseases[7,9-14].

Considering the analogy of the two parenchymatous organs, liver and thyroid, we tried to assess whether ultrasound-based elastography by means of the acoustic radiation force impulse (ARFI) technique could be useful for the evaluation of thyroid diffuse pathology.

The aim of our paper was to see whether, by using ARFI elastography, we can differentiate a normal thyroid from a pathological one (considering only diffuse thyroid diseases) and secondly, to establish technical parameters for thyroid stiffness (TS) evaluation using ARFI elastography.

MATERIALS AND METHODS

We evaluated 136 subjects (mean age 45.8 ± 15.6 years, 106 women and 30 men): 44 (32.3%) without thyroid pathology, 48 (35.3%) with Basedow-Graves’ disease (GD), 37 (27.2%) with chronic autoimmune thyroiditis (CAT), 4 (2.9%) with diffuse thyroid goiter and 3 (2.2%) cases with thyroid pathology induced by amiodarone. All patients agreed to participate in our study which was approved by the local Ethics Committee.

The diagnosis of GD was based on the following criteria: thyrotoxicosis at the beginning confirmed by low thyroid stimulating hormone (TSH), high FT4 and FT3; diffuse hypoechoic goiter on ultrasound; and high titers of anti-TSH receptor antibodies. Some of the cases were evaluated by ARFI at the onset of the disease and some while under antithyroid therapy.

The diagnosis of CAT was based on high titers of antithyroid antibodies (anti-TPO and/or antiTg); diffuse hypoechogenity of the thyroid parenchyma on ultrasound; and normal or low thyroid function. Some of the cases had goiters (Hashimoto type) and some had a normal thyroid volume on ultrasound examination. All amiodarone treated patients developed type II thyrotoxicosis, diagnosed by means of established criteria[15].

ARFI elastography was performed with a Siemens Acuson S2000™ ultrasound system. In all patients, 10 elastographic measurements were taken in the right thyroid lobe (RTL) and 10 in the left thyroid lobe (LTL) using a convex probe of 1-4.5 MHz. Median values were calculated and expressed in meters/second (m/s) (Figure 1).

Figure 1
Figure 1 Acoustic radiation force impulse measurement in the left thyroid lobe (with convex probe).

We calculated mean TS values in the RTL and LTL. To see whether the probe type (linear or convex) influences TS measurements, in 45 patients we performed 10 elastographic measurements each in the RTL and LTL, using a convex probe of 1-4.5 MHz and a linear probe of 4-9 MHz, respectively. We also calculated mean TS values for each probe (resulting from the median TS values in RTL and LTL).

Data obtained from our cases were collected in a Microsoft Excel file, the statistical analysis being performed using the MedCalc program. ARFI measurements were numeric variables, so the mean values and standard deviation were calculated. The t test was used to compare mean ARFI values of TS.

The diagnostic performance of ARFI elastography was assessed using ROC curves that were constructed for prediction of thyroid pathology. Optimal cut-off values were chosen to maximize the sum of sensitivity (Se) and specificity (Sp). Se and Sp were calculated according to standard methods.

RESULTS

The mean TS values assessed by ARFI in normal and pathologic thyroid for the LTL and RTL, and the median values for LTL plus RTL are presented in Table 1.

Table 1 Mean thyroid stiffness values assessed by acoustic radiation force impulse in normal patients and in patients with diffuse thyroid pathology.
RTL (m/s)LTL (m/s)P valueMean ARFI (m/s)
Normal1.98 ± 0.372.01 ± 0.480.74 (NS)2 ± 0.40
GD2.62 ± 0.582.72 ± 0.610.41 (NS)2.67 ± 0.53
CAT2.34 ± 0.612.53 ± 0.680.20 (NS)2.43 ± 0.58

TS assessed by means of ARFI in healthy subjects was significantly lower than in GD (P < 0.0001) and CAT patients (P = 0.0002), but the differences were not statistically significant between GD vs CAT cases (P = 0.053) (Figure 2).

Figure 2
Figure 2 Mean thyroid stiffness values assessed by acoustic radiation force impulse elastography in healthy subjects vs patients with thyroid pathology. GD: Graves’ disease; CAT: Chronic autoimmune thyroiditis.

The optimal cut-off value (in which the sum of Se and Sp was highest) for the prediction of diffuse thyroid pathology was 2.36 m/s. For this cut-off value, TS had 62.5% Se, 79.5% Sp, 87.6% positive predictive value (PPV), 55.5% negative predictive value (NPV) and 72.7% accuracy for the presence of diffuse thyroid pathology (AUROC = 0.804).

To obtain a Se > 90%, the best TS cut-off for predicting diffuse thyroid pathology was 1.81 m/s (90.2% Se, 40.9% Sp, 76.1% PPV, 66.6% NPV and 74.2% accuracy).

To obtain a Sp > 90% the best TS cut-off assessed by ARFI elastography was 2.53 m/s (54.3% Se, 90.9% Sp, 92.5% PPV, 48.7% NPV and 66.1% accuracy).

If we compared mean TS values obtained by convex vs linear probe, those obtained with the convex one were slightly higher, but not significantly so, than those obtained with the linear one (2.17 ± 0.51 m/s vs 2.04 ± 0.43 m/s, P = 0.19) (Table 2). Also, if only 5 ARFI measurements were performed in each thyroid lobe, their median values were not significantly different from the median values of 10 ARFI measurements (Table 2), in normal as well as in diffuse thyroid disease.

Table 2 Mean acoustic radiation force impulse thyroid stiffness values in normal and diffuse thyroid pathology, with convex and linear probes, median of 10 measurements vs median of 5 measurements.
10 measurements (m/s)5 measurements (m/s)P value
Normal2.01 ± 0.402.01 ± 0.401 (NS)
GD2.64 ± 0.522.59 ± 0.540.66 (NS)
CAT2.50 ± 0.562.45 ± 0.540.72 (NS)
Convex probe2.09 ± 0.392.11 ± 0.450.85 (NS)
Linear probe2.03 ± 0.362.06 ± 0.380.75 (NS)

Also, if only 5 ARFI measurements were performed, the TS assessed by means of convex probe was slightly higher, but not significantly so, than those obtained with the linear probe (2.11 ± 0.45 m/s vs 2.06 ± 0.38 m/s, P = 0.63).

The mean ARFI values were significantly higher in patients with thyroid pathology and low levels of TSH vs those with normal TSH (P = 0.03); however the mean ARFI values were similar in patients with low TSH vs higher TSH P = 0.34) and in patients with normal TSH vs higher TSH levels (P = 0.28) (Table 3, Figure 3). Also, TS was not correlated with the TSH levels: Spearman r coefficient = -0.157, P = 0.20.

Table 3 Thyroid stiffness acoustic radiation force impulse measurements according to thyroid stimulating hormone levels.
ARFI values in patients with normal TSH (m/s)ARFI values in patients with abnormal TSH (m/s)P value
All patients2.35 ± 0.49 (20 patients)2.64 ± 0.56 (46 patients)0.04
GD2.12 ± 0.27 (6 patients)2.67 ± 0.51 (29 patients)0.01
CAT2.42 ± 0.55 (11 patients)2.49 ± 0.52 (14 patients)0.74
Figure 3
Figure 3 Mean thyroid stiffness values according to thyroid stimulating hormone levels. TSH: thyroid stimulating hormone.
DISCUSSION

GD is an autoimmune thyroid disorder characterized by diffuse goiter, thyrotoxicosis, orbitopathy and occasionally, infiltrative dermopathy. The clinical exam of the goiter by palpation reveals a parenchymatous elastic consistency and a specific bruit. CAT is another autoimmune thyroid disease that can induce goiter and/or thyroid dysfunction. Thyroid function is normal, low or rarely high. The classic form of CAT (Hashimoto’s disease) presents a diffuse goiter with hard consistency at palpation. If GD is characterized by circulating anti-TSH immunoglobulins, CAT expresses serum antithyroid autoantibodies which, in time, damage the thyroid’s morphofunctionality.

In previously published papers, thyroid elastography has been used to evaluate thyroid nodule stiffness in order to differentiate malignant from benign ones[16-22], usually using real time elastography (Hi RT-E). There is only one published study (also by our group) that evaluated thyroid stiffness by means of ARFI elastography in a group of 74 subjects, as a predictor of diffuse thyroid pathology[23].

ARFI elastography involves targeting an anatomical region to be investigated for elastic properties with the use of an ROI cursor, while performing real-time B-mode imaging. Tissue in the ROI area is mechanically excited using short-duration (262 μs) acoustic pulses with a fixed transmit frequency of 2.67 MHz to generate localized tissue displacement. The displacement results in shear wave propagation away from the region of excitation and is tracked using ultrasound correlation-based methods[1,2]. The shear wave propagation velocity is proportional to the square root of tissue elasticity so that the propagation speed increases with fibrosis. Using image-based localization and a proprietary implementation of ARFI technology, shear wave speed may be quantified. Results are expressed in m/s. Measurement value and depth are also reported.

Considering that there are no manufacturer recommendations for TS evaluation, we performed 10 ARFI measurements in each thyroid lobe, after which a median value was calculated, similar to the evaluation of liver stiffness by means of transient elastography (TE) or ARFI. Thereafter, we retrospectively analyzed the results, when only the first 5 ARFI measurements were taken into consideration. TS values assessed by means of ARFI were not statistically significant different if 10 vs 5 ARFI measurements were performed in each thyroid lobe (Table 2), so that we can conclude that for TS assessment 5 measurements are enough.

In the practical evaluation of liver stiffness through elastographic methods (TE or ARFI), the high level of aminotransferases modifies the values obtained for liver stiffness[24-26]. For this reason, we wanted to see if a modified thyroid function plays a role in the TS evaluation. We found that ARFI values were not correlated with TSH: Spearman r coefficient = -0.157, P = 0.20. Considering all the patients with thyroid pathology, the mean ARFI values were significantly higher in patients with abnormal TSH, as compared with those with normal TSH (Table 3).

In a very recently published study by Friedrich-Rust et al[20], ARFI was used for the evaluation of 55 patients with 60 thyroid nodules. TS measured by ARFI in the healthy tissue surrounding the nodule was compared to the nodules’ stiffness. While no significant difference in median velocity was found between healthy thyroid tissue and benign thyroid nodules, a significant difference was found between malignant thyroid nodules on the one hand, and healthy thyroid tissue (P = 0.018) or benign thyroid nodules (P = 0.014) on the other hand.

Other elastographic methods have been used for TS assessment. In such a study, Bahn et al[27] used magnetic resonance elastography (MRE) to evaluate TS in cases without thyroid pathology (12 subjects), in patients with Hashimoto thyroiditis (5 subjects), in patients with benign thyroid nodules (8 subjects) and with malignant thyroid nodules (2 subjects). Statistically significant differences were found between TS values in normal subjects (1.9 ± 0.6 kPa at 100 Hz and 1.3 ± 0.5 kPa at 80 Hz) and those with Hashimoto thyroiditis (2.8 ± 0.6 kPa at 100 Hz and 1.8 ± 0.6 kPa at 80 Hz) (P = 0.004 at 100 Hz). In the same MRE study, elastographic parameters could not differentiate benign from malignant thyroid nodules in this small cohort of patients.

In our study, TS assessed by means of ARFI in healthy subjects was significantly lower than in GD (P < 0.0001) and CAT patients (P = 0.0002), but the differences were not statistically significant between GD vs CAT patients (P = 0.053), meaning that even if we cannot differentiate by means of ARFI patients with GD from those with CAT, ARFI elastography could be used in clinical practice for differentiating normal thyroid from diffuse disease of the thyroid, maybe even as a first-line method, immediately after performing routine ultrasound examination of the gland.

ARFI elastography of the thyroid is feasible with either linear or convex probes and 5 measurements in every lobe are enough (median values) for an accurate assessment. ARFI evaluation seems to be a useful method for predicting the presence of autoimmune diffuse thyroid pathology, with high Sp and PPV (> 90%) for cut-off values > 2.53 m/s; being able to make a first differentiation between a normal thyroid and diffuse thyroid diseases immediately after ultrasound evaluation, thus opening a new field in thyroid elastography.

COMMENTS
Background

Elastographic methods are non-invasive means used for liver fibrosis evaluation. There is very limited knowledge regarding the use of elastography for diffuse thyroid pathology assessment. Considering the analogy of the two parenchymatous organs, liver and thyroid, authors tried to assess whether ultrasound-based elastography, by means of the acoustic radiation force impulse (ARFI) technique, could be useful for the evaluation of thyroid diffuse pathology.

Innovations and breakthroughs

ARFI elastography is a new method, based on ultrasound, used for the evaluation of tissue stiffness. In this study, the authors measured mean thyroid stiffness values assessed by ARFI elastography in healthy subjects vs patients with thyroid pathology. In the study, for a cut-off value > 2.36 m/s, thyroid stiffness assessed by ARFI elastography was accurate enough to predict the presence of diffuse thyroid pathology (AUROC = 0.804). For a cut-off value > 2.53 m/s, the specificity and positive predictive value were higher than 90%.

Peer review

This study supports the conclusion that thyroid ARFI evaluation seems to be a useful method for diffuse thyroid gland pathology assessment, as a first-line method immediately after ultrasound evaluation.

Footnotes

Peer reviewer: AAK Abdel Razek, MD, Professor, Diagnostic Radiology Department, 62 El Nokri St, Meet Hadr, Mansoura Faculty of Medicine, Mansoura 35111, Egypt

S- Editor Cheng JX L- Editor Logan S E- Editor Xiong L

References
1.  Nightingale K, Soo MS, Nightingale R, Trahey G. Acoustic radiation force impulse imaging: in vivo demonstration of clinical feasibility. Ultrasound Med Biol. 2002;28:227-235.  [PubMed]  [DOI]
2.  Mauldin FW, Zhu HT, Behler RH, Nichols TC, Gallippi CM. Robust principal component analysis and clustering methods for automated classification of tissue response to ARFI excitation. Ultrasound Med Biol. 2008;34:309-325.  [PubMed]  [DOI]
3.  Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Lédinghen V, Marcellin P, Dhumeaux D, Trinchet JC. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48-54.  [PubMed]  [DOI]
4.  Castéra L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, Darriet M, Couzigou P, De Lédinghen V. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-350.  [PubMed]  [DOI]
5.  Afdhal N. Debate: Are non-invasive tests ready to replace liver biopsy. favor of the use of non-invasive tests. Clinical Care Options. 2006;7-19.  [PubMed]  [DOI]
6.  Talwalkar JA, Kurtz DM, Schoenleber SJ, West CP, Montori VM. Ultrasound-based transient elastography for the detection of hepatic fibrosis: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2007;5:1214-1220.  [PubMed]  [DOI]
7.  Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, Herrmann E. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134:960-974.  [PubMed]  [DOI]
8.  Castéra L, Foucher J, Bernard PH, Carvalho F, Allaix D, Merrouche W, Couzigou P, de Lédinghen V. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 2010;51:828-835.  [PubMed]  [DOI]
9.  Lupsor M, Badea R, Stefanescu H, Sparchez Z, Branda H, Serban A, Maniu A. Performance of a new elastographic method (ARFI technology) compared to unidimensional transient elastography in the noninvasive assessment of chronic hepatitis C. Preliminary results. J Gastrointestin Liver Dis. 2009;18:303-310.  [PubMed]  [DOI]
10.  Sporea I, Sirli RL, Deleanu A, Popescu A, Focsa M, Danila M, Tudora A. Acoustic radiation force impulse elastography as compared to transient elastography and liver biopsy in patients with chronic hepatopathies. Ultraschall Med. 2011;32 Suppl 1:S46-S52.  [PubMed]  [DOI]
11.  Goertz RS, Zopf Y, Jugl V, Heide R, Janson C, Strobel D, Bernatik T, Haendl T. Measurement of liver elasticity with acoustic radiation force impulse (ARFI) technology: an alternative noninvasive method for staging liver fibrosis in viral hepatitis. Ultraschall Med. 2010;31:151-155.  [PubMed]  [DOI]
12.  Sporea I, Sirli R, Deleanu A, Tudora A, Popescu A, Curescu M, Bota S. Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis: a comparative study. World J Gastroenterol. 2010;16:4832-4837.  [PubMed]  [DOI]
13.  Rigamonti C, Donato MF, Fraquelli M, Agnelli F, Ronchi G, Casazza G, Rossi G, Colombo M. Transient elastography predicts fibrosis progression in patients with recurrent hepatitis C after liver transplantation. Gut. 2008;57:821-827.  [PubMed]  [DOI]
14.  Riggio S, Mamone F, Mandraffino G, Maimone S, Alibrandi A, Manti L, Saitta C, Tripodi PF, Sardo MA, Squadrito G. Assessment of liver stiffness in subjects affected by familial combined hyperlipidaemia with hepatic steatosis. Eur J Clin Invest. 2010;40:722-728.  [PubMed]  [DOI]
15.  Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med. 2005;118:706-714.  [PubMed]  [DOI]
16.  Rago T, Santini F, Scutari M, Pinchera A, Vitti P. Elastography: new developments in ultrasound for predicting malignancy in thyroid nodules. J Clin Endocrinol Metab. 2007;92:2917-2922.  [PubMed]  [DOI]
17.  Kagoya R, Monobe H, Tojima H. Utility of elastography for differential diagnosis of benign and malignant thyroid nodules. Otolaryngol Head Neck Surg. 2010;143:230-234.  [PubMed]  [DOI]
18.  Wang Y, Dan HJ, Dan HY, Li T, Hu B. Differential diagnosis of small single solid thyroid nodules using real-time ultrasound elastography. J Int Med Res. 2010;38:466-472.  [PubMed]  [DOI]
19.  Hong Y, Liu X, Li Z, Zhang X, Chen M, Luo Z. Real-time ultrasound elastography in the differential diagnosis of benign and malignant thyroid nodules. J Ultrasound Med. 2009;28:861-867.  [PubMed]  [DOI]
20.  Friedrich-Rust M, Romenski O, Meyer G, Dauth N, Holzer K, Grünwald F, Kriener S, Herrmann E, Zeuzem S, Bojunga J. Acoustic Radiation Force Impulse-Imaging for the evaluation of the thyroid gland: a limited patient feasibility study. Ultrasonics. 2012;52:69-74.  [PubMed]  [DOI]
21.  Vorländer C, Wolff J, Saalabian S, Lienenlüke RH, Wahl RA. Real-time ultrasound elastography--a noninvasive diagnostic procedure for evaluating dominant thyroid nodules. Langenbecks Arch Surg. 2010;395:865-871.  [PubMed]  [DOI]
22.  Asteria C, Giovanardi A, Pizzocaro A, Cozzaglio L, Morabito A, Somalvico F, Zoppo A. US-elastography in the differential diagnosis of benign and malignant thyroid nodules. Thyroid. 2008;18:523-531.  [PubMed]  [DOI]
23.  Sporea I, Vlad M, Bota S, Sirli RL, Popescu A, Danila M, Sendroiu M, Zosin I. Thyroid stiffness assessment by acoustic radiation force impulse elastography (ARFI). Ultraschall Med. 2011;32:281-285.  [PubMed]  [DOI]
24.  Coco B, Oliveri F, Maina AM, Ciccorossi P, Sacco R, Colombatto P, Bonino F, Brunetto MR. Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat. 2007;14:360-369.  [PubMed]  [DOI]
25.  Bota S, Sporea I, Sirli R, Popescu A, Dănilă M, Sendroiu M. Factors that influence the correlation of acoustic radiation force impulse (ARFI), elastography with liver fibrosis. Med Ultrason. 2011;13:135-140.  [PubMed]  [DOI]
26.  Chan HL, Wong GL, Choi PC, Chan AW, Chim AM, Yiu KK, Chan FK, Sung JJ, Wong VW. Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. J Viral Hepat. 2009;16:36-44.  [PubMed]  [DOI]
27.  Bahn MM, Brennan MD, Bahn RS, Dean DS, Kugel JL, Ehman RL. Development and application of magnetic resonance elastography of the normal and pathological thyroid gland in vivo. J Magn Reson Imaging. 2009;30:1151-1154.  [PubMed]  [DOI]