ARFI Elastography for the Evaluation of Diffuse Thyroid Gland Pathology: Preliminary Results

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: +40-256-488003Abstract

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.

Keywords: 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 ​(Figure11).

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

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) .

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 1:Mean thyroid stiffness values assessed by acoustic radiation force impulse in normal patients and in patients with diffuse thyroid pathology

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

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). 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

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.

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REVISION of  GREY SCALE THYROID ULTRASOUND

 

With grey scale US, the normal thyroid has a peculiar echo density, making the gland well distinguishable from surrounding neck muscles. Thyroid echogenicity is due to the gland’s follicular structure: the interface between thyroid cell and colloid exhibits high acoustic impedance, causing high frequency acoustic waves to be reflected back to the probe. Conditions that change the normal anatomical structure of the gland cause this echo pattern to be altered.

Espinasse (1983) and Gutekunst et al. (1989) were the first to report abnormal thyroid ultrasound patterns, characterized by a diffuse low echogenicity, in patients with Hashimoto’s thyroiditis and Graves’ disease. Marcocci et al. found a diffuse low echogenicity in the thyroids of 44/238 patients with goiter and circulating thyroid autoantibodies.

The degree of hypoechogenicity was significantly correlated with the levels of circulating thyroid autoantibodies. While thyroid function was normal in all 194 patients with normal thyroid echogenicity, hypothyroidism was found in 64% of those with thyroid hypoechogencity. Histology of excised thyroid tissue from patients who underwent surgery for tracheal decompression showed diffuse lymphocytic infiltration in patients with thyroid hypoechogenicity, while in patients with normal thyroid echogenicity a histological pattern of colloid goiter with focal thyroiditis was found. These data clearly showed that thyroid hypoechogenicity was due to diffuse thyroiditis and was correlated with hypothyroidism. In the same paper 59/90 (65%) patients with Graves’ disease were found to have a diffusely low thyroid echogenicity. While diffuse lymphocytic infiltration accounts for thyroid hypoechogenicity in Hashimoto’s thyroiditis, in Graves’ disease the hypoechogenic pattern may be due to reduced colloid content with Increased cellularity and reduction of the cell–colloid interface and/or to the increased blood flow.

Using ultrasonography, Vitti et al. reported that about 70% of patients with Graves’ disease exhibit a low thyroid echogenicity. Whatever the reason for thyroid hypochogenicity in Graves’ patients, this pattern is significantly associated with a higher frequency of thyrotropin receptor antibody [TRAb] positivity and with the relapse of hyperthyroidism. The study group included 105 patients who underwent a course of methimazole treatment. Thyroid ultrasonography was performed at diagnosis, and TRAb levels were measured at the end of treatment. During a 6–18 month follow-up period after methimazole treatment, 87/105 (83%) patients had relapse of hyperthyroidism and 18/105 (17%) were in remission.

Recurrence of hyperthyroidism occurred in 71/76 (93%) patients with thyroid hypoechogenicity and in 16/29 (55%) of those with normal thyroid echogenicity.

Positive TRAb values at the end of methimazole treatment were found in 59/76 (78%) patients with thyroid hypoechogenicity and in 12/29 (41%) patients with normal thyroid echogenicity. Sixty-five of eighty-seven (74%) patients with relapse of hyperthyroidism and 6/18 (33%) of those who remained euthyroid were TRAb-positive at the end of methimazole treatment. The finding of thyroid hypoechogenicity at diagnosis had higher specificity (0.81) and sensitivity (0.72) compared with TRAb positivity at the end of methimazole treatment (0.74 and 0.66, respectively) for the prediction of relapse of hyperthyroidism. Therefore, the evaluation of thyroid echographic pattern promised to be a useful prognostic tool in patients with Graves’ disease.

Shieman et al., studying 53 patients with Graves’ disease, confirm that thyroid echogenicity is lower in these patients compared with that in 100 euthyroid volunteers. In agreement with the data of Vitti et al., significantly lower echogenicity was found in patients with elevated TRAb levels and in those with active ophthalmopathy, suggesting that in some way this echographic pattern is associated with a more active disease. The merit of the paper of Shieman is the effort the authors made to obtain an objective measurement of thyroid echogenicity. To this purpose, the thyroid images obtained with a 7.5MHz real-time transducer were recorded, keeping the operating conditions constant, and in selected regions of the thyroid the grey scale density was evaluated and translated into a numerical scale. The intraassay and interassay variations of grey determination were lesser than 5 %.

 

In the last few years (circa 2000), increasing evidence has been obtained indicating that thyroid US can be very useful in the diagnostic approach to thyroid autoimmune diseases, including Graves’ disease. At present, thyroid US provides skilled operators with a useful method for diagnosing Graves’ disease and for evaluating its severity. In the future, ultrasound imaging will prove increasingly useful as more sophisticated equipment is developed and operators increase their knowledge of color Doppler and three-dimensional technologies.

Thus, ultrasound imaging is likely to increase in importance for diagnosis and follow-up of Graves’ disease and become an essential technique for all thyroidologists.

 



NHÂN CA NHỒI MÁU MẠC NỐI LỚN tại MEDIC

Nhồi máu mạc nối lớn là nguyên nhân hiếm thấy của bụng cấp tính.

Biểu hiện đau bụng bên P có thể gây chẩn đoán nhầm nhồi máu mạc nối  lớn với viêm túi mật hay viêm ruột thừa; do đó cần chẩn đoán hình ảnh chính xác và để tránh mổ bụng hay điều trị kháng sinh không cần thiết.

Nhồi máu mạc nối lớn ít gặp ở bệnh nhi (khoảng 15% số ca).

Nhồi máu mạc nối lớn ít gặp hơn nhồi máu ruột non và ruột già vì mạc nối lớn được tưới máu phong phú nhờ tuần hoàn bên.

Nguyên nhân của nhồi máu mạc nối lớn không do xoắn thường gặp nhất là suy tuần hoàn tĩnh mạch do chấn thương hoặc huyết khối tĩnh mạch mạc nối.

Các yếu tố có xu hướng thiên về nhồi máu mạc nối lớn gồm béo phì, hoạt động gắng sức, suy tim sung huyết, dùng digitalis, mới phẫu thuật bụng và chấn thương bụng.

FURTHER READING:

NHÂN CA PRIMARY OMENTUM TORSION at MEDIC

Omental infarction: sonographic and CT findings, A. Hollerweger, P. Macheiner (2002, Mar 19).

URL: http://www.eurorad.org/case.php?id=1507

DOI: 10.1594/EURORAD/CASE.1507

 Male, 35 year(s)

Clinical History

A patient with acute right lower quadrant abdominal pain.

Imaging Findings
The patient presented with an 18-hour history of local tenderness in the right lower abdomen. No vomiting, nausea, or fever was present. He was admitted with suspected acute appendicitis and abdominal sonography and CT examinations were performed.

Discussion
Omental infarction is an acute abdominal condition, which is often clinically misdiagnosed as acute appendicitis (1, 2). Its most common localisation, in the right mid or lower abdomen, has been explained as a congenital vascular anomaly, but segmental infarction can be localised anywhere in the omentum. Omental infarction is a relatively rare condition and may occur at any age. Approximately 15% of patients are children (3).
Patients usually present with acute or subacute abdominal pain and localised tenderness; laboratory parameters are within the normal range or show slight elevation of white blood cell count or sedimentation rate. Vomiting and nausea are rare (1, 2).
Sonography typically shows an ovoid, non-compressible, moderately hyperechoic mass at the point of maximum tenderness (1, 2, 4, 5). The mass may be surrounded by a hypoechoic rim and is frequently adherent to the parietal peritoneum of the abdominal wall. On colour Doppler sonography vascularisation is not visible in the infarcted omentum, but adjacent tissue shows moderately increased colour flow due to the inflammatory reaction.

CT scans show a corresponding fatty lesion with hyperattenuating streaks (1, 2, 5). The parietal peritoneum is often thickened, whereas the bowel wall appears normal.
Follow-up examinations show a slow decrease in lesion size and disappearance of the lesion over a period of 1–2 months.
In cases of segmental omentum infarction, both sonography and CT show characteristic features that enable the correct diagnosis. Clinical symptoms gradually disappear when treated with analgesics and, with appropriate diagnosis, unnecessary surgery can be avoided.

    

References  

1. Puylaert JB. Right-sided segmental infarction of the omentum: clinical, US, and CT findings. Radiology. 1992 Oct;185(1):169-72..     

2. van Breda Vriesman AC, Lohle PN, Coerkamp EG, Puylaert JB. Infarction of omentum and epiploic appendage: diagnosis, epidemiology and natural history. Eur Radiol. 1999;9(9):1886-92..

3. Schlesinger AE, Dorfman SR, Braverman RM. Sonographic appearance of omental infarction in children. Pediatr Radiol. 1999 Aug;29(8):598-601..   
4. Puylaert JB. Ultrasound of acute GI tract conditions. Eur Radiol. 2001;11(10):1867-77..
5. Hollerweger A, Rettenbacher T, Macheiner P, Gritzmann N. Spontaneous fatty tissue necrosis of the omentum majus and epiploic appendices: clinical, ultrasonic and CT findings. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr. 1996 Dec;165(6):529-34..

   
Acute omental infarction
 Norbert Gritzmann, Gruppenpraxis  Radiologie Vienna Austria

Acute omental infarction most commonly manifests with acute lower quadrant pain, with the most frequent site in the right lower quadrant; acute appendicitis is the main clinical differential diagnosis. This is in contrast with another condition, acute epiploic appendagitis, which is most commonly adjacent to the sigmoid colon and presents with left lower quadrant pain. It is important to correctly diagnose both acute epiploic appendagitis and acute omental infarction on ultrasound as both these conditions may be mistaken for an "acute abdomen”, and this may lead to unnecessary surgery.

The ultrasound features of acute omental infarction include a well-circumscribed triangular or oval heterogeneous non compressible fatty mass with an echogenic alteration of the fat between the anterior abdominal wall and the transverse or ascending colon (Figure 1). The echogenic area of infarction may contain focal areas of hypo-echogenicity as well. Often this pseudo-tumour is fixed to the abdominal wall, readily identified during real-time ultrasound examination. With acute appendicitis a round non compressible tubular ending structure with a diameter of more than 6mm is usually identified on ultrasound, easily allowing differentiation from the echogenic mass of acute omental infarction seen on an ultrasound examination. With diverticulitis of the ascending colon an echogenic "out-pouching” of the colon with alteration of the surrounding fat is visualized on ultrasound.

Figure 1:A transverse view on ultrasound of the right lower quadrant in a 22 year old male patient with severe pain in this area. A 4 cm echogenic lesion is fixed to the abdominal wall (arrows). No movement of the lesion in regard to the hypo-echogenic abdominal wall muscles was seen during real time scanning.

The ultrasound pattern of acute omental infarction can be very similar to acute epiploic appendagitis, often needing a CT examination to confirm the suspicions raised on the ultrasound examination (Figure 2).

 Figure 2:An axial CT image of the lower abdomen demonstrating fat stranding adjacent to the ascending colon (arrows).

As ultrasound becomes increasingly used for the evaluation of acute abdomen, recognition of these conditions will allow appropriate management of acute abdominal pain and may help to prevent unnecessary surgery.

References
* Puylaert JB. Right-sided segmental infarction of the omentum: clinical, US, and CT findings. Radiology 1992;185:169–172.
* Hollerweger A, Macheiner P, Rettenbacher T, Gritzmann N. Primary epiploic appendagitis: sonographic findings with CT correlation. J Clin Ultrasound. 2002;30:481-95.
* Baldisserotto M, Maffazzoni DR, Dora MD. Omental Infarction in Children: Color Doppler Sonography Correlated with Surgery and Pathology Findings. AJR 2005;184:156–162.


Posted : EFSUMB Admin - Tue, Nov 8, 2011 8:44 PM.

TIÊN ĐOÁN CAO ÁP TĨNH MẠCH CỬA BẰNG ARFI

Abstract

Objective The purpose of this study was to assess the value of acoustic radiation force impulse (ARFI) for evaluating portal hypertension by correlating the elasticity of liver cirrhosis, as measured by ARFI, with haemodynamic indices measured by Doppler ultrasound.

Methods We evaluated the data of a total of 154 prospectively enrolled patients who underwent both duplex Doppler ultrasound and ARFI imaging. The duplex Doppler ultrasound indices, including the mean portal vein velocity, splenic index (SI) and splenoportal index (SPI) were evaluated to determine the statistical correlation with shear wave velocity (SWV) of ARFI. We also analysed the differences in the correlations between the SI, SPI and SWV of the group who had varices. The correlations were assessed with Spearman′s rank correlation coefficients.

Results There was an increase of SWV in parallel with the increase of the SI (ρ=0.409, under 0.01) and SPI (ρ=0.451, under  0.01). In the patient group who did not have varices (n=74), the Doppler indices were found to be more correlated with the SWV (SI: ρ=0.447, SPI: ρ=0.552, under 0.01). However, the group with varices showed no correlation between the SWV and the Doppler parameters.

Conclusion SWV of ARFI was well correlated statistically with Doppler parameters, but is of limited value in predicting portal hypertension directly owing to great variability of Doppler parameters. By evaluating the correlation between ARFI and Doppler ultrasound, we suggest that the SWV might be a non-invasive supplementary tool for predicting portal hypertension.

Introduction

Portal hypertension is a constant finding in the course of chronic liver disease and it causes serious complications such as variceal bleeding, which is responsible for significant mortality in patients with cirrhosis. Therefore, precise and regular assessment of the severity of portal hypertension is necessary for patients with cirrhosis during follow-up. The hepatic vein pressure gradient (HVPG) has been accepted as the gold standard for assessing the severity of portal hypertension and it is the best predictor of variceal formation [1-3]. However, this method is not feasible in clinical practice because of its invasiveness. Duplex Doppler ultrasound (DDUS) has recently emerged as a useful non-invasive modality to use in outpatient clinics for assessing the portal haemodynamics. Various portal haemodynamic parameters according to DDUS have been introduced. The previous reports on this have shown conflicting results for establishing DDUS as an acceptable modality for estimating the portal pressure. We chose some of the recently introduced parameters that are more acceptable and easier to perform. These were the splenic index (SI) and the splenoportal index (SPI), which are based on the spleen length and portal vein velocity (PVV) [4].

Acoustic radiation force impulse (ARFI) imaging is a radiation force-based imaging method that is provided by conventional B-mode ultrasound. With the increasing interest in finding new non-invasive methods for evaluating liver cirrhosis patients, ARFI can be applied for the measurement of liver stiffness as an alternative to needle biopsy. Many recent studies have shown that ARFI imaging is an accurate non-invasive modality compared with transient elastography and serum fibrosis marker tests [5-8].

The purpose of our study was to determine the correlations between the haemodynamic parameters measured with Doppler ultrasound and the liver stiffness measured with ARFI, and to evaluate the value of ARFI for predicting the presence of portal hypertension in patients with cirrhosis.

Methods and materials

Patients and control subjects

The study received institutional review board approval and informed written consent was obtained from all the subjects. The subjects were drawn from a consecutive series of 200 patients with liver cirrhosis and who visited the outpatient clinic of Dong-A University Hospital for routine follow-up between April 2010 and June 2010. The diagnosis of cirrhosis was established by histological examination or the combination of standard clinical, laboratory and imaging studies, including ultrasound and CT. The patients who did not provide informed consent or who had hepatocellular carcinoma, thrombosis in the inferior vena cava, hepatic vein or portal vein, or heart failure were excluded. After all the exclusions, 154 patients (91 males and 63 females; mean age 55.0±10.4 years) were finally included in this study. The cause of cirrhosis was viral in 133 patients (hepatitis C virus in 30 patients, hepatitis B virus in 102 patients, coinfection of B and C virus in 1 patient), alcohol abuse in 15 patients and cryptogenic in 6 patients. The severity of liver dysfunction, as classified by the Child–Pugh scoring system, was A in 142, B in 8 and C in 4. The patients who had undergone oesophago-gastro-duodenoscopy or CT in the previous 6 months were retrospectively evaluated for the presence of oesophageal or gastric varices. 47 patients were proven to have oesophageal or gastric varices, 74 patients were confirmed to not have varices and the other 33 patients did not undergo endoscopy or CT.

In addition, 15 healthy adult volunteers (10 men and 5 women) who did not have a history of relevant concomitant illness (heart, lung or liver disease or neoplasia) were examined with DDUS and ARFI imaging and they served as a control group in which to obtain benchmark median ARFI velocity and Doppler parameter measurements. The mean age of the control group (25.9±2.4 years) was significantly younger than that of the patient group (p under 0.001).

Greyscale and Doppler ultrasound

The examination was performed after the patients had fasted for 4–6 hours. B-mode standard ultrasonography scanning was initially performed using a Siemens Acuson S2000™ with a 4C1 transducer (Siemens Medical Solutions USA Inc., Malvern, PA). The spleen size was depicted after standard screening ultrasonography scanning of the abdomen. The SI was calculated in square centimetres using the transverse and vertical diameters of the spleen on the maximal cross-sectional images of the spleen (Figure 1) [9].

The portal vein was longitudinally scanned and the Doppler sampling cursor was placed approximately halfway between the venous confluence and the portal bifurcation. The PVV was the mean of three measurements with the patient holding their breath. It was automatically measured by the machine using the time-averaged velocity in two to three cardiac cycles and with an angle correction of  ; 60° [10] (Figure 1).

The SPI was calculated using the data acquired above with the formula SPI=SI/PVV_mean (SI is in cm²; PVV_mean is the mean PVV in cm s^–1).

All the ultrasound examinations were performed by one of two authors (HJK or JHC, with 7 and 14 years′ of experience with Doppler ultrasound, respectively) who were blinded to the clinical data throughout the study. The operators agreed on common rules to perform the ultrasound measurements before the start of the study.

Acoustic radiation force impulse imaging

After the B-mode standard ultrasonography and Doppler ultrasound were done, ARFI elastography was performed with the same curved arrays by the same authors as follows: the right lobe of the liver was accessed through an intercostal space while the patient was in the supine position with the right arm in maximum abduction and with a breath-hold. A region of interest (ROI) was placed 2–3 cm from the liver capsule at the right hepatic lobe, where the liver tissue was at least 5.5 cm thick (Figure 2) [11]. During each evaluation, the operator was careful not to include vessels and biliary structures in the ROI. The velocity of the shear wave from the liver tissue was calculated as the median value of five trials (m s^–1).

Statistical analysis

The data are expressed as mean ± standard deviation (SD). The Doppler ultrasound and ARFI results of the patients with cirrhosis and those of the healthy subjects were compared using the Mann–Whitney U-test.

Spearman rank correlation coefficients were used to assess the correlation between the parameters (the SI, the mean PVV and the SPI) measured by Doppler ultrasound and the velocity of the shear wave as measured by ARFI. The same test was used for both the groups with and without varices. The differences between the group with varices and the group without varices were compared with the Mann–Whitney U-test. The statistical analyses were performed by using SPSS® software (v. 18.0 for Windows; SPSS, Chicago, IL). p-values of p under 0.05 were considered to indicate significant differences.

Results

The parameters of Doppler ultrasound and ARFI are summarised in Table 1. There was a statistically significant difference between the patients and healthy subjects for all the measurements. The shear wave velocity (SWV) was correlated with the SI (ρ=0.409, p under 0.01) and the SPI (ρ=0.451, p under  0.01; Figure 3). Weak but significant correlations were found for the mean PVV (ρ=−0.205, p under 0.05). After excluding the patients who were confirmed to have varices (n=47) and the patients who were not assessed (n=33), the correlation between these two modalities became higher for the SI (n=74, ρ=0.447 p under 0.001), the SPI (n=74, ρ=0.552, p under 0.001) and the mean PVV (n=74, ρ= −0.25, p under  0.05). The results for the patients who had varices showed a statistical difference from those of the patients who did not have varices: the SWV, SI and SPI of the patients who had varices were 2.31±0.75 m s^–1 (p under 0.001), 73.95±24.4 cm² (p under 0.001) and 8.48±4.25 (p under 0.001), respectively, and they were significantly higher than those values of the patients who did not have varices (Table 2). No significant correlation was found between the ultrasound parameters and the SWV for the group of patients with varices (Figure 4).

Figure 4

Comparison between (a, b) the group without varices and (c, d) the group with varices. (a, b) Scatter-plots depict stronger correlation (splenic index: ρ=0.447, p under 0.001; splenoportal index: ρ=0.552, p under 0.001) than that for the total cirrhotic patients in Figure 1, but there was no correlation in (c, d) the group with varices (splenic index: ρ=0.211, p=0.154; splenoportal index: ρ=0.253, p=0.087).

Table 1 Comparison of shear wave velocity of ARFI and parameters of Doppler ultrasound between patients with and without cirrhosis

Table 2 Comparison of shear wave velocity of ARFI and parameters of Doppler ultrasound between patients with varices and without varices

Discussion

Duplex Doppler ultrasound is a non-invasive technique that can be used for estimating portal hypertension. Various portal haemodynamic parameters assessed by DDUS have been introduced and the previous studies have reported conflicting findings to presently establish DDUS as an acceptable modality for estimating the portal pressure [1-4]. The SI is the sonographic grading assessment to express the spleen size. The spleen size had traditionally been known to be the predictor of chronic liver disease and has been proven to correlate with portal pressure in recent studies [3,4,12]. With increasing portal pressure, the portal velocity decreases and fluctuations disappear with flow becoming continuous [4,13,14]. The SPI is a recently proposed index that amplifies the opposite effects that the mean PVV and SI exert, and the SPI can predict the presence of oesophageal varix in outpatient clinics [4].

ARFI sonoelastography has recently attracted a great deal of attention for its use to measure liver stiffness. ARFI imaging is an ultrasound-based technique in which the speed of wave propagation is evaluated to study the viscoelastic properties of the targeted tissue. The targeted region, the ROI, is mechanically excited by an acoustic pulse (∼262 µs) and this generates localised tissue displacement. By measuring the time to peak displacement, the shear wave speed of the tissue can be estimated at each lateral location of the ROI. The SWV is proportional to the square root of the tissue elasticity [5]. Many of the preliminary studies have yielded comparable results of the ARFI sonoelastographic velocity for determining the severity of liver fibrosis [5-8].

We compared the two modalities ARFI and DDUS on the assumption that the portal hypertension reflects the severity of cirrhosis. To the best of our knowledge, this is the first study that has assessed the correlation between ARFI and DDUS.

The results of the current study show that a significant relationship exists between liver stiffness, as measured by ARFI, and the parameters related to the portal pressure, as measured by Doppler ultrasound. Our study results demonstrated a positive correlation between the median ARFI sonoelastographic velocity, which reveals the liver stiffness, and the flow parameters of Doppler ultrasound, which reflect portal hypertension. Although liver stiffness appears to be a reliable method for identifying fibrosis, the pathophysiological basis for its correlation with portal hypertension remains poorly defined. The structural and biological changes in the liver may be responsible for increased portal pressure [15,16]. In individuals with cirrhosis, portal hypertension initially develops as the result of an increase in intrahepatic resistance to the portal blood flow due to profound morphological changes that are characterised by fibrosis and regenerative nodules compressing the sinusoids. This leads to vascular obliteration, activation of hepatic stellate cells and vasoconstriction, and this is all due in large part to intrahepatic nitric oxide deficiency and enhanced vasoconstrictor activity [17]. As a result, the progressive rise in portal pressure represents a reliable indicator of the tissue changes and, to a certain extent, the biological microenvironment of the cirrhotic liver.

While the correlations between Doppler parameters and SWV for patients without varices were approximately 0.557, the other 44.3% of the variation in SI and SPI was not explained by SWV. We hypothesised many factors that may influence Doppler indices, such as intrahepatic shunt and many portal–caval anastomoses other than gastro-oesophageal varices. Doppler parameters are still controversial for patients with cirrhosis owing to variability and reproducibility [12]. These factors may also affect the high variability of SI and SPI.

The results of the measurements of the patients with varices were significantly higher than those for the patients without varices. However, the results demonstrated a stronger correlation between the SWV and Doppler parameters when the patients who had varices were excluded. Further, there were no correlations between the SWV and Doppler parameters in the group of patients who had varices. In advanced cirrhosis, several extrahepatic factors (such as the hyperdynamic circulation, splanchnic vasodilation and the resistance opposed to portal blood flow by the portosystemic collaterals) contribute to the rise in portal pressure [16,18]. Beyond a certain degree of cirrhotic transformation, portal hypertension is maintained by these complex haemodynamic changes and these are mediated by nitric oxide [19,20]. Although liver stiffness and the SWV reflect a progressive rise in portal pressure due to morphological changes, they cannot measure the complex haemodynamic changes of late portal hypertension [21]. Its ability to predict the grade of varices in the case of severe portal hypertension was poor, suggesting a plateau effect in which further increases in liver stiffness are not reflected in the development of the late complications of portal hypertension.

The average of the Doppler parameters (SI, PVV, SPI) were slightly higher and the PVV was lower compared with the results of other studies [3,4,12,22]. We hypothesised this to be the consequence of the populations in different studies. The majority of our patients had hepatitis B virus-related cirrhosis with a Child–Pugh classification of A, while the subjects of the other studies had cirrhosis related to alcohol or hepatitis C virus. In alcoholic cirrhosis, the developing fibrous septae extend through the sinusoids from the central to the portal regions as well as from portal tract to portal tract. The hallmark of irreversible liver damage in chronic hepatitis is the deposition of fibrous tissue, which starts from the portal tract. Periportal septal fibrosis occurs with time and this is followed by linking of fibrous septa between lobules [23]. As the fibrosis in early cirrhosis starts from the portal tract, this may initially affect the haemodynamic change of the portal vein. However, this hypothesis should be further studied based on scientific evidence.

The major advantages of ARFI and DDUS are that these techniques are painless and rapid, they have no associated complications and they are easily accepted by patients. Both of the techniques can be performed with conventional ultrasound probes during routine ultrasound screening for hepatocellular carcinoma in patients with cirrhosis.

Although there were statistical correlations between both of the modalities, our study had some limitations. First, most of our patients had Child–Pugh class A virus-related cirrhosis. The potential bias due to the predominance of patients with chronic hepatitis B virus may have had an effect on the results. The value of ARFI in patients with other causes and severity of cirrhosis remains to be established. Doppler parameters are still controversial for patients with cirrhosis and definite standards have not been set for predicting portal hypertension. More extensive studies are needed to establish consistent measurements of the Doppler parameters. The study lacks interobserver agreement of Doppler indices and ARFI, although a previous study revealed 6.1±3.6% for mean PVV and 4.7±3.2% for the SI [4]. Another limitation is that only simple correlations were performed. Linear regression was not performed because interactions such as collaterals can affect the results.

In conclusion, substantial correlations were observed between liver stiffness and the Doppler parameters. It may have implications for the clinical assessment of patients who are at an early stage of liver cirrhosis that precedes the development of severe portal hypertension. However, because of the scattering of the data, the quantitative measurement of SPI or portal velocity has a limited utility in predicting portal hypertension directly. Further studies, including direct correlation with portal venous pressure, are needed to compare the prognostic values of Doppler ultrasound and ARFI.

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BÀN LUẬN

Siêu âm Duplex Doppler [DDUS] là kỹ thuật không xâm lấn được dùng để đánh giá tình trạng cao áp tĩnh mạch cửa. Các thông số huyết động tĩnh mạch cửa của DDUS đã được giới thiệu và nhiều nghiên cứu đã báo cáo việc dùng DDUS để đo áp lực tĩnh mạch cửa là không tương thích. Chỉ số lách SI là đánh giá siêu âm phân độ [grading] biểu hiện kích thước của lách. Kích thước lách theo truyền thống đã được dùng để tiên lượng bệnh gan mạn tính và được chứng minh có tương quan với áp lực tĩnh mạch cửa trong các nghiên cứu gần đây. Khi áp lực tĩnh mạch cửa tăng, tốc độ tĩnh mạch cửa giảm đi và mất dao động rồi trở thành dòng chảy liên tục. Chỉ số lách tĩnh mạch cửa SPI mới được đề xuất gần đây để khuếch đại tác dụng đối nghịch giữa tốc độ tĩnh mạch cửa [PVV] trung bình và chỉ số lách SI, và chỉ số lách tĩnh mạch cửa SPI có thể dự đoán sự xuất hiện của giãn tĩnh mạch thực quản tại phòng khám ngoại trú.

Siêu âm đàn hồi ARFI gần đây đã thu hút nhiều chú ý trong đo độ cứng gan. Tạo hình ARFI là một kỹ thuật siêu âm trong đó tốc độ truyền sóng âm được đánh giá để nghiên cứu các tính chất nhày đàn hồi [viscoelascity] các mô muốn khảo sát. Các khu vực mục tiêu, vùng ROI, được kích thích cơ học bởi một xung âm (~ 262 µs) gây ra dời chỗ mô khu trú. Bằng cách đo thời gian để dời chỗ cao nhất, tốc độ sóng biến dạng [SWV] của mô có thể được đo ở mỗi vị trí bên vùng ROI. Tốc độ SWV tỷ lệ thuận với căn bậc hai của độ đàn hồi mô. Nhiều nghiên cứu sơ bộ đã đạt được những kết quả của tốc độ đàn hồi ARFI có thể so sánh được để xác định độ nặng của xơ hoá gan. Chúng tôi so sánh ARFI và DDUS với giả định cao áp tĩnh mạch cửa phản ánh độ nặng của chai gan. Theo chúng tôi biết, đây là khảo sát đầu tiên nhằm đánh giá mối tương quan giữa ARFI và DDUS.

Kết quả của nghiên cứu này cho thấy có liên quan có ‎ý nghĩa giữa độ cứng gan, đo bằng ARFI, và các thông số liên quan đến áp lực tĩnh mạch cửa, được đo bằng siêu âm Doppler. Kết quả nghiên cứu đã chứng minh có tương quan giữa vận tốc đàn hồi trung bình ARFI, mà chúng cho thấy độ cứng gan, với các thông số dòng chảy của siêu âm Doppler, qua đó phản ánh cao áp tĩnh mạch cửa. Mặc dù độ cứng gan là  phương pháp xác định xơ hóa đáng tin cậy, cơ sở sinh lý bệnh của tương quan với cao áp tĩnh mạch cửa vẫn còn chưa được xác định. Những thay đổi cấu trúc và sinh học trong gan có thể là nguyên do của cao áp tĩnh mạch cửa. Ở bệnh nhân chai gan, cao áp tĩnh mạch cửa ban đầu  là kết quả của tăng trở kháng lưu lượng máu tĩnh mạch cửa trong gan do nhiều biến đổi hình thái học, đặc trưng bởi xơ hóa và nốt tái tạo chèn ép các xoang gan. Điều này dẫn đến tắc mạch máu, kích hoạt các tế bào gan hình sao và co mạch, và phần lớn là do thiếu oxit nitric trong gan và tăng co mạch. Kết quả là, tăng áp lực tĩnh mạch cửa diễn tiến biểu thị cho biến đổi mô và, đến một mức độ nhất định, cho vi môi trường sinh học của chai gan.

Trong khi những tương quan giữa các thông số Doppler và tốc độ SWV ở bệnh nhân không bị dãn tĩnh mạch thực quản khoảng 0,557, tỉ lệ 44,3% khác của sự thay đổi về SI và SPI không được giải thích bởi tốc độ SWV. Chúng tôi giả thiết có nhiều yếu tố có thể ảnh hưởng đến các chỉ số Doppler, chẳng hạn như shunt intrahepatic và các thông nối tĩnh mạch cửa-chủ khác hơn là dãn tĩnh mạch dạ dày-thực quản. Các thông số Doppler vẫn còn gây tranh cãi ở các bệnh nhân bị chai gan do tính biến thiên và tính lập lại. Những yếu tố này có thể tác động đến tính biến thiên cao của chỉ số lách SI và chỉ số lách tĩnh mạch cửa SPI.

Các kết quả đo ở bệnh nhân có dãn tĩnh mạch thực quản cao hơn đáng kể so với những bệnh nhân không có dãn tĩnh mạch thực quản. Tuy nhiên, kết quả đã chứng minh có tương quan mạnh giữa tốc độ SWV và các thông số Doppler khi bệnh nhân có dãn tĩnh mạch thực quản được loại trừ. Hơn nữa, không có tương quan giữa tốc độ SWV và các thông số Doppler trong nhóm bệnh nhân có dãn tĩnh mạch thực quản. Trong chai gan nặng, một số yếu tố ngoài gan (như hyperdynamic circulation, giãn mạch tạng và trở kháng trái ngược với lưu lượng máu tĩnh mạch cửa do portosystemic collaterals) đóng góp vào sự gia tăng áp lực tĩnh mạch cửa. Ngoài một mức độ nhất định của sự chuyển hóa chai gan, cao áp tĩnh mạch cửa được duy trì bởi những thay đổi huyết động phức tạp và đây là những trung gian nitric oxide. Mặc dù độ cứng gan và các SWV phản ánh sự tăng tiến triển của áp lực tĩnh mạch cửa do thay đổi hình thái học, không thể đo lường sự thay đổi huyết động phức tạp của cao áp tĩnh mạch cửa muộn. Khả năng dự đoán mức độ dãn tĩnh mạch thực quản trong trường hợp cao áp tĩnh mạch cửa nặng rất kém, cho thấy một hiệu ứng cao nguyên [plateau effect], trong đó sự tăng thêm độ cứng gan không được phản ánh trong các biến chứng muộn của cao áp tĩnh mạch cửa.

Trung bình của các thông số Doppler (SI, PVV, SPI) hơi cao hơn và tốc độ PVV là thấp hơn so với kết quả của các nghiên cứu khác. Chúng tôi nghĩ là do hậu quả của mẫu dân số trong các nghiên cứu khác nhau. Phần lớn các bệnh nhân của chúng tôi là chai gan do viêm gan virus B với phân loại Child-Pugh A, trong khi đối tượng của các nghiên cứu khác là chai gan liên quan đến rượu hoặc viêm gan siêu vi C. Trong chai gan do rượu, các vách xơ phát triển mở rộng thông qua các xoang từ trung tâm đến khoảng tĩnh mạch cửa cũng như từ đường tĩnh mạch cửa [portal tract] này đến đường tĩnh mạch cửa khác. Các dấu hiệu của tổn thương gan không hồi phục trong viêm gan mạn là sự lắng đọng các mô xơ, bắt đầu từ đường tĩnh mạch cửa. Xơ hóa vách ngăn quanh khoảng cửa xảy ra với thời gian và theo sau đó là liên kết với vách sợi giữa tiểu thùy. Khi xơ hóa trong chai gan sớm bắt đầu từ đường tĩnh mạch cửa, điều này ban đầu có thể ảnh hưởng đến sự thay đổi huyết động của các tĩnh mạch cửa. Tuy nhiên, giả thuyết này cần được tiếp tục nghiên cứu dựa trên bằng chứng khoa học.

Những lợi thế lớn của ARFI và DDUS là những kỹ thuật này không đau và thực hiện nhanh, không gây biến chứng và bệnh nhân dễ chấp nhận. Cả hai kỹ thuật có thể được thực hiện với đầu dò siêu âm thông thường trong quá trình kiểm tra siêu âm định kỳ tìm ung thư biểu mô tế bào gan ở bệnh nhân chai gan.

Mặc dù có mối tương quan có ý nghĩa thống kê giữa ARFI và DDUS, nghiên cứu của chúng tôi có một số hạn chế. Trước tiên, hầu hết bệnh nhân của chúng tôi là chai gan có Child-Pugh nhóm A liên quan đến virus. Các sai số [bias] tiềm ẩn do phần lớn là bệnh nhân viêm gan virus B mạn tính có thể có ảnh hưởng đến kết quả. Giá trị của ARFI ở những bệnh nhân với các nguyên nhân khác và mức độ nặng của chai gan vẫn còn đang thiết lập. Các thông số Doppler vẫn còn gây tranh cãi ở bệnh nhân chai gan và các tiêu chuẩn xác định đã không được thiết kế để dự đoán cao áp tĩnh mạch cửa. Nghiên cứu rộng rãi hơn là cần thiết để thiết lập cách đo các thông số Doppler phù hợp. Nghiên cứu này thiếu đồng thuận giữa các người khám [interobserver agreement] của các chỉ số Doppler và ARFI, mặc dù một nghiên cứu trước đây cho thấy tốc độ trung bình PVV là 6,1 ± 3,6% và cho SI là 4,7 ± 3,2%. Hạn chế khác là chỉ thực hiện được các tương quan đơn giản. Hồi quy tuyến tính không được thực hiện do sự tương tác [interactions] như tuần hoàn bàng hệ có thể có ảnh hưởng đến kết quả.

Để kết luận, có tương quan đáng kể giữa độ cứng gan và các thông số Doppler. Nó có thể có tác động đối với các đánh giá lâm sàng cho bệnh nhân ở giai đoạn sớm của chai gan trước sự phát triển của cao áp tĩnh mạch cửa nặng. Tuy nhiên, vì sự phân tán của dữ liệu, đo lường định lượng của chỉ số lách tĩnh mạch cửa SPI hoặc vận tốc tĩnh mạch cửa có hạn chế trong việc dự đoán trực tiếp cao áp tĩnh mạch cửa. Nghiên cứu sâu hơn, bao gồm cả sự tương quan trực tiếp với áp lực tĩnh mạch cửa, là cần thiết, để so sánh các giá trị tiên lượng của siêu âm Doppler và ARFI.