Shear wave elastography of the testes in a healthy study collective – Differences in standard values between ARFI and VTIQ techniques

Abstract

INTRODUCTION: Shear wave elastography (SWE) is a recent technique in the assessment of tissue elasticity. Different elastography techniques have been described over the years.

Acoustic Radiation Force Impulse Imaging (ARFI) uses mechanical excitation of tissue to create detectable shear waves, a higher shear wave velocity being associated with an increased tissue stiffness.

The Virtual Touch Tissue Imaging Quantification (VTIQ) method uses a mechanical push pulse as well, additionally creating a colour-coded map, in which tissue stiffness can be measured within a stored map on the ultrasound device after measurement.

ARFI has been used in determining standard values in testes of a healthy study collective, VTIQ has already been used in the evaluation of unclear scrotal masses.

Both techniques allow an operator-independent examination without application of mechanical pressure. The aim of this study was to determine whether there is a statistically significant difference between shear wave velocity values of both techniques in a healthy collective.

MATERIAL AND METHODS: Twenty patients without known testicular pathology underwent standard B-mode sonography and additional shear wave elastography in the ARFI mode as well as the VTIQ technique of both testes using the Siemens Acuson S2000™ and S3000™ ultrasound devices (Siemens HealthCare, Erlangen, Germany).

Measurements of shear wave velocity were performed in the upper pole, the central portion and the lower pole separately for each testis. Values were described in m/s.

Statistical evaluation was performed using paired t-test analysis.

RESULTS: We measured a mean shear wave velocity of 0.81 m/s using ARFI and 1.07 m/s with VTIQ.

Shear wave velocities determined by VTIQ were all significantly higher than values gained in the ARFI mode. (p < 0.001 to p = 0.007). Values were between 0.22 and 0.29 m/s higher, when the examination was performed using VTIQ.

CONCLUSION: ARFI and VTIQ elastography modes both proved to be feasible techniques in the assessment of testicular tissue elasticity. Consideration of higher values for VTIQ is important, when different elastography measurement results are compared, especially for the application of devices in a clinical setting, e.g. in the work-up of scrotal masses.

A calculable factor for a comparison between both devices is desirable, but to be further assessed in largerstudies.

Keywords

Testis ARFI VTIQ shear wave elastography ultrasonography

1 Introduction

Over the last few years shear wave elastography (SWE) has become an additional imaging tool in the evaluation of tissue elasticity. While routine imaging methods like B-mode sonography are still essential in the work-up of scrotal masses or as a screening tool in cases of male infertility, elastography techniques help to determine viscoelastic tissue properties by provoking a deformation response of mechanically stimulated tissue [1 , 14].

A propagating shear wave – induced by an acoustic push pulse emitted by an ultrasound probe – is moving perpendicularly to the stimulating pulse and is tracked by the same device via detection beams, measuring their velocity, which is displayed in a numerical value on the device. Higher shear wave velocities (SWV) have shown to be associated with greater tissue stiffness. Over the years, several different methods of shear wave elastography have been described [8].

Acoustic Radiation Force Impulse Imaging (ARFI) is based on the measurement of shear wave velocity in certain regions of interest (ROI), which can be applied in real time on a B-mode ultrasound image by the operator.

The technique has first been described for in vivo use in 2002 and is implemented in certain ultrasound devices in order to allow a parallel use of sonography and elastography [8, 16].

The method has been used in different studies concerning the assessment of liver fibrosis, liver lesions, thyroid nodules, sialolithiasis, unclear renal tumours and cystic pancreatic lesions [4 , 9–11].

Its main advantages compared to the classic strain imaging, which uses mechanical compression to induce axial displacement, are its operator-independence, quantifiability and reproducibility resulting from a reduced creation of artifacts and the generation of numerical values [17, 19].

The classic ARFI method is also known as Virtual Touch Tissue Quantification (VTQ) in certain devices.

The more recent technique of Virtual Touch Tissue Imaging Quantification (VTIQ) provides the examiner with an additional colour-coded map, representing the different tissue elasticity values qualitatively by colour, and with the possibility to store whole datasets for later analysis on the ultrasound device.

As part of determining the feasibility for VTIQ standard values have been described for different tissues, e.g. salivary glands as well as normal tissue and masses in the breast [12 , 22].

The ROI size in ARFI is about 5×6 millimeters, while in the VTIQ method a user-defined ROI is individually creatable (max. diameter 25×38 mm), with mostly used ROI sizes between one and two millimeters. Consequently, generated shear waves travel a distance of 6 mm during detection by tracking beams in the case of ARFI and only one or two millimeters in VTIQ, contributing to a better spatial resolution for the latter [7 , 21].

While both techniques have been proven feasible in different studies concerning scrotal imaging, a variability in values between the two methods has become obvious. So far, our group has conducted one study on the performance of VTIQ on scrotal masses and has found significant differences in tissue elasticity between testicular germ cell tumours and healthy testicular tissue. A different study on the application of ARFI on the testes of healthy men found significant age- and volume-related differences in shear wave velocities, and thus testicular tissue stiffness [5, 23].

The aim of this study was to use both methods in a healthy collective of male volunteers to evaluate the comparability between different SWE devices, as varying standard values would be of great relevance in clinical routine.

2 Material and methods

The study was conducted in accordance to the Declaration of Helsinki and the standards of the local ethics committee. The authors followed the ethical guidelines for publication in Clinical Hemorheology and Microcirculation [2].

We examined 20 male volunteers (mean age 57.1±15.28, range 27–81) without known history of testicular pathology from February to April of 2015. Informed consent was given in all cases. Testicular volumes were described between 5.3 and 20.6 ml (mean testicular volume was 13.2 ml).

We used the 9L4 linear transducer with a bandwidth of 4–9 MHz of the Siemens Acuson S2000™ and S3000™ ultrasound devices (Siemens HealthCare, Erlangen, Germany) for both B-mode sonography and shear wave elastography (ARFI and VTIQ techniques).

All examinations were performed separately for the right and left testis by a single investigator, with experience in sonography of more than two years, in order to rule out interobserver variability.

The examined volunteers were positioned in supine position, holding their penises up towards the abdominal wall to optimize imaging conditions.

Firstly, B-mode sonography was performed to screen the testes for irregularities and to determine testicular volume by measuring maximum distances in three dimensions using the formula for ellipsoid forms for volume calculation (length×width×height×0.523).

Then, we applied shear wave elastography via the machine’s linear transducer, firstly using the ARFI setting on the ultrasound device. We carefully tried to avoid manual pressure on the testes to not generate signal artifacts on the device.

Shear wave velocity was measured in three different regions – in the upper pole, center and the lower pole – using the application of provided, and graphically displayed, regions of interest (ROIs) on the B-mode image (Fig. 1).

Afterwards, a colour-coded image was gained using the VTIQ method, displaying blue and green areas as softer spots of lower shear wave velocity and red or yellow areas as stiffer spots of higher velocity. The ROIs were inserted afterwards into the stored image and were also applied in the three aforementioned testicular regions (Fig. 2). A separate colour-coded image was gathered using VTIQ, as part of an internal quality control, showing if the shear wave was of an adequate magnitude and whether it was associated with a good signal to noise ratio, and therefore good quality. A green colouring of the measured area represented good signal quality, yellow and red colour showed bad signal quality (Fig. 3) [12].

While both methods provided numerical results in m/s, VTIQ additionally delivered a colour-coded map, qualitatively illustrating tissue stiffness.

All results gained were statistically evaluated using the paired t test and IBP SPSS Statistics version 21 program for Macintosh (IBM, Armonk, NY).

Significant statistical differences were described by a p value < 0.05.

3 Results

We measured a mean shear wave velocity (SWV) value of 0.81 m/s (range 0.60 to 1.54 m/s) in the ARFI mode and a mean velocity of 1.07 m/s (range 0.79 m/s to 1.75 m/s) using VTIQ, thus showing a 24.3 percent higher velocity for VTIQ (Fig. 4).

All SWV values determined by VTIQ were significantly higher in all examined areas in comparison to values gained in the ARFI mode. (p < 0.001 to p = 0.007). Values were between 0.22 and 0.29 m/s higher when the examination was performed using VTIQ.

For the upper pole of the left and right testes shear wave velocity values were 0.26 m/s (95% CI: 0.17 – 0.35) and 0.24 m/s (95% CI: 0.15 – 0.34) higher (p < 0.001) for the VTIQ technique, respectively.

For the testicular middle portion values were 0.26 m/s (95% CI: 0.16 – 0.36) higher (p < 0.001) in the left testes and 0.25 m/s (95% CI: 0.13 – 0.37) higher in the right testes using VTIQ. The measurements in the lower testicular poles showed a higher shear wave velocity for VTIQ as well. In the left testes mean values were 0.22 m/s (95% CI: 0.06 – 0.38) higher (p = 0.007), in the right testes 0.29 m/s (95% CI: 0.15 – 0.42) higher (p < 0.001) compared to the ARFI technique.

4 Discussion

Testicular cancer makes up for about 5% of urologic tumours and has a rising incidence in younger men, with a peak between the third and fourth life decade.

Male infertility concerns about 15% of couples at reproductive age. Besides genetic and hormonal disorders, obstruction caused by infection is one of the main reasons for male infertility and can in some cases be evaluated by imaging modalities (e.g. calcifications, cysts).

B-mode sonography is an essential imaging tool in the routine urologic work-up of scrotal masses and male infertility as it is a feasible and easily accessible imaging modality for the detection of tissue inhomogeneities and irregularities. So far, additional information of suspicious lesions can be gathered by evaluating their perfusion by colour-coded Doppler sonography or – in specialized centres – by the application of contrast-enhanced ultrasound (CEUS) [1 , 20].

Supplementary information on tissue stiffness is gained by modern elastography techniques. Compared to older strain elastography devices newer SWE supporting systems provide operator-independent and reproducible results, as the needed manual compression of older transient elastography techniques often resulted in the generation of artifacts [19].

An earlier study by our group using ARFI for imaging of the testes has shown higher SWV in testes of smaller volume as well as in older patients, implying a great clinical relevance for those factors, while in this particular study there could be no difference found between different measurement regions with regard to tissue stiffness [5].

Concerning the application of SWE on suspicious findings our group has conducted a study of 22 testicular lesions in 20 patients with unclear scrotal masses using VTIQ, of which 15 were histopathologically confirmed to be malignant tumours.

Results in this study showed a significant difference in SWV between germ cell tumours and healthy testicular tissue. The mean SWV value of healthy tissue was 1.17 m/s, a little higher than our current findings [23].

A significant association between measurement localization, size of the testes and tissue stiffness could be shown in another study using Supersonic shear wave imaging elastography (SSI) on 66 healthy male volunteers.

After arranging the volunteers by age and testicular size into different subgroups we found the center of the testes in our measurements to be significantly softer, by having a lower SWV compared to the periphery. This location-dependent difference in SWV could not be shown in the previous ARFI-based study by our group. Also, bigger testes were associated with lower velocity compared to smaller volume testes, but only in the measurements of the upper testicular pole [4, 5].

The reason for those intra-testicular differences in density may be explained by the morphological specificities of the testis, with the rete testis and its greater density of presumably softer areas with more tubuli seminiferi as well as the mediastinum testis – consisting of larger lymphatic and blood vessels – found in the testicular center [3].

Our current study found VTIQ values to be about 24.3 percent higher than measurements performed by ARFI. In all examined areas VTIQ delivered statistically significantly higher values than ARFI. This fact is consistent with our findings in previous studies, showing a mean shear wave velocity of 1.17 m/s in normal testicular tissue in our previous VTIQ-based study on suspicious testicular lesions, while our study on the application of ARFI in testes of healthy volunteers showed that 95% of measured values were found between 0.62 and 1.01 m/s, with mean velocities in the different testicular areas ranging from 0.78 to 0.82 m/s [5, 23].

The present findings of higher SWV values may also be due to the higher patient age in our collective (mean patient age 57.1±15.28, range 27–81) compared to the patient age in the D’Anastasi study group of 2011 (mean patient age 45.13±17.3, range 23–75), and thus due to a higher age-related level of tissue stiffness explained by the physiological involution in aging human testes [5 , 18].

Indeed, an essential reason for the varying results between ARFI and VTIQ may be biological tissue itself due to its viscosity. In tests on phantoms there is almost negligible difference between ARFI and VTIQ values. More viscous tissue will have a greater impact of slowing down shear waves travelling at longer distances. Because of the above-mentioned different ROI sizes (6 mm in ARFI, 1-2 mm in VTIQ) between the two techniques generated shear waves in the ARFI mode may be effected and thus slowed down more by viscous tissue than those in the VTIQ-based technique. Also, there seem to be differences in values between different devices and even between transducers of the same ultrasound systems [7, 21].

Limitations of our study may be the subjective choice of ROI placement by the operator and thus a possible interobserver bias. All measurements were performed by a single examiner, so no assessment on interobserver-variability has been administered.

Another limitation may be the relatively small patient volume (n = 20) included in this study. The conduction of further studies with larger collectives will be of great importance in the future. An important factor may also be the location-dependent changes of SWV within the testis as seen in the previously performed study on SSI. In this present study, this factor has not been evaluated.

5 Conclusion

Both ARFI and VTIQ shear wave elastography techniques have proven to be practical in the assessment of testicular tissue stiffness. Noted differences between the two techniques in the gained SWV values are of great relevance with regard to use those devices in a clinical setting, as shear wave elastography does not seem to equal shear wave elastography. Differences in technology and in the examined biological tissue seem to be the amongst the most important reasons for differences in standardvalues.

Our previous findings from the SSI study suggesting a location-dependent difference of tissue stiffness may also be another essential factor. As a comparability between measured ARFI and VTIQ values is difficult at the moment, a larger study with higher patient numbers is desirable in order to find a calculable factor or formula to be able to transpose parameters from one device to another (e.g. ARFI to VTIQ).

While we found SWV values in VTIQ to be 24.3 percent higher than in ARFI, we would like to see those first numbers confirmed in larger study collectives to allow a useful and reliable comparison of values gained in the work-up of pathological scrotal findings.

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