Comparison of Testicular Stiffness Values Obtained by Ultrasound Shear-Wave Elastography and Magnetic Resonance Elastography in Normal Healthy Volunteers

1. Introduction

Ultrasonography (USG) is the most sensitive and specific examination method for the testes. However, it is limited to evaluating the surrounding vascular structures and arteries supplying the testicular parenchyma with Doppler, roughly observing the intrarenchymal structures on a greyscale, and providing objective data on the testicular parenchyma only for easily visible peripheral and intrarenchymal mass lesions and apparent vascular abnormalities.

Although normal radiological findings are detected on greyscale USG and color Doppler examination of the testicular parenchyma in a small number of patients presenting with infertility, obvious abnormalities in the testicular parenchyma, its size and volume, and pathological conditions other than varicocele are uncommon radiological findings in infertility [1].

It is not possible to detect more micro-level abnormalities in the testicular parenchyma on greyscale USG examination, except for space-occupying lesions in the parenchyma or point calcifications, known as microlithiasis and inflammatory processes. However, varicocele, atrophy, and parenchymal grayscale abnormalities have not been detected in many patients with infertility. As the testis is not a suitable organ for biopsy, hardness remains a measurable parenchyma parameter [2].

Elastography is a sonographic imaging technique that provides qualitative and/or quantitative information regarding tissue stiffness. It is based on the degree of deformation of the analyzed lesion compared with the surrounding tissue. Images are obtained in color tones from red to blue, or vice versa, and from soft to hard, depending on the tissue stiffness. This color map provides both relative and qualitative data. SW-E is a newly developed real-time sonographic imaging technique that provides quantitative information (in N/m² or kPa) on the elasticity of soft tissues by sending transverse waves to the examined tissue [1,2].

Elastography has been used as an additional examination to grey scale and Doppler in recent years because it provides additional diagnostic parameters while remaining faithful to the basic principles of ultrasonography. However, the procedure is operator dependent, and a wide range of unstandardized data has been presented in the literature. Therefore, the idea of standardizing this examination by comparing it with MR-E, which works with a similar logic but with different physical laws, has emerged. These comparison and standardization studies have been carried out extensively on liver imaging, in which elastography is extensively used.

2. Materials and Methods

Our study was conducted in the Radiology Department of BHT Clinic Istanbul Tema Hospital, with the approval and permission of the Academic Board and Ethics Committee of Istanbul Nişantaşı University (meeting number 2023/33-12).

A total of 26 healthy volunteers were examined using US-E and MR-E with permission from the university and hospital in August 2023. Our exclusion criterion was the presence of a herniated scrotal and/or epididymal abnormality on USG and/or MR. Four cases were excluded from the study due to microlithiasis in the testis, cysts in the epididymis, incidental and asymptomatic small testicular size (atrophy or hypoplasia), and hydrocele. Thus, 22 cases (44 testes) were evaluated in the present study. The obtained data were comparatively evaluated. SW-E and MR-E examinations were evaluated by two radiologists with more than 10 years of experience in scrotal USG and MR and more than 2 years of experience in elastography.

2.1. USG SW-E device, technique, assessment, data collection and outcomes

The study was conducted using a General Electric (GE) brand Logic S8 model (2019) USG device with elastography software, utilizing a 9 MHz linear transducer with elastography hardware (Figure 1).

Ultrasonographic examination was performed with the patient in the supine position and the penis was positioned on the abdomen with a blanket covering it, ensuring that it was removed from the examination area.

Light pressure was applied to measure the three dimensions of each testis while in the supine posture. Testicular volume was estimated by the USG machine using the following method, based on comparable earlier investigations: Volume of testis = width × length × height × 0.523, expressed in mililiters (ml) [3,4].

After completing the greyscale USG test, the radiologist initiated the SW-E examination. Two-dimensional SW-E was performed with the patient in a supine resting state. The probe was held as steady as possible during the SW-E evaluation to minimize artifacts and inaccurate measurements. The right window displays the elastography image, whereas the left window displays the simultaneous grayscale image (Figure 2). Elastographic examinations were conducted with minimal compression for at least 5 seconds to reduce motion artifacts. ROIs (regions of interest) were placed to measure a round area of 0.1 cm² in the central part of the normal testicular parenchyma, as it is known that measurements become more standardized in this region, and the area becomes smaller in SW-E [4,5]

The ROI area (0.1 cm² was our study's most optimum measurable standard (Figure 2). Quantitative data mean (E_mean) was obtained in kPa from the normal testicular parenchyma. In our study, the US-E images saved in our PACS archive and the measurements made during the procedure were retrospectively reviewed. The measured values were obtained in kPa units in the US-E. However, to compare them statistically with the values in Pa units in MR-E, they were multiplied by 1000 to obtain the Pa value equivalents.

Real-time US-E measurements were performed during the examination and evaluated by transferring the data to the closed-circuit Clear Canvas Picture Archiving and Communication Systems (PACS) module in our hospital. Data from both examinations were collected and documented.

2.2. MR and MR-E protocols assessment, data collection and outcomes

All MR-E examinations were conducted on a 3 Tesla General Electric Signa Architect MRI scanner with commercially available software and hardware (GE Healthcare, Waukesha, WI, and Resoundant Inc., Rochester, MN) [6,7].

Technically, there are two non-standard extra hardware apparatuses in the MR device: a special device called a "passive driver" (Figure 3) and another device called an "active driver" (Figure 4) for elastography [7].

The subjects were positioned supine, head first, with a body AIR coil centered at the level of the region of interest ⁶. Mechanical shear waves at 60 Hz were generated by using an active driver system outside the MRI room. A rigid passive driver secured against the anterior wall of the pelvis was used to transmit mechanical vibrations from the active transducer to the body (Figure 5). A rigid driver is the standard device used in the FDA-cleared commercially available implementation of MR-E technology. An experienced MRI technologist performed the MR-E examinations in this study.

The propagating shear waves were imaged using a motion-sensitized imaging sequence. An (Spin-Echo echo planar imaging (SE-EPI) sequence was used to acquire axial wave images with the following parameters: repetition time (ms)/echo time (ms), 50/23; continuous sinusoidal vibration, 60 Hz; field of view, 32–42 cm; matrix size, 256 × 64; flip angle, 30°; section thickness, 10 mm; four evenly spaced phase offsets; and four pairs of 60-Hz trapezoidal motion-encoding gradients with zeroth and first moment nulling along the through-plane direction. All processing steps were applied automatically, without manual intervention, to yield quantitative images of tissue shear stiffness in kilopascals. The MR elastographic images were interpreted by staff radiologists in the Department of Radiology.

MR-E images were processed using commercially available MR-Touch software (GE Healthcare, Waukesha, WI, and Resoundant Inc., Rochester, MN, USA) to generate magnitude, phase, and wave maps (Figure 6) [6,7]. Six relative-stiffness images were reconstructed for each slice location. The resulting data were measured using ROIs in the muscle on anatomical T1 images and copied onto MR-E stiffness maps to measure the stiffness values (or elastograms) in the Pascals.

2.3. Statistical analysis

The MR-E and US-E mean stiffness values were statistically analyzed in the Pascals. The US-E and MR-E data were compared using the analysis of variance test, and chi-square and binary comparisons were performed using Student's t-test. Pearson's correlation test was used to calculate the correlation between age and stiffness values, testicular volumes and stiffness values, and stiffness values from both examinations. Statistical analysis was performed using SPSS v.23.0 (IBM Corp., Armonk, NY, USA). Two-tailed values of p < 0.05 were considered statistically significant.

3. Results

The youngest patient was 23 years old, and the oldest patient was 48 years old, with a mean age of 36.2 ± 11 years (Table 1). When analyzing the right testicular volumes of our patients, the largest value was 15 ml, and the smallest value was 12 ml. The mean right testicular volume was 13.4 ± 3.1 ml. When analyzing the volumes of the left testes, the largest volume was 15.2 ml, and the smallest was 11 ml. The mean left testicular volume was 13.6 ± 3.2 ml (Table 2). No significant correlation was observed between age and testicular volume (Table 3).

When analyzing US-E stiffness values, the smallest stiffness value for the right testis, 4.216 kPa for the highest stiffness value was 7.312 kPa, and the mean stiffness value was 5.560 ± 3.1 kPa. For the left testis, the smallest and highest stiffness values were 4.324 kPa, 6.914 kPa, and 5.361 ± 2.9 kPa (Table 4).

Because MR-E stiffness values were given by the MR device in Pascal (Pa) units, data were collected in this unit. When analyzing the MR-E values, it was observed that the smallest stiffness value for the right testis was 5302.12 Pa, the highest stiffness value was 9211 Pa, and the mean stiffness value was 6960 ± 460 Pa. For the left testis, the smallest stiffness value was 5562 Pa, the highest stiffness value was 8913 Pa, and the average stiffness value was 6560 ± 310 Pa (Table 5).

In the statistical correlation analysis performed between the testicular volume obtained from USG and the USG-E stiffness values and the stiffness values measured by MR-E, the p-values were 0.17 and 0.093, respectively, and were found to be greater than 0.05, respectively (Table 6). This indicates that there were no statistically significant differences between the parameters.

When statistically correlating the US-E and MR-E stiffness values of the cases, no significant correlation was found between the values (Table 7).

4. Discussion

Numerous studies have been conducted on different normal distributions of testicular volume for different age groups [8]. When analyzing the testicular volumes of our patients, we observed that they were within the normal range for adults. This is because we included subjects from the normal population in the study. All of our patients were in the young and early middle age groups. When comparing age and testicular volume, no significant statistical correlation was found, which is consistent with most other data in the literature [9,10,11,12,13].

SW-E is a relatively novel, reliable, and non-invasive imaging technique that provides data on histopathological alterations in many tissues. It offers valuable quantitative assessment of tissue stiffness and is extremely helpful in assessing parenchymal diseases. SW-E has been used in very few comparative investigations of the impact of varicocele on testicular parenchyma [14,15].

When analyzing the US-E stiffness values, it was observed that they were similar to those in the literature. Most studies in the literature, especially in adults, aim to identify conditions that do not cause significant abnormalities in the testicular parenchyma on grayscale USG examination, especially varicocele. Although our number of cases and, therefore, our sample size was small, our similar stiffness value findings with the literature revealed that most pathologies that do not give significant findings in the testicular parenchyma on greyscale USG do not give significant findings on SW-E.

No significant difference was found in the statistical analysis of the volume obtained by ultrasonographic calculation by measuring three dimensions compared to US-E and MR-E. This result is consistent with data in the literature [13].

The MR device provided the MR-E stiffness values in the pascals. Currently, MR-E is mostly used for the liver, and researchers who use this examination also use the Pascal unit. The MR-E devices and software were calibrated to provide stiffness values in the Pascals.

The use of MR of the testis in the literature is mostly for the purpose of creating a multiparametric examination for recognizing malignant lesions [16]. Although the use of US-E for testes is considerable in the literature, the same is not the case for MR-E. We did not find any MR-E studies of the testes in the literature. The MR-E component of our study is a preliminary study. This may be criticized because it may produce meaningless results for statistical sampling and power analysis. However, since MR-E is a test whose standards are not fully established, except for liver fibrosis, only pioneering studies can contribute to the literature. Similarly, there is only one study in the literature on the spleen, consisting of 16 patients [17].

In the statistical comparative analysis of the data obtained for each testicle, there was no significant correlation between US-E and MR-E findings (p=0.096). This nonsignificant correlation may be due to several factors and limitations. One of the most important of these factors is that the current MR-E modality is not standardized enough to perform testicular examination.

Limitations

The lack of data on the MR-E examination of the testes in the literature constitutes our most significant limitation. Another limitation is the small number of patients. Another limitation is that we performed MR-E measurements from the whole parenchyma and US-E measurements from a single location.

5. Conclusions

In our study, we compared the MR-E and US-E stiffness values of normal testicular parenchyma but did not find a statistically significant correlation between the two values. In addition, no significant correlation was found between stiffness values and age and testicular volume. The lack of a significant correlation may be attributed to the limitations and absence of standardized application standards for MR-E in testicular examinations. Further research with more patients under more standardized conditions is needed to confirm this result. Despite the small number of patients, our study is significant, as it pioneers the literature on this subject.