Introduction
Classification of elastography technique
The details of the principles of the elastography currently used in the clinical field are shown in Table 1, largely divided into strain imaging and shear wave imaging [1]. Strain imaging can be strain elastography (SE), in which the tissue is manually compressed and deformed to measure and assess the generated strain, or acoustic radiation force impulse (ARFI) imaging, in which the displacement of the tissue generated by the acoustic radiation force from ultrasound is imaged. Shear wave imaging involves generating shear waves in the body and calculating the elasticity of the tissue from the propagation velocity; this is, in many cases, shear wave elastography (SWE), in which the acoustic radiation force is used for the generation of the shear waves. Distortion represents the elasticity with respect to a static deformation, while the propagation of shear waves represents the deformation in the band of the shear waves (up to 1 kHz); it is understood that the elasticities assessed by SE and SWE are not necessarily the same, in that the influence from viscosity is included as well as that of elasticity.
Strain elastography
Elastography of the prostate was first applied as SE in the same manner as cases involving the mammary glands. As in digital rectal examinations (DRE), a transrectal probe is used to compress the prostate. So far, many studies for the prostate elastography are mainly performed using SE. Even though elastography showed promising results for prostate cancer diagnosis, the technology is still not widely used because of many limitations. Not only manual compression, but also automatic compression system using balloon inflation, i.e. real-time balloon inflation elastography (RBIE) [2], is indicated for analysis. Using this technique, uniform stress field generated by balloon is more than two times wider than that by free-hand method (83.4° vs 39.6°) [3]. This technique is mentioned in “Scanning method” section. Transabdominal SE is not indicated for the prostate because of the reduction of SN due to the attenuation of echo signals and also because of the difficulty in applying sufficient compression from the body surface.
Acoustic radiation force impulse (ARFI) imaging
ARFI imaging has an advantage in that it is possible to deform the tissue with ultrasound pulses even in a relatively deep place without applying manual compression [4]. However, in comparison to ordinary ultrasound examinations, extremely long pulses are used to deform the tissue, so large ultrasonic waves are applied. It is necessary to provide time intervals between frames to prevent heat from accumulating; therefore, the real-time characteristics are lost. In addition, regarding the degree of the same deformation, SE calculates the deformation rate of strain, the difference in the displacement between the two locations, by dividing the distance between the two locations, whereas ARFI imaging expresses the displacement per se at a location.
Shear wave elastography
Recently, SWE that enables clinical applications mostly for the diagnoses of breast cancer and hepatic fibrosis is based on the theoretical formula that the elasticity modulus (Young’s modulus) is proportional to the square of the propagation velocity of shear waves, where it is assumed that shear waves are formed properly in the body and generally propagate directionally. In comparison with transabdominal scans of the mammary glands and liver, where it is possible to secure a sufficient probe aperture, the conditions for transrectal probes are severe in terms of the generation of shear waves. In addition, the fact that the object is small, roundish and the multiformal surrounding tissues are also among the inconvenient conditions for the measurement of the propagation velocity of shear waves. Therefore, there have been a few reports in an attempt to perform SWE of the prostate.
Scanning method
The elastography that is most widely applied to prostatic diagnoses using transrectal ultrasonography (TRUS) is SE. In SE, the color tone depends on a selected region of interest (ROI) to relatively assess the stiffness of the ROI and to use color tone expressions. In SE, a relatively hard tissue in an ROI is expressed in blue, an average stiffness in green, and a relatively soft tissue in red. The prostate is a relatively small organ, and it is possible to include the whole of the prostate in a scan area for observation. In addition, this is used mainly for the diagnosis of tumor lesions. From these characteristics and others, it is recommended that an ROI be set up by including the prostate and the tissue around it.
Elastography for the prostate is usually applied by convex or end-fire type probes; the patient is placed in left lateral or lithotomy position with transrectal probe. The prostate tissue is compressed by pushing a transrectal probe from above down. A probe movement should be repeated using different compression ratios until stable and reproducible image series are captured. When blue-colored signal was defined, it is necessary to check reproducibility with probe rotation. The surface of the prostate should be red color to get adequate compression, but not too much compression for avoiding false-negative result. Blue-colored signal around calcification is out of evaluation, because the region around calcification is hard and behind region is sonolucent. The examiner should be careful because a probe head is far from the hand; even a little shaking makes a large vibration at the probe head. To obtain stable elasographic moving images, RBIE [2] was developed. The prostate tissue is compressed by inflation and deflation of a balloon attached to an endorectal probe using pistol-type injector, which provides more consistent and reliable compression (Fig. 1).
Elastography of normal/prostatic hypertrophy
According to the Zonal anatomy [5] proposed by McNeal, the prostate is divided into four regions based on the histological characteristics; that is, peripheral zone (PZ), central zone (CZ), transitional zone (TZ), and anterior fibromuscular stroma (AFMS). As elastography images are overlapped with B-mode prostate images for display, first of all it is essential to recognize each region in the B-mode and to take the horizontal symmetry into consideration for the elastographic examination. In normal prostate images, the peripheral zone and the central zone present isoechoic and homogeneous echo images, which makes it difficult to identify the regions in sonograms. In SE of the normal prostate, the blood vessels and the surrounding adipose tissue are soft and thus presented in red (soft rim artifacts). The peripheral zone and the central zone are presented in green because they are generally of medium stiffness. As the normal patterns in this region, red and green are simultaneously shown as equal, mainly green regions are conspicuous with small red and blue portions, the parts with different color tones in the linear shape or in the curved line are shown, and others may be seen. However, they never show nodular forms. The size of a transitional zone is small and is expressed in green or blue. The urethra in the verumontanum is expressed in red as an upside-down V-shaped image [6, 7].
The enlargement of a transitional zone is related to the development of a nodular hyperplasia, which is easily recognizable in the B-mode. This nodular hyperplasia is homogeneous and recognized as a slightly hypoechoic lesion. SE in a transitional zone is expressed uniformly in green or blue or is sometimes seen mixed with green and blue portions, but the horizontal symmetry is maintained. The center part of a hypertrophic nodule is expressed in blue. In case of having huge BPH nodules, elastographic analysis is unreliable because of deep stiffness artifacts and lateral stiffness artifacts. This phenomenon is much remarkable in convex probe use because it is not possible to apply uniform compression to the prostate. A region about 5 cm distant from a transducer is out of evaluation, because the elasticity of the tissue may not be correctly expressed due to mechanical limitations, which sometimes happens in the case of huge BPH [6–8].
Elastography in prostate cancer diagnosis
Cancer regions usually show hard nodule, so that the regions are basically highlighted as blue in SE.
Pallwein et al. proposed a three-grade score system with respect to SE observations [9] (Table 2). Furthermore, Kamoi et al. proposed diagnostic criteria in a combination of gray scale and SE [10] (Table 3). In these diagnostic criteria, the echogenicity in the gray scale and the tissue elasticity obtained from the SE were combined and classified into scores from 1 to 5, where score 3 or higher was taken to be an observation that may indicate a malignant tumor.
Evidence of elastography for prostate cancer detection
The report by König et al. in 2005 [11] was the first application of SE to a prostate biopsy. The sensitivity of the conventional examination method in prostate biopsies was 64.2 %; they raised the sensitivity up to 84.1 % after the introduction of SE. Subsequently, in the report published by Pallwein et al., the sensitivity was 80 % [12]. SE raised expectations in the field of the diagnosis of prostate cancer.
In Japan, Miyanaga et al. [13] first reported elastographic use for prostate cancer detection. According to their report, among 29 prostate cancer patients, DRE captured 17 foci (59 %) and TRUS captured 16 foci (55 %), whereas SE captured 27 foci (93 %). So far, various reports have been published. In Japan, several reports are analyzing using SE. We need to recognize the sensitivity and specificity in SE which vary depending on whether the subjects are screened patients or step sections of prostatectomy specimens (Fig. 2).
SE for prostate cancer screening
There are six reports about the usability of SE in patient screening that examined over 100 cases. The results of each report are shown in Table 4 [10, 11, 14–17]. Both sensitivity and specificity are generally 60 % or higher. The advantage is the higher sensitivity than the B-mode, Doppler method, and other methods. An additional increase in prostate cancer detection by SE varies from 5 to 30 %, but the effects depend on prostate biopsy method or study design [14, 18–20].
There is one report about a randomized trial comparing with the B-mode and SE. In 353 randomized cases, the cancer detection rate of the former was 39.4 % (69/175), while that of the latter was 51.1 % (91/178) (p = 0.027). The sensitivity of the B-mode was 15 % while that of SE was very high at 60.8 %. These results indicate the superiority of SE. On the other hand, the specificity was lower in this result (92.3 vs 68.4 %) [16]. Furthermore, according to a report which analyzes the prostate cancer detection rate of SE-targeted biopsy in men with total prostate-specific antigen 1.25 ng/ml or greater and 4.00 ng/ml or less, SE detected cancer in 20 patients (21.3 %) and systematic biopsy detected it in 18 (19.1 %). Positive cancer cores were found in SE-targeted cores in 38 of 158 cases (24 %) and in systematic cores in 38 of 752 (5.1 %) (p < 0.0001). The cancer detection rate per core was 4.7-fold greater for targeted than for systematic biopsy. Thus, the superiority of SE was also demonstrated even though in the population whose prostate cancer is sometimes overlooked [21].
Comparison between SE and prostatectomy step sections
A comparison with prostatectomy specimens is the most accurate way to evaluate the feasibility of SE. Table 5 shows the results from five major papers [2, 22–25]. According to a comparison with prostatectomy step sections, generally 70–85 % of the cases were detected by SE. This is an excellent detection rate in comparison with the generally accepted detection rate of the B-mode (about 40 %). Some reports revealed excellent detection rate at anterior region or apex of the prostate, where it is hard to be palpable by DRE, but other reports say that there was not a large difference among location. So far, there is no obvious consensus elastographic detection regarding tumor location. As well as tumor location, the detection rate depending on Gleason score has no obvious consensus.
Ex vivo evaluation of stiffness of the prostate
An ex vivo evaluation of real stiffness of the prostate using stiffness testing apparatus is essential to evaluate the feasibility of elastography. There are three important reports.
Comparing elastic module difference, palpable lesion is harder than non-palpable lesion (median 46.5 kPa, SD 22.2 kPa vs median 31.0 kPa, SD 63.1 kPa) [26].
The tissue elastic modules of the prostate cancer increase with an increase of Gleason score; however, elastic modules of low Gleason tumor are similar to BPH nodule [27].
The mean elastic modulus of the regions containing cancer and non-cancer was 24.1 ± 14.5 and 17.0 ± 9.0 kPa, respectively. Dividing the prostate into five parts (lateral apex, medial apex, lateral-mid, lateral base, medial-mid and medial base), the elastic modulus is the hardest at medial base and much lower at apex. The difference is about twice (25.4 vs 11.04 kPa). The elastic modulus was greater in the tissue with a Gleason score of 8 than in the other tissue, and was significantly greater in the tissue with a tumor volume >5 cm than in the other tissue [28].
Summering these reports, it is feasible to indicate elastography for the prostate cancer detection; however, we should recognize the difference of stiffness at tumor location and grade.
SE for assessment of lower urinary tract obstruction
An article reported a stiffness of prostate urethra of chronological voiding kinetics using SE. In this report, the difference of urethral stiffness between normal prostate and BPH was analyzed [29].
Problems with interventional use
According to the reports mentioned above, it is clear that prostate cancers are detected with high sensitivity by the use of SE. On the other hand, there are various problems.
First of all, one of the problems is that the type of probe used in each report was different and the diagnosis criteria for a positive diagnosis were not as unified as those of breast cancer.
Secondary, other problems are that there are many useless images because of the dislocation of plane or inappropriate compression when compressing manually. The probe head is far from the hand; even a little shaking makes a large vibration at the probe head in TRUS. Therefore, a free-hand operation requires operator’s skill to obtain correct reproducibility, and the compression technique depends upon the examiner skill and experience. To solve the problems, as mentioned in “Introduction” and “Scanning method” sections, image stability has been enhanced with RBIE. Using this method, stable elastographic images are easily obtained; however, the operation has become cumbersome. An automatic compression system is future assignment.
One of the further problems in SE for the prostate is that there are many false-positive cases of enlarged inner glands as mentioned in “Elastography of normal/prostatic hypertrophy” section. The larger the prostate volume, the more conspicuous this problem becomes. The point of this lowness of specificity leads that SE is not able to reduce the number of biopsy cores in large BPH cases. In addition, we should not ignore the fact that low Gleason tumor is similar to BPH nodule [27]. Is this the limit of elastographic detection for prostate cancer? It will be necessary to construct a color map that corresponds to the elasticity modulus of the prostate tissue.
Perspective on elastography for the prostate
Although SE of the prostate has many disadvantages compared to that of the breast as mentioned previously, we should overcome these problems step by step. Recently, many articles have reported that MRI improves the prostate cancer detection; however, results indicating its superiority have not been shown [23, 30]. The superiority of target biopsy using SE to the current systematic biopsy has not yet been observed as well. There has been a report of combined study of MRI and SE [30]. The aim of this report is to compensate each weak point and to improve cancer detection. Combining both imaging methods contributes to improving the diagnostic accuracy of prostate cancer detection [23, 30].
At present, almost all existing research reports have used SE. Research in relation to applications of SWE in the diagnosis of prostate cancer has hardly been seen in Japan.
In summary, the application of elastography for prostate cancer detection is highly expected. Therefore, research reports in relation to further improvement in the diagnostic accuracy such as sensitivity and specificity are being awaited. It is understood that there is a need for advances in efforts by equipment performance and universal diagnostic criteria.
Recommendation: Elastography has an additional diagnostic effect to systemic biopsy for detection of prostate cancer.
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Terminology and Diagnostic Criteria Committee, Japan Society of Ultrasonics in Medicine
Chairperson: Yoshiki Hirooka
Subcommittee of Clinical Practice Guidelines for Ultrasound Elastography: Prostate of the Japan Society of Ultrasonics in Medicine
Chairperson: Tokunori Yamamoto
Vice Chairperson: Koji Okihara
Members: Masakazu Tsutsumi, Atsushi Ochiai, Masahiro Sumura, Yukihiro Umemoto, Tomoaki Miyagawa, Tsuyoshi Shiina
Appendix
Appendix
Yoshiki Hirooka
Department of Endoscopy, Nagoya University Hospital, Aichi, Japan
Tokunori Yamamoto
Department of Urology, Nagoya University Graduate School of Medicine, Aichi, Japan
Koji Okihara
Department of Urology, Kyoto Prefectural University of Medicine Clinical Medical Studies, Kyoto, Japan
Masakazu Tsutsumi
Department of Urology, Hitachi General Hospital, Ibaraki, Japan
Atsushi Ochiai
Department of Urology, Aiseikai Yamashina Hospital, Kyoto, Japan
Masahiro Sumura
Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan
Yukihiro Umemoto
Department of Nephrology and Urology, Nagoya City University Graduate School of Medical Sciences and Medical School, Aichi, Japan
Tomoaki Miyagawa
Department of Urology, Saitama Medical Center, Jichi Medical University, Tochigi, Japan
Tsuyoshi Shiina
Department of Human Health Sciences, Graduate School of Medicine Kyoto University, Kyoto, Japan
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Terminology and Diagnostic Criteria Committee, Japan Society of Ultrasonics in Medicine. Clinical practice guidelines for ultrasound elastography: prostate. J Med Ultrasonics 43, 449–455 (2016). https://doi.org/10.1007/s10396-016-0703-3
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DOI: https://doi.org/10.1007/s10396-016-0703-3