Stesura Seveso Archivio Italiano di Urologia e Andrologia 2024; 96(3):12690 1 ORIGINAL PAPER Asian countries (0.6-5.0%) and among populations of black African origin (0.1-3.5%). These differences are probably related to genetic, environmental, and lifestyle factors (3-12). It is hypothesized that the prevalence of PD in men is much higher due to the underreporting of symptoms, as patients may feel embarrassed and choose not to report their embarrassing problem (3). PD can result in penile deformity, penile pain, erectile dysfunc- tion, and psychological distress (anxiety and depression); penile deformities may involve curvature, shortening, tor- sion, indentations, and hourglass deformity (13-17). The precise cause of PD is not completely understood, but it is generally believed to be initiated by a local injury (18- 20). Although it can be triggered by traumatic sexual experience or injury, 70% of cases have no specific cause, and patients do not remember a traumatic event (21). When an injury occurs, fibrin is deposited and a small hematoma forms. In people without a genetic predisposi- tion to the disease, the hematoma is absorbed back into the penile corpora cavernosa. In individuals with a genet- ic predisposition, the hematoma causes the activation of inflammatory cells and proinflammatory cytokines, resulting in the formation of chronic inflammatory tissue that progresses to fibrosis over time (22-24). In the last two decades, studies have demonstrated that oxidative stress (OS) is crucial in the development of plaque and the progression of this disease (22-29). Diagnosing PD involves a medical history, physical exam- ination, penile palpation, photographic documentation of penile curvature, dynamic penile color Doppler US, com- puted tomography, and Magnetic Resonance Imaging (30-32). Computed tomography and radiography are excellent at visualizing penile plaque calcifications, while MRI is accurate at identifying plaques in complex locations, such as the corporal septum. B-mode US medical imaging is highly useful for localizing and characterizing Peyronie’s plaque. Regarding the ultra- sound appearance, penile plaques are typically observed as localized areas of hyperechoic thickening of the tunica albuginea, showing strong echogenicity with significant attenuation of the acoustic beam. Moreover, elastography is a new and emerging method Background: B-mode ultrasound (US) med- ical imaging is very effective in localizing and describing Peyronie's disease (PD). Moreover, elastography is a new technique used to evaluate tissue elasticity to detect penile Peyronie's plaques that are not visible using standard B- mode US. Objective: The main objective of this study was to evaluate the diagnostic efficacy of real-time elastography (RTE) or strain elastography (SE) in PD patients and to determine whether its combined use with standard US improved diagnostic accuracy. Additionally, this study aimed to assess whether RTE was useful for monitoring PD patients undergoing conservative treatment. Methods: A group of 37 patients with PD in the active phase was selected based on US examination showing isoechoic or hypo-isoechoic plaques, with or without associated hyperechoic or calcified plaque areas. All patients underwent traditional US combined with RTE before starting conservative treatment with antioxidants, during treatment and after treatment. After each examination with RTE, a specific “Strain Ratio”(SR) was used to identify the specific elasticity of the tissue. Results: Using B-mode US with RTE, we detected all 13 non-pal- pable penile plaques present in the 37 PD patients (100% of cases). Using only B-mode US, we detected only 8 of the 13 non- palpable plaques (61.5% of cases). The Deformation Index (DI) of the plaque decreased during and after treatment in all cases, indicating that RTE is effective for monitoring conservative PD treatment. A statistically significant correlation was found between the DI and plaque volume in all patients (p = 0.002). Conclusions: Our study has shown that the combination of US and RTE methods allowed for a more accurate diagnosis in PD patients. KEY WORDS: B-mode ultrasound; Peyronie's disease; Penile plaques; Elastography; Strain imaging. Submitted 26 May 2024; Accepted 13 June 2024 INTRODUCTION Peyronie's disease (PD) is a pathological condition that affects the tunica albuginea of the penis in males with a genetic predisposition, causing the formation of fibrous plaques (1, 2). The occurrence of PD is more common in Western countries (3.2-13.1%) and less common in Combining ultrasound and elastography for the detection of a non-palpable, non-sonographically visualized Peyronie's plaques. Our experience Gianni Paulis 1, Giovanni De Giorgio 2, Andrea Paulis 3 1 Department of Urology and Andrology, Peyronie’s Care Center, Castelfidardo Clinical Analysis Center, Rome, Italy; 2 Section of Ultrasound Diagnostics, Department of Urology and Andrology, Castelfidardo Clinical Analysis Center, Rome, Italy; 3 Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. DOI: 10.4081/aiua.2024.12690 Summary Archivio Italiano di Urologia e Andrologia 2024; 96(3):12690 G. Paulis, G. De Giorgio, A. Paulis 2 that studies the elastic properties of tissue to identify penile plaques that may not be visualized with tradition- al B-mode US studies. Furthermore, elastography is the most suitable imaging modality in PD because it allows for non-invasive highlighting of penile plaques and mon- itoring of the therapeutic response to various treatments. In addition, elastography has recently been suggested as a diagnostic tool for PD. Palpation of the penis is essential in the evaluation of the patient, as most patients with Peyronie's disease have a palpable plaque that is clearly distinguishable from the rest of the penile corpora caver- nosa. However, documentation with a diagnostic imaging method is often necessary to support the clinical diagno- sis. B-mode US examination can identify the location, number, size, and echogenicity of the plaques. The main bias and disadvantage of this method is that tra- ditional US can only detect between 40% and 84.2% of palpable plaques (33-36). Elastography is a non-invasive technique that uses an ultrasound probe to measure the mechanical properties of tissue, which can be affected by a disease process, making the tissue more rigid. The different levels of tissue elasticity under the pressure of the ultrasound probe are expressed in a more or less relevant way and evaluated using a color scale. Elastography diagnostic approaches were first developed at the end of the last century and, subsequently, numer- ous scientific studies have been published (37). Elastography is primarily used to diagnose soft tissue pathologies in the liver, breast, prostate, thyroid, pan- creas, nerves, tendons, muscles, and other conditions. Furthermore, elastography has also been suggested for studying PD (32-36, 38-44). The World Federation of Ultrasound Medicine and Biology categorized “elastographic techniques“ as strain elastography (SE), transient elastography, and acoustic radiation force impulse (ARFI). The ARFI techniques can be subcatego- rized into point shear wave elastography (SWE), 2D SWE, and 3D SWE techniques (45). SE, also known as real-time elastography (RTE), is a qual- itative method that assesses the relative stiffness of vari- ous tissues and examines how tissues can deform when subjected to external forces and then return to their orig- inal shape. SE assesses tissue deformation using manual compression or natural motion. SE measures the strain caused by "quasi-static" methods, such as manual com- pression or cardiovascular/respiratory pulsation, and dis- plays the distributions of the strain or normalized strain values within the region of interest (ROI). Tissue deforma- tion can be achieved by manually applying micro-pres- sure with the ultrasound probe or by using ultrasound pulses of appropriate intensity (44). In the second method of excitation, the ultrasound remains stationary while tissue displacement is induced via internal physio- logical movements such as cardiac and arterial pulsations and respiratory motion. In both cases, the ultrasound images are compared before and after the compression, and the equipment produces a color map that indicates the relative elasticity of the various tissue components, ultimately displaying a specific Strain Ratio (SR). SR is cal- culated by comparing the strain index of a lesion to that of healthy tissue at the same level. SR therefore indicates a measurement of the stiffness of the sampled tissue. SE measures the relative stiffness of tissues within the elastographic region of interest (ROI) overlaid on a B-mode US image; therefore, the ROI must be accurately aligned with the Peyronie’s plaque. The color map is shown in real time, overlaid on an ultrasound image of the tissues being examined. Usually, the color blue is utilized to indicate low strain (i.e., stiff tissue), while red is used to indicate high strain (i.e., soft tissue), although the exact color scale may differ depending on the manufacturer of the ultrasound equipment (35). Strain elastography is also used for the diagnostic study of PD. In the literature, there are four articles on this topic (33-35, 42). The objective of this study was to evaluate the diagnostic effi- cacy of RTE in patients with Peyronie's disease and to determine whether its combined use with traditional ultrasound imaging improves diagnostic accuracy. This study aimed to determine whether this diagnostic combi- nation could detect nonpalpable and/or isoechoic Peyronie's plaques with or without hyperechoic or calci- fied plaque areas, which cannot be detected with a simple standard US examination. This study also aimed to eval- uate whether US associated with RTE was effective for monitoring patients with PD undergoing conservative treatment. The secondary objective of this study was to examine the relationship between plaque stiffness and the degree of curvature and plaque volume, as well as to detect the prevalence of anxiety and depression in patients with PD. MATERIALS AND METHODS The authors conducted this study by collecting and ana- lyzing existing data of 249 patients who visited our Peyronie’s Care Center and underwent US and elastogra- phy of the penis from January 1, 2018, to December 31, 2023, and were found to be affected by PD. After applying the inclusion and exclusion criteria, 212 PD patients who were in the stabilized or active phase of the disease and presented exclusively hyperechoic and/or calcified plaques were excluded from the main study. Objectives The main objective of this retrospective study was to assess the diagnostic efficacy of RTE, also known as SE, in patients with Peyronie's disease (PD) and investigate if its integration with conventional ultrasound (US) imaging enhances diagnostic precision. Since this study primarily aimed to determine whether the diagnostic combination of US and RTE could detect non-palpable Peyronie's plaques that cannot be detected via physical examination of the PD patient or via a simple standard US, inclusion criteria were determined for the in-depth study of those PD patients in whom RTE could potentially increase the diagnostic level. Evaluation and diagnosis The diagnosis of Peyronie's disease was made for all patients after conducting the following assessments: pal- pation of the penis; photographic documentation of penile deformity (according to Kelâmi) with a goniomet- ric measurement of the angulation; penile US with RTE or penile color Doppler US with RTE (only for patients with Archivio Italiano di Urologia e Andrologia 2024; 96(3):12690 3 Elastographyfor Peyronie’s plaques associated erectile dysfunction) with plaque measure- ments (in three dimensions, in mm) and volume calcula- tion (mm3) using the ellipsoid formula (volume = 0.524 × length × width × thickness); and completion of the International Index of Erectile Function (IIEF) questionnaire for measuring erectile function, the visual analog scale (VAS) questionnaire for measuring pain, the Generalized Anxiety Disorder Questionnaire-7 (GAD-7, for anxiety), and the Patient Health Questionnaire-9 (PHQ-9, for depression) (46-52). Regarding the last two question- naires, we decided to also study the psychological condi- tion of these patients, as we believe that psychological distress is a symptom of PD, just like curvature, pain, and erectile dysfunction. To identify and confirm the presence of penile plaque, along with its location and volume, we subjected all 37 patients to combined US and RTE examination of the penis at the time of initial diagnosis and during the planned follow-up assessments during conservative treat- ment. A single andrologist operator performed and eval- uated conventional US and SE of the penis on all patients in one session using the same ultrasound device, the Philips Affinity 70 G, and a high-frequency linear array transducer, the Philips Linear Probe L12-5 (Philips, Washington, United States). The elasticity values were cal- culated and color-coded to represent tissue elasticity. The color scale ranged from red (i.e., soft tissue) to blue (i.e., stiff tissue), with components showing average strain dis- played as green. Finally, a calculation indicating a specific SR was displayed on the equipment monitor. The areas included in the Strain Ratio calculation are selected by the operator by pointing the probe at the stiffest area and then at the normal tissue (soft). Inclusion criteria Patients with Peyronie's disease in the active phase who underwent US examination and presented isoechoic or hypo-isoechoic plaques, with or without associated hyperechoic or calcified plaque areas. Exclusion criteria Patients with Peyronie's disease in the stabilized or active phase who underwent US examination and presented exclusively hyperechoic and/or calcified plaques. After applying the inclusion and exclusion criteria, 212 PD patients who were in the stabilized or active phase of the disease and presented exclusively hyperechoic and/or calcified plaques were excluded from the main study. Finally, a group of 37 patients with Peyronie's disease in the active phase was selected based on US examination and RTE (in the same diagnostic session) showing isoe- choic or hypo-isoechoic plaques, with or without associ- ated hyperechoic or calcified plaque areas. Treatment and follow up As previously indicated, in this study, we specifically focused on the analysis of data relating to US and RTE combination examinations in patients with PD to evaluate whether US associated with RTE is effective for monitor- ing PD patients undergoing conservative treatment. Therefore, after the first visit of the patients to our andro- logical center, we performed a combined diagnostic US and RTE on 37 PD patients before starting conservative treatment with antioxidants. Patients underwent US and RTE every six months during and after treatment. Conservative treatments to which these patients were subjected were retrospectively identified from the data in our clinical archive and are not the subject of this article. Some of these patients have undergone multiple treat- ment cycles. For completeness, we describe our standard conservative medical treatment: oral L-carnitine 1000 mg + propolis 700 mg + silymarin 400 mg + coenzyme Q-10 100 mg + bilberry 180 mg + ginkgo biloba 240 mg + vita- min E 48 mg + vitamin C 50 mg + superoxide dismutase 11000 IU/g 10 mg/daily and topical diclofenac gel 4%/2 times daily + peri-plaque penile injections (only in the case of plaques with volume ≥ 100 mm3) with pentoxi- fylline 100 mg (30 G needle) every month for 6 months. Statistical analysis We utilized CalculatorSoup® software (version of Mar 07, 2023, Ashland, MA,USA) to conduct the statistical analysis involving the calculation of standard deviation and mean, median, and interquartile range (IQR). The Pearson corre- lation coefficient was calculated using Statistics Kingdom statistical software (version 2017, Melbourne, Australia, http://www.statskingdom.com) and Excel (version 2011, MS Office, Redmond, WA, USA). In the statistical analyses, a significance level of 5% for alpha error (p-value < 0.05) was considered to demonstrate statistical significance. This study was carried out in accordance with the princi- ples outlined in the Declaration of Helsinki (Fortaleza, 2013). All participants were contacted and gave their informed consent for the study. However, sensitive data were anonymized in accordance with privacy regulations as per legislative decree 10 August 2018, n. 101 adapted to the General Data Protection Regulation/GDPR (Official Gazette of the Italian Republic, General Series n. 205, dated 4 September 2018). RESULTS The 37 patients with Peyronie's disease who were select- ed for this study (with isoechoic or hypo-isoechoic plaques, with or without associated hyperechoic or calci- fied plaque areas) were aged between 23 and 74 years, with a mean age = 51.3 years (SD ± 14.7). The plaque volume in the 37 selected patients ranged from 11.5 to 2660 mm3. Table 1 shows the physical and echo-elastographic char- acteristics of the plaques of the 37 patients. Non-palpable plaques Using B-mode US with RTE, we detected all 13 non-pal- pable penile plaques present in the 37 selected PD patients (100% of cases). Using only B-mode US, we detected only 8 of the 13 non-palpable plaques (61.5% of cases). Soft plaques When using US examination on 37 PD patients, only one out of seven barely palpable (soft) plaques were detected (14.2%). However, with RTE, all seven soft plaques were detected (100%). Archivio Italiano di Urologia e Andrologia 2024; 96(3):12690 G. Paulis, G. De Giorgio, A. Paulis 4 Isoechoic or hypo-isoechoic plaques When using US examination, 29 out of 37 isoechoic or hypo-isoechoic plaques, with or without associated hyperechoic or calcified plaque areas, were identified (78.3%), while the remaining 8 plaques (21.6%) were not identified. Specifically, the eight plaques that were not identified were completely isoechoic. Therefore, using US, entirely isoechoic plaques were found in only 2 out of 10 cases (20%). All 37 plaques were instead identified with RTE (100%). Ultrasound findings in relation to the volume of PD plaques Out of 21 plaques with a volume up to 500 mm3, 19 plaques (90.4%) were identified, and 2 plaques (9.5%) were not identified using only US, while all 21 plaques were identified with RTE (100%). All 16 remaining larg- er PD plaques over 500 mm3 were identified with US (100%) and also with RTE. A statistically significant correlation was found between the Deformation Index (Strain Ratio) and plaque volume in the 37 selected patients, p-value = 0.002 (p < 0.05). Figure 1 shows the graph that highlights this correlation. No statistically significant correlation was found between the Strain Ratio and the degree of angulation of the penile curvature of the 37 selected patients: r = 0.2848, r2 = 0.08109, p-value = 0.08759 (p > 0.05). In Figure 2 below, we present four examples of plaques that were not detected with traditional US but were instead detected with RTE. Please note that during each elastography scan, circles (light blue color) were placed by the operator on the stiffer (blue) and normal (soft) areas corresponding to the ROI. At the end of this proce- dure, the elastography software provided the Strain Ratio after the relative calculation. Treatment and follow up Figure 3 shows the Deformation Index (or Strain Ratio) values of the plaques before, during, and after the treat- ments The results presented demonstrate that the Strain Ratio decreased during the monitoring at each follow-up assessment. The Strain Ratio value is considered pathological when it is greater than 1. RTE measurements were performed every 6 months during the course of conservative treat- ment. The 37 selected patients underwent multiple treat- ment cycles, ranging from two to four cycles. Some patients underwent a greater number of follow-up assess- ments because they were observed before the others. Psychological assessment The results of the GAD-7 and PHQ-9 questionnaires showed that in the 37 patients with Peyronie's disease, significant anxiety was present in 70.2% of cases and severe anxiety in 18.9% of cases. Significant depression was present in 45.9% of cases, with no cases of severe depression. Table 1. Physical and echo-elastographic characteristics of the plaques of the 37 patients. Palpatory features of the plaque N. cases (out 37) (%) Non-palpable 13 (35.1) Soft 7 (18.9) Fibrous 11 (29.7) Fibrocalcific 6 (16.2) Ultrasound imaging of the plaque Hypo-isoechoic 12 (32.4) Isoechoic 10 (27.0) Iso-hyperechogenicity (mixed plaque) 1 (2.7) Iso-hyperechogenicity associated with calcification (mixed plaque) 3 (8.1) Hypo-isoecogenicity associated with hyperechogenicity (mixed plaque) 2 (5.4) Hypo-isoecogenicity associated with calcification (mixed plaque) 9 (24.3) Plaque volume (mm3) Up to 100 6 (16.2) From 101 to 300 10 (27.0) From 301 to 500 5 (13.5) From 501 to 1000 10 (27.0) From 1001 to 2000 5 (13.5) > 2000 1 (2.7) Strain Ratio of the plaque detected via strain elastography (SE) > 1 to 2 18 (48.6) > 2 to 3 16 (43.2) > 3 to 4.4 3 (8.1) The Strain Ratio is considered pathological when it is greater than 1. Figure 1. Graph highlighting the relationship between plaque volumes and Deformation Index (or Strain Ratio) values. Archivio Italiano di Urologia e Andrologia 2024; 96(3):12690 5 Elastographyfor Peyronie’s plaques DISCUSSION The authors specify that, for the elastography study, they preferred to use SE, also known as RTE. SE is preferable for studying superficial pathologies such as plaques that develop in Peyronie’s disease because it has high spatial res- olution. In fact, in this pathology, SE, owing to its high sensitivity, is important for visualizing the area of fibrosis associated with it, even in the absence of detectable B-mode images. We should also add that in order to use SE correctly, it is essential for the procedure to be conducted by an experienced operator and to use the latest technology to achieve the correct visualization of Peyronie’s plaque. Using B-mode US with RTE, we detected all 13 non-palpable penile plaques present in the 37 selected PD patients (100% of cases). Using only B-mode US, we detected only 8 of the 13 non- palpable plaques (61.5% of cases). In 11 out of these 13 cases, a penile curvature was present. Furthermore, in two of these patients with non- palpable penile plaque who did not report penile pain or erectile dysfunction problems, there was a penile deformity, including both penile curva- ture and shortening. In these two cases the ultra- sound diagnosis would have been completely negative without performing RTE. We believe that the penile plaques could not be palpated, mainly due to their small size, which in most cases never exceeded a volume of 300 mm3. In a study by Dell’Atti et al., using only B-mode Figure 3. Deformation Index (Strain Ratio) values of penile plaques in 37 patients with Peyronie's disease, before and after treatment. Figure 2. Examples of four non-palpable and isoechoic Peyronie's plaques that were not detectable with traditional ultrasound (US) but identified with real-time elastography (RTE). Archivio Italiano di Urologia e Andrologia 2024; 96(3):12690 G. Paulis, G. De Giorgio, A. Paulis 6 US to detect non-palpable Peyronie’s plaques, small plaque volumes and fairly similar ultrasound features were found; however, they found 41 non-palpable penile plaques in 386 patients with PD (10.6% of cases) (53). In our study, using only B-mode US, we detected non-palpa- ble plaques in 8 out of 37 cases (21.6% of cases). Regarding the incidence of non-palpable plaques in patients with Peyronie’s disease, other authors using only B-mode US studies, although with different ultrasound machines, have reported detection rates of 6.0%, 22.5%, and 32.4% in PD cases (33, 54, 55). Referring to the ultrasound appearance of the plaques (isoechoic or hypo-isoechoic, with associated hypere- chogenicity or calcification) using only B-mode US, we detected penile plaques in 29 out of 37 cases (78.3% of cases). However, when using B-mode US with RTE, we detected all 37 penile plaques (100% of cases) in the respective 37 patients. Penile plaques appear as localized areas of thickening in the tunica albuginea on ultrasound, showing strong echogenicity and significant attenuation of the acoustic beam. However, in our study, almost all noncalcified penile plaques were found to be isoechoic or slightly hyperechoic compared to the surrounding cavernous tis- sue. The peculiarity of our results is due to the selection of patients due to the inclusion criteria of our study. Nevertheless, there are few articles in the literature that specifically discuss the possibility of the existence of isoe- choic plaques (56-58). In our study, the isoechoic penile plaques detected using only B-mode US were only 2 out of 10 (20% of cases). Instead, using B-mode US with RTE, we detected all 10 isoechoic penile plaques (100% of cases) in the respective 10 patients. However, when the penile plaques were not isoechoic, B-mode US was consistently able to detect all the penile plaques. This demonstrates that when B-mode US is combined with RTE, the diagnostic accuracy is sig- nificantly improved. Similar results were obtained by other authors who used elastography associated with conventional B-mode US (33-36, 42). Our study has shown a strong statistical cor- relation between the Strain Ratio values of the plaque and its volume (p-value = 0.002). Of course, it seems logical that increasing the size of the plaque also increases its rigidity; however, this correlation had never been demon- strated in Peyronie’s disease. Otherwise, we did not find any statistically significant correlation between the Strain Ratio and the degree of angulation of the penile curvature angle (p > 0.05). It should be noted that, in our case series, 3 out of 37 patients did not have penile curvature due to the central location of the plaque (between the two corpora caver- nosa), and this may have resulted in the absence of this correlation. However, other authors, using a different method of elastography (shear wave elastography, SWE), have shown a relationship between the stiffness of the selected plaque area (expressed in kPa) and the curvature angle of the penis (41). Our study has shown that RTE combined with tradition- al US is very useful for monitoring patients with Peyronie's disease during conservative treatment with antioxidants and antifibrotics. In this way, in addition to the reduction in plaque volume, which we could have demonstrated using traditional US alone, we were also able to observe the progressive reduction in the stiffness of the affected area. A very similar observation has been made by other authors who, using another elastography method (SWE), have analyzed the changes in elastogra- phy after administering a compound made up of Ecklonia bicyclis, Tribulus terrestris, and water-soluble Chitosan (Biovis) (39). After researching the prevalence of anxiety in patients with PD, we found that 70.2% of cases had significant anxiety, and 18.9% of cases had severe anxiety. There are no precise data in the literature regarding the incidence of anxiety symptoms during PD; however, a study by Smith and colleagues found that 81% of PD patients reported "emotional difficulties" (59). After researching the preva- lence of depression in PD patients, we found that signifi- cant depression was present in 45.9% of cases, with no cases of severe depression. Nelson and colleagues found that 48% of PD patients exhibited clinically significant depression (14, 60). We believe that depressive and anx- iety symptoms, if not investigated in PD patients using specific questionnaires, may remain unknown or at least be underestimated in terms of severity and prevalence. Our data on the prevalence of anxiety in patients with PD confirm that the anxious and depressive states represent important symptoms of PD, as well as penile pain, penile curvature/deformation, and erectile dysfunction. In uro- andrological clinical practice, psychologists should be involved in providing supportive treatment to patients with PD. In this way, we could reduce the psychological impact of PD, which has been described by some impor- tant authors as a psychologically and physically devastat- ing disease (61-65). Although our findings are quite interesting, the limitation of our study is that the sample size was not very large. However, our limited sample was determined by very selective inclusion criteria. CONCLUSIONS RTE is a modern non-invasive technique that can accu- rately identify penile plaques in patients with Peyronie's disease, complementing B-mode US. Furthermore, RTE is very useful for diagnosing the disease at an earlier stage (isoechoic plaque) than B-mode US alone. Additionally, RTE is especially valuable when palpation and B-mode US are unable to identify a plaque. RTE can also accu- rately assess plaque stiffness, size, and volume. RTE offers an additional method for uro-andrologists to monitor conservative treatment in patients with Peyronie's dis- ease. More extensive prospective studies are needed to determine the diagnostic accuracy and clinical utility of this imaging technique. REFERENCES 1. Herati AS, Pastuszak AW. The Genetic Basis of Peyronie Disease: A Review. Sex Med Rev. 2016; 4:85-94. 2. Bias WB, Nyberg LM Jr, Hochberg MC, Walsh PC. Peyronie's dis- ease: a newly recognized autosomal-dominant trait. Am J Med Genet. 1982; 12:227-235. Archivio Italiano di Urologia e Andrologia 2024; 96(3):12690 7 Elastographyfor Peyronie’s plaques 3. Hellstrom WJ, Bivalacqua TJ. Peyronie’s disease: Etiology, med- ical, and surgical therapy. J. Androl. 2000, 21, 347-354. 4. Rhoden EL, Teloken C, Ting HY, et al. Prevalence of Peyronie's disease in men over 50-y-old from Southern Brazil. Int J Impot Res. 2001; 13:291-293. 5. La Pera G, Pescatori ES, Calabrese M, et al. Peyronie's disease: prevalence and association with cigarette smoking. A multicenter population-based study in men aged 50-69 years. Eur Urol. 2001; 40:525-530. 6. Schwarzer U, Sommer F, Klotz T, et al. The prevalence of Peyronie's disease: results of a large survey. BJU Int. 2001; 88:727-730. 7. Johnson HM, Weerakoon P, Stricker PD. The incidence, aetiology, and presentation of Peyronie’s disease in Sydney, Australia. J Sex Disabil. 2002; 20:109-116. 8. DiBenedetti DB, Nguyen D, Zografos L, et al. A Population-Based Study of Peyronie’s Disease: Prevalence and Treatment Patterns in the United States. Adv Urol 2011; 2011:282503. 9. Shiraishi K, Shimabukuro T, Matsuyama H. The prevalence of Peyronie’s disease in Japan: A study in men undergoing maintenance hemodialysis and routine health checks. J Sex Med. 2012; 9:2716-2723. 10. Stuntz M, Perlaky A, des Vignes F, et al. The Prevalence of Peyronie’s Disease in the United States: A Population-Based Study. PLoS ONE 2016; 11:e0150157. 11. Kyei MY, Mensah JE, Asante E, et al. Peyronie’s Disease in People of African Origin: A Mini Review. J. Ger. Ag. Res. 2017; 1:104. 12. Bella AJ, Lee JC, Grober ED, et al. 2018 Canadian Urological Association guideline for Peyronie’s disease and congenital penile curvature. Can Urol Assoc J. 2018; 12:E197-E209. 13. Weidner W, Schroeder-Printzen I, Weiske WH, et al. Sexual dys- function in Peyronie’s disease: An analysis of 222 patients without previous local plaque therapy. J Urol. 1997; 157:325-328. 14. Nelson CJ, Diblasio C, Kendirci M, et al. The Chronology of Depression and Distress in Men with Peyronie’s Disease. J Sex Med. 2008; 5:1985-1990. 15. Paulis G, Romano G, Paulis A. Prevalence, psychological impact, and risk factors of erectile dysfunction in patients with Peyronie’s dis- ease: A retrospective analysis of 309 cases. Res Rep Urol. 2016; 8:95- 103. 16. Wong A, Tsang SS, O RY, et al. Mp33-12 Prevalence of Peyronie’s disease and its psychosexual impact in the chinese popu- lation: A large cohort population-based cross-sectional study. J Urol. 2020; 203:e499. 17. Kuja-Halkola R, Henningsohn L, D’Onofrio BM, et al. Mental Disorders in Peyronie’s Disease: A Swedish Cohort Study of 3.5 Million Men. J Urol. 2021; 205:864-870. 18. Devine CJ Jr, Somers KD, Ladaga LE. Peyronie’s disease: Pathophysiology. Prog Clin Biol Res. 1991; 370:355-358. 19. Devine CJJ, Somers KD, Jordan GH, et al. Proposal: Trauma as a cause of Peyronie’s lesion. J Urol. 1997; 157:285-290. 20. Jarow JP, Lowe FC. Penile trauma: An etiologic factor in Peyronie’s disease and erectile dysfunction. J Urol. 1997; 158:1388-1390. 21. Segal RL, Burnett AL. Surgical Management for Peyronie's Disease. World J Mens Health. 2013; 31:1-11. 22. El-Sakka AI, Salabas E, Dinçer M, et al. The pathophysiology of Peyronie’s disease. Arab J Urol. 2013; 11:272-277. 23. Paulis G, Romano G, Paulis L, et al. Recent Pathophysiological Aspects of Peyronie’s Disease: Role of Free Radicals, Rationale, and Therapeutic Implications for Antioxidant Treatment-Literature Review. Adv Urol. 2017; 2017:4653512. 24. Paulis G, De Giorgio G, Paulis L. Role of Oxidative Stress in Peyronie’s Disease: Biochemical Evidence and Experiences of Treatment with Antioxidants. Int J Mol Sci. 2022; 23:15969. 25. Sikka SC, Hellstrom WJ. Role of oxidative stress and antioxidants in Peyronie’s disease. Int J Impot Res. 2002; 14:353-360. 26. Paulis G, Brancato T. Inflammatory mechanisms and oxidative stress in Peyronie’s disease: Therapeutic “rationale” and related emerging treatment strategies. Inflamm Allergy Drug Targets 2012; 11:48-57. 27. Davila HH, Magee TR, Vernet D, et al. Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie’s disease. Biol Reprod. 2004; 71:1568-1577. 28. Bivalacqua TJ, Champion HC, Hellstrom WJ. Implications of nitric oxide synthase isoforms in the pathophysiology of Peyronie’s disease. Int J Impot Res. 2002; 14:345-352. 29. Gonzalez-Cadavid NF, Magee TR, et al. Gene expression in Peyronie’s disease. Int J Impot Res. 2002; 14:361-374. 30. McCauley JF, Dean RC. Diagnostic utility of penile ultrasound in Peyronie's disease. World J Urol. 2020; 38:263-268. 31. Kelâmi A. Autophotography in evaluation of functional penile disorders. Urology 1983; 21:628-629. 32. Parmar M, Masterson JM, Masterson TA, 3rd. The role of imag- ing in the diagnosis and management of Peyronie's disease. Curr Opin Urol. 2020; 30:283-289. 33. Lahme S, Zimmermanns V, Liske P, et al. Real-Time Elastography (RTE) in Patients with Peyronie’s Disease: First Results of �a New Imaging Technique for the Detection and Mesurement of Plaques. J Urol. 2009; 181:280. 34. Morana C, Loiero G, Sangiorgio A, et al. Elastosonography in the Peyronie's disease: our preliminary experience. Arch Ital Urol Androl. 2010; 82:269-270. 35. Riversi V, Tallis V, Trovatelli S, et al. Realtime-elastosonography of the penis in patients with Peyronie's disease. Arch Ital Urol Androl. 2012; 84:174-177. 36. Zhao S, Wu X, Zhang,Y, et al. Role of Shear Wave Elastography in the Diagnosis of Peyronie Disease. J Ultrason Med. 2024; 43:397- 403. 37. Ophir J, Céspedes I, Ponnekanti H, et al. Elastography: a quan- titative method for imaging the elasticity of biological tissues. Ultrason Imaging 1991; 13:111-134. 38. Zhang X, Zhou B, Miranda AF, et al. A Novel Noninvasive Ultrasound Vibro-elastography Technique for Assessing Patients With Erectile Dysfunction and Peyronie Disease. Urology 2018; 116:99-105. 39. Trama F, Riccardo F, Ruffo A, et al. Elastosonographic Changes in Patients with Peyronie's Disease, before and after Treatment with a Compound Based on Ecklonia bicyclis, Tribulus terrestris, and Water-Soluble Chitosan. OJU Journal. 2018; 8:77-87. 40. Tyloch JF, Tyloch DJ, Adamowicz J, et al. Application of three- dimensional ultrasonography (3D ultrasound) to pretreatment eval- uation of plastic induration of the penis (Peyronie's disease). Med Ultrason. 2020; 22:159-163. 41. Trama F, Illiano E, Iacono F, et al. Use of penile shear wave elas- Archivio Italiano di Urologia e Andrologia 2024; 96(3):12690 G. Paulis, G. De Giorgio, A. Paulis 8 tosonography for the diagnosis of Peyronie's Disease: a prospective case-control study. Basic Clin Androl. 2022; 32:15. 42. Richards G, Goldenberg E, Pek H, et al. Penile sonoelastography for the localization of a non-palpable, non-sonographically visualized lesion in a patient with penile curvature from Peyronie's disease. J Sex Med. 2014; 11:516-520. 43. Dhawan S, Dhok A, Phatak S, et al. Peyronie's Disease Presenting as Curvature of the Penis: A Case Report. Cureus 2022; 14:e32055. 44. Simon V, Dudea SM, Crisan N, et al. Elastography in the Urological Practice: Urinary and Male Genital Tract, Prostate Excluded-Review. Diagnostics (Basel) 2022; 12:1727. 45. Shiina T, Nightingale KR, Palmeri ML, et al. WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 1: basic principles and terminology. Ultrasound Med Biol. 2015; 41:1126-1147. 46. Kelâmi A. Autophotography in evaluation of functional penile disorders. Urology 1983; 21:628-629. 47. Eri LM, Thomassen H, Brennhovd B, et al. Accuracy and repeatability of prostate volume measurements by transrectal ultra- sound. Prostate Cancer Prostatic Dis. 2002; 5:273-278. 48. Lee JS, Chung BH. Transrectal ultrasound versus magnetic reso- nance imaging in the estimation of prostate volume as compared with radical prostatectomy specimens. Urol Int. 2007; 78:323-327. 49. Rosen RC, Riley A, Wagner G, et al. The international index of erectile function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49:822-830. 50. Kahl C, Cleland JA. Visual analogue scale, numeric pain rating scale and the McGill pain Questionnaire: An overview of psychome- tric properties. Phys Ther Rev. 2005; 10:123-128. 51. Spitzer RL, Kroenke, K, Williams, JB, et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch. Intern. Med. 2006; 166:1092-1097. 52. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: Validity of a brief depression severity measure. J Gen Intern Med. 2001; 16:606-613. 53. Dell'Atti L, Galosi AB. Sonographic patterns of Peyronie's disease in patients with absence of palpable plaques. Int Braz J Urol 2018; 44:362-369. 54. Lopez JA, Jarow JP. Duplex ultrasound findings in men with Peyronie's disease. Urol Radiol. 1991; 12:199-202. 55. Odiase VO, Whitaker RH. Peyronie's disease in a district gener- al hospital. Postgrad Med J. 1980; 56, 773-776. 56. Prando D. New sonographic aspects of peyronie disease. J Ultrasound Med. 2009; 28:217-232. 57. Kalokairinou K, Konstantinidis C, Domazou M, et al. US Imaging in Peyronie's Disease. J Clin Imaging Sci. 2012; 2:63. 58. Liu Y, Zheng D, Liu X, et al. Ultrasound on Erect Penis Improves Plaque Identification in Patients With Peyronie's Disease. Front Pharmacol. 2019; 10:312. 59. Smith JF, Walsh TJ, Conti SL, et al. Risk factors for emotional and relationship problems in Peyronie's disease. J Sex Med. 2008; 5:2179-2184. 60. Nelson CJ, Mulhall JP. Psychological impact of Peyronie's dis- ease: a review. J Sex Med. 2013; 10:653-660. 61. Taylor FL, Levine A. Peyronie's Disease. Urol Clin North Am. 2007; 34:517-534. 62. Bella AJ, Perelman MA, Brant WO, et al. Peyronie's disease (CME). J Sex Med. 2007; 4:1527-1538. 63. Jordan GH, Carson CC, Lipshultz LI. Minimally invasive treat- ment of Peyronie's disease: evidence-based progress. BJU Int. 2014; 114:16-24. 64. Porst H, Burri A, European Society for Sexual Medicine (ESSM) Educational Committee Current Strategies in the Management of Peyronie's Disease (PD)-Results of a Survey of 401 Sexual Medicine Experts Across Europe. J Sex Med. 2019; 16:901-908. 65. El-Sakka AI. Medical, non-invasive, and minimally invasive treatment for Peyronie's disease: A systematic review. Andrology 2021; 9:511-528. Correspondence Gianni Paulis, MD (Corresponding Author) paulisg@libero.it Department of Urology and Andrology, Peyronie’s Care Center, Castelfidardo Clinical Analysis Center, 00185 Rome, Italy Giovanni De Giorgio, MD g.degiorgio@analisiclinichecastelfidardo.it Section of Ultrasound Diagnostics, Department of Urology and Andrology, Castelfidardo Clinical Analysis Center, 00185 Rome, Italy Andrea Paulis, PhD andrea.fx.94@gmail.com Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy Conflict of interest: The authors declare no potential conflict of interest.