Multimodal Ultrasound Imaging Assessment on Keloid

• ClinicalTrials.gov Identifier: NCT06034587
• Recruitment Status: Completed
• First Posted: September 13, 2023
• Last Update Posted: September 13, 2023
• Sponsor: Chongqing Medical University
• Information provided by (Responsible Party): Wang Zhigang, Chongqing Medical University

Study Description

Brief Summary:

Skin keloids are common dermatological conditions that can lead to physical limitations, functional impairments, and deformities. Beyond the physiological implications, the aesthetic ramifications of keloids can also result in significant psychological distress, including anxiety and depression, causing both physical and emotional suffering to the affected individuals. The incidence of keloids is high, characterized by their chronicity, resistance to treatment, and high recurrence rate. They have become one of the most challenging conditions to treat across burn surgery, plastic surgery, and dermatology disciplines. The lack of standardized clinical treatment guidelines globally, combined with an absence of a well-defined standardized evaluation system, means that the effectiveness of various treatments is not consistently and objectively assessed, creating significant challenges in clinical applications. This project integrates traditional high-frequency ultrasound with cutting-edge technologies like real-time shear wave elastography and ultra-micro blood flow imaging. By using multimodal ultrasound, investigators aim to observe the therapeutic response of 90Sr-90Y patch treatment on skin keloids. Investigators seek to determine the objectivity and quantification role of multimodal ultrasound data and indicators in assessing keloid severity, including blood flow information and elasticity hardness. Another goal is to obtain quantitative data on keloid thickness, volume, stiffness, and microvascular distribution before and after treatment to monitor the therapy response. This would address the current limitations of subjective keloid scoring scales. It would also serve as an objective assessment standard for precise diagnosis, treatment, and follow-up of keloids in a clinical setting, thereby standardizing the clinical diagnosis and treatment of keloids.

Condition or disease	Intervention/treatment
Keloid	Diagnostic Test: multimodal ultrasound; Radiation: radioisotope applicator therapy

Detailed Description:

Currently, no one-size-fits-all approach exists and a universally accepted, standardized evaluation and treatment protocol remains elusive, making it challenging to determine which method is the most effective. Commonly used methods for assessing keloids, such as the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS), rely heavily on subjective evaluations based on observer perception and patient-reported experiences. These methods lack objective quantitative evaluation indicators and the ability to visualize subcutaneous tissues, limiting their individual clinical applicability. The Vancouver Scar Scale (VSS) is the most established questionnaire used for the evaluation of pathological scarring. This scale evaluates aspects of scar vascularity, pigmentation, pliability, and height, with the scoring system ranging from 0 to 15, where 0 is the least severe and 15 is the most severe. In the study, keloids were classified into three categories based on the VSS score: mild (0-5), moderate (6-9), and severe (10-15).

Study Design

• Study Type: Observational
• Actual Enrollment: 34 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Prospective, Longitudinal, Intraindividual Clinical Study in Keloid With Multimodal Ultrasound Assessment
• Actual Study Start Date: July 21, 2021
• Actual Primary Completion Date: August 30, 2023
• Actual Study Completion Date: August 30, 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
good response group of treated keloids; The Vancouver Scar Scale (VSS) is the most established questionnaire used for the evaluation of pathological scarring. This scale evaluates aspects of scar vascularity, pigmentation, pliability, and height, with the scoring system ranging from 0 to 15, where 0 is the least severe and 15 is the most severe.All the keloids in the study were classified into three categories based on the VSS score: mild (0-5), moderate (6-9), and severe (10-15). For treatment assessment, investigators further divided the treated participants into two groups: a good response group (showing an improvement of 5 or more points in the VSS score) and a poor response group (less than 5 points improvement in the VSS score)	Diagnostic Test: multimodal ultrasound; An Aixplorer ultrasound machine (SuperSonic Imaging, Ltd, Aixen-Provence, France), equipped with AngioPLUS(AP) and shear wave elastography(SWE) functions, was used for all examinations using a 4-15MHz linear probe.AP function can detect microvessels of lesions,SWE can evaluate the stiffness of lesions and high frequency ultrasound can measure the thickness and volume of keloid.; Radiation: radioisotope applicator therapy; The radioisotope applicator therapy utilized 90Sr-90Y(0094SR814975) isotope, customized by the China Atomic Energy Research Institute. The element therapy instrument used had overall dimensions of 2.8cm x 2.8cm, with an effective treatment area of 2.0cm x 2.0cm. It delivered a radiation dose of 5.0Gy/h. Each patient received superficial radiation therapy through a single 90Sr source, administered in repeated doses. The isotope therapy instrument was customized to fit the exact size of the keloid, ensuring coverage the irradiation range extending 0.5cm beyond the keloid's edge. During treatment, the surface of the applicator was aligned with the irradiated area and directly contact the surface of the keloid tissue. The treatment was carried out low-dose irradiation method, over 5 sessions, with each session delivering a dose of 2Gy. Each irradiation lasted for 25min.
poor response group of treated keloids; The Vancouver Scar Scale (VSS) is the most established questionnaire used for the evaluation of pathological scarring. This scale evaluates aspects of scar vascularity, pigmentation, pliability, and height, with the scoring system ranging from 0 to 15, where 0 is the least severe and 15 is the most severe. All the keloids in the study keloids were classified into three categories based on the VSS score: mild (0-5), moderate (6-9), and severe(10-15). For treatment assessment, investigators further divided the treated participants into two groups: a good response group (showing an improvement of 5 or more points in the VSS score) and a poor response group (less than 5 points improvement in the VSS score)	Diagnostic Test: multimodal ultrasound; An Aixplorer ultrasound machine (SuperSonic Imaging, Ltd, Aixen-Provence, France), equipped with AngioPLUS(AP) and shear wave elastography(SWE) functions, was used for all examinations using a 4-15MHz linear probe.AP function can detect microvessels of lesions,SWE can evaluate the stiffness of lesions and high frequency ultrasound can measure the thickness and volume of keloid.; Radiation: radioisotope applicator therapy; The radioisotope applicator therapy utilized 90Sr-90Y(0094SR814975) isotope, customized by the China Atomic Energy Research Institute. The element therapy instrument used had overall dimensions of 2.8cm x 2.8cm, with an effective treatment area of 2.0cm x 2.0cm. It delivered a radiation dose of 5.0Gy/h. Each patient received superficial radiation therapy through a single 90Sr source, administered in repeated doses. The isotope therapy instrument was customized to fit the exact size of the keloid, ensuring coverage the irradiation range extending 0.5cm beyond the keloid's edge. During treatment, the surface of the applicator was aligned with the irradiated area and directly contact the surface of the keloid tissue. The treatment was carried out low-dose irradiation method, over 5 sessions, with each session delivering a dose of 2Gy. Each irradiation lasted for 25min.

Outcome Measures

Primary Outcome Measures :

1. Change in stiffness measured by SWE [ Time Frame: from baseline to 6 months ]
   The difference of stiffness in good response group and poor response group
2. Change in microvessel signal grade measured by AP [ Time Frame: from baseline to 6 months ]
   The difference of microvessel signal grade in good response group and poor response group
3. Change in thickness measured by high frequency ultrasound [ Time Frame: from baseline to 6 months ]
   The difference of thickness in good response group and poor response group

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

34 outpatients (mean age 43 ± 10.4 years, 14 male, 20 female) with untreated 63 keloids in different anatomical locations and 63 corresponding normal skin sites was performed

Criteria

Inclusion Criteria:

• Male and female patients aged 16 years and above
• Outpatients with no received any treatment in previous 6 months
• Willing to participate in this trial and have signed an informed consent form

Exclusion Criteria:

• Pregnant or breastfeeding women
• patients with malignant tumors, hypertension, diabetes, skin rupture, skin infection which may influence keloid healing and other dermatologic diseases

Contacts and Locations

Locations

China, Chongqing

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing, China, 400010

Sponsors and Collaborators

Chongqing Medical University

Investigators

• Study Chair: Wang Zhigang; Chongqing Medical University

More Information

Publications of Results:

DeJong H, Abbott S, Zelesco M, Spilsbury K, Ziman M, Kennedy BF, Martin L, Wood FM. Objective quantification of burn scar stiffness using shear-wave elastography: Initial evidence of validity. Burns. 2020 Dec;46(8):1787-1798. doi: 10.1016/j.burns.2020.05.009. Epub 2020 May 19.

Schwaiger H, Reinholz M, Poetschke J, Ruzicka T, Gauglitz G. Evaluating the Therapeutic Success of Keloids Treated With Cryotherapy and Intralesional Corticosteroids Using Noninvasive Objective Measures. Dermatol Surg. 2018 May;44(5):635-644. doi: 10.1097/DSS.0000000000001427.

Nast A, Gauglitz G, Lorenz K, Metelmann HR, Paasch U, Strnad V, Weidmann M, Werner RN, Bauerschmitz J. S2k guidelines for the therapy of pathological scars (hypertrophic scars and keloids) - Update 2020. J Dtsch Dermatol Ges. 2021 Feb;19(2):312-327. doi: 10.1111/ddg.14279. Epub 2020 Oct 4. No abstract available.

Yang Y, Wang L, Yan F, Xiang X, Tang Y, Zhang L, Liu J, Qiu L. Determination of Normal Skin Elasticity by Using Real-time Shear Wave Elastography. J Ultrasound Med. 2018 Nov;37(11):2507-2516. doi: 10.1002/jum.14608. Epub 2018 Mar 25.

Yang Y, Qiu L, Wang L, Xiang X, Tang Y, Li H, Yan F. Quantitative Assessment of Skin Stiffness Using Ultrasound Shear Wave Elastography in Systemic Sclerosis. Ultrasound Med Biol. 2019 Apr;45(4):902-912. doi: 10.1016/j.ultrasmedbio.2018.11.015. Epub 2019 Jan 18.

Tsai WY, Hsueh YY, Chen PY, Hung KS, Huang CC. High-Frequency Ultrasound Elastography for Assessing Elastic Properties of Skin and Scars. IEEE Trans Ultrason Ferroelectr Freq Control. 2022 Jun;69(6):1871-1880. doi: 10.1109/TUFFC.2022.3154235. Epub 2022 May 26.

Guo R, Xiang X, Wang L, Zhu B, Cheng S, Qiu L. Quantitative Assessment of Keloids Using Ultrasound Shear Wave Elastography. Ultrasound Med Biol. 2020 May;46(5):1169-1178. doi: 10.1016/j.ultrasmedbio.2020.01.010. Epub 2020 Feb 13.

Reinholz M, Schwaiger H, Poetschke J, Epple A, Ruzicka T, Von Braunmuhl T, Gauglitz GG. Objective and subjective treatment evaluation of scars using optical coherence tomography, sonography, photography, and standardised questionnaires. Eur J Dermatol. 2016 Dec 1;26(6):599-608. doi: 10.1684/ejd.2016.2873.

Elrefaie AM, Salem RM, Faheem MH. High-resolution ultrasound for keloids and hypertrophic scar assessment. Lasers Med Sci. 2020 Mar;35(2):379-385. doi: 10.1007/s10103-019-02830-4. Epub 2019 Jun 25.

DeJong H, Abbott S, Zelesco M, Spilsbury K, Martin L, Sanderson R, Ziman M, Kennedy BF, Wood FM. A Novel, Reliable Protocol to Objectively Assess Scar Stiffness Using Shear Wave Elastography. Ultrasound Med Biol. 2020 Jul;46(7):1614-1629. doi: 10.1016/j.ultrasmedbio.2020.03.003. Epub 2020 May 5.

Xu C, Ting W, Teng Y, Long X, Wang X. Laser Speckle Contrast Imaging for the Objective Assessment of Blood Perfusion in Keloids Treated With Dual-Wavelength Laser Therapy. Dermatol Surg. 2021 Apr 1;47(4):e117-e121. doi: 10.1097/DSS.0000000000002836.

Son Y, Phillips EON, Price KM, Rosenberg LZ, Stefanovic B, Wolfe CM, Shaath TS, Om A, Cohen GF, Gunjan A. Treatment of keloids with a single dose of low-energy superficial X-ray radiation to prevent recurrence after surgical excision: An in vitro and in vivo study. J Am Acad Dermatol. 2020 Nov;83(5):1304-1314. doi: 10.1016/j.jaad.2020.06.023. Epub 2020 Jun 12.

Tang Y, Cheng S, Tang X, Guo R, Zhang L, Qiu L. Quantification of skin lesions using high-frequency ultrasound and shear wave elastography in port-wine stain patients: a clinical study. Ann Transl Med. 2019 Dec;7(24):803. doi: 10.21037/atm.2019.12.57.

Xiang X, Yan F, Yang Y, Tang Y, Wang L, Zeng J, Qiu L. Quantitative Assessment of Healthy Skin Elasticity: Reliability and Feasibility of Shear Wave Elastography. Ultrasound Med Biol. 2017 Feb;43(2):445-452. doi: 10.1016/j.ultrasmedbio.2016.10.002. Epub 2016 Dec 2.

Poetschke J, Schwaiger H, Gauglitz GG. Current and Emerging Options for Documenting Scars and Evaluating Therapeutic Progress. Dermatol Surg. 2017 Jan;43 Suppl 1:S25-S36. doi: 10.1097/DSS.0000000000000698.

Other Publications:

Dirrichs T, Quack V, Gatz M, Tingart M, Rath B, Betsch M, Kuhl CK, Schrading S. Shear Wave Elastography (SWE) for Monitoring of Treatment of Tendinopathies: A Double-blinded, Longitudinal Clinical Study. Acad Radiol. 2018 Mar;25(3):265-272. doi: 10.1016/j.acra.2017.09.011. Epub 2017 Nov 16.

• Responsible Party: Wang Zhigang, chief physician, Chongqing Medical University
• ClinicalTrials.gov Identifier: NCT06034587
• Other Study ID Numbers: CQMUSAZL0619
• First Posted: September 13, 2023
• Last Update Posted: September 13, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wang Zhigang, Chongqing Medical University:

multimodal ultrasound; shear wave elastography; microvessel imaging

Additional relevant MeSH terms:

Keloid; Collagen Diseases; Connective Tissue Diseases; Cicatrix; Fibrosis; Pathologic Processes