Biomechanical Characterization of Skin Properties Using Impact Based-Analysis Method (IBAM)

Background and Rationale

Skin cancer is among the most frequent malignancies worldwide, and its incidence continues to rise. Early and accurate identification of tumor margins is essential both for diagnosis and for surgical planning, since incomplete excision increases the risk of local recurrence while unnecessarily wide excision increases morbidity, particularly in cosmetically or functionally sensitive areas.

In current clinical practice, the assessment of cutaneous lesions relies primarily on visual inspection and manual palpation. Palpation, in particular, is used empirically by clinicians to estimate tissue consistency and to help delineate the boundaries of a lesion. However, this examination is entirely subjective, strongly dependent on the experience of the examiner, and lacks any quantitative or reproducible basis. No simple, real-time, low-cost, non-invasive device is currently available in routine clinical practice to objectively characterize the mechanical properties of skin tissue and to assist clinicians in distinguishing pathological from healthy tissue.

Cutaneous tumors are known to exhibit altered biomechanical properties compared with healthy skin, reflecting changes in tissue composition, cellular density, and extracellular matrix organization. Several imaging and mechanical characterization techniques (elastography, indentation testing, suction devices) have been investigated to quantify these differences, but most require bulky equipment, are time-consuming, or are not adapted to intraoperative or bedside use.

The Impact-Based Analysis Method (IBAM) is a non-invasive, low-cost mechanical characterization technique developed collaboratively by the MSME laboratory (Modélisation et Simulation Multi-Échelle, UMR CNRS 8208, Université Paris Est Créteil) and the Mondor Institute for Biomedical Research (IMRB). The method relies on delivering a small, calibrated mechanical impact to the tissue surface and recording the resulting impactor motion. From this signal, a quantitative indicator (denoted Δt, corresponding to the time interval between successive impactor rebounds) is derived, which reflects the local stiffness and viscoelastic behavior of the underlying tissue. The device is portable, produces results in real time, requires no specific consumables, and involves no radiation or invasive procedure. Its reproducibility, spatial resolution, and sensitivity to changes in tissue mechanical properties have previously been established in preclinical (murine) models, including models of cutaneous neurofibromatosis.

Building on this preliminary work, the investigators hypothesize that IBAM measurements can discriminate malignant cutaneous tumor tissue from adjacent healthy skin, and that the mechanical signal progressively normalizes when measured at increasing distance from the tumor center. If confirmed, this would support the development of IBAM as a practical adjunct tool for intraoperative assessment of surgical margins.

Objectives

Primary objective: To determine whether malignant cutaneous tumor tissue (basal cell carcinoma, squamous cell carcinoma, or melanoma) can be differentiated from healthy cutaneous tissue based on mechanical properties measured by IBAM, using the Δt indicator as the primary outcome.

Secondary objective: To characterize the spatial evolution of the biomechanical signal from the center of the tumor toward increasingly distant peri-lesional areas, in order to explore the potential of IBAM to help define objective surgical safety margins.

Study Design

This is a prospective, single-center, ex vivo cohort study conducted within the Department of Plastic, Reconstructive and Aesthetic Surgery at Henri Mondor University Hospital (Assistance Publique - Hôpitaux de Paris, AP-HP), France. The study does not fall within the scope of the French law on research involving the human person ("Loi Jardé"), as it involves no modification of, or addition to, the patient's standard diagnostic or surgical care pathway. All measurements are performed ex vivo, directly on the surgical specimen, after excision and before transmission to the pathology department.

Study Population

Eligible patients are adults followed in the Department of Plastic Surgery at Henri Mondor University Hospital who present with a cutaneous lesion clinically or dermoscopically suspicious for malignancy (basal cell carcinoma, squamous cell carcinoma, or melanoma) and for whom surgical excision with safety margins is indicated as part of standard care.

Non-inclusion criteria:

Melanoma for which diagnostic excision has already been performed in sano prior to inclusion Cutaneous tumor related to a virally transmissible infection Ulcerated or fungating ("ulcéro-bourgeonnante") tumor

Based on a sample size calculation for a paired comparison design (two-sided alpha = 5%, statistical power = 80%), a total of 10 patients will be included. Recruitment is expected at a rate of approximately 2 to 6 patients per month, over an estimated inclusion period of 6 to 12 months.

Study Procedures

Patients meeting eligibility criteria are identified during routine dermato-plastic surgical consultation. Individual written information about the study is provided at the time of hospitalization (the day before or the day of surgery), and the patient's written consent or non-opposition is collected and documented, in accordance with the CNIL reference methodology MR-004.

Surgery proceeds according to the standard of care, with excision of the tumor and the surgically indicated safety margins. Immediately after excision, and before the specimen is transferred to the pathology laboratory for standard histological analysis, ex vivo IBAM measurements are performed directly on the surgical specimen at three predefined locations:

The center of the macroscopically visible tumor (malignant zone) The near peri-lesional area, close to the tumor edge The distant peri-lesional area, corresponding to the clinically healthy surgical margin

Measurements are recorded on a paper case report form at the time of testing, then transcribed the same day onto a secured, password-protected Excel file; the paper source is then destroyed. This additional ex vivo measurement step is performed without altering the specimen, without delaying or modifying its transmission to the pathology department beyond a negligible interval (estimated at less than one hour before fixation in formalin), and without any impact on the patient's subsequent management. The nature of the suspected tumor (from the pre-operative consultation report) and the final histopathological diagnosis (nature of the tumor, completeness of excision) are subsequently extracted from the institutional electronic medical record (ORBIS).

Outcome Measures

Primary endpoint: Variation of the Δt indicator (derived from the IBAM signal) between the malignant tumor zone and the healthy peri-lesional zone, measured on paired samples from the same surgical specimen.

Secondary endpoint: Trend of the Δt indicator across the three measurement locations (tumor center, near margin, distant margin), describing the spatial gradient of mechanical properties from the lesion to healthy tissue.

Statistical Analysis

The normality of data distribution will first be assessed using the Shapiro-Wilk test. Paired comparisons between the malignant and healthy zones will then be performed using the paired Student's t-test if data are normally distributed, or the Wilcoxon signed-rank test otherwise. A two-sided p-value below 0.05 will be considered statistically significant.

Data Management and Confidentiality

Personal data are collected exclusively from the patient's medical record (consultation report and histopathology results, via the institutional ORBIS system) and from the dedicated ex vivo mechanical measurements performed for the study. No data from the French National Health Data System (SNDS) are used. Data are pseudonymized using a patient identification number; the correspondence table linking this number to patient identity is accessible only to the coordinating investigator and the scientific lead. Pseudonymized data are stored on a password-protected Excel file, on a password-protected computer, in a locked office at Henri Mondor University Hospital. Data will be retained for 2 years. This research complies with Regulation (EU) 2016/679 (GDPR) and with the CNIL reference methodology MR-004 for studies not involving the human person.

Ethical and Regulatory Aspects

The study has been submitted for review to the Ethics Committee (IRB) of Henri Mondor University Hospitals. The sponsor (responsable de traitement) is Assistance Publique - Hôpitaux de Paris (AP-HP), represented by the Délégation à la Recherche Clinique et à l'Innovation (DRCI); the coordinating investigator (responsable de la mise en œuvre) is the physician responsible for the scientific conduct and data handling of the study within the Department of Plastic Surgery at Henri Mondor University Hospital.

Expected Significance

By providing a simple, real-time, low-cost, and non-invasive means of objectively characterizing the mechanical properties of cutaneous tissue, this study may contribute to the development of a practical adjunct tool for surgeons to help differentiate malignant from healthy skin tissue and to support more objective, standardized definition of surgical resection margins - ultimately aiming to improve the diagnostic and therapeutic management of patients with cutaneous malignancies.