Quantifying Fibrosis in Venous Disease: Mechanical Properties of Lipodermatosclerotic and Healthy Tissue

Advances in Skin & Wound Care, Apr 2004 by Geyer, Mary Jo, Brienza, David M, Chib, Vikram, Wang, Jue

ABSTRACT

OBJECTIVES: To quantify the mechanical properties of medioposterior bulk calf tissue in patients with lipodermatosclerotic venous-insufficient tissue and individuals with apparently healthy tissue using a novel ultrasound indentometry method, and to identify parameters with the potential for quantifying fibrosis in subsequent studies.

DESIGN: 2-group, quasi-experimental design

SETTING: Soft Tissue Mechanics Laboratory, University of Pittsburgh, Pittsburgh, PA

PARTICIPANTS: 9 healthy and 9 venous-insufficient individuals aged 35 to 85 years

INTERVENTIONS: Ultrasound indentometry and computed tomography (CT) of calf tissue

MAIN OUTCOME MEASURES: Between group differences and associations among quasi-linear viscoelastic (QLV) tissue parameters and CT descriptors

MAIN RESULTS: Established the accuracy, validity, and reliability of the QLV model and ultrasound indentometry method. Demonstrated a range of significant differences between the groups (P

CONCLUSION: Attempts to quantity fibrosis in lipodermatosclerosis have included histologic exams, palpation/pitting, durometer readings, and imaging techniques, but these efforts have failed to produce a clinically practical, noninvasive method. A novel ultrasound indentometry method was used to acquire in vivo data from which tissue parameters were derived. These data support the further development of ultrasound indentometry as a method to quantify fibrosis in venous disease.

ADV SKIN WOUND CARE 2004;17:131-42.

Management of venous disease has become a major health care challenge. Characterized by chronicity and relapse, venous disease management commonly leads to massive expenditures in developed countries. In the United States alone, this expenditure is estimated at $2 to $4 billion per year, with 200 million lost work days per year.1-3 The magnitude of these expenditures in conjunction with the relative lack of treatments demonstrating long-term effectiveness has stimulated renewed interest in research on venous disease. One aspect of such research has focused on the measurement of fibrotic soft tissue changes that occur almost universally with severe chronic venous disease. This progressive hardening of the skin and subcutaneous tissue is known as lipodermatosclerosis (LDS)4-8 (Figure 1).

Fibrosis is the primary distinguishing characteristic of LDS. Evidence suggests that the ability to accurately quantify tissue fibrosis would aid in the early detection, differential diagnosis, staging, and classification of venous disease, as well as in the prediction of healing rates and evaluation of treatment.7'9"12 Therefore, many previous attempts have been made to characterize and quantify tissue fibrosis, including histologie examination and weighing of biopsy specimens,13 semiquantitativc clinical assessments (palpation/pitting) with subsequent grading of the tissue response,14'10 and the use of tonometers/durometers to acquire force/displacement data (indentometry).10'15"21 Medical imaging techniques, such as computed tomography (CT), ultrasonic elasticity imaging (elastography), and magnetic resonance imaging (MRI) have also been used.22"36 However, these efforts have failed to produce a clinically practical, noninvasive method to measure the effects of fibrosis on the elastic and nonlinear, time-dependent tissue responses.

SOFT TISSUE MODELING

Human soft tissue consists of a variety of macro and molecular structures with widely varying individual properties. Mechanical properties are influenced by the unique geometry and composition of the tissue, as well as by the macromolecular structure of the tissue's extracellular matrices. Although the individual properties of soft tissue may vary, similarities are exhibited by its nonlinear, viscoelastic behaviors, including preconditioning, hysteresis, stress-relaxation, and creep.

Many theoretical models have been developed to describe soft tissue mechanical responses. The biomechanics literature is replete with studies of the material properties of soft tissue, most of which have consisted of in vitro tensile tests. However, the in vivo mechanical behavior of the skin and soft tissue is most commonly measured using compressive loading (indcntometry). Over the years, several generations of indentometry devices have been used to study soft tissue responses to loading under a variety of conditions.37"42 These studies sought to obtain tissue deformation characteristics from which estimates of lower extremity bulk tissue properties could be derived and subsequently used for finite element analysis.38'43"45 These studies demonstrated that in addition to exhibiting stressrelaxation, human bulk tissue responses to compressive loading are nonlinear, time-dependent, and may vary as a function of strain rate, state of muscle activity, and/or subject posture.

Valid characterization of tissue properties requires a model that accounts for both the nonlinear, stress-relaxation, and elastic characteristics of the tissue. The quasi-linear, viscoelastic (QLV) model proposed by Fung incorporates these features.46 However, until recently, limitations in accurately measuring time-dependent tissue responses and changes in the bulk tissue thickness during deformation prevented the ready application of Fung's model. The combination of ultrasound technology with indentometry has provided a means of overcoming these limitations. Ultrasound has been successfully used to monitor the changes in tissue deformation over time. Rather than using the surface displacement immediately beneath the indenter as a measure of deformation, ultrasound reflection permits a more direct measurement of the change in overall (bulk) tissue thickness.44-47'48