pH-induced contrast in viscoelasticity imaging of biopolymers

Abstract

Understanding contrast mechanisms and identifying discriminating features is at the heart of diagnostic imaging development. This report focuses on how pH influences the viscoelastic properties of biopolymers to better understand the effects of extracellular pH on breast tumour elasticity imaging. Extracellular pH is known to decrease as much as 1 pH unit in breast tumours, thus creating a dangerous environment that increases cellular mutatation rates and therapeutic resistance. We used a gelatin hydrogel phantom to isolate the effects of pH on a polymer network with similarities to the extracellular matrix in breast stroma. Using compressive unconfined creep and stress relaxation measurements, we systematically measured the viscoelastic features sensitive to pH by way of time domain models and complex modulus analysis. These results are used to determine the sensitivity of quasi-static ultrasonic elasticity imaging to pH. We found a strong elastic response of the polymer network to pH, such that the matrix stiffness decreases as pH was reduced, however the viscous response of the medium to pH was negligible. While physiological features of breast stroma such as proteoglycans and vascular networks are not included in our hydrogel model, observations in this study provide insight into viscoelastic features specific to pH changes in the collagenous stromal network. These observations suggest that the large contrast common in breast tumours with desmoplasia may be reduced under acidic conditions, and that viscoelastic features are unlikely to improve discriminability.

Fractional derivative models for ultrasonic characterization of polymer and breast tissue viscoelasticity

“…Indeed, the average value of α is lower in basic than in acidic inclusions, which indicates that basic gels are more elastic. The values of τ′ suggest that water moves more rapidly in the basic inclusion than in the acidic inclusion, which can be explained by differences in mobile charge density [40]. …”

Indentation Measurements to Validate Dynamic Elasticity Imaging Methods

“…The test material does not need to be tissue mimicking, but it should be reproducibly constructed in any lab, provide spatially uniform linear-elastic modulus values in the range of soft tissues (0.1-10 kPa), and remain stable for the duration of the measurement. We find gelatin gels meet those minimal requirements despite vulnerabilities to desiccation and swelling, as well as dependencies on thermal history, pH, ionic impurities, 5 and temporal instabilities when chemical cross-linkers are not added prior to gelation. 6 Gelatin gels can be manufactured precisely to offer elastic properties that are reproducible sample-to-sample, day-to-day, and remain stable for hours.…”

Ramp-hold relaxation solutions for the KVFD model applied to soft viscoelastic media

“…The mechanical properties of hydrogels are affected by the details of thermal history, including manufacturing temperature, heating duration, cooling rates and time and temperature at which the cream is added. The fact that gelatin stiffness varies over time when chemical cross linkers are not used and with pH further makes the sample elastic modulus vulnerable to measurement variations [35]. We were aware of these influences and made every effort to minimize all material property variations by standardizing the sample manufacturing process.…”