The effects of interstitial tissue pressure on the measured shear modulus in vivo

It is well known that many pathologic processes, like cancer, result in increased tissue stiffness but the biologic mechanisms which cause pathologies to be stiffer than normal tissues are largely unknown. Increased collagen density has been presumed to be largely responsible because it has been shown to cause variations in normal tissue stiffness. However, other effects such as increased tissue pressure are also thought to be significant. We examined the effects of tissue pressure on shear modulus measured using MR elastography (MRE) by comparing the shear modulus in the pre-mortem, edematous and post-mortem porcine brain and found that the measured shear modulus increases with tissue pressure as expected. The slope of a linear fit to this preliminary data varied from 0.3 kPa/mmHg to 0.1 kPa/mmHg. These results represent the first in vivo demonstration of tissue pressure affecting intrinsic mechanical properties and have several implications. First, if the linear relationship described is correct, tissue pressure could contribute significantly (∼20%) to the increase in stiffness observed in cancer. Second, tissue pressure effects must be considered when in vitro mechanical properties are extrapolated to in vivo settings. Moreover, MRE might provide a means to characterize pathologic conditions associated with increased or decreased tissue pressure, such as edema and ischemia, in a diverse set of diseases including cancer, diabetes, stroke, and transplant rejection.