Testing Foundations of Biological Scaling Theory Using Automated Measurements of Vascular Networks

Scientists have long sought to understand how vascular networks supply blood and oxygen to cells throughout the body. Recent work focuses on principles that constrain how vessel size changes through branching generations from the aorta to capillaries and uses scaling exponents to quantify these changes. Prominent scaling theories predict that combinations of these exponents explain how metabolic, growth, and other biological rates vary with body size. Nevertheless, direct measurements of individual vessel segments have been limited because existing techniques for measuring vasculature are invasive, time consuming, and technically difficult. We developed software that extracts the length, radius, and connectivity of in vivo vessels from contrast-enhanced 3D Magnetic Resonance Angiography. Using data from 20 human subjects, we calculated scaling exponents by four methods—two derived from local properties of branching junctions and two from whole-network properties. Although these methods are often used interchangeably in the literature, we do not find general agreement between these methods, particularly for vessel lengths. Measurements for length of vessels also diverge from theoretical values, but those for radius show stronger agreement. Our results demonstrate that vascular network models cannot ignore certain complexities of real vascular systems and indicate the need to discover new principles regarding vessel lengths.Author Summary: Vascular networks distribute resources and constrain metabolic rate. Founded on a few key principles, biological scaling theories predict characteristic patterns for vascular networks as they branch from large to small vessels. These theories also predict seemingly unrelated phenomena, such as size limits on mammals. However, vascular networks are difficult to measure because there are billions of vessels that range in size from meters to micrometers. To test the foundations of biological scaling theories, we developed software that quickly measures thousands of in vivo vessels based on MRI. Data for vessel radii match predicted patterns but lengths do not. Our work suggests the need for new theoretical principles and should facilitate comparisons across organisms, spatial scales, and healthy and diseased tissue.