![]() The fractal concept provides the theoretical basis to define the fractal dimension of an object that does not completely fill the surrounding space/volume 9. In this context, a certain attention was addressed to the fractal aspects of vascularization 8. In addition, this shift promoted the analysis of vascular structures as a whole, trying to keep trace of the structural and space-filling information coded into the spatial arrangement of vessels and capillaries by means of connected voxels. With the onset of the digital revolution, the focus switched from vessels to pixels, or voxels, representing vascular tubes. Based on these “objects”, the amounts, lengths, calibers, tortuosities and branching of vessels in a vascular tree could be calculated as statistical parameters and eventually correlated with specific physio-pathological states of the analyzed tissue 5, 6, 7. branching points) from which daughter vessels branch to reach other destinations. In the past, the classical approach focalized on each single vessel idealized as a tube connecting 2 nodes (i.e. Unfortunately, it is usually hardly possible to take into consideration all the details that characterize a tissue angioarchitecture without losing the possibility to perform a concise and meaningful description. ![]() Thus, the development of methods able to quantify vascular trees and their anomalies appears to be of pivotal importance for a better understanding of the neovascularization process in cancer and for the evaluation of vascular-targeted therapies. There, uncontrolled angiogenesis, together with other mechanisms 2, can cause abnormal vascular growth of dysfunctional vessels 3 reducing local blood fluxes to marginal speeds and fostering hypoxic conditions 4. Underdeveloped or occluded vascular trees can fail in this goal 1, but insufficient supply can also be observed in hypervascularized tumor tissues. The micro-angioarchitecture of a tissue is a major parameter underlying its functional properties in terms of oxygen supply, nutrient and drug delivery. The possibility offered by this procedure to describe and quantify the 3D features of the tumor micro-angioarchitecture paves the way to the analysis of the microvascular tree in human tumor specimens at different stages of tumor progression and after pharmacologic interventions, with possible diagnostic and prognostic implications. ![]() Notably, treatment of KMS-11 xenografts with anti-angiogenic drugs affected position and slope of the specific curves without degrading their near-linear properties. Position, slope and axial projections of this graphical outcome reflect biological features and summarize the properties of tumor micro-angioarchitecture. Using image analysis, we show that amounts, spatial dispersion and spatial relationships of adjacent classes of caliber-filtered microvessels provide a near-linear graphical “fingerprint” of tumor micro-angioarchitecture. We addressed this goal through 3D analysis of the functional microvascular network in sulfo-biotin-stained human multiple myeloma KMS-11 xenografts in NOD/SCID mice. To this aim, the development of a restricted set of indexes able to describe the arrangement of a microvascular tree is eagerly required. Thus, methods able to quantify microvascular trees and their anomalies may allow a better comprehension of the neovascularization process and evaluation of vascular-targeted therapies in cancer. Blood vessel micro-angioarchitecture plays a pivotal role in tumor progression, metastatic dissemination and response to therapy.
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