Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue

Abstract

It is well known that angiogenesis is a complex process that accompanies neoplastic growth, but pituitary tumours are less vascularized than normal pituitary glands. Several analytical methods aimed at quantifying the vascular system in two-dimensional histological sections have been proposed, with very discordant results. In this study we investigated the non-Euclidean geometrical complexity of the two-dimensional microvasculature of normal pituitary glands and pituitary adenomas by quantifying the surface fractal dimension that measures its space-filling property. We found a statistical significant difference between the mean vascular surface fractal dimension estimated in normal versus adenomatous tissues ( P = 0.01), normal versus secreting adenomatous tissues ( P = 0.0003), and normal versus non-secreting adenomatous tissues ( P = 0.047), whereas the difference between the secreting and non-secreting adenomatous tissues was not statistically significant. This study provides the first demonstration that fractal dimension is an objective and valid quantitator of the two-dimensional geometrical complexity of the pituitary gland microvascular network in physiological and pathological states. Further studies are needed to compare the vascular surface fractal dimension estimates in different subtypes of pituitary tumours and correlate them with clinical parameters in order to evaluate whether the distribution pattern of vascular growth is related to a particular state of the pituitary gland.

Fractal Structure and Entropy Production within the Central Nervous System

“…Furthermore, studies of hepatocelluar carcinomas have shown an increase in the fractal dimension of vasculature structures in malignant tissue compared to normal tissue, where the vessels of primary tumors showed greater fractal dimension when compared with hepatic metastases [55]. Conversely, fractal studies have also demonstrated that the microvasculature in normal pituitary tissue is more complex than in benign pituitary adenomas [56] and correlates with earlier findings demonstrating reduced microvascular complexity in malignant PRL producing carcinomas vs. benign pituitary adenomas [57]. Hence, it may be that some pituitary tumors may progress via a non-angiogenic pathway, which has also been demonstrated in a subclass of primary non-small cell lung cancers and glioblastomas which progress without neo-vascularisation and are more clinically aggressive than angiogenic tumors [58][59][60][61].…”

Antiangiogenic Strategies in Medulloblastoma: Reality or Mystery

“…It has been shown that angiogenesis is a hallmark of the progression of medulloblastoma and, over the last years, investigators have sought to develop effective and less toxic antiangiogenic strategies, including the inhibition or destruction of abnormal blood vessels using either antiangiogenic or vascular disrupting agents. However, the results are conflicting, principally because of the complex biology of tumor vasculature and the irregular geometry of the vascular system in real space (55)(56)(57)(58). In addition, current targets of antiangiogenic therapy, such as VEGF, are thought to be critical for both physiologic and pathologic angiogenesis, and clinical side effects of anti-VEGF therapy are beginning to emerge (59).…”

“…Currently, there are no markers of the net angiogenic activity of a tumor that can help investigators to design specific antiangiogenic treatment strategies (42,65), but it is reasonable to resume that the quantification of various aspects of tumor vasculature may provide an indication of angiogenic activity (55)(56)(57)(58).…”

“…The results of studies carried out over the last decade have suggested the value of using tumor MVD as a prognostic index in a wide variety of solid cancers, and it has recently been assumed that MVD may reveal the degree of angiogenic activity in a tumor (50,66 -70). However, MVD has a number of substantial limitations, mainly due to the complex biology characterizing tumor vasculature (64) and the highly irregular geometry that the vascular system assumes in real space (55)(56)(57)(58), which cannot be measured using the principles of Euclidean geometry because it is only capable of interpreting regular and smooth objects that are almost impossible to find in nature.…”

“…The human vascular system can be geometrically represented as a fractal network of vessels that irregularly branch with a systematic reduction in their length and diameter (55)(56)(57)(58).…”