Manfred Tschabitscher

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

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.

Magnetic resonance elastography: a general overview of its current and future applications in brain imaging

Magnetic resonance elastography (MRE) has been developed over the last few years as a non-invasive means of evaluating the elasticity of biological tissues. The presence of the skull has always prevented semeiotic palpation of the brain, but MRE now offers the possibility of “palpating by imaging” in order to detect brain consistency under physiological and pathological conditions. The aim of this article is to review the current state-of-the-art of MRE imaging and discuss its possible future diagnostic applications in neuroscience.

Angioarchitectural heterogeneity in human glioblastoma multiforme: A fractal-based histopathological assessment

There is currently no standard technique to objectively quantify the microvascularization of brain tumors. Fractal analysis has been proposed as a useful descriptor of tumor microvascularity. Standardization of the fractal analysis methodology could offer a new tool for this type of characterization. In this study, we applied fractal analysis to the characterization of the different angioarchitectures found in specimens of glioblastoma multiforme (GBM), the most common and most malignant type of human brain tumor. A retrospective series of 114 primary GBM specimens was carried out. To quantify neoplastic microvascularity, the level of two-dimensional geometrical complexity of the microvascular patterns was assessed using the box-counting algorithm, which estimates the microvascular fractal dimension (mvFD). mvFD makes information on the non-Euclidean space filled by vessels embedded in the tumor microenvironment available because it depends on vessel number, shape, magnitude and distribution pattern. A mean mvFD value of 1.44 ± 0.17 (range: 1.06-1.87) was found. The coefficient of variation was 44%. The high geometric variability, found objectively, in these samples reflects the angioarchitectural heterogeneity underlying GBM. The present study shows that angioarchitectural subtypes can be identified by mvFD, making this parameter a potential tool for quantifying different neoplastic microvascular patterns.

MICROSCOPIC AND ENDOSCOPIC EXTRACRANIAL APPROACHES TO THE CAVERNOUS SINUS: ANATOMIC STUDY

OBJECTIVE In the past 2 decades, various extracranial approaches to the cavernous sinus (CS), using either microscopic or endoscopic techniques, have been described. The aim of this study was to describe the distinctive anatomic features of these approaches and compare their efficacy in exposing the sella and parasellar areas. METHODS Ten adult cadaver heads with red latex injected in the arterial system were used. Five different approaches were performed: 1) endonasal microscopic transsphenoidal approach; 2) sublabial microscopic transsphenoidal approach, including its variation described by Fraioli et al. (12); 3) transmaxillary microscopic approach; 4) paraseptal endoscopic transsphenoidal approach; and 5) transethmoid-pterygoid-sphenoidal endoscopic approach. The CS exposition was evaluated for each approach and a grading system, which considers surgical maneuverability as well as visualization, was used. RESULTS The medial CS compartment is well exposed with all endoscopic and microscopic transsphenoidal approaches, but it is insufficiently exposed with the transmaxillary approach. The variation to the sublabial microscopic approach suggested by Fraioli et al. allows its widest microsurgical exposure. The lateral compartment is well visualized with the transmaxillary microscopic and the endoscopic approaches. The major anatomic structures that can limit exposure of the CS lateral compartment are the posterior ethmoid and medial pterygoid process. CONCLUSION The sublabial transsphenoidal microscopic approach, with its variations, allows the most versatile extracranial microscopic exposure of the sella and CS. The paraseptal, binostril endoscopic approach allows a very good exposure of the CS; the transethmoid-pterygoid-sphenoidal endoscopic approach achieves the best maneuverability in the lateral compartment of the CS.

Fractal Analysis of the Susceptibility Weighted Imaging Patterns in Malignant Brain Tumors During Antiangiogenic Treatment: Technical Report on Four Cases Serially Imaged by 7 T Magnetic Resonance During a Period of Four Weeks

OBJECTIVE The need for new and objective indexes for the neuroradiologic follow-up of brain tumors and for monitoring the effects of antiangiogenic strategies in vivo led us to perform a technical study on four patients who received computerized analysis of tumor-associated vasculature with ultra-high-field (7 T) magnetic resonance imaging (MRI). The image analysis involved the application of susceptibility weighted imaging (SWI) to evaluate vascular structures. METHODS Four patients affected by recurrent malignant brain tumors were enrolled in the present study. After the first 7-T SWI MRI procedure, the patients underwent antiangiogenic treatment with bevacizumab. The imaging was repeated every 2 weeks for a period of 4 weeks. The SWI patterns visualized in the three MRI temporal sequences were analyzed by means of a computer-aided fractal-based method to objectively quantify their geometric complexity. RESULTS In two clinically deteriorating patients we found an increase of the geometric complexity of the space-filling properties of the SWI patterns over time despite the antiangiogenic treatment. In one patient, who showed improvement with the therapy, the fractal dimension of the intratumoral structure decreased, whereas in the fourth patient, no differences were found. CONCLUSIONS The qualitative changes of the intratumoral SWI patterns during a period of 4 weeks were quantified with the fractal dimension. Because SWI patterns are also related to the presence of vascular structures, the quantification of their space-filling properties with fractal dimension seemed to be a valid tool for the in vivo neuroradiologic follow-up of brain tumors.

Euclidean and fractal geometry of microvascular networks in normal and neoplastic pituitary tissue

In geometrical terms, tumour vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic and the highly variable shapes of the vessels lead to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological characteristics are well known, quantitative analyses of newly formed vessels in two-dimensional histological sections still fail to view their architecture as a non-Euclidean geometrical entity, thus leading to errors in visual interpretation and discordant results from different laboratories concerning the same tumour. We here review the literature concerning microvessel density estimates (a Euclidean-based approach quantifying vascularity in normal and neoplastic pituitary tissues) and compare the results. We also discuss the limitations of Euclidean quantitative analyses of vascularity and the helpfulness of a fractal geometry-based approach as a better means of quantifying normal and neoplastic pituitary microvasculature.

Temporalis myofascial flap in maxillary reconstruction: anatomical study and clinical application.

The authors describe indications and advantages of temporalis myofascial flap in the reconstruction of surgical defects after partial maxillectomies. This flap is thin and reliable and can be used as an alternative to free flap tissue transfer in the reconstruction of partial defects of the upper maxilla. The surgical steps to raise the flap are simple, but the dissection must be careful to avoid damages to the fronto-temporal branches of the facial nerve on the outer surface, and to the feeding vessels on the inner surface of the temporal muscle. In the present series no major surgical complications were observed. No injuries to the facial nerve branches were reported. Neither total nor partial flap losses were experienced. Post-operative aesthetic and functional results were satisfying. Temporalis muscle flap can be considered as a first-line reconstructive option for limited resection of the upper maxilla with sparing of the orbital floor and of the anterior alveolar crest.

Transoral endoscopic anatomy of the parapharyngeal space: A step‐by‐step logical approach with surgical considerations

Surgical approaches to the parapharyngeal spaces are challenging. Little is known about the transoral perspective of the anatomy of the parapharyngeal space. Thus, transoral approaches are seldom performed, and only for small‐sized tumors.

Fully endoscopic transnasal approach to the jugular foramen: anatomic study and clinical considerations.

BACKGROUND AND IMPORTANCE To describe a transnasal endoscopic route to the jugular foramen and the endoscopic anatomy of the infratemporal fossa. CLINICAL PRESENTATION Endoscopic transnasal dissection of the infratemporal fossa was performed in 3 injected fresh heads (1 head only in arteries and 2 heads in arteries and veins). Two other double-injected specimens were dissected externally (2 of them side laterally and 1 anteriorly) to compare the different views and better understand the 3-dimensionality of the region. Detailed endoscopic anatomy of the infratemporal fossa was clearly observed. The realization of a septal and posterior maxillary window allows surgeons to gain space to the jugular foramen. The ability to manage the vessels, especially the veins, and identify the muscles is mandatory. The fundamental role of the vidian canal in targeting the anterior genu of the internal carotid artery is confirmed. The role of the maxillary and mandibular branches of the trigeminal nerve and the eustachian tube in this kind of approach is critical. CONCLUSION A fully transnasal endoscopic route to the jugular foramen is feasible. The most important landmark for this kind of approach is the eustachian tube.

Correlation of microvascular fractal dimension with positron emission tomography [11C]-methionine uptake in glioblastoma multiforme: Preliminary findings

Neuroradiological and metabolic imaging is a fundamental diagnostic procedure in the assessment of patients with primary and metastatic brain tumors. The correlation between objective parameters capable of quantifying the neoplastic angioarchitecture and imaging data may improve our understanding of the underlying physiopathology and make it possible to evaluate treatment efficacy in brain tumors. Only a few studies have so far correlated the quantitative parameters measuring the neovascularity of brain tumors with the metabolic profiles measured by means of amino acid uptake in positron emission tomography (PET) scans. Fractal geometry offers new mathematical tools for the description and quantification of complex anatomical systems, including microvascularity. In this study, we evaluated the microvascular network complexity of six cases of human glioblastoma multiforme quantifying the surface fractal dimension on CD34 immunostained specimens. The microvascular fractal dimension was estimated by applying the box-counting algorithm. As the fractal dimension depends on the density, size and shape of the vessels, and their distribution pattern, we defined it as an index of the whole complexity of microvascular architecture and compared it with the uptake of (11)C-methionine (MET) assessed by PET. The different fractal dimension values observed showed that the same histological category of brain tumor had different microvascular network architectures. Fractal dimension ranged between 1.19 and 1.77 (mean: 1.415+/-0.225), and the uptake of (11)C-methionine ranged between 1.30 and 5.30. A statistically significant direct correlation between the microvascular fractal dimension and the uptake of (11)C-methionine (p=0.02) was found. Our preliminary findings indicate that that vascularity (estimated on the histologic specimens by means of the fractal dimension) and (11)C-methionine uptake (assessed by PET) closely correlate in glioblastoma multiforme and that microvascular fractal dimension can be a useful parameter to objectively describe and quantify the geometrical complexity of the microangioarchitecture in glioblastoma multiforme.