Automatic image processing pipeline for tracking longitudinal vessel changes in magnetic resonance angiography.

BACKGROUND: Cerebral vessel diameter changes objectively and automatically derived from longitudinal magnetic resonance angiography (MRA) facilitate quantification of vessel changes and further modeling. PURPOSE: To characterize longitudinal changes in intracranial vessel diameter using time-of-flight (TOF) MRA. STUDY TYPE: Retrospective longitudinal study. SUBJECT POPULATION: IN all, 112 pediatric patients, aged 9.96 ± 4.59 years, with craniopharyngioma from 2006-2011 scanned annually. FIELD STRENGTH/SEQUENCE: 1.5T and 3T TOF MRA. STATISTICAL TESTS: Chi-square and Wilcoxon-Mann-Whitney tests. ASSESSMENT: Manual measurements using interventional angiography was established as a reference standard for diameter measurements. Constant and linear quantile regression with absolute difference, percentage difference, and relative difference was used for outlier detection. RESULTS: Major vessels surrounding the circle of Willis were successfully segmented except for posterior communicating arteries, mostly due to disease-related hypoplasia. Diameter measurements were calculated at 1-mm segments with a median computed vessel diameter of 1.25 mm. Diameter distortion due to registration was within 0.04 mm for 99% of vessel segments. Outlier detection using quantile regression detected less than 4.34% as being outliers. Outliers were more frequent in smaller vessels and proximity to bifurcations (P < 0.001). DATA CONCLUSION: Using the proposed method, objective changes in vessel diameter can be acquired noninvasively from routine longitudinal imaging. High-throughput analyses of imaging-derived vascular trees combined with clinical and treatment parameters will allow rigorous modeling of vessel diameter changes. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1063-1074.

Radiation-Induced Large Vessel Cerebral Vasculopathy in Pediatric Patients With Brain Tumors Treated With Proton Radiation Therapy.

PURPOSE: The purpose of this research was to evaluate the incidence, time to development, imaging patterns, risk factors, and clinical significance of large vessel cerebral vasculopathy in pediatric patients with brain tumors treated with proton radiation therapy. METHODS AND MATERIALS: A retrospective study was performed on 75 consecutive pediatric patients with primary brain tumors treated with proton radiation therapy. Radiation-induced large vessel cerebral vasculopathy (RLVCV) was defined as intracranial large vessel arterial stenosis or occlusion confirmed on magnetic resonance angiography, computed tomographic angiography, catheter angiography, or a combination of these within an anatomic region with previous exposure to proton beam therapy and not present before radiation therapy. Clinical records were used to determine the incidence, timing, radiation dose to the large vessels, and clinical significance associated with the development of large vessel vasculopathy in these patients. RESULTS: RLVCV was present in 5 of 75 (6.7%) patients and included tumor pathologic features of craniopharyngioma (n=2), ATRT (n=1), medulloblastoma (n=1), and anaplastic astrocytoma (n=1). The median time from completion of radiation therapy to development was 1.5 years (mean, 3.0 years; range, 1.0-7.5 years). Neither mean age at the time of radiation therapy (5.1 years) nor mean radiation therapy dose to the large vessels (54.5 Gy) was a statistically significant risk factor. Four of the 5 patients with RLVCV presented with acute stroke and demonstrated magnetic resonance imaging evidence of acute infarcts in the expected vascular distributions. Angiography studies demonstrated collateral vessel formation in only 2 of the patients with RLVCV. No patients demonstrated acute hemorrhage or aneurysm. Two patients were treated with pial synangiomatosis surgery. CONCLUSIONS: RLVCV can occur in pediatric patients with brain tumors treated with proton radiation therapy. Further studies are necessary to determine potential risk factors for large vessel vasculopathy with proton radiation therapy in comparison with conventional photon radiation therapy.

Staged 'intentional' bridging vein ligation: a safe strategy in gaining wide access to skull base tumors.

BACKGROUND: The venous drainage of the temporal lobe, through bridging veins to the middle cranial fossa, is pivotal in determining the surgical corridor for skull base lesions. In dealing with select cases, where venous drainage was an obstacle in the surgical approach, we hypothesized that staged 'intentional' ligation of the dominant pathway of venous drainage would provide a safer and wider access to skull base tumors. We study the indications and safety of this surgical strategy in the management of skull base lesions. MATERIALS AND METHODS: From 1995 to 2012, 318 patients with skull base tumors were treated at our institute by the fronto-orbito-zygomatic (FOZ) or transpetrosal approaches, eight of whom we planned for staged 'intentional' bridging vein ligation. Seven patients underwent planned ligation of the bridging veins from the temporal lobe to the middle cranial fossa floor in the first stage, followed by definitive surgery through the desired skull base approach, in the second stage, while in one patient the strategy was abandoned. These patients were evaluated with respect to their clinical presentation, pre- and post-operative radiology including venogram, intra-operative findings and post-operative course. RESULTS: Seven patients, four males and three females, with ages ranging from 16 to 63 years, underwent staged 'intentional' bridging vein ligation. The diagnoses were recurrent craniopharyngioma in four, and petroclival meningioma, sphenopetroclival meningioma and spheno-orbital meningioma in one each. Six of these lesions were approached from the dominant (left) side, while one lesion was on the right side. Venograms done after the first-stage procedure showed obliteration of the dominant venous drainage with opening up of anastomotic venous channels in all patients. All patients tolerated the first-stage procedure well; only one patient showed asymptomatic mild temporal lobe edema on MRI, which resolved in 3 weeks. None of the patients had venous complications after definitive surgery. One patient with recurrent chordoma, who was planned for staged ligation, did not undergo ligation as, intra-operatively, the draining channel turned out to be a cortical vein, which could be mobilized without ligation. CONCLUSION: In an attempt to detether the temporal lobe, the disconnection of the bridging veins from the temporal lobe to the middle cranial fossa floor in the first stage may lead to re-direction of the venous outflow over time. This may allow skull base surgeons a better surgical corridor and ensure safety of venous structures during the definitive surgery.

Controlled release of imatinib mesylate from PLGA microspheres inhibit craniopharyngioma mediated angiogenesis.

Poly(lactic-co-glycolic acid) microspheres loaded with imatinib mesylate has been developed as a new therapeutic strategy to prevent craniopharyngioma recurrence. Microspheres composed of different lactic/glycolic acid ratios, molecular weights and drug compositions were synthesized and loaded with imatinib mesylate by modified double-emulsion/solvent evaporation technique and subsequently characterized by particle-size distribution, scanning electron microscopy, encapsulation efficiency and in vitro drug release. Inhibitory potential of imatinib containing microspheres on tumor neovascularization was investigated on craniopharyngioma tumor samples by rat cornea angiogenesis assay. Results showed that microspheres in different LA:GA ratios [LA:GA 50:50 (G50), 75:25 (G25), 85:15 (G15)] considerably reduced neovascularization induced by recurrent tumor samples in an in vivo angiogenesis assay (P < 0.01). Our data indicate that local delivery of imatinib mesylate to the post-surgical tumoral cavity using biodegradable microspheres may be a promising biologically selective approach to prevent the recurrence of craniopharyngiomas, via inhibition of neovascularization.

Microvascular density and vascular endothelial growth factor have little correlation with prognosis of craniopharyngioma.

BACKGROUND: Craniopharyngioma is histologically a benign epithelial tumor located in the supersellar cistern that often presents aggressive growth and repeated recurrence. The authors hypothesized that craniopharyngioma recurrence and invasive growth are angiogenesis dependent and evaluated the significance of vascularization in the prognosis of craniopharyngioma by a prospective cohort study. METHODS: The cohorts consisted of 32 patients with AE and 31 patients with SP tumor. The primary and recurrence removal specimens of the cohort patients were gathered. Microvascular density and VEGF protein in the recurrence group and recurrence-free group were detected by the immunohistochemistry avidin-biotin-peroxidase method and analyzed quantitatively through computer-assisted microscopy to evaluate the correlation of MVD and VEGF with prognosis of craniopharyngiomas. RESULTS: The average follow-up phase was 63.34 months; 14 of 32 patients with AE and 6 of 31 patients with SP had recurrence and underwent operation again. Although MVD and VEGF have significant difference between AE and SP (P=.000, P=.018, respectively), MVD and VEGF have no statistical difference between the recurrence group and recurrence-free group (P>.05). CONCLUSIONS: Microvascular density and VEGF in craniopharyngioma tissue have no correlation with prognosis of the tumor, which may be explained by the minimal blood circulation in the craniopharyngioma. Adamantine epithelioma showed more tendency to recur than SP.

Angiogenesis and cell proliferation in human craniopharyngioma xenografts in nude mice.

OBJECT: Craniopharyngioma is one of the most common congenital tumors of the sellar and suprasellar regions and accounts for between 4 and 6% of all intracranial tumors. Its oncogenesis and biological behavior have not been well studied, and neither a cell line nor an animal model have been established. To better understand the tumor and improve its clinical management, the authors investigated the angiogenesis and cellular proliferation in subcutaneous craniopharyngioma xenografts obtained by implanting human tumor cells into athymic nude mice. METHODS: Human craniopharyngioma cells obtained from surgical specimens were subcutaneously implanted into BALB/c-nu/nu nude mice to establish a preliminary animal model of a transplanted tumor. Immunohistochemical staining with streptavidin-peroxidase complex was used to identify the cell phenotype and to evaluate the angiogenesis and proliferation in the xenografts. Expression of cytokeratin, minichromosome maintenance deficient 6 (MCM6) protein, and endothelial cell marker CD34 on the xenograft sections were assayed quantitatively by computer-assisted microscopy. Twenty-seven surviving subcutaneous xenografts were obtained in 15 nude mice. The total implantation success rate was 28.12% (adamantine epithelioma [AE], 37.50%; squamous papillary tumor [SPT], 18.75%). Formation of capillaries and cell proliferation were observed in all of these xenografts. Microvessel density and degree of MCM6 immunostaining were positively correlated in the surviving grafts (r = 0.410, p < 0.05), but there was no significant difference in these variables between the AE and SPT groups (p > 0.05). CONCLUSIONS: A preliminary animal model of human craniopharyngioma was established in the nude mouse by heterotopic implantation. Surviving xenografts maintained their vascularization and proliferation activities until harvesting at 12 weeks.

Angiogenesis and the growth potential of craniopharyngiomas.

The present study was performed to evaluate the role of neovascularization on the behavior of craniopharyngiomas as well as the contribution of endothelial cell proliferation and migration in the remodeling and expansion of the vascular network associated with angiogenesis. Fourteen primary tumors were studied, all of the adamantinomatous type. CD34 immunostaining, an endothelial cell marker, localized vessels within the connective tissue stroma. MIB-1 immunopositivity was apparent in the nuclei of neoplastic cells, few endothelial cells, and stromal elements. MIB-1 counts were higher in epithelial than connective tissue cells. A positive correlation was found between the number of MIB-1 immunopositive cells and microvessel density (MVD). Immunohistochemistry demonstrated that integrin alphavbeta3 expression was restricted to tumor vasculature; the tumor cells were immunonegative. Only 2.5% of vessels detected with CD34 were immunopositive for integrin alphavbeta3. At present, no therapeutic implications can be drawn from our observations. More studies are needed to assess whether integrin alphavbeta3 antagonists or drugs that arrest the cell cycle of endothelial cells can inhibit angiogenesis in craniopharyngiomas.

Angiogenesis in craniopharyngiomas: Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin.

Craniopharyngiomas are benign tumors of the sellar region generally associated with endocrine abnormality and often locally aggressive. Several studies have demonstrated that angiogenesis or neovascularization plays an important role in tumoral growth. The microvascular density (MVD) of craniopharyngiomas was determined in tumor tissue samples from a reference neurosurgery center located in southern Brazil using immunohistochemical methods for two endothelial markers, CD34 and CD105 (endoglin). In addition, tissue expression was determined for an angiogenesis stimulatory factor and for one of its inhibitors, the vascular endothelial growth factor (VEGF) and endostatin, respectively. Endothelial cell immunoreactivity for CD34 and CD105 was observed scattered within the stroma. MVD determined using CD105 antigen was significantly lower than the results obtained by using CD34 antigen. There was no association between the two endothelial markers and tumor extension. The epithelial component showed different degrees of immunoreactivity for VEGF and endostatin in all samples analyzed. We were not able to establish a relationship between angiogenesis in craniopharyngiomas and tumor extension with the endothelial markers used in this study. The investigated vascularization stimulatory and inhibitory factors showed no relation with MVD. We believe that CD105 antigen can be a more specific endothelial marker for tumor angiogenesis than CD34 antigen.

Metastatic papillary craniopharyngioma: case study and study of tumor angiogenesis.

We report a case of suprasellar papillary craniopharyngioma metastatic to the temporoparietal region 2 years after its initial resection. The literature documents examples of craniopharyngioma recurrences along the surgical tract, as well as remote ipsi- and contralateral metastases via cerebrospinal fluid seeding. Ours is the second report of a craniopharyngioma of papillary type to exhibit metastatic behavior. The tumor spread opposite the side of craniotomy. Although a rare occurrence, it confirms the limited capacity of histologically benign craniopharyngiomas to undergo meningeal seeding, likely the result of surgical manipulation. Immunohistochemical demonstration of increased microvascular density and vascular endothelial growth factor expression, as well as a high vascular endothelial growth receptor (VEGFR2) signal by in situ hybridization, suggests that tumor vascularity facilitated angiogenesis and may have been involved in the establishment and growth of the metastatic deposit.

Angiogenesis in patients with craniopharyngiomas: correlation with treatment and outcome.

BACKGROUND: Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that often exhibit aggressive and invasive growth. The authors hypothesized that tumor proliferation, spread, and recurrence are angiogenesis dependent and investigated the significance of vascularization relative to biologic behavior. To the authors' knowledge, angiogenesis for patients with craniopharyngiomas has not been examined to date. METHODS: The authors measured microvessel densities in resected, histologically proven craniopharyngiomas using immunostains for CD-34, a monoclonal antibody that selectively recognizes endothelial cells. Both histologic types of craniopharyngiomas, adamantinomatous and papillary, were included in the study. In addition, the cellular distribution of vascular endothelial growth factor (VEGF), a strong stimulator of new vessel formation, was assessed by both immunohistochemistry and in situ hybridization for VEGF receptor 2 (VEGFR-2) mRNA expression. RESULTS: Histologically, small numbers of capillaries were identified in temporal stroma but not in their epithelial components. Immunohistochemistry revealed strong, conclusive cytoplasmic immunoreactivity for VEGF in the epithelial cells of both adamantinomatous craniopharyngiomas and papillary craniopharyngiomas. In situ hybridization showed that VEGFR-2 mRNA was expressed widely, not only in neoplastic epithelium but also in capillary endothelium. CONCLUSIONS: Tumors with greater microvessel density regrow more frequently compared with tumors that have lower microvessel density, suggesting that the extent of angiogenesis is of prognostic value in patients with craniopharyngioma. VEGFR-2 may act as a key modulator of VEGF activity in endothelial cells and nonendothelial cells, indicating that VEGF plays an important role in the behavior of craniopharyngiomas.

[Single-photon emission-computed tomography of the brain in craniopharyngiomas in the late postoperative period]. / Odnofotonnaia émissionnaia komp'iuternaia tomografiia golovnogo mozga pri kraniofaringiomakh v otdalennom posleoperatsionnom periode.

The paper analyzes tomographic scanning images of 32 patients with craniopharyngiomas in the late postoperative period. Computed tomographic data allowed the patients to be divided into 3 groups: 1) 10 patients without signs of tumor recurrence or hydrocephalus; 2) 14 patients with recurrent cystic craniopharyngiomas; 3) 8 patients with severe hydrocephalus. Single photon emission computed tomography (SPECT) of the brain indicated regional disturbances of brain tissue blood supply in the frontobasal or frontobasotemporal regions of the right hemisphere (the area of an surgical access and of the removed tumor) and revealed them in the distal areas (frontobasotemporal regions of the left hemisphere, parietal and occipital cortices of the cerebral hemisphere or cerebellar tissue). The compensatory reserves of cerebral circulation were assessed by the foci of relative physiological hyperemia of brain tissue (the cerebellum and the medial portions of the occipital regions of the brain). The findings provide evidence for that the vascular factor is involved in the late postoperative pathological picture in patients with craniopharyngiomas.

Microsurgical anatomy and clinical significance of the anterior communicating artery and its perforating branches.

OBJECTIVE: Precise identification of the anomalous anterior communicating artery (ACoA) or the perforating branches of the ACoA is usually difficult on preoperative angiograms because of the vascular complexity around the ACoA and its small-caliber branches. The purpose of this study was to review the microsurgical anatomy of the ACoA and its branches to show their importance for the interhemispheric trans-lamina terminalis approach and ACoA aneurysmal surgery. METHODS: In 30 cadaver brains, the ACoA and its branches were examined under magnification using a surgical microscope. RESULTS: The ACoA was evident in all specimens and had variations consisting of plexiform (33%), dimple (33%), fenestration (21%), duplication (18%), string (18%), fusion (12%), median artery of the corpus callosum (6%), and azygous anterior cerebral artery (3%). The perforating branches were also observed in all cadaver brains. They were classified into subcallosal, hypothalamic, and chiasmatic branches according to their vascular territories. The subcallosal branch, usually single and the largest, supplied the bilateral subcallosal areas, branching off to the hypothalamic area. The hypothalamic branches, multiple and of small caliber, terminated in the hypothalamic area. CONCLUSION: The incidence of anomalous ACoA was higher than has been previously reported, and any segment of the anomalous ACoA may have perforating branches regardless of diameter. Among the three branches, the subcallosal branch is the most important because it feeds bilateral subcallosal areas branching to the hypothalamic area.

Functional perfusion and blood-brain barrier permeability images in the diagnosis of cerebral tumors by Angio CT.

We performed rapid sequential CT scanning following iv injection of a bolus of contrast medium and generated three functional images relating to intravascular circulation time (rABCT), vascular volume (Vv) density and blood-brain barrier (BBB) unidirectional constant uptake rate (Ki), respectively. This was accomplished by calculating the first mathematical moment of the monitored time-density curves about the injection time and from the multiple time graph analysis described by Patlack and co-workers. A satisfactory resolution was achieved, allowing separate appreciation of changes in rABCT both in large vessels and in tissue small vessels. Combined evaluation of rABCT and Vv images allowed us to differentiate between tumors.

[Pedicled craniopharyngioma of the 3d ventricle]. / Craniopharyngiome pédiculé du troisième ventricule.

A 62 year-old man suffered of headache and progressive walking difficulties for 4 years. Radiological examinations showed a calcified intraventricular tumor attached to the floor of the 3rd ventricle. Death, caused by septicemia, occurred before neurosurgery. On sagittal braincut the tumor appeared pediculated and was attached to the anterior part of the floor of the 3rd ventricle. The microscopic features were those of typical craniopharyngioma. The pedicle and the floor of the 3rd ventricule were devoid of tumoral cells. Numerous large vessels which originated in the basal leptomeninges were present in the ventricular floor and the pedicle and then branched out into the tumor. Pathologically proven purely intraventricular craniopharyngiomas have been seldom reported. To our knowledge an autopsy case of pediculated intraventricular craniopharyngioma has been previously described only once, without particular attention to the pedicle. The integrity of the floor of the 3rd ventricle constitutes the only feature that may differentiate with certainty an intraventricular extension of a suprasellar craniopharyngioma from a pure intraventricular form of this tumor.

Prolonged injection angiography for diagnosing intracranial neoplasms.

Prolonged injection angiography (PIA), in which large amounts of contrast material are administered for three or four seconds, was used to visualize the vasculature of 70 intracranial neoplasms. Tumor stains were demonstrated better with or solely by PIA in all pituitary adenomas with suprasellar extension and in most meningiomas. PIA was less effective in tumors with marked arteriovenous shunts or in low-grade gliomas. PIA is especially indicated when avascular or hypovascular masses are encountered on conventional angiography or when contrast enhancement is encountered on computed tomography (CT). PIA is also indicated to demonstrate neoplasms which are not enhanced with contrast media on CT since PIA demonstrates the venous anatomy surrounding the tumors especially well.

Vascular structures in brain tumors.

The blood vessels within brain tumors show alterations from the normal anatomy. Some of these seem to be related to an increased capacity to transfer materials between the lumen and the parenchyma and are probably intimately connected with the edema associated with the tumor. These alterations include fenestration, widened intercellular junctions, increase in pinocytotic vesicles, and infolding of the luminal surface. Other alterations are observed but their function is not as clear. The latter include an increase in the number of tubular bodies, the appearance of tubular structures within vacuoles, tubular arrays within the nuclear envelope and rough endoplasmic reticulum, and endothelial proliferation, among others.