Angiographic Neovascularization Research Articles

Volumetric Three-Dimensional Optical Coherence Tomography Angiography of Retinal Neovascularization in Proliferative Diabetic Retinopathy.

To evaluate structural and angiographic neovascularization in patients with proliferative diabetic retinopathy (PDR) using volumetric three-dimensional optical coherence tomography angiography (OCTA). This prospective, observational cross-sectional study included 29 eyes of 27 patients with PDR. The angiogenic structure, feeding vessel (epicenter), flow volume, and flow volume density (FVD) of the neovasculatures were evaluated using three-dimensional OCTA imaging. The flow area and the flow area density (FAD) were also measured using en face OCTA imaging. Sites of neovascularization were imaged successfully in 17 of the 29 eyes (58.6%). Three proposed types of neovascularization were identified on the basis of structural features seen on the three-dimensional OCTA images. Neovascularization of the adhesion type (9 of 17, 52.9%) adhered to the retinal vasculature. Those of the traction type (5 of 17, 29.4%) were partially separated from the retinal vascular plexus. Those of the mushroom type (3 of 17, 17.6%) were connected to the retinal vasculature via several epicenters. There was a significant difference between highly leaky (active) and faintly leaky (inactive) neovascularization for FVD, but not for flow area, flow volume, or FAD (P=0.01, 0.9, 0.6, and 0.1, respectively). Volumetric three-dimensional OCTA revealed three types of neovascularization in PDR, and may be useful for assessing neovascular activity and planning vitrectomies.

311 A Feasibility Study for a Multicenter Phase-III Randomized Clinical Trial of Encephaloduroarteriosynagiosis Revascularization for Symptomatic Intracranial Atherosclerosis

INTRODUCTION: Stroke due to intracranial-atherosclerotic-disease (ICAD) remains a major public health concern, accounting for more than one-tenth of all ischemic-strokes in the US. METHODS: New data from advanced cerebral imaging and angiographic studies showed that revascularization after indirect-bypass occurs earlier than appreciated before. A pilot study of EDAS in ICAD patients demonstrated angiographic neovascularization as early as 1 month. An NINDS-funded phase-II objective-performance-criterion trial demonstrated reduction in the rate of stroke and death from 21.1% in the medical group to 9.6% in the surgical group at 2 years, passing the threshold for advancement to phase III. In collaboration with the NIH-StrokeNet, a national feasibility survey was sent to sites across the country to evaluate the feasibility of a phase-III clinical trial of EDAS in ICAD. RESULTS: Among 72 surveys completed by prospective sites, 90% (n = 65) indicated interest in participating and 96% of these (n = 63) had neurosurgeons and anesthesiologists with sufficient experience in EDAS and cerebrovascular disorders. The mean number of direct/indirect cerebral bypass surgeries per year completed at the prospective 40 sites was 19 (Range = 10-37). StrokeNet sites cared for a median of 42.5 patients/site/year (IQR = 25-100 patients/site/year) who met enrollment criteria. With 40 participating sites, the rate of enrollment needed for successful recruitment of 516 patients in a phase-III trial is 0.28 patients/site/month (3-4 patients/year), which is an order of magnitude less than the number of relevant cases receiving care at the sites (3.54 patients/month). CONCLUSIONS: EDAS is a promising technique in the management of ICAD and its performance is feasible within 40 high volume institutions. Engagement of the neurosurgical community on revitalizing a surgical form of revascularization can expand the role of neurosurgery in stroke management.

EDAS Revascularization for Symptomatic Intracranial Atherosclerotic Steno-Occlusive Disease (ERSIAS) Phase-II Trial

Background: Intracranial atherosclerotic disease (ICAD) is one of the most challenging stroke etiologies, with frequent recurrences despite optimized medical management. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization method that produces collaterals from the extracranial circulation into cerebral hypoperfused areas. We present the results of a phase-II trial of EDAS in patients with ICAD failing medical management. Methods: ERSIAS was a prospective objective performance criterion (OPC) trial of EDAS plus intensive medical management (IMM) in patients with symptomatic ICAD despite optimized medical management, and poor angiographic collaterals. The primary endpoint was any stroke or death within 30 days postsurgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with the OPC of 10·1%, based on a 10% reduction from the 20·1% rate in the IMM arm of SAMMPRIS trial. The event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from the SAMPPRIS and COSS trials. Secondary endpoints included functional neurological outcome and angiographic neovascularization. Findings: Fifty-two patients underwent EDAS-plus-IMM. The median age was 52 years (IQR=38·3-65·8), and 32 were females (61·5%). The primary endpoint rate at one year was 9·6%, lower than the OPC of 10·1% (p=0·07), meeting the p<0·10 threshold for nonfutility and advancement to phase-III. In the sensitivity analysis, the primary endpoint event rate at two years was lower than in PSM control patients, 9·6 % vs. 21·2% (p<0·07). Overall, 86% of EDAS-plus-IMM patients were functionally independent at last follow-up, and 89% demonstrated neovascularization. There were two (3·8%) surgical complications (wound dehiscence) and no intracranial hemorrhages. Interpretation: ERSIAS phase-II provides evidence of safety and strong signals of the efficacy of EDAS-plus-IMM, supporting testing of the technique in a randomized controlled clinical trial. Trial Registration: NCT01819597. Funding Statement: Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH), under award no. K23NS079477. Declaration of Interests: None. Ethics Approval Statement: Protocol ID:IRB#12-000439 UCLA IRB Initial Approval Date: 7/19/2012 Committee: Medical IRB 3

Evaluation of Encephaloduroarteriosynangiosis Efficacy Using Probabilistic Independent Component Analysis Applied to Dynamic Susceptibility Contrast Perfusion MRI.

Indirect cerebral revascularization has been successfully used for treatment in Moyamoya disease and symptomatic intracranial atherosclerosis. While angiographic neovascularization has been demonstrated after surgery, measurements of local tissue perfusion are scarce and may not reflect the reported successful clinical outcomes. We investigated probabilistic independent component analysis and conventional perfusion parameters from DSC-MR imaging to measure postsurgical changes in tissue perfusion. In this prospective study, 13 patients underwent unilateral indirect cerebral revascularization and DSC-MR imaging before and after surgery. Conventional perfusion parameters (relative cerebral blood volume, relative cerebral blood flow, and TTP) and probabilistic independent components that reflect the relative contributions of DSC signals consistent with arterial, capillary, and venous hemodynamics were calculated and examined for significant changes after surgery. Results were compared with postsurgical DSA studies to determine whether changes in tissue perfusion were due to postsurgical neovascularization. Before surgery, tissue within the affected hemisphere demonstrated a high probability for hemodynamics consistent with venous flow and a low probability for hemodynamics consistent with arterial flow, whereas the contralateral control hemisphere demonstrated the reverse. Consistent with symptomatic improvement, the probability for venous hemodynamics within the affected hemisphere decreased with time after surgery (P = .002). No other perfusion parameters demonstrated this association. Postsurgical DSA revealed an association between an increased preoperative venous probability in the symptomatic hemisphere and neovascularization after surgery. Probabilistic independent component analysis yielded sensitive measurements of changes in local tissue perfusion that may be associated with newly formed vasculature after indirect cerebral revascularization surgery.

Abstract TMP15: Circulating Antiangiogenic Profile Predicts Lower Degrees of Neovascularization After Indirect Revascularization With Encephaloduroarteriosynangiosis (EDAS) in Patients With Intracranial Atherosclerosis (ICAS)

Objective: To evaluate the hypothesis that circulating pro and antiangiogenic profiles predict the degree of angiographic neovascularization in patients undergoing EDAS for the treatment of symptomatic ICAS. Methods: This is a prospective observational study of circulating angiogenic factors in patients with arterial stenosis greater than 70% due to ICAS. All patients received intensive medical management. Patients with persistent symptoms underwent in addition EDAS revascularization. Twenty-one angiogenic factors were analyzed in serum samples collected at baseline, before surgery, using multiplex ELISA. All samples were run in duplicate and accepted as valid if the intersample variability was less than 20%. Patients have angiographic follow up 6 months after EDAS and a Neovascularization Index (NI) based on Perren grades and ASITN collaterals were calculated. Angiogenic profiles (APs) were defined using Principal Component Analysis (PCA). Seven profiles were selected for each time-point (Eigenvalue greater than 1.0). A regression model was built for the outcome variable NI using as predictor variables age, smoking history diabetes, and the 7 APs. Forward stepwise modeling with minimum BIC stopping rule was used to select the best fitted model. Results: Fifteen patients were enrolled. Mean age was 62.1 ± 12.3, 75% were females. The regression model demonstrated significant associations of age, diabetes and the AP 1-6 with the NI. Whole model P=0.023, Rsquare=0.93. The solution of the regression formula for the significant AP components revealed a strong negative association of the antiangiogenic factors endostatin and angiostatin (regression parameters -1.8 and -4.5, respectively, p=0.02). At 6 months follow up no patients had suffer strokes. Conclusion: In this prospective study of angiogenic factors in patients with ICAS undergoing EDAS revascularization, we have found that baseline levels of the antiangiogenic factors endostatin and angiostatin are significantly negatively associated to the degree of postoperative revascularization at 6 months. This finding supports the concept that neutralization of antiangiogenic factors may serve as a new pharmacological target to treat cerebral ischemia in patients with ICAS.

Abstract TP143: Early Angiographic Neovascularization Response to EDAS Surgery in Adults with Intracranial Arterial Stenosis

Introduction: Significant neovascularization following indirect revascularization procedures, such as encephaloduroarteriosynangiosis (EDAS), has traditionally been considered to develop slowly over time. However, a recent study of angiography following indirect revascularization procedures demonstrated early signs of revascularization as early as 4 days following surgery. While we have previously published demonstration of robust revascularization at 6 months and later following surgery, here we present a subset of patients, all with non-moyamoya intracranial arterial stenosis (IAS), with earlier angiographic evaluation following EDAS. Methods: We retrospectively reviewed charts of adult patients who have undergone EDAS for non-moyamoya IAS. These early angiograms were evaluated for signs of revascularization and graded according to the scale presented by Perren et al (1, no sign of neoangiogenesis; 2, one-to-four new transcortical vessels; 3, &gt; four new transcortical vessels). Results: Ten patients (mean age 43 years, 8 females) were found with follow-up cerebral angiography within 6 months of surgery (1 each at 1, 2 &amp; 3 mo, 2 at 1.5 mo, 3 at 5 mo, and 4 at 6 mo). All angiograms demonstrated neovascularity, regardless of underlying diagnosis, including scores of 3 (extensive neoangiogenesis) in 80% of cases as early as 1.5 months after surgery. Two patients had grade 2 at 1 &amp; 2 months. Clinically, all patients’ ischemic symptomatology has resolved. Six patients have had no symptoms since surgery while 4 patients had transient episodes consistent with ischemia (TIA) that all resolved by 2 weeks post-operatively (3 at 1 week and 1 at 2 weeks). No patient suffered stroke following EDAS. Conclusion: This series adds to the growing evidence that indirect revascularization procedures can lead to significant neovascularity in a shorter time frame than previously expected in adult patients, including those with non-moyamoya IAS. Further study is required to better define the time course of neoangiogenesis and to evaluate angiogenic mechanisms that contribute to the success of this procedure.

Large asymptomatic Left Atrial Myxoma with ossification: case report

BackgroundAtrial myxomas are the most common primary cardiac tumors. They are usually small or moderate in size by the time of the diagnosis, exhibiting non specific cardiac or systemic symptoms, and are most frequently soft and friable without microscopic signs of ossification. We describe herein an extremely rare case of an asymptomatic giant left atrial myxoma with angiographic neovascularization and ossification.Case presentationAn asymptomatic 58-year-old male with a giant left atrial tumor, was transferred to our Unit for surgical treatment. The tumor was an incidental finding during a work-up for hemoptysis due to bronchectasis. The coronary angiogram showed tumor vessels originating from the RCA. The tumor macroscopically did not resemble a myxoma, considering its dimensions (12 × 10 cm) and its solid substance. The mass was excised together with the interatrial septum and the right lateral LA wall close to the right pulmonary veins orifices. The defect was closed with Dacron patches in order to prevent malformation of both atria. The pathology study revealed a benign myxoma with excessive osteoid (mature bone) content.ConclusionWe consider our case as extremely rare because of the asymptomatic course despite the large size of the tumor, the blood supply from the right coronary artery and the bone formation.

The Clinical Significance of Measurement of Serum Vascular Endothelial Growth Factor in Patients with Hemoptysis

Background: Hemoptysis is an often alarming presenting symptom and VEGF is a major regulator of both normal and abnormal angiogenesis, including many inflarrunatory diseases. In this report the clinical significance of the serum VEGF level in patients with hemoptysis was investigated. Methods: Thirty-two patients with hemoptysis were evaluated. The estimated amount of hemoptysis, etiology and serum VEGF level was examined at admission and bronchial angiography was performed in 22 patients. In order to objectify the neovascularization status, one point for the presence of the A-V shunt, hypervascularity, vascular tortuosity was designated for a total of 0-3 points. Results: Mean quantity of hemoptysis was . The mean angiographic neovascularization score was . The serum VEGF level correlated with the quantity of hemoptysis(r=0.524, p=0.002) and with the angiographic neovascularization score(r=0.441, p=0.04). Using the standard diagnostic criterion for massive hemoptysis, the serum VEGF level of patients with massive hemoptysis( pg/ml, n=13) was found to be higher than that of patients with non-massive hemoptysis( pg/ml, n=19) (p=0.069). Conclusion: Regardless of the etiology, the serum VEGF may contribute to abnormal neovascularization in patients with hemoptysis. Therefore, it is suggested that serum VEGF measurements may help in predicting a massive hemoptysis.

Angiogenesis and Brain Oedema in Intracranial Meningiomas: Influence of Vascular Endothelial Growth Factor

The correlation between angiographic neovascularization, peritumoural brain oedema (PTBOe) and the expression of vascular endothelial growth factor (VEGF), was analysed in 30 patients with intracranial meningiomas. Pre-operative angiograms were examined for the existence of either an exclusively dural tumour blush or an additionally pial tumour supply from cerebral arteries. Furthermore the presence of macroscopic tumour-neovascularization and dysplastic changes of tumour-draining cerebral veins was evaluated. VEGF expression was investigated on histological tissue samples, using immunohistochemical techniques. VEGF immunohistochemistry and neuroradiological evaluations were performed in double blind fashion. Tumour volume and the amount of oedema were calculated by computerized tomography (CT) or magnetic resonance imaging (MRI). The oedema-tumour volume ratio was defined as oedema index (OeI). Compared to VEGF-negative meningiomas, tumours with striking VEGF staining revealed a significant higher mean oedema index (OeI = 4.2 vs. OeI = 1.5; p < 0.018), and a higher oedema incidence (91.7% vs. 44.4%; p < 0.046). Equally, meningiomas with additionally tumour supply from cerebral arteries were associated with a significant higher mean OeI (OeI = 4.1 vs. OeI = 1.2; p < 0.01) and oedema incidence (94.7% vs. 20.0%; p < 0.0023) than meningiomas with exclusively tumour supply from dural arteries. All meningiomas with striking VEGF-expression were associated with vascular tumour supply from cerebral arteries, but VEGF-negative tumours only in 50% (p < 0.029). These data suggest a link between VEGF-expression, arterial tumour supply and peritumoural brain oedema. The development of tumour supply from cerebral arteries may be important for formation of meningioma-related oedema. Therefore, VEGF may represent a potent mediator in the evolution of this type of vascularization in meningiomas.

Vasoreconstructive Surgery for Radiation-Induced Vasculopathy in Childhood

Background Cerebral vasculopathy associated with the appearance of netlike vessels can develop following irradiation therapy for parasellar brain tumors, especially in children. However, little is known regarding the clinical course of this disease or the appropriate therapy for it. Case Reports We experienced two surgically-treated patients with radiation-induced vasculopathy and reviewed the previously reported cases. Both of our patients were treated with encephalo-duro-arterio-myo-synangiosis combined with superficial temporal artery to middle cerebral artery (STA-MCA) bypass. Their ischemic symptoms improved following the surgery, associated with a good angiographic neovascularization from the STA-MCA bypass, as well as dural and muscular arteries. Conclusion Our findings and the review of the previous reports suggested that surgical therapy may be beneficial for the patients with radiation-induced vasculopathy with the appearance of netlike vessels.