Angiographic Structural Differentiation between Native Arteriogenesis and Therapeutic Synangiosis in Intracranial Arterial Steno-Occlusive Disease.
ABSTRACT: BACKGROUND AND PURPOSE:Encephaloduroarteriosynangiosis has been shown to generate collateral vessels from the extracranial-to-intracranial circulation in patients with Moyamoya disease and intracranial arterial steno-occlusive disease. The mechanisms involved are not well-understood. We hypothesized that angiogenesis is the leading mechanism forming collaterals after encephaloduroarteriosynangiosis because there are no pre-existing connections. Angiogenesis-generated collaterals should exhibit higher architectural complexity compared with innate collaterals. MATERIALS AND METHODS:Pre- and postoperative digital subtraction angiograms were analyzed in patients enrolled in a prospective trial of encephaloduroarteriosynangiosis surgery. Branching angioscore, tortuosity index, and local connected fractal dimension were compared between innate and postoperative collaterals. RESULTS:One hundred one angiograms (50 preoperative, 51 postoperative) were analyzed from 44 patients (22 with intracranial atherosclerosis and 22 with Moyamoya disease). There was a significantly higher median branching angioscore (13 versus 4, P < .001) and a lower median tortuosity index (1.08 versus 1.76, P < .001) in the encephaloduroarteriosynangiosis collaterals compared with innate collaterals. Higher mean local fractal dimension peaks (1.28 ± 0.1 versus 1.16 ± 0.11, P < .001) were observed in the encephaloduroarteriosynangiosis collaterals compared with innate collaterals for both intracranial atherosclerosis (P < .001) and Moyamoya disease (P < .001) groups. The observed increase in high connectivity was greater in the intracranial atherosclerosis group compared with patients with Moyamoya disease (P = .01). CONCLUSIONS:The higher median branching angioscore and local connected fractal dimension, along with the lower median tortuosity index of encephaloduroarteriosynangiosis collaterals, are consistent with the greater complexity observed in the process of sprouting and splitting associated with angiogenesis.
Project description:PURPOSE:To quantify vessel tortuosity and fractal dimension of the superficial capillary plexus (SCP) of the macula in different stages of diabetic retinopathy (DR), and following panretinal photocoagulation (PRP) using optical coherence tomography angiography (OCTA). METHODS:75 eyes of 75 subjects were divided into five groups; healthy controls, diabetes with no clinical DR, non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and patients who received PRP for PDR (PDR+PRP).For vessel tortuosity, SCP slabs from 3x3 mm macular OCTA scans were processed using imageJ (NIH, USA), where large perifoveal vessels were traced and their length was measured with tortuosity calculated as the ratio between the actual length and the straight Euclidean length. For fractal dimension, SCP slabs were processed and imported to Fractalyse (ThéMA, France), where box-counting analyses produced fractal dimension values. RESULTS:We found a significant difference in vessel tortuosity and fractal dimension between the five groups (one-way ANOVA, p < 0.001both). NPDR and PDR had significantly more tortuous vessels and lower fractal dimension compared to healthy controls (Tukey HSD: p = 0.02, 0.015,0.015 and <0.001, respectively). Fractal dimension was also significantly lower in NPDR and PDR compared to eyes with no clinical DR (p <0.001 both), and in PDR compared to NPDR (p = 0.014). Following PRP, vessel tortuosity was significantly lower and fractal dimension was higher in PDR+PRP compared to PDR (p = 0.001 and 0.031, respectively). CONCLUSIONS:We used macular OCTA scans to demonstrate significantly higher perifoveal large vessel tortuosity, and lower fractal dimension in NPDR and PDR compared to healthy controls. Vessel tortuosity shows more dramatic normalization than fractal dimension and could be explored as a sensitive marker for successful PRP.
Project description:Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 μm vs 144.3 μm, p < 0.001; 227.7 μm vs 212.8 μm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x10(4)], p < 0.001; 0.849 vs 0.658 [x10(4)], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system.
Project description:Pulmonary hypertension (PH) can result in vascular pruning and increased tortuosity of the blood vessels. In this study we examined whether automatic extraction of lung vessels from contrast-enhanced thoracic computed tomography (CT) scans and calculation of tortuosity as well as 3D fractal dimension of the segmented lung vessels results in measures associated with PH. In this pilot study, 24 patients (18 with and 6 without PH) were examined with thorax CT following their diagnostic or follow-up right-sided heart catheterisation (RHC). Images of the whole thorax were acquired with a 128-slice dual-energy CT scanner. After lung identification, a vessel enhancement filter was used to estimate the lung vessel centerlines. From these, the vascular trees were generated. For each vessel segment the tortuosity was calculated using distance metric. Fractal dimension was computed using 3D box counting. Hemodynamic data from RHC was used for correlation analysis. Distance metric, the readout of vessel tortuosity, correlated with mean pulmonary arterial pressure (Spearman correlation coefficient: ? = 0.60) and other relevant parameters, like pulmonary vascular resistance (? = 0.59), arterio-venous difference in oxygen (? = 0.54), arterial (? = -0.54) and venous oxygen saturation (? = -0.68). Moreover, distance metric increased with increase of WHO functional class. In contrast, 3D fractal dimension was only significantly correlated with arterial oxygen saturation (? = 0.47). Automatic detection of the lung vascular tree can provide clinically relevant measures of blood vessel morphology. Non-invasive quantification of pulmonary vessel tortuosity may provide a tool to evaluate the severity of pulmonary hypertension.ClinicalTrials.gov NCT01607489.
Project description:The cerebral hypoperfusion caused by chronic progressive stenosis or occlusion of intracranial arteries in moyamoya disease can be treated by direct bypass or indirect revascularization procedures. The extent of collaterals from the external carotid artery (ECA) after indirect revascularization surgery is the key point of angiographic follow-up, and the invasiveness of angiography impelled us to investigate the role of ultrasonography in the evaluation of collaterals. We hypothesized that the collaterals shown on angiography might produce corresponding hemodynamic changes in color Doppler ultrasonography. We prospectively recruited moyamoya patients who underwent indirect revascularization surgery and received both preoperative and postoperative angiography and color Doppler ultrasound studies. The collaterals on angiography were graded according to Matsushima method. A total of 21 patients (age, 17 ± 10.2 years) with 24 operated hemispheres were enrolled. Patients who showed better collateral establishment by angiography had higher end-diastolic velocity (EDV), lower resistance index (RI), and larger flow volume in the superficial temporal artery (STA) and ECA (all p < 0.05). In STA, increase of EDV greater than 13.5 cm/sec or reduction of RI greater than 0.19 after operation corresponded to 94% of Matsushima grade A+B. In ECA, post-operative EDV greater than 22 cm/sec or increase of EDV greater than 6.4 cm/sec also corresponded to 94% of Matsushima grade A+B. Our findings revealed potential roles of color Doppler ultrasonography in identifying patients with poor collaterals after indirect revascularization procedures.
Project description:Microcirculatory insufficiency has been hypothesized in glaucoma pathogenesis. There is a scarcity of data to comprehensively examine the changes in retinal microvasculature and its role in normal tension glaucoma (NTG). We conducted a cross-sectional case-control study and included 168 eyes from 100 NTG patients and 68 healthy subjects. Quantitative retinal arteriolar and venular metrics were measured from retinal photographs using a computer-assisted program. Radial peripapillary capillary network was imaged with OCT-A and quantitative capillary metrics (circumpapillary vessel density (cpVD) and circumpapillary fractal dimension (cpFD)) were measured with a customized MATLAB program. We found that NTG was associated with decreased arteriolar and venular tortuosity, arteriolar branching angle, cpVD and cpFD. Decreased venular caliber, arteriolar and venular branching angles, cpVD and cpFD were associated with thinner average RNFL thickness. Decreased arteriolar and venular branching angles, cpVD and cpFD were also associated with worse standard automated perimetry measurements (mean deviation and visual field index). Compared with retinal arteriolar and venular metrics, regression models based on OCT-A capillary metrics consistently showed stronger associations with NTG and structural and functional measurements in NTG. We concluded that NTG eyes showed generalized microvascular attenuations, in which OCT-A capillary metrics attenuations were more prominent and strongly associated with NTG.
Project description:OBJECTIVE: Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12-20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol. RESULTS: In this study, 137 patients (18.8%) had diabetic retinopathy signs; of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023-1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02-7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21-1.56]). This association remained after additional adjustment for retinal vascular caliber. CONCLUSIONS: Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.
Project description:OBJECTIVE:The fractal dimension of retinal arteries and veins is a measure of the complexity of the vascular tree. We hypothesized that retinal fractal dimension would be associated with brain volume and white matter integrity in HIV-infected women. DESIGN:Nested case-control within longitudinal cohort study. METHODS:Women were recruited from the Brooklyn site of the Women's Interagency HIV study (WIHS); 34 HIV-infected and 21 HIV-uninfected women with analyzable MRIs and retinal photographs were included. Fractal dimension was determined using the SIVA software program on skeletonized retinal images. The relationship between predictors (retinal vascular measures) and outcomes (quantitative MRI measures) were analyzed with linear regression models. All models included age, intracranial volume, and both arterial and venous fractal dimension. Some models were adjusted for blood pressure, race/ethnicity, and HIV-infection. RESULTS:The women were 45.6 ± 7.3 years of age. Higher arterial dimension was associated with larger cortical volumes, but higher venous dimension was associated with smaller cortical volumes. In fully adjusted models, venous dimension was significantly associated with fractional anisotropy (standardized ? = -0.41, p = 0.009) and total gray matter volume (? = -0.24, p = 0.03), and arterial dimension with mean diffusivity (? = -0.33,.p = 0.04) and fractional anisotropy (? = 0.34, p = 0.03). HIV-infection was not associated with any retinal or MRI measure. CONCLUSIONS:Higher venous fractal dimension was associated with smaller cortical volumes and lower fractional anisotropy, whereas higher arterial fractal dimension was associated with the opposite patterns. Longitudinal studies are needed to validate this finding.
Project description:We compared intracranial collaterals on pretreatment and day 2 brain CT angiograms (CTA) to assess their evolution and relationship with functional outcomes in acute ischemic stroke (AIS) patients treated with IV tissue plasminogen activator (tPA).Consecutive AIS patients who underwent pretreatment and day 2 CTA and received IV tPA during 2010-2013 were included. Collaterals were evaluated by 2 independent neuroradiologists using 3 predefined criteria: the Miteff system, the Maas system, and 20-point collateral scale by the Alberta Stroke Program Early CT Score methodology. We stratified our cohort by baseline pre-tPA state of their collaterals and by recanalization status of the primary vessel for analysis. Good outcomes at 3 months were defined by a modified Rankin Scale score of 0-1.This study included 209 patients. Delayed collateral recruitment by any grading system was not associated with good outcomes. All 3 scoring systems showed that collateral recruitment on the follow-up CTA from a baseline poor collateral state was significantly associated with poor outcome and increased bleeding risk. When the primary vessel remained persistently occluded, collateral recruitment was significantly associated with worse outcomes. Interestingly, collateral recruitment was significantly associated with increased mortality in 2 of the 3 grading systems.Not all collateral recruitment is beneficial; delayed collateral recruitment may be different from early recruitment and can result in worse outcomes and higher mortality. Prethrombolysis collateral status and recanalization are determinants of how intracranial collateral evolution affects functional outcomes.
Project description:To prospectively determine if magnetic resonance (MR) angiography can depict intracranial vascular morphologic changes during treatment of brain metastases from breast cancer and if serial quantitative vessel tortuosity measurements can be used to predict tumor treatment response sooner than traditional methods.Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Twenty-two women aged 31-61 years underwent brain MR angiography prior to and 2 months after initiation of lapatinib therapy for brain metastases from breast cancer. Vessels were extracted from MR angiograms with a computer program. Changes in vessel number, radius, and tortuosity were calculated mathematically, normalized with values obtained in 34 healthy control subjects (19 women, 15 men; age range, 19-72 years), and compared with subsequent assessments of tumor volume and clinical course.All patients exhibited abnormal vessel tortuosity at baseline. Nineteen (86%) patients did not exhibit improvement in vessel tortuosity at 2-month follow-up, and all patients demonstrated tumor growth at 4-month follow-up. Vessel tortuosity measurements enabled us to correctly predict treatment failure 1-2 months earlier than did traditional methods. Three (14%) patients had quantitative improvement in vessel tortuosity at 2-month follow-up, with drop out of small abnormal vessels and straightening of large vessels. Each of the two patients for whom further follow-up data were available responded to treatment for more than 6 months.Study results established the feasibility of using MR angiography to quantify vessel shape changes during therapy. Although further research is required, results suggest that changes in vessel tortuosity might enable early prediction of tumor treatment response.
Project description:BACKGROUND AND PURPOSE:Moyamoya disease is a progressive neurovascular pathology defined by steno-occlusive disease of the distal internal carotid artery and associated with the development of compensatory vascular collaterals. The etiology and exact anatomy of vascular collaterals have not been extensively studied. The aim of this study was to describe the anatomy of collaterals developed between the ophthalmic artery and the anterior cerebral artery in a Moyamoya population. MATERIALS AND METHODS:All patients treated for Moyamoya disease from 2004 to 2016 in 4 neurosurgical centers with available cerebral digital subtraction angiography were included. Sixty-three cases were evaluated, and only 38 met the inclusion criteria. Two patients had a unilateral cervical internal carotid occlusion that limited analysis of ophthalmic artery collaterals to one hemisphere. This study is consequently based on the analysis of 74 cerebral hemispheres. RESULTS:Thirty-eight patients fulfilled the inclusion criteria. The most frequently encountered anastomosis between the ophthalmic artery and cerebral artery was a branch of the anterior ethmoidal artery (31.1%, 23 hemispheres). In case of proximal stenosis of the anterior cerebral artery, a collateral from the posterior ethmoidal artery could be visualized (16 hemispheres, 21.6%). One case (1.4%) of anastomosis between the lacrimal artery and the middle meningeal artery that permitted the vascularization of a middle cerebral artery territory was also noted. CONCLUSIONS:Collaterals from the ophthalmic artery are frequent in Moyamoya disease. Their development depends on the perfusion needs of the anterior cerebral artery territories. Three other systems of compensation could be present (callosal circle, leptomeningeal anastomosis, and duro-pial anastomoses).