Differences In Vascular Parameters Research Articles

Non-invasive ultrasound localization microscopy (ULM) in azoospermia: connecting testicular microcirculation to spermatogenic functions.

Rationale: Azoospermia is a significant reproductive challenge. Differentiating between non-obstructive azoospermia (NOA) and obstructive azoospermia (OA) is crucial as each type requires distinct management strategies. Testicular microcirculation plays a profound role in spermatogenic functions. However, current diagnostic methods are limited in their ability to effectively elucidate this crucial connection. Methods: We employed ultrasound localization microscopy (ULM) to visualize testicular microcirculation in NOA and OA patients and quantified the testicular hemodynamic parameters. Pearson correlation analysis was conducted to investigate the inner connection between parameters of testicular microcirculation and clinical spermatogenic functions. We conducted multiple logistic regression analysis to establish a new diagnostic model that integrates follicle-stimulating hormone (FSH) and mean vascular diameter to distinguish NOA from OA. Results: Our findings demonstrated significant differences in vascular parameters between NOA and OA, with NOA characterized by lower mean vascular diameter (p < 0.001), vessel density (p < 0.001), and fractal number (p < 0.001). Testicular volume showed a moderate positive correlation with mean vascular diameter (r = 0.419, p < 0.01) and vessel density (r = 0.415, p < 0.01); Mean vascular diameter exhibited negative correlations with both FSH (r = -0.214, p < 0.05) and age (r = -0.240, p < 0.05); FSH (r = -0.202, p < 0.05) and luteinizing hormone (LH) (r = -0.235, p < 0.05) were negatively correlated with mean blood flow velocity. The diagnostic model demonstrated an area under the curve (AUC) of 0.968. We also reported a method to map the vascular pressure distribution derived from the blood flow velocity generated by ULM. Conclusions: ULM provides a non-invasive and detailed assessment of testicular microvascular dynamics. The ULM-derived vascular parameters are able to connect testicular microcirculation to spermatogenic functions. The combination of FSH and mean vascular diameter enhances diagnostic precision and holds potential for distinguishing NOA from OA.

Abstract 11582: The Fingertip Artery is Better Than the Brachial Artery in Evaluating Vascular Endothelial Function for Coronary Artery Disease in Diabetic Patients

Introduction: Several studies demonstrated that endothelial function is impaired in diabetic patients, but no study evaluated vascular parameters in diabetic patients trough a combined analysis of macro and micro-endothelial function. In addition, the difference in vascular parameters between diabetes patients with coronary artery disease (CAD) and without CAD remains unknown. We assessed whether CAD is related to macro or micro vascular endothelial function in diabetic patients. Hypothesis: We measured vascular function in 219 diabetic patients (age 68±10 years), including 147 patients with CAD (CAD group) and 72 patients without CAD (control group). Flow mediated vasodilatation (FMD)indicating macro-endothelial function in the brachial artery was measured by ultrasound using a semi-automatic device: UNEXEF18G (UNEX Co. Nagoya, Japan). Reactive hyperemia index (RHI) indicating micro-endothelial function in the fingertip artery was measured by peripheral arterial tonometry (EndoPAT 2000). Vascular function tests were measured on the same day. Results: RHI was significantly impaired in CAD group (RHI: 2.0±0.7 vs.1.7±0.5 P=0.012), however FMD had no deference in the two groups. Logistic regression analysis revealed that RHI (odds ratio: 0.44, 95% confidence interval: 0.21-0.94) was an independent predictor for CAD in diabetic patients. Conclusions: RHI, an acknowledged marker of micro-endothelial function was a more sensitive method than FMD in evaluating the risk assessment of CAD in diabetic patients. more peripheral vascular endothelial function was associated with CAD in diabetic patients.

Effects of pupil dilation with topical 0.5% tropicamide on retinal vascular parameters assessed by VAMPIRE® software in healthy cats

Our study investigates the effects of mydriasis obtained with topical 0.5% tropicamide on retinal vascular parameters evaluated in cats using the retinal imaging software: Vascular Assessment and Measurement Platform for Images of the Retina (VAMPIRE®). Forty client-owned healthy adult cats were included in the study. Topical 0.5% tropicamide was applied to dilate only the right pupil. The left eye was used as a control. Before dilation (T0), infrared pupillometry of both pupils was performed and fundus oculi images were taken from both eyes. Right eye fundus images were then captured 30 min after topical application of tropicamide (T30), when mydriasis was achieved. The retinal vessel widths (3 arteries and 3 veins) were measured with VAMPIRE® in four standard measurement areas (SMA) identified with the letters A, B, C, D. Average value of the 3 vessel widths was used. After normality assessment, the t-test was used to analyse the mean difference in vascular parameters of the left and right eyes at T0 and T30, with p set <0.05. The two eyes showed no statistical differences in pupil and vascular parameter measurements at T0. At T30, only one artery measurement of the right eye (SMA A-peripapillary area) showed a small but statistically significant mean vasoconstriction of approximately 4%. The results indicate that local application of 0.5% tropicamide seems to be associated with a small retinal arteriolar vasoconstriction as assessed by VAMPIRE® in cats. However, this change is minimal, and should not affect the interpretation of the results when VAMPIRE® is used.

PS-C17-1: PERIPHERAL MICROVASCULAR DYSFUNCTION IN SUBJECTS WITH TYPE2 DIABETES(T2DM) IN ACCORDANCE WITH ABSENCE OR PRESENCE OF CORONARY ARTERY DISEASE.

Background: Several studies demonstrated that endothelial function is impaired in patients with T2DM, but no study evaluated vascular parameters in patients with T2DM trough a combined analysis of macro and micro-endothelial function and arterial stiffness indexes. In addition, the difference in vascular parameters between T2DM patients with CAD and without CAD remains unknown. We assessed whether coronary artery disease is associated with impairment of peripheral endothelial function and arterial stiffness indexes in patients with T2DM. Methods: We measured vascular function in 219 T2DM subjects (age 68 ± 10 years), including 147 subjects with CAD (CAD group) and 72 subjects without CAD (control group). Flow mediated vasodilatation (FMD) indicating endothelial function in a conduit artery was measured by ultrasound using a semi-automatic device: UNEXEF18G (UNEX Co. Nagoya, Japan). Reactive hyperemia index (RHI) indicating peripheral endothelial function and Augmentation index (AI) indicating arterial stiffness were measured by peripheral arterial tonometry (EndoPAT 2000). Vascular function tests were measured on the same day. Results: RHI and AI was significantly impaired in CAD group (RHI: 2.0 ± 0.7 vs.1.7 ± 0.5 P = 0.012, AI: 30.2 ± 18.1 vs.22.1 ± 19.1 P = 0.043), however FMD had no deference in the two groups. Logistic regression analysis revealed that RHI (odds ratio: 0.44, 95% confidence interval: 0.21–0.94) was an independent predictor for CAD in subjects with T2DM. Conclusions: RHI, an acknowledged marker of microcirculatory endothelial function was a more sensitive method in evaluating the risk assessment of CAD in subjects with T2DM.

2242-PUB: Retinal Biomarkers Indicative of Diabetic Peripheral Neuropathy

The purpose of this study was to identify biomarkers that are indicative of diabetic peripheral neuropathy (DPN). From a cohort of 21 DPN and 18 controls, optic disc- and macula-centered images were taken. Sixty vascular parameters were measured using computer-assisted software. Statistically significant differences in vascular parameters between subjects with DPN and controls showed that DPN subjects could be differentiated from controls using retinal biomarkers. Statistical significance (p &amp;lt; 0.05) was obtained for 13 retinal features, including fractal dimension, vein width, number of 1st branching vessels, and vessel tortuosity. The reduced fractal dimensions in DPN patients indicate a deterioration of the retinal vascular architecture. The reduced total number of vessels, as well as the total number of venules, contribute to the lower fractals in the DPN patients and supports the findings of a sparser retinal vascular network for DPN subjects. A difference in standard deviation for vessel width may suggest a greater loss of vascular tone and regulation in DPN subjects. A difference in the number of 1st branching vessels in venules was observed, which may indicate that the DPN subjects had fewer numbers of these first bifurcations. This feature would also contribute to the lower fractal dimension as well as a sparser retinal vascular network. Similarly, the statistical difference in the angle of the first daughter vessel suggests that the retinal vascular architecture has deviated from its optimal flow and/or function due to the disease process. The increased difference in curvature tortuosity in the arterioles in DPN correlates with chronic hypertensive retinopathy. We found statistically significant differences in 13 out of 60 retinal vascular features (22%) between control and DPN subjects. As such, the retina reflects the widespread vascular structural abnormalities occurring in diabetic patients with DPN. Disclosure S.C. Nemeth: None. M.R. Burge: None. J. Wigdahl: None. J.C. Carmichael: None. X. Guo: None. V. Joshi: None. P. Soliz: Stock/Shareholder; Self; VisionQuest Biomedical LLC. Funding National Institutes of Health (R43DK104578-01)

Comparison of arterial blood supply to the testicles in the preoperative and early postoperative period in patients undergoing subinguinal varicocelectomy

Objective. Varicocele, which is the abnormal dilatation of internal spermatic veins, is known as the most surgically correctable cause of male infertility. In the evaluation of testicular arterial and venous blood supply, the scrotal colour Doppler ultrasound (CDU) is a valuable diagnostic method. The aim of this study was to investigate how the testicular blood flow is affected after varicocelectomy, and the place of scrotal CDU in the follow-up after varicocelectomy. Material and methods. Thirty male patients who were diagnosed with left-sided varicocele were prospectively included in the study. Before the varicocelectomy, semen analyses were carried out, and peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI) and pulsatility index (PI) were measured by CDU. In the third postoperative month, scrotal CDU and semen analysis were performed again and compared with the preoperative results. Results. The arterial flow parameters PSV and EDV increased significantly, and the resistance parameters RI and PI decreased significantly, compared with the preoperative values. Sperm concentration, progressive motility and normal morphology improved in the postoperative semen analysis compared with the preoperative results. The increases in all three parameters were statistically significant. No statistically significant difference in vascular parameters was seen between the patients with improved and unimproved semen analysis. Conclusions. As confirmed by the results of semen analysis and CDU, testicular blood flow increases after varicocelectomy, resulting in the recovery of the haemodynamics of the testicle. CDU, which is generally used for diagnosis in the varicocele, can also be a valuable method of determining treatment success after surgery.

AB0301 Vascular Markers in Woman and in Men with Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is associated with increased morbidity and mortality rates due to cardiovascular disease, and this occurs early in the disease process. In RA an impairment of the number...

Study of microvessel density and the expression of vascular endothelial growth factors in adrenal gland pheochromocytomas.

Angiogenesis (neoangiogenesis), a process of neovascularization, is an essential step for local tumor growth and distant metastasis formation. We have analysed angiogenesis status: vascular architecture, microvessel density, and vascular endothelial growth factors expression in 62 adrenal pheochromocytomas: 57 benign and 5 malignant. Immunohistochemical evaluation revealed that vascular architecture and vessel density are different in the central and subcapsular areas of the tumor. Furthermore, we have observed a strong correlation between number of macrophages and microvessel density in the central and subcapsular areas of the tumor and between the expression of VEGF-A in tumor cells and microvessel density in central and subcapsular areas of the tumor. Secondary changes in these tumors influence the results and both vascular architecture and microvessel density are markedly disturbed by hemorrhagic and cystic changes in pheochromocytomas. These changes are partially caused by laparoscopic operation technique. However, no differences in vascular parameters were found between pheochromocytomas with benign and malignant clinical behavior. Our observation showed that analysis of angiogenesis, as a single feature, does not help in differentiating malignant and benign pheochromocytomas and has no independent prognostic significance. On the other hand, high microvessel density in pheochromocytoma is a promising factor for antiangiogenic therapy in malignant cases.

Computer-assisted image analysis of temporal retinal vessel width and tortuosity in retinopathy of prematurity for the assessment of disease severity and treatment outcome

To quantify the severity of retinopathy of prematurity (ROP) through temporal retinal vessel diameter and tortuosity by the use semiautomated analysis and to evaluate the effects of laser treatment on retinal vessel measurements. A total of 176 RetCam digital fundus images from 63 infants diagnosed with ROP between January 2005 and December 2008 were retrospectively analyzed with Retinal Vessel Measurement V5.8 software. Patients were classified into 1 of 3 groups: stage 1 and 2 (Group 1), stage 3 not requiring treatment (Group 2), and stage 3 requiring treatment (Group 3). Diameter and tortuosity of the 4 major temporal retinal arteries and veins close to the optic disk were quantified. Tortuosity was measured as central (within 2 disk diameters from the center of the optic disk) and paracentral (from 2 to 4 disk diameters). For Group 3, measurements of vessels immediately before treatment and all follow-up post-treatment measurements of vessels were analyzed. Differences in central and paracentral arteriolar tortuosity were pronounced. The average central arteriolar tortuosities were 1.12 ± 0.018 for Group 1, 1.13 ± 0.018 for Group 2, and 1.32 ± for Group 3; the paracentral arteriolar tortuosities were 1.11 ± 0.019 for Group 1, 1.12 ± 0.019 for Group 2, and 1.31 ± 0.02 for Group 3. In the post-treatment analysis of Group 3 patients, significant reductions in all vascular measurements were observed compared to pre-treatment, except for central and paracentral vein tortuosity. Computerized systems can be used to objectively assess differences in vascular parameters between ROP stages.

Different hemodynamic responses by color Doppler ultrasonography studies between sildenafil non-responders and responders

To determine if there are different penile hemodynamic patterns between sildenafil non-responders and responders by using color Doppler ultrasonography. A total of 69 erectile dysfunction (ED) patients aged 22-79 years were enrolled into the present study. Thirty-eight (55.1%) men with ED who did not respond to four attempts of treatment with 100 mg sildenafil after re-education were classified as sildenafil non-responders. A combination of three vasodilator drugs, 1.25 mg papaverine, 0.4 mg phentolamine and 5 mg prostaglandin E1, was given by intracavernous injection before penile Doppler ultrasonography was carried out. The erectile response to intracavernous injection and vascular parameters including peak systolic velocity (PSV), resistance index (RI), end diastolic velocity (EDV) and cavernosa artery diameter (CD) were measured and the results between sildenafil non-responders and responders were compared. No statistical difference in vascular parameters measured by Doppler ultrasonography studies between non-responders and responders was noted. Sildenafil non-responders had a poorer penile rigidity response to intracavernous injection than responders (P < 0.05). Among patients with adequate PSV (>or=30 cm/s) and abnormal EDV (> 5 cm/s), individuals in the non-responder group had fewer positive responses to intracavernous vasodilator injection than in the responder group (35.3% vs. 72.2%, P < 0.05). Advanced age and comorbidity with diabetes mellitus were significantly associated with sildenafil non-response (P < 0.05). Sildenafil non-responders were characterized by a poorer penile rigidity response to intracavernous injection and had an associated impaired veno-occlusive mechanism. Advanced age and comorbidity with diabetes mellitus were two common factors associated with non-response.

Paclitaxel encapsulated in cationic lipid complexes (MBT-0206) impairs functional tumor vascular properties as detected by dynamic contrast enhanced magnetic resonance imaging

Cationic lipid complexes have been shown to be bound and internalized selectively by angiogenic tumor endothelial cells after intravenous injection. Based on this phenomenon, the chemotherapeutic agent paclitaxel was encapsulated into these lipid complexes providing a vascular targeting agent (MBT-0206). As non-invasive imaging techniques are of critical importance for optimizing antivascular cancer treatment in the clinic, we have evaluated the antivascular effects of MBT-0206 in the A-MEL-3 solid tumor model using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).Twenty-four hours after 3 intravenous applications of MBT-0206, tumors of treated animals demonstrated a significant decrease of intratumoral blood volume and an increase of vascular permeability in comparison to size matched control tumors. In contrast, animals treated with conventional paclitaxel given as Taxol® at equal drug dose did not show any significant differences in vascular parameters acquired by DCE-MRI in comparison to controls. Immunohistological analysis confirmed a significant reduction of microvessel density in MBT-0206 treated tumors. Moreover, a significant increase of intratumoral microvascular occlusion following MBT-0206 treatment was observed compared to controls and paclitaxel treated animals.In conclusion, antivascular tumor therapy with MBT-0206 significantly impairs functional tumor microcirculation. DCE-MRI is a promising tool to quantify the antivascular effects of MBT-0206 during treatment.

Angiogenesis in neuroblastoma: relationship to survival and other prognostic factors in a cohort of neuroblastoma patients.

To study angiogenesis in neuroblastoma, using morphometric and computerized image analysis, and correlate the results with survival and other prognostic factors. Sixty-nine patients from the Spanish Cooperative Study for Neuroblastoma were studied. Tumoral angiogenesis was studied using an avidin-biotin immunoperoxidase technique with an anti-CD34 antibody. Vascular parameters (VPs) were analyzed by a computerized system. Statistical analysis was also performed. Sixty-six samples had adequate tumoral tissue, and their tumoral vessels were counted. Endothelial cells were more prominent in pure neuroblastomas than in maturing and more mature tumors. VPs showed no statistical difference between the groups of patients as defined by the levels of the other prognostic factors in neuroblastoma: age, stage, histopathology, TRK-A, P-glycoprotein expression, or MYCN copy number. In patients who relapsed, tumors did not show statistically significant difference in VPs when compared with tumors from patients who did not relapse. There was also no difference in VPs in tumors from living patients when compared with tumors from deceased patients. Overall survival was 75%, and event-free survival was 55% at 50 months. VPs could be adequately determined by a computerized system in neuroblastoma; however, VPs were not predictive of survival for our patients. In our patients, neither disseminated nor local relapses were influenced by the angiogenic characteristics of the tumors.

A Quantitative Analysis of Vascularization and Perfusion of Human Glioma Xenografts at Different Implantation Sites

The effect of tissue site of implantation of four different human gliomas on tumor vascularity and perfusion was examined. Vascular parameters of gliomas implanted subcutaneously in the nude mouse and intracerebrally in the nude rat were analyzed. Tumor vessels were stained with an antibody to collagen type IV and perfusion was investigated with the perfusion marker Hoechst 33342. Characteristic vascular patterns were observed in both intracerebral and subcutaneous xenografts belonging to the same tumor line. Major differences in vascular architecture and in the degree of vascularization were noted in comparisons of the two implantation sites for the same tumor line. Tumor perfusion was highly variable for both locations of tumor growth. Distinct differences between the implantation sites of similar tumor lines in vascular perfusion, intervascular distance, and vascular density were present. Incomplete perfusion of vascular structures, as seen in this study, may result in reduced delivery of oxygen to tumor areas. Therefore, measurements of vascular density and intervascular distance alone, without knowledge of the perfusion status, may not be sufficient to estimate the degree of tumor oxygenation. Furthermore, differences in vascular parameters may have important consequences for treatment modalities such as radiotherapy and chemotherapy. Thus, the findings in our study suggest that care has to be taken in extrapolating therapy results obtained with subcutaneous glioma tumor models to the original growth location of gliomas, the brain, due to major differences in vasculature.

The effect of the anti-angiogenic agent TNP-470 on tumor growth and vascularity in low passaged xenografts of human gliomas in nude mice.

The effect of the anti-angiogenic agent TNP-470 on tumor growth, vascular area, vascular density and tumor perfusion of two different subcutaneously implanted human glioma xenografts (E98 and E106) in nude mice was evaluated. Vascular parameters were investigated with an image analysis system. For both tumor lines a small but significant tumor growth suppression was observed. However, no differences in vascular parameters between TNP-470 treated tumors and controls could be found after 6 weeks of treatment. It is concluded that although TNP-470 is a promising anti-angiogenic agent in many tumor types, at least 2 glioma lines seem to be partly resistant to its anti-angiogenic effects. Further evaluation of the effects of combination of TNP-470 and cytostatic agents or radiotherapy in human glioma xenografts are required to determine the place of anti-angiogenic therapy in general and treatment with the anti-angiogenic agent TNP-470 more specifically in the treatment of human gliomas.

Vascularity and perfusion of human gliomas xenografted in the athymic nude mouse.

The vascularisation and perfusion of seven subcutaneously xenografted human glioma lines established from surgical specimens has been analysed using an anti-collagen type IV antibody to visualise the vascular walls in combination with a perfusion marker (Hoechst 33342). A computer-based digital image processing system was employed for quantitative analysis of the parameters. The vascular architecture of individual tumours belonging to the same tumour line showed a consistent similarity, while substantial differences occurred between the various tumour lines derived from different patients. Despite the presence of a large inter-tumour variation in vascular area as a proportion of the tumour area, this vascular parameter clearly showed tumour line-specific characteristics. The perfused fraction of the tumour vessels also showed a large inter-tumour variation for all tumour lines ranging from 20% to 85%, but the majority of tumours of all lines had perfusion fractions of more than 55%. Despite large variation, the perfused vascular area as a proportion of the tumour cross-sectional area exhibited clear tumour line-specific tendencies. These observations suggest that consistent differences in vascular parameters are present between glioma xenograft lines, although the tumour lines all originated from histologically similar human high-grade gliomas. These differences may have important consequences for treatment and clinical behaviour of this type of tumour.