Early cutaneous inflammatory response at different degree of burn and its significance for clinical diagnosis and management.

A complete characterization of the burn wound based on cutaneous architectural changes and inflammatory response is extremely important to provide evidence for progressive changes in the burn wound. Burn wounds are highly susceptible to conversion into deeper wounds, which need special care and attention; thereby, the complete characterization of burn wound type and their subsequent inflammatory status in the cutaneous system at the earliest is of paramount importance. Inflammatory markers at different degrees will help clinicians devise better and more specific treatment strategies for each burn type. The present study is carried out to profile pro-inflammatory gene expression along with immune cell quantification, vascular perfusion, and histopathological assessment in the cutaneous system of murine models. The study revealed that burn injury caused an immediate increase in vascular perfusion in superficial and partial-thickness burns, whereas there was a decrease in vascular perfusion in full-thickness burns. An influx of lymphocytes at the edges of burn wounds in each type of burn injury was well-orchestrated with the event of vascular perfusion. Further, pro-inflammatory gene expression profiling revealed significant upregulation vis-à-vis upregulation of TNF-α and MCP-1 genes, with an increase in the number of neutrophils following 72 h of injury that evidently cemented the conversion of superficial burn into partial-thickness burn. The molecular findings were profoundly supported by the histopathological changes. Thus, our foundational studies show distinct characteristic cutaneous changes correlated with the expression of key pro-inflammatory genes in three different types of burn injuries. Characterization of these cutaneous inflammatory responses provides a promising future for medical interventions involved with different degrees of burn injury, and it will also help in the pre-clinical testing of therapies for burn injury.

Development and characterization of a chick embryo chorioallantoic membrane (CAM) based platform for evaluation of vasoactive medications.

Among various anti-cancer therapies, tumor vascular disrupting agents (VDAs) play a crucial role, for which their off-targeting effects on normal vessels need also to be investigated. The purpose of this study was to set up an in-ovo platform that combines a laser speckle contrast imaging (LSCI) modality with chick embryo chorioallantoic membrane (CAM) to real-time monitor vascular diameters and perfusion without and with intravascular injection. Two eggshell windows for both observation or measurement and injection were opened. Dynamic blood perfusion images and corresponding statistic graphs were acquired by using a LSCI unit on CAMs from embryo date (ED) 9 to ED15. A dedicated fine needle catheter was made for slow intravascular administration over 30 min with simultaneous LSCI acquisition. To verify the connectivity between CAM vessels and the embryonic circulations in the egg, contrast-enhanced 3D micro computed tomography (µCT), 2D angiography and histology were executed. This platform was successfully established to acquire, quantify and demonstrate vascular and hemodynamic information from the CAM. Chick embryos even with air cell opened remained alive from ED9 to ED15. Through collecting LSCI derived CAM vascular diameter and perfusion parameters, ED12 was determined as the best time window for vasoactive drug studies. A reverse correlation between CAM vessel diameter and blood perfusion rate was found (p < 0.002). Intravascular infusion and simultaneous LSCI acquisition for 30 min in ovo proved feasible. Contrast-enhanced angiography and histomorphology could characterize the connectivity between CAM vasculature and embryonic circulation. This LSCI-CAM platform was proved effective for investigating the in-ovo hemodynamics, which paves the road for further preclinical research on vasoactive medications including VDAs.

Dynamic contrast-enhanced MRI of brown and beige adipose tissues.

PURPOSE: The vascular blood flow in brown adipose tissue (BAT) is important for handling triglyceride clearance, increased blood flow and oxygenation. We used dynamic contrast-enhanced (DCE)-MRI and fat fraction (FF) imaging for investigating vascular perfusion kinetics in brown and beige adipose tissues with cold exposure or treatment with ß3-adrenergic agonist. METHODS: FF imaging and DCE-MRI using gadolinium-diethylenetriaminepentaacetic acid were performed in interscapular BAT (iBAT) and beige tissues using male Wister rats (n = 38). Imaging was performed at thermoneutral condition and with either cold exposure, treatment with pharmacological agent CL-316,243, or saline. DCE-MRI and FF data were co-registered to enhance the understanding of metabolic activity. RESULTS: Uptake of contrast agent in activated iBAT and beige tissues were significantly (P < .05) higher than nonactivated iBAT. The Ktrans and kep increased significantly in iBAT and beige tissues after treatment with either cold exposure or ß3-adrenergic agonist. The FF decreased in activated iBAT and beige tissues. The Ktrans and FF from iBAT and beige tissues were inversely correlated (r = 0.97; r = 0.94). Significant increase in vascular endothelial growth factor expression and Ktrans in activated iBAT and beige tissues were in agreement with the increased vasculature and vascular perfusion kinetics. The iBAT and beige tissues were validated by measuring molecular markers. CONCLUSION: Increased Ktrans and decreased FF in iBAT and beige tissues were in agreement with the vascular perfusion kinetics facilitating the clearance of free fatty acids. The methodology can be extended for the screening of browning agents.

Vascular perfusion: A predictive tool for thermal burn injury.

Damage to the blood vascular system and their altered permeability is a prominent pathological event in case of dermal injury, particularly in burn trauma situations. Prediction of vascular perfusion at the site of damage could be an attractive tool in the estimation of thermal burn injury. A very few reports are available with reference to this tool in defining the thermal injury status. We have used the vascular perfusion estimation method as a tool in assessing the severity of thermal damage to the animal skin. To validate this tool, the mice were subjected to the thermal burn at 90 °C for 10, 20 & 30 s and excised burned skin samples were analyzed for vascular perfusion 24hr post-burn treatment. The vascular perfusion was significantly altered in a time-dependent fashion. This method also provided information regarding blood vessel damage at varied time points. The results of this study clearly indicate the severity of skin damage by the thermal burn. The finding of the present study could have greater implications in predicting the degree of burn. This method is very simple and cost-effective compared to other available modalities used for the estimation of thermal burn injury. The method certainly has the benefit of the estimation of burn injury in the animal models.

Correlation of retinal vascular perfusion density with dark adaptation in diabetic retinopathy.

PURPOSE: To evaluate the anatomic versus functional changes in diabetic retinopathy (DR) by studying the correlation of retinal vascular perfusion density and dark adaptation (DA). METHODS: Optical coherence tomography angiography (OCTA) and DA tests were performed in diabetic patients and nondiabetic controls. DA was measured using AdaptDx dark adaptometer and the rod intercept was recorded. Macular OCTA images were acquired using the RTVue XR Avanti with AngioVue. RESULTS: Eighty-six eyes from 57 patients with diabetes (19 with no DR, 19 with non-proliferative DR [NPDR], and 19 with proliferative DR [PDR] who had undergone photocoagulation) and 10 eyes from 10 patients without diabetes were recruited. A significant decrease in vascular density and a prolonged rod intercept were found as DR progressed (P < .01). A negative trend was found between vascular density and the rod intercept. The negative trend in the deep layer (R2 = 0.28) was more substantial than that in the superficial layer (R2 = 0.14). A prolonged rod intercept was associated with elevated HbA1c (R2 = 0.08). CONCLUSIONS: The vascular density of the macula could be assessed by OCTA and the functional change in the outer retina could be measured non-invasively by DA. The severity of decreasing vascular density and prolongation of DA are proportional to progression of DR. Decreased deep retinal vascular perfusion density and impaired DA response are correlated and show a negative trend according to the severity of DR.

Vascularization is delayed in long nerve constructs compared with nerve grafts.

INTRODUCTION: Nerve regeneration across nerve constructs, such as acellular nerve allografts (ANAs), is inferior to nerve auto/isografts especially in the case of long defect lengths. Vascularization may contribute to poor regeneration. The time course of vascular perfusion within long grafts and constructs was tracked to determine vascularization. METHODS: Male Lewis rat sciatic nerves were transected and repaired with 6 cm isografts or ANAs. At variable days following grafting, animals were perfused with Evans Blue albumin, and grafts were evaluated for vascular perfusion by a blinded observer. RESULTS: Vascularization at mid-graft was re-established within 3-4 days in 6 cm isografts, while it was established after 10 days in 6 cm ANAs. CONCLUSIONS: Vascular perfusion is reestablished over a shorter time course in long isografts when compared with long ANAs. The differences in vascularization of long ANAs compared with auto/isografts suggest regenerative outcomes across ANAs could be affected by vascularization rates. Muscle Nerve 54: 319-321, 2016.

Bioavailability of caffeic acid in rats and its absorption properties in the Caco-2 cell model.

CONTEXT: Caffeic acid (CA) is widely distributed in edible plants, and it is beneficial to human health by exerting various biological effects. The potential pharmacological activities of CA are dependent on its absorption in the gastrointestinal tract. OBJECTIVE: To investigate the bioavailability of CA in rats and its absorption properties in the Caco-2 cell model. MATERIALS AND METHODS: A sensitive LC-MS/MS method was successfully applied to determine CA in rat plasma, perfusate, and Hank's balanced salt solution (HBSS). The absolute bioavailability (Fabs) of CA was obtained after i.v. (2 mg/kg) or i.g. administration (10 mg/kg) to rats. Blood samples (approximately 250 µL) were collected from the jugular vein catheter. Pharmacokinetic parameters were calculated using the 3P97 software (version 2.0 PK software; Chinese Society of Mathematical Pharmacology, Anhui, China). The intestinal absorption of CA was explored by the in situ vascularly perfused rat intestinal preparation. CA (5 mg/kg) was administered into the duodenum. Samples (250 µL) were collected from reservoir at specific times, and the same volume fresh perfusate was replaced. The Caco-2 cell model was applied to measure the permeability of CA from the apical to basolateral side (A → B) and from the basolateral to apical side (B → A). RESULTS: The absolute bioavailability (Fabs) of CA was 14.7%, and its intestinal absorption was 12.4%. The Papp A→B values of CA were ranging from (4.87 ± 1.72) × 10(-7) cm/s to (5.05 ± 0.66) × 10(-7) cm/s as the concentration varied from 5 to 15 µg/mL. CONCLUSION: CA was shown to have low oral bioavailability in rats, low intestinal absorption, and poor permeability across Caco-2 cells.

Choriocapillaris Perfusion after 8 Weeks of High-Speed Circuit Training in Older Healthy Adults.

PURPOSE: The aim of this study was to examine the impact of an 8-week high-speed circuit resistance training program (HSCT) on choriocapillaris density (CCD) in healthy older adults. METHODS: Eighteen cognitively normal older adults were enrolled and randomly assigned to either the HSCT or the control group (CON). The HSCT group was comprised of 11 participants who trained three times a week for eight weeks, while the CON group consisted of 7 participants who did not engage in formal training. Optical coherence tomography angiography (OCTA) was employed to image both eyes of each subject at baseline and at the 8-week follow-up. The choriocapillaris density (CCD) of 2.5 mm in diameter centered on the fovea was measured. RESULTS: The average age of the HSCT group was 70.3 ± 5.7 years, which was not different from the CON group (average age: 71.6 ± 5.2 years, p = 0.62). There were no significant changes in CCD between baseline and the 8-week follow-up in either the HSCT or the CON group-specifically, the baseline CCD in the HSCT group was 63.3% ± 5% (Mean ± SD), which did not differ significantly from the 8-week follow-up after HSCT training (64.7% ± 4%, p = 0.19). Likewise, there was no significant difference in CCD between baseline and the 8-week follow-up in the CON group (63.3% ± 3% and 62.7% ± 5%, respectively, p = 0.66). CONCLUSION: CCD appeared to remain stable after 8 weeks of HSCT in healthy older individuals, possibly due to autoregulation. Further research with extended training may be necessary to verify these findings.

Study of ischemic progression in different intestinal tissue layers during acute intestinal ischemia using swept-source optical coherence tomography angiography.

In acute intestinal ischemia, the progression of ischemia varies across different layers of intestinal tissue. We established a mouse model and used swept-source optical coherence tomography (OCT) to observe the intestinal ischemic process longitudinally in different tissue layers. Employing a method that combines asymmetric gradient filtering with adaptive weighting, we eliminated the vessel trailing phenomenon in OCT angiograms, reducing the confounding effects of superficial vessels on the imaging of deeper vasculature. We quantitatively assessed changes in vascular perfusion density (VPD), vessel length, and vessel average diameter across various intestinal layers. Our results showed a significant reduction in VPD in all layers during ischemia. The mucosa layer experienced the most significant impact, primarily due to disrupted capillary blood flow, followed by the submucosa layer, where vascular constriction or decreased velocity was the primary factor.

Onward to Better Surgery - the Critical Need for Improved Ex Vivo Testing and Training Methods.

Guided surgery has demonstrated significant improvements in patient outcomes in some disease processes. Interest in this field has led to substantial growth in the technologies under investigation. Most likely no single technology will prove to be "best," and combinations of macro- and microscale guidance-using radiological imaging navigation, probes (activatable, perfusion, and molecular-targeted; large- and small-molecule), autofluorescence, tissue intrinsic optical properties, bioimpedance, and other characteristics-will offer patients and surgeons the greatest opportunity for high-success/low-morbidity medical interventions. Problems are arising, however, from the lack of valid testing formats; surgical training simulators suffer the same problems. Small animal models do not accurately recreate human anatomy, especially in terms of tissue volume. Large animal models are expensive and have difficulty replicating many pathological states, particularly when molecular specificity for individual cancers is required. Furthermore, the sheer number of technologies and the potential for synergistic combination leads to exponential growth of testing requirements that is unrealistic for in vivo testing. Therefore, critical need exists to expand the ex vivo/in vitro testing platforms available to investigators and, once validated, a need to increase the acceptance of these methods for funding and regulatory endpoints. Herein is a review of the available ex vivo/in vitro testing formats for guided surgery, a review of their advantages/disadvantages, and consideration for how our field may safely and more swiftly move forward through stronger adoption of these testing and validation methods.

Patient-specific arterial input function for accurate perfusion assessment in intraoperative fluorescence imaging.

Significance: The arterial input function (AIF) plays a crucial role in correcting the time-dependent concentration of the contrast agent within the arterial system, accounting for variations in agent injection parameters (speed, timing, etc.) across patients. Understanding the significance of the AIF can enhance the accuracy of tissue vascular perfusion assessment through indocyanine green-based dynamic contrast-enhanced fluorescence imaging (DCE-FI). Aim: We evaluate the impact of the AIF on perfusion assessment through DCE-FI. Approach: A total of 144 AIFs were acquired from 110 patients using a pulse dye densitometer. Simulation and patient intraoperative imaging were conducted to validate the significance of AIF for perfusion assessment based on kinetic parameters extracted from fluorescence images before and after AIF correction. The kinetic model accuracy was evaluated by assessing the variability of kinetic parameters using individual AIF versus population-based AIF. Results: Individual AIF can reduce the variability in kinetic parameters, and population-based AIF can potentially replace individual AIF for estimating wash-out rate ( k ep ), maximum intensity ( I max ), ingress slope with lower differences compared with those in estimating blood flow, volume transfer constant ( K trans ), and time to peak. Conclusions: Individual AIF can provide the most accurate perfusion assessment compared with assessment without AIF or based on population-based AIF correction.

Measurements of tumor vascular leakiness using DCE in brain tumors: clinical applications.

Various imaging techniques have been employed to evaluate blood-brain-barrier leakiness in brain tumors, as higher tumor vascular leakiness is known to be associated with higher grade and malignant potential of the tumor, and hence can help provide additional diagnostic and prognostic information. These imaging techniques range from routine post-contrast T1 -weighted images that highlight degree of contrast enhancement to absolute measurement of quantitative metrics of vascular leakiness employing complex pharmacokinetic modeling. The purpose of this article is to discuss the clinical applications of available imaging techniques, and in particular dynamic contrast-enhanced T1 -weighted MR imaging (DCE-MRI), to evaluate tumor vascular leakiness.

Perfusion-Based Fluorescent Dye Labeling to Sort Cancer Cells Based on Their Distance from Blood Vessels.

Tumor vasculature is the major extrinsic factor that shapes Intra-tumoral heterogeneity (ITH). Non-uniform exposure of microenvironmental cues greatly impacts cancer cell phenotypes leading to ITH, which exacerbates therapy resistance. This raises a need to study the influence of non-uniform perfusion patterns and the resulting heterogeneity that persists within the tumor microenvironment (TME). A method was developed to identify cancer cells based on their proximity to functional blood vessels (BVs) called perfusion-based fluorescent dye labeling of cells (PFDLC). PFDLC works on the principle of perfusion, where a freely diffusible nuclear binding fluorescent dye (Hoechst 33342) is injected intravenously (i.v.) through a tail vein into atumor-bearing mice. The tumors are retrieved post dye perfusion, dissociated into single cells, and sorted based on their dye uptake proportional to their distance from the nearest blood capillary. This method is amenable to multi-omics as well as functional assays.

Indocyanine green angiography for lower incidence of anastomotic leakage after transanal total mesorectal excision: a propensity score-matched cohort study.

Background: Anastomotic leakage (AL) is the most serious complication that can arise during colorectal surgery. Indocyanine green (ICG) angiography offers an intraoperative assessment of colonic vascular perfusion in real time. We aimed to assess ICG's effects on the AL rate in patients who have undergone transanal total mesorectal excision (TaTME) for rectal cancer. Methods: This retrospective cohort study was conducted at our center from October 2018 to March 2022 to analyze the clinical data of patients with rectal cancer who have undergone TaTME after propensity score matching (PSM). The primary outcome was the proximal colonic transection line modification and clinical AL rate. Results: A total of 143 patients in the non-ICG group and 143 patients in the ICG group were included after PSM. The proximal colonic transection line of seven patients in the non-ICG group was modified, while 18 were in the ICG group (4.9% vs. 12.5%, p = 0.023). Twenty-three patients (16.1%) in the non-ICG group and five patients (3.5%) in the ICG group were diagnosed with AL (p < 0.001). The ICG group had a less hospital readmission rate than the non-ICG group (0.7% vs. 7.7%, p = 0.003). The between-group differences in basic line and other outcomes were not significant. Conclusions: ICG angiography is a safe and feasible method to help surgeons identify potentially poor colonic vascular perfusion and modify the proximal colonic transection line, resulting in a significant reduction in AL and hospital readmission rates.

Relationship between placental pathology and neonatal outcomes.

Objective: To evaluate the relationship between maternal vascular malperfusion and acute intrauterine infection/inflammation with neonatal outcomes. Methods: This was a retrospective study of women with singleton pregnancies who completed placenta pathological examination. The aim was to study the distribution of acute intrauterine infection/inflammation and maternal placental vascular malperfusion among groups with preterm birth and/or rupture of membranes. The relationship between two subtypes of placental pathology and neonatal gestational age, birth weight Z-score, neonatal respiratory distress syndrome, and intraventricular hemorrhage was further explored. Results: 990 pregnant women were divided into four groups, including 651 term, 339 preterm, 113 women with premature rupture of membranes, and 79 with preterm premature rupture of membranes. The incidence of respiratory distress syndrome and intraventricular hemorrhage in four groups were (0.7%, 0.0%, 31.9%, 31.6%, P < 0.001) and (0.9%, 0.9%, 20.0%, 17.7%, P < 0.001), respectively. The incidence of maternal vascular malperfusion and acute intrauterine infection/inflammation were (82.0%, 77.0%, 75.8%, 72.1%, P = 0.06) and (21.9%, 26.5%, 23.1%, 44.3%, P = 0.010), respectively. Acute intrauterine infection/inflammation was associated with shorter gestational age (adjusted difference -4.7 weeks, P < 0.001) and decreased weight (adjusted Z score -2.6, P < 0.001) than those with no lesions in preterm birth. When two subtype placenta lesions co-occurrence, shorter gestational age (adjusted difference -3.0 weeks, P < 0.001) and decreased weight (adjusted Z score -1.8, P < 0.001) were observed in preterm. Consistent findings were observed in preterm births with or without premature rupture of membranes. In addition, acute infection/inflammation and maternal placenta malperfusion alone or in combination were associated with an increased risk of neonatal respiratory distress syndrome (adjusted odds ratio (aOR) 0.8, 1.5, 1.8), but the difference was not statistically significant. Conclusion: Maternal vascular malperfusion and acute intrauterine infection/inflammation alone or co-occurrence are associated with adverse neonatal outcomes, which may provide new ideas for clinical diagnosis and treatment.

Automated motion artifact correction for dynamic contrast-enhanced fluorescence imaging during open orthopedic surgery.

Indocyanine green (ICG)-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) can objectively assess bone perfusion intraoperatively. However, it is susceptible to motion artifacts due to patient's involuntary respiration during the 4.5-minute DCE-FI data acquisition. An automated motion correction approach based on mutual information (MI) frameby-frame was developed to overcome this problem. In this approach, MIs were calculated between the reference and the adjacent frame translated and the maximal MI corresponded to the optimal translation. The images obtained from eighteen amputation cases were utilized to validate the approach and the results show that this correction can significantly reduce the motion artifacts and can improve the accuracy of bone perfusion assessment.

Retinal and Choroidal Vascular Perfusion and Thickness Measurement in Diabetic Retinopathy Patients by the Swept-Source Optical Coherence Tomography Angiography.

Purpose: To observe the changes in retinal and choroidal microstructures in patients with different stages of diabetic retinopathy (DR) and to evaluate the vascular perfusion of retina and choroid retinal thickness, retinal and choroidal vessel density by the swept-source optical coherence tomography angiography (SS-OCTA). Methods: Subjects were divided into three groups: healthy control group (30 cases, 51 eyes), non-proliferative diabetic retinopathy (NPDR, 42 cases, 71 eyes) and proliferative diabetic retinopathy (PDR, 31 cases, 53 eyes). The area of the foveal avascular zone (FAZ), retinal and choroidal vascular perfusion, and the deep vascular complexes, including the intermediate capillary plexus (ICP) and deep capillary plexus (DCP) within the radius of 3, 6, 9, and 12 mm around the fovea were measured by SS-OCTA. Results: Compared with the healthy control group, DR patients presented significantly increased fovea avascular area, while vessel density (VD) in the ICP and DCP, vascular perfusion rate, and the retinal thickness were considerably decreased. There were significant differences in the retinal thickness, ICP, and DCP vessel densities between the control and NPDR groups, or control and PDR groups, or PDR and NPDR groups. The deep vascular perfusion rate also significantly differed between the control and PDR groups, but there was no significant difference between the PDR and NPDR groups. The choroidal perfusion exhibited significant differences across different areas and amongst the three groups. Furthermore, the choroidal thickness showed a significant difference between the PDR and NPDR groups. Conclusion: Our results showed significant differences in the area of the avascular fovea and the VD of deep vascular complexes between DR patients and healthy control subjects. Moreover, there were significant differences in retinal VD, especially in the deep-retinalregions, choroidal perfusion, and the volume of large vessel choroid in DR patients with different degrees of disease severity. Notably, SS-OCTA provided in-depth information for detecting the potential VD damage in DR patients caused by a multitudeof factors.

Long-Term Variations in Retinal Parameters after Uncomplicated Cataract Surgery.

Background: Cataract phacoemulsification surgery provides excellent refractive results; however, it also elicits changes in the posterior segment of the eye. This study aimed to determine changes in retinal parameters measured by spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) after an uncomplicated cataract surgery, including the impact of effective phacoemulsification time (EPT). Methods: The study included 44 patients without retinal abnormalities, followed up after unilateral uncomplicated cataract phacoemulsification in a single ophthalmological unit. Patients were evaluated for the following parameters at baseline and at 2 weeks, 3 months, and 12 months after the surgery: best corrected visual acuity, central retinal thickness (CRT), average central retinal thickness (CRTA), central retinal volume (cube volume (CV)), vessel density central (VDC), vessel density full (VDF), vessel perfusion central (VPC), and vessel perfusion full (VPF). The EPT recorded at each procedure was used as a covariant for the evaluation of changes in retinal parameters after the surgery. Analysis included 44 eyes for SD-OCT and 17 for OCTA evaluation, according to adopted scan quality thresholds. Results: A significant increase in CRT, CRTA, and CV was noted at each follow-up point compared with baseline. The rising tendency was observed in the first 3 months after the surgery, with a decline over the subsequent months. The VPF parameter showed a stable improvement after the surgery. The analysis of covariance did not confirm any significant effect of the EPT on variations in CRT, CV, CRTA, VDC, and VPF and there was a weak effect on the VDF parameter. Conclusions: Uncomplicated cataract surgery results in an increase in retinal thickness and volume in the first few months after the surgery, followed by a spontaneous decline in these parameters in the subsequent months. A long-standing improvement is noted in the VPF parameter.

OCT-Angiography Changes in Patients with Diabetic Macular Edema Treated with Intravitreal Dexamethasone Implant.

PURPOSE: To evaluate, using optical coherence tomography angiography (OCTA), the impact of intravitreal dexamethasone (DEX) implant on quantitative vascular measurements in patients with diabetic macular edema (DME). METHODS: Prospective, randomized, and open-label study. Primary endpoints were mean changes in vessel density (VD) and vascular perfusion (VP) in superficial capillary plexus (SCP) and VP in deep capillary plexus (DCP) and peripapillary capillary plexus (PCP). RESULTS: Thirty-four eyes from 19 patients were included. Mean age was 67.4±7.3 years and 24 (76.5%) were men. VD in SCP in the 6 mm × 6 mm perifoveal ring was significantly decreased from 15.2±2.7 mm/mm2 at baseline to 13.5±3.1 at month-2, p, 0.0029. VP in SCP in the 6 mm × 6 mm perifoveal ring decreased significantly from baseline to month-2 (mean change -3.8%; 95% confidence-interval: -7.7% to -1.7%, p, 0.0028). Compared to baseline, the VP in DCP was significantly reduced at month 2 in the perifoveal ring of the 6 mm × 6 mm scan (p, 0.0063), and in the parafoveal ring of the 6 mm × 6 mm scan (p, 0.0048). Foveal avascular zone (FAZ) area did not change throughout the study. Central macular thickness significantly decreased from baseline in 210.3 µm (149.9-270.8 µm) and 201.8 µm (140.4-263.3 µm), p < 0.0001 each at month-2 and month-3, respectively. CONCLUSIONS: Besides functional and anatomical improvements, DEX implant significantly reduced VD and VP in DME patients.

Modified microvessel density based on perfusion distance: a preferable NSCLC prognostic factor.

Background: Despite the vital role of blood perfusion in tumor progression, the prognostic value of typical blood perfusion markers, such as microvessel density (MVD) or microvessel area (MVA), in patients with non-small cell lung cancer (NSCLC) is still unclear. This study established a modified MVD (mMVD) measurement based on perfusion distance and determined its prognostic value in patients with NSCLC. Methods: A total of 100 patients with NSCLC were enrolled in this retrospective study. The intratumor microvessels of NSCLC patients were visualized using immunohistochemical staining for CD31. The blood perfusion distance was evaluated as the distance from each vessel to its nearest cancer cell (Dmvcc), and the cutoff value for prognosis was determined. Apart from the total MVD (tMVD), microvessels near cancer cells within the cutoff-Dmvcc were counted as mMVD. Predictive values for mortality and recurrence were evaluated and compared. Results: The Dmvcc ranged from 1.6 to 269.8 µm (median, 13.1 µm). The mMVD (range: 2-70; median 23) was counted from tMVD according to the cutoff-Dmvcc (~20 µm). Compared with tMVD, a larger fraction of mMVD (80% vs. 2.9%) played a significant role in overall survival, with an improved area under the receiver operating characteristic (ROC) curve (AUC) (0.74 vs. 0.56). A high mMVD was an independent positive indicator of overall survival (OS) and progression-free survival (PFS). In contrast, tMVD was only related to PFS at the optimal cutoff. Conclusions: Perfusion-distance-based mMVD is a promising prognostic factor for NSCLC patients with superior sensitivity, specificity, and clinical applicability compared to tMVD. This study provides novel insights into the prognostic role of tumor vessel perfusion in patients with NSCLC.