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Aim To investigate the characteristics of coronary artery bifurcation type (parallel or perpendicular type) using three-dimensional (3D) optical coherence tomography (OCT), and determine the feasibility, reproducibility, assessment time and correlation with bifurcation angles measured by 3D quantitative coronary angiography (QCA). Methods and results We evaluated 60 lesions at the coronary bifurcation that were treated by main vessel (MV) stenting with kissing balloon inflation (KBI) under OCT/optical frequency domain imaging (OFDI) guidance. Inter- and intra-observer agreement regarding the assessment of 3D bifurcation types were 0.88 and 0.94, respectively. The assessment times of 3D-OCT bifurcation type with OCT and OFDI were within about 30 seconds. 3D-OCT bifurcation types showed the greatest correlation with the distal bifurcation angle assessed by 3D-QCA among the three bifurcation angles (distal bifurcation angle, proximal bifurcation angle and main vessel angle), and the optimal cut-off distal bifurcation angle to predict a perpendicular type bifurcation, as determined by ROC analysis, was 51.0° (AUC 0.773, sensitivity 0.80, specificity 0.67). Based on this cut-off value for the distal bifurcation angle (51°), the diagnostic accuracy for perpendicular type bifurcation in cases with a BA ≥ 51° (n = 34) was 70.6% (24/34) and that of the parallel type bifurcation in cases of BA < 51° (n = 26) was 76.9% (20/26). Conclusion Performing 3D-OCT for assessment of coronary artery bifurcation type is feasible and simple, and can be done in a short time with high reproducibility.

Purpose To validate retinal capillary density and caliber associations with diabetic retinopathy (DR) severity in different clinical settings. Methods This cross-sectional study assessed retinal capillary density and caliber in the superficial retinal layer of 3-mm OCTA scans centered on the fovea. Images were collected from non-diabetic controls and subjects with mild or referable DR (defined DR worse than mild DR) between February 2016 and December 2019 at secondary and tertiary eye care centers. Vessel Skeleton Density (VSD), a measure of capillary density, and Vessel Diameter Index (VDI), a measure of vascular caliber, were calculated from these images. Discriminatory performance of VSD and VDI was evaluated using multivariable logistic regression models predicting DR severity with adjustments for sex, hypertension, and hyperlipidemia. Area under the curve (AUC) was estimated. Model performance was evaluated in two different cohorts. Results This study included 594 eyes from 385 subjects. Cohort 1 was a training cohort of 509 eyes including 159 control, 155 mild non-proliferative DR (NPDR) and 195 referable DR eyes. Cohort 2 was a validation cohort consisting of 85 eyes including 16 mild NPDR and 69 referable DR eyes. In Cohort 1, addition of VSD and VDI to a model using only demographic data significantly improved the model’s AUC for discrimination of eyes with any DR severity from controls (0.91 [95% CI, 0.88–0.93] versus 0.80 [95% CI, 0.76–0.83], p < 0.001) and eyes with referable DR from mild NPDR (0.90 [95% CI, 0.86–0.93] versus 0.69 [95% CI, 0.64–0.75], p < 0.001). The transportability of this regression model was excellent when implemented in Cohort 2 for the referable DR versus mild NPDR comparison. The odds ratio of having any DR compared to control subjects, and referable DR compared to mild DR decreased by 15% (95% CI: 12–18%), and 13% (95% CI: 10–15%), respectively, for every 0.001 unit increase in VSD after adjusting for comorbidities. Conclusion OCTA-derived capillary density has real world clinical value for rapidly assessing DR severity.

Purpose The present study aimed to evaluate the clinical characteristics of exudative age-related macular degeneration (AMD) in Japanese patients over a 10-year period and to compare the past our report. Methods We retrospectively reviewed 1,600 treatment-naïve patients (1,777 eyes) with exudative AMD. The 10 years were divided into 2-year phases I to V. Results Of the 1,600 patients, 720 (45.0%), 733 (45.8%), 98 (6.1%), and 49 (3.1%) were diagnosed with typical AMD, polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation, and combined subtypes, respectively. The prevalence of PCV decreased from 54.7% in phase I to 46.0% at phase V. Of the 1,777 eyes, the mean baseline logarithm of the minimum angle of resolution best-corrected visual acuities (BCVAs) in phases I, II, III, IV, and V were 0.70, 0.66, 0.55, 0.50, and 0.48, respectively. Phases III, IV, and V had significantly (P = 0.0012, P Conclusions Although the prevalence of PCV decreased from 54.7% in phase I to 46.0% at phase V, PCV has nevertheless been highly prevalent in Japanese patients with AMD compared with Caucasian patients. The annual better baseline VAs and smaller lesion sizes over time might be related to development of treatment and better concerns about AMD.

Background This study aimed to investigate the association between changes in brain natriuretic peptide (BNP) from discharge to 6-month visit and subsequent clinical outcomes in patients with acute heart failure (AHF). Methods Among 1246 patients enrolled in the prospective longitudinal follow-up study nested from the Kyoto Congestive Heart Failure registry, this study population included 446 patients with available paired BNP data at discharge and 6-month index visit. This study population was classified into 3 groups by percent change in BNP from discharge to 6-month visit; the low tertile (≤-44%, N = 149), the middle tertile (>-44% and ≤22%, N = 149) and the high tertile (>22%, N = 148). Findings The cumulative 180-day incidence after the index visit of the primary outcome measure (a composite endpoint of all-cause death or hospitalization for HF) was significantly higher in the high and middle tertiles than in the low tertile (26.8% and 14.4% versus 6.9%, log-rank P Conclusions Percent change in BNP was associated with a subsequent risk for a composite of all-cause death and hospitalization for HF after adjustment of the absolute BNP values, suggesting that observing the change in BNP levels, in addition to absolute BNP levels themselves, helps us to manage patient with HF.

Purpose To examine the usefulness of red channel fundus imaging to detect the ischemic status in eyes with central retinal vein occlusion (CRVO). Methods Ultra-widefield (UWF) fundus images were obtained from 42 eyes with CRVO. Twenty-one eyes were ischemic, and 21 eyes were non-ischemic. Rubeosis was found in 11 ischemic eyes. UWF images were split into red and green channels using ImageJ software. Both the color and red channel images were used to predict the presence or absence of ischemia when examined by masked graders. The sensitivity and specificity of UWF imagings for the detection of ischemia were calculated in Group A (total 42 eyes), Group B (32 eyes excluding non-rubeotic ischemic CRVO) and Group C (31 eyes excluding rubeotic ischemic CRVO), respectively. Moreover, a linear mixed model was conducted to investigate the relationship between the type of images and the accuracy of prediction in each group. Results No significant difference in the sensitivity of color fundus imaging was seen between Group A and Group B. By contrast, a significant difference in the sensitivity of red channel imaging was seen between Group A and Group B (p = 0.031). The accuracies of the predictions were not associated with the type of image in Group A and Group B, but were significantly associated in Group C (p = 0.026). Conclusions UWF red channel imaging enabled more accurate detection of the ischemic status, compared with color fundus images, especially in non-rubeotic CRVO eyes.

Aims Impaired renal function is a major contributor to the low proportion of mineralocorticoid receptor antagonist (MRA) treatment in patients with heart failure with reduced ejection fraction (HFrEF). Our aims were to investigate the impact of MRA treatment on all-cause mortality and worsening renal function (WRF) in patients with HFrEF and moderately impaired renal function. Methods Retrospective data between 2010–2018 on HFrEF patients from a single-centre hospital with estimated glomerular renal function (eGFR) < 60 ml/min/1.73 m2 were analysed. WRF was defined as a decline of by eGFR ≥ 20%. Results 416 patients were included, 131 patients on MRA and 285 without MRA, mean age was 77 years (SD ± 9) and 82 years (SD ± 9), respectively. Median follow-up was 2 years. 128 patients (32%) experienced WRF, 25% in the MRA group and 30% in patients without MRA (p = 0.293). In multivariable analysis, hospitalization for heart failure and systolic blood pressure were associated with WRF (p = 0.015 and p = Conclusion In this cohort of elderly HFrEF patients with moderately impaired renal function, MRA did not increase risk for WRF or all-cause mortality.

Purpose We aim to determine an advantageous approach for the acceleration of high spatial resolution 3D cardiac T2 relaxometry data by comparing the performance of different undersampling patterns and reconstruction methods over a range of acceleration rates. Methods Multi-volume 3D high-resolution cardiac images were acquired fully and undersampled retrospectively using 1) optimal CAIPIRINHA and 2) a variable density random (VDR) sampling. Data were reconstructed using 1) multi-volume sensitivity encoding (SENSE), 2) joint-sparsity SENSE and 3) model-based SENSE. Four metrics were calculated on 3 naïve swine and 8 normal human subjects over a whole left-ventricular region of interest: root-mean-square error (RMSE) of image signal intensity, RMSE of T2, the bias of mean T2, and standard deviation (SD) of T2. Fully sampled data and volume-by-volume SENSE with standard equally spaced undersampling were used as references. The Jaccard index calculated from one swine with acute myocardial infarction (MI) was used to demonstrate preservation of segmentation of edematous tissues with elevated T2. Results In naïve swine and normal human subjects, all methods had similar performance when the net reduction factor (Rnet) net>2.5, while VDR sampling with the joint-sparsity SENSE had the lowest bias of mean T2 (0.0–1.1ms) when Rnet>3. The RMSEs of parametric T2 values (9.2%-24.6%) were larger than for image signal intensities (5.2%-18.4%). In the swine with MI, VDR sampling with either joint-sparsity or model-based SENSE showed consistently higher Jaccard index for all Rnet (0.71–0.50) than volume-by-volume SENSE (0.68–0.30). Conclusions Retrospective exploration of undersampling and reconstruction in 3D whole-heart T2 parametric mapping revealed that maps were more sensitive to undersampling than images, presenting a more stringent limiting factor on Rnet. The combination of VDR sampling patterns with model-based or joint-sparsity SENSE reconstructions were more robust for Rnet>3.

Recently, there has been a renewed interest in low-field MRI. Contrast agents (CA) in MRI have magnetic behavior dependent on magnetic field strength. Therefore, the optimal contrast agent for low-field MRI might be different from what is used at higher fields. Ultra-small superparamagnetic iron-oxides (USPIOs), commonly used as negative CA, might also be used for generating positive contrast in low-field MRI. The purpose of this study was to determine whether an USPIO or a gadolinium based contrast agent is more appropriate at low field strengths. Relaxivity values of ferumoxytol (USPIO) and gadoterate (gadolinium based) were used in this research to simulate normalized signal intensity (SI) curves within a concentration range of 0–15 mM. Simulations were experimentally validated on a 0.25T MRI scanner. Simulations and experiments were performed using spin echo (SE), spoiled gradient echo (SGE), and balanced steady-state free precession (bSSFP) sequences. Maximum achievable SIs were assessed for both CAs in a range of concentrations on all sequences. Simulations at 0.25T showed a peak in SIs at low concentrations ferumoxytol versus a wide top at higher concentrations for gadoterate in SE and SGE. Experiments agreed well with the simulations in SE and SGE, but less in the bSSFP sequence due to overestimated relaxivities in simulations. At low magnetic field strengths, ferumoxytol generates similar signal enhancement at lower concentrations than gadoterate.

Respiratory motion management is crucial for high-resolution MRI of the heart, lung, liver and kidney. In this article, respiration guide using acoustic sound generated by pulsed gradient waveforms was introduced in the pulmonary ultrashort echo time (UTE) sequence and validated by comparing with retrospective respiratory gating techniques. The validated sound-guided respiration was implemented in non-contrast enhanced renal angiography. In the sound-guided respiration, breathe−in and–out instruction sounds were generated with sinusoidal gradient waveforms with two different frequencies (602 and 321 Hz). Performance of the sound-guided respiration was evaluated by measuring sharpness of the lung-liver interface with a 10–90% rise distance, w10-90, and compared with three respiratory motion managements in a free-breathing UTE scan: without respiratory gating (w/o gating), 0-dimensional k-space navigator (k-point navigator), and image-based self-gating (Img-SG). The sound-guided respiration was implemented in stack-of-stars balanced steady-state free precession with inversion recovery preparation for renal angiography. No subjects reported any discomfort or inconvenience with the sound-guided respiration in pulmonary or renal MRI scans. The lung-liver interface of the UTE images for sound-guided respiration (w10-90 = 6.99 ± 2.90 mm), k-point navigator (8.51 ± 2.71 mm), and Img-SG (7.01 ± 2.06 mm) was significantly sharper than that for w/o gating (17.13 ± 2.91 mm; p < 0.0001 for all of sound-guided respiration, k-point navigator and Img-SG). Sharpness of the lung-liver interface was comparable between sound-guided respiration and Img-SG (p = 0.99), but sound-guided respiration achieved better visualization of pulmonary vasculature. Renal angiography with the sound-guided respiration clearly delineated renal, segmental and interlobar arteries. In conclusion, the gradient sound guided respiration can facilitate a consistent diaphragm position in every breath and achieve performance of respiratory motion management comparable to image-based self-gating.

Purpose To investigate the differences in the choroidal biomarkers between two forms of flat irregular pigment epithelial detachment (FIPED): avascular (aFIPED) and vascularized (vFIPED) in eyes with chronic central serous chorioretinopathy (CSC). Materials and methods Enhanced depth imaging optical coherence tomography (EDI-OCT) was done in eyes with FIPED correlated to chronic CSC, fellow eyes, and also in healthy eyes from gender- and age-matched subjects. Eyes with FIPED were classified into two subgroups based on optical coherence tomography angiography (OCTA) findings: vFIPED and aFIPED. Different choroidal biomarkers such as subfoveal choroidal thickness (SFCT), total choroidal area (TCA), and choroidal vascular index (CVI) were compared between the groups. Results Forty-four eyes from 42 patients with chronic CSC and FIPED along with 40 eyes from 20 healthy subjects were included. OCTA identified vascularization in 14 eyes in the FIPED group (31.8%). Mean SFCT was higher in the FIPED group compared to two other groups (p = 0.005). In comparison to patients with aFIPED, patients with vFIPED had lower SFCT (p = 0.003) and higher CVI (p = 0.020) based on multivariate analysis. Conclusions It seems that measurement of CVI along with SFCT may help to differentiate aFIPED from vFIPED in patients with CSC. Further longitudinal studies would be required to confirm the clinical significance of these findings.

Background Myocardial perfusion imaging (MPI) is a well-established diagnostic tool to evaluate coronary artery disease (CAD) and also an effective prognostic tool for patients with CAD. However, few studies investigated the prognostic value of attenuation correction (AC) in MPI, and the results were controversial. Objectives To investigate the prognostic value of computed tomography (CT)-based AC thallium-201 (Tl-201) MPI. Methods A total of 108 consecutive patients who underwent Tl-201 MPI and received coronary angiography within 90 days were included. Medical records were reviewed and missing information was completed after telephone contact. The prognostic value was evaluated by Kaplan-Meier analysis, univariable and multivariable Cox proportional hazards model. Results After a mean follow-up of 7.72 ± 3.72 years, 27 patients had died, 41 had been readmitted for cardiovascular (CV)-related events and 44 had reached the composite of death plus CV-related re-admission. Kaplan-Meier curves for all-cause mortality for SSS with a cutoff value of 13 for AC and 16 for non-AC (NAC) images showed a significant difference between the two curves for both AC and NAC images (p = 0.011 for AC and p = 0.021 for NAC). In the multivariable model, SSS and SRS showed similar independent predictive values in predicting all-cause mortality and composite of all-cause mortality plus CV-related re-admission, in both AC and NAC images. Subgroup analysis implicated that AC MPI possibly provided better risk stratification in obese patients. Conclusion CT-based AC and NAC MPI showed similar value and were the only significant predictors for the composite of mortality and CV events.

Background Myocardial infarction is the most frequent cause for out-of-hospital cardiac arrest (OHCA) in adults. Patients with ST-segment elevations (STE) following return of spontaneous circulation (ROSC) are regularly admitted to the catheterisation laboratory for urgent coronary angiography. Whether patients without obvious STE (NSTE) should receive coronary angiography as part of a standardised diagnostic work-up following OHCA is still debated. Methods We analysed a cohort of 517 subsequent OHCA patients admitted at our institution who received a standardised diagnostic work-up including coronary angiography and therapeutic hypothermia. Patients were 63±14 years old, 76% were male. Overall, 180 (35%) had ST-elevation in the post-ROSC ECG, 317 (61%) had shockable rhythm (ventricular fibrillation or tachycardia) at first ECG. ROSC was achieved after 26±21 minutes. Results Critical coronary stenosis requiring PCI was present in 83% of shockable and 87% of non-shockable STE-OHCA and in 48% of shockable and 22% of non-shockable NSTE-OHCA patients. In-hospital survival was 61% in shockable and 55% in non-shockable STE-OHCA and 60% in shockable and 28% in non-shockable NSTE-OHCA. Conclusion Standardised admission diagnostics in OHCA patients undergoing therapeutic hypothermia with a strict admission protocol incorporating ECG and coronary catheterisation shows a high rate of relevant coronary stenosis in STE-OHCA irrespective of the initial rhythm and in NSTE-OHCA with initial shockable rhythm. Based on the unfavourable outcome and low PCI rate observed in NSTE-OHCA patients with a primary non-shockable ECG rhythm it might be reasonable to restrict routine early coronary angiography to patients with primary shockable rhythms and/or ST-segment elevations after ROSC.

Objective To investigate the effects of axial length (AL) on the peripapillary microvascular density acquired from optical coherence tomography angiography (OCTA). Methods Retrospective observational study. A total of 111 eyes from 111 normal healthy subjects were examined. The subjects were divided into three groups according to the AL: Group 1 (AL: < 24.0 mm; 35 eyes), Group 2 (AL: 24.0–25.99 mm; 37 eyes), and Group 3 (AL: ≥ 26 mm; 39 eyes). Peripapillary OCTA images were acquired using 6× 6 mm angiography scans, and vessel density (VD) and perfusion density (PD) of the superficial capillary plexus were calculated automatically. VD and PD were compared among the three groups according to the distance from the optic disc (inner and outer rings). Linear regression analyses were also performed to identify clinical factors associated with average VD. Results The average ALs of Groups 1–3 were 23.33± 0.57, 25.05± 0.60, and 27.42± 0.82, respectively. Average VD (P = 0.009) and PD (P = 0.029) in the inner ring increased with increasing AL. However, average VD (P < 0.001) and PD (P < 0.001) in the outer ring decreased with AL increased; the same trends were found for the full areas (VD, p Conclusions Peripapillary VD and PD were significantly associated with AL. Depending on the distance from the disc, peripapillary VDs and PDs of the inner and outer rings were differentially affected by AL. Physicians should therefore consider the effects of AL in the analyses of peripapillary microvasculature.

Surgery in humans is continuously evolving and promoted minimally invasive treatment. On the other hand, despite the importance of the 3Rs principles for experimental animals is well documented, no reports describe specific methodologies for implementing "refinement" in practice. Here, we describe a new technique, the "Ohta Method" for caudal arthrocentesis in the pursuit of the 3Rs for animal experiments and the development of innovative methods for investigating systemic organ arteries through minimally invasive procedures. This procedure requires only a percutaneous puncture of the caudal artery without any injury to the limb or body trunk. In addition, it does not cut down the artery, making hemostasis easier and recovering arterial damage easier. We will show multiple organ artery angiographies in marmoset for the first time in the world. The principle described in this paper could also be applied to many other small animals, such as rats. Moreover, using this method, multiple doses of the drug or cells can be administered to the target organ at the time of therapeutic intervention, thereby enabling the establishment of more sophisticated and complex therapeutic intervention studies as translational research.

Percutaneous transluminal angioplasty (PTA) is considered an effective treatment in patients with critical limb ischemia (CLI). However, the long-term durability of below-the-knee (BTK) PTA is known to be limited. This study sought to compare the 1-year clinical outcomes following stenting versus balloon angioplasty alone in BTK lesions. This study included 357 consecutive patients (400 limbs, 697 lesions) with BTK lesions who underwent PTA from September 2010 to December 2016. All enrolled patients were treated either by stenting (stent group; 111 limbs of 102 patients) or plain old balloon angioplasty (POBA group; 289 limbs of 255 patients). Stent group includes both primary and provisional stenting. Angiographic outcomes, procedural success, complications, and clinical outcomes were compared between the two groups up to 1 year. After propensity score matching (PSM) analysis, 56 pairs were generated, and the baseline and angiographic characteristics were balanced. The procedural success and complications were similar between the two groups; however, the incidence of procedure-related perforation was higher in the POBA group than in the stenting group [5(11.9%) vs.1 (0.9%), P = 0.009]. Six- to 9-month computed tomography or angiographic follow-up showed similar incidences of binary restenosis, primary patency, and secondary patency. In the 1-year clinical follow-up, there were similar incidences of individual hard endpoints, including mortality, myocardial infarction, limb salvage, and amputation rate, with the exception of target extremity revascularization (TER), which tended to be higher in the stenting group than in the POBA group [21 (20.8%) vs. 11 (10.9%), P = 0.054]. Although there was a trend toward a higher incidence of TER risk in the stenting group, stent implantation, particularly in bail-out stenting seemed to have acceptable 1-year safety and efficacy compared to POBA alone in patients undergoing BTK PTA.

Background Local envenomation following snakebites is accompanied by thermal changes, which could be visualized using infrared imaging. We explored whether infrared thermal imaging could be used to differentiate venomous snakebites from non-venomous and dry bites. Methods We prospectively enrolled adult patients with a history of snakebite in the past 24 hours presenting to the emergency of a teaching hospital in southern India. A standardized clinical evaluation for symptoms and signs of envenomation including 20-minute whole-blood clotting test and prothrombin time was performed to assess envenomation status. Infrared thermal imaging was done at enrolment, 6 hours, and 24 hours later using a smartphone-based device under ambient conditions. Processed infrared thermal images were independently interpreted twice by a reference rater and once by three novice raters. Findings We studied 89 patients; 60 (67%) of them were male. Median (IQR) time from bite to enrolment was 11 (6.5–15) hours; 21 (24%) patients were enrolled within 6 hours of snakebite. In all, 48 patients had local envenomation with/without systemic envenomation, and 35 patients were classified as non-venomous/dry bites. Envenomation status was unclear in six patients. At enrolment, area of increased temperature around the bite site (Hot spot) was evident on infrared thermal imaging in 45 of the 48 patients with envenomation, while hot spot was evident in only 6 of the 35 patients without envenomation. Presence of hot spot on baseline infrared thermal images had a sensitivity of 93.7% (95% CI 82.8% to 98.7%) and a specificity of 82.9% (66.3% to 93.4%) to differentiate envenomed patients from those without envenomation. Interrater agreement for identifying hot spots was more than substantial (Kappa statistic >0.85), and intrarater agreement was almost perfect (Kappa = 0.93). Paradoxical thermal changes were observed in 14 patients. Conclusions Point-of-care infrared thermal imaging could be useful in the early identification of non-venomous and dry snakebites., Author summary Most venomous snakebites cause swelling of the bitten body part within a few hours if venom had been injected. Usually, health care providers diagnose venomous snakebites by doing a clinical examination and by testing for incoagulable blood. If no abnormalities are found, then the snakebite is diagnosed as a non-venomous bite or a dry bite. Swelling of the bitten body part results from venom-induced inflammation and is accompanied by local increase in skin temperature. It is possible to capture visual images of these temperature changes by using infrared imaging, the same technology used in night vision cameras. This study found that most persons with venomous snakebites had hot areas on infrared images while such changes were observed in only a few persons with non-venomous or dry snakebites. This new knowledge could help doctors identify non-venomous and dry snakebites early.

Optical coherence tomography angiography (OCT-A) represents the most recent modality in retinal imaging for non-invasive and depth-selective visualization of blood flow in retinal vessels. With regard to quantitative OCTA measurements for early detection of subclinical alterations, it is of great interest, which intra- and extra-ocular factors affect the results of OCTA measurements. Here, we performed OCTA imaging of the central retina in 65 eyes of 65 young healthy female and male participants and evaluated individual physical fitness levels by standard lactate diagnostic using an incremental maximal performance running test. The main finding was that OCTA measurements of the foveal avascular zone (FAZ) area were associated with physical fitness. Using multivariate regression analysis, we found that running speed at the individual lactate threshold, a marker strongly associated with aerobic performance capacity, significantly contributed to differences in FAZ area (β = 0.111, p = 0.032). The data indicates that smaller FAZ areas are likely observed in individuals with higher aerobic exercise capacity. Our findings are also of interest with respect to the potential use of retinal OCTA imaging to detect exercise-induced microvascular adaptations in future studies.

Purpose To analyze ocular biometric parameters alterations of the posterior pole and choroidal abnormalities in patients with neurofibromatosis type 1 (NF1) by adopting multimodal imaging, especially focusing on the role of novel diagnostic devices like swept-source optical coherence tomography angiography (SS-OCTA). Methods In this prospective, case-controlled study, patients with NF1 and age-matched control subjects were quantitatively analyzed by using multimodal imaging. All the subjects underwent confocal scanning laser ophthalmoscopy (SLO), SS-OCT and SS-OCTA examinations. Results SS-OCT analysis revealed a lower macular retinal nerve fiber layer (RNFL) thickness in patients with NF1 compared with those with suspected NF1 (95.0±15.9 vs 109.7±11.3 μm; P = 0.001) and control subjects (106.8±14.4 μm, P = 0.003). Retinal thickness was significantly lower in NF1 patients compared to those with suspected NF1 (280.7±23.0 vs 304.2±15.3 μm; P < 0.001) and control subjects (298.7±23.8 μm, P = 0.003). The mean vascular flow area of the SCP was significantly higher in patients with NF1 (42.6±2.2%) and suspected NF1 (43.1±2.5%) compared to control subjects (41.0±2.0%; respectively, P = 0.017 and P = 0.002). In the second choroidal layer, the flow area was significantly lower in patients with NF1 compared to control subjects (45.4±4.8 vs 49.0±4.0%,; P = 0.011). Conclusions Retinal thicknesses alterations and choroidal nodules are described as ocular manifestations in patients with NF1. In addition, OCTA could represent an important novel advanced imaging technique, capable of detecting early altered retinal and choroidal vascular flow area in patients with NF1.

Objectives To assess the feasibility of quantitative analysis of dynamic computed tomography angiography (dCTA) for the detection of endoleaks in patients who underwent endovascular repair of abdominal aortic aneurysms (EVAR). Material and methods Twenty patients scheduled for contrast-enhanced CT angiography (CTA) of the abdominal aorta post-EVAR were prospectively enrolled. All patients received a standard triphasic CTA protocol, followed by an additional dCTA. The dCTA acquisition enabled reconstruction of color-coded maps depicting blood perfusion and a dCTA dataset of the aneurysm sac. Observers assessed the dCTA and dynamic CT perfusion (dCTP) images for the detection of endoleaks, establishing diagnostic confidence based on a modified 5-point Likert scale. An index was calculated for the ratio between the endoleak and aneurysm sac using blood flow for dCTP and Hounsfield units (HU) for dCTA. The Wilcoxon test compared the endoleak index and the diagnostic confidence of the observers. Results In total, 19 patients (18 males, median age 74 years [70.5–75.7]) were included for analysis. Nine endoleaks were detected in 7 patients using triphasic CTA as the reference standard. There was complete agreement for endoleak detection between the two techniques on a per-patient basis. Both dCTA and dCTP identified an additional endoleak in one patient. The diagnostic confidence using dCTP for detection of endoleaks was not significantly superior to dCTA (5.0 [5–5] vs. 4.5 [4–5], respectively; p = 0.11); however, dCTP demonstrated superior diagnostic confidence for endoleak exclusion compared to dCTA (1.0 [1–1] vs 1.5 [1.5–1.5], respectively; p Conclusions Quantitative analysis of dCTP imaging can aid in the detection of endoleaks and demonstrates a higher endoleak detection rate than triphasic CTA, as well as a strong correlation with visual assessment of dCTA images.

Since long-chain fatty acids work as the primary energy source for the myocardium, radiolabeled long-chain fatty acids play an important role as imaging agents to diagnose metabolic heart dysfunction and heart diseases. With the aim of developing radiogallium-labeled fatty acids, herein four fatty acid-based tracers, [67Ga]Ga-HBED-CC-PDA, [67Ga]Ga-HBED-CC-MHDA, [67Ga]Ga-DOTA-PDA, and [67Ga]Ga-DOTA-MHDA, which are [67Ga]Ga-HBED-CC and [67Ga]Ga-DOTA conjugated with pentadecanoic acid (PDA) and 3-methylhexadecanoic acid (MHDA), were synthesized, and their potential for myocardial metabolic imaging was evaluated. Those tracers were found to be chemically stable in 0.1 M phosphate buffered saline. Initial [67Ga]Ga-HBED-CC-PDA, [67Ga]Ga-HBED-CC-MHDA, [67Ga]Ga-DOTA-PDA, and [67Ga]Ga-DOTA-MHDA uptakes in the heart at 0.5 min postinjection were 5.01 ± 0.30%ID/g, 5.74 ± 1.02%ID/g, 5.67 ± 0.22%ID/g, and 5.29 ± 0.10%ID/g, respectively. These values were significantly lower than that of [123I]BMIPP (21.36 ± 2.73%ID/g). For their clinical application as myocardial metabolic imaging agents, further structural modifications are required to increase their uptake in the heart.

Background Exercise stress electrocardiography (ExECG) is recommended as a first-line tool to assess ischemia, but standard ST-analysis has limited diagnostic accuracy. ST elevation in lead aVR has been associated with left main and LAD disease in the population undergoing coronary angiography but has not been studied in the general population undergoing stress testing for the initial evaluation of CAD without coronary angiography. We sought to determine the predictive value of lead aVR elevation for ischemia, early revascularization, and subsequent cardiac events in consecutive patients undergoing ExECG. Methods and results The study cohort included 641 subjects referred for ExECG who were dichotomized by presence or absence of aVR elevation ≥1mm and compared for prevalence and predictors of ischemia and a composite of cardiac death, nonfatal myocardial infarction, and late revascularization. The cohort had a median age of 57 and 57% were male. The prevalence of aVR elevation was 11.5%. The prevalence of significant ischemia on patients who received imaging was significantly higher with aVR elevation (14.3% vs 2.3%, p Conclusions aVR elevation during ExECG predicts ischemia on imaging and early revascularization but not long-term outcomes and could serve as a useful adjunct to standard ST-analysis and potentially reduce the need for concurrent imaging.

Purpose To analyze the short-term therapeutic efficacy of intravitreal injection of bevacizumab (IVB) for chronic central serous chorioretinopathy (CSC) according to the presence of choroidal neovascularization (CNV) using optical coherence tomography angiography (OCTA). Methods A retrospective chart review was perfomed on cases of CSC with CNV (Group 1: n = 31) and an age-matched cases of CSC without CNV (Group 2: n = 30). The response to IVB was evaluated by changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), choroidal thickness (CT), and pachyvessel diameter. Univariate and multivariate linear regression analyses were performed to identify factors associated with the visual outcome of chronic CSC with CNV after IVB. Results At baseline, the CT values differed significantly between Groups 1 and 2 (371.55 ± 67.09 vs. 417.33 ± 71.32 μm, p = 0.01). In Group 1, BCVA improved significantly (p < 0.001), and CMT (p < 0.001), CT (p = 0.001) and pachyvessel diameter (p = 0.045) decreased significantly, after IVB. In Group 2, only pachyvessel diameter (p = 0.001) was significantly smaller after IVB. Univariate analysis showed that the initial CT (B = 0.002, p = 0.026) and pachyvessel diameter (B = 0.002, p = 0.001) significantly affected visual outcome. In multivariate analysis, the initial pachyvessel diameter exhibited significant results (B = 0.002, p = 0.001). Conclusions IVB showed less effective short-term outcomes in chronic CSC patients without CNV than in patients with CNV. In chronic CSC with CNV, the short-term visual outcome after IVB was better in patients with a thinner choroid and smaller pachyvessels.

Drusen are known to be the important hallmark to predict the development of age-related macular degeneration (AMD). The prevalence of drusen is lower in Asians compared with Caucasians so that the role of signs constituting early AMD is not well established in Asian populations as in Western countries. In this study, we retrospectively investigated clinical characteristics and 5-year incidence of neovascular AMD (nAMD) in the fellow eye of unilateral nAMD patients. Of 296 consecutive unilateral nAMD patients who had been followed up more than 5 years, 170 typical AMD, 119 polypoidal choroidal vasculopathy, and 7 retinal angiomatous proliferation were included. To examine factors associated with nAMD occurrence in the fellow eye, drusen and pigmentary abnormality in the fellow eye were classified into 4 categories; Category 1: no or small drusen < 63 μm (37.2%), Category 2: 63–125 μm medium drusen or pigmentary abnormality (22.2%), Category 3: large drusen > 125 μm (25.0%), Category P: pachydrusen (15.5%). The mean sub-foveal choroidal thickness (SFCT) was Category 1: 276 μm, Category 2: 308 μm, Category 3: 246 μm, and Category P: 302 μm, respectively. Of note, SFCT in Category 2 and Category P was significantly larger than those of Category 3. Finally, the 5-year incidence of nAMD in the fellow eye was 32/296 (10.8%); Category 1: 0/110 (0%), Category 2: 12/66 (18.2%), Category 3: 20/74 (27.0%), and Category P: 0/46 (0%). Thus, signs of intermediate AMD (large drusen) as well as those of early AMD, especially the pigmentary abnormality, may contribute to development of bilateral nAMD in Japanese patients.

Optical coherence tomography angiography (OCTA) performs non-invasive visualization and characterization of microvasculature in research and clinical applications mainly in ophthalmology and dermatology. A wide variety of instruments, imaging protocols, processing methods and metrics have been used to describe the microvasculature, such that comparing different study outcomes is currently not feasible. With the goal of contributing to standardization of OCTA data analysis, we report a user-friendly, open-source toolbox, OCTAVA (OCTA Vascular Analyzer), to automate the pre-processing, segmentation, and quantitative analysis of en face OCTA maximum intensity projection images in a standardized workflow. We present each analysis step, including optimization of filtering and choice of segmentation algorithm, and definition of metrics. We perform quantitative analysis of OCTA images from different commercial and non-commercial instruments and samples and show OCTAVA can accurately and reproducibly determine metrics for characterization of microvasculature. Wide adoption could enable studies and aggregation of data on a scale sufficient to develop reliable microvascular biomarkers for early detection, and to guide treatment, of microvascular disease., Comment: 37 pages, 9 figures

PurposeTo evaluate the retinal vessel density (VD) in the macular region and the foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) in patients with and without disorganization of retinal inner layers (DRILs) after resolution of diabetic macular edema.MethodsThirty-seven eyes of 37 DRIL patients (mean age 63 ± 13.97 years), 30 eyes of 30 no DRIL patients and 35 eyes of 35 controls were enrolled in this study. We evaluated the VD in the macular region of superficial capillary plexus (SCP), deep capillary plexus (DCP) and FAZ area.ResultsDRIL and no DRIL groups showed decreased VD in SCP and DCP (pConclusionOCTA highlights the role of retinal vascular ischemia in the pathogenesis of DRILs. This parameter could represent an important functional predictive factor in diabetic patients.

Background There are few reports of renal artery embolization (RAE) via transradial access (TRA) for renal hemorrhage, and none have compared outcomes of RAE via TRA and transfemoral access (TFA). The objective was to compare technical and clinical outcomes in patients undergoing RAE via TRA or TFA for iatrogenic renal hemorrhage. Materials and methods This study included 45 RAE procedures (16 TRA and 29 TFA) for iatrogenic renal hemorrhage in 43 patients performed at a tertiary referral center between October 2018 and December 2020. Information regarding underlying diseases, coagulation status, angiographic and embolization procedure details, technical and clinical successes, and complications were retrospectively evaluated. Results There were no differences in demographics, underlying diseases, updated Charlson comorbidity scores, angiographic findings, and volume of contrast material between the TRA and TFA groups. By contrast, prothrombin time and international normalized ratio were significantly lower in the TRA than in the TFA group. Embolic materials differed significantly in the two groups. Procedure duration, fluoroscopy time, digital subtraction angiography number, and dose area product were slightly lower in the TRA than in the TFA group, but the differences were not statistically significant. Technical and clinical success rates in the TRA and TFA groups were 100% and 96.6%, and 100% and 96.6%, respectively. No patient in either group experienced procedure-related complications during a 4 week follow-up period. Conclusion RAE via TRA in the management of iatrogenic renal hemorrhage was safe and feasible, with similar procedure duration and radiation exposure to RAE via TFA. TRA may be an acceptable alternative to TFA in these patients.

Purpose To analyze the structure of the choriocapillaris in healthy eyes by using averaged en face images acquired using swept source optical coherence tomography angiography and to examine the changes in the macular profile in relation to age, sex, axial length, and choroidal thickness. Methods This prospective, cross-sectional study included 81 eyes of 81 subjects without ophthalmologic or systemic diseases who underwent a full ophthalmologic examination, including 3 × 3-mm macular optical coherence tomography angiography. Four to nine choriocapillaris en face images were registered and averaged. The averaged images were then binarized and analyzed. Results The averaged choriocapillaris images showed a continuous capillary meshwork, whereas the unaveraged images had a granular appearance. The mean total area and size of flow voids were 0.99 ± 0.20 mm2 and 567.8 ± 201.5 μm2, respectively, and these values correlated positively with age (p = 0.002, R = 0.336 and p = 0.026, R = 0.247, respectively). Age-related gains in the mean total area and flow void size were 4.20 × 10−3 mm2 and 3.07 μm2 per year, respectively. However, the mean total area and flow void size had no significant correlation with axial length, subfoveal choroidal thickness, or sex. Conclusions Multiple averaged en face swept source optical coherence tomography angiography is more effective than a single optical coherence tomography angiography scan for better visualizing the choriocapillaris. The total area and size of flow voids within a 3 × 3-mm macular area positively correlated with age. This technique can be useful for investigating the changes arising in macular diseases.

Purpose To investigate the relationship between disruption in different photoreceptor layers and deep capillary plexus (DCP) telangiectasias in eyes with macular telangiectasia type 2 (MacTel). Methods 35 eyes (21 patients) with MacTel imaged with optical coherence tomography angiography (OCTA) were included. Circumscribed areas of DCP telangiectasia were traced from OCTA slabs and the corresponding spectral-domain OCT (SD-OCT) slabs were used to visualize the photoreceptor layer interdigitation zone (IZ) and ellipsoid zone (EZ). IZ attenuation, IZ loss, and EZ loss were graded by reviewing en face SD-OCT slabs for hypo-reflective areas and confirming their status on cross-sectional views. Total area of photoreceptor disruption and overlap with DCP telangiectasia were evaluated with respect to OCT-based MacTel stage. Longitudinal changes were evaluated in a subset of patients with follow-up imaging. Results Overlap of DCP telangiectasia with IZ attenuation significantly decreased with MacTel severity, while overlap with IZ and EZ loss significantly increased. Overlap with IZ loss peaked in moderate MacTel (Stages 3–5). Longitudinal imaging showed that new EZ loss at 6 months was largely predicted by baseline IZ loss. Conclusions Worsening MacTel severity is characterized by greater overlap between DCP telangiectasia and zones of increasing severity of photoreceptor disruption, with EZ loss enlarging over time within areas of preexisting IZ disruption. We suggest that IZ disruption may indicate early photoreceptor dysfunction that eventually progresses to EZ loss, with IZ loss being a more reliable metric than IZ attenuation. Additional studies will be necessary to further explore long-term photoreceptor changes and evaluate their relationship with visual function in MacTel.

BackgroundStent edge dissection (SED) is a well-known predictor of worse clinical outcomes. However, impact of SED after current-generation drug-eluting stent (DES) implantation remains unknown since there was no study using only current-generation DES to assess impact of SED. This study aimed to investigate a relationship between SED detected by optical coherence tomography (OCT) and clinical outcomes after current-generation DES implantation.MethodsThis study enrolled 175 patients receiving OCT after current-generation DES implantation. The SED group was compared with the non-SED group in terms of the primary study endpoints which was the cumulative incidence of major adverse cardiac event (MACE) composed of cardiac death, target vessel myocardial infarction (TV-MI), and clinically-driven target lesion revascularization (CD-TLR).ResultsOf 175 patients, SED detected by OCT was observed in 32 patients, while 143 patients did not show SED. In the crude population, the SED group showed a significantly higher incidence of CD-TLR, definite stent thrombosis, TV-MI and cardiac death relative to the non-SED group. After adjustment by an inverse probability weighted methods, the SED group showed a significantly higher incidence of MACE compared with the non-SED group (hazard ratio 3.43, 95% confidence interval 1.09–10.81, p = 0.035). Fibrocalcific or lipidic plaques, greater lumen eccentricity, and stent-oversizing were the predictors of SED.ConclusionsSED detected by OCT after the current-generation DES implantation led to unfavorable outcomes. Aggressive post-dilatation around the stent edge might worse clinical outcomes due to SED, although achievement of optimal stent expansion is strongly encouraged to improve clinical outcomes.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are inflammatory and demyelinating diseases that commonly manifest with optic neuritis (ON) but differ in the pathogenic mechanism. Although it was shown that retinal vessels might alter in MS and NMOSD, a comparative study has not been reported. This study evaluated the macular vessel density in 40 MS patients, 13 NMOSD patients, and 20 controls by using optical coherence tomography angiography. The vessel density of superficial capillary plexus (SCP) was significantly lower in ON eyes (MS + ON, NMOSD + ON) than in non-ON eyes (MS-ON, NMOSD-ON) and controls. The density of deep capillary plexus (DCP) was significantly increased in MS + ON, and MS-ON eyes compared to healthy eyes and decreased in NMOSD + ON compared to MS + ON. A significant positive correlation was noted between SCP and ganglion cell complex (GCC) thickness in MS + ON, MS-ON, and NMOSD + ON. The DCP did not significantly correlate with GCC thickness, but it increased or decreased with ganglion cell loss in MS and NMOSD, respectively. In conclusion, our findings suggest that the capillary changes in MS patients are secondary to the reduced metabolic demand of the atrophied ganglion cell layer, while the vasculopathy seems to be a primary process in NMOSD patients.

Purpose To evaluate the incidence and risk factors of neovascularization in unaffected fellow eyes of patients diagnosed with type 3 neovascularization in Korea. Methods This retrospective study included 93 unaffected fellow eyes of 93 patients diagnosed with type 3 neovascularization. For initial type 3 neovascularization diagnosis, optical coherence tomography and angiography were conducted. These baseline data were compared between patients with and without neovascularization in their fellow eyes during the follow-up period. Results The mean follow-up period was 66.1±31.1 months. Neovascularization developed in 49 (52.8%) fellow eyes after a mean period of 29.5±19.6 months. In the fellow eye neovascularization group, the incidence of soft drusen and reticular pseudodrusen was significantly higher than that in the non-neovascularization group (83.7% vs. 36.5%, p Conclusion Neovascularization developed in 52.8% of unaffected fellow eyes. The presence of soft drusen, reticular pseudodrusen, and lower CVI values can be considered risk factors of neovascularization in unaffected fellow eyes of patients with type 3 neovascularization. The lower CVI values suggest that choroidal ischemic change may affect the development of choroidal neovascularization in these patients.

Objective Quantitative assessment of pulmonary blood flow distribution is important when determining the clinical indications for treating pulmonary arterial branch stenosis. Lung perfusion scintigraphy is currently the gold standard for quantitative blood flow measurement. However, it is expensive, cannot provide a real-time assessment, requires additional sedation, and exposes the patient to ionizing radiation. The aim of this study was to investigate the feasibility of a novel technology for measuring pulmonary blood flow distribution in each lung by conventional X-ray pulmonary angiography and to compare its performance to that of lung perfusion scintigraphy. Methods Contrast-enhanced X-ray pulmonary angiography images were acquired at a frame rate of 30 frames per second. The baseline mask image, obtained before contrast agent injection, was subtracted from subsequent, consecutive images. The time-signal intensity curves of two regions of interest, established at each lung field, were obtained on a frame-to-frame basis. The net increase in signal intensity within each region at the torrent period during the second cardiac cycle before contrast agent enhancement over the total lung field was measured, and the right-to-left ratio of the signal intensity was calculated. The right-to-left ratio obtained with this approach was compared to that obtained with scintigraphy. Agreement of the right-to-left ratio between X-ray angiography and lung scintigraphy measurements was assessed using linear fitting with the Pearson correlation coefficient. Result The calculation of the right-to-left ratio of pulmonary blood flow by our kinetic model was feasible for seven children as a pilot study. The right-to-left ratio of pulmonary blood flow distribution calculated from pulmonary angiography was in good agreement with that of lung perfusion scintigraphy, with a Pearson correlation coefficient of 0.91 and a slope of linear fit of 1.2 (p Conclusion The novel diagnostic technology using X-ray pulmonary angiography from our kinetic model can feasibly quantify the right-to-left ratio of pulmonary blood flow distribution. This technology may serve as a substitute for lung perfusion scintigraphy, which is quite beneficial for small children susceptible to radiation exposure.

PLOS ONE 16(8), e0256473 (2021). doi:10.1371/journal.pone.0256473, Published by PLOS, San Francisco, California, US

Purpose To investigate any associations between cigarette smoking and retinal microvascular changes in diabetic patients without visible retinopathy. Design Retrospective, cross-sectional study. Participants 1099 eyes from 1099 diabetic patients with no clinical evidence of diabetic retinopathy (DR) were included in this study. Methods Diabetic patients underwent optical coherence tomography angiography (OCTA) scanning at Zuckerberg San Francisco General Hospital and Trauma Center between April 2018 and September 2019. Patient demographic and clinical information was collected. Standard bivariate statistics and multivariate linear regression were performed. Main outcome measures OCTA parameters included metrics related to the foveal avascular zone (FAZ; area, perimeter, circularity), perfusion density (PD; full, center, inner), and vessel length density (VLD; full, center, inner). Results The study population included 750 non-smokers and 349 smokers. FAZ perimeter was the only OCTA parameter that was significantly different between the two groups on uncontrolled analysis (P = 0.033). Multivariate regression analyses revealed significant associations between lower VLD full (β = -0.31, P = 0.048), lower VLD inner (β = -0.35, P = 0.046) and a history of smoking. No significant associations between cigarette smoking and either FAZ or PD were detected. Conclusions Our results suggest that smoking is likely associated with deleterious changes in the retinal microvasculature of patients with a history of diabetes and no visible DR. Based on these findings, diabetic patients with a history of smoking may benefit from higher prioritization in terms of ophthalmic screening.

Objective Acute pulmonary embolism (PE) is a life-threatening disease with a high mortality. Computed tomographic pulmonary angiography (CTPA) is used in clinical routine for diagnosis of PE. Many pulmonary obstruction scores were proposed to aid in stratifying clinical course of PE. The purpose of the present study was to compare common pulmonary obstruction scores in PE in regard of time efficiency and interreader agreement based upon a representative patient sample. Methods Overall, 50 patients with acute PE were included in this single center, retrospective analysis. Two readers scored the CT images blinded to each other and assessed the scores proposed by Mastora et al., Qanadli et al., Ghanima et al. and Kirchner et al. The required time was assessed of each reading for scoring. Results For reader 1, Mastora score took the longest time duration, followed by Kirchner score, Qanadli score and finally Ghanima score (every test, p Conclusion For the investigated obstruction scores, there are significant differences in regard of time consumption with no relevant differences in regard of interreader variability in patients with acute pulmonary embolism. Mastora score requires the most time effort, whereas the score by Ghanima the least time.

PurposeVolume indices and left ventricular ejection fraction (LVEF) are routinely used to assess cardiac function. Ventricular strain values may provide additional diagnostic information, but their reproducibility is unclear. This study therefore compares the repeatability and reproducibility of volumes, volume fraction, and regional ventricular strains, derived from cardiovascular magnetic resonance (CMR) imaging, across three software packages and between readers.MethodsSeven readers analysed 16 short-axis CMR stacks of a porcine heart. Endocardial contours were manually drawn using OsiriX and Simpleware ScanIP and repeated in both softwares. The images were also contoured automatically in Circle CVI42. Endocardial global, apical, mid-ventricular, and basal circumferential strains, as well as end-diastolic and end-systolic volume and LVEF were compared.ResultsBland-Altman analysis found systematic biases in contour length between software packages. Compared to OsiriX, contour lengths were shorter in both ScanIP (-1.9 cm) and CVI42 (-0.6 cm), causing statistically significant differences in end-diastolic and end-systolic volumes, and apical circumferential strain (all pConclusionOsiriX and CVI42 gave consistent results for all strain and volume metrics, with no statistical differences found between OsiriX and ScanIP for mid-ventricular, global or basal strains, or left ventricular ejection fraction. However, volumes were influenced by the choice of contouring software, suggesting care should be taken when comparing volumes across different software.

SPECT imaging has been identified as an effective medical modality for diagnosis, treatment, evaluation and prevention of a range of serious diseases and medical conditions. Bone SPECT scan has the potential to provide more accurate assessment of disease stage and severity. Segmenting hotspot in bone SPECT images plays a crucial role to calculate metrics like tumor uptake and metabolic tumor burden. Deep learning techniques especially the convolutional neural networks have been widely exploited for reliable segmentation of hotspots or lesions, organs and tissues in the traditional structural medical images (i.e., CT and MRI) due to their ability of automatically learning the features from images in an optimal way. In order to segment hotspots in bone SPECT images for automatic assessment of metastasis, in this work, we develop several deep learning based segmentation models. Specifically, each original whole-body bone SPECT image is processed to extract the thorax area, followed by image mirror, translation and rotation operations, which augments the original dataset. We then build segmentation models based on two commonly-used famous deep networks including U-Net and Mask R-CNN by fine-tuning their structures. Experimental evaluation conducted on a group of real-world bone SEPCT images reveals that the built segmentation models are workable on identifying and segmenting hotspots of metastasis in bone SEPCT images, achieving a value of 0.9920, 0.7721, 0.6788 and 0.6103 for PA (accuracy), CPA (precision), Rec (recall) and IoU, respectively. Finally, we conclude that the deep learning technology have the huge potential to identify and segment hotspots in bone SPECT images.

Background Dilated and tortuous vessels within elongated dermal papillae represent a histopathological clue of psoriasis. However, the number of dilated capillaries (capillary density) in psoriasis remains undefined as the results from the available studies differ significantly. Objectives To evaluate the capillary density in psoriasis using dermoscopy and horizontal histopathological sections (HHS), two techniques that share the horizontal view of the skin, and to compare the results with the existing data. Methods Twenty adult patients with stable plaque psoriasis were enrolled and, in each patient, a target area of the examined plaque, previously engraved by gently rotating a 5-mm biopsy punch device, underwent dermoscopy and biopsy for HHS. In all examined fields, capillary density was evaluated in a centered 4-mm diameter area, counting the number of red dots at dermoscopy and of dermal papillae at HHS. Results A total of 20 target lesions located on the trunk, arms and tights were evaluated. The mean capillary density resulting from dermoscopy was 43.02±6.60/mm 2 whereas that from HHS was 50.30±9.05/mm 2. These data showed a statistically significant difference (p = 0.006), with a strong correlation at Pearson’s test (r = 0.88). Conclusions Our results when compared with those from the existing literature showed some differences. The peculiarity of our work is represented by the precise measurement and correlation of the capillary density using two different methods, as the preliminary skin engraving allowed a perfect match between the area undergoing dermoscopy and that of skin sampling for HHS. Compared to dermoscopy in which deep-located vessels might have gone undetected, HHS seems to reflect more precisely and reliably the real capillary density showing an average of 50 capillaries/mm 2 that in a common 5x5 cm psoriatic patch corresponds to an average of 125.000 capillaries. These results highlight the extraordinary potential of psoriatic skin to develop such a complex and intricate vascular network.

The main arteries that supply blood to the brain originate from the Circle of Willis (CoW). The CoW exhibits considerable anatomical variations which may have clinical importance, but the variability is insufficiently characterised in the general population. We assessed the anatomical variability of CoW variants in a community-dwelling sample (N = 1,864, 874 men, mean age = 65.4, range 40–87 years), and independent and conditional frequencies of the CoW’s artery segments. CoW segments were classified as present or missing/hypoplastic (w/1mm diameter threshold) on 3T time-of-flight magnetic resonance angiography images. We also examined whether age and sex were associated with CoW variants. We identified 47 unique CoW variants, of which five variants constituted 68.5% of the sample. The complete variant was found in 11.9% of the subjects, and the most common variant (27.8%) was missing both posterior communicating arteries. Conditional frequencies showed patterns of interdependence across most missing segments in the CoW. CoW variants were associated with mean-split age (P = .0147), and there was a trend showing more missing segments with increasing age. We found no association with sex (P = .0526). Our population study demonstrated age as associated with CoW variants, suggesting reduced collateral capacity with older age. © 2020 Hindenes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Purpose We aimed to evaluate microvascular changes on optical coherence tomography angiography (OCTA) in patients with rhegmatogenous retinal detachment (RRD) who underwent silicone oil (SO) tamponade and compare changes according to macular involvement. Methods This retrospective study included 48 patients with unilateral RRD who underwent vitrectomy and SO tamponade and were stable after SO removal. Control data were obtained from the fellow healthy eye. Ophthalmic examinations, including best corrective visual acuity (BCVA) and OCTA, were conducted. Differences in vascular density (VD) in different sections of the macula and differences in the foveal avascular zone (FAZ) were analyzed between the affected eyes and control eyes. Subgroup analyses according to macular involvement were performed. Results Baseline BCVA and duration of SO tamponade were associated with postoperative BCVA (p Conclusion SO tamponade could cause microvascular changes, especially in the nasal parafoveal area. The macular-off RRD group were affected more than the macular-on RRD group.

Background Neurofibromatosis type 1 (NF-1) is an autosomal dominant disease that affects one in every 3000 individuals. This disease can present a wide range of clinical manifestations, ranging from skin abnormalities to severe vascular damage. Although not commonly recognized in the context of NF-1, cerebrovascular disease (CVD), can be often present since childhood and diagnosed just later in life. When present, NF-1-associated CVD clinical manifestations may include headache, cognitive deficits and ultimately aneurysm rupture, causing death. Thus, CVD plays an important role in the clinical manifestations, disease severity and prognosis of patients with NF-1. This systematic review aims to summarize the body of evidence linking NF-1 and CVD in children. Methods Two independent investigators performed a systematic review on the PubMed and EMBASE search platforms, using the following key terms: “neurofibromatosis type 1”, “Von Recklinghausen’s disease”, "children", "adolescents", "stroke", "Moyamoya disease", "vascular diseases", "cerebrovascular disorders", "aneurysm" and "congenital abnormalities". Studies focused on assessing the development of CVD in children with NF-1 were included. Results Seven studies met the inclusion criteria. Twelve different clinical manifestations have been associated with cerebrovascular changes in children with NF-1; 44,5% of diagnosed patients were asymptomatic. Conclusion The available evidence suggests that CVDs are related with the progression of NF-1, even in the absence of a clear clinical manifestation. In addition, improved prognosis was observed when imaging tests were performed to screen for cerebrovascular alterations early during the clinical investigation. Early diagnosis of CVD in NF-1 patients foster implementation of timely interventions, directly impacting clinical outcomes.

Optical coherence tomography angiography (OCTA) is a novel, non-invasive imaging tool used to detect vascular flow. The absence of a flow signal in OCTA in polyps revealed by indocyanine green angiography (ICGA) in patients with polypoidal choroidal vasculopathy (PCV) may indicate slow or compromised filling of blood flow from choroidal vessels. Naive patients with PCV treated with intravitreal injections of aflibercept (IVI-A) were enrolled in this study to validate the hypothesis that baseline flow may affect the outcome of polyp regression in ICGA. The flow signal of polyps in OCTA was detected by manual segmentation in the corresponding location by ICGA. Polyps were defined as high-flow if both OCTA and ICGA showed positive findings, and low-flow if OCTA showed a negative flow signal in 3 consecutive horizontal scans at the polyp area shown in ICGA. A total of 24 polyps were identified in 13 PCV patients at baseline. Of these 24 polyps, 22 (91.7%) were high-flow and 2 (8.3%) were low-flow. After 3 monthly IVI-A, all low-flow polyps had complete regression in ICGA. Among 17 (77%) high-flow polyps at baseline that had regression after treatment, 10 (58.8%) became low-flow, while 5 (22.7%) persistent polyps remained high-flow. Flow signal of polyps as detected by OCTA could be a predictive factor for treatment response in patients with PCV. Monitoring changes in flow signal after treatment is clinically relevant.

Objective Takayasu arteritis (TAK) is a rare immune-mediated vasculitis of the aorta and its branches. Aims were to calculate prevalence and incidence in Switzerland, to assess disease activity and performance of MR-Angiography (MRA). Methods 31 patients were recorded in a database, 27 were followed prospectively up to 3 years. Prevalence was calculated based on data of the national statistical bureau. Disease activity was defined using the revised EULAR criteria. MRA depicted stenotic changes and aortic wall enhancement. Results A disease prevalence of 14.5/1.000.000 inhabitants and an incidence of 0.3/1.000.000 per year was calculated. Aortic wall enhancement was found in 10 patients while in clinical and serological remission. EULAR criteria missed 5 patients with disease activity with isolated elevations of ESR/CRP. Arterial stenosis did not change over time in 5 cases, it improved in 2 and increased in 7. At follow-up 16 patients were treated with tocilizumab, 11/16 in monotherapy, 5 patients were treatment-free, 25/27 stayed in remission. Conclusion In addition to prevalence and incidence, our data show that MRA qualifies to detect subclinical disease activity, but, on the other hand, that EULAR criteria may miss disease activity in case of isolated elevation of ESR/CRP.

Purpose To compare peripapillary perfused capillary density (PCD) among eyes with true exfoliation syndrome (TEX), eyes with pseudoexfoliation syndrome (PEX), and healthy control eyes. Materials and methods In this observational cross-sectional study, eyes with and without TEX or PEX were assessed by optical coherence tomography angiography (OCTA) imaging. Bilateral OCTA images (4.5 × 4.5 mm2) centered at the optic nerve head were obtained using a commercial spectral domain OCTA system. Optic nerve head perfusion was quantified using the split-spectrum amplitude decorrelation angiography algorithm. Categorical and continuous variables were compared using the chi-squared test and one-way analysis of variance, respectively. The generalized estimating equation was used to adjust for confounding factors and determine inter-ocular associations. Results We enrolled 39 eyes with TEX, 31 eyes with PEX, and 32 control eyes. There were no significant differences among the three groups regarding age, intraocular pressure, cup-to-disc ratio, blood pressure, or axial length (all p>0.05). There were significant differences in global PCD among the three groups (p = 0.01). There were significant differences in annular PCD between the TEX and PEX groups (p = 0.027). Conclusions While both global and annular PCDs did not differ between the TEX and control groups, greater loss of annular PCD in the PEX group than in the TEX and control groups suggests more pronounced microvascular disturbance in PEX. Synopsis/Precis Greater microvascular attenuation in PEX compared with TEX and normal control measured by OCTA.

Background and purposeMR contrast-enhanced techniques are undergoing increased scrutiny since the FDA applied a warning for gadolinium-based MR contrast agents due to gadolinium deposition within multiple organ systems. While CE-MRA provides excellent image quality, is it required in a screening carotid study? This study compares 2D TOF and 3D TOF MRA vs. CE-MRA in defining carotid stenosis in a large clinical patient population, and with multiple readers with varying experience.Materials and methods200 consecutive patients had their carotid bifurcations evaluated with 2D TOF, 3D TOF and CE-MRA sequences by 6 board-certified neuroradiologists. Stenosis and quality of examinations were defined for each study. Inter-rater reliability was assessed using two-way random effects intraclass correlation coefficients. Intra-reader reliability was computed via weighted Cohen's κ. Weighted Cohen's κ were also computed to assess agreement in stenosis ratings between enhanced images and unenhanced images.ResultsAgreement between unenhanced and enhanced ratings was substantial with a pooled weighted κ of 0.733 (0.628-0.811). For 5 of the 6 readers, the combination of unenhanced 2D TOF and 3D TOF showed better agreement with contrast-enhanced than either 2D TOF or 3D TOF alone. Intra-reader reliability was substantial.ConclusionsThe combination of 2D TOF and 3D TOF MRA showed substantial agreement with CE-MRA regarding degree of carotid stenosis in this large outpatient population across multiple readers of varying experience. Given the scrutiny that GBCA are undergoing due to concerns regarding CNS and soft tissue deposition, it seems prudent to reserve CE-MRA for cases which are not satisfactorily answered by the nonenhanced study or other noninvasive examinations.

The instantaneous wave-free ratio (iFR) is used for assessing the hemodynamic severity of a lesion, as an alternative to the fractional flow reserve (FFR). We evaluated the relationship between iFR and FFR in detail and the clinical significance of iFR in patients with mild to intermediate coronary artery stenosis. We recruited consecutive 323 patients (421 lesions) with lesions exhibiting 30% to 80% diameter stenosis on angiography in whom FFR and iFR were measured. In the total lesions, mean diameter stenosis was 48.6% ± 9.0%, and physiological significance, defined by FFR of 0.80 or less or by iFR of 0.92 or less, was observed in 32.5% or 33.5%, respectively. Mismatch between iFR and FFR was observed in 18.1% of the lesions. Clinical factors did not predict FFR value; however, gender, diabetes mellitus, aortic stenosis, anemia, high-sensitivity CRP value, and renal function predicted iFR value. In multivariate logistic analysis after adjustment for FFR value, gender (p < 0.001), diabetes mellitus (p = 0.005), aortic stenosis (p = 0.016), high-sensitivity CRP (p < 0.001), and renal function (p = 0.003) were all independent predictors of iFR value. In Kaplan-Meier analysis, the baseline iFR predicted the subsequent major cardiovascular events (MACE) (hazard ratio, 2.40; 95% CI, 1.16-4.93; p = 0.018) and the results of the iFR-guided strategy for predicting rates of MACE and myocardial infarction/revascularization were superior to those of the FFR-guided strategy. In conclusion, significant clinical factors predicted iFR value, which affected the prognostic capacity. The iFR-guided strategy may be superior in patients with mild to intermediate stenosis.

Purpose To characterize changes in the retinal nerve fiber layer (RNFL) and peripapillary vessel density (VD) at the site of disc hemorrhage (DH) in nonglaucomatous eyes. Materials and methods This retrospective cross-sectional study included nonglaucomatous eyes diagnosed with unilateral DH. The change of DH was recorded using disc photography. Both anatomical data and functional visual field (VF) data were collected using optical coherence tomography angiography and Humphrey VF examination. Results Sixteen patients were included with average follow-up duration of 95 months. Almost half of DH episodes was initially presented at the inferotemporal area of the optic disc. Pigment formation at the previous DH site after resolution was noted in 12.5% of eyes. Sectoral radial peripapillary VD at the DH site was significantly lower in DH eyes than in the control group; however, the sectoral RNFL thickness at the DH site was not significantly decreased. Progression of the VF defect corresponding to the DH site was found in 81.3% of eyes despite regular use of antiglaucoma agents. The mean change in the VF mean deviation was -0.64 dB/year in DH eyes. Conclusion During long follow-up periods, decreased peripapillary VD at the DH site and progression of the VF defect corresponding to the DH site were detected in nonglaucomatous eyes. Retinal pigmentation with an RNFL defect is a clue for DH, although RNFL showed no significant change. Antiglaucoma treatment may not prevent the deterioration of visual function.

BackgroundPreclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack of a suitable large animal model.PurposeTo develop and characterize a porcine model of pancreatic cancer. Unlike small animals, pigs have similar physiology, drug dosing, and immune response to humans. Locoregional therapy in pigs can be performed using the same size catheters and devices as in humans.MethodsThe Oncopig is a transgenic pig with Cre-inducible TP53R167H and KRASG12D mutations. In 12 Oncopigs, CT-guided core biopsy of the pancreas was performed. The core biopsy was incubated with an adenoviral vector carrying the Cre recombinase gene. The transformed core biopsy was injected back into the pancreas (head, tail, or both). The resulting tumors (n = 19) were characterized on multi-phase contrast-enhanced CT, and on pathology, including immunohistochemistry. Angiographic characterization of the tumors was performed in 3 pigs.ResultsPancreatic tumors developed at 19 out of 22 sites (86%) that were inoculated. Average tumor size was 3.0 cm at 1 week (range: 0.5-5.1 cm). H&E and immunohistochemical stains revealed undifferentiated carcinomas, similar to those of the pancreatobiliary system in humans. Neoplastic cells were accompanied by a major inflammatory component. 1 of 12 pigs only had inflammatory nodules without evidence of neoplasia. On multiphase CT, tumors were hypovascular compared to the normal pancreas. There was no pancreatic duct dilation. In 3 pigs, angiography was performed, and in all 3 cases, the artery supplying the pancreatic tumor could be catheterized using a 2.4 F microcatheter. Selective angiography showed the pancreatic tumor, without extra-pancreatic perfusion.ConclusionPancreatic cancer can be induced in a transgenic pig. Intra-arterial procedures using catheters designed for human interventions were technically feasible in this large animal model.

ObjectiveTo meet increasing demands to train neuroendovascular techniques, we developed a dedicated simulator applying individualized three-dimensional intracranial aneurysm models ('HANNES'; Hamburg Anatomic Neurointerventional Endovascular Simulator). We hypothesized that HANNES provides a realistic and reproducible training environment to practice coil embolization and to exemplify disparities between neurointerventionalists, thus objectively benchmarking operators at different levels of experience.MethodsSix physicians with different degrees of neurointerventional procedural experience were recruited into a standardized training protocol comprising catheterization of two internal carotid artery (ICA) aneurysms and one basilar tip aneurysm, followed by introduction of one framing coil into each aneurysm and finally complete coil embolization of one determined ICA aneurysm. The level of difficulty increased with every aneurysm. Fluoroscopy was recorded and assessed for procedural characteristics and adverse events.ResultsPhysicians were divided into inexperienced and experienced operators, depending on their experience with microcatheter handling. Mean overall catheterization times increased with difficulty of the aneurysm model. Inexperienced operators showed longer catheterization times (median; IQR: 47; 30-84s) than experienced operators (21; 13-58s, p = 0.011) and became significantly faster during the course of the attempts (rho = -0.493, p = 0.009) than the experienced physicians (rho = -0.318, p = 0.106). Number of dangerous maneuvers throughout all attempts was significantly higher for inexperienced operators (median; IQR: 1.0; 0.0-1.5) as compared to experienced operators (0.0; 0.0-1.0, p = 0.014).ConclusionHANNES represents a modular neurointerventional training environment for practicing aneurysm coil embolization in vitro. Objective procedural metrics correlate with operator experience, suggesting that the system could be useful for assessing operator proficiency.

BackgroundAlthough optical coherence tomography (OCT)-detected suboptimal findings (SF-OCT) such as malapposition, edge dissection, tissue protrusion, thrombus and small minimal stent area (MSA) are frequently observed after the implantation of drug-eluting stents (DES), their clinical implications are controversial.HypothesisClinical outcomes may differ between patients with SF-OCTs and without SF-OCTs after DES implantation.MethodsA total of 576 patients undergoing OCT analysis after DES implantation were divided into SF-OCT group (n = 379, 379 lesions) and No SF-OCT group (n = 197, 197 lesions). The study population had no significant abnormal finding in final angiography. Quantification was performed for each SF-OCT. The incidences of major adverse cardiovascular events (MACE: all-cause death, non-fatal myocardial infarction, target vessel revascularization, and stent thrombosis) were compared between the two groups. A median follow-up duration was 21.5 months.ResultsAmong 379 patients with SF-OCT, 32.4% had multiple SF-OCTs. Malapposition (32.1%, IQR of maximal depth 315-580 μm) was the most frequent, followed by small MSA (31.6%), edge dissection (12.5%, IQR of maximal flap of opening 0.27-0.52 mm), thrombus (7.6%, IQR of diameter 1.31-1.97mm) and tissue protrusion (6.8%, IQR of diameter 1.05-1.67 mm). The SF-OCT group showed smaller stent diameter and longer stent length, and lower in-stent lumen expansion rate. The incidence of MACE did not differ between the two groups (3.0% for No SF-OCT vs. 5.0% for SF-OCT; HR 1.601; 95% CI 0.639 to 4.011; P = 0.310).ConclusionsThe presence of angiographically insignificant SF-OCTs were not associated with clinical outcomes in this study.