Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model.

BACKGROUND: Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved. METHODS: Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. RESULTS: The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P<0.0001) and conduction velocity (85±26 versus 55±13 cm/s, P=0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P=0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P=0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. CONCLUSIONS: Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

Construction and Validation of a Benchtop Model for Testing of Mechanical Thrombectomy Devices for Pulmonary Embolism.

PURPOSE: This study aims to define the process of designing and manufacturing 3D printed and glass models of the pulmonary artery (PA) and utilizing them in a test bed for evaluation of devices for mechanical thrombectomy of pulmonary embolism (PE). MATERIALS AND METHODS: Patient derived computed tomography angiography (CTA) images of the PA were digitally converted into a hollowed-out structure and translated into clear 3D printed and glass models. A test bed was created using a peristaltic pump and silicone tubing connected to the models. Human clot analogs were then prepared and injected within the models. Thrombectomy testing was done using clinically used predicates and baseline characteristics of the models were evaluated by independent interventionalists. RESULTS: The mean sizes of the main pulmonary artery (MPA) for the 3D printed model and glass model were 30.4 mm and 29.2 mm, mimicking those of the patient's PA obtained on CTA. Heterogeneous human clot analogs were created with fibrin composition ranging from 60 to 30%. Mechanical thrombectomy was successfully attempted by independent interventionalists. Both the 3D printed, and glass model were appraised as very good for multiple attributes. CONCLUSION: A complete test bed using 3D printed and glass models of the PA with human clot analogs was created for testing of mechanical thrombectomy devices for PE.

Effects of Pulsed Electric Fields on the Coronary Arteries in Swine.

BACKGROUND: Previous animal studies have shown no significant vascular injury from pulsed electrical field (PEF) ablation. We sought to assess the effect of PEF on swine coronary arteries. METHODS: We performed intracoronary and epicardial (near the coronary artery) PEF ablations in swine pretreated with dual antiplatelet and antiarrhythmic therapy. Intracoronary PEF was delivered using MapiT catheters (Biotronik, Berlin), whereas epicardial PEF was delivered using EPT catheters (Boston Scientific, MA). PEF pulse duration was microseconds (Nanoknife 3.0, Angio Dynamics, NY) or nanoseconds (CellFX, Pulse Biosciences, CA). RESULTS: We performed 39 intracoronary ablations in 10 swine and 20 epicardial-pericoronary ablations in 4 separate swine. Intracoronary PEF was delivered at higher energy compared with epicardial PEF (46 [interquartile range, IQR 20-85] J versus 10 [IQR 10-11] J, P < 0.01). Reversible coronary spasm occurred in 49% intracoronary ablations and 45% epicardial ablations (P=0.80). At the end study, fixed coronary stenosis was demonstrated in 44% intracoronary ablations (80% for microsecond PEF and 18% for nanosecond PEF) and 0% epicardial ablations. Visible hemorrhagic and/or fibrotic myocardial lesions were observed at necropsy with similar frequency between intracoronary and epicardial PEF (45% versus 50%, P=0.70). Nanosecond PEF (49 ablations in 11 swine), when compared with microsecond PEF (10 intracoronary ablations in 3 swine), resulted in lower energy delivery (21 [IQR 10-46] J versus 129 [IQR 24-143] J, P=0.03) and less incidence of fixed coronary stenosis (18% versus 80%, P=0.04). CONCLUSIONS: In the swine model, intracoronary PEF resulted both in significant coronary spasm and fixed coronary stenosis. Epicardial PEF, delivered at lower energy, resulted in reversible spasm but no fixed coronary stenosis.

Bipolar Electroporation Across the Interventricular Septum: Electrophysiological, Imaging, and Histopathological Characteristics.

BACKGROUND: Pulsed electric field (PEF) ablation is an emerging modality for the treatment of cardiac arrhythmias. Data regarding effects on the interventricular septum are limited, and the optimal delivery protocol and electrode configuration remain undefined. OBJECTIVES: This study sought to evaluate the electrophysiological, imaging, and histological characteristics of bipolar direct-current PEF delivered across the interventricular septum. METHODS: PEF was applied between identical solid-tip ablation catheters positioned on either side of the septum in a chronic canine model. Intracardiac and surface electrophysiological data were recorded following delivery. In 4 animals, cardiac magnetic resonance (CMR) was performed early (6 ± 2 days) and late (30 ± 2 days) postablation. After 4 weeks of survival, cardiac specimens were sectioned for histopathological analysis. RESULTS: In 8 canines, PEF was delivered in 27 separate septal sites (45 ± 17 J/site) with either microsecond or nanosecond PEF. Acute complications included transient complete atrioventricular block in 5 animals (63%) after delivery at the anterobasal septum, with right bundle branch block persisting in 3 (38%). Ventricular fibrillation occurred in 1 animal during microsecond but not nanosecond PEF. Postprocedural CMR showed prominent edema and significant left ventricular systolic dysfunction, which recovered with late imaging. At 4 weeks, 36 individual well-demarcated lesions were demonstrated by CMR and histopathology. Lesion depth measured by histology was 2.6 ± 2.1 mm (maximum 10.9 mm and near transmural). CONCLUSIONS: Bipolar PEF ablation of the interventricular septum is feasible and can produce near transmural lesions. Myocardial stunning, edema, and conduction system injury may occur transiently. Further studies are required to optimize safe delivery and efficacious lesions.

Open-chest Pulsed Electric Field Ablation of Cardiac Ganglionated Plexi in Acute Canine Models.

This study aimed to evaluate the safety and acute effect on markers of cardiac autonomic tone following pulsed electric fields (PEFs) delivered to epicardial ganglionated plexi (GP) during a cardiac surgical procedure. Ablation of GP as a treatment for atrial fibrillation (AF) has shown promise, but thermal ablation energy sources are limited by the risk of inadvertent collateral tissue injury. In acute canine experiments, median sternotomy was performed to facilitate the identification of 5 epicardial GP regions using an anatomy-guided approach. Each site was targeted with saline-irrigated PEF (1000 V, 100 µs, 10 electrocardiogram [ECG]-synchronized pulse sequences). Atrial effective refractory period (AERP) and local electrogram (EGM) amplitude were measured before and after each treatment. Histology was performed on samples from treatment-adjacent structures. In 5 animals, 30 (n = 2) and 60 (n = 3) pulses were successfully delivered to each of the 5 target sites. There was no difference in local atrial EGM amplitude before and after PEF application at each site (1.83 ± 0.41 vs. 1.92 ± 0.53 mV, P = .72). The mean AERP increased from 97 ± 15 ms at baseline to 115 ± 7 ms following treatment at all sites (18.6% increase; 95% confidence interval, 1.9-35.2; P = .037). There were no sustained ventricular arrhythmias or acute evidence of ischemia following delivery. Histology showed complete preservation of adjacent atrial myocardium, phrenic nerves, pericardium, and esophagus. Use of PEF to target regions rich in cardiac GP in open-chest canine experiments was feasible and effective at acutely altering markers of cardiac autonomic tone.

Ventricular nanosecond pulsed electric field delivery using active fixation leads: a proof-of-concept preclinical study.

BACKGROUND: Mid-myocardial ventricular arrhythmias are challenging to treat. Cardiac electroporation via pulsed electric fields (PEFs) offers significant promise. We therefore tested PEF delivery using screw-in pacemaker leads as proof-of-concept. METHODS: In 5 canine models, we applied nanosecond PEF (pulse width 300 ns) across the right ventricular (RV) septum using a single lead bipolar configuration (n = 2) and between two leads (n = 3). We recorded electrograms (EGMs) prior to, immediately post, and 5 min after PEF. Cardiac magnetic resonance imaging (cMRI) and histopathology were performed at 2 weeks and 1 month. RESULTS: Nanosecond PEF induced minimal extracardiac stimulation and frequent ventricular ectopy that terminated post-treatment; no canines died with PEF delivery. With 1 lead, energy delivery ranged from 0.64 to 7.28 J. Transient ST elevations were seen post-PEF. No myocardial delayed enhancement (MDE) was seen on cMRI. No lesions were noted on the RV septum at autopsy. With 2 leads, energy delivery ranged from 56.3 to 144.9 J. Persistent ST elevations and marked EGM amplitude decreases developed post-PEF. MDE was seen along the septum 2 weeks and 1 month post-PEF. There were discrete fibrotic lesions along the septum; pathology revealed dense connective tissue with < 5% residual cardiomyocytes. CONCLUSIONS: Ventricular electroporation is feasible and safe with an active fixation device. Reversible changes were seen with lower energy PEF delivery, whereas durable lesions were created at higher energies. Central illustration: pulsed electric field delivery into ventricular myocardium with active fixation leads.

Evaluation of a novel cardiac signal processing system for electrophysiology procedures: The PURE EP 2.0 study.

BACKGROUND: Intracardiac electrogram data remain one of the primary diagnostic inputs guiding complex ablation procedures. However, the technology to collect, process, and display intracardiac signals has known shortcomings and has not advanced in several decades. OBJECTIVE: The purpose of this study was to evaluate a new signal processing platform, the PURE EP™ system (PURE), in a multi-center, prospective study. METHODS: Intracardiac signal data of clinical interest were collected from 51 patients undergoing ablation procedures with PURE, the signal recording system, and the 3D mapping system at the same time stamps. The samples were randomized and subjected to blinded, controlled evaluation by three independent electrophysiologists to determine the overall quality and clinical utility of PURE signals when compared to conventional sources. Each reviewer assessed the same (92) signal sample sets and responded to (235) questions using a 10-point rating scale. If two or more reviewers rated the PURE signal higher than the control, it was deemed superior. RESULTS: A total of 93% of question responses showed consensus amongst the blinded reviewers. Based on the ratings for each pair of signals, a cumulative total of 164 PURE signals out of 218 (75.2%) were statistically rated as Superior for this data set (p < .001). Only 14 PURE signals out of 218 were rated as Inferior (6.4%). CONCLUSION: The PURE intracardiac signals were statistically rated as superior when compared to conventional systems.

Incremental benefit of a novel signal recording system during mapping and ablation.

AIMS: Current electrophysiology signal recording and mapping systems have limited dynamic range (DR) and bandwidth, which causes loss of valuable information during acquisition of cardiac signals. We evaluated a novel advanced signal processing platform with the objective to obtain and assess additional information of clinical importance. METHODS AND RESULTS: Over 10 canines, we compared intracardiac recordings within all cardiac chambers, in various rhythms, in pacing and during radiofrequency (RF) ablation across two platforms; a conventional system and the PURE EP™ [(PEP); Bio Sig Technologies, Inc., Los Angeles, CA, USA]. Recording cardiac signals with varying amplitudes were consistently and reproducibly observed, without loss of detail or introduction of artefact. Further the amplitude of current of injury (COI) on the unipolar signals correlated with the instantaneous contact force (CF) recorded on the sensing catheter in all the animals (r2 = 0.94 in ventricle). The maximum change in the unipolar COI correlated with the change in local electrogram amplitude during non-irrigated RF ablation (r2 = 0.61 in atrium). Reduction in artefact attributable to pacing (20 sites) and noise during ablation (48 sites) was present on the PEP system. Within the PEP system, simultaneous display of identical signals, filtered differently, aided the visualization of discrete conduction tissue signals. CONCLUSION: Compared to current system, the PEP system provided incremental information including identifying conduction tissue signals, estimates of CF and a surrogate for lesion formation. This novel signal processing platform with increased DR and minimal front-end filtering may be useful in clinical practice.

Fibroplasty (venoplasty) to facilitate transvenous lead placement: A single-center experience.

INTRODUCTION: Venous stenosis is a well-recognized complication of transvenous leads (TVLs) that is encountered during lead revisions or device upgrades. We here report the outcomes of TVL placement facilitated by fibroplasty or tunneling (TUN) procedure. METHODS: We conducted a single-center retrospective cohort study of all patients undergoing TVL implantation requiring fibroplasty or TUN from 2005 to 2017. Medical records and procedure reports were reviewed for relevant data. Outcomes for fibroplasty and TUN to facilitate TVL placement were compared. RESULTS: Sixty patients had fibroplasty and thirty-five patients had a TUN procedure. There was no difference in procedure success rates between the two groups (97% fibroplasty vs. 100% TUN; p = .98). The fluoroscopy time was longer (fibroplasty = 39.7 ± 21.5 min vs. TUN = 29.2 ± 21.3 min; p = .01) and the total procedural time was shorter in the fibroplasty group (fibroplasty = 247 ± 77.8 min vs. TUN = 287 ± 77.1 min; p = .01). TUN was associated with a significantly higher incidence of acute complications (fibroplasty = 0 vs. TUN = 8; p = .002) most requiring invasive intervention and/or transfusion with blood products. Long-term complications requiring additional device-related procedures were comparable between the two groups (fibroplasty = 6 vs. TUN = 6; logrank p = .21). CONCLUSIONS: For patients with venous stenosis requiring additional TVL, balloon fibroplasty is associated with similar rates of success and a significantly decreased incidence of acute complications when compared with subcutaneous TUN.

Combined local impedance and contact force for radiofrequency ablation assessment.

BACKGROUND: The combination of contact force (CF) and local impedance (LI) may improve tissue characterization and lesion prediction during radiofrequency (RF) ablation. OBJECTIVE: The purpose of this study was to evaluate the utility of LI combined with CF in assessing RF ablation efficacy. METHODS: An LI catheter with CF sensing was evaluated in swine (n = 11) and in vitro (n = 14). The relationship between LI and CF in different tissue types was evaluated in vivo. Discrete lesions were created in vitro and in vivo at a range of forces, powers, and durations. Finally, an intercaval line was created in 3 groups at 30 W: 30s, Δ20Ω, and Δ30Ω. In the Δ20Ω and Δ30Ω groups, the user ablated until a 20 or 30 Ω LI drop. In the 30s group, the user was blinded to LI. RESULTS: In vivo, distinction in LI was found between the blood pool and the myocardium (blood pool: 122 ± 7.02 Ω; perpendicular contact: 220 ± 29 Ω; parallel contact: 207 ± 31 Ω). LI drop correlated with lesion depth both in vitro (R = 0.84) and in vivo (R = 0.79), informing sufficient lesion creation (LI drop >20 Ω) and warning of excessive heating (LI drop >65 Ω). When creating an intercaval line, the total RF time was significantly reduced when using LI guidance (6.4 ± 2 minutes in Δ20Ω and 8.1 ± 1 minutes in Δ30Ω) compared with a standard 30-second workflow (18 ± 7 minutes). Acute conduction block was achieved in all Δ30Ω and 30s lines. CONCLUSION: The addition of LI to CF provides feedback on both electrical and mechanical loads. This provides information on tissue type and catheter-tissue coupling; provides feedback on whether volumetric tissue heating is inadequate, sufficient, or excessive; and reduces ablation time.

Injectable Flexible Subcutaneous Electrode Array Technology for Electrocardiogram Monitoring Device.

Implantable cardiac monitors have undergone considerable miniaturization. However, they continue to be associated with complications such as infection, bleeding/bruising, and device extrusion or migration. In this paper, we demonstrate the feasibility of using a small, flexible, injectable, subcutaneous microelectrode-based device to record electrocardiograms (ECGs). We describe the fabrication process and demonstrate the ease of insertion of the injectable ECG device in vivo swine model. We also demonstrate our device's high-density channel microelectrode array's ability to detect the P, R, and T waves. The amplitude of these waves showed excellent correlation with distance of the bipolar electrodes used to detect them. Given the success of our initial studies, this device has the potential to improve the safety profile of implantable cardiac monitors and simplify the implantation procedure to allow for placement in a primary care setting.

A novel percutaneous stabilizing sheath for minimal invasive epicardial echocardiography and ablation.

PURPOSE: Epicardial ablation and mapping are critical adjuncts to the electrophysiologist's approach to arrhythmias; however, ablation within the epicardial space requires the avoidance of coronary arteries (CA). We aimed to evaluate the feasibility and performance of a novel-stabilizing ablation sheath housing an intracardiac echocardiography (ICE) catheter to (1) obtain Epicardial Echocardiography (EE) images, (2) visualize CAs, and (3) enable targeted delivery of radiofrequency energy away from visualized CAs. METHODS: We designed a sheath that could enclose a regular ICE catheter. This sheath has flanges and a balloon, with three interspersed windows surrounded by an electrode. In an acute canine model (N = 6), the sheath was manipulated within the pericardial space to visualize cardiac structures and CAs. Visualization of CAs was confirmed with angiography. Ablation was then performed through the window either proximal or distal to the CA. RESULTS: The novel sheath was successfully deployed in six canines, with no acute procedural complications. Images with an excellent spatial resolution of cardiac structures were obtained including the right ventricular outflow tract; aortic, pulmonary, and mitral valves; and left atrial appendage. CAs were successfully visualized, and ablation from a sheath window either proximal or distal to the CA did not produce angiographic or histopathological evidence of CA damage despite evidence of acute injury to the adjacent ablated myocardium. CONCLUSIONS: This novel percutaneous stabilizing sheath was able to successfully obtain high-quality EE images as well as provide a non-fluoroscopic intra-procedural means to visualize CAs. Use of this sheath enabled successful delivery of energy to avoided CA damage.

Development of a novel ablation hood to prevent systemic embolization of microbubbles and particulate emboli.

BACKGROUND: Atrial fibrillation ablation results in microbubbles and particulate emboli formation. We aimed to develop and test the early feasibility of a novel ablation hood to contain microbubbles and particulate emboli with the ultimate goal of preventing systemic embolization. METHODS: In seven canines, we developed, iterated, and tested a novel retractable hood that can cover the catheter-tissue ablation site. The number and volume (nL) of microbubbles formed during ablation with and without the hood was measured using an extracorporeal circulation loop. Wilcoxon's signed-rank test was used to compare the number of bubbles detected with and without the hood. RESULTS: The hood reduced systemic embolization of microbubbles in 21/28 (75%) of ablations. Both atrial and ventricular ablations showed a statistically significant reduction in bubble number (476 ± 811 without hood vs 173 ± 226 with hood, p = 0.02; 2669 ± 1623 without hood vs 1417 ± 970 with hood, p = 0.04, respectively) and bubble volume (3.3 ± 7.6 nL without hood vs 0.2 ± 0.56 nL with hood, p = 0.006; 6.1 ± 5.2 nL without hood vs 1.9 ± 1.4 nL with hood, p = 0.05, respectively). CONCLUSIONS: Use of a novel hood to cover the ablation catheter at the site of catheter-tissue contact has the potential to provide a means to reduce systematic embolization of microbubbles. Further work is required to examine particulate emboli, but these data show the early feasibility of this design concept.

Irreversible electroporation for catheter-based cardiac ablation: a systematic review of the preclinical experience.

INTRODUCTION: Irreversible electroporation (IRE) utilizing high voltage pulses is an emerging strategy for catheter-based cardiac ablation with considerable growth in the preclinical arena. METHODS: A systematic search for articles was performed from three sources (PubMed, EMBASE, and Google Scholar). The primary outcome was the efficacy of tissue ablation with characteristics of lesion formation evaluated by histologic analysis. The secondary outcome was focused on safety and damage to collateral structures. RESULTS: Sixteen studies met inclusion criteria. IRE was most commonly applied to the ventricular myocardium (n = 7/16, 44%) by a LifePak 9 Defibrillator (n = 9/16, 56%), NanoKnife Generator (n = 2/16, 13%), or other custom generators (n = 5/16, 31%). There was significant heterogeneity regarding electroporation protocols. On histological analysis, IRE was successful in creating ablation lesions with variable transmurality depending on the electric pulse parameters and catheter used. CONCLUSION: Preclinical studies suggest that cardiac tissue ablation using IRE shows promise in delivering efficacious, safe lesions.

Radiofrequency ablation of the cavotricuspid isthmus for management of atrial flutter in patients with congenital heart disease after tricuspid valve surgery: A single-center experience.

BACKGROUND: Typical atrial flutter involving the cavotricuspid isthmus (CTI) is the most common reentrant arrhythmia in congenital heart disease and ablation is effective in its management. However, congenital heart disease patients often require surgical interventions on their tricuspid valve that utilize prosthetic material, making CTI ablation technically challenging. OBJECTIVE: To describe the techniques and outcomes of CTI ablation in the presence of prior tricuspid valve repair or replacement. METHODS: We included all patients who had undergone tricuspid valve repair utilizing an annuloplasty ring or tricuspid valve replacement who underwent CTI ablation for treatment of atrial arrhythmias between 2005 and 2017. Acute procedural success was defined as demonstration of bidirectional conduction block across the CTI. Long-term success was defined as lack of arrhythmia recurrence on monitoring or related symptoms. RESULTS: Sixteen patients met the inclusion criteria. Twelve (75%) patients had Ebstein's anomaly, 14 (88%) patients had a prosthetic tricuspid valve, and 2 (12%) patients had annuloplasty ring. Acute success was achieved in all cases, with no complications. Radiofrequency ablation was required on the ventricular side in 9 (56%) patients. In 1 case, ablation in the small cardiac vein was required. All patients remained free from atrial flutter during 18 months follow-up (range, 1-101 months). CONCLUSION: Our study demonstrates the safety and efficacy of catheter ablation of the CTI in the presence of a tricuspid annuloplasty ring or a prosthetic tricuspid valve. This may require ablation from the ventricular side of the valve to target atrial tissue rendered inaccessible as a result of tricuspid valve surgery.

Comparing the incidence of ventricular arrhythmias during epicardial ablation in swine versus canine models.

BACKGROUND: Choosing the appropriate animal model for development of novel technologies requires an understanding of anatomy and physiology of these different models. There are little data about the characteristics of different animal models for the study of technologies used for epicardial ablation. We aimed to compare the incidence of ventricular arrhythmias during epicardial radiofrequency ablation between swine and canine models using novel epicardial ablation catheters. METHODS: We conducted a retrospective study using data obtained from epicardial ablation experiments performed on swine (Sus Scrofa) and canine (Canis familiaris) models. We compared the incidence of ventricular arrhythmias during ablation between swine and canine using multivariate regression analysis. Six swine and six canine animals underwent successful epicardial radiofrequency ablation. A total of 103 ablation applications were recorded. RESULTS: Ventricular arrhythmias requiring cardioversion occurred in 13.11% of radiofrequency ablation applications in swine and 9.75% in canine (relative risk: 117.6%, 95% confidence interval [CI]: 83.97-164.69, animal-based odds ratio [OR]: .55, 95% CI: .23-61.33; P = .184). When adjusting for application position, duration of ablation and power, the odds of developing potentially lethal ventricular arrhythmia in swine increased significantly compared to canine (OR: 3.60, 95% CI: 1.35-9.55; P = .010). CONCLUSIONS: The swine myocardium is more susceptible to developing ventricular arrhythmias compared to canine model during epicardial ablation. This issue should be carefully considered in future studies.

Quantitative fundus autofluorescence in smokers compared to non-smokers.

Increased fundus autofluorescence is directly related to increased RPE lipofuscin deposition in the retina and has been observed in eyes with age-related macular degeneration (AMD). Smoking is the most significant modifiable risk factor for the development and progression of AMD, in which one of the main mechanisms is oxidative damage from smoking leading to RPE cell toxicity. The relationship between smoking and autofluorescence is not established and could provide insight into pathogenic mechanism of AMD. Therefore, our objective was to compare quantitative fundus autofluorescence (qAF) in the retinae of healthy non-smokers to smokers. We conducted a cross-sectional study at the 2016 Minnesota State Fair. Participants self-reported past medical and ocular history and underwent eye examination as well as qAF imaging with Spectralis confocal scanning laser ophthalmoscope (cSLO) equipped with an internal fluorescent reference. Two sets of images were obtained per eye. Stepwise multiple mixed effects regression model was used to examine the relationship between mean qAF values and smoking status. We enrolled 105 individuals (54 smokers, 61 females, mean age 41 years with range 18-78 years old). Fundus autofluorescence images were analyzable for 85 of 105 individuals contributing 161 eyes (80 right, 81 left). The repeatability coefficients between the first set and second set of images were ±21% of their mean qAF values. Older age and female gender were independently associated with higher qAF. Positive smoking history tended to result in higher qAF values after adjusting for age and gender but was not statistically significant (0.118, 95%CI -0.003, 0.240, P = 0.056). Among smokers, the number of pack-years smoked was not significantly associated with higher qAF. Our study's results are consistent with existing literature in which older age is predictive of intensified autofluorescence, while smoking history does not have as important of an impact on autofluorescence as hypothesized. Several large epidemiological studies have shown that smoking is significantly associated with AMD, and qAF is likely not the appropriate modality to clinically assess smoking's impact on retinae.

Detection of Human Chorionic Gonadotropin (hCG) Hormone using Digital Lateral Flow Immunoassay.

The main goal of this work was to establish a hybrid device incorporating an electrochemical-based transducer on a conventional lateral flow assay strip in order to perform an on-chip fast testing method for the detection of various bio-analyses. In this context, the expected development of the digital lateral-flow immunoassay to be considered a reliable low-cost instrument improves the future of the very simple and flexible approach oflateral-flow assays. It is anticipated to achieve a digital quantitative lateral-flow immunoassay by exploring the electrochemical transducers alongwith recognition elements for digitization of commercially available rapid tests. As a preliminary step, the described technique will be validated using two standard electrochemical measurements (amperometric and impedimetric) across two electrodes fixed onto the surface of LFA strip. The LFA strips were prepared at the factory for pregnancy tests and modified by adding two parallel copper electrodes at the lab. These strips were proven by in-vitro experiments to be reusable lasting for 20-30 multiple days. Further on, the detection of hCG Ab-Ag interaction using these strips was performed. Two different types of measurements, namely amperometric and impedimetric, were used which yielded similar results to those reported in literature with screen-printed micro-electrodes. In addition, different concentrations of NaCl and hCG Ag solution were investigated. However, the expected linear concentration response was obtained. A promising proof-of-concept have been achieved through this study. Further studies are needed to complete the development of fully printed disposable electrochemical devices that are able to either display a digital result directly or transmit data to a mobile phone using RFID/NFC.