Validated model of platelet slip at stenosis and device surfaces.

Platelets are central to thrombosis. However, it is unknown whether platelets slip at vascular or device surfaces. The presence of platelet slip at a surface would interrupt physical contact between the platelet and that surface, and therefore diminish adhesion and thrombosis. Unfortunately, no existing technology can directly measure platelet slip in a biological environment. The objective of this study was to explore whether microspheres-modeling platelets-slip at different vascular and device surfaces in an acrylic scaled-up model coronary artery. The microspheres (3.12 µm diameter) were suspended in a transparent glycerol/water experimental fluid, which flowed continuously at Reynolds numbers typical of coronary flow (200-400) through the model artery. We placed a series of axisymmetric acrylic stenoses (cross-sectional area reduction [CSAr], 20-90%) into the model artery, both without and with a central cylinder present (modeling a percutaneous interventional guide wire, and with a scaled-up Doppler catheter mounted upstream). We used laser Doppler velocimetry (LDV) to measure microsphere velocities within, proximal and distal to each stenosis, and compared to computer simulations of fluid flow with no-slip. For validation, we replaced the acrylic with paraffin stenoses (more biologically relevant from a surface roughness perspective) and then analyzed the signal recorded by the scaled-up Doppler catheter. Using the LDV, we identified progressive microsphere slip proportional to CSAr inside entrances for stenoses ≥60% and ≥40% without and with cylinder present, respectively. Additionally, microsphere slip occurred universally along the cylinder surface. Computer simulations indicated increased fluid shear rates (velocity gradients) at these particular locations, and logistic regression analysis comparing microsphere slip with fluid shear rate resulted in a c-index of 0.989 at a cut-point fluid shear rate of (10.61 [cm-1]×mean velocity [cm×sec-1]). Moreover, the presence of the cylinder caused disordering of microsphere shear rates distal to higher grade stenoses, indicating a disturbance in their flow. Finally, despite lower precision, the signal recorded by the scaled-up Doppler catheter nonetheless indicated slip at the entry into and at most locations distal to the 90% stenosis. Our validated model establishes proof of concept for platelet slip, and platelet slip explains several important basic and clinical observations. If technological advances allow confirmation in a true biologic environment, then our results will likely influence the development of shear-dependent antiplatelet drugs. Also, adding shear rate information, our results provide a direct experimental fluid dynamic foundation for antiplatelet-focused antithrombotic therapy during coronary interventions directed towards higher grade atherosclerotic stenoses.

Assessment of bioresorbable scaffold with a novel high-definition 60 MHz IVUS imaging system: Comparison with 40-MHz IVUS referenced to optical coherence tomography.

BACKGROUND: In vivo assessment of bioresorbable scaffold (BRS) is of growing clinical interest. The novel 60MHz high-definition intravascular ultrasound (HD-IVUS) has been developed to overcome the limitations of conventional 40 MHz IVUS. This study aimed to evaluate the performance and limitations of 60 MHz HD-IVUS compared with 40 MHz IVUS with respect to polymeric-strut visualization, quantitative and qualitative analysis, and feasibility of high-speed pullback in the assessment of BRS. METHODS AND RESULTS: In a bench-test model, 361 struts were analyzed to evaluate the influence of ultrasound-beam angles and proximity of adjacent struts on IVUS visualization of BRS struts. Various settings were created by deforming the BRS and positioning the transducer offcenter. In an in vivo swine coronary model, scaffold and lumen areas, degree of visible external elastic membrane, incomplete strut apposition, and strut fracture were evaluated in 59 matched cross-sections obtained at conventional (0.5 mm/sec) and high speed (10 mm/sec) pullbacks. Both studies utilized optical coherence tomography (OCT) as reference. Overall, 60 MHz HD-IVUS demonstrated significantly improved visualization of polymeric struts compared with 40 MHz IVUS (well-visualized: 84.5% vs 62.3%, not visible: 4.4% vs 13.9%, respectively. P < 0.001), which was less affected by the beam angle and adjacent strut proximity. In the in vivo model, 60-MHz HD-IVUS showed better agreement of area measurements and strut abnormalities with OCT than 40 MHz IVUS. These findings were also confirmed on high-speed pullback images of 60 MHz HD-IVUS. CONCLUSION: As referenced to OCT, this study showed superiority of 60 MHz HD-IVUS over 40 MHz IVUS in the assessment of BRS with feasibility of high-speed pullback imaging.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction.

Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.

Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article.

Intracoronary and retrograde coronary venous myocardial delivery of adipose-derived stem cells in swine infarction lead to transient myocardial trapping with predominant pulmonary redistribution.

OBJECTIVES: To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery. BACKGROUND: Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. METHODS: In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery. RESULTS: IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. CONCLUSIONS: Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise.

Intravascular ultrasound analysis of small vessel lesions treated with the Sparrow coronary stent system: results of the CARE II trial.

OBJECTIVES: The aim of this study was to evaluate the Sparrow sirolimus-eluting stent (Sparrow-SES) against the Sparrow bare-metal stent (Sparrow-BMS) and conventional balloon-expandable bare-metal stent (BMS: Driver/Micro-Driver stent, Medtronic Vascular, Santa Rosa, CA). BACKGROUND: The Sparrow stent (Biosensors International, Singapore) consists of a guide wire-based, self-expandable, ultra-thin nitinol stent. The performance of this device with sirolimus in a fully biodegradable polymer has not been determined. METHODS: A total of 74 patients were included in this intravascular ultrasound (IVUS) sub-study of the CARE II trial, which was a prospective, randomized, multicenter trial in the treatment of single de novo native coronary artery lesions in vessels ranging from 2.0 mm to 2.75 mm in diameter (Sparrow-SES: n = 31, Sparrow-BMS: n = 22, BMS: n = 21). RESULTS: Stent volume index (VI) was significantly increased 8-month later in Sparrow-SES and Sparrow-BMS, but not in BMS (4.0 ± 1.0 to 4.6 ± 1.0 mm(3) /mm, p<0.0001, 4.0 ± 0.6 to 4.4 ± 0.8 mm(3) /mm, p<0.05, and 5.2 ± 1.0 to 5.1 ± 0.9 mm(3) /mm, p=0.421, respectively). % neointimal obstruction in Sparrow-SES was significantly smaller than those in Sparrow-BMS and BMS at follow-up (17.6 ± 9.4 vs. 36.2 ± 13.8 and 39.9 ± 11.1%, p<0.001). Sparrow-SES showed a mean 15% stent expansion and good suppression of neointimal proliferation, resulting in a significantly lower percentage of change in lumen VI during follow-up period (Sparrow-SES: -6.2 ± 16.2%, Sparrow-BMS: -30.4 ± 11.6%, BMS: -40.4 ± 10.0%, p<0.001). CONCLUSIONS: The self-expanding Sparrow-SES demonstrated chronic stent expansion, good suppression of neointimal proliferation and resulted in a more preserved lumen in stented small vessels compared with the Sparrow-BMS and conventional balloon expandable BMS.

Improved automated lumen contour detection by novel multifrequency processing algorithm with current intravascular ultrasound system.

OBJECTIVES: The aim of this study was to evaluate a new fully automated lumen border tracing system based on a novel multifrequency processing algorithm. BACKGROUND: We developed the multifrequency processing method to enhance arterial lumen detection by exploiting the differential scattering characteristics of blood and arterial tissue. The implementation of the method can be integrated into current intravascular ultrasound (IVUS) hardware. METHODS: This study was performed in vivo with conventional 40-MHz IVUS catheters (Atlantis SR Pro™, Boston Scientific Corp, Natick, MA) in 43 clinical patients with coronary artery disease. A total of 522 frames were randomly selected, and lumen areas were measured after automatically tracing lumen borders with the new tracing system and a commercially available tracing system (TraceAssist™) referred to as the "conventional tracing system." The data assessed by the two automated systems were compared with the results of manual tracings by experienced IVUS analysts. RESULTS: New automated lumen measurements showed better agreement with manual lumen area tracings compared with those of the conventional tracing system (correlation coefficient: 0.819 vs. 0.509). When compared against manual tracings, the new algorithm also demonstrated improved systematic error (mean difference: 0.13 vs. -1.02 mm(2) ) and random variability (standard deviation of difference: 2.21 vs. 4.02 mm(2) ) compared with the conventional tracing system. CONCLUSIONS: This preliminary study showed that the novel fully automated tracing system based on the multifrequency processing algorithm can provide more accurate lumen border detection than current automated tracing systems and thus, offer a more reliable quantitative evaluation of lumen geometry.

Lessons from Developing Multimedia Learning Materials for the Digital Generation.

Recognizing that traditional textbooks on need-driven health technology innovation were increasingly misaligned with the needs of today's undergraduate biomedical engineering students and the faculty who teach them, we initiated an effort to develop new learning materials for this audience. To guide our efforts, we conducted literature searches on best practices in the development of online content and engaging digital learners (primarily Gen-Z). We further held a series of discussions with biomedical engineering students and instructors at universities across the United States. This input led us to the development of a set of modular, online, multimedia learning materials specifically designed for the new generation of undergraduate learners. In this article, we present the key decisions that helped shape the project. We also share the results of feedback surveys and focus groups that shed light on how the materials have been preliminarily received. Finally, we reflect on challenges, opportunities, and lessons from this project that may be helpful to other initiatives focused on the creation of multimedia content for the digital generation.

Impact of myocardial bridging on coronary artery plaque formation and long-term mortality after heart transplantation.

OBJECTIVES: This study aimed to explore the impact of myocardial bridging (MB) on early development of cardiac allograft vasculopathy and long-term graft survival after heart transplantation. BACKGROUND: MB has been reported to be associated with acceleration of proximal plaque development and endothelial dysfunction in native coronary atherosclerosis. However, its clinical significance in heart transplantation remains unclear. METHODS: In 103 heart-transplant recipients, serial (baseline and 1-year post-transplant) volumetric intravascular ultrasound (IVUS) analyses were performed in the first 50 mm of the left anterior descending (LAD) artery. Standard IVUS indices were evaluated in 3 equally divided LAD segments (proximal, middle, and distal segments). MB was defined by IVUS as an echolucent muscular band lying on top of the artery. The primary endpoint was death or re-transplantation, assessed for up to 12.2 years (median follow-up: 4.7 years). RESULTS: IVUS identified MB in 62% of the study population. At baseline, MB patients had smaller intimal volume in the distal LAD than non-MB patients (p = 0.002). During the first year, vessel volume decreased diffusely irrespective of the presence of MB. Intimal growth diffusely distributed in non-MB patients, whereas MB patients demonstrated significantly augmented intimal formation in the proximal LAD. Kaplan-Meier analysis revealed significantly lower event-free survival in patients with versus without MB (log-rank p = 0.02). In multivariate analysis, the presence of MB was independently associated with late adverse events [hazard ratio 5.1 (1.6-22.2)]. CONCLUSION: MB appears to relate to accelerated proximal intimal growth and reduced long-term survival in heart-transplant recipients.

Applying a structured innovation process to interventional radiology: a single-center experience.

PURPOSE: To determine the feasibility and efficacy of applying an established innovation process to an active academic interventional radiology (IR) practice. MATERIALS AND METHODS: The Stanford Biodesign Medical Technology Innovation Process was used as the innovation template. Over a 4-month period, seven IR faculty and four IR fellow physicians recorded observations. These observations were converted into need statements. One particular need relating to gastrostomy tubes was diligently screened and was the subject of a single formal brainstorming session. RESULTS: Investigators collected 82 observations, 34 by faculty and 48 by fellows. The categories that generated the most observations were enteral feeding (n = 9, 11%), biopsy (n = 8, 10%), chest tubes (n = 6, 7%), chemoembolization and radioembolization (n = 6, 7%), and biliary interventions (n = 5, 6%). The output from the screening on the gastrostomy tube need was a specification sheet that served as a guidance document for the subsequent brainstorming session. The brainstorming session produced 10 concepts under three separate categories. CONCLUSIONS: This formalized innovation process generated numerous observations and ultimately 10 concepts to potentially to solve a significant clinical need, suggesting that a structured process can help guide an IR practice interested in medical innovation.

Head-to-head comparison of quantitative measurements between intravascular imaging systems: An in vitro phantom study.

INTRODUCTION: The present study aimed to compare the accuracy of quantitative measurements by contemporary intravascular imaging systems including optical frequency domain imaging (OFDI), frequency domain optical coherence tomography (FD-OCT), and 6 intravascular ultrasound (IVUS) systems. METHODS: We imaged five cylindrical phantom models made from an acrylic resin with known lumen diameters (1.51, 2.03, 3.04, 4.04, and 5.04 mm, respectively) using OFDI (FastView and LUNAWAVE, Terumo), FD-OCT (Dragonfly JP and ILUMIEN OPTIS, Abbott Vascular), and 6 mechanically rotating IVUS systems including a system, two 40-MHz, one 45-MHz, two 60-Mhz and one broad-band frequency IVUS systems. The OFDI, FD-OCT, and IVUS images were obtained using automated motorized pullback in a tank filled with 37-degree Celsius saline and, in cases of OFDI and FD-OCT, contrast-saline mixture (1:1 ratio) and contrast under the system setting of the refractive index for the corresponding flush medium. RESULTS: All the imaging systems showed good accuracy and excellent precision of lumen measurement with the relative differences between the measured diameter and actual phantom diameter being ranging from -2.9% to 8.0% and minimum standard deviations of the measured diameters (≤0.02 mm). CONCLUSION: The present study demonstrated that contemporary intravascular imaging systems including OFDI, FD-OCT, and IVUS provided clinically acceptable accuracy and excellent precision of quantitative lumen measurement in phantom models in vitro across a wide range of dimensions. Future research to confirm these findings in vivo are warranted.

Deep learning-based intravascular ultrasound segmentation for the assessment of coronary artery disease.

BACKGROUND: Accurate segmentation of the coronary arteries with intravascular ultrasound (IVUS) is important to optimize coronary stent implantation. Recently, deep learning (DL) methods have been proposed to develop automatic IVUS segmentation. However, most of those have been limited to segmenting the lumen and vessel (i.e. lumen-intima and media-adventitia borders), not applied to segmenting stent dimension. Hence, this study aimed to develop a DL method for automatic IVUS segmentation of stent area in addition to lumen and vessel area. METHODS: This study included a total of 45,449 images from 1576 IVUS pullback runs. The datasets were randomly split into training, validation, and test datasets (0.7:0.15:0.15). After developing the DL-based system to segment IVUS images using the training and validation datasets, we evaluated the performance through the independent test dataset. RESULTS: The DL-based segmentation correlated well with the expert-analyzed segmentation with a mean intersection over union (± standard deviation) of 0.80 ± 0.20, correlation coefficient of 0.98 (95% confidence intervals: 0.98 to 0.98), 0.96 (0.95 to 0.96), and 0.96 (0.96 to 0.96) for lumen, vessel, and stent area, and the mean difference (± standard deviation) of 0.02 ± 0.57, -0.44 ± 1.56 and - 0.17 ± 0.74 mm2 for lumen, vessel and stent area, respectively. CONCLUSION: This automated DL-based IVUS segmentation of lumen, vessel and stent area showed an excellent agreement with manual segmentation by experts, supporting the feasibility of artificial intelligence-assisted IVUS assessment in patients undergoing coronary stent implantation.

Impact of Diastolic Vessel Restriction on Quality of Life in Symptomatic Myocardial Bridging Patients Treated With Surgical Unroofing: Preoperative Assessments With Intravascular Ultrasound and Coronary Computed Tomography Angiography.

[Figure: see text].

Intravascular ultrasound predictors of long-term outcomes following ABSORB bioresorbable scaffold implantation: A pooled analysis of the ABSORB III and ABSORB Japan trials.

BACKGROUND: The long-term prognostic impact of IVUS findings following Absorb BVS implantation remains uncertain. This study aimed to identify the IVUS predictors of long-term clinical outcomes following ABSORB bioresorbable vascular scaffold (BVS) implantation from the pooled IVUS substudy cohorts of the ABSORB III and Japan trials. METHODS: A total of 298 lesions in 286 patients were enrolled with 2:1 randomization to ABSORB BVS vs. cobalt-chromium everolimus-eluting stents. This sub-analysis included 168 lesions of 160 patients in the Absorb arm whose post-procedural quantitative IVUS were available. The primary endpoint of this analysis was device-oriented composite endpoint (DOCE) of target lesion failure, including cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization. The median follow-up duration was 4.9 [3.1-5.0] years. RESULTS: During follow-up, DOCE occurred in 10.1% of lesions treated with Absorb BVS. Among several post-procedural IVUS indices associated with DOCE, non-uniform device expansion (defined as uniformity index = minimum / maximum device area) (hazard ratio 0.47 per 0.1 increase [95%CI 0.28 to 0.77]; p = 0.003) and residual reference plaque burden (hazard ratio 4.01 per 10% increase [95%CI 1.50 to 10.77]; p = 0.006) were identified as independent predictors of DOCE by Cox multivariable analysis. CONCLUSIONS: Nonuniform device expansion and substantial untreated residual plaque in reference segments were associated with long-term adverse events following BVS implantation. Baseline imaging to identify the appropriate device landing zone and procedural imaging to achieve uniform device expansion if possible (e.g. through post-dilatation) may improve clinical outcomes of BVS implantation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01751906 (ABSORB III); NCT01844284 (ABSORB Japan).

Toward a 21st-century health care system: recommendations for health care reform.

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges.

Analysis of Gender Perceptions in Health Technology: A Call to Action.

Gender diversity has been linked to positive business results. Yet limited data exist to characterize the gender landscape in health technology, a field that draws employees from both biomedical engineering and medicine. To better understand the state of gender diversity in this industry, we developed a survey to explore leadership representation and perceptions of workplace equality, job satisfaction, and work-life balance. Data from 400 + health technology professionals revealed that women are significantly underrepresented in senior leadership and that men and women experience the workplace differently. Men believe in greater numbers than females that senior leaders are focused on recruiting and promoting women, promotion criteria are equitable, and the major barrier to leadership roles for women is work/family balance. In contrast, women perceive a less meritocratic and inclusive workplace in which their ability to rise is hampered by exclusion from influential communication networks and stereotyping/bias. Perhaps as a result, more than one-third of female respondents are considering leaving their current jobs, citing dissatisfaction with management and a desire for greater advancement opportunities. This study highlights significant gender perception differences in health technology that require further study and proactive remediation for the field to fully realize the benefits of gender diversity.

Scaffold underexpansion and late lumen loss after bioresorbable scaffold implantation: Insights from ABSORB JAPAN trial.

BACKGROUND: Device underexpansion is associated with late adverse outcomes after bioresorbable vascular scaffold (BVS) implantation. This study, representing official IVUS results of the ABSORB Japan trial, aimed to characterize IVUS findings, focusing specifically on acute device expansion, and to investigate its impact on late lumen loss (LLL) with Absorb-BVS compared with cobalt-chromium everolimus-eluting stents (CoCr-EES). METHODS: ABSORB Japan enrolled 148 patients (2:1 randomization) in the IVUS cohort. Serial IVUS was prescheduled at post-procedure and 3 years. Acute device expansion was evaluated with respect to the degree and uniformity of the implanted device. RESULTS: Overall, Absorb-BVS showed smaller and more nonuniform device expansion at post-procedure, compared with CoCr-EES, which was particularly prominent in small-vessel lesions. In serial analysis, Absorb-BVS showed unique associations of smaller device expansion (r = 0.40, p = 0.001) and more nonuniformity (r = 0.29, p = 0.007) at post-procedure with greater LLL at 3 years, primarily attributable to greater negative remodeling (r = 0.39, p = 0.006). In contrast, acute device expansion showed no relation with subsequent lumen change in CoCr-EES. In Absorb-BVS, ischemic-driven target lesion or vessel revascularization (ID-TLR or ID-TVR) at 3 years occurred more frequently in small- versus large-vessel lesions (12.5% vs. 0%, p = 0.04 for ID-TLR and 15.6% vs. 2.3%, p = 0.08 for ID-TVR). Conversely, Absorb BVS had no target lesion nor vessel failure, even in small-vessel lesions, when adequate device expansion was achieved at post-procedure. CONCLUSIONS: Unlike CoCr-EES, underexpansion was associated with greater negative remodeling and LLL in Absorb-BVS. This may in part account for the poorer outcomes of Absorb-BVS than CoCr-EES when under-expanded.

Imaging gene expression in human mesenchymal stem cells: from small to large animals.

PURPOSE: To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning. MATERIALS AND METHODS: Animal protocols were approved by the Institutional Administrative Panel on Laboratory Animal Care. Transduction of human MSCs by using different doses of adenovirus that contained a cytomegalovirus (CMV) promoter driving the mutant herpes simplex virus type 1 thymidine kinase reporter gene (Ad-CMV-HSV1-sr39tk) was characterized in a cell culture. A total of 2.25 x 10(6) transduced (n = 5) and control nontransduced (n = 5) human MSCs were injected into the myocardium of 10 rats, and reporter gene expression in human MSCs was visualized with micro-PET by using the radiotracer 9-(4-[fluorine 18]-fluoro-3-hydroxymethylbutyl)-guanine (FHBG). Different numbers of transduced human MSCs suspended in either phosphate-buffered saline (PBS) (n = 4) or matrigel (n = 5) were injected into the myocardium of nine swine, and gene expression was visualized with a clinical PET-CT. For analysis of cell culture experiments, linear regression analyses combined with a t test were performed. To test differences in radiotracer uptake between injected and remote myocardium in both rats and swine, one-sided paired Wilcoxon tests were performed. In swine experiments, a linear regression of radiotracer uptake ratio on the number of injected transduced human MSCs was performed. RESULTS: In cell culture, there was a viral dose-dependent increase of gene expression and FHBG accumulation in human MSCs. Human MSC viability was 96.7% (multiplicity of infection, 250). Cardiac FHBG uptake in rats was significantly elevated (P < .0001) after human MSC injection (0.0054% injected dose [ID]/g +/- 0.0007 [standard deviation]) compared with that in the remote myocardium (0.0003% ID/g +/- 0.0001). In swine, myocardial radiotracer uptake was not elevated after injection of up to 100 x 10(6) human MSCs (PBS group). In the matrigel group, signal-to-background ratio increased to 1.87 after injection of 100 x 10(6) human MSCs and positively correlated (R(2) = 0.97, P < .001) with the number of administered human MSCs. CONCLUSION: Reporter gene imaging in human MSCs can be translated to large animals. The study highlights the importance of co-administering a "scaffold" for increasing intramyocardial retention of human MSCs.