Dynamic X-ray elastography using a pulsed photocathode source.

X-ray absorption of breast cancers and surrounding healthy tissue can be very similar, a situation that sometimes leads to missed cancers or false-positive diagnoses. To increase the accuracy of mammography and breast tomosynthesis, we describe dynamic X-ray elastography using a novel pulsed X-ray source. This new imaging modality provides both absorption and mechanical properties of the imaged material. We use a small acoustic speaker to vibrate the sample while a synchronously pulsed cold cathode X-ray source images the mechanical deformation. Using these stroboscopic images, we derive two-dimensional stiffness maps of the sample in addition to the conventional X-ray image. In a breast phantom composed of ZrO2 powder embedded in gel, dynamic elastography derived stiffness maps were able to discriminate a hard inclusion from surrounding material with a contrast-to-noise ratio (CNR) of 4.5. The CNR on the corresponding absorption image was 1.1. This demonstrates the feasibility of dynamic X-ray elastography with a synchronously pulsed X-ray source.

De Novo Powered Air-Purifying Respirator Design and Fabrication for Pandemic Response.

The rapid spread of COVID-19 and disruption of normal supply chains has resulted in severe shortages of personal protective equipment (PPE), particularly devices with few suppliers such as powered air-purifying respirators (PAPRs). A scarcity of information describing design and performance criteria for PAPRs represents a substantial barrier to mitigating shortages. We sought to apply open-source product development (OSPD) to PAPRs to enable alternative sources of supply and further innovation. We describe the design, prototyping, validation, and user testing of locally manufactured, modular, PAPR components, including filter cartridges and blower units, developed by the Greater Boston Pandemic Fabrication Team (PanFab). Two designs, one with a fully custom-made filter and blower unit housing, and the other with commercially available variants (the "Custom" and "Commercial" designs, respectively) were developed; the components in the Custom design are interchangeable with those in Commercial design, although the form factor differs. The engineering performance of the prototypes was measured and safety validated using National Institutes for Occupational Safety and Health (NIOSH)-equivalent tests on apparatus available under pandemic conditions at university laboratories. Feedback was obtained from four individuals; two clinicians working in ambulatory clinical care and two research technical staff for whom PAPR use is standard occupational PPE; these individuals were asked to compare PanFab prototypes to commercial PAPRs from the perspective of usability and suggest areas for improvement. Respondents rated the PanFab Custom PAPR a 4 to 5 on a 5 Likert-scale 1) as compared to current PPE options, 2) for the sense of security with use in a clinical setting, and 3) for comfort compared to standard, commercially available PAPRs. The three other versions of the designs (with a Commercial blower unit, filter, or both) performed favorably, with survey responses consisting of scores ranging from 3 to 5. Engineering testing and clinical feedback demonstrate that the PanFab designs represent favorable alternatives to traditional PAPRs in terms of user comfort, mobility, and sense of security. A nonrestrictive license promotes innovation in respiratory protection for current and future medical emergencies.

Assessing the filtration efficiency and regulatory status of N95s and nontraditional filtering face-piece respirators available during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has severely disrupted supply chains for many types of Personal Protective Equipment (PPE), particularly surgical N95 filtering facepiece respirators (FFRs; "masks"). As a consequence, an Emergency Use Authorization (EUA) from the FDA has allowed use of industrial N95 respirators and importation of N95-type masks manufactured to international standards; these include KN95 masks from China and FFP2 masks from the European Union. METHODS: We conducted a survey of masks in the inventory of major academic medical centers in Boston, MA to determine provenance and manufacturer or supplier. We then assembled a testing apparatus at a university laboratory and performed a modified test of filtration performance using KCl and ambient particulate matter on masks from hospital inventories; an accompanying website shows how to build and use the testing apparatus. RESULTS: Over 100 different makes and models of traditional and nontraditional filtering facepiece respirators (N95-type masks) were in the inventory of surveyed U.S. teaching hospitals as opposed to 2-5 models under normal circumstances. A substantial number of unfamiliar masks are from unknown manufacturers. Many are not correctly labelled and do not perform to accepted standards and a subset are obviously dangerous; many of these masks are likely to be counterfeit. Due to the absence of publicly available information on mask suppliers and inconsistent labeling of KN95 masks, it is difficult to distinguish between legitimate and counterfeit products. CONCLUSIONS: Many FFRs available for procurement during the COVID-19 pandemic do not provide levels of fit and filtration similar to those of N95 masks and are not acceptable for use in healthcare settings. Based on these results, and in consultation with occupational health officers, we make six recommendations to assist end users in acquiring legitimate products. Institutions should always assess masks from non-traditional supply chains by checking their markings and manufacturer information against data provided by NIOSH and the latest FDA EUA Appendix A. In the absence of verifiable information on the legitimacy of mask source, institutions should consider measuring mask fit and filtration directly. We also make suggestions for regulatory agencies regarding labeling and public disclosure aimed at increasing pandemic resilience.

3D Printed frames to enable reuse and improve the fit of N95 and KN95 respirators.

BACKGROUND: In response to supply shortages caused by the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs or "masks"), which are typically single-use devices in healthcare settings, are routinely being used for prolonged periods and in some cases decontaminated under "reuse" and "extended use" policies. However, the reusability of N95 masks is limited by degradation of fit. Possible substitutes, such as KN95 masks meeting Chinese standards, frequently fail fit testing even when new. The purpose of this study was to develop an inexpensive frame for damaged and poorly fitting masks using readily available materials and 3D printing. RESULTS: An iterative design process yielded a mask frame consisting of two 3D printed side pieces, malleable wire links that users press against their face, and cut lengths of elastic material that go around the head to hold the frame and mask in place. Volunteers (n = 45; average BMI = 25.4), underwent qualitative fit testing with and without mask frames wearing one or more of four different brands of FFRs conforming to US N95 or Chinese KN95 standards. Masks passed qualitative fit testing in the absence of a frame at rates varying from 48 to 94 % (depending on mask model). For individuals who underwent testing using respirators with broken or defective straps, 80-100 % (average 85 %) passed fit testing with mask frames. Among individuals who failed fit testing with a KN95, ~ 50 % passed testing by using a frame. CONCLUSIONS: Our study suggests that mask frames can prolong the lifespan of N95 and KN95 masks by serving as a substitute for broken or defective bands without adversely affecting fit. Use of frames made it possible for ~ 73 % of the test population to achieve a good fit based on qualitative and quantitative testing criteria, approaching the 85-90 % success rate observed for intact N95 masks. Frames therefore represent a simple and inexpensive way of expanding access to PPE and extending their useful life. For clinicians and institutions interested in mask frames, designs and specifications are provided without restriction for use or modification. To ensure adequate performance in clinical settings, fit testing with user-specific masks and PanFab frames is required.

A Crisis-Responsive Framework for Medical Device Development Applied to the COVID-19 Pandemic.

The disruption of conventional manufacturing, supply, and distribution channels during the COVID-19 pandemic caused widespread shortages in personal protective equipment (PPE) and other medical supplies. These shortages catalyzed local efforts to use nontraditional, rapid manufacturing to meet urgent healthcare needs. Here we present a crisis-responsive design framework designed to assist with product development under pandemic conditions. The framework emphasizes stakeholder engagement, comprehensive but efficient needs assessment, rapid manufacturing, and modified product testing to enable accelerated development of healthcare products. We contrast this framework with traditional medical device manufacturing that proceeds at a more deliberate pace, discuss strengths and weakness of pandemic-responsive fabrication, and consider relevant regulatory policies. We highlight the use of the crisis-responsive framework in a case study of face shield design and production for a large US academic hospital. Finally, we make recommendations aimed at improving future resilience to pandemics and healthcare emergencies. These include continued development of open source designs suitable for rapid manufacturing, education of maker communities and hospital administrators about rapidly-manufactured medical devices, and changes in regulatory policy that help strike a balance between quality and innovation.

De novo Powered Air-Purifying Respirator Design and Fabrication for Pandemic Response.

The rapid spread of COVID-19 and disruption of normal supply chains resulted in severe shortages of personal protective equipment (PPE), particularly devices with few suppliers such as powered air-purifying respirators (PAPRs). A scarcity of information describing design and performance criteria represents a substantial barrier to new approaches to address these shortages. We sought to apply open-source product development to PAPRs to enable alternative sources of supply and further innovation. We describe the design, prototyping, validation, and user testing of locally manufactured, modular, PAPR components, including filter cartridges and blower units, developed by the Greater Boston Pandemic Fabrication Team (PanFab). Two designs, one with a fully custom-made filter and blower unit housing, and the other with commercially available variants (the "Custom" and "Commercial" designs respectively) were developed. Engineering performance of the prototypes was measured and safety validated using NIOSH-equivalent tests on apparatus available under pandemic conditions, at university laboratories. Feedback on designs was obtained from four individuals, including two clinicians working in an ambulatory clinical setting and two research technical staff for whom PAPR use is a standard part of occupational PPE. Respondents rated the PanFab Custom PAPR a 4 to 5 on a 5 Likert-scale 1) as compared to current PPE options, 2) for the sense of security with use in a clinical setting, and 3) for comfort. The three other versions of the designs (with a commercial blower unit, filter, or both) performed favorably, with survey responses consisting of scores ranging from 3-5. Engineering testing and clinical feedback demonstrate that the PanFab designs represents favorable alternative PAPRs in terms of user comfort, mobility, and sense of security. A nonrestrictive license promotes innovation in respiratory protection for current and future medical emergencies.

Analysis of SteraMist ionized hydrogen peroxide technology in the sterilization of N95 respirators and other PPE.

The COVID-19 pandemic has led to widespread shortages of personal protective equipment (PPE) for healthcare workers, including of N95 masks (filtering facepiece respirators; FFRs). These masks are intended for single use but their sterilization and subsequent reuse has the potential to substantially mitigate shortages. Here we investigate PPE sterilization using ionized hydrogen peroxide (iHP), generated by SteraMist equipment (TOMI; Frederick, MD), in a sealed environment chamber. The efficacy of sterilization by iHP was assessed using bacterial spores in biological indicator assemblies. After one or more iHP treatments, five models of N95 masks from three manufacturers were assessed for retention of function based on their ability to form an airtight seal (measured using a quantitative fit test) and filter aerosolized particles. Filtration testing was performed at a university lab and at a National Institute for Occupational Safety and Health (NIOSH) pre-certification laboratory. The data demonstrate that N95 masks sterilized using SteraMist iHP technology retain filtration efficiency up to ten cycles, the maximum number tested to date. A typical iHP environment chamber with a volume of ~ 80 m3 can treat ~ 7000 masks and other items (e.g. other PPE, iPADs), making this an effective approach for a busy medical center.

Assessing the quality of nontraditional N95 filtering face-piece respirators available during the COVID-19 pandemic.

BACKGROUND: During the current COVID-19 pandemic, supply chains for Personal Protective Equipment (PPE) have been severely disrupted and many products, particularly surgical N95 filtering facepiece respirators (FFRs; "masks") are in short supply. As a consequence, an Emergency Use Authorization (EUA) from the FDA has allowed importation of N95-type masks manufactured to international standards; these include KN95 masks from China and FFP2 masks from the European Union. METHODS: We conducted a survey of mask in the inventory of major academic medical centers in Boston, MA to determine provenance and manufacturer. We then assembled a simple apparatus for performing a necessary (but not sufficient) test of filtration performance and tested masks from the inventory; an accompanying website shows how to build and use the testing apparatus. RESULTS: Our survey showed that, seven months after the start of the COVID-19 pandemic, over 100 different makes and models of N95-type masks are in the inventory of local hospitals as opposed to 2-5 models under normal circumstances. A substantial number of unfamiliar masks are from unknown manufacturers. Many did not perform to accepted standards and are likely to be counterfeit. Due to the absence of publicly available information on mask suppliers in the FDA EUA and confusing or inconsistent labeling of KN95 masks, it is difficult to distinguish legitimate and counterfeit products. CONCLUSIONS: Many of the FFR masks available for procurement during the COVID-19 pandemic do not provide levels of fit and filtration similar to those of N95 masks and are not acceptable for use in healthcare settings. Based on these results, and in consultation with occupational health officers, we make six recommendations for end users to assist in acquiring legitimate products. In particular, institutions should always assess masks from non-traditional supply chains by checking their markings and manufacturer information against data provided by NIOSH and the latest FDA EUA Appendix A. In the absence of verifiable information on the legitimacy of mask source, institutions should consider measuring mask fit and filtration directly. We also make suggestions for U.S and Chinese regulatory agencies with regard to labeling and public disclosure aimed at increase pandemic resilience.

3D Printed frames to enable reuse and improve the fit of N95 and KN95 respirators.

BACKGROUND: In response to supply shortages during the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs or "masks"), which are typically single-use devices in healthcare settings, are routinely being used for prolonged periods and in some cases decontaminated under "reuse" and "extended use" policies. However, the reusability of N95 masks is often limited by degradation or breakage of elastic head bands and issues with mask fit after repeated use. The purpose of this study was to develop a frame for N95 masks, using readily available materials and 3D printing, which could replace defective or broken bands and improve fit. RESULTS: An iterative design process yielded a mask frame consisting of two 3D-printed side pieces, malleable wire links that users press against their face, and cut lengths of elastic material that go around the head to hold the frame and mask in place. Volunteers (n= 41; average BMI= 25.5), of whom 31 were women, underwent qualitative fit with and without mask frames and one or more of four different brands of FFRs conforming to US N95 or Chinese KN95 standards. Masks passed qualitative fit testing in the absence of a frame at rates varying from 48 - 92% (depending on mask model and tester). For individuals for whom a mask passed testing, 75-100% (average = 86%) also passed testing with a frame holding the mask in place. Among users for whom a mask failed in initial fit testing, 41% passed using a frame. Success varied with mask model and across individuals. CONCLUSIONS: The use of mask frames can prolong the lifespan of N95 and KN95 masks by serving as a substitute for broken or defective bands without adversely affecting fit. Frames also have the potential to improve fit for some individuals who cannot fit existing masks. Frames therefore represent a simple and inexpensive way of extending the life and utility of PPE in short supply. For clinicians and institutions interested in mask frames, designs and specifications are provided without restriction for use or modification. To ensure adequate performance in clinical settings, qualitative fit testing with user-specific masks and frames is required.

Analysis of SteraMist ionized hydrogen peroxide technology in the sterilization of N95 respirators and other PPE: a quality improvement study.

OBJECTIVE: The COVID-19 pandemic has led to widespread shortages of personal protective equipment (PPE) for healthcare workers, including filtering facepiece respirators (FFRs) such as N95 masks. These masks are normally intended for single use, but their sterilization and subsequent reuse could substantially mitigate a world-wide shortage. DESIGN: Quality assurance. SETTING: A sealed environment chamber installed in the animal facility of an academic medical center. INTERVENTIONS: One to five sterilization cycles using ionized hydrogen peroxide (iHP), generated by SteraMist equipment (TOMI; Frederick, MD). MAIN OUTCOME MEASURES: Personal protective equipment, including five N95 mask models from three manufacturers, were evaluated for efficacy of sterilization following iHP treatment (measured with bacterial spores in standard biological indicator assemblies). Additionally, N95 masks were assessed for their ability to efficiently filter particles down to 0.3um and for their ability to form an airtight seal using a quantitative fit test. Filtration efficiency was measured using ambient particulate matter at a university lab and an aerosolized NaCl challenge at a National Institute for Occupational Safety and Health (NIOSH) pre-certification laboratory. RESULTS: The data demonstrate that N95 masks sterilized using SteraMist iHP technology retain function up to five cycles, the maximum number tested to date. Some but not all PPE could also be sterilized using an iHP environmental chamber, but pre-treatment with a handheld iHP generator was required for semi-enclosed surfaces such as respirator hoses. CONCLUSIONS: A typical iHP environment chamber with a volume of ~80 m3 can treat ~7000 masks per day, as well as other items of PPE, making this an effective approach for a busy medical center.

Stationary Computed Tomography for Space and other Resource-constrained Environments.

Computed tomography (CT) is used to diagnose many emergent medical conditions, including stroke and traumatic brain injuries. Unfortunately, the size, weight, and expense of CT systems make them largely inaccessible for patients outside of major hospitals. We have designed a module containing multiple miniature x-ray sources that could allow for CT systems to be significantly lighter, smaller, and cheaper, and to operate without any moving parts. We have developed a novel photocathode-based x-ray source, created by depositing a thin film of magnesium on an electron multiplier. When illuminated by a UV LED, this photocathode emits a beam of electrons, with a beam current of up to 1 mA. The produced electrons are accelerated through a high voltage to a tungsten target. These sources are individually addressable and can be pulsed rapidly, through electronic control of the LEDs. Seven of these sources are housed together in a 17.5 degree arc within a custom vacuum manifold. A full ring of these modules could be used for CT imaging. By pulsing the sources in series, we are able to demonstrate x-ray tomosynthesis without any moving parts. With a clinical flat-panel detector, we demonstrate 3D acquisition and reconstructions of a cadaver swine lung.

Polarization sensitive optical coherence microscopy for brain imaging.

Optical coherence tomography (OCT) and optical coherence microscopy (OCM) have demonstrated the ability to investigate cyto- and myelo-architecture in the brain. Polarization-sensitive OCT provides sensitivity to additional contrast mechanisms, specifically the birefringence of myelination and, therefore, is advantageous for investigating white matter fiber tracts. In this Letter, we developed a polarization-sensitive optical coherence microscope (PS-OCM) with a 3.5 µm axial and 1.3 µm transverse resolution to investigate fiber organization and orientation at a finer scale than previously demonstrated with PS-OCT. In a reconstructed mouse brain section, we showed that at the focal depths of 20-70 µm, the PS-OCM reliably identifies the neuronal fibers and quantifies the in-plane orientation.

Real-time prostate motion assessment: image-guidance and the temporal dependence of intra-fraction motion.

BACKGROUND: The rapid adoption of image-guidance in prostate intensity-modulated radiotherapy (IMRT) results in longer treatment times, which may result in larger intrafraction motion, thereby negating the advantage of image-guidance. This study aims to qualify and quantify the contribution of image-guidance to the temporal dependence of intrafraction motion during prostate IMRT. METHODS: One-hundred and forty-three patients who underwent conventional IMRT (n=67) or intensity-modulated arc therapy (IMAT/RapidArc, n=76) for localized prostate cancer were evaluated. Intrafraction motion assessment was based on continuous RL (lateral), SI (longitudinal), and AP (vertical) positional detection of electromagnetic transponders at 10 Hz. Daily motion amplitudes were reported as session mean, median, and root-mean-square (RMS) displacements. Temporal effect was evaluated by categorizing treatment sessions into 4 different classes: IMRTc (transponder only localization), IMRTcc (transponder + CBCT localization), IMATc (transponder only localization), or IMATcc (transponder + CBCT localization). RESULTS: Mean/median session times were 4.15/3.99 min (IMATc), 12.74/12.19 min (IMATcc), 5.99/5.77 min (IMRTc), and 12.98/12.39 min (IMRTcc), with significant pair-wise difference (p<0.0001) between all category combinations except for IMRTcc vs. IMATcc (p>0.05). Median intrafraction motion difference between CBCT and non-CBCT categories strongly correlated with time for RMS (t-value=17.29; p<0.0001), SI (t-value=-4.25; p<0.0001), and AP (t-value=2.76; p<0.0066), with a weak correlation for RL (t-value=1.67; p=0.0971). Treatment time reduction with non-CBCT treatment categories showed reductions in the observed intrafraction motion: systematic error (Σ)<0.6 mm and random error (σ)<1.2 mm compared with ≤0.8 mm and <1.6 mm, respectively, for CBCT-involved treatment categories. CONCLUSIONS: For treatment durations >4-6 minutes, and without any intrafraction motion mitigation protocol in place, patient repositioning is recommended, with at least the acquisition of the lateral component of an orthogonal image pair in the absence of volumetric imaging.