Detection of C-Reactive Protein Using an ELISA Immunodot as a Proof-of-Concept for Paper Microfluidics

Medicine relies heavily on diagnostic testing. Before the end of 2019 – the beginning of 2020, the modernized world took for granted accurate and available diagnostic tests. The COVID-19 pandemic taught the world, even the wealthiest countries, how fragile human health can become when tests are lacking. The assumption of available testing and the confidence in test results has been seriously challenged. With these challenges, Point-of-Care (PoC) tests has transgressed medicine and science to include politics, finance, and humanity at its core. This Bard senior project is rooted in the science of a proof-of-concept paper-based ELISA Immunodot assay for the detection of C-reactive protein (CRP). CRP can be identified at varying blood concentrations found in humans physiology and disease. CRP testing is used for clinical diagnoses millions of times per month in the United States. The results confirm that the ELISA Immunodot can both distinguish CRP+ and CRP- standards and semi-quantitively predict the CRP concentration of the standard. The ability to relate the intensity of the CRP colorimetric output to a standard CRP concentration has potential applicability in future medical testing

Medical 3D printing: methods to standardize terminology and report trends.

BackgroundMedical 3D printing is expanding exponentially, with tremendous potential yet to be realized in nearly all facets of medicine. Unfortunately, multiple informal subdomain-specific isolated terminological 'silos' where disparate terminology is used for similar concepts are also arising as rapidly. It is imperative to formalize the foundational terminology at this early stage to facilitate future knowledge integration, collaborative research, and appropriate reimbursement. The purpose of this work is to develop objective, literature-based consensus-building methodology for the medical 3D printing domain to support expert consensus.ResultsWe first quantitatively survey the temporal, conceptual, and geographic diversity of all existing published applications within medical 3D printing literature and establish the existence of self-isolating research clusters. We then demonstrate an automated objective methodology to aid in establishing a terminological consensus for the field based on objective analysis of the existing literature. The resultant analysis provides a rich overview of the 3D printing literature, including publication statistics and trends globally, chronologically, technologically, and within each major medical discipline. The proposed methodology is used to objectively establish the dominance of the term "3D printing" to represent a collection of technologies that produce physical models in the medical setting. We demonstrate that specific domains do not use this term in line with objective consensus and call for its universal adoption.ConclusionOur methodology can be applied to the entirety of medical 3D printing literature to obtain a complete, validated, and objective set of recommended and synonymous definitions to aid expert bodies in building ontological consensus

The residual STL volume as a metric to evaluate accuracy and reproducibility of anatomic models for 3D printing: application in the validation of 3D-printable models of maxillofacial bone from reduced radiation dose CT images.

BackgroundThe effects of reduced radiation dose CT for the generation of maxillofacial bone STL models for 3D printing is currently unknown. Images of two full-face transplantation patients scanned with non-contrast 320-detector row CT were reconstructed at fractions of the acquisition radiation dose using noise simulation software and both filtered back-projection (FBP) and Adaptive Iterative Dose Reduction 3D (AIDR3D). The maxillofacial bone STL model segmented with thresholding from AIDR3D images at 100 % dose was considered the reference. For all other dose/reconstruction method combinations, a "residual STL volume" was calculated as the topologic subtraction of the STL model derived from that dataset from the reference and correlated to radiation dose.ResultsThe residual volume decreased with increasing radiation dose and was lower for AIDR3D compared to FBP reconstructions at all doses. As a fraction of the reference STL volume, the residual volume decreased from 2.9 % (20 % dose) to 1.4 % (50 % dose) in patient 1, and from 4.1 % to 1.9 %, respectively in patient 2 for AIDR3D reconstructions. For FBP reconstructions it decreased from 3.3 % (20 % dose) to 1.0 % (100 % dose) in patient 1, and from 5.5 % to 1.6 %, respectively in patient 2. Its morphology resembled a thin shell on the osseous surface with average thickness <0.1 mm.ConclusionThe residual volume, a topological difference metric of STL models of tissue depicted in DICOM images supports that reduction of CT dose by up to 80 % of the clinical acquisition in conjunction with iterative reconstruction yields maxillofacial bone models accurate for 3D printing

3D printed ventricular septal defect patch: a primer for the 2015 Radiological Society of North America (RSNA) hands-on course in 3D printing.

Hand-held three dimensional models of the human anatomy and pathology, tailored-made protheses, and custom-designed implants can be derived from imaging modalities, most commonly Computed Tomography (CT). However, standard DICOM format images cannot be 3D printed; instead, additional image post-processing is required to transform the anatomy of interest into Standard Tessellation Language (STL) format is needed. This conversion, and the subsequent 3D printing of the STL file, requires a series of steps. Initial post-processing involves the segmentation-demarcation of the desired for 3D printing parts and creating of an initial STL file. Then, Computer Aided Design (CAD) software is used, particularly for wrapping, smoothing and trimming. Devices and implants that can also be 3D printed, can be designed using this software environment. The purpose of this article is to provide a tutorial on 3D Printing with the test case of complex congenital heart disease (CHD). While the infant was born with double outlet right ventricle (DORV), this hands-on guide to be featured at the 2015 annual meeting of the Radiological Society of North America Hands-on Course in 3D Printing focused on the additional finding of a ventricular septal defect (VSD). The process of segmenting the heart chambers and the great vessels will be followed by optimization of the model using CAD software. A virtual patch that accurately matches the patient's VSD will be designed and both models will be prepared for 3D printing

Saturn in hot water: viscous evolution of the Enceladus torus

The detection of outgassing water vapor from Enceladus is one of the great breakthroughs of the Cassini mission. The fate of this water once ionized has been widely studied; here we investigate the effects of purely neutral-neutral interactions within the Enceladus torus. We find that, thanks in part to the polar nature of the water molecule, a cold (~180 K) neutral torus would undergo rapid viscous heating and spread to the extent of the observed hydroxyl cloud, before plasma effects become important. We investigate the physics behind the spreading of the torus, paying particular attention to the competition between heating and rotational line cooling. A steady-state torus model is constructed, and it is demonstrated that the torus will be observable in the millimeter band with the upcoming Herschel satellite. The relative strength of rotational lines could be used to distinguish between physical models for the neutral cloud.Comment: submitted to Icarus updated: references fixe

Automated axial right ventricle to left ventricle diameter ratio computation in computed tomography pulmonary angiography

Automated medical image analysis requires methods to localize anatomic structures in the presence of normal interpatient variability, pathology, and the different protocols used to acquire images for different clinical settings. Recent advances have improved object detection in the context of natural images, but they have not been adapted to the 3D context of medical images. In this paper we present a 2.5D object detector designed to locate, without any user interaction, the left and right heart ventricles in Computed Tomography Pulmonary Angiography (CTPA) images. A 2D object detector is trained to find ventricles on axial slices. Those detections are automatically clustered according to their size and position. The cluster with highest score, representing the 3D location of the ventricle, is then selected. The proposed method is validated in 403 CTPA studies obtained in patients with clinically suspected pulmonary embolism. Both ventricles are properly detected in 94.7% of the cases. The proposed method is very generic and can be easily adapted to detect other structures in medical images

Automated Axial Right Ventricle to Left Ventricle Diameter Ratio Computation in Computed Tomography Pulmonary Angiography

Background and Purpose Right Ventricular to Left Ventricular (RV/LV) diameter ratio has been shown to be a prognostic biomarker for patients suffering from acute Pulmonary Embolism (PE). While Computed Tomography Pulmonary Angiography (CTPA) images used to confirm a clinical suspicion of PE do include information of the heart, a numerical RV/LV diameter ratio is not universally reported, likely because of lack in training, inter-reader variability in the measurements, and additional effort by the radiologist. This study designs and validates a completely automated Computer Aided Detection (CAD) system to compute the axial RV/LV diameter ratio from CTPA images so that the RV/LV diameter ratio can be a more objective metric that is consistently reported in patients for whom CTPA diagnoses PE. Materials and Methods The CAD system was designed specifically for RV/LV measurements. The system was tested in 198 consecutive CTPA patients with acute PE. Its accuracy was evaluated using reference standard RV/LV radiologist measurements and its prognostic value was established for 30-day PE-specific mortality and a composite outcome of 30-day PE-specific mortality or the need for intensive therapies. The study was Institutional Review Board (IRB) approved and HIPAA compliant. Results The CAD system analyzed correctly 92.4% (183/198) of CTPA studies. The mean difference between automated and manually computed axial RV/LV ratios was 0.03±0.22. The correlation between the RV/LV diameter ratio obtained by the CAD system and that obtained by the radiologist was high (r=0.81). Compared to the radiologist, the CAD system equally achieved high accuracy for the composite outcome, with areas under the receiver operating characteristic curves of 0.75 vs. 0.78. Similar results were found for 30-days PE-specific mortality, with areas under the curve of 0.72 vs. 0.75. Conclusions An automated CAD system for determining the CT derived RV/LV diameter ratio in patients with acute PE has high accuracy when compared to manual measurements and similar prognostic significance for two clinical outcomes.Madrid-MIT M+Vision Consortiu

Simulated 50 % radiation dose reduction in coronary CT angiography using adaptive iterative dose reduction in three-dimensions (AIDR3D)

To compare the image quality of coronary CT angiography (CTA) studies between standard filtered back projection (FBP) and adaptive iterative dose reduction in three-dimensions (AIDR3D) reconstruction using CT noise additional software to simulate reduced radiation exposure. Images from 93 consecutive clinical coronary CTA studies were processed utilizing standard FBP, FBP with 50 % simulated dose reduction (FBP50 %), and AIDR3D with simulated 50 % dose reduction (AIDR50 %). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured within 5 regions-of-interest, and image quality for each reconstruction strategy was assessed by two independent readers using a 4-point scale. Compared to FBP, the SNR measured from the AIDR50 % images was similar or higher (airway: 38.3 ± 12.7 vs. 38.5 ± 14.5, p = 0.81, fat: 5.5 ± 1.9 vs. 5.4 ± 2.0, p = 0.20, muscle: 3.2 ± 1.2 vs. 3.1 ± 1.3, p = 0.38, aorta: 22.6 ± 9.4 vs. 20.2 ± 9.7, p < 0.0001, liver: 2.7 ± 1.0 vs. 2.3 ± 1.1, p < 0.0001), while the SNR of the FBP50 % images were all lower (p values < 0.0001). The CNR measured from AIDR50 % images was also higher than that from the FBP images for the aorta relative to muscle (20.5 ± 9.0 vs. 18.3 ± 9.2, p < 0.0001). The interobserver agreement in the image quality score was excellent (κ = 0.82). The quality score was significantly higher for the AIDR50 % images compared to the FBP images (3.6 ± 0.6 vs. 3.3 ± 0.7, p = 0.004). Simulated radiation dose reduction applied to clinical coronary CTA images suggests that a 50 % reduction in radiation dose can be achieved with adaptive iterative dose reduction software with image quality that is at least comparable to images acquired at standard radiation exposure and reconstructed with filtered back projection

Chandra ACIS Survey of M33 (ChASeM33): The enigmatic X-ray emission from IC131

We present the first X-ray analysis of the diffuse hot ionized gas and the point sources in IC131, after NGC604 the second most X-ray luminous giant HII region in M33. The X-ray emission is detected only in the south eastern part of IC131 (named IC131-se) and is limited to an elliptical region of ~200pc in extent. This region appears to be confined towards the west by a hemispherical shell of warm ionized gas and only fills about half that volume. Although the corresponding X-ray spectrum has 1215 counts, it cannot conclusively be told whether the extended X-ray emission is thermal, non-thermal, or a combination of both. A thermal plasma model of kT_e=4.3keV or a single power law of Gamma=2.1 fit the spectrum equally well. If the spectrum is purely thermal (non-thermal), the total unabsorbed X-ray luminosity in the 0.35-8keV energy band amounts to L_X = 6.8(8.7)x10^35erg/s. Among other known HII regions IC131-se seems to be extreme regarding the combination of its large extent of the X-ray plasma, the lack of massive O stars, its unusually high electron temperature (if thermal), and the large fraction of L_X emitted above 2keV (~40-53%). A thermal plasma of ~4keV poses serious challenges to theoretical models, as it is not clear how high electron temperatures can be produced in HII regions in view of mass-proportional and collisionless heating. If the gas is non-thermal or has non-thermal contributions, synchrotron emission would clearly dominate over inverse Compton emission. It is not clear if the same mechanisms which create non-thermal X-rays or accelerate CRs in SNRs can be applied to much larger scales of 200pc. In both cases the existing theoretical models for giant HII regions and superbubbles do not explain the hardness and extent of the X-ray emission in IC131-se.Comment: 28 pages, 7 figures and 2 tables. Accepted for publication in ApJ. For a high resolution version of the paper see http://hea-www.harvard.edu/vlp_m33_public/publications.htm