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

Two Alternating Motor Programs Drive Navigation in Drosophila Larva

When placed on a temperature gradient, a Drosophila larva navigates away from excessive cold or heat by regulating the size, frequency, and direction of reorientation maneuvers between successive periods of forward movement. Forward movement is driven by peristalsis waves that travel from tail to head. During each reorientation maneuver, the larva pauses and sweeps its head from side to side until it picks a new direction for forward movement. Here, we characterized the motor programs that underlie the initiation, execution, and completion of reorientation maneuvers by measuring body segment dynamics of freely moving larvae with fluorescent muscle fibers as they were exposed to temporal changes in temperature. We find that reorientation maneuvers are characterized by highly stereotyped spatiotemporal patterns of segment dynamics. Reorientation maneuvers are initiated with head sweeping movement driven by asymmetric contraction of a portion of anterior body segments. The larva attains a new direction for forward movement after head sweeping movement by using peristalsis waves that gradually push posterior body segments out of alignment with the tail (i.e., the previous direction of forward movement) into alignment with the head. Thus, reorientation maneuvers during thermotaxis are carried out by two alternating motor programs: (1) peristalsis for driving forward movement and (2) asymmetric contraction of anterior body segments for driving head sweeping movement

Establishing the Clinical Feasibility of a Transparent Computed-Tomography Based Fractional Flow Reserve (CT-FFR) Algorithm

Coronary artery disease, a condition where plaque buildup in a coronary artery restricts blood flow to the myocardium, is a leading cause of heart disease, which is responsible for a high mortality rate in the US each year. While stress testing and echocardiography have traditionally been the gatekeepers for referrals to invasive coronary angiography (ICA) with possible revascularization, the inclusion of coronary computed tomography angiography (CTA) in risk assessment has been shown to reduce the number of normal coronary arteries found at ICA, i.e. false positives. Coronary CTA, however, provides only anatomic information. An important physiologic metric that has grown to become the gold standard in evaluation of lesion hemodynamic significance is fractional flow reserve (FFR). While FFR has traditionally been recorded in the cath lab, deriving FFR from coronary CTA imaging (CT-FFR) is gaining traction as a desirable noninvasive alternative. Already, CT FFR has been shown in various clinical trials to have superior diagnostic performance compared to CT anatomic analysis of stenosis alone. There are four essential components to the CT-FFR computational workflow: 1) CTA image segmentation and 3-D coronary tree reconstruction 2) determination of boundary conditions, including estimation of total coronary flow at rest 3) simulation of hyperemic conditions, including accounting for changes in microvascular and/or epicardial coronary resistance, and distribution of blood flow among various branches and finally 4) solving Navier-Stokes fluid dynamics equations with a computational fluid dynamics (CFD) solver. The purpose of this study was to examine how variations in several of these components individually affected the diagnostic accuracy of an open, non-proprietary CT-FFR algorithm developed and validated by the Applied Imaging Science Laboratory (AISL) at Brigham and Women’s Hospital that can be performed on a standard radiology workstation in 1 hour, using invasive FFR measurements as the reference standard. A secondary goal of this study was to investigate whether endothelial shear stress, an alternative metric that does not require hyperemic simulation, is associated with FFR and can therefore be used in lesion risk assessment. A retrospective study in 61 patients at a single medical center in Japan who underwent CTA followed by ICA show that the computational CT-FFR algorithm is fairly robust to changes in patient-specific and image specific characteristics, with a few exceptions. Optimal inlet flow boundary conditions for achieving the best CT-FFR diagnostic performance involve scaling total flow to myocardial mass. In addition, endothelial shear stress in the segment 5 mm distal to the plaque center is significantly correlated with FFR. High ESS in this segment appears to be a high-risk marker for hemodynamically significant FFR. These findings are useful for enhancing the accuracy of future CT-FFR calculations because they shed light on the optimal set of parameters that should be inputted in the CT-FFR algorithm and further establish the clinical feasibility of CT-FFR as an efficacious gatekeeper to invasive testing, able to identify those with functionally obstructive coronary artery stenosis but also reduce the number of normal arteries referred to angiography

Liver proteomic analysis reveals the key proteins involved in host immune response to sepsis

Background Sepsis is a serious infection-induced response in the host, which can result in life-threatening organ dysfunction. It is of great importance to unravel the relationship between sepsis and host immune response and its mechanisms of action. Liver is one of the most vulnerable organs in sepsis, however, the specific pathogenesis of septic liver injury has not been well understood at the protein level. Methods A total of 12 healthy Sprague–Dawley (SD) male rats aged from 6 to 8 weeks were adaptively housed in individual cages in the specific pathogen free animal room. These lab rats were grouped into two groups: treatment (N = 9) and control (N = 3) groups; only three mice from the treatment group survived and were used for subsequent experiments. A TMT-based proteomic analysis for liver tissue was performed in the septic rat model. Results A total of 37,012 unique peptides were identified, and then 6,166 proteins were determined, among which 5,701 were quantifiable. Compared to the healthy control group, the septic rat group exhibited 162 upregulated and 103 downregulated differentially expressed proteins (DEPs). The upregulated and downregulated DEPs were the most significantly enriched into the complement and coagulation cascades and metabolic pathways. Protein-protein interaction (PPI) analysis further revealed that the upregulated and downregulated DEPs each clustered in a PPI network. Several highly connected upregulated and downregulated DEPs were also enriched into the complement and coagulation cascades pathways and metabolic pathways, respectively. The parallel reaction monitoring (PRM) results of the selected DEPs were consistent with the results of the TMT analysis, supporting the proteomic data. Conclusion Our findings highlight the roles of complement and coagulation cascades and metabolic pathways that may play vital roles in the host immune response. The DEPs may serve as clinically potential treatment targets for septic liver injury

Additional file 1: Appendix 1. of Medical 3D printing: methods to standardize terminology and report trends

Sample representative terms for major disciplines, technologies, and applications. (DOCX 16 kb

The transluminal attenuation gradient in coronary CT angiography for the detection of hemodynamically significant disease: can all arteries be treated equally?

OBJECTIVE:Results of the use of the transluminal attenuation gradient (TAG) at coronary CT angiography (CCTA) to predict hemodynamically significant disease vary widely. This study tested whether diagnostic performance of TAG to predict fractional flow reserve (FFR) ≤ 0.8 is improved when applied separately to subsets of coronary arteries that carry similar physiological flow. METHODS:28 patients with 64 × 0.5 mm CCTA and invasive FFR in ≥1 major coronary artery were retrospectively evaluated. Two readers assessed TAG in each artery. The receiver operating characteristic (ROC) area under the curve (AUC) was used to assess the diagnostic performance of TAG to detect hemodynamically significant disease following a clinical use rule [negative: FFR > 0.8 or ≤ 25% diameter stenosis (DS) at invasive catheter angiography; positive: FFR ≤ 0.8 or ≥ 90% DS at invasive catheter angiography]. ROC AUC was compared for all arteries pooled together, vs separately for arteries carrying similar physiological flow (Group 1: all left anterior descending plus right-dominant left circumflex; Group 2: right-dominant RCA plus left/co-dominant left circumflex). RESULTS:Of the 84 arteries, 30 had FFR measurements, 30 had ≤25% DS and 13 had ≥90% DS. 11 arteries with 26-89% DS and no FFR measurement were excluded. TAG interobserver reproducibility was excellent (Pearson r = 0.954, Bland-Altman bias: 0.224 Hounsfield unit cm-1). ROC AUC to detect hemodynamically significant disease was higher when considering arteries separately (Group 1 AUC = 0.841, p = 0.039; Group 2 AUC = 0.840, p = 0.188), than when pooling all arteries together (AUC = 0.661). CONCLUSION:Incorporating information on the physiology of coronary flow via the particular vessel interrogated and coronary dominance may improve the accuracy of TAG, a simple measurement that can be quickly performed at the time of CCTA interpretation to detect hemodynamically significant stenosis in individual coronary arteries. Advances in knowledge: The interpretation of TAG may benefit by incorporating information regarding which coronary artery is being interrogated

Fractional Flow Reserve Estimated at Coronary CT Angiography in Intermediate Lesions: Comparison of Diagnostic Accuracy of Different Methods to Determine Coronary Flow Distribution.

Purpose To compare the diagnostic accuracy of different computed tomographic (CT) fractional flow reserve (FFR) algorithms for vessels with intermediate stenosis. Materials and Methods This cross-sectional HIPAA-compliant and human research committee-approved study applied a four-step CT FFR algorithm in 61 patients (mean age, 69 years ± 10; age range, 29-89 years) with a lesion of intermediate-diameter stenosis (25%-69%) at CT angiography who underwent FFR measurement within 90 days. The per-lesion diagnostic performance of CT FFR was tested for three different approaches to estimate blood flow distribution for CT FFR calculation. The first two, the Murray law and the Huo-Kassab rule, used coronary anatomy; the third used contrast material opacification gradients. CT FFR algorithms and CT angiography percentage diameter stenosis (DS) measurements were compared by using the area under the receiver operating characteristic curve (AUC) to detect FFRs of 0.8 or lower. Results Twenty-five lesions (41%) had FFRs of 0.8 or lower. The AUC of CT FFR determination by using contrast material gradients (AUC = 0.953) was significantly higher than that of the Huo-Kassab (AUC = 0.882, P = .043) and Murray law models (AUC = 0.871, P = .033). All three AUCs were higher than that for 50% or greater DS at CT angiography (AUC = 0.596, P < .001). Correlation of CT FFR with FFR was highest for gradients (Spearman ρ = 0.80), followed by the Huo-Kassab rule (ρ = 0.68) and Murray law (ρ = 0.67) models. All CT FFR algorithms had small biases, ranging from -0.015 (Murray) to -0.049 (Huo-Kassab). Limits of agreement were narrowest for gradients (-0.182, 0.147), followed by the Huo-Kassab rule (-0.246, 0.149) and the Murray law (-0.285, 0.256) models. Conclusion Clinicians can perform CT FFR by using a four-step approach on site to accurately detect hemodynamically significant intermediate-stenosis lesions. Estimating blood flow distribution by using coronary contrast opacification variations may improve CT FFR accuracy. © RSNA, 2017 Online supplemental material is available for this article