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Objective: Catheters and wires are used extensively in cardiac catheterization procedures. Detecting their positions in fluoroscopic X-ray images is important for several clinical applications such as motion compensation and co-registration between 2D and 3D imaging modalities. Detecting the complete length of a catheter or wire object as well as electrode positions on the catheter or wire is a challenging task. Method: In this paper, an automatic detection framework for catheters and wires is developed. It is based on path reconstruction from image tensors, which are eigen direction vectors generated from a multiscale vessel enhancement filter. A catheter or a wire object is detected as the smooth path along those eigen direction vectors. Furthermore, a real-time tracking method based on a template generated from the detection method was developed. Results: The proposed framework was tested on a total of 7,754 X-ray images. Detection errors for catheters and guidewires are 0.56 0.28 mm and 0.68 0.33 mm, respectively. The proposed framework was also tested and validated in two clinical applications. For motion compensation using catheter tracking, the 2D target registration errors (TRE) of 1.8 mm 0.9 mm was achieved. For co-registration between 2D X-ray images and 3D models from MRI images, a TRE of 2.3 0.9 mm was achieved. Conclusion: A novel and fully automatic detection framework and its clinical applications are developed. Significance: The proposed framework can be applied to improve the accuracy of image-guidance systems for cardiac catheterization procedures.

Electrostatic powder coating of osmotic pump tablets becomes increasingly attractive in pharmaceutical industry due to its dry coating process. The present study aimed to investigate the influence factors of electrostatic powder coating of osmotic pump tablets with ultrafine powders during the powder adhesion and film formation. The results of the powder adhesion evaluation indicated that the powder adhesion was significantly influenced by the liquid plasticizers and the charging voltage of the electrostatic spray gun. SEM and drug dissolution tests illustrated that coating particle size and curing time and temperature could significantly influenced the film formation process, a finer coating particle size and-/or higher curing temperature and-/or longer curing time led to a more continuous and uniform coating film. Those results indicate that a well-controlled coating film with high qualities could be fabricated by a well-designed electrostatic powder coating, suggesting it is a promising alternative for preparing osmotic drug delivery systems.

Accurate real-time catheter segmentation is an important pre-requisite for robot-assisted endovascular intervention. Most of the existing learning-based methods for catheter segmentation and tracking are only trained on small-scale datasets or synthetic data due to the difficulties of ground-truth annotation. Furthermore, the temporal continuity in intraoperative imaging sequences is not fully utilised. In this paper, we present FW-Net, an end-to-end and real-time deep learning framework for endovascular intervention. The proposed FW-Net has three modules: a segmentation network with encoder-decoder architecture, a flow network to extract optical flow information, and a novel flow-guided warping function to learn the frame-to-frame temporal continuity. We show that by effectively learning temporal continuity, the network can successfully segment and track the catheters in real-time sequences using only raw ground-truth for training. Detailed validation results confirm that our FW-Net outperforms state-of-the-art techniques while achieving real-time performance., ICRA 2020

In the present study, novel controlled porosity osmotic pump were formed by an electrostatic coating technology with ultrafine powders. Containing film forming polymer (cellulose acetate, CA) and pore former, ultrafine coating powders were electrostatically deposited onto the surface of osmotic pump cores with an electrostatic spray gun, followed by a curing step to allow those deposited ultrafine particles to coalesce and form a continuous coating film. Colloidal silicon dioxide was found to be efficient in increasing the flowability of the ultrafine coating powders, leading to a higher coating powder adhesion rate and more uniform coating film. Longer curing time and/or higher curing temperature resulted in a better and more continuous coating film. The results of dissolution tests and the modeling of the drug release profiles showed that the drug release from the electrostatic coated controlled porosity osmotic pump followed a zero-order drug release kinetics. A desirable drug release rate could be achieved by adjusting the coating level and/or the pore former ratio in the coating formulation.

Derived from dry powder coating of metals, electrostatic powder coating for pharmaceuticals is a technology for coating drug solid dosage forms. In this technology, coating powders, containing coating polymers, pigments, and other excipients, are directly sprayed onto the surface of the solid dosage forms through an electrostatic gun without using any organic solvent or water. The deposited coating powders are further cured to form a coating film. Electrostatic powder coating technology has many advantages compared to other pharmaceutical coating methods. It can eliminate the limitations caused by the organic solvent in solvent coating such as environmental issues and health problems. And electrostatic powder coating technology also surpasses aqueous coating due to its shorter processing time and less energy consumption, leading to a lower overall cost. Furthermore, the utilization of electrical attraction can promote the movement of coating powders towards the substrate, leading to an enhanced coating powder adhesion and coating efficiency, which make it more promising compared to other dry coating technologies. The objective of this review is to summarize the coating principles, apparatus, and formulations of different electrostatic powder coating technologies, giving their advantages and limitations and also analyzing the future application in the industry for each technology.

In the present study, tablets were successfully coated with ultrafine ethylcellulose powders by using an electrostatic dry powder coating technology and sustained drug release was successfully achieved. The angle of repose (AOR) of the ultrafine powders of ethylcellulose was significantly reduced by adding nano sized colloidal silicon dioxide, indicating a significant improvement of flowability. Variations in charging voltage of the electrostatic gun had a significant influence on the coating powder adhesion and coating efficiency. Lactose and triethyl citrate (TEC) were used as the solid and liquid plasticizers to reduce the glass transition temperature (Tg) of ethylcellulose. The presence of liquid plasticizer could also increase the electrical conductivity of drug tablets so as to promote the coating powder adhesion. Other factors that affect the film formation include curing time and curing temperature. Dissolution tests indicated that the drug release from electrostatic dry powder coated tablets could be altered by adjusting coating level or pore former ratio in the coating formulation.

Three-dimensional (3D) transesophageal echocardiography (TEE) is one of the most significant advances in cardiac imaging. Although TEE provides real-time 3D visualization of heart tissues and blood vessels and has no ionizing radiation, x-ray fluoroscopy still dominates in guidance of cardiac interventions due to TEE having a limited field of view and poor visualization of surgical instruments. Therefore, fusing 3D echo with live x-ray images can provide a better guidance solution. This paper proposes a novel framework for image fusion by detecting the pose of the TEE probe in x-ray images in real-time. The framework does not require any manual initialization. Instead it uses a cascade classifier to compute the position and in-plane rotation angle of the TEE probe. The remaining degrees of freedom are determined by fast marching against a template library. The proposed framework is validated on phantoms and patient data. The target registration error for the phantom was 2.1 mm. In addition, 10 patient datasets, seven of which were acquired from cardiac electrophysiology procedures and three from trans-catheter aortic valve implantation procedures, were used to test the clinical feasibility as well as accuracy. A mean registration error of 2.6 mm was achieved, which is well within typical clinical requirements.

Mechanical ventilation may contribute to the impairment of the pulmonary surfactant system, which is one of the mechanisms leading to the progression of acute lung injury. To investigate the potential protective effects of pulmonary surfactant in a rat model of ventilator-induced lung injury, the surfactant powder was aerosolized using an in-house made device designed to deliver the aerosolized powder to the inspiratory line of a rodent ventilator circuit. Rats were randomized to (i) administration of aerosolized recombinant surfactant protein C based pulmonary surfactant, (ii) intratracheally instillation of the same surfactant re-constituted in saline, and (iii) no treatment. Animals were monitored during 2 h of high-tidal volume mechanical ventilation, after which rats were sacrificed, and further analysis of lung mechanics and surfactant function were completed. Blood gas measurements during ventilation showed extended maintenance of oxygen levels above 400 mmHg in aerosol treated animals over non-treated and instilled groups, while total protein analysis showed reduced levels in the aerosol compared to non-treated groups. Dynamic captive bubble surface tension measurements showed the activity of surfactant recovered from aerosol treated animals is maintained below 1 mN/m. The prophylactic treatment of aerosolized surfactant powder reduced the severity of lung injury in this model.

Derived from powder coating of metals, pharmaceutical dry powder coatings have received great attention in the past ten years, owing to their striking potential to replace the organic solvent coating and aqueous coating used in the current pharmaceutical industry. After several initial trials of dry coating, electrostatic dry powder coating was developed and has attracted more attention due to its high coating efficiency and low overall cost. In this technology, coating powders containing coating polymers, pigments, and other excipients are directly sprayed onto the surface of the solid dosage forms without using any organic solvent or water. The deposited coating powders are cured to form a coating film. This dry powder coating technology has many advantages compared to organic solvent coating and aqueous coating. It eliminates the limitations caused by the organic solvent in solvent coating such as environmental issues and health problems. It also surpasses aqueous coating due to its shorter processing time and much greatly reduced energy consumption, leading to a lower overall cost. Specifically, electrostatic powder coating utilizes electrical attraction to promote the movement of coating powders towards the dosage forms, resulting in an enhanced coating powder adhesion, uniformity and coating efficiency, making it more promising compared to other dry coating technologies. This technology has already been developed and applied to various solid dosage forms successfully.

The present study aimed to apply a novel dry powder technology to coat pellets with different coating materials grounded into fine powders. Piroxicam, a non-steroidal anti-inflammatory drug, was used as the active pharmaceutical ingredient (API). Eudragit® EPO, Eudragit® RS/RL and Acryl EZE were used as the coating materials to achieve immediate release, sustained release and delayed release, respectively. Three steps including preheating, powder adhesion and curing were carried out to form the coating film while liquid plasticizers were used to decrease the glass transition temperature of coating powders and also served to reduce the electrical resistance of pellets. Results of SEM indicated coating film could be better formed by increasing curing temperature or extending curing time. Dissolution tests showed that three different drug release profiles, including immediate release, sustained release and delayed release, were achieved by this coating technology with different coating formulations. And the dry powder coated pellets using this developed technology exhibited an excellent stability with 1 month at 40 °C/75% RH. The coating procedure could be shortened to within 120 min and the use of fluidized hot air was minimized, both cutting down the overall cost dramatically compared to organic solvent coating and aqueous coating. All results demonstrated that the novel electrostatic dry powder coating method is a promising technology in the pharmaceutical coating industry.

Long-bone fractures such as femur fractures are very common in trauma centers. Robotic assisted fracture surgery (RAFS) can facilitate the minimally invasive surgery which reduces scarring, infection risk and long hospital stays. One important step in RAFS is to establish the coordinate system link between patient joint (rigidly connected with the robotic system) and an external tracking system. As X-ray fluoroscopic images are routinely used during the procedure, an automatic method is proposed to detect and localize landmarks on the tracking tool using live X-ray image. The proposed method uses combination of block detection, geometric model matching and principle component analysis. A successful rate of 91.3% is achieved after testing on 650 X-ray images and accuracy is within 0.5 mm.

The motion and deformation of catheters that lie inside cardiac structures can provide valuable information about the motion of the heart. In this paper we describe the formation of a novel statistical model of the motion of a coronary sinus (CS) catheter based on principal component analysis of tracked electrode locations from standard mono-plane x-ray fluoroscopy images. We demonstrate the application of our model for the purposes of retrospective cardiac and respiratory gating of x-ray fluoroscopy images in normal dose x-ray fluoroscopy images, and demonstrate how a modification of the technique allows application to very low dose scenarios. We validated our method on ten mono-plane imaging sequences comprising a total of 610 frames from ten different patients undergoing radiofrequency ablation for the treatment of atrial fibrillation. For normal dose images we established systole, end-inspiration and end-expiration gating with success rates of 100%, 92.1% and 86.9%, respectively. For very low dose applications, the method was tested on the same ten mono-plane x-ray fluoroscopy sequences without noise and with added noise at signal to noise ratio (SNR) values of √50, √10, √8, √6, √5, √2 and √1 to simulate the image quality of increasingly lower dose x-ray images. The method was able to detect the CS catheter even in the lowest SNR images with median errors not exceeding 2.6 mm per electrode. Furthermore, gating success rates of 100%, 71.4% and 85.7% were achieved at the low SNR value of √2, representing a dose reduction of more than 25 times. Thus, the technique has the potential to extract useful information whilst substantially reducing the radiation exposure.

BackgroundDeterminants for undetected dementia and late-life depression have been not well studied.AimsTo investigate risk factors for undetected dementia and depression in older communities.MethodUsing the method of the 10/66 algorithm, we interviewed a random sample of 7072 participants aged ⩽60 years in six provinces of China during 2007–2011. We documented doctor-diagnosed dementia and depression in the interview. Using the validated 10/66 algorithm we diagnosed dementia (n= 359) and depression (n= 328).ResultsWe found that 93.1% of dementia and 92.5% of depression was undetected. Both undetected dementia and depression were significantly associated with low levels of education and occupation, and living in a rural area. The risk of undetected dementia was also associated with ‘help available when needed‘, and inversely, with a family history of mental illness and having functional impairment. Undetected depression was significantly related to female gender, low income, having more children and inversely with having heart disease.ConclusionsOlder adults in China have high levels of undetected dementia and depression. General socioeconomic improvement, associated with mental health education, targeting high-risk populations are likely to increase detection of dementia and depression in older adults, providing a backdrop for culturally acceptable service development.

Dry powder coated osmotic drug delivery system (ODDS) were prepared and characterized using an innovative powder coating technology. Coating powder adhesion to the surface of the ODDS core was firstly performed through an electrostatic spray gun, followed by a curing step to allow those electrically deposited particles coalesce and form a continuous, uniform and strong coating film, which is the semipermeable membrane of the ODDS. Triethyl citrate (TEC) was found to be a better liquid plasticizer than PEG 400 both in reducing the glass transition temperature of the coating polymer (cellulose acetate) and in increasing the electrical conductivity of the ODDS cores, both of which led to an enhanced coating powder adhesion and film formation. Results of SEM indicated that the uniformity of the coating film varied significantly with the difference of curing time and temperature. Salbutamol sulfate and ibuprofen were used as the model drugs. Release profiles of both showed that zero-order drug release kinetics was achieved. Release rate of both drugs from powder coated ODDS could be adjusted by changing the coating level but was independent of the agitation speed and of the pH of the release media.

Guiding catheters and guidewires are used extensively in pediatric cardiac catheterization procedures for congenital heart diseases (CHD). Detecting their positions in fluoroscopic X-ray images is important for several clinical applications, such as visibility enhancement for low dose X-ray images, and co-registration between 2D and 3D imaging modalities. As guiding catheters are made from thin plastic tubes, they can be deformed by cardiac and breathing motions. Therefore, detection is the essential step before automatic tracking of guiding catheters in live X-ray fluoroscopic images. However, there are several wire-like artifacts existing in X-ray images, which makes developing a real-time robust detection method very challenging. To solve those challenges in real-time, a localized machine learning algorithm is built to distinguish between guiding catheters and artifacts. As the machine learning algorithm is only applied to potential wire-like objects, which are obtained from vessel enhancement filters, the detection method is fast enough to be used in real-time applications. The other challenge is the low contrast between guiding catheters and background, as the majority of X-ray images are low dose. Therefore, the guiding catheter might be detected as a discontinuous curve object, such as a few disconnected line blocks from the vessel enhancement filter. A minimum energy method is developed to trace the whole wire object. Finally, the proposed methods are tested on 1102 images which are from 8 image sequences acquired from 3 clinical cases. Results show an accuracy of 0.87 ± 0.53 mm which is measured as the error distances between the detected object and the manually annotated object. The success rate of detection is 83.4%.

A novel active and multi-dose dry powder inhaler (DPI) was developed and evaluated to deliver a small quantity (100-500 μg) of pure drug without any excipient. This dry powder inhaler utilized two compressed air flows to dispense and deliver drug powder: the primary flow aerosolizes the drug powder from its pocket and the secondary flow further disperses the aerosol. In vitro tests by Anderson Cascade Impactor (ACI) indicated that the fine particle fraction (FPF) (4.7 μm) of drug delivery could reach over a range of 50-70% (w/w). Emitted dose tests showed that delivery efficiency was above 85% and its relative standard deviation (RSD) was under 10%. Confocal microscopy was used to confirm the deposition of fluorescently labeled spray-dried powder in rabbit lungs. Also, a chromatographic method was used to quantify drug deposition. The results of animal tests showed that 57% of aerosol deposited in the rabbit lung and 24% deposited in its trachea. All the results implied that this novel active dry powder inhaler could efficiently deliver a small quantity of fine drug particles into the lung with quite high fine particle fraction.

Background: It is not clear whether there is a large difference in acute hemodynamic response (AHR) to left ventricle (LV) pacing in different regions of the same coronary sinus (CS) vein. Using the four electrodes available on a Quartet LV lead, we evaluated the AHR to pacing within individual branches of the CS. Methods: An acute hemodynamic study was attempted in 20 patients. In each patient, we assessed AHR in a number of CS veins and along a significant proportion of each CS branch using three different bipolar configurations. We compared the AHR achieved when pacing using each different vector and also the highest AHR achieved in any position within the same patient with the lowest achieved in that patient. Results: Sixty-four different CS positions in 19 patients were successfully assessed. No significant difference in AHR was found overall between the three vectors tested. The mean percentage difference in AHR between the CS branch vectors with the lowest and highest dP/dt(max) was +6.5 +/- 5.4% (P

Aims Multi-site left ventricular (LV) pacing may be superior to single-site stimulation in correcting dyssynchrony and avoiding areas of myocardial scar. We sought to characterize myocardial scar using cardiac magnetic resonance imaging (CMR). We aimed to quantify the acute haemodynamic response to single-site and multi-site LV stimulation and to relate this to the position of the LV leads in relation to myocardial scar. Methods Twenty patients undergoing cardiac resynchronization therapy had implantation of two LV leads. One lead (LV1) was positioned in a postero-lateral vein, the second (LV2) in a separate coronary vein. LV d P /d t max was recorded using a pressure wire during stimulation at LV1, LV2, and both sites simultaneously (LV1 + 2). Patients were deemed acute responders if ΔLV d P /d t max was ≥10%. Cardiac magnetic resonance imaging was performed to assess dyssynchrony as well as location and burden of scar. Scar anatomy was registered with fluoroscopy to assess LV lead position in relation to scar. Results LV d P /d t max increased from 726 ± 161 mmHg/s in intrinsic rhythm to 912 ± 234 mmHg/s with LV1, 837 ± 188 mmHg/s with LV2, and 932 ± 201 mmHg/s with LV1 and LV2. Nine of 19 (47%) were acute responders with LV1 vs. 6/19 (32%) with LV2. Twelve of 19 (63%) were acute responders with simultaneous LV1 + 2. Two of three patients benefitting with multi-site pacing had the LV1 lead positioned in postero-lateral scar. Conclusion Multi-site LV pacing increased acute response by 16% vs. single-site pacing. This was particularly beneficial in patients with postero-lateral scar identified on CMR.

Background Previous studies indicated overall relatively low prevalence of dementia in older people in China, which may be biased by studied samples or methods. We determined the prevalence of dementia cases and subcases in China and examined their socio-economic correlates. Methods Using the Geriatric Mental State interview, we examined random samples of 2917 participants aged ≥ 65 years in urban and rural Anhui, China in 2001–2003, and 3327 in four other provinces in 2008–2009. Dementia cases and subcases were diagnosed by Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy. Results Age-standardised prevalence for cases and subcases of dementia in the Anhui elders was 7.20% (95%CI 6.29%–8.20%) and 10.5% (9.38%–11.6%), and in the four provinces, 9.86% (8.80%–10.9%) and 8.51% (7.51%–9.52%). The matched figures among the participants who were literate were 3.05% (2.08%–4.02%) and 10.0% (8.38%–11.6%), and 4.92% (3.89%–5.96%) and 6.76% (5.55%–7.96%), respectively. There were higher prevalence rates of dementia cases and subcases in the rural elders than in the urban. Both the Anhui and four-province studies showed an obvious association of dementia with higher and lower incomes among elders who had lower educational levels or had the lowest occupational class. The highest risk of dementia was found in those who were illiterate but had the highest income or had the job of business/nonmanual labouring. Conclusions People in China have a higher prevalence of dementia than previously reported. Its U-shaped relationship with income and the excess subcases prevalence predicates a significant burden of disease, both now and for the future, suggesting preventive strategy for dementia in China. Copyright © 2011 John Wiley & Sons, Ltd.

Background: Failure rate for left ventricular (LV) lead implantation in cardiac resynchronization therapy (CRT) is up to 12%. The use of segmentation tools, advanced image registration software, and high-fidelity images from computerized tomography (CT) and cardiac magnetic resonance (CMR) of the coronary sinus (CS) can guide LV lead implantation. We evaluated the feasibility of advanced image registration onto live fluoroscopic images to allow successful LV lead placement. Methods: Twelve patients (11 male, 59 ± 16.8 years) undergoing CRT had three-dimensional (3D) whole-heart imaging (six CT, six CMR). Eight patients had at least one previously failed LV lead implant. Using segmentation software, anatomical models of the cardiac chambers, CS, and its branches were overlaid onto the live fluoroscopy using a prototype version of the Philips EP Navigator software to guide lead implantation. Results: We achieved high-fidelity segmentations of cardiac chambers, coronary vein anatomy, and accurate registration between the 3D anatomical models and the live fluoroscopy in all 12 patients confirmed by balloon occlusion angiography. The CS was cannulated successfully in every patient and in 11, an LV lead was implanted successfully. (One patient had no acceptable lead values due to extensive myocardial scar.) Conclusion: Using overlaid 3D segmentations of the CS and cardiac chambers, it is feasible to guide CRT implantation in real time by fusing advanced imaging and fluoroscopy. This enabled successful CRT in a group of patients with previously failed implants. This technology has the potential to facilitate CRT and improve implant success. (PACE 2011; 34:226–234)

We present a feasibility study on hybrid echocardiography (echo) and x-ray image guidance for cardiac catheterization procedures. A self-tracked, remotely operated robotic arm with haptic feedback was developed that attached to a standard x-ray table. This was used to safely manipulate a three-dimensional (3D) trans-thoracic echo probe during simultaneous x-ray fluoroscopy and echo acquisitions. By a combination of calibration and tracking of the echo and x-ray systems, it was possible to register the 3D echo images with the 2D x-ray images. Visualization of the combined data was achieved by either overlaying triangulated surfaces extracted from segmented echo data onto the x-ray images or by overlaying volume rendered 3D echo data. Furthermore, in order to overcome the limited field of view of the echo probe, it was possible to create extended field of view (EFOV) 3D echo images by co-registering multiple tracked echo data to generate larger roadmaps for procedure guidance. The registration method was validated using a cross-wire phantom and showed a 2D target registration error of 3.5 mm. The clinical feasibility of the method was demonstrated during two clinical cases for patients undergoing cardiac pacing studies. The EFOV technique was demonstrated using two healthy volunteers.

For many image-guided interventions there exists a need to compute the registration between preprocedure image(s) and the physical space of the intervention. Real-time intraprocedure imaging such as ultrasound (US) can be used to image the region of interest directly and provide valuable anatomical information for computing this registration. Unfortunately, real-time US images often have poor signal-to-noise ratio and suffer from imaging artefacts. Therefore, registration using US images can be challenging and significant preprocessing is often required to make the registrations robust. In this paper we present a novel technique for computing the image-to-physical registration for minimally invasive cardiac interventions using 3-D US. Our technique uses knowledge of the physics of the US imaging process to reduce the amount of preprocessing required on the 3-D US images. To account for the fact that clinical US images normally undergo significant image processing before being exported from the US machine our optimization scheme allows the parameters of the US imaging model to vary. We validated our technique by computing rigid registrations for 12 cardiac US/magnetic resonance imaging (MRI) datasets acquired from six volunteers and two patients. The technique had mean registration errors of 2.1-4.4 mm, and 75% capture ranges of 5-30 mm. We also demonstrate how the same approach can be used for respiratory motion correction: on 15 datasets acquired from five volunteers the registration errors due to respiratory motion were reduced by 45%-92%.

Determination of the cardiorespiratory phase of the heart has numerous applications during cardiac imaging. In this article we propose a novel view-angle independent near-real time cardiorespiratory motion gating and coronary sinus (CS) catheter tracking technique for x-ray fluoroscopy images that are used to guide cardiac electrophysiology procedures. The method is based on learning CS catheter motion using principal component analysis and then applying the derived motion model to unseen images taken at arbitrary projections, using the epipolar constraint. This method is also able to track the CS catheter throughout the x-ray images in any arbitrary subsequent view. We also demonstrate the clinical application of our model on rotational angiography sequences. We validated our technique in normal and very low dose phantom and clinical datasets. For the normal dose clinical images we established average systole, end-expiration and end-inspiration gating success rates of 100%, 85.7%, and 92.3%, respectively. For very low dose applications, the technique was able to track the CS catheter with median errors not exceeding 1 mm for all tracked electrodes. Average gating success rates of 80.3%, 71.4%, and 69.2% were established for the application of the technique on clinical datasets, even with a dose reduction of more than 10 times. In rotational sequences at normal dose, CS tracking median errors were within 1.2 mm for all electrodes, and the gating success rate was 100%, for view angles from RAO 90° to LAO 90°. This view-angle independent technique can extract clinically useful cardiorespiratory motion information using x-ray doses significantly lower than those currently used in clinical practice.

We present a fast, accurate, and robust method to compute the minimum distance between two 2D and 3D NURBS curves. This is carried out by first decomposing both of the NURBS curves into their piecewise-Bezier forms. Candidate pairs, as a subset of all possible pairs, are extracted based on a two-level selection process. The first-level selection uses upper-lower bounds of Bezier subcurves to remove pairs. The second-level selection is based on the spatial relationship test between a pair of Bezier curves. An iterative multidimensional Newton-Raphson method is applied on all candidate pairs in order to calculate the approximate local minimum distances. Finally, by comparing all local minimum distances between a pair of Bezier subcurves, we are able to find the global minimum distance. The accuracy is improved by further use of the multidimensional Newton-Raphson method to give high accuracy. Source code is available online.

This paper concentrates on CAD/CAM for a special yet useful type of 3D cellular woven structure. Mathematical algorithms have been developed for the creation of weave diagrams and lifting plans for the design and manufacture of this type of 3D woven structure. The algorithms are implemented in a newly created CAD/CAM package which has proven to be useful. As an inportant aspect of the work, the NURBS technique is used for the visualisation of the structures. The advantages of NURBS include more controllable curves and surfaces and therefore more realistic images for woven structures.

This paper presents an accurate and efficient method to solve both point projection and point inversion for NURBS curves and surfaces. We first subdivide the NURBS curve or surface into a set of Bezier subcurves or patches. Based on the relationship between the test point and the control polygon of Bezier curve or the control point net of the Bezier patch, we extract candidate Bezier subcurves or Bezier patches and then find the approximate candidate points. Finally, by comparing the distances between the test point and candidate points, we are able to find the closest point. We improve its accuracy by using the Newton-Raphson method.

Cardiorespiratory phase determination has numerous applications during cardiac imaging. We propose a novel view-angle independent prospective cardiorespiratory motion gating technique for X-ray fluoroscopy images that are used to guide cardiac electrophysiology procedures. The method is based on learning coronary sinus catheter motion using principal component analysis and then applying the derived motion model to unseen images taken at arbitrary projections. We validated our technique on 7 sequential biplane sequences in normal and very low dose scenarios and on 5 rotational sequences in normal dose. For the normal dose images we established average systole, end-inspiration and end-expiration gating success rates of 100 %, 97.4 % and 95.2 %, respectively. For very low dose applications, the method was tested on images with added noise. Average gating success rates were 93.4 %, 90 % and 93.4 % even at the low SNR value of \(\sqrt{5}\), representing a dose reduction of more than 10 times. This technique can extract clinically useful motion information whilst minimising exposure to ionising radiation.

Image-guided cardiac interventions involve the use of fluoroscopic images to guide the insertion and movement of interventional devices. Cardiorespiratory gating can be useful for 3D reconstruction from multiple x-ray views and for reducing misalignments between 3D anatomical models overlaid onto fluoroscopy.The authors propose a novel and potentially clinically useful retrospective cardiorespiratory gating technique. The principal component analysis (PCA) statistical method is used in combination with other image processing operations to make our proposed masked-PCA technique suitable for cardiorespiratory gating. Unlike many previously proposed techniques, our technique is robust to varying image-content, thus it does not require specific catheters or any other optically opaque structures to be visible. Therefore, it works without any knowledge of catheter geometry. The authors demonstrate the application of our technique for the purposes of retrospective cardiorespiratory gating of normal and very low dose x-ray fluoroscopy images.For normal dose x-ray images, the algorithm was validated using 28 clinical electrophysiology x-ray fluoroscopy sequences (2168 frames), from patients who underwent radiofrequency ablation (RFA) procedures for the treatment of atrial fibrillation and cardiac resynchronization therapy procedures for heart failure. The authors established end-systole, end-expiration, and end-inspiration success rates of 97.0%, 97.9%, and 97.0%, respectively. For very low dose applications, the technique was tested on ten x-ray sequences from the RFA procedures with added noise at signal to noise ratio (SNR) values of √50, √10, √8, √6, √5, √2 and √1 to simulate the image quality of increasingly lower dose x-ray images. Even at the low SNR value of √2, representing a dose reduction of more than 25 times, gating success rates of 89.1%, 88.8%, and 86.8% were established.The proposed technique can therefore extract useful information from interventional x-ray images while minimizing exposure to ionizing radiation.

For most cardiac catheterization interventions, X-ray imaging is currently used as a standard imaging technique. However, lack of 3D soft tissue information and harmful radiation mean that X-ray imaging is not an ideal modality. In contrast, 3D echocardiography can overcome these disadvantages. In this paper, we propose a fast catheter tracking strategy for 3D ultrasound sequences. The main advantage of our strategy is low use of X-ray imaging, which significantly decreases the radiation exposure. In addition, 3D soft tissue imaging can be introduced by using ultrasound. To enable the tracking procedure, initialization is carried out on the first ultrasound frame. Given the location of the catheter in the previous frame, which is in the form of a set of ordered landmarks, 3D Speeded-Up Robust Feature SURF responses are calculated for candidate voxels in the surrounding region of each landmark on the next frame. One candidate is selected among all voxels for each landmark based on Fast Primal-Dual optimization Fast-PD. As a result, a new set of ordered landmarks is extracted, corresponding to the potential location of the catheter on the next frame. In order to adapt the tracking to the changing length of the catheter in the view, landmarks which may not be located on the catheter are ruled out. Then a catheter growing strategy is performed to extend the tracked part of the catheter to the untracked part. Based on 10 ultrasound phantom sequences and two clinical sequences, comprising more than 1300 frames, our experimental results show that the tracking system can track catheters with an error of less than 2.5mm and a speed of more than 3 fps.

We present a novel and clinically useful method to automatically determine the regions that carry cardiac and respiratory motion information directly from standard mono-plane X-ray fluoroscopy images. We demonstrate the application of our method for the purposes of retrospective cardiac and respiratory gating of X-ray images. Validation is performed on five mono-plane imaging sequences comprising a total of 284 frames from five patients undergoing radiofrequency ablation for the treatment of atrial fibrillation. We established end-inspiration, end-expiration and systolic gating with success rates of 100%, 100% and 95.3%, respectively. This technique is useful for retrospective gating of X-ray images and, unlike many previously proposed techniques, does not require specific catheters to be visible and works without any knowledge of catheter geometry.

Real-time imaging is required to guide minimally invasive catheter-based cardiac interventions. While transesophageal echocardiography allows for high-quality visualization of cardiac anatomy, X-ray fluoroscopy provides excellent visualization of devices. We have developed a novel image fusion system that allows real-time integration of 3-D echocardiography and the X-ray fluoroscopy. The system was validated in the following two stages: 1) preclinical to determine function and validate accuracy; and 2) in the clinical setting to assess clinical workflow feasibility and determine overall system accuracy. In the preclinical phase, the system was assessed using both phantom and porcine experimental studies. Median 2-D projection errors of 4.5 and 3.3 mm were found for the phantom and porcine studies, respectively. The clinical phase focused on extending the use of the system to interventions in patients undergoing either atrial fibrillation catheter ablation (CA) or transcatheter aortic valve implantation (TAVI). Eleven patients were studied with nine in the CA group and two in the TAVI group. Successful real-time view synchronization was achieved in all cases with a calculated median distance error of 2.2 mm in the CA group and 3.4 mm in the TAVI group. A standard clinical workflow was established using the image fusion system. These pilot data confirm the technical feasibility of accurate real-time echo-fluoroscopic image overlay in clinical practice, which may be a useful adjunct for real-time guidance during interventional cardiac procedures.

X-ray fluoroscopically guided cardiac electrophysiology (EP) procedures are commonly carried out to treat patients with arrhythmias. X-ray images have poor soft tissue contrast and, for this reason, overlay of a three-dimensional (3D) roadmap derived from preprocedural volumetric images can be used to add anatomical information. It is useful to know the position of the catheter electrodes relative to the cardiac anatomy, for example, to record ablation therapy locations during atrial fibrillation therapy. Also, the electrode positions of the coronary sinus (CS) catheter or lasso catheter can be used for road map motion correction.In this paper, the authors present a novel unified computational framework for image-based catheter detection and tracking without any user interaction. The proposed framework includes fast blob detection, shape-constrained searching and model-based detection. In addition, catheter tracking methods were designed based on the customized catheter models input from the detection method. Three real-time detection and tracking methods are derived from the computational framework to detect or track the three most common types of catheters in EP procedures: the ablation catheter, the CS catheter, and the lasso catheter. Since the proposed methods use the same blob detection method to extract key information from x-ray images, the ablation, CS, and lasso catheters can be detected and tracked simultaneously in real-time.The catheter detection methods were tested on 105 different clinical fluoroscopy sequences taken from 31 clinical procedures. Two-dimensional (2D) detection errors of 0.50 ± 0.29, 0.92 ± 0.61, and 0.63 ± 0.45 mm as well as success rates of 99.4%, 97.2%, and 88.9% were achieved for the CS catheter, ablation catheter, and lasso catheter, respectively. With the tracking method, accuracies were increased to 0.45 ± 0.28, 0.64 ± 0.37, and 0.53 ± 0.38 mm and success rates increased to 100%, 99.2%, and 96.5% for the CS, ablation, and lasso catheters, respectively. Subjective clinical evaluation by three experienced electrophysiologists showed that the detection and tracking results were clinically acceptable.The proposed detection and tracking methods are automatic and can detect and track CS, ablation, and lasso catheters simultaneously and in real-time. The accuracy of the proposed methods is sub-mm and the methods are robust toward low-dose x-ray fluoroscopic images, which are mainly used during EP procedures to maintain low radiation dose.

Surface flattening in medical imaging has seen widespread use in neurology and more recently in cardiology to describe the left ventricle using the bull's-eye plot. The method is particularly useful to standardize the display of functional information derived from medical imaging and catheter-based measurements. We hypothesized that a similar approach could be possible for the more complex shape of the left atrium (LA) and that the surface flattening could be useful for the management of patients with atrial fibrillation (AF). We implemented an existing surface mesh parameterization approach to flatten and unfold 3D LA models. Mapping errors going from 2D to 3D and the inverse were investigated both qualitatively and quantitatively using synthetic data of regular shapes and computer tomography scans of an anthropomorphic phantom. Testing of the approach was carried out using data from 14 patients undergoing ablation treatment for AF. 3D LA meshes were obtained from magnetic resonance imaging and electroanatomical mapping systems. These were unfolded using the developed approach and used to demonstrate proof-of-concept applications, such as the display of scar information, electrical information and catheter position. The work carried out shows that the unfolding of complex cardiac structures, such as the LA, is feasible and has several potential clinical uses for the management of patients with AF.

Although X-ray imaging has played a dominant role in cardiac catheter-based interventions, sometimes 3D soft tissue information, which X-ray images cannot provide, may be required. In contrast, 3D echocardiographic imaging is able to visualise soft tissue. In this paper, we propose a real-time catheter tracking strategy in echocardiographic sequences based on catheter tracking in 2D X-ray images and registration between these two modalities. The catheter tracking in X-ray images can be divided into catheter initialization and tracking. For initialization, an extraction algorithm based on SURF features, patch analysis and Kalman filtering is used to locate the catheter in the first X-ray image. Following this, a tracking algorithm based on patch analysis and Fast-PD optimization is used to track the catheter in the following images. The tracking result of each X-ray frame, as well as the transformation between X-ray and ultrasound images obtained from registration, is used to reduce the search space in the echo volume to only a curved surface. Using a graphical model and shortest path optimization, the position of the catheters in each echo frame can be estimated. Based on 10 pairs of X-ray and US sequences, comprising more than 800 frames, our experimental results show that the tracking system can track catheters with an average error of less than 1mm in X-ray images and less than 2mm in US. Also, our strategy for tracking in X-ray outperforms previous methods using only Fast-PD. The speed in total can reach 1.5 fps.

A 60-year-old man underwent attempted cardiac resynchronization with defibrillator therapy utilizing a left-sided approach. A persistent left-sided superior vena cava (SVC) was identified and a dual-coil defibrillator lead (Sprint Fidelis; Medtronic) and atrial lead were deployed via this route ( Figure 1A ). No left ventricular (LV) branches of …

Body surface potential mapping (BSPM) can be used to non-invasively measure the electrical activity of the heart using a dense set of thorax electrodes and a CT/MR scan of the thorax to solve the inverse problem of electrophysiology (ECGi). This technique now shows potential clinical value for the assessment and treatment of patients with arrhythmias. Co-localisation of the electrode positions and the CT/MR thorax scan is essential. This manuscript describes a method to perform the co-localisation using multiple biplane X-ray images. The electrodes are automatically detected and paired in the X-ray images. Then the 3D positions of the electrodes are computed and mapped onto the thorax surface derived from CT/MR. The proposed method is based on a multi-scale blob detection algorithm and the generalized Hough transform, which can automatically discriminate the leads used for BSPM from other ECG leads. The pairing method is based on epi-polar constraint matching and line pattern detection which assumes that BSPM electrodes are arranged in strips. The proposed methods are tested on a thorax phantom and two clinical cases. Results show an accuracy of 0.33 ± 0.20mm for detecting electrodes in the X-ray images and a success rate of 95.4%. The automatic pairing method achieves a 91.2% success rate.

This paper presents collated results from the Delayed Enhancement MRI (DE-MRI) segmentation challenge at MICCAI 2012. DE-MRI Images from fifteen patients and fifteen pigs were randomly selected from two different imaging centres. Three independent sets of manual segmentations were obtained for each image and included in this study. A ground truth consensus segmentation based on all human rater segmentations was obtained using an Expectation-Maximization (EM) method (the STAPLE method). Automated segmentations from five groups contributed to this challenge.

Image guidance of minimally invasive cardiac interventions can be augmented by registering together different imaging modalities. In this paper, we propose a method to combine three modalities: X-ray fluoroscopy, trans-esophageal ultrasound and pre-procedure MRI or CT. The registration of the pre-procedure image involves a potentially unreliable manual initialisation of its position in an X-ray projection view. The method therefore includes an automatic correction using the esophagus location as an additional constraint. We test the method in a phantom experiment and find that initialising the pre-procedure image with up to 9mm offset from its correct position results in a 92% registration success rate. The esophagus constraint improves the capture range in the out-of-plane direction, which simplifies the manual initialisation.

Delayed-enhancement magnetic resonance imaging (DE-MRI) is an effective technique for imaging left ventricular (LV) infarct. Existing techniques for LV infarct segmentation are primarily threshold-based making them prone to high user variability. In this work, we propose a segmentation algorithm that can learn from training images and segment based on this training model. This is implemented as a Markov random field (MRF) based energy formulation solved using graph-cuts. A good agreement was found with the Full-Width-at-Half-Maximum (FWHM) technique.

Objectives Environmental tobacco smoke (ETS) has a range of adverse health effects, but its association with dementia remains unclear and with dementia syndromes unknown. We examined the dose–response relationship between ETS exposure and dementia syndromes. Methods Using a standard method of GMS, we interviewed 5921 people aged ≥60 years in five provinces in China in 2007–2009 and characterised their ETS exposure. Five levels of dementia syndrome were diagnosed using the Automated Geriatric Examination for Computer Assisted Taxonomy instrument. The relative risk (RR) of moderate (levels 1–2) and severe (levels 3–5) dementia syndromes among participants exposed to ETS was calculated in multivariate adjusted regression models. Results 626 participants (10.6%) had severe dementia syndromes and 869 (14.7%) moderate syndromes. Participants exposed to ETS had a significantly increased risk of severe syndromes (adjusted RR 1.29, 95% CI 1.05 to 1.59). This was dose-dependently related to exposure level and duration. The cumulative exposure dose data showed an adjusted RR of 0.99 (95% CI 0.76 to 1.28) for >0–24 level years of exposure, 1.15 (95% CI 0.93 to 1.42) for 25–49 level years, 1.18 (95% CI 0.87 to 1.59) for 59–74 level years, 1.39 (95% CI 1.03 to 1.84) for 75–99 level years and 1.95 (95% CI 1.34 to 2.83) for ≥100 level years. Significant associations with severe syndromes were found in never smokers and in former/current smokers. There were no positive associations between ETS and moderate dementia syndromes. Conclusions ETS should be considered an important risk factor for severe dementia syndromes. Avoidance of ETS may reduce the rates of severe dementia syndromes worldwide.

Gating of X-ray fluoroscopy images is required for catheter reconstruction for registration of pre-procedural images with fluoroscopy for guidance and biophysical modelling. We propose a novel and clinically useful retrospective method for automatic image-based cardiac and respiratory motion gating. The technique is based on tracking and statistical analysis of the shape of the coronary sinus catheter. We applied our method on five mono-plane imaging sequences comprising a total of 322 frames from five different patients undergoing radiofrequency ablation for the treatment of atrial fibrillation. We established systole, end-inspiration and end-expiration gating with success rates of 100%, 89.47% and 81.25% respectively.

Cardiac electrophysiology procedures are routinely used to treat patients with rhythm disorders. The success rates of ablation procedures and cardiac resynchronization therapy are still sub-optimal. Recent advances in medical imaging, image processing and cardiac biophysical modeling have the potential to improve patient outcome. This manuscript provides an overview of how these advances have been translated into the clinical environment.

Cardiac resynchronization therapy (CRT) is an effective procedure for patients with heart failure but 30% of patients do not respond. This may be due to sub-optimal placement of the left ventricular (LV) lead. It is hypothesized that the use of cardiac anatomy, myocardial scar distribution and dyssynchrony information, derived from cardiac magnetic resonance imaging (MRI), may improve outcome by guiding the physician for optimal LV lead positioning. Whole heart MR data can be processed to yield detailed anatomical models including the coronary veins. Cine MR data can be used to measure the motion of the LV to determine which regions are late-activating. Finally, delayed Gadolinium enhancement imaging can be used to detect regions of scarring. This paper presents a complete platform for the guidance of CRT using pre-procedural MR data combined with live x-ray fluoroscopy. The platform was used for 21 patients undergoing CRT in a standard catheterization laboratory. The patients underwent cardiac MRI prior to their procedure. For each patient, a MRI-derived cardiac model, showing the LV lead targets, was registered to x-ray fluoroscopy using multiple views of a catheter looped in the right atrium. Registration was maintained throughout the procedure by a combination of C-arm/x-ray table tracking and respiratory motion compensation. Validation of the registration between the three-dimensional (3D) roadmap and the 2D x-ray images was performed using balloon occlusion coronary venograms. A 2D registration error of 1.2 ± 0.7 mm was achieved. In addition, a novel navigation technique was developed, called Cardiac Unfold, where an entire cardiac chamber is unfolded from 3D to 2D along with all relevant anatomical and functional information and coupled to real-time device detection. This allowed more intuitive navigation as the entire 3D scene was displayed simultaneously on a 2D plot. The accuracy of the unfold navigation was assessed off-line using 13 patient data sets by computing the registration error of the LV pacing lead electrodes which was found to be 2.2 ± 0.9 mm. Furthermore, the use of Unfold Navigation was demonstrated in real-time for four clinical cases.

An electrostatic dry coating process based on a liquid pan coater was developed for enteric coating of tablets with Eudragit® L 100-55. Two different liquid plasticizers of triethyl citrate (TEC) and PEG400 were used in the coating process. In contrast to TEC, PEG400 produced good powder adhesion and successful coating. DSC results showed that PEG400 lowered the glass transition temperature (Tg) of Eudragit® L 100-55 to a greater extent than TEC at the same blend ratio, indicating that PEG400 was more effective in plasticizing the polymer. PEG400 showed higher contact angle on both surfaces of tablet cores and coating powders as well as lower absorption into the tablet cores than TEC, suggesting that more PEG400 existed at the interface between tablet core and coating powders. The combination effects of higher plasticizing efficiency and more PEG400 available at the tablet surface produced higher plasticization of Eudragit® L 100-55, leading to the successfully initial powder adhesion. The powder adhesion was further enhanced by the electrostatically assisted coating process, as confirmed by the higher coating level and coating efficiency with electrical charging (60 kV) than the ones without it (0 kV). The micrographs of scanning electron microscopy and in vitro drug release tests of the coated tablets showed that higher curing temperature and longer curing time led to enhanced film formation and acid resistance. The electrostatic dry coating process has been demonstrated to be a promising process for enteric coating of tablets.