Enhancing transvenous lead extraction risk prediction: Integrating imaging biomarkers into machine learning models.

BACKGROUND: Machine learning (ML) models have been proposed to predict risk related to transvenous lead extraction (TLE). OBJECTIVE: The purpose of this study was to test whether integrating imaging data into an existing ML model increases its ability to predict major adverse events (MAEs; procedure-related major complications and procedure-related deaths) and lengthy procedures (≥100 minutes). METHODS: We hypothesized certain features-(1) lead angulation, (2) coil percentage inside the superior vena cava (SVC), and (3) number of overlapping leads in the SVC-detected from a pre-TLE plain anteroposterior chest radiograph (CXR) would improve prediction of MAE and long procedural times. A deep-learning convolutional neural network was developed to automatically detect these CXR features. RESULTS: A total of 1050 cases were included, with 24 MAEs (2.3%) . The neural network was able to detect (1) heart border with 100% accuracy; (2) coils with 98% accuracy; and (3) acute angle in the right ventricle and SVC with 91% and 70% accuracy, respectively. The following features significantly improved MAE prediction: (1) ≥50% coil within the SVC; (2) ≥2 overlapping leads in the SVC; and (3) acute lead angulation. Balanced accuracy (0.74-0.87), sensitivity (68%-83%), specificity (72%-91%), and area under the curve (AUC) (0.767-0.962) all improved with imaging biomarkers. Prediction of lengthy procedures also improved: balanced accuracy (0.76-0.86), sensitivity (75%-85%), specificity (63%-87%), and AUC (0.684-0.913). CONCLUSION: Risk prediction tools integrating imaging biomarkers significantly increases the ability of ML models to predict risk of MAE and long procedural time related to TLE.

A Tensor-Based Catheter and Wire Detection and Tracking Framework and Its Clinical Applications.

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.

Edge-enhancement densenet for X-ray fluoroscopy image denoising in cardiac electrophysiology procedures.

PURPOSE: Reducing X-ray dose increases safety in cardiac electrophysiology procedures but also increases image noise and artifacts which may affect the discernibility of devices and anatomical cues. Previous denoising methods based on convolutional neural networks (CNNs) have shown improvements in the quality of low-dose X-ray fluoroscopy images but may compromise clinically important details required by cardiologists. METHODS: In order to obtain denoised X-ray fluoroscopy images whilst preserving details, we propose a novel deep-learning-based denoising framework, namely edge-enhancement densenet (EEDN), in which an attention-awareness edge-enhancement module is designed to increase edge sharpness. In this framework, a CNN-based denoiser is first used to generate an initial denoising result. Contours representing edge information are then extracted using an attention block and a group of interacted ultra-dense blocks for edge feature representation. Finally, the initial denoising result and enhanced edges are combined to generate the final X-ray image. The proposed denoising framework was tested on a total of 3262 clinical images taken from 100 low-dose X-ray sequences acquired from 20 patients. The performance was assessed by pairwise voting from five cardiologists as well as quantitative indicators. Furthermore, we evaluated our technique's effect on catheter detection using 416 images containing coronary sinus catheters in order to examine its influence as a pre-processing tool. RESULTS: The average signal-to-noise ratio of X-ray images denoised with EEDN was 24.5, which was 2.2 times higher than that of the original images. The accuracy of catheter detection from EEDN denoised sequences showed no significant difference compared with their original counterparts. Moreover, EEDN received the highest average votes in our clinician assessment when compared to our existing technique and the original images. CONCLUSION: The proposed deep learning-based framework shows promising capability for denoising interventional X-ray fluoroscopy images. The results from the catheter detection show that the network does not affect the results of such an algorithm when used as a pre-processing step. The extensive qualitative and quantitative evaluations suggest that the network may be of benefit to reduce radiation dose when applied in real time in the catheter laboratory.

Real-time registration of 3D echo to x-ray fluoroscopy based on cascading classifiers and image registration.

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.

Protective effects of aerosolized pulmonary surfactant powder in a model of ventilator-induced lung injury.

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.

A novel real-time computational framework for detecting catheters and rigid guidewires in cardiac catheterization procedures.

PURPOSE: Catheters and guidewires are used extensively in cardiac catheterization procedures such as heart arrhythmia treatment (ablation), angioplasty, and congenital heart disease treatment. Detecting their positions in fluoroscopic X-ray images is important for several clinical applications, for example, motion compensation, coregistration between 2D and 3D imaging modalities, and 3D object reconstruction. METHODS: For the generalized framework, a multiscale vessel enhancement filter is first used to enhance the visibility of wire-like structures in the X-ray images. After applying adaptive binarization method, the centerlines of wire-like objects were extracted. Finally, the catheters and guidewires were detected as a smooth path which is reconstructed from centerlines of target wire-like objects. In order to classify electrode catheters which are mainly used in electrophysiology procedures, additional steps were proposed. First, a blob detection method, which is embedded in vessel enhancement filter with no additional computational cost, localizes electrode positions on catheters. Then the type of electrode catheters can be recognized by detecting the number of electrodes and also the shape created by a series of electrodes. Furthermore, for detecting guiding catheters or guidewires, a localized machine learning algorithm is added into the framework to distinguish between target wire objects and other wire-like artifacts. The proposed framework were tested on total 10,624 images which are from 102 image sequences acquired from 63 clinical cases. RESULTS: Detection errors for the coronary sinus (CS) catheter, lasso catheter ring and lasso catheter body are 0.56 ± 0.28 mm, 0.64 ± 0.36 mm, and 0.66 ± 0.32 mm, respectively, as well as success rates of 91.4%, 86.3%, and 84.8% were achieved. Detection errors for guidewires and guiding catheters are 0.62 ± 0.48 mm and success rates are 83.5%. CONCLUSION: The proposed computational framework do not require any user interaction or prior models and it can detect multiple catheters or guidewires simultaneously and in real-time. The accuracy of the proposed framework is sub-mm and the methods are robust toward low-dose X-ray fluoroscopic images, which are mainly used during procedures to maintain low radiation dose.

Dry powder coated osmotic drug delivery system.

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.

ECG imaging of ventricular tachycardia: evaluation against simultaneous non-contact mapping and CMR-derived grey zone.

ECG imaging is an emerging technology for the reconstruction of cardiac electric activity from non-invasively measured body surface potential maps. In this case report, we present the first evaluation of transmurally imaged activation times against endocardially reconstructed isochrones for a case of sustained monomorphic ventricular tachycardia (VT). Computer models of the thorax and whole heart were produced from MR images. A recently published approach was applied to facilitate electrode localization in the catheter laboratory, which allows for the acquisition of body surface potential maps while performing non-contact mapping for the reconstruction of local activation times. ECG imaging was then realized using Tikhonov regularization with spatio-temporal smoothing as proposed by Huiskamp and Greensite and further with the spline-based approach by Erem et al. Activation times were computed from transmurally reconstructed transmembrane voltages. The results showed good qualitative agreement between the non-invasively and invasively reconstructed activation times. Also, low amplitudes in the imaged transmembrane voltages were found to correlate with volumes of scar and grey zone in delayed gadolinium enhancement cardiac MR. The study underlines the ability of ECG imaging to produce activation times of ventricular electric activity-and to represent effects of scar tissue in the imaged transmembrane voltages.

Image-based view-angle independent cardiorespiratory motion gating and coronary sinus catheter tracking for x-ray-guided cardiac electrophysiology procedures.

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.

Applying a novel electrostatic dry powder coating technology to pellets.

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.

Fast catheter segmentation from echocardiographic sequences based on segmentation from corresponding X-ray fluoroscopy for cardiac catheterization interventions.

Echocardiography is a potential alternative to X-ray fluoroscopy in cardiac catheterization given its richness in soft tissue information and its lack of ionizing radiation. However, its small field of view and acoustic artifacts make direct automatic segmentation of the catheters very challenging. In this study, a fast catheter segmentation framework for echocardiographic imaging guided by the segmentation of corresponding X-ray fluoroscopic imaging is proposed. The complete framework consists of: 1) catheter initialization in the first X-ray frame; 2) catheter tracking in the rest of the X-ray sequence; 3) fast registration of corresponding X-ray and ultrasound frames; and 4) catheter segmentation in ultrasound images guided by the results of both X-ray tracking and fast registration. The main contributions include: 1) a Kalman filter-based growing strategy with more clinical data evalution; 2) a SURF detector applied in a constrained search space for catheter segmentation in ultrasound images; 3) a two layer hierarchical graph model to integrate and smooth catheter fragments into a complete catheter; and 4) the integration of these components into a system for clinical applications. This framework is evaluated on five sequences of porcine data and four sequences of patient data comprising more than 3000 X-ray frames and more than 1000 ultrasound frames. The results show that our algorithm is able to track the catheter in ultrasound images at 1.3 s per frame, with an error of less than 2 mm. However, although this may satisfy the accuracy for visualization purposes and is also fast, the algorithm still needs to be further accelerated for real-time clinical applications.

A statistical method for retrospective cardiac and respiratory motion gating of interventional cardiac x-ray images.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The proposed technique can therefore extract useful information from interventional x-ray images while minimizing exposure to ionizing radiation.

Surface flattening of the human left atrium and proof-of-concept clinical applications.

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.

Novel System for Real-Time Integration of 3-D Echocardiography and Fluoroscopy for Image-Guided Cardiac Interventions: Preclinical Validation and Clinical Feasibility Evaluation.

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.

Real-time x-ray fluoroscopy-based catheter detection and tracking for cardiac electrophysiology interventions.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Extended-field-of-view three-dimensional transesophageal echocardiography using image-based X-ray probe tracking.

The use of ultrasound imaging for guidance of cardiac interventional procedures is limited by the small field of view of the ultrasound volume. A larger view can be created by image-based registration of several partially overlapping volumes, but automatic registration is likely to fail unless the registration is initialized close to the volumes' correct alignment. In this article, we use X-ray images to track a transesophageal ultrasound probe and thereby provide initial position information for the registration of the ultrasound volumes. The tracking is possible using multiple X-rays or just a single X-ray for each probe position. We test the method in a phantom experiment and find that with at least 50% overlap, 88% of volume pairs are correctly registered when tracked using three X-rays and 86% when using single X-rays. Excluding failed registrations with errors greater than 10 mm, the average registration accuracy is 2.92 mm between ultrasound volumes and 4.75 mm for locating an ultrasound volume in X-ray space. We conclude that the accuracy and robustness of the registrations are sufficient to provide useful images for interventional guidance.

A novel electrostatic dry coating process for enteric coating of tablets with Eudragit® L 100-55.

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.

The development of a novel dry powder inhaler.

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.

Registration of 3D trans-esophageal echocardiography to X-ray fluoroscopy using image-based probe tracking.

Two-dimensional (2D) X-ray imaging is the dominant imaging modality for cardiac interventions. However, the use of X-ray fluoroscopy alone is inadequate for the guidance of procedures that require soft-tissue information, for example, the treatment of structural heart disease. The recent availability of three-dimensional (3D) trans-esophageal echocardiography (TEE) provides cardiologists with real-time 3D imaging of cardiac anatomy. Increasingly X-ray imaging is now supported by using intra-procedure 3D TEE imaging. We hypothesize that the real-time co-registration and visualization of 3D TEE and X-ray fluoroscopy data will provide a powerful guidance tool for cardiologists. In this paper, we propose a novel, robust and efficient method for performing this registration. The major advantage of our method is that it does not rely on any additional tracking hardware and therefore can be deployed straightforwardly into any interventional laboratory. Our method consists of an image-based TEE probe localization algorithm and a calibration procedure. While the calibration needs to be done only once, the GPU-accelerated registration takes approximately from 2 to 15s to complete depending on the number of X-ray images used in the registration and the image resolution. The accuracy of our method was assessed using a realistic heart phantom. The target registration error (TRE) for the heart phantom was less than 2mm. In addition, we assess the accuracy and the clinical feasibility of our method using five patient datasets, two of which were acquired from cardiac electrophysiology procedures and three from trans-catheter aortic valve implantation procedures. The registration results showed our technique had mean registration errors of 1.5-4.2mm and 95% capture range of 8.7-11.4mm in terms of TRE.

Multi-site left ventricular pacing as a potential treatment for patients with postero-lateral scar: insights from cardiac magnetic resonance imaging and invasive haemodynamic assessment.

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 dP/dtmax was recorded using a pressure wire during stimulation at LV1, LV2, and both sites simultaneously (LV1 + 2). Patients were deemed acute responders if ΔLV dP/dtmax 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 dP/dtmax 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.