The CathEye: A Forward-Looking Ultrasound Catheter for Image-Guided Cardiovascular Procedures.

Catheter based procedures are typically guided by X-Ray, which suffers from low soft tissue contrast and only provides 2D projection images of a 3D volume. Intravascular ultrasound (IVUS) can serve as a complementary imaging technique. Forward viewing catheters are useful for visualizing obstructions along the path of the catheter. The CathEye system mechanically steers a single-element transducer to generate a forward-looking surface reconstruction from an irregularly spaced 2-D scan pattern. The steerable catheter leverages an expandable frame with cables to manipulate the distal end independently of vessel tortuosity. The tip position is estimated by measuring the cable displacements and used to create surface reconstructions of the imaging workspace with the single-element transducer. CathEye's imaging capabilities were tested with an agar phantom and an ex vivo chronic total occlusion (CTO) sample while the catheter was confined to various tortuous paths. The CathEye maintained similar scan patterns regardless of path tortuosity and was able to recreate major features of the imaging targets, such as holes and extrusions. The feasibility of forward-looking IVUS with the CathEye is demonstrated in this study. The CathEye mechanism can be applied to other imaging modalities with field-of-view (FOV) limitations and represents the basis for an interventional device fully integrated with image guidance.

The CathCam: A Novel Angioscopic Solution for Endovascular Interventions.

Peripheral arterial diseases are commonly managed with endovascular procedures, which often face limitations in device control and visualization under X-ray fluoroscopy guidance. In response, we developed the CathCam, an angioscope integrated into an expandable cable-driven parallel mechanism to enhance real-time visualization, precise device positioning and catheter support for successful plaque crossing. The primary objective of this study was to assess and compare the performance of the novel CathCam with respect to conventional catheters and the CathPilot (i.e., CathCam without the angioscope), for applications in crossing chronic total occlusions (CTO). We first assessed the system in 3D-printed phantom models, followed by an ex vivo evaluation with CTO samples from a patient's superficial femoral artery. We measured and compared success rates, crossing times, and fluoroscopy times in both experiments. The CathCam demonstrated a 100% success rate in phantom experiments and a 75% success rate in ex vivo experiments with CTO samples, compared to conventional catheters, with 35% and 25% success rates, respectively. The average crossing times for the CathCam and the conventional catheter were 31 s and 502 s for the phantom experiments and 210 s and 511 s for the actual CTO lesions. The Cathcam also showed to be a reliable endovascular imaging approach in an in vivo experiment. Compared to conventional catheters, the CathCam significantly increased the success rate and reduced crossing and fluoroscopy times in both phantom and ex vivo setups. CathCam can potentially improve clinical outcomes for minimally invasive endovascular interventions by offering high-resolution real-time imaging alongside accurate device control.

The CathPilot: Performance Validation and Preclinical Safety and Feasibility Assessment.

OBJECTIVES: Peripheral endovascular revascularization procedures often fail due to technical limitations of guidewire support, steering, and visualization. The novel CathPilot catheter aims to address these challenges. This study assesses the safety and feasibility of the CathPilot and compares its performance to conventional catheters for peripheral vascular interventions. METHODS: The study compared the CathPilot to non-steerable and steerable catheters. The success rates and access times for a relevant target inside a tortuous vessel phantom model were assessed. The reachable workspace within the vessel and the guidewire's force delivery capabilities were also evaluated. To validate the technology, chronic total occlusion tissue samples were used ex vivo to compare crossing success rates with conventional catheters. Finally, in vivo experiments in a porcine aorta were conducted to evaluate safety and feasibility. RESULTS: The success rates for reaching the set targets were 31%, 69%, and 100% with the non-steerable catheter, the steerable catheter, and the CathPilot, respectively. CathPilot had a significantly larger reachable workspace, and allowed for up to four times higher force delivery and pushability. In crossing of chronic total occlusion samples, the CathPilot achieved a success rate of 83% and 100%, for fresh and fixed lesions respectively, which was also significantly higher than conventional catheters. The device was fully functional in the in vivo study, and there were no signs of coagulation or damage to the vessel wall. CONCLUSION: This study shows the safety and feasibility of the CathPilot system and its potential to reduce failure and complication rates in peripheral vascular interventions. The novel catheter outperformed conventional catheters in all defined metrics. This technology can potentially improve the success rate and outcome of peripheral endovascular revascularization procedures.

Quantification of Mechanical Characteristics of Conventional Steerable Ablation Catheters for Treatment of Atrial Fibrillation Using a Heart Phantom.

PURPOSE: Accurate and reliable catheter navigation is important in formation of adequate lesions during radiofrequency cardiac catheter ablation. To inform future device design efforts and to characterize the limitations of conventional devices, the focus of this study is to assess and quantify the mechanical performance of manual ablation catheters for pulmonary vein isolation procedures within a phantom heart model. METHODS: We measured three important metrics: accuracy of catheter tip navigation to target anatomical landmarks at the pulmonary veins (PVs), orientation of the catheter relative to the tissue at the targets, and the delivered force values and their stability and variations at those targets. A stereovision system was used for navigational guidance and to measure the catheter's tip position and orientation relative to the targets. To measure force, piezoelectric sensors were used which were integrated at the targets, whereby operators were instructed to stabilize the catheter to achieve a chosen reference force value. RESULTS: An overall positioning accuracy of 1.57 ± 1.71 mm was achieved for all targets. No statistical significance was observed in position accuracy between the right and left PVs (p = 0.5138). The orientation of the catheter relative to tissue surface was 41° ± 21° with no statistical significance between targets. The overall force stability was 41 ± 6 g with higher difficulty in force stabilization in the right compared to the left PV (40 ± 8 vs. 43 ± 2 g, p < 0.0001). CONCLUSION: Based on our results, future improvements to manual catheter navigation for ablation should focus on improving device performance in orientation control and improved force stability.

Experimental Protocol and Phantom Design and Development for Performance Characterization of Conventional Devices for Peripheral Vascular Interventions.

Conventional catheter-based interventions for treating peripheral artery disease suffer high failure and complication rates. The mechanical interactions with the anatomy constrain catheter controllability, while their length and flexibility limit their pushability. Also, the 2D X-ray fluoroscopy guiding these procedures fails to provide sufficient feedback about the device location relative to the anatomy. Our study aims to quantify the performance of conventional non-steerable (NS) and steerable (S) catheters in phantom and ex vivo experiments. In a 10 mm diameter, 30 cm long artery phantom model, with four operators, we evaluated the success rate and crossing time in accessing 1.25 mm target channels, the accessible workspace, and the force delivered through each catheter. For clinical relevance, we evaluated the success rate and crossing time in crossing ex vivo chronic total occlusions. For the S and NS catheters, respectively, users successfully accessed 69 and 31% of the targets, 68 and 45% of the cross-sectional area, and could deliver 14.2 and 10.2 g of mean force. Using a NS catheter, users crossed 0.0 and 9.5% of the fixed and fresh lesions, respectively. Overall, we quantified the limitations of conventional catheters (navigation, reachable workspace, and pushability) for peripheral interventions; this can serve as a basis for comparison with other devices.

Modeling and Prediction of a Guidewire's Reachable Workspace and Deliverable Forces.

Goal: In this study, we investigated the feasibility of predicting the performance of a specific guidewire in terms of its ability to cover a lesion cap surface and apply force to the lesion for a given patient's vessel anatomy. The aim of this research was to provide information that could be used to plan occlusion crossings and peripheral revascularization procedures preoperatively in a way that reduces the risk of potential intraoperative complications and increases the likelihood of success. Methods: We used finite element (FE) analysis to simulate the interaction between the guidewire and a model of a tortuous vessel, and we used this simulation to predict the reachable workspace and deliverable forces of the device for various entry positions and angles. We then validated these predictions through experiments in which we advanced a guidewire through an identical vessel phantom using a robotic manipulator. Conclusions: Our findings suggest that it may be possible to predict the performance of a guidewire and forecast the likelihood of success or failure for a given vessel anatomy and lesion morphology, which could enable improved planning and device selection.

Decreased Expression of Bioinformatically Predicted piwil2-targetting microRNAs, miR-1267 and miR-2276 in Breast Cancer.

PURPOSE: Human Piwil2, a member of Piwi subfamily of Argonaute proteins, is primarily expressed in testis, where it regulates self-renewal of germ cells. However, its ectopic expression has been reported with several tumors, including breast cancer. The upregulation of piwil2 in various stages of breast cancer suggested its suitability as a novel tumor biomarker. Considering the vital role of microRNAs (miRNAs) in regulating the expression of most human genes, we hypothesized a concomitant downregulation of the bioinformatically-predicted piwil2-targetting microRNAs in breast cancer.  METHOD: We employed different bioinformatic tools to predict piwil2-targeting miRNAs. Then, from the list of predicted miRNAs, we chose two less studied miRNAs (miR-1267 and miR-2276) for experimental validation. Using a real-time RT-PCR approach, we quantified the relative expression of the miRNAs in 31 pairs of formalin-fixed paraffin-embedded tumor/non-tumor tissue samples. RESULTS: Our data revealed a noticeable but not statistically significant (P = 0.133) downregulation of miR-1267 in tumor samples, compared to non-tumor samples obtained from the same patients. Downregulation of miR-1267 was more significant in higher grades of malignancies (fold change = 2.39, P = 0.033) and also in lymph nodes containing high-grade tumor cells (fold change = 6.66, P = 0.02).  Interestingly, a significant upregulation of miR-1267 was observed in tumors at high stages (stage 3a, 3b), compared to low stages (stage 2a, 2b) (fold change = 8.05, P = 0.048). Similar patterns of expression alteration were also observed for miR-2276. CONCLUSION: Altogether, our findings suggest a probable tumor suppressor role for miR-1267 and miR-2276 in breast tumor initiation and progression, but a probable promoting role for them in invasion and metastasis.

Magnetic resonance imaging compatible remote catheter navigation system with 3 degrees of freedom.

PURPOSE: To facilitate MRI-guided catheterization procedures, we present an MRI-compatible remote catheter navigation system that allows remote navigation of steerable catheters with 3 degrees of freedom. METHODS: The system consists of a user interface (master), a robot (slave), and an ultrasonic motor control servomechanism. The interventionalist applies conventional motions (axial, radial and plunger manipulations) on an input catheter in the master unit; this user input is measured and used by the servomechanism to control a compact catheter manipulating robot, such that it replicates the interventionalist's input motion on the patient catheter. The performance of the system was evaluated in terms of MRI compatibility (SNR and artifact), feasibility of remote navigation under real-time MRI guidance, and motion replication accuracy. RESULTS: Real-time MRI experiments demonstrated that catheter was successfully navigated remotely to desired target references in all 3 degrees of freedom. The system had an absolute value error of [Formula: see text]1 mm in axial catheter motion replication over 30 mm of travel and [Formula: see text] for radial catheter motion replication over [Formula: see text]. The worst case SNR drop was observed to be [Formula: see text]3 %; the robot did not introduce any artifacts in the MR images. CONCLUSION: An MRI-compatible compact remote catheter navigation system has been developed that allows remote navigation of steerable catheters with 3 degrees of freedom. The proposed system allows for safe and accurate remote catheter navigation, within conventional closed-bore scanners, without degrading MR image quality.

Two lung development-related microRNAs, miR-134 and miR-187, are differentially expressed in lung tumors.

INTRODUCTION: MicroRNAs (miRNAs) are involved in various cellular events needed for embryonic development and tumorigenesis. As some of the development-specific gene expression patterns could be observed in cancers, we speculated that the expression pattern of lung development-specific miRNAs miR-134 and miR-187 might be altered in lung tumor samples. Lung cancer is the first cause of cancer related deaths worldwide, mostly due to its late diagnosis. Therefore, finding a reliable diagnostic tumor marker, based on molecular profile of tumorigenesis, would be critical in lowering lung cancer mortality. METHODS: We employed a real-time RT-PCR approach to evaluate the expression alteration of two lung development-related miRNAs in lung tumor tissues. The suitability of miRs expression alterations as lung tumor biomarkers was tested by receiver operating characteristic (ROC) curve analysis. The effect of miR-187 overexpression on a lung carcinoma cell cycle was assessed using flow cytometry analysis. RESULTS: Our data revealed a significant upregulation (7.8 times, p<0.02) of miR-134 in lung tumors. However, its expression level failed to discriminate different tumor types and grades of malignancies from each other. Moreover, the ROC curves analysis did not give it a good score as a reliable biomarker (AUC=0.522, P=0.729). In contrast, miR-187 showed a significant down-regulation (P=0.008) in lung tumors. Similarly, its expression level failed to differentiate different tumor types or grades of malignancies. Nevertheless, ROC curve analysis gave it an AUC score of 0.669 (P=0.012), which suggests its suitability as a potential biomarker for lung cancer. Furthermore, ectopic expression of miR-187 in A549 cells caused a cell cycle arrest in G1 phase (P=0.013). CONCLUSION: Altogether, our data demonstrated an altered expression of two development-related miRNAs namely miR-134 and miR-187 in lung tumors for the first time. Moreover we have shown that miR-134 and miR-187 expression alternation were in accordance with their approved regulatory roles, therefore these miRNAs could serve as new biomarkers with potential usefulness in lung cancer diagnosis and treatments. In addition, miR-187 expression in tumor cells could perturb cell cycle which supported its possible role as tumor suppressor.

Differential gene expression and alternative splicing of survivin following mouse sciatic nerve injury.

STUDY DESIGN: In vivo studies using an axotomy model in adult male Naval Medical Research Institute mice. OBJECTIVE: Survivin, a unique member of the inhibitor of the apoptosis (IAP) protein family, is expressed during embryonal development, but is undetectable in terminally differentiated cells and tissues. Owing to the vital role of survivin in cellular proliferation and apoptotic cell death, and also to the necessity of treatment of the nervous system injuries, we have monitored survivin gene expression as well as its alternative splicing changes at different time points within injured mouse sciatic nerves. SETTING: Department of Genetics, School of Basic Sciences, Tarbiat Modares University, Tehran, Iran. METHODS: The sciatic nerves of adult male Naval Medical Research Institute mice were transected and the expression of survivin was examined in the distal and proximal parts of the dissected nerves as well as in the corresponding segments within the spinal cord of the animals, using semi-quantitative RT-PCR and immunohistochemistry. RESULTS: Survivin is not expressed in undamaged sciatic nerves, but, after sciatic nerve injury, it is gradually upregulated in proximal and distal parts of the dissected nerve (P<0.05). Survivin140 is the main variant expressed after injury, accompanied by a low expression of survivin40 (P<0.05). There was no expression of the survivin121 variant after injury. CONCLUSIONS: Survivin is differentially expressed and spliced in damaged nerve and spinal cord. Future works on the manipulation of expression and/or the splicing of survivin could decipher the potential effects of survivin variants on the regeneration of nerve and/or spinal cord injuries.