Amandeep Thind

Hybrid intravascular ultrasound and optical coherence tomography catheter for imaging of coronary atherosclerosis.

To demonstrate the feasibility of imaging human coronary atherosclerosis using a novel hybrid intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging catheter.

Innovations in imaging for chronic total occlusions: a glimpse into the future of angiography’s blind-spot

Chronic total occlusions (CTOs) are a subset of lesions that present a considerable burden to cardiovascular patients. There exists a strong clinical desire to improve non-surgical options for CTO revascularization. While several techniques, devices, and guide wires have been developed and refined for use in CTOs, the inability of angiography to adequately visualize occluded arterial segments makes interventions in this setting technically challenging. This review describes the current status of several invasive and non-invasive imaging techniques that may facilitate improved image guidance during CTO revascularization, with the goals of improving procedure safety and efficacy while reducing the time required to complete these interventions. Cardiac imaging also has important potential roles in selecting patients most likely to benefit from revascularization as well as pre-procedural planning, post-procedural assessment of revascularized segments and long-term outcomes studies. Modalities discussed include non-invasive techniques, such as CT(computed tomography) angiography and cardiac magnetic resonance imaging (MRI), as well as invasive techniques, such as intravascular ultrasound, optical coherence tomography, intravascular MRI, and conventional angiography. While some of these techniques have some evidence to support their use at present, others are at earlier stages of development. Strategies that combine imaging techniques with the use of interventional therapies may provide significant opportunities to improve results in CTO interventions and represent an active area of investigation.

A novel method for the measurement of proximal fibrous cap puncture force in chronic total occlusions: the effect of increasing age.

AIMS The composition of CTO lesions changes significantly as they age. These changes may adversely affect PCI outcome. We present a robust ex vivo technique to measure the force required to puncture the proximal cap of CTOs, and to determine whether the puncture force differs according occlusion age to examine the effects of compositional changes over time on lesion stiffness. METHODS AND RESULTS Occlusions were created in 44 rabbit femoral arteries by thrombin injection. Between two and 15 weeks following induction, vessels were harvested and tested in a custom setup to determine the force required to puncture the proximal cap. The puncture force mean values at 2, 6, 12, and 15 weeks were 0.61N, 0.78N, 1.21N and 1.52N, respectively. The puncture force required in occlusions of ≤6 weeks was significantly lower those≥12 weeks (0.72±0.10N versus 1.45±0.13N, p<0.01). Using a cutoff point of 1N, 86% of lesions≤6 weeks of age required<1N compared to 30% of those≥12 weeks. CONCLUSIONS We have shown an objective and reproducible testing system for measuring CTO puncture force. Puncture force is correlated with occlusion age. This technique would be useful to evaluate therapies that alter CTO composition/compliance, as well as guidewire testing.

Investigation of micro-ultrasound for microvessel imaging in a model of chronic total occlusion.

The aim of the current study is to investigate the ability of micro-ultrasound (μUS) to identify microvasculature in CTOs in vivo. Results are compared with MRI studies. CTOs were developed in nine porcine superficial femoral arteries (SFA) by percutaneous insertion of a dissolvable polymer plug. This model is characterized by acute thrombosis that later organizes into a fibrotic CTO containing abundant microchannels. 3D μUS images with Power Doppler (PD) overlays from the arteries were acquired at two timepoints: one and eight weeks after placement of the polymer plug. Phase contrast MRI and contrast enhanced MRI was also performed. Imaging was performed transcutaneously. Microvessels were identified in vivo in six of eight CTOs using μUS, and in three of seven CTO vessels with MRI, compared with five of seven seen histologically. PW Doppler profiles showed pulsatile blood velocities of ∼2 cm/s. Intraluminal microvessels within CTOs can be consistently identified by 3D μUS. This technique appears to be more sensitive than MRI. μUS may play a role in guiding CTO interventions.

In vivo feasibility study of ultrasound potentiated collagenase therapy of chronic total occlusions.

Arterial chronic total occlusions (CTOs) pose considerable challenges for percutaneous interventions, due primarily to the presence of stiff proximal fibrous caps (PFCs) which act as a barrier to the penetration of guide wires. A new approach under development for improving the success rate of guide wire crossing in CTOs is to employ collagenase to degrade the mechanical integrity of the PFCs. This has been shown to be feasible in preclinical work and in a Phase 1 clinical trial. In a recent study we demonstrated using ex vivo experimental CTO specimens that ultrasound-stimulated microbubbles (USMBs) could potentiate the effects of collagenase and result in increased mechanical degradation of the PFCs of CTOs. Here we report the results of the first in vivo study examining the feasibility of this approach, which demonstrates that the force required to puncture through the PFCs of CTOs is reduced with combined USMB+collagenase treatments relative to collagenase only treatments. This approach has the potential to further improve the efficacy of the emerging technique of collagenase facilitation of percutaneous interventions for CTO.

The use of ultrasound-stimulated contrast agents as an adjuvant for collagenase therapy in chronic total occlusions

AIMS To investigate the effectiveness of combining collagenase and ultrasound-stimulated microbubble (USMB) treatments in reducing the mechanical force required for crossing a guidewire through CTOs. METHODS AND RESULTS Experiments were conducted on ex vivo specimens of a rabbit femoral artery CTO model (n=45 total samples). Four primary groups were employed: control (n=6), collagenase only (n=15), USMB only (1 MHz frequency) (n=5), and collagenase+USMB (n=19). In one set of experiments the force required to puncture through CTO samples was measured and it was found that the puncture force was 2.31-fold lower for the combined treatment group relative to the comparable collagenase-only group (p<0.05). In a second set of experiments, the total protein and hydroxyproline content of the supernatant solution adjacent to the CTO was analysed. Significantly higher hydroxyproline levels were measured in collagenase+USMB treated CTOs (0.065 g/mL) compared to collagenase (0.030 g/mL), USMB (0.003 g/mL) and control (0.004 g/mL) (p<0.05), indicating that the combined treatment augmented collagenase degradation. CONCLUSIONS Ultrasound-stimulated microbubbles improved the effectiveness of collagenase in reducing the force required to cross experimental CTOs. This new approach may have the potential to reduce treatment times and improve the success rates of emerging collagenase-based treatments of CTO.

P3C-7 Microvascular Imaging of Chronic Total Occlusions

Chronic total occlusion (CTO) is a condition that occurs when an artery is completely occluded for > 1 month. The ability of ultrasound to detect microvasculature in CTOs is the focus of this study. The development of a superficial porcine femoral model of CTO by percutaneously placing a dissolvable polymer plug in the artery to promote thrombosis has provided a means by which to examine the formation and characteristics of these channels. The arteries, which are ~2-3 mm in diameter, accurately model thrombosis in CTO arteries. Studies have been performed on n = 8 porcine arteries. 3D power Doppler (PD) datasets from the arteries were acquired in vivo using a Vevo 770 system operating at 40 MHz at 1 week and 8 week timepoints. The scanning was performed transcutaneously through ~2 mm of skin to the artery. The formation of microvessels >100 mum in diameter were detected in vivo, as 6 of the 8 arteries self recanalized. At points where PD imaging suggested the presence of microvasculature, PW Doppler profiles were taken showing pulsatile flow rates of ~2 cm/s. The results were correlated with histology. The ability to detect microvessels in vivo with ultrasound suggests a potential method for real time guidance of CTO interventions