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Biomedical subjects

Alexander J Dick

Publications and source records attributed to Alexander J Dick.

16 recordsLinked to original sources

Ex vivo imaging of chronic total occlusions using forward-looking optical coherence tomography.

BACKGROUND AND OBJECTIVES: Percutaneous coronary interventions (PCI) of chronic total occlusions (CTOs) of arteries are more challenging lesions to treat with angioplasty and stenting than stenotic vessels due primarily to the difficulty in guiding the wire across the lesion. Angiography alone is unable to differentiate between the occluded lumen and the vessel wall and to characterize the content of the occlusion. New technologies to aid in interventional guidance are therefore highly desirable. We sought to evaluate tissue characterization in arterial (CTOs) by imaging ex vivo peripheral arterial samples with optical coherence tomography (OCT). STUDY DESIGN/MATERIALS AND METHODS: Ex vivo arterial samples were obtained from patients undergoing peripheral limb amputation. Samples were imaged in an enface orientation using an OCT system, enabling sequential acquisition of longitudinal images and volumetric reconstruction of cross-sectional views of the occluded arteries. Histology was performed for comparison. RESULTS: OCT imaging reliably differentiated between the occluded lumen and the underlying arterial wall in peripheral CTOs. OCT correctly identified tissue composition within the CTO, such as the presence of collagen and calcium and was also able to identify intraluminal microchannels. CONCLUSIONS: OCT imaging of CTO anatomy and tissue characteristics may potentially lead to substantial improvements in PCI interventions by providing novel guiding capabilities.

Angiography↗

Real-time magnetic resonance imaging-guided endovascular recanalization of chronic total arterial occlusion in a swine model.

BACKGROUND: Endovascular recanalization (guidewire traversal) of peripheral artery chronic total occlusion (CTO) can be challenging. X-ray angiography resolves CTO poorly. Virtually "blind" device advancement during x-ray-guided interventions can lead to procedure failure, perforation, and hemorrhage. Alternatively, MRI may delineate the artery within the occluded segment to enhance procedural safety and success. We hypothesized that real-time MRI (rtMRI)-guided CTO recanalization can be accomplished in an animal model. METHODS AND RESULTS: Carotid artery CTO was created by balloon injury in 19 lipid-overfed swine. After 6 to 8 weeks, 2 underwent direct necropsy analysis for histology, 3 underwent primary x-ray-guided CTO recanalization attempts, and the remaining 14 underwent rtMRI-guided recanalization attempts in a 1.5-T interventional MRI system. Real-time MRI intervention used custom CTO catheters and guidewires that incorporated MRI receiver antennae to enhance device visibility. The mean length of the occluded segments was 13.3+/-1.6 cm. The rtMRI-guided CTO recanalization was successful in 11 of 14 swine and in only 1 of 3 swine with the use of x-ray alone. After unsuccessful rtMRI (n=3), x-ray-guided attempts were also unsuccessful. CONCLUSIONS: Recanalization of long CTO is entirely feasible with the use of rtMRI guidance. Low-profile clinical-grade devices will be required to translate this experience to humans.

Angioplasty↗

Positive-contrast imaging in the rabbit hind-limb of transplanted cells bearing endocytosed superparamagnetic beads.

Positive-contrast methods can augment negative-contrast methods for CMR evaluation of transplanted cell fate in vivo. This study correlated positive-contrast signal characteristics in the rabbit hind-limb with xenograft cell number (rat fibroblasts bearing endocytosed 1 microm Bang's particles) at different stages of Gd-DTPA administration and 1 mm2 in-plane resolution (2 minute scans, 1.5 Tesla). Linear regressions modeled satisfactorily the cell number dependencies of signal-to-noise (SNR) and area-of-enhancement (R > 0.83), over approximately a 50-fold fluctuation in cell number to a lowest detected limit of 25k cells during Gd-DTPA administration. Gd-DTPA administration elevated the slopes of parameter regressions by four or more standard deviations.

Animals↗

Real-time magnetic resonance-guided endovascular repair of experimental abdominal aortic aneurysm in swine.

OBJECTIVES: This study tested the hypotheses that endografts can be visualized and navigated in vivo solely under real-time magnetic resonance imaging (rtMRI) guidance to repair experimental abdominal aortic aneurysms (AAA) in swine, and that MRI can provide immediate assessment of endograft apposition and aneurysm exclusion. BACKGROUND: Endovascular repair for AAA is limited by endoleak caused by inflow or outflow malapposition. The ability of rtMRI to image soft tissue and flow may improve on X-ray guidance of this procedure. METHODS: Infrarenal AAA was created in swine by balloon overstretch. We used one passive commercial endograft, imaged based on metal-induced MRI artifacts, and several types of homemade active endografts, incorporating MRI receiver coils (antennae). Custom interactive rtMRI features included color coding the catheter-antenna signals individually, simultaneous multislice imaging, and real-time three-dimensional rendering. RESULTS: Eleven repairs were performed solely using rtMRI, simultaneously depicting the device and soft-tissue pathology during endograft deployment. Active devices proved most useful. Intraprocedural MRI provided anatomic confirmation of stent strut apposition and functional corroboration of aneurysm exclusion and restoration of laminar flow in successful cases. In two cases, there was clear evidence of contrast accumulation in the aneurysm sac, denoting endoleak. CONCLUSIONS: Endovascular AAA repair is feasible under rtMRI guidance. Active endografts facilitate device visualization and complement the soft tissue contrast afforded by MRI for precise positioning and deployment. Magnetic resonance imaging also permits immediate post-procedural anatomic and functional evaluation of successful aneurysm exclusion.

Angioplasty↗

Invasive human magnetic resonance imaging: feasibility during revascularization in a combined XMR suite.

We tested the feasibility and safety of invasive magnetic resonance imaging (MRI) during peripheral angioplasty. Real-time MRI can image soft tissue and may potentially guide therapeutic procedures without ionizing radiation or nephrotoxic contrast. MRI-guided diagnostic catheterization has been described recently, but safe and conspicuous catheter devices are not widely available. An active guidewire, which serves as an MRI receiver antenna, might be useful to guide catheterization or even to image atheroma. We describe a combined interventional suite offering both X-ray fluoroscopy and real-time MRI. We used a 0.030'' active guidewire receiver coil for invasive MRI after X-ray lesion traversal in patients undergoing percutaneous iliofemoral artery revascularization. Intravascular MRI was compared with noninvasive MRI, X-ray angiography, and intravascular ultrasound (IVUS). Seven eligible patients consented to participate, but three were excluded because of lengthy revascularization procedures. Four remaining patients safely underwent combined X-ray fluoroscopy and real-time magnetic resonance imaging (XMR) transport, continuous monitoring, and all imaging modalities. There was no device dislodgment, contamination or evidence of heating. The intravascular MRI coil was well visualized except at the tip, but did not provide superior mural imaging compared with IVUS. Therefore, because an adequate safety and workflow experience was obtained, enrollment was terminated after only four subjects. Invasive MRI is feasible and apparently safe during peripheral angioplasty. Patients can safely be transported and monitored in an XMR interventional suite. An active quarter-wavelength guidewire coil does not provide superior imaging compared with IVUS, but provides satisfactory guidewire visualization. These tools may prove useful for advanced therapeutic procedures in the future.

Aged↗

Microvessels in chronic total occlusions: pathways for successful guidewire crossing?

Arterial chronic total occlusions (CTO) are a common and clinically relevant problem in patients with coronary artery disease. Percutaneous coronary intervention (PCI) success rates in a wide range of CTO are low, primarily due to inability of guidewire crossing. The pathophysiology of CTO is poorly understood and limits our ability to introduce innovative therapies. Recent studies from our laboratory have suggested that microvessel formation within arterial CTO is a complex process with temporal and regional differences. Moreover, there is evidence from pilot studies that the presence of either microvessels or the particular extracellular matrix environment in the adjacent perivascular tissue can facilitate guidewire crossing and successful PCI. Currently, studies are underway in our experimental CTO model to delineate the pathophysiology of microvessel formation in CTO and its potential role in PCI.

Animals↗

Reduced field of view and undersampled PR combined for interventional imaging of a fully dynamic field of view.

Active catheter imaging was investigated using real-time undersampled projection reconstruction (PR) combined with the temporal filtering technique of reduced field of view (rFOV). Real-time rFOV processing was interactively enabled during highly undersampled catheter imaging, resulting in improved artifact suppression with better temporal resolution than that obtained by view-sharing. Imaging with 64 to 32 projections provided a resolution of 2 x 2 x 8 mm, and four to eight true frames per second. Image artifacts were reduced when rFOV processing was applied to the undersampled images. A comparison with Cartesian rFOV showed that PR image quality is less susceptible to aliasing that results from rFOV imaging with a wholly dynamic outer FOV. Simulations and MRI experiments demonstrated that PR rFOV provides significant artifact suppression, even for a fully dynamic FOV. The near doubling of temporal resolution that is possible with PR rFOV permits accurate monitoring of highly dynamic events, such as catheter movements, and arrhythmias, such as ventricular ectopy.

Animals↗

Imaging of myocardial infarction for diagnosis and intervention using real-time interactive MRI without ECG-gating or breath-holding.

Current methods for MRI of infarcted myocardium require ECG-gating and breath-holding during contrast-enhanced segmented k-space inversion-recovery (IR) imaging. However, ECG-gating can be problematic in MRI, and breath-holding can be difficult for some patients. This work demonstrates that infarcted tissue can be visualized without ECG-gating or breath-holding with the use of intermittent inversion pulses during real-time (RT) interactive imaging with steady-state free precession (SSFP). The sequence generates a RT image stream containing a myocardium-nulled image every few frames, which allows nearly simultaneous observation of both infarcted regions and wall motion. First-pass perfusion and wall motion can be simultaneously observed with minor parameter modifications. This method may reduce diagnostic scan time, expand the target population, improve patient comfort, and facilitate targeted, interventional treatment of infarcted myocardium. Supplementary material for this article can be found on the MRM website at http://www.interscience.wiley.com/jpages/0740-3194/suppmat/index.html.

Animals↗

Magnetic resonance fluoroscopy allows targeted delivery of mesenchymal stem cells to infarct borders in Swine.

BACKGROUND: The local environment of delivered mesenchymal stem cells (MSCs) may affect their ultimate phenotype. MR fluoroscopy has the potential to guide intramyocardial MSC injection to desirable targets, such as the border between infarcted and normal tissue. We tested the ability to (1) identify infarcts, (2) navigate injection catheters to preselected targets, (3) inject safely even into fresh infarcts, and (4) confirm injection success immediately. METHODS AND RESULTS: A 1.5-T MRI scanner was customized for interventional use, with rapid imaging, independent color highlighting of catheter channels, multiple-slice 3D rendering, catheter-only viewing mode, and infarct-enhanced imaging. MRI receiver coils were incorporated into guiding catheters and injection needles. These devices were tested for heating and used for targeted MSC delivery. In infarcted pigs, myocardium was targeted by MR fluoroscopy. Infarct-enhanced imaging included both saturation preparation MRI after intravenous gadolinium and wall motion. Porcine MSCs were MRI-labeled with iron-fluorescent particles. Catheter navigation and multiple cell injections were performed entirely with MR fluoroscopy at 8 frames/s with 1.7x3.3x8-mm voxels. Infarct-enhanced MR fluoroscopy permitted excellent delineation of infarct borders. All injections were safely and successfully delivered to their preselected targets, including infarct borders. Iron-fluorescent particle-labeled MSCs were readily visible on delivery in vivo and post mortem. CONCLUSIONS: Precise targeted delivery of potentially regenerative cellular treatments to recent myocardial infarction borders is feasible with an MR catheter delivery system. MR fluoroscopy permits visualization of catheter navigation, myocardial function, infarct borders, and labeled cells after injection.

Animals↗

Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells.

BACKGROUND: Delivery and tracking of endomyocardial stem cells are limited by the inability to image transplanted cells noninvasively in the beating heart. We hypothesized that mesenchymal stem cells (MSCs) could be labeled with a iron fluorophore particle (IFP) to provide MRI contrast in vivo to assess immediate and long-term localization. METHODS AND RESULTS: MSCs were isolated from swine. Short-term incubation of MSCs with IFP resulted in dose-dependent and efficient labeling. Labeled cells remained viable for multiple passages and retained in vitro proliferation and differentiation capacity. Labeled MSCs (10(4) to 10(6) cells/150 microL) were injected percutaneously into normal and freshly infarcted myocardium in swine. One, 3, and 1 animals underwent serial cardiac MRI (1.5T) for 4, 8, and 21 days, respectively. MRI contrast properties were measured both in vivo and in vitro for cells embedded in agar. Injection sites containing as few as 10(5) MSCs could be detected and contained intact IFP-bearing MSCs on histology. CONCLUSIONS: IFP labeling of MSCs imparts useful MRI contrast, enabling ready detection in the beating heart on a conventional cardiac MR scanner after transplantation into normal and infarcted myocardium. The dual-labeled MSCs can be identified at locations corresponding to injection sites, both ex vivo using fluorescence microscopy and in vivo using susceptibility contrast on MRI. This technology may permit effective in vivo study of stem cell retention, engraftment, and migration.

Animals↗

Endocardial versus epicardial electrical synchrony during LV free-wall pacing.

Cardiac resynchronization therapy has been most typically achieved by biventricular stimulation. However, left ventricular (LV) free-wall pacing appears equally effective in acute and chronic clinical studies. Recent data suggest electrical synchrony measured epicardially is not required to yield effective mechanical synchronization, whereas endocardial mapping data suggest synchrony (fusion with intrinsic conduction) is important. To better understand this disparity, we simultaneously mapped both endocardial and epicardial electrical activation during LV free-wall pacing at varying atrioventricular delays (AV delay 0-150 ms) in six normal dogs with the use of a 64-electrode LV endocardial basket and a 128-electrode epicardial sock. The transition from dyssynchronous LV-paced activation to synchronous RA-paced activation was studied by constructing activation time maps for both endo- and epicardial surfaces as a function of increasing AV delay. The AV delay at the transition from dyssynchronous to synchronous activation was defined as the transition delay (AVt). AVt was variable among experiments, in the range of 44-93 ms on the epicardium and 47-105 ms on the endocardium. Differences in endo- and epicardial AVt were smaller (-17 to +12 ms) and not significant on average (-5.0 +/- 5.2 ms). In no instance was the transition to synchrony complete on one surface without substantial concurrent transition on the other surface. We conclude that both epicardial and endocardial synchrony due to fusion of native with ventricular stimulation occur nearly concurrently. Assessment of electrical epicardial delay, as often used clinically during cardiac resynchronization therapy lead placement, should provide adequate assessment of stimulation delay for inner wall layers as well.

Animals↗

Undersampled projection reconstruction for active catheter imaging with adaptable temporal resolution and catheter-only views.

In this study undersampled projection reconstruction (PR) was used for rapid catheter imaging in the heart, employing steady-state free precession (SSFP) contrast. Active catheters and phased-array coils were used for combined imaging of anatomy and catheter position in swine. Real-time imaging of catheter position was performed with relatively high spatial and temporal resolution, providing 2 x 2 x 8 mm spatial resolution and four to eight frames per second. Two interactive features were introduced. The number of projections (Np) was adjusted interactively to trade off imaging speed and artifact reduction, allowing acquisition of high-quality or high-frame-rate images. Thin-slice imaging was performed, with interactive requests for thick-slab projection images of the signal received solely from the active catheter. Briefly toggling on catheter-only projection images was valuable for verifying that the catheter tip was contained within the selected slice, or for locating the catheter when part of it was outside the selected slice.

Animals↗

Real-time accelerated interactive MRI with adaptive TSENSE and UNFOLD.

Reduced field-of-view (FOV) acceleration using time-adaptive sensitivity encoding (TSENSE) or unaliasing by Fourier encoding the overlaps using the temporal dimension (UNFOLD) can improve the depiction of motion in real-time MRI. However, increased computational resources are required to maintain a high frame rate and low latency in image reconstruction and display. A high-performance software system has been implemented to perform TSENSE and UNFOLD reconstructions for real-time MRI with interactive, on-line display. Images were displayed in the scanner room to investigate image-guided procedures. Examples are shown for normal volunteers and cardiac interventional experiments in animals using a steady-state free precession (SSFP) sequence. In order to maintain adequate image quality for interventional procedures, the imaging rate was limited to seven frames per second after an acceleration factor of 2 with a voxel size of 1.8 x 3.5 x 8 mm. Initial experiences suggest that TSENSE and UNFOLD can each improve the compromise between spatial and temporal resolution in real-time imaging, and can function well in interactive imaging. UNFOLD places no additional constraints on receiver coils, and is therefore more flexible than SENSE methods; however, the temporal image filtering can blur motion and reduce the effective acceleration. Methods are proposed to overcome the challenges presented by the use of TSENSE in interactive imaging. TSENSE may be temporarily disabled after changing the imaging plane to avoid transient artifacts as the sensitivity coefficients adapt. For imaging with a combination of surface and interventional coils, a hybrid reconstruction approach is proposed whereby UNFOLD is used for the interventional coils, and TSENSE with or without UNFOLD is used for the surface coils.

Animals↗

Catheter-based endomyocardial injection with real-time magnetic resonance imaging.

BACKGROUND: We tested the feasibility of targeted left ventricular (LV) mural injection using real-time MRI (rtMRI). METHODS AND RESULTS: A 1.5T MRI scanner was customized with a fast reconstruction engine, transfemoral guiding catheter-receiver coil (GCC), MRI-compatible needle, and tableside consoles. Commercial real-time imaging software was customized to facilitate catheter navigation and visualization of injections at 4 completely refreshed frames per second. The aorta was traversed and the left ventricular cavity was entered under direct rtMRI guidance. Pigs underwent multiple injections with dilute gadolinium-DTPA. All myocardial segments were readily accessed. The active GCC and the passive Stiletto needle injector were readily visualized. More than 50 endomyocardial injections were performed with the aid of rtMRI; 81% were successful with this first-generation prototype. CONCLUSION: Percutaneous endomyocardial drug delivery is feasible with the aid of rtMRI, which permits precise 3-dimensional localization of injection within the LV wall.

Animals↗