Integration of arterial spin labeling into stereotactic radiosurgery planning of cerebral arteriovenous malformations.

PURPOSE: To test whether the combined use of 4D arterial spin labeling angiography (4D ASL) and contrast-enhanced magnetic resonance angiography (4D CE-MRA) can work as a prospective alternative to digital subtraction angiography (DSA) for the delineation of the arteriovenous malformation (AVM) nidus in stereotactic radiosurgery (SRS) planning. MATERIALS AND METHODS: A custom 4D ASL sequence and a proof-of-concept software tool to integrate 4D ASL data to SRS planning were implemented. Ten AVM patients were scanned at 3T. Two observers independently contoured niduses in two separate sessions. Reference niduses were contoured using DSA, 4D ASL, and 4D CE-MRA. Test niduses were contoured using 4D ASL and 4D CE-MRA only. Reference and test niduses from both observers were compared in terms of volume, distance between centers of volumes (dCOV), and the Jaccard index (JI). RESULTS: In volume comparisons, excellent intraobserver and interobserver agreements were obtained (intraclass correlation coefficients: 0.99 and 0.98, respectively). Median dCOV, JIs between reference and test niduses were 0.55 mm, 0.78 for Observer 1 and were 0.6 mm, 0.78 for Observer 2. None of the dCOV and JI parameters varied significantly among the delineation methods or the observers (P = 0.84, P = 0.39). CONCLUSION: Our preliminary results indicate that reproducibility of the target volumes with high agreement levels is achievable without using DSA. The combined use of high temporal resolution 4D ASL and high spatial resolution and vessel-to-background contrast 4D CE-MRA provided sufficient spatiotemporal angiographic information for the delineation of AVM niduses. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1718-1727.

Identification of fluocinolone acetonide to prevent paclitaxel-induced peripheral neuropathy.

Paclitaxel (PTX) is among the most commonly used cancer drugs that cause chemotherapy-induced peripheral neuropathy (CIPN), a debilitating and serious dose-limiting side effect. Currently, no drugs exist to prevent CIPN, and symptomatic therapy is often ineffective. In order to identify therapeutic candidates to prevent axonal degeneration induced by PTX, we carried out a phenotypic drug screening using primary rodent dorsal root ganglion sensory neurons. We identified fluocinolone acetonide as a neuroprotective compound and verified it through secondary screens. Furthermore, we showed its efficacy in a mouse model of PTX-induced peripheral neuropathy and confirmed with four different cancer cell lines that fluocinolone acetonide does not interfere with PTX's antitumor activity. Our study identifies fluocinolone acetonide as a potential therapy to prevent CIPN caused by PTX.

Bayesian network prior: network analysis of biological data using external knowledge.

MOTIVATION: Reverse engineering GI networks from experimental data is a challenging task due to the complex nature of the networks and the noise inherent in the data. One way to overcome these hurdles would be incorporating the vast amounts of external biological knowledge when building interaction networks. We propose a framework where GI networks are learned from experimental data using Bayesian networks (BNs) and the incorporation of external knowledge is also done via a BN that we call Bayesian Network Prior (BNP). BNP depicts the relation between various evidence types that contribute to the event 'gene interaction' and is used to calculate the probability of a candidate graph (G) in the structure learning process. RESULTS: Our simulation results on synthetic, simulated and real biological data show that the proposed approach can identify the underlying interaction network with high accuracy even when the prior information is distorted and outperforms existing methods. AVAILABILITY: Accompanying BNP software package is freely available for academic use at http://bioe.bilgi.edu.tr/BNP. CONTACT: hasan.otu@bilgi.edu.tr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Pathway analysis of high-throughput biological data within a Bayesian network framework.

MOTIVATION: Most current approaches to high-throughput biological data (HTBD) analysis either perform individual gene/protein analysis or, gene/protein set enrichment analysis for a list of biologically relevant molecules. Bayesian Networks (BNs) capture linear and non-linear interactions, handle stochastic events accounting for noise, and focus on local interactions, which can be related to causal inference. Here, we describe for the first time an algorithm that models biological pathways as BNs and identifies pathways that best explain given HTBD by scoring fitness of each network. RESULTS: Proposed method takes into account the connectivity and relatedness between nodes of the pathway through factoring pathway topology in its model. Our simulations using synthetic data demonstrated robustness of our approach. We tested proposed method, Bayesian Pathway Analysis (BPA), on human microarray data regarding renal cell carcinoma (RCC) and compared our results with gene set enrichment analysis. BPA was able to find broader and more specific pathways related to RCC. AVAILABILITY: Accompanying BPA software (BPAS) package is freely available for academic use at http://bumil.boun.edu.tr/bpa.

RT-GROG: parallelized self-calibrating GROG for real-time MRI.

A real-time implementation of self-calibrating Generalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) operator gridding for radial acquisitions is presented. Self-calibrating GRAPPA operator gridding is a parallel-imaging-based, parameter-free gridding algorithm, where coil sensitivity profiles are used to calculate gridding weights. Self-calibrating GRAPPA operator gridding's weight-set calculation and image reconstruction steps are decoupled into two distinct processes, implemented in C++ and parallelized. This decoupling allows the weights to be updated adaptively in the background while image reconstruction threads use the most recent gridding weights to grid and reconstruct images. All possible combinations of two-dimensional gridding weights G(x)(m)G(y)(n) are evaluated for m,n = {-0.5, -0.4, ..., 0, 0.1, ..., 0.5} and stored in a look-up table. Consequently, the per-sample two-dimensional weights calculation during gridding is eliminated from the reconstruction process and replaced by a simple look-up table access. In practice, up to 34x faster reconstruction than conventional (parallelized) self-calibrating GRAPPA operator gridding is achieved. On a 32-coil dataset of size 128 x 64, reconstruction performance is 14.5 frames per second (fps), while the data acquisition is 6.6 fps.

Mitral cerclage annuloplasty, a novel transcatheter treatment for secondary mitral valve regurgitation: initial results in swine.

OBJECTIVES: We developed and tested a novel transcatheter circumferential annuloplasty technique to reduce mitral regurgitation in porcine ischemic cardiomyopathy. BACKGROUND: Catheter-based annuloplasty for secondary mitral regurgitation exploits the proximity of the coronary sinus to the mitral annulus, but is limited by anatomic variants and coronary artery entrapment. METHODS: The procedure, "cerclage annuloplasty," is guided by magnetic resonance imaging (MRI) roadmaps fused with live X-ray. A coronary sinus guidewire traverses a short segment of the basal septal myocardium to re-enter the right heart where it is exchanged for a suture. Tension is applied interactively during imaging and secured with a locking device. RESULTS: We found 2 feasible suture pathways from the great cardiac vein across the interventricular septum to create cerclage. Right ventricular septal re-entry required shorter fluoroscopy times than right atrial re-entry, which entailed a longer intramyocardial traversal but did not cross the tricuspid valve. Graded tension progressively reduced septal-lateral annular diameter, but not end-systolic elastance or regional myocardial function. A simple arch-like device protected entrapped coronary arteries from compression even during supratherapeutic tension. Cerclage reduced mitral regurgitation fraction (from 22.8 +/- 12.7% to 7.2 +/- 4.4%, p = 0.04) by slice tracking velocity-encoded MRI. Flexible cerclage reduced annular size but preserved annular motion. Cerclage also displaced the posterior annulus toward the papillary muscles. Cerclage introduced reciprocal constraint to the left ventricular outflow tract and mitral annulus that enhanced leaflet coaptation. A sample of human coronary venograms and computed tomography angiograms suggested that most have suitable venous anatomy for cerclage. CONCLUSIONS: Transcatheter mitral cerclage annuloplasty acutely reduces mitral regurgitation in porcine ischemic cardiomyopathy. Entrapped coronary arteries can be protected. MRI provided insight into the mechanism of cerclage action.

Real-time MR imaging-guided laser atrial septal puncture in swine.

PURPOSE: The authors performed this study to report their initial preclinical experience with real-time magnetic resonance (MR) imaging-guided atrial septal puncture by using a MR imaging-conspicuous blunt laser catheter that perforates only when energized. MATERIALS AND METHODS: The authors customized a 0.9-mm clinical excimer laser catheter with a receiver coil to impart MR imaging visibility at 1.5 T. Seven swine underwent laser transseptal puncture under real-time MR imaging. MR imaging signal-to-noise ratio profiles of the device were obtained in vitro. Tissue traversal force was tested with a calibrated meter. Position was corroborated with pressure measurements, oximetry, angiography, and necropsy. Intentional non-target perforation simulated serious complication. RESULTS: Embedded MR imaging antennae accurately reflected the position of the laser catheter tip and profile in vitro and in vivo. Despite having an increased profile from the microcoil, the 0.9-mm laser catheter traversed in vitro targets with similar force (0.22 N +/- 0.03) compared with the unmodified laser. Laser puncture of the atrial septum was successful and accurate in all animals. The laser was activated an average of 3.8 seconds +/- 0.4 before traversal. There were no sequelae after 6 hours of observation. Necropsy revealed 0.9-mm holes in the fossa ovalis in all animals. Intentional perforation of the aorta and atrial free wall was evident immediately. CONCLUSIONS: MR imaging-guided laser puncture of the interatrial septum is feasible in swine and offers controlled delivery of perforation energy by using an otherwise blunt catheter. Instantaneous soft tissue imaging provides immediate feedback on safety.

Technology preview: X-ray fused with magnetic resonance during invasive cardiovascular procedures.

BACKGROUND: We have developed and validated a system for real-time X-ray fused with magnetic resonance imaging, MRI (XFM), to guide catheter procedures with high spatial precision. Our implementation overlays roadmaps-MRI-derived soft-tissue features of interest-onto conventional X-ray fluoroscopy. We report our initial clinical experience applying XFM, using external fiducial markers, electrocardiogram (ECG)- gating, and automated real-time correction for gantry and table movement. METHODS: This prospective case series for technical development was approved by the NHLBI Institutional Review Board and included 19 subjects. Multimodality external fiducial markers were affixed to patients' skin before MRI, which included contrast-enhanced, 3D T1-weighted, or breath-held and ECG-gated 2D steady state free precession imaging at 1.5T. MRI-derived roadmaps were manually segmented while patients were transferred to a calibrated X-ray fluoroscopy system. Image spaces were registered using the fiducial markers and thereafter permitted unrestricted gantry rotation, table panning, and magnification changes. Static and ECG-gated MRI data were transformed from 3D to 2D to correspond with gantry and table position and combined with live X-ray images. RESULTS: Clinical procedures included graft coronary arteriography, right ventricular free-wall biopsy, and iliac and femoral artery recanalization and stenting. MRI roadmaps improved operator confidence, and in the biopsy cases, outperformed the best available alternative imaging modality. Registration errors were increased when external fiducial markers were affixed to more mobile skin positions, such as over the abdomen. CONCLUSION: XFM using external fiducial markers is feasible during X-ray guided catheter treatments. Multimodality image fusion may prove a useful adjunct to invasive cardiovascular procedures.

Endoventricular patch plasty for dyskinetic anteroapical left ventricular aneurysm increases systolic circumferential shortening in sheep.

OBJECTIVE: Endoventricular patch plasty (Dor procedure) has gained favor as a surgical treatment for heart failure associated with large anteroapical myocardial infarction. We tested the hypotheses that the Dor procedure increases systolic circumferential shortening and longitudinal shortening in noninfarcted left ventricular regions in sheep. METHODS: In 6 male Dorsett sheep, the left anterior descending coronary artery and its second diagonal branch were ligated 40% of the distance from the apex to the base. Sixteen weeks after myocardial infarction, a Dor procedure was performed with a Dacron patch that was 50% of the infarct neck dimension. Two weeks before and 2 and 6 weeks after the Dor procedure, animals underwent magnetic resonance imaging with tissue tagging in multiple short-axis and long-axis slices. Fully three-dimensional strain analyses were performed. All 6 end-systolic strain components were compared in regions 1 cm, 2 cm, 3 cm, and 4 cm below the valves, as well as in the anterior, posterior, and lateral left ventricular walls and the interventricular septum. RESULTS: Circumferential shortening increased from before the Dor procedure to 6 weeks after repair in nearly every left ventricular region (13/16). The greatest regional change in circumferential shortening was found in the equatorial region or 2 cm below the base and in the posterior wall (from 9.0% to 18.4%; P < .0001). Longitudinal shortening increased 2 weeks after the Dor procedure but then returned near baseline by 6 weeks after the Dor procedure. CONCLUSION: The Dor procedure significantly increases systolic circumferential shortening in nearly all noninfarcted left ventricular regions in sheep.

X-ray fused with magnetic resonance imaging (XFM) to target endomyocardial injections: validation in a swine model of myocardial infarction.

BACKGROUND: Magnetic resonance imaging (MRI) permits 3-dimensional (3D) cardiac imaging with high soft tissue contrast. X-ray fluoroscopy provides high-resolution, 2-dimensional (2D) projection imaging. We have developed real-time x-ray fused with MRI (XFM) to guide invasive procedures that combines the best features of both imaging modalities. We tested the accuracy of XFM using external fiducial markers to guide endomyocardial cell injections in infarcted swine hearts. METHODS AND RESULTS: Endomyocardial injections of iron-labeled mesenchymal stromal cells admixed with tissue dye were performed in previously infarcted hearts of 12 Yucatan miniswine (weight, 33 to 67 kg). Features from cardiac MRI were displayed combined with x-ray in real time to guide injections. During 130 injections, operators were provided with 3D surfaces of endocardium, epicardium, myocardial wall thickness (range, 2.6 to 17.7 mm), and infarct registered with live x-ray images to facilitate device navigation and choice of injection location. XFM-guided injections were compared with postinjection MRI and with necropsy specimens obtained 24 hours later. Visual inspection of the pattern of dye staining on 2,3,5-triphenyltetrazolium chloride-stained heart slices agreed (kappa=0.69) with XFM-derived injection locations mapped onto delayed hyperenhancement MRI and the susceptibility artifacts seen on the postinjection T2*-weighted gradient echo MRI. The distance between the predicted and actual injection locations in vivo was 3.2+/-2.6 mm (n=64), and 75% of injections were within 4.1 mm of the predicted location. CONCLUSIONS: Three-dimensional to two-dimensional registration of x-ray and MR images with the use of external fiducial markers accurately targets endomyocardial injection in a swine model of myocardial infarction.

The effect of anteroapical aneurysm plication on end-systolic three-dimensional strain in the sheep: a magnetic resonance imaging tagging study.

OBJECTIVES: Although repair of left ventricular aneurysm has been extensively studied, its effect on regional ventricular function remains unclear. The primary goal of this study was to quantify the effect of anteroapical aneurysm plication on systolic deformation in noninfarcted adjacent (border zone) and remote left ventricular regions in sheep. METHODS: Eight sheep underwent anteroapical myocardial infarction (25% of left ventricular mass). Ten weeks later, animals underwent aneurysm plication. Two and 6 weeks after this operation, animals underwent magnetic resonance imaging with tissue tagging in multiple short-axis and long-axis slices. Fully 3-dimensional strain analyses were performed. All 6 end-systolic strain components were compared at midwall in the border zone of the aneurysm or repair and in regions 1 cm, 2 cm, and 3 cm below the valves. RESULTS: Circumferential shortening progressively increases from before plication to 2 weeks after plication to 6 weeks after plication toward the border zone. The effect on circumferential shortening is most pronounced in the anterior wall and septum. The biggest change is from 2 to 6 weeks after plication (from 4.3% to 11.3% in anterior wall, P < .0001; from 3.5% to 6.5% in septum, P < .0007). Longitudinal shortening is decreased at 2 weeks after plication but then returns to baseline (with slight improvement in the border zone) at 6 weeks after plication. CONCLUSIONS: Repair of left ventricular aneurysm significantly increases systolic circumferential shortening at the border zone in sheep.

Real-time MRI guided atrial septal puncture and balloon septostomy in swine.

Cardiac perforation during atrial septal puncture (ASP) might be avoided by improved image guidance. X-ray fluoroscopy (XRF), which guides ASP, visualizes tissue poorly and does not convey depth information. Ultrasound is limited by device shadows and constrained imaging windows. Alternatively, real-time MRI (rtMRI) provides excellent tissue contrast in any orientation and may enable ASP and balloon atrial septostomy (BAS) in swine. Custom MRI catheters incorporated "active" (receiver antenna) and "passive" (iron or gadolinium) elements. Wholly rtMRI-guided transfemoral ASP and BAS were performed in 10 swine in a 1.5T interventional suite. Hemodynamic results were measured with catheters and velocity encoded MRI. Successful ASP was performed in all 10 animals. Necropsy confirmed septostomy confined within the fossa ovalis in all. BAS was successful in 9/10 animals. Antenna failure in a re-used needle led to inadvertent vena cava tear prior to BAS in 1 animal. ASP in the same animal was easily performed using a new needle. rtMRI illustrated clear device-tissue-lumen relationships in multiple orientations, and facilitated simple ASP and BAS. The mean procedure time was 19 +/- 10 minutes. Septostomy achieved a mean left to right shunt ratio of 1.3:1 in these healthy animals. Interactive rtMRI permits rapid transcatheter ASP and BAS in swine. Further technical development may enable novel applications.

Real-time magnetic resonance imaging-guided stenting of aortic coarctation with commercially available catheter devices in Swine.

BACKGROUND: Real-time MR imaging (rtMRI) is now technically capable of guiding catheter-based cardiovascular interventions. Compared with x-ray, rtMRI offers superior tissue imaging in any orientation without ionizing radiation. Translation to clinical trials has awaited the availability of clinical-grade catheter devices that are both MRI visible and safe. We report a preclinical safety and feasibility study of rtMRI-guided stenting in a porcine model of aortic coarctation using only commercially available catheter devices. METHOD AND RESULTS: Coarctation stenting was performed wholly under rtMRI guidance in 13 swine. rtMRI permitted procedure planning, device tracking, and accurate stent deployment. "Active" guidewires, incorporating MRI antennas, improved device visualization compared with unmodified "passive" nitinol guidewires and shortened procedure time (26+/-11 versus 106+/-42 minutes; P=0.008). Follow-up catheterization and necropsy showed accurate stent deployment, durable gradient reduction, and appropriate neointimal formation. MRI immediately identified aortic rupture when oversized devices were tested. CONCLUSIONS: This experience demonstrates preclinical safety and feasibility of rtMRI-guided aortic coarctation stenting using commercially available catheter devices. Patients may benefit from rtMRI in the future because of combined device and tissue imaging, freedom from ionizing radiation, and the ability to identify serious complications promptly.

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.

Magnetic resonance imaging-guided vascular interventions.

Magnetic resonance imaging (MRI), which provides superior soft-tissue imaging and no known harmful effects, has the potential as an alternative modality to guide various medical interventions. This review will focus on MR-guided endovascular interventions and present its current state and future outlook. In the first technical part, enabling technologies such as developments in fast imaging, catheter devices, and visualization techniques are examined. This is followed by a clinical survey that includes proof-of-concept procedures in animals and initial experience in human subjects. In preclinical experiments, MRI has already proven to be valuable. For example, MRI has been used to guide and track targeted cell delivery into or around myocardial infarctions, to guide atrial septal puncture, and to guide the connection of portal and systemic venous circulations. Several investigational MR-guided procedures have already been reported in patients, such as MR-guided cardiac catheterization, invasive imaging of peripheral artery atheromata, selective intraarterial MR angiography, and preliminary angioplasty and stent placement. In addition, MR-assisted transjugular intrahepatic portosystemic shunt procedures in patients have been shown in a novel hybrid double-doughnut x-ray/MRI system. Numerous additional investigational human MR-guided endovascular procedures are now underway in several medical centers around the world. There are also significant hurdles: availability of clinical-grade devices, device-related safety issues, challenges to patient monitoring, and acoustic noise during imaging. The potential of endovascular interventional MRI is great because as a single modality, it combines 3-dimensional anatomic imaging, device localization, hemodynamics, tissue composition, and function.