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Biomedical subjects

Robert J Lederman

Publications and source records attributed to Robert J Lederman.

At least 19 recordsLinked to original sources

High-resolution 3D arteriography of chronic total peripheral occlusions using a T1-W turbo spin-echo sequence with inner-volume imaging.

Percutaneous revascularization of peripheral artery chronic total occlusion (CTO) is challenging under X-ray guidance without direct image feedback, due to poor visualization of the obstructed segment and underappreciation of vessel tortuosity. Operators are required to steer interventional devices relatively "blindly," and therefore procedural failure or perforation may occur. Alternatively, MRI may allow complete visualization of both patent and occluded arterial segments. We designed and implemented a 3D high-resolution, T(1)-weighted (T(1)-W) turbo spin-echo (TSE) MRI sequence with inner-volume (IV) imaging to enable detailed peripheral artery CTO imaging. Using this sequence, high-resolution volumes of interest (VOIs) around the vessel were achieved within 5-10 min. This imaging approach may be used for rapid pre- and postprocedural evaluations, and as a 3D roadmap that can be overlaid during real-time X-, MR-, or XMR-guided catheterization. Experiments were successfully performed on a carotid CTO model in swine ex vivo, and in peripheral arteries in normal volunteers and patients in vivo. Delineation of the vascular architecture, including contrast differences between the patent and occluded artery segments, and lesion morphology heterogeneity were visualized.

Animals↗

Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome.

Hyper IgE recurrent infection syndrome (HIES, or Job's syndrome) is a primary immunodeficiency characterized by recurrent skin and lung infections, eczema, elevated serum immunoglobulin E (IgE) levels, and various connective tissue and skeletal system abnormalities including characteristic facies, scoliosis, joint hyperextensibility, retained primary dentition, craniosynostosis, osteopenia, and pathologic fractures. We have identified two patients with aneurysmal coronary artery disease. One was a forty-three-year-old man with HIES and coronary artery aneurysms and ectasia identified on cardiac catheterization following myocardial infarction. The other was a 48-year-old man with coronary artery ectasia-aneurysm identified after cardiac catheterization for evaluation of chest pain. Although connective tissue abnormalities are common in HIES, this is the first report of coronary artery aneurysms in HIES. Further studies are necessary to determine the incidence, pathogenesis, and optimal therapy of these arterial abnormalities in HIES.

Adult↗

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.

Animals↗

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↗

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.

Angioplasty, Balloon, Coronary↗

Usefulness of translesional pressure gradient and pharmacological provocation for the assessment of intermediate renal artery disease.

OBJECTIVE: We sought to determine the hemodynamic significance of intermediate RAS by measuring translesional systolic pressure gradients (TSPG), using a pressure-sensing guidewire at baseline and after acetylcholine (ACh) induced hyperemia, following selective renal artery angiography. BACKGROUND: Renal artery stenosis (RAS) is a cause of reversible hypertension and nephropathy. Stenting effectively relieves RAS, however improvement in blood pressure control or renal function is variable and unpredictable. Hemodynamic significance is usually present with RAS when diameter stenosis is >75%, but is less predictable in intermediate (30%-75%) RAS. METHODS: Twenty-two patients (26 renal arteries) with uncontrolled hypertension underwent invasive hemodynamic assessment because of intermediate RAS, defined as radiocontrast angiographic diameter stenosis (DS) between 30% and 75% (quantitative DS was measured prospectively). Translesional pressure gradients were measured using a 0.014" pressure-sensing wire. Hyperemia was induced by administration of intrarenal ACh. RESULTS: Visual and measured angiographic lesion severity did not correlate with TSPG either at baseline (visual DS, R(2) = 0.091, P = 0.13; measured DS, R(2) = 0.124, P = 0.07) or with hyperemia (visual DS, R(2) = 0.057, P = 0.24; measured DS, R(2) = 0.101, P = 0.12). Baseline and maximal hyperemic gradient did correlate (R(2) = 0.567; P < 0.05). Pharmacological provocation produced a significant increase in TSPG (mean; baseline, 18 +/- 21 vs. hyperemia, 34 +/- 41 mm Hg; P < 0.05). A hemodynamically significant lesion (TSPG > 20 mm Hg) was found in 14/26 (54%) arteries (13 patients); 13 (60%) patients subsequently underwent renal artery stenting for hemodynamically significant RAS. At follow-up (at least 30 days), there was a significant decrease in systolic blood pressure (mean; 167 +/- 24 vs. 134 +/- 19 mm Hg; P < 0.001). CONCLUSIONS: Intrarenal administration of ACh induces hyperemia and can be used to unmask resistive renal artery lesions. Gradient measurement and induced hyperemia may be warranted in the invasive assessment of intermediate renal artery stenoses, rather than relying on stenosis severity alone. Further study is needed to determine whether translesional pressure gradients and pharmacological provocation predict clinical benefit after renal artery stenting.

Acetylcholine↗

Real-time interactive MRI-guided cardiac surgery: aortic valve replacement using a direct apical approach.

Minimally invasive cardiac surgery requires arresting and emptying of the heart, which compromises visualization of the surgical field. In this feasibility study a novel surgical procedure is demonstrated in which real-time MRI is used to guide the placement of a prosthetic aortic valve in the beating heart via direct apical access in eight porcine hearts. A clinical stentless bioprosthetic valve affixed to a platinum stent was compressed onto a balloon-tipped catheter. This was fed through a 15-18-mm delivery port inserted into the left ventricular (LV) apex via a minimally invasive subxyphoid incision. Using interactive real-time MRI, the surgeon implanted the prosthetic valve in the correct location at the aortic annulus within 90 s. In four of the animals immediately after implantation, ventricular function, blood flow through the valve, and myocardial perfusion were evaluated with MRI. MRI-guided beating-heart surgery may provide patients with a less morbid and more durable solution to structural heart disease.

Animals↗

Advances in interventional cardiovascular MRI.

Because of its superior soft tissue imaging, MRI has become a valuable diagnostic tool in cardiovascular disease. These strengths make MRI attractive to guide therapeutic catheter-based procedures, both conventional and novel. We review how to configure an interventional MRI suite, how MRI catheter devices differ from conventional radiographic catheters, and finally developments in preclinical and investigational clinical applications.

Cardiac Catheterization↗

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.

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↗

Magnetic resonance image-guided trans-septal puncture in a swine heart.

PURPOSE: To test the feasibility of performing magnetic resonance (MR)-guided trans-septal punctures in the swine heart. MATERIALS AND METHODS: All procedures were performed in a 1.5-T MR scanner. A novel, active MR intravascular needle system was utilized for needle tracking and septal punctures. Trans-septal punctures were performed in five swine using electrocardiogram (ECG)-gated high resolution and non-ECG-gated, real-time MR imaging techniques. The intravascular needle was advanced over a guidewire from the femoral vein. Once the needle was in proper position, trans-septal punctures were made. RESULTS: Active tracking of the needle traversing the septum was possible. The location of the catheter tip was confirmed using real time gradient recalled echo (GRE). After a confirmatory ventriculogram with gadolinium-DTPA, a 0.014-inch guidewire was advanced into the left atrium and left ventricle. All punctures were made with no change in cardiac rhythm or rate; postmortem analysis was performed on all animals and demonstrated that 18/19 (95%) punctures were directly through the fossa ovalis. CONCLUSION: Using only MR guidance and a novel active intravascular needle system, we were able to repeatedly puncture the fossa ovalis in a swine heart from a transfemoral approach, with direct visualization of all components, including the needle, the atria, the fossa ovalis, and the surrounding vasculature.

Animals↗

Measurement of skeletal muscle perfusion during postischemic reactive hyperemia using contrast-enhanced MRI with a step-input function.

The regional distribution of skeletal muscle blood flow was measured during postischemic reactive hyperemia using Gd-DTPA contrast-enhanced (CE) MRI. The release of an occlusive thigh cuff was used to deliver a step-input of contrast concentration that was coincident with the onset of reactive hyperemia. A first-order tracer kinetic equation was used to estimate the unidirectional influx constant, Ki (ml/100 g/min), and the distribution volume of Gd-DTPA in the tissue, v(e), from T1-weighted images acquired with saturation recovery (SR) steady-state free precession (SSFP) and spoiled gradient-echo (SPGR) protocols. The capillary permeability surface (PS) area increased significantly during reactive hyperemia, which facilitated rapid extraction of Gd-DTPA during the first pass. Regional muscle group studies from 11 normal volunteers yielded blood flow (Ki) values of 108.3 +/- 34.1 ml/100 g/min in the gastrocnemius, 184.3 +/- 41.3 ml/100 g/min in the soleus, and 122.4 +/- 34.4 ml/100 g/min in the tibialis anterior. The distribution volumes (v(e)) in the corresponding muscle groups were respectively 8.3% +/- 2.1%, 9.3% +/- 1.9%, and 7.9% +/- 1.8% from the kinetic model, and 8.8% +/- 2.4%, 9.1% +/- 1.9%, and 7.2% +/- 1.4% from tissue relaxometry studies. Bulk blood flow studies in the same volunteers using phase-contrast velocimetry (popliteal artery) yielded significantly lower flow values, but with a correlation coefficient R2 = 0.62 and P = 0.004.

Algorithms↗

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.

Animals↗