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Biomedical subjects

Gregory M Lanza

Publications and source records attributed to Gregory M Lanza.

33 records · Page 2Linked to original sources
PubMed2004

Clinical utility of rapid prescreening magnetic resonance angiography of peripheral vascular disease prior to cardiac catheterization.

PURPOSE: The presence of peripheral vascular disease, in particular iliofemoral disease, is responsible in part for vascular complications from femoral artery cannulation. We investigated whether prescreening for vascular obstructions with magnetic resonance angiography (MRA) in high-risk patients with peripheral vascular disease (PVD) would provide useful information to angiographers seeking to improve the safety and efficiency of femoral artery access at cardiac catheterization. METHODS: Twelve consecutive patients with known or suspected PVD underwent contrast-enhanced, aorto-iliofemoral MRA using a real-time BolusTrak technique. Contrast-to-noise ratios for each patient were calculated. The cardiac angiographer reviewed the MRA prior to catheterization and selected an access site. The patients' subsequent clinical course was evaluated, and a postprocedure questionnaire was completed by the angiographer to define the value of the prescreening MRA. RESULTS: No significant vascular complications occurred in these patients as defined by failure of initially chosen access site, arterial dissection, limb ischemia, pseudoaneurysm formation, hemorrhage (including retroperitoneal hematoma), or need for blood transfusion or emergency vascular surgical repair. Statistical frequency analysis of the responses in the postprocedure questionnaire demonstrated that the MR data were clinically valuable in (1) influencing the initial choice of access site; (2) influencing technical alterations to the standard access; and, (3) enhancing confidence in the selection of access site. CONCLUSIONS: MRA prescreening in patients with PVD is an effective, novel adjunct to cardiac catheterization in selected patients that improves physician confidence and influences technical choices during coronary angiography from the femoral artery approach.

Adult↗
PubMed2004

Ultrasonic delineation of aortic microstructure: the relative contribution of elastin and collagen to aortic elasticity.

Aortic elasticity is an important factor in hemodynamic health, and compromised aortic compliance affects not only arterial dynamics but also myocardial function. A variety of pathologic processes (e.g., diabetes, Marfan's syndrome, hypertension) can affect aortic elasticity by altering the microstructure and composition of the elastin and collagen fiber networks within the tunica media. Ultrasound tissue characterization techniques can be used to obtain direct measurements of the stiffness coefficients of aorta by measurement of the speed of sound in specific directions. In this study we sought to define the contributions of elastin and collagen to the mechanical properties of aortic media by measuring the magnitude and directional dependence of the speed of sound before and after selective isolation of either the collagen or elastin fiber matrix. Formalin-fixed porcine aortas were sectioned for insonification in the circumferential, longitudinal, or radial direction and examined using high-frequency (50 MHz) ultrasound microscopy. Isolation of the collagen or elastin fiber matrices was accomplished through treatment with NaOH or formic acid, respectively. The results suggest that elastin is the primary contributor to aortic medial stiffness in the unloaded state, and that there is relatively little anisotropy in the speed of sound or stiffness in the aortic wall.

Algorithms↗
PubMed2004

Novel paramagnetic contrast agents for molecular imaging and targeted drug delivery.

Molecular biology and genomic sciences are revealing the early biological signatures for many diseases. In response, the Molecular Imaging community is rapidly developing contrast agents to visualize the nascent pathological changes and to concomitantly deliver treatment directly to the site of disease. The evaluation, development and use of these new agents require a complementary understanding of contrast chemistry and imaging techniques. The fundamental issues surrounding magnetic contrast agent development, rational drug delivery, MR molecular imaging, and their interdependence are elucidated.

Animals↗
PubMed2003

Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles.

BACKGROUND: Angiogenesis is a critical feature of plaque development in atherosclerosis and might play a key role in both the initiation and later rupture of plaques that lead to myocardial infarction and stroke. The precursory molecular or cellular events that initiate plaque growth and that ultimately contribute to plaque instability, however, cannot be detected directly with any current diagnostic modality. METHODS AND RESULTS: Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for approximately 80 days. alpha(v)beta3-Integrin-targeted, paramagnetic nanoparticles were injected intravenously and provided specific detection of the neovasculature within 2 hours by routine magnetic resonance imaging (MRI) at a clinically relevant field strength (1.5 T). Increased angiogenesis was detected as a 47+/-5% enhancement in MRI signal averaged throughout the abdominal aortic wall among rabbits that received alpha(v)beta3-targeted, paramagnetic nanoparticles. Pretreatment of atherosclerotic rabbits with alpha(v)beta3-targeted, nonparamagnetic nanoparticles competitively blocked specific contrast enhancement of the alpha(v)beta3-targeted paramagnetic agent. MRI revealed a pattern of increased alpha(v)beta3-integrin distribution within the atherosclerotic wall that was spatially heterogeneous along both transverse and longitudinal planes of the abdominal aorta. Histology and immunohistochemistry confirmed marked proliferation of angiogenic vessels within the aortic adventitia, coincident with prominent, neointimal proliferation among cholesterol-fed, atherosclerotic rabbits in comparison with sparse incidence of neovasculature in the control animals. CONCLUSIONS: This molecular imaging approach might provide a method for defining the burden and evolution of atherosclerosis in susceptible individuals as well as responsiveness of individual patients to antiatherosclerotic therapies.

Animals↗
PubMed2003

Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(nu)beta3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging.

Early noninvasive detection and characterization of solid tumors and their supporting neovasculature is a fundamental prerequisite for effective therapeutic intervention, particularly antiangiogenic treatment regimens. Emerging molecular imaging techniques now allow recognition of early biochemical, physiological, and anatomical changes before manifestation of gross pathological changes. Although new tumor, vascular, extracellular matrix, and lymphatic biomarkers continue to be discovered, the alpha(nu)beta(3)-integrin remains an attractive biochemical epitope that is highly expressed on activated neovascular endothelial cells and essentially absent on mature quiescent cells. In this study, we report the first in vivo use of a magnetic resonance (MR) molecular imaging nanoparticle to sensitively detect and spatially characterize neovascularity induced by implantation of the rabbit Vx-2 tumor using a common clinical field strength (1.5T). New Zealand White rabbits (2 kg) 12 days after implantation of fresh Vx-2 tumors (2 x 2 x 2 mm(3)) were randomized into one of three treatment groups: (a) alpha(nu)beta(3)-targeted, paramagnetic formulation; (b) nontargeted, paramagnetic formulation; and (c) alpha(nu)beta(3)-targeted nonparamagnetic nanoparticles followed by (2 h) the alpha(nu)beta(3)-targeted, paramagnetic formulation to competitively block magnetic resonance imaging (MRI) signal enhancement. After i.v. systemic injection (0.5 ml of nanoparticles/kg), dynamic T(1)-weighted MRI was used to spatially and temporally determine nanoparticle deposition in the tumor and adjacent tissues, including skeletal muscle. At 2-h postinjection, alpha(nu)beta(3)-targeted paramagnetic nanoparticles increased MRI signal by 126% in asymmetrically distributed regions primarily in the periphery of the tumor. Similar increases in MR contrast were also observed within the walls of some vessels proximate to the tumor. Despite their relatively large size, nanoparticles penetrated into the leaky tumor neovasculature but did not appreciably migrate into the interstitium, leading to a 56% increase in MR signal at 2 h. Pretargeting of the alpha(nu)beta(3)-integrin with nonparamagnetic nanoparticles competitively blocked the specific binding of alpha(nu)beta(3)-targeted paramagnetic nanoparticles, decreasing the MR signal enhancement (50%) to a level attributable to local extravasation. The MR signal of adjacent hindlimb muscle or contralateral control tissues was unchanged by either the alpha(nu)beta(3)-targeted or control paramagnetic agents. Immunohistochemistry of alpha(nu)beta(3)-integrin corroborated the extent and asymmetric distribution of neovascularity observed by MRI. These studies demonstrate the potential of this targeted molecular imaging agent to detect and characterize (both biochemically and morphologically) early angiogenesis induced by minute solid tumors with a clinical 1.5 Tesla MRI scanner, facilitating the localization of nascent cancers or metastases, as well as providing tools to phenotypically categorize and segment patient populations for therapy and to longitudinally follow the effectiveness of antitumor treatment regimens.

Animals↗
PubMed2003

Improved molecular imaging contrast agent for detection of human thrombus.

Molecular imaging of microthrombus within fissures of unstable atherosclerotic plaques requires sensitive detection with a thrombus-specific agent. Effective molecular imaging has been previously demonstrated with fibrin-targeted Gd-DTPA-bis-oleate (BOA) nanoparticles. In this study, the relaxivity of an improved fibrin-targeted paramagnetic formulation, Gd-DTPA-phosphatidylethanolamine (PE), was compared with Gd-DTPA-BOA at 0.05-4.7 T. Ion- and particle-based r(1) relaxivities (1.5 T) for Gd-DTPA-PE (33.7 (s*mM)(-1) and 2.48 x 10(6) (s*mM)(-1), respectively) were about twofold higher than for Gd-DTPA-BOA, perhaps due to faster water exchange with surface gadolinium. Gd-DTPA-PE nanoparticles bound to thrombus surfaces via anti-fibrin antibodies (1H10) induced 72% +/- 5% higher change in R(1) values at 1.5 T (deltaR(1) = 0.77 +/- 0.02 1/s) relative to Gd-DTPA-BOA (deltaR(1) = 0.45 +/- 0.02 1/s). These studies demonstrate marked improvement in a fibrin-specific molecular imaging agent that might allow sensitive, early detection of vascular microthrombi, the antecedent to stroke and heart attack.

Contrast Media↗
PubMed2003

Targeted ultrasonic contrast agents for molecular imaging and therapy.

Targeted contrast agents are expanding the detectability and diagnosis of pathology from a strict anatomic to biochemical basis. Moreover, these new agents, in their various forms, offer the potential for site-specific drug and gene delivery, i.e., the "magic bullet" first postulated by Paul Erhlich 100 years ago. The ability to direct drugs to the molecular signatures of disease, to confirm noninvasively their presence at the site-of-interest, and to quantify the adequacy of local drug concentration at the time of treatment, ie, rational targeted drug delivery, offers exciting new clinical paradigms in the near future.

Antibodies, Monoclonal↗
PubMed2002

Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent: implications for rational therapy of restenosis.

BACKGROUND: Restenosis is a serious complication of coronary angioplasty that involves the proliferation and migration of vascular smooth muscle cells (VSMCs) from the media to the intima, synthesis of extracellular matrix, and remodeling. We have previously demonstrated that tissue factor-targeted nanoparticles can penetrate and bind stretch-activated vascular smooth muscles in the media after balloon injury. In the present study, the concept of VSMC-targeted nanoparticles as a drug-delivery platform for the prevention of restenosis after angioplasty is studied. METHODS AND RESULTS: Tissue factor-targeted nanoparticles containing doxorubicin or paclitaxel at 0, 0.2, or 2.0 mole% of the outer lipid layer were targeted for 30 minutes to VSMCs and significantly inhibited their proliferation in culture over the next 3 days. Targeting of the nanoparticles to VSMC surface epitopes significantly increased nanoparticle antiproliferative effectiveness, particularly for paclitaxel. In vitro dissolution studies revealed that nanoparticle drug release persisted over one week. Targeted antiproliferative results were dependent on the hydrophobic nature of the drug and noncovalent interactions with other surfactant components. Molecular imaging of nanoparticles adherent to the VSMC was demonstrated with high-resolution T1-weighted MRI at 4.7T. MRI 19F spectroscopy of the nanoparticle core provided a quantifiable approach for noninvasive dosimetry of targeted drug payloads. CONCLUSIONS: These data suggest that targeted paramagnetic nanoparticles may provide a novel, MRI-visualizable, and quantifiable drug delivery system for the prevention of restenosis after angioplasty.

Animals↗
PubMed2002

Molecular imaging, targeted therapeutics, and nanoscience.

The recent emergence of "molecular imaging" as an academic discipline has set the stage for an evolutionary leap in diagnostic imaging. Recent advances in nuclear, ultrasound, optical, and magnetic resonance imaging have generated interest in molecular imaging across all modalities and across various academic, industrial, and governmental agencies. In this perspective, examples of the progress and the prospects for the future of molecular imaging and linked targeted therapeutics are reviewed.

Animals↗
PubMed2002

Improvements in the ultrasonic contrast of targeted perfluorocarbon nanoparticles using an acoustic transmission line model.

Targeted acoustic contrast agents offer the potential for sensitive ultrasonic detection of pathologic tissues. We have previously reported the development of a ligand-targeted, lipid-encapsulated, liquid perfluorodichlorooctane ultrasonic contrast system with a small nominal particle size (approximately 250-nm diameter). Perfluorocarbon nanoparticles substantially increase reflectivity when bound to targeted surfaces, and we propose that this system can be approximated physically as a simple, thin layer, acoustic transmission line. In this study, we evaluate this model and compare the ultrasonic reflectivity of different perfluorocarbon formulations with widely varying acoustic impedances targeted to either nitrocellulose membranes or plasma thrombi in vitro. Five perfluorocarbons were investigated: perfluorohexane (PFH), perfluorooctane (PFO), perfluorooctyl bromide (PFOB), perfluorodichlorooctane (PFDCO), and perfluorodecalin (PFD). Ultrasonic reflection was measured by acoustic microscopy (17 to 35 MHz). Acoustic reflectivity was increased (P < 0.05) by all targeted perfluorocarbon formulations, and the magnitude of the contrast effect was inversely correlated with the perfluorocarbon acoustic impedance. PFH nanoparticles exhibited the greatest enhancement, and PFD nanoparticles showed the least. The acoustic transmission line model predicted well the relative differences in acoustic reflectivity and frequency dependence among the perfluorocarbon formulations. For future clinical applications, PFO nanoparticles may provide the best combination of acoustic enhancement, in vivo physical stability, and safety.

Acoustics↗
PubMed2002

Temperature dependence of acoustic impedance for specific fluorocarbon liquids.

Recent studies by our group have demonstrated the efficacy of perfluorocarbon liquid nanoparticles for enhancing the reflectivity of tissuelike surfaces to which they are bound. The magnitude of this enhancement depends in large part on the difference in impedances of the perfluorocarbon, the bound substrate, and the propagating medium. The impedance varies directly with temperature because both the speed of sound and the mass density of perfluorocarbon liquids are highly temperature dependent. However, there are relatively little data in the literature pertaining to the temperature dependence of the acoustic impedance of these compounds. In this study, the speed of sound and density of seven different fluorocarbon liquids were measured at specific temperatures between 20 degrees C and 45 degrees C. All of the samples demonstrated negative, linear dependencies on temperature for both speed of sound and density and, consequently, for the acoustic impedance. The slope of sound speed was greatest for perfluorohexane (-278 +/- 1.5 cm/s-degrees C) and lowest for perfluorodichlorooctane (-222 +/- 0.9 cm/s-degrees C). Of the compounds measured, perfluorohexane exhibited the lowest acoustic impedance at all temperatures, and perfluorodecalin the highest at all temperatures. Computations from a simple transmission-line model used to predict reflectivity enhancement from surface-bound nanoparticles are discussed in light of these results.

Contrast Media↗
PubMedDate not supplied

Magnetic resonance molecular imaging with nanoparticles.

Molecular imaging agents are extending the potential of noninvasive medical diagnosis from basic gross anatomic descriptions to complicated phenotypic characterizations based on the recognition of unique cell surface biochemical signatures. Although originally the purview of nuclear medicine, molecular imaging is now a prominent feature of most clinically relevant imaging modalities, in particular magnetic resonance (MR) imaging. MR nanoparticulate agents afford the opportunity not only for targeted diagnostic studies but also for image-monitored site-specific therapeutic delivery, much like the "magic bullet" envisioned by Paul Erhlich 100 years ago. Combining high-resolution MR molecular imaging with drug delivery will facilitate verification and quantification of treatment (ie, rational targeted therapy) and will offer new clinical approaches to many diseases.

Cell Movement↗