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Biomedical subjects

Aharon Blank

Publications and source records attributed to Aharon Blank.

5 recordsLinked to original sources

Electron spin resonance microscopy applied to the study of controlled drug release.

We describe our recent developments towards 3D micron-scale imaging capability, based on electron spin resonance (ESR), and its application to the study of controlled release. The method, termed ESR microscopy (ESRM), is an extension of the conventional "millimeter-scale" ESR imaging technique. It employs paramagnetic molecules (such as stable radicals or spin-labeled drugs) and may enable one to obtain accurate 3D spatially resolved information about the drug concentration, its self-diffusion tensor, rotational correlation time and the pH in the release matrix. Theoretical calculations, along with initial experimental results, suggest that a 3D resolution of approximately 1 microm is feasible with this method. Here we were able to image successfully a high spin concentration sample with a resolution of approximately 3 x 3 x 8 microm and subsequently study a single approximately 120 microm biodegradable microsphere, internalized with a dilute solution of trityl radical, with a resolution of approximately 12.7 x 13.2 x 26 microm. Analysis of the microsphere ESR imaging data revealed a likely increase in the viscosity inside the sphere and/or binding of the radical molecule to the sphere matrix. Future directions for progress are also discussed.

Drug Delivery Systems↗

Diagnosis of thin-cap fibroatheromas by a self-contained intravascular magnetic resonance imaging probe in ex vivo human aortas and in situ coronary arteries.

OBJECTIVES: We sought to correlate findings obtained from a self-contained magnetic resonance imaging (MRI) probe with plaque morphology of ex vivo human aortas and coronary arteries. BACKGROUND: Early detection of thin-cap fibroatheromas (TCFAs) may allow for early preventive treatment of acute coronary syndromes. We developed an intravascular MRI catheter capable of imaging the arterial wall without external magnets or coils by differentiating lipid-rich and fibrotic-rich areas of the atherosclerotic plaque on the basis of differential water diffusion. METHODS: Aortic samples (n = 16) and coronary arteries were obtained within 12 h of death. Coronary specimens were intermediate in angiographic severity (30% to 60% luminal narrowing, n = 18). Blinded histologic and immunohistochemical analyses of the tissues were performed and correlated to MRI findings. RESULTS: The 16 aortic lesions included four ulcerated plaques, two TCFAs, two thick-cap fibrous atheromas, two intimal xanthomas, and six adaptive intimal thickenings. The MRI scan correctly correlated with the histologic diagnosis in 15 (94%) of 16 lesions. The 18 coronary lesions included one plaque rupture, three TFCAs, seven thick-cap fibrous atheromas, four fibrocalcific plaques, two intimal xanthomas, and one adaptive intimal thickening. The MRI scan correlated with the histologic diagnosis in 16 of 18 lesions (sensitivity 100%, specificity 89%). CONCLUSIONS: The self-contained intravascular MRI catheter successfully identified TCFA and may prove to be an important diagnostic approach to determining the presence of lesions with increased risk of causing death or myocardial infarction.

Aorta↗

Miniature self-contained intravascular magnetic resonance (IVMI) probe for clinical applications.

A miniature (1.73 mm in diameter) NMR probe, which contains a magnet and a radiofrequency (RF) coil, is presented. This probe is integrated at the tip of a standard catheter and can be inserted into the human coronary arteries, creating local magnetic fields needed to obtain the NMR signal from the blood vessel walls, without the need for external magnet or RF coils. The basic theory governing the probe performance in terms of signal-to-noise-ratio and contrast parameters is presented, along with measured results from test samples. The NMR signal can be analyzed to obtain tissue contrast parameters such as T1, T2 and the diffusion coefficient, which may be used to detect lipid-rich vulnerable plaques in the coronary arteries.

Blood Vessel Prosthesis↗

High resolution electron spin resonance microscopy.

NMR microscopy is routinely employed in fields of science such as biology, botany, and materials science to observe magnetic parameters and transport phenomena in small scale structures. Despite extensive efforts, the resolution of this method is limited (>10 microm for short acquisition times), and thus cannot answer many key questions in these fields. We show, through theoretical prediction and initial experiments, that ESR microscopy, although much less developed, can improve upon the resolution limits of NMR, and successfully undertake the 1 mum resolution challenge. Our theoretical predictions demonstrate that existing ESR technology, along with advanced imaging probe design (resonator and gradient coils), using solutions of narrow linewidth radicals (the trityl family), should yield 64 x 64 pixels 2D images (with z slice selection) with a resolution of 1 x 1 x 10 microm at approximately 60 GHz in less than 1h of acquisition. Our initial imaging results, conducted by CW ESR at X-band, support these theoretical predictions and already improve upon the previously reported state-of-the-art for 2D ESR image resolution achieving approximately 10 x 10 mum, in just several minutes of acquisition time. We analyze how future progress, which includes improved resonators, increased frequency of measurement, and advanced pulsed techniques, should achieve the goal of micron resolution.

Electron Spin Resonance Spectroscopy↗

Filling factor in a pulsed electron paramagnetic resonance experiment.

A definition and mathematical treatment to calculate the filling factor in a pulsed electron paramagnetic resonance (EPR) experiment are presented. The differences between filling factors in traditional, continuous wave (CW)-EPR experiments (eta), and in pulsed-EPR experiments (eta(p)), are discussed. We present some examples to demonstrate how eta(p) depends upon the particular pulse sequence and sample characteristics.

Biophysical Phenomena↗