Audrius Brazdeikis

Design Maps for the Hyperthermic Treatment of Tumors with Superparamagnetic Nanoparticles

A plethora of magnetic nanoparticles has been developed and investigated under different alternating magnetic fields (AMF) for the hyperthermic treatment of malignant tissues. Yet, clinical applications of magnetic hyperthermia are sporadic, mostly due to the low energy conversion efficiency of the metallic nanoparticles and the high tissue concentrations required. Here, we study the hyperthermic performance of commercially available formulations of superparamagnetic iron oxide nanoparticles (SPIOs), with core diameter of 5, 7 and 14 nm, in terms of absolute temperature increase ΔT and specific absorption rate (SAR). These nanoparticles are operated under a broad range of AMF conditions, with frequency f varying between 0.2 and 30 MHz; field strength H ranging from 4 to 10 kA m−1; and concentration cMNP varying from 0.02 to 3.5 mg ml−1. At high frequency field (∼30 MHz), non specific heating dominates and ΔT correlates with the electrical conductivity of the medium. At low frequency field (<1 MHz), non specific heating is negligible and the relaxation of the SPIO within the AMF is the sole energy source. We show that the ΔT of the medium grows linearly with cMNP, whereas the SARMNP of the magnetic nanoparticles is independent of cMNP and varies linearly with f and H2. Using a computational model for heat transport in a biological tissue, the minimum requirements for local hyperthermia (Ttissue >42°C) and thermal ablation (Ttissue >50°C) are derived in terms of cMNP, operating AMF conditions and blood perfusion. The resulting maps can be used to rationally design hyperthermic treatments and identifying the proper route of administration – systemic versus intratumor injection – depending on the magnetic and biodistribution properties of the nanoparticles.

Synthesis of multifunctional magnetic nanoflakes for magnetic resonance imaging, hyperthermia, and targeting.

Iron oxide nanoparticles (IOs) are intrinsically theranostic agents that could be used for magnetic resonance imaging (MRI) and local hyperthermia or tissue thermal ablation. Yet, effective hyperthermia and high MR contrast have not been demonstrated within the same nanoparticle configuration. Here, magnetic nanoconstructs are obtained by confining multiple, ∼ 20 nm nanocubes (NCs) within a deoxy-chitosan core. The resulting nanoconstructs—magnetic nanoflakes (MNFs)—exhibit a hydrodynamic diameter of 156 ± 3.6 nm, with a polydispersity index of ∼0.2, and are stable in PBS up to 7 days. Upon exposure to an alternating magnetic field of 512 kHz and 10 kA m–1, MNFs provide a specific absorption rate (SAR) of ∼75 W gFe–1, which is 4–15 times larger than that measured for conventional IOs. Moreover, the same nanoconstructs provide a remarkably high transverse relaxivity of ∼500 (mM s)−1, at 1.41T. MNFs represent a first step toward the realization of nanoconstructs with superior relaxometric and ablation properties for more effective theranostics.

Gold-silver alloy nanoshells: a new candidate for nanotherapeutics and diagnostics

We have developed novel gold-silver alloy nanoshells as magnetic resonance imaging (MRI) dual T1 (positive) and T2 (negative) contrast agents as an alternative to typical gadolinium (Gd)-based contrast agents. Specifically, we have doped iron oxide nanoparticles with Gd ions and sequestered the ions within the core by coating the nanoparticles with an alloy of gold and silver. Thus, these nanoparticles are very innovative and have the potential to overcome toxicities related to renal clearance of contrast agents such as nephrogenic systemic fibrosis. The morphology of the attained nanoparticles was characterized by XRD which demonstrated the successful incorporation of Gd(III) ions into the structure of the magnetite, with no major alterations of the spinel structure, as well as the growth of the gold-silver alloy shells. This was supported by TEM, ICP-AES, and SEM/EDS data. The nanoshells showed a saturation magnetization of 38 emu/g because of the presence of Gd ions within the crystalline structure with r1 and r2 values of 0.0119 and 0.9229 mL mg-1 s-1, respectively (Au:Ag alloy = 1:1). T1- and T2-weighted images of the nanoshells showed that these agents can both increase the surrounding water proton signals in the T1-weighted image and reduce the signal in T2-weighted images. The as-synthesized nanoparticles exhibited strong absorption in the range of 600-800 nm, their optical properties being strongly dependent upon the thickness of the gold-silver alloy shell. Thus, these nanoshells have the potential to be utilized for tumor cell ablation because of their absorption as well as an imaging agent.

Nondestructive testing of PEM fuel cells

We report on electric and magnetic nondestructive testing (NDT) of proton exchange membrane (PEM) fuel cells. Fuel cells are electrochemical devices that convert hydrogen and oxygen gas into water, heat and useable electricity. Fuel cell membrane health can affect the cells overall performance and lifetime. We have explored several NDT techniques employing highly sensitive HTS and LTS SQUID and fluxgate magnetometers. Magnetic fields generated by electrochemical currents flowing in the fuel cell are studied in the spatial, time and frequency domain under various operating conditions. Frequency domain electric and magnetic signals are compared under extreme conditions and membrane failure.

Assembly of Iron Oxide Nanocubes for Enhanced Cancer Hyperthermia and Magnetic Resonance Imaging

Multiple formulations of iron oxide nanoparticles (IONPs) have been proposed for enhancing contrast in magnetic resonance imaging (MRI) and for increasing efficacy in thermal ablation therapies. However, insufficient accumulation at the disease site and low magnetic performance hamper the clinical application of IONPs. Here, 20 nm iron oxide nanocubes were assembled into larger nanoconstructs externally stabilized by a serum albumin coating. The resulting assemblies of nanocubes (ANCs) had an average diameter of 100 nm and exhibited transverse relaxivity (r2 = 678.9 ± 29.0 mM‒1·s‒1 at 1.41 T) and heating efficiency (specific absorption rate of 109.8 ± 12.8 W·g‒1 at 512 kHz and 10 kA·m‒1). In mice bearing glioblastoma multiforme tumors, Cy5.5-labeled ANCs allowed visualization of malignant masses via both near infrared fluorescent and magnetic resonance imaging. Also, upon systemic administration of ANCs (5 mgFe·kg‒1), 30 min of daily exposure to alternating magnetic fields for three consecutive days was sufficient to halt tumor progression. This study demonstrates that intravascular administration of ANCs can effectively visualize and treat neoplastic masses.

Magnetic imaging method based on magnetic relaxation of magnetic nanoparticles

We present a well-posed magnetic imaging method based on magnetic relaxation of magnetic nanoparticles for obtaining high-spatial resolution image of magnetic tracers. The method relies on the principle that Neel relaxation of the magnetic nanoparticles is faster in a finite magnetic field than in the absence of the field. The magnetic nanoparticles are used as signal generator and a superconducting quantum interference device is used as the signal detector. An image of superparamagnetic iron oxide nanoparticle tracer is obtained directly by mapping the magnetization decays. The experimental imaging capability is demonstrated using commercially available gamma-ferric oxide (γ-Fe2O3) magnetic nanoparticles.

Non-invasive assessment of the heart function in unshielded clinical environment by SQUID gradiometry

Bioelectrical activity of the heart produces minute magnetic fields that may be measured above the torso with superconducting quantum interference device (SQUID) sensors. A new application has been developed which permits noninvasive assessment of the heart function in unshielded magnetically harsh clinical environment. The system incorporates a multichannel SQUID system, a supine nonmagnetic ergometer, a peripheral data interface and software tools for processing magnetocardiographic data. To demonstrate the performance of the method, biomagnetic measurements have been performed both at rest and during physical exercise. Signal processing, signal-to-noise ratio and artifact rejection procedures have been discussed.

Cardiovascular impact of manual and automated turns in ICU

Mechanically ventilated patients in the intensive care unit (ICU) are typically turned manually by nursing staff to reduce the risk of developing ventilator associated pneumonia and other problems in the lungs. However, turning can induce changes in the heart rate and blood pressure that can at times have a destabilizing effect. We report here on the early stage of a study that has been undertaken to measure the cardiovascular impact of manual turning, and compare it to changes induced when patients lie on automated beds that turn continuously. Heart rate and blood pressure data were analyzed over ensembles of turns with autoregressive models for comparing baseline level to the dynamic response. Manual turning stimulated a response in the heart rate that lasted for a median of 20 minutes and was of magnitude 5 to 13 bpm. The corresponding response in mean arterial pressure was 11 to 19 mm Hg, lasting for 8 to 21 minutes. There was no discernible response of either variable to automated turns.

A comparison of fetal and neonatal heart rate variability at similar post-menstrual ages

Substantial differences of heart rate variability (HRV) were found between fetuses and prematurely born neonates in the high-frequency band of the power spectrum. The range of post-menstrual ages of the fetuses and neonates were closely matched in this study. Growth of HRV was observed in low-frequency and high-frequency bands, reflecting maturation of the autonomic nervous system. The higher level of fetal HRV in the high-frequency band persisted even after accounting for age-related changes. Multiscale entropy was also higher in fetuses than in prematurely born neonates. These results suggest that the autonomic balance is poorer among neonates born prematurely than in fetuses of identical post-menstrual age.

Monitoring fetal development with magnetocardiography

Fetal heart rate variability (fHRV) is useful for noninvasive assesssment of the status of the autonomic nervous system of the developing fetus. In this pilot study we acquired fetal magnetocardiograms (fMCG) in a magnetically shielded environment. Each recording was of 5-minute duration and was subsequently repeated in a high-frequency noise environment to examine the feasibility of conducting future recordings in clinical environments that lack facilities for magnetic shielding. The fMCG (n=17) were recorded at 9 spatial locations above the pregnant abdomen at 26 to 35 weeks gestational age (GA) by a second-order SQUID gradiometer. The signal-to-noise was adequate for reliable QRS detection even in the noisy environment, especially for GA ≥ 30. The total spectral power of the RR-series, as well as band powers at low (0.05 to 0.25 Hz) and high (0.25 to 1.00 Hz) frequencies independently exhibited an increasing trend with GA. There was no evidence of bias in spectral power due to lack of shielding. These results provide experimental evidence supporting further studies in magnetically unshielded environments and may have an important implication for future clinical use of fMCG in the assessment of fHRV.