Magnetic relaxometry as applied to sensitive cancer detection and localization

Abstract

Background: Here we describe superparamagnetic relaxometry (SPMR), a technology that utilizes highly sensitive magnetic sensors and superparamagnetic nanoparticles for cancer detection. Using SPMR, we sensitively and specifically detect nanoparticles conjugated to biomarkers for various types of cancer. SPMR offers high contrast in vivo, as there is no superparamagnetic background, and bones and tissue are transparent to the magnetic fields. Methods: In SPMR measurements, a brief magnetizing pulse is used to align superparamagnetic nanoparticles of a discrete size. Following the pulse, an array of superconducting quantum interference detectors (SQUID) sensors detect the decaying magnetization field. NP size is chosen so that, when bound, the induced field decays in seconds. They are functionalized with specific biomarkers and incubated with cancer cells in vitro to determine specificity and cell binding. For in vivo experiments, functionalized

Development of advanced signal processing and source imaging methods for superparamagnetic relaxometry

“…The system contains 7 SQUID sensors in the form of a second-order axial gradiometer with 4 cm baselines (De Haro et al 2015). The centers of the pick-up coils of these 7 sensors form a hexagon with one sensor located at the center and the other sensors at the six vertices of the hexagon.…”

“…(1B) depends on the nature of the SPIONs. Since the purpose of this paper is to demonstrate new methods in analyzing SPMR data, we refer the characterization and synthesis process of SPION to previous studies: The details of the SPION characterization is provided in (De Haro et al 2015), whereas the synthesis of these SPION is described in great detail in (Vreeland et al 2015). In initial experiments, the logarithm term was used primarily to fit the later part of the signal in order to establish the DC component of the signal which was then subtracted from the signal to make all data relative to 0 volts.…”

“…Furthermore, the rapid decay in the early time interval of the decay curve is also highly sensitive to the changes in phase and magnitude of the 60 Hz power-line noises. Thus, fitting the early time interval of the decay curve with the second and fourth decay terms as done previously (Flynn and Bryant 2005, Hathaway et al 2011, Adolphi et al 2012, De Haro et al 2015) in Eq. (1A) and Eq.…”

Phase-sensitive small-angle neutron scattering experiment

“…The PrecisionMRX® core-shell particles for PS-SANS were produced by Imagion Biosystems for use in magnetic relaxometry, an experimental technique for the diagnosis of cancer [13]. The particles consist of Fe 3 O 4 cores coated with a monolayer of oleic acid, a monolayer of amphiphilic polymer and a layer of polyethylene glycol.…”

Magnetic nanoparticles for biomedical applications

“…These techniques make directly use of the superparamagnetism of the particles to obtain quantitative information on their distribution in the tissue. Such methods may be useful for therapy control [9,16] as well as for the general diagnosis and detection of cancerous tissue [4]. Note that also MPI has the potential to provide such quantitative information with outstanding sensitivity and resolution.…”