A biomagnetic system for<i>in vivo</i>cancer imaging

The discrimination of immobilised superparamagnetic iron oxide nanoparticles (SPIONs) against SPIONs in fluid environments via their magnetic relaxation behaviour is a powerful tool for bio-medical imaging.Here we demonstrate that a gradiometer of laser-pumped atomic magnetometers can be used to record accurate time series of the relaxing magnetic field produced by pre-polarised SPIONs. We have investigated dry in vitro maghemite nanoparticle samples with different size distributions (average radii ranging from 14 to 21 nm) and analysed their relaxation using the Néel-Brown formalism. Fitting our model function to the magnetorelaxation (MRX) data allows us to extract the anisotropy constant K and the saturation magnetisation M S of each sample. While the latter was found not to depend on the particle size, we observe that K is inversely proportional to the (time-and size-) averaged volume of the magnetised particle fraction. We have identified the range of SPION sizes that are best suited for MRX detection considering our specific experimental conditions and sample preparation technique.

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“…From Eqs. (13), (15) and (16) it follows that the (orientationally averaged) magnetic moment per particle at time t is then given by…”

Section: Time Evolution Of the Sample Magnetisationmentioning

confidence: 99%

“…Many of the earlier studies used multi-core particles, while more recently larger single-core magnetic particles have shown large magnetic signals in observation windows ranging from 50 ms to 2 s [15]. Those and others studies [16][17][18] have demonstrated that (SQUID-based) MRX has a high potential for biomedical imaging applications.…”

Section: Introductionmentioning

confidence: 99%

A quantitative study of particle size effects in the magnetorelaxometry of magnetic nanoparticles using atomic magnetometry

Dolgovskiy

Lebedev

Colombo

et al. 2015

Journal of Magnetism and Magnetic Materials

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“…The direct methods that have been applied to SPION quantitation include both nonmagnetic schemes, such as positron emission tomography-computed tomography 5,6 and those utilizing the magnetic properties of the SPIONs, which include SQUID studies. [7][8][9] An attractive alternative to direct detection of the particles is to indirectly measure their concentration by examining their influence on the magnetic resonance relaxation characteristics of tissue water 10 or on the MRI-determined phase of the water signal, as in quantitative susceptibility mapping (QSM). 11 These indirect techniques offer the promise of high sensitivity due to the large number of water protons present in biological tissues (∼10 22 /g), although it is still not clear whether QSM is sensitive enough to measure SPION iron concentrations less than millimolar.…”

Section: Introductionmentioning

confidence: 99%

Quantitative [Fe]MRI of PSMA-targeted SPIONs specifically discriminates among prostate tumor cell types based on their PSMA expression levels

Sillerud

2016

IJN

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We report the development, experimental verification, and application of a general theory called [Fe]MRI (pronounced fem-ree) for the non-invasive, quantitative molecular magnetic resonance imaging (MRI) of added magnetic nanoparticles or other magnetic contrast agents in biological tissues and other sites. [Fe]MRI can easily be implemented on any MRI instrument, requiring only measurements of the background nuclear magnetic relaxation times (T 1 , T 2 ) of the tissue of interest, injection of the magnetic particles, and the subsequent acquisition of a pair of T 1 -weighted and T 2 -weighted images. These images, converted into contrast images, are subtracted to yield a contrast difference image proportional to the absolute nanoparticle, iron concentration, ([Fe]) image. [Fe]MRI was validated with the samples of superparamagnetic iron oxide nanoparticles (SPIONs) both in agarose gels and bound to human prostate tumor cells. The [Fe]MRI measurement of the binding of anti-prostate specific membrane antigen (PSMA) conjugated SPIONs to PSMA-positive LNCaP and PSMA-negative DU145 cells in vitro allowed a facile discrimination among prostate tumor cell types based on their PSMA expression level. The low [Fe] detection limit of ~2 μM for SPIONs allows sensitive MRI of added iron at concentrations considerably below the US Food and Drug Administration’s human iron dosage guidelines (<90 μM, 5 mg/kg).

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“…The following discussion outlines the materials and method used in this approach to detecting transplant rejection [5]. This methodology, when used on human beings, is intended to reduce the need for biopsies and to monitor a transplant for the effects of chemotherapy.…”

mentioning

confidence: 99%

“…(c) A brief magnetizing field is applied to the cells and particles. (d) The SQUID array detects the decaying remanence fields from these labeled cells after termination of the pulse [5,7]. (d) The field amplitudes are extracted from the data after signal averaging and removal of line-frequency artifacts.…”

mentioning

confidence: 99%

Use of a SQUID array to detect T-cells with magnetic nanoparticles in determining transplant rejection

Flynn¹,

Bryant

Bergemann

et al. 2007

Journal of Magnetism and Magnetic Materials

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Acute rejection in organ transplant is signaled by the proliferation of T-cells that target and kill the donor cells requiring painful biopsies to detect rejection onset. An alternative non-invasive technique is proposed using a multi-channel superconducting quantum interference device (SQUID) magnetometer to detect T-cell lymphocytes in the transplanted organ labeled with magnetic nanoparticles conjugated to antibodies specifically attached to lymphocytic ligand receptors. After a magnetic field pulse, the T-cells produce a decaying magnetic signal with a characteristic time of the order of a second. The extreme sensitivity of this technique, 10 5 cells, can provide early warning of impending transplant rejection and monitor immune-suppressive chemotherapy. KeywordsMagnetic nanoparticle; SQUID sensor; Remanence field; Transplant rejection; Antibody A methodology using superparamagnetic nanoparticles in conjunction with extremely sensitive magnetometers has been developed to determine if a transplanted organ is undergoing acute rejection by the immune system without requiring biopsies. Rejection of transplanted organs is a significant problem. Transplants replace many different diseased organs such as the kidney, heart, liver and lungs. In kidney disease alone, there are about 52,000 people in the United States on waiting lists for kidney transplants. In addition, 60,000 people die each year of kidney disease. Between 1996 and 1998, 94,000 kidney transplants were done in the United States [1]. One-third of the donors are not good matches. Currently, biopsy is the method to ascertain impending rejection, once the symptoms have occurred, and to monitor the progress of chemotherapy.Most rejections result from actions of the adaptive immune system. Rejection occurs through several mechanisms including antibodies produced by B-cells, cytokine release, and proliferation of T-cells. The technique described here, focuses on a non-invasive method of detecting, in vivo, T-cell lymphocytes that target and destroy the cells of the transplant, that they recognize as foreign, in the same manner as they destroy true pathogens [2][3][4]. To offset this response, transplanted organs are selected carefully for compatibility between donor and recipient. The procedure is usually accompanied by chemotherapy designed to minimize the immune system response. This care is often insufficient and the organ is rejected by the *Corresponding author. Tel.: +505 294 1298. E-mail address: seniorsci@nmia.com (E.R. Flynn).. The large number of lymphocyte cells in the body, approximately 10 12 , primarily reside in the lymphatic system and the lymphoid organs (thymus, spleen and appendix). Lymphocytic cells are not normally present in other organs but, on recognition of a foreign substance, exponentially multiply and invade the organ. The patient will suffer fever or other responses to this immune system response. A biopsy of the transplant will be made to determine the presence of lymphocytes through microscopic observation or other mean...

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A biomagnetic system forin vivocancer imaging

Cited by 97 publications

References 28 publications

A quantitative study of particle size effects in the magnetorelaxometry of magnetic nanoparticles using atomic magnetometry

A quantitative study of particle size effects in the magnetorelaxometry of magnetic nanoparticles using atomic magnetometry

Quantitative [Fe]MRI of PSMA-targeted SPIONs specifically discriminates among prostate tumor cell types based on their PSMA expression levels

Use of a SQUID array to detect T-cells with magnetic nanoparticles in determining transplant rejection

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