Correction to: LyP-1 Conjugated Nanoparticles for Magnetic Resonance Imaging of Triple Negative Breast Cancer.

This article was updated to correct the spelling of B. Gino Fallone's name; it is correct as displayed above. Correction to: Mol Imaging Biol (2017). DOI: https://doi.org/10.1007/s11307-017-1140-4.

LyP-1 Conjugated Nanoparticles for Magnetic Resonance Imaging of Triple Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, or Her2/neu. Both diagnosis and treatment of TNBC remain a clinical challenge. LyP-1 is a cyclic 9 amino acid peptide that can bind to breast cancer cells. The goal of this study was to design and characterize LyP-1 conjugated to fluorescent iron oxide nanoparticles (LyP-1-Fe3O4-Cy5.5) as a contrast agent for improved and specific magnetic resonance imaging (MRI) in a preclinical model of TNBC. PROCEDURES: The binding of LyP-1-Fe3O4-Cy5.5 to MDA-MB-231 TNBC cells was evaluated and compared to scrambled peptide bio-conjugated to iron oxide nanoparticles (Ctlpep-Fe3O4-Cy5.5) as a negative control. Following the in vitro study, the MDA-MB-231 cells were injected into mammary glands of nude mice. Mice were divided into two groups: control group received Ctlpep- Fe3O4-Cy5.5 and LyP-1 group received LyP-1-Fe3O4-Cy5.5 (tail vein injection at 2 mg/kg of Fe3O4). Mice were imaged with an in vivo fluorescence imager and a 9.4 T MRI system at various time points after contrast agent injection. The T2 relaxation time was measured to observe accumulation of the contrast agent in breast tumor and muscle for both targeted and non-targeted contrast agents. RESULTS: Immunofluorescence revealed dense binding of the LyP-1-Fe3O4-Cy5.5 contrast agent to MDA-MB-231 cells; while little appreciable binding was observed to the scrambled negative control (Ctlpep-Fe3O4-Cy5.5). Optical imaging performed in tumor-bearing mice showed increased fluorescent signal in mammary gland of animals injected by LyP-1-Fe3O4-Cy5.5 but not Ctlpep- Fe3O4-Cy5.5. The results were confirmed ex vivo by the 2.6-fold increase of fluorescent signal from LyP-1-Fe3O4-Cy5.5 in extracted tumors when compared to the negative control. In MR imaging studies, there was a statistically significant (P < 0.01) difference in normalized T2 between healthy breast and tumor tissue at 1, 2, and 24 h post injection of the LyP-1-Fe3O4-Cy5.5. In animals injected with LyP-1-Fe3O4, distinct ring-like structures were observed with clear contrast between the tumor core and rim. CONCLUSION: The results demonstrate that LyP-1-Fe3O4 significantly improves MRI contrast of TNBC, hence has the potential to be exploited for the specific delivery of cancer therapeutics.

A non-axial superconducting magnet design for optimized patient access and minimal SAD for use in a Linac-MR hybrid: proof of concept.

A prototype rotating hybrid magnetic resonance imaging system and linac has been developed to allow for simultaneous imaging and radiation delivery parallel to B 0. However, the design of a compact magnet capable of rotation in a small vault with sufficient patient access and a typical clinical source-to-axis distance (SAD) is challenging. This work presents a novel superconducting magnet design as a proof of concept that allows for a reduced SAD and ample patient access by moving the superconducting coils to the side of the yoke. The yoke and pole-plate structures are shaped to direct the magnetic flux appropriately. The outer surface of the pole plate is optimized subject to the minimization of a cost function, which evaluates the uniformity of the magnetic field over an ellipsoid. The magnetic field calculations required in this work are performed with the 3D finite element method software package Opera-3D. Each tentative design strategy is virtually modeled in this software package, which is externally controlled by MATLAB, with its key geometries defined as variables. The optimization variables are the thickness of the pole plate at control points distributed over the pole plate surface. A novel design concept as a superconducting non-axial magnet is introduced, which could create a large uniform B 0 magnetic field with fewer geometric restriction. This non-axial 0.5 T superconducting magnet has a moderately reduced SAD of 123 cm and a vertical patient opening of 68 cm. This work is presented as a proof of principle to investigate the feasibility of a non-axial magnet with the coils located around the yoke, and the results encourage future design optimizations to maximize the benefits of this non-axial design.

Incorporating homonuclear polarization transfer into PRESS for proton spectral editing: illustration with lactate and glutathione.

A proton spectral editing pulse sequence for the detection of metabolites with spin systems that involve weak coupling is presented. The sequence is based on homonuclear polarization transfer incorporated into the standard PRESS (Point RESolved Spectroscopy) sequence, which is a volume-selective double spin echo method, to enable spatial localization. All peaks in the region of interest are initially suppressed whether they are peaks from the target metabolite or from contaminating background. The target signal is then restored by polarization transfer from a proton that has a resonance outside the suppressed region and to which the target spins are weakly coupled. This is achieved by the application of a 90 degrees hard pulse with phase orthogonal to that of the PRESS excitation pulse at the location of the first echo in PRESS and by optimizing the two PRESS timings, TE(1) and TE(2), for most efficient yield. Background signal not coupled to any protons outside the initially saturated region remains suppressed. The advantage of this sequence compared to multiple quantum filters is that signal from singlet peaks outside the suppressed area are preserved and can thus be used as a reference. The efficacy of the sequence was verified experimentally on phantom solutions of lactate and glutathione at 3.0 T. For the AX(3) spin system of lactate, the sequence timings were optimized by product operator calculations whereas for the ABX spin system of the cysteinyl group of glutathione numerical calculations were performed for sequence timing optimization.