Barbara Blasiak

NaDyF4 Nanoparticles as T2 Contrast Agents for Ultrahigh Field Magnetic Resonance Imaging.

A major limitation of the commonly used clinical MRI contrast agents (CAs) suitable at lower magnetic field strengths (<3.0 T) is their inefficiency at higher fields (>7 T), where next-generation MRI scanners are going. We present dysprosium nanoparticles (β-NaDyF4 NPs) as T2 CAs suitable at ultrahigh fields (9.4 T). These NPs effectively enhance T2 contrast at 9.4 T, which is 10-fold higher than the clinically used T2 CA (Resovist). Evaluation of the relaxivities at 3 and 9.4 T show that the T2 contrast enhances with an increase in NP size and field strength. Specifically, the transverse relaxivity (r2) values at 9.4 T were ∼64 times higher per NP (20.3 nm) and ∼6 times higher per Dy(3+) ion compared to that at 3 T, which is attributed to the Curie spin relaxation mechanism. These results and confirming phantom MR images demonstrate their effectiveness as T2 CAs in ultrahigh field MRIs.

Evaluation of brain tumor vessels specific contrast agents for glioblastoma imaging

A mouse model of glioblastoma multiforme was used to determine the accumulation of a targeted contrast agent in tumor vessels. The contrast agent, consisting of superparamagnetic iron oxide coated with dextran, was functionalized with an anti-insulin-like-growth-factor binding protein 7 (anti-IGFBP7) single domain antibody. The near infrared marker, Cy5.5, was also attached for an in vivo fluorescence study. A 9.4T magnetic resonance imaging (MRI) system was used for in vivo studies on days 10 and 11 following tumor inoculation. T(2) relaxation time was used to measure the accumulation of the contrast agent in the tumor. Changes in tumor to brain contrast because of active targeting were compared with a nontargeted contrast agent. Effective targeting was confirmed with near infrared measurements and fluorescent microscopic analysis. The results showed that there was a statistically significant (P < .01) difference in normalized T(2) between healthy brain and tumor tissue 10 min, 1 h, and 2 h point postinjection of the anti-IGFBP7 single domain antibody targeted and nontargeted iron oxide nanoparticles. A statistical difference remained in animals treated with targeted nanoparticles 24 h postinjection only. The MRI, near infrared imaging, and fluorescent microscopy studies showed corresponding spatial and temporal changes. We concluded that the developed anti-IGFBP7-iron oxide single domain antibody-targeted MRI contrast agent selectively binds to abnormal vessels within a glioblastoma. T(2)-weighted MRI and near infrared imaging are able to detect the targeting effects in brain tumors.

Applications of nanoparticles for MRI cancer diagnosis and therapy

Recent technological advances in nanotechnology, molecular biology, and imaging technology allow the application of nanomaterials for early and specific cancer detection and therapy. As early detection is a prerequisite for successful treatment, this area of research has been rapidly growing. This paper provides an overview of recent advances in production, functionalization, toxicity reduction, and application of nanoparticles to cancer diagnosis, treatment, and treatment monitoring. This review focuses on superparamagnetic nanoparticles used as targeted contrast agents in MRI, but it also describes nanoparticles applied as contrasts in CT and PET. A very recent development of core/shell nanoparticles that promises to provide positive contrast in MRI of cancer is provided. The authors concluded that despite unenviable obstacles, the progress in the area will lead to rapidly approaching applications of nanotechnology to medicine enabling patient-specific diagnosis and treatment.

Hyperpolarized and Inert Gas MRI: The Future

Magnetic resonance imaging (MRI) is a potentially ideal imaging modality for noninvasive, nonionizing, and longitudinal assessment of disease. Hyperpolarized (HP) agents have been developed in the past 20 years for MR imaging, and they have the potential to vastly improve MRI sensitivity for the diagnosis and management of various diseases. The polarization of nuclear magnetic resonance (NMR)-sensitive nuclei other than 1H (e.g., 3He, 129Xe) can be enhanced by a factor of up to 100,000 times above thermal equilibrium levels, which enables direct detection of the HP agent with no background signal. In this review, a number of HP media applications in MR imaging are discussed, including HP 3He and 129Xe lung imaging, HP 129Xe brain imaging, and HP 129Xe biosensors. Inert fluorinated gas MRI, which is a new lung imaging technique that does not require hyperpolarization, is also briefly discussed. This technique will likely be an important future direction for the HP gas lung imaging community.

Molecular susceptibility weighted imaging of the glioma rim in a mouse model

BACKGROUND Glioma is the most common and most difficult to treat brain cancer. Despite many efforts treatment, efficacy remains low. As neurosurgical removal is the standard procedure for glioma, a method, allowing for both early detection and exact determination of the location, size and extent of the tumor, could improve a patients positive response to therapy. NEW METHOD We propose application of susceptibility weighted molecular magnetic resonance imaging using, targeted contrast agents, based on superparamagnetic iron oxide nanoparticles, for imaging of the, glioma rim, namely brain-tumor interface. Iron oxide attached to the targeted cells increases, susceptibility differences at the boundary between tumor and normal tissue, providing the opportunity, to utilize susceptibility weighted imaging for improved tumor delineation. We investigated potential, enhancement of the tumor-brain contrast, including tumor core and rim when using susceptibility, weighted MRI for molecular imaging of glioma. RESULTS There were significant differences in contrast-to-noise ratio before, 12 and 120min after contrast, agent injection between standard gradient echo pulse sequence and susceptibility weighted molecular, magnetic resonance imaging for the core-brain, tumor rim-core and tumor rim-brain areas. COMPARISON WITH EXISTING METHODS Currently, the most common MRI contrast agent used for glioma diagnosis is a non-specific, gadolinium-based agent providing T1-weighted enhancement. Susceptibility-weighted magnetic, resonance imaging is much less efficient when no targeted superparamagnetic contrast agents are, used. CONCLUSION The improved determination of glioma extent provided by SWI offers an important new tool for, diagnosis and surgical planning.

Detection of T2 changes in an early mouse brain tumor

The aim of the study was to determine the effect of early tumor growth on T(2) relaxation times in an experimental glioma model. A 9.4-T magnetic resonance imaging (MRI) system was used for the investigations. An animal model (n=12) of glioma was established using an intracranial inoculation of U87MGdEGFRvIII cells. The imaging studies were performed from Day 10 through Day 13 following tumor inoculation. Tumor blood vessel density was determined using quantitative immunochemistry. Tumor volume was measured daily using MR images. T(2) values of the tumor were measured in five areas across the tumor and calculated using a single exponential fitting of the echo train. The measurements on Days 10 and 13 after tumor inoculation showed a 20% increase in T(2). The changes in T(2) correlated with the size of the tumor. Statistically significant differences in T(2) values were observed between the edge of the tumor and the brain tissue on Days 11, 12 and 13 (P=.014, .008, .001, respectively), but not on Day 10 (P=.364). The results show that T(2)-weighted MRI may not detect glioma during an early phase of growth. T(2) increases in growing glioma and varies heterogenously across the tumor.

An optimized solenoidal head radiofrequency coil for low-field magnetic resonance imaging.

Applications of low-field magnetic resonance imaging (MRI) systems (<0.3 T) are limited due to the signal-to-noise ratio (SNR) being lower than that provided by systems based on superconductive magnets (> or = 1.5 T). Therefore, the design of radiofrequency (RF) coils for low-field MRI requires careful consideration as significant gains in SNR can be achieved with the proper design of the RF coil. This article describes an analytical method for the optimization of solenoidal coils. Coil and sample losses are analyzed to provide maximum SNR and optimum B(1) field homogeneity. The calculations are performed for solenoidal coils optimized for the human head at 0.2 T, but the method could also be applied to any solenoidal coil for imaging other anatomical regions at low field. Several coils were constructed to compare experimental and theoretical results. A head magnetic resonance image obtained at 0.2 T with the optimum design is presented.

A comparison of MR imaging of a mouse model of glioma at 0.2 T and 9.4 T.

Both 0.2 T and 9.4 T MRI systems were used to image a mouse model of glioma. RF coils were designed for both fields. A spin-echo, multi-echo pulse sequence was used to determine T(2) relaxation times of both brain and tumor tissues. Contrast-to-noise ratio was calculated based on the selected echo time. The results showed that 0.2 T is suitable for mouse model imaging, however total scan time must be long to achieve high enough SNR. T(2) relaxation times of the tumor and brain tissues can be measured at 0.2 T and are 2.1 and 1.8 times respectively longer at 0.2 T than at 9.4 T. Contrast to noise ratio for tumor and brain was better at high field than at the low field. We concluded that 0.2 T may be used to study mouse model of glioma using spin echo pulse sequence, yet the total scan time is long (about 40 min), resolution is lower (∼250 μm × 250 μm) and slice thickness (3mm) must be large enough to obtain sufficient SNR.

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

AbstractThis 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

Synthesis, characterization, and evaluation of PEGylated first-row transition metal ferrite nanoparticles as T2 contrast agents for high-field MRI

Poly(ethylene glycol) (PEG)-coated transition metal ferrite (MFe2O4; M = Co, Cu, Fe, Mn, Ni, Zn) nanoparticles (NPs) were generated by a one-pot synthetic protocol and found to be small, fairly monodisperse, and superparamagnetic in nature. When evaluated for high-field magnetic resonance imaging, these showed high values of r2 and r2/r1 at 9.4 T. The well-documented biocompatibility of PEG coatings makes these NPs attractive candidates as T2 contrast agents for high-field MRI. A systematic comparison of magnetic and relaxivity measurements reveals MnFe2O4 and CoFe2O4 NPs to be superior T2 MRI contrast agents compared to Fe3O4 NPs.