Earlier detection of tumor treatment response using magnetic resonance diffusion imaging with oscillating gradients

An improved method for detecting early changes in tumors in response to treatment, based on a modification of diffusion-weighted magnetic resonance imaging, has been demonstrated in an animal model. Early detection of therapeutic response in tumors is important both clinically and in pre-clinical assessments of novel treatments. Noninvasive imaging methods that can detect and assess tumor response early in the course of treatment, and before frank changes in tumor morphology are evident, are of considerable interest as potential biomarkers of treatment efficacy. Diffusion-weighted magnetic resonance imaging is sensitive to changes in water diffusion rates in tissues that result from structural variations in the local cellular environment, but conventional methods mainly reflect changes in tissue cellularity and do not convey information specific to microstructural variations at sub-cellular scales. We implemented a modified imaging technique using oscillating gradients of the magnetic field for evaluating water diffusion rates over very short spatial scales that are more specific for detecting changes in intracellular structure that may precede changes in cellularity. Results from a study of orthotopic 9L gliomas in rat brains indicate that this method can detect changes as early as 24 h following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea, when conventional approaches do not find significant effects. These studies suggest that diffusion imaging using oscillating gradients may be used to obtain an earlier indication of treatment efficacy than previous magnetic resonance imaging methods.     

A model for quantitative changes in the magnetic resonance parameters of muscle in children after therapeutic irradiation

Purpose/ObjectiveThis study aimed to develop objective models of radiation effects on musculature in children with soft tissue sarcoma using treatment dosimetry and clinical and quantitative magnetic resonance imaging (MRI) parameters that may be used to guide treatment planning or predict side effects.MethodsIn the initial 13 patients undergoing external beam radiation therapy (RT) on a Phase II study of conformal or intensity-modulated RT for the treatment of soft tissue sarcoma approved by an Institutional Review Board, we evaluated quantitative MRI changes in the musculature to assess radiation-related treatment effects. Patients with soft tissue sarcoma, including Ewing's sarcoma, had quantitative T₁, T₂ and dynamic enhanced MRI (DEMRI) performed before, during (Week 4) and after RT (Week 12). Regions of interest were selected in consistent locations within and outside the high-dose regions (on ipsilateral and contralateral sides when available). Mean RT dose, T₁, T₂ and DEMRI parameters were calculated and modeled using a mixed random coefficient dose model.ResultsThe mean doses to the high- and low-dose regions were 56.4 Gy (41.8–75.3 Gy) and 13.0 Gy (0.1–37.5 Gy), respectively. Compared with tissues distant from the tumor bed, maximal enhancement was significantly increased in tissues adjacent to the tumor/tumor bed prior to RT (60.6 vs. 44.2, P=.045) and remained elevated after 12 weeks. T₁ was significantly elevated in tissues adjacent to the tumor bed prior to RT (942.4 vs. 759.0, P=.0078). The slope of longitudinal change in T₁ was greater for tissues that received low-dose irradiation than those that received high-dose irradiation (P=.0488). The effect of dose on the slope of T₂ was different (P=.0333) when younger and older patients are compared.ConclusionsAcute affects of irradiation in muscle are quantifiable via MRI. These models provide evidence that quantifiable MRI parameters may be correlated with patient parameters of radiation dose and clinical factors including patient age. Long-term follow-up will be required to determine if acute changes correlate with clinically significant late effects.     

Diffusion-weighted MR imaging for assessing synovitis of wrist and hand in patients with rheumatoid arthritis: A feasibility study

The purpose of this study was to investigate the feasibility of diffusion-weighted imaging (DWI) in detecting synovitis of wrist and hand in patients with rheumatoid arthritis (RA) and evaluate its sensitivity, specificity and accuracy as compared to T₂-weighted imaging (T2WI) with short tau inversion recovery (STIR) with the reference standard contrast-enhanced magnetic resonance imaging (CE-MRI). Twenty-five patients with RA underwent MR examinations including DWI, T2WI with STIR and CE-MRI. MR images were reviewed for the presence and location of synovitis of wrist and hand. The sensitivity, specificity and accuracy of DWI and T2WI with STIR were calculated respectively and then compared. All patients included in this study completed MR examinations and yielded diagnostic image quality of DWI. For individual joint, there was good to excellent inter-observer agreement (k = 0.62–0.83) using DWI images, T2WI with STIR images and CE-MR images, respectively. There was a significance between DWI and T2WI with STIR in analyzing proximal interphalangeal joints II–V, respectively (P < 0.05). The k-values for the detection of synovitis indicated excellent overall inter-observer agreements using DWI images (k = 0.86), T2WI with STIR images (k = 0.85) and CE-MR images (k = 0.91), respectively. Overall, DWI demonstrated a sensitivity, specificity and accuracy of 75.6%, 89.3% and 84.6%, respectively, for detection of synovitis, while 43.0%, 95.7% and 77.6% for T2WI with STIR, respectively. DWI showed positive lesions much better and more than T2WI with STIR. Our results indicate that DWI presents a novel non-invasive approach to contrast-free imaging of synovitis. It may play a role as an addition to standard protocols.     

Labeling of macrophages using bacterial magnetosomes and their characterization by magnetic resonance imaging

This work investigated macrophages labeled with magnetosomes for the possible detection of inflammations by MR molecular imaging. Pure magnetosomes and macrophages containing magnetosomes were analyzed using a clinical 1.5 T MR-scanner. Relaxivities of magnetosomes and relaxation rates of cells containing magnetosomes were determined. Peritonitis was induced in two mice. T₁, T₂ and T₂* weighted images were acquired following injection of the probes. Pure magnetosomes and labeled cells showed slight effects on T₁, but strong effects on T₂ and T₂* images. Labeled macrophages were located with magnetic resonance imaging (MRI) in the colon area, thus demonstrating the feasibility of the proposed approach.     

Multiparametric magnetic immunoassays utilizing non-linear signatures of magnetic labels

A powerful route to utilizing magnetic nanoparticles as labels in magnetic immunoassays is to exploit their non-linear response when they are exposed to a multi-frequency alternating magnetic field. We have upgraded this non-linear method allowing for the detection, discrimination and quantification of particles of two kinds when mixed together, with no need for spatial resolution. Each kind of particle is characterized by a specific magnetic signature based on d²B(H)/dH². Appropriate data processing of the signature measured on a mixture of both particles allows for obtaining the amount of each particle. This will enable utilizing magnetic labels for multiparametric magnetic immunoassays.     

Magnetic and in vitro heating properties of implants formed in situ from injectable formulations and containing superparamagnetic iron oxide nanoparticles (SPIONs) embedded in silica microparticles for magnetically induced local hyperthermia

The biological and therapeutic responses to hyperthermia, when it is envisaged as an anti-tumor treatment modality, are complex and variable. Heat delivery plays a critical role and is counteracted by more or less efficient body cooling, which is largely mediated by blood flow. In the case of magnetically mediated modality, the delivery of the magnetic particles, most often superparamagnetic iron oxide nanoparticles (SPIONs), is also critically involved. We focus here on the magnetic characterization of two injectable formulations able to gel in situ and entrap silica microparticles embedding SPIONs. These formulations have previously shown suitable syringeability and intratumoral distribution in vivo. The first formulation is based on alginate, and the second on a poly(ethylene-co-vinyl alcohol) (EVAL). Here we investigated the magnetic properties and heating capacities in an alternating magnetic field (141 kHz, 12 mT) for implants with increasing concentrations of magnetic microparticles. We found that the magnetic properties of the magnetic microparticles were preserved using the formulation and in the wet implant at 37 °C, as in vivo. Using two orthogonal methods, a common SLP (20 W g⁻¹) was found after weighting by magnetic microparticle fraction, suggesting that both formulations are able to properly carry the magnetic microparticles in situ while preserving their magnetic properties and heating capacities.     

Imaging magnetic responses of nanomagnets by XPEEM

The Spin-resolved Photoelectron Emission Microscope (SPEEM) is a permanently installed set-up at Helmholtz-Zentrum Berlin (HZB). Due to its specific contrast it is mainly used for magnetic imaging and micro-spectroscopy with quantitative analysis. A crucial point in magnetic imaging is the application of magnetic fields. Many experiments require observation of magnetic responses or the preparation of a certain magnetic state during the measurement. We present a dedicated magnetic sample holder combining magnetic field during imaging with additional temperature control. This set-up enables SPEEM to measure magnetization curves of individual Fe nanocubes (18 nm)³ in size. If additionally alternating magnetic fields are applied we can image the local magnetic AC susceptibility (χ_AC) as a function of temperature. The latter is ideally suited to visualize local variations of the Curie temperature (T_C) in nano- and microstructures.     

Highly sensitive room-temperature method of non-invasive in vivo detection of magnetic nanoparticles

Methods of non-invasive in vivo quantification of magnetic nanoparticles (MP) have been proposed and realized. The methods are based on non-linear MP magnetization at two frequencies and measuring the response at combinatorial frequencies. The first method is developed for real-time study of MP dynamics and their clearance from the blood system of animals. High sensitivity of 3 ng of Fe₃O₄ in 0.1 ml was achieved for MP detection in mice tail veins. The second technique is proposed for MP detection inside animal tissues by an external probe. The proposed methods could essentially widen capabilities of biomedical research which involves magnetic nanoparticles.     

Dynamic half-Fourier single-shot turbo spin echo for assessment of deep venous thrombosis: initial observations

Objective

The objective of this study was to retrospectively analyze the value of dynamic half-Fourier single-shot turbo spin echo (HASTE) imaging in patients with suspected deep venous thrombosis (DVT).

Materials and Methods

Fifty-five veins in 24 patients were interrogated using a HASTE sequence with the patients relaxed and in various degrees of Valsalva. Veins were analyzed for changes in caliber (+CAL) and signal intensity (+SI) or in their absence (−CAL and −SI, respectively) and compared with the presence of thrombus on gadolinium-enhanced magnetic resonance imaging.

Results

There was no thrombus in veins with the +CAL, +SI pattern (n=40) (P<.01). Five of seven veins (71.4%) with the −CAL, −SI pattern had thrombus (P<.01). A qualitative change in CAL had a sensitivity of 100% and a specificity of 91% for the presence of thrombus. An increase of 1.5 mm in CAL had a sensitivity of 100% and a specificity of 93% for this diagnosis.

Conclusion

Dynamic HASTE imaging offers a physiological method to evaluate veins for deep venous thrombosis.     

Quantification of low fat contents: a comparison of MR imaging and spectroscopy methods at 1.5 and 3 T

Magnetic resonance spectroscopy (MRS) has long been considered the golden standard for non-invasive measurement of tissue fat content. With improved techniques for fat/water separation, imaging has become an alternative to MRS for fat quantification. Several imaging models have been proposed, but their performance relative to MRS at very low fat contents is yet not fully established. In this work, imaging and spectroscopy were compared at 1.5 T and 3 T in phantoms with 0-3% fat fraction (FF). We propose a multispectral model with individual a priori R₂ relaxation rates for water and fat, and a common unknown R₂′ relaxation. Magnitude and complex image reconstructions were also compared. Best accuracy was obtained with the imaging method at 1.5 T. At 3 T, the FFs were underestimated due to larger fat-water phase shifts. Agreement between measured and true FF was excellent for the imaging method at 1.5 T (imaging: FF_meas= 0.98 FF_true− 0.01%, spectroscopy: FF_meas= 0.77 FF_true+ 0.08%), and fair at 3 T (imaging: FF_meas= 0.91 FF_true− 0.19%, spectroscopy: FF_meas= 0.79 FF_true+ 0.02%). The imaging method was able to quantify FFs down to approx. 0.5%. We conclude that the suggested imaging model is capable of fat quantification with accuracy and precision similar to or better than spectroscopy and offers an improvement vs. a model with a common R₂* relaxation only.     

Basic concepts for nuclear magnetic resonance imaging

The basic concepts necessary to understand the physical basis of NMR imaging are presented in this didactic article. It is intended as a starting point for the radiologist or medical physicist who is addressing the topic of NMR for the first time. The basis of the NMR phenomena is described with introduction of the concepts of magnetic moment, magnetic fields, magnetic resonance, net magnetic moment of a sample, NMR excitation and NMR emission. The equipment necessary to observe these NMR properties of matter is summarized as well as the procedures for basic pulsed NMR experiments. The physical concepts for spatial localization of NMR emissions are introduced with physical analogies to stringed musical instruments. Several alternative imaging modalities are compared with greatest emphasis on the inversion recovery technique which yields images weighted by tissue T₁ values. The six subsystems of an NMR imaging device (primary magnet, computer, radio equipment, magnetic gradient, data storage and display subsystems) are described in an overview fashion. The paper is followed by a series of study questions to test the reader's comprehension of basic NMR imaging concepts.     

Development of a magnetic system for the treatment of Helicobacter pylori infections

We report a study to develop a magnetic system for local delivery of amoxicillin. Magnetite microparticles produced by coprecipitation were coated with a solution of amoxicillin and Eudragit^®S100 by spray drying. Scanning electron microscopy, optical microscopy, X-ray powder diffraction and vibrating sample magnetometry revealed that the particles were superparamagnetic, with an average diameter of 17.2 μm, and an initial susceptibility controllable by the magnetite content in the suspension feeding the sprayer. Our results suggest a possible way to treat Helicobacter pylori infections, using an oral drug delivery system, and open prospects to coat magnetic microparticles by spray drying for biomedical applications.     

Simulating magnetic nanoparticle behavior in low-field MRI under transverse rotating fields and imposed fluid flow

In the presence of alternating-sinusoidal or rotating magnetic fields, magnetic nanoparticles will act to realign their magnetic moment with the applied magnetic field. The realignment is characterized by the nanoparticle's time constant, τ. As the magnetic field frequency is increased, the nanoparticle's magnetic moment lags the applied magnetic field at a constant angle for a given frequency, Ω, in rad s⁻¹. Associated with this misalignment is a power dissipation that increases the bulk magnetic fluid's temperature which has been utilized as a method of magnetic nanoparticle hyperthermia, particularly suited for cancer in low-perfusion tissue (e.g., breast) where temperature increases of between 4 and 7 °C above the ambient in vivo temperature cause tumor hyperthermia. This work examines the rise in the magnetic fluid's temperature in the MRI environment which is characterized by a large DC field, B₀. Theoretical analysis and simulation is used to predict the effect of both alternating-sinusoidal and rotating magnetic fields transverse to B₀. Results are presented for the expected temperature increase in small tumors ( radius) over an appropriate range of magnetic fluid concentrations (0.002-0.01 solid volume fraction) and nanoparticle radii (1-10 nm). The results indicate that significant heating can take place, even in low-field MRI systems where magnetic fluid saturation is not significant, with careful the goal of this work is to examine, by means of analysis and simulation, the concept of interactive fluid magnetization using the dynamic behavior of superparamagnetic iron oxide nanoparticle suspensions in the MRI environment. In addition to the usual magnetic fields associated with MRI, a rotating magnetic field is applied transverse to the main B₀ field of the MRI. Additional or modified magnetic fields have been previously proposed for hyperthermia and targeted drug delivery within MRI. Analytical predictions and numerical simulations of the transverse rotating magnetic field in the presence of B₀ are investigated to demonstrate the effect of Ω, the rotating field frequency, and the magnetic field amplitude on the fluid suspension magnetization. The transverse magnetization due to the rotating transverse field shows strong dependence on the characteristic time constant of the fluid suspension, τ. The analysis shows that as the rotating field frequency increases so that Ωτ approaches unity, the transverse fluid magnetization vector is significantly non-aligned with the applied rotating field and the magnetization's magnitude is a strong function of the field frequency. In this frequency range, the fluid's transverse magnetization is controlled by the applied field which is determined by the operator. The phenomenon, which is due to the physical rotation of the magnetic nanoparticles in the suspension, is demonstrated analytically when the nanoparticles are present in high concentrations (1-3% solid volume fractions) more typical of hyperthermia rather than in clinical imaging applications, and in low MRI field strengths (such as open MRI systems), where the magnetic nanoparticles are not magnetically saturated. The effect of imposed Poiseuille flow in a planar channel geometry and changing nanoparticle concentration is examined. The work represents the first known attempt to analyze the dynamic behavior of magnetic nanoparticles in the MRI environment including the effects of the magnetic nanoparticle spin-velocity. It is shown that the magnitude of the transverse magnetization is a strong function of the rotating transverse field frequency. Interactive fluid magnetization effects are predicted due to non-uniform fluid magnetization in planar Poiseuille flow with high nanoparticle concentrations.     

Gd complexes of diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide as a new liver-specific MRI contrast agent

This study was to describe the synthesis of complexes of gadolinium diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide Gd-DTPA-CSn (n = 6, 8, 11) as a new class of contrast agent as well as its magnetic property in a pilot magnetic resonance imaging. The efficacy of the contrast agent was assessed by measuring the longitudinal relaxivity (r₁), FLASH imaging in phantoms in vitro and signal intensity in vivo of the rat abdominal axial imaging. The r₁ of Gd-DTPA-CS₁₁ was up to 11.65 mM^− 1·s^− 1, which was 3 times higher than that of the analogous MRI contrast agent Gd-DTPA in commercial use. In vivo MR images of rat obtained with Gd-DTPA-CS₁₁ showed strong signal enhancement in liver and the vessels of the liver parenchyma during the extended period of time. The present study suggests that the new synthesized gadolinium complexes can be used as a new class of practical liver-specific MRI contrast agent because of its superior performance compared with Gd-DTPA.     

In vivo fluorescence imaging of threadlike tissues (Bonghan ducts) inside lymphatic vessels with nanoparticles

We describe the in vivo fluorescence imaging method of novel threadlike tissues (Bonghan ducts) inside the lymphatic vessels of rats with fluorescent magnetic nanoparticles. This threadlike structure was not visible by a stereomicroscope because of its transparency. Its thickness was about 20 μm and floated in the lymphatic fluid without adhering to the lymphatic wall. Injecting the nanoparticles into the lymph nodes and applying static magnetic fields on the lymphatic vessels, we were able to obtain the in vivo fluorescence imaging of the threadlike structures under the fluorescence reflectance imaging system. The specimen was analyzed with a confocal laser scanning microscopes and transmission electron microscopes which exhibited the preferential absorption of the nanoparticles by the threadlike structures compared with the lymphatic walls. This preferential absorption was due to the loose extracellular matrix of the threadlike structures. These results show new applications of nanoparticles for in vivo imaging of hardly detectable tissues using fluorescence reflectance imaging and magnetophoretic control.     

Thickness-dependent magnetic domain structures of Co ultra-thin film investigated by scanning transmission X-ray microscopy

Thickness-dependent magnetic domain structure of ultrathin Co wedge films (0.3 nm–1.0 nm) sandwiched by Pt layers was investigated by scanning transmission x-ray microscopy (STXM) employing X-ray magnetic circular dichroism (XMCD), utilizing elliptically polarized soft x-rays and electromagnetic fields, with a spatial resolution of 50 nm. The magnetic domain images measured at the Co L₃ edge showed the evolution of the magnetic domain structures from maze-like form to the bubble-like form as the perpendicular magnetic field was applied. The asymmetric domain expansion of a 500 nm-scale bubble domain was also measured when the in-plane and perpendicular external magnetic field were applied simultaneously.     

Scanning Hall probe microscopy of vortex matter

Scanning Hall probe microscopy (SHPM) is a novel scanned probe magnetic imaging technique whereby the stray fields at the surface of a sample are mapped with a sub-micron semiconductor heterostructure Hall probe. In addition an integrated scanning tunnelling microscope (STM) or atomic force microscope (AFM) tip allows the simultaneous measurement of the sample topography, which can then be correlated with magnetic images. SHPM has several advantages over alternative methods; it is almost completely non-invasive, can be used over a very wide range of temperatures (0.3–300 K) and magnetic fields (0–7 T) and yields quantitative maps of the z-component of magnetic induction. The approach is particularly well suited to low temperature imaging of vortices in type II superconductors with very high signal:noise ratios and relatively high spatial resolution (>100 nm). This paper will introduce the design principles of SHPM including the choice of semiconductor heterostructure for different measurement conditions as well as surface tracking and scanning mechanisms. The full potential of the technique will be illustrated with results of vortex imaging studies of three distinct superconducting systems: (i) vortex chains in the “crossing lattices” regime of highly anisotropic cuprate superconductors, (ii) vortex–antivortex pairs spontaneously nucleated in ferromagnetic-superconductor hybrid structures, and (iii) vortices in the exotic p-wave superconductor Sr₂RuO₄ at milliKelvin temperatures.     

Synthesis of water-soluble FeOOH nanospindles and their performance for magnetic resonance imaging

Water soluble FeOOH nanospindles with small size were synthesized by a simple hydrolysis method of inorganic salts and water bath treatment with different incubation time. The morphology, microstructure, magnetic resonance imaging (MRI) performance and cytotoxicity of the as-prepared FeOOH nanospindles were investigated, respectively. The results showed that the longitudinal length of FeOOH nanospindles was about 40-50 nm, and the incubation time had important effect for the morphology and production rate of FeOOH nanospindles. MRI test showed that the longitudinal and transverse relaxivities (r₁ and r₂ values) of FeOOH nanospindles were about 3.06 mM⁻¹ s⁻¹ and 5.06 mM⁻¹ s⁻¹, respectively. Furthermore, the experimental results of the Prussian Blue staining showed the clusters of FeOOH nanospindles in the cytoplasm of the labeled cells, and the cytotoxicity characterization indicated that FeOOH nanospindles have low cytotoxicity. Therefore, the as-prepared FeOOH nanospindles will have potential applications as T₁- and T₂-weighted MRI contrast agents.     

Preoperative demonstration of neurovascular relationship in trigeminal neuralgia by using 3D FIESTA sequence

Purpose

The purpose of the study was to evaluate the value of high-resolution three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) imaging in the visualization of neurovascular relationship in patients with trigeminal neuralgia (TN).

Methods

Thirty-seven patients with unilateral typical TN underwent 3D FIESTA imaging. Neurovascular relationship at the trigeminal root entry zone was reviewed by an experienced neuroradiologist, who was blinded to the clinical details. The imaging results were compared with the operative findings in all patients.

Results

In 37 patients with TN, 3D FIESTA imaging identified surgically verified neurovascular contact in 35 of 36 symptomatic nerves. Based on surgical findings, the sensitivity and specificity of magnetic resonance (MR) imaging were 97.2% and 100%, respectively. Agreement between the position (medial, lateral, superior and inferior) of the compressing vessel relative to the trigeminal nerve identified by MR imaging and surgery was excellent (K=0.81; 95% confidence interval, 0.56–1.00). A statistically significant difference was found between the site of neurovascular contact and the clinical symptom related to the trigeminal branch (Fisher's Exact Test, P<.001).

Conclusions

Use of 3D FIESTA sequence enables accurate visualization of neurovascular contact in patients with TN. Anatomic relationships defined by this method can be useful in surgical planning and predicting surgical findings.     

Constraining WIMP magnetic moment from CDMS II experiment

We consider a degenerate or a nearly degenerate dark matter sector where a sizable magnetic moment of a (almost) Dirac type neutral dark matter candidate N is anticipated. Then, due to soft photon exchange, the cross-section in direct detection of N   can be enhanced at low Q²$Q^2$ region. We discuss the implication of this type of models in view of the recent CDMS II report.