Detection and Compensation of Periodic Motion in Magnetic Particle Imaging.

The temporal resolution of the tomographic imaging method magnetic particle imaging (MPI) is remarkably high. The spatial resolution is degraded for measured voltage signal with low signal-to-noise ratio, because the regularization in the image reconstruction step needs to be increased for system-matrix approaches and for deconvolution steps in x -space approaches. To improve the signal-to-noise ratio, blockwise averaging of the signal over time can be advantageous. However, since block-wise averaging decreases the temporal resolution, it prevents resolving the motion. In this paper, a framework for averaging motion-corrupted MPI raw data is proposed. The motion is considered to be periodic as it is the case for respiration and/or the heartbeat. The same state of motion is thus reached repeatedly in a time series exceeding the repetition time of the motion and can be used for averaging. As the motion process and the acquisition process are, in general, not synchronized, averaging of the captured MPI raw data corresponding to the same state of motion requires to shift the starting point of the individual frames. For high-frequency motion, a higher frame rate is potentially required. To address this issue, a binning method for using only parts of complete frames from a motion cycle is proposed that further reduces the motion artifacts in the final images. The frequency of motion is derived directly from the MPI raw data signal without the need to capture an additional navigator signal. Using a motion phantom, it is shown that the proposed method is capable of averaging experimental data with reduced motion artifacts. The methods are further validated on in-vivo data from mouse experiments to compensate the heartbeat.

Evaluation of PEG-coated iron oxide nanoparticles as blood pool tracers for preclinical magnetic particle imaging.

Superparamagnetic iron oxide (SPIO) nanoparticles with optimized and well-characterized properties are critical for Magnetic Particle Imaging (MPI). MPI is a novel in vivo imaging modality that promises to integrate the speed of X-ray CT, safety of MRI and sensitivity of PET. Since SPIOs are the source of MPI signal, both the core and surface properties must be optimized to enable efficient in vivo imaging with pharmacokinetics tailored for specific imaging applications. Existing SPIOs like Resovist (ferucarbotran) provide a suboptimal MPI signal, and further limit MPI's in vivo utility due to rapid systemic clearance. An SPIO agent with a long blood half-life (t1/2) would be a versatile MPI tracer with widespread applications. Here we show that a long circulating polyethylene glycol (PEG)-coated SPIO tracer, LS-008, provides excellent colloidal stability and a persistent intravascular MPI signal, showing its potential as the first blood pool tracer optimized for MPI. We evaluated variations of PEG coating and found that colloidal stability of tracers improved with the increasing PEG molecular weight (keeping PEG loading constant). Blood circulation in mice, evaluated using Magnetic Particle Spectrometry (MPS), showed that the t1/2 of SPIO tracers varied with both PEG molecular weight and loading. LS-008, coated with 20 kDa PEG at 18.8% loading capacity, provided the most promising long-term colloidal stability with a t1/2 of about 105 minutes in mice. In vivo MPI imaging with LS-008 using a 7 T/m/µ0 3D x-space MPI mouse scanner revealed a prolonged intravascular signal (3-5 hours) post-injection. Our results show the optimized magnetic properties and long systemic retention of LS-008 making it a promising blood pool MPI tracer, with potential to enable MPI imaging in cardio- and cerebrovascular disease models, and solid tumor quantification and imaging via enhanced permeation and retention.

Drive-field Frequency Dependent MPI Performance of Single-Core Magnetite Nanoparticle Tracers.

The drive-field frequency of Magnetic Particle Imaging (MPI) systems plays an important role for system design, safety requirements and tracer selection. Because the commonly utilized MPI drive-field frequency of 25 kHz might be increased in future system generations to avoid peripheral nerve stimulation, a performance evaluation of tracers at higher frequencies is desirable. We have studied single-core magnetite nanoparticles that were optimized for MPI applications, utilizing Magnetic Particle Spectrometers (MPS) with drive-field frequencies in the range from 1 kHz up to 100 kHz. The particles have core diameters of 25 nm and a hydrodynamic size of 77 nm. Measurements in the frequency range above 5 kHz were carried out with a newly designed MPS system. In addition, to exclude possible particle interaction, samples of different concentrations were characterized and compared.

Quantitative "Hot Spot" Imaging of Transplanted Stem Cells using Superparamagnetic Tracers and Magnetic Particle Imaging (MPI).

Magnetic labeling of stem cells enables their non-invasive detection by magnetic resonance imaging (MRI). Practically, most MRI studies have been limited to visualization of local engraftment as other sources of endogenous hypointense contrast complicate the interpretation of systemic (whole body) cell distribution. In addition, MRI cell tracking is inherently non-quantitative in nature. We report here on the potential of magnetic particle imaging (MPI) as a novel tomographic technique for non-invasive hot spot imaging and quantification of stem cells using superparamagnetic iron oxide (SPIO) tracers. Neural and mesenchymal stem cells, representing small and larger cell bodies, were labeled with three different SPIO tracer formulations, including two preparations that have previously been used in clinical MRI cell tracking studies (Feridex® and Resovist®). Magnetic particle spectroscopy (MPS) measurements demonstrated a linear correlation between MPI signal and iron content, for both homogeneous solutions of free particles in solution and for internalized and aggregated particles in labeled cells over a wide range of concentrations. The overall MP signal ranged from 1×10-3 - 3×10-4 Am2/g Fe, which was equivalent to 2×10-14 - 1×10-15 Am2 per cell, indicating that cell numbers can be quantified with MPI analogous to the use of radiotracers in nuclear medicine or fluorine tracers in 19F MRI. When SPIO-labeled cells were transplanted in mouse brain, they could be readily detected by MPI at a detection threshold of about 5×104 cells, with MPI/MRI overlays showing an excellent agreement between the hypointense MRI areas and MPI hot spots. The calculated tissue MPI signal ratio for 100,000 vs. 50,000 implanted cells was 2.08. Hence, MPI has potential to be further developed for quantitative and easy-to-interpret, tracer-based non-invasive imaging of cells, preferably with MRI as an adjunct anatomical imaging modality.

Slew-rate dependence of tracer magnetization response in magnetic particle imaging.

Magnetic Particle Imaging (MPI) is a new biomedical imaging technique that produces real-time, high-resolution tomographic images of superparamagnetic iron oxide nanoparticle tracers. Currently, 25 kHz and 20 mT/µ0 excitation fields are common in MPI, but lower field amplitudes may be necessary for patient safety in future designs. Here, we address fundamental questions about MPI tracer magnetization dynamics and predict tracer performance in future scanners that employ new combinations of excitation field amplitude (Ho ) and frequency (ω). Using an optimized, monodisperse MPI tracer, we studied how several combinations of drive field frequencies and amplitudes affect the tracer's response, using Magnetic Particle Spectrometry and AC hysteresis, for drive field conditions at 15.5, 26, and 40.2 kHz, with field amplitudes ranging from 7 to 52 mT/µ0. For both fluid and immobilized nanoparticle samples, we determined that magnetic response was dominated by Néel reversal. Furthermore, we observed that the peak slew-rate (ωHo) determined the tracer magnetic response. Smaller amplitudes provided correspondingly smaller field of view, sometimes resulting in excitation of minor hysteresis loops. Changing the drive field conditions but keeping the peak slew-rate constant kept the tracer response almost the same. Higher peak slew-rates led to reduced maximum signal intensity and greater coercivity in the tracer response. Our experimental results were in reasonable agreement with Stoner-Wohlfarth model based theories.

Study of tumour cellularity in locally advanced breast carcinoma on neo-adjuvant chemotherapy.

BACKGROUND: Breast cancer is the most common invasive malignancy which occurs in women worldwide. The advent of neoadjuvant chemotherapy has radically changed the management of locally advanced breast cancer and a complete response is reported to significantly improve disease free survival. Traditionally, clinical response is assessed on basis of tumour size. In this study, an attempt was made to check whether tumour cellularity could be a better prognostic factor and also to check as to what impact the correlation of tumour size with cellularity had on the response assessment in locally advanced breast cancer patients. MATERIALS AND METHODS: Thirty seven patients with locally advanced breast cancer, who were treated by neoadjuvant chemotherapy during the period of December 2008 to May 2009, were selected for the study and from their case records, tumour size, clinical response and demographic details were gathered. Tumour cellularity was assessed prior to chemotherapy in core needle biopsy sections and it was matched with that seen in subsequent mastectomy specimens. Tumour size and cellularity were then correlated with the different treatment response groups and they were statistically analyzed by using the SPSS, version 13.0 software. RESULTS: After neoadjuvant chemotherapy, the tumour size and cellularity were found to be significantly reduced in breast carcinomas (p<0.05, paired t-test). The relative changes in cellularity which were seen were highly variable between individual patients and different clinical response groups, particularly in the partial response and no response categories. The product of cellularity and size dramatically changed the distribution of residual tumour pathology, thus causing a shift towards a complete response. CONCLUSION: The current study showed that the product of tumour size and cellularity may be a better prognostic indicator of clinical response in patients with neoadjuvant chemotherapy treated locally advanced breast cancer and that it would enable a new definition for clinical response in the future.

Hip resurfacing revision rates: radiological audit of risk factors.

INTRODUCTION: We performed a retrospective radiological audit of the hip resurfacings carried out in our trust over a five-year period. Abnormal cup inclination angle (CIA) and stem shaft angle (SSA) are recognised risk factors for revision in hip resurfacing. Our aims were to identify the CIA and SSA for hip resurfacings in our trust, to determine the revision rate in a CIA of ≥60° and an SSA of >0° varus, thereby identifying a high risk group for close, long-term follow up. METHODS: A total of 247 patients underwent hip resurfacing in our trust between April 2003 and March 2008. The CIA and SSA were recorded. Of the 247 patients, 26 were excluded as there were no appropriate radiographs and so results were analysed for 221 patients. RESULTS: The mean CIA was 47.6°. Over a third of the patients (34%) had a CIA of >50° and 13% had >60°. The mean SSA was 1.4° varus. Over two-thirds of the patients (67%) had a varus SSA. There were six revisions but one was excluded as it was secondary to infection. The revision rate was 10% in patients with a CIA of ≥60° and 1% in those with a CIA of <60° (p=0.017), and 1% in a varus and 4% in a valgus SSA ((p)>0.05) respectively. CONCLUSIONS: The measurement of the CIA and SSA in hip resurfacings has identified a high risk group for close long-term follow up. There is already a 10% revision rate in those patients with a CIA of >60°. Hip resurfacing may generate a large revision burden in the 'average' surgeon's hands and all hospitals/surgeons should review their radiological outcomes critically and identify those at risk of revision.

The position of the centre of the distal radial articular surface in the sagittal plane: a radiological study.

Using a digital vernier calliper, measurements of the position of the centre of the distal radial articular surface in the sagittal plane with respect to the long axis of the distal radius were made on 50 lateral radiographs of normal wrists. In all 50 cases, the centre of the distal radial articular surface was palmar on the long axis of the radius. The mean value for this palmar position was 5.3mm (44% of the radial shaft width). There was no correlation between the position of the centre of the distal radial articular surface and either the width of the radial shaft, the length of the articular surface of the distal radius or the age or sex of the individuals. However, the position of the centre of rotation was found to correlate with palmar tilt. The palmar position of the centre of the distal radial articular surface on the long axis of the radius may be biomechanically important.

Palmar cortical angle of the distal radius: a radiological study.

Fifty lateral radiographs of normal wrists were viewed to determine the palmar cortical angle of the distal radius. The palmar cortical angle is different to its previously described palmar tilt or angulation. The mean value for the palmar cortical angle was 37 degrees (range, 26-50 degrees). This may be clinically important in the design of palmar plates for the distal radius.

Scaling of the interface roughness in Fe-Cr superlattices: self-affine versus non-self-affine.

We have analyzed kinetic roughening in Fe-Cr superlattices by energy-filtered transmission electron microscopy. The direct access to individual interfaces provides both static and dynamic roughness exponents. We find an anomalous non-self-affine scaling of the interface roughness with a time dependent local roughness at short length scales. While the deposition conditions affect strongly the long-range dynamics, the anomalous short-range exponent remains unchanged. The different short- and long-range dynamics outline the importance of long-range interactions in kinetic roughening.

Direct evidence for block-by-block growth in high-temperature superconductor ultrathin films.

Charge neutrality and stoichiometry impose severe restrictions on the mechanisms of epitaxial growth of complex oxides. The fundamental question arises of what is the minimum growth unit when sample thickness is reduced beyond the size of the unit cell. We have investigated the growth mechanism of YBa2Cu3O7 cuprate superconductor, using a consistent approach based on the growth of noninteger numbers of YBa2Cu3O7 layers in YBa(2)Cu(3)O(7)/PrBa(2)Cu3O7 superlattices. Ex situ chemical and structural analysis evidence a 2D block-by-block mechanism in which the minimum growth units are complete unit cell blocks, growing coherently over large lateral distances.

Colloidal nanocrystal shape and size control: the case of cobalt.

We show that a relatively simple approach for controlling the colloidal synthesis of anisotropic cadmium selenide semiconductor nanorods can be extended to the size-controlled preparation of magnetic cobalt nanorods as well as spherically shaped nanocrystals. This approach helps define a minimum feature set needed to separately control the sizes and shapes of nanocrystals. The resulting cobalt nanocrystals produce interesting two- and three-dimensional superstructures, including ribbons of nanorods.