Bennie ten Haken

Differentiation of Prostatitis and Prostate Cancer by Using Diffusion-weighted MR Imaging and MR-guided Biopsy at 3 T

PURPOSE To determine if prostatitis and prostate cancer (PCa) can be distinguished by using apparent diffusion coefficients (ADCs) on magnetic resonance (MR) images, with specimens obtained at MR-guided biopsy as the standard of reference. MATERIALS AND METHODS The need for institutional review board approval and informed consent was waived. MR-guided biopsies were performed in 130 consecutive patients with cancer-suspicious regions (CSRs) on multiparametric MR images obtained at 3 T. In this retrospective study, 88 patients met the inclusion criteria. During the biopsy procedure, an axial diffusion-weighted sequence was performed and ADC maps were generated (repetition time msec/echo time msec, 2000/67; section thickness, 4 mm; in-plane resolution, 1.8 × 1.8 mm; and b values of 0, 100, 500, and 800 sec/mm(2)). Subsequently, a confirmation image with the needle left in situ was acquired and projected on the ADC map. The corresponding ADCs at the biopsy location were compared with the histopathologic outcomes of the biopsy specimens. Linear mixed-model regression analyses were used to test for ADC differences between the histopathologic groups. RESULTS The study included 116 biopsy specimens. Median ADCs of normal prostate tissue, prostatitis, low-grade PCa (Gleason grade components 2 or 3), and high-grade PCa (Gleason grade components 4 or 5) were 1.22 × 10(-3) mm(2)/sec (standard deviation, ± 0.21), 1.08 × 10(-3) mm(2)/sec (± 0.18), 0.88 × 10(-3) mm(2)/sec (± 0.15), and 0.88 × 10(-3) mm(2)/sec (± 0.13), respectively. Although the median ADCs of biopsy specimens with prostatitis were significantly higher compared with low- and high-grade PCa (P < .001), there is a considerable overlap between the tissue types. CONCLUSION Diffusion-weighted imaging is a noninvasive technique that shows differences between prostatitis and PCa in both the peripheral zone and central gland, although its usability in clinical practice is limited as a result of significant overlap in ADCs.

Architectural configuration and microstructural properties of the sacral plexus: A diffusion tensor MRI and fiber tractography study

The ability to investigate microstructural properties of the central nervous system with diffusion tensor imaging (DTI) has been shown in many studies. More recently, DTI is being applied outside the brain showing promising results, for instance, for investigating muscle tissue. In this work, we demonstrate the feasibility of diffusion tensor imaging (DTI) and fiber tractography to study the nerves of the sacral plexus in humans in vivo and to assess the architectural configuration and microstructural properties of these peripheral nerves. For this research goal we optimized the acquisition parameters of a DTI sequence and acquired data from 10 healthy adults and one 12-year patient having spina bifida and neurogenic bladder dysfunction. For the healthy volunteers, we estimated the fractional anisotropy (FA) and mean (MD), axial (AD), and radial diffusivities (RD) of the sacral plexus nerves which may serve as a baseline for future studies. We demonstrated that tractography of the sacral plexus on a 3 Tesla MR scanner is feasible, giving 3D insight in the general anatomy and organization of the nerves L4 to S3. In addition, branches to the pudendal nerve were also found in 4 volunteers. There were no significant differences in any of the estimated diffusion measures between the right and left sided nerves or between the nerves L4 to S3 on an intra-subject basis. Furthermore, clinical feasibility of DTI and tractography in a child having spina bifida and neurogenic bladder dysfunction is demonstrated. The architectural configuration of the childs sacral plexus was comparable with the healthy volunteers and no significant disrupted nerve fibers were observed. However, there are strong indications that abnormal diffusion characteristics are present at the level of the neural tube defect due to incomplete segments of the nerves that are close to the vertebrae. These findings are encouraging for using DTI as a means to investigate changes in microstructural properties of the nerves of the sacral plexus. Moreover, this new methodology may provide a new avenue to a better analysis and diagnosis of neurogenic bladder dysfunctions.

Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages

UNLABELLED Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes. Using recombinant forms of the globular regions of human C1q (gC1q) as inhibitors of CNT-mediated classical pathway activation, we show that C1q, the first recognition subcomponent of the classical pathway, binds CNTs via the gC1q domain. Complement opsonisation of CNTs significantly enhances their uptake by U937 cells, with concomitant downregulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines in both U937 cells and human monocytes. We propose that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. FROM THE CLINICAL EDITOR This study highlights the importance of the complement system in response to carbon nanontube administration, suggesting that the ensuing complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response.

Evaluation of superparamagnetic iron oxide nanoparticles (Endorem) as a photoacoustic contrast agent for intra-operative nodal staging

Detection of tumor metastases in the lymphatic system is essential for accurate staging of malignancies. Commercially available superparagmagnetic nanoparticles (SPIOs) accumulate in normal lymph tissue after injection at a tumor site, whereas less or no accumulation takes place in metastatic nodes, thus enabling lymphatic staging using MRI. We verify for the first time the potential of SPIOs, such as Endorem(®) as a novel photoacoustic (PA) contrast agent in biological tissue. We injected five Wistar rats subcutaneously with variable amounts of Endorem(®) and scanned the resected lymph nodes using a tomographic PA setup. Findings were compared using histology, vibrating sample magnetometry (VSM) and 14 T MR-imaging. Our PA setup was able to detect the iron oxide accumulations in all the nodes containing the nanoparticles. The distribution inside the nodes corresponded with both MRI and histological findings. VSM revealed that iron quantities inside the nodes varied between 51 ± 4 and 11 ± 1 µg. Nodes without SPIO enhancement did not show up in any of the PA scans. Iron oxide nanoparticles (Endorem(®)) can be used as a PA contrast agent for lymph node analysis and a distinction can be made between nodes with and nodes without the agent. This opens up possibilities for intra-operative nodal staging for patients undergoing nodal resections for metastatic malignancies.

Magnetization and AC loss in a superconductor with an elliptical cross-section and arbitrary aspect ratio

An analytical approximation is developed for the magnetization of an infinitely long superconductor with an elliptical transverse cross-section. The superconductor is modeled in the critical state with a critical current density that is not dependent on the magnetic field. The aspect ratio of the ellipse is varied from one (=circle) to infinitely large. The magnetic field is applied perpendicular or parallel to the broadest face. The analytical expression is compared with a more detailed model that utilizes a numerically optimized contour for the boundary of the saturated zone. The two methods are compared and the maximum error is estimated at 2% for the optimized contour approach and 5% for the analytical approximation. The analytical model is compared with a magnetization loss measurement on a high-Tc superconducting tape with an aspect ratio of nearly 20. A good agreement is obtained for a magnetic field pointing perpendicular as well as parallel to the broadest face of the tape. An interesting result for the magnetic behavior determined for the ellipse is that it contradicts with the behavior that is predicted for an infinitely thin strip in perpendicular field. The difference is attributed to the two specific assumptions made in the thin strip model: the constant critical current density distribution across the tape and the magnetic-field profile that does not exclude unsaturated currents in the shielded zone.

Neural Dynamics during Anoxia and the “Wave of Death”

Recent experiments in rats have shown the occurrence of a high amplitude slow brain wave in the EEG approximately 1 minute after decapitation, with a duration of 5–15 s (van Rijn et al, PLoS One 6, e16514, 2011) that was presumed to signify the death of brain neurons. We present a computational model of a single neuron and its intra- and extracellular ion concentrations, which shows the physiological mechanism for this observation. The wave is caused by membrane potential oscillations, that occur after the cessation of activity of the sodium-potassium pumps has lead to an excess of extracellular potassium. These oscillations can be described by the Hodgkin-Huxley equations for the sodium and potassium channels, and result in a sudden change in mean membrane voltage. In combination with a high-pass filter, this sudden depolarization leads to a wave in the EEG. We discuss that this process is not necessarily irreversible.

Pre-operative sentinel lymph node localization in breast cancer with superparamagnetic iron oxide MRI: the SentiMAG Multicentre Trial imaging subprotocol

OBJECTIVE Sentinel lymph node biopsy (SLNB) with a superparamagnetic iron oxide (SPIO) tracer was shown to be non-inferior to the standard combined technique in the SentiMAG Multicentre Trial. The MRI subprotocol of this trial aimed to develop a magnetic alternative for pre-operative lymphoscintigraphy (LS). We evaluated the feasibility of using MRI following the administration of magnetic tracer for pre-operative localization of sentinel lymph nodes (SLNs) and its potential for non-invasive identification of lymph node (LN) metastases. METHODS Patients with breast cancer scheduled to undergo SLNB were recruited for pre-operative LS, single photon emission CT (SPECT)-CT and SPIO MRI. T1 weighted turbo spin echo and T2 weighted gradient echo sequences were used before and after interstitial injection of magnetic tracer into the breast. SLNs on MRI were defined as LNs with signal drop and direct lymphatic drainage from the injection site. LNs showing inhomogeneous SPIO uptake were classified as metastatic. During surgery, a handheld magnetometer was used for SLNB. Blue or radioactive nodes were also excised. The number of SLNs and MR assessment of metastatic involvement were compared with surgical and histological outcomes. RESULTS 11 patients were recruited. SPIO MRI successfully identified SLNs in 10 of 11 patients vs 11 of 11 patients with LS/SPECT-CT. One patient had metastatic involvement of four LNs, and this was identified in one node on pre-operative MRI. CONCLUSION SPIO MRI is a feasible technique for pre-operative localization of SLNs and, in combination with intraoperative use of a handheld magnetometer, provides an entirely radioisotope-free technique for SLNB. Further research is needed for the evaluation of MRI characterization of LN involvement using subcutaneous injection of magnetic tracer. ADVANCES IN KNOWLEDGE This study is the first to demonstrate that an interstitially administered magnetic tracer can be used both for pre-operative imaging and intraoperative SLNB, with equal performance to imaging and localization with radioisotopes.

Total AC losses in twisted and untwisted multifilamentary Bi-2223 superconducting tapes carrying AC transport current in AC longitudinal magnetic field

In some electrical apparatuses, superconducting tapes are exposed to the longitudinal magnetic field. In this work, AC losses were measured in twisted and untwisted Bi-2223 tapes carrying AC transport current in the AC longitudinal magnetic field. In twisted tapes, the transport, magnetization and total losses depend on the relative direction of the longitudinal magnetic field to the direction of the transport current, while the field direction does not influence the AC loss characteristics in untwisted tapes. In the Z-twisted tapes, the total AC loss is larger in the longitudinal magnetic field that is anti-parallel to the transport current than in the longitudinal magnetic field of another direction. Numerical analysis shows that this field direction dependence of the total AC loss results from the change in the current distribution. In the longitudinal magnetic field that is anti-parallel to the transport current, the total AC loss in the Z-twisted tape is more than that in the untwisted tape. This dependence on the field direction is reversed in S-twisted tapes. It is to be noted that the twist increases the total AC loss in a longitudinal magnetic field of a certain direction, while it reduces the AC loss in the transverse magnetic field.

How does spreading depression spread? Physiology and modeling.

Abstract Spreading depression (SD) is a wave phenomenon in gray matter tissue. Locally, it is characterized by massive redistribution of ions across cell membranes. As a consequence, there is sustained membrane depolarization and tissue polarization that depress any normal electrical activity. Despite these dramatic events, SD remains difficult to observe in humans noninvasively, which, for long, has slowed advances in this field. The growing appreciation of its clinical importance in migraine and stroke is therefore consistent with an increasing need for computational methods that tackle the complexity of the problem at multiple levels. In this review, we focus on mathematical tools to investigate the question of spread and its two complementary aspects: What are the physiological mechanisms and what is the spatial extent of SD in the cortex? This review discusses two types of models used to study these two questions, namely, Hodgkin-Huxley type and generic activator-inhibitor models, and the recent advances in techniques to link them.

Au coated Ni nanowires with tuneable dimensions for biomedical applications

Due to their shape anisotropy, high aspect ratio magnetic nanoparticles offer many advantages in biomedical applications. For biocompatibility, it is essential to have full control over the dimensions and surface chemistry of the particles. The aim of this study was to synthesize biocompatible nanowires with tuneable dimensions. This was achieved by electrodeposition of Ni in polycarbonate membranes. To ensure biocompatibility, a continuous gold coating was deposited onto the Ni wires by a newly developed electroless deposition method. The coating was analysed using electron microscopy and X-ray diffraction. Magnetic properties, anisotropy and Au film thickness were studied using vibrating sample magnetometry. After biofunctionalization, no significant cytotoxic effects were found in studies involving a diverse range of primary and tumour cells exposed to increasing concentrations of nanowires for up to 7 days. These nanowires may thus be used for in vivo applications such as magnetic drug delivery.