Clemens Bos

Passive tracking of catheters and guidewires by contrast‐enhanced MR fluoroscopy

Passive MR tracking of catheters and guidewires is usually done by dynamically imaging a single thick slab, subtracting a baseline image, and combining the result with a previously acquired MR angiogram. In the in vitro and in vivo experiments reported here, it is demonstrated that this approach may be greatly simplified by using a suitable intravascular contrast agent. The proposed method, contrast‐enhanced MR fluoroscopy, combines tracking and angiography into a single sequence and allows direct visualization of the magnetically prepared parts of catheters and guidewires with respect to the vasculature at a frame rate of about one image per 1.5 seconds. Contrast‐enhanced MR fluoroscopy, although still limited in temporal resolution, thus obviates the need for subtraction and overlay techniques and eliminates the sensitivity of tracking to subject motion between acquisitions. Magn Reson Med 45:17–23, 2001.

Placement of an inferior vena cava filter in a pig guided by high-resolution MR fluoroscopy at 1.5 T.

Percutaneous placement of an inferior vena cava filter is a means for long‐term prevention of pulmonary thromboembolism. In this study we investigated the magnetic resonance (MR) imaging properties of a Nitinol vena cava filter, in various anatomic and angiographic scans, as well as the feasibility of placing this filter under near real‐time, high‐resolution MR fluoroscopy. We made use of the passive tracking strategy, with on‐line image processing and visualization, both in vitro and in a pig. The artifacts provoked by the metallic filter were such that the position and orientation of the filter were well depicted in all scans. Considerable radiofrequency caging obscured the interior of the filter. Our experiments showed that an MR‐guided vena cava filter placement, with sufficient temporal and spatial resolution, is possible. Three‐dimensional phase contrast MRA allowed direct evaluation of the filter placement procedure, without the use of contrast agent. J. Magn. Reson. Imaging 2000;12:599–605.

Selective contrast-enhanced MR angiography

In this study the feasibility of intraarterial contrast administration was investigated. Its use for navigation and treatment evaluation during MR‐guided intravascular interventions was explored in phantom and animal experiments. An injection protocol was developed, which accounts for sequence parameters and vessel flow rate. Tracking a bolus of contrast agent was useful to verify the catheter tip position and to assess flow conditions. Compared to intravenous contrast‐enhanced magnetic resonance angiography (CE‐MRA), selective contrast administration permitted a strongly reduced dose. In two‐dimensional (2D) acquisitions overlap of vessels was prevented. Injection and acquisition were easily and accurately synchronized in selective 3D CE‐MRA, and a high contrast concentration could be maintained during the entire acquisition. Selective injection is useful in the course of an intervention, to facilitate navigation, provide information on flow conditions, and to evaluate treatment progress repeatedly. Magn Reson Med 44:575–582, 2000.

Interventional MR: vascular applications

Abstract. Three strategies for visualisation of MR-dedicated guidewires and catheters have been proposed, namely active tracking, the technique of locally induced field inhomogeneity and passive susceptibility-based tracking. In this article the pros and cons of these techniques are discussed, including the development of MR-dedicated guidewires and catheters, scan techniques, post-processing tools, and display facilities for MR tracking. Finally, some of the results obtained with MR tracking are discussed.

On the Artifact of a Subvoxel Susceptibility Deviation in Spoiled Gradient-Echo Imaging

In MRI, susceptibility‐based negative contrast amplifies the effect of objects that are too small to be detected by water displacement or intrinsic contrast properties. In this work, a simplified description of the susceptibility artifact of a subvoxel object in spoiled gradient‐echo imaging is presented that focuses on the elimination of signal in its vicinity: the dephased‐volume. The size and position of the dephased‐volume are investigated using 3D time‐domain simulations and in vitro experiments in which scan parameters and object magnetic moment are systematically varied. Overall signal loss is found to be linearly related to a dephasing parameter that contains the susceptibility difference with tissue, object volume, and echo time (TE), and thus allows the magnetic moment of the object to be assessed. Gradient strength, in‐plane resolution, fractional echo, and slice orientation have limited influence. For the settings used, the center of mass of the artifact was always within 0.5 mm of the objects in‐plane position. Magn Reson Med 50:400–404, 2003.

Interstitial heating: experiments in artificially perfused bovine tongues

Isolated perfused bovine tongues were heated with a 2 x 2 hot water tube interstitial hyperthermia system (tube outer diameter 2.0 mm, spacing 16 mm). Tongue blood flow ranged between 0 and 17 ml min-1/100 g. The temperature distribution was mapped with 5 to 8 single thermocouples (diameter 50 microns). Model predictions using both the conventional bioheat transfer equation and the effective conductivity model were compared to the experimental results, with emphasis on the role of blood flow. Results indicate a better qualitative agreement with the k-effective model than with the heat sink model. In this set up a 16 mm spacing proved sufficient for adequate heating between the needles at normal blood flow rates, in the absence of large vessels.

The magnetic susceptibility effect of gadolinium-based contrast agents on PRFS-based MR thermometry during thermal interventions

BackgroundProton resonance frequency shift (PRFS) magnetic resonance (MR) thermometry exploits the local magnetic field changes induced by the temperature dependence of the electron screening constant of water protons. Any other local magnetic field changes will therefore translate into incorrect temperature readings and need to be considered accordingly. Here, we investigated the susceptibility changes induced by the inflow and presence of a paramagnetic MR contrast agent and their implications on PRFS thermometry.MethodsPhantom measurements were performed to demonstrate the effect of sudden gadopentetate dimeglumine (Gd-DTPA) inflow on the phase shift measured using a PRFS thermometry sequence on a clinical 3 T magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) system. By proton nuclear magnetic resonance spectroscopy, the temperature dependence of the Gd-DTPA susceptibility was measured, as well as the effect of liposomal encapsulation and release on the bulk magnetic susceptibility of Gd-DTPA. In vivo studies were carried out to measure the temperature error induced in a rat hind leg muscle upon intravenous Gd-DTPA injection.ResultsThe phantom study showed a significant phase shift inside the phantom of 0.6 ± 0.2 radians (mean ± standard deviation) upon Gd-DTPA injection (1.0 mM, clinically relevant amount). A Gd-DTPA-induced magnetic susceptibility shift of ΔχGd-DTPA = 0.109 ppm/mM was measured in a cylinder parallel to the main magnetic field at 37°C. The temperature dependence of the susceptibility shift showed dΔχGd-DTPA/dT = -0.00038 ± 0.00008 ppm/mM/°C. No additional susceptibility effect was measured upon Gd release from paramagnetic liposomes. In vivo, intravenous Gd-DTPA injection resulted in a perceived temperature change of 2.0°C ± 0.1°C at the center of the hind leg muscle.ConclusionsThe use of a paramagnetic MR contrast agent prior to MR-HIFU treatment may influence the accuracy of the PRFS MR thermometry. Depending on the treatment workflow, Gd-induced temperature errors ranging between -4°C and +3°C can be expected. Longer waiting time between contrast agent injection and treatment, as well as shortening the ablation duration by increasing the sonication power, will minimize the Gd influence. Compensation for the phase changes induced by the changing Gd presence is difficult as the magnetic field changes are arising nonlocally in the surroundings of the susceptibility change.

MRI contrast variation of thermosensitive magnetoliposomes triggered by focused ultrasound: a tool for image-guided local drug delivery

Improved drug delivery control during chemotherapy has the potential to increase the therapeutic index. MRI contrast agent such as iron oxide nanoparticles can be co-encapsulated with drugs in nanocarrier liposomes allowing their tracking and/or visualization by MRI. Furthermore, the combination of a thermosensitive liposomal formulation with an external source of heat such as high intensity focused ultrasound guided by MR temperature mapping allows the controlled local release of the content of the liposome. MRI-guided high-intensity focused ultrasound (HIFU), in combination represents a noninvasive technique to generate local hyperthermia for drug release. In this study we used ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) encapsulated in thermosensitive liposomes to obtain thermosensitive magnetoliposomes (TSM). The transverse and longitudinal relaxivities of this MRI contrast agent were measured upon TSM membrane phase transition in vitro using a water bath or HIFU. The results showed significant differences for MRI signal enhancement and relaxivities before and after heating, which were absent for nonthermosensitive liposomes and free nanoparticles used as controls. Thus, incorporation of USPIO as MRI contrast agents into thermosensitive liposomes should, besides TSM tumor accumulation monitoring, allow the visualization of TSM membrane phase transition upon temperature elevation. In conclusion, HIFU under MR image guidance in combination with USPIO-loaded thermosensitive liposomes as drug delivery system has the potential for a better control of drug delivery and to increase the drug therapeutic index.

Sonochemotherapy : From bench to bedside

The combination of microbubbles and ultrasound has emerged as a promising method for local drug delivery. Microbubbles can be locally activated by a targeted ultrasound beam, which can result in several bio-effects. For drug delivery, microbubble-assisted ultrasound is used to increase vascular- and plasma membrane permeability for facilitating drug extravasation and the cellular uptake of drugs in the treated region, respectively. In the case of drug-loaded microbubbles, these two mechanisms can be combined with local release of the drug following destruction of the microbubble. The use of microbubble-assisted ultrasound to deliver chemotherapeutic agents is also referred to as sonochemotherapy. In this review, the basic principles of sonochemotherapy are discussed, including aspects such as the type of (drug-loaded) microbubbles used, the routes of administration used in vivo, ultrasound devices and parameters, treatment schedules and safety issues. Finally, the clinical translation of sonochemotherapy is discussed, including the first clinical study using sonochemotherapy.

Duration of ultrasound-mediated enhanced plasma membrane permeability

Ultrasound (US) induced cavitation can be used to enhance the intracellular delivery of drugs by transiently increasing the cell membrane permeability. The duration of this increased permeability, termed temporal window, has not been fully elucidated. In this study, the temporal window was investigated systematically using an endothelial- and two breast cancer cell lines. Model drug uptake was measured as a function of time after sonication, in the presence of SonoVue™ microbubbles, in HUVEC, MDA-MB-468 and 4T1 cells. In addition, US pressure amplitude was varied in MDA-MB-468 cells to investigate its effect on the temporal window. Cell membrane permeability of HUVEC and MDA-MB-468 cells returned to control level within 1-2 h post-sonication, while 4T1 cells needed over 3h. US pressure affected the number of cells with increased membrane permeability, as well as the temporal window in MDA-MB-468 cells. This study shows that the duration of increased membrane permeability differed between the cell lines and US pressures used here. However, all were consistently in the order of 1-3 h after sonication.