Characterizing Diffusion from Microdialysis Catheters in the Human Brain: A Magnetic Resonance Imaging Study With Gadobutrol.

Cerebral microdialysis (CMD) catheters allow continuous monitoring of patients' cerebral metabolism in severe traumatic brain injury (TBI). The catheters consist of a terminal semi-permeable membrane that is inserted into the brain's interstitium to allow perfusion fluid to equalize with the surrounding cerebral extracellular environment before being recovered through a central non-porous channel. However, it is unclear how far recovered fluid and suspended metabolites have diffused from within the brain, and therefore what volume or region of brain tissue the analyses of metabolism represent. We assessed diffusion of the small magnetic resonance (MR)-detectible molecule gadobutrol from microdialysis catheters in six subjects (complete data five subjects, incomplete data one subject) who had sustained a severe TBI. Diffusion pattern and distance in cerebral white matter were assessed using T1 (time for MR spin-lattice relaxation) maps at 1 mm isotropic resolution in a 3 Tesla MR scanner. Gadobutrol at 10 mmol/L diffused from cerebral microdialysis catheters in a uniform spheroidal (ellipsoid of revolution) pattern around the catheters' semipermeable membranes, and across gray matter-white matter boundaries. Evidence of gadobutrol diffusion was found up to a mean of 13.4 ± 0.5 mm (mean ± standard deviation [SD]) from catheters, but with a steep concentration drop off so that ≤50% of maximum concentration was achieved at ∼4 mm, and ≤10% of maximum was found beyond ∼7 mm from the catheters. There was little variation between subjects. The relaxivity of gadobutrol in human cerebral white matter was estimated to be 1.61 ± 0.38 L.mmol-1sec-1 (mean ± SD); assuming gadobutrol remained extracellular thereby occupying 20% of total tissue volume (interstitium), and concentration equilibrium with perfusion fluid was achieved immediately adjacent to catheters after 24 h of perfusion. No statistically significant change was found in the concentration of the extracellular metabolites glucose, lactate, pyruvate, nor the lactate/pyruvate ratio during gadobutrol perfusion when compared with period of baseline microdialysis perfusion. Cerebral microdialysis allows continuous monitoring of regional cerebral metabolism-the volume of which is now clearer from this study. It also has the potential to deliver small molecule therapies to focal pathologies of the human brain. This study provides a platform for future development of new catheters optimally designed to treat such conditions.

Simultaneous MRI water-fat separation and quantitative susceptibility mapping of carotid artery plaque pre- and post-ultrasmall superparamagnetic iron oxide-uptake.

PURPOSE: Imaging carotid artery plaques to identify features of vulnerability typically requires a multicontrast MRI protocol. The identification of regions of inflammation with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles requires separate pre- and postcontrast scans. We propose a method of joint water-fat separation and quantitative susceptibility mapping (QSM) to aid classification of atherosclerotic plaques and offer a positive contrast mechanism in USPIO-imaging. METHODS: Ten healthy volunteers (3 women and 7 men; aged, 30.7 ± 10.7 years) were imaged at 1.5T to develop an acquisition and postprocessing protocol. Five patients (1 woman and 4 men; mean age, 71 ± 7.5 years) with moderate to severe luminal stenosis were imaged pre- and postadministration of a USPIO contrast agent. We used a multiecho gradient echo acquisition to perform water/fat separation and subsequently QSM. The results were compared with a conventional multicontrast MRI protocol, CT images, and histopathology data. RESULTS: In the volunteer scans, a multiecho gradient echo acquisition with bipolar readout gradients demonstrated to be a reliable acquisition methodology to produce high-quality susceptibility maps in conjunction with the proposed postprocessing methodology. In the patient study, water/fat separation provided a tool to identify lipid-rich necrotic cores and QSM provided a qualitative and quantitative evaluation of plaque features and positive contrast when evaluating USPIO uptake. Plaque calcification could be identified by strong diamagnetism (-1.27 ± 0.71 ppm), while USPIO uptake demonstrated a strong paramagnetism (1.32 ± 0.61 ppm). CONCLUSION: QSM was able to identify multiple plaque features in a single acquisition, providing positive contrast for plaques demonstrating USPIO uptake and negative contrast for calcification.

Introduction to Quantitative Susceptibility Mapping and Susceptibility Weighted Imaging.

Quantitative Susceptibility Mapping (QSM) and Susceptibility Weighted Imaging (SWI) are MRI techniques that measure and display differences in the magnetization that is induced in tissues, i.e. their magnetic susceptibility, when placed in the strong external magnetic field of an MRI system. SWI produces images in which the contrast is heavily weighted by the intrinsic tissue magnetic susceptibility. It has been applied in a wide range of clinical applications. QSM is a further advancement of this technique that requires sophisticated post-processing in order to provide quantitative maps of tissue susceptibility. This review explains the steps involved in both SWI and QSM as well as describing some of their uses in both clinical and research applications.

A Comparison of Black-blood T2 Mapping Sequences for Carotid Vessel Wall Imaging at 3T: An Assessment of Accuracy and Repeatability.

PURPOSE: This study is to compare the accuracy of four different black-blood T2 mapping sequences in carotid vessel wall. METHODS: Four different black-blood T2 mapping sequences were developed and tested through phantom experiments and 17 healthy volunteers. The four sequences were: 1) double inversion-recovery (DIR) prepared 2D multi-echo spin-echo (MESE); 2) DIR-prepared 2D multi-echo fast spin-echo (MEFSE); 3) improved motion-sensitized driven-equilibrium (iMSDE) prepared 3D FSE and 4) iMSDE prepared 3D fast spoiled gradient echo (FSPGR). The concordance correlation coefficient and Bland-Altman statistics were used to compare the sequences with a gold-standard 2D MESE, without blood suppression in phantom studies. The volunteers were scanned twice to test the repeatability. Mean and standard deviation of vessel wall T2, signal-to-noise (SNR), the coefficient of variance and interclass coefficient (ICC) of the two scans were compared. RESULTS: The phantom study demonstrated that T2 measurements had high concordance with respect to the gold-standard (all r values >0.9). In the volunteer study, the DIR 2D MEFSE had significantly higher T2 values than the other three sequences (P < 0.01). There was no difference in T2 measurements obtained using the other three sequences (P > 0.05). iMSDE 3D FSE had the highest SNR (P < 0.05) compared with the other three sequences. The 2D DIR MESE has the highest repeatability (ICC: 0.96, [95% CI: 0.88-0.99]). CONCLUSION: Although accurate T2 measurements can be achieved in phantom by the four sequences, in vivo vessel wall T2 quantification shows significant differences. The in vivo images can be influenced by multiple factors including black-blood preparation and acquisition method. Therefore, a careful choice of acquisition methods and analysis of the confounding factors are required for accurate in vivo carotid vessel wall T2 measurements. From the settings in this study, the iMSDE prepared 3D FSE is preferred for the future volunteer/patient scans.

The development and optimisation of 3D black-blood R2* mapping of the carotid artery wall.

PURPOSE: To develop and optimise a 3D black-blood R2* mapping sequence for imaging the carotid artery wall, using optimal blood suppression and k-space view ordering. METHODS: Two different blood suppression preparation methods were used; Delay Alternating with Nutation for Tailored Excitation (DANTE) and improved Motion Sensitive Driven Equilibrium (iMSDE) were each combined with a three-dimensional (3D) multi-echo Fast Spoiled GRadient echo (ME-FSPGR) readout. Three different k-space view-order designs: Radial Fan-beam Encoding Ordering (RFEO), Distance-Determined Encoding Ordering (DDEO) and Centric Phase Encoding Order (CPEO) were investigated. The sequences were evaluated through Bloch simulation and in a cohort of twenty volunteers. The vessel wall Signal-to-Noise Ratio (SNR), Contrast-to-Noise Ratio (CNR) and R2*, and the sternocleidomastoid muscle R2* were measured and compared. Different numbers of acquisitions-per-shot (APS) were evaluated to further optimise the effectiveness of blood suppression. RESULTS: All sequences resulted in comparable R2* measurements to a conventional, i.e. non-blood suppressed sequence in the sternocleidomastoid muscle of the volunteers. Both Bloch simulations and volunteer data showed that DANTE has a higher signal intensity and results in a higher image SNR than iMSDE. Blood suppression efficiency was not significantly different when using different k-space view orders. Smaller APS achieved better blood suppression. CONCLUSION: The use of blood-suppression preparation methods does not affect the measurement of R2*. DANTE prepared ME-FSPGR sequence with a small number of acquisitions-per-shot can provide high quality black-blood R2* measurements of the carotid vessel wall.