Design and testing of microbubble‐based MRI contrast agents for gastric pressure measurement

Purpose: This work demonstrates specifically tailored microbubble‐based preparations and their suitability as MRI contrast agents for ingestion and measuring temporal and spatial pressure variation in the human stomach. Methods: Enhanced alginate spheres were prepared by incorporating gas‐filled microbubbles into sodium alginate solution followed by the polymerization of the mixture in an aqueous calcium lactate solution. The microbubbles were prepared with a phospholipid shell and perfluorocarbon gas filling, using a mechanical cavitational agitation regime. The NMR signal changes to externally applied pressure and coming from the enhanced alginate spheres were acquired and compared with that of alginate spheres without microbubbles. In vivo investigations were also carried out on healthy volunteers to measure the pressure variation in the stomach. Results: The MR signal changes in the contrast agent exhibits a linear sensitivity of approximately 40% per bar, as opposed to no measurable signal change seen in the control gas‐free spheres. This novel contrast agent also demonstrates an excellent stability in simulated gastric conditions, including at body temperature. In vivo studies showed that the signal change exhibited in the meal within the antrum region is between 5% and 10%, but appears to come from both pressure changes and partial volume artifacts. Conclusion: This study demonstrates that alginate spheres with microbubbles can be used as an MRI contrast agent to measure pressure changes. The peristaltic movement within the stomach is seen to substantially alter the overall signal intensity of the contrast agent meal. Future work must focus on improving the contrast agent's sensitivity to pressure changes

Human hippocampal CA3 damage disrupts both recent and remote episodic memories

Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not remote, episodic retrieval. In this study, we demonstrated that recent and remote memories were susceptible to a loss of episodic detail in human participants with focal bilateral damage to CA3. Graph theoretic analyses of 7.0-Tesla resting-state fMRI data revealed that CA3 damage disrupted functional integration across the medial temporal lobe (MTL) subsystem of the default network. The loss of functional integration in MTL subsystem regions was predictive of autobiographical episodic retrieval performance. We conclude that human CA3 is necessary for the retrieval of episodic memories long after their initial acquisition and functional integration of the default network is important for autobiographical episodic memory performance

In Vivo Assessment of Cold Adaptation in Insect Larvae by Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy

Background Temperatures below the freezing point of water and the ensuing ice crystal formation pose serious challenges to cell structure and function. Consequently, species living in seasonally cold environments have evolved a multitude of strategies to reorganize their cellular architecture and metabolism, and the underlying mechanisms are crucial to our understanding of life. In multicellular organisms, and poikilotherm animals in particular, our knowledge about these processes is almost exclusively due to invasive studies, thereby limiting the range of conclusions that can be drawn about intact living systems. Methodology Given that non-destructive techniques like 1H Magnetic Resonance (MR) imaging and spectroscopy have proven useful for in vivo investigations of a wide range of biological systems, we aimed at evaluating their potential to observe cold adaptations in living insect larvae. Specifically, we chose two cold-hardy insect species that frequently serve as cryobiological model systems–the freeze-avoiding gall moth Epiblema scudderiana and the freeze-tolerant gall fly Eurosta solidaginis. Results In vivo MR images were acquired from autumn-collected larvae at temperatures between 0°C and about -70°C and at spatial resolutions down to 27 µm. These images revealed three-dimensional (3D) larval anatomy at a level of detail currently not in reach of other in vivo techniques. Furthermore, they allowed visualization of the 3D distribution of the remaining liquid water and of the endogenous cryoprotectants at subzero temperatures, and temperature-weighted images of these distributions could be derived. Finally, individual fat body cells and their nuclei could be identified in intact frozen Eurosta larvae. Conclusions These findings suggest that high resolution MR techniques provide for interesting methodological options in comparative cryobiological investigations, especially in vivo

Rapid quantitation of magnetization transfer using pulsed off-resonance irradiation and echo planar imaging.

A technique for producing a quantitative measure of magnetization transfer parameters in a clinically feasible time scale is proposed. The combination of pulsed off-resonance irradiation and echo planar imaging has produced an imaging sequence that negates the need for continuous wave irradiation and allows the approach to steady-state conditions to be studied. Data analysis involves the step-by-step numerical solution of the modified Bloch equations to generate a quantitative model of the measured signal intensity based on the relative size of the bound proton pool and the bound proton pool transverse relaxation time. The sequence and model are applied to the study of a series of agar gels of varying concentrations and the results are compared to those from the literature

Perturbation of the BOLD response by a contrast agent and interpretation through a modified balloon model.

This study used an infusion of a paramagnetic contrast agent to perturb intravascular blood susceptibility and investigate its effect on the BOLD hemodynamic response. A three compartment BOLD signal model combined with a modified balloon model was developed to interpret the MR signal. This model incorporated arterial blood volume in order to simulate signal changes resulting from the contrast agent. The BOLD signal model was fitted to the experimental data to test the hypothesis that arterial blood volume changes during activation. It was found that allowing arterial blood volume to change, rather than assuming this change is negligible as often assumed in the literature, provides a better fit to the experimental data, particularly during the BOLD overshoot. The post-stimulus undershoot was fitted well, regardless of whether the arterial blood volume was allowed to change, by assuming that this feature is due to delayed venous compliance. However the resultant elevation in post-stimulus blood volume decays with an extremely long time constant, taking more than 55 s to recover to baseline following a 4.8 s stimulus. The post-stimulus signal changes measured here could alternatively be described by a post-stimulus elevation in metabolism. An alternative model of oxygen extraction, in place of the Oxygen Limitation model, would be required to test this hypothesis

Rapid and accurate measurement of transverse relaxation times using a single shot multi-echo echo-planar imaging sequence.

Methods for making rapid and accurate measurements and maps of the transverse relaxation time from a single free induction decay (FID) are proposed. The methods use a multi-echo sequence in combination with B1 insensitive (hyperbolic secant or BIREF2b) refocusing pulses and rapid echo-planar imaging techniques. The results were calibrated against a single spin echo echo-planar imaging sequence using a phantom containing a range of CuSO4 concentrations. The mean percentage absolute difference between the multi-echo and single-echo results was 3% for the multi-echo sequence using the hyperbolic secant refocusing pulse, and 7% for the multi-echo sequence using the BIREF2b refocusing pulse, compared to 13% for a multi-echo sequence using a nonselective sinc refocusing pulse. The use of the sequences in vivo has been demonstrated in studies of gastric function, i.e., the measurement of gastric dilution and monitoring of formation of a raft of alginate polysaccharide within the stomach

An improved method for acquiring cerebrovascular reactivity maps.

This study aims to improve the method used to produce cerebrovascular reactivity (CVR) maps by MRI. Previous methods have used a standard boxcar presentation of carbon dioxide (CO(2)). Here this is replaced with a sinusoidally modulated CO(2) stimulus. This allowed the use of Fourier analysis techniques to measure both the amplitude and phase delay of the BOLD CVR response, and hence characterize the arrival sequence of blood to different regions of the brain. This characterization revealed statistically significant relative delays between regions of the brain (ANOVA < 0.0001). In addition, post hoc comparison showed that the frontal (P < 0.001) and parietal (P = 0.004) lobes reacted earlier than the occipital lobe. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc

Measuring venous blood volume changes during activation using hyperoxia.

This study describes a novel method for measuring relative changes in venous cerebral blood volume (CBVv) using hyperoxia as a contrast agent. This method exploits the extravascular BOLD effect and its dependency on both task-related activation induced changes in venous blood oxygenation and changes due to breathing an oxygen enriched gas mixture. Changes in CBVv on activation can be estimated by comparing the change in transverse relaxation rate, R2*, due to hyperoxia in both baseline and activation states. Furthermore these measurements can be converted into a measure of the percentage change in CBVv. Experiments were performed to measure changes in a CBVv-weighted signal in response to a simple motor task. Both positive and negative changes in CBVv-weighted signal were detected in the positively activated BOLD region