Publications

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS) is a complex procedure due to the subtleties of ultrasound interpretation, the small field of observation, and the uncertainty of probe position and orientation. Animal studies demonstrated that Image Registered Gastroscopic Ultrasound (IRGUS) is feasible and may be superior to conventional EUS in efficiency and image interpretation. This study explores whether these attributes of IRGUS will be evident in human subjects, with the aim of assessing the feasibility, effectiveness, and efficiency of IRGUS in patients with suspected pancreatic lesions. PATIENTS AND METHODS: This was a prospective feasibility study at a tertiary care academic medical center in human patients with pancreatic lesions on computed tomography (CT) scan. Patients who were scheduled to undergo conventional EUS were randomly chosen to undergo their procedure with IRGUS. Main outcome measures included feasibility, ease of use, system function, validated task load (TLX) assessment instrument, and IRGUS experience questionnaire. RESULTS: Five patients underwent IRGUS without complication. Localization of pancreatic lesions was accomplished efficiently and accurately (TLX temporal demand 3.7 %; TLX effort 8.6 %). Image synchronization and registration was accomplished in real time without procedure delay. The mean assessment score for endoscopist experience with IRGUS was positive (66.6 ± 29.4). Real-time display of CT images in the EUS plane and echoendoscope orientation were the most beneficial characteristics. CONCLUSIONS: IRGUS appears feasible and safe in human subjects, and efficient and accurate at identification of probe position and image interpretation. IRGUS has the potential to broaden the adoption of EUS techniques and shorten EUS learning curves. Clinical studies comparing IRGUS with conventional EUS are ongoing.

A fundamental tenet of the "disconnectivity" theories of schizophrenia is that the disorder is ultimately caused by abnormal communication between spatially disparate brain structures. Given that the white matter fasciculi represent the primary infrastructure for long distance communication in the brain, abnormalities in these fiber bundles have been implicated in the etiology of schizophrenia. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that enables the visualization of white matter macrostructure in vivo, and which has provided unprecedented insight into the existence and nature of white matter abnormalities in schizophrenia. The paper begins with an overview of DTI and more commonly used diffusion metrics and moves on to a brief review of the schizophrenia literature. The functional implications of white matter abnormalities are considered, particularly with respect to myelin’s role in modulating the transmission velocity of neural discharges. The paper concludes with a speculative hypothesis about the relationship between gray and white matter abnormalities associated with schizophrenia.

Iodine added to iodide-based ionic liquids leads to extraordinarily efficient charge transport, vastly exceeding that expected for such viscous systems. Using terahertz time-domain spectroscopy, in conjunction with dc conductivity, diffusivity and viscosity measurements we unravel the conductivity pathways in 1-methyl-3-propylimidazolium iodide melts. This study presents evidence of the Grotthuss mechanism as a significant contributor to the conductivity, and provides new insights into ion pairing processes as well as the formation of polyiodides. The terahertz and transport results are reunited in a model providing a quantitative description of the conduction by physical diffusion and the Grotthuss bond-exchange process. These novel results are important for the fundamental understanding of conduction in molten salts and for applications where ionic liquids are used as charge-transporting media such as in batteries and dye-sensitized solar cells.

A recently developed protocol for pulsed gradient spin echo (PGSE) NMR is applied for the size determination of multilamellar vesicles (MLVs). By monitoring the self-diffusion behavior of water, the technique yields an estimate of the homogeneous length scale λ(hom), i.e. the maximum length scale at which there is local structural heterogeneity in a globally homogeneous material. A cross-over between local non-Gaussian to global Gaussian diffusion is observed by varying the experimentally defined length- and time-scales. Occasional observation of a weak Bragg peak in the PGSE signal attenuation curves permits the direct estimation of the MLV radius in favorable cases, thus yielding the constant of proportionality between λ(hom) and radius. The microstructural origin of the Bragg peak is verified through Brownian dynamics simulations and a theoretical analysis based on the center-of-mass diffusion propagator. λ(hom) is decreasing with increasing shear rate in agreement with theoretical expectations and results from (2)H NMR lineshape analysis.

Water exchange through the cell membranes is an important feature of cells and tissues. The rate of exchange is determined by factors such as membrane lipid composition and organization, as well as the type and activity of aquaporins. A method for noninvasively estimating the rate of water exchange would be useful for characterizing pathological conditions, e.g., tumors, multiple sclerosis, and ischemic stroke, expected to be associated with a change of the membrane barrier properties. This study describes the filter exchange imaging method for determining the rate of water exchange between sites having different apparent diffusion coefficients. The method is based on the filter-exchange pulsed gradient spin-echo NMR spectroscopy experiment, which is here modified to be compatible with the constraints of clinical MR scanners. The data is analyzed using a model-free approach yielding maps of the apparent exchange rate, here being introduced in analogy with the concept of the apparent diffusion coefficient. Proof-of-principle experiments are performed on microimaging and whole-body clinical scanners using yeast suspension phantoms. The limitations and appropriate experimental conditions are examined. The results demonstrate that filter exchange imaging is a fast and reliable method for characterizing exchange, and that it has the potential to become a powerful diagnostic tool.

INTRODUCTION: Alterations in white matter connections in schizophrenia have been investigated using diffusion tensor imaging (DTI). There is also evidence from post-mortem studies as well as from magnetic resonance imaging morphometry studies that the anterior commissure (AC) might be implicated in schizophrenia, but no studies, to date, have investigated the AC using DTI or tractography. METHOD: DTI scans were analyzed from 25 patients and 23 controls. Mean fractional anisotropy (FA) and trace were measured from the AC tracts. SANS and SAPS were used to evaluate clinical symptoms, and the Iowa Gambling Task, related to decision making, was also examined. RESULTS: Results revealed a significant decrease in mean FA and a significant increase in mean trace of AC tracts in patients compared with controls. In addition, patients, but not controls, showed a negative correlation between age and AC integrity. Statistically significant positive correlations were also found between AC FA and total positive symptom score. Decision making was negatively correlated with FA in patients on the Iowa Gambling Task, but not in controls. CONCLUSION: This study provides quantitative evidence for a reduction of interhemispheric connectivity in schizophrenia within the AC. Negative correlation between age and AC FA in the patients is consistent with the idea that schizophrenia may be a disorder of white matter maturation. Positive correlation between FA and positive symptom is discussed in the context of white matter’s established role in modulating neural conduction velocity.

BACKGROUND: Several theories of schizophrenia have emphasized the role of aberrant neural timing in the etiology of the disease, possibly as a consequence of conduction delays caused by structural damage to the white-matter fasciculi. Consistent with this theory, increased inter-hemispheric transmission times (IHTTs) to unilaterally-presented visual stimuli have been reported in patients with schizophrenia. The present study investigated whether or not these IHTT abnormalities could be underpinned by structural damage to the visual fibers of the corpus callosum. METHODS: Thirty three schizophrenia patients and 22 matched controls underwent Event Related Potential (ERP) recording, and a subset of 19 patients and 16 controls also underwent 3T Diffusion-Tensor Imaging (DTI). Unilateral visual stimuli (squares, 2×2 degrees) were presented 6 degrees lateral to either side of a central fixation point. IHTTs (ipsilateral minus contralateral latencies) were calculated for the P1 and N1 components at parietal-occipital sites in current source density-transformed ERPs. The visual fibers of the corpus callosum were extracted with streamline tractography and the diffusion metrics of Fractional Anisotropy (FA) and Mode calculated. RESULTS: While both subject groups exhibited highly significant IHTTs across a range of posterior electrode pairs, and significantly shorter IHTTs from left-to-right hemisphere than vice versa, no significant groupwise differences in IHTT were observed. However, participants’ IHTTs were linearly related to their FA and Mode, with longer IHTTs being associated with lower FA and more prolate diffusion ellipsoids. CONCLUSIONS: These results suggest that IHTTs are estimable from DTI measures of white matter integrity. In light of the range of diffusion abnormalities that have been reported in patients with schizophrenia, particularly in frontal fasciculi, these results support the conjecture that schizophrenia is associated with abnormalities in neural timing.

AIM: The influences on the signal-to-noise ratio (SNR) of Displacement ENcoding with Stimulated Echoes (DENSE) MRI of field strength, receiver coil sensitivity and choice of flip angle strategy have been previously investigated individually. In this study, all of these parameters have been investigated in the same setting, and a mutual comparison of their impact on SNR is presented. MATERIALS AND METHODS: Ten healthy volunteers were imaged in a 1.5 T and a 3 T MRI system, using standard five- or six-channel cardiac coils as well as 32-channel coils, with four different excitation patterns. Variation of spatial coil sensitivity was assessed by regional SNR analysis. RESULTS: SNR ranging from 2.8 to 30.5 was found depending on the combination of excitation patterns, coil sensitivity and field strength. The SNR at 3 T was 53±26% higher than at 1.5 T (P

BACKGROUND: Diffusion tensor imaging (DTI) infers the trajectory and location of large white matter tracts by measuring the anisotropic diffusion of water. DTI data may then be analyzed and presented as tractography for visualization of the tracts in 3 dimensions. Despite the important information contained in tractography images, usefulness for neurosurgical planning has been limited by the inability to define which are critical structures within the mass of demonstrated fibers and to clarify their relationship to the tumor. OBJECTIVE: To develop a method to allow the interactive querying of tractography data sets for surgical planning and to provide a working software package for the research community. METHODS: The tool was implemented within an open source software project. Echo-planar DTI at 3 T was performed on 5 patients, followed by tensor calculation. Software was developed that allowed the placement of a dynamic seed point for local selection of fibers and for fiber display around a segmented structure, both with tunable parameters. A neurosurgeon was trained in the use of software in 1 hour and used it to review cases. RESULTS: Tracts near tumor and critical structures were interactively visualized in 3 dimensions to determine spatial relationships to lesion. Tracts were selected using 3 methods: anatomical and functional magnetic resonance imaging-defined regions of interest, distance from the segmented tumor volume, and dynamic seed-point spheres. CONCLUSION: Interactive tractography successfully enabled inspection of white matter structures that were in proximity to lesions, critical structures, and functional cortical areas, allowing the surgeon to explore the relationships between them.