Brain edema : a valid endpoint for measuring hepatic encephalopathy?

Hepatic encephalopathy (HE) is a major complication of liver failure/disease which frequently develops during the progression of end-stage liver disease. This metabolic neuropsychiatric syndrome involves a spectrum of symptoms, including cognition impairment, attention deficits and motor dysfunction which eventually can progress to coma and death. Pathologically, HE is characterized by swelling of the astrocytes which consequently leads to brain edema, a common feature found in patients with acute liver failure (ALF) as well as in cirrhotic patients suffering from HE. The pathogenic factors involved in the onset of astrocyte swelling and brain edema in HE are unresolved. However, the role of astrocyte swelling/brain edema in the development of HE remains ambiguous and therefore measuring brain edema as an endpoint to evaluate HE is questioned. The following review will determine the effect of astrocyte swelling and brain edema on neurological function, discuss the various possible techniques to measure brain edema and lastly to propose a number of neurobehavioral tests to evaluate HE

Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications.

Quantitative susceptibility mapping (QSM) is a recently developed MRI technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It first uses the frequency shift in the MRI signal to map the magnetic field profile within the tissue. The resulting field map is then used to determine the spatial distribution of the underlying magnetic susceptibility by solving an inverse problem. The solution is achieved by deconvolving the field map with a dipole field, under the assumption that the magnetic field is a result of the superposition of the dipole fields generated by all voxels and that each voxel has its unique magnetic susceptibility. QSM provides improved contrast to noise ratio for certain tissues and structures compared to its magnitude counterpart. More importantly, magnetic susceptibility is a direct reflection of the molecular composition and cellular architecture of the tissue. Consequently, by quantifying magnetic susceptibility, QSM is becoming a quantitative imaging approach for characterizing normal and pathological tissue properties. This article reviews the mechanism generating susceptibility contrast within tissues and some associated applications

Fast Absolute Quantification of In Vivo Water and Fat Content with Magnetic Resonance Imaging

Quantitative water fat imaging offers a non-invasive method for monitoring and staging diseases associated with changes in either water or fat content in tissue. In this work absolute water and fat mass density measurement with in vivo Magnetic Resonance Imaging (MRI) is demonstrated. T1 independent, T2* corrected chemical shift based water-fat separated images are acquired. By placing a phantom with known mass density in the field of view for signal intensity calibration, absolute water or fat mass density can be computed, assuming the B1+ (transmit) and B1- (receive) fields can be measured. Phantom experiments with known water fat concentration were conducted to validate the feasibility of proposed method and in vivo data was collected from healthy volunteers. Results show good agreement with known values of in vivo water density. Each measurement was within one breath hold. Fast absolute quantification of water and fat with MRI is feasible in the abdomen

MENGA: a new comprehensive tool for the integration of neuroimaging data and the Allen human brain transcriptome atlas

Brain-wide mRNA mappings offer a great potential for neuroscience research as they can provide information about system proteomics. In a previous work we have correlated mRNA maps with the binding patterns of radioligands targeting specific molecular systems and imaged with positron emission tomography (PET) in unrelated control groups. This approach is potentially applicable to any imaging modality as long as an efficient procedure of imaging-genomic matching is provided. In the original work we considered mRNA brain maps of the whole human genome derived from the Allen human brain database (ABA) and we performed the analysis with a specific region-based segmentation with a resolution that was limited by the PET data parcellation. There we identified the need for a platform for imaging-genomic integration that should be usable with any imaging modalities and fully exploit the high resolution mapping of ABA dataset.In this work we present MENGA (Multimodal Environment for Neuroimaging and Genomic Analysis), a software platform that allows the investigation of the correlation patterns between neuroimaging data of any sort (both functional and structural) with mRNA gene expression profiles derived from the ABA database at high resolution.We applied MENGA to six different imaging datasets from three modalities (PET, single photon emission tomography and magnetic resonance imaging) targeting the dopamine and serotonin receptor systems and the myelin molecular structure. We further investigated imaging-genomic correlations in the case of mismatch between selected proteins and imaging targets

Magnetic susceptibility anisotropy of myocardium imaged by cardiovascular magnetic resonance reflects the anisotropy of myocardial filament α-helix polypeptide bonds.

BackgroundA key component of evaluating myocardial tissue function is the assessment of myofiber organization and structure. Studies suggest that striated muscle fibers are magnetically anisotropic, which, if measurable in the heart, may provide a tool to assess myocardial microstructure and function.MethodsTo determine whether this weak anisotropy is observable and spatially quantifiable with cardiovascular magnetic resonance (CMR), both gradient-echo and diffusion-weighted data were collected from intact mouse heart specimens at 9.4 Tesla. Susceptibility anisotropy was experimentally calculated using a voxelwise analysis of myocardial tissue susceptibility as a function of myofiber angle. A myocardial tissue simulation was developed to evaluate the role of the known diamagnetic anisotropy of the peptide bond in the observed susceptibility contrast.ResultsThe CMR data revealed that myocardial tissue fibers that were parallel and perpendicular to the magnetic field direction appeared relatively paramagnetic and diamagnetic, respectively. A linear relationship was found between the magnetic susceptibility of the myocardial tissue and the squared sine of the myofiber angle with respect to the field direction. The multi-filament model simulation yielded susceptibility anisotropy values that reflected those found in the experimental data, and were consistent that this anisotropy decreased as the echo time increased.ConclusionsThough other sources of susceptibility anisotropy in myocardium may exist, the arrangement of peptide bonds in the myofilaments is a significant, and likely the most dominant source of susceptibility anisotropy. This anisotropy can be further exploited to probe the integrity and organization of myofibers in both healthy and diseased heart tissue

Temperature and pH Imaging using Chemical Exchange Saturation Transfer (CEST) MRI Contrast

Chemical exchange saturation transfer (CEST) is a novel mechanism used to generate contrast in magnetic resonance imaging (MRI). Recently, CEST contrast was proposed to noninvasively measure physiological parameters including temperature and pH. Tissue temperature and pH are known markers of pathological processes in many diseases including stroke and cancer. CEST contrast can be generated using endogenous proteins and peptides (endogenous CEST) or using exogenous paramagnetic lanthanide agents (PARACEST). The general problem of optimizing applications of endogenous CEST and PARACEST contrast to measure temperature and pH is addressed in this thesis. Highlights of the thesis include a novel application of PARACEST contrast to measure extracellular pH and temperature in-vivo and a novel ratiometric approach that uses endogenous CEST contrast to measure intracellular pH in-vivo. Using a Tm3+-based PARACEST agent (Tm3+-DOTAM-Gly-Lys), the PARACEST amide peak chemical shift and linewidth were shown to depend on pH and temperature in a deterministic manner. Quantitative temperature and pH maps were simultaneously measured in a normal mouse leg following agent injection using empirical relations derived in-vitro. A ratio of endogenous amide and amine proton CEST effects was developed to measure absolute tissue pH that is heavily weighted to the intracellular compartment. The technique called amine and amide concentration-independent detection (AACID) was developed using in-vitro phantoms and numerical simulations. Following in-vivo pH-calibration using 31P-magnetic resonance spectroscopy (MRS), tissue pH measurement was demonstrated in mice following focal cerebral ischemia. Local acidosis was measured in ischemic regions and found to correlate with regions of tissue damage. Finally, two endogenous CEST metrics including the AACID ratio were used to monitor cancer treatment using an anticancer drug called lonidamine. Lonidamine selectively acidifies cancer cells. In-vivo experiments demonstrate that endogenous CEST imaging is sensitive to intracellular acidification by lonidamine in a glioblastoma brain tumor mouse model. Overall, the results presented in this thesis demonstrate quantitative measurement of pH and temperature using CEST and/or PARACEST contrast in-vivo. Some of the novel techniques developed in this thesis were demonstrated in stroke and cancer mouse models. Future work should focus on 1) development of PARACEST agents with higher sensitivity in-vivo to improve accuracy of temperature and pH maps; 2) application of AACID for absolute pH measurement to differentiate high- and low-grade tumors in-vivo; and 3) application of endogenous CEST measurement to monitor tumor response to different clinically approved chemotherapy treatments

Joint Total Variation ESTATICS for Robust Multi-Parameter Mapping

Quantitative magnetic resonance imaging (qMRI) derives tissue-specific parameters -- such as the apparent transverse relaxation rate R2*, the longitudinal relaxation rate R1 and the magnetisation transfer saturation -- that can be compared across sites and scanners and carry important information about the underlying microstructure. The multi-parameter mapping (MPM) protocol takes advantage of multi-echo acquisitions with variable flip angles to extract these parameters in a clinically acceptable scan time. In this context, ESTATICS performs a joint loglinear fit of multiple echo series to extract R2* and multiple extrapolated intercepts, thereby improving robustness to motion and decreasing the variance of the estimators. In this paper, we extend this model in two ways: (1) by introducing a joint total variation (JTV) prior on the intercepts and decay, and (2) by deriving a nonlinear maximum \emph{a posteriori} estimate. We evaluated the proposed algorithm by predicting left-out echoes in a rich single-subject dataset. In this validation, we outperformed other state-of-the-art methods and additionally showed that the proposed approach greatly reduces the variance of the estimated maps, without introducing bias.Comment: 11 pages, 2 figures, 1 table, conference paper, accepted at MICCAI 202