Clinical Studies at Ultra-high Magnetic Fields

A window into brain microstructure

The Center for High-Field Magnetic Resonance offers a unique setting for clinical studies at the scientific forefront that may open up new windows into the complexity of pathophysiologic processes.
Since December 2012 we are investigating the capability of UHF to unravel fine-grained tissue alterations by coupling advanced MRI methods to the latest discoveries in medical research. We use high-resolution MR methods with image contrast tailored to enhance pathology related alterations of tissue structure and/or function by exploiting recent developments in UHF technology. Opens external link in new window

In close collaboration with our clinical partners at the Medical Faculty of the University of Tübingen, we explore the clinical use of MRI, like quantitative mapping of T1, T2*, and Magnetic Susceptibility (QSM), along with neurochemical investigations based on chemical shift imaging and single voxel MRS. In the past two years, 30 patients and as many healthy volunteers have participated in clinical studies, with no drop-out so far.

On-going cooperative projects:

MRI/MRS of Glial Brain Tumors

Brain tumors occur as a result of rapid cellular growth of malignant cells, triggering angiogenesis and alterations of the neurochemical pattern.Opens external link in new windowCombined use of imaging and spectroscopic methods at UHF enables observation of these changes with great detail and improved specificity. Susceptibility weighted imaging of the venous vessels and Time-of-flight imaging of the arteries showed signs of the poorly regulated blood and oxygen supply in tumors. In order to further elucidate tissue heterogeneity and characterize alterations of the local microstructure, we performed quantitative susceptibility mapping. This enabled the identification of calcifications Opens external link in new windowthat could be clearly separated from blood clots and small veins at 9.4T. Key to these results was the development of methods to process the MRI phase images that are used for QSM quantification.

Diagnostics of Multiple Sclerosis Lesions with MRI at 9.4 Tesla

The initial goal of this study was to explore the detectability of intracortical lesions at 9.4T that often go undetected at lower field strengths. In a pilot study including three patients, Double Inversion Recovery (DIR) at 3T was used to identify cortical lesions. The location of DIR lesions could be confirmed by MP2RAGE Opens external link in new windowimaging at 9.4T while further characterization was possible in quantitative T2* maps. In light of recent findings in the clinical literature, these patterns may indicate the presence of a core of iron-rich macrophages, and/or a vessel, surrounded by an area characterized by injured myelin and decreased iron levels in case of oligodendrocyte loss. The next step in this project is to explore different double-inversion MR sequences apt to enhance the contrast between cortical lesions and the grey matter.

High Resolution Structural Magnetic Resonance Imaging in Anxiety Disorders

Recent neuroanatomical models of fear and anxiety reactions indicate anxiety disorder-specific pathways assuming dysfunctions in different neural structures such as the amygdala or the bed nucleus of the stria terminalis (BNST). Here, high resolution MRI provides the advantage to directly target specific key structures. In this project, MRI sequence protocols will be optimized to delineate the BNST in a high resolution with the aim to subsequently investigate the structure in anxious participants and as a long term goal in anxiety disorder patients to elucidate the pivotal role of the BNST.

High-resolution MRI of Alzheimer’s disease

A known consequence of Alzheimer’s disease is ß-amyloid plaque formation, likely associated with iron accumulation. With ultra-high field magnetic resonance it is possible to visualize these changes through quantitative susceptibility mapping (QSM) Opens external link in new windowand R2* mapping. The enhancement of the susceptibility effect at UHF may prove valuable to identify affected cortical areas. This hypothesis is currently investigated in an MRI protocol based on anatomical MP2RAGE-based imaging for T1mapping and automatic definition of cortical brain regions; multi-echo 3D GRE for quantitative R2* mapping; and acquisition weighted MRI Opens external link in new windowto boost SNR for high-resolution QSM. First results show highly localized effects that may indeed have been caused by iron accumulation.

Function and anatomy of deep brain nuclei

In the brain, several structures that are vital for normal human functioning and most often involved in pathophysiological changes, are located at or in the vicinity of the skull-base. This is a region of concern owing to its great variations in magnetic susceptibility that make UHF imaging a challenge. Here we target this difficult area and plan to establish anatomical imaging sequences that allow us to identify the brainstem nuclei with submillimeter resolution. This methodology is extended to functional investigations that enable fine-grained mapping of the activation profile Opens external link in new windowof these structures.

Quantitative MRI and Multi-parametric mapping of brain anatomy

Recent studies suggest that the combined use of several quantitative MR parameters observed at clinical field strengths may improve tissue segmentation. At ultrahigh magnetic field strengths, the image resolution can be pushed well below 1mm, without the need for additional acquisition times, owing to an improved signal-to-noise ratio. Moreover, most MR parameters undergo significant changes at UHF. In this study we explore whether a) the technical challenges at UHF can be overcome to yield robust estimates of the different MR parameters, and b) whether the combined use of quantitative maps allows brain parcellation Opens external link in new windowat the individual level.

MRI and histology of post-mortem samples

Important knowledge about the impact of pathology Opens external link in new windowon tissue microstructure can be achieved by dedicated stains and histology of post-mortem brain samples using optical methods. In this project we aim to create links between this microscopic world and the mesoscopic scale probed by clinical UHF techniques. Post-mortem samples Opens external link in new windowfrom healthy and diseased patients will be investigated, both by clinical MRI protocols and by protocols adapted to fixed tissue at 3T, 9.4T and 14T. By this approach we foresee to gain insight into the contrast mechanisms underlying MRI, besides obtain valuable anatomical information about brain tissue microstructure.

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