Jan Sedlacik

BACKGROUND AND PURPOSE: MR gradient echo imaging is sensitive to the magnetic susceptibility of different tissue types. The purpose of this study was to investigate the diagnostic potential of MR phase imaging of the human brain. METHODS: High-spatial-resolution, T2*-weighted, single-echo images were acquired in five volunteers and one patient with a brain tumor on a 1.5T system by applying a 3D, first-order, velocity-compensated gradient echo sequence by using a quadrature transmit-receive head coil. Phase images were reconstructed from the raw data and unwrapped by using a region-growing phase-unwrapping algorithm. Low-spatial-frequency components originating from static background susceptibility effects were removed by high-pass filtering. RESULTS: Phase images showed excellent image contrast and revealed anatomic structures that were not visible on the corresponding magnitude images. CONCLUSION: Improved processing of susceptibility-weighted MR phase images offers a new means of contrast for neuroimaging applications.

The fast and accurate assessment of cerebral perfusion is fundamental for the diagnosis and successful treatment of stroke patients. Magnetic particle imaging (MPI) is a new radiation-free tomographic imaging method with a superior temporal resolution, compared to other conventional imaging methods. In addition, MPI scanners can be built as prehospital mobile devices, which require less complex infrastructure than computed tomography (CT) and magnetic resonance imaging (MRI). With these advantages, MPI could accelerate the stroke diagnosis and treatment, thereby improving outcomes. Our objective was to investigate the capabilities of MPI to detect perfusion deficits in a murine model of ischemic stroke. Cerebral ischemia was induced by inserting of a microfilament in the internal carotid artery in C57BL/6 mice, thereby blocking the blood flow into the medial cerebral artery. After the injection of a contrast agent (superparamagnetic iron oxide nanoparticles) specifically tailored for MPI, cerebral perfusion and vascular anatomy were assessed by the MPI scanner within seconds. To validate and compare our MPI data, we performed perfusion imaging with a small animal MRI scanner. MPI detected the perfusion deficits in the ischemic brain, which were comparable to those with MRI but in real-time. For the first time, we showed that MPI could be used as a diagnostic tool for relevant diseases in vivo, such as an ischemic stroke. Due to its shorter image acquisition times and increased temporal resolution compared to that of MRI or CT, we expect that MPI offers the potential to improve stroke imaging and treatment.

Atypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs). TAOK2 is one of several genes in the 16p11.2 microdeletion region, but whether it contributes to NDDs is unknown. We performed behavioral analysis on Taok2 heterozygous (Het) and knockout (KO) mice and found gene dosage-dependent impairments in cognition, anxiety, and social interaction. Taok2 Het and KO mice also have dosage-dependent abnormalities in brain size and neural connectivity in multiple regions, deficits in cortical layering, dendrite and synapse formation, and reduced excitatory neurotransmission. Whole-genome and -exome sequencing of ASD families identified three de novo mutations in TAOK2 and functional analysis in mice and human cells revealed that all the mutations impair protein stability, but they differentially impact kinase activity, dendrite growth, and spine/synapse development. Mechanistically, loss of Taok2 activity causes a reduction in RhoA activation, and pharmacological enhancement of RhoA activity rescues synaptic phenotypes. Together, these data provide evidence that TAOK2 is a neurodevelopmental disorder risk gene and identify RhoA signaling as a mediator of TAOK2-dependent synaptic development.

We present numerical simulations and experimental results for susceptibility weighted imaging (SWI) at 7 T. Magnitude, phase, and SWI contrast were simulated for different voxel geometries and imaging parameters, resulting in an echo time of 14 msec for optimum contrast between veins and surrounding tissue. Slice thickness of twice the in-plane voxel size or more resulted in optimum vessel visibility. Phantom and in vivo data are in very good agreement with the simulations and the delineation of vessels at 7 T was superior compared to lower field strengths. The phase of the complex data reveals anatomical details that are complementary to the corresponding magnitude images. Susceptibility weighted imaging at very high field strengths is a promising technique because of its high sensitivity to tissue susceptibility, its low specific absorption rate, and the phase's negligible sensitivity to B(1) inhomogeneities.

Susceptibility weighted imaging (SWI) is a BOLD-sensitive method for visualizing anatomical features such as small cerebral veins in high detail. The purpose of this study was to evaluate high-resolution SWI in combination with a modulation of blood oxygenation by breathing of air, carbogen, and oxygen and to directly visualize the effects of changing blood oxygenation on the magnetic field inside and around venous blood vessels. Signal changes associated with the response to carbogen and oxygen breathing were evaluated in different anatomic regions in healthy volunteers and in two patients with brain tumors. In the magnitude images inhalation of carbogen led to significant signal intensity changes ranging from +4.4 +/- 1.9% to +9.5 +/- 1.4% in gray matter and no significant changes in thalamus, putamen, and white matter. During oxygen breathing mean signal changes were smaller than during carbogen breathing. The method is capable of producing high-resolution functional maps of BOLD response to carbogen and oxygen breathing as well as high-resolution images of venous vasculature. Its sensitivity to changes in blood oxygenation was demonstrated by in vivo visualization of the BOLD effect via phase imaging.