Jürgen R. Reichenbach

Susceptibility weighted imaging (SWI)

Susceptibility differences between tissues can be utilized as a new type of contrast in MRI that is different from spin density, T1‐, or T2‐weighted imaging. Signals from substances with different magnetic susceptibilities compared to their neighboring tissue will become out of phase with these tissues at sufficiently long echo times (TEs). Thus, phase imaging offers a means of enhancing contrast in MRI. Specifically, the phase images themselves can provide excellent contrast between gray matter (GM) and white matter (WM), iron‐laden tissues, venous blood vessels, and other tissues with susceptibilities that are different from the background tissue. Also, for the first time, projection phase images are shown to demonstrate tissue (vessel) continuity. In this work, the best approach for combining magnitude and phase images is discussed. The phase images are high‐pass‐filtered and then transformed to a special phase mask that varies in amplitude between zero and unity. This mask is multiplied a few times into the original magnitude image to create enhanced contrast between tissues with different susceptibilities. For this reason, this method is referred to as susceptibility‐weighted imaging (SWI). Mathematical arguments are presented to determine the number of phase mask multiplications that should take place. Examples are given for enhancing GM/WM contrast and water/fat contrast, identifying brain iron, and visualizing veins in the brain. Magn Reson Med 52:612–618, 2004.

Quantitative imaging of intrinsic magnetic tissue properties using MRI signal phase: an approach to in vivo brain iron metabolism?

Quantitative susceptibility mapping (QSM) based on gradient echo (GRE) magnetic resonance phase data is a novel technique for non-invasive assessment of magnetic tissue susceptibility differences. The method is expected to be an important means to determine iron distributions in vivo and may, thus, be instrumental for elucidating the physiological role of iron and disease-related iron concentration changes associated with various neurological and psychiatric disorders. This study introduces a framework for QSM and demonstrates calculation of reproducible and orientation-independent susceptibility maps from GRE data acquired at 3T. The potential of these susceptibility maps to perform anatomical imaging is investigated, as well as the ability to measure the venous blood oxygen saturation level in large vessels, and to assess the local tissue iron concentration. In order to take into account diamagnetic susceptibility contributions induced by myelin, a correction scheme for susceptibility based iron estimation is demonstrated. The findings suggest that susceptibility contrast, and therewith also phase contrast, are not only linked to the storage iron concentration but are also significantly influenced by other sources such as myelin. After myelin correction the linear dependence between magnetic susceptibilities and previously published iron concentrations from post mortem studies was significantly improved. Finally, a comparison between susceptibility maps and processed phase images indicated that caution should be exercised when drawing conclusions about iron concentrations when directly assessing processed phase information.

Clinical applications of neuroimaging with susceptibility-weighted imaging

Susceptibility‐weighted imaging (SWI) consists of using both magnitude and phase images from a high‐resolution, three‐dimensional, fully velocity compensated gradient‐echo sequence. Postprocessing is applied to the magnitude image by means of a phase mask to increase the conspicuity of the veins and other sources of susceptibility effects. This article gives a background of the SWI technique and describes its role in clinical neuroimaging. SWI is currently being tested in a number of centers worldwide as an emerging technique to improve the diagnosis of neurological trauma, brain neoplasms, and neurovascular diseases because of its ability to reveal vascular abnormalities and microbleeds. J. Magn. Reson. Imaging 2005.

Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study

Quantitative susceptibility mapping (QSM) is a novel technique which allows determining the bulk magnetic susceptibility distribution of tissue in vivo from gradient echo magnetic resonance phase images. It is commonly assumed that paramagnetic iron is the predominant source of susceptibility variations in gray matter as many studies have reported a reasonable correlation of magnetic susceptibility with brain iron concentrations in vivo. Instead of performing direct comparisons, however, all these studies used the putative iron concentrations reported in the hallmark study by Hallgren and Sourander (1958) for their analysis. Consequently, the extent to which QSM can serve to reliably assess brain iron levels is not yet fully clear. To provide such information we investigated the relation between bulk tissue magnetic susceptibility and brain iron concentration in unfixed (in situ) post mortem brains of 13 subjects using MRI and inductively coupled plasma mass spectrometry. A strong linear correlation between chemically determined iron concentration and bulk magnetic susceptibility was found in gray matter structures (r = 0.84, p < 0.001), whereas the correlation coefficient was much lower in white matter (r = 0.27, p < 0.001). The slope of the overall linear correlation was consistent with theoretical considerations of the magnetism of ferritin supporting that most of the iron in the brain is bound to ferritin proteins. In conclusion, iron is the dominant source of magnetic susceptibility in deep gray matter and can be assessed with QSM. In white matter regions the estimation of iron concentrations by QSM is less accurate and more complex because the counteracting contribution from diamagnetic myelinated neuronal fibers confounds the interpretation.

Toward in vivo histology: A comparison of quantitative susceptibility mapping (QSM) with magnitude-, phase-, and R2⁎-imaging at ultra-high magnetic field strength

Quantitative magnetic susceptibility mapping (QSM) has recently been introduced to provide a novel quantitative and local MRI contrast. However, the anatomical contrast represented by in vivo susceptibility maps has not yet been compared systematically and comprehensively with gradient (recalled) echo (GRE) magnitude, frequency, and R(2)(*) images. Therefore, this study compares high-resolution quantitative susceptibility maps with conventional GRE imaging approaches (magnitude, frequency, R(2)(*)) in healthy individuals at 7 T with respect to anatomic tissue contrast. Volumes-of-interest were analyzed in deep and cortical gray matter (GM) as well as in white matter (WM) on R(2)(*) and susceptibility maps. High-resolution magnetic susceptibility maps of the human brain exhibited superb contrast that allowed the identification of substructures of the thalamus, midbrain and basal ganglia, as well as of the cerebral cortex. These were consistent with histology but not generally visible on magnitude, frequency or R(2)(*)-maps. Common target structures for deep brain stimulation, including substantia nigra pars reticulata, ventral intermediate nucleus, subthalamic nucleus, and the substructure of the internal globus pallidus, were clearly distinguishable from surrounding tissue on magnetic susceptibility maps. The laminar substructure of the cortical GM differed depending on the anatomical region, i.e., a cortical layer with increased magnetic susceptibility, corresponding to the Stria of Gennari, was found in the GM of the primary visual cortex, V1, whereas a layer with reduced magnetic susceptibility was observed in the GM of the temporal cortex. Both magnetic susceptibility and R(2)(*) values differed substantially in cortical GM depending on the anatomic regions. Regression analysis between magnetic susceptibility and R(2)(*) values of WM and GM structures suggested that variations in myelin content cause the overall contrast between gray and white matter on susceptibility maps and that both R(2)(*) and susceptibility values provide linear measures for iron content in GM. In conclusion, quantitative magnetic susceptibility mapping provides a non-invasive and spatially specific contrast that opens the door to the assessment of diseases characterized by variation in iron and/or myelin concentrations. Its ability to reflect anatomy of deep GM structures with superb delineation may be useful for neurosurgical applications.

High-resolution MR venography at 3.0 Tesla.

Purpose The aim of this study was to investigate the visualization of small venous vessels in the normal human brain at a field strength of 3 Tesla. Methods T2*-weighted, three-dimensional gradient-echo images were acquired by exploiting the magnetic susceptibility difference between oxygenated and deoxygenated hemoglobin in the vasculature and microvasculature. The spatial resolution was 0.5 × 0.5 × 1 mm3, and sequence parameters were varied to obtain good vessel delineation. Improved visibility of venous vessels was obtained by creating phase mask images from the magnetic resonance phase images and multiplying these by the magnitude images. Venograms were created by performing a minimum intensity projection over targeted volumes. Results Highly detailed visualization of venous structures deep in the brain and in the superficial cortical areas were obtained without administration of an exogenous contrast agent; compared with similar studies performed at 1.5 T, the echo time could be reduced from typically 40–50 ms to 17–28 ms. Conclusion Imaging at high-field strength offers the possibility of improved resolution and the delineation of smaller vessels compared with lower field strengths.

In vivo measurement of blood oxygen saturation using magnetic resonance imaging: A direct validation of the blood oxygen level-dependent concept in functional brain imaging

A novel noninvasive magnetic resonance imaging (MRI) method was developed to determine in vivo blood oxygen saturation and its changes during motor cortex activation in small cerebral veins. Specifically, based on susceptibility measurements in the resting states, pial veins were found to have a mean oxygen saturation of Yrest = 0.544 ± 0.029 averaged over 14 vessels in 5 volunteers. During activation, susceptibility measurements revealed an oxygen saturation change of ΔYsusc = 0.14 ± 0.02. Independent evaluation from blood flow velocity measurements yielded a value of ΔYflow = 0.14 ± 0.04 for this change. These results validate the blood oxygenation level‐dependent (BOLD) model in functional MRI (fMRI). Hum. Brain Mapping 5:341–346, 1997.

Brain activation to phobia-related pictures in spider phobic humans: an event-related functional magnetic resonance imaging study

Using event-related functional magnetic resonance imaging we investigated blood oxygen level dependent brain activation in spider phobic and non-phobic subjects while exposed to phobia-related pictures (spiders) and non-phobia-related pictures (snakes and mushrooms). In contrast to previous studies, we show significantly increased amygdala activation in spider phobics, but not in controls, during presentation of phobia-relevant visual stimuli. Furthermore, phobia-specific increased activation was also found in the insula, the orbitofrontal cortex and the uncus. Our study confirms the role of the amygdala in fear processing and provides insights into brain activation patterns when animal phobics are confronted with phobia-related stimuli.

Susceptibility-weighted imaging to visualize blood products and improve tumor contrast in the study of brain masses.

To evaluate the diagnostic value of susceptibility‐weighted imaging (SWI) for studying brain masses.

Differentiation between diamagnetic and paramagnetic cerebral lesions based on magnetic susceptibility mapping.

PURPOSE Identification of calcifications and hemorrhages is essential for the etiological diagnosis of cerebral lesions. The purpose of this work was to develop a robust method for characterization of para- and diamagnetic intracerebral lesions based on clinical gradient-echo magnetic resonance phase data acquired at 1.5 Tesla. METHODS The magnetic susceptibility distribution of biological tissue produces a distinct magnetic field pattern, which is directly reflected in gradient-echo magnetic resonance phase images. Compared to brain parenchyma, iron-laden tissues are more paramagnetic, whereas mineralized tissues usually possess more diamagnetic susceptibilities. Magnetic resonance phase data were inverted to the underlying susceptibility distribution utilizing additional geometrical information about the lesions, which was obtained from the gradient-echo magnitude signal void corresponding to the lesions. Clinical magnetic resonance exams of three patients with multiple brain lesions (total n = 70) were processed and evaluated. For one patient, the results were validated by an additionally available computed tomography scan. Numerical simulations were conducted to evaluate the robustness of the method. RESULTS The obtained susceptibility maps showed impressive delineation of lesions, vessels, and potentially iron-laden tissue. Compensation of the nonlocal field perturbations was clearly discernable on the susceptibility maps. In all cases, discrimination of para- from diamagnetic lesions was achieved and the results were confirmed by the additional computed tomography. The numerical simulations demonstrated that robust determination of the total magnetic moment of lesions is possible. Thus, the proposed method is able to yield quantitative values for the minimum magnetic susceptibility of lesions. CONCLUSIONS A method has been developed for noninvasive, semiautomatic characterization of brain lesions based on magnetic resonance imaging data. Initial clinical results demonstrated that the proposed technique can be applied to diagnosis of lesions with calcifications or hemorrhages. If confirmed by larger studies, it bears the potential to obviate the need for confirmation with computed tomography.