A novel gradient echo data based vein segmentation algorithm and its application for the detection of regional cerebral differences in venous susceptibility.

Accurate segmentation of cerebral venous vasculature from gradient echo data is of central importance in several areas of neuroimaging such as for the susceptibility-based assessment of brain oxygenation or planning of electrode placement in deep brain stimulation. In this study, a vein segmentation algorithm for single- and multi-echo gradient echo data is proposed. First, susceptibility maps, true susceptibility-weighted images, and, in the multi-echo case, R2* maps were generated from the gradient echo data. These maps were filtered with an inverted Hamming filter to suppress background contrast as well as artifacts from field inhomogeneities at the brain boundaries. A shearlet-based scale-wise representation was generated to calculate a vesselness function and to generate segmentations based on local thresholding. The accuracy of the proposed algorithm was evaluated for different echo times and image resolutions using a manually generated reference segmentation and two vein segmentation algorithms (Frangi vesselness-based, recursive vesselness filter) as a reference with the Dice and Cohen's coefficients as well as the modified Hausdorff distance. The Frangi-based and recursive vesselness filter methods were significantly outperformed with regard to all error metrics. Applying the algorithm, susceptibility differences likely related to differences in blood oxygenation between superficial and deep venous territories could be demonstrated.

Multiparametric MRI for Characterization of the Basal Ganglia and the Midbrain.

Objectives To characterize subcortical nuclei by multi-parametric quantitative magnetic resonance imaging. Materials and Methods: The following quantitative multiparametric MR data of five healthy volunteers were acquired on a 7T MRI system: 3D gradient echo (GRE) data for the calculation of quantitative susceptibility maps (QSM), GRE sequences with and without off-resonant magnetic transfer pulse for magnetization transfer ratio (MTR) calculation, a magnetization-prepared 2 rapid acquisition gradient echo sequence for T1 mapping, and (after a coil change) a density-adapted 3D radial pulse sequence for 23Na imaging. First, all data were co-registered to the GRE data, volumes of interest (VOIs) for 21 subcortical structures were drawn manually for each volunteer, and a combined voxel-wise analysis of the four MR contrasts (QSM, MTR, T1, 23Na) in each structure was conducted to assess the quantitative, MR value-based differentiability of structures. Second, a machine learning algorithm based on random forests was trained to automatically classify the groups of multi-parametric voxel values from each VOI according to their association to one of the 21 subcortical structures. Results The analysis of the integrated multimodal visualization of quantitative MR values in each structure yielded a successful classification among nuclei of the ascending reticular activation system (ARAS), the limbic system and the extrapyramidal system, while classification among (epi-)thalamic nuclei was less successful. The machine learning-based approach facilitated quantitative MR value-based structure classification especially in the group of extrapyramidal nuclei and reached an overall accuracy of 85% regarding all selected nuclei. Conclusion Multimodal quantitative MR enabled excellent differentiation of a wide spectrum of subcortical nuclei with reasonable accuracy and may thus enable sensitive detection of disease and nucleus-specific MR-based contrast alterations in the future.

Susceptibility-Based Characterization of Cerebral Arteriovenous Malformations.

OBJECTIVES: The aim of this study was to explore blood deoxygenation across cerebral arteriovenous malformations (AVMs) for functional characterization of AVM vasculature. MATERIALS AND METHODS: Fifteen patients with cerebral arteriovenous vascular malformation were prospectively studied by digital subtraction angiography and using a 3 T magnetic resonance imaging system, with which three-dimensional (3D) gradient echo data for the calculation of quantitative susceptibility maps, velocity-encoded 3D gradient echo data for 3D flow assessment, and contrast-enhanced 3D time-of-flight data were acquired.The nidus, major supplying artery, and major draining veins were identified on digital subtraction angiography, and volumes of interest of the AVM nidus, AVM-related inflow and outflow vessels, and non-AVM-related normal veins were drawn on coregistered contrast-enhanced 3D time-of-flight data. The resulting volumes of interest were applied to quantitative susceptibility mapping and flow data. RESULTS: All patients showed a significant stepwise increase in susceptibility between feeding artery and nidus as well as between nidus and draining vein (Padjusted = 0.035, Padjusted= 0.007, respectively). Results revealed between 9.3% and 50.9% of the normal transcapillary blood deoxygenation-related susceptibility change between the feeding artery and the draining vein of the AVMs. When normalized by nidal blood flow velocity, this change was correlated with the presence of perinidal blood products. The mean susceptibility change across cerebral AVMs normalized with nidal volume inversely correlated with mean nidal flow velocity. CONCLUSIONS: Susceptibility changes indicating blood deoxygenation across cerebral AVMs were shown for the first time in this study and were associated with the presence of perinidal blood products. Deoxygenation measures may serve as functional characterization of AVM vasculature and may offer the potential for individual treatment assessment and possible risk stratification.

Assessment of Melanin Content and its Influence on Susceptibility Contrast in Melanoma Metastases.

PURPOSE: To quantify the influence of melanin content on magnetic susceptibility of cerebral melanoma metastases. METHODS: Patients with non-hemorrhagic metastases were included based on the absence of susceptibility blooming artifacts. Susceptibility maps were calculated from 3D gradient echo data, using Laplacian-based phase unwrapping, sophisticated harmonic artefact reduction for phase data (V-SHARP) with varying spherical kernel sizes for background field removal and the iLSQR algorithm for the inversion of phase data. Susceptibility maps were referenced to cerebrospinal fluid. Non-hemorrhagic metastases were identified on contrast-enhanced T1-weighted images and susceptibility weighted images. Metastases masks were drawn on T1-weighted post-contrast images and used to compute mean susceptibility values of each metastasis. RESULTS: A total of 33 non-hemorrhagic melanoma brain metastases in 20 patients were quantitatively evaluated. Metastases without and with hyperintense signal on T1-weighted images, which corresponds to the melanin content, showed median susceptibility values of -0.028 ppm and -0.020 ppm, respectively. The susceptibility differences between metastases without and with T1-weighted hyperintense signal was not statistically significant (p ≥ 0.05). CONCLUSION: Non-hemorrhagic cerebral melanoma metastases showed weak diamagnetic susceptibility values and susceptibility did not significantly correlate to T1-weighted signals. Therefore, melanin does not seem to be a major contributor to susceptibility in cerebral melanoma metastases.

Quantitative susceptibility mapping and 23 Na imaging-based in vitro characterization of blood clotting kinetics.

Blood clotting is a fundamental biochemical process in post-hemorrhagic hemostasis. Although the varying appearance of coagulating blood in T1 - and T2 -weighted images is widely used to qualitatively determine bleeding age, the technique permits only a rough discrimination of coagulation stages, and it remains difficult to distinguish acute and chronic hemorrhagic stages because of low T1 - and T2 -weighted signal intensities in both instances. To investigate new biomedical parameters for magnetic resonance imaging-based characterization of blood clotting kinetics, sodium imaging and quantitative susceptibility mapping (QSM) were compared with conventional T1 - and T2 -weighted imaging, as well as with biochemical hemolysis parameters. For this purpose, a blood-filled spherical agar phantom was investigated daily for 14 days, as well as after 24 days at 7 T after initial preparation with fresh blood. T1 - and T2 -weighted sequences, a three-dimensional (3D) gradient echo sequence and a density-adapted 3D radial projection reconstruction pulse sequence for 23 Na imaging were applied. For hemolysis estimations, free hemoglobin and free potassium concentrations were measured photometrically and with the direct ion-selective electrode method, respectively, in separate heparinized whole-blood samples along the same timeline. Initial mean susceptibility was low (0.154 ± 0.020 ppm) and increased steadily during the course of coagulation to reach up to 0.570 ± 0.165 ppm. The highest total sodium (NaT) values (1.02 ± 0.06 arbitrary units) in the clot were observed initially, dropped to 0.69 ± 0.13 arbitrary units after one day and increased again to initial values. Compartmentalized sodium (NaS) showed a similar signal evolution, and the NaS/NaT ratio steadily increased over clot evolution. QSM depicts clot evolution in vitro as a process associated with hemoglobin accumulation and transformation, and enables the differentiation of the acute and chronic coagulation stages. Sodium imaging visualizes clotting independent of susceptibility and seems to correspond to clot integrity. A combination of QSM and sodium imaging may enhance the characterization of hemorrhage.

Spectral Domain-Optical Coherence Tomography As a New Diagnostic Marker for Idiopathic Normal Pressure Hydrocephalus.

PURPOSE: Characterized by a progressive onset of gait disturbances, dementia, and urinary incontinence, idiopathic normal pressure hydrocephalus (iNPH) is considered a rare, but under-diagnosed disease. Non-invasive diagnostic markers are still insufficient to enable the diagnosis of iNPH with certainty and yet early treatment with ventriculoperitoneal (VP) shunting can reverse symptoms and stop disease progression. Vascular circulation abnormalities in iNPH may be reflected by changes in subfoveal and peripapillary choroidal thickness (PPChT). This study uses spectral domain-optical coherence tomography (SD-OCT)-based measures of retinal and choroidal thickness to test this hypothesis and to assess ophthalmological non-invasive markers for iNPH. METHODS: Twelve patients who displayed neurological and neuroradiological characteristics of iNPH were subject to a full ophthalmological examination including enhanced depth imaging (EDI) SD-OCT. Of the 12 included iNPH patients, 6 had undergone VP shunting with beneficial outcome. Parameters studied with EDI SD-OCT were macular retinal thickness (MT), subfoveal choroidal thickness (SFChT), retinal nerve fiber layer thickness (RNFL), and PPChT. Results were compared with 13 healthy, age-matched controls. RESULTS: Macular thickness and RNFL and MT values of iNPH patients did not reflect atrophy. Non-shunted iNPH patients showed significantly lowered median PPChT and SFChT values compared to healthy controls. Shunted iNPH patients displayed a significantly higher median PPChT and SFChT compared to non-shunted iNPH patients. SFChT and PPChT values in shunted patients were not significantly different to values in healthy controls. CONCLUSION: Although limited by small sample size, SD-OCT measures in this study reveal significant changes of choroidal thickness and support the hypothesis of choroidal susceptibility to hemodynamic alterations in iNPH. Non-shunted iNPH patients in this study show choroidal thinning in combination with normal RNFL and MT values. In addition to neurological and neuroradiological exams, this pattern may aid in the challenging diagnosis of iNPH.

Suitable reference tissues for quantitative susceptibility mapping of the brain.

PURPOSE: Since quantitative susceptibility mapping (QSM) quantifies magnetic susceptibility relative to a reference value, a suitable reference tissue has to be available to compare different subjects and stages of disease. METHODS: To find such a suitable reference tissue for QSM of the brain, melanoma patients with and without brain metastases were measured. Twelve reference regions were chosen and assessed for stability of susceptibility values with respect to multiple intra-individual and inter-individual measurements, age, and stage of disease. RESULTS: Cerebrospinal fluid (CSF), the internal capsule and one region in the splenium of the corpus callosum are the regions with the smallest standard deviations of the mean susceptibility value. The mean susceptibility is 0.010 ± 0.014 ppm for CSF in the atrium of the lateral ventricles (csfpost ), -0.060 ± 0.019 ppm for the posterior limb of the internal capsule (ci2), and -0.008 ± 0.019 ppm for the splenium of the corpus callosum. csfpost and ci2 show nearly no dependence on age or stage of disease, whereas some other regions, e.g., the red nucleus, show moderate dependence on age or disease. CONCLUSION: The internal capsule and CSF appear to be the most suitable reference regions for QSM of the brain in the melanoma patients studied. Both showed virtually no dependence on age or disease and small variations among patients. Magn Reson Med 78:204-214, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Susceptibility Sensitive Magnetic Resonance Imaging Displays Pallidofugal and Striatonigral Fiber Tracts.

BACKGROUND: The pallidofugal and striatonigral fiber tracts form a functional part of the basal ganglionic neuronal networks. For deep brain stimulation, a surgical procedure applied in the treatment of Parkinson disease and dystonia, precise localization of pallidofugal pathways may be of particular clinical relevance for correct electrode positioning. OBJECTIVE: To investigate whether the pallidofugal and striatonigral pathways can be visualized with magnetic resonance imaging in vivo by exploiting their intrinsic magnetic susceptibility. METHODS: Three-dimensional gradient-echo imaging of 5 volunteers was performed on a 7 T magnetic resonance imaging system. To demonstrate that the displayed tubular structures in the vicinity of the subthalamic nucleus and substantia nigra truly represent fiber tracts rather than veins, gradient-echo data of a formalin-fixated brain and a volunteer during inhalation of ambient air and carbogen were collected at 3 T. Susceptibility weighted images, quantitative susceptibility maps, and effective transverse relaxation maps were reconstructed and the depiction of fiber tracts was qualitatively assessed. RESULTS: High-resolution susceptibility-based magnetic resonance imaging contrasts enabled visualization of pallidofugal and striatonigral fiber tracts noninvasively at 3 T and 7 T. We verified that the stripe-like pattern observed on susceptibility-sensitive images is not caused by veins crossing the internal capsule but by fiber tracts traversing the internal capsule. CONCLUSION: Pallidofugal and striatonigral fiber tracts have been visualized in vivo for the first time by using susceptibility-sensitive image contrasts. Considering the course of pallidofugal pathways, in particular for deep brain stimulation procedures in the vicinity of the subthalamic nucleus, could provide landmarks for optimal targeting during stereotactic planning.

Deep brain stimulation of the lateral habenular complex in treatment-resistant depression: traps and pitfalls of trajectory choice.

BACKGROUND: Deep brain stimulation (DBS) has recently been discussed as a promising treatment option for severe cases of major depression. Experimental data have suggested that the lateral habenular complex (LHb-c) is a central region of depression-related neuronal circuits. Because of its location close to the midline, stereotactic targeting of the LHb-c presents surgeons with distinct challenges. OBJECTIVE: To define the obstacles of DBS surgery for stimulation of the LHb-c and thus to establish safe trajectories. METHODS: Stereotactic magnetic resonance imaging data sets of 54 hemispheres originating from 27 DBS patients were taken for analysis on a stereotactic planning workstation. After alignment of images according to the anterior commissure--posterior commissure definition, analyses focused on vessels and enlarged ventricles interfering with trajectories. RESULTS: As major trajectory obstacles, enlarged ventricles and an interfering superior thalamic vein were found. A standard frontal trajectory (angle > 40° relative to the anterior commissure--posterior commissure in sagittal images) for bilateral stimulation was safely applicable in 48% of patients, whereas a steeper frontal trajectory (angle <40 relative to the anterior commissure--posterior commissure in sagittal images) for bilateral stimulation was possible in 96%. Taken together, safe bilateral targeting of the LHb-c was possible in 98% of all patients. CONCLUSION: Targeting LHb-c is a feasible and safe technique in the majority of patients undergoing surgery for DBS. However, meticulous individual planning to avoid interference with ventricles and thalamus-related veins is mandatory because an alternative steep frontal entry point has to be considered in about half of the patients.