Generalized magnetostatic target field method for shielded magnetic field coils in a separable coordinate system.

A theoretical method is described to analytically calculate a pair of surface current densities, which produce a desired static magnetic field in one region of the space and zero magnetic field in another. The analysis is based on the known relationship between a surface current density and a stream function, the equivalence of stream functions and surface magnetic dipole density, and the scalar potential representation of the associated magnetic field in free space. From these relations, we formulate the magnetostatic problem, which is often treated as a vector field problem, as a scalar field problem in which a two-dimensional scalar field (stream function) is related to a three-dimensional one (magnetic scalar potential) via the differentiation of the electrostatic Green's function 1/|r-rs|. It is shown that, in a coordinate system in which a separated form of the Green's function exists (separable coordinate system), there exists a simple relationship between a harmonic component of a stream function and a harmonic component of the magnetic scalar potential. The method is applied to calculate idealized surface current patterns for actively shielded, linear gradient field coils in the Cartesian, cylindrical, and spherical coordinates.

Magnetic susceptibility imaging of human habenula at 3 T.

The habenula plays an important role in brain reward circuitry and psychiatric conditions. While much work has been done on the function and structure of the habenula in animal models, in vivo imaging studies of the human habenula have been relatively scarce due to its small size, deep brain location, and lack of clear biomarkers for its heterogeneous substructure. In this paper, we report high-resolution (0.5 × 0.5 × 0.8 mm3) MRI of the human habenula with quantitative susceptibility mapping (QSM) at 3 T. By analyzing 48 scan datasets collected from 21 healthy subjects, we found that magnetic susceptibility contrast is highly non-uniform within the habenula and across the subjects. In particular, we observed high prevalence of elevated susceptibility in the posterior subregion of the habenula. Correlation analysis between the susceptibility and the effective transverse relaxation rate (R2*) indicated that localized susceptibility enhancement in the habenula is more associated with increased paramagnetic (such as iron) rather than decreased diamagnetic (such as myelin) sources. Our results suggest that high-resolution QSM could make a potentially useful tool for substructure-resolved in vivo habenula imaging, and provide a groundwork for the future development of magnetic susceptibility as a quantitative biomarker for human habenula studies.

Lightweight, compact, and high-performance 3T MR system for imaging the brain and extremities.

PURPOSE: To build and evaluate a small-footprint, lightweight, high-performance 3T MRI scanner for advanced brain imaging with image quality that is equal to or better than conventional whole-body clinical 3T MRI scanners, while achieving substantial reductions in installation costs. METHODS: A conduction-cooled magnet was developed that uses less than 12 liters of liquid helium in a gas-charged sealed system, and standard NbTi wire, and weighs approximately 2000 kg. A 42-cm inner-diameter gradient coil with asymmetric transverse axes was developed to provide patient access for head and extremity exams, while minimizing magnet-gradient interactions that adversely affect image quality. The gradient coil was designed to achieve simultaneous operation of 80-mT/m peak gradient amplitude at a slew rate of 700 T/m/s on each gradient axis using readily available 1-MVA gradient drivers. RESULTS: In a comparison of anatomical imaging in 16 patients using T2 -weighted 3D fluid-attenuated inversion recovery (FLAIR) between the compact 3T and whole-body 3T, image quality was assessed as equivalent to or better across several metrics. The ability to fully use a high slew rate of 700 T/m/s simultaneously with 80-mT/m maximum gradient amplitude resulted in improvements in image quality across EPI, DWI, and anatomical imaging of the brain. CONCLUSIONS: The compact 3T MRI system has been in continuous operation at the Mayo Clinic since March 2016. To date, over 200 patient studies have been completed, including 96 comparison studies with a clinical 3T whole-body MRI. The increased gradient performance has reliably resulted in consistently improved image quality.

Contributions to magnetic susceptibility of brain tissue.

This review discusses the major contributors to the subtle magnetic properties of brain tissue and how they affect MRI contrast. With the increased availability of high-field scanners, the use of magnetic susceptibility contrast for the study of human brain anatomy and function has increased dramatically. This has not only led to novel applications, but has also improved our understanding of the complex relationship between MRI contrast and magnetic susceptibility. Chief contributors to the magnetic susceptibility of brain tissue have been found to include myelin as well as iron. In the brain, iron exists in various forms with diverse biological roles, many of which are now only starting to be uncovered. An interesting aspect of magnetic susceptibility contrast is its sensitivity to the microscopic distribution of iron and myelin, which provides opportunities to extract information at spatial scales well below MRI resolution. For example, in white matter, the myelin sheath that surrounds the axons can provide tissue contrast that is dependent on the axonal orientation and reflects the relative size of intra- and extra-axonal water compartments. The extraction of such ultrastructural information, together with quantitative information about iron and myelin concentrations, is an active area of research geared towards the characterization of brain structure and function, and their alteration in disease. Copyright © 2016 John Wiley & Sons, Ltd.

Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale.

An initiative to design and build magnetic resonance imaging (MRI) and spectroscopy (MRS) instruments at 14 T and beyond to 20 T has been underway since 2012. This initiative has been supported by 22 interested participants from the USA and Europe, of which 15 are authors of this review. Advances in high temperature superconductor materials, advances in cryocooling engineering, prospects for non-persistent mode stable magnets, and experiences gained from large-bore, high-field magnet engineering for the nuclear fusion endeavors support the feasibility of a human brain MRI and MRS system with 1 ppm homogeneity over at least a 16-cm diameter volume and a bore size of 68 cm. Twelve neuroscience opportunities are presented as well as an analysis of the biophysical and physiological effects to be investigated before exposing human subjects to the high fields of 14 T and beyond.

Peripheral nerve stimulation characteristics of an asymmetric head-only gradient coil compatible with a high-channel-count receiver array.

PURPOSE: To characterize peripheral nerve stimulation (PNS) of an asymmetric head-only gradient coil that is compatible with a commercial high-channel-count receive-only array. METHODS: Two prototypes of an asymmetric head-only gradient coil set with a 42-cm inner diameter were constructed for brain imaging at 3T with maximum performance specifications of up to 85 mT/m and 708 T/m/s. Tests were performed in 24 volunteers to measure PNS thresholds with the transverse (x = left-right; y = anterior-posterior [A/P]) gradient coils of both prototypes. Fourteen of these 24 volunteers were also tested for the z-gradient PNS in the second prototype and were scanned with high-slew-rate echo planar imaging (EPI) immediately after the PNS tests. RESULTS: For both prototypes, the y-gradient PNS threshold was markedly higher than the x-gradient threshold. The z-gradient threshold was intermediate between those for the x- and y-coils. Of the 24 volunteers, only two experienced y-gradient PNS at 80 mT/m and 500 T/m/s. All volunteers underwent the EPI scan without PNS when the readout direction was set to A/P. CONCLUSION: Measured PNS characteristics of asymmetric head-only gradient coil prototypes indicate that such coils, especially in the A/P direction, can be used for fast EPI readout in high-performance neuroimaging scans with substantially reduced PNS concerns compared with conventional whole body gradient coils. Magn Reson Med 76:1939-1950, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

iSTAPLE: Improved Label Fusion for Segmentation by Combining STAPLE with Image Intensity.

Multi-atlas based methods have been a trend for robust and automated image segmentation. In general these methods first transfer prior manual segmentations, i.e., label maps, on a set of atlases to a given target image through image registration. These multiple label maps are then fused together to produce segmentations of the target image through voting strategy or statistical fusing, e.g., STAPLE. STAPLE simultaneously estimates the true segmentation and the label map performance level, but has been shown inaccurate for multi-atlas segmentation because it is determined completely on the propagated label maps without considering the target image intensity. We develop a new method, called iSTAPLE, that combines target image intensity into a similar maximum likelihood estimate (MLE) framework as in STAPLE to take advantage of both intensity-based segmentation and statistical label fusion based on atlas consensus and performance level. The MLE framework is then solved using a modified EM algorithm to simultaneously estimate the intensity profiles of structures of interest as well as the true segmentation and atlas performance level. Unlike other methods, iSTAPLE does not require the target image to have same image contrast and intensity range as the atlas images, which greatly extends the use of atlases. Experiments on whole brain segmentation showed that iSTAPLE performed consistently better than STAPLE.

Deformable atlas for multi-structure segmentation.

We develop a novel deformable atlas method for multistructure segmentation that seamlessly combines the advantages of image-based and atlas-based methods. The method formulates a probabilistic framework that combines prior anatomical knowledge with image-based cues that are specific to the subject's anatomy, and solves it using expectation-maximization method. It improves the segmentation over conventional label fusion methods especially around the structure boundaries, and is robust to large anatomical variation. The proposed method was applied to segment multiple structures in both normal and diseased brains and was shown to significantly improve results especially in diseased brains.

Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast.

Recent advances in high-field MRI have dramatically improved the visualization of human brain anatomy in vivo. Most notably, in cortical gray matter, strong contrast variations have been observed that appear to reflect the local laminar architecture. This contrast has been attributed to subtle variations in the magnetic properties of brain tissue, possibly reflecting varying iron and myelin content. To establish the origin of this contrast, MRI data from postmortem brain samples were compared with electron microscopy and histological staining for iron and myelin. The results show that iron is distributed over laminae in a pattern that is suggestive of each region's myeloarchitecture and forms the dominant source of the observed MRI contrast.

Experimental determination of human peripheral nerve stimulation thresholds in a 3-axis planar gradient system.

In MRI, strong, rapidly switched gradient fields are desirable because they can be used to reduce imaging time, obtain images with better resolution, or improve image signal-to-noise ratios. Improvements in gradient strength can be made by either increasing the gradient amplifier strength or by enhancing gradient efficiency. Unfortunately, many MRI pulse sequences, in combination with high-performance amplifiers and existing gradient hardware, can cause peripheral nerve stimulation (PNS). This makes improvements in gradient amplifiers ineffective at increasing safely usable gradient strength. Customized gradient coils are one way to achieve significant improvements in gradient performance. One specific gradient configuration, a planar gradient system, promises improved gradient strength and switching time for cardiac imaging. The PNS thresholds for planar gradients were characterized through human stimulation experiments on all three gradient axes. The specialized gradient was shown to have significantly higher stimulation thresholds than traditional cylindrical designs (y-axis SR(min) = 210 +/- 18 mT/m/ms and DeltaG(min) = 133 +/- 13 mT/m; x-axis SR(min) = 222 +/- 24 mT/m/ms and DeltaG(min) = 147 +/- 17 mT/m; z-axis SR(min) = 252 +/- 26 mT/m/ms and DeltaG(min) = 218 +/- 26 mT/m). This system could be operated at gradient strengths 2 to 3 times higher than cylindrical configurations without causing stimulation.

Iron accumulation in the substantia nigra of patients with Alzheimer disease and parkinsonism.

BACKGROUND: Preliminary studies have shown an increase in iron accumulation in the substantia nigra but not in the hippocampus in patients with Parkinson disease without dementia and the reverse in patients with Alzheimer disease (AD) and no parkinsonism. OBJECTIVE: To determine whether iron levels (measured as T2 shortening on magnetic resonance images) are greater in the substantia nigra of patients with AD who have parkinsonism than in those with AD alone. DESIGN: Case-control study. SETTING: Albany Medical College, Albany, New York. PARTICIPANTS: Fifteen patients with only AD (controls) and 18 with AD as well as parkinsonism, aged 56 to 89 years, and with a total Clinical Dementia Rating of 5.0 to 11.5. Patients were selected according to the purity of their disease; patients with a Unified Parkinson's Disease Rating Scale motor score of 15 or greater were considered to have parkinsonism. Main Outcome Measure Area under the curve for short T2 (30 milliseconds) in patients with only AD vs patients with AD who developed parkinsonism. RESULTS: Patients who developed parkinsonism along with their existing dementia had significantly more iron in their substantia nigra than did patients with AD alone (P = .03, 2-sample t test). CONCLUSIONS: Iron accumulation may be a predictor of parkinsonism. The development of parkinsonism during the course of AD appears to be associated with the accumulation of iron, which in turn may contribute to the pathogenesis of neurologic decline.

Magnetic field correlation as a measure of iron-generated magnetic field inhomogeneities in the brain.

The magnetic field correlation (MFC) at an applied field level of 3 Tesla was estimated by means of MRI in several brain regions for 21 healthy human adults and 1 subject with aceruloplasminemia. For healthy subjects, highly elevated MFC values compared with surrounding tissues were found within the basal ganglia. These are argued as being primarily the result of microscopic magnetic field inhomogeneities generated by nonheme brain iron. The MFC in the aceruloplasminemia subject was significantly higher than for healthy adults in the globus pallidus, thalamus and frontal white matter, consistent with the known increased brain iron concentration associated with this disease.

High-field magnetic resonance imaging of brain iron in Alzheimer disease.

OBJECTIVES: Increased iron deposition in the brain may occur in several neurodegenerative diseases, including Alzheimer disease (AD). Iron deposits shorten T2 relaxation times on T2-weighted magnetic resonance (MR) images. Iron-dependent contrast increases with magnetic field strength. We hypothesized that T2 mapping using 3 T MR imaging (MRI) can disclose differences between normal controls and AD subjects. METHODS: High-resolution brain imaging protocols were developed and applied to 24 AD patients and 20 age-matched controls using 3 T MRI. Eight anatomical regions of interest were manually segmented, and T2 histograms were computed. A visual analysis technique, the heat map, was modified and applied to the large image data sets generated by these protocols. RESULTS: A large number (163) of features from these histograms were examined, and 38 of these were significantly different (P < 0.05) between the groups. In the hippocampus, evidence was found for AD-related increases in iron deposition (shortened T2) and in the concentration of free tissue water (lengthened T2). Imaging of a section of postmortem brain before and after chemically extracting the iron established the presence of MRI-detectable iron in the hippocampus, cortex, and white matter in addition to brain regions traditionally viewed as containing high iron concentrations.

Severe primary hypothyroidism manifesting with torsades de pointes.

Hypothyroidism can manifest with myriad cardiac abnormalities, often consisting of a combination of morphologic and functional changes. Low voltage, sinus bradycardia, and slowed conduction are usually found on electrocardiography. We describe a patient with severe hypothyroidism who presented with presyncope, prolongation of the QT interval, and polymorphic ventricular tachycardia (torsades de pointes). No other cause for the malignant ventricular ectopy was evident. With levothyroxine therapy, the QT interval normalized and the ventricular tachycardia was abolished. In addition to its commonly known cardiac effects, myxedema can predispose to the potentially life-threatening arrhythmia of torsades de pointes. Conversely, in patients presenting with QT interval prolongation and polymorphic ventricular tachycardia, hypothyroidism should be considered in the differential diagnosis.

Macular degeneration in a patient with aceruloplasminemia, a disease associated with retinal iron overload.

PURPOSE: To provide the first ophthalmic case report of a Caucasian patient with the rare autosomal recessive disease aceruloplasminemia, which results in iron overload in the retina, brain, and pancreas. DESIGN: Single observational case report. METHODS: Perls' staining of a conjunctival biopsy was used to detect elevated iron levels in the conjunctival epithelium. Fundus photography, fluorescein angiography, and electroretinography were used to document retinal appearance and function. RESULTS: Unlike a report of a Japanese patient with aceruloplasminemia, who had midperipheral retinal pigment epithelium (RPE) cell atrophy and yellowish discoloration of the fundus, our Caucasian patient had a maculopathy. Beginning at age 47, he had development and progression of multiple subretinal yellowish-white lesions and RPE cell atrophy. To confirm tissue iron overload in our patient, we took the novel approach of a conjunctival biopsy, which showed Perls' Prussian blue-positive epithelial cells. CONCLUSIONS: Given our recent finding of elevated iron levels in the RPE of patients with age-related macular degeneration (AMD), it is interesting that retinal iron overload in aceruloplasminemia is associated with a maculopathy that clinically resembles AMD. This finding supports the hypothesis that retinal iron homeostasis is essential for normal retinal function. Disruption of iron homeostasis could contribute to the pathogenesis of AMD.

Physical interactions of static magnetic fields with living tissues.

Clinical magnetic resonance imaging (MRI) was introduced in the early 1980s and has become a widely accepted and heavily utilized medical technology. This technique requires that the patients being studied be exposed to an intense magnetic field of a strength not previously encountered on a wide scale by humans. Nonetheless, the technique has proved to be very safe and the vast majority of the scans have been performed without any evidence of injury to the patient. In this article the history of proposed interactions of magnetic fields with human tissues is briefly reviewed and the predictions of electromagnetic theory on the nature and strength of these interactions are described. The physical basis of the relative weakness of these interactions is attributed to the very low magnetic susceptibility of human tissues and the lack of any substantial amount of ferromagnetic material normally occurring in these tissues. The presence of ferromagnetic foreign bodies within patients, or in the vicinity of the scanner, represents a very great hazard that must be scrupulously avoided. As technology and experience advance, ever stronger magnetic field strengths are being brought into service to improve the capabilities of this imaging technology and the benefits to patients. It is imperative that vigilance be maintained as these higher field strengths are introduced into clinical practice to assure that the high degree of patient safety that has been associated with MRI is maintained.

High-field magnetic resonance imaging of brain iron: birth of a biomarker?

The brain has an unusually high concentration of iron, which is distributed in an unusual pattern unlike that in any other organ. The physiological role of this iron and the reasons for this pattern of distribution are not yet understood. There is increasing evidence that several neurodegenerative diseases are associated with altered brain iron metabolism. Understanding these dysmetabolic conditions may provide important information for their diagnosis and treatment. For many years the iron distribution in the human brain could be studied effectively only under postmortem conditions. This situation was changed dramatically by the finding that T2-weighted MR imaging at high field strength (initially 1.5 T) appears to demonstrate the pattern of iron distribution in normal brains and that this imaging technique can detect changes in brain iron concentrations associated with disease states. Up to the present time this imaging capability has been utilized in many research applications but it has not yet been widely applied in the routine diagnosis and management of neurodegenerative disorders. However, recent advances in the basic science of brain iron metabolism, the clinical understanding of neurodegenerative diseases and in MRI technology, particularly in the availability of clinical scanners operating at the higher field strength of 3 T, suggest that iron-dependent MR imaging may soon provide biomarkers capable of characterizing the presence and progression of important neurological disorders. Such biomarkers may be of crucial assistance in the development and utilization of effective new therapies for Alzheimer's and Parkinson's diseases, multiple sclerosis and other iron-related CNS disorders which are difficult to diagnose and treat.