Fiber tract trajectories in coherently organized brain white matter pathways were computed from in vivo diffusion tensor magnetic resonance imaging (DT-MRI) data. First, a continuous diffusion tensor field is constructed from this discrete, noisy, measured DT-MRI data. Then a Frenet equation, describing the evolution of a fiber tract, was solved. This approach was validated using synthesized, noisy DT-MRI data. Corpus callosum and pyramidal tract trajectories were constructed and found to be consistent with known anatomy. The method's reliability, however, degrades where the distribution of fiber tract directions is nonuniform. Moreover, background noise in diffusion-weighted MRIs can cause a computed trajectory to hop from tract to tract. Still, this method can provide quantitative information with which to visualize and study connectivity and continuity of neural pathways in the central and peripheral nervous systems in vivo, and holds promise for elucidating architectural features in other fibrous tissues and ordered media.

/pdf/in-vivo-fiber-tractography-using-dt-mri-data-2svl53vsnk.pdf

In vivo fiber tractography using DT-MRI data

Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data. Classification of thalamic gray matter based on cortical connectivity patterns revealed distinct subregions whose locations correspond to nuclei described previously in histological studies. The connections that we found between thalamus and cortex were similar to those reported for non-human primates and were reproducible between individuals. Our results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.

Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging

The structural and functional integrity of the brain depends on the delicate balance between substrate delivery through blood flow and energy demands imposed by neural activity. Complex cerebrovascular control mechanisms ensure that active brain regions receive an adequate amount of blood, but the nature of these mechanisms remains elusive. Recent findings implicate perivascular neurons, gliovascular interactions and intramural vascular signalling in the control of the cerebral microcirculation. Neurons, astrocytes and vascular cells seem to constitute a functional unit, the primary purpose of which is to maintain the homeostasis of the brain's microenvironment. Alterations of these vascular regulatory mechanisms lead to brain dysfunction and disease. The emerging view is that cerebrovascular dysregulation is a feature not only of cerebrovascular pathologies, such as stroke, but also of neurodegenerative conditions, such as Alzheimer's disease.

Neurovascular regulation in the normal brain and in Alzheimer's disease.

Various inorganic nanoparticles have been used as magnetic resonance imaging (MRI) contrast agents due to their unique properties, such as large surface area and efficient contrasting effect. Since the first use of superparamagnetic iron oxide (SPIO) as a liver contrast agent, nanoparticulate MRI contrast agents have attracted a lot of attention. Magnetic iron oxide nanoparticles have been extensively used as MRI contrast agents due to their ability to shorten T2* relaxation times in the liver, spleen, and bone marrow. More recently, uniform ferrite nanoparticles with high crystallinity have been successfully employed as new T2 MRI contrast agents with improved relaxation properties. Iron oxide nanoparticles functionalized with targeting agents have been used for targeted imaging via the site-specific accumulation of nanoparticles at the targets of interest. Recently, extensive research has been conducted to develop nanoparticle-based T1 contrast agents to overcome the drawbacks of iron oxide nanoparticle-based negative T2 contrast agents. In this report, we summarize the recent progress in inorganic nanoparticle-based MRI contrast agents.

http://nanomag.ucsd.edu/wp-content/uploads/2011/12/MRI-contrast-particles.pdf

Inorganic Nanoparticles for MRI Contrast Agents

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade-offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo-continuous labeling, background suppression, a segmented three-dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model.

/pdf/recommended-implementation-of-arterial-spin-labeled-ytbu2toil8.pdf

Recommended Implementation of Arterial Spin Labeled Perfusion MRI for Clinical Applications: A consensus of the ISMRM Perfusion Study Group and the European Consortium for ASL in Dementia

Manganese-enhanced MRI (MEMRI) is being increasingly used for MRI in animals due to the unique T1 contrast that is sensitive to a number of biological processes. Three specific uses of MEMRI have been demonstrated: to visualize activity in the brain and the heart; to trace neuronal specific connections in the brain; and to enhance the brain cytoarchitecture after a systemic dose. Based on an ever-growing number of applications, MEMRI is proving useful as a new molecular imaging method to visualize functional neural circuits and anatomy as well as function in the brain in vivo. Paramount to the successful application of MEMRI is the ability to deliver Mn2+ to the site of interest at an appropriate dose and in a time-efficient manner. A major drawback to the use of Mn2+ as a contrast agent is its cellular toxicity. Therefore, it is critical to use as low a dose as possible. In the present work the different approaches to MEMRI are reviewed from a practical standpoint. Emphasis is given to the experimental methodology of how to achieve significant, yet safe, amounts of Mn2+ to the target areas of interest.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/nbm.945

Manganese-enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations.

Development of efficient imaging techniques to trace neuro nal connections would be very useful Manganese ion (Mn2+) is an excellent T1 contrast agent for magnetic resonance imaging (MRI) Four reports utilizing radioactive Mn2+ in fish and rat brain indicate that Mn2+ may be useful for tracing neuronal connections Therefore, the purpose of this work was to determine if Mn2+ can be used as an in vivo MRI neuronal tract tracer The results indicate that topical admin istration of MnCI2 solution to the naris of mice as well as to the retinal ganglion cells via intravitreal injection leads to en hancement of contrast along the respective pathways There fore, application of Mn2+ to neurons allows the use of MRI to visualize neuronal connections

In vivo neuronal tract tracing using manganese-enhanced magnetic resonance imaging.

In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has opened new doors to study structure–function relationships in the human brain. Initially developed to map the trajectory of major white matter tracts, dMRI is used increasingly to infer long-range anatomical connections of the cortex. Because axonal projections originate and terminate in the gray matter but travel mainly through the deep white matter, the success of tractography hinges on the capacity to follow fibers across this transition. Here we demonstrate that the complex arrangement of white matter fibers residing just under the cortical sheet poses severe challenges for long-range tractography over roughly half of the brain. We investigate this issue by comparing dMRI from very-high-resolution ex vivo macaque brain specimens with histological analysis of the same tissue. Using probabilistic tracking from pure gray and white matter seeds, we found that ∼50% of the cortical surface was effectively inaccessible for long-range diffusion tracking because of dense white matter zones just beneath the infragranular layers of the cortex. Analysis of the corresponding myelin-stained sections revealed that these zones colocalized with dense and uniform sheets of axons running mostly parallel to the cortical surface, most often in sulcal regions but also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated that at least some axonal fibers pass directly through these fiber systems. Current and future high-resolution dMRI studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately.

https://www.pnas.org/content/pnas/112/21/E2820.full.pdf

Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography

Quantitative magnetic resonance measurements of regional tissue perfusion can be obtained using magnetically labeled arterial water as a diffusable tracer. Continuous labeling is achieved in flowing spins using adiabatic inversion. The effects of continuous labeling of proximal arterial spins and T1 relaxation in distal tissue magnetization result in a steady-state change in tissue magnetization which is tissue specific, i.e., it can be quantified in units of blood flow per gram of tissue per unit time. This magnetization is sampled using standard imaging sequences. The theoretical basis for this method, including the effects of macromolecular spin saturation, is reviewed. Recent results demonstrating the successful implementation of this technique in vitro and in vivo in rat brain, heart, and kidney, and in human brain and kidney are presented, as well as the use of a separate RF coil for arterial labeling to produce selective perfusion images in rat brain. This approach allows quantitative perfusion images to be obtained completely non-invasively at the resolution of 1H MRI, and is useful in the clinical and investigational evaluation of organ physiology.

Tissue specific perfusion imaging using arterial spin labeling.

Manganese ion (Mn 2þ ) is an essential metal that participates as a cofactor in a number of critical biological functions, such as electron transport, detoxification of free radicals and synthesis of neurotransmitters. Mn 2þ can enter excitable cells using some of the same transport systems as Ca 2þ and it can bind to a number of intracellular sites because it has high affinity for Ca 2þ and Mg 2þ binding sites on proteins and nucleic acids. Paramagnetic forms of manganese ions are potent MRI relaxation agents. Indeed, Mn 2þ was the first contrast agent proposed for use in MRI. Recently, there has been renewed interest in combining the strong MRI relaxation effects of Mn 2þ with its unique biology, in order to further expand the already broad assortment of useful information that can be measured by MRI. Such an approach has been continuously developed in the past several years to provide unique tissue contrast, to assess tissue viability, to act as a surrogate marker of calcium influx into cells and to trace neuronal connections. This special issue of NMR in Biomedicine on manganese- enhanced MRI (MEMRI) is aimed at providing the readers of this journal with an extensive review of some of the most prominent applications of MEMRI in biological systems. Written by several of the leaders in the field, the reviews and original research articles featured in this special issue are likely to offer an exciting and inspiring view of the broad range of applications of MEMRI. Copyright # 2004 John Wiley & Sons, Ltd.

/pdf/manganese-enhanced-magnetic-resonance-imaging-memri-4pubuzdiht.pdf

Afonso C. Silva

Papers

Manganese-enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations.

In vivo neuronal tract tracing using manganese-enhanced magnetic resonance imaging.

Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography

Tissue specific perfusion imaging using arterial spin labeling.

Manganese-enhanced magnetic resonance imaging (MEMRI)