Since its development about 15 years ago, functional magnetic resonance imaging (fMRI) has become the leading research tool for mapping brain activity. The technique works by detecting the levels of oxygen in the blood, point by point, throughout the brain. In other words, it relies on a surrogate signal, resulting from changes in oxygenation, blood volume and flow, and does not directly measure neural activity. Although a relationship between changes in brain activity and blood flow has long been speculated, indirectly (...) examined and suggested and surely anticipated and expected, the neural basis of the fMRI signal was only recently demonstrated directly in experiments using combined imaging and intracortical recordings. In the present paper, we discuss the results obtained from such combined experiments. We also discuss our current knowledge of the extracellularly measured signals of the neural processes that they represent and of the structural and functional neurovascular coupling, which links such processes with the hemodynamic changes that offer the surrogate signal that we use to map brain activity. We conclude by considering applications of invasive MRI, including injections of paramagnetic tracers for the study of connectivity in the living animal and simultaneous imaging and electrical microstimulation. D 2004 Elsevier Inc. All rights reserved. (shrink)

In this project, a spiral fast imaging sequence was implemented on a Bruker Avance MR system. Acquisition and processing schemes were developed to measure the experimental k-space trajectories. Since errors in k-space are reflected as errors in the corresponding image, we used different strategies to measure and calculate corrections for deviation of the experimental k-space trajectory from the theoretical one. Even if the k-space trajectories deviate from the theoretical ones, an experimentally measured trajectory can be incorporated in the spiral reconstruction (...) and a reduction of image artifacts can be obtained. (shrink)

‘Smart’ contrast agents (CA) exhibit dynamic and reversible modulation of their relaxivity by specific physiological or biochemical triggers such as changes in pH, Ca2+ concentration or enzymatic activity (1-3). The extracellular concentration of Ca2+ plays important role in physiological and pathological processes in the nervous system. This led to the designing of a chelating system in which relaxivity is influenced as a function of Ca2+ concentration by changing coordination number around the paramagnetic metal ion. We synthesized a novel bifunctional bismacrocycle (...) [Gd-(DO3A-DTPA- DO3A); Fig.] based on DO3A-EA [{4,7-Bis-carboxymethyl-10-(2-aminoethyl)-1,4,7,10-tetraazacyclododec-1-yl}-acetic acid] coupled to DTPA-bis-anhydride via a flexible alkyl spacer to form the.. (shrink)

Smart MR contrast agents exhibit modulation of their relaxivity by specific physiological or biochemical trigger-events, while targeted MR contrast agents are envisioned to deliver the large gadolinium chelates into the target tissue. In an effort to develop novel smart and targeted MR contrast agents, the series of the DO3A based multifunctional chelating agents with the variable length of the side chain has been synthesized. They serve as valuable multipurpose precursors for contrast agents based on gadolinium chelates in the design of (...) relaxometric MR probes. The presence of the amino group in the side chain of the macrocycle allows for conversion into various functional groups (aminophosponates, aminocarboxylates, etc.) or for conjugation with different biomolecules, dyes, and polymers. Choice of the functional groups depends on the.. (shrink)

Calcium plays an important role in regulating a great variety of neuronal processes, and many efforts are made to generate gadolinium complexes that can act as calcium-dependent MRI contrast agents. A series of gadolinium chelate complexes based on DO3A were developed, bearing phosphonate groups as an additional coordination sites, which is hypothesized to change relaxivity in magnetic resonance experiments dynamically with Ca2+ concentration. Different lengths of the phosphonate side chains are expected to lead to different binding constants of the phosphonate (...) - gadolinium bonds. The latter property can be exploited for fine-tuning the sensitivity of the agent to calcium ion concentration. (shrink)

The ability of non-invasively observing changes in the Ca2+ concentrations is important in the understanding of a great variety of neuronal processes. Several compounds were designed (Fig.1) to take advantage of the different binding abilities of carboxylates and phosphonates to gadolinium. Furthermore the different affinities of the two functional groups to Ca2+ permit to obtain free coordination sites at gadolinium. The generation of these coordination sites, which are mandatory for water relaxivity, depends on the structure of the complexes and the (...) Ca2+ concentration. Gadolinium complexes 1 and 2 were synthesized and relaxivity studies were performed. (shrink)

Functionally distinct anatomic subdivisions of the brain can often be only a few millimeters in one or more dimensions. The study of metabolic differences in such structures by means of localized in vivo MR spectroscopy is therefore challenging, if not impossible. In fact, the spatial resolution of chemical shift imaging (CSI) in humans is typically in the range of centimeters. The aim of the present study was to optimize 1H CSI in monkeys and demonstrate the feasibility of high spatial resolutions (...) up to 1.4 ؋ 2 ؋ 1.4 mm3. The obtained spatial resolution permitted the segregation of gray and white matter in the visual cortex based on the concentration of different metabolites and neurotrans- mitters like N-acetylaspartate, glutamate, and creatine. Con- centration ratios of white matter versus gray matter tissue as well as between metabolites matched those reported in the literature from healthy human brain, demonstrating the consis- tency and reliability of the procedure. Magn Reson Med 54: 1541–1546, 2005. © 2005 Wiley-Liss, Inc. Key words: in vivo 1H NMR spectroscopy; spectroscopic imag- ing; chemical shift imaging; spatial resolution; monkey visual cortex.. (shrink)