Search

The human lung and its functions are extremely sensitive to gravity; however, the conventional high-field magnets used for most laser-polarized 3He MRI of the human lung restrict subjects to lying horizontally. Imaging of human lungs using inhaled laser-polarized 3He gas is demonstrated in an open-access very-low-magnetic-field (<5 mT) MRI instrument. This prototype device employs a simple, low-cost electromagnet, with an open geometry that allows variation of the orientation of the imaging subject in a two-dimensional plane. As a demonstration, two-dimensional lung images were acquired with 4-mm in-plane resolution from a subject in two orientations: lying supine and sitting in a vertical position with one arm raised. Experience with this prototype device will guide optimization of a second-generation very-low-field imager to enable studies of human pulmonary physiology as a function of subject orientation. Magn Reson Med 53:745-749, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We introduce a new magnetic field geometry, Bx(x, y) = gyy cos(qxx), to spatially encode magnetic resonance imaging (MRI). The field is called the PERL field since it is PERiodic in x and Linear in y. A technique is proposed to acquire two-dimensional (2D) data without switching the encoding fields. The time-domain PERL signal and image are not related by a two-dimensional Fourier transform (2DFT). They are related by a 1DFT in the x-dimension and a new Bessel function integral transform, called the PERL transform, in the y-dimension. We numerically solve this equation and develop a reconstruction algorithm. The algorithm is evaluated by assuming a known spin density which is then used to calculate the PERL signal. This signal is the input for the algorithm. We show the reconstructed image matches the convolution of the initial assumed spin density and a point spread function (PSF). We identify the PSF and describe the conditions under which it approaches δ. © 1999 John Wiley & Sons, Inc. Int J Imaging Syst Technol 10, 209–215, 1999 [ABSTRACT FROM AUTHOR]

A new magnetic field geometry for spatial encoding of magnetic resonance imaging (MRI) is presented. The field is given by: Bz(x, y) = gyy cos(qxx), and is called a PERL field because it is PERiodic in x and Linear in y. Both imaging pulse sequences and encoding field design are analyzed theoretically. A two-dimensional (2D) imaging sequence is shown to require a Fourier transform to resolve the x dimension and the solution of a Bessel function integral transform equation to resolve the y dimension. By examining solutions to Laplace's equation that approximate the PERL field, it is shown that the PERL field can only be produced in a limited spatial region. An unusual feature is that the number of gradient switches needed during a 2D data acquisition depends on the field of view and is fundamentally determined by the finite penetration depth δ of the PERL field into the sample. For very thin sections near the PERL coil, no gradient switching is required. To increase δ, qx is decreased. To keep the spatial resolution in y constant however, a phase θ is added: Bz(x, y) = gyy cos(qxx + θ), together with additional data acquisitions (and additional gradient switches) for different values of θ. In addition, an explicit example of a PERL coil with rectangular geometry is presented and its field plotted. © 1999 John Wiley & Sons, Inc. Int J Imaging Syst Technol 10, 216–224, 1999 [ABSTRACT FROM AUTHOR]

Neurotrophins are essential factors for the structural, neurochemical and functional maturation of the brain including developmental and adult plasticity. Northern blots and polymerase chain reaction revealed the expression of neurotrophin 4 (NT4), neurotrophin 3 (NT3), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the cortex. The cellular producers of NT3 and BDNF have been characterized by anatomical methods as being mostly pyramidal, and the tyrosine kinase B (TrkB) receptor is expressed by many cortical neurons. However, these methods have so far failed to identify the cells producing NT4 and NGF mRNA. These factors are much lower in expression than, e.g. BDNF, and apparently remain below detection levels of in situ hybridization. Given their specific actions on cell types and afferent systems, knowledge about the producing cell types is highly desirable. To narrow down on the producing cell types, we quantified by reverse transcriptase-polymerase chain reaction (RT-PCR) the developmental changes of BDNF, NT3, NT4, NGF and TrkB mRNA expression in total visual cortex lysates, and in the cortical layers dissected by tangential cryostat sectioning. We found dramatic changes in laminar expression of NT3 and NGF, mild changes of NT4, and no changes of BDNF and TrkB mRNA. For instance, NT3 is important early on for thalamocortical axons, and we found transient peaks of NT3 mRNA expression first in layer VI, then in layer IV. NT4 mRNA was in layers IV and VI, suggesting NT4 protein production in thalamorecipient layers, but peak expression gradually shifted to upper layers as did NGF expression. The layer-specific developmental expression shifts of neurotrophin mRNAs correlate with morphogenetic processes.

Neuronal activity, hormones, transmitters, physical exercise and enrichment influence cortical neurotrophin expression. Neurotrophins then elicit structural and physiological changes, and regulate gene expression. This prompted the hypothesis that neurotrophins themselves are involved in regulating neurotrophin expression. Here we investigated the mRNA expression level of brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), NT-3 and nerve growth factor (NGF) as well as the tyrosine receptor kinases TrkB and TrkC receptor in response to BDNF, NT-4, NT-3 and NGF pulses in organotypic cortex cultures. Single neurotrophin pulses evoked a dramatic up- or down-regulation of some, but not all four, neurotrophin mRNAs, even within 3-24 h, indicating an immediate impact on neurotrophin transcription. Most strikingly, neurotrophin pulses during the first 10 days in vitro (DIV) potentiated the expression of some neurotrophin mRNAs at 20 DIV, suggesting that early trophic factor experience influences the expression levels seen later in development. The NT-3 mRNA expression, for example, was consistently promoted by NGF and BDNF, suggesting that these two factors help to maintain the low level of NT-3 found in adult cortex. Rapid bidirectional changes characterized the NT-4 mRNA expression. A single pulse of NT-4 transiently increased NT-4 mRNA, whereas a BDNF pulse transiently reduced NT-4 mRNA. Surprisingly, NGF strongly potentiated BDNF mRNA and in particular NT-4 mRNA. By contrast, TrkB mRNA remained constant at ages or time points at which other mRNAs amplified from the very same cDNA libraries revealed dramatic increases or decreases. Our study suggests the existence of a complex regulatory neurotrophin network controlling the expression of other neurotrophins.

Environmental factors are known to regulate the molecular differentiation of neocortical interneurons. Their class-defining transmitter synthetic enzymes are the glutamic acid decarboxylases (GAD); yet, fairly little is known about the developmental regulation of transcription and translation of the GAD-65/67 isoforms. We have characterized the role of neuronal activity, neurotrophins and afferent systems for GAD-65/67 expression in visual cortex in organotypic cultures (OTC) compared with in vivo in order to identify cortex-intrinsic regulatory mechanisms. Spontaneously active OTC prepared at postnatal day 0 displayed from 10 days in vitro (DIV) onwards 12-14% GAD-65/GAD-67 neurons similar to in vivo. However, GAD-65 mRNA was higher, whereas GAD-67 protein was lower, than in vivo. During the first week neurotrophins increased whereas the Trk receptor inhibitor K252a and MEK inhibitors decreased both GAD mRNAs and proteins. After 10 DIV GAD expression no longer depended on neurotrophin signalling. Activity-deprived OTC revealed only 6% GAD-67 neurons and mRNA and protein were reduced by 50%. GAD-65 mRNA was less reduced, but protein was reduced by half, suggesting translational regulation. Upon recovery of activity GAD mRNAs, cell numbers, and both proteins quickly returned to normal and these 'adult' levels were resistant to late-onset deprivation. In 20 DIV activity-deprived OTC, only neurotrophin 4 increased GAD-65/67 mRNAs, rescued the percentage of GAD-67 neurons and increased both proteins in a TrkB-dependent manner. Activity deprivation had thus shifted the period of neurotrophin sensitivity to older ages. The results suggested neuronal activity as a major regulator differentially affecting transcription and translation of the GAD isoforms. The early presence of neuronal activity promoted the GAD expression in OTC to a neurotrophin-independent state suggesting that neurotrophins play a context-dependent role.