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Russell E Jacobs

Publications and source records attributed to Russell E Jacobs.

16 recordsLinked to original sources
PubMed2007

Two-dimensional and three-dimensional time-lapse microscopic magnetic resonance imaging of Xenopus gastrulation movements using intrinsic tissue-specific contrast.

The amphibian embryo undergoes radical tissue transformations during blastula and gastrula stages, but live observation of internal morphogenetic events by optical microscopy is not feasible due to the opacity of the early embryo. Here, we report on the use of microscopic magnetic resonance imaging (MRI) to directly follow morphogenetic movements during blastula and gastrula stages of the Xenopus laevis embryo. We compare three different MRI modalities that take advantage of the intrinsic contrast present in embryonic tissues: three-dimensional (3D) fat-imaging, 3D water-imaging, and 2D high-speed high-resolution imaging of early embryonic stages. We show that the features revealed by the intrinsic contrast correlate with the histological structure of the embryo. Using this tissue specific intrinsic contrast, the main embryonic tissues and internal tissue movements as well as archenteron invagination can be differentiated without cell labeling. We present 2D and 3D time-lapse sequences of early Xenopus embryonic development, spanning the stages from early blastula to the end of gastrula, which show the complex internal rearrangements of gastrulation in essentially real-time.

Animals↗
PubMed2006

T(2)-weighted microMRI and evoked potential of the visual system measurements during the development of hypomyelinated transgenic mice.

Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.

Animals↗
PubMed2006

Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis.

Brain atrophy measured by MRI is an important correlate with clinical disability and disease duration in multiple sclerosis (MS). Unfortunately, neuropathologic mechanisms which lead to this grey matter atrophy remain unknown. The objective of this study was to determine whether brain atrophy occurs in the mouse model, experimental autoimmune encephalomyelitis (EAE). Postmortem high-resolution T2-weighted magnetic resonance microscopy (MRM) images from 32 mouse brains (21 EAE and 11 control) were collected. A minimum deformation atlas was constructed and a deformable atlas approach was used to quantify volumetric changes in neuroanatomical structures. A significant decrease in the mean cerebellar cortex volume in mice with late EAE (48-56 days after disease induction) as compared to normal strain, gender, and age-matched controls was observed. There was a direct correlation between cerebellar cortical atrophy and disease duration. At an early time point in disease, 15 days after disease induction, cerebellar white matter lesions were detected by both histology and MRM. These data demonstrate that myelin-specific autoimmune responses can lead to grey matter atrophy in an otherwise normal CNS. The model described herein can now be used to investigate neuropathologic mechanisms that lead to the development of gray matter atrophy in this setting.

Animals↗
PubMed2006

Time-lapse tracing of mitotic cell divisions in the early Xenopus embryo using microscopic MRI.

Mitotic cell division is a highly regulated cellular event in all organisms, but its direct visualization in the vertebrates is limited to animals with transparent embryos. Here, we report on the use of microscopic magnetic resonance imaging (mMRI) to noninvasively observe mitotic cell division of early blastomeres in the optically opaque Xenopus laevis embryo. Due to intrinsic tissue contrast, cell nuclei can be directly visualized without the need for contrast enhancing labeling. By taking two-dimensional in vivo time-lapse image sequences, the karyokinesis of a blastomere is followed. Timing and orientation of the cleavages can be traced for five cell divisions to establish a cell lineage tree, including orientation and timing of the mitosis. This work demonstrates for the first time the use of MRI for the visualization of cell divisions and expands the experimental scope of the Xenopus embryo.

Animals↗
PubMed2006

Myelin deficiencies visualized in vivo: visually evoked potentials and T2-weighted magnetic resonance images of shiverer mutant and wild-type mice.

Visually evoked potentials (VEPs) and micro magnetic resonance imaging (micro MRI) are widely used as noninvasive techniques for diagnosis of central nervous system (CNS) diseases, especially myelin diseases, such as multiple sclerosis. Here we use these techniques in tandem to validate the in vivo data in mouse models. We used the shiverer mutant mouse, which has little or no CNS myelin, as a test model. These data show that shiverer (MBP(shi)/MBP(shi)) has a VEP latency that is 30% longer than that of its wild-type sibling. Surprisingly, the heterozygous (MBP(shi)/+) mouse, with apparently normal myelin, nevertheless has a 7% increase in its VEP latency vs. wild type. The micro MRIs of the same animals show that myelinated white matter is hypointense compared with gray matter as a result of the shorter T2 in myelinated regions of the CNS. T2-weighted images of wild-type and heterozygous shiverer mice show regions of hypointensity corresponding to the major myelinated tracts, including the optic nerve and the optic tract of the CNS, whereas shiverer mice have no regions of low intensity and therefore no detectable myelinated areas. In shiverer mice, micro MRI can discern hypomyelination throughout the brain, including the optic tract, and these changes correlate with longer VEP latencies. In addition, VEPs can also detect changes in the molecular make up of myelin that are not discernible with histology or micro MR. These data show the potential of using micro MRI in combination with VEPs to follow changes in both the quality and the quantity of myelin in vivo. These combined methods would be useful for longitudinal studies and therapy testing.

Animals↗
PubMed2005

Standard atlas space for C57BL/6J neonatal mouse brain.

A standard atlas space with stereotaxic co-ordinates for the postnatal day 0 (P0) C57BL/6J mouse brain was constructed from the average of eight individual co-registered MR image volumes. Accuracy of registration and morphometric variations in structures between subjects were analyzed statistically. We also applied this atlas coordinate system to data acquired using different imaging protocols as well as to a high-resolution histological atlas obtained from separate animals. Mapping accuracy in the atlas space was examined to determine the applicability of this atlas framework. The results show that the atlas space defined here provides a stable framework for image registration for P0 normal mouse brains. With an appropriate feature-based co-registration strategy, the probability atlas can also provide an accurate anatomical map for images acquired using invasive imaging methods. The atlas templates and the probability map of the anatomical labels are available at http://www.loni.ucla.edu/MAP/ .

Anatomy, Artistic↗
PubMed2005

Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant.

Shiverer is an important model of central nervous system dysmyelination characterized by a deletion in the gene encoding myelin basic protein with relevance to human dysmyelinating and demyelinating diseases. Perfusion fixed brains from shiverer mutant (C3Fe.SWV Mbp(shi)/Mbp(shi)n = 6) and background control (C3HeB.FeJ, n = 6) mice were compared using contrast enhanced volumetric diffusion tensor magnetic resonance microscopy with a nominal isotropic spatial resolution of 80 mum. Images were accurately coregistered using non-linear warping allowing voxel-wise statistical parametric mapping of tensor invariant differences between control and shiverer groups. Highly significant differences in the tensor trace and both the axial and radial diffusivity were observed within the major white matter tracts and in the thalamus, midbrain, brainstem and cerebellar white matter, consistent with a high density of myelinated axons within these regions. The fractional anisotropy was found to be much less sensitive than the trace and eigenvalues to dysmyelination and associated microanatomic changes.

Animals↗
PubMed2005

Region-specific myelin pathology in mice lacking the golli products of the myelin basic protein gene.

The myelin basic protein (MBP) gene encodes two families of proteins, the classic MBP constituents of myelin and the golli-MBPs, the function of which is less well understood. In this study, targeted ablation of the golli-MBPs, but not the classic MBPs, resulted in a distinct phenotype unlike that of knock-outs (KOs) of the classic MBPs or other myelin proteins. Although the golli KO animals did not display an overt dysmyelinating phenotype, they did exhibit delayed and/or hypomyelination in selected areas of the brain, such as the visual cortex and the optic nerve, as determined by Northern and Western blots and immunohistochemical analysis with myelin protein markers. Hypomyelination in some areas, such as the visual cortex, persisted into adulthood. Ultrastructural analysis of the KOs confirmed both the delay and hypomyelination and revealed abnormalities in myelin structure and in some oligodendrocytes. Abnormal visual-evoked potentials indicated that the hypomyelination in the visual cortex had functional consequences in the golli KO brain. Evidence that the abnormal myelination in these animals was a consequence of intrinsic problems with the oligodendrocyte was indicated by an impaired ability of oligodendrocytes to form myelin sheets in culture and by the presence of abnormal Ca2+ transients in purified cortical oligodendrocytes studied in vitro. The Ca2+ results reported in this study complement previous results implicating golli proteins in modulating intracellular signaling in T-cells. Together, all these findings suggest a role for golli proteins in oligodendrocyte differentiation, migration, and/or myelin elaboration in the brain.

Animals↗
PubMed2005

Magnetic resonance microscopy: recent advances and applications.

Magnetic resonance microscopy is receiving increased attention as more researchers in the biological sciences are turning to non-invasive imaging to characterize development, perturbations, phenotypes and pathologies in model organisms ranging from amphibian embryos to adult rodents and even plants. The limits of spatial resolution are being explored as hardware improvements address the need for increased sensitivity. Recent developments include in vivo cell tracking, restricted diffusion imaging, functional magnetic resonance microscopy and three-dimensional mouse atlases. Important applications are also being developed outside biology in the fields of fluid mechanics, geology and chemistry.

Image Enhancement↗
PubMed2004

A multimodal, multidimensional atlas of the C57BL/6J mouse brain.

Strains of mice, through breeding or the disruption of normal genetic pathways, are widely used to model human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison. We have developed a digital atlas of the adult C57BL/6J mouse brain as a comprehensive framework for storing and accessing the myriad types of information about the mouse brain. Our implementation was constructed using several different imaging techniques: magnetic resonance microscopy, blockface imaging, classical histology and immunohistochemistry. Along with raw and annotated images, it contains database management systems and a set of tools for comparing information from different techniques. The framework allows facile correlation of results from different animals, investigators or laboratories by establishing a canonical representation of the mouse brain and providing the tools for the insertion of independent data into the same space as the atlas. This tool will aid in managing the increasingly complex and voluminous amounts of information about the mammalian brain. It provides a framework that encompasses genetic information in the context of anatomical imaging and holds tremendous promise for producing new insights into the relationship between genotype and phenotype. We describe a suite of tools that enables the independent entry of other types of data, facile retrieval of information and straightforward display of images. Thus, the atlas becomes a framework for managing complex genetic and epigenetic information about the mouse brain. The atlas and associated tools may be accessed at http://www.loni.ucla.edu/MAP.

Anatomy, Artistic↗
PubMed2003

Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: a magnetic resonance microscopy and stereologic analysis.

High-resolution magnetic resonance microscopy (MRM) was used to determine regional brain volumetric changes in a mouse model of Alzheimer's disease. These transgenic (Tg) mice overexpress human mutant amyloid precursor protein (APP) V717F under control of platelet-derived growth factor promoter (PDAPP mice), and cortical and hippocampal beta-amyloid (Abeta) deposits accumulate in heterozygotes after 8-10 mos. We used MRM to obtain 3D volumetric data on mouse brains imaged in their skulls to define genotype- and age-related changes. Hippocampal, cerebellar, and brain volumes and corpus callosum length were quantified in 40-, 100-, 365-, and 630-day-old mice. Measurements taken at age 100 days, before Abeta deposition, revealed a 12.3% reduction of hippocampus volume in Tg mice compared with WT controls. This reduction persisted without progression to age 21 mos. A significant 18% increase in hippocampal volume occurred between 40 and 630 days in WT mice, and no corresponding significant increase occurred in Tg mice. Cavalieri volume estimates of hippocampal subfields from 100-day-old Tg mice further localized a 28% volume deficit in the dentate gyrus. In addition, corpus callosum length was reduced by approximately 25% in Tg mice at all ages analyzed. In summary, reduced hippocampal volume and corpus callosum length can be detected by MRM before Abeta deposition. We conclude that overexpression of APP and amyloid may initiate pathologic changes before the appearance of plaques, suggesting novel targets for the treatment of Alzheimer's disease and further reinforcing the need for early diagnosis and treatment.

Alzheimer Disease↗
PubMed2003

In vivo trans-synaptic tract tracing from the murine striatum and amygdala utilizing manganese enhanced MRI (MEMRI).

Small focal injections of manganese ion (Mn(2+)) deep within the mouse central nervous system combined with in vivo high-resolution MRI delineate neuronal tracts originating from the site of injection. Previous work has shown that Mn(2+) can be taken up through voltage-gated Ca(2+) channels, transported along axons, and across synapses. Moreover, Mn(2+) is a paramagnetic MRI contrast agent, causing positive contrast enhancement in tissues where it has accumulated. These combined properties allow for its use as an effective MRI detectable neuronal tract tracer. Injections of low concentrations of MnCl(2) into either the striatum or amygdala produced significant contrast enhancement along the known neuronal circuitry. The observed enhancement pattern is different at each injection site and enhancement of the homotopic areas was observed in both cases. Ten days postinjection, the Mn(2+) had washed out, as evidenced by the absence of positive contrast enhancement within the brain. This methodology allows imaging of neuronal tracts long after the injection of the ion because Mn(2+) concentrates in active neurons and resides for extended periods of time. With appropriate controls, differentiation of subsets of neuronal pathways associated with behavioral and pharmacological paradigms should be feasible.

Amygdala↗
PubMed2002

Senile plaques do not induce susceptibility effects in T2*-weighted MR microscopic images.

Senile plaques are the hallmarks of Alzheimer's disease. They typically range from 16 to 150 microm in size with most less than 25 microm. Mechanisms by which they might affect MR contrast and thus be made visible in this imaging modality are still unknown. Plausibility studies suggested that they might have a different magnetic susceptibility than surrounding tissue. A large difference would cause the plaque and a relatively large volume of adjacent tissue to be hypo-intense in T2*-weighted MRI scans, thus causing them to appear larger than their actual sizes and perhaps visible even when their size is below the nominal resolution limit of the imaging experiment. To evaluate this hypothesis, formalin-fixed superior temporal gyrus samples obtained from two Alzheimer's disease and two control subjects were imaged using magnetic resonance microscopy at 11.7 T. Three dimensional T2*-weighted gradient echo images were recorded with an isotropic resolution of 23.4 microm. The imaging protocol was especially sensitive to susceptibility effects. Samples were then stained for amyloid and/or iron deposits. Hypo- and hyper-intense structures were clearly visible in MR images from all samples. Hyper-intense structures reflected fixative penetration within the vascular system. Almost all the hypo-intense structures were blood vessels. Their hypo-intense profile was probably caused by iron deposits associated with the cell aggregates that they contained. Only one hypo-intense spot could be matched with a plaque and this was one of the largest plaques in our samples. The remainder of the several hundred plaques were not visible in MR images. In histological slices the senile plaques were often larger than small blood vessels that were visible in the MR images. This suggests that susceptibility effects are not associated with senile plaques and do not provide a mechanism to differentiate them from surrounding tissue.

Aged↗
PubMed2002

Towards a Tralfamadorian view of the embryo: multidimensional imaging of development.

Biological problems such as embryonic development require tools to follow cell and tissue movements as well as the distribution of active genes. A variety of emerging imaging techniques offer the capability of fully rendering the three-dimensional structure of the embryo, and some offer the possibility of following changes directly over time. The data sets that result offer both new insights and new challenges. A framework of digital atlases will soon offer the integration of different imaging modalities and permit users to interact with multidimensional data sets.

Animals↗