Signal-, set- and movement-related activity in the human brain: an event-related fMRI study.
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Electrophysiological studies on monkeys have been able to distinguish sensory and motor signals close in time by pseudorandomly delaying the cue that instructs the movement from the stimulus that triggers the movement. We have used a similar experimental design in functional magnetic resonance imaging (fMRI), scanning subjects while they performed a visuomotor conditional task with instructed delays. One of four shapes was presented briefly. Two shapes instructed the subjects to flex the index finger; the other two shapes coded the flexion of the middle finger. The subjects were told to perform the movement after a tone. We have exploited a novel use of event-related fMRI. By systematically varying the interval between the visual and acoustic stimuli, it has been possible to estimate the significance of the evoked haemodynamic response (EHR) to each of the stimuli, despite their temporal proximity in relation to the time constant of the EHR. Furthermore, by varying the phase between events and image acquisition, we have been able to achieve high temporal resolution while scanning the whole brain. We dissociated sensory and motor components of the sensorimotor transformations elicited by the task, and assessed sustained activity during the instructed delays. In calcarine and occipitotemporal cortex, the responses were exclusively associated with the visual instruction cues. In temporal auditory cortex and in primary motor cortex, they were exclusively associated with the auditory trigger stimulus. In ventral prefrontal cortex there were movement-related responses preceded by preparatory activity and by signal-related activity. Finally, responses associated with the instruction cue and with sustained activity during the delay period were observed in the dorsal premotor cortex and in the dorsal posterior parietal cortex. Where the association between a visual cue and the appropriate movement is arbitrary, the underlying visuomotor transformations are not achieved exclusively through frontoparietal interactions. Rather, these processes seem to rely on the ventral visual stream, the ventral prefrontal cortex and the anterior part of the dorsal premotor cortex. (+info)
Optical mapping of Plasmodium falciparum chromosome 2.
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Detailed restriction maps of microbial genomes are a valuable resource in genome sequencing studies but are toilsome to construct by contig construction of maps derived from cloned DNA. Analysis of genomic DNA enables large stretches of the genome to be mapped and circumvents library construction and associated cloning artifacts. We used pulsed-field gel electrophoresis purified Plasmodium falciparum chromosome 2 DNA as the starting material for optical mapping, a system for making ordered restriction maps from ensembles of individual DNA molecules. DNA molecules were bound to derivatized glass surfaces, cleaved with NheI or BamHI, and imaged by digital fluorescence microscopy. Large pieces of the chromosome containing ordered DNA restriction fragments were mapped. Maps were assembled from 50 molecules producing an average contig depth of 15 molecules and high-resolution restriction maps covering the entire chromosome. Chromosome 2 was found to be 976 kb by optical mapping with NheI, and 946 kb with BamHI, which compares closely to the published size of 947 kb from large-scale sequencing. The maps were used to further verify assemblies from the plasmid library used for sequencing. Maps generated in silico from the sequence data were compared to the optical mapping data, and good correspondence was found. Such high-resolution restriction maps may become an indispensable resource for large-scale genome sequencing projects. (+info)
Examination of the transverse tubular system in living cardiac rat myocytes by 2-photon microscopy and digital image-processing techniques.
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The transverse tubular system (t-system) of cardiac muscle is a structure that allows rapid propagation of excitation into the cell interior. Using 2-photon molecular excitation microscopy and digital image-processing methods, we have obtained a comprehensive overview of the t-system of rat ventricular myocytes in living cells. We show that it is possible to quantify the morphology of the t-system in terms of average local tubule diameter, branching pattern, and local abundance of the t-system by immersing living myocytes in a dextran-linked fluorescein solution. Our data suggest that previous electron microscopic examinations of t-system structure have underestimated both the geometric complexity of the t-system morphology and the fraction of cell volume occupied by the t-system (3.6% in this species). About 40% of tubules occur between Z-lines, and the t-tubule diameter is 255+/-0.85 nm (mean+/-SEM). The t-tubules leave the outer surface of the cell in an approximately rectangular array; however, at some points junctions between the t-tubules and the surface membrane are missing. In view of the complexity of the t-system apparent from our images, we propose that the t-system be renamed the "sarcolemmal Z rete." The methods presented here are generally applicable to the quantification of the sarcolemmal Z rete and other structures within cells by fluorescence microscopy in a variety of cell types. (+info)
Interleaved echo-planar imaging (EPI) is an ultrafast imaging technique important for applications that require high time resolution or short total acquisition times. Unfortunately, EPI is prone to significant ghosting artifacts, resulting primarily from system time delays that cause data matrix misregistration. In this work, it is shown mathematically and experimentally that system time delays are orientation dependent, resulting from anisotropic physical gradient delays. This analysis characterizes the behavior of time delays in oblique coordinates, and a new ghosting artifact caused by anisotropic delays is described. "Compensation blips" are proposed for time delay correction. These blips are shown to remove the effects of anisotropic gradient delays, eliminating the need for repeated reference scans and postprocessing corrections. Examples of phantom and in vivo images are shown. (+info)
Parametric mapping of cerebral blood flow deficits in Alzheimer's disease: a SPECT study using HMPAO and image standardization technique.
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This study assessed the accuracy and reliability of Automated Image Registration (AIR) for standardization of brain SPECT images of patients with Alzheimer's disease (AD). Standardized cerebral blood flow (CBF) images of patients with AD and control subjects were then used for group comparison and covariance analyses. METHODS: Thirteen patients with AD at an early stage (age 69.8+/-7.1 y, Clinical Dementia Rating Score 0.5-1.0, Mini-Mental State Examination score 19-23) and 20 age-matched normal subjects (age 69.5+/-8.3 y) participated in this study. 99mTc-hexamethyl propylenamine oxime (HMPAO) brain SPECT and CT scans were acquired for each subject. SPECT images were transformed to a standard size and shape with the help of AIR. Accuracy of AIR for spatial normalization was evaluated by an index calculated on SPECT images. Anatomical variability of standardized target images was evaluated by measurements on corresponding CT scans, spatially normalized using transformations established by the SPECT images. Realigned brain SPECT images of patients and controls were used for group comparison with the help of statistical parameter mapping. Significant differences were displayed on the respective voxel to generate three-dimensional Z maps. CT scans of individual subjects were evaluated by a computer program for brain atrophy. Voxel-based covariance analysis was performed on standardized images with ages and atrophy indices as independent variables. RESULTS: Inaccuracy assessed by functional data was 2.3%. The maximum anatomical variability was 4.9 mm after standardization. Z maps showed significantly decreased regional CBF (rCBF) in the frontal, parietal and temporal regions in the patient group (P < 0.001). Covariance analysis revealed that the effects of aging on rCBF were more pronounced compared with atrophy, especially in intact cortical areas at an early stage of AD. Decrease in rCBF was partly due to senility and atrophy, however these two factors cannot explain all the deficits. CONCLUSION: AIR can transform SPECT images of AD patients with acceptable accuracy without any need for corresponding structural images. The frontal regions of the brain, in addition to parietal and temporal lobes, may show reduced CBF in patients with AD even at an early stage of dementia. The reduced rCBF in the cortical regions cannot be explained entirely by advanced atrophy and fast aging process. (+info)
Integrated visualization of functional and anatomic brain data: a validation study.
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Two-dimensional SPECT display and three methods for integrated visualization of SPECT and MRI patient data are evaluated in a multiobserver study to determine whether localization of functional data can be improved by adding anatomical information to the display. METHODS: SPECT and MRI data of 30 patients were gathered and presented using four types of display: one of SPECT in isolation, two integrated two-dimensional displays and one integrated three-dimensional display. Cold and hot spots in the peripheral cortex were preselected and indicated on black-and-white hard copies of the image data. Nuclear medicine physicians were asked to assign the corresponding spots in the image data on the computer screen to a lobe and a gyrus and give a confidence rating for both localizations. Interobserver agreement using kappa statistics and average confidence ratings were assessed to interpret the reported observations. RESULTS: Both the interobserver agreement and the confidence of the observers were greater for the integrated two-dimensional displays than for the two-dimensional SPECT display. An additional increase in agreement and confidence was seen with the integrated three-dimensional display. CONCLUSION: Integrated display of SPECT and MR brain images provides better localization of cerebral blood perfusion abnormalities in the peripheral cortex in relation to the anatomy of the brain than single-modality display and increases the confidence of the observer. (+info)
Anatomic validation of spatial normalization methods for PET.
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Spatial normalization methods, which are indispensable for intersubject analysis in current PET studies, have been improved in many aspects. These methods have not necessarily been evaluated as anatomic normalization methods because PET images are functional images. However, in view of the close relation between brain function and morphology, it is very intriguing how precisely normalized brains coincide with each other. In this report, the anatomic precision of spatial normalization is validated with three different methods. METHODS: Four PET centers in Japan participated in this study. In each center, six normal subjects were recruited for both H2(15)O-PET and high-resolution MRI studies. Variations in the location of the anterior commissure (AC) and size and contours of the brain and the courses of major sulci were measured in spatially normalized MR images for each method. Spatial normalization was performed as follows. (a) Linear: The AC-posterior commissure and midsagittal plane were identified on MRI and the size of the brain was adjusted to the Talairach space in each axis using linear parameters. (b) Human brain atlas (HBA): Atlas structures were manually adjusted to MRI to determine linear and nonlinear transformation parameters and then MRI was transformed with the inverse of these parameters. (c) Statistical parametric mapping (SPM) 95: PET images were transformed into the template PET image with linear and nonlinear parameters in a least-squares manner. Then, coregistered MR images were transformed with the same parameters used for the PET transformation. RESULTS: The AC was well registered in all methods. The size of the brain normalized with SPM95 varied to a greater extent than with other approaches. Larger variance in contours was observed with the linear method. Only SPM95 showed significant superiority to the linear method when the courses of major sulci were compared. CONCLUSION: The results of this study indicate that SPM95 is as effective a spatial normalization as HBA, although it does not use anatomic images. Large variance in structures other than the AC and size of the brain in the linear method suggests the necessity of nonlinear transformations for effective spatial normalization. Operator dependency of HBA also must be considered. (+info)
Using vascular structure for CT-SPECT registration in the pelvis.
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The authors outline a method for three-dimensional registration of pelvic CT and 111In-labeled monoclonal antibody capromab pendetide (111In MoAb 7E11.C5) images using 99mTc-labeled red blood cell SPECT data. METHODS: This method of CT-SPECT registration relies on the identification of major blood vessels in the CT and 99mTc SPECT images. The vessels are segmented from the image datasets by outlining them on transverse planar slices using a mouse-based drawing tool. Stacking the transverse outlines provides a three-dimensional representation of the vascular structures. Registration is performed by matching the surfaces of the segmented volumes. Dual isotope acquisition of 111In and 99mTc activities provides precise SPECT-SPECT registration so that registration in three dimensions of the 111In MoAb and CT images is achieved by applying the same transformation obtained from the 99mTc SPECT-CT registration. RESULTS: This method provided accurate registration of pelvic structures and significantly improved interpretation of 111In MoAb 7E11.C5 exams. Furthermore, sites of involvement by prostate cancer suggested by the 111In MoAb examination could be interpreted with the bony and soft tissue (nodal) anatomy seen on CT. CONCLUSION: This method is a general clinical tool for the registration of pelvic CT and SPECT imaging data. There are immediate applications in conformal radiation therapy treatment planning for certain prostate cancer patients. (+info)