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Statistical parametric mapping of (99m)Tc-HMPAO-SPECT images for the diagnosis of Alzheimer's disease: normalizing to cerebellar tracer uptake.

BACKGROUND: For a quantitative comparison of images obtained during (99m)Tc-hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT), brain activity values are usually normalized to a reference region. In studies of Alzheimer-type dementia (ATD), the cerebellum is often used as a reference region, assuming that it is spared any major pathological involvement. Statistical parametric mapping (SPM) may enhance the evaluation of SPECT scans in ATD patients. However, current SPM software only allows scaling to average whole brain activity (i.e., global normalization). The aim of this study was to develop an easily applied, objective, and reproducible method for determining average cerebellar tracer uptake so that images can be scaled specifically to cerebellar activity prior to the performance of SPM analysis. We also investigated whether cerebellar normalization increases the sensitivity and specificity of SPM analysis of ATD patients compared with global normalization. METHODS: Image files were taken from a parallel study investigating the use of SPECT as a diagnostic tool for early onset of ATD. Two methods for determining cerebellar activity were developed: one manually, using templates, the other automated, using specified coordinates entered into a Matlab routine. Group comparison of ATD patients versus controls (= healthy volunteers and depressed patients) was performed on a voxel-by-voxel basis using SPM 96 on Windows 95. Receiver operator characteristics (ROC) were computed for 20 student raters examining patient and control scans with and without single-subject SPMs. RESULTS: The reduction of cerebral blood flow in the group of ATD patients appeared 1.7 times greater in spatial extent when the tracer uptake was normalized to cerebellum rather than to average whole brain activity. Computing the reverse contrast (reductions in the control group compared with ATD patients) produced clusters of significance in globally normalized images which were not manifest after normalizing to cerebellum. This is consistent with the notion that the cerebellum is spared in ATD. Analysis of the area under the ROC curve showed that cerebellar-normalized SPM produced significantly improved accuracy over perfusion scans alone. CONCLUSION: An easily applied, objective, reproducible method was developed for normalizing images to cerebellum prior to the performance of SPM analysis. Cerebellar normalization produced more extensive abnormalities in SPM analyses of ATD patients than global normalization. Furthermore, cerebellar normalization produced marginally more accurate diagnostic results in single-scan SPM analysis of ATD patients than did global normalization.

Aged↗

Clinical experience with paraspinal mapping. I: Neurophysiology of the paraspinal muscles in various spinal disorders.

OBJECTIVE: To assess the extent of denervation of the paraspinal muscles in spinal disorders. DESIGN: Nonrandomized prospective trial. SETTING: Electrodiagnostic laboratory of a university spine center and of a private practice in a small community. SUBJECTS: One hundred fourteen consecutive persons referred for electrodiagnosis of spinal or lower extremity disorders. INTERVENTION: The paraspinal mapping (PM) electromyography (EMG) protocol along with codified history, physical examination, extremity EMG, and in 44 cases, radiologic imaging results. MAIN OUTCOME MEASURES: PM scores compared with recently established norms (95% of normal subjects scoring less than < 6), lower extremity (LE) EMG findings, and imaging results. RESULTS: Fifty-eight subjects had normal PM scores; 62 were abnormal. Compared to imaging studies, false positive rate was 8% (1/13). False negative rate (normal PM with definite nerve involvement on imaging) was 33% (6/18), but this decreased to 5% when PM was combined with LE EMG. Four of 4 high lumbar lesions were detected by PM. Of 14 apparent false negatives (13%) compared to LE EMG, 6 had S1 root lesions and 5 had nonspinal lesions. All 7 subjects with isolated S1 radiculopathy had PM scores within normal limits. Occasional polyneuropathies presented with normal PM and abnormal distal findings or with abnormal PM but normal distal findings. No patient with isolated paraspinal findings had evidence of malignancy on follow-up. This report also describes the distribution of denervation in the multifidus, longissimus, and iliocostalis in various disorders. CONCLUSIONS: PM related well to imaging studies and LE EMG. It detects uncommon high lumbar root lesions. S1 may not innervate the paraspinal muscles. There are isolated paraspinal findings in persons without malignancy. The effects of specific muscle denervation on biomechanics, rehabilitation exercise, and prognosis are not known.

Adult↗

Use of an automated anesthesia information system to determine reference limits for vital signs during cesarean section.

INTRODUCTION: We evaluated whether automated anesthesia information systems can be used to calculate reference limits (population-based "normal values") for vital signs. We considered four populations of women undergoing cesarean section: healthy under spinal anesthesia, healthy under general anesthesia, pre-eclamptic/eclamptic under spinal anesthesia, and pre-eclamptic/eclamptic under general anesthesia. METHODS: Reference limits were calculated for each of the study populations by determination of percentiles for: minimum heart rate, maximum heart rate, minimum arterial oxyhemoglobin saturation (SaO2), minimum mean arterial pressure (MAP), maximum MAP, decrease in MAP, and increase in MAP. RESULTS: There was one adverse anesthetic outcome among the 1,300 women in the study; the woman sustained a post-dural puncture headache. The 5th percentiles of SaO2 were at least 95% saturation under spinal versus 90% under general. Under spinal anesthesia, 95th percentiles for decreases in MAP from baseline were 63 mmHg for healthy and 75 mmHg for pre-eclamptic/eclamptic women. Under general anesthesia, the 95th percentiles for maximum MAP were 161 and 177 mmHg, respectively. Two women of the 1,300 patients experienced simultaneously a minimum SaO2 < 92% and minimum MAP < 50 mmHg. DISCUSSION: Automated anesthesia information systems can be used to determine reference limits for vital signs during anesthesia. Reference limits may play a role in malpractice cases when an expert claims that care by an anesthesiologist was sub-standard as shown by vital signs that were not maintained within the normal range during the critical portions of an anesthetic. Automated anesthesia information systems may enhance expert witnesses' clinical judgment.

Adult↗

Intracranial dural arteriovenous fistulas with retrograde cortical venous drainage: assessment with cerebral blood volume by dynamic susceptibility contrast magnetic resonance imaging.

BACKGROUND AND PURPOSE: Retrograde cortical venous drainage (RCVD) is the most major risk factor for aggressive behavior of intracranial dural arteriovenous fistulas (DAVF). The purpose of this study was to assess the efficacy of relative cerebral blood volume (rCBV) map for RCVD in patients with DAVF. METHODS: Ten patients with angiographically proven DAVF with RCVD, 2 reference patients with DAVF without RCVD, and 10 control subjects underwent examinations with dynamic susceptibility contrast (DSC)-MR imaging. Four patients with DAVF with unilateral RCVD were evaluated, before and after treatment. The calculation of mean rCBV ratio was performed on a hemispheric basis. The mean rCBV ratio was defined as the value on one side (higher value side) divided by that on the other side (lower value side). RESULTS: In all patients with DAVF with RCVD, the rCBV map showed an increase in rCBV of the angiographically proved affected hemisphere. In 2 reference patients with DAVF without RCVD and all control subjects, the rCBV map showed no increase of rCBV. The mean rCBV ratio in patients with DAVF with RCVD was significantly higher than that of control subjects (P = .0002). Treatment response for RCVD was indicated by a decrease of CBV on the rCBV map and by a decrease of 22% in the mean rCBV ratio. CONCLUSIONS: Increased rCBV by DSC-MR correlated with RCVD in patients with DVAF. The assessment with rCBV for RCVD may be more quantitative than that with angiogram.

Aged↗

A new DNA marker (D4S90) is located terminally on the short arm of chromosome 4, close to the Huntington disease gene.

Genetic linkage studies have mapped Huntington's disease (HD) to the distal portion of the short arm of chromosome 4 (4p16.3), 4 cM distal to D4S10 (G8). To date, no definite flanking marker has been identified. A new DNA marker, D4S90 (D5); which maps to the distal region of 4p16.3, is described. The marker was used in a genetic linkage study in the CEPH reference families with seven other markers at 4p16. The study, together with knowledge of the physical map of the region, places D4S90 as the most distal marker, 6 cM from D4S10. A provisional linkage study with HD gave a maximum lod score of 2.14 at a theta of 0.00 and no evidence of linkage disequilibrium. As D4S90 appears to be located terminally, it should play an important role in the accurate mapping and cloning of the HD gene.

Blotting, Southern↗

New method for titrating differences in scalp topographic patterns in brain evoked potential mapping.

A method is described for computing a Z estimator for the quantitative comparison of topographical patterns in 2 maps. Z can assume values between 1 and -1. The procedure is illustrated on a 3-shell head model for different configurations of current dipoles in the head space. The sensitivity of Z estimation can be adjusted by different weighting procedures or by using an average reference. When Z = 1 indicates identity of the set of active dipoles in the 2 maps compared, a dilation factor can be computed to estimate the enhanced or reduced activity of these generators.

Brain↗

A recombinant antigen from the heartwater agent (Cowdria ruminatium) reactive with antibodies in some southeastern United States white-tailed deer (Odocoileus virginianus), but not cattle, sera.

Recombinant baculovirus techniques were used to express the 260 amino acid carboxyterminal portion of the 32 kilodalton (kDa) major antigenic protein (MAP 1) of Cowdria ruminantium, the heartwater agent, as a fusion protein. The recombinant MAP 1 was fused to an aminoterminal independently antigenic octapeptide sequence (FLAG peptide). Recombinant MAP 1 was used as an immunoblotting antigen to evaluate numerous reference antisera against organisms of the tribe Ehrlichieae. Monoclonal and polyclonal C. ruminantium antibodies, monoclonal anti-FLAG ascites, and antisera to Ehrlichia canis and Ehrlichia chaffeensis reacted with this antigen. Twelve of 79 sera collected 1980 to 1992 from southeastern U.S. white-tailed deer (Odocoileus virginianus) were also unexpectedly immunoblot-positive to MAP 1. These 12 deer sera had, as a group, significantly (P < 0.01) greater anti-E. chaffeensis titers (previously determined) than the sera from MAP 1 immunoblot-negative deer living in the same areas. None of the 262 sera from cattle living in the same areas were immunoblot-positive to MAP 1. All of an additional 50 cervine sera from Michigan (USA), 72 bovine sera from northern U.S. cattle, and 72 sera from Puerto Rican cattle were also immunoblot-negative to MAP 1. Sera from African sheep which were falsely seropositive to authentic MAP 1 were also immunoblot-positive to the recombinant MAP 1. Unidentified Ehrlichia spp. capable of serologic crossreactivity with the heartwater agent appear to be present in some southeastern U.S. white-tailed deer but not cattle. These or related Ehrlichia spp. may also be found elsewhere in the world in non-cervine species.

Animals↗

Analysis of neuroreceptor PET-data based on cytoarchitectonic maximum probability maps: a feasibility study.

Three-dimensional maximum probability maps (MPMs) of cytoarchitectonically defined cortical regions based on postmortem histological studies have recently been made available in the stereotaxic reference space of the Montreal Neurological Institute (MNI) single subject template. This permits the use of cytoarchitectonic maps for the analysis of functional in vivo datasets, including neuroreceptor positron emission tomography (PET) studies. In this feasibility study, we used 5-hydroxytryptamine 2A (5-HT2A) receptor PET to test the applicability of maximum cytoarchitectonic probability maps for quantitative analysis. As the outcome parameter, we extracted local distribution volume ratios (DVRs) from 19 cytoarchitectonically defined volumes of interest (VOIs) per hemisphere from five healthy subjects. The experimental design included a forward ('PET to atlas' normalization) and a backward ('atlas to PET' normalization) procedure to double-check the stability of transformation and overlay. Resulting DVRs were compared with receptor densities (RDs) obtained from postmortem [3H]ketanserin autoradiography of multiple areas. Correlations between the bi-directional normalization procedures (r = 0.89; 38 VOIs) as well as between in vivo and vitro data (nine VOIs; r = 0.64 and r = 0.47 for forward and backward procedure, respectively) suggest that the implementation of cytoarchitectonic maximum probability maps is a promising method for an accurate and observer-independent analysis of neuroreceptor PET data.

Adult↗

Intra-atrial reentrant tachycardia after palliation of congenital heart disease: characterization of multiple macroreentrant circuits using fluoroscopically based three-dimensional endocardial mapping.

INTRODUCTION: The anatomic substrate of intra-atrial reentrant tachycardia (IART) following congenital heart surgery is poorly understood, but is presumed to be different than common atrial flutter. METHODS AND RESULTS: To study the mechanisms of IART, we used a new technique for high-density endocardial mapping using recordings from a multipolar basket recording catheter (25 bipolar pairs). For each recording, biplane fluorographic reference points were digitized to obtain the spatial locations of electrode pairs, and activation times were calculated using temporal reference points from the surface ECG. Using custom software, data were combined to create three-dimensional atrial activation sequence maps, which were displayed as animated sequences. Using this technique, recordings were made in induced and/or spontaneous IART in 8 patients following congenital heart surgery (5 Fontan, 2 tetralogy of Fallot repair, 1 ventricular septal defect repair), and in 3 patients with normal intracardiac anatomy (1 with type I atrial flutter). Ten discrete IART activation sequences were recorded; 2 patients had 2 sequences each. IART maps were constructed using a median of 108 electrode positions (range 27 to 197) from a median of 6 recordings/sequence (range 3 to 11). Sinus or paced atrial rhythms were also recorded, and maps were created in a similar fashion. Visual analysis of activation sequences of sinus and paced rhythm were anatomically concordant with known mechanisms of atrial activation. IART sequences revealed diverse mechanisms; only 1 IART circuit was similar to that associated with common atrial flutter. Activation wavefront emergence from presumed zones of slow conduction, lines of conduction block, and apparent bystander activation were observed. CONCLUSIONS: High-density atrial activation sequence maps demonstrate that IART following congenital heart surgery utilizes diverse circuits and is distinct from common atrial flutter. The technique used to create these three-dimensional activation sequences may improve understanding of these complex atrial arrhythmias and assist in the development of ablative therapies.

Adolescent↗

Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking.

Human personality has been considered to have a neurochemical background. We examined the relation between extrastriatal dopamine D2 receptor binding in living human brain and the personality trait of novelty seeking that has been proposed to be related to dopaminergic function in the brain. We measured extrastriatal dopamine D2 receptors of 24 healthy young male subjects using [(11)C]FLB 457 positron emission tomography. The personality trait of each subject was assessed by the Temperament and Character Inventory (TCI). Correlation of dopamine D2 receptor binding with novelty seeking was calculated using region-of-interest analysis and statistical parametric mapping based on the binding potential images generated using a reference tissue model. A significant negative correlation was observed between binding potential values and the novelty seeking scores on TCI in the right insular cortex. No significant correlation was observed in any other region. Our result indicates that there is a significant association between dopamine D2 receptor binding and the human novelty seeking trait in the right insular cortex.

Adult↗

Closing in on the MEN2A locus.

The mapping of the locus for multiple endocrine neoplasia type 2A (MEN 2A) to chromosome 10 using linkage is briefly reviewed including a discussion of linkage strategy and reference to some of the exclusions before the assignment. The subsequent development of the map of the centromeric region of the chromosome and the linking of what appear to be the four closest flanking markers and the centromeric alphoid sequence to the disease locus are reviewed. To date no recombination has been observed between the centromeric marker and the MEN2A locus among, at least, 26 informative meioses, 11 of which are phase known. While no obligate recombination has been observed between the markers FNRB, D10S34, and RBP3 and the MEN2A locus in males, it has been observed in females and is as much as 10% for the marker RBP3. The sex difference in recombination frequency is significant. The four polymorphic flanking markers, FNRB, D10S34, RBP3, and D10S5, along with the centromeric marker D10Z1 will prove to be useful for management of the families with the disease. It will be possible in most families to give a very high (or low) probability for "at risk" members of the families and in some cases the DNA results will be virtually diagnostic.

Chromosome Aberrations↗

Two-dimensional deghosting for EPI.

A residual ghost artefact in echo-planar imaging (EPI) remains after the standard correction procedure based on a 1-dimensional phase-modulation of the spectra of even or odd echoes. A better reduction of this artefact is demonstrated using a 2-dimensional phase correction. The phase correction map is measured inside the ghost-free region of the image, preferably in a reference scan with an increased field of view, as the phase difference between complex images reconstructed separately from even and odd echoes. An extrapolated map consisting of spatial components up to the second order (constant, x, y, xy and x2-y2) is then found by a fit to the measured values. This map is used to correct the phase of even- and odd-reconstructed images before adding them. This procedure may cause some spatially dependent loss of signal, but if the level of the residual artefact is less than 20% of the image intensity, such losses are negligible.

Artifacts↗

Accuracy of stereotaxic positioning of transcranial magnetic stimulation.

In cognitive neuroscience, optically tracked frameless stereotaxic navigation has been successfully used to precisely guide transcranial magnetic stimulation (TMS) to desired cortical areas for brain-mapping purposes. Thereby, potential sources of imprecision are the fixation of a reference frame to the head of the subject and the referencing procedure according to certain landmarks (LM). The aim of our study was to evaluate the accuracy of frameless stereotaxic coil positioning in a standard experimental setting. A parameter for accuracy is the reproducibility of LM coordinates. In order to test the stability of the referencing for stereotaxic positioning within a single TMS session (within-session stability), the coordinates of six predefined facial LM in nine subjects were recorded first after the initial registration and second after a 20 minutes TMS session. The two sets of coordinates were then compared. The reliability of the positioning coordinates between different TMS sessions (inter-session repeatability) was addressed by registering the subjects LM coordinates in two independent TMS sessions. The variance of the recorded coordinates was analyzed. Altogether, LM were registered 1728 times (192 measures per subject). Within-session stability: The mean Euclidean distance (MED) between the LM position coordinates before and after a TMS session was 1.6 mm, when pooling over all LM. Inter-session repeatability: The MED between the LM positions recorded after the reference procedures of two different sessions showed an average deviation of 2.5 mm. In conclusion, optically tracked frameless stereotaxic coil positioning is from the technical viewpoint of high stability and repeatability. It is therefore a precise method for TMS brain mapping studies or for repeated TMS treatments, with the need of topographically exact stimulation.

Adult↗

A three-dimensional musculoskeletal model for gait analysis. Anatomical variability estimates.

Three-dimensional coordinates defining the origin and insertion of 40 muscle units, and bony landmarks for osteometric scaling were identified on dry bone specimens. Interspecimen coordinate differences along the anterior-posterior axis of the pelvis and the long bone axes of the pelvis, femur and leg were reduced by scaling but landmark differences along the other axes were not. The coordinates were mapped to living subjects using close-range photogrammetry to locate superficial reference markers. The error of predicting the positions of internal coordinates was assessed by comparing joint centre locations calculated from local axes defining the orientation of segments superior and inferior to a joint. A difference was attributed to: anatomical variability not accounted for by scaling; errors in identifying and placing reference landmarks; the accuracy of locating markers using photogrammetry and error introduced by marker oscillation during movement. Anatomical differences between specimens are one source of error in defining a musculoskeletal model but larger errors are introduced when such models are mapped to living subjects.

Anthropometry↗

A comprehensive genetic map of the cattle genome based on 3802 microsatellites.

A microsatellite-based high-density genetic map facilitates for fine mapping of hereditary traits of interest, characterization of meiosis, and providing a foundation for physical map construction. Here, we developed a comprehensive genetic map on the basis of >880,000 genotypes across the USDA MARC cattle reference families with a potential genetic resolution of 0.8 cM at the 95% confidence level ( approximately 800 kb in the bovine genome). We incorporated 2325 microsatellites into the second-generation genetic map by linkage analysis based on sex-averaged two-point LOD scores (>3.0), of which 2293 were fine-mapped by multipoint linkage analysis. The new 3160-cM map comprised of 29 sex-averaged autosomal linkage groups and a sex-specific X-chromosome linkage group includes 3960 markers with 2389 positions, resulting in an average interval size of 1.4 cM. More than half (51%) of the total length of the map is covered with intervals of 2.0 cM or less, and the largest gap is a 10.2-cM interval on the X-linkage group. The new map should accelerate fine mapping and positional cloning of genes for genetic diseases and economically important traits in cattle, as well as related livestock species, such as sheep and goat.

Animals↗

High resolution physical map of porcine chromosome 7 QTL region and comparative mapping of this region among vertebrate genomes.

BACKGROUND: On porcine chromosome 7, the region surrounding the Major Histocompatibility Complex (MHC) contains several Quantitative Trait Loci (QTL) influencing many traits including growth, back fat thickness and carcass composition. Previous studies highlighted that a fragment of approximately 3.7 Mb is located within the Swine Leucocyte Antigen (SLA) complex. Internal rearrangements of this fragment were suggested, and partial contigs had been built, but further characterization of this region and identification of all human chromosomal fragments orthologous to this porcine fragment had to be carried out. RESULTS: A whole physical map of the region was constructed by integrating Radiation Hybrid (RH) mapping, BAC fingerprinting data of the INRA BAC library and anchoring BAC end sequences on the human genome. 17 genes and 2 reference microsatellites were ordered on the high resolution IMNpRH212000rad Radiation Hybrid panel. A 1000:1 framework map covering 550 cR12000 was established and a complete contig of the region was developed. New micro rearrangements were highlighted between the porcine and human genomes. A bovine RH map was also developed in this region by mapping 16 genes. Comparison of the organization of this region in pig, cattle, human, mouse, dog and chicken genomes revealed that 1) the translocation of the fragment described previously is observed only on the bovine and porcine genomes and 2) the new internal micro rearrangements are specific of the porcine genome. CONCLUSION: We estimate that the region contains several rearrangements and covers 5.2 Mb of the porcine genome. The study of this complete BAC contig showed that human chromosomal fragments homologs of this heavily rearranged QTL region are all located in the region of HSA6 that surrounds the centromere. This work allows us to define a list of all candidate genes that could explain these QTL effects.

Animals↗

Cerebrocerebellar circuits for the perceptual cancellation of eye-movement-induced retinal image motion.

Despite smooth pursuit eye movements, we are unaware of resultant retinal image motion. This example of perceptual invariance is achieved by comparing retinal image slip with an internal reference signal predicting the sensory consequences of the eye movement. This prediction can be manipulated experimentally, allowing one to vary the amount of self-induced image motion for which the reference signal compensates and, accordingly, the resulting percept of motion. Here we were able to map regions in CRUS I within the lateral cerebellar hemispheres that exhibited a significant correlation between functional magnetic resonance imaging signal amplitudes and the amount of motion predicted by the reference signal. The fact that these cerebellar regions were found to be functionally coupled with the left parieto-insular cortex and the supplementary eye fields points to these cortical areas as the sites of interaction between predicted and experienced sensory events, ultimately giving rise to the perception of a stable world despite self-induced retinal motion.

Brain Mapping↗

Differences of nucleoproteins of human and avian influenza A virus strains shown by polyacrylamide gel electrophoresis and by the peptide mapping technique.

Electrophoretic mobility differences in polyacrylamide gels were detected between (35S)-methionine-labelled nucleoproteins (NPs) induced in monolayer cells by 15 human and 4 avian reference strains of influenza viruses. The (35S)-methionine-labelled tryptic peptides of nucleoproteins of these strains were also analyzed by peptide mapping technique. Based on several detectable hydrophilic peptides the NPs could be arranged in 7 clearly differentiable groups. After radioiodination of NPs from 4 human and 3 avian reference strains the tryptic peptide patterns showed one clear difference between human and avian strains.

Electrophoresis, Polyacrylamide Gel↗