Automatic segmentation of medical images using image registration: diagnostic and simulation applications

Automatic identification of the boundaries of significant structure (segmentation) within a medical image is an are of ongoing research. Various approaches have been proposed but only two methods have achieved widespread use: manual delineation of boundaries and segmentation using intensity values. In this paper we describe an approach based on image registration. A reference image is prepared and segmented, by hand or otherwise. A patient image is registered to the reference image and the mapping then applied to ther reference segmentation to map it back to the patient image. In general a high-resolution nonlinear mapping is required to achieve accurate segmentation. This paper describes an algorithm that can efficiently generate such mappings, and outlines the uses of this tool in two relevant applications. An important feature of the approach described in this paper is that the algorithm is independent of the segmentation problem being addresses. All knowledge about the problem at hand is contained in files of reference data. A secondary benefit is that the continuous three-dimensional mapping generated is well suited to the generation of patient-specific numerical models (e.g. finite element meshes) from the library models. Smoothness constraints in the morphing algorithm tend to maintain the geometric quality of the reference mesh.     

RDCI, the vasoactive intestinal peptide receptor: a candidate gene for the features of Albright hereditary osteodystrophy associated with deletion of 2q37.

Albright hereditary osteodystrophy (AHO) is an autosomal dominant disorder characterised by the presence of brachymetaphalangism, short stature, obesity, and mental retardation. Variable biochemical changes many represent either pseudohypoparathyroidism (PHP) owing to resistance to parathormone (PTH) or pseudopseudohypoparathyroidism (PPHP) with no hormone resistance. In most cases of AHO, reduced levels of Gs alpha have been found and a number of deactivating mutations in the gene for Gs alpha located on chromosome 20q13 have been described. Recently a number of people with an AHO-like phenotype have been reported in whom a deletion of chromosomal region 2q37 has been found in the absence of biochemical abnormalities or a reduction in Gs alpha activity. We present a further female patient with a cytogenetically visible deletion of 2q37, an AHO-like phenotype, and unusual biochemistry suggesting moderate PTH resistance. The vasoactive intestinal peptide receptor (RDCI) has recently been mapped to 2q37 and we propose that this is a candidate gene, hemizygosity of which affects signal transduction and leads to the AHO-like phenotype found in patients with 2q37 deletions.     

Patterns of reactivity to lipid transfer proteins of plant foods and Artemisia pollen: an in vivo study

BACKGROUND: Lipid transfer proteins (LTPs) are major allergens of Rosaceae fruits in the Mediterranean area. IgE-cross-reactivity has been demonstrated in vitro among LTPs from peach, apple, chestnut and Artemisia pollen. The aim of this study was to evaluate the reactivity to LTPs from peach, apple, chestnut and Artemisia pollen by means of skin prick tests (SPTs). METHODS: Forty-seven patients allergic to peach (peach group), 20 patients sensitized to Artemisia pollen with no food allergies (Artemisia group), and 12 control subjects were skin tested with fresh peach, as well as with whole extracts and purified LTPs of peach, apple, chestnut and Artemisia pollen. RESULTS: The rates of positive SPTs for peach, apple, chestnut and Artemisia LTPs were, respectively, 91, 77, 23, and 36% in the peach group, and 30, 5, 15 and 40% in the Artemisia group. No response was observed in the control subjects. SPTs with peach LTP strongly correlated with SPTs conducted with fresh peach. In the peach group, the most frequent pattern of reactivity to LTPs was the combination peach-apple (45%), followed by peach-apple-Artemisia-chestnut (21%). Significant correlations were found between peach and apple LTPs, and between Artemisia and chestnut LTPs. Positive SPTs to chestnut LTP were only observed in patients with positive SPTs to Artemisia LTP. All the patients with positive case histories to chestnut reacted to chestnut LTP. CONCLUSIONS: LTPs are plant panallergens with different patterns of cross-reactivity. They are major allergens of Rosaceae fruits and seem to be involved in allergic reactions to unrelated foodstuffs such as chestnut, probably through sensitization to the cross-reactive Artemisia LTP. Rosaceae LTPs could be useful tools for in vivo diagnosis of Rosaceae fruit allergy.     

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling

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Rabies virus glycoprotein pseudotyping of lentiviral vectors enables retrograde axonal transport and access to the nervous system after peripheral delivery

In this report it is demonstrated for the first time that rabies-G envelope of the rabies virus is sufficient to confer retrograde axonal transport to a heterologous virus/vector. After delivery of rabies-G pseudotyped equine infectious anaemia virus (EIAV) based vectors encoding a marker gene to the rat striatum, neurons in regions distal from but projecting to the injection site, such as the dopaminergic neurons of the substantia nigra pars compacta, become transduced. This retrograde transport to appropriate distal neurons was also demonstrated after delivery to substantia nigra, hippocampus and spinal cord and did not occur when vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped vectors were delivered to these sites. In addition, peripheral administration of rabies-G pseudotyped vectors to the rat gastrocnemius muscle leads to gene transfer in motoneurons of lumbar spinal cord. In contrast the same vector pseudotyped with VSV-G transduced muscle cells surrounding the injection site, but did not result in expression in any cells in the spinal cord. Long-term expression was observed after gene transfer in the nervous system and a minimal immune response which, together with the possibility of non-invasive administration, greatly extends the utility of lentiviral vectors for gene therapy of human neurological disease.     

Visual field deficits in cats reared with cyclodeviations of the eyes

Summary Visual fields of ten cats which had one or both eyes rotated at 8 days of age were measured by two forms of perimetry and compared to visual fields of two normal cats and of four cats with monocular rotations at 16 days, 3 months or 6 months of age. All animals showed excellent localization of visual stimuli and responded to the actual location of stimuli in space rather than to the retinal locus normally associated with that location. In cats with monocular rotations, the field of the normal eye was always normal, extending from 90 ° ipsilateral to 30 ° contralateral. Cats with rotations of one eye at 3 or 6 months of age had essentially normal fields in the rotated eye as well, while cats with surgery at 8 or 16 days had restricted horizontal fields. They responded only to stimuli in the ipsilateral hemifield; they were blind in the contralateral hemifield. Their superior and inferior visual fields were normal. The field deficits related consistently to visual field coordinates and not to the angle or direction of rotation. In cats with binocular rotations the visual field of at least one eye extended across the midline. Thus, the extent of the field depended upon sensorimotor experiences of the cat both before and after surgery. It is argued that these monocular field deficits have a central origin, not a retinal one.When tested with both eyes open, seven of 14 experimental animals did not respond throughout the visual field seen by each eye alone. The total visual field with both eyes open was less than the sum of the two monocular fields; greatest losses were most pronounced in the extreme periphery of the field ipsilateral to the rotated eye. Since changes in eye position (e.g., convergence during bincocular viewing) were not observed, it is suggested that the binocular losses indicate suppression of the deviated eye which has a central origin.All animals were tested for visual following, visually-triggered extension (placing), and visually-guided reaching. Cats which had been routinely encouraged to use the rotated eye(s) by occlusion of the other eye showed skilful performance within a few weeks after surgery as previously reported by Peck and Crewther (1975), Mitchell et al. (1976) and others. In contrast, two cats reared with both eyes open after unilateral rotation in infancy were profoundly handicapped, as previously reported by Yinon (1975, 1976).This research was supported by Grant NS 14116 from the US Public Health Service     

A structural analysis of the carbohydrate side chains on class I and class II histocompatibility antigens of the swine facilitated by heteroantisera specific for the denatured polypeptides

Rabbit heteroantisera specific for the denatured glycoprotein subunits of swine class I and class II major histocompatibility complex (MHC) antigens have been prepared and utilized to monitor changes in the mobilities of these polypeptides on SDS-polyacrylamide gel electrophoresis subsequent to various deglycosylation procedures. This information, in combination with lectin reactivity patterns for the glycoproteins bound to nitrocellulose, has made it possible to define specific structural features of the MHC antigen-associated carbohydrate side chains. Both the class I heavy (alpha) chain and the class II light (beta) chain bear a single, N-linked, complex-type oligosaccharide which reacts with lentil lectin (LcH), but not concanavalin A (Con A); a reactivity pattern suggesting the possibility of a special triantennary structure. In contrast, the class II heavy (alpha) chains appear to possess two carbohydrate units, one an N-linked, LcH-reactive, complex-type side chain, and the other, an N-linked, Con A-reactive, high-mannose-type of oligosaccharide. The data suggest considerable homology between the swine and human MHC antigens with respect to the structure of their carbohydrate side chains. The analysis also serves to illustrate how antibodies specific for the denatured polypeptide backbone of individual glycoproteins, along with lectin reactivity patterns, can be used to extract structural information about the attached carbohydrate moieties using minimal amounts of partially purified glycoproteins.     

Adjuvant-independent immunization by immunotargeting antigens to MHC and non-MHC determinants in vivo.

Using avidin as a model protein antigen, and biotinylated monoclonal antibodies as a convenient means of forming stable complexes with avidin, we have investigated the adjuvant-independent immunization of three mouse strains, C57BL/6, C3H and (C57BL/6 x C3H)F1, with immunoconjugates targeted to different class II MHC and non-MHC sites. The results confirm the effectiveness of anti-I-Ak and anti-I-Ab immunoconjugates with respect to priming for secondary IgG responses in (H-2b x H-2k)F1 mice, while indicating a lack of response in strains which are homozygous for the targeted allele. In terms of non-MHC targets in the monocyte-macrophage lineage, neither anti-MAC-1 nor anti-MAC-2 immunoconjugates were effective in any of the three strains. However, the 33D1 anti-dendritic cell antibody gave significant responses in all three strains, with the F1 response being more than 10-fold greater than the anti-class II immunoconjugates in either strain. These findings indicate that immunotargeting a protein antigen to a non-MHC determinant on dendritic cells in vivo can be an effective means of inducing an adjuvant-independent serological response, and that this approach can have significant advantages over anti-class II MHC immunotargeting.