Semantic localization-driven partial image retrieval in CT series.

BACKGROUND: Picture archiving and communication systems (PACS) contain very large amounts of computed tomography (CT) data. When querying a PACS for a particular series, the user is often not interested in the complete series but in a certain region of interest (ROI), described e.g. by an example view in another series or an anatomical concept. OBJECTIVES: Restricting a retrieval query to such an ROI saves both loading time and navigational effort. In this paper, we propose an efficient method for defining and retrieving ROIs. METHODS: We employ interpolation and regression techniques for mapping the slices of a series to a newly generated standardized height atlas of the human body. RESULTS: Examinations of the accuracy and the saved input/output (I/O) costs of our new method on a repository of 1,360 CT series demonstrate the advantages of our system. Depending on the scope of the retrieval query, we can economize up to 99% of the total loading time. CONCLUSION: Our proposed method for flexible, context-based, partial image retrieval enables the user to directly focus on the relevant portion of the image material and it targets the high potential of I/O cost reduction of a common PACS.

Nearest neighbor classification in 3D protein databases.

In molecular databases, structural classification is a basic task that can be successfully approached by nearest neighbor methods. The underlying similarity models consider spatial properties such as shape and extension as well as thematic attributes. We introduce 3D shape histograms as an intuitive and powerful approach to model similarity for solid objects such as molecules. Errors of measurement, sampling, and numerical rounding may result in small displacements of atomic coordinates. These effects may be handled by using quadratic form distance functions. An efficient processing of similarity queries based on quadratic forms is supported by a filter-refinement architecture. Experiments on our 3D protein database demonstrate the high classification accuracy of more than 90% and the good performance of the technique.

Solvent accessible surface representation in a database system for protein docking.

Protein docking is a new and challenging application for query processing in database systems. Our architecture for an efficient support of docking queries is based on the multistep query processing paradigm, a technique well-known from spatial database system. Along with physicochemical parameters, the geometry of the molecules plays a fundamental role for docking retrieval. Thus, 3D structures and 3D surfaces of molecules are basic objects in molecular databases. We specify a molecular surface representation based on topology, define a class of neighborhood queries, and sketch some applications with respect to the docking problem. We suggest a patch-based data structure called the TriEdge structure, first, to efficiently support topological query processing, and second, to save space in comparison to common planar graph representations such as the quad-edge structure. In analogy to the quad-edge structure, the TriEdge structure has an algebraic interface and is implemented via complex pointers. However, we achieve a reduction of the space requirement by a factor of four. Finally, we investigate the time performance of our prototype.

Autoradiography of lymph nodes with 99mTc-dextran in rabbits.

99mTc-dextran (D) was further evaluated in the present study as a lymphoscintigraphic agent compared to radiocolloids. It was injected intra-dermally into the web space between the second and third toes in both hind feet of two rabbits. 99mTc-nanocolloid (NC) was injected subcutaneously in both hind feet of two other rabbits. Popliteal lymph nodes were taken out and frozen in liquid nitrogen after the animals were sacrificed at 2 h post-injection. Three frozen sections in 10 microns thickness were prepared from each node for autoradiographic studies. The lymph node slices were exposed for 18 h using Ilford G 5 emulsion. The obtained autoradiographs showed that the distribution of 99mTc-D radioactivity within lymph nodes was more uniform indicating better tissue penetration compared to 99mTc-NC which remained mostly in the lymph canaliculi.

Curative radioimmunotherapy of human mammary carcinoma xenografts with iodine-131-labeled monoclonal antibodies.

The radioiodinated monoclonal antibody BW 495/36 showed an exceptionally high uptake and long residence time in human ductal mammary carcinoma xenografts in nude mice. There was a mean tumor uptake of 82%/g 24 hr p.i., decreasing with a biologic half-life of approximately 6 days, to 15%/g by Day 16. The tumor-to-blood ratio increased from 2.8 to 21.4 and the percentage of the whole-body retention recovered in the tumor from 47% to 80% during the same time interval. The therapeutic efficiency of two injections of 7.4 MBq 131I-BW 495/36 was evaluated by comparing the tumor size with that in mice injected with either the same amount of the unlabeled MoAb, the same radioactivity of an 131I-labeled nonspecific MoAb, or with saline only. The high tumor accumulation of 131I-BW 495/36 led to a total tumor dose of 77 Gy resulting in a mean reduction in tumor diameter of 50%, corresponding to a reduction in tumor volume of 88% within 42 days p.i. Unlabeled MoAb had no effect on tumor growth compared with controls, whereas 131I nonspecific antibody caused a slight inhibition of tumor growth. Histologic tumor sections showed large areas of necrosis and a pronounced vacuolation of the tumor cell cytoplasm between Days 7 and 30 p.i. By Day 42 all remaining tissue in the tumor was identified as mouse connective tissue.

Improved radioimmunoscintigraphy of human mammary carcinoma xenografts after injection of an anti-antibody.

The low tumor-to-background ratio obtained after administration of radiolabeled whole monoclonal antibodies (MAbs) is one of the major problems in immunoscintigraphy and -therapy. To reduce the blood pool label caused by the circulation of radiolabeled MAb we have investigated the advantage of injecting an anti-antibody after administration of a tumor-specific MAb in nude mice bearing human mammary carcinoma xenografts. The MAb MA 10-11 of rat origin, used in these studies, had shown a high affinity to human mammary carcinoma tissue on frozen sections and low cross-reactivity with various normal human tissues. 24 h after injection of 1.5 MBq 131I-labeled MAb containing 10 micrograms IgG2a one group of mice received an additional injection of 100 micrograms anti-rat antibody. Blood taken 2 min after the second antibody injection showed nearly the whole activity bound to antibody aggregates, that cleared very rapidly from the circulation and accumulated in liver and spleen. The transitory high liver activity decreased within several hours because of rapid deiodination of the antibody-complex in this organ. The release of radioactivity from the spleen, however, was found to be much slower. The rapid excretion of the radioactivity from the blood pool combined with a nearly constant tumor activity allowed early tumor detection with tumor-to-blood ratios of 250:1 at 48 h after anti-antibody injection compared to 1.1:1 obtained for the control animals. In addition the results may explain the reported reduction of imaging quality and high uptake of radioactivity in the spleen of patients having repeated injections of mouse MAbs due to complex formation after development of human anti-mouse antibodies.

Measurement of myocardial fatty acid metabolism: kinetics of iodine-123 heptadecanoic acid in normal dog hearts.

To define the potential of iodine-123 heptadecanoic acid (IHA) for the noninvasive assessment of myocardial fatty acid metabolism with gamma camera imaging, the influence of myocardial oxygen consumption (MVO2) and blood flow (MBF) on extraction and half-times of IHA were investigated in dogs. Following IHA injection into the left circumflex coronary artery, extraction fraction and half-times were derived from the peak and slope of the IHA time activity curve, which consisted of a vascular, early, and late phase. Single-pass extraction fraction of IHA averaged 0.53 +/- 0.11 s.d. at control and was not influenced by MVO2 and MBF. The half-time of the early phase (T = 9.3 min +/- 2.8 s.d. in controls) as well as the ratio between the size of the early and late phase increased with MVO2 (r = 0.82, r = 0.87, respectively). Thus, early phase intracellular turnover of IHA increased, yet clearance of 123I activity was slowed by augmented cardiac work. Preliminary data of HPLC and electrophoretic analysis of myocardial arterial and venous blood samples over time indicate that the early phase is characterized by a decreasing washout of IHA and a relative increase of radioiodine washout. The half-time of the late phase (T = 245 min +/- 156 s.d. at control) was not related to MVO2 and MBF. In conclusion, myocardial fatty acid metabolism cannot be measured from the half-time of the early phase but might be analyzed from the ratio between the size of the early and late phase when using IHA.

Comparative distribution on niobium-95 in maternal and fetal rats and rabbits.

Pregnant rats and rabbits were injected with Nb95 towards the end of gestation. In rats, all maternal tissues showed higher concentrations compared to the fetal organs; the highest ratio was 0.6 in bone. In rabbits a different distribution was found. The fetal bone exhibited a 3.5 times higher concentration of Nb95 than the maternal one.

The ingrowth quota of autologous spongiosa from different points of removal--experimental study in sheep. A preliminary report.

The importance of the point of removal for the ingrowth quota of autologous spongiosa was examined in seven sheep. In six sheep spongiosa was taken from five different regions (proximal radius, olecranon, pelvic crest, trochanter major, and proximal tibia) and was transplanted autologously. Defined corticalis defects of the tibia were the chosen sites for the heterotopic implantations. The ingrowth quota were tested by X-ray as well as scintigraphically, histologically, and fluorescent-microscopically; one animal was taken for control. A judgement was made by quantifying scintigraphy and fluorescent-microscopic histometry. Better ingrowth quota were found for spongiosa from the pelvic crest, proximal tibia, and trochanter major as compared to qualitatively clearly worse transplants from radius base and olecranon. The results from the animal experiments prove the clinical experience.

Performance of two new solid-phase ligand assays for TSH using monoclonal antibodies.

Three ligand assays for TSH using monoclonal antibodies, an IRMA, an ELISA and a DELFIA were compared with a standard DAB RIA technique. The IRMA proved to be superior in respect to sensitivity, precision, reproducibility and practicality. The highest sensitivity yet, was achieved by DELFIA. IRMA, ELISA and DELFIA are performable on a daily routine basis. ELISA and DELFIA have the additional advantage of being non-isotopic immunoassays (NIIA). Under routine conditions IRMA reveals the best discrimination of hyperthyroid from euthyroid patients by basal TSH. This fact improves the TSH determination's clinical value considerably and may in the future--if confirmed--change the diagnostic schemes in use at present, e.g. rendering most of the TRH-tests unnecessary.

Uptake mechanism of interstitially injected 99mTc-labeled antimony trisulphide colloid in the popliteal lymph node of rabbits.

The right popliteal lymph node was studied in rabbits by well counting, histoautoradiography and electron microscopy, after interstitial injection of 99mTc-labeled antimony trisulphide (Sb2S3) colloid into the right hind pad. The highest radioactivity concentration (96.8%/g) was measured 6 hr following injection. At 24 hr, the concentration had dropped to nearly half of the maximum (51.5%/g). At each time, only a single or a few lymph node sectors were found to contain 99mTc. Initially, the radioactivity distribution pattern in the draining lymph node was stripy. Beginning at 15 min p.i., there was a progressive change from stripy to focal radioactivity distribution pattern. Until 6 hr after injection, the bulk of radioactivity was trapped by macrophages in the lumen and wall of the lymph node sinus system, predominantly in medullary sinuses. Surprisingly, at 24 hr the majority of labeled cells were eosinophilic polymorphonuclear leukocytes located in medullary sinuses and medullary cords. Up to 24 hr p.i., no accumulation of radioactivity could be detected in the cortical and paracortical lymph node parenchyma. In conclusion, interstitially injected 99mTc-Sb2S3 colloid is not homogeneously but sectorially distributed in the draining lymph node. Moreover, both macrophages and eosinophilic polymorphonuclear leukocytes are involved in the filtration process.

Evaluation of 99mTc-dextran as a lymphoscintigraphic agent in rabbits.

Dextran (clinical grade, average mol. wt. 82,200) was labelled with 99mTc and the labelling efficiency was checked by paper and thin-layer chromatography and electrophoresis. The amount of free 99mTcO-4 was always less than 1%. The radiopharmaceutical was injected ID into the web space in hind legs of ten rabbits (200-600 microCi/0.05 ml). Scintigrams were taken at 10-min intervals up to 3 h in three rabbits. The injection site and the hind legs were massaged after injection in the other seven rabbits and scintigrams were taken at 10-min intervals up to 2 h. Blood samples were obtained at 5, 15, 30, 90 and 120 min in both groups. In addition a 180-min sample was also taken in the first group. At the end of the study the rabbits were killed and the popliteal lymph nodes and the organs were removed to be weighed and counted. Our results indicated a high concentration of radioactivity in the popliteal lymph nodes and massage at the injection site increased the average uptake of the popliteal lymph node from 1.12% +/- 0.77% to 4.28% +/- 1.57% at 3 and 2 h, respectively (P less than 0.001). In scintigrams the lymph channels and the nodes were very well visualised. The blood radioactivity levels were too low to present a background problem. With massage 30% of the injected dose was removed from the injection site in 2 h. We have shown that 99mTc-dextran is a good radiopharmaceutical for the visualisation of the lymph system and deserves further experimental and clinical studies.

Correlations between the degree and type of forebrain malformations and the simultaneous neuro-oncogenic properties of ethylnitrosourea after diaplacental exposure in rats, alone and in combination with X-irradiation.

Single and combined treatments were performed in rats on day 13 of gestation with either ENU or ENU subsequent to various X-irradiation doses between 0.5 and 1.5 Gy. At this time of gestation, developmental anomalies of the brain are still inducible by any of these treatments, in addition to neurocarcinogenic effects after ENU alone or in combination with X-irradiation. We looked for correlations between the degree of brain malformations still detectable in the adult animals and the simultaneous occurrence of brain tumors. These evaluations were based on a histopathological analysis regarding the type and degree of malformation residues, as well as the type and distribution pattern of the tumors (especially regarding gliomas) within the forebrain. Both after ENU and X-irradiation plus ENU-treatment, the occurrence of glioma in the offspring was positively correlated with the degree of brain dysplasia. This effect was not only restricted to the total glioma incidence but also confirmed by the higher glioma multiplicity in major dysplastic brains. Additionally, gliomas were preferentially located within the subependymal layer, which simultaneously was most severely affected by the teratogenic effects after prenatal treatment. Although forebrain dysplasia generally presents a significant predisposition for glioma inducibility, this oncogenic event is apparently strictly inversely related to a certain type of forebrain malformation, namely the occurrence of heterotopic neuronal nodules within the telencephalic roof. They emerge from "rosettes," which are typical radiation lesions occurring only after doses above 1.0 Gy. In none of the forebrains which still revealed rosette-residues in later life could a simultaneous occurrence of gliomas be observed. This explains not only the substantial decrease of glioma incidence after combined treatment with 1.0 and 1.5 Gy X-irradiation doses, but also the consistent glioma multiplicity despite the decrease of frequency.

Transfer and distribution of niobium-95 in adult, fetal, and newborn rats after injection during pregnancy.

Following i.v. injection of Nb-95 into pregnant rats, fetuses and newborns were dissected and measured for radioactivity after several time intervals. At any time only a small quantity of the administered radioactivity was transferred to fetus and newborn and the fetal tissue concentrations were always lower than the maternal ones. The highest ratio (0.6) between fetal and maternal tissue concentrations was found in bone.

Embryotoxicity of 5-azacytidine in mice. Phase- and dose-specificity studies.

The agent 5-azacytidine, which directly affects nucleic acid metabolism, is a potent teratogen in NMRI mice. The establishment of general teratological data revealed clear-cut dose-response relationships after administration of this agent on either day 12 or day 14 of gestation. Inspection of skeletal abnormalities revealed a clear-cut phase specificity of this drug when administered on days 10 or 11 of pregnancy. Additional histological studies showed that central nervous system anomalies were induced mainly after administration of azacytidine on days 10, 11, 12, or 13 of pregnancy. A most conspicuous finding was the formation of anomalous glioblast islets within the ventricular zone covering the basal ganglia. The latter malformation mainly occurred after treatment on day 11 or 12 of pregnancy. Another important malformation syndrome was the appearance of capillary ectasias and hind paw hematomas, together with an intense necrotic cardiomyopathy after treatment on either day 11 or 12 of gestation.

Biokinetics and metabolism of radiogallium.

The large number of publications dealing with biokinetics, metabolism and factors influencing tissue uptake of 67Ga-citrate could not clarify the mechanism responsible for the uptake of this compound into tumor tissue. The present paper reviews biokinetic data obtained from clinical investigations and animal experiments and briefly points out some possible pathways of the mechanism for gallium localisation in tumors as well as in abscesses and inflammatory lesions.