Quantitative Analysis of Geometry and Lateral Symmetry of Proximal Middle Cerebral Artery.

BACKGROUND: The purpose of our work is to quantitatively assess clinically relevant geometric properties of proximal middle cerebral arteries (pMCA), to investigate the degree of their lateral symmetry, and to evaluate whether the pMCA can be modeled by using state-of-the-art deformable image registration of the ipsi- and contralateral hemispheres. METHODS: Individual pMCA segments were identified, quantified, and statistically evaluated on a set of 55 publicly available magnetic resonance angiography time-of-flight images. Rigid and deformable image registrations were used for geometric alignment of the ipsi- and contralateral hemispheres. Lateral symmetry of relevant geometric properties was evaluated before and after the image registration. RESULTS: No significant lateral differences regarding tortuosity and diameters of contralateral M1 segments of pMCA were identified. Regarding the length of M1 segment, 44% of all subjects could be considered laterally symmetrical. Dominant M2 segment was identified in 30% of men and 9% of women in both brain hemispheres. Deformable image registration performed significantly better (P < .01) than rigid registration with regard to distances between the ipsi- and the contralateral centerlines of M1 segments (1.5 ± 1.1 mm versus 2.8 ± 1.2 mm respectively) and between the M1 and the anterior cerebral artery (ACA) branching points (1.6 ± 1.4 mm after deformable registration). CONCLUSIONS: Although natural lateral variation of the length of M1 may not allow for sufficient modeling of the complete pMCA, deformable image registration of the contralateral brain hemisphere to the ipsilateral hemisphere is feasible for localization of ACA-M1 branching point and for modeling 71 ± 23% of M1 segment.

A quantitative symmetry-based analysis of hyperacute ischemic stroke lesions in noncontrast computed tomography.

PURPOSE: Early identification of ischemic stroke plays a significant role in treatment and potential recovery of damaged brain tissue. In noncontrast CT (ncCT), the differences between ischemic changes and healthy tissue are usually very subtle during the hyperacute phase (< 8 h from the stroke onset). Therefore, visual comparison of both hemispheres is an important step in clinical assessment. A quantitative symmetry-based analysis of texture features of ischemic lesions in noncontrast CT images may provide an important information for differentiation of ischemic and healthy brain tissue in this phase. METHODS: One hundred thirty-nine (139) ncCT scans of hyperacute ischemic stroke with follow-up magnetic resonance diffusion-weighted (MR-DW) images were collected. The regions of stroke were identified in the MR-DW images, which were spatially aligned to corresponding ncCT images. A state-of-the-art symmetric diffeomorphic image registration was utilized for the alignment of CT and MR-DW, for identification of individual brain hemispheres, and for localization of the region representing healthy tissue contralateral to the stroke cores. Texture analysis included extraction and classification of co-occurrence and run-length texture-based image features in the regions of ischemic stroke and their contralateral regions. RESULTS: The classification schemes achieved area under the receiver operating characteristic [Az] ≈ 0.82 for the whole dataset. There was no statistically significant difference in the performance of classifiers for the data sets with time between 2 and 8 hours from symptom onset. The performance of the classifiers did not depend on the size of the stroke regions. CONCLUSIONS: The results provide a set of optimal texture features which are suitable for distinguishing between hyperacute ischemic lesions and their corresponding contralateral brain tissue in noncontrast CT. This work is an initial step toward development of an automated decision support system for detection of hyperacute ischemic stroke lesions on noncontrast CT of the brain.

The Xanthomonas campestris pv. vesicatoria Type-3 Effector XopB Inhibits Plant Defence Responses by Interfering with ROS Production.

The bacterial pathogen Xanthomonas campestris pv. vesicatoria 85-10 (Xcv) translocates about 30 type-3 effector proteins (T3Es) into pepper plants (Capsicum annuum) to suppress plant immune responses. Among them is XopB which interferes with PTI, ETI and sugar-mediated defence responses, but the underlying molecular mechanisms and direct targets are unknown so far. Here, we examined the XopB-mediated suppression of plant defence responses in more detail. Infection of susceptible pepper plants with Xcv lacking xopB resulted in delayed symptom development compared to Xcv wild type infection concomitant with an increased formation of salicylic acid (SA) and expression of pathogenesis-related (PR) genes. Expression of xopB in Arabidopsis thaliana promoted the growth of the virulent Pseudomonas syringae pv. tomato (Pst) DC3000 strain. This was paralleled by a decreased SA-pool and a lower induction of SA-dependent PR gene expression. The expression pattern of early flg22-responsive marker genes indicated that MAPK signalling was not altered in the presence of XopB. However, XopB inhibited the flg22-triggered burst of reactive oxygen species (ROS). Consequently, the transcript accumulation of AtOXI1, a ROS-dependent marker gene, was reduced in xopB-expressing Arabidopsis plants as well as callose deposition. The lower ROS production correlated with a low level of basal and flg22-triggered expression of apoplastic peroxidases and the NADPH oxidase RBOHD. Conversely, deletion of xopB in Xcv caused a higher production of ROS in leaves of susceptible pepper plants. Together our results demonstrate that XopB modulates ROS responses and might thereby compromise plant defence.

Novel registration-based framework for CT angiography in lower legs.

Proper subtraction and visualization of contrast-enhanced blood vessels in lower extremities using computed tomography angiography (CTA) is based on precise masking of all non-contrasted structures in the area, and it is the main prerequisite for correct diagnosis and decision on treatment for peripheral arterial occlusive disease (PAOD). Because of possible motion of patients during the CTA examination, precise elimination of non-contrasted tissues, including bones, calcifications, and soft tissue, is still very challenging for lower legs, that is, from knees to toes. We propose novel registration-based framework for detection and correction of the motion in lower legs, which typically occurs between and during CTA pre-contrast and post-contrast acquisitions. Within the framework, two registration cores are proposed as alternatives, and resulting CTA subtraction images are compared with Advanced Vessel Analysis considered one of the reference commercial tools among clinical applications for CTA of lower extremities. The CTA subtraction images of 55 patients examined for PAOD are evaluated visually by four expert observers on the Philips Extended Brilliance Workspace using four criteria assessing the overall robustness of tested methods. According to the complex evaluation, the proposed framework enabled valuable improvements of CTA examination of lower legs.

Registration of FA and T1-weighted MRI data of healthy human brain based on template matching and normalized cross-correlation.

In this work, we propose a new approach for three-dimensional registration of MR fractional anisotropy images with T1-weighted anatomy images of human brain. From the clinical point of view, this accurate coregistration allows precise detection of nerve fibers that is essential in neuroscience. A template matching algorithm combined with normalized cross-correlation was used for this registration task. To show the suitability of the proposed method, it was compared with the normalized mutual information-based B-spline registration provided by the Elastix software library, considered a reference method. We also propose a general framework for the evaluation of robustness and reliability of both registration methods. Both registration methods were tested by four evaluation criteria on a dataset consisting of 74 healthy subjects. The template matching algorithm has shown more reliable results than the reference method in registration of the MR fractional anisotropy and T1 anatomy image data. Significant differences were observed in the regions splenium of corpus callosum and genu of corpus callosum, considered very important areas of brain connectivity. We demonstrate that, in this registration task, the currently used mutual information-based parametric registration can be replaced by more accurate local template matching utilizing the normalized cross-correlation similarity measure.

Influence of RET/PTC1 and RET/PTC3 oncoproteins in radiation-induced papillary thyroid carcinomas on amounts of cytoskeletal protein species.

Radiation-induced human papillary thyroid carcinomas (PTCs) show a high prevalence of fusions of the RET proto-oncogene to heterologous genes H4 (RET/PTC1) and ELE1 (RET/PTC3), respectively. In contrast to the normal membrane-bound RET protein, aberrant RET fusion proteins are constitutively active oncogenic cytosolic proteins that can lead to malignant transformation of thyroid epithelia. To detect specific tumor-associated protein changes that reflect the effect of RET/PTC fusion proteins, we analyzed normal thyroid tissues, thyroid tumors of the RET/PTC1 and RET/PTC3 type and their respective lymph node metastases by a combination of high-resolution two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-mass spectrometry. PTCs without RET rearrangements served as controls. Several cytoskeletal protein species showed quantitative changes in tumors and lymph node metastases harboring RET/PTC1 or RET/PTC3. We observed prominent C-terminal actin fragments assumedly generated by protease cleavages induced due to enhanced amounts of the active actin-binding protein cofilin-1. In addition, three truncated vimentin species, one of which was proven to be headless, were shown to be highly abundant in tumors and metastases of both RET/PTC types. The observed protein changes are closely connected with the constitutive activation of RET-rearranged oncoproteins and reflect the importance to elucidate disease-related typical signatures on the protein species level.

Improved disparity based image processing in 3D CT subtractive angiography.

The paper describes a set of approaches and routines designed to improve results in CT based 3D subtractive angiography of lower extremities via better global locally defined image data registration. Starting from the generic concept of 3D disparity-based flexible registration, modifications of this idea are made founded on prior anatomical knowledge, as segmentation into individual bone areas, their rigid registration followed by constrained flexible registration, and flexible registration of soft tissue volumes. After final subtraction, fusion of the individually derived volumes into the full volume of extremities provides the medically assessable results. The level of detail in minor vessels, and continuity of vessels including those in direct contact with the bones, have been found much better clinically than those achieved by standard contemporary commercial software.

Detection and identification of tumor-associated protein variants in human hepatocellular carcinomas.

The proteomic approach is a valuable tool to detect and identify proteins that are associated with cancer. In previous investigations on experimentally induced rat hepatomas, we detected aldose reductase-like protein (ARLP) as a highly significant marker protein. Our present study was intended to look for the presence of similar tumor-associated marker proteins on human hepatocellular carcinomas (HCC). We found several novel tumor-associated protein variants that represent members of the aldo-keto reductase (AKR) superfamily. Human aldose reductase-like protein-1 (hARLP-1) was the most prominent tumor-associated AKR member detected in HCC by 2-dimensional electrophoresis (2-DE) and identified by mass spectrometric fingerprinting. The enzyme was found in 4 distinct forms (hARLP-1, 36/7.4 (kd/pI); hARLP-2, 36/7.2; hARLP-3, 36/6.4; and hARLP-4, 33/7.35). In addition, a human aldose reductase-like protein (hARLP-5, 36/7.6) was identified that differed from hARLP-1 by 1 amino acid (D313N), indicating 2 allelic forms of the human aldose reductase-like gene. A novel antibody directed against common parts of the hARLPs revealed hARLP reactivity in human HCC by immunohistochemistry. Furthermore, aldose reductase (AR) was identified and characterized as a tumor-associated variant. In conclusion, in all investigated human HCCs at least one of the various types of the described tumor-associated proteins of the AKR superfamily was clearly present. Of these HCC samples, 95% were positive for hARLPs as proven by 2-DE analysis and/or by use of the antibody directed against hARLP. Thus, hARLP is a strong candidate for use as an immunohistochemical diagnostic marker of human HCC.

Generalized crystal-storing histiocytosis associated with monoclonal gammopathy: molecular analysis of a disorder with rapid clinical course and review of the literature.

Crystal-storing histiocytosis (CSH) is a rare event in disorders associated with monoclonal gammopathy. The intracellular crystal formation is almost always accompanied by the expression of kappa light chains. However, the exact mechanism for the storage has not been clarified until now. We report a case of generalized CSH in a 73-year-old man who presented with IgA kappa paraproteinemia and paraproteinuria. The initially observed CSH in the bone marrow biopsy was associated with the clinical and pathomorphologic features of a monoclonal gammopathy of undetermined significance. The progression of disease could not be affected by steroid therapy and the patient died of septic shock 7 months after detection of CSH. At the time of autopsy there was evidence for multiple myeloma and generalized CSH. Two-dimensional gel electrophoresis of liver tissue combined with immunoblotting revealed the massive storage of heavy chains of alpha type and light chains of kappa type, each in a monoclonal pattern. Analysis of the stored kappa light chain by nanoelectrospray-ionization mass spectrometry indicated that it belongs to the variable (kappa)I variability subgroup. We identified some unusual amino acid substitutions including Leu59, usually important for hydrophobic interactions within a protein, at a position where it has never been previously described in plasma cell disorders. In conclusion, we present the first case of CSH with molecular identification of the stored kappa subgroup and detection of unusual amino acid substitutions. Our results suggest that conformational alterations induced by amino acid exchanges represent a crucial pathogenic factor in CSH.