Advances and challenges in deformable image registration: From image fusion to complex motion modelling.

Over the past 20 years, the field of medical image registration has significantly advanced from multi-modal image fusion to highly non-linear, deformable image registration for a wide range of medical applications and imaging modalities, involving the compensation and analysis of physiological organ motion or of tissue changes due to growth or disease patterns. While the original focus of image registration has predominantly been on correcting for rigid-body motion of brain image volumes acquired at different scanning sessions, often with different modalities, the advent of dedicated longitudinal and cross-sectional brain studies soon necessitated the development of more sophisticated methods that are able to detect and measure local structural or functional changes, or group differences. Moving outside of the brain, cine imaging and dynamic imaging required the development of deformable image registration to directly measure or compensate for local tissue motion. Since then, deformable image registration has become a general enabling technology. In this work we will present our own contributions to the state-of-the-art in deformable multi-modal fusion and complex motion modelling, and then discuss remaining challenges and provide future perspectives to the field.

Labeling of microvessel density, lymphatic vessel density and potential role of proangiogenic and lymphangiogenic factors as a predictive/prognostic factors after radiotherapy in patients with cervical cancer.

INTRODUCTION: Angiogenesis, formation of a new blood vessel from the existing vascular network, is essential for tumor growth, progression and metastasis. Vascular endothelial growth factor (VEGF) has been identified to be one of the most important factors of angiogenesis. VEGF-C, a novel member of the family, is a relatively specific lymphangiogenic growth factor. It is tempting to suggest that cervical cancer is one of the most common malignancies in a woman's life. Its prognostic factors are tumor stage, lymph node status, histologic type, level of hemoglobin. However, little is known about prognostic or/and predictive significance of angiogenesis in cervical cancer. OBJECTIVE: This prospective study is an attempt to evaluate serum VEGF-A, VEGF-C, microvessel density (MVD), and lymphatic vessel density (LMVD) in cervical cancer and the correlations with clinicopathologic features. MATERIAL AND METHODS: Blood samples were collected from 58 patients affected by FIGO I-IV stage cervical cancer, who were admitted to the Department of Oncology and Brachytherapy Collegium Medicum in Bydgoszcz of Nicolaus Copernicus University. Serum VEGF-A/VEGF-C concentrate was determined by means of a quantitative sandwich enzyme immunoassay (ELISA). All tumor samples were taken from cross section during the first brachytherapy. Then they were examined by immunohistochemical studies with podoplanin antibody and anti-CD31 antibody. The present analysis was used to evaluate MVD and LMVD. RESULTS: The median serum VEGF-A was 734.76 pg/ml (range from 86.39 pg/ml - 2200.00 pg/ml), and VEGF-A was only correlated with after treatment hemoglobin concentration (p = 0.046, R = -0.3450). The median serum VEGF-C was 145.72 pg/ml (range 131.08 - 233.60 pg/ml). Serum VEGF-C levels measured in patients were associated with primary tumor size. We observed significantly higher serum VEGF-C in localized disease (FIGO I, II) in comparison to advanced tumors (232.44 pg/ml vs 152.45 pg/ml; p = 0.034). The median LMVD was 6.25 (range 3.5-10.0) and median blood vessel density was 12.5 (range 9.5-23.0). We found significantly higher lymphatic vessel density in patients with Gl/G2 grade of differentiation than in those with G3 (9.93 vs 6.25; p = 0.0398). We observed a statistically significant correlation between MVD and LMVD; (p = 0.032). CONCLUSION: In conclusion, our study suggests that serum VEGF-A, VEGF-C, LMVD and MVD play an important role in tumor growth and progression in cervical cancer. Nonetheless, further studies are essential to explore the underlying mechanism.

Primary cultures from rat vibrissae as a potential cell source for in vitro construction of urinary bladder wall grafts.

BACKGROUND: In vitro-constructed grafts can be used for human bladder augmentation. There are many diseases in which autologous cells cannot be used for this purpose. The aim of the present study was to examine the potential of rat vibrissae hair follicle cells to form cultures, which could serve as a source for in vitro creation of urinary bladder wall grafts. METHODS: Two hundred vibrissae were excised from young Wistar male rats. Two different digestions were performed, in dispase and in collagenase. All follicles were additionally incubated in trypsin and ethylenediamine tetraacetic acid. Two different culture media based on DMEM (Dulbecco's Modified Eagle's Medium) were used: the first was supplemented with keratinocyte growth factor (KGF) and the second with epidermal growth factor. Immunocytochemical detection of cytokeratin, CD34, p63, Ki-67 (proliferation index), and HMB45 (Human Melanoma Black 45) was performed. RESULTS: Forty-eight primary cultures of rat follicle vibrissae cells were established from 200 hair follicles (24% successful rate). Twenty-four primary cultures were obtained after dispase digestion and 24 after collagenase treatment. Each group was cultured in 2 different media. A heterogeneity of primary cultures was observed. Cells formed a monolayer within a period of 2 to 4 weeks. The 24 primary cultures established after dispase treatment exhibited monolayers of small cuboid cells expressing cytokeratin and CD34. In the 40th passage 20%-40% of cells expressed p63; 85% of these cells from late passages were positive for Ki-67, indicating preserved mitotic potential. Epithelial-like phenotype was observed after dispase digestion and cultivation in KGF-supplemented medium. After 3 weeks, the morphology of these cells changed into fibroblast-like. These cultures were negative for CD34. Fibroblast-like cell growth was observed after collagenase treatment in both KGF- and EGF-supplemented media. These cells were positive for the melanocyte cell marker (HMB45). CONCLUSIONS: Culture media and isolation conditions influence hair follicle stem cell differentiation. The stem cell niche within the hair follicles is a reservoir of cells, which can be potentially used for in vitro creation of urinary bladder wall grafts.

BRCA1-positive breast cancers in young women from Poland.

We identified 4316 unselected incident cases of early-onset breast cancers (<51 ears of age at diagnosis) in 18 Polish hospitals between 1996 and 2003. We were able to obtain a blood sample for DNA analysis from 3472 of these (80.4%). All cases were tested for the presence of three founder mutations in BRCA1. The proportion of cases with a BRCA1 mutation was 5.7%. The hereditary proportions were higher than this for women with breast cancer diagnosed before age 40 (9%), for women with cancer of medullary or atypical medullary histology (28%), for those with bilateral cancer (29%) or with a family history of breast or ovarian cancer (13%). It is reasonable to offer genetic testing to women with early-onset breast cancer in Poland.

Scaffold seeded with cells is essential in urothelium regeneration and tissue remodeling in vivo after bladder augmentation using in vitro engineered graft.

OBJECTIVE: Tissue-engineering methods using synthetic biodegradable scaffolds seeded with cells have potential to induce regeneration to a functional bladder wall. The aim of the study was to induce in vivo urothelial growth on implanted scaffolds previously seeded with stromal cells as compared with matrices implanted without cells for rat cystoplasty augmentation. MATERIALS AND METHODS: 3T3 mouse fibroblasts were multiplied up to total of 10(8) cells. Cells were grown on Dulbecco's modified essential medium supplemented with 10% of fetal bovine serum and antibiotics in CO(2) chambers. Cells were seeded on biodegradable polyglycolic acid (PGA) scaffolds in eight rats: four bladders were augmented with cell-seeded grafts and the other four with acellular scaffolds. Rats were sacrificed after 4 months in preparation for hematoxylin and eosin staining. RESULTS: One death in the acellular cystoplasty group was observed after 3 weeks. No epithelial layer was observed in the central part of the acellular graft. The cell-seeded grafts showed good visible multilayered epithelium with at least five layers of epithelial cells in the central part. The epithelium resembled rat native urothelium. The cell-seeded grafts showed a high degree of implanted 3T3 cells infiltration with good degradation of PGA fibers. CONCLUSIONS: Our data indicated that urothelial proliferation on PGA grafts was intensified using a "feeder layer" of fibroblasts.

Activity of cathepsin D and alpha(1)-antitrypsin in the blood serum of patients with mammary carcinoma.

UNLABELLED: THE AIM of this study was to determine the activity of cathepsin D and alpha(1)-antitrypsin in the blood serum of patients with mammary carcinoma. PATIENTS AND METHODS: The study was conducted on 52 women operated for a unilateral breast tumor, divided into two groups, according to the number of metastases and tumor size. Cathepsin D activity was determined using the method of Anson, while alpha(1)-antitrypsin activity was determined according to the Eriksson method. RESULTS: Both groups of patients with mammary carcinoma were found to have higher activity of cathepsin D before the treatment compared to healthy females. After the surgery the enzyme activity increased significantly, whereas 6 months after the surgery it generally decreased. The activity of alpha(1)-antitrypsin was significantly lower in patients before the treatment than in the controls, while after 6 months an increase in alpha(1)-antitrypsin activity was observed. The correlation between activity of cathepsin D and alpha(1)-antitrypsin was revealed. High enzyme activity and low alpha(1)-antitrypsin activity may result from the stage of neoplastic transformation. CONCLUSION: The determination of cathepsin D activity together with alpha(1)-antitrypsin activity may serve as useful biochemical marker in monitoring of malignant changes in breast tumor.

Comparison of photometric and weight estimation of Mycobacterium content in homogenous BCG cultures containing Tween 80.

A comparison of the weight and photometric methods of primary assay of BCG vaccine has been made, using a vaccine prepared in albumin-free medium but containing Tween 80. In the weight method, the bacteria were trapped on a membrane filter; for photometry a Pulfrich Elpho photometer and an instrument of Czech origin were used. The photometric results were the more precise, provided that the measurements were made within two days of completion of growth; after this time the optical density of the suspension began to decrease slowly. The lack of precision of the weighing method is probably due to the small weight of culture deposit (which was almost on the limit of accuracy of the analytical balance) and to difficulties in the manipulation of the ultrafilter.