The diagnosis and management of patients with idiopathic osteolysis

Idiopathic osteolysis or disappearing bone disease is a condition characterized by the spontaneous onset of rapid destruction and resorption of a single bone or multiple bones. Disappearing bone disorder is a disease of several diagnostic types. We are presenting three patients with osteolysis who have different underlying pathological features. Detailed phenotypic assessment, radiologic and CT scanning, and histological and genetic testing were the baseline diagnostic tools utilized for diagnosis of each osteolysis syndrome. The first patient was found to have Gorham-Stout syndrome (non-heritable). The complete destruction of pelvic bones associated with aggressive upward extension to adjacent bones (vertebral column and skull base) was notable and skeletal angiomatosis was detected. The second patient showed severe and aggressive non-hereditary multicentric osteolysis with bilateral destruction of the hip bones and the tarsal bones as well as a congenital unilateral solitary kidney and nephropathy. The third patient was phenotypically and genotypically compatible with Winchester syndrome resulting in multicentric osteolysis (autosomal recessive). Proven mutation of the (MMP2-Gen) was detected in this third patient that was associated with 3MCC deficiency (3-Methylcrontonyl CoA Carboxylase deficiency). The correct diagnoses in our 3 patients required the exclusion of malignant osteoclastic tumours, inflammatory disorders of bone, vascular disease, and neurogenic arthropathies using history, physical exam, and appropriate testing and imaging. This review demonstrates how to evaluate and treat these complex and difficult patients. Lastly, we described the various management procedures and treatments utilized for these patients

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Purpose: The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation. Material and Methods: The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 mu m. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed. Results: GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders. Conclusion: In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney

Structural a priori information in near-infrared optical tomography

Recent interest in the use of dual modality imaging in the field of optical Near Infrared (NIR) Tomography has increased, specifically with use of structural information, from for example, MRI. Although MRI images provide high resolution structural information about tissue, they lack the contrast and functional information needed to investigate physiology, whereas NIR data has been established as a high contrast imaging modality, but one which suffers from low resolution. To this effect, the use of dual modality data has been shown to increase the qualitative and quantitative accuracy of clinical information that can be obtained from tissue. Results so far have indicated that providing accurate apriori structural information is available, such dual modality imaging techniques can be used for the detection and characterization of breast cancer in-vivo, as well as the investigation of brain function and physiology in both human and small animal studies. Although there has been much interest and research into the best suitable and robust use of a-priori structural information within the reconstruction of optical properties of tissue, little work has been done into the investigation of how much accuracy is needed from the structural MRI images in order to obtain the most clinically reliable information. In this paper, we will present and demonstrate the two most common application of a-priori information into image reconstruction, namely soft and hard priori. The effect of inaccuracies of the a-priori structural information within the reconstructed NIR images are presented showing that providing that the error of the a-priori information is within 20% in terms of size and location, adequate NIR images can be reconstructed.</p

Experimental investigation of perturbation Monte-Carlo based derivative estimation for imaging low-scattering tissue

Experimental results for imaging the low-scattering tissue phantoms based on the derivative estimation through perturbation Monte-Carlo (pMC) method are presented. It is proven that pMC-based methods give superior reconstructions compared to diffusion-based reconstruction methods. An easy way to estimate the Jacobian using analytical expression obtained from perturbation Monte-Carlo method is employed. Simulation studies on the same objects, considered in the experiment, are performed and corresponding results are found to be in reasonable agreement with the experimental studies. It is shown that inter-parameter cross talk in diffusion based methods lead to false results for the low-scattering tissue, where as the pMC-based method gives accurate results

Population differences in brain morphology: Need for population specific brain template

Brain templates provide a standard anatomical platform for population based morphometric assessments. Typically, standard brain templates for such assessments are created using Caucasian brains, which may not be ideal to analyze brains from other ethnicities. To effectively demonstrate this, we compared brain morphometric differences between T1 weighted structural MRI images of 27 healthy Indian and Caucasian subjects of similar age and same sex ratio. Furthermore, a population specific brain template was created from MRI images of healthy Indian subjects and compared with standard Montreal Neurological Institute (MNI-152) template. We also examined the accuracy of registration of by acquiring a different T1 weighted MRI data set and registering them to newly created Indian template and MNI-152 template. The statistical analysis indicates significant difference in global brain measures and regional brain structures of Indian and Caucasian subjects. Specifically, the global brain measurements of the Indian brain template were smaller than that of the MNI template. Also, Indian brain images were better realigned to the newly created template than to the MNI-152 template. The notable variations in Indian and Caucasian brains convey the need to build a population specific Indian brain template and atlas

Ovarian cancer targeted adenoviral-mediated mda-7/IL-24 gene therapy

Objective. We have previously shown that adenoviral-mediated melanoma differentiation-associated gene-7 (Ad.mda-7) therapy induces apoptosis in ovarian cancer cells. However, the apoptosis induction was low and directly correlated with infectivity of Ad.mda-7. The objective of this study was to derive ovarian cancer targeted infectivity-enhanced adenoviral vectors encoding mda-7 and evaluate their enhancement in therapeutic efficacy for ovarian carcinoma. Methods. Infectivity-enhanced adenoviral vectors encoding mda-7 Ad.RGD.mda-7 and Ad.RGD.pK7.mda-7 were derived by incorporation of RGD and or RGD and Pk7 motifs in the fiber knobs by genetic modification. Viruses were validated by PCR for presence of mda-7 and by Western blot for expression of MDA-7 protein. To test the enhancement of therapeutic efficacy of these viruses, a panel of human ovarian carcinoma cells, OV-4, HEY, SKOV3, SKOV3.ipl, were infected by either Ad.mda-7 or Ad.RGD.mda-7 and Ad.RGD.pK7.mda-7 or their respective control viruses and the cell killing was evaluated by crystal violet staining in vitro. Further, therapeutic efficacy was evaluated in vivo using human ovarian cancer xenograft mouse models. Results. Both Ad.RGD.pK7.mda-7 and Ad.RGD.mda-7 showed significant increase in cell killing in vitro compared to unmodified Ad.mda-7 with Ad.RGD.pK7.mda-7 showing highest cell killing. Further, Ad.RGD.pK7.mda-7 showed a significant increase in survival of mice bearing human ovarian cancer xenografts compared to Ad.mda-7 and other control groups. Conclusion. Infectivity-enhanced Ad.RGD.rnda-7 and Ad.RGD.pK7.mda-7 viruses significantly enhanced ovarian cancer tumor cell killing in vitro. Significant prolongation of survival by Ad.RGD.pK7.mda-7 in murine ovarian cancer models demonstrates the high clinical translational potential of these viruses for ovarian cancer therapy. (C) 2005 Elsevier Inc. All rights reserved