Advanced image fusion algorithms for Gamma Knife treatment planning. Evaluation and proposal for clinical use.

Image fusion is a process of combining information from multiple sensors. It is a useful tool implemented in the treatment planning programme of Gamma Knife Radiosurgery. In this paper we evaluate advanced image fusion algorithms for Matlab platform and head images. We develop nine level grayscale image fusion methods: average, principal component analysis (PCA), discrete wavelet transform (DWT) and Laplacian, filter - subtract - decimate (FSD), contrast, gradient, morphological pyramid and a shift invariant discrete wavelet transform (SIDWT) method in Matlab platform. We test these methods qualitatively and quantitatively. The quantitative criteria we use are the Root Mean Square Error (RMSE), the Mutual Information (MI), the Standard Deviation (STD), the Entropy (H), the Difference Entropy (DH) and the Cross Entropy (CEN). The qualitative are: natural appearance, brilliance contrast, presence of complementary features and enhancement of common features. Finally we make clinically useful suggestions.     

Endovascular treatment of popliteal artery aneurysms.

OBJECTIVE: To present the results of the endovascular treatment of popliteal artery aneurysms. METHODS: From April 1999 to January 2002, 11 patients, aged 40-94 years, with 12 popliteal aneurysms were treated. Nine (75%) underwent an endoluminal repair, of whom three were done emergently due to an aneurysm rupture. Aneurysm diameter was 28-105 (mean 69) mm. A Hemobahn stent graft was inserted in six, Wallgraft in two and Passager in one case. RESULTS: During a mean follow-up of 14 (3-31) months, four (44%) thromboses occurred: two in the early postoperative period (30 days) and two during the late postoperative period. Two of the four occluded grafts were successfully reopened, and in the one a stenosis of the distal end of the stent graft was treated with balloon dilatation. Patency rates at 1 and 12 months were 64/47% (primary patency) and 88/75% (secondary patency), respectively. CONCLUSION: Initial experience with endovascular treatment of the popliteal aneurysm in high-risk patients yielded modest results. Larger number of patients and further follow-up time is necessary to evaluate the long-term results.     

Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate

We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on 2-nitropropane- induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.      

Imaging biomarkers of inflammation <Emphasis Type="Italic">in situ</Emphasis> with fun ctionalized quantum dots in the dextran sodium sulfate (DSS) model of mouse colitis

Objective and design: Myeloperoxidase (MPO) and proinflammatory cytokines play an important role in the development of inflammation. These markers are generally measured using tedious ELISA procedures. In this study, a novel technique utilizing antibody conjugated quantum dot nanoparticles was developed to detect Myeloperoxidase, Interleukin-1α (IL-1α) and Tumor Necrosis Factor-α (TNF-α) in vivo in the dextran sodium sulfate (DSS) model of experimental colitis. Materials and methods: Colitis was induced in animals (n = 8 animals/group) by feeding 4% DSS solution ad libitum for seven to eight days. Quantum Dots (QDs) exhibiting fluorescence at various wavelengths were conjugated to MPO, IL-1α and TNF-α polyclonal antibodies and tested in vivo at various stages of colitis. Tissue sections obtained were imaged with confocal microscope. The image intensity obtained from the tissue specimen was correlated with clinical activity measured as Disease Activity Index (DAI). Results: Myeloperoxidase, IL-1α and TNF-α were visualized with quantum dots on various days of disease. The intensity of quantum dots increased with the increase in inflammation. The increase in intensity showed an excellent correlation with the DAI based on the clinical parameters. Conclusion: The study demonstrated that multiple biomarkers can be detected simultaneously and their quantitative expression correlated well with clinical disease severity. This novel technology should facilitate design of a novel optical platform for imaging various biomarkers of inflammation, early detection of acute and chronic disease markers and inflammation-mediated cancer markers. This detection may also facilitate determination of therapeutic success. Received 14 March 2007; returned for revision 8 May 2007; accepted by M. Parnham 27 June 2007     

A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.