Automatic quantification of multi-modal rigid registration accuracy using feature detectors.

In radiotherapy, the use of multi-modal images can improve tumor and target volume delineation. Images acquired at different times by different modalities need to be aligned into a single coordinate system by 3D/3D registration. State of the art methods for validation of registration are visual inspection by experts and fiducial-based evaluation. Visual inspection is a qualitative, subjective measure, while fiducial markers sometimes suffer from limited clinical acceptance. In this paper we present an automatic, non-invasive method for assessing the quality of intensity-based multi-modal rigid registration using feature detectors. After registration, interest points are identified on both image data sets using either speeded-up robust features or Harris feature detectors. The quality of the registration is defined by the mean Euclidean distance between matching interest point pairs. The method was evaluated on three multi-modal datasets: an ex vivo porcine skull (CT, CBCT, MR), seven in vivo brain cases (CT, MR) and 25 in vivo lung cases (CT, CBCT). Both a qualitative (visual inspection by radiation oncologist) and a quantitative (mean target registration error-mTRE-based on selected markers) method were employed. In the porcine skull dataset, the manual and Harris detectors give comparable results but both overestimated the gold standard mTRE based on fiducial markers. For instance, for CT-MR-T1 registration, the mTREman (based on manually annotated landmarks) was 2.2 mm whereas mTREHarris (based on landmarks found by the Harris detector) was 4.1 mm, and mTRESURF (based on landmarks found by the SURF detector) was 8 mm. In lung cases, the difference between mTREman and mTREHarris was less than 1 mm, while the difference between mTREman and mTRESURF was up to 3 mm. The Harris detector performed better than the SURF detector with a resulting estimated registration error close to the gold standard. Therefore the Harris detector was shown to be the more suitable method to automatically quantify the geometric accuracy of multimodal rigid registration.

Regulation of virus neutralization and the persistent fraction by TRIM21.

Despite a central role in immunity, antibody neutralization of virus infection is poorly understood. Here we show how the neutralization and persistence of adenovirus type 5, a prevalent nonenveloped human virus, are dependent upon the intracellular antibody receptor TRIM21. Cells with insufficient amounts of TRIM21 are readily infected, even at saturating concentrations of neutralizing antibody. Conversely, high TRIM21 expression levels decrease the persistent fraction of the infecting virus and allows neutralization by as few as 1.6 antibody molecules per virus. The direct interaction between TRIM21 and neutralizing antibody is essential, as single-point mutations within the TRIM21-binding site in the Fc region of a potently neutralizing antibody impair neutralization. However, infection at high multiplicity can saturate TRIM21 and overcome neutralization. These results provide insight into the mechanism and importance of a newly discovered, effector-driven process of antibody neutralization of nonenveloped viruses.

A chemically modified antibody mediates complete eradication of tumours by selective disruption of tumour blood vessels.

BACKGROUND: The possibility of eradicating cancer by selective destruction of tumour blood vessels may represent an attractive therapeutic avenue, but most pharmaceutical agents investigated so far did not achieve complete cures and are not completely specific. Antibody conjugates now allow us to evaluate the impact of selective vascular shutdown on tumour viability and to study mechanisms of action. METHODS: We synthesised a novel porphyrin-based photosensitiser suitable for conjugation to antibodies and assessed anticancer properties of its conjugate with L19, a clinical-stage human monoclonal antibody specific to the alternatively spliced EDB domain of fibronectin, a marker of tumour angiogenesis. RESULTS: Here we show in two mouse model of cancer (F9 and A431) that L19 is capable of highly selective in vivo localisation around tumour blood vessels and that its conjugate with a photosensitiser allows selective disruption of tumour vasculature upon irradiation, leading to complete and long-lasting cancer eradication. Furthermore, depletion experiments revealed that natural killer cells are essential for the induction of long-lasting complete responses. CONCLUSIONS: These results reinforce the concept that vascular shutdown can induce a curative avalanche of tumour cell death. Immuno-photodynamic therapy may be particularly indicated for squamous cell carcinoma of the skin, which we show to be strongly positive for markers of angiogenesis.