Statistical modeling of the eye for multimodal treatment planning for external beam radiation therapy of intraocular tumors

Ocular anatomy and radiation-associated toxicities provide unique challenges for external beam radiation therapy. For treatment planning, precise modeling of organs at risk and tumor volume are crucial. Development of a precise eye model and automatic adaptation of this model to patients' anatomy remain problematic because of organ shape variability. This work introduces the application of a 3-dimensional (3D) statistical shape model as a novel method for precise eye modeling for external beam radiation therapy of intraocular tumors.

High interstitial fluid pressure is associated with low tumour penetration of diagnostic monoclonal antibodies applied for molecular imaging purposes

The human epithelial cell adhesion molecule (EpCAM) is highly expressed in a variety of clinical tumour entities. Although an antibody against EpCAM has successfully been used as an adjuvant therapy in colon cancer, this therapy has never gained wide-spread use. We have therefore investigated the possibilities and limitations for EpCAM as possible molecular imaging target using a panel of preclinical cancer models. Twelve human cancer cell lines representing six tumour entities were tested for their EpCAM expression by qPCR, flow cytometry analysis and immunocytochemistry. In addition, EpCAM expression was analyzed in vivo in xenograft models for tumours derived from these cells. Except for melanoma, all cell lines expressed EpCAM mRNA and protein when grown in vitro. Although they exhibited different mRNA levels, all cell lines showed similar EpCAM protein levels upon detection with monoclonal antibodies. When grown in vivo, the EpCAM expression was unaffected compared to in vitro except for the pancreatic carcinoma cell line 5072 which lost its EpCAM expression in vivo. Intravenously applied radio-labelled anti EpCAM MOC31 antibody was enriched in HT29 primary tumour xenografts indicating that EpCAM binding sites are accessible in vivo. However, bound antibody could only be immunohistochemically detected in the vicinity of perfused blood vessels. Investigation of the fine structure of the HT29 tumour blood vessels showed that they were immature and prone for higher fluid flux into the interstitial space. Consistent with this hypothesis, a higher interstitial fluid pressure of about 12 mbar was measured in the HT29 primary tumour via "wick-in-needle" technique which could explain the limited diffusion of the antibody into the tumour observed by immunohistochemistry.

Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease

Interleukin-8 (IL-8) activates neutrophils via the chemokine receptors CXCR1 and CXCR2. However, the airways of individuals with cystic fibrosis are frequently colonized by bacterial pathogens, despite the presence of large numbers of neutrophils and IL-8. Here we show that IL-8 promotes bacterial killing by neutrophils through CXCR1 but not CXCR2. Unopposed proteolytic activity in the airways of individuals with cystic fibrosis cleaved CXCR1 on neutrophils and disabled their bacterial-killing capacity. These effects were protease concentration-dependent and also occurred to a lesser extent in individuals with chronic obstructive pulmonary disease. Receptor cleavage induced the release of glycosylated CXCR1 fragments that were capable of stimulating IL-8 production in bronchial epithelial cells via Toll-like receptor 2. In vivo inhibition of proteases by inhalation of alpha1-antitrypsin restored CXCR1 expression and improved bacterial killing in individuals with cystic fibrosis. The cleavage of CXCR1, the functional consequences of its cleavage, and the identification of soluble CXCR1 fragments that behave as bioactive components represent a new pathophysiologic mechanism in cystic fibrosis and other chronic lung diseases.

Dynamic registration using ultrasound for anatomical referencing

This paper proposes methods to circumvent the need to attach physical markers to bones for anatomical referencing in computer-assisted orthopedic surgery. Using ultrasound, a bone could be non-invasively referenced, and so the problem is formulated as the need for dynamic registration. A method for correspondence establishment is presented, and the matching step is based on three least-squares algorithms: two that are typically used in registration methods such as ICP, and the third is a form of the Unscented Kalman filter that was adapted to work in this context. A simulation was developed in order to reliably evaluate and compare the dynamic registration methods

CT data-based navigation for post-mortem biopsy-a feasibility study

INTRODUCTION: Recent advances in medical imaging have brought post-mortem minimally invasive computed tomography (CT) guided percutaneous biopsy to public attention. AIMS: The goal of the following study was to facilitate and automate post-mortem biopsy, to suppress radiation exposure to the investigator, as may occur when tissue sampling under computer tomographic guidance, and to minimize the number of needle insertion attempts for each target for a single puncture. METHODS AND MATERIALS: Clinically approved and post-mortem tested ACN-III biopsy core needles (14 gauge x 160 mm) with an automatic pistol device (Bard Magnum, Medical Device Technologies, Denmark) were used for probe sampling. The needles were navigated in gelatine/peas phantom, ex vivo porcine model and subsequently in two human bodies using a navigation system (MEM centre/ISTB Medical Application Framework, Marvin, Bern, Switzerland) with guidance frame and a CT (Emotion 6, Siemens, Germany). RESULTS: Biopsy of all peas could be performed within a single attempt. The average distance between the inserted needle tip and the pea centre was 1.4mm (n=10; SD 0.065 mm; range 0-2.3 mm). The targets in the porcine liver were also accurately punctured. The average of the distance between the needle tip and the target was 0.5 mm (range 0-1 mm). Biopsies of brain, heart, lung, liver, pancreas, spleen, and kidney were performed on human corpses. For each target the biopsy needle was only inserted once. The examination of one body with sampling of tissue probes at the above-mentioned locations took approximately 45 min. CONCLUSIONS: Post-mortem navigated biopsy can reliably provide tissue samples from different body locations. Since the continuous update of positional data of the body and the biopsy needle is performed using optical tracking, no control CT images verifying the positional data are necessary and no radiation exposure to the investigator need be taken into account. Furthermore, the number of needle insertions for each target can be minimized to a single one with the ex vivo proven adequate accuracy and, in contrast to conventional CT guided biopsy, the insertion angle may be oblique. Navigation for minimally invasive tissue sampling is a useful addition to post-mortem CT guided biopsy.

Effect of chest compressions only during experimental basic life support on alveolar collapse and recruitment

AIM: The importance of ventilatory support during cardiac arrest and basic life support is controversial. This experimental study used dynamic computed tomography (CT) to assess the effects of chest compressions only during cardiopulmonary resuscitation (CCO-CPR) on alveolar recruitment and haemodynamic parameters in porcine model of ventricular fibrillation. MATERIALS AND METHODS: Twelve anaesthetized pigs (26+/-1kg) were randomly assigned to one of the following groups: (1) intermittent positive pressure ventilation (IPPV) both during basic life support and advanced cardiac life support, or (2) CCO during basic life support and IPPV during advanced cardiac life support. Measurements were acquired at baseline prior to cardiac arrest, during basic life support, during advanced life support, and after return of spontaneous circulation (ROSC), as follows: dynamic CT series, arterial and central venous pressures, blood gases, and regional organ blood flow. The ventilated and atelectatic lung area was quantified from dynamic CT images. Differences between groups were analyzed using the Kruskal-Wallis test, and a p<0.05 was considered statistically significant. RESULTS: IPPV was associated with cyclic alveolar recruitment and de-recruitment. Compared with controls, the CCO-CPR group had a significantly larger mean fractional area of atelectasis (p=0.009), and significantly lower PaO(2) (p=0.002) and mean arterial pressure (p=0.023). The increase in mean atelectatic lung area observed during basic life support in the CCO-CPR group remained clinically relevant throughout the subsequent advanced cardiac life support period and following ROSC, and was associated with prolonged impaired haemodynamics. No inter-group differences in myocardial and cerebral blood flow were observed. CONCLUSION: A lack of ventilation during basic life support is associated with excessive atelectasis, arterial hypoxaemia and compromised CPR haemodynamics. Moreover, these detrimental effects remain evident even after restoration of IPPV.

MARVIN: a medical research application framework based on open source software

This paper describes the open source framework MARVIN for rapid application development in the field of biomedical and clinical research. MARVIN applications consist of modules that can be plugged together in order to provide the functionality required for a specific experimental scenario. Application modules work on a common patient database that is used to store and organize medical data as well as derived data. MARVIN provides a flexible input/output system with support for many file formats including DICOM, various 2D image formats and surface mesh data. Furthermore, it implements an advanced visualization system and interfaces to a wide range of 3D tracking hardware. Since it uses only highly portable libraries, MARVIN applications run on Unix/Linux, Mac OS X and Microsoft Windows.