Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model

The only curative treatment for patients with liver metastases to date is surgery, but few patients are suitable candidates for hepatic resection. The majority of patients will have to rely on other treatment modalities for palliation. Photodynamic therapy (PDT) could be a selective, minimally invasive treatment for patients with liver metastases. We studied PDT in an implanted colon carcinoma in the liver of Wag/Rij rats, using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). mTHPC tissue kinetics were studied using ex vivo extractions and in vivo fluorescence measurements. Both methods showed that mTHPC kinetics were different for liver and tumour tissue. After initial high levels at 4 h after administration (0.1 and 0.3 mg kg−1) mTHPC in liver tissue decreased rapidly in time. In tumour tissue no decrease in photosensitizer levels occurred, with mTHPC remaining high up to 48 h after administration. Both concentration data and fluorescence data showed an increase in tumour to liver ratios of up to 6.3 and 5.0 respectively. Illumination with 652 nm (15 J) resulted in extensive damage to tumour tissue, with necrosis of up to 13 mm in diameter. Damage to normal liver tissue was mild and transient as serum aspartate aminotransferase and alanine aminotransferase levels normalized within a week after PDT treatment. Long-term effects of mTHPC-PDT were studied on day 28 after treatment. Regardless of drug dose and drug–light interval, PDT with mTHPC resulted in complete tumour remission in 27 out of 31 treated animals (87%), with only four animals in which tumour regrowth was observed. Non-responding tumours proved to be significantly larger (P < 0.001) in size before PDT treatment. This study demonstrates that mTHPC is retained in an intrahepatic tumour and that mTHPC-PDT is capable of inducing complete tumour remission of liver tumours. © 1999 Cancer Research Campaig

In vivo quantification of photosensitizer fluorescence in the skin-fold observation chamber using dual-wavelength excitation and NIR imaging

A major challenge in biomedical optics is the accurate quantification of in vivo fluorescence images. Fluorescence imaging is often used to determine the pharmacokinetics of photosensitizers used for photodynamic therapy. Often, however, this type of imaging does not take into account differences in and changes to tissue volume and optical properties of the tissue under interrogation. To address this problem, a ratiometric quantification method was developed and applied to monitor photosensitizer meso-tetra (hydroxyphenyl) chlorin (mTHPC) pharmacokinetics in the rat skin-fold observation chamber. The method employs a combination of dual-wavelength excitation and dualwavelength detection. Excitation and detection wavelengths were selected in the NIR region. One excitation wavelength was chosen to be at the Q band of mTHPC, whereas the second excitation wavelength was close to its absorption minimum. Two fluorescence emission bands were used; one at the secondary fluorescence maximum of mTHPC centered on 720 nm, and one in a region of tissue autofluorescence. The first excitation wavelength was used to excite the mTHPC and autofluorescence and the second to excite only autofluorescence, so that this could be subtracted. Subsequently, the autofluorescence-corrected mTHPC image was divided by the autofluorescence signal to correct for variations in tissue optical properties. This correction algorithm in principle results in a linear relation between the corrected fluorescence and photosensitizer concentration. The limitations of the presented method and comparison with previously published and validated techniques are discussed

Moving interdisciplinary science forward: integrating participatory modelling with mathematical modelling of zoonotic disease in Africa

This review outlines the benefits of using multiple approaches to improve model design and facilitate multidisciplinary research into infectious diseases, as well as showing and proposing practical examples of effective integration. It looks particularly at the benefits of using participatory research in conjunction with traditional modelling methods to potentially improve disease research, control and management. Integrated approaches can lead to more realistic mathematical models which in turn can assist with making policy decisions that reduce disease and benefit local people. The emergence, risk, spread and control of diseases are affected by many complex bio-physical, environmental and socio-economic factors. These include climate and environmental change, land-use variation, changes in population and people’s behaviour. The evidence base for this scoping review comes from the work of a consortium, with the aim of integrating modelling approaches traditionally used in epidemiological, ecological and development research. A total of five examples of the impacts of participatory research on the choice of model structure are presented. Example 1 focused on using participatory research as a tool to structure a model. Example 2 looks at identifying the most relevant parameters of the system. Example 3 concentrates on identifying the most relevant regime of the system (e.g., temporal stability or otherwise), Example 4 examines the feedbacks from mathematical models to guide participatory research and Example 5 goes beyond the so-far described two-way interplay between participatory and mathematical approaches to look at the integration of multiple methods and frameworks. This scoping review describes examples of best practice in the use of participatory methods, illustrating their potential to overcome disciplinary hurdles and promote multidisciplinary collaboration, with the aim of making models and their predictions more useful for decision-making and policy formulation

Toward an Open-Access Global Database for Mapping, Control, and Surveillance of Neglected Tropical Diseases

There is growing interest in the scientific community, health ministries, and other organizations to control and eventually eliminate neglected tropical diseases (NTDs). Control efforts require reliable maps of NTD distribution estimated from appropriate models and survey data on the number of infected people among those examined at a given location. This kind of data is often available in the literature as part of epidemiological studies. However, an open-access database compiling location-specific survey data does not yet exist. We address this problem through a systematic literature review, along with contacting ministries of health, and research institutions to obtain disease data, including details on diagnostic techniques, demographic characteristics of the surveyed individuals, and geographical coordinates. All data were entered into a database which is freely accessible via the Internet (http://www.gntd.org). In contrast to similar efforts of the Global Atlas of Helminth Infections (GAHI) project, the survey data are not only displayed in form of maps but all information can be browsed, based on different search criteria, and downloaded as Excel files for further analyses. At the beginning of 2011, the database included over 12,000 survey locations for schistosomiasis across Africa, and it is continuously updated to cover other NTDs globally

A method to improve the dose distribution of interstitial breast implants using geometrically optimized stepping source techniques and dose normalization

BACKGROUND AND PURPOSE: The standard linear source breast implant of our institution was compared with alternative linear source implant geometries and a stepping source implant, to evaluate the possibility of minimizing the treated volume. Normalization to a higher isodose than the conventional 85% of the mean central dose (MCD) was investigated for the stepping source implant to reduce the thickness of the treated volume and to increase dose uniformity. The purpose of this study was to develop an implant geometry yielding a high conformity and a more uniform dose distribution over the target volume. MATERIALS AND METHODS: The dose distributions of four implant geometries were compared for a planning target volume (PTV) of 48 cm(3). Implants #1 (standard) and #2 had linear sources arranged in a triangular pattern of equal lengths and lengths adapted to the shape of the PTV. Implants #3 and #4 were squared pattern arranged implants with linear sources and a stepping source with geometric optimized dwell times. The active lengths were adapted to the shape of the PTV. Using implant #4 for PTVs of different volumes, the reference dose (RD) was normalized to 85 and 91% of the MCD. RESULTS: Comparing implants #2, #3, and #4 with #1, the treated volume (V(100)) encompassed by the reference isodose was reduced by 22, 35, and 37%, respectively. The volumes receiving a dose of at least 125% (V(125)) of the reference dose was reduced by 16, 30, and 30%, respectively. The conformation number increased being 0.30, 0.39, 0.47, and 0.48 for implants #1, #2, #3, and #4, respectively. The average reduction of V(125) when the dose was normalized to 91% compared with 85% of the MCD was 18%. CONCLUSIONS: A conformal treatment to a PTV could be best achieved with a geometrically optimized stepping source plan with needles arranged in a squared pattern. Reduction of high dose volumes within the implant was obtained by normalizing the RD to 91% instead of 85% of the MC

Accuracy of internal mammary lymph node localization using lymphoscintigraphy, sonography and CT

BACKGROUND AND PURPOSE: An accurate internal mammary (IM) lymph node localization technique is required for proper irradiation of the IM lymph nodes in breast cancer patients. In this study the measurement accuracy of three techniques for direct or indirect localization of the IM nodes was estimated. MATERIALS AND METHODS: In 40 patients the IM lymph node depth and lateral distance from the patient midline were measured with lymphoscintigraphy in intercostal spaces 2, 3 and 4. The corresponding position of an IM vessel was measured with sonography and CT in intercostal spaces 1-4. The sonography and CT vessel measurements in the four intercostal spaces were compared to determine the measurement accuracy of sonography. The node and vessel data in intercostal space 2 were inserted into a mathematical model to determine the measurement accuracy of lymphoscintigraphy and CT for node detection. RESULTS: Vessel depths measured by sonography were systematically too shallow and the lateral vessel position could not be accurately determined. The mathematical model showed that the node depth and lateralization in one intercostal space can be measured directly by lymphoscintigraphy within an accuracy (1 SD) of 5 mm in depth and 6 mm in the lateral direction. The accuracy of CT for indirect node detection was 6 mm in depth and 7 mm in the lateral direction. CONCLUSIONS: Sonography is not a suitable technique for measuring the IM vessel or node position. Lymphoscintigraphy and CT have measurement accuracies for node detection that are acceptable for radiotherap

Virtual globes and geospatial health: the potential of new tools in the management and control of vector-borne diseases

The rapidly growing field of three-dimensional software modeling of the Earth holds promise for applications in the geospatial health sciences. Easy-to-use, intuitive virtual globe technologies such as Google Earth™ enable scientists around the world to share their data and research results in a visually attractive and readily understandable fashion without the need for highly sophisticated geographical information systems (GIS) or much technical assistance. This paper discusses the utility of the rapid and simultaneous visualization of how the agents of parasitic diseases are distributed, as well as that of their vectors and/or intermediate hosts together with other spatially-explicit information. The resulting better understanding of the epidemiology of infectious diseases, and the multidimensional environment in which they occur, are highlighted. In particular, the value of Google Earth™, and its web-based pendant Google Maps™, are reviewed from a public health view point, combining results from literature searches and experiences gained thus far from a multidisciplinary project aimed at optimizing schistosomiasis control and transmission surveillance in sub-Saharan Africa. Although the basic analytical capabilities of virtual globe applications are limited, we conclude that they have considerable potential in the support and promotion of the geospatial health sciences as a userfriendly, straightforward GIS tool for the improvement of data collation, visualization and exploration. The potential of these systems for data sharing and broad dissemination of scientific research and results is emphasize

Influence of tumour depth, blood absorption and autofluorescence on measurements of exogenous fluorophores in tissue

We investigated the influence of tumour depth and differences in blood concentration and autofluorescence between tumour and normal tissue on the fluorescence of a tumour-localising agent. Carotenoporphyrin, CP(Me)(3), mas injected into rats and nude mice with intradermal tumours. On the tumours an incision was made, uncovering 2 mm(2) of the tumour, and fluorescence measurements, including excitation-emission maps and fluorescence ratios, were made on skin. covered and uncovered tumour, The measured fluorescence ratio in the uncovered tumour showed a three- to tenfold increase compared to the covered tumour, We used a one-dimensional layered tissue model to analyse the data, In conclusion, even with a high tumour-selectivity deeper lying tumours cannot always be detected, particularly if the tumour has a high blood concentration or low autofluorescence intensit