Editorial – a light diagnosis

The name optical diagnosis suggests diagnosis of disease states using optical methods. This themed edition has been formulated on the back of two very successful spectroscopy conferences, namely the International Conference on Raman Spectroscopy held in London in August 2008 and the SPEC 2008 Conference held in São José dos Campos close to São Paulo in October 2008. Over the course of these two conferences various papers were presented highlighting recent advances in the use of optical spectroscopies to aid in the diagnosis of disease. Ultimately, diagnosis of disease and appropriate treatment is decided by a clinician; however, to aid the clinician, development of existing methodologies for new disease states is required to expand and improve the speed with which a clinician can make their diagnosis and prescribe appropriate treatment. There are many ways in which optical diagnosis can be viewed and the simplest way of diagnosing disease optically is to look at colorimetric changes in very simple indicator systems which indicate changes in biomarkers corresponding to disease. Perhaps the most common methodology that is employed for this purpose is that of lateral flow immunoassays followed by the optical (visual) detection of gold nanoparticles. The most widely used application of this technique is for pregnancy testing; however, we must not confuse pregnancy with a disease although that parallel was made mistakenly in an early lecture by one of the Editors of this themed edition!!

The themed issue can be broken down into three clear themes which are led by a critical review on part of the theme followed by a number of original research papers. In total there are 3 critical reviews and 24 papers and the three thematic areas which have emerged for this themed edition are a focus on specific diseases for improved diagnosis using optical spectroscopies, the use of optical spectroscopy in cell and tissue analysis relating to disease and improvements to the techniques employed. In the first critical review of the disease-focused area, Nick Stone and colleagues cover the role of vibrational spectroscopy as a clinical tool for cancer diagnostics. In this review he covers the benefits of early detection to prevent cancer and the use of Raman and infrared spectroscopy to analyse biochemical signatures from tissue samples and relate this to the diagnosis of cancer. This review then leads very nicely into the paper of Diem and co-workers where detection of breast micro-metastases by infrared spectral imaging is reported. This paper is complemented by the work of Poletti et al. where small angle X-ray scattering is used to analyse breast cancer which resulted in a specificity of 100% in discriminating benign and malignant lesions. Huang et al. report the use of near-infrared Raman spectroscopy to diagnose laryngeal melanoma in combination with classification of the spectra by chemometrics. The final paper focusing on cancer diagnosis is that of Gardner et al. where the factors that influence the discrimination on classification of prostate cancer cells by FTIR microspectroscopy are discussed and again give rise to excellent sensitivity and specificity.

Petrich et al. move the emphasis from cancer to vascular disease with the diagnosis and triaging of patients with acute chest pains based on mid-infrared spectroscopy which is complemented by the paper of Wetzel et al. on the assessment of an imminent cardiac risk using optical intravascular biochemical analysis. In keeping with the vascular disease diagnosis, Kazarian et al. report on micro ATR-FTIR imaging of atherosclerosis and demonstrate the ability of this technique to investigate the differences in structure and chemical composition of the atherosclerotic lesions in mice. Infectious disease is also covered in this issue. Malaria is one of the most prevalent diseases worldwide and obviously early and accurate detection of malaria is key to a successful treatment. McNaughton et al. report the use of resonance Raman microscopy with partial dark-field microscopy to highlight a new target for use in malaria diagnostics. Spectra were obtained in less than one second and potentially infected cells were analysed by multi-variate analysis, indicating the potential of this technique for early diagnosis. In a similar study, Frosch's group used resonance Raman spectroscopy to investigate the morphology-sensitive modes of the malaria pigment hemozoin. The remaining papers in this theme focus on a variety of different diseases. The paper of Buffington et al. focuses on the use of infrared microspectroscopy to diagnose interstitial cystitis using classification of analysis from serum from humans and cats. Quaroni and Casson also report the use of infrared microspectroscopy to characterise esophageal tissue and diagnose Barrett esophagus and esophageal adenocarcinoma. In the final paper focused on specific disease state analysis Dieter Naumann et al. report the use of whole cell MALDI-ToF MS to take the first steps towards the diagnosis of pathogens from sputum samples from cystic fibrosis patients.

The second theme within this issue is that of single-cell and tissue-based analysis. Jürgen Popp and colleagues provide an excellent introduction to this area in the form of a critical review which covers Raman and CARS spectroscopy in relation to cellular and tissue analysis. This leads very appropriately into the first paper of this theme by Dieter Naumann et al. on the use of confocal Raman microscopy to investigate and illustrate the spatial heterogeneity of microbial cell populations. An important aspect of analysing biological samples by vibrational and optical spectroscopies is the manner in which they are treated prior to analysis. In a comprehensive study Deckert et al. report the impact of fixation of cells by different methods for Raman microscopy and propose a method to retain the largest degree of integrity between the original sample and that observed. Lasch et al. report the use of confocal Raman microscopic measurements on a single microbial spore and were able to relate the signals with the morphology of the spore. Byrne et al. examined single biological cells using FTIR spectra and reported on the artefact observed from the optically dense nuclease. This paper discusses the contributions from reflection and transmission in relation to optically dense regions when using cellular mapping techniques. In the final paper in this theme, Manfait and co-workers examined the spectroscopic signatures of single, isolated cancer cell nuclei using synchrotron infrared microscopy.

The final theme area covered in this themed edition is that of the development of specific techniques for optical diagnosis. The theme starts off with Pavel Matousek and Nick Stone describing the concepts of deep Raman spectroscopy for the study of biological tissue and how depth penetration can be a factor in the ability of optical diagnosis techniques to be used on intact samples in a non-invasive manner. Knief et al. follow on from this by reporting the use of Raman spectroscopy as a potential platform for the rapid measurement of carbon nanotube-induced cytotoxicity. There is obviously a large degree of interest in carbon-based cytotoxicity and this is a very promising method for rapid assessment. Ariese et al. report the use of picosecond Raman spectroscopy with a fast CCD camera to provide depth analysis of diffusely scattered media and compare this technique to other Raman techniques for diffusely scattering media. One of the major issues in any optical diagnosis approach is the contamination from known species. In the paper of Beier and Berger an automated method of removal of broad or a moderately featured background is described in relation to Raman microscopy. And in the final Raman paper of the edition de Paula Jr. et al. propose a software package, which can be used to classify Raman spectra according to a variety of different variables. In the final section of this technique development, infrared spectral imaging with pattern recognition for the diagnosis of cutaneous carcinomas is described by Manfait and co-workers and a new procedure for strain classification of fungal mycelium by cluster and artificial neural network analysis of IR spectra is proposed by Annette Naumann. In the final paper, Shaw et al. report the progress towards point-of-care diagnostic metabolomic fingerprinting. In this approach, infrared spectroscopy was used to accurately quantify several serum and urine metabolites.

In summary, this themed edition aims to provide a comprehensive and diverse overview of the latest developments in optical diagnosis. The papers featured in the issue fall into three different areas; however, there is significant overlap between all of these themes and one area should not be considered on its own. The future of using light in aiding and enabling disease diagnosis is assured. With continued innovation and dedicated thinking, the scientific community can embrace this approach and involve end-user clinicians to make a significant difference to the quality of life of many. We hope you enjoy reading these articles and that it provides stimulus and debate amongst the community.

Duncan Graham

University of Strathclyde, Glasgow, UK

Volker Deckert

Friedrich-Schiller University, Jena, Germany

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