Raman spectroscopy of bladder tissue in the presence of 5-aminolevulinic acid.
ABSTRACT Raman spectroscopy has the ability to provide differential diagnosis of different cancers with high sensitivity and specificity. A major limitation in its clinical application is the weak nature of Raman signal, which inhibits scanning large surface areas of tissues. In bladder cancer diagnosis, fluorescence-guided endoscopy with 5-aminolevulinic acid (5-ALA) has gained interest as a technique that can provide such spatial differentiation, thus improving early detection and more complete removal of superficial tumors. However, several studies have demonstrated the poor specificity of this modality. Combining fluorescence with Raman spectroscopy could improve its diagnostic capability. However, little is known about the effect of agents such as 5-ALA on Raman spectra of tissue. In this paper, we present measuring Raman spectroscopy from benign and malignant bladder tissues in the presence of 5-ALA and attempt to evaluate the potential to discriminate between different pathologies. Raman spectra were recorded from 92 bladder biopsies without 5-ALA and 38 biopsies with 5-ALA using a Raman microspectrometer system at 830nm excitation. Empirical and multivariate statistical techniques were used for data analysis. Algorithms were developed to determine the effect of 5-ALA on tissue and its influence on the prediction ability of a preliminary benign/malignant prediction model. In samples with 5-ALA, an overall decrease in Raman intensity was observed when compared to the Raman spectra from samples without 5-ALA. Additionally, differences in relative intensities at 1270 and 1330cm(-1) were also noted. However, significant differences were observed in the Raman spectra of benign and malignant samples with 5-ALA indicating the potential of using Raman spectroscopy for discriminating bladder cancer in the presence of 5-ALA. The Principal-Component fed Linear-Discriminant Analysis (PCA/LDA) algorithm derived from biopsies in the absence of 5-ALA used to predict biopsies in the presence of 5-ALA resulted in an overall sensitivity and specificity of 42.6% and 71.1%, respectively. This suggests the presence of 5-ALA in tissue affects the Raman spectra. A PCA/LDA algorithm based on fluorescence information (i.e. PpIX fluorescence positive or negative) and the Raman spectrum of 5-ALA biopsies, had a sensitivity and specificity of 100% and 80.8%, respectively. This study demonstrates that applying 5-ALA affects the Raman spectra of bladder tissues. However, benign/malignant differentiation can be accomplished with a preliminary PCA/LDA algorithm, suggesting the potential of a combined diagnostic modality in vivo.
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ABSTRACT: Cerebral metastases are the most frequent cerebral tumours. Surgery of cerebral metastases plays an indispensible role in a multimodal therapy concept. Conventional white-light, microscopy assisted microsurgical and circumferential stripping of cerebral metastases is neurosurgical standard therapy, but is associated with an extraordinarily high recurrence rate of more than 50% without subsequent whole-brain radiotherapy. Therefore, neurosurgical standard therapy fails to achieve local tumour control in many patients. The present conceptual paper focuses on this issue and discusses the possible causes of the high recurrence rates such as intraoperative dissemination of tumour cells or the lack of sharp delimitation of metastases from the surrounding brain tissue resulting in incomplete resections. Adjuvant whole-brain radiotherapy reduces the risk of local and distant recurrences, but is associated with a well-documented impairment of neurocognitive function. New surgical strategies, such as supramarginal or fluorescence-guided resection, address the possibility of infiltrating tumour parts to achieve more complete resection of cerebral metastases. Supramarginal resection was shown to significantly reduce the risk of a local recurrence and prolongs two-year survival rates. Furthermore, radiosurgery in combination with surgery represents a promising approach.ecancermedicalscience 01/2013; 7:306.
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ABSTRACT: Microsurgical, circumferential stripping of intracerebral metastases often proves to be insufficient to prevent local tumor recurrence. We were interested in the potential impact of 5-aminolevulinic acid (5-ALA)-induced-fluorescence (5-AIF) as a diagnostic tool for the resection of intracerebral metastases. A retrospective analysis was performed for 52 patients who underwent 5-AIF-guided resection for intracerebral mass lesions that histologically corresponded to metastases from tumors outside the central nervous system. The presence of ALA fluorescence in the tumor was determined in each patient. In 42 patients, fluorescence of the resection cavity after tumor removal was additionally recorded. Data were correlated with neuropathological findings in tissue specimens. A total of 32 of the 52 metastases (62%) exhibited 5-AIF in tumor parts. All 5-AIF-positive metastases exhibited an inhomogeneous fluorescence pattern. 5-AIF was neither associated with the histological type nor with the site of origin of the metastases. Residual fluorescence of the resection cavity was detected after macroscopically complete white light resection in 24 patients with 5-AIF positive metastases. Residual tumor tissue was histologically confirmed in 6 of 18 patients with available tissue specimens from such 5-AIF positive areas (33%). The majority of metastases (62%) were 5-AIF positive, suggesting a potential impact of 5-AIF for improved visualization of metastatic tumor tissue within the brain. However, residual 5-AIF after macroscopically complete resection of a metastasis needs to be interpreted with caution because of the limited specificity for detection of residual tumor tissue.Acta Neurochirurgica 11/2011; 154(2):223-8; discussion 228. · 1.55 Impact Factor
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ABSTRACT: Urothelial carcinomas of the bladder are a heterogeneous group of tumours, although some histological sub-variants are rare and sparsely reported in the literature. Diagnosis of sub-variants from conventional urothelial carcinoma can be challenging, as they may mimic the morphology of other malignancies or benign tumours and therefore their distinction is important. For the first time, the spectral pathology of some of these sub-variants has been documented by infrared microspectroscopy and an attempt made to profile their biochemistry. It is important not only to identify and separate the cancer-associated epithelial tissue spectra from common tissue features such as stroma or blood, but also to detect the signatures of tumour sub-variants. As shown, their spectroscopic signals can change dramatically as a consequence of differentiation. Example cases are discussed and compared with histological evaluations. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).Journal of Biophotonics 11/2012; · 3.10 Impact Factor