A novel method for rapidly detecting metastatic breast cancer within excised sentinel lymph node(s) of the axilla is presented. Elastic scattering spectroscopy (ESS) is a point-contact technique that collects broadband optical spectra sensitive to absorption and scattering within the tissue. A statistical discrimination algorithm was generated from a training set of nearly 3000 clinical spectra and used to test clinical spectra collected from an independent set of nodes. Freshly excised nodes were bivalved and mounted under a fiber-optic plate. Stepper motors raster-scanned a fiber-optic probe over the plate to interrogate the node's cut surface, creating a 20×20 grid of spectra. These spectra were analyzed to create a map of cancer risk across the node surface. Rules were developed to convert these maps to a prediction for the presence of cancer in the node. Using these analyses, a leave-one-out cross-validation to optimize discrimination parameters on 128 scanned nodes gave a sensitivity of 69% for detection of clinically relevant metastases (71% for macrometastases) and a specificity of 96%, comparable to literature results for touch imprint cytology, a standard technique for intraoperative diagnosis. ESS has the advantage of not requiring a pathologist to review the tissue sample.
We present the results of a clinical study using ESS to detect dysplasia in the esophagus. We focus on the use of novel statistical techniques and the clinical benefits this technique provides.
Sentinel node biopsy is the new standard for lymphatic staging of breast carcinoma. Intraoperative detection of sentinel node metastases avoids a second operation for those patients with metastatic lymph nodes. Elastic scattering spectroscopy is an optical technique which is sensitive to cellular and subcellular changes occurring in malignancy. We analyzed 2078 ESS spectra from 324 axillary sentinel nodes from patients with breast carcinoma. ESS was able to detect metastatic lymph nodes with an overall sensitivity of 60% and specificity of 94%, which is comparable to existing pathological techniques. Nodes completely replaced with metastatic tumour were detected with 100% sensitivity, suggesting that further improvement in sensitivity is likely with more intensive optical sampling of the nodes.
The ability to provide the best treatment for breast cancer depends on establishing whether or not the cancer has spread to the lymph nodes under the arm. Conventional assessment requires tissue removal, preparation, and expert microscopic interpretation. In this study, elastic scattering spectroscopy (ESS) is used to interrogate excised nodes with pulsed broadband illumination and collection of the backscattered light. Multiple spectra are taken from 139 excised nodes (53 containing cancer) in 68 patients, and spectral analysis is performed using a combination of principal component analysis and linear discriminant analysis to correlate the spectra with conventional histology. The data are divided into training and test sets. In test sets containing spectra from only normal nodes and nodes with complete replacement by cancer, ESS detects the spectra from cancerous nodes with 84% sensitivity and 91% specificity (per-spectrum analysis). In test sets that included normal nodes and nodes with partial as well as complete replacement by cancer, ESS detects the nodes with cancer with an average sensitivity of 75% and specificity of 89% (per-node analysis). These results are comparable to those from conventional touch imprint cytology and frozen section histology, but do not require an expert pathologist for interpretation. With automation of the technique, results could be made available almost instantaneously. ESS is a promising technique for the rapid, accurate, and straightforward detection of metastases in excised sentinel lymph nodes.
Successful management of malignant melanoma depends on early detection and diagnostic accuracy. However studies have found a diagnostic accuracy of malignant melanoma amongst dermatologists of only 80% compared with histological diagnosis, results are generally poorer with family practitioners and dermatology trainees. Elastic scattering spectroscopy (ESS) is a non-invasive procedure that utilises elastically scattered light. A related technique, reflectance spectrometry, may discriminate between benign and malignant pigmented lesions in vivo.
Objectives: We have therefore assessed an ESS biopsy system in the diagnosis of melanocytic lesions in vivo and compared the results to both clinical and histopathological diagnosis.
Patients/Methods: One hundred melanocytic lesions from 77 patients attending our pigmented lesion clinic between 1999 and 2001 or seen at our Melanoma Day were examined clinically and divided into benign, dysplastic or malignant lesions. ESS spectra were acquired at several points from each lesion and adjacent normal skin. Lesions were then excised and sent for histological examination.
Results: Lesions were histologically classified as 12 malignant melanoma (3 in-situ), 14 dysplastic naevi and 57 benign naevi (a further 17 clinically benign naevi were included which were not selected for excision). Clinical examination had a sensitivity of 75% and specificity of 91% for detection of malignant melanoma from other melanocytic lesions and overall diagnostic accuracy of differentiating melanocytic lesions of 71%. ESS spectral diagnosis classified by linear discriminant analysis indicated a sensitivity of 84% and specificity of 65% for detection of malignant melanoma from other melanocytic lesions. However the ESS spectral diagnosis included several readings per lesion and clinically this is not relevant. Therefore an ESS per lesional diagnosis was taken as the most aggressive diagnosis. This had a sensitivity of 100% and specificity of 75% for detection of malignant melanoma from other melanocytic lesions and overall diagnostic accuracy of differentiating melanocytic lesions of 69%.
Discussion: These data suggest that ESS may be capable of differentiating malignant melanoma, dysplastic and benign naevi with a high sensitivity and provide adjuvant information to clinical examination by a dermatologist, which could be useful in the triage of melanocytic lesions.
We report the experimentally measured polarized small signal gain for Ce:LiLuF at 309 nm and 327 nm. The gain was found to be anisotropic and temperature dependent. Using a rate equation based model we have simulated the affect of excited state absorption (ESA) on the small signal gain in Ce:LiLuF. As a result we report the polarized emission and ESA cross-sections for Ce:LiLuF at 309 nm and 327 nm. We show the ESA to be temperature dependent and consequently demonstrate that ESA is the cause of the change in small signal gain with temperature in Ce:LiLuF. Further, we experimentally show the decrease, with temperature, of the ESA cross-sections at 309 nm causes a 70% increase in the laser output at 309 nm. We demonstrate how the introduction of a σ-biased loss into the cavity suppresses σ-polarized lasing at 327 nm. This counteracts the decrease in laser output below ~10°C caused by the anisotopic nature and temperature dependence of the ESA in Ce:LiLuF at 327 nm.
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