Significance: Screening and early detection of oral potentially malignant lesions (OPMLs) are of great significance in reducing the mortality rates associated with head and neck malignancies. Intra-oral multispectral optical imaging of tissues in conjunction with cloud-based machine learning (CBML) can be used to detect oral precancers at the point-of-care (POC) and guide the clinician to the most malignant site for biopsy.
Aim: Develop a bimodal multispectral imaging system (BMIS) combining tissue autofluorescence and diffuse reflectance (DR) for mapping changes in oxygenated hemoglobin (HbO2) absorption in the oral mucosa, quantifying tissue abnormalities, and guiding biopsies.
Approach: The hand-held widefield BMIS consisting of LEDs emitting at 405, 545, 575, and 610 nm, 5MPx monochrome camera, and proprietary Windows-based software was developed for image capture, processing, and analytics. The DR image ratio (R610/R545) was compared with pathologic classification to develop a CBML algorithm for real-time assessment of tissue status at the POC.
Results: Sensitivity of 97.5% and specificity of 92.5% were achieved for discrimination of OPML from patient normal in 40 sites, whereas 82% sensitivity and 96.6% specificity were obtained for discrimination of abnormal (OPML + SCC) in 89 sites. Site-specific algorithms derived for buccal mucosa (27 sites) showed improved sensitivity and specificity of 96.3% for discrimination of OPML from normal.
Conclusions: Assessment of oral cancer risk is possible by mapping of HbO2 absorption in tissues, and the BMIS system developed appears to be suitable for biopsy guidance and early detection of oral cancers.
This clinical study was to demonstrate the applicability of diffuse reflectance (DR) intensity ratio R620/R575 in the quantification and discrimination of periodontitis and gingivitis from healthy gingiva. DR spectral measurements were carried out with white-light illumination from 70 healthy sites in 30 healthy volunteers, and 63 gingivitis- and 58 periodontitis-infected sites in 60 patients. Clinical parameters such as probing pocket depth, clinical attachment level, and gingival index were recorded in patient population. Diagnostic accuracies for discrimination of gingivitis and periodontitis from healthy gingiva were determined by comparison of spectral signatures with clinical parameters. Divergence of average DR spectral intensity ratio between control and test groups was studied using analysis of variance. The mean DR spectrum on normalization at 620 nm showed marked differences between healthy tissue, gingivitis, and periodontitis. Hemoglobin concentration and apparent SO2 (oxygen saturation) were also calculated for healthy, gingivitis, and periodontitis sites. DR spectral intensities at 545 and 575 nm showed a decreasing trend with progression of disease. Among the various DR intensity ratios studied, the R620/R575 ratio provided a sensitivity of 90% and specificity of 94% for discrimination of healthy tissues from gingivitis and a sensitivity of 91% and specificity of 100% for discrimination of gingivitis from periodontitis.
In clinical diagnostic procedures, gingival inflammation is considered as the initial stage of periodontal breakdown. This
is often detected clinically by bleeding on probing as it is an objective measure of inflammation. Since conventional
diagnostic procedures have several inherent drawbacks, development of novel non-invasive diagnostic techniques
assumes significance. This clinical study was carried out in 15 healthy volunteers and 25 patients to demonstrate the
applicability of diffuse reflectance (DR) spectroscopy for quantification and discrimination of various stages of
inflammatory conditions in periodontal disease. The DR spectra of diseased lesions recorded using a point monitoring
system consisting of a tungsten halogen lamp and a fiber-optic spectrometer showed oxygenated hemoglobin absorption
dips at 545 and 575 nm. Mean DR spectra on normalization shows marked differences between healthy and different
stages of gingival inflammation. Among the various DR intensity ratios investigated, involving oxy Hb absorption peaks,
the R620/R575 ratio was found to be a good parameter of gingival inflammation. In order to screen the entire diseased
area and its surroundings instantaneously, DR images were recorded with an EMCCD camera at 620 and 575 nm. We
have observed that using the DR image intensity ratio R620/R575 mild inflammatory tissues could be discriminated
from healthy with a sensitivity of 92% and specificity of 93%, and from moderate with a sensitivity of 83% and
specificity of 96%. The sensitivity and specificity obtained between moderate and severe inflammation are 82% and 76%
respectively.
Accurate diagnosis of premalignant or malignant oral lesions depends on the quality of the biopsy, adequate clinical
information and correct interpretation of the biopsy results. The major clinical challenge is to precisely locate the biopsy
site in a clinically suspicious lesion. Dips due to oxygenated hemoglobin absorption have been noticed at 545 and 575
nm in the diffusely reflected white light spectra of oral mucosa and the intensity ratio R545/R575 has been found suited
for early detection of oral pre-cancers. A multi-spectral diffuse reflectance (DR) imaging system has been developed
consisting of an electron multiplying charge coupled device (EMCCD) camera and a liquid crystal tunable filter for
guiding the clinician to an optimal biopsy site. Towards this DR images were recorded from 27 patients with potentially
malignant lesions on their tongue (dorsal, lateral and ventral sides) and from 44 healthy controls at 545 and 575 nm with
the DR imaging system. False colored ratio image R545/R575 of the lesion provides a visual discerning capability that
helps in locating the most malignant site for biopsy. Histopathological report of guided biopsy showed that out of the 27
patients 16 were cancers, 9 pre-cancers and 2 lichen planus. In this clinical trial DR imaging has correctly guided 25
biopsy sites, yielding a sensitivity of 93% and a specificity of 98%, thereby establishing the potential of DR imaging as a
tool for guided biopsy.
We present the clinical applicability of fluorescence ratio reference standard (FRRS) to discriminate different stages of dental caries. Toward this, laser-induced autofluorescence emission spectra are recorded in vivo in the 400- to 800-nm spectral range on a miniature fiber optic spectrometer from 65 patients, with a 404-nm diode laser as the excitation source. Autofluorescence spectra of sound teeth consist of a broad emission at 500 nm that is typical of natural enamel, whereas in caries teeth additional peaks are seen at 635 and 680 nm due to emission from porphyrin compounds in oral bacteria. Scatter plots are developed to differentiate sound teeth from enamel caries, sound teeth from dentinal caries, and enamel caries from dentinal caries using the mean fluorescence intensity (FI) and ratios F500/F635 and F500/F680 measured from 25 sites of sound teeth and 65 sites of carious teeth. The sensitivity and specificity of both the FI and FRRS are determined. It is observed that a diagnostic algorithm based on FRRS scatter plots is able to discriminate enamel caries from sound teeth, dentinal caries from sound teeth, and enamel from dentinal caries with overall sensitivities of 85, 100, and 88% and specificities of 90, 100, and 77%, respectively.
Diffuse reflectance (DR) spectroscopy is a simple, low-cost, and noninvasive modality with potential for distinguishing oral precancer. Recently, in an ex vivo study, the DR spectral ratio (R545/R575) of oxygenated hemoglobin bands at 545 and 575 nm was used for grading malignancy. This work presents the results of clinical trials conducted in 29 patients to detect oral precancer using this ratio. We use site-specific normal spectra from a group of 36 healthy volunteers for comparison with those of patients. Toward this, in vivo DR spectra from 14 anatomical sites of the oral cavity of healthy volunteers are recorded on a miniature fiber optic spectrometer with white light excitation. The R545/R575 ratio is lowest for healthy tissues and appears to increase with the grade of malignancy. As compared to scatter plots that use the mean DR ratio from all anatomical sites, those using site-specific data show improved sensitivity and specificity for early diagnosis and grading of oral cancer. In the case of buccal mucosa, using scatter plots of R545/R575 ratio, we obtain a sensitivity of 100% and specificity of 86% for discriminating precancer (dysplasia) from hyperplasia, and a sensitivity of 97% and specificity of 86% for discriminating hyperplasia from normal.
A low-cost, fast, and noninvasive method for early diagnosis of malignant lesions of oral mucosa based on diffuse reflectance spectral signatures is presented. In this technique, output of a tungsten halogen lamp is guided to the tissue through the central fiber of a reflection probe whose surrounding six fibers collects tissue reflectance. Ex vivo diffuse reflectance spectra in the 400 to 600-nm region is measured from surgically removed oral cavity lesions using a miniature fiber optic spectrometer connected to a computer. Reflectance spectral intensity is higher in malignant tissues and shows dips at 542 and 577 nm owing to absorption from oxygenated hemoglobin (HbO2). Measurements carried out, within an hour of surgical excision, on malignant lesion and adjoining uninvolved mucosa show that these absorption features are more prominent in neoplastic tissues owing to increased microvasculature and blood content. It is observed that reflectance intensity ratio of hemoglobin bands, R540/R575, from malignant sites are always lower than that from normal sites and vary according to the histological grade of malignancy. The diffuse reflectance intensity ratio R540/R575 of the hemoglobin bands appears to be a useful tool to discriminate between malignant lesions and normal mucosa of the oral cavity in a clinical setting.
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