Limits...
Discerning the differential molecular pathology of proliferative middle ear lesions using Raman spectroscopy.

Pandey R, Paidi SK, Kang JW, Spegazzini N, Dasari RR, Valdez TA, Barman I - Sci Rep (2015)

Bottom Line: Despite its widespread prevalence, middle ear pathology, especially the development of proliferative lesions, remains largely unexplored and poorly understood.Diagnostic evaluation is still predicated upon a high index of clinical suspicion on otoscopic examination of gross morphologic features.In addition to revealing signatures consistent with the known pathobiology of these lesions, our observations provide the first evidence of the presence of carbonate- and silicate-substitutions in the calcium phosphate plaques found in myringosclerosis.

View Article: PubMed Central - PubMed

Affiliation: Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA.

ABSTRACT
Despite its widespread prevalence, middle ear pathology, especially the development of proliferative lesions, remains largely unexplored and poorly understood. Diagnostic evaluation is still predicated upon a high index of clinical suspicion on otoscopic examination of gross morphologic features. We report the first technique that has the potential to non-invasively identify two key lesions, namely cholesteatoma and myringosclerosis, by providing real-time information of differentially expressed molecules. In addition to revealing signatures consistent with the known pathobiology of these lesions, our observations provide the first evidence of the presence of carbonate- and silicate-substitutions in the calcium phosphate plaques found in myringosclerosis. Collectively, these results demonstrate the potential of Raman spectroscopy to not only provide new understanding of the etiology of these conditions by defining objective molecular markers but also aid in margin assessment to improve surgical outcome.

No MeSH data available.


Related in: MedlinePlus

(A) Multi-dimensional radial visualization plot of selected principal component scores obtained from the entire spectral dataset. The plot illustrates the clustering behavior of the data points corresponding to the myringosclerosis sites that exhibit mineralization. (B) ROC curve for PLS-DA derived algorithm for the diagnosis of mineralized myringosclerosis sites. The ROC curve in red plots sensitivity versus (1-specificity) for the PLS-DA decision algorithm as the discrimination threshold is varied. For comparison, the ROC curve of two indistinguishable classes (represented by the solid black line) is also shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4542608&req=5

f4: (A) Multi-dimensional radial visualization plot of selected principal component scores obtained from the entire spectral dataset. The plot illustrates the clustering behavior of the data points corresponding to the myringosclerosis sites that exhibit mineralization. (B) ROC curve for PLS-DA derived algorithm for the diagnosis of mineralized myringosclerosis sites. The ROC curve in red plots sensitivity versus (1-specificity) for the PLS-DA decision algorithm as the discrimination threshold is varied. For comparison, the ROC curve of two indistinguishable classes (represented by the solid black line) is also shown.

Mentions: In addition to identifying a robust set of biologically relevant spectral markers, we also sought to develop a decision algorithm that could rapidly delineate the pathology of the tissue in a label-free, real-time manner. First, a nonlinear radial visualization map was constructed to plot the PC data dimensions onto a two dimensional space for the purpose of clustering (Fig. 4(A))35. These PC scores were extracted from the entire spectral dataset – and not from separate loadings as identified in Fig. 4. The PCs describing tissue site biochemical characteristics are equally spaced around the perimeter of a circle and provide dimension anchors, where the values of each dimension (PC score) are standardized between 0 and 1. Each tissue site is shown as a point inside the unit circle with its location governed by its dimension anchors. The radial visualization plot reveals an almost clearly separable cluster for the biomineralized myringosclerosis sites with substantial overlap between the cholesteatoma sites and the other myringosclerosis sites, stemming from the lack of distinctive spectral markers that separates the latter two. The few incorrectly segregated myringosclerosis sites can be attributed to the spectroscopy-histopathology registration error. It is worth noting that a high degree of reproducibility when replicate measurements were performed on the same sites in each tissue specimen. Expectedly, the inter-sample variations were larger than the intra-sample changes – which can be attributed to the intrinsic heterogeneity of tissue specimen acquired from different individuals.


Discerning the differential molecular pathology of proliferative middle ear lesions using Raman spectroscopy.

Pandey R, Paidi SK, Kang JW, Spegazzini N, Dasari RR, Valdez TA, Barman I - Sci Rep (2015)

(A) Multi-dimensional radial visualization plot of selected principal component scores obtained from the entire spectral dataset. The plot illustrates the clustering behavior of the data points corresponding to the myringosclerosis sites that exhibit mineralization. (B) ROC curve for PLS-DA derived algorithm for the diagnosis of mineralized myringosclerosis sites. The ROC curve in red plots sensitivity versus (1-specificity) for the PLS-DA decision algorithm as the discrimination threshold is varied. For comparison, the ROC curve of two indistinguishable classes (represented by the solid black line) is also shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542608&req=5

f4: (A) Multi-dimensional radial visualization plot of selected principal component scores obtained from the entire spectral dataset. The plot illustrates the clustering behavior of the data points corresponding to the myringosclerosis sites that exhibit mineralization. (B) ROC curve for PLS-DA derived algorithm for the diagnosis of mineralized myringosclerosis sites. The ROC curve in red plots sensitivity versus (1-specificity) for the PLS-DA decision algorithm as the discrimination threshold is varied. For comparison, the ROC curve of two indistinguishable classes (represented by the solid black line) is also shown.
Mentions: In addition to identifying a robust set of biologically relevant spectral markers, we also sought to develop a decision algorithm that could rapidly delineate the pathology of the tissue in a label-free, real-time manner. First, a nonlinear radial visualization map was constructed to plot the PC data dimensions onto a two dimensional space for the purpose of clustering (Fig. 4(A))35. These PC scores were extracted from the entire spectral dataset – and not from separate loadings as identified in Fig. 4. The PCs describing tissue site biochemical characteristics are equally spaced around the perimeter of a circle and provide dimension anchors, where the values of each dimension (PC score) are standardized between 0 and 1. Each tissue site is shown as a point inside the unit circle with its location governed by its dimension anchors. The radial visualization plot reveals an almost clearly separable cluster for the biomineralized myringosclerosis sites with substantial overlap between the cholesteatoma sites and the other myringosclerosis sites, stemming from the lack of distinctive spectral markers that separates the latter two. The few incorrectly segregated myringosclerosis sites can be attributed to the spectroscopy-histopathology registration error. It is worth noting that a high degree of reproducibility when replicate measurements were performed on the same sites in each tissue specimen. Expectedly, the inter-sample variations were larger than the intra-sample changes – which can be attributed to the intrinsic heterogeneity of tissue specimen acquired from different individuals.

Bottom Line: Despite its widespread prevalence, middle ear pathology, especially the development of proliferative lesions, remains largely unexplored and poorly understood.Diagnostic evaluation is still predicated upon a high index of clinical suspicion on otoscopic examination of gross morphologic features.In addition to revealing signatures consistent with the known pathobiology of these lesions, our observations provide the first evidence of the presence of carbonate- and silicate-substitutions in the calcium phosphate plaques found in myringosclerosis.

View Article: PubMed Central - PubMed

Affiliation: Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA.

ABSTRACT
Despite its widespread prevalence, middle ear pathology, especially the development of proliferative lesions, remains largely unexplored and poorly understood. Diagnostic evaluation is still predicated upon a high index of clinical suspicion on otoscopic examination of gross morphologic features. We report the first technique that has the potential to non-invasively identify two key lesions, namely cholesteatoma and myringosclerosis, by providing real-time information of differentially expressed molecules. In addition to revealing signatures consistent with the known pathobiology of these lesions, our observations provide the first evidence of the presence of carbonate- and silicate-substitutions in the calcium phosphate plaques found in myringosclerosis. Collectively, these results demonstrate the potential of Raman spectroscopy to not only provide new understanding of the etiology of these conditions by defining objective molecular markers but also aid in margin assessment to improve surgical outcome.

No MeSH data available.


Related in: MedlinePlus