Raman Spectroscopy Applied to Parathyroid Tissues: A New Diagnostic Tool to Discriminate Normal Tissue from Adenoma

Abstract

Primary hyperparathyroidism is an endocrine disorder characterized by autonomous production of parathyroid hormone. Patients with the symptomatic disease should be referred for parathyroidectomy. However, the distinction between the pathological condition and the benign one is very challenging in the surgical setting; therefore, accurate recognition is important to ensure success during minimally invasive surgery. At present, all intraoperative techniques significantly increase surgical time and, consequently, cost. In this proof-of-concept study, Raman microscopy was used to differentiate between healthy parathyroid tissue and parathyroid adenoma from 18 patients. The data showed different spectroscopic features for the two main tissue types of healthy and adenoma. Moreover, the parathyroid adenoma subtypes (chief cells and oxyphil cells) were characterized by their own Raman spectra. The partial least-squares discriminant analysis (PLS-DA) model built to discriminate healthy from adenomatous parathyroid tissue was able to correctly classify all samples in the calibration and validation data sets, providing 100% prediction accuracy. The PLS-DA model built to discriminate chief cell adenoma from oxyphil cell adenoma allowed us to correctly classify >99% of the spectra during calibration and cross-validation and to correctly predict 100% of oxyphil and 99.8% of chief cells in the external validation data set. The results clearly demonstrate the great potential of Raman spectroscopy. The final goal would be development of a Raman portable fiber probe device for intraoperative optical biopsy, both to improve the surgical success rate and reduce surgical cost.

Preoperative and Intraoperative Methods of Parathyroid Gland Localization and the Diagnosis of Parathyroid Adenomas

“…After that, the Raman effect was particularly useful for medical applications because the scattered radiation measured is unique for each biomolecule [108]. Since that time, Raman spectroscopy has been applied in skin cancer margin assessment, diagnosis of endometriosis, differentiation between tumor and normal brain tissues, or between parathyroid adenomas and hyperplasia [46,[109][110][111]. In this method, the frequency of a molecule, either vibrational or rotational can be changed with the use of laser light.…”

“…Das et al have discussed applications of Raman spectroscopy which may significantly improve or even replace the need of intraoperative frozen sections for tissue pathology [47]. Palermo et al showed that usage of Raman spectroscopy enables the possibility to distinguish between healthy and adenomatous parathyroid tissues, as the results of his study showed a 100% accuracy in an investigated sample of 18 patients [46]. Apart from distinguishing between adenomas and hyperplasia, Raman spectroscopy allows for specific identification of adenomatous histology -whether a parathyroid adenoma is primarily composed of a chief or oxyphil cells.…”

“…Other disadvantages include additional costs and potentially higher post-operative side effects due to the probable prolongation of a surgery. Nonetheless, Raman spectroscopy seems to be a promising method of intraoperative differentiation between healthy and pathologically changed parathyroid tissues, as well as their further diagnosis [46,47].…”

Thyroid cancer diagnosis by Raman spectroscopy

“…5 Present address: Dipartimento di Fisica, Sapienza Universitá di Roma, Rome, Italy. * email: armida.sodo@uniroma3.it bacteria, and in particular to differentiate between healthy and cancer tissues [9][10][11][12] . Preliminary studies on thyroid tissues by RS suggest that this technique may have high impact in thyroid cancer diagnosis [13][14][15][16][17][18] .…”

Raman Spectroscopy as a Diagnostic Tool Applied for Tissue Pathologies to Support Histological Analysis

“…In this work, we applied RS for several tasks, among them to differentiate between thyroid follicular patterned lesions and among thyroid nodule pathologies [1,2]; to discriminate normal parathyroid tissue from adenoma [3]; to discriminates malignant follicular lymphoma from benign follicular hyperplasia, from tumor metastasis and to classify follicular lymphomas according to tumor grade and BCL2 protein expression [4].…”