Accounting for tissue heterogeneity in infrared spectroscopic imaging for accurate diagnosis of thyroid carcinoma subtypes

Abstract

Fourier transform infrared (FT-IR) microscopy was used to image tissue samples from twenty patients diagnosed with thyroid carcinoma. The spectral data were then used to differentiate between follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma using principle component analysis coupled with linear discriminant analysis and a Naïve Bayesian classifier operating on a set of computed spectral metrics. Classification of patients’ disease type was accomplished by using average spectra from a wide region containing follicular cells, colloid, and fibrosis; however, classification of disease state at the pixel level was only possible when the extracted spectra were limited to follicular epithelial cells in the samples, excluding the relatively uninformative areas of fibrosis. The results demonstrate the potential of FT-IR microscopy as a tool to assist in the difficult diagnosis of these subtypes of thyroid cancer, and also highlights the importance of selectively and separately analyzing spectral information from different features of a tissue of interest.

Application Value of Color Doppler Ultrasonography Combined with Thyroid Autoantibody Tests in Early Diagnosis of Thyroid Cancer

“…The thyroid gland, the largest and most important endocrine gland in the human body, is relatively accessible because of its superficial location and fewer variation in vascularity, which also provides good congenital conditions for ultrasonography. Color Doppler ultrasonography, with its advantages of easy operation, low cost, and high safety and accuracy, is considered to be the first choice for clinically diagnosing the nature of thyroid nodules and is often used in the preoperative diagnosis of thyroid cancer and the development of a surgical protocol [ 14 – 16 ]. The diagnosis and differentiation of thyroid cancer by color Doppler ultrasonography are mainly based on the two-dimensional morphological features and color Doppler flow status, which are generally reflected in the following aspects: (1) the morphology of the foci is irregular, and many of them are unifocal, accompanied by a spiculated margin; (2) the foci show heterogeneous echogenicity, uneven intensity, and attenuation posteriorly; (3) there are calcifications and abundant blood flow signals within the foci, which often show penetrating blood flow and relatively disorganized vascularity; and (4) pulsed Doppler shows that the flow in the feeding arteries appears as high velocity and hyperresistance, which may also be accompanied by a reverse flow spectrum in some patients [ 17 – 20 ].…”

Metabolic Profile Characterization of Different Thyroid Nodules Using FTIR Spectroscopy: A Review

“…Nevertheless, over the past few years, the metabolomics approach in terms of thyroid diagnosis has shown an enormous evolution, which is due, in part, to the application of several analytical techniques that allow the study of the complete set of small biomolecules that make up a biological sample. The main metabolomics techniques that have mostly been adopted in the thyroid, in an attempt to identify biomarkers, classify the thyroid cancer, facilitate an earlier diagnosis and prevent the development and invasion at the systemic level of the cancer itself, are Mass Spectrometry (MS) [53][54][55], Nuclear Magnetic Resonance (NMR) [53,56,57], Raman Spectroscopy [58][59][60] and Fourier Transform Infrared (FTIR) Spectroscopy [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79]. This increase in the number of studies is attributed to the greater availability of improved and accurate metabolomics techniques that exist and also due to the development of appropriate statistical tools that are able to handle the huge amount of data resulting from the samples under analysis [80].…”

“…As previously mentioned, in order to improve the prognosis of patients who present thyroid carcinomas, and taking into account that the majority of these nodular thyroid lesions are receptive to medical and surgical management, it is important to use diagnostic methods that allow their early detection; FTIR spectroscopy seems to be an excellent option to be applied in this context [47]. The available thyroid cancer studies discriminate and characterize both healthy and pathological thyroid samples and the analysis is performed in tissue anatomic pieces obtained after thyroidectomy [61,[66][67][68][69][70][72][73][74][75][76][77][78][79], in cytological samples obtained from the realization of FNA biopsies [62,72,75] or even through the application of the FTIR spectroscopy technique in a non-invasive way; that is, applied to the skin surface on thyroid nodules [63][64][65]71].…”

Infrared spectroscopic imaging: Label-free biochemical analysis of stroma and tissue fibrosis

“…The spatial information can be correlated to histopathology information from adjacent serial sections, or from the IR sample itself if it is stained following imaging. This dataset can then be analyzed through a diverse array of techniques, by selectively extracting spectra from features of interest within the tissue being studied (Bird and Rowlette, 2017; Martinez-Marin et al, 2016; Sreedhar et al, 2016). …”

“…The exploration of the biochemistry of stromal regions remains largely untapped with future research required to determine whether these areas hold useful and clinically actionable information. Recently, it was demonstrated that interrogating regions of fibrosis in the setting of thyroid carcinoma was not able to discriminate between two types of cancer whereas the epithelial cells could (Martinez-Marin et al, 2016), demonstrating that these regions do not always hold diagnostic value. Future work must focus on adapting IR imaging technology for clinical implementation to provide useful answers to clinicians, and delve deeper into the nature of the precise stromal components contributing to diseased IR signatures.…”