Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies

Abstract

The in vivo optical and hemodynamic properties of the healthy (n = 22) and pathological (n = 2) human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs') at three wavelengths (690, 785 and 830 nm) to derive total hemoglobin concentration (THC) and oxygen saturation (StO2). DCS measured the microvascular blood flow index (BFI). Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s) compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s), while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%), yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.

Fig 1. Protocol schematics with measurement locations, tissue dimensions and probe geometry.

Panel (A) Shows the location of the thyroid, its dimensions and the defined measurement points for this study together with a head turn used to expose the thyroid. The ultrasound images illustrate the locations of the jugular vein (JV), carotid artery (CA), esophagus (EPG), the (left) thyroid gland, its position and superficial structures (sternocleidomastoid muscle, skin and adipose layers) in normal neck (right) and rotated neck (left) position; Panel (B) shows an excerpt of an ultrasound image from a thyroid gland. The total tissue depth (TTD) is defined by the sum of the superficial tissues (STT) and the tissue thickness (TT). Typical values vary between different tissue types; Panel (C) illustrates the three different measurement points per side. The probe size and its placement are shown in relation to the thyroid gland size; Panel (D) shows the hybrid diffuse optics probe which consisted of one source per modality (DCS and TRS) and two different detector locations per source. For a good overlap for the probed regions by both modalities, we have used a cross-geometry with the DCS source on the left side, its detectors on the right side of the probe and for TRS vice-versa. The shorter source-detector separation (SD) was used in a subset of eleven subjects, which is half of the study population, as well as the two pathology cases.

Fig 2. Thyroid schematics and results for the nodule cases.

(A) CASE 1: Two locations were added to the standard protocol. The nodule was located within the left thyroid gland with a maximum diameter of 65 mm, as indicated by the shaded region. (B) CASE 1: One location was added on the right lobe to the standard protocol. This case had a maximum diameter 40 mm nodule (shaded region) together with a second nodule of 3 mm diameter, both located in the right thyroid gland. The results ((C) and (D)) are shown for the total hemoglobin concentration (THC), oxygen saturation (StO₂), blood flow index (BFI) and the reduced scattering coefficient (μ_s′) for 785 nm. Note, that these color plots do not include the muscle locations. For the detailed representation please refer to the Tables in S4 Table and in S5 Table.