Contrast improvement of terahertz images of thin histopathologic sections

Abstract

We present terahertz images of 10 μm thick histopathologic sections obtained in reflection geometry with a time-domain spectrometer, and demonstrate improved contrast for sections measured in paraffin with water. Automated segmentation is applied to the complex refractive index data to generate clustered terahertz images distinguishing cancer from healthy tissues. The degree of classification of pixels is then evaluated using registered visible microscope images. Principal component analysis and propagation simulations are employed to investigate the origin and the gain of image contrast.

Pulsed terahertz imaging of breast cancer in freshly excised murine tumors

“…4 However, several classification methods have been applied to FFPE tissue applications and/ or spectroscopy of tissues, including wavelet transformation for osteosarcoma, 22 orthogonal signal correction and fuzzy rulebending expert system for cervical cancer, 23 multispectral classification of FFPE basal cell carcinoma, 24 and PCA for potentially malignant skin nevi 25 and FFPE liver cancer. 26,27 This work investigates a Bayesian mixture model utilizing a Markov chain Monte Carlo (MCMC) scheme for THz image classification of both fresh and FFPE murine breast tumors. 28 This work is different from the authors' previous work where they performed qualitative THz imaging and characterization of FFPE breast cancer tissue 8,9 as well as THz imaging and image processing of three-dimensional FFPE breast cancer tissue and characterization of carbon nanoparticles for THz contrast enhancement.…”

Terahertz in-line digital holography of human hepatocellular carcinoma tissue

“…Similar to microwave radiation, and in contrast to X-rays, terahertz radiation can penetrate non-conducting materials, such as clothes, without causing ionising radiation damage. These properties make terahertz waves suitable for non-invasive biomedical imaging and cancer diagnosis 1 2 3 4 5 6 7 8 9 10 11 12 13 .…”

“…For most cancers, confident diagnosis at an early stage is a challenging task, and several cross-checking tests are typically performed. Diseased or cancerous tissues contain more interstitial water than healthy tissues as a result of oedema or increased vascularity 3 , and the analysis of water content can be performed by measuring the absorption of terahertz radiation 1 2 3 4 5 6 7 8 9 10 11 12 . However, the absorption contrast is affected not only by the water content but also by the structural changes caused by cancer 4 .…”

“…Terahertz time domain spectroscopy (THz-TDS) 14 15 is capable of extracting both the amplitude and phase information of the pulsed terahertz signal, enabling the absorption coefficient and the refractive index of the object to be obtained simultaneously 3 4 5 . To further determine the histological features of the tissue, the image is mapped out pixel by pixel by raster scanning the object based on THz-TDS in the reflective mode 6 7 8 9 , also referred to as terahertz pulsed imaging (TPI) 16 . However, TPI has the following disadvantages: the sample size must be larger than 5 mm × 5 mm to avoid diffraction effects at the sample's edges, and dehydration must be prevented during the slow acquisition time, which varies from 10 min for a 26 mm × 20 mm sample 6 to 6 hours for an 18.7 mm × 18.7 mm 9 sample depending on the hardware and the scanning step.…”

“…To further determine the histological features of the tissue, the image is mapped out pixel by pixel by raster scanning the object based on THz-TDS in the reflective mode 6 7 8 9 , also referred to as terahertz pulsed imaging (TPI) 16 . However, TPI has the following disadvantages: the sample size must be larger than 5 mm × 5 mm to avoid diffraction effects at the sample's edges, and dehydration must be prevented during the slow acquisition time, which varies from 10 min for a 26 mm × 20 mm sample 6 to 6 hours for an 18.7 mm × 18.7 mm 9 sample depending on the hardware and the scanning step. Continuous-wave (CW) terahertz imaging of cancerous tissues has become more popular due to the ready availability of commercial high-power terahertz laser systems.…”