Tyler Bowman

Terahertz Imaging of Excised Breast Tumor Tissue on Paraffin Sections

This paper presents imaging and analysis of heterogeneous breast cancer tissue using pulsed terahertz (THz) imaging technology. The goal of this research is to validate and standardize a methodology for THz imaging capable of differentiating between heterogeneous regions of breast tumors. The specimens utilized here were obtained from breast tumors diagnosed as triple negative infiltrating ductal carcinoma (IDC). These tissues were fixed in formalin, embedded in paraffin, and cut into sections of three thicknesses: 10, 20, and 30 μm. All tissues were prepared on standard glass slides used in regular histopathology of hematoxylin and eosin (H&E) stained sections. The THz pulsed system is used to scan the two dimensional tissue sections with step size of 400, 200, and 50 μm. The experimentally measured THz fields reflected from single pixels identified in each region of the tumor are validated with the Fresnel reflection coefficient formulation. A variety of signal normalization and processing methods are investigated. The images are also validated with the standard histopathology images. The obtained results of three different tumors demonstrate strong capability of THz reflection imaging mode to distinguish between the heterogeneous regions in the tumor.

Terahertz spectroscopy for the characterization of excised human breast tissue

This paper presents experimental terahertz spectroscopy measurements of normal and breast cancer tissue in the range 0.1 to 4 THz. Both tissue types are prepared on microscope glass and polystyrene slides. The preliminary results of a particular tumor tissue using terahertz spectroscopy align with the pathology diagnosis of poorly differentiated tumor. The results demonstrate the potential of terahertz spectroscopy for the characterization of cancer, fibro, and normal breast tissue. More research into the sample thickness, microscopic slide material, embedding medium and cancer type will be presented using a large number of samples in order to establish the technique.

Terahertz transmission vs reflection imaging and model-based characterization for excised breast carcinomas

This work presents experimental and analytical comparison of terahertz transmission and reflection imaging modes for assessing breast carcinoma in excised paraffin-embedded human breast tissue. Modeling for both transmission and reflection imaging is developed. The refractive index and absorption coefficient of the tissue samples are obtained. The reflection measurements taken at the systems fixed oblique angle of 30° are shown to be a hybridization of TE and TM modes. The models are validated with transmission spectroscopy at fixed points on fresh bovine muscle and fat tissues. Images based on the calculated absorption coefficient and index of refraction of bovine tissue are successfully compared with the terahertz magnitude and phase measured in the reflection mode. The validated techniques are extended to 20 and 30 μm slices of fixed human lobular carcinoma and infiltrating ductal carcinoma mounted on polystyrene microscope slides in order to investigate the terahertz differentiation of the carcinoma with non-cancerous tissue. Both transmission and reflection imaging show clear differentiation in carcinoma versus healthy tissue. However, when using the reflection mode, in the calculation of the thin tissue properties, the absorption is shown to be sensitive to small phase variations that arise due to deviations in slide and tissue thickness and non-ideal tissue adhesion. On the other hand, the results show that the transmission mode is much less sensitive to these phase variations. The results also demonstrate that reflection imaging provides higher resolution and more clear margins between cancerous and fibroglandular regions, cancerous and fatty regions, and fibroglandular and fatty tissue regions. In addition, more features consistent with high power pathology images are exhibited in the reflection mode images.

The linear sampling method for the acceleration of the level set algorithm

The robust shape reconstruction level set algorithm has proven its capability for reconstructing the exact shape and location of unknown 2D and 3D targets. However, the computational time of the level set algorithm can be extensive especially for complex multi-scale targets. In order to eliminate this burden, the qualitative Linear Sampling Method (LSM) is investigated to generate the initial guess for the level set algorithm. In this case, the obtained results show a reduction of almost 90% of the CPU time required by the level set algorithm.

A phantom study of terahertz spectroscopy and imaging of micro- and nano-diamonds and nano-onions as contrast agents for breast cancer

THz imaging is effective in distinguishing between cancerous, healthy, and fatty tissues in breast tumors, but a challenge remains in the contrast between cancerous and fibroglandular (healthy) tissues. This work investigates carbon-based nanoparticles as potential contrast agents for terahertz imaging of breast cancer. Microdiamonds, nanodiamonds, and nanometer-scale onion-like carbon are characterized with terahertz transmission spectroscopy in low-absorption backgrounds of polydimethylsiloxane or polyethylene. The refractive index and absorption coefficients are calculated based on the measured electric fields. Nanodiamonds show little effect on the terahertz signal, microdiamonds express resonance-like, size-dependent absorption peaks, and onion-like carbon provides a uniform increase in the optical properties even at low concentration. Due to its strong interaction with terahertz frequencies and ability to be activated for selective binding to cancer cells, onion-like carbon is implemented into engineered three-dimensional breast tumor models composed of phantom tissue mimicking infiltrating ductal carcinoma surrounded by a phantom mimicking healthy fibroglandular tissue. This model is imaged using the terahertz reflection mode to examine the effectiveness of contrast agents for differentiation between the two tissue types. In both spectroscopy and imaging, a 10% concentration of onion-like carbon shows the strongest impact on the terahertz signal and holds promise as a terahertz contrast agent.

Time of flight estimation for breast cancer margin thickness using embedded tumors

This work aims to enact a quick and reasonable estimation of breast cancer margin thickness using time of flight analysis of embedded breast cancer tissue. A pulsed terahertz system is used to obtain reflection imaging scans from breast cancer tumors that are formalin-fixed and embedded in paraffin blocks. Time of flight analysis is then used to compare the reflection patterns seen within the block to pathology sections and paraffin-embedded sections that are taken throughout the depth of the tumor in order to estimate the three-dimensional boundaries of the tumor.

Pulsed terahertz imaging of breast cancer in freshly excised murine tumors

Abstract. This paper investigates terahertz (THz) imaging and classification of freshly excised murine xenograft breast cancer tumors. These tumors are grown via injection of E0771 breast adenocarcinoma cells into the flank of mice maintained on high-fat diet. Within 1 h of excision, the tumor and adjacent tissues are imaged using a pulsed THz system in the reflection mode. The THz images are classified using a statistical Bayesian mixture model with unsupervised and supervised approaches. Correlation with digitized pathology images is conducted using classification images assigned by a modal class decision rule. The corresponding receiver operating characteristic curves are obtained based on the classification results. A total of 13 tumor samples obtained from 9 tumors are investigated. The results show good correlation of THz images with pathology results in all samples of cancer and fat tissues. For tumor samples of cancer, fat, and muscle tissues, THz images show reasonable correlation with pathology where the primary challenge lies in the overlapping dielectric properties of cancer and muscle tissues. The use of a supervised regression approach shows improvement in the classification images although not consistently in all tissue regions. Advancing THz imaging of breast tumors from mice and the development of accurate statistical models will ultimately progress the technique for the assessment of human breast tumor margins.

Regional spectroscopy of paraffin-embedded breast cancer tissue using pulsed terahertz transmission imaging

This work seeks to obtain the properties of paraffin-embedded breast cancer tumor tissues using transmission imaging and spectroscopy. Formalin-fixed and paraffin-embedded breast tumors are first sectioned into slices of 20 μm and 30 μm and placed between two tsurupica slides. The slides are then scanned in a pulsed terahertz system using transmission imaging. The tissue regions in adjacent pathology section are compared to the transmission imaging scan in order to define a region of points over which to average the electrical properties results from the scan.

Adaptive enhancement and visualization techniques for 3D THz images of breast cancer tumors

This paper evaluates image enhancement and visualization techniques for pulsed terahertz (THz) images of tissue samples. Specifically, our research objective is to effectively differentiate between heterogeneous regions of breast tissues that contain tumors diagnosed as triple negative infiltrating ductal carcinoma (IDC). Tissue slices and blocks of varying thicknesses were prepared and scanned using our lab’s THz pulsed imaging system. One of the challenges we have encountered in visualizing the obtained images and differentiating between healthy and cancerous regions of the tissues is that most THz images have a low level of details and narrow contrast, making it difficult to accurately identify and visualize the margins around the IDC. To overcome this problem, we have applied and evaluated a number of image processing techniques to the scanned 3D THz images. In particular, we employed various spatial filtering and intensity transformation techniques to emphasize the small details in the images and adjust the image contrast. For each of these methods, we investigated how varying filter sizes and parameters affect the amount of enhancement applied to the images. Our experimentation shows that several image processing techniques are effective in producing THz images of breast tissue samples that contain distinguishable details, making further segmentation of the different image regions promising.

Z-scan terahertz imaging of embedded three-dimensional breast cancer tissue

The terahertz (THz) frequency range is a rapidly developing field in electromagnetics today. Biomedical imaging has become a key area of focus for THz applications due to improved depth resolution over microwave imaging while still having greater penetration than optical frequencies. THz imaging is sensitive to water content, which serves as a strong contrast factor in cancer detection and imaging.