One of the leading causes of cancer-related death is gastrointestinal cancer, which has a significant morbidity and mortality rate. Although preoperative risk assessment is essential for directing patient care, its biological behavior cannot be accurately predicted by conventional imaging investigations. Potential pathophysiological information in anatomical imaging that cannot be visually identified can now be converted into high-dimensional quantitative image features thanks to the developing discipline of molecular imaging. In order to enable molecular tissue profile in vivo, molecular imaging has most recently been utilized to phenotype the expression of single receptors and targets of biological therapy. It is expected that molecular imaging will become increasingly important in the near future, driven by the expanding range of biological therapies for cancer. With this live molecular fingerprinting, molecular imaging can be utilized to drive expression-tailored customized therapy. The technical aspects of molecular imaging are first briefly discussed in this review, followed by an examination of the most recent research on the diagnosis, prognosis, and potential future clinical methods of molecular imaging for GI tract malignancies.

Targeted anticancer drugs block cancer cell growth by interfering with specific signaling pathways vital to carcinogenesis and tumor growth rather than harming all rapidly dividing cells as in cytotoxic chemotherapy. The Response Evaluation Criteria in Solid Tumor (RECIST) system has been used to assess tumor response to therapy via changes in the size of target lesions as measured by calipers, conventional anatomically based imaging modalities such as computed tomography (CT), and magnetic resonance imaging (MRI), and other imaging methods. However, RECIST is sometimes inaccurate in assessing the efficacy of targeted therapy drugs because of the poor correlation between tumor size and treatment-induced tumor necrosis or shrinkage. This approach might also result in delayed identification of response when the therapy does confer a reduction in tumor size. Innovative molecular imaging techniques have rapidly gained importance in the dawning era of targeted therapy as they can visualize, characterize, and quantify biological processes at the cellular, subcellular, or even molecular level rather than at the anatomical level. This review summarizes different targeted cell signaling pathways, various molecular imaging techniques, and developed probes. Moreover, the application of molecular imaging for evaluating treatment response and related clinical outcome is also systematically outlined. In the future, more attention should be paid to promoting the clinical translation of molecular imaging in evaluating the sensitivity to targeted therapy with biocompatible probes. In particular, multimodal imaging technologies incorporating advanced artificial intelligence should be developed to comprehensively and accurately assess cancer-targeted therapy, in addition to RECIST-based methods.

Tumors usually become localized absorbers at near infrared (NIR) wavelengths due to the increase in hemoglobin amount around the tumor, which is caused by angiogenesis. When a tumor is small and/or deeply seated, the contrast by the hemoglobin only, however, may not be strong. For such situation, contrast agents may be helpful, because they are preferentially accumulated in the tumor due to the unorganized tumor vasculature. In this study, indocyanine green (ICG) was used as a contrast enhancer. ICG is safe, absorbs NIR, and also generates fluorescence. A breast tissue-like model, embedded with a tumor model (1.2 x 0.7 x 0.5 cm) with/without ICG at a 1 cm depth, was constructed and the surface was scanned by a NIR time-resolved spectroscopy instrument. Enhanced contrast by ICG was confirmed in both absorption and fluorescence. For absorption, transmittance contrast was approximately two times higher than reflectance. In reflectance, the contrast by fluorescence was approximately four times higher than absorption. This study result shows that the information on both the absorption and fluorescence by ICG can be effectively used in detecting a tumor. A study of the ICG effect on deeper absorber detection is in progress.

A typical tumor releases angiogenesis factor that induces the capillary growth around the tumor and, therefore, a greater amount of blood is present around the tumor. A tumor usually, therefore, becomes a local absorber due to its higher hemoglobin concentration. The ultimate goal of this project is to localize the position of a tumor in a breast tissue at an early stage using near infrared spectroscopy. Computer simulations were performed to obtain TRS spectra at various locations in a system with optical properties of human breast. The time domain output pulses, then, were transferred to the frequency domain and the data were analyzed at various modulated frequencies. The changes in the photon path with respect to the frequency were systematically studied for absorber localization in three-dimensions. Two different source-detector configurations, transmittance and reflectance were studied to explore the best TRS spectra acquisition procedure for tumor localization. Our previous study results have shown that in reflectance measurements the photon penetration depth is dependent on both the source-detector (S-D) separation distance and the modulation frequency. More specifically, the photon penetration depth decreases at smaller source and detector separations and higher frequencies. In this study, the effects of these two parameters on the photon path were studied in both transmittance and reflectance. This study results may be used effectively in determining the position.

Breast cancer causes the death of more than 150,000 women in the United States each year. Pregnant women cannot undergo mammography due to its dangerous side effects and, for younger women, a mammogram does not differentiate tumor from their dense breast tissue. Breast tumors usually become a localized absorber in the near infrared (NIR) wavelength region, because of the increased hemoglobin concentration around the area of the tumor. Therefore, NIR has a high potential to detect breast cancer without side effects. A computer simulation solving the photon transfer equation was used to study the detectability of various tumor sizes embedded in the breast model at various depths, for both reflectance and transmittance. Previous reflectance studies demonstrated that increasing the S-D separation does not necessarily allow the photons to penetrate deeper in the medium. The optimum S-D separation for breast tissue was found to be 3.0 cm, where the light penetrates up to 1.7 cm. Studies on the photon path in transmittance demonstrate that, at high modulation frequencies, (e.g. 1.0 GHz), the photon path becomes more coherent. Therefore, for transmittance measurements, high modulation frequencies can be useful to localize deep tumors. Multi frequency, multi- S-D separation reflectance can be used to provide information on tumor depth.

Frequency response analysis is applied for the analysis of liquid chromatography output of protein separation. Reduced data from simple chromatograms suggest that various Bode plot parameters, magnitude ratios, phase shift, the steady state gain, break frequency, and system order in the frequency domain, can be used to gain phenomenological insights on the system. Such an approach is advantageous because the validity of the model can be checked for two plots, the magnitude ratio vs. frequency and the phase shift vs. frequency, as compared to a single plot in the time domain. This approach also provides a useful empirical-tool which can be quantifiably used for process validation and scale-up, especially for immunoaffinity and immobilized metal affinity chromatographic systems used for protein C purification.