Photon Counting CT and Radiomic Analysis Enables Differentiation of Tumors Based on Lymphocyte Burden

Abstract

The purpose of this study was to investigate if radiomic analysis based on spectral micro-CT with nanoparticle contrast-enhancement can differentiate tumors based on lymphocyte burden. High mutational load transplant soft tissue sarcomas were initiated in Rag2+/− and Rag2−/− mice to model varying lymphocyte burden. Mice received radiation therapy (20 Gy) to the tumor-bearing hind limb and were injected with a liposomal iodinated contrast agent. Five days later, animals underwent conventional micro-CT imaging using an energy integrating detector (EID) and spectral micro-CT imaging using a photon-counting detector (PCD). Tumor volumes and iodine uptakes were measured. The radiomic features (RF) were grouped into feature-spaces corresponding to EID, PCD, and spectral decomposition images. The RFs were ranked to reduce redundancy and increase relevance based on TL burden. A stratified repeated cross validation strategy was used to assess separation using a logistic regression classifier. Tumor iodine concentration was the only significantly different conventional tumor metric between Rag2+/− (TLs present) and Rag2−/− (TL-deficient) tumors. The RFs further enabled differentiation between Rag2+/− and Rag2−/− tumors. The PCD-derived RFs provided the highest accuracy (0.68) followed by decomposition-derived RFs (0.60) and the EID-derived RFs (0.58). Such non-invasive approaches could aid in tumor stratification for cancer therapy studies.

Prognostic value of different discretization parameters in 18fluorodeoxyglucose positron emission tomography radiomics of oropharyngeal squamous cell carcinoma

“…Future work studying CT-based radiomic features, particularly those on HRCT systems such as photon-counting CT, may provide complementary information about the biology of HNSCC tumors. 21 Combining radiomic features from both modalities can provide a more comprehensive understanding of the disease phenotype. Of course, optimal discretization techniques (i.e., FBN and FBS) are likely modality-specific, and future work will need to characterize accordingly.…”

“…The availability of intra-treatment PET/CT is a significant advantage for radiomic applicability in radiation oncology, particularly for future biologically-guided adaptative treatment paradigms. Future work studying CT-based radiomic features, particularly those on HRCT systems such as photon-counting CT, may provide complementary information about the biology of HNSCC tumors 21 . Combining radiomic features from both modalities can provide a more comprehensive understanding of the disease phenotype.…”

The National Cancer Institute’s Co-Clinical Quantitative Imaging Research Resources for Precision Medicine in Preclinical and Clinical Settings

“…These challenges include increasing SNR, reducing motion artifacts, optimizing protocols for improving repeatability and reproducibility, and improving sensitivity and specificity. Several manuscripts in this special issue contributed by the CIRP teams present the progress on the development of new technology and methodology [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

“…Spectral micro-CT with nanoparticle (NP) contrast enhancement can differentiate the lymphocyte (TL) burden in tumors. Allphin et al are using a liposomal iodine (Lip-I) NP contrast agent for CT imaging in Rag2 −/− (TL deficient) and littermate control Rag2 +/− (TL present) mice, followed by radiomic analysis, to quantitatively assess TL burden [ 38 ].…”

Imaging in translational cancer research

“…In a similar study, iodine and gadolinium based intravenous contrast agent injections in rats have been demonstrated to feasibly differentiate peritoneal metastases in colorectal carcinoma with a specificity of 100% 31 . Furthermore, in a mouse model of soft tissue sarcoma receiving radiation therapy, the radiomic features from PCD CT with iodine contrast have been found to be superior to those of conventional micro-CT in differentiating among various tumor metrics 32 . Such functional characterizations of tumor tissue are expected to be important in future preclinical research and may be used in whole-body PCD CT imaging for translational research from rodents to humans 33 .…”