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Hypoxia is a common feature of solid tumors, and develops because of the rapid growth of the tumor that outstrips the oxygen supply, and impaired blood flow due to the formation of abnormal blood vessels supplying the tumor. It has been reported that tumor hypoxia can: activate angiogenesis, thereby enhancing invasiveness and risk of metastasis; increase survival of tumor, as well as suppress anti-tumor immunity and hamper the therapeutic response. Hypoxia mediates these effects by several potential mechanisms: altering gene expression, the activation of oncogenes, inactivation of suppressor genes, reducing genomic stability and clonal selection. We have reviewed the effects of hypoxia on tumor biology and the possible strategiesto manage the hypoxic tumor microenvironment (TME), highlighting the potential use of cancer stem cells in tumor treatment.

Purpose To retrospectively validate a first-pass analysis (FPA) technique that combines computed tomographic (CT) angiography and dynamic CT perfusion measurement into one low-dose examination. Materials and Methods The study was approved by the animal care committee. The FPA technique was retrospectively validated in six swine (mean weight, 37.3 kg ± 7.5 [standard deviation]) between April 2015 and October 2016. Four to five intermediate-severity stenoses were generated in the left anterior descending artery (LAD), and 20 contrast material-enhanced volume scans were acquired per stenosis. All volume scans were used for maximum slope model (MSM) perfusion measurement, but only two volume scans were used for FPA perfusion measurement. Perfusion measurements in the LAD, left circumflex artery (LCx), right coronary artery, and all three coronary arteries combined were compared with microsphere perfusion measurements by using regression, root-mean-square error, root-mean-square deviation, Lin concordance correlation, and diagnostic outcomes analysis. The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were also determined. Results FPA and MSM perfusion measurements (P and P) in all three coronary arteries combined were related to reference standard microsphere perfusion measurements (P), as follows: P = 1.02 P + 0.11 (r = 0.96) and P = 0.28 P + 0.23 (r = 0.89). The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were 10.8 and 17.8 mGy, respectively. Conclusion The FPA technique was retrospectively validated in a swine model and has the potential to be used for accurate, low-dose vessel-specific morphologic and physiologic assessment of coronary artery disease. RSNA, 2017.

Background Computerized tomography (CT) angiography is an important tool for evaluation of coronary artery disease (CAD), but often correlates poorly with myocardial ischemia. Current dynamic CT perfusion techniques can assess ischemia, but have limited accuracy and deliver high radiation dose. Therefore, an accurate, low-dose, dynamic CT perfusion technique is needed. Methods and Results A total of 20 contrast enhanced CT volume scans were acquired in 5 swine (40 ± 10 kg) to generate CT angiography and perfusion images. Varying degrees of stenosis were induced using a balloon catheter in the proximal left anterior descending (LAD) coronary artery and a pressure wire was used for reference fractional flow reserve (FFR) measurement. Perfusion measurements were made with only two volume scans using a new first-pass analysis (FPA) technique and with 20 volume scans using an existing maximum slope model (MSM) technique. Perfusion (P) and FFR measurements were related by PFPA = 1.01 FFR − 0.03 (R2 = 0.85) and PMSM = 1.03 FFR − 0.03 (R2 = 0.80) for FPA and MSM techniques, respectively. Additionally, the effective radiation doses were calculated to be 2.64 and 26.4 mSv for FPA and MSM techniques, respectively. Conclusions A new FPA-based dynamic CT perfusion technique was validated in a swine animal model. The results indicate that the FPA technique can potentially be used for improved anatomical and functional assessment of CAD at a relatively low radiation dose.

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