Clinical Scholar, Radiology
- Artificial Intelligence Applications in Aortic Dissection Imaging. Seminars in roentgenology 2022; 57 (4): 357-363
Overcoming a Technological Hurdle: Coronary CT Angiography with Photon-counting CT
2022; 303 (2)
View details for Web of Science ID 000788099000013
Long-term expression changes of immune-related genes in prostate cancer after radiotherapy.
Cancer immunology, immunotherapy : CII
The expression of immune-related genes in cancer cells can alter the anti-tumor immune response and thereby impact patient outcomes. Radiotherapy has been shown to modulate immune-related genes dependent on the fractionation regimen. To identify long-term changes in gene expression after irradiation, PC3 (p53 deleted) and LNCaP (p53 wildtype) prostate cancer cells were irradiated with either a single dose (SD, 10Gy) or a fractionated regimen (MF) of 10 fractions (1Gy per fraction). Whole human genome arrays were used to determine gene expression at 24h and 2months after irradiation. Immune pathway activation was analyzed with Ingenuity Pathway Analysis software. Additionally, 3D colony formation assays and T-cell cytotoxicity assays were performed. LNCaP had a higher basal expression of immunogenic genes and was more efficiently killed by cytotoxic T-cells compared to PC3. In both cell lines, MF irradiation resulted in an increase in multiple immune-related genes immediately after irradiation, while at 2months, SD irradiation had a more pronounced effect on radiation-induced gene expression. Both immunogenic and immunosuppressive genes were upregulated in the long term in PC3 cells by a 10Gy SD irradiation but not in LNCaP. T-cell-mediated cytotoxicity was significantly increased in 10Gy SD PC3 cells compared to the unirradiated control and could be further enhanced by treatment with immune checkpoint inhibitors. Irradiation impacts the expression of immune-related genes in cancer cells in a fractionation-dependent manner. Understanding and targeting these changes may be a promising strategy for primary prostate cancer and recurrent tumors.
View details for DOI 10.1007/s00262-021-03036-w
View details for PubMedID 34435232
The lncRNAs LINC00261 and LINC00665 are upregulated in long-term prostate cancer adaptation after radiotherapy.
Molecular therapy. Nucleic acids
2021; 24: 175–87
Long non-coding RNAs (lncRNAs) have been shown to impact important biological functions such as proliferation, survival, and genomic stability. To analyze radiation-induced lncRNA expression in human tumors, we irradiated prostate cancer cells with a single dose of 10Gy or a multifractionated radiotherapeutic regimen of 10 fractions with a dose of 1Gy (10* 1 Gy) during 5days. We found a stable upregulation of the lncRNA LINC00261 and LINC00665 at 2months after radiotherapy that was more pronounced after single-dose irradiation. Analysis of the The Cancer Genome Atlas (TCGA) and The Atlas of Non-coding RNAs in Cancer (TANRIC) databases showed that high expression of these two lncRNAs may be a potential negative prognostic marker for overall survival of prostate cancer patients. Knockdown of LINC00261 and LINC00665 in long-term survivors decreased survival after re-irradiation and affected DNA double-strand break repair. Mechanistically, both lncRNAs showed an interdependent expression and regulated expression of the DNA repair proteins CtIP (RBBP8) and XPC as well as the microRNA miR-329. Identifying long-term tumor adaptation mechanisms can lead to the discovery of new molecular targets, in effect opening up new research directions and improving multimodal radiation oncologic treatment.
View details for DOI 10.1016/j.omtn.2021.02.024
View details for PubMedID 33767914
- CT of the Heart: Expanding Clinical Applications in Pulmonary Hypertension. Radiology 2021: 204468
Hepatic Steatosis: CT-based Prevalence in Adults in China and the United States and Associations with Age, Sex, and Body Mass Index.
AJR. American journal of roentgenology
Background: Calibrated CT fat fraction (FFCT) measurements derived from non-enhanced abdominal CT reliably reflect liver fat content, allowing largescale population-level investigations of steatosis prevalence and associations. Objective: To compare prevalence of hepatic steatosis, assessed by calibrated CT measurements, between population-based Chinese and U.S. cohorts, and to investigate in these populations the relationship of steatosis with age, sex, and body mass index (BMI). Methods: This retrospective study included 3176 adults (1985 women, 1191 men) from seven Chinese provinces and 8748 adults (4834 women, 3914 men) from a single U.S. medical center, drawn from earlier studies. All participants were at least 40 years old and underwent unenhanced abdominal CT for the earlier studies. Liver fat content measurements on CT were cross-calibrated to MRI proton density fat fraction measurements using phantoms and expressed as adjusted FFCT. Mild, moderate, and severe steatosis were defined as adjusted FFCT of 5.0%-14.9%, 15.0%-24.9%, and ≥25.0%, respectively. The two cohorts were compared. Results: Median adjusted FFCT was for women 4.7% and 4.8%, and for men 5.8% and 6.2%, in the Chinese and U.S. cohorts, respectively. Steatosis prevalence was for women 46.3% and 48.7%, and for men 58.9% and 61.9%, in the Chinese and U.S. cohorts, respectively. Severe steatosis prevalence was for women 0.9% and 1.8%, and for men, 0.2% and 2.6%, in the Chinese and U.S. cohorts, respectively. Adjusted FFCT did not vary across age decades in women or men in the Chinese cohort, though increased across age decades in women and men in the U.S. cohort. Adjusted FFCT and BMI exhibited weak correlation (r=0.312-0.431). Among participants with normal BMI, 36.8% and 38.5% of those in the Chinese and U.S. cohorts had mild steatosis, and 3.0% and 1.5% had moderate or severe steatosis, respectively. Among U.S. participants with BMI ≥40.0, 17.7% had normal liver content. Conclusion: Steatosis and severe steatosis had higher prevalence in the U.S. than Chinese cohort in both women and men. BMI did not reliably predict steatosis. Clinical Impact: The findings provide new information on the dependence of hepatic steatosis on age, sex, and BMI.
View details for DOI 10.2214/AJR.21.26728
View details for PubMedID 34817193
Spectral photon-counting CT in cardiovascular imaging.
Journal of cardiovascular computed tomography
Photon-counting computed tomography (PCCT) is an emerging technology promising to substantially improve cardiovascular imaging. Recent engineering and manufacturing advances by several vendors are expected to imminently launch this new technology into clinical reality. Photon-counting detectors (PCDs) have multiple potential advantages over conventional energy integrating detectors (EIDs) such as the absence of electronic noise, multi-energy capability, and increased spatial resolution. These developments will have different timescales for implementation and will affect different clinical scopes. We describe the technical aspects of PCCT, explain the current developments, and finally discuss potential advantages of PCCT in cardiovascular imaging.
View details for DOI 10.1016/j.jcct.2020.12.005
View details for PubMedID 33358186
Reliable segmentation of 2D cardiac magnetic resonance perfusion image sequences using time as the 3rd dimension.
OBJECTIVES: Cardiac magnetic resonance (CMR) first-pass perfusion is an established noninvasive diagnostic imaging modality for detecting myocardial ischemia. A CMR perfusion sequence provides a time series of 2D images for dynamic contrast enhancement of the heart. Accurate myocardial segmentation of the perfusion images is essential for quantitative analysis and it can facilitate automated pixel-wise myocardial perfusion quantification.METHODS: In this study, we compared different deep learning methodologies for CMR perfusion image segmentation. We evaluated the performance of several image segmentation methods using convolutional neural networks, such as the U-Net in 2D and 3D (2D plus time) implementations, with and without additional motion correction image processing step. We also present a modified U-Net architecture with a novel type of temporal pooling layer which results in improved performance.RESULTS: The best DICE scores were 0.86 and 0.90 for LV myocardium and LV cavity, while the best Hausdorff distances were 2.3 and 2.1 pixels for LV myocardium and LV cavity using 5-fold cross-validation. The methods were corroborated in a second independent test set of 20 patients with similar performance (best DICE scores 0.84 for LV myocardium).CONCLUSIONS: Our results showed that the LV myocardial segmentation of CMR perfusion images is best performed using a combination of motion correction and 3D convolutional networks which significantly outperformed all tested 2D approaches. Reliable frame-by-frame segmentation will facilitate new and improved quantification methods for CMR perfusion imaging.KEY POINTS: Reliable segmentation of the myocardium offers the potential to perform pixel level perfusion assessment. A deep learning approach in combination with motion correction, 3D (2D + time) methods, and a deep temporal connection module produced reliable segmentation results.
View details for DOI 10.1007/s00330-020-07474-5
View details for PubMedID 33247342
Cardiac cine CT approaching 1mSv: implementation and assessment of a 58-ms temporal resolution protocol.
The international journal of cardiovascular imaging
Clinical use of cardiac cine CT imaging is limited by high radiation dose and low temporal resolution. To evaluate a low radiation dose, high temporal resolution cardiac cine CT protocol in human cardiac CT and phantom scans. CT scans of a circulating iodine target were reconstructed using the conventional single heartbeat half-scan (HS, approx. 175ms temporal resolution) and the 3-heartbeat multi-segment (MS, approx. 58ms) algorithms. Motion artifacts were quantified by the root-mean-square error (RMSE). Low-dose cardiac cine CT scans were performed in 55 subjects at a tube potential of 80 kVp and current of 80mA. Image quality of HS and MS scans was assessed by blinded reader quality assessment, left ventricular (LV) free wall motion, and LV ejection rate. Motion artifacts in phantom scans were higher in HS than in MS reconstructions (RSME 188 and 117 HU, respectively; p=0.001). Median radiation dose in human scans was 1.2mSv. LV late diastolic filling was observed more frequently in MS than in HS images (42 vs. 26 subjects, respectively; p<0.001). LV free wall systolic motion was more physiologic and had less error in MS than in HS reconstructions (sum-of-squared errors 34 vs. 45 mm2, respectively; p<0.001), and LV peak ejection rate was higher in MS than in HS reconstructions (166 vs. 152mL/s, respectively; p<0.001). Cardiac cine CT imaging is feasible at a low radiation dose of 1.2mSv. MS reconstruction showed improved imaging of rapid motion in phantom studies and human cardiac CTs.
View details for DOI 10.1007/s10554-020-01863-z
View details for PubMedID 32367189
53BP1/RIF1 signaling promotes cell survival after multifractionated radiotherapy.
Nucleic acids research
Multifractionated irradiation is the mainstay of radiation treatment in cancer therapy. Yet, little is known about the cellular DNA repair processes that take place between radiation fractions, even though understanding the molecular mechanisms promoting cancer cell recovery and survival could improve patient outcome and identify new avenues for targeted intervention. To address this knowledge gap, we systematically characterized how cells respond differentially to multifractionated and single-dose radiotherapy, using a combination of genetics-based and functional approaches. We found that both cancer cells and normal fibroblasts exhibited enhanced survival after multifractionated irradiation compared with an equivalent single dose of irradiation, and this effect was entirely dependent on 53BP1-mediated NHEJ. Furthermore, we identified RIF1 as the critical effector of 53BP1. Inhibiting 53BP1 recruitment to damaged chromatin completely abolished the survival advantage after multifractionated irradiation and could not be reversed by suppressing excessive end resection. Analysis of the TCGA database revealed lower expression of 53BP1 pathway genes in prostate cancer, suggesting that multifractionated radiotherapy might be a favorable option for radio-oncologic treatment in this tumor type. We propose that elucidation of DNA repair mechanisms elicited by different irradiation dosing regimens could improve radiotherapy selection for the individual patient and maximize the efficacy of radiotherapy.
View details for DOI 10.1093/nar/gkz1139
View details for PubMedID 31822909