Prediction of endovascular leaks after thoracic endovascular aneurysm repair though machine learning applied to pre-procedural computed tomography angiographs.

To predict endoleaks after thoracic endovascular aneurysm repair (TEVAR) we submitted patient characteristics and vessel features observed on pre- operative computed tomography angiography (CTA) to machine-learning. We evaluated 1-year follow-up CT scans (arterial and delayed phases) in patients who underwent TEVAR for the presence or absence of an endoleak. We evaluated the effect of machine learning of the patient age, sex, weight, and height, plus 22 vascular features on the ability to predict post-TEVAR endoleaks. The extreme Gradient Boosting (XGBoost) for ML system was trained on 14 patients with- and 131 without endoleaks. We calculated their importance by applying XGBoost to machine learning and compared our findings between with those of conventional vessel measurement-based methods such as the 22 vascular features by using the Pearson correlation coefficients. Pearson correlation coefficient and 95% confidence interval (CI) were r = 0.86 and 0.75 to 0.92 for the machine learning, r = - 0.44 and - 0.56 to - 0.29 for the vascular angle, and r = - 0.19 and - 0.34 to - 0.02 for the diameter between the subclavian artery and the aneurysm (Fig. 3a-c, all: p < 0.05). With machine-learning, the univariate analysis was significant higher compared with the vascular angle and in the diameter between the subclavian artery and the aneurysm such as the conventional methods (p < 0.05). To predict the risk for post-TEVAR endoleaks, machine learning was superior to the conventional vessel measurement method when factors such as patient characteristics, and vascular features (vessel length, diameter, and angle) were evaluated on pre-TEVAR thoracic CTA images.

Using Patient-Specific Contrast Enhancement Optimizer Simulation Software During the Transcatheter Aortic Valve Implantation-Computed Tomography Angiography in Patients With Aortic Stenosis.

OBJECTIVES: This study assessed whether patient-specific contrast enhancement optimizer simulation software (p-COP) can reduce the contrast material (CM) dose compared with the conventional body weight (BW)-tailored scan protocol during transcatheter aortic valve implantation-computed tomography angiography (TAVI-CTA) in patients with aortic stenosis. METHODS: We used the CM injection protocol selected by the p-COP in group A (n = 30). p-COP uses an algorithm that concerns data on an individual patient's cardiac output. Group B (n = 30) was assigned to the conventional BW-tailored CM injection protocol group. We compared the CM dose, CM amount, injection rate, and computed tomography (CT) values in the abdominal aorta between the 2 groups and classified them as acceptable (>280 Hounsfield units (HU)) or unacceptable (<279 HU) based on the optimal CT value and visualization scores for TAVI-CTA. We used the Mann-Whitney U test to compare patient characteristics and assess the interpatient variability of subjects in both groups. RESULTS: Group A received 56.2 mL CM and 2.6 mL/s of injection, whereas group B received 76.9 mL CM and 3.4 mL/s of injection (P < 0.01). The CT value for the abdominal aorta at the celiac level was 287.0 HU in group A and 301.7HU in group B (P = 0.46). The acceptable (>280 HU) and unacceptable (<280 HU) CT value rates were 22 and 8 patients in group A and 24 and 6 patients in group B, respectively (P = 0.76). We observed no significant differences in the visualization scores between groups A and B (visualization score = 3, P = 0.71). CONCLUSION: The utilization of p-COP may decrease the CM dosage and injection rate by approximately 30% in individuals with aortic stenosis compared with the body-weight-tailored scan protocol during TAVI-CTA.

Histone methyltransferase SUV39H1 regulates the Golgi complex via the nuclear envelope-spanning LINC complex.

Cell motility is related to the higher-order structure of chromatin. Stimuli that induce cell migration change chromatin organization; such stimuli include elevated histone H3 lysine 9 trimethylation (H3K9me3). We previously showed that depletion of histone H3 lysine 9 methyltransferase, SUV39H1, suppresses directional cell migration. However, the molecular mechanism underlying this association between chromatin and cell migration remains elusive. The Golgi apparatus is a cell organelle essential for cell motility. In this study, we show that loss of H3K9 methyltransferase SUV39H1 but not SETDB1 or SETDB2 causes dispersion of the Golgi apparatus throughout the cytoplasm. The Golgi dispersion triggered by SUV39H1 depletion is independent of transcription, centrosomes, and microtubule organization, but is suppressed by depletion of any of the following three proteins: LINC complex components SUN2, nesprin-2, or microtubule plus-end-directed kinesin-like protein KIF20A. In addition, SUN2 is closely localized to H3K9me3, and SUV39H1 affects the mobility of SUN2 in the nuclear envelope. Further, inhibition of cell motility caused by SUV39H1 depletion is restored by suppression of SUN2, nesprin-2, or KIF20A. In summary, these results show the functional association between chromatin organization and cell motility via the Golgi organization regulated by the LINC complex.

Usefulness of electrocardiogram mA modulation during the electrocardiogram-gated CT scan in paediatrics with high heart rate for different helical pitch: a phantom-based assessment study.

We investigated the effect of electrocardiographic (ECG) mA-modulation of ECG-gated scans of computed tomography (CTA) on radiation dose and image noise at high heart rates (HR) above 100 bpm between helical pitches (HP) 0.16 and 0.24. ECG mA-modulation range during ECG-gated CTA is 50-100 mA, the phase setting is 40-60% and the scan range is 90 mm for clinical data during HR for 90, 120 and 150 bpm. Radiation dose and image noise in Housfield units are measured for CT equipment during HR for 90, 120 and 150 bpm between HP 0.16 and 0.24. ECG mA-modulation, dose reduction ratio for HR 90, 120 and 150 bpm are 19.1, 13.4 and 8.7% at HP 0.16 and 17.1, 13.3 and 7.7% at HP 0.24, respectively. No significant differences were observed in image noise between both HP. Dose reductions of 8-24% are achieved with ECG mA-modulation during ECG-gated CCTA scan, which is beneficial even in high HR more than 100 bpm.

RADIATION DOSE REDUCTION AT LOW TUBE VOLTAGE WITH CORONARY ARTERY BYPASS GRAFT COMPUTED TOMOGRAPHY ANGIOGRAPHY BASED ON THE CONTRAST NOISE RATIO INDEX.

To compare the radiation dose and diagnostic ability of the 100-kVp protocol, based on the contrast noise ratio (CNR) index, during coronary artery bypass graft (CABG) vessels with those of the 120-kVp protocol. For the 120-kVp scans (150 patients), the targeted image level was set at 25 Hounsfield units (HU) (CNR120 = iodine contrast/25 HU). For the 100-kVp scans (150 patients), the targeted noise level was set at 30 HU to obtain the same CNR as in the 120-kVp scans (i.e. using 1.2-fold higher iodine contrast, CNR100 = 1.2 × iodine contrast/(1.2 × 25 HU) = CNR120). We compared the CNRs, radiation doses, detection of CABG vessels and visualisation scores of the scans acquired at 120 and 100 kVp, respectively. At the same CNR, the 100-kVp protocol may help reduce the radiation dose by ⁓30% compared with the 120-kVp protocol, without degradation of diagnostic ability during CABG.

Effect of patient characteristics on vessel enhancement on arterio-venous fistula CT angiography in a retrospective cohort study.

To evaluate the effects of various patient characteristics on vessel enhancement on arterio-venous fistula (AVF) computed tomography (CT) angiography (AVF-CT angiography). A total of 127 patients with suspected or confirmed shunt stenosis and internal AVF complications were considered for inclusion in a retrospective cohort study. The tube voltage was 120 kVp, and the tube current was changed from 300 to 770 mA to maintain the image quality (noise index: 14) using automatic tube current modulation. To evaluate the effects of age, sex, body size, and scan delay on the CT number of the brachial artery or vein, we used correlation coefficients and multivariate regression analyses. There was a significant positive correlation between the CT number of the brachial artery or vein and age (R = 0.21 or 0.23, P < .01). The correlations were inverse with the height (r = -0.45 or -0.42), total body weight (r = -0.52 or -0.50), body mass index (r = -0.21 or -0.23), body surface area (body surface area [BSA]; r = -0.56 or -0.54), and lean body weight (r = -0.55 or -0.53) in linear regression analysis (P < .01 for all). There was a significant correlation between the CT number of the brachial artery or vein and scan delay (R = 0.19 or 01.9, P < .01). Only the BSA had significant effects on the CT number in multivariate regression analysis (P < .01). The BSA was significantly correlated with the CT number of the brachial artery or vein on AVF-CT angiography.

The linker of nucleoskeleton and cytoskeleton complex is required for X-ray-induced epithelial-mesenchymal transition.

The linker of nucleoskeleton and cytoskeleton (LINC) complex has been implicated in various functions of the nuclear envelope, including nuclear migration, mechanotransduction and DNA repair. We previously revealed that the LINC complex component Sad1 and UNC84 domain containing 1 (SUN1) is required for sublethal-dose X-ray-enhanced cell migration and invasion. This study focused on epithelial-mesenchymal transition (EMT), which contributes to cell migration. Hence, the present study aimed to examine whether sublethal-dose X-irradiation induces EMT and whether LINC complex component SUN1 is involved in low-dose X-ray-induced EMT. This study showed that low-dose (0.5 Gy or 2 Gy) X-irradiation induced EMT in human breast cancer MDA-MB-231 cells. Additionally, X-irradiation increased the expression of SUN1. Therefore, SUN1 was depleted using siRNA. In SUN1-depleted cells, low-dose X-irradiation did not induce EMT. In addition, although the SUN1 splicing variant SUN1_916-depleted cells (containing 916 amino acids [AA] of SUN1) were induced EMT by low-dose X-irradiation like as non-transfected control cells, SUN1_888-depleted cells (which encodes 888 AA) were not induced EMT by low-dose X-irradiation. Moreover, since the Wnt/ß-catenin signaling pathway regulates E-cadherin expression via the expression of the E-cadherin repressor Snail, the expression of ß-catenin after X-irradiation was examined. After 24 hours of irradiation, ß-catenin expression increased in non-transfected cells or SUN1_916-depleted cells, whereas ß-catenin expression remained unchanged and did not increase in SUN1- or SUN1_888-depleted cells. Therefore, in this study, we found that low-dose X-irradiation induces EMT, and LINC complex component SUN1, especially SUN1_888, is required for X-ray-induced EMT via activation of the Wnt/ß-catenin signaling pathway.

Usefulness of the patient-specific contrast enhancement optimizer simulation software during the whole-body computed tomography angiography.

To evaluate whether the patient-specific contrast enhancement optimizer simulation software (p-COP) is useful for predicting contrast enhancement during whole-body computed tomography angiography (WBCTA). We randomly divided the patients into two groups using a random number table. We used the contrast material (CM) injection protocol selected by p-COP in group A (n = 52). The p-COP used an algorithm including data on the individual patient's cardiac output. Group B (n = 50) was assigned to the conventional CM injection protocol based on body weight. We compared the CT number in the abdominal aorta at the celiac artery level between the two groups and classified them as acceptable (> 280 HU) and unacceptable (< 279 HU) based on the optimal CT number for the WBCTA scans. To evaluate the difference in both injection protocols, we compared the visual inspection of the images of the artery of Adamkiewicz in both protocols. The CM dosage and injection rate in group A were significantly lower than those in group B (480.8 vs. 501.1 mg I/kg and 3.1 vs. 3.3 ml/s, p < 0.05). The CT number of the abdominal aorta at the celiac level was 382.4 ± 62.3 HU in group A and 363.8 ± 71.3 HU in group B (p = 0.23). CM dosage and injection rate were positively correlated to cardiac output for group A (r = 0.80, p < 0.05) and group B (r = 0.16, p < 0.05). The number of patients with an acceptable CT number was higher in group A [46/6 (86.7%)] than in group B [43/7 (71.4%)], but not significant (p = 0.71). The visualization rate for the Adamkiewicz artery was not significantly different between groups A and B (p = 0.89). The p-COP was useful for predicting contrast enhancement during WBCTA with a lower CM dosage and a lower contrast injection rate than that based on the body weight protocol. In patients with lower cardiac output a reduction in contrast injection rate and CM dosage did not lead to a reduced imaging quality, thus particularly in this group CM dosage can be reduced by p-COP.

Radiobiological effects of flattening filter-free photon beams on A549 non-small-cell lung cancer cells.

Flattening filter-free (FFF) photon beams minimize the intrafraction motion of tumors, and this feature is useful in pulmonary malignancies, such as non-small-cell lung cancer (NSCLC). However, the radiobiological effects of such beams on NSCLC cells, which are often treated with stereotactic body radiotherapy (SBRT), have not been investigated sufficiently. Although cell motility may be promoted by photon beams with a low dose, the relationship between cell motility and the dose rate of photon beams has not been evaluated. The purpose of this study was to evaluate the radiobiological effects of FFF photon beams on cell survival and motility in NSCLC. A human lung cancer cell line (A549) was irradiated with conventional flattening filter (FF) and FFF photon beams at dose rates of 300 (FF), 500 and 2000 MU/min (FFF). While cell survival was estimated using the colony formation assay, cell motility was evaluated using the Boyden chamber and Matrigel invasion assays. FFF photon beams with a high dose rate neither affected the survival of A549 cells nor caused any significant difference in their motility. On the other hand, high-dose irradiation reduced cell survival and motility regardless of the dose rate. Photon beams with a high dose rate used for radiation therapy are suitable for SBRT from the standpoint of both cell survival and motility, in addition to their physical characteristics.

X-ray-enhanced cancer cell migration requires the linker of nucleoskeleton and cytoskeleton complex.

The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, including nuclear migration, mechanotransduction, chromatin tethering and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1), a component of the LINC complex, has a critical function in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown. Here, we examined the involvement of the LINC complex in radiation-enhanced cell migration and invasion. A sublethal dose of X-ray radiation promoted human breast cancer MDA-MB-231 cell migration and invasion, whereas carbon ion beam radiation suppressed these processes in a dose-dependent manner. Depletion of SUN1 and SUN2 significantly suppressed X-ray-enhanced cell migration and invasion. Moreover, depletion or overexpression of each SUN1 splicing variant revealed that SUN1_888 containing 888 amino acids of SUN1 but not SUN1_916 was required for X-ray-enhanced migration and invasion. In addition, the results suggested that X-ray irradiation affected the expression level of SUN1 splicing variants and a SUN protein binding partner, nesprins. Taken together, our findings supported that the LINC complex contributed to photon-enhanced cell migration and invasion.

Irradiation strongly reduces tumorigenesis of human induced pluripotent stem cells.

Induced pluripotent stem (iPS) cells have demonstrated they can undergo self-renewal, attain pluripotency, and differentiate into various types of functional cells. In clinical transplantation of iPS cells, however, a major problem is the prevention of tumorigenesis. We speculated that tumor formation could be inhibited by means of irradiation. Since the main purpose of this study was to explore the prevention of tumor formation in human iPS (hiPS) cells, we tested the effects of irradiation on tumor-associated factors such as radiosensitivity, pluripotency and cell death in hiPS cells. The irradiated hiPS cells showed much higher radiosensitivity, because the survival fraction of hiPS cells irradiated with 2 Gy was < 10%, and there was no change of pluripotency. Irradiation with 2 and 4 Gy caused substantial cell death, which was mostly the result of apoptosis. Irradiation with 2 Gy was detrimental enough to cause loss of proliferation capability and trigger substantial cell death in vitro. The hiPS cells irradiated with 2 Gy were injected into NOG mice (NOD/Shi-scid, IL-2 Rγnull) for the analysis of tumor formation. The group of mice into which hiPS cells irradiated with 2 Gy was transplanted showed significant suppression of tumor formation in comparison with that of the group into which non-irradiated hiPS cells were transplanted. It can be presumed that this diminished rate of tumor formation was due to loss of proliferation and cell death caused by irradiation. Our findings suggest that tumor formation following cell therapy or organ transplantation induced by hiPS cells may be prevented by irradiation.

SUN1 splice variants, SUN1_888, SUN1_785, and predominant SUN1_916, variably function in directional cell migration.

The LINC complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, such as nuclear migration, mechanotransduction and chromatin tethering in the meiotic phase. However, it remains unknown how these functions are regulated in different cell contexts. An inner nuclear membrane component of the LINC complex, SUN1, is ubiquitously expressed. The human SUN1 gene produces over 10 variants by alternative splicing. Although functions of SUN1 are relatively well characterized, functional differences among SUN1 splice variants are poorly characterized. LINC complex components are associated with a wide range of human diseases; therefore, it is important to understand the functional diversity among SUN1 splice variants. Here, we identified a novel human SUN1 splice variant, SUN1_888. overexpression of the SUN1 splice variants, SUN1_888 or SUN1_785, but not the predominant isoform, SUN1_916, activated directional cell migration. Knockdown of SUN1_888 suppressed cell migration; in contrast depletion of SUN1_916 activated cell migration. In addition, all of investigated SUN1 splicing variants rescued cell migration in SUN1 knock out cell. These results indicate that redundant and non-redundant functions of SUN1 splice variant in directional cell migration and suggest that variable LINC complexes with distinct task may exit. Furthermore, in contrast to previous studies, we showed association between SUN1 and B-type lamins. Interestingly, B-type lamin preferentially interacts with SUN1 but not SUN2. These results suggest that tissue-specific SUN1 variants variably interact with nucleoplasmic partners and allow variable assembly of LINC complexes that can be assigned to distinct tasks.