Superb Microvascular Imaging Ultrasound for Cervical Carotid Artery Stenosis for Prediction of the Development of Microembolic Signals on Transcranial Doppler during Carotid Exposure in Endarterectomy

Introduction: During exposure of the carotid arteries, embolism from the surgical site is recognized as a primary cause of neurological deficits or new cerebral ischemic lesions following carotid endarterectomy (CEA), and associations have been reported between histological neovascularization in the carotid plaque and both plaque vulnerability and the development of artery-to-artery embolism. Superb microvascular imaging (SMI) enables accurate visualization of neovessels in the carotid plaque without the use of intravenous contrast. This study aimed to determine whether preoperative SMI ultrasound for cervical carotid artery stenosis predicts the development of microembolic signals (MES) on transcranial Doppler (TCD) during exposure of the carotid arteries in CEA. Methods: Preoperative cervical carotid artery SMI ultrasound followed by CEA under TCD monitoring of MES in the ipsilateral middle cerebral artery was conducted in 70 patients previously diagnosed with internal carotid artery stenosis (defined as ≥70%). First, observers visually identified intraplaque microvascular flow (IMVF) signals as moving enhancements located near the surface of the carotid plaque within the plaque on SMI ultrasonograms. Next, regions of interest (ROI) were manually placed at the identified IMVF signals (or at arbitrary places within the plaque when no IMVF signals were identified within the carotid plaque) and the carotid lumen, and time-intensity curves of the IMVF signal and lumen ROI were generated. Ten heartbeat cycles of both time-intensity curves were segmented into each heartbeat cycle based on gated electrocardiogram findings and averaged with respect to the IMVF signal and lumen ROI. The difference between the maximum and minimum intensities (ID) was calculated based on the averaged IMVF signal (IDIMVF) and lumen (IDl) curves. Finally, the ratio of IDIMVF to IDl was calculated. Results: MES during exposure of the carotid arteries were detected in 17 patients (24%). The incidence of identification of IMVF signals was significantly greater in patients with MES (94%) than in those without (57%; p = 0.0067). The IDIMVF/IDl ratio was significantly greater in patients with MES (0.108 ± 0.120) than in those without (0.017 ± 0.042; p < 0.0001). The specificity and positive predictive value for the IDIMVF/IDl ratio for prediction of the development of MES were significantly higher than those for the identification of IMVF signals. Logistic regression analysis revealed that only the IDIMVF/IDl ratio was significantly associated with the development of MES (95% CI 101.1–3,628.9; p = 0.0048). Conclusion: Preoperative cervical carotid artery SMI ultrasound predicts the development of MES on TCD during exposure of the carotid arteries in CEA

Spatial distribution of DNA double strand breaks in microbeam targeted human cells

Unlike X- and γ-rays, swift ions with comparatively high linear energy transfer (LET) induce more complex DNA damage, called double strand break (DSB) or clustered DNA lesions. These complexities make the DNA repair process more difficult, leading to increased chromosome aberrations and cell inactivation. However, molecular mechanisms underlying damage and repair of DNA has not been well understood. Taking advantage of SPICE-QST microbeam, we focus on the localized dose distribution in the targeted cell nucleus irradiated with a defined number of protons and its correlation with fluorescent intensity and area of the DNA DSBs region, visualized by immunostaining against γ-H2AX. Finally, the γ-H2AX spot intensity increased linearly with increasing protons from 50 up to 300p/pos, while it showed a saturation tendency at 500p/pos, implying that the histone protein H2AX was exhausted for a large number of protons per position due to densely ionizing protons. In addition, super-linear dependence of the γ-H2AX spot area to the microbeam area was interestingly observed for more than 50p/pos, indicating that the DSBs induction in the targeted cell nucleus was enhanced beyond the microbeam area for a large number of protons per position. A comparison of dose profiles with beam profiles gives further insight into the super-linear dependence, suggesting that the penumbra dose fraction in the localized dose distribution significantly contributed to the DSBs induction. This study was supported in part by a Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research(B) (20H03634).日本マイクロビーム生物研究会2021年度シンポジウ

Development of micromachining technology in ion microbeam system at TIARA, JAEA

An ion-beam-lithography technique has been progressed in the microbeam systems at JAEA Takasaki. In order to obtain a high-precision measure for microbeam size estimation with a high precision, we applied this technique combined with the electroplating process to make a Ni relief pattern as a resolution standard used in secondary electron imaging. As a result, the smallest beam size could be recorded. The scattering of ions in the materials influenced the spatial resolution and this is also discussed