Real-World Patent Foramen Ovale (PFO) Closure in Japan　- 30-Day Clinical Outcomes From the AmplatzerTM PFO Occluder Japan Post-Marketing Surveillance Study.

BACKGROUND: The AmplatzerTM PFO Occluder was approved for marketing in Japan in May 2019, and the Amplatzer PFO Occluder Japan Post-marketing Surveillance (PFO Japan PMS) study was initiated in December 2019. This analysis presents 30-day clinical outcomes for PFO Japan PMS study patients.Methods and Results: PFO Japan PMS is a prospective single-arm non-randomized multicenter clinical study. Eligible patients were indicated for patent foramen ovale (PFO) closure and underwent an implant attempt with the AmplatzerTM PFO Occluder. Technical success was defined as successful delivery and release of the occluder; procedural success was defined as technical success with no serious adverse events (SAEs) within 1 day of the procedure. The primary safety endpoint includes predefined device- and/or procedure-related SAEs through 30 days after the procedure. From December 2019 to July 2021, 500 patients were enrolled across 53 Japanese sites. The mean (±SD) patient age was 52.7±15.4 years, and 29.8% of patients were aged >60 years. Technical and procedural success rates were both high (99.8% and 98.8%, respectively). Further, there was only one primary safety endpoint event (0.2%): an episode of asymptomatic paroxysmal atrial fibrillation that occurred 26 days after the procedure. CONCLUSIONS: In this real-world Japanese study with almost one-third of patients aged >60 years, PFO closure with the AmplatzerTM PFO Occluder was performed successfully and safely, with a low incidence of procedure-related atrial arrhythmias.

Stent-retriever characteristics and strategies associated with recanalization in thrombectomy for acute ischemic stroke.

INTRODUCTION: Predictive factors for successful reperfusion in mechanical thrombectomy for acute ischemic stroke, and especially technical factors, remain controversial. We investigated various techniques for better angiographic outcomes. METHODS: In this retrospective study, acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy with combined technique were included. Scoring of the reperfusion grade for each attempt was conducted, and each attempt was divided into two groups based on successful reperfusion, which was defined using the presence or absence of modified thrombolysis in cerebral infarction 2b-3. The following characteristics were evaluated: the choice of stent-retriever, its length, occlusion site, thrombus position relative to deployed stent-retriever, methods of thrombectomy, and successful advancement of the distal access catheter to the proximal end of the thrombus. RESULTS: Among 251 patients who underwent mechanical thrombectomy, 154 patients (255 attempts: mTICI 0-2a group, n = 119; mTICI 2b-3 group, n = 136) were included in the analysis. The thrombus position relative to the deployed stent-retriever was likely associated with successful reperfusion, although it was not statistically significant (proximal two-thirds 56.8 %; distal one-third 44.3 %, p = 0.09). Successful advancement of the distal access catheter was related to successful reperfusion both in univariate analysis (success 57.9 %; fail 35.8 %, p < 0.01) and in multivariate regression analysis (odds ratio 2.45; 95 % confidence interval: 1.30-4.61, p < 0.01). CONCLUSIONS: Successful advancement of the distal access catheter to the proximal end of thrombus might be a key component for successful reperfusion in mechanical thrombectomy.

Evidence and Recommendations for Acute Stroke Rehabilitation from the Japan Stroke Society: Abridged Secondary Publication of the Japanese-language Version.

Objectives: In Japan, acute stroke rehabilitation has been expanding more steadily than previously with the nationwide establishment of primary stroke centers. However, Japan previously had no established guidelines for the rehabilitation. Consequently, rehabilitation programs and the provision systems for acute stroke varied among the facilities. To equalize and standardize acute stroke rehabilitation in Japan, it is necessary to develop clinical recommendations for rehabilitation. Therefore, the rehabilitation project team of the Japan Stroke Society aimed to develop the first recommendations for acute stroke rehabilitation in Japan. Methods: The recommendations are based on the results of a survey on the current status of acute stroke rehabilitation at primary stroke centers in Japan, which was completed in 2022, and on a literature review conducted by the rehabilitation project team. Results: The recommendations consist of 19 clinical questions regarding the following topics of acute stroke rehabilitation: (1) head elevation and mobilization training, (2) acute complications, (3) training time and frequency for acute stroke rehabilitation, (4) dysphagia in the acute phase, and (5) acute rehabilitation during pandemics of novel and re-emerging infections, particularly novel coronavirus disease 2019 (COVID-19). The team members agreed on all answers for these 19 clinical questions. Conclusions: These recommendations suggest broad principles of rehabilitative intervention in the acute phase of stroke. In the near future, it is expected that the dissemination of these recommendations will result in an increase in the quality of acute stroke rehabilitation in Japan.

National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study.

OBJECTIVES: To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan. DESIGN: Retrospective study. SETTING: Six hundred and thirty-one primary care institutions in Japan. PARTICIPANTS: Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database. PRIMARY AND SECONDARY OUTCOME MEASURES: Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3-6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1-25 points). RESULTS: In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality. CONCLUSIONS: The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

[Subdural hematoma with reversible cerebral vasoconstriction syndrome: a case report].

A 71-year-old man had persistent cervical pain secondary to thunderclap headache during sleep. MRI conducted the next morning revealed subdural hematoma and convexity subdural hemorrhage on the right occipital region, and the patient was hospitalized. MRA showed vascular narrowing in the bilateral PCA. Follow-up MRA on day 8 of admission showed aggravated vascular narrowing of PCA, indicative of reversible cerebral vasoconstriction syndrome (RCVS). The patient was treated with a calcium-channel antagonist. Post-discharge MRA showed improvement of PCA narrowing, and the diagnosis of RCVS was confirmed.

Lasmiditan for single migraine attack in Japanese patients with cardiovascular risk factors: subgroup analysis of a phase 2 randomized placebo-controlled trial.

BACKGROUND: Some migraine treatments are contraindicated for patients with cardiovascular disease (CVD) or risk factors (CVRFs). We report safety and efficacy of lasmiditan, a new oral acute migraine treatment with no cardiovascular contraindication, in Japanese patients with CVRFs. RESEARCH DESIGN AND METHODS: MONONOFU was a multicenter, randomized, double-blind, placebo-controlled, phase 2 study of Japanese patients with migraine (met International Headache Society criteria, Migraine Disability Assessment score ≥11, disabling migraine for ≥1 year). Eligible patients were randomized (7:3:7:6) to placebo or lasmiditan 50, 100, 200 mg. This prespecified analysis described CVDs, CVRFs, and cardiovascular treatment-emergent adverse events (TEAEs). Efficacy (proportion pain-free, experienced pain relief, most bothersome symptom-free, or disability-free 2 hours post-dose) was evaluated within CVRF subgroups (≤1, ≥2). RESULTS: Of 846 randomized patients, 691 were analyzed (CVRF≤1: 375; CVRF≥2: 316). The proportion of lasmiditan-treated patients with ≥1 TEAE was not related to CVRF numbers. Eighteen (3.8%) lasmiditan-treated and three (1.4%) placebo-treated patients reported likely cardiovascular TEAEs. Lasmiditan was more effective than placebo at relieving pain, symptoms, and disability in both CVRF subgroups. There was no consistent relationship between CVRF subgroups and efficacy. CONCLUSIONS: Lasmiditan was well tolerated and effective in Japanese patients with migraine and CVRFs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03962738.

Impact of COVID-19 on the Volume of Acute Stroke Admissions: A Nationwide Survey in Japan.

This study aimed to measure the impact of the COVID-19 pandemic on the volumes of annual stroke admissions compared with those before the pandemic in Japan. We conducted an observational, retrospective nationwide survey across 542 primary stroke centers in Japan. The annual admission volumes for acute stroke within 7 days from onset between 2019 as the pre-pandemic period and 2020 as the pandemic period were compared as a whole and separately by months during which the epidemic was serious and prefectures of high numbers of infected persons. The number of stroke patients declined from 182,660 in 2019 to 178,083 in 2020, with a reduction rate of 2.51% (95% confidence interval [CI], 2.58%-2.44%). The reduction rates were 1.92% (95% CI, 1.85%-2.00%; 127,979-125,522) for ischemic stroke, 3.88% (95% CI, 3.70%-4.07%, 41,906-40,278) for intracerebral hemorrhage, and 4.58% (95% CI, 4.23%-4.95%; 13,020-12,424) for subarachnoid hemorrhage. The admission volume declined by 5.60% (95% CI, 5.46%-5.74%) during the 7 months of 2020 when the epidemic was serious, whereas it increased in the remaining 5 months (2.01%; 95% CI, 1.91%-2.11%). The annual decline in the admission volume was predominant in the five prefectures with the largest numbers of infected people per million population (4.72%; 95% CI, 4.53%-4.92%). In conclusion, the acute stroke admission volume declined by 2.51% in 2020 relative to 2019 in Japan, especially during the months of high infection, and in highly infected prefectures. Overwhelmed healthcare systems and infection control practices may have been associated with the decline in the stroke admission volume during the COVID-19 pandemic.

Long-Term Prevalence of Disaster-Related Deep Vein Thrombosis in Minamiaso Village After the 2016 Kumamoto Earthquakes: A Prospective Cross-Sectional Analysis.

OBJECTIVE: This study aimed to examine the prevalence of deep vein thrombosis (DVT) among evacuees in Minamiaso, a village which was temporarily isolated after the earthquakes, from the acute to recovery phase after the 2016 Kumamoto Earthquakes (GLIDE no: EQ-2016-000033-JPN). METHODS: This prospective study, which was approved by Fukui University Medical Research Ethics Committee (approval no. 20160024 and 20160089), enrolled 181 evacuees (73.9 ± 11.6 y) who participated in a series of 3 DVT screenings using portable ultrasound machines conducted over 19 mo. All participants completed a questionnaire before the screenings, and none of the participants attended all 3 screenings. Data analysis was performed using EZR version 1.41. RESULTS: The DVT prevalence was 14.3% (79.4 ± 8.2 y) at first screening of evacuees staying in shelters and 18.5% (71.5 ± 13.1 y) and 12.2% (72.8 ± 10.9 y) in second and third screenings of evacuees staying in temporary housing, respectively. Multivariate analysis revealed age ≥75 y and alcohol consumption as independent risk factors in the entire cohort and in patients aged ≤74 y, respectively. CONCLUSIONS: A high DVT prevalence over a long time period of 19 mo was observed where survivors were temporarily isolated after the disaster.

[A case of antepartum reversible cerebral vasoconstriction syndrome].

A 35-year-old pregnant woman with mild migraine experienced thunderclap headache at 37 weeks of gestation. Her cerebral MRA showed arterial segmental narrowing of right middle cerebral artery and bilateral posterior cerebral artery. When admitted, she had no sign of eclampsia/preeclampsia. After 4 days, she had premature rupture of the membrane and gave birth by caesarean section. Caesarean section immediately resolved the headache. The postpartum course of the patient and her baby was uneventfull. One month after her onset, her cerebral MRA showed improvement in arterial segmental narrowing of cerebral artery. We diagnosed reversible cerebral vasoconstriction syndrome (RCVS) assoiated with pregnancy. Pregnancy-related RCVS develops primarily during the puerperal period, but our case was a rare case that developed just before delivery and was successful with aggressive intervention. When antepartum RCVS develops, early cesarean section with epidural anesthesia in parallel with active treatment for headache may lead to good outcomes for both mother and child.

[Cerebral vein/venous sinus thrombosis with thrombocytopenia syndrome after COVID-19 vaccination].

Vaccines are important in managing the COVID-19 pandemic caused by SARS-CoV-2. Despite the very low incidence, severe cases of thrombosis with thrombocytopenia after COVID-19 vaccination termed as Thrombosis with Thrombocytopenia Syndrome (TTS) have been reported. TTS clinically resembles autoimmune heparin-induced thrombocytopenia. TTS can cause disability and even death. It usually presents 4-28 days after vaccination characterized by thrombocytopenia and progressive thrombosis, often causing cerebral vein/venous thrombosis (CVT) and splanchnic venous thrombosis. We should avoid all forms of heparin and platelet transfusion. While awaiting further information on the pathophysiological mechanism and treatment of TTS, clinicians should be aware of TTS with CVT in patients receiving COVID-19 vaccinations. This new syndrome of TTS is an active area of investigation globally. Here, we review the available literature.

Preceding direct oral anticoagulant administration reduces the severity of stroke in patients with atrial fibrillation - K-PLUS registry.

BACKGROUND: Stroke severity can be mitigated by preceding anticoagulant administration in acute ischemic stroke patients with atrial fibrillation (AF). We investigated if such mitigative effects are different between warfarin and direct oral anticoagulants (DOACs). MATERIAL AND METHODS: We collected data from a regional multicenter stroke registry. Ischemic stroke or transient ischemic attack patients with AF were included. Background characteristics, National Institutes of Health Stroke Scale (NIHSS) score on admission, lesion characteristics, and in-hospital death were analyzed according to preceding antithrombotic agents at onset. RESULTS: A total of 2173 patients had AF; 628 were prescribed warfarin, 272 DOACs, 429 antiplatelets alone, and 844 no antithrombotics. The NIHSS score on admission was lowest in the DOACs group compared to the other groups. In neuroimaging analysis, small ischemic lesions were observed more frequently in the DOACs group, while large ischemic lesions were less frequent in this group. When the no antithrombotics group was used as a reference, the adjusted odds ratio for moderate to severe stroke was 0.56 (95% confidence interval, 0.40-0.78) in the DOACs group, while it was 0.98 (0.77-1.24) in the warfarin group and 0.94 (0.72-1.22) in the antiplatelets group. In-hospital mortality was lowest in the DOACs group compared to the other groups. CONCLUSION: Preceding DOAC administration might mitigate the severity of stroke in AF patients more strongly than other antithrombotics, possibly leading to a better outcome in patients with stroke.

Clinical characteristics of patients with ischemic stroke after the 2016 Kumamoto earthquake, a multi-center study.

OBJECTIVE: To investigate the clinical characteristics of patients with ischemic stroke following the 2016 Kumamoto earthquake. METHODS: We retrospectively studied patients with ischemic stroke admitted to 5 stroke centers for 1 year after the earthquake. We compared clinical characteristics in these patients (the post-earthquake group) to those in the patients with ischemic stroke admitted during the same period from the previous 3 years (the pre-earthquake group). Additionally, we analyzed the trend of the incidence rate of stroke before and after the earthquake. RESULTS: A total of 1979 patients were admitted after the earthquake; 5670 (1,890/year on average) patients were admitted before the earthquake. A first-ever ischemic stroke (71 vs. 75%) and premorbid modified Rankin Scale > 1 (26 vs. 29%) were found significantly more frequently in patients after the earthquake. National Institutes of Health Stroke Scale score ≤ 2 at discharge (60 vs. 65%) was found more frequently in patients after the earthquake, although non-discharge to home (65 vs. 70%) was more frequent in patients after the earthquake. Trend analysis revealed a decrease of small vessel occlusion and large artery atherosclerosis in the month after the earthquake. CONCLUSIONS: The 2016 Kumamoto earthquake may have affected the characteristics of stroke during the early phase of the earthquake and increased the difficulty in returning home.

Damage-less observation of polymers by electron dose control in scanning electron microscope.

Methodology for quantitative evaluation of electron radiation damage and calculation of tolerable electron dose was developed to achieve damage-less scanning electron microscope (SEM) observation of beam-sensitive polymer film. The radiation damage is typically evaluated with visual impressions of SEM images; however, this method may be unreliable because observer's subjectivity may affect the results. Evaluation with quantitative value is crucial to improve reliability. In this study, the radiation damage was evaluated by using normalized correlative coefficient (RNCC) between an initial frame and latter frames of the multiple SEM images that were taken consecutively. Tolerable dose was obtained by defining a threshold point of RNCC where rapid reduction of RNCC started. A SEM image with less damage and acceptable signal-to-noise ratio was obtained by integrating the images from the initial frame to the tolerable frame.

Measuring Quality of Care for Ischemic Stroke Treated With Acute Reperfusion Therapy in Japan　- The Close The Gap-Stroke.

BACKGROUND: In Japan there is no consensus on how to efficiently measure quality indicators (QIs), defined as a standard of care, for acute ischemic stroke (AIS). Using information from a health insurance claims database and electronic medical records, we evaluated the feasibility and validity of measuring QIs for AIS patients who received intravenous recombinant tissue plasminogen activator (IV rt-PA) or endovascular therapy (EVT).Methods and Results:AIS patients receiving rt-PA or EVT between 2013 and 2015 were identified. We selected 17 AIS QI measures for primary stroke centers (PSCs) and 8 for comprehensive stroke centers (CSCs). Defined QIs were calculated for each hospital and then averaged. In total, the data of 8,206 patients (rt-PA 83.7%, EVT 34.9%) from 172 hospitals were obtained. Median National Institute of Health Stroke Scale score at admission was 14, and 37.7% of the patients were functionally independent at discharge. All target QIs were successfully measured with fewer missing values, and the accuracy of preset data was about 90%. Adherence rates were low (<50%) in 5 QI measures among PSCs, including door-to-needle time ≤1 h, and in 1 QI measure among CSCs (door-to-brain and vascular imaging time ≤30 min). CONCLUSIONS: Measuring QIs for AIS by this novel approach was feasible and reliable in the provision of a national benchmark.

[COVID-19 and stroke].

Due to the pandemic of corona virus disease 2019 (COVID-19), the stroke medical care system is unavoidably undergoing major changes such as a decrease in the number of stroke patients receiving consultation, delay in consultation, and a decrease in the number of intravenous thrombolysis and mechanical thrombectomy procedures. Stroke incidence in COVID-19 patients is approximately 1.1%. The features of stroke with COVID-19 have been elucidated: higher incidence in ischemic stroke than hemorrhagic stroke, increasing number of young patients, high D-dimer levels, and higher risk in elderly patients with cardiovascular risk factors such as hypertension and diabetes. In patients with COVID-19, venous thromboembolism is more common than arterial thromboembolism, and stroke is more common than acute coronary syndrome. Protected code stroke (PCS) has been proposed which provides safe, effective and prompt treatment under complete infection control.

Pre-Hospital Delay in Patients with Acute Ischemic Stroke in a Multicenter Stroke Registry: K-PLUS.

PURPOSE: There is scant data related to prehospital delay in cases of acute ischemic stroke from multicenter studies conducted after change of the therapeutic window of intravenous tissue plasminogen activator (iv-tPA) administration to within 4.5 h of onset. We investigated factors causing prehospital delay and their associations with clinical outcomes using data from a regional multicenter stroke registry. METHODS: Data from the multicenter regional stroke registry were analyzed. Patients admitted within 24 h of the last known well time were categorized according to whether their admission was early (≤ 4 h; n = 2350) or delayed (> 4 h; n = 2752). We then compared patients' backgrounds and outcomes between the two groups. RESULTS: Five-thousand, one-hundred two patients presented at hospitals within 24 h of onset. On multivariate analysis, atrial fibrillation, higher NIHSS score on admission, anterior circulation stroke, detection of symptoms immediately after onset, and emergency system use were positively associated with early admission, whereas modified Rankin Scale (mRS) score before onset, onset at home, diabetes, current smoking, dementia and symptom detection between 00:00 and 06:00 h were negatively associated. Early admission was associated with mRS scores of 0-2 at discharge independent of backgrounds, stroke severity, and thrombolytic therapy (odds ratio, 1.56; 95% confidence interval, 1.32-1.84). CONCLUSIONS: Certain patient factors relating to prehospital delay, such as lack of awareness of onset or non-cardioembolic etiology, are crucial but often inevitable. However, earlier admission was associated mRS scores of 0-2 independent of other factors. This study may help to plan educational activities to general population or public awareness campaigns.

Enhancement of image contrast for carbon nanotube and polymer composite film in scanning electron microscope.

Image contrast between carbon nanotubes (CNTs) and polytetrafluoroethylene (PTFE) in a CNT/PTFE composite film, which is difficult to obtain by conventional backscattered electron (BSE) imaging, was optimized to better elucidate the distribution of CNT in the film. Ultra-low landing energy condition (0.3 keV in this study) was used to prevent specimen damage due to electron beam irradiation. Signal acceptance maps, which represent the distributions of energy and take-off angle, were calculated to evaluate the features of the signal detection system used in this study. SEM images of this composite film were taken under several sets of conditions and analyzed using these acceptance maps. CNT and PTFE in the composite film can be clearly distinguished with material and topographic contrasts using the BSE signal under optimized energy and take-off angle ranges, even at ultra-low landing energy conditions.

Effects of case volume and comprehensive stroke center capabilities on patient outcomes of clipping and coiling for subarachnoid hemorrhage.

OBJECTIVE: Improved outcomes in patients with subarachnoid hemorrhage (SAH) treated at high-volume centers have been reported. The authors sought to examine whether hospital case volume and comprehensive stroke center (CSC) capabilities affect outcomes in patients treated with clipping or coiling for SAH. METHODS: The authors conducted a nationwide retrospective cohort study in 27,490 SAH patients who underwent clipping or coiling in 621 institutions between 2010 and 2015 and whose data were collected from the Japanese nationwide J-ASPECT Diagnosis Procedure Combination database. The CSC capabilities of each hospital were assessed by use of a validated scoring system based on answers to a previously reported 25-item questionnaire (CSC score 1-25 points). Hospitals were classified into quartiles based on CSC scores and case volumes of clipping or coiling for SAH. RESULTS: Overall, the absolute risk reductions associated with high versus low case volumes and high versus low CSC scores were relatively small. Nevertheless, in patients who underwent clipping, a high case volume (> 14 cases/yr) was significantly associated with reduced in-hospital mortality (Q1 as control, Q4 OR 0.71, 95% CI 0.55-0.90) but not with short-term poor outcome. In patients who underwent coiling, a high case volume (> 9 cases/yr) was associated with reduced in-hospital mortality (Q4 OR 0.69, 95% CI 0.53-0.90) and short-term poor outcomes (Q3 [> 5 cases/yr] OR 0.75, 95% CI 0.59-0.96 vs Q4 OR 0.65, 95% CI 0.51-0.82). A high CSC score (> 19 points) was significantly associated with reduced in-hospital mortality for clipping (OR 0.68, 95% CI 0.54-0.86) but not coiling treatment. There was no association between CSC capabilities and short-term poor outcomes. CONCLUSIONS: The effects of case volume and CSC capabilities on in-hospital mortality and short-term functional outcomes in SAH patients differed between patients undergoing clipping and those undergoing coiling. In the modern endovascular era, better outcomes of clipping may be achieved in facilities with high CSC capabilities.

Voltage contrast imaging with energy filtered signal in a field-emission scanning electron microscope.

A new band-pass energy filter (BPF) technique of secondary electron (SE) detection using scanning electron microscope (SEM) was developed to enhance voltage contrast (VC) in SEM images. The energy filtering condition was optimized to enhance VC of dopant distribution using Si p-n structure. The relation between VC and SE energy was investigated by BPF as well as a conventional high-pass filter (HPF). Whereas the p-type regions were always brighter than the n-type region in the case of HPF, the contrast reversal between p region and n region occurred at the low SE energy range in the case of BPF. The variation of signal intensity of BPF against specimen bias voltage can be considered as SE spectrum analysis, and the peak split of the spectra between n-type and p-type regions was obtained. The peak split can be explained with a model with metal-semiconductor contact. This peak split causes the contrast reversal.