Tohoku University Repository (TOUR) / 東北大学機関リポジトリ

Tohoku University修士（環境科学）thesi

前田, 裕介

固体廃棄物と再生可能キレート剤を用いた100℃ 以下の温度スイング式CO2 回収・鉱物固定プロセス

Hou, Xiaoxi

 
 1 
 
氏名（本籍地）  HOU
ホ ウ
 XIAOXI
シ ョ シ
（中国） 
学 位 の 種 類  博 士（医工学） 
学 位 記 番 号  医工博 第１４１号 
学位授与年月日  ２０２５年３月２５日 
学位授与の要件  学位規則第４条第１項該当 
研究科、専攻  東北大学大学院医工学研究科（博士課程）医工学専攻 
学位論文題目  Pre-clinical Evaluation of a Bare Metal Stent Therapeutic for Aortic 
Dissection (大動脈解離疾患治療ベアメタルステントの非臨床評価研究) 
論文審査委員  （主査）東北大学教 授 山家 智之  
             東北大学教 授 芳賀 洋一                  
                          東北大学教 授 杉田 典大  
 
論 文 内 容 の 要 旨 
 
第１章 Overview 
Aortic dissection (AD) is a complex and dynamic vascular disease. When a tear is formed in the 
intima, blood flows into the media layer, splitting the aortic wall and forming a dissection room 
called “false lumen (FL)”. The original aortic lumen is named “true lumen (TL)”. The layer 
comprising the intima and some parts of the media is called the intimal flap (IF). Dissection may 
gradually develop and dilate upstream or downstream, and the split can extend to the bifurcation 
and branch arteries with blood continuously entering the FL. Japan has a higher AD incidence 
than the worldwide level. The total mortality rate can reach 51.1%, and the in-hospital mortality 
rate is 28.9%.  
The most popular treatment method is endovascular aortic repair by stent graft (SG), can induce 
many complications that need further reinterventions, such as endoleak, stent migration, SINE 
(stent-induced new entry), re-dissection, and stent thrombosis; furthermore, it can not used in the 
aortic sections with major branch arteries. Therefore, a novel application of self-expandable bare 
metal stent (BMS) was first introduced to treat both type A and type B AD. Meanwhile, it 
overcame the limitations and drawbacks of current endovascular aortic repair.   
This study is part of pre-clinical evaluations of BMS therapeutic for AD. It aims to use in vivo, in 
vitro, and in silico approaches to predict the outcomes, evaluate the safety of utilization, and 
foresee the risks of this novel treatment. The results of this study are believed to accelerate 
clinical use in the future. 
 
第 2 章 Introduction 
The self-expandable BMS is made of Nickel-titanium alloy, a superelastic and shape-memory 
material with good biocompatibility and fatigue characteristics. The initial structure of BMS is 
 
 2 
manufactured from thin nitinol tubes, and the laser cut finishes the mesh pattern. The initial size 
of BMS is 3 mm in diameter. After that, BMS is expanded from the inside by several tapered 
metal pipes and one straight metal pipe until it reaches the target diameter. Then, BMS and the 
last straight metal pipe are moved to the heater and undergone heat treatment to fix the shape. 
Finally, the BMS with a fixed size is compressed into the catheter by a crimper. When there is no 
constraint from the catheter after release in the aorta, the elastic strain energy reverses BMS to 
its fixed shape, achieving self-expanding behavior. The expansion force expands and pushes IF 
back to the aortic wall so as to close the tears.  
Before this new treatment method is developed for clinics, pre-clinical evaluations are mandatory 
to evaluate its safety, effectiveness, outcomes, and biological activity. Typically, in-vitro, in-vivo, 
and in-silico approaches are used. 
Because the deformation degree of IF is a key factor that determines the outcome, the first study 
of this research is to obtain the mechanical characteristics of IF. The AD samples tended to 
undergo the tensile tests by other studies.  
Finite element analysis (FEA) is an in silico approach to deploy a BMS into an AD model virtually, 
which can quantitatively analyze many parameters that other pre-clinical methods can not obtain, 
but the validation and verification of FEA methods are crucial to ensure the accuracy.  
 
第 3 章 Mechanical Characteristics of AD 
This study extracted the goats’ AD specimens after the in vivo experiments. Specimens 
underwent the uniaxial tensile tests immediately after the extraction without storage or freezing. 
The tensile test results were applied as the material properties in the 2D simulations to restore 
the mechanical response of the AD layers.  
This in vivo study was approved by the Institutional Laboratory Animal Care and Use Committee 
of TOHOKU University (2022-AcA-009). All animal experiments were assessed and allowed by 
the Tohoku University Animal Committee, with the Guide for the Care and Use of Laboratory 
Animals. 
Three goats’ aorta were extracted for the tensile test. After the removal of BMS in the aorta, 
ring-shaped aortic samples were extracted. Unlike other studies, we did not cut off small 
rectangular specimens on the aortic samples but used the whole ring-shaped aortic samples as 
the tested specimens. The FL, surgically reproduced during the operation, was expanded by 
extensional peeling at the aortic media layer, and then two ring-shaped short-axis specimens were 
formed. The IF consists of intima and media was named internal layer, and the other wall made 
of adventitia and media was named external layer. There was a total of 8 ring-shaped aortic 
samples. The excising process of the aorta was completed approximately 15 minutes after the 
euthanasia and underwent the tensile test. The results of the tensile tests were applied to a 
simplified 2D AD model to simulate the expansion of IF by the BMS’s radial force. The radial 
forces were mimicked by a constant pressure in the TL acting on the internal layer, equaling 0.01 
MPa, 0.02 MPa, and 0.03 MPa. 
From the mechanical point of view, the deformation of IF consumes most of the expansion energy 
 
 3 
from the BMS, reducing the effect of the BMS on the external layer. From the clinical perspective, 
BMS treatment needs to consider the stiffness and elasticity of IF of specific patients in advance 
to ensure sufficient deformation of IF from stent expansion; moreover, safe intervention should 
avoid overexpansion of the external layer of FL, decreasing the risk of aneurysm and rupture.  
 
第 4 章 Virtual BMS Deployment 
Based on the in vivo experiments on goats and previous in vitro studies, a healthy aorta model 
was designed. The aortic wall consists of two layers: the internal layer thickness is 1.2 mm, and 
the external layer thickness is 1.0 mm. The whole structure is tapered with 55 mm length. The 
outer and inner diameters of the proximal opening are 25.6 and 21.2 mm, respectively. The outer 
and inner diameters of the distal opening are 21.2 and 16.8 mm, respectively. A section of the 
internal layer is extracted as the IF.  
The peeling of IF was achieved through additional simulations, in which the IF dropped from the 
internal layer, forming the FL. Firstly, a uniform blood pressure of 120 mmHg, mimicking the 
systolic pressure in the aorta, was applied to the surface of the internal layer during the 
simulation. The whole aorta was constrained to movement just in the radial direction. To 
simulate the IF separation, the aortic pressure was reduced from 120 mmHg to 0 mmHg, 
resulting in the detachment of the IF from the aortic wall, thereby forming the FL. The peeling of 
IF was simulated by Abaqus/Explicit (Dassault Systèmes, France). The ratio between the arc 
height and the internal diameter defines the size of FL. Three different AD models with varying 
FL sizes were created by changing this ratio to 10%, 30%, and 50%.  
After the creation of AD models, 30, 32, and 34 mm BMS were virtually deployed in these models.  
In the first step, a sheath was initially created to compress the BMS and was narrowed towards 
the center line, and then the BMS was delivered to its landing zone. In the second step, the sheath 
expands in a direction contrary to the BMS's crimping step, progressively allowing the BMS to 
self-expand into the TL and contact the IF and aortic wall.  
In the results, tears configurations, area ratio between the FL and TL, incomplete stent 
apposition, aortic diameter, and stress distribution before and after the BMS deployment were 
compared. These results arouse many hints. For an area ratio less than 13%, oversizing 1.3 BMS 
is sufficient to close the tears. BMS deployment may cause TL stenosis while treating a large FL 
with a large oversizing BMS. Promoting neointimal formation can reduce complications caused by 
deployments. The large porosity of this BMS will not seriously affect the blood perfusion to the 
branch arteries regardless of major arteries or minor arteries along the aorta. Based on this study, 
instructions for use recommended that the proposed therapeutic is applicable for both Type B and 
Type A AD with a small FL without complications, in which FL is about 15% of the TL. 
 
第 5 章 Z- and Straight-type BMS Mechanical Performance 
In this chapter, Z- and straight-type BMS manufactured by JMR Co., Ltd underwent radial force 
tests using the in silico method. 12 plates were placed in the radial pattern and moved radially. 
The sum of the forces acting on the plates from the BMS was considered the radial force. Besides 
 
 4 
the radial force trends, the foreshortening rate and the stress and strain distribution on the BMS 
were also calculated. 
Radial force performance is a crucial factor in evaluating the outcomes of BMS. For these BMS, 
unlike other self-expandable stents, the radial force gradually increases to the peak value, the 
peak radial force can be archived once the stent is compressed slightly, and the radial force can be 
maintained very close to the peak level. Considering the oversizing condition, the best support to 
the TL from the BMS can be maintained to face the arterial and IF elastic recoil. On the contrary, 
the rapid decrease in expansion radial force seems to show insufficient expansion ability in the 
late stage, but it also indicates that extra damage to the external layer and potential degeneration 
of the lesion can be avoided. For the BMS used for AD in this study, the foreshortening rate was 
much more significant than other small BMS used in small arteries, resulting in damage owing to 
frictional contact between the stent surface and the arterial wall. In addition, the larger 
foreshortening can also make the landing of BMS inaccurate, and significant shortening of the 
stent with expansion poses a danger that it may not cover the complete length of the lesion, 
resulting in an untreated diseased segment. Along with the self-expandable property, the landing 
displacement might become more serious because this property can also induce stent shooting 
forward due to the instant energy release. The stress and strain concentrations were always 
located at the connection points, and the frequent high-strain cycles may lead to material fatigue 
over time. 
 
第 6 章 Future Work and Conclusion 
Multiple limitations of studies were mentioned in the previous chapters, so some future work 
needs to be conducted to overcome them and optimize this pre-clinical evaluation. The uniaxial 
tensile test in Chapter 3 will be replaced by the biaxial tensile test to cover the anisotropic 
property of aortic tissue. In the real in vivo condition, the aorta is curved, so BMS must undergo 
bending momentum. The uniform deformation of the BMS may cause springback force, which 
may complicate the interaction between the BMS and the aortic wall and IF. Thus, in the future, 
the assessment of such a phenomenon will also be conducted. In addition, patient-specific AD 
models with complex pathology will also used in the virtual deployment. The release function 
used in Chapter 4 will also be replaced by a function that is closer to the actual deployment 
procedure; moreover, hemodynamics analysis will be added to evaluate the blood flow 
interventions of the proposed treatment. To further study the potential stenosis of HSD, AD 
models with large FL will be studied using both in vitro and in silico approaches.  
To conclude this thesis, the positive application of neointima formation may avoid most 
complications aroused by stent graft, and the bare metal stent may not affect the blood perfusion 
in the branch arteries. Consequently, the interpretive pre-clinical evaluation has a predominant 
potential to analyze risks in dealing with large dissection lumens for more sophisticated 
therapeutics to ameliorate both Type A and Type B aortic dissections.  
 
東北大学大学院医工学研究科 
別紙１ 
論文審査結果の要旨及びその担当者 
論文提出者氏名 Hou Xiaoxi (ホウ ショシ) 
論 文 題 目 
Pre-clinical Evaluation of a Bare Metal Stent Therapeutic for Aortic 
Dissection（大動脈解離疾患治療ベアメタルステントの非臨床評価研究） 
論文審査担当者 （主査）教 授 山家智之 
教 授 芳賀洋一       教 授 杉田典大 
論 文 審 査 結 果 の 要 旨 
 大動脈解離は致命的な血管疾患で、持続的な痛み、大動脈破裂、臓器虚血、大動脈弁不全、脳卒
中、大動脈瘤などの生命を脅かす合併症が発生するため、早期の適切な管理が重要であるが、最近
の介入デバイスであるステントグラフトには欠点があり、余分な合併症や適用の制限につながる。
これらの欠点を克服し、合併症を回避するために、大型の自己拡張型ベアメタルステントが大動脈
解離の新しい治療法として開発され始めている。 
本研究は、in vivo、in vitro、in silico 実験を使用し、潜在的なリスクを予測し、この新治療法
の将来の改善策を提案するものである。 
この新しい治療法は、ベアメタルステントの放射状拡張焦点を利用して内膜フラップを拡張し、
大動脈壁に押し戻すことで裂傷を閉じるメカニズムによって治療効果をもたらす。そのためまず内
層と大動脈壁の機械的応答を測定した。動物実験から抽出した内膜フラップ（内層）と偽腔を形成
する外層に引張試験を実施し、大動脈解離の機械的特性を測定した。 
内膜フラップ拡張の理想的な 2D シミュレーションを適用して機械的応答を予測した。この結果
から、内膜フラップは外層よりも弾性が低く、剛性が高いことが示され、この研究は、内膜フラッ
プがステントから偽腔の外層への拡張力を軽減し、それによって過拡張を回避して解離変性を引き
起こすことを明らかにしたものである。内膜層の剛性と弾性は、治療を適切に計画するための重要
な基礎となる。 
この治療の介入結果をさらに予測するために、理想的な大動脈解離モデルにおけるベアメタルス
テントの仮想展開シミュレーションを行った。その結果サイズ比が 1.3 を超えるベアメタルステン
トは裂傷を完全に閉じ、TL の 16% 未満の FL の解離病変を改善すると考えられ、合併症を回避
できる新生内膜被覆が決定された。また、さらなる研究で、2 つのベアメタルステントの機械的性
能を評価し、正のラジアル力傾向は、この治療が外層に最小限の影響しか与えないことを裏付けた。
ただし、ベアメタルステントの避けられない大幅な短縮により、着地位置の縦方向のずれが生じ、
介入が失敗する可能性がある。さらに、応力集中に関係なく、高いひずみ集中は接続点付近で破損
の危険につながる。したがって、ステントの足場パターンとデリバリー システムをアップグレー
ドする必要がある。 
その結果、解釈的前臨床評価は、A 型と B 型の両方の大動脈解離を改善するためのより洗練さ
れた治療法のために、大きな解離腔を扱う際のリスクを分析する上で必要になる、臨床展開上の大
きな可能性を秘めており,]よって、本論文は博士（医工学）の学位論文として合格と認める。 


English

大動脈解離疾患治療ベアメタルステントの非臨床評価研究

東北大学大学院環境科学研究科

Japanese

環境科学研究科 アクティビティレポート 2024

東北大学電気通信研究所

THE RECORD OF ELECTRICAL AND COMMUNICATION ENGINEERING CONVERSAZIONE TÔHOKU UNIVERSITY Vol. 94 No.1

Tohoku University博士（学術）要約のみthesi

小坪, 将輝

Doctoral dissertation summary 
Internal migration in Japan in the age of depopulation 
Masaki Kotsubo (C2GD4001) 
 
In Japan, the national population has been decreasing since 2008 amid low fertility and continued 
ageing. Regional differences in fertility and mortality will significantly impact local population 
changes; however, migration will also contribute to altering local population structures and future 
population reproduction.  
Internal migration is a key component in the changes in regional population size and structure 
within a country. It has been attracting attention in academic and policy arenas in Japan. The direct 
(numerical and short-term) demographic effects of internal migration can be reduced due to the 
shrinking size and share of the mobile group (i.e., young adults), low fertility, and population ageing. 
However, in the age of depopulation, indirect (qualitative and long-term) demographic effects—that 
is, the changing spatial distribution of young adults who contribute to population reproduction through 
migration—will be more important for discussions of future regional populations in Japan. It is, 
therefore, necessary to grasp the current state of internal migration—who is moving from where to 
where, how the patterns are persisting or changing, and who intends to move and why they do so—to 
examine the determinants of migration patterns and define the direct and indirect effects in the age of 
depopulation. This thesis emphasises these primary but necessary perspectives. It has seven chapters: 
Introduction (Chapter 1), data review (Chapter 2), empirical analyses (Chapters 3-6), and Conclusions 
(Chapter 7).  
The overall research aim of this thesis is to advance our understanding of internal migration 
in Japan in the age of depopulation. To achieve this, the following specific objectives were set: 
 
1. To review internal migration data and summaries the advantages, disadvantages, recent 
updates, and potential of the available data for a better understanding of internal 
migration in the age of depopulation. 
2. To grasp variations in the internal migration rate with the disaggregation of major 
temporal inter-relations. 
3. To investigate individual variations in migration intentions and motives as future 
migration behaviours and explore the relationships between migration intentions and past 
migration experiences. 
4. To explore the overall internal migration patterns and changes in these patterns in the age 
of depopulation. 
5. To examine the variations in internal migration patterns by age and sex using the latest 
datasets. 
 
The first objective was met in Chapter 2, which explored the current state of internal migration 
data and the way it is provided in Japan. There are three major data sources in Japan: the resident 
register, census, and migration surveys. Migration definitions and temporal/objective coverage of data 
differ not only among, but also within, data sources. Chapter 2 summarised the measurement of 
migration and temporal coverage of the data for each data source. The observation frequencies and 
spatial resolution of the data were then summarised as the advantages and disadvantages of each data 
source. The chapter also introduced previous studies that have used each data source. I also described 
two major features of internal migration in Japan: the decline in internal migration and urbanisation 
trends. 
Chapter 2 showed that recent updates to the data have mitigated their disadvantages to 
advance our understanding of internal migration in Japan in the age of depopulation. For example, the 
coarse geographical resolution of the resident register (i.e., annual inter-prefectural migration flows) 
is not an issue with the available inter-municipal migration flows published since 2012. In addition, 
the increased number of unreported cases in the censuses was considered in the publication of the 
census results, where they were imputed to provide reliable data.  
This chapter also discussed different views and potential uses of the data from those presented 
in previous studies. For instance, though the census data have high spatial resolution and demographic 
information on migration, previous studies have used only one of these aspects, and cases 
simultaneously considering the migration directions and characteristics of migrants are few. In terms 
of the migration surveys, previous studies have used migration histories and have not focused on 
migration intentions and motives behind them. In addition, the migration surveys cover a long period; 
however, multiple surveys have not been used to compare tabulation results and no analysis of repeated 
cross-sectional data has been performed. These updates and views are useful for understanding 
Japanese internal migration features in the age of depopulation. 
The second objective was met in Chapter 3, which used six migration surveys conducted from 
1991 to 2016 and measured migration to determine whether migrants’ current prefecture of residence 
differed from their prefectures of residence five years earlier. It used the surveys as repeated cross-
sectional data and applied the age-period-cohort-interaction model to the dynamics of internal 
migration rates in Japan.  
Chapter 3 focused on the period from 1986 to 2016, based on the adopted definition of 
migration. It discusses the migration patterns in Japan not only in the age of depopulation, but also in 
a period when the national population continued to increase in the context of rapid population ageing. 
The results showed the regularity of age-specific migration patterns, fluctuating period effects, inter-
cohort differences (especially in young generations), and intra-cohort dynamics. Age effects reflect 
general patterns of migration, known as the migration schedule, and period effects capture the 
economic conditions in Japan. However, the cohort effects indicated constant high and low migration 
rates of the cohorts that experienced an economic boom and stagnation in the 1990s during their most 
mobile ages. In generations that experienced economic stagnation or an upturn in the economy during 
childhood, the low or high migration rates levelled off as the cohorts aged.  
The third objective was met in Chapter 4. This chapter focused on migration intentions and 
the motives behind them in the migration survey, which have been underrepresented in previous studies, 
as future migration behaviours. Taking advantage of the available data, it investigated who intends to 
move and the associations between migration intentions and individual characteristics and past 
migration experiences. Recent studies have suggested that past migration experiences are crucial 
factors in explaining migration intentions and behaviours. 
Chapter 4 used migration prospects for the next five years in the 7th and 8th surveys, 
conducted in 2011 and 2016, to represent migration intentions. The analysis, thus, focused on the 
period from 2011 to 2021. The results showed that individuals who were likely to move were younger, 
highly educated, never married, had a high occupational status, were students, did not own a house, 
lived in the Tokyo metropolitan area, and had resided in more prefectures. Past migration experience, 
measured by the number of prefectures in which individuals had resided, was a consistent factor across 
all motives. The analysis of respondents intending to move showed that individuals who had lived in 
more prefectures were likely to have education and employment motives and were less likely to have 
family motives behind their migration intentions.  
The fourth objective is described in Chapter 5, which attempted to estimate the suppressed 
numbers of migrants in the origin-destination matrix of annual intermunicipal migration flows from 
the resident register. It then investigated the relationship between net migration and population density 
at the municipal level and examined the in- and out-migration flows aggregated by the centres and 
suburbs of the three major metropolitan areas in Japan using estimated inter-municipal flows. 
The analysis covered the period from 2012 to 2023, when the national population decline 
continued, including the pre-, peri-, and post-pandemic periods. The chapter showed that the 
urbanisation trend, that is, larger sizes of migration flow from rural to urban areas than their 
counterparts, continued during the age of depopulation. Although the trend weakened during the 
COVID-19 pandemic, it did not reverse the counter-urbanisation patterns. In addition, urban exodus 
and net out-migration from metropolitan areas were not observed. In line with studies on the impacts 
of the COVID-19 pandemic, this chapter presented empirical evidence showing that the impacts were 
temporal and that migration patterns have been recovering to pre-pandemic patterns. 
The fifth objective was met in Chapter 6, which examined migration patterns by age and sex 
using the latest census data. The data were published by the Statistical Bureau, and unreported cases 
were imputed. This chapter is one of the early works based on the imputed results of the 2020 census 
and takes advantage of data on detailed age groups. The hierarchical representation of migration 
efficiency to examine migrants’ migration directions and characteristics simultaneously. 
Owing to the migration measurement of the census as a five-year transition, Chapter 6 covered 
the period from 2015 to 2020. Using the urban hierarchy in Japan, based on the 2015 Urban 
Employment Area, the chapter showed that predominant upward migration, such as migration from 
non-metropolitan to small metropolitan areas, small metropolitan areas to medium or large 
metropolitan areas, medium or large metropolitan areas to the Tokyo metropolitan areas, and jumping 
across the hierarchy, was observed as the overall pattern. Regarding age-specific patterns, young adults 
tended to move up the urban hierarchy efficiently (unidirectionally) and contributed to overall upward 
trends. The efficiency decreased and directionality reversed with age; however, old older adults, aged 
≥75 years, also tended to move up the hierarchy. The upward migration of women was dominant in 
almost all age groups. 
In conclusions, the updated data sources, underrepresented topics, and methodological 
developments covered have advanced our understanding of internal migration patterns in Japan. 
However, there are of course areas that must still be improved, updated, and honed. It is hoped that the 
emergence of new technical approaches and the accumulation of data over time, as described in this 
thesis, will further advance our understanding of internal migration in Japan. 


人口減少時代における日本の国内人口移動

長神, 風二

サイエンスコミュニケーションと図書館

紀要類 (bulletin)原著departmental bulletin pape

菊地,  史子

伊藤, 美智子

中條,  庸子

嶋,  育子

赤間,  和子

石上,  節子

緩和ケアセンターに従事する看護師のケアに対する自己評価の検討 : 現任教育の課題に焦点を当てて

紀要類（bulletin）departmental bulletin pape

手嶋, 泰伸

旧国有財産法の成立と地域行政 ―大正期仙台の都市計画と軍用地管理換え問題―

狩野, 雄

張華と楚辞―「雑詩」に見える「蘭膏」の語をめぐって

SAWADA, Tetsuo

Phantasy and Vulnerability in Children’s Drawing: From the Perspective of Husserl’s Theory of Phantasy and Merleau-Ponty’s Sorbonne Lectures

Not a member yet