혈관 플라크 예측과 진단 번역(한국어 원본)순환기 질환은 노화, 식습관, 유전적 요인 등이 복합적으로 작용하여 발생하기에 그 mechanism을 정확히 규명하기가 어려우며 관련된 대부분의 연구는 질환이 발생한 환자를 대상으로 이뤄진다. 이는 대부분의 medical imaging이 lesion 진행된 혈관을 대상으로 얻어지기 때문이다. 그러나 lesion 발생 부위의 예측이나 lesion의 진행 과정을 이해하기 위해서는 diseased 상태뿐만 아니라 healthy state의 blood flow 특성을 함께 고려한 복합적인 연구가 필수적이다.
본 논문에서는 인체 혈관 plaque의 발생을 예측하고 plaque의 rupture 가능성을 진단하기 위하여 Fluid-Structure Interaction(FSI)이 적용된 Hemodynamic numerical analysis technique를 구현하였다. 이를 위하여 medical imaging의 재구성(reconstruction), generating healthy arterial model, simplified modeling technique, hemodynamic numerical model, arterial wall model, two-way FSI model, hemodynamic parameters 검토 등의 세부 연구들을 수행하였다.
Healthy arterial model을 생성하기 위하여 CT(Computed Tomography)영상을 통해 생성된 삼차원 혈관 geometry와 IVUS(Intravascular Ultrasound)영상의 cross-sectional information을 활용하여 가상적으로 plaque를 제거하였으며 healthy arterial model의 plaque가 제거된 영역에서 낮은 averaged wall shear stress (AWSS)와 높은 oscillatory shear index (OSI)가 나타났다. 이는 plaque의 발생이나 진전과 연관이 높은 hemodynamic 특성이며 또한 그 부위가 lesion이 주로 발생하는 혈관의 curved area, bifurcation라는 점에서 healthy arterial model이 합리적으로 plaque의 발생 부위를 예측하는데 활용할 수 있다고 판단된다.
Diseased arterial wall model을 모사하기 위하여 VH-IVUS(Virtual Histology Intravascular Ultrasound)를 통해 stenosis의 type을 진단하였으며 이를 모사한 wall model을 생성하였다. 이 때 wall model은 경화반의 주요 component인 necrotic core, fibrous and fibrofatty, calcified component 등으로 모사되었다. 실제로 rupture가 발생된 TCFA(Thin Cap Fibro-Atheroma) 환자의 단면에서 plaque를 감싸는 inner wall에 높은 stress가 발생하였으며 이를 통해 plaque가 파열된 현상을 추측하였다. 제안된 arterial wall model은 TCFA형태의 plaque가 rupture의 가능성이 높으며 high mechanical stress distribution이 inner wall을 손상 시킬 가능성이 높다는 점을 모두 충족시켰으며 이를 통해 plaque rupture의 가능성을 진단하는데 활용이 가능하다고 판단된다.
이와 같이 본 논문에서 제시한 two-way FSI technique가 적용된 healthy 및 diseased arterial model은, stenosis가 발생하는 부위의 prediction과 plaque의 rupture 가능성을 진단하는데 활용이 가능하다. 이는 기존의 의학적 연구 결과들을 정량적 수치로 뒷받침 한다는 점에서 기존의 독립적인 의학분야와 공학분야의 연구결과를 종합할 수 있으며 이를 활용하여 lesion 발생의 mechanism을 이해하고 질환의 진전 있어서 정량적인 진단 기준을 제시할 수 있을 것으로 기대된다.
Specific Comments:
Comment #1.
In the section 3.2 “Geometric paragraph”, explain that total case number of shape is 33 by 3 factors and 3 levels.
Answer #1 : 본 논문의 geometric parameter는 3-factor(X1, X2, X3)이고 각각의 factor는 3-level의 value를 가지고 있습니다(ex: X1= 75, 50, 25). 이에 factor와 level의 조합에 의한 parameter는 3x3x3의 27개 이며 geometric factor의 singularity를 검토하기 위하여 일반적인 Design of Experiment(DOE, 최소의 실험으로 최대의 효과를 얻기 위한 계획방법)을 활용하였습니다. 아래의 그림과 같이 3-factor 3-level의 DOE에서는 factor의 조합에 따른 parameter와 parameter를 circle 혹은 sphere로 가정하여 나열하였을 때 얻을 수 있는 maximum/minimum 수치들을 parameter의 경우에 추가할 수 있습니다. 따라서 본 연구에서는 3-factor 3-level에 의한 parameter 27개와 DOE에 의한 parameter 6개를 추가하여 총 33개의 numerical cases를 수행하였습니다. 명확한 이해를 위하여 본문에 다음과 같은 내용을 추가하였습니다. 또한 논문의 결과에는 영향을 미치지 않으나 Table 2(case : C28, D28)잘 못된 수치를 발견하여 이를 정정하였습니다. 정정된 수치는 C28의 X1 : 33 >> 8, Tc : 102.6 >> 102.2, Tb : 104.6 >> 103.8, D28의 Tc : 99.1>>98.8, Tb :101 >>100.2 입니다.
>> Numerical의 총 case는 DOE을 활용하여 3-factor 3-level에 의한 27가지 cases와 각 factor의 singularity를 검토하기 위한 6가지 추가 경우를 더해 총 33가지이다.
Comment #2.
In the section 4.4 “Temperature of four heaters”, explain why the range of Tc is 97.6 ~ 100.3 degreeC. Isn’t the minimum range 96.4 ?
Answer #2 : 온도범위는 저자의 실수입니다. 지적하신 바와 같이 최저 온도는 96.4℃이며 이에 본문을 수정하였습니다. 수정된 내용은 다음과 같습니다.
During the evaluation of cases with four heaters (D01–D33), it was found that Tc was 97.6–100.3℃ and Tb was 98.1–101.3℃
>> During the evaluation of cases with four heaters (D01–D33), it was found that Tc was 96.4–100.3℃ and Tb was 98.1–101.3℃
Comment #3.
In the section 4.2 “Effects of geometric parameters”, what is the meaning of ‘Table x’ and (a), (b)? Provide detail analysis results about effects of geometric parameters.
Answer #3 : Table x는 Table 3을 의미하며 글자 (a), (b)역시 잘 못된 표현입니다. 이에 본문에 해당내용을 수정하였습니다. 또한 geometric parameters의 영향에 대한 추가적인 설명을 본문에 추가하였습니다. 수정되고 추가된 내용은 다음과 같습니다.
Table 3 lists the Tc and Tb values when the initial dryer shape and X1, X2, and X3 parameters were independently modified. X1(outlet of height)가 줄어들었을 때 Tc는 각각 0.4, 0.5, 0.3, 0.4℃(C10, C19, D10, D19)증가 하였고 Tb는 큰 변화가 나타나지 않았다. 이는 작아진 dryer outlet으로 인해 유입된 고온의 공기가 내부에서 더 순환하여 dryer 내부 평균 온도를 상승 시키는 것을 의미한다. 또한 X2(distance between conveyer line and air knives)의 간격이 initial dryer 보다 가까워 질 수록(작아질 수록) Tc는 -0.5, -0.6, -0.7, -0.7℃도 감소하였으며 Tb는 -1.9, -1.7, -1.9, -1.6℃(C04, C07, D04, D07)감소하였다. X2가 감소할 경우 air knives와 conveyer line의 거리가 가까워지는 것을 의미한다. 이에 air knives에서 나오는 고온의 공기가 conveyer line에서 circulation하여 상승하는 air flow가 감소되고 직접 conveyer line을 따라 outlet를 통해 유출되는 air flow의 양이 증가되기 때문이다. X3(distance between the air knife and the ceiling of the dryer)의 경우 initial dryer에 비해 Tc가 0.4, 0.8, 0.3, 0.8℃증가하였으나 Tb의 경우 -0.3, -0.7, -0.2, -0.5℃(C02, C03, D02, D03) 감소하였다. X3는 dryer의 크기와 관계 있는 parameter다. 따라서 x3가 감소할 경우 dryer 내부 크기가 감소되어 유입된 고온의 공기가 dryer 전체의 평균 온도를 상승 시키게 된다. 그러나 국부적인 conveyer line의 온도 변화에는 큰 영향을 미치지 못하는 것을 알 수 있다. |
혈관 플라크 예측과 진단 번역(영어 번역본)Because several factors including aging, eating habits, and genetics caused the circulatory disease to occur, the mechanism could not be accurately identified so most related research done on circulatory disease was performed on patients in which the disease occurred. This is because most medical imaging is intended for a blood vessel of which a lesion has progressed. But, to predict the part where the lesion occurred or to understand the progression of the lesion, integrated research is required that considers not only the diseased state, but the healthy state of blood flow.
In this study, the occurrence of human vascular plaque is predicted and to diagnose the possibility of rupture the Hemodynamic numerical analysis technique was realized which applies the Fluid-Structure Interaction(FSI). To accomplish this, detailed research was carried out including a reconstruction of medical imaging, generating a healthy arterial model, simplified modeling technique, hemodynamic numerical model, arterial wall model, two-way FSI model, and a review of hemodynamic parameters.
To create a healthy arterial model, 3D blood vessel geometry was created through CT(Computed Tomography) footage and footage of the cross-sectional information IVUS(Intravascular Ultrasound) was used to hypothetically remove the plaque and areas where the plaque in the healthy arterial model was removed, it showed that there was an averaged wall shear stress (AWSS) and a high oscillatory shear index (OSI). The occurrence or development of plaque is closely related to the close relation of hemodynamic features, and also from the standpoint of the curved area, and bifurcation of the curved area of the blood vessel where lesions usually occur and it was judged that the healthy arterial model could be used for rationally predicting the area of occurrence of plaque.
To copy the Diseased arterial wall model the type of stenosis was diagnosed using the VH-IVUS(Virtual Histology Intravascular Ultrasound) and to copy this a wall model was produced. Here, the wall model made copies of the main components of plaque, necrotic core, fibrous and fibrofatty, and calcified components. Actually from the cross section of the TCFA(Thin Cap Fibro-Atheroma) patient where the rupture actually occurred, there occurred a high level of stress in the inner wall that was surrounded by plaque, and it was guessed that through this the phenomenon of plaque rupturing took place. There was a high possibility of the form of the TCFA of plaque rupturing in the proposed arterial wall model and it completely satisfied the high possibility that high mechanical stress distribution could damage the inner wall and through this the possibility of a plaque rupture was deemed possible.
Likewise, in this study the healthy and diseased arterial model to which the two-way FSI technique was applied was used to predict the places stenosis was likely to occur and could be used to diagnose the rupture of plaque. From the perspective of supporting existing medical results with quantitative numerical values, this study can integrate the existing independent medical field and the results of the engineering field and using this one can understand the mechanism of the occurrence of lesions, and with the development of the disease it is estimated to present the standard for qualitative diagnosis.
Specific Comments:
Comment #1.
In the section 3.2 “Geometric paragraph”, explain that total case number of shape is 33 by 3 factors and 3 levels.
Answer #1 : This geometric parameters of this study has 3-factors(X1, X2, X3)each factor has a 3-level value(ex: X1= 75, 50, 25). The parameters of a combination of this following factor and level is 3x3x3 or 27, and the Design of Experiment(DOE, or a planning method for obtaining the best results with the least amount of experimenting) was used. As seen in the figure below, the maximum/minimum numerical values, which are obtained when the circle or sphere assumes and lists parameter and parameter according to a combination in the DOE in the 3-factor 3-level, can be added in case of the parameters. Accordingly, in this study, 27 parameters regarding the 3-factor 3-level, and the 6 parameters regarding the DOE were added for a total of 33 numerical cases conducted. The following content was added to the text to facilitate understanding. Also, the results of the thesis did not cause any affects, but in Table 2(case : C28, D28) erroneous numerical values were discovered and deleted. The deleted numerical values for C28 were X1 : 33 >> 8, Tc : 102.6 >> 102.2, Tb : 104.6 >> 103.8, and for D28 the deleted numerical values were Tc : 99.1>>98.8, and Tb :101 >>100.2.
>> Using DOE, the numerical cases totaled 33 which include 27 cases and 6 that were added to review the singularity of each factor.
Comment #2.
In the section 4.4 the “Temperature of the four heaters”, explains why the range of Tc was 97.6 ~ 100.3 degreeC. Isn’t the minimum range 96.4 ?
Answer #2 : The author made a mistake with the range of temperature. As outlined the minimum temperature was 96.4℃, which was revised in this text. The revised and added content is as follows.
During the evaluation of cases with four heaters (D01–D33), it was found that Tc was 97.6–100.3℃ and Tb was 98.1–101.3℃
>> During the evaluation of cases with four heaters (D01–D33), it was found that Tc was 96.4–100.3℃ and Tb was 98.1–101.3℃
Comment #3.
In the section 4.2 “Effects of geometric parameters”, what is the meaning of ‘Table x’ and (a), (b)? Provide detail analysis results about effects of geometric parameters.
Answer #3 : Table x means Table 3 and the letters (a), and (b) are obviously incorrect labels. The relevant content in the text was revised. Also, an additional description of the influence of geometric parameters was added to the text. The revised and added content is as follows.
Table 3 lists the Tc and Tb values when the initial dryer shape and X1, X2, and X3 parameters were independently modified. When the X1(outlet of height) was reduced Tc increased in increments of 0.4, 0.5, 0.3, and 0.4℃ (C10, C19, D10, D19) and Tb did not display any great changes. Due to the shrunken dryer outlet the hot air induced from the inside circulated, meaning it further boosted the average temperature inside the dryer. Also, the narrower the interval between X2(distance between conveyer line and air knives) (the smaller it gets) the temperature of Tc was reduced to -0.5, -0.6, -0.7, and -0.7℃ and Tb was reduced to -1.9, -1.7, -1.9, and -1.6℃(C04, C07, D04, D07). When X2 is reduced it means the interval between the air knives and the conveyer line narrows. Following this the hot air coming out of the air knives circulates from the conveyer line reducing the amount of air flow and increasing the quantity of the air flow that is released through the outlet directly following the conveyer line. In case of X3(distance between the air knife and the ceiling of the dryer) compared with the initial dryer Tc increased by 0.4, 0.8, 0.3, and 0.8℃, but in case of Tb it was reduced by -0.3, -0.7, -0.2, and -0.5℃(C02, C03, D02, D03). X3 is the parameter that is greatly related with the size of the dryer. Accordingly, when the x3 shrinks the interior of the dryer is reduced and the average overall hot air induced into the dryer is raised. But, it is considered that a change in conveyer line temperature would not have a big effect. |
