Disertasi

Klasifikasi Morfologi Intima Media Arteri Karotis dengan Pencitraan Ultrasonografi pada Aterosklerosis Dini: suatu penelitian hewan model Macaca nemestrina dan aplikasinya. = Morphological Classification of Carotid Intima Media with Ultrasound Imaging on Early Atherosclerosis: an animal model studies of Macaca nemestrina and its applications.

Latar belakang: Modalitas diagnostik yang ada saat ini belum mampu menggambarkan fase-fase aterosklerosis dini seperti yang sudah dilakukan pada klasifikasi histopatologi aterosklerosis. Tujuan: Menilai hubungan morfologi intima-media dan distribusi sel-sel busa subendotel arteri karotis pada Macaca nemestrina yang diberi diet aterogenik. Menilai keterandalan aplikasi klasifikasi morfologi dini USG tersebut pada subjek manusia; serta hubungannya dengan kadar serum Nitrite Oxide dan mediator- mediator inflamasi secara sistemik. Metode: Penelitian hewan model Macaca nemestrina yang diberi diet aterogenik sampai terbentuk morfologi intima-media yang diinginkan. Morfologi intima- media arteri karotis dibedakan menjadi morfologi tipe 0, tipe 1, tipe 2a, tipe 2b dan tipe 3 berdasarkan ekogenisitas, homogenitas dan regularitas & kontinuitas permukaan. Arteri karotis kanan dan kiri diambil untuk pemeriksaan histopatologi dengan pewarnaan Verhoff-van Gieson (VVG). Sensitivitas, spesifitas, degree of agreement ditentukan. Penelitian pada subjek manusia dilakukan pada 4 subgrup tipe 0, tipe 1, tipe 2a dan tipe 2b sesuai gambaran morfologi intima-media seperti pada klasifikasi hewan model. Dilakukan penilaian interobserver agreement dan hubungan tipe-tipe morfologi intima-media dengan kadar serum nitrite oxide dan mediator inflamasi TNF-a, IL-l, IL-6 dan MCP-l. Hasil: Penelitian hewan model memperlihatkan morfologi intima-media berupa morfologi tipe 0, tipe 1, tipe 2a, tipe 2b dan tipe 3 mempunyai pola distribusi sel- sel busa subendotel yang berbeda sesuai fase aterosklerosis. Ekogenisitas dan homogenitas USG yang hiperekoik dan inhomogen dalam mendeteksi sel busa mempunyai sensitivitas 56 % dan spesifisitas 100 % dengan area under the curve 0,78. Uji keterandalan morfologi USG memperlihatkan degree of agreement sebesar 62,96 % dengan nilai kappa 0,46. Penelitian subjek manusia memperlihatkan degree of agreement sebesar 79,42 % dan nilai kappa sebesar 0,694. Sim pulan: Tipe-tipe morfologi USG intima-media arteri karotis berhubungan dengan pola distribusi sel-sel busa subendotel dan dapat diaplikasikan pada subjek manusia untuk stratifikasi aterosklerosis dini.
Kata Kunci: arteri karotis, aterosklerosis, klasifikasi morfologi USG.



Background: The existing diagnostic modalities today have not been able to describe the phases of early atherosclerosis as it has been done in the histopathological classification of atherosclerosis. Objective: To correlate the carotid intima media USG morphology and the distribution of subendothelial foam cells of Macaca nemestrina. To assess the application reliability of USG carotid intima media morphological classification in Macaca nemestrina to human subjects and its correlation with serum levels of NO and inflammatory mediators systemically. Methods: A diagnostic study using animal models of Macaca nemesfrina fed with atherogenic diet to form an appropriate types of intima media morphology. Morphology of carotid intima-media was differentiated into type 0, type 1, type 2a, type 2b and type 3 by echogenicity, homogeneity and surface regularity. Right and left carotid artery were taken for histopathological examination with Verhoff- van Gieson staining (VVG). Sensitivity, specificity, degree of agreement was determined. A human subject study was conducted at 4 subgroups of type 0, type 1, type 2a and type 2b according to its intima-media morphology as it has been done in animal models. Interobserver agreement has been done and correlation of each subgroup with serum levels of nitrite oxide, TNF -u, IL-l, IL-6 and MCP-I had been evaluated. Results: The hyperechoic echogenicity and inhomogeneous homogeneity of intima media has a sensitivity of 56 % and a specificity of 100 % in detecting foam cell. Reliability testing on USG morphology shows degree of agreement of 62.96 % with a kappa value of 0.46. The USG intima media morphology could be divided to the morphological of type 0, type 1, type 2a or type 2b and each type has a different distribution pattern of subendothelial foam cells appropriate to phases of atherosclerosis. The interobserver agreement in type 0, type 1, type 2a and type 2b USG morphology of carotid intima-media showed degree of agreement of 79.42 % and a kappa value ofO.694. Conclusions: Types of carotid intima-media USG morphology correlated with a specific distribution of subendothelial foam cells as the histological classification of atherosclerosis and it is applicable to human subject as a stratification of early atherosclerosis.
Keywords: atherosclerosis, carotid intima media, USG morphology classification.