近藤 功, 大森 浩二, 水重 克文

Isao KONDO, Koji OHMORI, Katsufumi MIZUSHIGE

香川医科大学第二内科

Second Department of Internal Medicine, Kagawa Medical University

キーワード : contrast echocardiography, leukocyte-imaging, inflammation, transplanted heart

コントラストエコー法の応用として, 臓器血液灌流の画像化に加えて血栓や炎症へのターゲットイメージングが報告されている. 本稿では, 微小気泡(バブル)と白血球の相互作用や炎症の画像化について基礎的検討から述べる. 1) 白血球ターゲッティングとバブルの安定性：活性化白血球に, リン脂質(BR 14)とアルブミン(optison^®)を成分とするバブルそれぞれを貪食させてもその音響特性(超音波照射に対するバブルの容積変化)は変化なく, 超音波照射に対してはBR 14がより安定であった. 2) 各種腎炎モデルでのターゲットイメージング：ラット腎虚血再灌流(I/R)モデルでは髄質と皮質の境界部分で, 抗Thy-1抗体誘導腎炎モデル(Thy-1 Nephritis)では皮質で染影が認められ, それぞれ炎症細胞の分布と一致した. 染影強度は, I/Rモデルでは24時間後のクレアチニンクリアランスと, Thy-1 Nephritisでは腎炎発症から10日目の尿中蛋白量と有意に相関した. 本法は, 炎症細胞による各種病態の診断に有用である. 3) 心移植後急性拒絶反応への免疫抑制剤の効果判定：ラット同種異系間心移植モデルでの心移植後3日目の急性炎症期, サイクロスポリンA非投与群では心臓全周が染影され, 投与群では用量依存性に染影強度が低下した. 本法は心移植後拒絶反応に対する免疫抑制剤の効果判定にも応用できる.

In addition to the tissue perfusion imaging by contrast echography, leukocytes- or thrombus-targeted imaging has been newly developed. In this review, we introduce the interaction between phagocytosed microbubbles and leukocytes, and the applications of leukocyte-imaging by contrast echography based on our in vitro and in vivo experimental studies. 1) Leukocytestargeted imaging and stability of phagocytosed microbubbles under insonation : Phospholipid-stabilized (BR 14) or albuminshell (optison^®) microbubbles were incubated with activated human neutrophils. Acoustic properties of each microbubble indicated as deflection rate were not affected by phagocytosis, and BR 14 was more stable than optison^® under insonation. 2) Leukocyte-imaging by contrast echography in renal inflammation models of ischemia/perfusion or anti-Thy-1 antibody induced glomerulonephritis: The opacification patterns of leukocyte-imaging were compared with the histopathological observation of leukocyte infiltration in these two types of renal dysfunction. This new imaging method facilitates assess to the spatial pattern of infiltration and residual function in renal inflammation models. 3) Leukocyte-targeted myocardial contrast echocardiography in acute allograft rejection in rat model: The heart from BN rats were transplanted into Levis rats and were divided into untreated, 3 mg/kg/day and 10 mg/kg/day cyclophosphamide (CyA) treated groups. Signal intensity of myocardial contrast echo significantly correlated with CyA doses. The leukocyte-targeted image can quantitatively assess the magnitude of leukocyte infiltration in transplanted hearts, which is impossible by functional evaluation or by perfusion imaging.