Assessment of Myocardial Iron Content and Electromechanical Remodeling in an Animal Model of Iron-Overload Cardiomyopathy --- Validation and Application of Tissue Doppler Imaging, Strain Rate Imaging, and Superconducting Quantum Interference Device

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Project title/計畫英文名

Project Number/計畫編號

NSC99-2314-B002-021-MY3

Translated Name/計畫中文名

以新進影像技術於鐵質過渡沉積引起之心肌病變的動物模式中評估心肌鐵質含量並探討電氣機械性心肌重塑之過程---組織杜卜勒影像、應變速率影像、與超導量子干涉元件之驗證與應用

Project Principal Investigator/計畫主持人

CHUN-AN CHEN

Co-Investigator(s)/共同執行人

MEI-HWAN WU
JOU-KOU WANG
CHAU-CHUNG WU

Funding Organization

Ministry of Science and Technology

Co-Investigator(s)/共同執行人

謝振傑

Department/Unit

Pediatrics

Start date/計畫起

01-08-2010

Expected Completion/計畫迄

31-07-2011

Description

Abstract

摘要：心肌鐵質過度沉積所引起的心臟衰竭是造成長期輸血的病患死亡之主因。心臟核磁共振T2*的數值雖與心肌中鐵質含量有一定之相關性，但在臨床使用上仍有其限制。本團隊過去已建立穩定之超導量子干涉元件(SQUID)交流磁化檢測裝置平台，且初步研究也證實此裝置可偵測出注射入活體內微量之磁性物質。而利用SQUID所獲取之心磁圖已證實可以評估心肌功能失全與心律不整的發生。此外，組織杜卜勒心臟超音波影像(TDI)及應變速率影像(SRI)已在臨床上使用於評估局部心肌之收縮與舒張功能。因此，本轉譯研究計畫之目的在於以非侵襲性之新進影像技術，利用鐵質過度沉積的動物模式，測試本研究團隊所研發之可移動式SQUID檢測心臟中鐵沉積量之可行性與準確性，並以心磁圖及TDI/SRI探討鐵沉積對心臟功能影響之序列變化。在第一部分的實驗中，我們將在大鼠體內連續十六個星期注射iron dextran (對照組僅接受dextran之注射)。過程中大鼠將定期接受SQUID及TDI/SRI之檢測，並依序在第2, 4, 6, 8, 12, 16個星期犧牲，以計算心臟中的總鐵含量，並在左右心室進行切片及染色。組織學以及總鐵含量的結果將與SQUID之訊號強度做相關性之迴歸分析，並且與一系列之心磁圖、TDI/SRI之數據進行比較分析。在第二部分的實驗中，大鼠將先接受連續十六個星期的iron dextran注射，而後平均分成三組，包括注射安慰劑、注射Deferoxamine、以及服用Deferasirox，分別在使用排鐵劑8及16星期後接受SQUID及TDI/SRI檢測並取得組織進行分析，以探討這些影像檢測是否可用於評估排鐵劑對於移除心臟中鐵質沉積之療效。若此等技術可在動物的鐵質過度沉積之模式中精確地反映出心臟中的鐵沉積量以及早期之功能變化，將可為未來的人體試驗及臨床應用建立重要的理論基礎。
Abstract: Heart failure caused by iron-overload cardiomyopathy remains the major cause of mortality in patients with transfusion-dependent diseases. In previous studies, our research group has established a stable portable system of superconducting quantum interference device (SQUID). In our preliminary experiment, the portable-SQUID biomagnetic system has been shown to be able to detect trace amount of paramagnetic particles in living animals. We have also proved that magnetocardiogram (MCG) obtained by SQUID could predict the occurrence of cardiac dysfunction and arrhythmias. Besides, regional myocardial systolic and diastolic function could now be evaluated by tissue Doppler imaging (TDI) and strain rate imaging (SRI). Therefore, the purpose of this pilot translational research was to test the feasibility, effectiveness, and validity of novel imaging modalities, including TDI/SRI, SQUID MCG system, and the portable-SQUID biomagnetic system, in the early detection of myocardial dysfunction and iron content in a rat model of iron-overload cardiomypathy.In part I experiment, rats will be injected with iron dextran for a total of 16 weeks (control animals will be injected with dextran). During the course of iron loading, rats in both groups will be serially evaluated with SQUID and TDI/SRI, and scarified 2, 4, 6, 8, 12, and 16 weeks after iron loading. The heart will be harvested and tissue iron content of the left and right ventricles will be measured. Tissue samples from the left and right ventricles will also be stained for histopathology examinations. Correlation between signals obtained by the portable-SQUID biomagnetic system and tissue iron contents will then be tested. Serial results of MCG, and TDI/SRI will be compared with tissue iron contents and histological changes. In part II experiment, we attempt to evaluate the usefulness of these imaging modalities in the evaluation of the treatment responses to chelation therapy. Rats pre-loaded with iron dextran for 16 weeks will be separated into 3 groups (sham-chelated, Deferoxamine-chelated, and Deferasirox-chelated). Animals will be evaluated with SQUID and TDI/SRI, and then sacrificed 8 and 16 weeks after chelation therapy.If these novel techniques could precisely assess cardiac iron load and detect early changes in myocardial electromechanical properties in the animal model of iron overload, the results from this study would provide theoretical evidence for future clinical trials and applications.