Ultrasound Imaging of Acute Cardiac Transplant Rejection With Microbubbles Targeted to Intercellular Adhesion Molecule-1

Weller, Gregory E.; Lu, Erxiong; Csikari, Melissa; Klibanov, Alexander L.; Fischer, David W.; Wagner, William R.; Villanueva, Flordeliza S.

doi:10.1161/01.cir.0000080287.74762.60

Cited by 240 publications

(167 citation statements)

References 20 publications

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“…Few methods have directly targeted the immunological alterations of the graft, such as the endothelial adhesion molecule overexpression 11 and immune cell infiltration, until recently. 10,11,13 In acute transplant rejection, T cells are known to play a critical role in the initiation of the rejection process.…”

Section: Kondo Et Al Allograft Rejection With Contrast Echomentioning

confidence: 99%

“…10,11,13 In acute transplant rejection, T cells are known to play a critical role in the initiation of the rejection process. 12 However, macrophages are also recruited via chemokines, including interferon-␥ derived from T cells.…”

Section: Kondo Et Al Allograft Rejection With Contrast Echomentioning

confidence: 99%

“…Weller et al 11 were the first to apply MCE to detection of allograft rejection. By using anti-intercellular adhesion molecule-1 antibody-conjugated microbubbles, they demonstrated increased microbubble retention in grafts undergoing severe rejection.…”

Section: Kondo Et Al Allograft Rejection With Contrast Echomentioning

confidence: 99%

“…Although T cells play a central role in graft rejection, 12 infiltration of T cells is accompanied by monocyte/macrophage infiltration [11][12][13][14][15] because of their close interactions. 10,15 Agents that affect primarily T cells, 12 including CsA, 16,17 can also limit monocyte/macrophage infiltration.…”

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confidence: 99%

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Leukocyte-Targeted Myocardial Contrast Echocardiography Can Assess the Degree of Acute Allograft Rejection in a Rat Cardiac Transplantation Model

et al. 2004

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Background-Repetitive endomyocardial biopsies are necessary to monitor the effects of immunosuppressants after cardiac transplantation. Contrast ultrasound with microbubble targeting of leukocytes detects acute leukocyte infiltration. We examined whether leukocyte-targeted myocardial contrast echocardiography (MCE) could provide for the quantitative assessment of acute cardiac rejection. Methods and Results-Hearts from Brown Norway rats or Lewis rats were transplanted into other Brown Norway rats. Isografts and groups of allografts either untreated or treated with cyclosporin A (CsA) at a low dose (3 mg · kg) from 3 days before transplantation were compared at posttransplantation day 3. Echocardiography-derived left ventricular wall thickening was comparable among the 4 groups. Myocardial blood flow assessed with MCE, relating pulsing intervals with signal intensity (SI), was slightly decreased only in untreated allografts. However, myocardial SI (in gray levels) obtained after a 10-minute period allowing microbubble-leukocyte interactions after contrast injection exhibited a clear gradient in these groups (12Ϯ2 in untreated allografts, 9Ϯ5 in allografts treated with low-dose CsA, 6Ϯ3 in allografts treated with high-dose CsA, and 2Ϯ1 in isografts, PϽ0.001). The pattern of difference in SI among the groups agreed well with that in ED-1-positive cell (macrophage) count (25Ϯ7, 12Ϯ4, 5Ϯ3, and 1Ϯ0 cells per high-power field, respectively, PϽ0.001), which correlated with CD3-positive cell (T lymphocyte) count (33Ϯ5, 22Ϯ5, 9Ϯ4, and 1Ϯ0 cells per high-power field, respectively, PϽ0.001). Conclusions-Leukocyte-targeted MCE can noninvasively assess the degree of rejection in transplanted hearts by directly revealing the magnitude of intramyocardial infiltration of macrophages and T lymphocytes.

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Section: Kondo Et Al Allograft Rejection With Contrast Echomentioning

confidence: 99%

Section: Kondo Et Al Allograft Rejection With Contrast Echomentioning

confidence: 99%

Section: Kondo Et Al Allograft Rejection With Contrast Echomentioning

confidence: 99%

mentioning

confidence: 99%

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Leukocyte-Targeted Myocardial Contrast Echocardiography Can Assess the Degree of Acute Allograft Rejection in a Rat Cardiac Transplantation Model

et al. 2004

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“…Upon examination with an ultrasound medical imaging system, the adherent microbubbles generate an acoustic response signal that is displayed as video enhancement of the target tissue on the system screen. Targeted ultrasound contrast agents have been used to assess vascular pathology associated with several intravascular markers, including P-selectin [3], ICAM-1 [4,5], GpIIb/IIIa [6,7], the α v integrins [8,9] and other markers of tumor angiogenesis [10]. Successful targeted contrast ultrasound imaging in these systems is possible in part due to extremely high microbubble detection sensitivity of ultrasound imaging, with the capability to visualize individual microbubbles [11].…”

Section: Introductionmentioning

confidence: 99%

Deformable gas-filled microbubbles targeted to P-selectin

Rychak

Lindner

Ley

et al. 2006

Journal of Controlled Release

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116

104

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Ultrasound contrast microbubbles have been successfully targeted to a number of intravascular disease markers. We hypothesized that targeted delivery could be improved further, by making the microbubbles deformable, leading to increased microbubble-endothelium adhesion contact area and stabilized adhesion. Activated leukocytes utilize such strategy; they deform after binding to inflamed endothelium in the vasculature. Lipid-shell microbubbles were targeted to the endothelial inflammatory protein P-selectin with a monoclonal anti-P-selectin antibody attached to the microbubble shell. Deformable microbubbles were created by controlled pressurization with partial gas loss, which generated an average excess shell surface area of ∼30% and the formation of outward-projected wrinkles and folds. Targeted microbubble adhesion and deformability were assessed in the parallel plate flow chamber under shear flow. Sustained adhesion of deformable microbubbles at wall shear stresses between 0.4 and 1.35 dyn/cm 2 was consistently better than adhesion of wrinkle-free microbubbles. Over this shear range, targeted wrinkled microbubbles were deformed by shear flow, unlike wrinkle-free microbubbles. In a murine cremaster inflammation model, a significant improvement of deformable microbubble targeting was observed by intravital microscopy. Overall, the mechanical aspects of adhesion, such as particle shape, deformability and surface microstructure, are important in engineering efficient site-targeted particle-based agents for medical imaging and therapy.

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Microparticle‐ and Nanoparticle‐Based Contrast‐Enhanced Ultrasound Imaging

Deshpande¹,

Willmann²

2011

Nanoplatform‐Based Molecular Imaging

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Ultrasound Imaging of Acute Cardiac Transplant Rejection With Microbubbles Targeted to Intercellular Adhesion Molecule-1

Cited by 240 publications

References 20 publications

Leukocyte-Targeted Myocardial Contrast Echocardiography Can Assess the Degree of Acute Allograft Rejection in a Rat Cardiac Transplantation Model

Leukocyte-Targeted Myocardial Contrast Echocardiography Can Assess the Degree of Acute Allograft Rejection in a Rat Cardiac Transplantation Model

Deformable gas-filled microbubbles targeted to P-selectin

Microparticle‐ and Nanoparticle‐Based Contrast‐Enhanced Ultrasound Imaging

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