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Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic 201Tl Single-Photon Emission Computed Tomography/Computed Tomography Imaging for Evaluation of Early Post-Myocardial Infarction Remodeling.

ABSTRACT: BACKGROUND:The induction of matrix metalloproteinases (MMPs) and reduction in tissue inhibitors of MMPs (TIMPs) plays a role in ischemia/reperfusion (I/R) injury post-myocardial infarction (MI) and subsequent left ventricular remodeling. We developed a hybrid dual isotope single-photon emission computed tomography/computed tomography approach for noninvasive evaluation of regional myocardial MMP activation with 99mTc-RP805 and dynamic 201Tl for determination of myocardial blood flow, to quantify the effects of intracoronary delivery of recombinant TIMP-3 (rTIMP-3) on I/R injury. METHODS:Studies were performed in control pigs (n=5) and pigs following 90-minute balloon occlusion-induced ischemia/reperfusion (I/R) of left anterior descending artery (n=9). Before reperfusion, pigs with I/R were randomly assigned to intracoronary infusion of rTIMP-3 (1.0 mg/kg; n=5) or saline (n=4). Three days post-I/R, dual isotope imaging was performed with 99mTc-RP805 and 201Tl along with contrast cineCT to assess left ventricular function. RESULTS:The ischemic to nonischemic ratio of 99mTc-RP805 was significantly increased following I/R in saline group (4.03±1.40), and this ratio was significantly reduced with rTIMP-3 treatment (2.22±0.57; P=0.03). This reduction in MMP activity in the MI-rTIMP-3 treatment group was associated with an improvement in relative MI region myocardial blood flow compared with the MI-saline group and improved myocardial strain in the MI region. CONCLUSIONS:We have established a novel hybrid single-photon emission computed tomography/computed tomography imaging approach for the quantitative assessment of regional MMP activation, myocardial blood flow, and cardiac function post-I/R that can be used to evaluate therapeutic interventions such as intracoronary delivery of rTIMP-3 for reduction of I/R injury in the early phases of post-MI remodeling.

SUBMITTER: Thorn SL

PROVIDER: S-EPMC7250243 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic <sup>201</sup>Tl Single-Photon Emission Computed Tomography/Computed Tomography Imaging for Evaluation of Early Post-Myocardial Infarction Remodeling.

Thorn Stephanie L SL Barlow Shayne C SC Feher Attila A Stacy Mitchel R MR Doviak Heather H Jacobs Julia J Zellars Kia K Renaud Jennifer M JM Klein Ran R deKemp Robert A RA Khakoo Aarif Y AY Lee TaeWeon T Spinale Francis G FG Sinusas Albert J AJ

Circulation. Cardiovascular imaging 20191111 11

<h4>Background</h4>The induction of matrix metalloproteinases (MMPs) and reduction in tissue inhibitors of MMPs (TIMPs) plays a role in ischemia/reperfusion (I/R) injury post-myocardial infarction (MI) and subsequent left ventricular remodeling. We developed a hybrid dual isotope single-photon emission computed tomography/computed tomography approach for noninvasive evaluation of regional myocardial MMP activation with <sup>99m</sup>Tc-RP805 and dynamic <sup>201</sup>Tl for determination of myoc ...[more]

PMID: 31707811

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Project description:We present the attenuated spline reconstruction technique (aSRT) which provides an innovative algorithm for single photon emission computed tomography (SPECT) image reconstruction. aSRT is based on an analytic formula of the inverse attenuated Radon transform. It involves the computation of the Hilbert transforms of the linear attenuation function and of two sinusoidal functions of the so-called attenuated sinogram These computations are achieved by employing the attenuation information provided by computed tomography (CT) scans and by utilizing custom-made cubic spline interpolation. The purpose of this work is: (i) to present the mathematics of aSRT, (ii) to reconstruct simulated and real SPECT/CT data using aSRT and (iii) to evaluate aSRT by comparing it to filtered backprojection (FBP) and to ordered subsets expectation minimization (OSEM) reconstruction algorithms. Simulation studies were performed by using an image quality phantom and an appropriate attenuation map. Reconstructed images were generated for 45, 90 and 180 views over 360 degrees with 20 realizations and involved Poisson noise of three different levels (NL), namely 100% (NL1), 50% (NL2) and 10% (NL3) of the total counts, respectively. Moreover, real attenuated SPECT sinograms were reconstructed from a real study of a Jaszczak phantom, as well as from a real clinical myocardial SPECT/CT study. Comparisons between aSRT, FBP and OSEM reconstructions were performed using contrast, bias and image roughness. The results suggest that aSRT can efficiently produce accurate attenuation-corrected reconstructions for simulated and real phantoms, as well as for clinical data. In particular, in the case of the clinical myocardial study, aSRT produced reconstructions with higher cold contrast than both FBP and OSEM. aSRT, by incorporating the attenuation correction within itself, may provide an improved alternative to FBP. This is particularly promising for 'cold' regions as those occurring in myocardial ischaemia.

Dataset Information

Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic 201Tl Single-Photon Emission Computed Tomography/Computed Tomography Imaging for Evaluation of Early Post-Myocardial Infarction Remodeling.

Publications

Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic <sup>201</sup>Tl Single-Photon Emission Computed Tomography/Computed Tomography Imaging for Evaluation of Early Post-Myocardial Infarction Remodeling.

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