Interventional magnetic resonance imaging for guiding gene and cell transfer in the heart

Abstract

Background: Interventional magnetic resonance imaging (iMRI) has the potential for guiding interventional cardiac procedures in real time.

Objectives: To test the feasibility of iMRI guided gene and cell transfer to the heart and to monitor myocardial remodelling after myocardial infarction in a rat model.

Methods: The MRI contrast agent GdDTPA, together with either Evans blue dye, or a recombinant adenovirus encoding the LacZ gene, or primary fibroblasts tagged by BrdU, were injected into the myocardium of rats under iMRI guidance. Rats were killed seven days after the injection and the hearts sectioned to identify the blue dye, LacZ expression, or fibroblast presence, respectively. In a parallel study, left ventricular area was measured before and after myocardial infarction and in sham operated rats by T1 weighted MRI and by echocardiography.

Results: Location of GdDTPA enhancement observed with iMRI at the time of injection was correlated with Evans blue stain, beta-gal expression, and the primary fibroblast location in histological studies. iMRI and echocardiography measured a comparable increase in left ventricular area at seven and 30 days after myocardial infarction. A good correlation was found between the iMRI and echocardiographic assessment of left ventricular area (r = 0.70; p < 0.0001) and change in left ventricular area with time (r = 0.75; p < 0.0001).

Conclusions: The results show the feasibility and efficiency of iMRI guided intramyocardial injections, and the ability to monitor heart remodelling using iMRI. Genes, proteins, or cells for tissue engineering could be injected accurately into the myocardial scar under iMRI guidance.

Figure 1

Intramyocardial injection guided by interventional magnetic resonance imaging (iMRI). Panels (A) and (C) show the location of the leading edge of the needle at the anterior wall of the left ventricle (LV). The left ventricle looks like a bagel. Panels (B) and (D) show GdDTPA related enhancement in the location of the injections. T, thorax.

Figure 2

Macroscopic view of heart injected by methylene blue dye with real time interventional magnetic resonance imaging (iMRI). (A) The site of GdDTPA related enhancement in anterior wall of the heart. (B) The actual location of the injection at the anterior wall of the heart, as indicated with the methylene blue dye in transverse histological sections of the heart.

Figure 3

Microscopic views of transgene expression in the myocardium of a rat heart treated by injection of recombinant adenovirus encoding the LacZ marker gene guided by magnetic resonance imaging. There is robust transgene expression in the myocardium.

Figure 4

Histological slides of hearts injected with primary fibroblasts tagged with BrdU. The implanted cells are positively brown stained (arrows).

Figure 5

Left ventricular area assessment following myocardial infarction. (A) Left ventricular area assessed by magnetic resonance (MR) imaging. The increase in left ventricular area was by a factor of 1.4 (0.3) at seven days and 1.9 (0.9) at 30 days after the infarction (p  =  0.0002). (B) MR image of left ventricular area before myocardial infarction. (C) Left ventricular area seven days after the infarction. (D) Left ventricular area 30 days after the infarction. (E) Echocardiographic image of the left ventricular area 30 days after the infarction. Note the resolution as compared with the MR image in (D). (F) Pathological transverse sections of the heart 30 days after infarction.

Figure 6

Correlation between interventional magnetic resonance imaging (iMRI) and echocardiography. (A) Correlation in the assessment of the left ventricular area (cm²) (y = 1.044x+0.0248). (B) Correlation in the assessment of the change in the left ventricular area up to 30 day follow up (y = 0.7485x+0.3326).