One option being investigated by researchers in Canada is the use of late gadolinium enhancement (LGE) and diffusion-weighted (DWI) MRI techniques. Writing in Physics in Medicine and Biology, the team presents a combined MRI-histopathological study to examine the fine remodelling features of chronic infarction in a pre-clinical swine model (Phys. Med. Biol. 58 5009).

"The pre-clinical swine model that we used mimics the chronic infarction in humans; therefore, we are confident that our results will translate to human studies," Mihaela Pop from the University of Toronto told medicalphysicsweb. "Our broad aim was to better understand the relationship between tissue heterogeneities in chronic infarction and MR signal."

Post-infarction changes

Following an acute infarction, collagen deposition forms part of a prolonged ventricular remodelling process. However, even after just four weeks, the myocardial architecture in the scar will have altered significantly, with mature fibrosis replacing necrotic myocytes.

"The deposition of fibrosis is due to a continuous collagen turnover – a degradation that is a key feature in characterizing hearts with structural damage of ischaemic origin," explained Pop. "We wanted to generate parametric maps of fibrosis from high-resolution LGE and DWI and confirm tissue categorization using histology. Ultimately, we would like to understand the structural characteristics of potentially arrhythmogenic substrates."

Combining MRI and histology

Pop and her colleagues used five juvenile swine and induced myocardial infarction in the animals percutaneously. In all cases, the scar was allowed to heal for between five and six weeks. Then, 15 minutes prior to sacrifice, each animal was injected with the MR contrast agent Gd-DTPA, and LGE studies were completed within two hours of the heart's explantation. DWI studies were carried out between three and four days later.

Following the DWI measurements, slabs of 5 mm thickness were produced from each heart; thin 4 µm slices were cut from the surfaces of each slab and stained with haematoxylin and eosin, as well as picrosirius red. The authors then defined three grades of fibrosis for their histology images: below 20% fibrosis for normal healthy tissue; 20– 70% fibrosis for border zone (BZ); and above 70% fibrosis for dense scar. Likewise, in the MR images, tissue heterogeneities were categorized by a Gaussian mixture model into healthy, BZ and scar.

The group reports that both MRI methods were capable of qualitatively distinguishing sharp edges between dense scar and healthy tissue from regions of heterogeneous BZ. In addition, they noted that the BZ and dense scar areas had intermediate-to-high increased values of signal intensity in the LGE images and of apparent diffusion coefficient in the DWI.

"We found that the extent of the BZ and fibrotic scar, as well as the edge demarcation between healthy tissue and scar, can be determined by both MRI methods with no statistically significant differences," said Pop. "The identification of tissue categories in LGE and DWI led to good correlation compared to histological grades of fibrosis. We believe that MR imaging represents an important tool for non-invasive detection of BZ, where potential arrhythmia substrates reside."

The team now plans to apply these findings to help with better MR data interpretation in vivo. "Future work will focus on characterizing post-infarction remodelling using in vivo MRI methods histopathology and electrophysiology studies to confirm the relation of BZ and dense scar to actual electrical measurements," said Pop.

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