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Assessment of Myocardial Fibrosis in Mice Using a T2*-Weighted 3D Radial Magnetic Resonance Imaging Sequence.

van Nierop BJ, Bax NA, Nelissen JL, Arslan F, Motaal AG, de Graaf L, Zwanenburg JJ, Luijten PR, Nicolay K, Strijkers GJ - PLoS ONE (2015)

Bottom Line: Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts.However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue.

View Article: PubMed Central - PubMed

Affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

ABSTRACT

Background: Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.

Objective: To goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart.

Methods: C57BL/6 mice were studied with MI (n = 20, replacement fibrosis), transverse aortic constriction (TAC) (n = 18, diffuse fibrosis), and as control (n = 10). 3D center-out radial T2*-weighted images with varying TE were acquired in vivo and ex vivo (TE = 21 μs-4 ms). Ex vivo T2*-weighted signal decay with TE was analyzed using a 3-component model. Subtraction of short- and long-TE images was used to highlight fibrotic tissue with short T2*. The presence of fibrosis was validated using histology and correlated to MRI findings.

Results: Detailed ex vivo T2*-weighted signal analysis revealed a fast (T2*fast), slow (T2*slow) and lipid (T2*lipid) pool. T2*fast remained essentially constant. Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts. T2*slow correlated with the presence of diffuse fibrosis in TAC hearts (r = 0.82, P = 0.01). Ex vivo and in vivo subtraction images depicted a positive contrast in the infarct co-localizing with the scar. Infarct volumes from histology and subtraction images linearly correlated (r = 0.94, P<0.001). Region-of-interest analysis in the in vivo post-MI and TAC hearts revealed significant T2* shortening due to fibrosis, in agreement with the ex vivo results. However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue.

No MeSH data available.


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Relative infarct size determined from histology compared to MRI.(A) Long axis cross sections through ex vivo ΔUTE images in post-MI mouse hearts obtained from subtraction of a long-TE (4 ms) from a short-TE (21 μs) T2*-weighted image. The left panels show a post-MI heart 2 days after surgery. The right panels show a post-MI heart with a chronic MI 7 days after surgery. A positive contrast is observed in the ΔUTE image, which corresponds to the location of the chronic MI. Corresponding Picrosirius red stained slices showed hardly any collagen in the MI heart 2 days after surgery, whereas excessive replacement fibrosis was present (arrows) in the chronic MI. (B) Correlation between the infarct size as percentage of the total heart volume determined from histology and the ex vivo ΔUTE images of control (n = 3) and MI hearts (n = 8). The solid line is a linear fit.
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pone.0129899.g002: Relative infarct size determined from histology compared to MRI.(A) Long axis cross sections through ex vivo ΔUTE images in post-MI mouse hearts obtained from subtraction of a long-TE (4 ms) from a short-TE (21 μs) T2*-weighted image. The left panels show a post-MI heart 2 days after surgery. The right panels show a post-MI heart with a chronic MI 7 days after surgery. A positive contrast is observed in the ΔUTE image, which corresponds to the location of the chronic MI. Corresponding Picrosirius red stained slices showed hardly any collagen in the MI heart 2 days after surgery, whereas excessive replacement fibrosis was present (arrows) in the chronic MI. (B) Correlation between the infarct size as percentage of the total heart volume determined from histology and the ex vivo ΔUTE images of control (n = 3) and MI hearts (n = 8). The solid line is a linear fit.

Mentions: Having established that the most prominent signal difference between infarct and remote tissue concerns the T2*slow, we exploited this finding to obtain image contrast on long- and short-TE subtraction images (referred to as ΔUTE images), which is a common approach to improve contrast and suppress background signal. A representative ex vivo ΔUTE image of a chronic post-MI heart with a considerable fibrotic scar in the apical region is shown in Fig 2A. The image is shown next to a MI heart 2 days after surgery with substantial wall thinning but without a collagenous scar. A clear hyperenhancement in the ΔUTE image was observed in the apex of the chronic post-MI heart, which co-localized with the area of fibrous scarring observed by histology. The relative infarct volume (% of the whole heart volume) as determined from the ΔUTE images correlated linearly with infarct volume from histology (r = 0.94, P<0.001) (Fig 2B). T2* is often associated with the presence of iron in tissue. However, hardly any iron was visible on Prussian blue stained tissue sections (S4 Fig), ruling out iron as the source of T2* decrease.


Assessment of Myocardial Fibrosis in Mice Using a T2*-Weighted 3D Radial Magnetic Resonance Imaging Sequence.

van Nierop BJ, Bax NA, Nelissen JL, Arslan F, Motaal AG, de Graaf L, Zwanenburg JJ, Luijten PR, Nicolay K, Strijkers GJ - PLoS ONE (2015)

Relative infarct size determined from histology compared to MRI.(A) Long axis cross sections through ex vivo ΔUTE images in post-MI mouse hearts obtained from subtraction of a long-TE (4 ms) from a short-TE (21 μs) T2*-weighted image. The left panels show a post-MI heart 2 days after surgery. The right panels show a post-MI heart with a chronic MI 7 days after surgery. A positive contrast is observed in the ΔUTE image, which corresponds to the location of the chronic MI. Corresponding Picrosirius red stained slices showed hardly any collagen in the MI heart 2 days after surgery, whereas excessive replacement fibrosis was present (arrows) in the chronic MI. (B) Correlation between the infarct size as percentage of the total heart volume determined from histology and the ex vivo ΔUTE images of control (n = 3) and MI hearts (n = 8). The solid line is a linear fit.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4482648&req=5

pone.0129899.g002: Relative infarct size determined from histology compared to MRI.(A) Long axis cross sections through ex vivo ΔUTE images in post-MI mouse hearts obtained from subtraction of a long-TE (4 ms) from a short-TE (21 μs) T2*-weighted image. The left panels show a post-MI heart 2 days after surgery. The right panels show a post-MI heart with a chronic MI 7 days after surgery. A positive contrast is observed in the ΔUTE image, which corresponds to the location of the chronic MI. Corresponding Picrosirius red stained slices showed hardly any collagen in the MI heart 2 days after surgery, whereas excessive replacement fibrosis was present (arrows) in the chronic MI. (B) Correlation between the infarct size as percentage of the total heart volume determined from histology and the ex vivo ΔUTE images of control (n = 3) and MI hearts (n = 8). The solid line is a linear fit.
Mentions: Having established that the most prominent signal difference between infarct and remote tissue concerns the T2*slow, we exploited this finding to obtain image contrast on long- and short-TE subtraction images (referred to as ΔUTE images), which is a common approach to improve contrast and suppress background signal. A representative ex vivo ΔUTE image of a chronic post-MI heart with a considerable fibrotic scar in the apical region is shown in Fig 2A. The image is shown next to a MI heart 2 days after surgery with substantial wall thinning but without a collagenous scar. A clear hyperenhancement in the ΔUTE image was observed in the apex of the chronic post-MI heart, which co-localized with the area of fibrous scarring observed by histology. The relative infarct volume (% of the whole heart volume) as determined from the ΔUTE images correlated linearly with infarct volume from histology (r = 0.94, P<0.001) (Fig 2B). T2* is often associated with the presence of iron in tissue. However, hardly any iron was visible on Prussian blue stained tissue sections (S4 Fig), ruling out iron as the source of T2* decrease.

Bottom Line: Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts.However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue.

View Article: PubMed Central - PubMed

Affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

ABSTRACT

Background: Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.

Objective: To goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart.

Methods: C57BL/6 mice were studied with MI (n = 20, replacement fibrosis), transverse aortic constriction (TAC) (n = 18, diffuse fibrosis), and as control (n = 10). 3D center-out radial T2*-weighted images with varying TE were acquired in vivo and ex vivo (TE = 21 μs-4 ms). Ex vivo T2*-weighted signal decay with TE was analyzed using a 3-component model. Subtraction of short- and long-TE images was used to highlight fibrotic tissue with short T2*. The presence of fibrosis was validated using histology and correlated to MRI findings.

Results: Detailed ex vivo T2*-weighted signal analysis revealed a fast (T2*fast), slow (T2*slow) and lipid (T2*lipid) pool. T2*fast remained essentially constant. Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts. T2*slow correlated with the presence of diffuse fibrosis in TAC hearts (r = 0.82, P = 0.01). Ex vivo and in vivo subtraction images depicted a positive contrast in the infarct co-localizing with the scar. Infarct volumes from histology and subtraction images linearly correlated (r = 0.94, P<0.001). Region-of-interest analysis in the in vivo post-MI and TAC hearts revealed significant T2* shortening due to fibrosis, in agreement with the ex vivo results. However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue.

No MeSH data available.


Related in: MedlinePlus