Self-gated, dynamic contrast-enhanced magnetic resonance imaging with compressed-sensing reconstruction for evaluating endothelial permeability in the aortic root of atherosclerotic mice.

High-risk atherosclerotic plaques are characterized by active inflammation and abundant leaky microvessels. We present a self-gated, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquisition with compressed sensing reconstruction and apply it to assess longitudinal changes in endothelial permeability in the aortic root of Apoe-/- atherosclerotic mice during natural disease progression. Twenty-four, 8-week-old, female Apoe-/- mice were divided into four groups (n = 6 each) and imaged with self-gated DCE-MRI at 4, 8, 12, and 16 weeks after high-fat diet initiation, and then euthanized for CD68 immunohistochemistry for macrophages. Eight additional mice were kept on a high-fat diet and imaged longitudinally at the same time points. Aortic-root pseudo-concentration curves were analyzed using a validated piecewise linear model. Contrast agent wash-in and washout slopes (b1 and b2 ) were measured as surrogates of aortic root endothelial permeability and compared with macrophage density by immunohistochemistry. b2 , indicating contrast agent washout, was significantly higher in mice kept on an high-fat diet for longer periods of time (p = 0.03). Group comparison revealed significant differences between mice on a high-fat diet for 4 versus 16 weeks (p = 0.03). Macrophage density also significantly increased with diet duration (p = 0.009). Spearman correlation between b2 from DCE-MRI and macrophage density indicated a weak relationship between the two parameters (r = 0.28, p = 0.20). Validated piecewise linear modeling of the DCE-MRI data showed that the aortic root contrast agent washout rate is significantly different during disease progression. Further development of this technique from a single-slice to a 3D acquisition may enable better investigation of the relationship between in vivo imaging of endothelial permeability and atherosclerotic plaques' genetic, molecular, and cellular makeup in this important model of disease.

Regional assessment of carotid artery pulse wave velocity using compressed sensing accelerated high temporal resolution 2D CINE phase contrast cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) allows for non-invasive assessment of arterial stiffness by means of measuring pulse wave velocity (PWV). PWV can be calculated from the time shift between two time-resolved flow curves acquired at two locations within an arterial segment. These flow curves can be derived from two-dimensional CINE phase contrast CMR (2D CINE PC CMR). While CMR-derived PWV measurements have proven to be accurate for the aorta, this is more challenging for smaller arteries such as the carotids due to the need for both high spatial and temporal resolution. In this work, we present a novel method that combines retrospectively gated 2D CINE PC CMR, high temporal binning of data and compressed sensing (CS) reconstruction to accomplish a temporal resolution of 4 ms. This enables accurate flow measurements and assessment of PWV in regional carotid artery segments. METHODS: Retrospectively gated 2D CINE PC CMR data acquired in the carotid artery was binned into cardiac frames of 4 ms length, resulting in an incoherently undersampled ky-t-space with a mean undersampling factor of 5. The images were reconstructed by a non-linear CS reconstruction using total variation over time as a sparsifying transform. PWV values were calculated from flow curves by using foot-to-foot and cross-correlation methods. Our method was validated against ultrasound measurements in a flow phantom setup representing the carotid artery. Additionally, PWV values of two groups of 23 young (30 ± 3 years, 12 [52%] women) and 10 elderly (62 ± 10 years, 5 [50%] women) healthy subjects were compared using the Wilcoxon rank-sum test. RESULTS: Our proposed method produced very similar flow curves as those measured using ultrasound at 1 ms temporal resolution. Reliable PWV estimation proved possible for transit times down to 7.5 ms. Furthermore, significant differences in PWV values between healthy young and elderly subjects were found (4.7 ± 1.0 m/s and 7.9 ± 2.4 m/s, respectively; p < 0.001) in accordance with literature. CONCLUSIONS: Retrospectively gated 2D CINE PC CMR with CS allows for high spatiotemporal resolution flow measurements and accurate regional carotid artery PWV calculations. We foresee this technique will be valuable in protocols investigating early development of carotid atherosclerosis.

High frame rate retrospectively triggered Cine MRI for assessment of murine diastolic function.

To assess left ventricular (LV) diastolic function in mice with Cine MRI, a high frame rate (>60 frames per cardiac cycle) is required. For conventional electrocardiography-triggered Cine MRI, the frame rate is inversely proportional to the pulse repetition time (TR). However, TR cannot be lowered at will to increase the frame rate because of gradient hardware, spatial resolution, and signal-to-noise limitations. To overcome these limitations associated with electrocardiography-triggered Cine MRI, in this paper, we introduce a retrospectively triggered Cine MRI protocol capable of producing high-resolution high frame rate Cine MRI of the mouse heart for addressing left ventricular diastolic function. Simulations were performed to investigate the influence of MRI sequence parameters and the k-space filling trajectory in relation to the desired number of frames per cardiac cycle. An optimized protocol was applied in vivo and compared with electrocardiography-triggered Cine for which a high-frame rate could only be achieved by several interleaved acquisitions. Retrospective high frame rate Cine MRI proved superior to the interleaved electrocardiography-triggered protocols. High spatial-resolution Cine movies with frames rates up to 80 frames per cardiac cycle were obtained in 25 min. Analysis of left ventricular filling rate curves allowed accurate determination of early and late filling rates and revealed subtle impairments in left ventricular diastolic function of diabetic mice in comparison with nondiabetic mice.

Accelerated high-frame-rate mouse heart cine-MRI using compressed sensing reconstruction.

We introduce a new protocol to obtain very high-frame-rate cinematographic (Cine) MRI movies of the beating mouse heart within a reasonable measurement time. The method is based on a self-gated accelerated fast low-angle shot (FLASH) acquisition and compressed sensing reconstruction. Key to our approach is that we exploit the stochastic nature of the retrospective triggering acquisition scheme to produce an undersampled and random k-t space filling that allows for compressed sensing reconstruction and acceleration. As a standard, a self-gated FLASH sequence with a total acquisition time of 10 min was used to produce single-slice Cine movies of seven mouse hearts with 90 frames per cardiac cycle. Two times (2×) and three times (3×) k-t space undersampled Cine movies were produced from 2.5- and 1.5-min data acquisitions, respectively. The accelerated 90-frame Cine movies of mouse hearts were successfully reconstructed with a compressed sensing algorithm. The movies had high image quality and the undersampling artifacts were effectively removed. Left ventricular functional parameters, i.e. end-systolic and end-diastolic lumen surface areas and early-to-late filling rate ratio as a parameter to evaluate diastolic function, derived from the standard and accelerated Cine movies, were nearly identical.

Functional imaging of murine hearts using accelerated self-gated UTE cine MRI.

We introduce a fast protocol for ultra-short echo time (UTE) Cine magnetic resonance imaging (MRI) of the beating murine heart. The sequence involves a self-gated UTE with golden-angle radial acquisition and compressed sensing reconstruction. The self-gated acquisition is performed asynchronously with the heartbeat, resulting in a randomly undersampled kt-space that facilitates compressed sensing reconstruction. The sequence was tested in 4 healthy rats and 4 rats with chronic myocardial infarction, approximately 2 months after surgery. As a control, a non-accelerated self-gated multi-slice FLASH sequence with an echo time (TE) of 2.76 ms, 4.5 signal averages, a matrix of 192 × 192, and an acquisition time of 2 min 34 s per slice was used to obtain Cine MRI with 15 frames per heartbeat. Non-accelerated UTE MRI was performed with TE = 0.29 ms, a reconstruction matrix of 192 × 192, and an acquisition time of 3 min 47 s per slice for 3.5 averages. Accelerated imaging with 2×, 4× and 5× undersampled kt-space data was performed with 1 min, 30 and 15 s acquisitions, respectively. UTE Cine images up to 5× undersampled kt-space data could be successfully reconstructed using a compressed sensing algorithm. In contrast to the FLASH Cine images, flow artifacts in the UTE images were nearly absent due to the short echo time, simplifying segmentation of the left ventricular (LV) lumen. LV functional parameters derived from the control and the accelerated Cine movies were statistically identical.

Small animal cardiovascular MR imaging and spectroscopy.

The use of MR imaging and spectroscopy for studying cardiovascular disease processes in small animals has increased tremendously over the past decade. This is the result of the remarkable advances in MR technologies and the increased availability of genetically modified mice. MR techniques provide a window on the entire timeline of cardiovascular disease development, ranging from subtle early changes in myocardial metabolism that often mark disease onset to severe myocardial dysfunction associated with end-stage heart failure. MR imaging and spectroscopy techniques play an important role in basic cardiovascular research and in cardiovascular disease diagnosis and therapy follow-up. This is due to the broad range of functional, structural and metabolic parameters that can be quantified by MR under in vivo conditions non-invasively. This review describes the spectrum of MR techniques that are employed in small animal cardiovascular disease research and how the technological challenges resulting from the small dimensions of heart and blood vessels as well as high heart and respiratory rates, particularly in mice, are tackled.

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

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.