Study population
For this single-center observational study, we screened patients who were referred for CMR at the Erasmus Medical Center, Rotterdam, the Netherlands, with proven or suspected ICM or NICM between March 2019 and April 2019. A total of 60 consecutive patients who underwent CMR including LGE images in the context of clinical care were included. No other in- or exclusion criteria were used. According to the institutional review board, this study did not meet the requirements of a study that is subject to the Medical Research Involving Human Subjects Acts.
DL image reconstruction
The vendor-provided DLRecon prototype (GE Healthcare) uses a feed-forward deep convolutional neural network (CNN) that reconstructs images with higher SNR, reduced truncation artifacts, and higher spatial resolution [18]. This network architecture is a residual encoder, variants of which have been demonstrated as effective for highly related tasks, including image denoising, super resolution, and JPEG deblocking [19]. The CNN is integrated inside the standard reconstruction pipeline; accepts raw, unfiltered, complex-valued input images, and desired noise reduction (NR) level; and produces improved output images. The improved images have a noise variance that is reduced by the requested NR level, expressed as a percentage between 0 and 100% to accommodate user preference. NR 100% corresponds to removing of all the predicted noise from the image. The network also recognizes that Gibbs ringing occurs in the vicinity of sharp edges and achieves de-ringing to improve image sharpness. The result is an image with higher SNR and edge sharpness that is nearly free of truncation artifacts. The CNN contains over 4.4 million trainable parameters in over 10,000 kernels. It was trained with a supervised learning approach, using pairs of images representing near-perfect and conventional MRI images. The near-perfect training data consisted of high-resolution images with minimal ringing and very low noise levels. The conventional training data were synthesized from near-perfect images using established methods to create lower resolution versions with more truncation artifacts and with higher noise levels. A diverse set of training images spanning a broad range of image content were employed to enable generalizability of the CNN across all anatomies. Image augmentations, including rotations and flips, intensity gradients, phase manipulations, and additional Gaussian noise, were applied for added robustness, resulting in a training database of 4 million unique image/augmentation combinations. The network was trained with gradient backpropagation via the ADAM optimizer. This DLRecon method is developed for 2-dimensional (2D) anatomical sequences and is compatible with many standard sequences and options, including magnitude LGE short-axis (SA) views, long-axis views, fast single-shot acquisition, and phase-sensitive inversion recovery images.
CMR patient protocol
CMR examinations were performed on a 1.5T whole body clinical MR system (SIGNA Artist, GE Healthcare) with a dedicated anterior array coil, electrocardiographic gating, and breath-hold techniques. The imaging protocol consisted of balanced steady-state free precession cine images and 2D LGE imaging. LGE imaging was performed 10–20 min after intravenous administration of a gadolinium-based contrast agent (0.15 to 0.2 mmol/kg; Gadovist, Bayer Healthcare), using a breath-held 2D-segmented inversion recovery gradient echo pulse sequence with magnitude reconstruction. LGE images were obtained in standard long-axis and SA views, with coverage from base to apex. Typical scan parameters were slice thickness 8 mm, interslice gap 2 mm, TR/TE 6.5/3.0 ms, flip angle 25°, ASSET 1.5, NEX 1, field of view 256–410 × 320–430 mm, acquired matrix 200 × 192, and reconstructed to a pixel size of 1.3–2.1 × 1.1–1.5 mm. If necessary, the preset inversion time was adjusted to null normal myocardium.
LGE images were reconstructed multiple times from the same source data: once using the vendor standard reconstruction, then again using the vendor-supplied DLRecon prototype. For this study, LGE images were reconstructed with a NR level of 25%, 50%, 75%, and 100%.
Phantom scan protocol
Static phantom scans were performed, with the application of tunable NR levels of 25%, 50%, and 75%, to demonstrate the relationship between different NR levels and improvement in SNR. Scans were performed on the same 1.5T MR system with a doped static phantom and 32-channel anterior array coil. A 2D-segmented inversion recovery gradient echo pulse sequence with magnitude reconstruction was used, with an inversion preparation time of 110 ms, emulated heart rate at 100 bpm, and otherwise identical parameters as in the patient study. To quantify NR levels, the data acquisition was repeated with multiple averages from 1 to 16 NEX. Mean SI and SD were measured by taking the average of three circularly drawn regions of interest (ROI) outside the phantom, and SNR was calculated by the quotient of SI and SD, according to IEC standards [20].
CMR analysis
All 2D SA LGE images were analyzed to determine the effect of DLRecon on image quality and LGE quantification. Image quality and myocardial nulling were assessed on standard LGE images and DLRecon images with 75% NR level. These assessments were performed blinded and independently in all 60 patients by two experienced imaging cardiologists (A.H. and C.H.) and one experienced researcher (N.vdV.) using a 5-point Likert scale (1 = poor, 2 = fair, 3 = good, 4 = very good, 5 = excellent). Moreover, the visibility of artifacts (1 = severe image artifacts, 2 = moderate to severe image artifacts, 3 = moderate image artifacts, 4 = mild image artifacts, 5 = no image artifacts) and the presence of hyperenhancement (yes or no) was scored. Also, image sharpness, as a more objective method for image quality, was calculated in standard LGE images as well as in the DLRecon images with NR levels of 25%, 50%, 75%, and 100% using open-source software ImageJ (National Institutes of Health). In each mid ventricular SA slice with the least myocardial trabeculations, a single profile was selected along the septal myocardium (Fig. 1). This profile was copied between the standard LGE images and the DLRecon images. Sharpness was calculated by taking the inverse of the distance between 20 and 80% of the pixel intensity range of the profile [21].
In addition, SNR and contrast-to-noise ratio (CNR) were determined, as criteria for image quality, in patients with hyperenhancement (n = 30). These measurements were performed by drawing ROIs in remote myocardium, hyperenhanced myocardium, and air signal outside the patient. SNR of the scar was measured as mean SI of the hyperenhanced myocardium divided by SD of the air signal outside the patient. CNR between scar and remote myocardium was calculated as (mean SI of hyperenhanced myocardium − mean SI of remote myocardium)/(1.5 × SD of the air signal outside the patient) [5].
In the same subset of patients with hyperenhancement, additional analyses were performed with regard to LGE analysis. Epicardial and endocardial contours (excluding papillary muscles) of the left ventricle (LV) were manually drawn on each slice of the SA LGE images, using dedicated software (QMass software version 8.1, Medis Medical Imaging Systems bv). Subsequently, two regions of interest ROIs, one in hyperenhanced myocardium and one in normal remote myocardium, were drawn automatically in the SA slice where hyperenhancement was visually most pronounced. After visual inspection and manual adjustments if necessary, the contours were copied between standard LGE images and DLRecon images with NR levels of 25%, 50%, 75%, and 100%. Thereafter, hyperenhanced myocardium was automatically quantified as percentage of the LV using different quantification techniques: the thresholding technique with 2SD, 4SD, and 6SD above remote myocardium and the FWHM method [10]. For the manual technique, hyperenhanced myocardium was drawn by visual assessment of each SA slice.
Statistical analysis
All continuous data were tested for normality before analysis using the Kolmogorov-Smirnov test or Shapiro-Wilk test, depending on the number of patients, and were expressed as mean ± SD or median (interquartile range (IQR)), as appropriate. Categorical variables were presented as number (%). Wilcoxon signed-rank tests were used for the comparison of differences in image quality, severity of artifacts, myocardial nulling, and for the comparison of extent of LGE between different quantification techniques. Intraclass correlations (ICC) were used to evaluate the agreement between observers and were interpreted as follows: < 0.2 = poor, 0.21–0.40 = fair, 0.41–0.60 = moderate, 0.61–0.80 = good, and 0.81–1.00 = excellent. Paired t tests were used for the comparison of the image sharpness. For each quantification method, the amount of LGE as percentage of the LV between the standard LGE images and the images with different NR levels was compared by performing the Friedman’s test. If a significant difference was found, a Wilcoxon signed-rank test with Bonferroni correction was performed to determine the exact difference between the standard LGE images and images with varying NR levels. All analyses were two-tailed; after correction for multiple testing, a p < 0.0125 was considered as statistically significant. Statistical analyses were performed using SPSS (version 21, IBM SPSS Statistics, IBM corporation).