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3D whole-heart isotropic sub-millimeter resolution coronary magnetic resonance angiography with non-rigid motion-compensated PROST
Aurélien Bustin ORCID: orcid.org/0000-0002-2845-86171,
Imran Rashid1,
Gastao Cruz1,
Reza Hajhosseiny1,2,
Teresa Correia1,
Radhouene Neji1,3,
Ronak Rajani1,4,
Tevfik F. Ismail1,
René M. Botnar1,5 &
Claudia Prieto1,5
To enable free-breathing whole-heart sub-millimeter resolution coronary magnetic resonance angiography (CMRA) in a clinically feasible scan time by combining low-rank patch-based undersampled reconstruction (3D-PROST) with a highly accelerated non-rigid motion correction framework.
Non-rigid motion corrected CMRA combined with 2D image-based navigators has been previously proposed to enable 100% respiratory scan efficiency in modestly undersampled acquisitions. Achieving sub-millimeter isotropic resolution with such techniques still requires prohibitively long acquisition times. We propose to combine 3D-PROST reconstruction with a highly accelerated non-rigid motion correction framework to achieve sub-millimeter resolution CMRA in less than 10 min. Ten healthy subjects and eight patients with suspected coronary artery disease underwent 4–5-fold accelerated free-breathing whole-heart CMRA with 0.9 mm3 isotropic resolution. Vessel sharpness, vessel length and image quality obtained with the proposed non-rigid (NR) PROST approach were compared against translational correction only (TC-PROST) and a previously proposed NR motion-compensated technique (non-rigid SENSE) in healthy subjects. For the patient study, image quality scoring and visual comparison with coronary computed tomography angiography (CCTA) were performed.
Average scan times [min:s] were 6:01 ± 0:59 (healthy subjects) and 8:29 ± 1:41 (patients). In healthy subjects, vessel sharpness of the left anterior descending (LAD) and right (RCA) coronary arteries were improved with the proposed non-rigid PROST (LAD: 51.2 ± 8.8%, RCA: 61.2 ± 9.1%) in comparison to TC-PROST (LAD: 43.8 ± 5.1%, P = 0.051, RCA: 54.3 ± 8.3%, P = 0.218) and non-rigid SENSE (LAD: 46.1 ± 5.8%, P = 0.223, RCA: 56.7 ± 9.6%, P = 0.50), although differences were not statistically significant. The average visual image quality score was significantly higher for NR-PROST (LAD: 3.2 ± 0.6, RCA: 3.3 ± 0.7) compared with TC-PROST (LAD: 2.1 ± 0.6, P = 0.018, RCA: 2.0 ± 0.7, P = 0.014) and non-rigid SENSE (LAD: 2.3 ± 0.5, P = 0.008, RCA: 2.5 ± 0.7, P = 0.016). In patients, the proposed approach showed good delineation of the coronaries, in agreement with CCTA, with image quality scores and vessel sharpness similar to that of healthy subjects.
We demonstrate the feasibility of combining high undersampling factors with non-rigid motion-compensated reconstruction to obtain high-quality sub-millimeter isotropic CMRA images in ~ 8 min. Validation in a larger cohort of patients with coronary artery disease is now warranted.
Three-dimensional (3D) whole-heart coronary magnetic resonance angiography (CMRA) has shown potential for the non-invasive diagnosis of coronary artery disease (CAD) without radiation exposure [1, 2]. However, CMRA still requires long scan times to achieve whole-heart coverage and sub-millimeter isotropic spatial resolution. Moreover, scan time is highly unpredictable due to the need of dealing with respiratory motion. Therefore, enabling free-breathing whole-heart sub-millimeter isotropic resolution CMRA in a short and predictable scan time by combining advanced motion correction and reconstruction techniques with a highly undersampled acquisition would be a major advance.
Conventional CMRA relies on a 1D diaphragmatic navigator [3, 4] to minimize respiratory motion by acquiring data only within a pre-defined small gating window and using a fixed correction factor of 0.6 [5]. This approach however requires a model to relate the motion of the diaphragm with the motion of the heart [6, 7] and a broad deviation in optimal correction factors can be found between subjects [8]. Furthermore, it leads to low respiratory scan efficiency and unpredictable scan times, since rejected data needs to be re-acquired. Self-navigation has been proposed to estimate the 1D foot-head [9,10,11] and 3D [12] translational motion of the heart from the data itself and has been used to enable 100% respiratory scan efficiency. However, since this approach does not account for the complex motion of the heart, residual motion artefacts may affect image quality. Moreover, due to the projection nature of the 1D self-navigated signal, the presence of static tissue in the field-of-view (FOV) may affect the accuracy of motion estimation. Translational respiratory motion correction using low-resolution two-dimensional (2D) or 3D image-based navigators (iNAVs) has recently been proposed for CMRA [9, 10, 13,14,15,16,17]. With these approaches, the heart can be spatially isolated from surrounding static tissues and 2D/3D translational respiratory motion can be estimated and corrected in a beat-to-beat fashion. To correct for remaining non-rigid (NR) motion, and thus to further improve CMRA image quality, respiratory binning techniques [18,19,20,21] have been employed in concert with iNAV-based translational motion correction and motion-compensated reconstruction [22, 23]. Most of these approaches have been successfully applied to fully sampled or mildly undersampled acquisitions with spatial resolution in the order of 1.2 mm [22,23,24,25], however further modifications are needed to extend these techniques to the higher undersampling factors needed to enable sub-millimeter Cartesian CMRA.
Several approaches have been proposed to accelerate CMRA data acquisition including undersampling reconstruction techniques and the previously mentioned motion correction approaches with 100% respiratory scan efficiency. While parallel imaging reconstruction techniques are conventionally used to reduce the acquisition time in CMRA [26, 27], these techniques are still limited to undersampling factors of 2–3 times. Further acceleration can be achieved using compressed sensing [28] at the expense of potential unnatural image appearance (so called staircasing artefacts) for very high undersampling factors. More recently, undersampled 2D and 3D patch-based reconstruction techniques, that exploit the inherent redundancies of the complex anatomy of the coronary arteries in an effective and efficient low-rank framework, have been proposed for CMRA [28, 29]. Those techniques have been successfully combined with diaphragmatic navigator [30] and 2D iNAV-based translational motion-correction [29] to achieve whole-heart sub-millimeter isotropic resolution CMRA with high image quality in less than 10 min. However, remaining NR respiratory motion may degrade image quality, especially affecting the visualization of distal coronary segments [22].
In this study, we aim to achieve sub-millimeter resolution 3D whole-heart CMRA in a predictable scan time of less than 10 min and accounting for the complex non-rigid respiratory motion of the heart. This is achieved by combining a 3D patch-based low-rank reconstruction (PROST) [29] with the matrix formalism for NR motion correction [22, 31]. This so-called NR-PROST framework is investigated in healthy subjects and a small cohort of patients with suspected coronary artery disease.
In vivo acquisitions were performed on a 1.5 T CMR scanner (Magnetom Aera, Siemens Healthineers, Erlangen, Germany) with a dedicated 32-channel spine coil and an 18-channel body coil. Written informed consent was obtained from all subjects before undergoing CMRA scans and the study was approved by the National Research Ethics Committee. Image reconstructions and coronary analysis were performed offline on a workstation with a 16-core Dual Intel Xeon Processor (2.3 GHz, 256 GB RAM).
Accelerated CMRA acquisition
An accelerated free-breathing 3D whole-heart electrocardiogram (ECG)-triggered, balanced steady-state free precession (bSSFP) sequence with a 3D variable density (VD) spiral-like Cartesian trajectory (VD-CASPR) with golden-angle step was employed as previously proposed [29] (Fig. 1a and Additional file 1). A low-resolution 2D iNAV preceded each spiral-like interleave to allow for 100% scan efficiency, predictable scan time and 2D translational motion correction of the heart on a beat-to-beat basis. The 2D iNAVs were obtained by spatially encoding the startup profiles of the bSSFP sequence [9]. A SPIR (spectral presaturation with inversion recovery) fat saturation pulse with a constant flip angle (FA) of 130° was used to improve coronary depiction and minimize fat-related aliasing artefacts. An adiabatic T2-preparation pulse [32, 33] was played at each heartbeat in order to enhance the contrast between blood and cardiac muscle and avoid the use of extracellular contrast agents.
Schematic overview of the proposed accelerated free-breathing 3D coronary magnetic resonance angiography (CMRA) acquisition with sub-millimeter isotropic resolution, 100% scan efficiency and non-rigid motion-compensated patch-0based low-rank reconstruction (PROST) reconstruction. 1) CMRA acquisition is performed with an undersampled 3D variable density spiral-like Cartesian trajectory with golden angle between spiral-like interleaves (VD-CASPR), preceded by 2D image navigators (iNAV) to allow for 100% scan efficiency and beat-to-beat translational respiratory-induced motion correction of the heart. 2) Foot-head respiratory signal is estimated from the 2D iNAVs and used to assign the acquired data into 5 respiratory bins and translation-corrected respiratory bins. Subsequent reconstruction of each bin is performed using soft-gated SENSE and 3D non-rigid motion fields are then estimated from the 5 reconstructed datasets. 3) The final 3D whole-heart motion-corrected CMRA image is obtained using the proposed 3D patch-based (PROST) non-rigid motion-compensated reconstruction. Abbreviations: CMRA, coronary magnetic resonance angiography; PROST, patch-based undersampled reconstruction; ADMM, alternating direction method of multipliers
Motion correction and image reconstruction
The proposed framework for sub-millimeter free-breathing CMRA consists of 3 different stages that are described in more details hereafter: i) iNAVs-based 2D translational beat-to-beat respiratory motion estimation and correction; ii) respiratory binning and bin-to-bin non-rigid motion estimation; and iii) non-rigid motion-corrected 3D PROST reconstruction. The first two stages have been previously proposed for fully sampled non-rigid motion-corrected SENSE reconstruction [22]. A schematic overview of the proposed framework is shown in Fig. 1.
Beat-to-beat 2D translational motion correction
Beat-to-beat 2D translational motion correction was performed as previously proposed in [22, 23]. Briefly, foot-head (FH) and right-left (RL) translational respiratory motion of the heart was extracted from the iNAVs using a template-matching algorithm with normalized cross-correlation as similarity measure [9]. The reference template was manually selected during scan planning on a region encompassing the subject's heart. The FH respiratory signal was used to sort the acquired data into 5 respiratory states or bins. Intra-bin 2D translational motion correction was performed by correcting the data for each bin to the same respiratory position (taken as the bin center). This correction was implemented by modulating the k-space data with a linear phase shift according to the previously estimated respiratory motion [22].
Bin-to-bin non-rigid motion estimation
Since the acquired 3D CMRA data is accelerated (5-fold), the resulting binned k-spaces are highly accelerated (~ 25-fold). Soft-gating sensitivity encoding reconstruction [22] was employed to reconstruct each respiratory bin. Bin-to-bin 3D non-rigid motion estimation was subsequently performed using spline-based free-form deformation [34], considering the end-expiration bin as the reference image (Fig. 1).
3D patch-based non-rigid motion-compensated reconstruction (NR-PROST)
The estimated 3D non-rigid motion fields are then directly incorporated into a general matrix description reconstruction framework [31, 35]. As opposed to previous CMRA studies where 3D data was acquired fully sampled [22] or with mild acceleration factors [23], our proposed sub-millimeter CMRA framework exploits higher undersampling factors (5-fold) to reach sub 10-min acquisition times for sub-millimeter spatial resolution, leading to noise amplification associated with the ill-posed reconstruction problem.
3D-PROST has recently been proposed to highly accelerate sub-millimeter CMRA imaging with translational motion correction only [29]. 3D-PROST reconstruction exploits the inherent redundancies of the complex 3D anatomy of the coronary arteries on a local (i.e., within a patch) and non-local (i.e., between similar patches within a neighborhood) basis, through an efficient iterative low-rank decomposition and thresholding. The proposed NR-PROST framework combines 3D-PROST with the matrix formalism for non-rigid motion correction, and can be formulated as the following unconstrained optimization:
$$ {\mathcal{L}}_{NR- PROST}\left(X,\mathcal{T},Y\right):= \underset{X,\mathcal{T},Y}{\mathrm{argmin}}\ {\left\Vert EX-K\right\Vert}_F^2+\lambda {\left\Vert \mathcal{T}\right\Vert}_{\ast }+\frac{\mu }{2}{\left\Vert \mathcal{T}-X-\frac{Y}{\mu}\right\Vert}_F^2 $$
$$ E=\sum \limits_{b=1}^{N_{bins}}{A}_b FS{U}_b $$
where X is the non-rigid motion-corrected 3D CMRA volume, K is the 2D translation corrected k-space data, E is the encoding operator composed of: Ab the sampling matrix for bin b, F the 3D Fourier transform, S the coil sensitivities, Ub the estimated 3D non-rigid motion fields for bin b and Nbins the number of respiratory bins. ‖.‖F and ‖.‖∗ denote the Frobenius and nuclear norms respectively, \( \mathcal{T} \) is a self-similarity matrix built on a patch scale (see Optimization 2 below) and Y is the Lagrangian parameter. The positive parameter μ controls the tradeoff between the regularization and the fidelity of the reconstructed motion-corrected 3D CMRA image with regard to the acquired data, whereas λ controls the denoising level.
Similar to [29, 36], Eq. (1) can be efficiently solved by operator-splitting via alternating direction method of multipliers (ADMM), which divides the optimization process into three iterative simpler sub-problems:
Optimization on X: non-rigid motion-compensated reconstruction
The first optimization is a motion-compensated reconstruction that incorporates the dealiased/denoised 3D volume \( \mathcal{T} \) obtained at the end of optimization 2 as prior information:
$$ {\mathcal{L}}_{NR}(X):= \underset{X}{\mathrm{argmin}}\ {\left\Vert EX-K\right\Vert}_F^2+\frac{\mu }{2}{\left\Vert \mathcal{T}-X-\frac{Y}{\mu}\right\Vert}_F^2 $$
The above optimization reduces to a regularized non-rigid SENSE reconstruction where an a priori guess (\( {X}^{\ast }=\mathcal{T}-\frac{Y}{\mu } \)) of the desired solution is incorporated into a Tikhonov-type regularization. This equation can be efficiently solved using the conjugate gradient (CG) algorithm.
Optimization on \( \mathcal{T} \): 3D patch-based denoising
The second optimization is a 3D patch-based dealiasing/denoising applied to the previously reconstructed motion-compensated 3D CMRA volume X. This problem is formulated on a patch scale as:
$$ {\mathcal{L}}_{PROST}\left(\mathcal{T}\right):= \underset{\mathcal{T}}{\mathrm{argmin}\ }\frac{2\lambda }{\mu}\sum \limits_p{\left\Vert {\mathcal{T}}_p\right\Vert}_{\ast }+\sum \limits_p{\left\Vert {\mathcal{T}}_p-{P}_p(X)-\frac{Y_p}{\mu}\right\Vert}_F^2 $$
The details to solve the above equation can be found in [29]. In brief, the operator Pp(.) extracts similar 3D patches from a reference patch centered at pixel p and builds a self-similarity 2D matrix \( {\mathcal{T}}_p \) made by vectorizing and concatenating each similar 3D patch. The high degree of redundancy in \( {\mathcal{T}}_p \) is exploited through low-rank matrix decomposition and singular value thresholding [37]. The truncation of the singular values, controlled by the thresholding parameter λ, acts as a dealiasing/denoising filter by providing a low-rank approximation of the original self-similarity 2D matrix. This procedure is repeated in a sliding window manner for all the pixels in the image and the final 3D volume \( \mathcal{T} \) is obtained after aggregation. The aggregation step consists on positioning each denoised patch back onto the image and performing averaging if patches have been selected multiple times. A video describing the 3D patch-based dealiasing/denoising step for CMRA images is provided in Additional file 2.
Additional file 2 Schematic video of the Optimization 2 involved in the proposed non-rigid motion-compensated NR-PROST reconstruction. In this step, 3D dealiasing/denoising is performed using 3D block-matching, which groups similar 3D patches in the 3D volume, followed by a low-rank decomposition and thresholding of each group. This step is repeated for all the voxels, and the final 3D volume is obtained by aggregating the dealiased/denoised groups. This volume is then used as a prior in the motion-compensated reconstruction (Optimization 1) in order to regularize the reconstruction process.
Lagrangian multiplier Y update
Finally, the Lagrangian multiplier Y is updated by integration of the residual between the reconstructed motion-compensated 3D CMRA image and the dealiased/denoised 3D prior:
$$ Y=Y+X-\mathcal{T} $$
Healthy subject acquisitions
Ten healthy subjects (31 ± 7 years, range 25–52 years; 4 females) underwent CMRA imaging using the proposed approach. Relevant scan parameters included: 3D bSSFP sequence, coronal plane, echo time = 1.6 ms, repetition time = 3.7 ms, bandwidth per pixel = 890 Hz, FOV = 320 × 320 × 86–115 mm3, FA = 90°, T2-preparation duration = 40 ms, SPIR fat-saturation FA = 130°, 0.9 mm3 acquired isotropic resolution (reconstructed resolution 0.6 mm3), acceleration factor of 5x, and 14 linear ramp-up pulses for iNAV. Free-breathing cardiac cine imaging was performed prior to CMRA to determine subject-dependent mid-diastolic trigger delay and acquisition window length.
Patient acquisitions
The feasibility and preliminary clinical performance of the proposed framework was assessed in 8 patients with suspected coronary artery disease (51 ± 7 years; 3 females). Acquisition parameters were the same as described above for the healthy subject cohort. The acceleration factor was adjusted (between 4x and 5x) in order to achieve sub 10-min acquisition time irrespective of the number of slices required to cover the whole-heart. Baseline clinical characteristics of the patients are shown in Table 1. Prior to the CMRA acquisitions, the eight patients underwent a clinically-indicated coronary computed tomography angiography (CCTA) with third generation dual source CT 192 × 2-sections (SOMATOM Force, Siemens Healthineers) which included sublingual glyceryl trinitrate and intravenous beta-blocker (metoprolol). CCTA images were reconstructed to 0.6 mm3 isotropic resolution.
Table 1 Baseline characteristics and sequence-relevant parameters for the patient study (N = 8)
Motion-compensated CMRA reconstruction
Reconstruction parameters for the proposed NR-PROST approach were empirically optimized on several datasets (not reported here) and were maintained for all reconstructions. Similar patches were searched in a 3D window of size 403 voxels. The size of the 3D patches, controlling the degree of structural information within each patch, was set to 53 voxels. The number of selected similar patches was set to 20. The performance of NR-PROST was evaluated by comparing reconstruction quality (not reported here) with several thresholding parameters λ and regularization parameters μ. The chosen parameters were λ = 0.1 and μ = 0.3. A good tradeoff between image quality and computational speed was obtained for 5 outer ADMM iterations, each performing 7 CG iterations for optimization 1. A gain in reconstruction speed can be further obtained by adding a small patch offset when searching for similar patches [38]. An offset of 4 voxels in the three dimensions showed small to no impact on the reconstructed image quality, while the gain in computational speed was substantial. We therefore set this offset to 4 in all reconstructions. The acquired data was also reconstructed with: 1) 3D-PROST and 2D beat-to-beat translational motion correction only [29], referred to as TC-PROST; and 2) non-rigid motion-compensated SENSE (termed NR-SENSE) reconstruction [22], which consists of solving Eq. [3] without prior (i.e., μ = 0). Reconstruction parameters were set to match those of the proposed NR-PROST technique.
All reconstructions were implemented in MATLAB (v7.1, The MathWorks, Natick, Massachusetts, USA). Optimization 2 of NR-PROST was implemented in C using multi-core CPUs and interfacing with MATLAB. Coil sensitivity maps were estimated from the k-space center using the eigenvalue-based approach ESPIRiT [39].
To evaluate the performance of the proposed approach in healthy subjects, each reconstructed CMRA image was reformatted along the left anterior descending (LAD) and right (RCA) coronary arteries using a dedicated software [40]. Vessel sharpness (first 4 cm and full vessel length) and maximum visible vessel length of both coronary arteries were computed. A vessel sharpness of 100% indicates an abrupt change in normalized signal intensity (0 to 1) whereas a sharpness value of 0% implies the absence of an edge. Additionally, two blinded experienced cardiologists (I.R. and T.F.I. with 4 and 10 years of experience, respectively, SCCT accreditation and SCMR level III certification) reviewed in a randomized order the reconstructed images (i.e., NR-PROST, NR-SENSE and TC-PROST) for each subject and evaluated the quality of the CMRA images. For each subject, and both LAD and RCA, the reconstruction techniques were given a rank from worst (score 1) to best (score 3). Additionally, the quality of both LAD and RCA delineations was assessed using a 4-point scoring system where 1: indicates uninterpretable images, 2: poor image quality (blurred edges, noise and residual artefacts), 3: acceptable image quality (LAD/RCA adequately visualized, only mildly blurred edges), 4: excellent image quality with sharply defined coronary borders. In those cases where the two experts disagreed, the images were reviewed again together, and a consensus was made.
Statistical analyses using repeated-measures one-way analysis of variance (ANOVA) with Bonferroni correction for post-hoc comparisons (vessel sharpness and vessel length) and Wilcoxon signed rank test (experts scoring and ranking) were performed to examine whether the values obtained with the three reconstruction techniques were statistically different. All statistical analyses were performed using MATLAB (v7.1, The MathWorks), and statistical significances were defined as two-tailed values of P < 0.05.
For the patient study, the reconstructed 3D CMRA and CCTA images were transferred to a workstation and 3D curved planar reformations were conducted (Horos software, v3.3.4). Vessel sharpness was measured for the first 4 cm of the proximal segments of the LAD and the RCA in the 8 patients for the proposed CMRA approach. Image quality of the reconstructed CMRA images using NR-PROST and breath-held contrast-enhanced CCTA was assessed by the same two blinded experts who assessed the healthy subject data, for both LAD and RCA. The same 4-point scoring system, as described above for the healthy subjects, was used.
Free-breathing whole-heart CMRA was successfully completed in all healthy subjects and patients. Average total reconstruction times were ~ 2 min (TC-PROST), ~ 20 min (NR-SENSE) and ~ 50 min for NR-PROST.
Healthy subject study
The average total scan time for the healthy subject study was 6:01 ± 0:59 [min:s] (range 4:19–7:32), with 100% respiratory scan efficiency. The mean heart rate (in beats per minute [bpm]) and data acquisition window were 58 ± 8 bpm (range 42–68 bpm) and 106 ± 13 ms (range 78–125 ms), respectively. Mean subject-dependent mid-diastolic trigger delay was 697 ms (range 508–963 ms). CMRA images reformatted along the LAD and RCA for 3 representative healthy subjects are shown in Fig. 2. While TC-PROST reconstruction provides high image quality with good visualization of the coronary arteries, correcting for remaining non-rigid motion with NR-SENSE enables improved coronary visualization, particularly of the distal segments, at the cost of some noise amplification. NR-PROST further improves image quality and the delineation of both LAD and RCA (Fig. 2). Clear depiction of the coronary arteries, including distal segments and major branches, can be observed with a comparable image quality between subjects (Additional file 3). Vessel sharpness, defined by the maximum signal intensity change at the vessel edge, was higher with NR-PROST (first 4 cm, LAD: 51.2 ± 8.8%, RCA: 61.2 ± 9.1%) than NR-SENSE (first 4 cm, LAD: 46.1 ± 5.8%, P = 0.223, RCA: 56.7 ± 9.6%, P = 0.50) and TC-PROST (first 4 cm, LAD: 43.8 ± 5.1%, P = 0.051, RCA: 54.3 ± 8.3%, P = 0.218) but showed no statistical significance, as observed in Fig. 3a-b. The same observation applies for the visible vessel length (Fig. 3c) where NR-PROST shows improved depiction of the coronary vessel (full vessel length, LAD: 11.8 ± 3.3 cm, RCA: 12.2 ± 1.6 cm) compared with NR-SENSE (LAD: 11.5 ± 3.5 cm, P = 0.980, RCA: 11.8 ± 1.7 cm, P = 0.91) and TC-PROST (LAD: 9.7 ± 3.5 cm, P = 0.336, RCA: 10.3 ± 2.1 cm, P = 0.71), although differences were not statistically significant. The average visual score (Fig. 3d), as given by the two experts, was significantly higher for NR-PROST (LAD: 3.2 ± 0.6, RCA: 3.3 ± 0.7) compared with NR-SENSE (LAD: 2.3 ± 0.5, P = 0.008, RCA: 2.5 ± 0.7, P = 0.016) and TC-PROST (LAD: 2.1 ± 0.6, P = 0.018, RCA: 2.0 ± 0.7, P = 0.014), ranking NR-PROST as the best reconstruction technique in 80% of the cases for both LAD and RCA visualizations (Fig. 3e).
CMRA images reformatted along the left anterior descending (LAD) and right coronary artery (RCA) for 3 representative healthy subjects. Acquisitions were performed with 0.9 mm3 isotropic resolution and 100% respiratory scan efficiency. 3D CMRA images were obtained using the proposed non-rigid motion-compensated PROST reconstruction (NR-PROST, bottom row), non-rigid motion-compensated SENSE (NR-SENSE, middle row) and translational motion correction only with PROST reconstruction (TC-PROST, top row). Scan times are expressed as min:s
Quantitative and qualitative coronary metrics for sub-millimeter isotropic CMRA images for 10 healthy subjects for translational motion correction only (TC-PROST, black), non-rigid motion-compensated SENSE reconstruction (NR-SENSE, grey) and the proposed non-rigid motion-compensated PROST (NR-PROST, white). Vessel sharpness results are shown for the first 4 cm (a) and the full length (b), and coronary vessel length are depicted in (c). Qualitative visual scores of the LAD and RCA (d) and reconstruction rankings (e) are shown for the three reconstruction techniques. Results are expressed as mean ± standard deviation. Differences with statistical significance are identified by *P < 0.05. The dotted red lines depict the median values. Abbreviations: LAD, left anterior descending artery; RCA, right coronary artery
Patient study
The average total scan time for the patient study was 8:29 ± 1:41 [min:s] (range 4:53–10:07), with 100% respiratory scan efficiency. The mean heart rate and data acquisition window were 60 ± 5 bpm (range 51–66 bpm) and 87 ± 13 ms (range 75–113 ms), respectively. Five out of the 8 patients presented with CAD. The mean time interval between the CCTA and the CMRA acquisitions was 32 days (range 4 to 150 days).
A representative CMRA dataset from a 53-year-old healthy male patient and a 35-year-old male patient with normal coronary arteries are shown in Fig. 4 and Fig. 5, respectively, with the corresponding CCTA images. CMRA with 0.9 mm3 isotropic resolution combined with NR-PROST reconstruction allows for good visualization of the LAD, RCA and left circumflex (LCX) territories from the proximal to the distal segments with good image quality and visual image sharpness. Additional non-contrast whole-heart sub-millimeter isotropic 3D CMRA images in three patients are shown in Additional file 4.
Non-contrast whole-heart sub-millimeter isotropic CMRA images of a 53-year-old male patient with normal coronary arteries (patient 6). Accelerated free-breathing CMRA images reconstructed with non-rigid motion-compensated PROST are shown in the top row, revealing the RCA, LAD, left circumflex (LCX) and first diagonal territories. The 3D CMRA dataset was acquired in 9min48s (heart rate of 51 bpm). The corresponding reformatted images obtained with contrast enhanced CCTA are shown in the bottom row. Left anterior three-dimensional volume-rendered images for both modalities are shown in the right-hand column, showing good delineation of the left and right coronary systems. Abbreviations: CMRA, coronary magnetic resonance angiography; LAD, left anterior descending artery; RCA, right coronary artery; LCX, left circumflex artery; PDA, posterior descending artery; PA, pulmonary artery; Ao, aorta
Non-contrast whole-heart sub-millimeter isotropic CMRA images of a 35-year-old male patient with normal coronary arteries (patient 7). Accelerated free-breathing coronary MR angiography (CMRA) images reconstructed with non-rigid motion-compensated PROST are shown in the top row, revealing the LAD and RCA coronary arteries. The 3D CMRA dataset was acquired in 7 min 58 s (heart rate of 57 bpm). The corresponding reformatted images obtained with contrast-enhanced CT coronary angiography are shown in the bottom row. Three-dimensional volume-rendered images for both imaging modalities are shown in the right-hand column. Abbreviations: LAD, left anterior descending artery; RCA, right coronary artery; LCX, left circumflex artery; LM, left main; Ao, aorta; PA, pulmonary artery
Reformatted non-contrast enhanced CMRA images obtained in a 54-year-old male patient with left and RCA disease are shown in Fig. 6, with the corresponding CCTA images. The CCTA images demonstrate mild (25–49%) disease with calcified plaque within the proximal RCA segment, a severe stenosis (70–90%) with partially calcified plaque within the mid-segment of the RCA, and a minimal (0–24%) disease with calcified plaque in the mid LCX segment. Luminal narrowing of the arteries can be seen on the cross-sectional views at the sites of coronary plaque on the CMRA images (Fig. 6, yellow arrows). Another CMRA dataset obtained in a 52-year-old female patient with left and RCA disease is shown in Fig. 7. The CMRA reformat (Fig. 7a) and corresponding volume rendering (Fig. 7b) reveal a plaque visible in the proximal RCA which is confirmed on the CCTA image. A significant stenosis of the mid segment of the LAD is also observed leading to luminal narrowing of the coronary artery on the CMRA and CCTA images.
Reformatted non-contrast whole-heart sub-millimeter isotropic CMRA (left) and CCTA (right) images along the LCX (top) and RCA (bottom) are shown for a 54-year-old male patient (patient 8). The CMRA dataset was acquired in 9 min with 100% scan efficiency (heart rate of 57 bpm). The CCTA images demonstrate mild (25–49%) disease with a calcified plaque within the proximal RCA and severe disease (70–90%) with a partially calcified plaque in the mid-segment of RCA (red arrows), and minimal (0–24%) disease with calcified plaque in the mid-segment of the LCX. Luminal narrowing is seen on the cross-sectional views at the sites of coronary plaque on the CMRA images (yellow arrows). Abbreviations: CMRA, coronary magnetic resonance angiography; LAD, left anterior descending artery; RCA, right coronary artery; LCX, left circumflex artery; Ao, aorta
CMRA (0.9 mm3 resolution) in a 52-year-old female patient (patient 1) with coronary artery disease. The CMRA data was acquired in 8 min 37 s with 100% scan efficiency at an average heart rate of 58 bpm. a The reformatted CMRA images (left-hand column) disclose a stenosis (arrow) in the mid RCA that matches the lesion observed on the CCTA (right-hand column). A significant narrowing was observed on both modalities with a 50% diameter reduction, compared with normal reference proximal diameter. The same patient showed calcified coronary plaque in the mid LAD (calcium mass: 2.88 mg, Agatston score: 16.1) leading to luminal narrowing of the mid and distal segments of the coronary artery observed on the CMRA and CCTA (arrow). b Volume rendered image of the 3D CMRA dataset is shown. Abbreviations: CMRA, coronary magnetic resonance angiography; CCTA, coronary computed tomography angiography; LAD, left anterior descending artery; RCA, right coronary artery; SVC, superior vena cava; AO, aorta; PA, pulmonary artery
Vessel sharpness of the first 4 cm was in agreement with the healthy subject results (LAD: 54.8 ± 7.7%, RCA: 57.8 ± 6.3%) and no statistical difference was found between LAD and RCA (P = 0.336). Good CMRA image quality scores were obtained in the patient study for both the LAD and RCA (Fig. 8, LAD: 3.8 ± 0.5, RCA: 3.8 ± 0.5) similar to CCTA (LAD: 3.8 ± 0.5, P = 1.00, RCA: 3.8 ± 0.5, P = 1.00), and were comparable to those obtained in the healthy subject study. Additional file 5 shows the image quality improvement achieved in three patients when correcting for non-rigid motion in addition to translational motion correction only.
Qualitative coronary results for the patients (N = 8) who underwent accelerated free-breathing whole-heart sub-millimeter isotropic CMRA with the proposed non-rigid motion-compensated PROST reconstruction and CCTA are provided for both coronary arteries. A score of 4 indicates excellent image quality with sharply defined coronary borders. Abbreviations: LAD, left anterior descending artery; RCA, right coronary artery
In this study, we demonstrate the feasibility of combining high undersampling factors with non-rigid motion-compensated PROST reconstruction to obtain high-quality free-breathing 0.9 mm3 resolution 3D whole-heart Cartesian CMRA images in a clinically feasible scan time of ~ 8 min. Similar to [22, 29], the proposed reconstruction framework estimates 2D translational motion (FH and LR) from low-resolution iNAVs, which are then used to correct for beat-to-beat respiratory motion. Non-rigid motion-compensated highly-undersampled 3D CMRA images are then obtained using a novel NR-PROST reconstruction which explicitly integrates the estimated inter-bin non-rigid motion in an iterative undersampled 3D patch-based reconstruction framework.
The proposed CMRA acquisition and reconstruction framework was first evaluated in 10 healthy subjects. An acceleration factor of 5x was used to achieve total imaging times of ~ 6 min for 0.9 mm3 spatial resolution with 100% respiratory scan efficiency and predictable scan time. The proposed NR-PROST reconstruction was compared to the previously published TC-PROST [29] and non-rigid motion-compensated NR-SENSE [22] reconstruction techniques. Translation correction with undersampled PROST reconstruction enables the visualization of the left and right coronaries with high image quality. However, although sub-millimeter resolution permits the visualization of small structures down to approximately 1 mm, the distal segments of the coronary arteries can be missed in subjects with more complex non-rigid respiratory-induced motion of the heart. Incorporating non-rigid motion correction in NR-SENSE allows for better visualization of the distal segments of the coronary arteries with sharp edges. This advantage, however, has to be balanced with some increase in noise in the reconstructed CMRA image, mainly due to the severely ill-posed reconstruction problem. The proposed NR-PROST approach overcomes this limitation by reconstructing CMRA images with higher image quality (as attested by two clinical experts), with good visualization of distal segments of the coronary arteries and high image sharpness.
The preliminary performance of the proposed CMRA framework in a clinical setting was assessed by imaging 8 patients with suspected coronary artery disease. The proposed approach allowed for the acquisition of the CMRA images in a total acquisition time of ~ 8 min with 100% respiratory scan efficiency. Three of the patients had normal coronary arteries, whereas the remaining five patients had evidence of coronary disease both on non-contrast CMRA and contrast-enhanced CCTA. The proposed non-rigid motion-compensated NR-PROST reconstruction generated high-quality images (with quality scores similar to the healthy subject study) despite high acceleration factors, with good delineation of the coronary vasculature and preservation of local features and luminal narrowing in calcified coronary segments. While the preliminary results on healthy subjects and patients show the potential of the proposed framework, further validation on a larger cohort of patients needs to be performed in future studies. The sensitivity and particularly, the negative predictive values of the presented approach need to be assessed, and its accuracy in detecting coronary stenosis and coronary artery occlusion remains to be evaluated.
In this study, a VD-CASPR sampling was employed with an acceleration factor of 5x to achieve sub 10-min acquisition time with 100% scan efficiency, whereas a fully sampled acquisition would have required clinically impractical scan times (> 40 mins). Besides the use of undersampling, respiratory motion compensation (2D beat-to-beat translation and 3D bin-to-bin non-rigid) also permits a substantial reduction in scan time by allowing 100% scan efficiency and predictable scan time, as opposed to other CMRA techniques based on diaphragmatic-navigator-gated acquisition [3, 4]. For the proposed approach, each of the 5 respiratory bins were reconstructed independently using a fast (i.e., less than 18 s per bin) soft-gating SENSE reconstruction that provides sufficient quality to extract non-rigid motion fields. However, motion-resolved CMRA images with higher image quality could be obtained by jointly reconstructing the bins using recently developed motion-resolved reconstructions, such as XD-GRASP [41] or XD-ORCCA [42], which also exploit sparsity along the respiratory dimension. While those techniques have shown great potential in providing high-quality motion-resolved CMRA images, their computational costs (currently ~ 2 h at a resolution of 1 × 1 × 2 mm3 [42]) and memory requirements may not be justified when the objective is solely motion estimation, as in this study.
A first beat-to-beat 2D translational motion correction with iterative SENSE reconstruction was performed inline in the scanner software, to provide a preliminary motion corrected CMRA image that can be visualized immediately after scanning. However, the proposed NR-PROST reconstruction was implemented and performed offline, with its main implementation in Matlab and the multi-threaded 3D patch-based denoising in C, resulting in total reconstruction times of ~ 50 min. Nonetheless, future implementations taking advantage of GPUs and coil compression strategies may significantly reduce the reconstruction time. It should also be emphasized that, compared to other CMRA sequences such as volume-targeted CMRA [2, 43] or diaphragmatic-based navigation [3, 4], the use of 2D iNAVs substantially reduce the operator dependence since only a small 2D box has to be positioned approximately around the heart to track the respiratory motion. Moreover, this 2D box can be defined (or re-defined) off-line during reconstruction. Furthermore, isotropic acquisitions allow whole-heart acquisition without knowledge of the position and course of the coronary arteries, providing almost full independence of the plane of acquisition and therefore avoiding long and tedious planning.
Our data demonstrated that free-breathing whole-heart 0.9 mm3 isotropic resolution CMRA permits the evaluation of the coronary arteries over a length of about 12 cm (LAD) and 14 cm (RCA). This is not only important for the non-invasive interrogation of the proximal and mid- segments of the coronary arteries and their collateral branches but, together with curved multiplanar reconstruction, it shows the capacity to localize small coronary lesions and related pathology. While comparison with CCTA showed good agreement and delineation of the coronary arteries with the proposed CMRA framework, CCTA still has the advantage of being less sensitive to motion (faster acquisition, breath-holding) and provides higher spatial resolution (in the order of 0.6 mm3). Nonetheless, initial clinical results from this feasibility study demonstrate that free-breathing non-contrast whole-heart sub-millimeter isotropic CMRA using NR-PROST reconstruction holds promise for the safe non-invasive assessment of coronary stenosis without the requirement for intravenous contrast or exposure to ionizing radiation. Future clinical studies comparing the proposed CMRA images with CCTA in a larger cohort of patients under similar pharmacological preparation are needed.
A framework was developed to enable free-breathing 3D whole-heart sub-millimeter isotropic resolution Cartesian CMRA. The proposed approach achieved fast and predictable acquisition times in healthy subjects and patients (~ 8 min) with good image quality and sharp delineation of the coronary arteries. Ultimately, this non-invasive and radiation-free framework might be a useful tool for rapid screening and comprehensive examination of the coronary vasculature, including the distal segments, in patients with suspected coronary artery disease. Future clinical validation is now warranted.
3D:
ADMM:
Alternating direction method of multipliers
bSSFP:
Balanced steady state free precession
CAD:
CCTA:
Coronary computed tomography angiography
CMRA:
Coronary magnetic resonance angiography
ECG:
FA:
Flip angle
FH:
Foot-head
FOV:
Field-of-view
iNAV:
Image based navigator
LAD:
Left anterior descending coronary artery
LCA:
LCX:
Left circumflex coronary artery
NR:
Non-rigid
PDA:
Posterior descending coronary artery
PROST:
Patch-based low-rank reconstruction
RL:
Right-left
SPIR:
Spectral presaturation with Inversion recovery
VD-CASPR:
Variable density spiral like Cartesian trajectory
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Dr. Matthias Stuber served as a JCMR Guest Editor for this manuscript.
The authors acknowledge financial support from: [1] EPSRC EP/P001009/, EP/P032311/1, EP/R511559/1 and EPSRC EP/P007619, [2] Wellcome EPSRC Centre for Medical Engineering (NS/ A000049/1) and [3] the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, 3rd Floor, Lambeth Wing, London, SE1 7EH, UK
Aurélien Bustin, Imran Rashid, Gastao Cruz, Reza Hajhosseiny, Teresa Correia, Radhouene Neji, Ronak Rajani, Tevfik F. Ismail, René M. Botnar & Claudia Prieto
National Heart and Lung Institute, Imperial College London, London, UK
Reza Hajhosseiny
MR Research Collaborations, Siemens Healthcare Limited, Frimley, UK
Radhouene Neji
Department of Cardiology, Guy's & St Thomas' Hospitals, London, UK
Ronak Rajani
Escuela de Ingeniería, Pontificia Universidad Católica de Chile, Santiago, Chile
René M. Botnar & Claudia Prieto
Aurélien Bustin
Imran Rashid
Gastao Cruz
Teresa Correia
Tevfik F. Ismail
René M. Botnar
Claudia Prieto
AB, RMB and CP contributed substantially to the conception and design of the study. AB implemented the undersampled trajectory and the reconstruction framework, acquired and analyzed the data, and wrote the main draft of the manuscript. IR, RH, RR, and TFI recruited the patients. GC, TC and RN contributed to the implementation of the CMRA sequence and the motion compensated reconstruction framework. All authors read, revised, and approved the final manuscript.
Correspondence to René M. Botnar.
This study was approved by the National Research Ethics Committee. All volunteers and patients provided written informed consent for participation in this study.
All healthy subjects and patients gave written informed consent for publication.
RN is an employee of Siemens Healthcare. The other authors declare that they have no competing interests.
Additional file 1.
Undersampled 3D variable-density spiral-like Cartesian trajectory (VD-CASPR) to allow for fast acquisition of the high-resolution 3D CMRA data. The Cartesian trajectory with spiral-like order samples the ky-kz phase encoding plane following approximate spiral interleaves on the Cartesian grid with variable density along each spiral arm. In this sketch, the 2 first acquired spirals are shown, each spiral containing 20 segments. A golden angle rotation between successive spirals is applied to allow for pseudo-random distribution of the spiral interleaves during respiratory binning.
Example CMRA reconstructions from 3 healthy subjects acquired with the proposed approach with acceleration 5x and 0.9 mm3 isotropic resolution are shown. The total acquisition time, with 100% scan efficiency, is expressed as [min:s].
Non-contrast whole-heart sub-millimeter isotropic CMRA images of 3 patients acquired at 0.9 mm3 isotropic resolution and reconstructed with the proposed non-rigid PROST framework. The total acquisition time, with 100% scan efficiency, is provided for each patient.
Reformatted CMRA for 3 patients acquired with isotropic resolution of 0.9 mm3 and reconstructed with translational PROST (TC-PROST) and the non-rigid PROST framework (NR-PROST). Reformatted sub-millimeter isotropic CMRA along the LAD and RCA for 3 patients with suspected coronary artery disease and reconstructed with translational correction only (TC-PROST, top row) and the proposed non-rigid PROST approach (NR-PROST, bottom row). Accelerated non-rigid PROST allows for improved visualization of both LAD and RCA compared to translation-only corrected PROST. Abbreviations: bpm, beat per minute; CCTA, coronary CT angiography; TC-PROST, translational correction PROST; NR-PROST, non-rigid PROST.
Bustin, A., Rashid, I., Cruz, G. et al. 3D whole-heart isotropic sub-millimeter resolution coronary magnetic resonance angiography with non-rigid motion-compensated PROST. J Cardiovasc Magn Reson 22, 24 (2020). https://doi.org/10.1186/s12968-020-00611-5
Received: 19 July 2019
Accelerated imaging
Coronary MR angiography
Isotropic sub-millimeter resolution. PROST reconstruction non-rigid motion compensation


text:
package com.anriku.imcheck.MainInterface.View;

import android.content.Intent;
import android.databinding.DataBindingUtil;
import android.os.Bundle;
import android.support.annotation.Nullable;
import android.support.v4.app.Fragment;
import android.support.v7.widget.RecyclerView;
import android.view.LayoutInflater;
import android.view.View;
import android.view.ViewGroup;
import android.widget.Toast;

import com.anriku.imcheck.MainInterface.Interface.IFriendsFrg;
import com.anriku.imcheck.MainInterface.Interface.IFriendsPre;
import com.anriku.imcheck.MainInterface.Presenter.FriendsPresenter;
import com.anriku.imcheck.R;
import com.anriku.imcheck.databinding.FragmentFriendsBinding;
import com.hyphenate.EMContactListener;
import com.hyphenate.chat.EMClient;

import java.util.ArrayList;
import java.util.List;

/**
 * Created by Anriku on 2017/8/16.
 */

public class FriendsFragment extends Fragment implements IFriendsFrg{

    private IFriendsPre iFriendsPre;
    private FragmentFriendsBinding binding;
    private List<String> names = new ArrayList<>();
    private List<String> reasons = new ArrayList<>();

    @Nullable
    @Override
    public View onCreateView(LayoutInflater inflater, @Nullable ViewGroup container, @Nullable Bundle savedInstanceState) {
        binding = DataBindingUtil.inflate(inflater,R.layout.fragment_friends,container,false);
        return binding.getRoot();
    }

    @Override
    public void onViewCreated(View view, @Nullable Bundle savedInstanceState) {
        super.onViewCreated(view, savedInstanceState);
        iFriendsPre = new FriendsPresenter(this);
        iFriendsPre.getFriends(getContext(),binding);
        iFriendsPre.handleApply(getContext(),names,reasons,binding);
        iFriendsPre.refreshFriends(getContext(),binding);
    }

}

redpajama_set_name: RedPajamaGithub


text:
The Peter Debye Award in Physical Chemistry is awarded annually by the American Chemical Society "to encourage and reward outstanding research in physical chemistry". The award is named after Peter Debye and
granted without regard to age or nationality.

Recipients

2020 Laura Gagliardi
2019 Daniel M. Neumark
2018
2017
2016 Mark A. Ratner
2015 Xiaoliang Sunney Xie
2014 Henry F. Schaefer III
2013 William E. Moerner
2012 David Chandler
2011 Louis E. Brus
2010 George Schatz
2009 Richard J. Saykally
2008 Michael L. Klein
2007 John T. Yates, Jr.
2006 Donald Truhlar
2005 Stephen Leone
2004 William Carl Lineberger
2003 William H. Miller
2002 Giacinto Scoles
2001 John Ross
2000 Peter G. Wolynes
1999 Jesse L. Beauchamp
1998 Graham R. Fleming
1997 Robin M. Hochstrasser
1996 Ahmed Zewail
1995 John C. Tully
1994 William A. Klemperer
1993 F. Sherwood Rowland
1992 Frank H. Stillinger
1991 Richard N. Zare
1990 Harden M. McConnell
1989 Gabor A. Somorjai
1988 Rudolph A. Marcus
1987 Harry G. Drickamer
1986 Yuan T. Lee
1985 Stuart A. Rice
1984 B. Seymour Rabinovitch
1983 George C. Pimentel
1982 Peter M. Rentzepis
1981 Richard B. Bernstein
1976 Robert W. Zwanzig
1975 Herbert S. Gutowsky
1974 Walter H. Stockmayer
1973 William N. Lipscomb, Jr.
1972 Clyde A. Hutchison, Jr.
1971 Norman Davidson
1970
1969 Paul J. Flory
1968 George B. Kistiakowsky
1967 Joseph E. Mayer
1966 Joseph O. Hirschfelder
1965 Lars Onsager
1964 Henry Eyring
1963 Robert S. Mulliken
1962 E. Bright Wilson, Jr.

See also

 List of chemistry awards

References

Awards of the American Chemical Society
Physical chemistry
Awards established in 1962
Peter Debye

redpajama_set_name: RedPajamaWikipedia


Over at the Wall Street Journal, they are reporting that young men have been hit hardest by the recession, especially if they didn't go to college.
For men with a high school diploma between 20 and 24 the unemployment rate is over 22%, and over 14% for those between 25 and 30. These rates are only slightly lower than those who didn't even finish high school.
This is partly because the job sectors that hire young men who didn't go to college are down, like construction and manufacturing. Women in these groups, without high school, fare 3 or 4 points better, but only because helping and service jobs are hiring, if not paying well.
And keep in mind that these high rates of unemployment among young men are occurring while we have two or three wars going. As soldiers return, with more discipline and experience, it can only get worse for 20 something men who didn't go to college or join the army.
On the other hand, the unemployment rate for men and women who did finish college is 7.7% for those under 24, and 4.2% for those between 25 and 34. Even factoring in their huge school bills, they are probably better off—since their unemployment rate is even lower than the national average.
You wish they would have more faith in God. Historically hard times have prompted more prayer. But these kids have parents who have been less likely to go to church and their schools have been much less likely to recognize God in any way.
I've met these guys. The county where our church is has a lot of them, a county where finishing high school and getting a job in an automotive-related plant has been the standard of success for decades.
Churches should engage them. But how do we find these guys? How do we help them? Where can we point them? They often lack the right attitudes. And the right skills.
What is our responsibility to a generation of angry young men, men who drink too much and fight too much? And how is the problem in rural counties compounded in the larger cities? How can the demons be cast out, except by prayer and fasting?
Such needs should be enough to drive them, and us, to our knees. Great need could be the fertile soil of revival, as it has been in times past.
We could, of course, keep waiting for the lenders and the legislators to solve this problem for us. Another war tends to be their preferred solution.
Or we could love, mentor and hire a generation of young people, men and women, college educated or not, who need more skills than we've taught them, more hope than we've given them, and more character than we've shown them.
When we do this, and when our churches do this, charity will thrive and entrepreneurship will emerge. Those of means will creatively engage those with needs, next door and in our neighborhoods.
What can churches do? Or individuals?
What I find interesting here is a lack of fellowship, (koinonia,) or what would be described as intimate relationship in our society. A majority of people have embraced the idea that we should be able to take of ourselves, or if we don't we have a weakness. In years past we were able to connect our young men and women within our church community and people in our friendship networks to help guide them to employment. It is almost as if when we sent our jobs to the ends of the world to save money in production, it evaporated those links that helped us grow "community". Now the elite members of our society who benefited from the foreign job labor desire to quickly quell this rebellion and disorder. Sadly they are without much interest in trying to reconnect our youth in a healthy community of networking to find work. What will probably result, is another example of what happened in the 60's where they will develop their own network of anger that will disrupt our society even more.
Wally, thanks for this post these words resonated with me as a 29 year old who went through a year of part time employment and who is now thankfully employed as a science teacher.
"Or we could love, mentor and hire a generation of young people, men and women, college educated or not, who need more skills than we've taught them, more hope than we've given them, and more character than we've shown them.


Consider this: according to Inc Magazine , the average US consumer sees about 3,000 advertisements per day. Can a startup really spend enough money to break through that clutter and build awareness?
For at least the first year or two, online consumer/prosumer/smb targeted startups should focus 100% of their non-PR media budget on acquiring customers. Rather than buying a microsecond of awareness, you can actually use your limited funds to engage users in a real brand experience. Even for users that don't convert to paying customers, you create a deeper impact by engaging people on your website. And you can gain intelligence about such things as where and why potential customers are abandoning your acquisition funnel.
Focusing on customer acquisition over "awareness" takes discipline. There is always some amazing advertising opportunity that could lead to explosive growth. Your odds are probably better buying a lottery ticket.
Building a strong customer acquisition engine is the best chance you have of creating long-term awareness. At a certain scale, awareness/brand building makes sense. But for the first year or two it's a total waste of money.
This entry was posted in Acquiring Customers, Building Awareness by seanwellis. Bookmark the permalink.
I agree 100%. You are much better off focusing all of your energy on your first 1,000 customers, build a base and then things will explode. Another great post Sean.
I agree, adding to your customer list drives real word of mouth (vs. buzz about "what a cool app/technology/website"). Paying customers are the fastest way to positive cash flow.
Excellent post. There is still a fixation on brand and building brands awareness often at the expense of response and knowledge. Brand awareness sounds so old school or limiting. Learn first through carefully calibrated spending and research. Talk to customers. Listen. Refine. That doesn't feel quite so macho or expensive as running a big ad campaign but at the end of the year you'll have customers and know fairly well how they got there.
Totally agree with this post. Consumers have already been trained to tune out advertisements so paid advertising is very low ROI. I can't name one ad I've seen online today. Instead, startups should focus on driving user engagement & quality experience. By doing this, you're leveraging the word-of-mouth and viral nature of the web to drive adoption. Really enjoy reading your blog Sean.
Thanks Leo, glad you are enjoying the blog. Very good point that user acquisition is best way to leverage WOM and viral nature of web… I checked out your blog. Good luck with the new venture.
I came across this article by chance and I must say, I disagree with it. Awareness relates to how many people (usually a %) in your target market know you AND what they know about you, or associate you with. This is important for any kind of business, a start up or the Apple iPad. A level of relevant or desired awareness supports interest-generating activities, such as the kind of engagement tactics offered by websites, that then lead to positive disposition and sales. Awareness building is an important strategy that supports customer acquisition and should not be seen as an alternative. Many start-ups fail because they are simply focussed on selling X, and forget about selling works best as part of an integrated marketing effort, that ought to address all stakeholders in the market. And awareness-building can be done in different ways depending on your needs, market and budget. Just think of it this way, Google can probably sell you a new MS Office alternative, but would you buy one from say Asus or AT&T? Why?
Hey Sean, great post. I totally agree especially since I am currently going through it myself. We have an innovative product that is borderline revolutionary and people still won't flock to it. If you have any tips on how to get the first 1000 customers, be sure to email me. We are doing our best over here literally giving 100% bonus to anyone who deposits.


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Renewology: How the Renew/Cancel Model Fared in 2019-20
Another year is (almost completely) finished in renew/cancel world, so let's talk about it by evaluating my "ratings-only" renewal/cancellation model. Here are the recaps of 2018-19 and 2017-18.
Were the Tiers Well Calibrated?
Average R%
Actual Renewal Rate
Renewals/Total
Dark Red (0-19%) 9% 25% 2/8
Light Red (20-39%) 29% 50% 3/6
White (40-59%) 53% 50% 5/10
Light Green (60-79%) 70% 64% 7/11
Dark Red (80-100%) 95% 95% 39/41
At first glance, this looks like a much bigger year for reach renewals than last year. There was at least one more renewal than expected in both the dark red and light red tiers. I would point out a couple shows like Bless the Harts (dark red) and The Blacklist (light red) that are graded in their respective tiers based on renewal timing but spent very little of their actual seasons there, which might throw the numbers a bit off kilter. (But there's also Zoey's Extraordinary Playlist, which was dark red all season and barely snuck into light red at the end.)
The last three tiers (where the nets were extremely generous last year) were much better calibrated. The bubble was truly a bubble and there were about the right amount of cancellations in the light green and dark green tiers. We even got a freak cancellation in the very dark green territory (Hawaii Five-0) after not having one for a couple years. As I said in past years, it was probably overdue, and I'm just glad to have it at 97% and not 100%. That three point difference is supposed to mean something, and we saw it this year!
One thing that was nice to see this year was that the overall picture was much better calibrated, following a 2018-19 in which the misses were mostly in one direction. Last year we basically had three networks that were much more generous than expected, leading to about a six-show gap between expected and actual renewals. This year, that was greatly improved; the sum of R% at the time of decision was 54.25 renewals, and the networks renewed 56 shows. If Katy Keene gets cancelled, that would mean we were only off by one renewal across the five networks (great!), and if she gets renewed it would be a little over two. Pretty good either way.
Results By Network
Sum of R%
ABC 11.05 11
CBS 18.51 16
NBC 8.02 10
Fox 6.95 9
CW 9.71 10
ABC: For the second year in a row, the model did an incredible job of setting the renewal bar for ABC. The alphabet renewed exactly the number of shows expected. What was a little more questionable was the relative standing of the shows; ideally, Renewology probably would've wanted one more renewal out of the glut of comedies in the 50-60% range and a cancellation of Stumptown.
CBS: I've talked before about the two ways to grade this model: the "bar" (total number of shows renewed) and the "curve" (the relative standing of shows). ABC did great with the bar but a bit shakier with the curve. CBS was much more of a bar problem, as the network reversed course from last year (when they were generous) and cancelled 2-3 more shows than expected. Of course, some of this is explained by freakish incidents like the cancellations of Hawaii Five-0 and (to a much lesser extent) Man with a Plan. But CBS was harsher than expected even if you completely take those out of the equation.
It wasn't really a "curve" problem; other than Five-0, the cancellations were all out of a fairly closely bunched tier of the nine weakest shows on the network. The problem was that this tier was way too high across the board: of the eight shows from The Unicorn through Man with a Plan, we expected a 73% renewal rate (most likely six renewals) and it should've been far closer to 50% (as only four survived).
My main theory on this is that the loss of The Big Bang Theory depressed the network's average, but CBS did not really depress its renewal standards to match. So we may need to adjust CBS' network generosity to account for that.
NBC: If there's one consistency year after year, it's that NBC renews more shows than expected. I keep jacking up NBC's expected generosity, and they keep taking it to another level. This year, the main culprit was Zoey's Extraordinary Playlist, then (as explained above) we got a little unlucky that they renewed The Blacklist at one of its relative low points, then they renewed two of the three bubble shows (Manifest, Good Girls, Lincoln Rhyme: Hunt for the Bone Collector) and didn't touch anything in the green.
Fox: The model did pretty well with Fox... if you throw out the animated newbies. Maybe it was a little unlucky that Bless the Harts got renewed after week three, because it was never in the dark red after that point and actually improved all the way to renewal favorite territory after its last couple post-football episodes. But there's no such consolation with Duncanville, which was in the teens throughout. I think this was a pretty hard one to see coming. They have no DVRing, so looking at delayed numbers doesn't explain it. In what small sample size we have for Fox animation, there is very little history of the network going out of their way to make reach renewals, much less two in one season. It's hard for me to envision a version of the model, with the info available prior to this season, in which these wouldn't have been big misses. Shrug.
CW: Basically everything was listed as a renewal lock and everything got renewed. Yawn. Throw in the still-undecided Katy Keene (currently listed at 65%) and you're talking about 10.4 renewals projected, and we're going to end up at either 10 or 11. Hard to do much better than that, especially considering (like with All American last year) it seems that there was at least some chance of a Katy cancel, based on the decision coming this late. So whatever the result, I feel all right with asserting that it was not a dark green type of show. (And incidentally, this is a show where not having the un-roundeds makes a real difference. If we'd known it was getting very high 0.1's in the early part of the run, followed by south of 0.10 at the end, my guess is it'd probably have been rated much more consistently around 55-60%ish.) From a modeling perspective, I'm kind of rooting for a cancellation, just because I think it would help justify this model's reason for existing with respect to the CW. It'd be nice to know they still can cancel something.
I am consistent every year (even when I do well) in mentioning that simple "win-loss record" is a bad way to judge something like this that puts out percentages. Evaluating calibration is much more important. That being said, this was a relatively bad year. The final record was 60-16 (79%). I've always said I need a little luck to be competitive with the people who are including many factors beyond ratings, and the luck ran out this time. All three of the NBC bubble shows mentioned above were "wins" for the majority of their seasons and slipped into "loss" territory in their final weeks, and there was really only one example in the other direction (Deputy). I was only 5-5 on the ten bubble shows, barely above .500 (15-12) combining light red, white and light green, and there were also more losses than usual in the dark red/dark green territory. A lot of this I view as reversion to the mean; we had a couple lucky seasons and this one was maybe a little unlucky.
I did not apply any sort of theory as to how COVID-19 would affect these decisions, and considering the model ended up very close to the mark in terms of total big five renewals, with misses in both directions, that was probably a good decision. If I had to evaluate after the fact, I would be more inclined to say that it was a better year than usual for the "conventional wisdom" and the "internal favorites." You could say that this is just part of a progression over time of ratings mattering less and less, but my guess is that the general craziness in the country exacerbated it a bit this year. This model has usually had some value even when compared against people who are just regurgitating the insiders' bubble watch articles, but I don't think that was really the case this year. Perhaps we saw more networks throwing up their hands, considering the whole ratings landscape a bit of a wash, and renewing the stuff they liked.
For years I've been trying to evaluate whether it's worth going through all the trouble of adding a Renewology component based on actual DVR ratings. This has to clear a couple of bars: 1) Will it actually improve the results? and 2) Will it improve the results enough to be worth going through all the logistical hoops?
In past years, there have always been counter-examples where using DVR ratings would hurt the result, perhaps most famously Man with a Plan (a very lightly DVRed show that was a narrow favorite even with the True formula, and almost certainly would've been a "loss" after DVRing). While MWAP got the axe this year, ironically after it finally scored high in Renewology, there were still some counter-examples this year; the big ones that spring to mind are CBS' All Rise and the much-aforementioned Fox cartoons.
This might be the year that finally tipped me to being fully convinced on #1. But clearing the bar for question #2 is not as easy as you might think, because the True formula already makes a guess at how difficult timeslots are. Particularly comparing across hours, that translates pretty well in a broad sense to how much DVRing occurs. So, as an example, I'm not sure a DVR component would help that much with something like Good Girls, because it's already judged to be in a brutal timeslot. It definitely wouldn't explain most of the freak misses this year, like Five-0, Zoey, or the Fox cartoons. But it seems like there are a lot of shows along the margins where there would be value added. It probably would've helped some with Stumptown, but even more with stuff like Manifest and Prodigal Son that are judged to be in "easy" timeslots yet still have good DVRing. There were also shows in "hard" timeslots that under-indexed in DVRing, like Tommy and The Baker and the Beauty.
If I actually put something like this together, it would probably be less about overhauling the True formula (which seems like way too much trouble at this point) and more about something separate. Maybe I could translate what was once called "Sitch" (a measurement of timeslot difficulty) into a guess for how much Live+7 would result, then make a simple adjustment to the True number once the actual Live+7 comes in. I'm not making any promises, but that's just an idea for something that could happen. Thanks for reading!
Labels: Renewology, spotlight
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SpotVault - Hollywood Game Night (NBC) - Summer 20...
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SpotVault - Dirty John (USA) - Summer 2020 Ratings
SpotVault - Bulletproof (CW) - Summer 2020 Ratings
The Breakdown: ABC Tuesday in 2019-20 (The Conners...
The Breakdown: CW Monday in 2019-20 (All American,...
Renewology: How the Renew/Cancel Model Fared in 20...
The Breakdown: Fox Monday in 2019-20 (9-1-1, 9-1-1...
The Breakdown: NBC Monday in 2019-20 (The Voice, B...
The Breakdown: CBS Monday in 2019-20 (The Neighbor...
The Breakdown: ABC Monday in 2019-20 (Dancing with...
SpotVault - Press Your Luck (ABC) - Summer 2020 Ra...
SpotVault - Match Game (ABC) - Summer 2020 Ratings
SpotVault - Celebrity Family Feud (ABC) - Summer 2...
Final League Averages for 2019-20

redpajama_set_name: RedPajamaCommonCrawl


Are Rats Really Dirty And Nasty?
Yes they are! But they have good reasons.
As you may know, rats have had a reputation problem for some time. They really could use some better PR. They travel a lot, they're all over the place, and are not always welcome. Some have even referred to them as 'kinda creepy'.
Well some of them are creepy (how about Ben that starred in Willard, he was creepy).
But the road to fortune, or at least being liked, has had some serious road blocks for rats, as you can plainly see here. The living conditions they inherited, would make anyone cranky, and nasty, and especially dirty. I thought the president was going to fix this kind of low living. Maybe he's on the road again and too busy. It's on to the next golf course for him, most likely.
But, after years of traveling around to see the world's classiest garbage dumps, seeking to upscale a bit, they started to develop a serious road rage, some have even referred to them as road hogs.
So they made the decision to call it quits.
"We're hungry, let's get off the road, go home and stay put.
We want our own cans tonight," they both agreed.
As cranky, nasty, and dirty as these rats were, the road home was sweet.
You can get the cool Dirty Rat poster, t-shirt, cards and more at Zazzle.


Yea, go easy on yourself. . . That's what I'd do.
HAPPY NEW YEAR Dave and dear readers/comment providers – you really make my days – and I'm looking very much forward to many exchanges serious and not, funny & sad, over the next 364 days. THANK YOU, thank you, Thank You so much for all your wonderful input over the past time I enjoyed endlessly, dear unknown and yet so well known friend!
Laughing. Still laughing. You make my day Kiki. Happy New Year!
Hear! Hear! Down with resolutions designed to make you fail! Down with "New Year, New You"! Let us just learn to love ourselves, which doesn't stop us from bettering ourselves but removes the pressure unnecessary!
And we think DK is pretty fab!
Happy New Year! How profound.
It is! Thanks Marlin. Happy New Year to you too….
Excellent. Thanks for sharing Keith. Happy New Year!
Love this! Happiest & Healthiest New Year!
Me too Cindy! Happy New Year!
Oh yeah. I've refused to drink the New Year's Day koolaid for awhile now. You can pass the wine though. HappyNew Year!
Happiest of New Years David! So grateful for our connection!
Me too Yvonne! Happy New Year!
I never tasted the "new year's resolution koolaid" in my life.
Aries doesn't function this way. When we're tired of our own BS, that's it, we're done!
Boom! There u have it!
Thanks for the support. I agree. No guilt this year. I'm not making resolutions. Well, not ones that I announce to the world. I'm just looking forward to new projects.
New projects. New beginnings. Exciting!
Oh Dear, Caroline Foran…couldn't read the article, but clicked on the 6 something-or-others. Yikes! What happened to learning to live in the moment? With all that other noise going on about other people's lives and possible evaluations, being sane would be challenging.
Smiling. "Holy Instants". Love that! Happy New Year Valerie!


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I Don't Look Forward to Fred Phelps Rotting in Hell
March 17, 2014 Wayne K. Spear Leave a comment
ACCORDING TO A Facebook post of his estranged son, Nathan, Fred Phelps Sr, the founder of the notorious Westboro Baptist Church, is dying. There's an undeniable aesthetic appeal in the prospect of Mr. Phelps soon meeting his Maker, but this indulgence presumes far more than I can manage. My own view, if you care to know, is that Phelps will die and dissolve and remain forever in a condition of no condition whatsoever.
This anti-theistic position is the most through repudiation of the man and everything he stood for. In life, Phelps evaded prison on several occasions, and in my view at least he'll also escape the punishments of the non-existent hereafter. This means I'll never be able to enjoy the comfort, or whatever it is, of contemplating his eternal damnation. But then again, what if I did avail myself of this sadistic revelry, like the early Christian theologian Tertullian "admiring, laughing and rejoicing" at the sight of the tormented?
The answer to this is that I would be much like Phelps himself. It's not that I have any kind feelings toward a man who, in the words of Mary Elizabeth Williams, lived a life of "the most callous, consistent viciousness." Nate Phelps has spent the past two and a-half decades exposing and condemning the actions of the Westboro Baptist Church, characterizing his father as "cruelly, viciously violent – physically, verbally and psychologically." In Nate's view, Fred Phelps established the church in 1955 for the purpose of venting his hate, which by all accounts is considerable.
Phelps has described himself as a "Primitive Baptist," although he is condemned by representatives of this theological tradition. His beliefs, as they concern damnation and salvation, conform to the doctrines of Calvinism. Phelps, according to an exhaustive Q&A posted on the church's website, believes in the doctrines of pre-destination and the elect, meaning that at the beginning of the world God chose the saved as well as the damned.
Needless to say, the chosen are few, the damned many. The Westboro Baptist Church therefore protests and vilifies entire nations, as well as entire religious traditions, including Judaism and Roman Catholicism. Phelps' targets have included American Presidents Reagan and Bush Sr., Supreme Court Justice William Rehnquist, Conservative Washington Republicans and Bill O'Reilly. The list of those Phelps at one time courted, and even in some cases praised, is short, but just as odd: it includes Al Gore, Bill Clinton and Saddam Hussein.
The unifying theme and active principle of Phelps' apparenty scattershot theology is sadism. Phelps' theological determinism claims that God has elected you, long before you were even born, for eternal perdition and torment. There's nothing that you can do about it: it's God's will. And in the short time that you are a wretch and alive on this Earth, it is fitting and proper that you should be abused, cajoled and otherwise baited and attacked by God's Chosen Few.
The point often missed, even by his harshest critics, is that Phelps was not your ordinary "repent and be saved" crusader. The redemption or "saveability" of his targets was never a consideration – Phelps was in the sadistic business of rubbing salt into the wounds it was the pleasure and will of God to have inflicted. The cruelty of Phelps' psychology is perfectly summarized in a metaphor employed by King Lear's Gloucester. "As flies to wanton boys are we to the gods. They kill us for their sport." Phelps was a sportsman-accomplice, gleefully attending as the wings are capriciously pulled from the victims.
As vicious and stupidly mean-spirited as Phelps was, there is nothing in his theological handbag that is without historical precedent. His doctrines have enjoyed wide currency throughout the Christian era, and only his erratic and exhibitionist applications have distinguished him. "God hates fags" was a clever piece of marketing, a way to get free press (an obsession of his), but it was also a forceful re-statement of existing prejudices. For this reason Phelps was able, as recently as 2005, to hold successful signature drives for motions that would have repealed anti-hate-crime and anti-workplace-discrimination city ordinances. He lost this Topeka battle by a 53–47% margin, just as he was denied the 1998 Governorship of Kansas primary in a vote that yielded him 14% of the ballots, "only" 15,233 citizens considering him fit for the state's highest office.
In August of last year, Fred Phelps was ejected from the Westboro Baptist Church for reasons that have been kept to the church's membership. Given the subsequent behavior of the congregation, the expulsion is not indicative of a change of heart or a change of direction. Westboro Baptist continues to picket funerals and to applaud every American misfortune, from earthquakes to school mass shootings, as the glorious work of an angry, hateful and vindictive God. Along the way encouraging grassroots movements, like the Patriot Guard Riders, have emerged to repudiate the work of this church and to spread a contrasting message of respect and decency.
The current face of the Westboro Baptist Church is spokesman Steve Drain, a filmmaker who went from documenting the church to embracing it. His daughter Lauren, a nurse and ex-member, today calls for peace and change: "As a nurse I can say that every man & woman deserves the right to make peace with themselves, their family & their God on their death bed." A commendable sentiment, and a decisive breaking with Westboro's ugly legacy. An even more thorough repudiation would be to further confront the church's beliefs head-on, and to finish the work of people like Nate Phelps and the Patriot Guard Riders, by making it clear to this church that hate in all its forms is not the work of God, but instead of small and broken people.
AmericaCalvinismChristianityCurrent EventsFred PhelpsNathan PhelpsNewsReligionTertullianWestboro Baptist Church
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What is a Full Body Exfoliation?
A full body exfoliation, also known as a scrub or body polish, is a treatment which exfoliates the top layer of skin on your body. A coarse product, either sea salt or sugar, is mixed with massage oils or essential oils and is scrubbed vigorously, and massaged across and into your skin. It is then rinsed away to reveal a clean layer of skin underneath.
-it prepares your skin for an even spray tan by removing dead skin cells.
-it opens the pores before a wrap or mud treatment so that the product can be absorbed.
What are the benefits of a Full Body Exfoliation?
Exfoliates the skin removing dead skin cells rubbing away hard and flaky skin.
Body scrubs include an oil base which moisturises and soothes your skin.
What are the different types of scrubs?
Sugar body scrub - the most common type of body scrubs are sugar-based scrubs. Sugar scrubs are much less-abrasive and used for sensitive skin types.
Sea salt body scrub – are coarse and therefore more rejuvenating and vigorous. These types of scrubs are beneficial for bringing toxins to your skins surface and have healing properties.
Coffee body scrub - is beneficial for cellulite prone areas as it is a natural stimulant.