Prospective motion correction for brain MRI using spherical navigators.

PURPOSE: To demonstrate for the first time the feasibility of performing prospective motion correction using spherical navigators (SNAVs). METHODS: SNAVs were interleaved in a 3D FLASH sequence with an additional short baseline scan (6.8 s) for fast rotation estimation. Assessment of SNAV-based prospective motion correction was performed in six volunteers. Participant motion was guided using randomly generated stepwise prompts as well as prompts derived from real motion cases. Experiments were performed on a 3 T MRI scanner using a 32-channel head coil. RESULTS: When optimized for real-time application, SNAV-based motion estimates were computed in 25.8 ± 1.3 ms. Phantom-based quantification of rotation and translation accuracy indicated mean absolute errors of 0.10 ± 0.09° and 0.25 ± 0.14 mm, respectively. Implementing SNAV-based motion estimates for prospective motion correction led to a clear improvement in image quality with minimal increase in scan time (<5%). CONCLUSION: Optimization of SNAV processing for real-time application enables prospective motion correction with low latency and minimal scan time requirements.

Deep-learning-based motion correction using multichannel MRI data: a study using simulated artifacts in the fastMRI dataset.

Deep learning presents a generalizable solution for motion correction requiring no pulse sequence modifications or additional hardware, but previous networks have all been applied to coil-combined data. Multichannel MRI data provide a degree of spatial encoding that may be useful for motion correction. We hypothesize that incorporating deep learning for motion correction prior to coil combination will improve results. A conditional generative adversarial network was trained using simulated rigid motion artifacts in brain images acquired at multiple sites with multiple contrasts (not limited to healthy subjects). We compared the performance of deep-learning-based motion correction on individual channel images (single-channel model) with that performed after coil combination (channel-combined model). We also investigate simultaneous motion correction of all channel data from an image volume (multichannel model). The single-channel model significantly (p < 0.0001) improved mean absolute error, with an average 50.9% improvement compared with the uncorrected images. This was significantly (p < 0.0001) better than the 36.3% improvement achieved by the channel-combined model (conventional approach). The multichannel model provided no significant improvement in quantitative measures of image quality compared with the uncorrected images. Results were independent of the presence of pathology, and generalizable to a new center unseen during training. Performing motion correction on single-channel images prior to coil combination provided an improvement in performance compared with conventional deep-learning-based motion correction. Improved deep learning methods for retrospective correction of motion-affected MR images could reduce the need for repeat scans if applied in a clinical setting.

Effective magnetic susceptibility of 3D-printed porous metal scaffolds.

PURPOSE: 3D-printed porous metal scaffolds are a promising emerging technology in orthopedic implant design. Compared to solid metal implants, porous metal implants have lower magnetic susceptibility values, which have a direct impact on imaging time and image quality. The purpose of this study is to determine the relationship between porosity and effective susceptibility through quantitative estimates informed by comparing coregistered scanned and simulated field maps. METHODS: Five porous scaffold cylinders were designed and 3D-printed in titanium alloy (Ti-6Al-4V) with nominal porosities ranging from 60% to 90% using a cellular sheet-based gyroid design. The effective susceptibility of each cylinder was estimated by comparing acquired B0 field maps against simulations of a solid cylinder of varying assigned magnetic susceptibility, where the orientation and volume of interest of the simulations was informed by a custom alignment phantom. RESULTS: Magnitude images and field maps showed obvious decreases in artifact size and field inhomogeneity with increasing porosity. The effective susceptibility was found to be linearly correlated with porosity (R2  = 0.9993). The extrapolated 100% porous (no metal) magnetic susceptibility was -9.9 ppm, closely matching the expected value of pure water (-9 ppm), indicating a reliable estimation of susceptibility. CONCLUSION: Effective susceptibility of porous metal scaffolds is linearly correlated with porosity. Highly porous implants have sufficiently low effective susceptibilities to be more amenable to routine imaging with MRI.

Left atrial vortex size and velocity distributions by 4D flow MRI in patients with paroxysmal atrial fibrillation: Associations with age and CHA2 DS2 -VASc risk score.

BACKGROUND: Characterization of left atrial (LA) hemodynamics in paroxysmal atrial fibrillation (PAF) may provide valuable insights for thromboembolic risk. PURPOSE: To evaluate LA vortex formation and velocity distributions by 4D flow MRI and identify associations with age, LA/LV (left ventricle) function, and established risk scores. STUDY TYPE: Prospective clinical. POPULATION: Patients with PAF (n = 45, 46 ± 14 years) and healthy controls (n = 15, 54 ± 9 years) were enrolled. MRI SEQUENCES: 3T standardized cardiac MRI protocol inclusive of 4D flow MRI. ASSESSMENT: Flow analysis planes were prescribed at each pulmonary vein. Velocity distribution analysis and vortex size quantification by the Lambda2 (λ2 ) method were performed in the LA. STATISTICS: Pearson or Spearman's correlation coefficients, r, were calculated to identify relationships between 4D flow-derived LA parameters and age, LA/LV function, and CHA2 DS2 -VASc stroke risk score. Univariate and multivariate determinants of stroke risk were assessed using linear regressions. To compare parameters within multiple groups, one-way analysis of variance or Kruskal-Wallis was used. RESULTS: LA vortice sizes were observed in all subjects using λ2 showing inverse correlations with peak pulmonary vein inflow velocities (P < 0.05), and positive correlations with LA volume (P < 0.05). Vortex size was elevated in PAF at all phases of the cardiac cycle, being most prominent at end early diastole (3.98 ± 1.84 cm3 vs. 6.93 ± 3.11 cm3 , P = 0.001). Velocity distribution analysis showed a greater incidence of flow stasis among patients with PAF (P < 0.05). In univariate regression, vortex size was associated with the CHA2 DS2 -VASc risk score at peak systole (0.457 ± 0.038, P ≤ 0.001). However, in multivariate regression age was the dominant determinant of stroke risk (0.348 ± 0.012, P = 0.006). DATA CONCLUSION: This study demonstrated that LA vortex size is increased among low-risk patients with PAF and is associated with the CHA2 DS2 -VASc risk score. Age remained the dominant determinant of stroke risk. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:871-884.

Hip capsular strain varies between ligaments dependent on both hip position- and applied rotational force.

PURPOSE: To noninvasively characterize the ligament strain in the hip capsule using a novel CT-based imaging technique. METHODS: The superior iliofemoral ligament (SIFL), inferior iliofemoral ligament (IIFL), ischiofemoral ligament (IFL) and pubofemoral ligament (PFL) were identified and beaded in seven cadavers. Specimens were mounted on a joint motion simulator within an O-arm CT scanner in - 15°, 0°, 30°, 60°, and 90° of flexion. 3 Nm of internal rotation (IR) and external rotation (ER) were applied and CT scans obtained. Strains were calculated by comparing bead separation in loaded and unloaded conditions. Repeated-measures ANOVA was used to evaluate differences in strain within ligaments between hip positions. RESULTS: For the SIFL, strain significantly decreased in IR at 30° (p = 0.045) and 60° (p = 0.043) versus 0°. For ER, there were no significant position-specific changes in strain (n.s.). For the IIFL, strain decreased in IR and increased in ER with no significant position-specific differences. For the IFL, strain increased with IR and decreased with ER with no significant position-specific differences. Finally, in the PFL there was a significant flexion angle-by-load interaction (p < 0.001; ES = 0.566), with peak strains noted at 60˚, however pair-wise comparisons failed to identify significant differences between positions (n.s.). Strain decreased in ER, with no significant position-specific differences. CONCLUSION: The SIFL and IIFL limit hip external rotation with greater effect in higher flexion angles, while the IFL and PFL limit hip internal rotation. Following hip arthroscopy, consideration should be given to restricting external rotation as traditional capsulotomies cause injury to the SIFL and IIFL.

Conditional generative adversarial network for 3D rigid-body motion correction in MRI.

PURPOSE: Subject motion in MRI remains an unsolved problem; motion during image acquisition may cause blurring and artifacts that severely degrade image quality. In this work, we approach motion correction as an image-to-image translation problem, which refers to the approach of training a deep neural network to predict an image in 1 domain from an image in another domain. Specifically, the purpose of this work was to develop and train a conditional generative adversarial network to predict artifact-free brain images from motion-corrupted data. METHODS: An open source MRI data set comprising T2 *-weighted, FLASH magnitude, and phase brain images for 53 patients was used to generate complex image data for motion simulation. To simulate rigid motion, rotations and translations were applied to the image data based on randomly generated motion profiles. A conditional generative adversarial network, comprising a generator and discriminator networks, was trained using the motion-corrupted and corresponding ground truth (original) images as training pairs. RESULTS: The images predicted by the conditional generative adversarial network have improved image quality compared to the motion-corrupted images. The mean absolute error between the motion-corrupted and ground-truth images of the test set was 16.4% of the image mean value, whereas the mean absolute error between the conditional generative adversarial network-predicted and ground-truth images was 10.8% The network output also demonstrated improved peak SNR and structural similarity index for all test-set images. CONCLUSION: The images predicted by the conditional generative adversarial network have quantitatively and qualitatively improved image quality compared to the motion-corrupted images.

Eliminating the effects of motion during radiofrequency lesion delivery using a novel contact-force controller.

INTRODUCTION: Catheter-tissue contact force is a determinant of radiofrequency (RF) ablation lesion effectiveness. However, ablation on a beating heart is subject to force variability, making it difficult to optimally deliver consistently durable and transmural lesions. This work evaluates improvements in contact force stability and lesion reproducibility by using a catheter contact-force controller (CFC) during lesion delivery in vitro and in vivo. METHODS AND RESULTS: Using a sheath and force-sensing catheter, an experienced operator attempted to maintain a constant force of 20 g at targets within the atria and left ventricle of a pig manually and using the CFC; the average force and contact-force variation (CFV) achieved using each approach were compared. Ablation lesions (20 W, 30 seconds, 17 mL/min irrigation) were created in bovine tissue samples mounted on a platform programmed to reproduce clinically relevant motion. CFC-assisted lesions were delivered to stationary and moving tissue with forces of 5 to 35 g. Mimicking manual intervention, lesions were also delivered to moving tissue while the CFC was disabled. Resultant lesion volumes were compared using two-way analysis of variance. When using the CFC, the average force was within 1 g of the set level, with a CFV less than 5 g, during both in vitro and in vivo experiments. Reproducible and statistically identical (P = .82) lesion volumes proportional to the set force were achieved in both stationary and moving tissue when the CFC was used. CONCLUSIONS: CFC assistance maintains constant force in vivo and removes effect of motion on lesion volume during RF lesion delivery.

Intervention with citrus flavonoids reverses obesity and improves metabolic syndrome and atherosclerosis in obese Ldlr-/- mice.

Obesity and its associated metabolic dysfunction and cardiovascular disease risk represent a leading cause of adult morbidity worldwide. Currently available pharmacological therapies for obesity have had limited success in reversing existing obesity and metabolic dysregulation. Previous prevention studies demonstrated that the citrus flavonoids, naringenin and nobiletin, protect against obesity and metabolic dysfunction in Ldlr-/- mice fed a high-fat cholesterol-containing (HFHC) diet. However, their effects in an intervention model are unknown. In this report, we show that, in Ldlr-/- mice with diet-induced obesity, citrus flavonoid supplementation to a HFHC diet reversed existing obesity and adipocyte size and number through enhanced energy expenditure and increased hepatic fatty acid oxidation. Caloric intake was unaffected and no evidence of white adipose tissue browning was observed. Reversal of adiposity was accompanied by improvements in hyperlipidemia, insulin sensitivity, hepatic steatosis, and a modest reduction in blood monocytes. Together, this resulted in atherosclerotic lesions that were unchanged in size, but characterized by reduced macrophage content, consistent with a more stable plaque phenotype. These studies further suggest potential therapeutic utility of citrus flavonoids, especially in the context of existing obesity, metabolic dysfunction, and cardiovascular disease.

Single multi-echo GRE acquisition with short and long echo spacing for simultaneous quantitative mapping of fat fraction, B0 inhomogeneity, and susceptibility.

Multi-echo gradient echo (mGRE) sequences have been widely adapted in clinical and scientific practice for different purposes to their capability of performing Dixon MRI, generating multi-contrast images and extracting multi-parametric maps. This work aims to extend mGRE-based techniques for imaging whole head, where further technical developments are required due to the co-existence of fat and large B0 inhomogeneity in regions such as the skull base and neck. Specifically, bipolar mGRE data were acquired with a single sequence that contains both a short echo-spacing (ΔTE) echo train to capture water-fat and B0 phase shifts (for proton density fat-fraction (FF) and B0 mapping) and a longer ΔTE echo train (and long echo times) to capture subtle susceptibility variations and R2* information. The mGRE images covering the whole head (spatial resolution 1.0 × 1.0 × 2.0 mm3) were acquired in 5 min. An automated processing pipeline was implemented to use the FF and B0 maps determined from the short-TE train to compensate for the effects of fat, remove the background phase for whole-head quantitative susceptibility mapping, and reduce the difficulty of spatial phase unwrapping of the long echo-time data. Data from healthy volunteers imaged on a 3 T scanner along with phantom validation are presented. Co-registered quantitative multi-parametric maps (FF, B0 inhomogeneity, R2*, local frequency shift and quantitative susceptibility) and multi-contrast images covering the whole head were successfully generated in processing times of several minutes.

Polymer Assembly Encapsulation of Lanthanide Nanoparticles as Contrast Agents for In Vivo Micro-CT.

Despite recent technological advancements in microcomputed tomography (micro-CT) and contrast agent development, preclinical contrast agents are still predominantly iodine-based. Higher contrast can be achieved when using elements with higher atomic numbers, such as lanthanides; lanthanides also have X-ray attenuation properties that are ideal for spectral CT. However, the formulation of lanthanide-based contrast agents at the high concentrations required for vascular imaging presents a significant challenge. In this work, we developed an erbium-based contrast agent that meets micro-CT imaging requirements, which include colloidal stability upon redispersion at high concentrations, evasion of rapid renal clearance, and circulation times of tens of minutes in small animals. Through systematic studies with poly(ethylene glycol) (PEG)-poly(propylene glycol), PEG-polycaprolactone, and PEG-poly(l-lactide) (PLA) block copolymers, the amphiphilic block copolymer PEG114-PLA53 was identified to be ideal for encapsulating oleate-coated lanthanide-based nanoparticles for in vivo intravenous administration. We were able to synthesize a contrast agent containing 100 mg/mL of erbium that could be redispersed into colloidally stable particles in saline after lyophilization. Contrast enhancement of over 250 HU was achieved in the blood pool for up to an hour, thereby meeting the requirements of live animal micro-CT.

Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE): A Translational, Integrated, and Transdisciplinary Approach.

BACKGROUND: It has been hypothesized that ischemic stroke can cause atrial fibrillation. By elucidating the mechanisms of neurogenically mediated paroxysmal atrial fibrillation, novel therapeutic strategies could be developed to prevent atrial fibrillation occurrence and perpetuation after stroke. This could result in fewer recurrent strokes and deaths, a reduction or delay in dementia onset, and in the lessening of the functional, structural, and metabolic consequences of atrial fibrillation on the heart. METHODS: The Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE) study is an investigator-driven, translational, integrated, and transdisciplinary initiative. It comprises 3 complementary research streams that focus on atrial fibrillation detected after stroke: experimental, clinical, and epidemiological. The experimental stream will assess pre- and poststroke electrocardiographic, autonomic, anatomic (brain and heart pathology), and inflammatory trajectories in an animal model of selective insular cortex ischemic stroke. The clinical stream will prospectively investigate autonomic, inflammatory, and neurocognitive changes among patients diagnosed with atrial fibrillation detected after stroke by employing comprehensive and validated instruments. The epidemiological stream will focus on the demographics, clinical characteristics, and outcomes of atrial fibrillation detected after stroke at the population level by means of the Ontario Stroke Registry, a prospective clinical database that comprises over 23,000 patients with ischemic stroke. CONCLUSIONS: PARADISE is a translational research initiative comprising experimental, clinical, and epidemiological research aimed at characterizing clinical features, the pathophysiology, and outcomes of neurogenic atrial fibrillation detected after stroke.

Method of B0 mapping with magnitude-based correction for bipolar two-point Dixon cardiac MRI.

PURPOSE: The conventional two-point (2pt) Dixon technique explicitly estimates B0 map by performing phase unwrapping. When signal loss, phase singularity, artifacts, or spatially isolated regions corrupt the measured phase images, this unwrapping-based technique will face difficulty. This work aims to improve the reliability of B0 mapping by performing unwrapping error correction. METHOD: To detect the unwrapping-caused phase errors, we determined a magnitude-based fat/water mask and used it as reference to identify pixels being mismatched by the phase-based mask, which was derived from the B0-corrected phase term of the Hermitian product between echoes. Then, we corrected the afore-determined phase error on a region-by-region basis. We tested the developed method with nine patients' data, and the results were compared with a well-established region-growing technique. RESULTS: By adding the step to correct unwrapping-caused error, we improved the robustness of B0 mapping, resulting in better fat-water separation when compared with the conventional 2pt and the phasor-based region-growing techniques. CONCLUSION: We showed the feasibility of B0 mapping with bipolar 2pt human cardiac data. The software is freely available to the scientific community. Magn Reson Med 78:1862-1869, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Susceptibility-weighted imaging using inter-echo-variance channel combination for improved contrast at 7 tesla.

PURPOSE: To implement and optimize a new approach for susceptibility-weighted image (SWI) generation from multi-echo multi-channel image data and compare its performance against optimized traditional SWI pipelines. MATERIALS AND METHODS: Five healthy volunteers were imaged at 7 Tesla. The inter-echo-variance (IEV) channel combination, which uses the variance of the local frequency shift at multiple echo times as a weighting factor during channel combination, was used to calculate multi-echo local phase shift maps. Linear phase masks were combined with the magnitude to generate IEV-SWI. The performance of the IEV-SWI pipeline was compared with that of two accepted SWI pipelines-channel combination followed by (i) Homodyne filtering (HPH-SWI) and (ii) unwrapping and high-pass filtering (SVD-SWI). The filtering steps of each pipeline were optimized. Contrast-to-noise ratio was used as the comparison metric. Qualitative assessment of artifact and vessel conspicuity was performed and processing time of pipelines was evaluated. RESULTS: The optimized IEV-SWI pipeline (σ = 7 mm) resulted in continuous vessel visibility throughout the brain. IEV-SWI had significantly higher contrast compared with HPH-SWI and SVD-SWI (P < 0.001, Friedman nonparametric test). Residual background fields and phase wraps in HPH-SWI and SVD-SWI corrupted the vessel signal and/or generated vessel-mimicking artifact. Optimized implementation of the IEV-SWI pipeline processed a six-echo 16-channel dataset in under 10 min. CONCLUSION: IEV-SWI benefits from channel-by-channel processing of phase data and results in high contrast images with an optimal balance between contrast and background noise removal, thereby presenting evidence of importance of the order in which postprocessing techniques are applied for multi-channel SWI generation. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:1113-1124.

Effect of Left Atrial Wall Thickness on Radiofrequency Ablation Success.

INTRODUCTION: Radiofrequency (RF) ablation in thicker regions of the left atrium (LA) may require increased ablation energy in order to achieve effective transmural lesions. Consequently, many cases of recurrent atrial fibrillation (AF) postablation may be due to thicker-than-normal atrial tissue. The aim of this study was to test the hypotheses that patients with recurrent AF have thicker tissue overall and that electrical reconnection is more likely in regions of thicker tissue. METHODS AND RESULTS: Retrospective analysis was performed on 86 CT images acquired preoperatively from a cohort of 119 patients who had undergone RF ablation for AF. Of these, 33 patients experienced recurrence of AF within 1 year of initial treatment and 29 returned for a repeat ablation. For each patient, LA wall thickness (LAWT) was measured from the images in 12 anatomical regions using custom software. Patients with recurrent AF had larger LAWT compared to successfully treated patients (1.6 ± 0.6 mm vs. 1.5 ± 0.5 mm, P < 0.001) and reconnection was found to be at regions of thicker tissue (1.6 ± 0.6 mm, P = 0.038) compared to nonreconnected regions (1.5 ± 0.5 mm). The superior right posterior wall of the LA was significantly related to both recurrence (P = 0.048) and reconnection (P = 0.014). CONCLUSION: Increased LAWT has a small but significant effect on postablation recurrence and reconnection. Measures of LAWT may facilitate appropriate dosing of RF energy, but other factors will be critical in transmural lesion formation and ablation success.

Method for B0 off-resonance mapping by non-iterative correction of phase-errors (B0-NICE).

PURPOSE: To develop and evaluate a multiecho phase-unwrapping-based B0 mapping method. METHODS: The proposed method estimates a B0 map by Non-Iterative Correction of phase-Errors (B0-NICE). The B0-NICE method generates an initial B0 map from a "pseudo in-phase" data set by introducing a bias frequency shift to the multipeak fat model, followed by correcting the phase errors using both phase and magnitude information. The performance of the B0-NICE method was evaluated with all data cases from the 2012 ISMRM Challenge. RESULTS: The B0 field estimates from B0-NICE were compared with those generated by GlObally Optimal Surface Estimation (GOOSE). In the presence of large B0 inhomogeneity, the B0-NICE method was able to generate more realistic B0 maps from multiecho data, compared with GOOSE. Accurate estimation of fat-fraction (FF) map was also achieved using the proposed algorithm. CONCLUSION: The primary finding of the present study is that accurate FF and B0 maps are achievable if magnitude data is processed independently and used to correct phase errors existing in B0 maps generated by phase unwrapping. The B0-NICE software is freely available to the scientific community.

Inter-echo variance as a weighting factor for multi-channel combination in multi-echo acquisition for local frequency shift mapping.

PURPOSE: To develop and evaluate a local frequency shift (LFS) mapping method specifically designed for multi-echo acquisitions and multi-channel receive coils. METHODS: The proposed method uses the pixel-by-pixel inter-echo variance (IEV) as a weighting factor during channel-combination. Five healthy volunteers were scanned at 7 T. The IEV-weighted method was quantitatively compared to established (adaptive and Hermitian product) channel-combination methods with respect to IEV of LFS over the entire brain. RESULTS: In all experiments, the IEV-weighted method generated LFS maps free of artifacts caused by unwrapping errors. Based on measurements of the inter-echo frequency variance throughout the whole brain, the IEV-weighted method produced the lowest variation and the best contrast at the edge of the brain. CONCLUSION: The primary finding of the present study is that accurate LFS maps are achievable if the data from each channel is processed independently prior to combination followed by a weighted combination using IEV as the weighting term. The software is freely available to the scientific community.

Influence of phase correction of late gadolinium enhancement images on scar signal quantification in patients with ischemic and non-ischemic cardiomyopathy.

BACKGROUND: Myocardial fibrosis imaging using late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) has been validated as a quantitative predictive marker for response to medical, surgical, and device therapy. To date, all such studies have examined conventional, non-phase corrected magnitude images.  However, contemporary practice has rapdily adopted phase-corrected image reconstruction. We sought to investigate the existence of any systematic bias between threshold-based scar quantification performed on conventional magnitude inversion recovery (MIR) and matched phase sensitive inversion recovery (PSIR) images. METHODS: In 80 patients with confirmed ischemic (N = 40), or non-ischemic (n = 40) myocardial fibrosis, and also in a healthy control cohort (N = 40) without fibrosis, myocardial late enhancement was quantified using a Signal Threshold Versus Reference Myocardium technique (STRM) at ≥2, ≥3, and ≥5 SD threshold, and also using the Full Width at Half Maximal (FWHM) technique. This was performed on both MIR and PSIR images and values compared using linear regression and Bland-Altman analyses. RESULTS: Linear regression analysis demonstrated excellent correlation for scar volumes between MIR and PSIR images at all three STRM signal thresholds for the ischemic (N = 40, r = 0.96, 0.95, 0.88 at 2, 3, and 5 SD, p < 0.0001 for all regressions), and non ischemic (N = 40, r = 0.86, 0.89, 0.90 at 2, 3, and 5 SD, p < 0.0001 for all regressions) cohorts. FWHM analysis demonstrated good correlation in the ischemic population (N = 40, r = 0.83, p < 0.0001). Bland-Altman analysis demonstrated a systematic bias with MIR images showing higher values than PSIR for ischemic (3.3 %, 3.9 % and 4.9 % at 2, 3, and 5 SD, respectively), and non-ischemic (9.7 %, 7.4 % and 4.1 % at ≥2, ≥3, and ≥5 SD thresholds, respectively) cohorts. Background myocardial signal measured in the control population demonstrated a similar bias of 4.4 %, 2.6 % and 0.7 % of the LV volume at 2, 3 and 5 SD thresholds, respectively. The bias observed using FWHM analysis was -6.9 %. CONCLUSIONS: Scar quantification using phase corrected (PSIR) images achieves values highly correlated to those obtained on non-corrected (MIR) images. However, a systematic bias exists that appears exaggerated in non-ischemic cohorts. Such bias should be considered when comparing or translating knowledge between MIR- and PSIR-based imaging.

Stress-inducible phosphoprotein 1 has unique cochaperone activity during development and regulates cellular response to ischemia via the prion protein.

Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the STI1 gene, supported a unique role for STI1 during embryonic development. The response of STI1 haploinsufficient mice to cellular stress seemed compromised, and mutant mice showed increased vulnerability to ischemic insult. At the cellular level, ischemia increased the secretion of STI1 from wild-type astrocytes by 3-fold, whereas STI1 haploinsufficient mice secreted half as much STI1. Interesting, extracellular STI1 prevented ischemia-mediated neuronal death in a prion protein-dependent way. Our study reveals essential roles for intracellular and extracellular STI1 in cellular resilience.

Mice with selective elimination of striatal acetylcholine release are lean, show altered energy homeostasis and changed sleep/wake cycle.

Cholinergic neurons are known to regulate striatal circuits; however, striatal-dependent physiological outcomes influenced by acetylcholine (ACh) are still poorly under;?>stood. Here, we used vesicular acetylcholine transporter (VAChT)(D2-Cre-flox/flox) mice, in which we selectively ablated the vesicular acetylcholine transporter in the striatum to dissect the specific roles of striatal ACh in metabolic homeostasis. We report that VAChT(D) (2-Cre-flox/flox) mice are lean at a young age and maintain this lean phenotype with time. The reduced body weight observed in these mutant mice is not attributable to reduced food intake or to a decrease in growth rate. In addition, changed activity could not completely explain the lean phenotype, as only young VAChT(D) (2-Cre-flox/flox) mice showed increased physical activity. Interestingly, VAChT(D) (2-Cre-flox/flox) mice show several metabolic changes, including increased plasma levels of insulin and leptin. They also show increased periods of wakefulness when compared with littermate controls. Taken together, our data suggest that striatal ACh has an important role in the modulation of metabolism and highlight the importance of striatum cholinergic tone in the regulation of energy expenditure. These new insights on how cholinergic neurons influence homeostasis open new avenues for the search of drug targets to treat obesity.

Validation of sub-segmental visual scoring for the quantification of ischemic and nonischemic myocardial fibrosis using late gadolinium enhancement MRI.

PURPOSE: To determine the accuracy and reproducibility of late gadolinium enhancement (LGE) MRI scar quantification using visual sub-segmental analysis (VSSA) versus signal threshold-based analysis in ischemic and nonischemic cardiomyopathy. MATERIALS AND METHODS: One-hundred sixty-one patients with abnormal LGE imaging underwent VSSA and signal threshold-based analysis. VSSA was performed using a 68 sub-segmental model. Signal threshold-based analysis was performed using cutoffs of ≥2, ≥3, and ≥5 standard deviations (SD) above the mean signal of normal myocardium. Comparison of VSSA and signal threshold-based analysis was performed by linear regression and Bland Altman plots. RESULTS: Seventy (44%) patients had ischemic scar, 76 (47%) had nonischemic scar, and 15 (9%) had a combined pattern. Correlation coefficients for VSSA versus signal threshold-based analysis at ≥2, ≥3, and ≥5SD thresholds were r = 0.63, r = 0.79, r = 0.81 (P < 0.001) for all patients, r = 0.74, r = 0.81, r = 0.81 (P < 0.001) in those with ischemic scar, and r = 0.46, r = 0.69, r = 0.72 (P < 0.001) in those with nonischemic scar. Bland Altman analysis revealed no significant bias in total scar volume among all patients (-4.3 ± 7.9%), those with ischemic scar (-4.8 ± 7.8%), or those with nonischemic scar (-2.6 ± 7.6%). Intra-observer and inter-observer variability of the VSSA technique was excellent with a mean difference in total percent scar of 0.3% (-8.3-8.9%) and -0.4% (-9.5-8.5%), respectively. CONCLUSION: A VSSA-based model of myocardial scar quantification is accurate and reproducible in ischemic and nonischemic cardiomyopathy.