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OBJECTIVES Clinical assessment of uterine artery (UtA) hemodynamics is currently limited to Doppler ultrasound (US) velocimetry. We have demonstrated previously the feasibility of applying four-dimensional (4D) flow magnetic resonance imaging (MRI) to evaluate UtA hemodynamics during pregnancy, allowing flow quantification of the entire course of the vessel. In this study, we sought to further validate the physiological relevance of 4D flow MRI measurement of UtA blood flow by exploring its association with pregnancy outcome relative to US-based metrics. METHODS Recruited into this prospective, cross-sectional study were 87 women with a singleton pregnancy who underwent 4D flow MRI between May 2016 and April 2019 to measure the UtA pulsatility index (MRI-PI) and blood flow rate (MRI-flow, in mL/min). UtA-PI was also measured using US (US-PI). The primary outcome was a composite (COMP) of pre-eclampsia (PE) and/or small-for-gestational-age (SGA) neonate, and secondary outcomes were PE and SGA neonate individually. We assessed the ability of MRI-flow, MRI-PI and US-PI to distinguish between outcomes, and evaluated whether MRI-flow changed as gestation progressed. RESULTS Following 4D flow postprocessing and exclusions from the analysis, 74 women had 4D flow MRI data analyzed for both UtAs. Of these, 18 developed a COMP outcome: three developed PE only, 11 had a SGA neonate only and four had both. A comparison of the COMP group vs the no-COMP group found no differences in maternal age, body mass index, nulliparity, gravidity or race. For 66 of the 74 subjects, US data were also available. In these subjects, both median MRI-PI (0.95 vs 0.70; P

This study was to evaluate the effects of ischemic mitral regurgitation (IMR) on vortex formation and leaflet dynamics using an established porcine infarct model of IMR. Using direct coronary ligation, five animals were subjected to a posterolateral myocardial infarction (MI) followed by an MRI at 12-weeks post MI. MR imaging consisted of 4D time-resolved left ventricular (LV) flow, full coverage 2D LV cine, and high resolution 2D cine of mitral valve dynamics. Five additional naive animals underwent identical imaging protocols to serve as controls. Image analysis was performed to obtain mitral transvalvular flows as well as LV volumes throughout the cardiac cycle. In addition, anterior to posterior mid-leaflet tip distances were measured throughout the cardiac cycle for determination of temporal leaflet dynamics. It was found IMR caused asymmetric vortex ring formation with the anterior vortex having a lower vorticity relative to its posterior counterpart. In contrast, normal ventricles create symmetric and tightly curled vortices in the basal chamber just underneath the mitral leaflets which conserve kinetic energy and aid in effective ejection. IMR animals were also evaluated for leaflet separation and were found to have a greater leaflet opening and achieved peak vorticity and peak leaflet opening later than control animals. In conclusion, this study shows the effects that altered vortex formation, due to IMR, can have on ventricular filling and leaflet dynamics. These findings have important implications for understanding blood flow through the dilated heart and how ring annuloplasty and volume reduction interventions may influence mitral valve dynamics.

Hypertensive pregnancy disorders (HPDs), such as pre-eclampsia, are leading sources of both maternal and fetal morbidity in pregnancy. Noninvasive imaging, such as ultrasound (US) and magnetic resonance imaging (MRI), is an important tool for predicting and monitoring these high risk pregnancies. While imaging can measure hemodynamic parameters, such as uterine artery pulsatility and resistivity indices (PI and RI), the interpretation of such metrics for disease assessment relies on ad hoc standards, which provide limited insight to the physical mechanisms underlying the emergence of hypertensive pregnancy disorders. To provide meaningful interpretation of measured hemodynamic data in patients, advances in computational fluid dynamics can be brought to bear. In this work, we develop a patient-specific computational framework that combines Bayesian inference with a reduced-order fluid dynamics model to infer parameters, such as vascular resistance, compliance, and vessel cross-sectional area, known to be related to the development of hypertension. The proposed framework enables the prediction of hemodynamic quantities of interest, such as pressure and velocity, directly from sparse and noisy MRI measurements. We illustrate the effectiveness of this approach in two systemic arterial network geometries: an aorta with branching carotid artery and a maternal pelvic arterial network. For both cases, the model can reconstruct the provided measurements and infer parameters of interest. In the case of the maternal pelvic arteries, the model can make a distinction between the pregnancies destined to develop hypertension and those that remain normotensive, expressed through the value range of the predicted absolute pressure.

To explore the presence of new resonances beyond 9.4 ppm from the human brain, down-field proton MRS was performed in vivo in the human brain on 6 healthy volunteers at 7 T.To maximize the SNR, a large voxel was placed within the brain to cover the maximal area in such a way that sinus cavities were avoided. A spectrally selective 90° E-BURP pulse with an excitation bandwidth of 2 ppm was used to probe the spectral chemical shift range between 9.1 and 10.5 ppm. The E-BURP pulse was integrated with PRESS spatial localization to obtain non-water-suppressed proton MR spectra from the desired spectral region.In the down-field proton MRS obtained from all of the volunteers scanned, we identified a new peak consistently resonating at 10.1 ppm. Protons associated with this resonance are in cross-relaxation with the bulk water, as demonstrated by the water saturation and deuterium exchange experiments.Based on the chemical shift, this new peak was identified as the indole (-NH) proton of l-tryptophan (l-TRP) and was further confirmed from phantom experiments on l-TRP. These promising preliminary results potentially pave the way to investigate the role of cerebral metabolism of l-TRP in healthy and disease conditions.

The purpose of this systematic review is to identify trends and extent of variability in intracranial vessel wall MR imaging (VWI) techniques and protocols. Although variability in selection of protocol design and pulse sequence type is known, data on what and how protocols vary are unknown. Three databases were searched to identify publications using intracranial VWI. Publications were screened by predetermined inclusion/exclusion criteria. Technical development publications were scored for completeness of reporting using a modified Nature Reporting Summary Guideline to assess reproducibility. From 2,431 articles, 122 met the inclusion criteria. Trends over the last 23 years (1995-2018) show increased use of 3-Tesla MR (P < .001) and 3D volumetric T1-weighted acquisitions (P < .001). Most (65%) clinical VWI publications report achieving a noninterpolated in-plane spatial resolution of ≤.55 mm. In the last decade, an increasing number of technical development (n = 20) and 7 Tesla (n = 12) publications have been published, focused on pulse sequence development, improving cerebrospinal fluid suppression, scan efficiency, and imaging ex vivo specimen for histologic validation. Mean Reporting Summary Score for the technical development publications was high (.87, range: .63-1.0) indicating strong scientific technical reproducibility. Innovative work continues to emerge to address implementation challenges. Gradual adoption into the research and scientific community was suggested by a shift in the name in the literature from "high-resolution MR" to "vessel wall imaging," specifying diagnostic intent. Insight into current practices and identifying the extent of technical variability in the literature will help to direct future clinical and technical efforts to address needs for implementation.

Chronic excessive alcohol use has neurotoxic effects, which may contribute to cognitive decline and the risk of early-onset dementia. Elevated peripheral iron levels have been reported in individuals with alcohol use disorder (AUD), but its association with brain iron loading has not been explored. We evaluated whether (1) serum and brain iron loading are higher in individuals with AUD than non-dependent healthy controls and (2) serum and brain iron loading increase with age. A fasting serum iron panel was obtained and a magnetic resonance imaging scan with quantitative susceptibility mapping (QSM) was used to quantify brain iron concentrations. Although serum ferritin levels were higher in the AUD group than in controls, whole-brain iron susceptibility did not differ between groups. Voxel-wise QSM analyses revealed higher susceptibility in a cluster in the left globus pallidus in individuals with AUD than controls. Whole-brain iron increased with age and voxel-wise QSM indicated higher susceptibility with age in various brain areas including the basal ganglia. This is the first study to analyze both serum and brain iron loading in individuals with AUD. Larger studies are needed to examine the effects of alcohol use on iron loading and its associations with alcohol use severity, structural and functional brain changes, and alcohol-induced cognitive impairments.

Hypertensive pregnancy disorders, such as preeclampsia, are leading sources of both maternal and fetal morbidity in pregnancy. Non-invasive imaging, such as ultrasound and magnetic resonance imaging (MRI), is an important tool in predicting and monitoring these high risk pregnancies. While imaging can measure hemodynamic parameters, such as uterine artery pulsatility and resistivity indices, the interpretation of such metrics for disease assessment rely on ad-hoc standards, which provide limited insight to the physical mechanisms underlying the emergence of hypertensive pregnancy disorders. To provide meaningful interpretation of measured hemodynamic data in patients, advances in computational fluid dynamics can be brought to bear. In this work, we develop a patient-specific computational framework that combines Bayesian inference with a reduced-order fluid dynamics model to infer remodeling parameters, such as vascular resistance, compliance and vessel cross-sectional area, known to be related to the development of hypertension. The proposed framework enables the prediction of hemodynamic quantities of interest, such as pressure and velocity, directly from sparse and noisy MRI measurements. We illustrate the effectiveness of this approach in two systemic arterial network geometries: an aorta with carotid and a maternal pelvic arterial network. For both cases, the model can reconstruct the provided measurements and infer parameters of interest. In the case of the maternal pelvic arteries, the model can make a distinction between the pregnancies destined to develop hypertension and those that remain normotensive, expressed through the value range of the predicted absolute pressure.

BACKGROUND Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) tumor microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, here we investigated non-invasive quantitative susceptibility mapping (QSM) and T2* MRI relaxometry to quantify iron as imaging biomarkers for TAMs in adult patients with GBM. METHODS In this prospective study, 21 adult patients with GBM were enrolled between 2016 to 2019. Patients underwent a 3D single echo gradient echo sequence in addition to standard anatomical sequences on a 3 Tesla MRI. QSM images were reconstructed using the morphology-enabled dipole inversion (MEDI) algorithm. In 3 subjects, ex vivo imaging of surgical specimens was performed on a Bruker 9.4 Tesla 8.9 cm vertical bore MR using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated by a pixel-wise monoexponential fitting. Each specimen was stained with hematoxylin and eosin, as well as with CD68, CD86, CD206, and L-Ferritin. RESULTS Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the L-ferritin positivity percent (r =0.56, p=0.018) and the combination of tumor’s enhancing zone and necrotic core and the L-Ferritin positivity percent (r=0.72; p=0.001). Moreover, the mean susceptibility significantly correlated with positivity percent for CD68 (ρ=0.52, p=0.034) and CD86 (r=0.7 p=0.001), but not for CD206 (ρ=0.09; p=0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r =0.6, p=0.016). Similarly, mean R2* values significantly correlated with CD86 (r=0.54, p=0.03) but not with CD206 (r=0.15, p=0.5). High mean susceptibility in the necrotic core was associated with inferior PFS (hazard ratio,4.5, p=0.016). CONCLUSION MR Susceptibility Imaging can quantify the iron content of GBM and provide a non-invasive method for TAM quantification and phenotyping.

Purpose Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, we investigated MRI to quantify iron as an imaging biomarker for TAMs in GBM patients. Methods 21 adult patients with GBM underwent a 3D single echo gradient echo MRI sequence and quantitative susceptibility maps were generated. In 3 subjects, ex vivo imaging of surgical specimens was performed on a 9.4 Tesla MRI using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated. Each specimen was stained with hematoxylin and eosin, as well as CD68, CD86, CD206, and L-Ferritin. Results Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the L-ferritin positivity percent (r =0.56, p=0.018) and the combination of tumor’s enhancing zone and necrotic core and the L-Ferritin positivity percent (r=0.72; p=0.001). The mean susceptibility significantly correlated with positivity percent for CD68 (ρ = 0.52, p=0.034) and CD86 (r=0.7 p=0.001), but not for CD206 (ρ = 0.09; p=0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r =0.6, p=0.016). Similarly, mean R2* values significantly correlated with CD86 (r=0.54, p=0.03) but not with CD206 (r=0.15, p=0.5). Conclusion MR quantitative susceptibility mapping can quantify the iron content of GBM and provide a non-invasive method for TAM quantification and phenotyping.

Nonalcoholic fatty liver disease is common and highly heritable. Genetic studies of hepatic fat have not sufficiently addressed non-European and rare variants. In a medical biobank, we quantitate hepatic fat from clinical computed tomography (CT) scans via deep learning in 10,283 participants with whole-exome sequences available. We conduct exome-wide associations of single variants and rare predicted loss-of-function (pLOF) variants with CT-based hepatic fat and perform cross-modality replication in the UK Biobank (UKB) by linking whole-exome sequences to MRI-based hepatic fat. We confirm single variants previously associated with hepatic fat and identify several additional variants, including two (FGD5 H600Y and CITED2 S198_G199del) that replicated in UKB. A burden of rare pLOF variants in LMF2 is associated with increased hepatic fat and replicates in UKB. Quantitative phenotypes generated from clinical imaging studies and intersected with genomic data in medical biobanks have the potential to identify molecular pathways associated with human traits and disease.

Background Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity. T1ρ utilizes a spin-lock pulse to decrease the effect of unwanted relaxation. The objective of this study was to study T1ρ as compared to T1, ECV, and LGE in HCM patients. Methods HCM patients were recruited as part of the Novel Markers of Prognosis in Hypertrophic Cardiomyopathy study, and healthy controls were matched for comparison. In addition to cardiac functional imaging, subjects underwent T1 and T1ρ cardiovascular magnetic resonance imaging at short-axis positions at 1.5T. Subjects received gadolinium and underwent LGE imaging 15–20 min after injection covering the entire heart. Corresponding basal and mid short axis LGE slices were selected for comparison with T1 and T1ρ. Full-width half-maximum thresholding was used to determine the percent enhancement area in each LGE-positive slice by LGE, T1, and T1ρ. Two clinicians independently reviewed LGE images for presence or absence of enhancement. If in agreement, the image was labeled positive (LGE + +) or negative (LGE −−); otherwise, the image was labeled equivocal (LGE + −). Results In 40 HCM patients and 10 controls, T1 percent enhancement area (Spearman’s rho = 0.61, p Conclusions Hyperenhancement areas as measured by T1ρ and LGE are moderately correlated. T1, T1ρ, and ECV were elevated in HCM patients compared to controls, irrespective of the presence of LGE. These findings warrant additional studies to investigate the prognostic utility of T1ρ imaging in the evaluation of HCM patients.

PURPOSE Reliable monitoring of tissue nicotinamide adenine dinucleotide (NAD+ ) concentration may provide insights on its roles in normal and pathological aging. In the present study, we report a 1 H MRS pulse sequence for the in vivo, localized 1 H MRS detection of NAD+ from the human brain. METHODS Studies were carried out on a 7T Siemens MRI scanner using a 32-channel product volume coil. The pulse sequence consisted of a spectrally selective low bandwidth E-BURP-1 90° pulse. PRESS localization was achieved using optimized Shinnar-Le Roux 180° pulses and overlapping gradients were used to minimize the TE. The reproducibility of NAD+ quantification was measured in 11 healthy volunteers. The association of cerebral NAD+ with age was assessed in 16 healthy subjects 26-78 years old. RESULTS Spectra acquired from a voxel placed in subjects' occipital lobe consisted of downfield peaks from the H2 , H4 , and H6 protons of the nicotinamide moiety of NAD+ between 8.9-9.35 ppm. The mean ± SD within-session and between-session coefficients of variation were found to be 6.14 ± 2.03% and 6.09 ± 3.20%, respectively. In healthy volunteers, an age-dependent decline of the NAD+ levels in the brain was also observed (β = -1.24 μM/y, SE = 0.21, P < 0.001). CONCLUSION We demonstrated the feasibility and robustness of a newly developed 1 H MRS technique to measure localized cerebral NAD+ at 7T MRI using a commercially available RF head coil. This technique may be further applied to detect and quantify NAD+ from different regions of the brain as well as from other tissues.

Opiates play an important role in the control of pain associated with thoracotomy in both people and animals. However, key side effects, including sedation and respiratory depression, could limit the use of opiates in animals that are lethargic due to cardiac disease. In addition, a rare side effect-neuroexcitation resulting in pathologic behavioral changes (seizures, mania, muscle fasciculation)-after the administration of morphine or hydromorphone is well-documented in many species. In pigs, however, these drugs have been shown to stimulate an increase in normal activity. In the case presented, we describe a Yorkshire-cross pig which, after myocardial infarction surgery, went from nonresponsive to alert, responsive, and eating within 30 min of an injection of hydromorphone. This pig was not demonstrating any signs associated with pain at this time, suggesting that the positive response was due to neural stimulation. This case report is the first to describe the use of hydromorphone-a potent, pure μ opiate agonist-for its neurostimulatory effect in pigs with experimentally-induced cardiac disease.

Injectable biomaterials are being developed for a wide range of biomedical applications; however, characterization of materials (e.g., distribution, chemical composition) after injection is often difficult and relies on invasive and destructive procedures. To address this problem, this study utilizes a new magnetic resonance imaging (MRI) acquisition technique based on chemical exchange saturation transfer (CEST), where the signal relies on the exchange of protons in specific molecules with bulk water protons. Such a signal can be generated from specific functional groups endogenous to or engineered into a desired material. Here, CEST MRI was used to visualize injectable hyaluronic acid (HA) hydrogels either alone or after injection into tissue. The CEST effect was shown to track with changes in material properties-as hydrogel macromer concentration was increased, the CEST contrast increased linearly. Furthermore, CEST MRI was used to detect hydrogels injected into cardiac explants with an increase in signal at the hydrogel site relative to the surrounding myocardial signal. Unlike conventional MRI, CEST can simultaneously visualize and discriminate between different injectable materials based on their unique chemistry. To illustrate this, we tuned the CEST signal to detect differences in two hydrogel systems based on their dominant functional groups. The covalent addition of an arginine-based peptide to HA hydrogels led to a 2-fold increase in signal when the exchangeable amine (-NH

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic alanine aminotransferase elevation (cALT) without other liver diseases, we performed a trans-ancestry genome-wide association study in the Million Veteran Program including 90,408 cALT cases and 128,187 controls. In the Discovery stage, seventy-seven loci exceeded genome-wide significance – including 25 without prior NAFLD or ALT associations – with one additional locus identified in European-American-only and two in African-American-only analyses (P-8). External replication in cohorts with NAFLD defined by histology (7,397 cases, 56,785 controls) or liver fat extracted from radiologic imaging (n=44,289) validated 17 SNPs (P-4) of which 9 were novel (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH, and IFI30). Pleiotropy analysis showed that 61 of 77 trans-ancestry and all 17 validated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P < 5 × 10(−8)). External replication in histology-defined NAFLD cohorts (7,397 cases and 56,785 controls) or radiologic imaging cohorts (n = 44,289) replicated 17 single-nucleotide polymorphisms (SNPs) (P < 6.5 × 10(−4)), of which 9 were new (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH and IFI30). Pleiotropy analysis showed that 61 of 77 multiancestry and all 17 replicated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD.

Quantitative traits obtained from computed tomography (CT) scans performed in routine clinical practice have the potential to enhance translational research and genomic discovery when linked to electronic health record (EHR) and genomic data. For example, both liver fat and abdominal adipose mass are highly relevant to human disease; non-alcoholic fatty liver disease(NAFLD) is present in 30% of the US adult population, is strongly associated with obesity, and can progress to hepatic inflammation, cirrhosis, and hepatocellular carcinoma. We built a fully automated image curation and organ labeling technique using deep learning to identify liver, spleen, subcutaneous and visceral fat compartments in the abdomen and extract 12 quantitative imaging traits from 161,748 CT scans in 19,624 patients enrolled in the Penn Medicine Biobank (PMBB). The average liver fat, as defined by a difference in attenuation between spleen and liver, was −6.4 ± 9.1 Hounsfield units (HU). In 135 patients who had undergone both liver biopsy and imaging, receiver operating characteristic (ROC) analysis revealed an area under the curve(AUC) of 0.81 for hepatic steatosis. The mean fat volume within the abdominal compartment for subcutaneous fat was 4.9 ± 3.1 L and for visceral fat was 2.9 ± 2.1 L. We performed integrative analyses of liver fat with the phenome extracted from the EHR and found highly significant associations with chronic liver disease/cirrhosis, chronic non-alcoholic liver disease, diabetes mellitus, obesity, hypertension, renal failure, alcoholism, hepatitis C, use of therapeutic adrenal cortical steroids, respiratory failure and pancytopenia. Liver fat was significantly associated with two of the most robust genetic variants associated with NAFLD, namely rs738409 in PNPLA3 and rs58542926 in TM6SF2. Finally, we performed multivariate principle component analysis (PCA) to show the importance of each of the quantitative imaging traits to NAFLD and their interrelationships with the phenome. This work demonstrates the power of automated image quantitative trait analyses applied to routine clinical imaging studies to fuel translational scientific discovery.

BACKGROUND Uterine artery (UtA) hemodynamics might be used to predict risk of hypertensive pregnancy disorders, including preeclampsia and intrauterine growth restriction. PURPOSE OR HYPOTHESIS To determine the feasibility of 4D flow MRI in pregnant subjects by characterizing UtA anatomy, computing UtA flow, and comparing UtA velocity, and pulsatility and resistivity indices (PI, RI) with transabdominal Doppler ultrasound (US). STUDY TYPE Prospective cross-sectional study from June 6, 2016, to May 2, 2018. POPULATION OR SUBJECTS OR PHANTOM OR SPECIMEN OR ANIMAL MODEL Forty-one singleton pregnant subjects (age [range] = 27.0 ± 5.9 [18-41] years) in their second or third trimester. We additionally scanned three subjects who had prepregnancy diabetes or chronic hypertension. FIELD STRENGTH/SEQUENCE The subjects underwent UtA and placenta MRI using noncontrast angiography and 4D flow at 1.5T. ASSESSMENT UtA anatomy was described based on 4D flow-derived noncontrast angiography, while UtA flow properties were characterized by net flow, systolic/mean/diastolic velocity, PI and RI through examination of 4D flow data. PI and RI are standard hemodynamic parameters routinely reported on Doppler US. STATISTICAL TESTS Spearman's rank correlation, Wilcoxon signed rank tests, and Bland-Altman plots were used to preliminarily investigate the relationships between flow parameters, gestational age, and Doppler US. or RESULTS: 4D flow MRI and UtA flow quantification was feasible in all subjects. There was considerable heterogeneity in UtA geometry in each subject between left and right UtAs and between subjects. Mean 4D flow-based parameters were: mean bilateral flow rate = 605.6 ± 220.5 mL/min, PI = 0.72 ± 0.2, and RI = 0.47 ± 0.1. Bilateral flow did not change with gestational age. We found that MRI differed from US in terms of lower PI (mean difference -0.1) and RI (mean difference

OBJECTIVE We assessed whether poor glycemic control is associated with an increase in myocardial fibrosis among adults with diabetes. RESEARCH DESIGN AND METHODS We studied 47 adults with type 2 diabetes and stratified them into three groups according to their hemoglobin A1c (HbA1c) level: 7.5% (group 3; n = 15). Left ventricular (LV) mass was assessed using cardiac MRI. The extracellular volume fraction (ECVF), an index of myocardial fibrosis, was measured by using myocardial T1 mapping before and after the administration of a gadolinium-based contrast agent. RESULTS Mean HbA1c was 5.84 ± 0.16%, 6.89 ± 0.14%, and 8.57 ± 0.2% in groups 1, 2, and 3, respectively. LV mass was not significantly different between the groups. The myocardial ECVF was significantly greater in groups 2 (mean 27.6% [95% CI 24.8–30.3]) and 3 (27.6% [24.4–30.8]) than in group 1 (21.1% [17.5–24.7]; P = 0.015). After adjusting for age, sex, BMI, blood pressure, and estimated glomerular filtration rate, the myocardial ECVF was significantly greater in groups 2 (27.4% [24.4–30.4]) and 3 (28% [24.5–31.5]) than in group 1 (20.9% [17.1–24.6]; P = 0.0156, ANCOVA). CONCLUSIONS An increased myocardial ECVF, suggesting myocardial fibrosis, is independently associated with poor glycemic control among adults with diabetes. Further research should assess whether tight glycemic control can revert fibrosis to healthy myocardium or ameliorate it and its adverse clinical consequences.

Background: Pulmonary arterial hypertension (PAH) and severe aortic valve stenosis (AS) are diseases characterized by increased afterload of the right and left heart, respectively. Our study aims to investigate the differences of myocardial tissue characteristics in the pressure overloaded left and right hearts, especially in the shared interventricular septum, as detected by native T1 and T2 relaxation times. Methods: Eighteen patients with PAH and 19 patients with severe AS in addition to 5 healthy volunteers underwent 1.5-T CMR examination with native T1 and T2 mapping. Mean T1 and T2 value were measured at the right ventricular (RV) free wall, superior RV insertion, inferior RV insertion, interventricular septum and left ventricular (LV) lateral wall. Results: Compared with controls and AS group, T1 was significantly elevated in the RV insertion in PAH group (P=0.015), while no statistically significant differences were seen in other segments among the three groups. There was an increase of T2 in the RV insertion in AS and PAH groups (P=0.01). Significant T2 elevation was also observed in the RV free wall of PAH group, and the LV lateral wall of AS group compared with the control group. RV insertion T2 was significantly correlated with RV end-diastolic volume index (r=0.608, P=0.016) and RV mass index (r=0.57, P=0.026) in the PAH group. LV lateral wall T2 and RV insertion T2 were significantly correlated with aortic valve mean gradients in the AS group (r=0.56, P=0.02; r=0.58, P=0.01, respectively). Conclusions: In pressure overload diseases, both T1 and T2 values increase in the myocardium. The alterations seen in the RV insertion sites in the septum was more pronounced with RV pressure overload. T2 values also correlated with structural and functional remodeling in both diseases. Combining T1 and T2 mapping may help to better characterize the alternation of myocardial composition in pressure overloaded heart diseases.

Conventional X-ray mammography has low diagnostic sensitivity for women with dense breasts. As a result, alternative contrast-enhanced screening tools such as dual energy mammography (DEM), computed tomography (CT), magnetic resonance imaging (MRI), and near-infrared fluorescence (NIRF) imaging are being used or investigated for these women. However, currently available contrast agents are non-ideal, have safety issues, and each imaging technique requires a different contrast agent. We therefore sought to develop a multimodal contrast agent that is functional for each breast imaging modality to simplify the diagnosis process and address the issues of existing contrast agents. Herein, we present a novel “all-in-one” nanoparticle (AION) multimodal imaging probe that has potent DEM, CT, MRI, and NIRF contrast properties and improved biocompatibility. AION were formed by co-encapsulation of a near-infrared fluorophore (DiR), silver sulfide nanoparticles (Ag(2)S-NP), and iron oxide nanoparticles (IO-NP) in PEGylated micelles. AION showed negligible cytotoxicity, which was in agreement with its minimal silver ion release profiles. AION generated strong contrast with all imaging modalities as demonstrated in phantom imaging. AION allowed in vivo tumor imaging as evidenced by the increase in contrast after injection. This study indicates the potential of AION as an effective multimodal contrast agent for breast cancer diagnosis with a range of imaging methods.

Background Segmented cine cardiac MRI combines data from multiple heartbeats to achieve high spatiotemporal resolution cardiac images, yet predefined k-space segmentation trajectories can lead to suboptimal k-space sampling. In this work, we developed and evaluated an autonomous and closed-loop control system for radial k-space sampling (ARKS) to increase sampling uniformity. Methods The closed-loop system autonomously selects radial k-space sampling trajectory during live segmented cine MRI and attempts to optimize angular sampling uniformity by selecting views in regions of k-space that were not previously well-sampled. Sampling uniformity and the ability to detect cardiac phase in vivo was assessed using ECG data acquired from 10 normal subjects in an MRI scanner. The approach was then implemented with a fast gradient echo sequence on a whole-body clinical MRI scanner and imaging was performed in 4 healthy volunteers. The closed-loop k-space trajectory was compared to random, uniformly distributed and golden angle view trajectories via measurement of k-space uniformity and the point spread function. Lastly, an arrhythmic dataset was used to evaluate a potential application of the approach. Results The autonomous trajectory increased k-space sampling uniformity by 15±7%, main lobe point spread function (PSF) signal intensity by 6±4%, and reduced ringing relative to golden angle sampling. When implemented, the autonomous pulse sequence prescribed radial view angles faster than the scan TR (0.98 ± 0.01 ms, maximum = 1.38 ms) and increased k-space sampling mean uniformity by 10±11%, decreased uniformity variability by 44±12%, and increased PSF signal ratio by 6±6% relative to golden angle sampling. Conclusion The closed-loop approach enables near-uniform radial sampling in a segmented acquisition approach which was higher than predetermined golden-angle radial sampling. This can be utilized to increase the sampling or decrease the temporal footprint of an acquisition and the closed-loop framework has the potential to be applied to patients with complex heart rhythms.

BACKGROUND: Over the last quarter-century, the number of publications using vessel wall MR imaging has increased. Although many narrative reviews offer insight into technique and diagnostic applications, a systematic review of publication trends and reporting quality has not been conducted to identify unmet needs and future directions. PURPOSE: We aimed to identify which intracranial vasculopathies need more data and to highlight areas of strengths and weaknesses in reporting. DATA SOURCES: PubMed, EMBASE, and MEDLINE databases were searched up to September 2018 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA ANALYSIS: Two independent reviewers screened and extracted data from 128 articles. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines were used to assess the reporting quality of analytic observational studies. DATA SYNTHESIS: There has been an exponentially increasing trend in the number of vessel wall MR imaging publications during the past 24 years (P

BACKGROUND: Quantitative susceptibility mapping (QSM) uses prior information to reconstruct maps, but prior information may not show pathology and introduce inconsistencies with susceptibility maps, degrade image quality and inadvertently smoothing image features. PURPOSE: To develop a local field data-driven QSM reconstruction that does not depend on spatial edge prior information. STUDY TYPE: Retrospective. SUBJECTS, ANIMAL MODELS: A dataset from 2016 ISMRM QSM Challenge, 11 patients with glioblastoma, a patient with microbleeds and porcine heart. SEQUENCE/FIELD STRENGTH: 3D gradient echo sequence on 3T and 7T scanners. ASSESSMENT: Accuracy was compared to Calculation of Susceptibility through Multiple Orientation Sampling (COSMOS), and several published techniques using region of interest (ROI) measurements, root-mean-squared error (RMSE), structural similarity index metric (SSIM), and high-frequency error norm (HFEN). Numerical ranking and semiquantitative image grading was performed by three expert observers to assess overall image quality (IQ) and image sharpness (IS). STATISTICAL TESTS: Bland–Altman, Friedman test, and Conover multiple comparisons. RESULTS: Loss adaptive dipole inversion (LADI) (β = 0.82, R(2) = 0.96), morphology-enabled dipole inversion (MEDI) (β = 0.91, R(2) = 0.97), and fast nonlinear susceptibility inversion (FANSI) (β = 0.81, R(2) = 0.98) had excellent correlation with COSMOS and no bias was detected (bias = 0.006 ± 0.014, P < 0.05). In glioblastoma patients, LADI showed consistently better performance (IQ(Grade) = 2.6 ± 0.4, IS(Grade) = 2.6 ± 0.3, IQ(Rank) = 3.5 ± 0.4, IS(Rank) = 3.9 ± 0.2) compared with MEDI (IQ(Grade) = 2.1 ± 0.3, IS(Grade) = 2 ± 0.5, IQ(Rank) = 2.4 ± 0.5, IS(Rank) = 2.8 ± 0.2) and FANSI (IQ(Grade) = 2.2 ± 0.5, IS(Grade) = 2 ± 0.4, IQ(Rank) = 2.8 ± 0.3, IS(Rank) = 2.1 ± 0.2). Dark artifact visible near the infarcted region in MEDI (Inf(MEDI) = −0.27 ± 0.06 ppm) was better mitigated by FANSI (Inf(FANSI-TGV) = −0.17 ± 0.05 ppm) and LADI (Inf(LADI) = −0.18 ± 0.05 ppm). CONCLUSION: For neuroimaging applications, LADI preserved image sharpness and fine features in glioblastoma and microbleed patients. LADI performed better at mitigating artifacts in cardiac QSM. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY STAGE: 1

Opiates play an important role in the control of pain associated with thoracotomy in both people and animals. However, key side effects, including sedation and respiratory depression, could limit the use of opiates in animals that are lethargic due to cardiac disease. In addition, a rare side effect—neuroexcitation resulting in pathologic behavioral changes (seizures, mania, muscle fasciculation)—after the administration of morphine or hydromorphone is well-documented in many species. In pigs, however, these drugs have been shown to stimulate an increase in normal activity. In the case presented, we describe a Yorkshire-cross pig which, after myocardial infarction surgery, went from nonresponsive to alert, responsive, and eating within 30 min of an injection of hydromorphone. This pig was not demonstrating any signs associated with pain at this time, suggesting that the positive response was due to neural stimulation. This case report is the first to describe the use of hydromorphone—a potent, pure μ opiate agonist —for its neurostimulatory effect in pigs with experimentally-induced cardiac disease.

PURPOSE: Reliable monitoring of tissue nicotinamide adenine dinucleotide (NAD(+)) concentration may provide insights on its roles in normal and pathological aging. In the present study, we report a (1)H MRS pulse sequence for the in vivo, localized (1)H MRS detection of NAD(+) from the human brain. METHODS: Studies were performed on a 7T Siemens MRI scanner using a 32-channel product volume coil. The pulse sequence consisted of a spectrally selective low bandwidth E-BURP-1 90° pulse. PRESS localization was achieved using optimized Shinnar-Le Roux 180° pulses and overlapping gradients were used to minimize the echo time. The reproducibility of NAD(+) quantification was measured in 11 healthy volunteers. The association of cerebral NAD(+) with age was assessed in 16 healthy subjects 26–78 years old. RESULTS: Spectra acquired from a voxel placed in subjects’ occipital lobe consisted of downfield peaks from the H2, H4 and H6 protons of the nicotinamide moiety of NAD(+) between 8.9–9.35 ppm. The mean ± SD within-session and between-session coefficients of variation were found to be 6.14 ± 2.03 and 6.09 ± 3.20 % respectively. In healthy volunteers, an age-dependent decline of the NAD(+) levels in the brain was also observed (β = −1.24 μM/yr, SE=0.21, p

To evaluate the capability of T2-weighted magnetic resonance (MR) imaging to monitor electrolytic ablation-induced cell death in real time.Agarose phantoms arranged as an electrolytic cell were exposed to varying quantities of electric charge under constant current to create a pH series. The pH phantoms were subjected to T2-weighted imaging with region of interest quantitation of the acquired signal intensity. Subsequently, hepatocellular carcinoma (HCC) cells encapsulated in an agarose gel matrix were subjected to 10 V of electrolytic ablation for variable lengths of time with and without concurrent T2-weighted MR imaging. Cellular death was confirmed by a fluorescent reporter. Finally, to confirm that real-time MR images corresponded to ablation zones, 10 V electrolytic ablations were performed followed by the addition of pH-neutralizing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer.Analysis of MR imaging from agarose gel pH phantoms demonstrated a relationship between signal intensity and pH at the anodes and cathodes. The steep negative phase of the anode model (pH3.55) and global minimum of the cathode model (pH ≈ 11.62) closely approximated established cytotoxic pH levels. T2-weighted MR imaging demonstrated a strong correlation of ablation zones with regions of HCC cell death (r = 0.986; RT2-weighted MR imaging enabled the real-time detection of electrolytic ablation zones, demonstrating a strong correlation with histologic cell death.

PURPOSE: To perform automated myocardial segmentation and uptake classification from whole-body fluorine 18 fluorodeoxyglucose (FDG) PET. MATERIALS AND METHODS: In this retrospective study, consecutive patients who underwent FDG PET imaging for oncologic indications were included (July–August 2018). The left ventricle (LV) on whole-body FDG PET images was manually segmented and classified as showing no myocardial uptake, diffuse uptake, or partial uptake. A total of 609 patients (mean age, 64 years ± 14 [standard deviation]; 309 women) were included and split between training (60%, 365 patients), validation (20%, 122 patients), and testing (20%, 122 patients) datasets. Two sequential neural networks were developed to automatically segment the LV and classify the myocardial uptake pattern using segmentation and classification training data provided by human experts. Linear regression was performed to correlate findings from human experts and deep learning. Classification performance was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: There was moderate agreement of uptake pattern between experts and deep learning (as a fraction of correctly categorized images) with 78% (36 of 46) for no uptake, 71% (34 of 48) for diffuse uptake, and 71% (20 of 28) for partial uptake. There was no bias in LV volume for partial or diffuse uptake categories (P = .56); however, deep learning underestimated LV volumes in the no uptake category. There was good correlation for LV volume (R(2) = 0.35, b = .71). ROC analysis showed the area under the curve for classifying no uptake and diffuse uptake was high (> 0.90) but lower for partial uptake (0.77). The feasibility of a myocardial uptake index (MUI) for quantifying the degree of myocardial activity patterns was shown, and there was excellent visual agreement between MUI and uptake patterns. CONCLUSION: Deep learning was able to segment and classify myocardial uptake patterns on FDG PET images. Keywords: PET, Heart, Computer Aided Diagnosis, Computer Application-Detection/Diagnosis Supplemental material is available for this article. ©RSNA, 2021

Despite substantial evidence for the central role of hemodynamic shear stress in the functional integrity of vascular endothelial cells, hemodynamic and molecular regulation of the endocardial endothelium lining the heart chambers remains understudied. We propose that regional differences in intracardiac hemodynamics influence differential endocardial gene expression leading to phenotypic heterogeneity of this cell layer. Measurement of intracardiac hemodynamics was performed using 4-dimensional flow MRI in healthy humans (n=8) and pigs (n=5). Local wall shear stress (WSS) and oscillatory shear indices (OSI) were calculated in three distinct regions of the LV – base, mid-ventricle (midV), and apex. In both the humans and pigs, WSS values were significantly lower in the apex and midV relative to the base. Additionally, both the apex and midV had greater oscillatory shear indices (OSI) than the base. To investigate regional phenotype, endocardial endothelial cells (EEC) were isolated from an additional 8 pigs and RNA sequencing was performed. A false discovery rate of 0.10 identified 1051 differentially expressed genes between the base and apex, and 321 between base and midV. Pathway analyses revealed apical upregulation of genes associated with translation initiation. Furthermore, tissue factor pathway inhibitor (TFPI; mean 50-fold) and prostacyclin synthase (PTGIS; 5-fold), genes prominently associated with antithrombotic protection, were consistently upregulated in LV apex. These spatio-temporal WSS values in defined regions of the left ventricle link local hemodynamics to regional heterogeneity in endocardial gene expression.

Background Regional changes in diastolic and systolic properties after myocardial infarction contribute to adverse left ventricular (LV) remodeling. Regional function is currently assessed using load-dependent measures such as slice ejection fraction (sEF), wall motion abnormalities, or strain imaging. However, load-independent measures of cardiac function may be useful in the study of the infarction-induced remodeling. Methods In this study, we used a recently validated 2-dimensional (2D) real-time magnetic resonance imaging (MRI) technique to evaluate regional variations in load-independent slice-by-slice measures of systolic and diastolic function and compared the values to a load-dependent measure in 11 sheep at rest and during inotropic agent infusion. Results Slice-derived ejection fraction (sEF) was greater in the apex relative to the midventricular and basal regions, and inotropic infusion increased sEF in the base more than in the apex and midventricle. Slice-derived ESPVR (sESPVR) in the apex was significantly lower than in the midventricle and the base, and inotropic infusion increased sESPVR in the apical slices more than in the midventricle. Similarly, slice-derived volume-axis intercept V 0 (sV 0 ) was higher in the base relative to the midventricle and apex. sEDPVR did not demonstrate significant regional variations, but inotropic infusion resulted in a small increase in the apex. Conclusions In conclusion, acquisition of slice-derived load-independent measures demonstrated variations that contradict those observed with load-dependent sEF. The approach may provide advanced slice-based measures of function during the LV remodeling process and aid in the development of therapies.

Purpose Develop self-gated MRI for distinct heartbeat morphologies in subjects with arrhythmias. Methods Golden angle radial data was obtained in seven sinus and eight arrhythmias subjects. An image-based cardiac navigator was derived from single-shot images, distinct beat types were identified, and images were reconstructed for repeated morphologies. Image sharpness, contrast, and volume variation were quantified and compared with self-gated MRI. Images were scored for image quality and artifacts. Hemodynamic parameters were computed for each distinct beat morphology in bigeminy and trigeminy subjects and for sinus beats in patients with infrequent premature ventricular contractions. Results Images of distinct beat types were reconstructed except for two patients with infrequent premature ventricular contractions. Image contrast and sharpness were similar to sinus self-gated images (contrast = 0.45 ± 0.13 and 0.43 ± 0.15; sharpness = 0.21 ± 0.11 and 0.20 ± 0.05). Visual scoring was highest in self-gated images (4.1 ± 0.3) compared with real-time (3.9 ± 0.4) and ECG-gated cine (3.4 ± 1.5). ECG-gated cine had less artifacts than self-gating (2.3 ± 0.7 and 2.1 ± 0.2), but was affected by misgating in two subjects. Among arrhythmia subjects, post-extrasystole/sinus (58.1 ± 8.6 mL) and interrupted sinus (61.4 ± 5.9 mL) stroke volume was higher than extrasystole (32.0 ± 16.5 mL; P

Background The role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement ( AVR ). Methods and Results We enrolled 38 participants with symptomatic severe aortic stenosis scheduled to undergo surgical AVR . Aortic root characteristic impedance, wave reflections parameters (reflection magnitude, reflected wave transit time), and myocardial extracellular mass were measured with cardiac magnetic resonance imaging and arterial tonometry Cardiac magnetic resonance imaging was repeated at 6 months in 30 participants. A reduction in cellular mass (133.6 versus 113.9 g; P =0.002) but not extracellular mass (42.3 versus 40.6 g; P =0.67) was seen after AVR . Participants with higher extracellular mass exhibited greater reflection magnitude (0.68 versus 0.54; P =0.006) and lower aortic root characteristic impedance (56.3 versus 96.9 dynes/s per cm 5 ; P =0.006). Reflection magnitude was a significant predictor of smaller improvement in the quality of life (Kansas City Cardiomyopathy Questionnaire score) after AVR ( R =−0.51; P =0.0026). The 6‐minute walk distance at 6 months after AVR was positively correlated with the reflected wave transit time ( R =0.52; P =0.01). Conclusions Consistent with animal studies, arterial wave reflections are associated with interstitial volume expansion in severe aortic stenosis and predict a smaller improvement in quality of life following AVR . Future trials should assess whether wave reflections represent a potential therapeutic target to mitigate myocardial interstitial remodeling and to improve the clinical status of this patient population.

Cardiovascular magnetic resonance imaging has been the noninvasive method of choice for the evaluation of regional myocardial movement since myocardial tagging was invented almost 30 years ago. A number of developments and improvements on the technique have taken place to improve image resolution, quality, three-dimensional image acquisition, and scan duration. These techniques have also been applied in a variety of heart diseases spanning ischemic heart disease, hypertrophic cardiomyopathy, and other forms of nonischemic cardiomyopathy, pericardial diseases, valvular heart disease, right heart diseases, and congenital heart diseases. In recent years, feature tracking on cine images allowed generation of much greater amount of data on regional function of cardiac diseases. The clinical decision-making with integration of regional myocardial motion analyses is on the horizon.