Tailored Chemical Reactivity Probes for Systemic Imaging of Aldehydes in Fibroproliferative Diseases.

During fibroproliferation, protein-associated extracellular aldehydes are formed by the oxidation of lysine residues on extracellular matrix proteins to form the aldehyde allysine. Here we report three Mn(II)-based, small-molecule magnetic resonance probes that contain α-effect nucleophiles to target allysine in vivo and report on tissue fibrogenesis. We used a rational design approach to develop turn-on probes with a 4-fold increase in relaxivity upon targeting. The effects of aldehyde condensation rate and hydrolysis kinetics on the performance of the probes to detect tissue fibrogenesis non-invasively in mouse models were evaluated by a systemic aldehyde tracking approach. We showed that, for highly reversible ligations, off-rate was a stronger predictor of in vivo efficiency, enabling histologically validated, three-dimensional characterization of pulmonary fibrogenesis throughout the entire lung. The exclusive renal elimination of these probes allowed for rapid imaging of liver fibrosis. Reducing the hydrolysis rate by forming an oxime bond with allysine enabled delayed phase imaging of kidney fibrogenesis. The imaging efficacy of these probes, coupled with their rapid and complete elimination from the body, makes them strong candidates for clinical translation.

Gadolinium-based Contrast Agent Biodistribution and Speciation in Rats.

Background Gadolinium retention has been observed in organs of patients with normal renal function; however, the biodistribution and speciation of residual gadolinium is not well understood. Purpose To compare the pharmacokinetics, distribution, and speciation of four gadolinium-based contrast agents (GBCAs) in healthy rats using MRI, mass spectrometry, elemental imaging, and electron paramagnetic resonance (EPR) spectroscopy. Materials and Methods In this prospective animal study performed between November 2021 and September 2022, 32 rats received a dose of gadoterate, gadoteridol, gadobutrol, or gadobenate (2.0 mmol/kg) for 10 consecutive days. GBCA-naive rats were used as controls. Three-dimensional T1-weighted ultrashort echo time images and R2* maps of the kidneys were acquired at 3, 17, 34, and 52 days after injection. At 17 and 52 days after injection, gadolinium concentrations in 23 organ, tissue, and fluid specimens were measured with mass spectrometry; gadolinium distribution in the kidneys was evaluated using elemental imaging; and gadolinium speciation in the kidney cortex was assessed using EPR spectroscopy. Data were assessed with analysis of variance, Kruskal-Wallis test, analysis of response profiles, and Pearson correlation analysis. Results For all GBCAs, the kidney cortex exhibited higher gadolinium retention at 17 days after injection than all other specimens tested (mean range, 350-1720 nmol/g vs 0.40-401 nmol/g; P value range, .001-.70), with gadoteridol showing the lowest level of retention. Renal cortex R2* values correlated with gadolinium concentrations measured ex vivo (r = 0.95; P < .001), whereas no associations were found between T1-weighted signal intensity and ex vivo gadolinium concentration (r = 0.38; P = .10). EPR spectroscopy analysis of rat kidney cortex samples showed that all GBCAs were primarily intact at 52 days after injection. Conclusion Compared with other macrocyclic GBCAs, gadoteridol administration led to the lowest level of retention. The highest concentration of gadolinium was retained in the kidney cortex, but T1-weighted MRI was not sensitive for detecting residual gadolinium in this tissue. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tweedle in this issue.

Magnetic susceptibility and R2* of myocardial reperfusion injury at 3T and 7T.

PURPOSE: Magnetic susceptibility (Δχ) alterations have shown association with myocardial infarction (MI) iron deposition, yet there remains limited understanding of the relationship between relaxation rates and susceptibility or the effect of magnetic field strength. Hence, Δχ and R2∗ in MI were compared at 3T and 7T. METHODS: Subacute MI was induced by coronary artery ligation in male Yorkshire swine. 3D multiecho gradient echo imaging was performed at 1-week postinfarction at 3T and 7T. Quantitative susceptibility mapping images were reconstructed using a morphology-enabled dipole inversion. R2∗ maps and quantitative susceptibility mapping were generated to assess the relationship between R2∗ , Δχ, and field strength. Infarct histopathology was investigated. RESULTS: Magnetic susceptibility was not significantly different across field strengths (7T: 126.8 ± 41.7 ppb; 3T: 110.2 ± 21.0 ppb, P = NS), unlike R2∗ (7T: 247.0 ± 14.8 Hz; 3T: 106.1 ± 6.5 Hz, P < .001). Additionally, infarct Δχ and R2∗ were significantly higher than remote myocardium. Magnetic susceptibility at 7T versus 3T had a significant association (ß = 1.02, R2 = 0.82, P < .001), as did R2∗ (ß = 2.35, R2 = 0.98, P < .001). Infarct pathophysiology and iron deposition were detected through histology and compared with imaging findings. CONCLUSION: R2∗ showed dependence and Δχ showed independence of field strength. Histology validated the presence of iron and supported imaging findings.

MR susceptibility imaging for detection of tumor-associated macrophages in glioblastoma.

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). CONCLUSIONS: This study demonstrated the potential of MR quantitative susceptibility mapping as a non-invasive method for in vivo TAM quantification and phenotyping. Validation of these findings with large multicenter studies is needed.

Endogenous T1ρ cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

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 < 1e-5) and T1ρ percent enhancement area (Spearman's rho = 0.48, p < 0.001e-3) correlated with LGE percent enhancement area. T1 and T1ρ percent enhancement areas were also correlated (Spearman's rho = 0.28, p = 0.047). For both T1 and T1ρ, HCM patients demonstrated significantly longer relaxation times compared to controls in each LGE category (p < 0.001 for all). HCM patients also showed significantly higher ECV compared to controls in each LGE category (p < 0.01 for all), and LGE -- slices had lower ECV than LGE + + (p = 0.01). 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.

Data-Driven Quantitative Susceptibility Mapping Using Loss Adaptive Dipole Inversion (LADI).

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) (ß = 0.82, R2 = 0.96), morphology-enabled dipole inversion (MEDI) (ß = 0.91, R2 = 0.97), and fast nonlinear susceptibility inversion (FANSI) (ß = 0.81, R2 = 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 (IQGrade = 2.6 ± 0.4, ISGrade = 2.6 ± 0.3, IQRank = 3.5 ± 0.4, ISRank = 3.9 ± 0.2) compared with MEDI (IQGrade = 2.1 ± 0.3, ISGrade = 2 ± 0.5, IQRank = 2.4 ± 0.5, ISRank = 2.8 ± 0.2) and FANSI (IQGrade = 2.2 ± 0.5, ISGrade = 2 ± 0.4, IQRank = 2.8 ± 0.3, ISRank = 2.1 ± 0.2). Dark artifact visible near the infarcted region in MEDI (InfMEDI = -0.27 ± 0.06 ppm) was better mitigated by FANSI (InfFANSI-TGV = -0.17 ± 0.05 ppm) and LADI (InfLADI = -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 J. Magn. Reson. Imaging 2020;52:823-835.

Assessment of uterine artery geometry and hemodynamics in human pregnancy with 4d flow mri and its correlation with doppler ultrasound.

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 < -0.1) with Wilcoxon signed rank test P = 0.05 and P = 0.13, respectively. DATA CONCLUSION: 4D flow MRI is a feasible approach for describing UtA anatomy and flow in pregnant subjects. LEVEL OF EVIDENCE: Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:59-68.

Assessment of brain structure and volume reveals neurodevelopmental abnormalities in preterm infants with low-grade intraventricular hemorrhage.

There is increasing evidence of abnormal neurodevelopmental outcomes in preterm infants with low-grade intraventricular hemorrhage (IVH). The purpose of the study was to explore whether brain microstructure and volume are associated with neuro-behavioral outcomes at 40 weeks corrected gestational age in preterm infants with low-grade IVH. MR imaging at term-equivalent age (TEA) was performed in 25 preterm infants with mild IVH (Papile grading I/II) and 40 control subjects without IVH. These subjects all had neonatal behavioral neurological assessment (NBNA) at 40 weeks' corrected age. Microstructure and volume evaluation of the brain were performed by using diffusion kurtosis imaging (DKI) and Synthetic MRI. Correlations among microstructure parameters, volume, and developmental outcomes were explored by using Spearman's correlation. In preterm infants with low-grade IVH, the volume of brain parenchymal fraction (BPF) was reduced. In addition, mean kurtosis (MK), fractional anisotropy (FA), radial kurtosis (RK), axial kurtosis (AK) in several major brain regions were reduced, while mean diffusivity (MD) was increased (P < 0.05). BPF, RK in the cerebellum, MK in the genu of the corpus callosum, and MK in the thalamus of preterm infants with low-grade IVH were associated with lower NBNA scores (r = 0.831, 0.836, 0.728, 0.772, P < 0.05). DKI and Synthetic MRI can quantitatively evaluate the microstructure alterations and brain volumes in preterm infants with low-grade IVH, which provides clinicians with a more comprehensive and accurate neurobehavioral assessment of preterm infants with low-grade IVH.

Associations between diffusion kurtosis imaging metrics and neurodevelopmental outcomes in neonates with low-grade germinal matrix and intraventricular hemorrhage.

Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P < 0.05). The MK value in the thalamus was associated with Mental Development Index (MDI) (r = 0.810, 95% CI 0.695-0.13; P < 0.001) and Psychomotor Development Index (PDI) (r = 0.852, 95% CI 0.722-0.912; P < 0.001) scores. RK value in the caudate nucleus significantly and positively correlated with MDI (r = 0.496, 95% CI 0.657-0.933; P < 0.001) and PDI (r = 0.545, 95% CI 0.712-0.942; P < 0.001) scores. The area under the curve (AUC) were used to assess diagnostic performance of MK and RK in thalamus (AUC = 0.866, 0.787) and caudate nucleus (AUC = 0.833, 0.671) for predicting neurodevelopmental outcomes. As quantitative neuroimaging markers, MK in thalamus and RK in caudate nucleus may help predict neurodevelopmental outcomes in neonates with low-grade GMH-IVH.

Simultaneous Positron Emission Tomography and Molecular Magnetic Resonance Imaging of Cardiopulmonary Fibrosis in a Mouse Model of Left Ventricular Dysfunction.

BACKGROUND: Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. METHODS AND RESULTS: Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P<0.0001) and Δlung-to-muscle ratio (P<0.0001). Hydroxyproline in the heart (P<0.0001) and lungs (P<0.01) were elevated in TAC mice, which corresponded to an increase in heart (myocardium-to-muscle ratio, P=0.02) and lung (lung-to-muscle ratio, P<0.001) PET measurements. Pressure-volume loop and echocardiography demonstrated adverse left ventricular remodeling, function, and increased right ventricular systolic pressure in TAC mice. CONCLUSIONS: Administration of collagen-targeted PET and allysine-targeted MR probes led to elevated PET-magnetic resonance imaging signals in the myocardium and lungs of TAC mice. The study demonstrates the potential to detect fibrosis and fibrogenesis in cardiopulmonary disease through a dual molecular PET-magnetic resonance imaging protocol.

Evaluation of white matter microstructural alterations in premature infants with necrotizing enterocolitis.

Background: Preterm infants with necrotizing enterocolitis (NEC) are at high risk of adverse neurodevelopmental outcomes. The aim of this study was to explore the value of diffusion tensor imaging (DTI) combined with serum C-reactive protein (CRP) and procalcitonin (PCT) in evaluating alterations of white matter (WM) microstructure in preterm infants with NEC. Methods: A retrospective cross-sectional study was conducted in which all participants were consecutively enrolled at The Third Affiliated Hospital of Zhengzhou University from June 2017 and October 2021. Data from 30 preterm infants with NEC [mean gestational age at birth 31.41±1.15 weeks; mean age at magnetic resonance imaging (MRI) 37.53±3.08 weeks] and 40 healthy preterm infants with no NEC were recorded (mean gestational age at birth 32.27±2.09 weeks; mean age at MRI 37.15±3.23 weeks). WM was used to obtain the fractional anisotropy (FA) and mean diffusivity (MD) values of the regions of interest (ROIs). Additionally, serum levels of CRP and PCT were determined. Spearman correlation analysis was performed between the WM-derived parameters, CRP level, and the PCT serum index. Results: Preterm infants with NEC had reduced FA values and elevated MD values in WM regions [posterior limbs of the internal capsule (PLIC), lentiform nucleus (LN), frontal white matter (FWM)] compared to the control group (P<0.05). Additionally, the FA of the PLIC was negatively correlated with serum CRP (r=-0.846; P<0.05) and PCT (r=-0.843; P<0.05). Meanwhile, the MD of PLIC was positively correlated with serum CRP (r=0.743; P<0.05) and PCT (r=0.743; P<0.05, respectively). The area under the curve (AUC) of FA and MD combined with CRP and PCT in the diagnosis of WM microstructure alterations with NEC was 0.968, representing a considerable improvement in predicted efficacy over single indicators, including FA [AUC: 0.938; 95% confidence interval (CI): 0.840-0.950], MD (AUC: 0.807; 95% CI: 0.722-0.838), CRP (AUC: 0.867; 95% CI: 0.822-0.889), and PCT (AUC: 0.706; 95% CI: 0.701-0.758). Conclusions: WM can noninvasively and quantitatively assess the WM microstructure alterations in preterm infants with NEC. WM combined with serum CRP and PCT demonstrated superior performance in detecting and evaluating WM microstructure alterations in preterm infants with NEC.

Tailored chemical reactivity probes for systemic imaging of aldehydes in fibroproliferative diseases.

During fibroproliferation, protein-associated extracellular aldehydes are formed by the oxidation of lysine residues on extracellular matrix proteins to form the aldehyde allysine. Here we report three Mn(II)-based, small molecule magnetic resonance (MR) probes that contain α-effect nucleophiles to target allysine in vivo and report on tissue fibrogenesis. We used a rational design approach to develop turn-on probes with a 4-fold increase in relaxivity upon targeting. The effects of aldehyde condensation rate and hydrolysis kinetics on the performance of the probes to detect tissue fibrogenesis noninvasively in mouse models were evaluated by a systemic aldehyde tracking approach. We showed that for highly reversible ligations, off-rate was a stronger predictor of in vivo efficiency, enabling histologically validated, three-dimensional characterization of pulmonary fibrogenesis throughout the entire lung. The exclusive renal elimination of these probes allowed for rapid imaging of liver fibrosis. Reducing the hydrolysis rate by forming an oxime bond with allysine enabled delayed phase imaging of kidney fibrogenesis. The imaging efficacy of these probes, coupled with their rapid and complete elimination from the body, make them strong candidates for clinical translation.

Quantitative susceptibility mapping using plug-and-play alternating direction method of multipliers.

Quantitative susceptibility mapping employs regularization to reduce artifacts, yet many recent denoisers are unavailable for reconstruction. We developed a plug-and-play approach to QSM reconstruction (PnP QSM) and show its flexibility using several patch-based denoisers. We developed PnP QSM using alternating direction method of multiplier framework and applied collaborative filtering denoisers. We apply the technique to the 2016 QSM Challenge and in 10 glioblastoma multiforme datasets. We compared its performance with four published QSM techniques and a multi-orientation QSM method. We analyzed magnetic susceptibility accuracy using brain region-of-interest measurements, and image quality using global error metrics. Reconstructions on glioblastoma data were analyzed using ranked and semiquantitative image grading by three neuroradiologist observers to assess image quality (IQ) and sharpness (IS). PnP-BM4D QSM showed good correlation (ß = 0.84, R2 = 0.98, p < 0.05) with COSMOS and no significant bias (bias = 0.007 ± 0.012). PnP-BM4D QSM achieved excellent quality when assessed using structural similarity index metric (SSIM = 0.860), high frequency error norm (HFEN = 58.5), cross correlation (CC = 0.804), and mutual information (MI = 0.475) and also maintained good conspicuity of fine features. In glioblastoma datasets, PnP-BM4D QSM showed higher performance (IQGrade = 2.4 ± 0.4, ISGrade = 2.7 ± 0.3, IQRank = 3.7 ± 0.3, ISRank = 3.9 ± 0.3) compared to MEDI (IQGrade = 2.1 ± 0.5, ISGrade = 2.1 ± 0.6, IQRank = 2.4 ± 0.6, ISRank = 2.9 ± 0.2) and FANSI-TGV (IQGrade = 2.2 ± 0.6, ISGrade = 2.1 ± 0.6, IQRank = 2.7 ± 0.3, ISRank = 2.2 ± 0.2). We illustrated the modularity of PnP QSM by interchanging two additional patch-based denoisers. PnP QSM reconstruction was feasible, and its flexibility was shown using several patch-based denoisers. This technique may allow rapid prototyping and validation of new denoisers for QSM reconstruction for an array of useful clinical applications.

Classification of Myocardial 18F-FDG PET Uptake Patterns Using Deep Learning.

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/DiagnosisSupplemental material is available for this article.©RSNA, 2021.

MR Intracranial Vessel Wall Imaging: A Systematic Review.

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.

Iron imaging in myocardial infarction reperfusion injury.

Restoration of coronary blood flow after a heart attack can cause reperfusion injury potentially leading to impaired cardiac function, adverse tissue remodeling and heart failure. Iron is an essential biometal that may have a pathologic role in this process. There is a clinical need for a precise noninvasive method to detect iron for risk stratification of patients and therapy evaluation. Here, we report that magnetic susceptibility imaging in a large animal model shows an infarct paramagnetic shift associated with duration of coronary artery occlusion and the presence of iron. Iron validation techniques used include histology, immunohistochemistry, spectrometry and spectroscopy. Further mRNA analysis shows upregulation of ferritin and heme oxygenase. While conventional imaging corroborates the findings of iron deposition, magnetic susceptibility imaging has improved sensitivity to iron and mitigates confounding factors such as edema and fibrosis. Myocardial infarction patients receiving reperfusion therapy show magnetic susceptibility changes associated with hypokinetic myocardial wall motion and microvascular obstruction, demonstrating potential for clinical translation.

An all-in-one nanoparticle (AION) contrast agent for breast cancer screening with DEM-CT-MRI-NIRF imaging.

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 (Ag2S-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.

A comparison of iopromide and iopamidol, two acidoCEST MRI contrast media that measure tumor extracellular pH.

Acidosis within tumor and kidney tissues has previously been quantitatively measured using a molecular imaging technique known as acidoCEST MRI. The previous studies used iopromide and iopamidol, two iodinated contrast agents that are approved for clinical CT diagnoses and have been repurposed for acidoCEST MRI studies. We aimed to compare the performance of the two agents for measuring pH by optimizing image acquisition conditions, correlating pH with a ratio of CEST effects from an agent, and evaluating the effects of concentration, endogenous T1 relaxation time and temperature on the pH-CEST ratio correlation for each agent. These results showed that the two agents had similar performance characteristics, although iopromide produced a pH measurement with a higher dynamic range while iopamidol produced a more precise pH measurement. We then compared the performance of the two agents to measure in vivo extracellular pH (pHe) within xenograft tumor models of Raji lymphoma and MCF-7 breast cancer. Our results showed that the pHe values measured with each agent were not significantly different. Also, iopromide consistently measured a greater region of the tumor relative to iopamidol in both tumor models. Therefore, an iodinated contrast agent for acidoCEST MRI should be selected based on the measurement properties needed for a specific biomedical study and the pharmacokinetic properties of a specific tumor model.

Evaluations of Tumor Acidosis Within In Vivo Tumor Models Using Parametric Maps Generated with Acido CEST MRI.

PURPOSE: We aimed to develop pixelwise maps of tumor acidosis to aid in evaluating extracellular tumor pH (pHe) in cancer biology. PROCEDURES: MCF-7 and MDA-MB-231 mouse models were imaged during a longitudinal study. AcidoCEST MRI and a series of image processing methods were used to produce parametric maps of tumor pHe, and tumor pHe was also measured with a pH microsensor. RESULTS: Sufficient contrast-to-noise for producing pHe maps was achieved by using standard image processing methods. A comparison of pHe values measured with acidoCEST MRI and a pH microsensor showed that acidoCEST MRI measured tumor pHe with an accuracy of 0.034 pH units. The MCF-7 tumor model was found to be more acidic compared to the MDA-MB-231 tumor model. The pHe was not related to tumor size during the longitudinal study. CONCLUSIONS: These results show that acidoCEST MRI can create pixelwise tumor pHe maps of mouse models of cancer.