Congenital lung abnormalities on magnetic resonance imaging: the CLAM study.

OBJECTIVES: Follow-up of congenital lung abnormalities (CLA) is currently done with chest computer tomography (CT). Major disadvantages of CT are exposure to ionizing radiation and need for contrast enhancement to visualise vascularisation. Chest magnetic resonance imaging (MRI) could be a safe alternative to image CLA without using contrast agents. The objective of this cohort study was to develop a non-contrast MRI protocol for the follow-up of paediatric CLA patients, and to compare findings on MRI to postnatal CT in school age CLA patients. METHODS: Twenty-one CLA patients, 4 after surgical resection and 17 unoperated (mean age 12.8 (range 9.4-15.9) years), underwent spirometry and chest MRI. MRI was compared to postnatal CT on appearance and size of the lesion, and lesion associated abnormalities, such as hyperinflation and atelectasis. RESULTS: By comparing school-age chest MRI to postnatal CT, radiological appearance and diagnostic interpretation of the type of lesion changed in 7 (41%) of the 17 unoperated patients. In unoperated patients, the relative size of the lesion in relation to the total lung volume remained stable (0.9% (range - 6.2 to + 6.7%), p = 0.3) and the relative size of lesion-associated parenchymal abnormalities decreased (- 2.2% (range - 0.8 to + 2.8%), p = 0.005). CONCLUSION: Non-contrast-enhanced chest MRI was able to identify all CLA-related lung abnormalities. Changes in radiological appearance between MRI and CT were related to CLA changes, patients' growth, and differences between imaging modalities. Further validation is needed for MRI to be introduced as a safe imaging method for the follow-up of paediatric CLA patients. KEY POINTS: • Non-contrast-enhanced chest MRI is able to identify anatomical lung changes related to congenital lung abnormalities, including vascularisation. • At long-term follow-up, the average size of congenital lung abnormalities in relation to normal lung volume remains stable. • At long-term follow-up, the average size of congenital lung abnormalities associated parenchymal abnormalities such as atelectasis in relation to normal lung volume decreases.

129 Xe and Free-Breathing 1 H Ventilation MRI in Patients With Cystic Fibrosis: A Dual-Center Study.

BACKGROUND: Free-breathing 1 H ventilation MRI shows promise but only single-center validation has yet been performed against methods which directly image lung ventilation in patients with cystic fibrosis (CF). PURPOSE: To investigate the relationship between 129 Xe and 1 H ventilation images using data acquired at two centers. STUDY TYPE: Sequence comparison. POPULATION: Center 1; 24 patients with CF (12 female) aged 9-47 years. Center 2; 7 patients with CF (6 female) aged 13-18 years, and 6 healthy controls (6 female) aged 21-31 years. Data were acquired in different patients at each center. FIELD STRENGTH/SEQUENCE: 1.5 T, 3D steady-state free precession and 2D spoiled gradient echo. ASSESSMENT: Subjects were scanned with 129 Xe ventilation and 1 H free-breathing MRI and performed pulmonary function tests. Ventilation defect percent (VDP) was calculated using linear binning and images were visually assessed by H.M., L.J.S., and G.J.C. (10, 5, and 8 years' experience). STATISTICAL TESTS: Correlations and linear regression analyses were performed between 129 Xe VDP, 1 H VDP, FEV1 , and LCI. Bland-Altman analysis of 129 Xe VDP and 1 H VDP was carried out. Differences in metrics were assessed using one-way ANOVA or Kruskal-Wallis tests. RESULTS: 129 Xe VDP and 1 H VDP correlated strongly with; each other (r = 0.84), FEV1 z-score (129 Xe VDP r = -0.83, 1 H VDP r = -0.80), and LCI (129 Xe VDP r = 0.91, 1 H VDP r = 0.82). Bland-Altman analysis of 129 Xe VDP and 1 H VDP from both centers had a bias of 0.07% and limits of agreement of -16.1% and 16.2%. Linear regression relationships of VDP with FEV1 were not significantly different between 129 Xe and 1 H VDP (P = 0.08), while 129 Xe VDP had a stronger relationship with LCI than 1 H VDP. DATA CONCLUSION: 1 H ventilation MRI shows large-scale agreement with 129 Xe ventilation MRI in CF patients with established lung disease but may be less sensitive to subtle ventilation changes in patients with early-stage lung disease. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Lung structure and function on MRI in preterm born school children with and without BPD: A feasibility study.

BACKGROUND AND OBJECTIVE: The most common respiratory complication of prematurity is bronchopulmonary dysplasia (BPD), leading to structural lung changes and impaired respiratory outcomes. However, also preterm children without BPD may show similar adverse respiratory outcomes. There is a need for a safe imaging modality for preterm children with and without BPD for disease severity assessment and risk stratification. Our objective was to develop a magnetic resonance imaging (MRI) protocol in preterm children with and without BPD at school age. METHODS: Nine healthy volunteers (median age 11.6 [range: 8.8-12.8] years), 11 preterm children with BPD (11.0 [7.2-15.6] years), and 9 without BPD (11.1 [10.7-12.6] years) underwent MRI. Images were scored on hypo- and hyperintense abnormalities, bronchopathy, and architectural distortion. MRI data were correlated to spirometry. Ventilation and perfusion defects were analyzed using Fourier Decomposition (FD) MRI. RESULTS: On MRI, children with BPD had higher %diseased lung (9.1 (interquartile range [IQR] 5.9-11.6)%) compared to preterm children without BPD (3.4 (IQR 2.5-5.4)%, p < 0.001) and healthy volunteers (0.4 (IQR 0.1-0.8)%, p < 0.001). %Diseased lung correlated negatively with %predicted FEV1 (r = -0.40, p = 0.04), FEV1 /FVC (r = -0.49, p = 0.009) and FEF75 (r = -0.63, p < 0.001). Ventilation and perfusion defects on FD sequence corresponded to hypointense regions on expiratory MRI. CONCLUSION: Chest MRI can identify structural and functional lung damage at school age in preterm children with and without BPD, showing a good correlation with spirometry. We propose MRI as a sensitive and safe imaging method (without ionizing radiation, contrast agents, or the use of anesthesia) for the long-term follow-up of preterm children.

MR imaging for the quantitative assessment of brain iron in aceruloplasminemia: A postmortem validation study.

AIMS: Non-invasive measures of brain iron content would be of great benefit in neurodegeneration with brain iron accumulation (NBIA) to serve as a biomarker for disease progression and evaluation of iron chelation therapy. Although magnetic resonance imaging (MRI) provides several quantitative measures of brain iron content, none of these have been validated for patients with a severely increased cerebral iron burden. We aimed to validate R2* as a quantitative measure of brain iron content in aceruloplasminemia, the most severely iron-loaded NBIA phenotype. METHODS: Tissue samples from 50 gray- and white matter regions of a postmortem aceruloplasminemia brain and control subject were scanned at 1.5 T to obtain R2*, and biochemically analyzed with inductively coupled plasma mass spectrometry. For gray matter samples of the aceruloplasminemia brain, sample R2* values were compared with postmortem in situ MRI data that had been obtained from the same subject at 3 T - in situ R2*. Relationships between R2* and tissue iron concentration were determined by linear regression analyses. RESULTS: Median iron concentrations throughout the whole aceruloplasminemia brain were 10 to 15 times higher than in the control subject, and R2* was linearly associated with iron concentration. For gray matter samples of the aceruloplasminemia subject with an iron concentration up to 1000 mg/kg, 91% of variation in R2* could be explained by iron, and in situ R2* at 3 T and sample R2* at 1.5 T were highly correlated. For white matter regions of the aceruloplasminemia brain, 85% of variation in R2* could be explained by iron. CONCLUSIONS: R2* is highly sensitive to variations in iron concentration in the severely iron-loaded brain, and might be used as a non-invasive measure of brain iron content in aceruloplasminemia and potentially other NBIA disorders.

Impaired pulmonary vasomotor control in exercising swine with multiple comorbidities.

Pulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). Here, we tested the hypothesis that comorbidities [diabetes mellitus (DM, streptozotocin), hypercholesterolemia (HC, high-fat diet) and chronic kidney disease (CKD, renal microembolization)] directly impair pulmonary vasomotor control in a DM + HC + CKD swine model. 6 months after induction of DM + HC + CKD, pulmonary arterial pressure was similar in chronically instrumented female DM + HC + CKD (n = 19) and Healthy swine (n = 18). However, cardiac output was lower both at rest and during exercise, implying an elevated pulmonary vascular resistance (PVR) in DM + HC + CKD swine (153 ± 10 vs. 122 ± 9 mmHg∙L-1∙min∙kg). Phosphodiesterase 5 inhibition and endothelin receptor antagonism decreased PVR in DM + HC + CKD (- 12 ± 12 and - 22 ± 7 mmHg∙L-1∙min∙kg) but not in Healthy swine (- 1 ± 12 and 2 ± 14 mmHg∙L-1∙min∙kg), indicating increased vasoconstrictor influences of phosphodiesterase 5 and endothelin. Inhibition of nitric oxide synthase produced pulmonary vasoconstriction that was similar in Healthy and DM + HC + CKD swine, but unmasked a pulmonary vasodilator effect of endothelin receptor antagonism in Healthy (- 56 ± 26 mmHg∙L-1∙min∙kg), whereas it failed to significantly decrease PVR in DM + HC + CKD, indicating loss of nitric oxide mediated inhibition of endothelin in DM + HC + CKD. Scavenging of reactive oxygen species (ROS) had no effect on PVR in either Healthy or DM + HC + CKD swine. Cardiovascular magnetic resonance imaging, under anesthesia, showed no right ventricular changes. Finally, despite an increased contribution of endogenous nitric oxide to vasomotor tone regulation in the systemic vasculature, systemic vascular resistance at rest was higher in DM + HC + CKD compared to Healthy swine (824 ± 41 vs. 698 ± 35 mmHg∙L-1∙min∙kg). ROS scavenging induced systemic vasodilation in DM + HC + CKD, but not Healthy swine. In conclusion, common comorbidities directly alter pulmonary vascular control, by enhanced PDE5 and endothelin-mediated vasoconstrictor influences, well before overt left ventricular backward failure or pulmonary hypertension develop.

T2 mapping of healthy knee cartilage: multicenter multivendor reproducibility.

BACKGROUND: T2 mapping is increasingly used to quantify cartilage degeneration in knee osteoarthritis (OA), yet reproducibility studies in a multicenter setting are limited. The purpose of this study was to determine the longitudinal reproducibility and multicenter variation of cartilage T2 mapping, using various MRI equipment and acquisition protocols. METHODS: In this prospective multicenter study, four traveling, healthy human subjects underwent T2 mapping twice at five different centers with a 6-month-interval. Centers had various MRI scanners, field strengths, and T2 mapping acquisition protocols. Mean T2 values were calculated in six cartilage regions of interest (ROIs) as well as an average value per patient. A phantom was scanned once at each center. To evaluate longitudinal reproducibility, intraclass correlation coefficients (ICC), root-mean-square coefficient of variation (RMS-CV), and a Bland-Altman plot were used. To assess the variation of in vivo and phantom T2 values across centers, ANOVA was performed. RESULTS: ICCs of the T2 mapping measurements per ROI and the ROI's combined ranged from 0.73 to 0.91, indicating good to excellent longitudinal reproducibility. RMS-CVs ranged from 1.1% to 1.5% (per ROI) and 0.6% to 1.6% (ROIs combined) across the centers. A Bland-Altman plot did not reveal a systematic error. Evident, but consistent, discrepancies in T2 values were observed across centers, both in vivo and in the phantom. CONCLUSIONS: The results of this study suggest that T2 mapping can be used to longitudinal assess cartilage degeneration in multicenter studies. Given the differences in absolute cartilage T2 values across centers, absolute T2 values derived from various centers in multicenter multivendor trials should not be pooled.

Chest MRI to diagnose early diaphragmatic weakness in Pompe disease.

BACKGROUND: In Pompe disease, an inherited metabolic muscle disorder, severe diaphragmatic weakness often occurs. Enzyme replacement treatment is relatively ineffective for respiratory function, possibly because of irreversible damage to the diaphragm early in the disease course. Mildly impaired diaphragmatic function may not be recognized by spirometry, which is commonly used to study respiratory function. In this cross-sectional study, we aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. METHODS: Pompe patients covering the spectrum of disease severity, and sex and age matched healthy controls were prospectively included and studied using spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. The motions of the diaphragm and thoracic wall were evaluated by measuring thoracic cranial-caudal and anterior-posterior distance ratios between inspiration and expiration. The diaphragm shape was evaluated by measuring the height of the diaphragm curvature. We used multiple linear regression analysis to compare different groups. RESULTS: We included 22 Pompe patients with decreased spirometry results (forced vital capacity in supine position < 80% predicted); 13 Pompe patients with normal spirometry results (forced vital capacity in supine position ≥ 80% predicted) and 18 healthy controls. The mean cranial-caudal ratio was only 1.32 in patients with decreased spirometry results, 1.60 in patients with normal spirometry results and 1.72 in healthy controls (p < 0.001). Anterior-posterior ratios showed no significant differences. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry results, 1.08 in patients with normal spirometry results and 0.82 in healthy controls (p = 0.001), indicating an increased curvature of the diaphragm during inspiration in Pompe patients. CONCLUSIONS: Even in early-stage Pompe disease, when spirometry results are still within normal range, the motion of the diaphragm is already reduced and the shape is more curved during inspiration. MRI can be used to detect early signs of diaphragmatic weakness in patients with Pompe disease, which might help to select patients for early intervention to prevent possible irreversible damage to the diaphragm.

Improvement of late gadolinium enhancement image quality using a deep learning-based reconstruction algorithm and its influence on myocardial scar quantification.

OBJECTIVES: The aim of this study was to assess the effect of a deep learning (DL)-based reconstruction algorithm on late gadolinium enhancement (LGE) image quality and to evaluate its influence on scar quantification. METHODS: Sixty patients (46 ± 17 years, 50% male) with suspected or known cardiomyopathy underwent CMR. Short-axis LGE images were reconstructed using the conventional reconstruction and a DL network (DLRecon) with tunable noise reduction (NR) levels from 0 to 100%. Image quality of standard LGE images and DLRecon images with 75% NR was scored using a 5-point scale (poor to excellent). In 30 patients with LGE, scar size was quantified using thresholding techniques with different standard deviations (SD) above remote myocardium, and using full width at half maximum (FWHM) technique in images with varying NR levels. RESULTS: DLRecon images were of higher quality than standard LGE images (subjective quality score 3.3 ± 0.5 vs. 3.6 ± 0.7, p < 0.001). Scar size increased with increasing NR levels using the SD methods. With 100% NR level, scar size increased 36%, 87%, and 138% using 2SD, 4SD, and 6SD quantification method, respectively, compared to standard LGE images (all p values < 0.001). However, with the FWHM method, no differences in scar size were found (p = 0.06). CONCLUSIONS: LGE image quality improved significantly using a DL-based reconstruction algorithm. However, this algorithm has an important impact on scar quantification depending on which quantification technique is used. The FWHM method is preferred because of its independency of NR. Clinicians should be aware of this impact on scar quantification, as DL-based reconstruction algorithms are being used. KEY POINTS: • The image quality based on (subjective) visual assessment and image sharpness of late gadolinium enhancement images improved significantly using a deep learning-based reconstruction algorithm that aims to reconstruct high signal-to-noise images using a denoising technique. • Special care should be taken when scar size is quantified using thresholding techniques with different standard deviations above remote myocardium because of the large impact of these advanced image enhancement algorithms. • The full width at half maximum method is recommended to quantify scar size when deep learning algorithms based on noise reduction are used, as this method is the least sensitive to the level of noise and showed the best agreement with visual late gadolinium enhancement assessment.

The clinical impact of phase offset errors and different correction methods in cardiovascular magnetic resonance phase contrast imaging: a multi-scanner study.

BACKGROUND: Cardiovascular magnetic resonance (CMR) phase contrast (PC) flow measurements suffer from phase offset errors. Background subtraction based on stationary phantom measurements can most reliably be used to overcome this inaccuracy. Stationary tissue correction is an alternative and does not require additional phantom scanning. The aim of this study was 1) to compare measurements with and without stationary tissue correction to phantom corrected measurements on different GE Healthcare CMR scanners using different software packages and 2) to evaluate the clinical implications of these methods. METHODS: CMR PC imaging of both the aortic and pulmonary artery flow was performed in patients on three different 1.5 T CMR scanners (GE Healthcare) using identical scan parameters. Uncorrected, first, second and third order stationary tissue corrected flow measurement were compared to phantom corrected flow measurements, our reference method, using Medis QFlow, Circle cvi42 and MASS software. The optimal (optimized) stationary tissue order was determined per scanner and software program. Velocity offsets, net flow, clinically significant difference (deviation > 10% net flow), and regurgitation severity were assessed. RESULTS: Data from 175 patients (28 (17-38) years) were included, of which 84% had congenital heart disease. First, second and third order and optimized stationary tissue correction did not improve the velocity offsets and net flow measurements. Uncorrected measurements resulted in the least clinically significant differences in net flow compared to phantom corrected data. Optimized stationary tissue correction per scanner and software program resulted in net flow differences (> 10%) in 19% (MASS) and 30% (Circle cvi42) of all measurements compared to 18% (MASS) and 23% (Circle cvi42) with no correction. Compared to phantom correction, regurgitation reclassification was the least common using uncorrected data. One CMR scanner performed worse and significant net flow differences of > 10% were present both with and without stationary tissue correction in more than 30% of all measurements. CONCLUSION: Phase offset errors had a significant impact on net flow quantification, regurgitation assessment and varied greatly between CMR scanners. Background phase correction using stationary tissue correction worsened accuracy compared to no correction on three GE Healthcare CMR scanners. Therefore, careful assessment of phase offset errors at each individual scanner is essential to determine whether routine use of phantom correction is necessary. TRIAL REGISTRATION: Observational Study.

Computed Tomography and Magnetic Resonance Imaging.

Imaging in Oncology is rapidly moving from the detection and size measurement of a lesion to the quantitative assessment of metabolic processes and cellular and molecular interactions. Increasing insights into cancer as a complex disease with involvement of the tumor stroma in tumor pathobiological processes have made it clear that for successful control of cancer, treatment strategies should not only be directed at the cancer cells but should also take aspects of the tumor microenvironment into account. This requires an understanding of the complex molecular and cellular interactions in cancer tissue. Recent developments in imaging technology have increased the possibility to image various pathobiological processes in cancer development and response to treatment. For computed tomography (CT) and magnetic resonance imaging (MRI) various improvements in hardware, software, and imaging probes have lifted these modalities from classical anatomical imaging techniques to techniques suitable to image and quantify various physiological processes and molecular and cellular interactions. Next to a more general overview of possible imaging targets in oncology, this chapter provides an overview of the various developments in CT and MRI technology and some specific applications.

Hospital implementation of minimally invasive autopsy: A prospective cohort study of clinical performance and costs.

OBJECTIVES: Autopsy rates worldwide have dropped significantly over the last decades and imaging-based autopsies are increasingly used as an alternative to conventional autopsy. Our aim was to evaluate the clinical performance and cost of minimally invasive autopsy. METHODS: This study was part of a prospective cohort study evaluating a newly implemented minimally invasive autopsy consisting of MRI, CT, and biopsies. We calculated diagnostic yield and clinical utility-defined as the percentage successfully answered clinical questions-of minimally invasive autopsy. We performed minimally invasive autopsy in 46 deceased (30 men, 16 women; mean age 62.9±17.5, min-max: 18-91). RESULTS: Ninety-six major diagnoses were found with the minimally invasive autopsy of which 47/96 (49.0%) were new diagnoses. CT found 65/96 (67.7%) major diagnoses and MRI found 82/96 (85.4%) major diagnoses. Eighty-four clinical questions were asked in all cases. Seventy-one (84.5%) of these questions could be answered with minimally invasive autopsy. CT successfully answered 34/84 (40.5%) clinical questions; in 23/84 (27.4%) without the need for biopsies, and in 11/84 (13.0%) a biopsy was required. MRI successfully answered 60/84 (71.4%) clinical questions, in 27/84 (32.1%) without the need for biopsies, and in 33/84 (39.8%) a biopsy was required. The mean cost of a minimally invasive autopsy was €1296 including brain biopsies and €1087 without brain biopsies. Mean cost of CT was €187 and of MRI €284. CONCLUSIONS: A minimally invasive autopsy, consisting of CT, MRI and CT-guided biopsies, performs well in answering clinical questions and detecting major diagnoses. However, the diagnostic yield and clinical utility were quite low for postmortem CT and MRI as standalone modalities.

Technical challenges of quantitative chest MRI data analysis in a large cohort pediatric study.

OBJECTIVES: This study was conducted in order to evaluate the effect of geometric distortion (GD) on MRI lung volume quantification and evaluate available manual, semi-automated, and fully automated methods for lung segmentation. METHODS: A phantom was scanned with MRI and CT. GD was quantified as the difference in phantom's volume between MRI and CT, with CT as gold standard. Dice scores were used to measure overlap in shapes. Furthermore, 11 subjects from a prospective population-based cohort study each underwent four chest MRI acquisitions. The resulting 44 MRI scans with 2D and 3D Gradwarp were used to test five segmentation methods. Intraclass correlation coefficient, Bland-Altman plots, Wilcoxon, Mann-Whitney U, and paired t tests were used for statistics. RESULTS: Using phantoms, volume differences between CT and MRI varied according to MRI positions and 2D and 3D Gradwarp correction. With the phantom located at the isocenter, MRI overestimated the volume relative to CT by 5.56 ± 1.16 to 6.99 ± 0.22% with body and torso coils, respectively. Higher Dice scores and smaller intraobject differences were found for 3D Gradwarp MR images. In subjects, semi-automated and fully automated segmentation tools showed high agreement with manual segmentations (ICC = 0.971-0.993 for end-inspiratory scans; ICC = 0.992-0.995 for end-expiratory scans). Manual segmentation time per scan was approximately 3-4 h and 2-3 min for fully automated methods. CONCLUSIONS: Volume overestimation of MRI due to GD can be quantified. Semi-automated and fully automated segmentation methods allow accurate, reproducible, and fast lung volume quantification. Chest MRI can be a valid radiation-free imaging modality for lung segmentation and volume quantification in large cohort studies. KEY POINTS: • Geometric distortion varies according to MRI setting and patient positioning. • Automated segmentation methods allow fast and accurate lung volume quantification. • MRI is a valid radiation-free alternative to CT for quantitative data analysis.

Diagnostic accuracy of postmortem computed tomography, magnetic resonance imaging, and computed tomography-guided biopsies for the detection of ischaemic heart disease in a hospital setting.

Aims: The autopsy rate worldwide is alarmingly low (0-15%). Mortality statistics are important, and it is, therefore, essential to perform autopsies in a sufficient proportion of deaths. The imaging autopsy, non-invasive, or minimally invasive autopsy (MIA) can be used as an alternative to the conventional autopsy in an attempt to improve postmortem diagnostics by increasing the number of postmortem procedures. The aim of this study was to determine the diagnostic accuracy of postmortem magnetic resonance imaging (MRI), computed tomography (CT), and CT-guided biopsy for the detection of acute and chronic myocardial ischaemia. Methods and results: We included 100 consecutive adult patients who died in hospital, and for whom next-of-kin gave permission to perform both conventional autopsy and MIA. The MIA consists of unenhanced total-body MRI and CT followed by CT-guided biopsies. Conventional autopsy was used as reference standard. We calculated sensitivity and specificity and receiver operating characteristics curves for CT and MRI as the stand-alone test or combined with biopsy for detection of acute and chronic myocardial infarction (MI). Sensitivity and specificity of MRI with biopsies for acute MI was 0.97 and 0.95, respectively and 0.90 and 0.75, respectively for chronic MI. MRI without biopsies showed a high specificity (acute: 0.92; chronic: 1.00), but low sensitivity (acute: 0.50; chronic: 0.35). CT (total Agatston calcium score) had a good diagnostic value for chronic MI [area under curve (AUC) 0.74, 95% confidence interval (CI) 0.64-0.84], but not for acute MI (AUC 0.60, 95% CI 0.48-0.72). Conclusion: We found that the combination of MRI with biopsies had high sensitivity and specificity for the detection of acute and chronic myocardial ischaemia.

Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening.

Aims: More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction. Here, we tested this hypothesis in a swine model chronically exposed to three common comorbidities. Methods and results: DM (induced by streptozotocin), HC (produced by high fat diet), and HT (resulting from renal artery embolization), were produced in 10 female swine, which were followed for 6 months. Eight female healthy swine on normal pig-chow served as controls. The DM + HC + HT group showed hyperglycemia, HC, hypertriglyceridemia, renal dysfunction and HT, which were associated with systemic inflammation. Myocardial superoxide production was markedly increased, due to increased NOX activity and eNOS uncoupling, and associated with reduced NO production, and impaired coronary small artery endothelium-dependent vasodilation. These abnormalities were accompanied by increased myocardial collagen content, reduced capillary/fiber ratio, and elevated passive cardiomyocyte stiffness, resulting in an increased left ventricular end-diastolic stiffness (measured by pressure-volume catheter) and a trend towards a reduced E/A ratio (measured by cardiac MRI), while ejection fraction was maintained. Conclusions: The combination of three common comorbidities leads to systemic inflammation, myocardial oxidative stress, and coronary microvascular dysfunction, which associate with myocardial stiffening and LV diastolic dysfunction with preserved ejection fraction.

Possibility of quantitative T2-mapping MRI of cartilage near metal in high tibial osteotomy: A human cadaver study.

T2-mapping is a widely used quantitative MRI technique in osteoarthritis research. An important challenge for its application in the context of high tibial osteotomy (HTO) is the presence of metallic fixation devices. In this study, we evaluated the possibility of performing T2-mapping after a HTO, by assessing the extent of magnetic susceptibility artifacts and the influence on T2 relaxation times caused by two commonly used fixation devices. T2-mapping with a 3D fast spin-echo sequence at three Tesla was performed on 11 human cadaveric knee joints before and after implantation of a titanium plate and screws (n = 5) or cobalt chrome staples (n = 6). Mean T2 relaxation times were calculated in six cartilage regions, located in the distal and posterior cartilage of femoral condyles and the cartilage of tibial plateaus, both medially and laterally. T2 relaxation times before and after the implantation were compared with paired t-tests and Wilcoxon rank tests. Due to the extent of the magnetic susceptibility artifact, it was not possible to segment the knee cartilage and thus calculate T2 relaxation times in the lateral weight-bearing femoral and tibial cartilage regions only in the cobalt chrome group. In all cartilage regions of the titanium implanted knees and those unaffected by artifacts due to cobalt chrome implants, T2 relaxation times did not significantly differ between the two scans. Our results suggest that accurate T2-mapping after a HTO procedure is possible in all areas after implantation of a titanium fixation device and in most areas after implantation of a cobalt chrome fixation device. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1206-1212, 2018.

Total-body CT and MR features of postmortem change in in-hospital deaths.

OBJECTIVES: To evaluate the frequency of total-body CT and MR features of postmortem change in in-hospital deaths. MATERIALS AND METHODS: In this prospective blinded cross-sectional study, in-hospital deceased adult patients underwent total-body postmortem CT and MR followed by image-guided biopsies. The presence of PMCT and PMMR features related to postmortem change was scored retrospectively and correlated with postmortem time interval, post-resuscitation status and intensive care unit (ICU) admittance. RESULTS: Intravascular air, pleural effusion, periportal edema, and distended intestines occurred more frequently in patients who were resuscitated compared to those who were not. Postmortem clotting was seen less often in resuscitated patients (p = 0.002). Distended intestines and loss of grey-white matter differentiation in the brain showed a significant correlation with postmortem time interval (p = 0.001, p<0.001). Hyperdense cerebral vessels, intravenous clotting, subcutaneous edema, fluid in the abdomen and internal livores of the liver were seen more in ICU patients. Longer postmortem time interval led to a significant increase in decomposition related changes (p = 0.026). CONCLUSIONS: There is a wide variety of imaging features of postmortem change in in-hospital deaths. These imaging features vary among clinical conditions, increase with longer postmortem time interval and must be distinguished from pathologic changes.

Intermittent pacing therapy favorably modulates infarct remodeling.

Despite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown. We therefore investigated the effects of IPT on global LV remodeling and infarct geometry in swine with a 3-day old AMI. For this purpose, fifteen pigs underwent 2 h ligation of the left circumflex coronary artery followed by reperfusion. An epicardial pacing lead was implanted in the peri-infarct zone. After three days, global LV remodeling and infarct geometry were assessed using magnetic resonance imaging (MRI). Animals were stratified into MI control and IPT groups. Thirty-five days post-AMI, follow-up MRI was obtained and myofibroblast content, markers of extracellular matrix (ECM) turnover and Wnt/frizzled signaling in infarct and non-infarct control tissue were studied. Results showed that IPT had no significant effect on global LV remodeling, function or infarct mass, but modulated infarct healing. In MI control pigs, infarct mass reduction was principally due to a 26.2 ± 4.4% reduction in infarct thickness (P ≤ 0.05), whereas in IPT pigs it was mainly due to a 35.7 ± 4.5% decrease in the number of infarct segments (P ≤ 0.05), with no significant change in infarct thickness. Myofibroblast content of the infarct zone was higher in IPT (10.9 ± 2.1%) compared to MI control (5.4 ± 1.6%; P ≤ 0.05). Higher myofibroblast presence did not coincide with alterations in expression of genes involved in ECM turnover or Wnt/frizzled signaling at 5 weeks follow-up. Taken together, IPT limited infarct expansion and altered infarct composition, showing that IPT influences remodeling of the infarct zone, likely by increasing regional myofibroblast content.

Cloud-processed 4D CMR flow imaging for pulmonary flow quantification.

OBJECTIVES: In this study, we evaluated a cloud-based platform for cardiac magnetic resonance (CMR) four-dimensional (4D) flow imaging, with fully integrated correction for eddy currents, Maxwell phase effects, and gradient field non-linearity, to quantify forward flow, regurgitation, and peak systolic velocity over the pulmonary artery. METHODS: We prospectively recruited 52 adult patients during one-year period from July 2014. The 4D flow and planar (2D) phase-contrast (PC) were acquired during same scanning session, but 4D flow was scanned after injection of a gadolinium-based contrast agent. Eddy-currents were semi-automatically corrected using the web-based software. Flow over pulmonary valve was measured and the 4D flow values were compared against the 2D PC ones. RESULTS: The mean forward flow was 92 (±30) ml/cycle measured with 4D flow and 86 (±29) ml/cycle measured with 2D PC, with a correlation of 0.82 and a mean difference of -6ml/cycle (-41-29). For the regurgitant fraction the correlation was 0.85 with a mean difference of -0.95% (-17-15). Mean peak systolic velocity measured with 4D flow was 92 (±49) cm/s and 108 (±56) cm/s with 2D PC, having a correlation of 0.93 and a mean difference of 16cm/s (-24-55). CONCLUSION: 4D flow imaging post-processed with an integrated cloud-based application accurately quantifies pulmonary flow. However, it may underestimate the peak systolic velocity.

Visualization of Sliding and Deformation of Orbital Fat During Eye Rotation.

PURPOSE: Little is known about the way orbital fat slides and/or deforms during eye movements. We compared two deformation algorithms from a sequence of MRI volumes to visualize this complex behavior. METHODS: Time-dependent deformation data were derived from motion-MRI volumes using Lucas and Kanade Optical Flow (LK3D) and nonrigid registration (B-splines) deformation algorithms. We compared how these two algorithms performed regarding sliding and deformation in three critical areas: the sclera-fat interface, how the optic nerve moves through the fat, and how the fat is squeezed out under the tendon of a relaxing rectus muscle. The efficacy was validated using identified tissue markers such as the lens and blood vessels in the fat. RESULTS: Fat immediately behind the eye followed eye rotation by approximately one-half. This was best visualized using the B-splines technique as it showed less ripping of tissue and less distortion. Orbital fat flowed around the optic nerve during eye rotation. In this case, LK3D provided better visualization as it allowed orbital fat tissue to split. The resolution was insufficient to visualize fat being squeezed out between tendon and sclera. CONCLUSION: B-splines performs better in tracking structures such as the lens, while LK3D allows fat tissue to split as should happen as the optic nerve slides through the fat. Orbital fat follows eye rotation by one-half and flows around the optic nerve during eye rotation. TRANSLATIONAL RELEVANCE: Visualizing orbital fat deformation and sliding offers the opportunity to accurately locate a region of cicatrization and permit an individualized surgical plan.

Qualitative grading of aortic regurgitation: a pilot study comparing CMR 4D flow and echocardiography.

Over the past 10 years there has been intense research in the development of volumetric visualization of intracardiac flow by cardiac magnetic resonance (CMR).This volumetric time resolved technique called CMR 4D flow imaging has several advantages over standard CMR. It offers anatomical, functional and flow information in a single free-breathing, ten-minute acquisition. However, the data obtained is large and its processing requires dedicated software. We evaluated a cloud-based application package that combines volumetric data correction and visualization of CMR 4D flow data, and assessed its accuracy for the detection and grading of aortic valve regurgitation using transthoracic echocardiography as reference. Between June 2014 and January 2015, patients planned for clinical CMR were consecutively approached to undergo the supplementary CMR 4D flow acquisition. Fifty four patients(median age 39 years, 32 males) were included. Detection and grading of the aortic valve regurgitation using CMR4D flow imaging were evaluated against transthoracic echocardiography. The agreement between 4D flow CMR and transthoracic echocardiography for grading of aortic valve regurgitation was good (j = 0.73). To identify relevant,more than mild aortic valve regurgitation, CMR 4D flow imaging had a sensitivity of 100 % and specificity of 98 %. Aortic regurgitation can be well visualized, in a similar manner as transthoracic echocardiography, when using CMR 4D flow imaging.