Diagnosing ARVC in Pediatric Patients Applying the Revised Task Force Criteria: Importance of Imaging, 12-Lead ECG, and Genetics.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a potentially lethal disease that is well described in adults. In pediatric patients, however, identification of patients at risk of adverse events of ARVC remains a challenge. We aimed to determine which criteria of the revised Task Force Criteria (rTFC), alone or combined, have an impact on diagnosis of ARVC when compared to disease-specific genetic mutations in pediatric patients ≤ 18 years. Between September 2010 and December 2013, 48 consecutive young patients ≤ 18 years of age (mean 14, range of 12.9-15.1 years) underwent contrast-enhanced magnetic resonance imaging (CMR), genetic testing, and comprehensive clinical work-up for ARVC criteria to test for clinically suspected ARVC. As specified by the rTFC, patients were grouped into four categories: "definite," "borderline," "possible," and "none" ARVC. Of the 48 patients, 12 were found to have gene mutations of either the desmoplakin (9/12) or plakophilin (3/12) locus. According to rTFC 12/48 patients were considered as "definite" ARVC (25%), while 10/12 (83.3%) had an ARVC-specific gene mutation. Of the remaining 36 patients, 6 (12.5%) were grouped as "borderline" ARVC, 7 (14.6%) as "possible" ARVC (including the remaining two genetic mutations), and 22 (45.8%) as "none" ARVC, respectively. Statistical analysis of ARVC criteria in patients diagnosed with "definite" ARVC revealed high prevalence of positive findings by imaging (CMR and echocardiography) and positive genetics. The positive predictive value to detect "definite" ARVC by genotyping was 83.3%, while the negative predictive value was 94%. Logistic regression analyses for different criteria combinations revealed that imaging modalities (echo and CMR combined) and abnormalities of 12-lead ECG were significant markers (p < 0.01). Positive results of endomyocardial biopsies or arrhythmia on ECG or Holter as defined by the rTFC were not significant in this analysis. The rTFC for ARVC should be used with caution in children and adolescents suspected for ARVC. 12-Lead ECG and imaging modalities (CMR and echo) were of major value, positive results should prompt genetic testing.

Targeted endomyocardial biopsy guided by real-time cardiovascular magnetic resonance.

BACKGROUND: Endomyocardial biopsies (EMB) are an important diagnostic tool for myocarditis and other infiltrative cardiac diseases. Routinely, biopsies are obtained under fluoroscopic guidance with a substantial radiation burden. Despite procedural success, there is a large sampling error caused by missing the affected myocardium. Therefore, multiple (>6) biopsies are taken in the clinical setting. In cardiovascular magnetic resonance (CMR), late gadolinium enhancement (LGE) depicts areas of affected myocardium in myocarditis or in other infiltrative cardiomyopathies. Thus, targeted biopsy under real-time CMR image guidance might reduce the problem of sampling error. METHODS: Seven minipigs of the Goettingen strain underwent radiofrequency ablation in the left ventricle. At least two focal lesions were induced on the lateral wall in five and the apex in two animals. Each ablation lesion was created by two consecutive 30 sec ablations (max. 30 W, temperature 60-64 °C). Biopsies were taken immediately after lesion induction using a commercially available 7 F conventional bioptome under fluoroscopic guidance at the ablation site. Afterwards the animals underwent CMR and lesion visualization by LGE at 3T. The lesions were then targeted and biopsied under CMR-guidance using a MR-conditional bioptome guided by a steerable catheter. Interactive real-time (RT) visualization of the intervention on an in-room monitor was based on radial FLASH with nonlinear inverse reconstruction (NLINV) at a temporal resolution of 42 ms. All samples underwent a standard histological evaluation. RESULTS: Radiofrequency ablation was successful in all animals. Fluoroscopy-guided biopsies were performed with a success rate of 6/6 minipigs - resulting in a nonlethal pericardial effusion in one animal. Visualization of radiofrequency lesions by CMR was successful in 7/7 minipig, i.e. at least one lesion was clearly visible. Localization and tracking of the catheters and the bioptome using interactive control of the imaging plane was achieved in 6/6 MP; however in the animal with a large pericardial effusion after EMB under fluoroscopy no further EMB was attempted for safety reasons. Biopsies under interactive RT-CMR guidance were successfully performed in 5/6 animals, in one animal the bioptome reached the lesion, however the forceps did not cut out a sample. Specimens obtained under CMR guidance contained part of the lesion in 6/15 (40%) myocardial specimens and in 4/5 (80%) animals in which samples were achieved. Conventional biopsies revealed ablation lesions in 4/17 (23.5%) specimens in 3/6 minipigs (50%). CONCLUSION: Focal lesions induced by radiofrequency ablation in a minipig model are a useful tool for CMR-guided biopsy studies. In contrast to fluoroscopy, CMR provides excellent visualization of lesions. Interactive real-time CMR allows excellent passive tracking of the instruments and EMB provides significantly superior sampling accuracy compared to fluoroscopy-guided biopsies. Nonetheless, further improvements of MR-compatible bioptomes and guiding catheters are essential before applying this method in a clinical setting.

A model-based reconstruction technique for quantitative myocardial perfusion imaging.

PURPOSE: To reduce saturation effects in the arterial input function (AIF) estimation of quantitative myocardial first-pass saturation recovery perfusion imaging by employing a model-based reconstruction. THEORY AND METHODS: Imaging was performed with a saturation recovery prepared radial FLASH sequence. A model-based reconstruction was applied for reconstruction. By exploiting prior knowledge about the relaxation process, an image series with different saturation recovery times was reconstructed. By evaluating images with an effective saturation time of approximately 3 ms, saturation effects in the AIF determination were reduced. In a volunteer study, this approach was compared with a standard prebolus technique. RESULTS: In comparison to the low-dose injection of a prebolus acquisition, saturation effects were further reduced in the AIFs determined using the model-based approach. These effects, which were clearly visible for all six volunteers, were reflected in a statistically significant difference of up to 20% in the absolute perfusion values. CONCLUSION: The application of model-based reconstruction algorithms in quantitative myocardial perfusion imaging promises a significant improvement of the AIF determination. In addition to greatly reducing saturation effects that occur even for the prebolus methods, only a single bolus has to be applied. Magn Reson Med 76:880-887, 2016. © 2015 Wiley Periodicals, Inc.

Biphasic 68Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma.

PURPOSE: Binding of (68)Ga-PSMA-HBED-CC ((68)Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) (68)Ga-PSMA-PET/CT in patients with prostate cancer. METHODS: Retrospective analysis of 35 consecutive patients (49-78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140-392 MBq (300 MBq median) (68)Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target-to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes. RESULTS: One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively. CONCLUSIONS: In contrast to benign tissues, the uptake of proven tumor lesions increases on (68)Ga-PSMA-PET/CT over time. A biphasic PET-study may lead to a better detection of tumor lesions in unequivocal findings.

High resolution myocardial first-pass perfusion imaging with extended anatomic coverage.

PURPOSE: To evaluate and to compare Parallel Imaging and Compressed Sensing acquisition and reconstruction frameworks based on simultaneous multislice excitation for high resolution contrast-enhanced myocardial first-pass perfusion imaging with extended anatomic coverage. MATERIALS AND METHODS: The simultaneous multislice imaging technique MS-CAIPIRINHA facilitates imaging with significantly extended anatomic coverage. For additional resolution improvement, equidistant or random undersampling schemes, associated with corresponding reconstruction frameworks, namely Parallel Imaging and Compressed Sensing can be used. By means of simulations and in vivo measurements, the two approaches were compared in terms of reconstruction accuracy. Comprehensive quality metrics were used, identifying statistical and systematic reconstruction errors. RESULTS: The quality measures applied allow for an objective comparison of the frameworks. Both approaches provide good reconstruction accuracy. While low to moderate noise enhancement is observed for the Parallel Imaging approach, the Compressed Sensing framework is subject to systematic errors and reconstruction induced spatiotemporal blurring. CONCLUSION: Both techniques allow for perfusion measurements with a resolution of 2.0 × 2.0 mm(2) and coverage of six slices every heartbeat. Being not affected by systematic deviations, the Parallel Imaging approach is considered to be superior for clinical studies.

Density weighted turbo spin echo imaging.

PURPOSE: To optimize the spatial response function (SRF) while maintaining optimal signal to noise ratio (SNR) in T2 weighted turbo spin echo (TSE) imaging by prospective density weighting. MATERIALS AND METHODS: Density weighting optimizes the SRF by sampling the k-space with variable density without the need of retrospective filtering, which would typically result in nonoptimal SNR. For TSE, the T2 decay needs to be considered when calculating an optimized sampling pattern. Simulations were carried out and T2 weighted in vivo TSE measurements were performed on a 3 Tesla MRI system. To evaluate the SNR, reversed centric density weighted and retrospectively filtered Cartesian acquisitions with identical measurement parameters and SRFs were compared with TE(eff) = 90 ms and a density weighted k-space sampling optimized to yield a Kaiser function for SRF side lobe suppression for white matter. RESULTS: Density weighting of a reversed centric reordering scheme resulted in an SNR increase of (43 ± 13)% compared with the Cartesian acquisition with retrospective filtering while maintaining comparable contrast behavior. CONCLUSION: Density weighting is applicable to TSE imaging and results in significantly increased SNR. The gain can be used to shorten the measurement time, which suggests applying density weighting in both time and SNR constrained MRI.

CAIPIRINHA accelerated SSFP imaging.

Exciting multiple slices at the same time, "controlled aliasing in parallel imaging results in higher acceleration" (CAIPIRINHA) and "phase-offset multiplanar" have shown to be very effective techniques in 2D multislice imaging. Being provided with individual rf phase cycles, the simultaneously excited slices are shifted with respect to each other in the FOV and, thus, can be easily separated. For SSFP sequences, however, similar rf phase cycles are required to maintain the steady state, impeding a straightforward application of phase-offset multiplanar or controlled aliasing in parallel imaging results in higher acceleration. In this work, a new flexible concept for applying the two multislice imaging techniques to SSFP sequences is presented. Linear rf phase cycles are introduced providing both in one, the required shift between the slices and steady state in each slice throughout the whole measurement. Consequently, the concept is also appropriate for real-time and magnetization prepared imaging. Steady state properties and shifted banding behavior of the new phase cycles were investigated using simulations and phantom experiments. Moreover, the concept was applied to perform whole heart myocardial perfusion SSFP imaging as well as real-time and cine SSFP imaging with increased coverage. Showing no significant penalties in SNR or image quality, the results successfully demonstrate the general applicability of the concept.

Automatic postprocessing for the assessment of quantitative human myocardial perfusion using MRI.

OBJECTIVE: Quantitative determination of myocardial perfusion currently involves time-consuming postprocessing. This retrospective study presents automatic postprocessing consisting of image registration and image segmentation to obtain regional signal intensity time courses and quantitative perfusion values. METHODS: The automatic postprocessing was tested in 75 examinations in volunteers and patients, 57 at rest and 18 under adenosine-induced stress, and compared with a manual evaluation. In a substudy consisting of 10 examinations, the interobserver variability of the manual evaluation was investigated. RESULTS: Manual evaluation resulted in perfusion values with a median of 0.70 ml/g/min ranging from 0.03 to 3.68 ml/g/min. For all 75 examinations, the variability (standard deviation of the differences) between automatic and manual evaluation was 0.34 ml/g/min. Interobserver variability was of a similar order, 0.35 ml/g/min for all measurements. CONCLUSIONS: Automatic evaluation was successfully applied to all datasets giving results equivalent to manual evaluation. The time of user interaction for one single slice could be reduced from 25 min for manual evaluation to less than 1 min using the automatic algorithm. This reduction may allow quantitative magnetic resonance perfusion imaging to become a routine clinical procedure.

Atrio-ventricular deformation and heart failure in Ebstein's Anomaly - A cardiovascular magnetic resonance study.

PURPOSE: We aimed to quantify atrial and ventricular myocardial deformation in Ebstein's Anomaly (EA) in a case-control study with cardiovascular magnetic resonance (CMR) feature tracking and to correlate changes in cardiac performance with the severity of disease and clinical heart failure parameters. MATERIALS AND METHODS: Atrial and ventricular deformation was measured using CMR feature tracking in 30 EA and 20 healthy control subjects. Atrial performance was characterized using longitudinal strain and strain rate parameters for reservoir function, conduit function and booster pump function. Ventricular performance was characterized using RV and LV global longitudinal strain (εl) and LV circumferential and radial strain (εc and εr). Volumetric measurements for the ventricles including the Total Right/Left-Volume-Index (R/L-Volume-Index) and heart failure markers (BNP, NYHA class) were also quantified. RESULTS: EA patients showed significantly impaired right atrial performance, which correlated with heart failure markers (NYHA, BNP, R/L-Volume-Index). LA function in EA patients was also impaired with atrial contractile function correlating with NYHA class. EA patients exhibited impaired RV myocardial deformation, also with a significant correlation with heart failure markers. CONCLUSION: CMR feature tracking can be used to quantify ventricular and atrial function in a complex cardiac malformation such as EA. EA is characterized by impaired quantitative right heart atrio-ventricular deformation, which is associated with heart failure severity. While LV function remains preserved, there is also significant impairment of LA function. These quantitative performance parameters may represent early markers of cardiac deterioration of potential value in the clinical management of EA.

Quantification of left atrial volume and phasic function using cardiovascular magnetic resonance imaging-comparison of biplane area-length method and Simpson's method.

Left atrial (LA) enlargement and dysfunction are markers of chronic diastolic dysfunction and an important predictor of adverse cardiovascular and cerebrovascular outcomes. Accordingly, accurate quantification of left atrial volume (LAV) and function is needed. In routine clinical cardiovascular magnetic resonance (CMR) imaging the biplane area-length method (Bi-ALM) is frequently applied due to time-saving image acquisition and analysis. However, given the varying anatomy of the LA we hypothesized that the diagnostic accuracy of the Bi-ALM is not sufficient and that results would be different from a precise volumetric assessment of transversal multi-slice cine images using Simpson's method. Thirty one patients of the FIND-AFRANDOMISED-study with status post acute cerebral ischemia (mean age 70.5 ± 6.2 years) received CMR imaging at 3T. The study protocol included cine SSFP sequences in standard 2- and 4 CV and a stack of contiguous slices in transversal orientation. Total, passive and active LA emptying fractions were calculated from LA maximal volume, minimal volume and volume prior to atrial contraction. Intra- and inter-observer variability was assessed in ten patients. Significant differences were found for LA volume and phasic function. The Bi-ALM significantly underestimated LA volume and overestimated LA function in comparison to Simpson's method (Bi-ALM vs. Simpson's method: LAVmax: 80.18 vs. 98.80 ml; LAVpre-ac: 61.09 vs. 80.41 ml; LAVmin: 36.85 vs. 52.66 ml; LAEFTotal: 55.17 vs. 47.85%; LAEFPassive: 23.96 vs. 19.15%; LAEFBooster: 40.87 vs. 35.64%). LA volumetric and functional parameters were reproducible on an intra- and inter-observer levels for both methods. Intra-observer agreement for LA function was better for Simpson's method (Bi-ALM vs. Simpson's method; ICC LAEFTotal: 0.84 vs. 0.96; ICC LAEFPassive: 0.74 vs. 0.92; ICC LAEFBooster: 0.86 vs. 0.89). The Bi-ALM is based on geometric assumptions that do not reflect the complex individual LA geometry. The assessment of transversal slices covering the left atrium with Simpson's method is feasible and might be more suitable for an accurate quantification of LA volume and phasic function.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Quantitative Lung Perfusion Imaging Using the Dual-Bolus Approach: Comparison of 3 Contrast Agents and Recommendation of Feasible Doses.

OBJECTIVE: The aims of this study were to compare 3 contrast agents and to define feasible doses for quantitative lung perfusion imaging using the dual-bolus approach in dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Ten healthy volunteers (6 males, 4 females; mean age, 23.5 years) underwent DCE-MRI at 1.5 T using a 3D FLASH sequence. After a prebolus, 3 doses of gadopentetate dimeglumine (Gd-DTPA), gadofosveset, and gadobenate dimeglumine (Gd-BOPTA) were evaluated. Dose regimes were as follows: Gd-DTPA: 3.0 mL, 6.0 mL, and 12.0 mL with 1.5 mL prebolus; gadofosveset: 1.5 mL, 3.0 mL, and 6.0 mL with 0.8 mL prebolus; and Gd-BOPTA: 1.5 mL, 3.0 mL, and 6.0 mL with 0.8 mL prebolus. Pulmonary blood flow (PBF), pulmonary distribution volume, and mean transit time were assessed for each bolus. Region of interest measurements were used to determine the arterial input function (AIF) in the pulmonary trunk and signal intensities in lung parenchyma. Two radiologists independently rated the subjective image quality of the quantitative perfusion maps based on a 4-point Likert scale. RESULTS: Dose-dependent signal saturation effects were observed for all 3 contrast agents concerning AIF and parenchyma measurements. Signal yields were comparable using Gd-BOPTA (AIF, 214.49 arbitrary units [AU]; parenchyma, 41.7 AU) and Gd-DTPA (207.43 AU; 36.3 AU). Gadofosveset showed significantly lower signal yield (165.74 AU; 25.2 AU; p < 0.008). Highest signal increase was observed for Gd-DTPA. Using Gd-DTPA, mean PBF values for the 3 doses (3 mL, 6 mL, 12 mL) in mL/min per milliliter lung volume were 2.9 ± 1.5, 2.4 ± 1.1, and 1.6 ± 1.0. For the 3 doses of gadofosveset (1.5 mL, 3 mL, 6 mL) mean PBF results were 3.1 ± 1.1, 1.9 ± 0.7, and 1.2 ± 0.6. Last, mean PBF values for Gd-BOPTA (1.5 mL, 3 mL, 6 mL) were 3.4 ± 1.7, 2.8 ± 1.3, and 2.0 ± 0.8. Measurements provided consistent values for all perfusion parameters (PBF, pulmonary distribution volume, mean transit time) when compared with reference literature. Contrast dose volume and the applied contrast agent had no relevant effects on the image quality scores. CONCLUSIONS: The dual-bolus approach using a 3D FLASH sequence is a feasible tool for quantitative lung perfusion imaging. Small boluses of 3 mL for Gd-DTPA, 1.5 mL for Gd-BOPTA, and 1.5 mL for gadofosveset provide sufficient signal yield for quantitative parenchyma measurements. Using higher boluses falsely lower perfusion values have to be considered due to signal saturation effects. Although gadofosveset yielded the lowest signal, the generated quantitative perfusion maps were of diagnostic quality.

The cardiomyopathy in Friedreich's ataxia - New biomarker for staging cardiac involvement.

BACKGROUND: Patients with autosomal-recessively inherited Friedreich's ataxia (FA) may develop a hypertrophic cardiomyopathy (CM), which potentially progresses towards a life-limiting problem. The typical features of this CM and the sequence of progression are widely unknown. METHODS: Thirty-two consecutive patients with genetically confirmed FA were included. All patients received resting electrocardiogram (ECG), 24-hour Holter-ECG, echocardiography with speckle tracking imaging, cardiac magnetic resonance imaging (cMRI) with late enhancement imaging (for replacement fibrosis), and measurement of high-sensitive troponin-T (hsTNT). In addition, morphological parameters were retrospectively compared to data obtained five years before. RESULTS: Based on criteria comprising ejection fraction (<55%), left ventricular end-diastolic posterior wall thickness (LVPWT ≥ 11 mm), fibrosis on cMRI, hsTNT ≥ 14 ng/ml, or T-wave-inversion, in all but two patients a CM could be detected (94%). Using these criteria we propose the following staging: a) mild CM (n=5, 16%; T-wave-inversion only); b) intermediate CM (n=4, 13%; T-wave-inversion with hypertrophy but no fibrosis); c) severe CM (n=13, 41%; fibrosis with raised hsTNT); and d) end-stage CM (n=8; 25%; ejection-fraction<55%). All patients with end-stage CM also showed fibrosis on cMRI, T-wave-inversion, marked elevation in hsTNT, and a decrease in LVPWT during the last five years (from 10.7 ± 1.2mm to 9.5 ± 1.3mm, p=0.025). In addition, 38% suffered from supraventricular tachycardia on Holter-ECG. CONCLUSIONS: A comprehensive cardiac assessment will unravel established CM in almost all patients with FA with electrocardiographic abnormalities as earliest signs. Advanced stages can be characterized by elevated hsTNT and replacement fibrosis leading to recession of hypertrophy, reduction of global myocardial function, and electrical instability.

Iatrogenic perforation of the left heart during placement of a chest drain.

Chest drain placement is a standard procedure for treating pneumothorax and pleural effusions and has a low complication rate. It is a safe and efficient procedure if image guidance is used. If the anatomic orientation is hampered and neither air nor fluids can be initially aspirated, more complex imaging than a chest x-ray is indicated to avoid major complications. We report the case of an 88-year-old male patient suffering from chronic heart failure who was admitted to another hospital following acute cardiac decompensation. Because of dyspnea with voluminous bilateral effusions, an attempt was made to drain the left pleural cavity. A malposition of the chest drain was suspected because blood was initially draining from the catheter. The hemodynamically stable patient was referred to our university hospital, where computed tomography of the chest revealed the location of the intercostal drain. The drain had perforated the left ventricle, run through the mitral valve and exited the left atrium via a pulmonary vein, ending in the middle lobe. The patient was brought to the surgical theater, where cardiac surgeons performed a left anterolateral thoracotomy and extracted the drain successfully. Three days later, the patient was discharged from our hospital in a good general condition.