Publications
74 results found
Khalique Z, Scott AD, Ferreira PF, et al., 2019, Diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy: a comparison of motion-compensated spin echo and stimulated echo techniques, Magnetic Resonance Materials in Physics, Biology and Medicine, Vol: 33, Pages: 331-342, ISSN: 0968-5243
ObjectivesDiffusion tensor cardiovascular magnetic resonance (DT-CMR) interrogates myocardial microstructure. Two frequently used in vivo DT-CMR techniques are motion-compensated spin echo (M2-SE) and stimulated echo acquisition mode (STEAM). Whilst M2-SE is strain-insensitive and signal to noise ratio efficient, STEAM has a longer diffusion time and motion compensation is unnecessary. Here we compare STEAM and M2-SE DT-CMR in patients.Materials and methodsBiphasic DT-CMR using STEAM and M2-SE, late gadolinium imaging and pre/post gadolinium T1-mapping were performed in a mid-ventricular short-axis slice, in ten hypertrophic cardiomyopathy (HCM) patients at 3 T.ResultsAdequate quality data were obtained from all STEAM, but only 7/10 (systole) and 4/10 (diastole) M2-SE acquisitions. Compared with STEAM, M2-SE yielded higher systolic mean diffusivity (MD) (p = 0.02) and lower fractional anisotropy (FA) (p = 0.02, systole). Compared with segments with neither hypertrophy nor late gadolinium, segments with both had lower systolic FA using M2-SE (p = 0.02) and trend toward higher MD (p = 0.1). The negative correlation between FA and extracellular volume fraction was stronger with STEAM than M2-SE (r2 = 0.29, p < 0.001 STEAM vs. r2 = 0.10, p = 0.003 M2-SE).DiscussionIn HCM, only STEAM reliably assesses biphasic myocardial microstructure. Higher MD and lower FA from M2-SE reflect the shorter diffusion times. Further work will relate DT-CMR parameters and microstructural changes in disease.
Tayal U, Wage R, Ferreira P, et al., 2019, The feasibility of a novel limited field of view spiral cine DENSE sequence to assess myocardial strain in dilated cardiomyopathy, Magnetic Resonance Materials in Physics, Biology and Medicine, Vol: 32, Pages: 317-329, ISSN: 0968-5243
ObjectiveDevelop an accelerated cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) sequence to enable clinically feasible myocardial strain evaluation in patients with dilated cardiomyopathy (DCM).Materials and methodsA spiral cine DENSE sequence was modified by limiting the field of view in two dimensions using in-plane slice-selective pulses in the stimulated echo. This reduced breath hold duration from 20RR to 14RR intervals. Following phantom and pilot studies, the feasibility of the sequence to assess peak radial, circumferential, and longitudinal strain was tested in control subjects (n = 18) and then applied in DCM patients (n = 29).ResultsDENSE acquisition was possible in all participants. Elements of the data were not analysable in 1 control (6%) and 4 DCM r(14%) subjects due to off-resonance or susceptibility artefacts and low signal-to-noise ratio. Peak radial, circumferential, short-axis contour strain and longitudinal strain was reduced in DCM patients (p < 0.001 vs. controls) and strain measurements correlated with left ventricular ejection fraction (with circumferential strain r = − 0.79, p < 0.0001; with vertical long-axis strain r = − 0.76, p < 0.0001). All strain measurements had good inter-observer agreement (ICC > 0.80), except peak radial strain.DiscussionWe demonstrate the feasibility of CMR strain assessment in healthy controls and DCM patients using an accelerated cine DENSE technique. This may facilitate integration of strain assessment into routine CMR studies.
Rose JN, Nielles-Vallespin S, Ferreira PF, et al., 2019, Novel insights into in-vivo diffusion tensor cardiovascular magnetic resonance using computational modelling and a histology-based virtual microstructure, Magnetic Resonance in Medicine, Vol: 81, Pages: 2759-2773, ISSN: 0740-3194
PurposeTo develop histology‐informed simulations of diffusion tensor cardiovascular magnetic resonance (DT‐CMR) for typical in‐vivo pulse sequences and determine their sensitivity to changes in extra‐cellular space (ECS) and other microstructural parameters.MethodsWe synthesised the DT‐CMR signal from Monte Carlo random walk simulations. The virtual tissue was based on porcine histology. The cells were thickened and then shrunk to modify ECS. We also created idealised geometries using cuboids in regular arrangement, matching the extra‐cellular volume fraction (ECV) of 16–40%. The simulated voxel size was 2.8 × 2.8 × 8.0 mm3 for pulse sequences covering short and long diffusion times: Stejskal–Tanner pulsed‐gradient spin echo, second‐order motion‐compensated spin echo, and stimulated echo acquisition mode (STEAM), with clinically available gradient strengths.ResultsThe primary diffusion tensor eigenvalue increases linearly with ECV at a similar rate for all simulated geometries. Mean diffusivity (MD) varies linearly, too, but is higher for the substrates with more uniformly distributed ECS. Fractional anisotropy (FA) for the histology‐based geometry is higher than the idealised geometry with low sensitivity to ECV, except for the long mixing time of the STEAM sequence. Varying the intra‐cellular diffusivity (DIC) results in large changes of MD and FA. Varying extra‐cellular diffusivity or using stronger gradients has minor effects on FA. Uncertainties of the primary eigenvector orientation are reduced using STEAM.ConclusionsWe found that the distribution of ECS has a measurable impact on DT‐CMR parameters. The observed sensitivity of MD and FA to ECV and DIC has potentially interesting applications for interpreting in‐vivo DT‐CMR parameters.
Gorodezky M, Ferreira P, Nielles-Vallespin S, et al., 2019, High resolution in-vivo DT-CMR using an interleaved variable density spiral STEAM sequence, Magnetic Resonance in Medicine, Vol: 81, Pages: 1580-1594, ISSN: 0740-3194
Purpose: Diffusion tensor cardiovascular magnetic resonance (DT-CMR) has a limited spatial resolution. Thepurpose of this study was to demonstrate high-resolution DT-CMR using a segmented variable density spiralsequence with correction for motion, off-resonance and T2* related blurring.Methods: A single-shot STEAM EPI DT-CMR sequence at 2.8x2.8x8mm3 and 1.8x1.8x8mm3 was compared to asingle shot spiral at 2.8x2.8x8mm3 and an interleaved spiral sequence at 1.8x1.8x8mm3resolution in 10 healthyvolunteers at peak-systole and diastasis. Motion-induced phase was corrected using the densely sampledcentral k-space data of the spirals. STEAM field maps and T2* measures were obtained using a pair ofstimulated echoes each with a double spiral readout, the first used to correct the motion-induced phase of thesecond.Results: The high resolution spiral sequence produced similar DT-CMR results and quality measures to thestandard resolution sequence in both cardiac phases. Residual differences in fractional anisotropy and helixangle gradient between the resolutions could be due to spatial resolution and/or signal to noise ratio. The dataquality increased after both motion-induced phase correction and off-resonance correction and sharpnessincreased after T2* correction. The high resolution EPI sequence failed to provide sufficient data quality forDT-CMR reconstruction.Conclusion: In this study an in-vivo DT-CMR acquisition at 1.8x1.8mm2in-plane resolution was demonstratedusing a segmented spiral STEAM sequence. The motion-induced phase and off-resonance corrections areessential for high resolution spiral DT-CMR. Segmented variable density spiral STEAM was found to be theoptimal method for acquiring high resolution DT-CMR data.
Khalique Z, Ferreira P, Scott A, et al., 2018, Diffusion Tensor Cardiovascular Magnetic Resonance of Microstructural Recovery in Dilated Cardiomyopathy, JACC: Cardiovascular Imaging, Vol: 11, Pages: 1548-1550, ISSN: 1936-878X
Schlemper J, Yang G, Ferreira P, et al., 2018, Stochastic deep compressive sensing for the reconstruction of diffusion tensor cardiac MRI, Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), Vol: 11070 LNCS, Pages: 295-303, ISSN: 0302-9743
© Springer Nature Switzerland AG 2018. Understanding the structure of the heart at the microscopic scale of cardiomyocytes and their aggregates provides new insights into the mechanisms of heart disease and enables the investigation of effective therapeutics. Diffusion Tensor Cardiac Magnetic Resonance (DT-CMR) is a unique non-invasive technique that can resolve the microscopic structure, organisation, and integrity of the myocardium without the need for exogenous contrast agents. However, this technique suffers from relatively low signal-to-noise ratio (SNR) and frequent signal loss due to respiratory and cardiac motion. Current DT-CMR techniques rely on acquiring and averaging multiple signal acquisitions to improve the SNR. Moreover, in order to mitigate the influence of respiratory movement, patients are required to perform many breath holds which results in prolonged acquisition durations (e.g., ~ 30 min using the existing technology). In this study, we propose a novel cascaded Convolutional Neural Networks (CNN) based compressive sensing (CS) technique and explore its applicability to improve DT-CMR acquisitions. Our simulation based studies have achieved high reconstruction fidelity and good agreement between DT-CMR parameters obtained with the proposed reconstruction and fully sampled ground truth. When compared to other state-of-the-art methods, our proposed deep cascaded CNN method and its stochastic variation demonstrated significant improvements. To the best of our knowledge, this is the first study using deep CNN based CS for the DT-CMR reconstruction. In addition, with relatively straightforward modifications to the acquisition scheme, our method can easily be translated into a method for online, at-the-scanner reconstruction enabling the deployment of accelerated DT-CMR in various clinical applications.
Pennell DJ, Khalique Z, Ferreira PF, et al., 2018, Deranged myocyte microstructure in situs inversus totalis demonstrated by diffusion tensor cardiovascular magnetic resonance, JACC: Cardiovascular Imaging, Vol: 11, Pages: 1360-1362, ISSN: 1936-878X
Gorodezky M, Scott AD, Ferreira PF, et al., 2018, Diffusion tensor cardiovascular magnetic resonance with a spiral trajectory: An in vivo comparison of echo planar and spiral stimulated echo sequences, Magnetic Resonance in Medicine, Vol: 80, Pages: 648-654, ISSN: 0740-3194
PURPOSE: Diffusion tensor cardiovascular MR (DT-CMR) using stimulated echo acquisition mode (STEAM) with echo-planar-imaging (EPI) readouts is a low signal-to-noise-ratio (SNR) technique and therefore typically has a low spatial resolution. Spiral trajectories are more efficient than EPI, and could increase the SNR. The purpose of this study was to compare the performance of a novel STEAM spiral DT-CMR sequence with an equivalent established EPI technique. METHODS: A STEAM DT-CMR sequence was implemented with a spiral readout and a reduced field of view. An in vivo comparison of DT-CMR parameters and data quality between EPI and spiral was performed in 11 healthy volunteers imaged in peak systole and diastasis at 3 T. The SNR was compared in a phantom and in vivo. RESULTS: There was a greater than 49% increase in the SNR in vivo and in the phantom measurements (in vivo septum, systole: SNREPI = 8.0 ± 2.2, SNRspiral = 12.0 ± 2.7; diastasis: SNREPI = 8.1 ± 1.6, SNRspiral = 12.0 ± 3.7). There were no significant differences in helix angle gradient (HAG) (systole: HAGEPI = -0.79 ± 0.07 °/%; HAGspiral = -0.74 ± 0.16 °/%; P = 0.11; diastasis: HAGEPI = -0.63 ± 0.05 °/%; HAGspiral = -0.56 ± 0.14 °/%; P = 0.20), mean diffusivity (MD) in systole (MDEPI = 0.99 ± 0.06 × 10-3 mm2 /s, MDspiral = 1.00 ± 0.09 × 10-3 mm2 /s, P = 0.23) and secondary eigenvector angulation (E2A) (systole: E2AEPI = 61 ± 10 °; E2Aspiral = 63 ± 10 °; P&thi
Khalique Z, Ferreira PF, Scott AD, et al., 2018, ASSESSMENT OF THE MICROSTRUCTURE IN RECOVERED DILATED CARDIOMYOPATHY WITH DIFFUSION TENSOR CARDIOVASCULAR MAGNETIC RESONANCE, Joint Meeting of the British-Society-of-Cardiovascular-Imaging/British-Society-of-Cardiovascular-CT, British-Society-of-Cardiovascular-Magnetic-Resonance and British-Nuclear-Cardiac-Society on British Cardiovascular Imaging, Publisher: BMJ PUBLISHING GROUP, Pages: A6-A7, ISSN: 1355-6037
Scott AD, Nielles-Vallespin S, Ferreira P, et al., 2018, An in-vivo comparison of stimulated-echo and motion compensated spin-echo sequences for 3T diffusion tensor cardiovascular magnetic resonance at multiple cardiac phases, Journal of Cardiovascular Magnetic Resonance, Vol: 20, ISSN: 1097-6647
BackgroundStimulated-echo (STEAM) and, more recently, motion-compensated spin-echo (M2-SE) techniques have been used for in-vivo diffusion tensor cardiovascular magnetic resonance (DT-CMR) assessment of cardiac microstructure. The two techniques differ in the length scales of diffusion interrogated, their signal-to-noise ratio efficiency and sensitivity to both motion and strain. Previous comparisons of the techniques have used high performance gradients at 1.5 T in a single cardiac phase. However, recent work using STEAM has demonstrated novel findings of microscopic dysfunction in cardiomyopathy patients, when DT-CMR was performed at multiple cardiac phases. We compare STEAM and M2-SE using a clinical 3 T scanner in three potentially clinically interesting cardiac phases.MethodsBreath hold mid-ventricular short-axis DT-CMR was performed in 15 subjects using M2-SE and STEAM at end-systole, systolic sweet-spot and diastasis. Success was defined by ≥50% of the myocardium demonstrating normal helix angles. From successful acquisitions DT-CMR results relating to tensor orientation, size and shape were compared between sequences and cardiac phases using non-parametric statistics. Strain information was obtained using cine spiral displacement encoding with stimulated echoes for comparison with DT-CMR results.ResultsAcquisitions were successful in 98% of STEAM and 76% of M2-SE cases and visual helix angle (HA) map scores were higher for STEAM at the sweet-spot and diastasis. There were significant differences between sequences (p < 0.05) in mean diffusivity (MD), fractional anisotropy (FA), tensor mode, transmural HA gradient and absolute second eigenvector angle (E2A). Differences in E2A between systole and diastole correlated with peak radial strain for both sequences (p ≤ 0.01).ConclusionM2-SE and STEAM can be performed equally well at peak systole at 3 T using standard gradients, but at the sweet-spot and diastole STEAM is more rel
Ferreira PF, Nielles-Vallespin S, Scott AD, et al., 2017, Evaluation of the impact of strain correction on the orientation of cardiac diffusion tensors with in vivo and ex vivo porcine hearts, Magnetic Resonance in Medicine, Vol: 79, Pages: 2205-2215, ISSN: 0740-3194
PurposeTo evaluate the importance of strain-correcting stimulated echo acquisition mode echo-planar imaging cardiac diffusion tensor imaging.MethodsHealthy pigs (n = 11) were successfully scanned with a 3D cine displacement-encoded imaging with stimulated echoes and a monopolar-stimulated echo-planar imaging diffusion tensor imaging sequence at 3 T during diastasis, peak systole, and strain sweet spots in a midventricular short-axis slice. The same diffusion tensor imaging sequence was repeated ex vivo after arresting the hearts in either a relaxed (KCl-induced) or contracted (BaCl2-induced) state. The displacement-encoded imaging with stimulated echoes data were used to strain-correct the in vivo cardiac diffusion tensor imaging in diastole and systole. The orientation of the primary (helix angles) and secondary (E2A) diffusion eigenvectors was compared with and without strain correction and to the strain-free ex vivo data.ResultsStrain correction reduces systolic E2A significantly when compared without strain correction and ex vivo (median absolute E2A = 34.3° versus E2A = 57.1° (P = 0.01), E2A = 60.5° (P = 0.006), respectively). The systolic distribution of E2A without strain correction is closer to the contracted ex vivo distribution than with strain correction, root mean square deviation of 0.027 versus 0.038.ConclusionsThe current strain-correction model amplifies the contribution of microscopic strain to diffusion resulting in an overcorrection of E2A. Results show that a new model that considers cellular rearrangement is required.
Lota A, Wassall R, Scott A, et al., 2017, T2 mapping by cardiovasular magnetic resonance in acute and recovered myocarditis: potential role in clinical surveillance, European Journal of Heart Failure, Supplement, Vol: 19, Pages: 258-258, ISSN: 1567-4215
Nielles-Vallespin S, Khalique Z, Ferreira PF, et al., 2017, Assessment of myocardial microstructural dynamics by in vivo diffusion tensor cardiac magnetic resonance, Journal of the American College of Cardiology, Vol: 69, Pages: 661-676, ISSN: 0735-1097
BackgroundCardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function.ObjectivesThis study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM.MethodsIn vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients.ResultsIn swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001).ConclusionsMyocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with alte
Scott AD, Tayal U, Nielles-Vallespin S, et al., 2016, Accelerating cine DENSE using a zonal excitation, Journal of Cardiovascular Magnetic Resonance, Vol: 18, Pages: 1-3, ISSN: 1097-6647
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Scott AD, Ferreira P, Nielles-Vallespin S, et al., 2016, Can we predict the diffusion “sweet-spot” based on a standard cine?, Journal of Cardiovascular Magnetic Resonance, Vol: 18, Pages: 1-3, ISSN: 1097-6647
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Scott AD, Nielles-Vallespin S, Ferreira P, et al., 2016, In-vivo cardiac DTI: An initial comparison of M012 compensated spin-echo and STEAM, Journal of Cardiovascular Magnetic Resonance, Vol: 18, Pages: 1-3, ISSN: 1097-6647
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McGill LA, Ferreira PF, Scott AD, et al., 2016, Relationship between cardiac diffusion tensor imaging parameters and anthropometrics in healthy volunteers, Journal of Cardiovascular Magnetic Resonance, Vol: 18, Pages: 2-2
Scott AD, Nielles-Vallespin S, Ferreira PF, et al., 2016, The effects of noise in cardiac diffusion tensor imaging and the benefits of averaging complex data, NMR in Biomedicine, Vol: 29, Pages: 588-599
Wylezinska M, Pinkstone M, Hay N, et al., 2015, Impact of orthodontic appliances on the quality of craniofacial anatomical magnetic resonance imaging and real-time speech imaging, EUROPEAN JOURNAL OF ORTHODONTICS, Vol: 37, Pages: 610-617, ISSN: 0141-5387
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McGill LA, Scott AD, Ferreira P, et al., 2015, Heterogeneity of diffusion tensor imaging measurements of fractional anisotropy and mean diffusivity in normal human hearts in vivo, Journal of Cardiovascular Magnetic Resonance, Vol: 17, ISSN: 1097-6647
Scott AD, Nielles-Vallespin S, Ferreira P, et al., 2015, Improving the accuracy of cardiac DTI by averaging the complex data, Journal of Cardiovascular Magnetic Resonance, Pages: 1-3, ISSN: 1097-6647
Scott AD, Ferreira P, Nielles-Vallespin S, et al., 2015, Directions vs. averages: An in-vivo comparison for cardiac DTI, Journal of Cardiovascular Magnetic Resonance, Pages: 1-2, ISSN: 1097-6647
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Kilner PJ, McCarthy K, Murillo M, et al., 2015, Histology of human myocardial laminar microstructure and consideration of its cyclic deformations with respect to interpretation of in vivo cardiac diffusion tensor imaging, Journal of Cardiovascular Magnetic Resonance, Pages: 1-3, ISSN: 1097-6647
McGill L-A, Scott AD, Ferreira PF, et al., 2015, Heterogeneity of fractional anisotropy and mean diffusivity measurements by in vivo diffusion tensor imaging in normal human hearts, PloS one, Vol: 10, Pages: e0132360-e0132360
Scott AD, Ferreira PFADC, Nielles-Vallespin S, et al., 2015, Optimal diffusion weighting for in vivo cardiac diffusion tensor imaging, Magnetic resonance in medicine, Vol: 74, Pages: 420-430
Ferreira PF, Kilner PJ, McGill L-A, et al., 2014, In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy, Journal of Cardiovascular Magnetic Resonance, Vol: 16, Pages: 1-16, ISSN: 1097-6647
BackgroundCardiac diffusion tensor imaging (cDTI) measures the magnitudes and directions of intramyocardial water diffusion. Assuming the cross-myocyte components to be constrained by the laminar microstructures of myocardium, we hypothesized that cDTI at two cardiac phases might identify any abnormalities of laminar orientation and mobility in hypertrophic cardiomyopathy (HCM).MethodsWe performed cDTI in vivo at 3 Tesla at end-systole and late diastole in 11 healthy controls and 11 patients with HCM, as well as late gadolinium enhancement (LGE) for detection of regional fibrosis.ResultsVoxel-wise analysis of diffusion tensors relative to left ventricular coordinates showed expected transmural changes of myocardial helix-angle, with no significant differences between phases or between HCM and control groups. In controls, the angle of the second eigenvector of diffusion (E2A) relative to the local wall tangent plane was larger in systole than diastole, in accord with previously reported changes of laminar orientation. HCM hearts showed higher than normal global E2A in systole (63.9° vs 56.4° controls, p =0.026) and markedly raised E2A in diastole (46.8° vs 24.0° controls, p < 0.001). In hypertrophic regions, E2A retained a high, systole-like angulation even in diastole, independent of LGE, while regions of normal wall thickness did not (LGE present 57.8°, p =0.0028, LGE absent 54.8°, p =0.0022 vs normal thickness 38.1°).ConclusionsIn healthy controls, the angles of cross-myocyte components of diffusion were consistent with previously reported transmural orientations of laminar microstructures and their changes with contraction. In HCM, especially in hypertrophic regions, they were consistent with hypercontraction in systole and failure of relaxation in diastole. Further investigation of this finding is required as previously postulated effects of strain might be a confounding factor.
Scott AD, Wylezinska M, Birch MJ, et al., 2014, Speech MRI: Morphology and function, PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS, Vol: 30, Pages: 604-618, ISSN: 1120-1797
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Scott AD, Ferreira P, Nielles-Vallespin S, et al., 2014, Improved in-vivo cardiac DTI using optimal b-values, Journal of Cardiovascular Magnetic Resonance, Vol: 16, ISSN: 1097-6647
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Giannakidis A, Ferreira P, Scott AD, et al., 2014, Scanner-efficient diffusion tensor imaging of human cardiac microstructure using the fast composite splitting reconstruction algorithm, Journal of Cardiovascular Magnetic Resonance, Vol: 16, ISSN: 1097-6647
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Tunnicliffe EM, Scott AD, Ferreira P, et al., 2014, Inter-centre reproducibility of cardiac diffusion tensor measures, Journal of Cardiovascular Magnetic Resonance, Vol: 16, ISSN: 1097-6647
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