As a physician, epidemiologist, biomedical engineer and scientist, I am optimizing healthcare by translating clinical needs into technical solutions. I am working at Stanford University and have 8 years of research and clinical experience in radiology.

My clinical experience as a physician in diagnostic radiology and research experience in the field of cardiovascular and chest imaging allow me to recognize medical shortcomings. While my technical background with a PhD (cum laude) in the application of medical image reconstruction allows me to solve these with adequate technical solutions.

I have leadership experience from active involvement in multiple (inter)national scientific organizations, co-directing educational courses, and supervising >15 graduate students.

I have published >70 peer-reviewed papers, have been invited to present >15 lectures at international scientific meetings, am a Fulbright laureate and received >$300,000 of funding from the American Heart Association, Philips Healthcare, Stanford University and more. I am designated as a Fellow of the Society of Cardiovascular Computed Tomography (SCCT), co-director of the UMC Utrecht Spectral CT Academy, and an active member of multiple European and North American clinical scientific societies. My work has been recognized with awards from the Radiological Society of North America, European Society of Radiology, Society of Thoracic Radiology, European Society of Thoracic Imaging, among others.

Academic Appointments

  • Instructor, Radiology

Honors & Awards

  • Introduction to Academic Radiology for Scientists (ITARSc 2019) Program Awardee, Radiological Society of North America (RSNA) (2019)
  • AHA Postdoctoral Fellowship Grant (18POST34030192), American Heart Association (AHA) (2018-2020)
  • Stanford-Philips Fellowship Training Award, Stanford University / Philips Healthcare (2018)
  • Stanford Cardiovascular Institute Travel Award, Stanford University (September 2017)
  • Frederik Philips Prize 2016, Philips Healthcare (September 2016)
  • ImagO Best Thesis Award, Graduate Programme Medical Imaging (ImagO), Utrecht University (May 2016)
  • European Radiology Most Cited Paper Award 2013, European Society of Radiology (March 2016)
  • Niels Stensen Fellowship, Niels Stensen Fellowship (October 2015)
  • Cum Laude PhD Thesis, Utrecht University (June 2015)
  • Award for Best Oral Presentation by a Resident, Society of Thoracic Imaging Annual Meeting 2015, Carlsbad, CA (March 2015)
  • Conference Travel Grant, Circulatory Health, UMC Utrecht (February 2015)
  • Fulbright Scholarship, Fulbright Center (April 2014)
  • Jack Westcott Award, Society of Thoracic Imaging Annual Meeting 2014, San Antonio, USA (March 2014)
  • Research Travel Grant, Circulatory Health, UMC Utrecht (March 2014)
  • Van Wijck-Stam-Caspers Fund for Cardiovascular Research, Van Wijck-Stam-Caspers Fund for Cardiovascular Research (October 2013)
  • European Society of Thoracic Imaging Travel Grant, European Society of Thoracic Imaging (September 2013)
  • Radiological Society of the Netherlands Travel Grant, 18de Radiologendagen, Den Bosch, The Netherlands (September 2013)
  • Magna Cum Laude Award for Oral Presentation, 3rd World Congress of Thoracic Imaging in Seoul, Korea (June 2013)
  • Young Investigator Scholarship, World Congress of Thoracic Imaging (June 2013)
  • Cum Laude Award for Oral Presentation, 20th Annual Meeting of the European Society of Thoracic Imaging in London, UK (June 2012)
  • Nomination for the Professor Rein Zwierstra Award for best clinical lesson of the academic year, University of Groningen (September 2011)

Boards, Advisory Committees, Professional Organizations

  • Member of the Radiology & Imaging Clinical Science Peer Review Committee (Reviewer-in-Training), American Heart Association (AHA) (2019 - Present)
  • Member/Faculty, American Roentgen Ray Society (ARRS) (2019 - Present)
  • Member/Faculty, Society of Computed Body Tomography & Magnetic Resonance (SCBT-MR) (2019 - Present)
  • Junior Deputy Editor at European Radiology, European Society of Radiology (ESR) (2019 - Present)
  • Member/Faculty, North American Society for Cardiovascular Imaging (NASCI) (2018 - Present)
  • Fellow of the Society of Cardiovascular Computed Tomography (FSCCT), Society of Cardiovascular Computed Tomography (SCCT) (2018 - Present)
  • Trainee Member, American Heart Association (AHA) (2017 - Present)
  • Co-director of the Spectral CT Academy, UMC Utrecht, The Netherlands (2016 - Present)
  • Member of the Fellow and Resident Leaders Committee (FiRST), Society for Cardiovascular Computed Tomography (SCCT) (2015 - 2017)
  • Member of the Imaging Techniques Course Committee, Radiological Society of The Netherlands (2015 - 2017)
  • Member in Training, European Society of Radiology (ESR) (2013 - Present)
  • Member in Training, Radiological Society of North America (RSNA) (2012 - Present)

Professional Education

  • Ph.D. (cum laude), Utrecht University, Life Sciences (2015)
  • M.Sc. (GPA 4.0), Utrecht University, Clinical Epidemiology (2014)
  • M.D. (GPA 4.0), University of Groningen, Medicine (2011)
  • B.Sc., Twente University, Biomedical Engineering (2006)


All Publications

  • The Project Baseline Health Study: a step towards a broader mission to map human health NPJ DIGITAL MEDICINE Arges, K., Assimes, T., Bajaj, V., Balu, S., Bashir, M. R., Beskow, L., Blanco, R., Califf, R., Campbell, P., Carin, L., Christian, V., Cousins, S., Das, M., Dockery, M., Douglas, P. S., Dunham, A., Eckstrand, J., Fleischmann, D., Ford, E., Fraulo, E., French, J., Gambhir, S. S., Ginsburg, G. S., Green, R. C., Haddad, F., Hernandez, A., Hernandez, J., Huang, E. S., Jaffe, G., King, D., Koweek, L. H., Langlotz, C., Liao, Y. J., Mahaffey, K. W., Marcom, K., Marks, W. J., Maron, D., McCabe, R., McCall, S., McCue, R., Mega, J., Miller, D., Muhlbaier, L. H., Munshi, R., Newby, L., Pak-Harvey, E., Patrick-Lake, B., Pencina, M., Peterson, E. D., Rodriguez, F., Shore, S., Shah, S., Shipes, S., Sledge, G., Spielman, S., Spitler, R., Schaack, T., Swamy, G., Willemink, M. J., Wong, C. A. 2020; 3 (1): 84


    The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

    View details for DOI 10.1038/s41746-020-0290-y

    View details for Web of Science ID 000538242900001

    View details for PubMedID 32550652

    View details for PubMedCentralID PMC7275087

  • Preparing Medical Imaging Data for Machine Learning. Radiology Willemink, M. J., Koszek, W. A., Hardell, C., Wu, J., Fleischmann, D., Harvey, H., Folio, L. R., Summers, R. M., Rubin, D. L., Lungren, M. P. 2020: 192224


    Artificial intelligence (AI) continues to garner substantial interest in medical imaging. The potential applications are vast and include the entirety of the medical imaging life cycle from image creation to diagnosis to outcome prediction. The chief obstacles to development and clinical implementation of AI algorithms include availability of sufficiently large, curated, and representative training data that includes expert labeling (eg, annotations). Current supervised AI methods require a curation process for data to optimally train, validate, and test algorithms. Currently, most research groups and industry have limited data access based on small sample sizes from small geographic areas. In addition, the preparation of data is a costly and time-intensive process, the results of which are algorithms with limited utility and poor generalization. In this article, the authors describe fundamental steps for preparing medical imaging data in AI algorithm development, explain current limitations to data curation, and explore new approaches to address the problem of data availability.

    View details for DOI 10.1148/radiol.2020192224

    View details for PubMedID 32068507

  • Computed Tomographic Angiography-Based Fractional Flow Reserve Compared With Catheter-Based Dobutamine-Stress Diastolic Fractional Flow Reserve in Symptomatic Patients With a Myocardial Bridge and No Obstructive Coronary Artery Disease. Circulation. Cardiovascular imaging Jubran, A., Schnittger, I., Tremmel, J., Pargaonkar, V., Rogers, I., Becker, H. C., Yang, S., Mastrodicasa, D., Willemink, M., Fleischmann, D., Nieman, K. 2020; 13 (2): e009576

    View details for DOI 10.1161/CIRCIMAGING.119.009576

    View details for PubMedID 32069114

  • Coronary artery calcium: A technical argument for a new scoring method JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY Willemink, M. J., van der Werf, N. R., Nieman, K., Greuter, M. W., Koweek, L. M., Fleischmann, D. 2019; 13 (6): 347–52
  • The role of coronary CT angiography for acute chest pain in the era of high-sensitivity troponins. Journal of cardiovascular computed tomography Yang, S., Manjunath, L., Willemink, M. J., Nieman, K. 2019


    Accurate and efficient diagnostic triage for acute chest pain (ACP) remains one of the most challenging problems in the emergency department (ED). While the proportion of patients that present with myocardial infarction (MI), aortic dissection, or pulmonary embolism is relatively low, a missed diagnosis can be life threatening. Coronary computed tomography angiography (CCTA) has developed into a robust diagnostic tool in the triage of ACP over the past decade, with several trials showing that it can reliably identify patients at low risk of major adverse cardiovascular events, shorten the length of stay in the ED, and reduce cost associated with the triage of patients with undifferentiated chest pain. Recently, however, high-sensitivity troponin assays have been increasingly incorporated as a rapid and efficient diagnostic test in the triage of ACP due to their higher sensitivity and negative predictive value of myocardial infarction. As more EDs adopt high-sensitivity troponin assays into routine clinical practice, the role of CCTA will likely change. In this review, we provide an overview of CCTA and high-sensitivity troponins for evaluation of patients with suspected ACS in the ED. Moreover, we discuss the changing role of CCTA in the era of high-sensitivity troponins.

    View details for DOI 10.1016/j.jcct.2019.05.007

    View details for PubMedID 31235403

  • Coronary CT in Patients with a History of PCI or CABG: Helpful or Harmful? CURRENT CARDIOVASCULAR IMAGING REPORTS Jubran, A., Willemink, M. J., Nieman, K. 2019; 12 (6)
  • Aortic growth and development of partial false lumen thrombosis are associated with late adverse events in type B aortic dissection. The Journal of thoracic and cardiovascular surgery Higashigaito, K., Sailer, A. M., van Kuijk, S. M., Willemink, M. J., Hahn, L. D., Hastie, T. J., Miller, D. C., Fischbein, M. P., Fleischmann, D. 2019


    Patients with medically treated type B aortic dissection (TBAD) remain at significant risk for late adverse events (LAEs). We hypothesize that not only initial morphological features, but also their change over time at follow-up are associated with LAEs.Baseline and 188 follow-up computed tomography (CT) scans with a median follow-up time of 4 years (range, 10 days to 12.7 years) of 47 patients with acute uncomplicated TBAD were retrospectively reviewed. Morphological features (n = 8) were quantified at baseline and each follow-up. Medical records were reviewed for LAEs, which were defined according to current guidelines. To assess the effects of changes of morphological features over time, the linear mixed effects models were combined with Cox proportional hazards regression for the time-to-event outcome using a joint modeling approach.LAEs occurred in 21 of 47 patients at a median of 6.6 years (95% confidence interval [CI], 5.1-11.2 years). Among the 8 investigated morphological features, the following 3 features showed strong association with LAEs: increase in partial false lumen thrombosis area (hazard ratio [HR], 1.39; 95% CI, 1.18-1.66 per cm2 increase; P < .001), increase of major aortic diameter (HR, 1.24; 95% CI, 1.13-1.37 per mm increase; P < .001), and increase in the circumferential extent of false lumen (HR, 1.05; 95% CI, 1.01-1.10 per degree increase; P < .001).In medically treated TBAD, increases in aortic diameter, new or increased partial false lumen thrombosis area, and increases of circumferential extent of the false lumen are strongly associated with LAEs.

    View details for DOI 10.1016/j.jtcvs.2019.10.074

    View details for PubMedID 31839226

  • Photon-counting CT: Technical Principles and Clinical Prospects RADIOLOGY Willemink, M. J., Persson, M., Pourmorteza, A., Pelc, N., Fleischmann, D. 2018; 289 (2): 293–312
  • The impact of dose reduction on the quantification of coronary artery calcifications and risk categorization: A systematic review JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY Vonder, M., van der Werf, N. R., Leiner, T., Greuter, M. W., Fleischmann, D., Vliegenthart, R., Oudkerk, M., Willemink, M. J. 2018; 12 (5): 352–63


    Multiple dose reduction techniques have been introduced for coronary artery calcium (CAC) computed tomography (CT), but few have emerged into clinical practice while an increasing number of patients undergo CAC scanning. We sought to determine to what extend the radiation dose in CAC CT can be safely reduced without a significant impact on cardiovascular disease (CVD) risk stratification. A systematic database-review of articles published from 2002 until February 2018 was performed in Pubmed, WebOfScience, and Embase. Eligible studies reported radiation dose reduction for CAC CT, calcium scores and/or risk stratification for phantom or patient studies. Twenty-eight studies were included, under which 17 patient studies, 10 phantom/ex-vivo studies, and 1 study evaluated both phantom and patients. Dose was reduced with tube voltage reduction and tube current reduction with and without iterative reconstruction (IR), and tin-filter spectral shaping. The different dose reduction techniques resulted in varying final radiation doses and had varying impact on CAC scores and CVD risk stratification. In 78% of the studies the radiation dose was reduced by ≥ 50% ranging from (CTDIvol) 0.6-5.5 mGy, leading to reclassification rates ranging between 3% and 21%, depending on the acquisition technique. Specific dose reduced protocols, including either tube current reduction and IR or spectral shaping with tin filtration, that showed low reclassification rates may potentially be used in CAC scanning and in future population-based screening for CVD risk stratification.

    View details for PubMedID 29960743

  • THE PROGNOSTIC VALUE OF COMPUTED TOMOGRAPHY FRAILTY MEASURES FOR PROLONGED HOSPITAL STAY AFTER TAVR IN 429 PATIENTS Maret, E., Willemink, M., Moneghetti, K., Kim, J., Haddad, F., Kobayashi, Y., Miller, C., Yeung, A., Fishbein, M., Fearon, W., Fleischmann, D. ELSEVIER SCIENCE INC. 2018: 1414
  • PREDICTING MORTALITY WITH AORTOMITRAL CALCIFICATIONS IN 317 TAVR PATIENTS Willemink, M., Maret, E., Moneghetti, K., Kim, J., Haddad, F., Kobayashi, Y., Higashigaito, K., Yeung, A., Lee, A., Miller, D., Fischbein, M., Fearon, W., Fleischmann, D. ELSEVIER SCIENCE INC. 2018: 1591
  • Acute Limited Intimal Tears of the Thoracic Aorta. Journal of the American College of Cardiology Chin, A. S., Willemink, M. J., Kino, A., Hinostroza, V., Sailer, A. M., Fischbein, M. P., Mitchell, R. S., Berry, G. J., Miller, D. C., Fleischmann, D. 2018; 71 (24): 2773–85


    Limited intimal tears (LITs) of the aorta (Class 3 dissection variant) are the least common form of aortic pathology in patients presenting with acute aortic syndrome (AAS). LITs are difficult to detect on imaging and may be underappreciated.This study sought to describe the frequency, pathology, treatment, and outcome of LITs compared with other AAS, and to demonstrate that LITs can be detected pre-operatively by contemporary imaging.The authors retrospectively reviewed 497 patients admitted for 513 AAS events at a single academic aortic center between 2003 and 2012. AAS were classified into classic dissection (AD), intramural hematoma, LIT, penetrating atherosclerotic ulcer, and rupturing thoracic aortic aneurysm. The prevalence, pertinent risk factors, and detailed imaging findings with surgical and pathological correlation of LITs are described. Management, early outcomes, and late mortality are reported.Among 497 patients with AAS, the authors identified 24 LITs (4.8% of AAS) in 16 men and 8 women (17 type A, 7 type B). Patients with LITs were older than those with AD, and type A LITs had similarly dilated ascending aortas as type A AD. Three patients presented with rupture. Eleven patients underwent urgent surgical aortic replacement, and 2 patients underwent endovascular repair. Medial degeneration was present in all surgical specimens. In-hospital mortality was 4% (1 of 24), and in total, 5 patients with LIT died subsequently at 1.5 years (interquartile range [IQR]: 0.3 to 2.5 years). Computed tomography imaging detected all but 1 LIT, best visualized on volume-rendered images.LITs are rare acute aortic lesions within the dissection spectrum, with similar presentation, complications, and outcomes compared with AD and intramural hematoma. Awareness of this lesion allows pre-operative diagnosis using high-quality computed tomography angiography.

    View details for PubMedID 29903350

  • Emphysema quantification using chest CT: influence of radiation dose reduction and reconstruction technique. European radiology experimental den Harder, A. M., de Boer, E., Lagerweij, S. J., Boomsma, M. F., Schilham, A. M., Willemink, M. J., Milles, J., Leiner, T., Budde, R. P., de Jong, P. A. 2018; 2 (1): 30


    Computed tomography (CT) emphysema quantification is affected by both radiation dose (i.e. image noise) and reconstruction technique. At reduced dose, filtered back projection (FBP) results in an overestimation of the amount of emphysema due to higher noise levels, while the use of iterative reconstruction (IR) can result in an underestimation due to reduced noise. The objective of this study was to determine the influence of dose reduction and hybrid IR (HIR) or model-based IR (MIR) on CT emphysema quantification.Twenty-two patients underwent inspiratory chest CT scan at routine radiation dose and at 45%, 60% and 75% reduced radiation dose. Acquisitions were reconstructed with FBP, HIR and MIR. Emphysema was quantified using the 15th percentile of the attenuation curve and the percentage of voxels below -950 HU. To determine whether the use of a different percentile or HU threshold is more accurate at reduced dose levels and with IR, additional measurements were performed using different percentiles and HU thresholds to determine the optimal combination.Dose reduction resulted in a significant overestimation of emphysema, while HIR and MIR resulted in an underestimation. Lower HU thresholds with FBP at reduced dose and higher HU thresholds with HIR and MIR resulted in emphysema percentages comparable to the reference. The 15th percentile quantification method showed similar results as the HU threshold method.This within-patients study showed that CT emphysema quantification is significantly affected by dose reduction and IR. This can potentially be solved by adapting commonly used thresholds.

    View details for DOI 10.1186/s41747-018-0064-3

    View details for PubMedID 30402740

    View details for PubMedCentralID PMC6220000

  • The evolution of image reconstruction for CT-from filtered back projection to artificial intelligence. European radiology Willemink, M. J., Noël, P. B. 2018


    The first CT scanners in the early 1970s already used iterative reconstruction algorithms; however, lack of computational power prevented their clinical use. In fact, it took until 2009 for the first iterative reconstruction algorithms to come commercially available and replace conventional filtered back projection. Since then, this technique has caused a true hype in the field of radiology. Within a few years, all major CT vendors introduced iterative reconstruction algorithms for clinical routine, which evolved rapidly into increasingly advanced reconstruction algorithms. The complexity of algorithms ranges from hybrid-, model-based to fully iterative algorithms. As a result, the number of scientific publications on this topic has skyrocketed over the last decade. But what exactly has this technology brought us so far? And what can we expect from future hardware as well as software developments, such as photon-counting CT and artificial intelligence? This paper will try answer those questions by taking a concise look at the overall evolution of CT image reconstruction and its clinical implementations. Subsequently, we will give a prospect towards future developments in this domain. KEY POINTS: • Advanced CT reconstruction methods are indispensable in the current clinical setting. • IR is essential for photon-counting CT, phase-contrast CT, and dark-field CT. • Artificial intelligence will potentially further increase the performance of reconstruction methods.

    View details for PubMedID 30377791

  • Coronary artery calcium: A technical argument for a new scoring method. Journal of cardiovascular computed tomography Willemink, M. J., van der Werf, N. R., Nieman, K., Greuter, M. J., Koweek, L. M., Fleischmann, D. 2018


    Coronary artery calcium (CAC) is a strong predictor for future cardiovascular events. Traditionally CAC has been quantified using the Agatston score, which was developed in the late 1980s for electron beam tomography (EBT). While EBT has been completely replaced by modern multiple-detector row CT technology, the traditional CAC scoring method by Agatston remains in use, although the literature indicates suboptimal reproducibility and subjects being incorrectly classified. The traditional Agatston scoring method counteracts the technical advances of CT technology, and prevents the use of thinner sections, obtained at lower tube voltage and overall decreased radiation exposure that has become available to other CT applications. Moreover, recent studies have shown that not only the total amount of CAC, but also its density and distribution in the coronary arterial tree may be of prognostic value. Acquisition and reconstruction techniques thus need to be adapted for modern CT technology and optimized for CAC quantification. In this review we describe the technical limitations of the Agatston score followed by our suggestions for developing a new and more robust CAC quantification method.

    View details for PubMedID 30366859

  • Contrast agent concentration optimization in CTA using low tube voltage and dual-energy CT in multiple vendors: a phantom study. The international journal of cardiovascular imaging van Hamersvelt, R. W., Eijsvoogel, N. G., Mihl, C., de Jong, P. A., Schilham, A. M., Buls, N., Das, M., Leiner, T., Willemink, M. J. 2018


    We investigated the feasibility and extent to which iodine concentration can be reduced in computed tomography angiography imaging of the aorta and coronary arteries using low tube voltage and virtual monochromatic imaging of 3 major dual-energy CT (DECT) vendors. A circulation phantom was imaged with dual source CT (DSCT), gemstone spectral imaging (GSI) and dual-layer spectral detector CT (SDCT). For each scanner, a reference scan was acquired at 120 kVp using routine iodine concentration (300 mg I/ml). Subsequently, scans were acquired at lowest possible tube potential (70, 80, 80 kVp, respectively), and DECT-mode (80/150Sn, 80/140 and 120 kVp, respectively) in arterial phase after administration of iodine (300, 240, 180, 120, 60, 30 mg I/ml). Objective image quality was evaluated using attenuation, CNR and dose corrected CNR (DCCNR) measured in the aorta and left main coronary artery. Average DCCNR at reference was 227.0, 39.7 and 60.2 for DSCT, GSI and SDCT. Maximum iodine concentration reduction without loss of DCCNR was feasible down to 180 mg I/ml (40% reduced) for DSCT (DCCNR 467.1) and GSI (DCCNR 46.1) using conventional CT low kVp, and 120 mg I/ml (60% reduced) for SDCT (DCCNR 171.5) using DECT mode. Low kVp scanning and DECT allows for 40-60% iodine reduction without loss in image quality compared to reference. Optimal scan protocol and to which extent varies per vendor. Further patient studies are needed to extend and translate our findings to clinical practice.

    View details for DOI 10.1007/s10554-018-1329-x

    View details for PubMedID 29516228

  • Cardiac imaging to detect coronary artery disease in athletes aged 35 years and older. A scoping review. Scandinavian journal of medicine & science in sports Braber, T. L., Reitsma, J. B., Mosterd, A., Willemink, M. J., Prakken, N. H., Halle, M., Sharma, S., Velthuis, B. K. 2018; 28 (3): 1036–47


    Sudden cardiac death (SCD) is a devastating event in athletes. Screening efforts that were first directed at athletes younger than 35 years are now focusing on the rapidly growing group of older sportspersons. Athletes aged ≥35 years have a 10-fold increased risk of exercise-related cardiac arrest, mostly due to coronary artery disease (CAD). Although cardiac imaging is pivotal in identifying CAD, the role of imaging modalities in screening asymptomatic older sportspersons remains unclear. We performed a scoping review to identify the role of cardiac imaging to detect CAD in older sportspersons and to identify gaps in the existing literature. We searched MEDLINE, EMBASE and the Cochrane library for studies reporting data on cardiac imaging of CAD in sportspersons ≥35 years. The systematic search yielded 1737 articles, and 14 were included in this scoping review. Imaging modalities included two echocardiography, one unenhanced computed tomography (CT) for coronary artery calcium scoring (CACS), three CACS and contrast-enhanced CT angiography (CCTA), two CACS and cardiac magnetic resonance (CMR), one CCTA with CMR and echocardiography, two CCTA, two CMR, and one myocardial perfusion imaging article. The low number of relevant articles and the selection bias introduced by studying specific groups, like veteran marathon runners, indicate the need for future research. Cardiac CT (CACS and CCTA) probably has the highest potential for pre-participation screening, with high diagnostic value to detect CAD and low radiation dose. However, currently there is insufficient evidence for incorporating routine cardiac imaging in the pre-participation screening of asymptomatic sportspersons over 35 years.

    View details for DOI 10.1111/sms.12974

    View details for PubMedID 28833626

  • Radiation dose reduction for CT assessment of urolithiasis using iterative reconstruction: A prospective intra-individual study. European radiology den Harder, A. M., Willemink, M. J., van Doormaal, P. J., Wessels, F. J., Lock, M. T., Schilham, A. M., Budde, R. P., Leiner, T., de Jong, P. A. 2018; 28 (1): 143–50


    To assess the performance of hybrid (HIR) and model-based iterative reconstruction (MIR) in patients with urolithiasis at reduced-dose computed tomography (CT).Twenty patients scheduled for unenhanced abdominal CT for follow-up of urolithiasis were prospectively included. Routine dose acquisition was followed by three low-dose acquisitions at 40%, 60% and 80% reduced doses. All images were reconstructed with filtered back projection (FBP), HIR and MIR. Urolithiasis detection rates, gall bladder, appendix and rectosigmoid evaluation and overall subjective image quality were evaluated by two observers.74 stones were present in 17 patients. Half the stones were not detected on FBP at the lowest dose level, but this improved with MIR to a sensitivity of 100%. HIR resulted in a slight decrease in sensitivity at the lowest dose to 72%, but outperformed FBP. Evaluation of other structures with HIR at 40% and with MIR at 60% dose reductions was comparable to FBP at routine dose, but 80% dose reduction resulted in non-evaluable images.CT radiation dose for urolithiasis detection can be safely reduced by 40 (HIR)-60 (MIR) % without affecting assessment of urolithiasis, possible extra-urinary tract pathology or overall image quality.• Iterative reconstruction can be used to substantially lower the radiation dose. • This allows for radiation reduction without affecting sensitivity of stone detection. • Possible extra-urinary tract pathology evaluation is feasible at 40-60% reduced dose.

    View details for DOI 10.1007/s00330-017-4929-2

    View details for PubMedID 28695359

    View details for PubMedCentralID PMC5717126

  • Aortic Valve and Thoracic Aortic Calcification Measurements: How Low Can We Go in Radiation Dose? Journal of computer assisted tomography van Hamersvelt, R. W., den Harder, A. M., Willemink, M. J., Schilham, A. M., Lammers, J. J., Nathoe, H. M., Budde, R. P., Leiner, T., de Jong, P. A. 2017; 41 (1): 148–55


    This study aimed to determine the lowest radiation dose and iterative reconstruction level(s) at which computed tomography (CT)-based quantification of aortic valve calcification (AVC) and thoracic aortic calcification (TAC) is still feasible.Twenty-eight patients underwent a cardiac CT and 20 patients a chest CT at 4 different dose levels (routine dose and approximately 40%, 60%, and 80% reduced dose). Data were reconstructed with filtered back projection, 3 iDose levels, and 3 iterative model-based reconstruction levels. Two observers scored subjective image quality. The AVC and TAC were quantified using mass and compared to the reference scan (routine dose reconstructed with filtered back projection).In cardiac CT at 0.35 mSv (60% reduced), all scans reconstructed with iDose (all levels) were diagnostic, calcification detection errors occurred in only 1 patient, and there were no significant differences in mass scores compared to the reference scan. Similar results were found for chest CT at 0.48 mSv (75% reduced) with iDose levels 4 and 6 and iterative model reconstruction levels 1 and 2.Iterative reconstruction enables AVC and TAC quantification on CT at submillisievert dose.

    View details for DOI 10.1097/RCT.0000000000000477

    View details for PubMedID 27560017

  • Influence of heart rate on coronary calcium scores: a multi-manufacturer phantom study. The international journal of cardiovascular imaging van der Werf, N. R., Willemink, M. J., Willems, T. P., Vliegenthart, R., Greuter, M. J., Leiner, T. 2017


    To evaluate the influence of heart rate on coronary calcium scores (CCS) using a dynamic phantom on four high-end computed tomography (CT) systems from different manufacturers. Artificial coronary arteries were moved in an anthropomorphic chest phantom at linear velocities, corresponding to < 60, 60-75 and > 75 beats per minute (bpm). Data was acquired with routinely used clinical protocols for CCS on four high-end CT systems (CT1-CT4). CCS, quantified as Agatston and mass scores were compared to reference scores at < 60 bpm. Influence of heart rate was assessed for each system with the cardiac motion susceptibility (CMS) Index. At increased heart rates (> 75 bpm), Agatston scores of the low mass calcification were similar to the reference score, while Agatston scores of the medium and high mass calcification increased significantly up to 50% for all CT systems. Threefold CMS increases at > 75 bpm in comparison with < 60 bpm were shown. For medium and high mass calcifications, significant differences in CMS between CT systems were found. Heart rate substantially influences CCS for high-end CT systems of four major manufacturers, but CT systems differ in motion susceptibility. Follow-up CCS CT scans should be acquired on the same CT system and protocol, and preferably with comparable heart rates.

    View details for DOI 10.1007/s10554-017-1293-x

    View details for PubMedID 29285727

  • Influence of iterative reconstruction on coronary calcium scores at multiple heart rates: a multivendor phantom study on state-of-the-art CT systems. The international journal of cardiovascular imaging van der Werf, N. R., Willemink, M. J., Willems, T. P., Greuter, M. J., Leiner, T. 2017


    The objective of this study was to evaluate the influence of iterative reconstruction on coronary calcium scores (CCS) at different heart rates for four state-of-the-art CT systems. Within an anthropomorphic chest phantom, artificial coronary arteries were translated in a water-filled compartment. The arteries contained three different calcifications with low (38 mg), medium (80 mg) and high (157 mg) mass. Linear velocities were applied, corresponding to heart rates of 0, < 60, 60-75 and > 75 bpm. Data were acquired on four state-of-the-art CT systems (CT1-CT4) with routinely used CCS protocols. Filtered back projection (FBP) and three increasing levels of iterative reconstruction (L1-L3) were used for reconstruction. CCS were quantified as Agatston score and mass score. An iterative reconstruction susceptibility (IRS) index was used to assess susceptibility of Agatston score (IRSAS) and mass score (IRSMS) to iterative reconstruction. IRS values were compared between CT systems and between calcification masses. For each heart rate, differences in CCS of iterative reconstructed images were evaluated with CCS of FBP images as reference, and indicated as small (< 5%), medium (5-10%) or large (> 10%). Statistical analysis was performed with repeated measures ANOVA tests. While subtle differences were found for Agatston scores of low mass calcification, medium and high mass calcifications showed increased CCS up to 77% with increasing heart rates. IRSASof CT1-T4 were 17, 41, 130 and 22% higher than IRSMS. Not only were IRS significantly different between all CT systems, but also between calcification masses. Up to a fourfold increase in IRS was found for the low mass calcification in comparison with the high mass calcification. With increasing iterative reconstruction strength, maximum decreases of 21 and 13% for Agatston and mass score were found. In total, 21 large differences between Agatston scores from FBP and iterative reconstruction were found, while only five large differences were found between FBP and iterative reconstruction mass scores. Iterative reconstruction results in reduced CCS. The effect of iterative reconstruction on CCS is more prominent with low-density calcifications, high heart rates and increasing iterative reconstruction strength.

    View details for DOI 10.1007/s10554-017-1292-y

    View details for PubMedID 29285725

  • The Effects of Iodine Attenuation on Pulmonary Nodule Volumetry using Novel Dual-Layer Computed Tomography Reconstructions. European radiology den Harder, A. M., Bangert, F., van Hamersvelt, R. W., Leiner, T., Milles, J., Schilham, A. M., Willemink, M. J., de Jong, P. A. 2017; 27 (12): 5244–51


    To assess the effect of iodine attenuation on pulmonary nodule volumetry using virtual non-contrast (VNC) and mono-energetic reconstructions.A consecutive series of patients who underwent a contrast-enhanced chest CT scan were included. Images were acquired on a novel dual-layer spectral CT system. Conventional reconstructions as well as VNC and mono-energetic images at different keV levels were used for nodule volumetry.Twenty-four patients with a total of 63 nodules were included. Conventional reconstructions showed a median (interquartile range) volume and diameter of 174 (87 - 253) mm3and 6.9 (5.4 - 9.9) mm, respectively. VNC reconstructions resulted in a significant volume reduction of 5.5% (2.6 - 11.2%; p<0.001). Mono-energetic reconstructions showed a correlation between nodule attenuation and nodule volume (Spearman correlation 0.77, (0.49 - 0.94)). Lowering the keV resulted in increased volumes while higher keV levels resulted in decreased pulmonary nodule volumes compared to conventional CT.Novel dual-layer spectral CT offers the possibility to reconstruct VNC and mono-energetic images. Those reconstructions show that higher pulmonary nodule attenuation results in larger nodule volumes. This may explain the reported underestimation in nodule volume on non-contrast enhanced compared to contrast-enhanced acquisitions.• Pulmonary nodule volumes were measured on virtual non-contrast and mono-energetic reconstructions • Mono-energetic reconstructions showed that higher attenuation results in larger volumes • This may explain the reported nodule volume underestimation on non-contrast enhanced CT • Mostly metastatic pulmonary nodules were evaluated, results might differ for benign nodules.

    View details for DOI 10.1007/s00330-017-4938-1

    View details for PubMedID 28677062

    View details for PubMedCentralID PMC5674131

  • Accuracy of bone mineral density quantification using dual-layer spectral detector CT: a phantom study. European radiology van Hamersvelt, R. W., Schilham, A. M., Engelke, K., den Harder, A. M., de Keizer, B., Verhaar, H. J., Leiner, T., de Jong, P. A., Willemink, M. J. 2017


    To investigate the accuracy of bone mineral density (BMD) quantification using dual-layer spectral detector CT (SDCT) at various scan protocols.Two validated anthropomorphic phantoms containing inserts of 50-200 mg/cm(3) calcium hydroxyapatite (HA) were scanned using a 64-slice SDCT scanner at various acquisition protocols (120 and 140 kVp, and 50, 100 and 200 mAs). Regions of interest (ROIs) were placed in each insert and mean attenuation profiles at monochromatic energy levels (90-200 keV) were constructed. These profiles were fitted to attenuation profiles of pure HA and water to calculate HA concentrations. For comparison, one phantom was scanned using dual energy X-ray absorptiometry (DXA).At both 120 and 140 kVp, excellent correlations (R = 0.97, P < 0.001) were found between true and measured HA concentrations. Mean error for all measurements at 120 kVp was -5.6 ± 5.7 mg/cm(3) (-3.6 ± 3.2%) and at 140 kVp -2.4 ± 3.7 mg/cm(3) (-0.8 ± 2.8%). Mean measurement errors were smaller than 6% for all acquisition protocols. Strong linear correlations (R(2) ≥ 0.970, P < 0.001) with DXA were found.SDCT allows for accurate BMD quantification and potentially opens up the possibility for osteoporosis evaluation and opportunistic screening in patients undergoing SDCT for other clinical indications. However, patient studies are needed to extend and translate our findings.• Dual-layer spectral detector CT allows for accurate bone mineral density quantification. • BMD measurements on SDCT are strongly linearly correlated to DXA. • SDCT, acquired for several indications, may allow for evaluation of osteoporosis. • This potentially opens up the possibility for opportunistic osteoporosis screening.

    View details for DOI 10.1007/s00330-017-4801-4

    View details for PubMedID 28374079

  • Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography. PloS one Gerritsen, M. G., Willemink, M. J., Pompe, E., van der Bruggen, T., van Rhenen, A., Lammers, J. W., Wessels, F., Sprengers, R. W., de Jong, P. A., Minnema, M. C. 2017; 12 (2): e0172256


    We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

    View details for DOI 10.1371/journal.pone.0172256

    View details for PubMedID 28235014

  • Accuracy of iodine quantification using dual energy CT in latest generation dual source and dual layer CT. European radiology Pelgrim, G. J., van Hamersvelt, R. W., Willemink, M. J., Schmidt, B. T., Flohr, T., Schilham, A., Milles, J., Oudkerk, M., Leiner, T., Vliegenthart, R. 2017


    To determine the accuracy of iodine quantification with dual energy computed tomography (DECT) in two high-end CT systems with different spectral imaging techniques.Five tubes with different iodine concentrations (0, 5, 10, 15, 20 mg/ml) were analysed in an anthropomorphic thoracic phantom. Adding two phantom rings simulated increased patient size. For third-generation dual source CT (DSCT), tube voltage combinations of 150Sn and 70, 80, 90, 100 kVp were analysed. For dual layer CT (DLCT), 120 and 140 kVp were used. Scans were repeated three times. Median normalized values and interquartile ranges (IQRs) were calculated for all kVp settings and phantom sizes.Correlation between measured and known iodine concentrations was excellent for both systems (R = 0.999-1.000, p < 0.0001). For DSCT, median measurement errors ranged from -0.5% (IQR -2.0, 2.0%) at 150Sn/70 kVp and -2.3% (IQR -4.0, -0.1%) at 150Sn/80 kVp to -4.0% (IQR -6.0, -2.8%) at 150Sn/90 kVp. For DLCT, median measurement errors ranged from -3.3% (IQR -4.9, -1.5%) at 140 kVp to -4.6% (IQR -6.0, -3.6%) at 120 kVp. Larger phantom sizes increased variability of iodine measurements (p < 0.05).Iodine concentration can be accurately quantified with state-of-the-art DECT systems from two vendors. The lowest absolute errors were found for DSCT using the 150Sn/70 kVp or 150Sn/80 kVp combinations, which was slightly more accurate than 140 kVp in DLCT.• High-end CT scanners allow accurate iodine quantification using different DECT techniques. • Lowest measurement error was found in scans with largest photon energy separation. • Dual-source CT quantified iodine slightly more accurately than dual layer CT.

    View details for DOI 10.1007/s00330-017-4752-9

    View details for PubMedID 28168368

  • Feasibility and accuracy of dual-layer spectral detector computed tomography for quantification of gadolinium: a phantom study. European radiology van Hamersvelt, R. W., Willemink, M. J., de Jong, P. A., Milles, J., Vlassenbroek, A., Schilham, A. M., Leiner, T. 2017


    The aim of this study was to evaluate the feasibility and accuracy of dual-layer spectral detector CT (SDCT) for the quantification of clinically encountered gadolinium concentrations.The cardiac chamber of an anthropomorphic thoracic phantom was equipped with 14 tubular inserts containing different gadolinium concentrations, ranging from 0 to 26.3 mg/mL (0.0, 0.1, 0.2, 0.4, 0.5, 1.0, 2.0, 3.0, 4.0, 5.1, 10.6, 15.7, 20.7 and 26.3 mg/mL). Images were acquired using a novel 64-detector row SDCT system at 120 and 140 kVp. Acquisitions were repeated five times to assess reproducibility. Regions of interest (ROIs) were drawn on three slices per insert. A spectral plot was extracted for every ROI and mean attenuation profiles were fitted to known attenuation profiles of water and pure gadolinium using in-house-developed software to calculate gadolinium concentrations.At both 120 and 140 kVp, excellent correlations between scan repetitions and true and measured gadolinium concentrations were found (R > 0.99, P < 0.001; ICCs > 0.99, CI 0.99-1.00). Relative mean measurement errors stayed below 10% down to 2.0 mg/mL true gadolinium concentration at 120 kVp and below 5% down to 1.0 mg/mL true gadolinium concentration at 140 kVp.SDCT allows for accurate quantification of gadolinium at both 120 and 140 kVp. Lowest measurement errors were found for 140 kVp acquisitions.• Gadolinium quantification may be useful in patients with contraindication to iodine. • Dual-layer spectral detector CT allows for overall accurate quantification of gadolinium. • Interscan variability of gadolinium quantification using SDCT material decomposition is excellent.

    View details for DOI 10.1007/s00330-017-4737-8

    View details for PubMedID 28124106

  • Influence of dose reduction and iterative reconstruction on CT calcium scores: a multi-manufacturer dynamic phantom study. The international journal of cardiovascular imaging van der Werf, N. R., Willemink, M. J., Willems, T. P., Greuter, M. J., Leiner, T. 2017


    To evaluate the influence of dose reduction in combination with iterative reconstruction (IR) on coronary calcium scores (CCS) in a dynamic phantom on state-of-the-art CT systems from different manufacturers. Calcified inserts in an anthropomorphic chest phantom were translated at 20 mm/s corresponding to heart rates between 60 and 75 bpm. The inserts were scanned five times with routinely used CCS protocols at reference dose and 40 and 80% dose reduction on four high-end CT systems. Filtered back projection (FBP) and increasing levels of IR were applied. Noise levels were determined. CCS, quantified as Agatston and mass scores, were compared to physical mass and scores at FBP reference dose. For the reference dose in combination with FBP, noise level variation between CT systems was less than 18%. Decreasing dose almost always resulted in increased CCS, while at increased levels of IR, CCS decreased again. The influence of IR on CCS was smaller than the influence of dose reduction. At reference dose, physical mass was underestimated 3-30%. All CT systems showed similar CCS at 40% dose reduction in combinations with specific reconstructions. For some CT systems CCS was not affected at 80% dose reduction, in combination with IR. This multivendor study showed that radiation dose reductions of 40% did not influence CCS in a dynamic phantom using state-of-the-art CT systems in combination with specific reconstruction settings. Dose reduction resulted in increased noise and consequently increased CCS, whereas increased IR resulted in decreased CCS.

    View details for DOI 10.1007/s10554-017-1061-y

    View details for PubMedID 28102510

  • Submillisievert coronary calcium quantification using model-based iterative reconstruction: A within-patient analysis. European journal of radiology den Harder, A. M., Wolterink, J. M., Willemink, M. J., Schilham, A. M., de Jong, P. A., Budde, R. P., Nathoe, H. M., Išgum, I., Leiner, T. 2016; 85 (11): 2152-2159


    To determine the effect of model-based iterative reconstruction (IR) on coronary calcium quantification using different submillisievert CT acquisition protocols.Twenty-eight patients received a clinically indicated non contrast-enhanced cardiac CT. After the routine dose acquisition, low-dose acquisitions were performed with 60%, 40% and 20% of the routine dose mAs. Images were reconstructed with filtered back projection (FBP), hybrid IR (HIR) and model-based IR (MIR) and Agatston scores, calcium volumes and calcium mass scores were determined.Effective dose was 0.9, 0.5, 0.4 and 0.2mSv, respectively. At 0.5 and 0.4mSv, differences in Agatston scores with both HIR and MIR compared to FBP at routine dose were small (-0.1 to -2.9%), while at 0.2mSv, differences in Agatston scores of -12.6 to -14.6% occurred. Reclassification of risk category at reduced dose levels was more frequent with MIR (21-25%) than with HIR (18%).Radiation dose for coronary calcium scoring can be safely reduced to 0.4mSv using both HIR and MIR, while FBP is not feasible at these dose levels due to excessive noise. Further dose reduction can lead to an underestimation in Agatston score and subsequent reclassification to lower risk categories. Mass scores were unaffected by dose reductions.

    View details for DOI 10.1016/j.ejrad.2016.09.028

    View details for PubMedID 27776671

  • Inter-observer and inter-examination variability of manual vertebral bone attenuation measurements on computed tomography EUROPEAN RADIOLOGY Pompe, E., de Jong, P. A., de Jong, W. U., Takx, R. A., Eikendal, A. L., Willemink, M. J., Oudkerk, M., Budde, R. P., Lammers, J. J., Hoesein, F. A. 2016; 26 (9): 3046-3053


    To determine inter-observer and inter-examination variability of manual attenuation measurements of the vertebrae in low-dose unenhanced chest computed tomography (CT).Three hundred and sixty-seven lung cancer screening trial participants who underwent baseline and repeat unenhanced low-dose CT after 3 months because of an indeterminate lung nodule were included. The CT attenuation value of the first lumbar vertebrae (L1) was measured in all CTs by one observer to obtain inter-examination reliability. Six observers performed measurements in 100 randomly selected CTs to determine agreement with limits of agreement and Bland-Altman plots and reliability with intraclass correlation coefficients (ICCs). Reclassification analyses were performed using a threshold of 110 HU to define osteoporosis.Inter-examination reliability was excellent with an ICC of 0.92 (p < 0.001). Inter-examination limits of agreement ranged from -26 to 28 HU with a mean difference of 1 ± 14 HU. Inter-observer reliability ICCs ranged from 0.70 to 0.91. Inter-examination variability led to 11.2 % reclassification of participants and inter-observer variability led to 22.1 % reclassification.Vertebral attenuation values can be manually quantified with good to excellent inter-examination and inter-observer reliability on unenhanced low-dose chest CT. This information is valuable for early detection of osteoporosis on low-dose chest CT.• Vertebral attenuation values can be manually quantified on low-dose unenhanced CT reliably. • Vertebral attenuation measurements may be helpful in detecting subclinical low bone density. • This could become of importance in the detection of osteoporosis.

    View details for DOI 10.1007/s00330-015-4145-x

    View details for Web of Science ID 000381122400021

    View details for PubMedID 26801161

  • New horizons in cardiac CT CLINICAL RADIOLOGY den Harder, A. M., Willemink, M. J., de Jong, P. A., Schilham, A. M., Rajiah, P., Takx, R. A., Leiner, T. 2016; 71 (8): 758-767


    Until recently, cardiovascular computed tomography angiography (CCTA) was associated with considerable radiation doses. The introduction of tube current modulation and automatic tube potential selection as well as high-pitch prospective ECG-triggering and iterative reconstruction offer the ability to decrease dose with approximately one order of magnitude, often to sub-millisievert dose levels. In parallel, advancements in computational technology have enabled the measurement of fractional flow reserve (FFR) from CCTA data (FFRCT). This technique shows potential to replace invasively measured FFR to select patients in need of coronary intervention. Furthermore, developments in scanner hardware have led to the introduction of dual-energy and photon-counting CT, which offer the possibility of material decomposition imaging. Dual-energy CT reduces beam hardening, which enables CCTA in patients with a high calcium burden and more robust myocardial CT perfusion imaging. Future-generation CT systems will be capable of counting individual X-ray photons. Photon-counting CT is promising and may result in a substantial further radiation dose reduction, vastly increased spatial resolution, and the introduction of a whole new class of contrast agents.

    View details for DOI 10.1016/j.crad.2016.01.022

    View details for Web of Science ID 000383353400006

    View details for PubMedID 26932775

  • Pulmonary Nodule Volumetry at Different Low Computed Tomography Radiation Dose Levels With Hybrid and Model-Based Iterative Reconstruction: A Within Patient Analysis JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY den Harder, A. M., Willemink, M. J., van Hamersvelt, R. W., Vonken, E. P., Schilham, A. M., Lammers, J. J., Luijk, B., Budde, R. P., Leiner, T., de Jong, P. A. 2016; 40 (4): 578-583


    The aim of the study was to determine the effects of dose reduction and iterative reconstruction (IR) on pulmonary nodule volumetry.In this prospective study, 25 patients scheduled for follow-up of pulmonary nodules were included. Computed tomography acquisitions were acquired at 4 dose levels with a median of 2.1, 1.2, 0.8, and 0.6 mSv. Data were reconstructed with filtered back projection (FBP), hybrid IR, and model-based IR. Volumetry was performed using semiautomatic software.At the highest dose level, more than 91% (34/37) of the nodules could be segmented, and at the lowest dose level, this was more than 83%. Thirty-three nodules were included for further analysis. Filtered back projection and hybrid IR did not lead to significant differences, whereas model-based IR resulted in lower volume measurements with a maximum difference of -11% compared with FBP at routine dose.Pulmonary nodule volumetry can be accurately performed at a submillisievert dose with both FBP and hybrid IR.

    View details for DOI 10.1097/RCT.0000000000000408

    View details for Web of Science ID 000381476100014

    View details for PubMedID 27096400

  • Cardiac CT Imaging of Plaque Vulnerability: Hype or Hope? CURRENT CARDIOLOGY REPORTS Willemink, M. J., Leiner, T., Maurovich-Horvat, P. 2016; 18 (4)


    Advances in cardiovascular computed tomography (CT) have resulted in an excellent ability to exclude coronary heart disease (CHD). Anatomical information, functional information, and spectral information can already be obtained with current CT technologies. Moreover, novel developments such as targeted nanoparticle contrast agents, photon-counting CT, and phase contrast CT will further enhance the diagnostic value of cardiovascular CT. This review provides an overview of current state of the art and future cardiovascular CT imaging.

    View details for DOI 10.1007/s11886-016-0714-0

    View details for Web of Science ID 000372279900006

    View details for PubMedID 26922591

  • Assessment of Coronary Artery Calcium on Low-Dose Coronary Computed Tomography Angiography With Iterative Reconstruction JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Braber, T. L., Willemink, M. J., Bohte, E. H., Mosterd, A., Leiner, T., Velthuis, B. K. 2016; 40 (2): 266-271


    This study aims to evaluate whether coronary calcium scoring (CCS) is also feasible using low-radiation-dose coronary computed tomography angiography (CCTA) in combination with iterative reconstruction.Forty-three individuals without known coronary artery disease underwent both noncontrast CCS (±1 mSv) for reference Agatston scores and low-dose CCTA (±3 mSv). Raw CCTA data were reconstructed with filtered back projection (FBP), hybrid iterative reconstruction (HIR), and model-based iterative reconstruction (MIR). Calcification volumes were derived with thresholds of >351 and >600 Hounsfield units (HU) and converted to proxy Agatston scores with linear regression analysis.Intraclass correlation coefficients for Agatston scores versus CCTA volumes with FBP and iterative reconstruction were excellent (ranges 0.94-0.99 and 0.96-0.99 for >351 HU and >600 HU thresholds, respectively). The >351 HU threshold resulted in higher CCTA volume scores ranging from 65.9 (15.1-347.0) for HIR to 94.8 (42.0-423.0) for MIR (P = 0.001 and <0.001, respectively). The >600 HU threshold scores ranged from 14.1 (0.0-159.3) for HIR to 28.6 (0.0-215.6) for MIR (P = 0.003 and 0.027, respectively). At >351 HU, reclassification occurred in 21 individuals (49%) for FBP and HIR and 25 individuals (58%) for MIR. Reclassifications decreased with >600 HU to 10 (HIR, 23%), 8 (FBP, 19%), and 4 (MIR, 9%).The CCS is feasible using iteratively reconstructed low-dose CCTA with a calcium threshold of >600 HU. Using MIR, only 9% of individuals were reclassified.

    View details for DOI 10.1097/RCT.0000000000000347

    View details for Web of Science ID 000373455100014

    View details for PubMedID 26720203

  • Effect of radiation dose reduction and iterative reconstruction on computer-aided detection of pulmonary nodules: Intra-individual comparison EUROPEAN JOURNAL OF RADIOLOGY den Harder, A. M., Willemink, M. J., van Hamersvelt, R. W., Vonken, E. P., Milles, J., Schilham, A. M., Lammers, J., de Jong, P. A., Leiner, T., Budde, R. P. 2016; 85 (2): 346-359


    To evaluate the effect of radiation dose reduction and iterative reconstruction (IR) on the performance of computer-aided detection (CAD) for pulmonary nodules.In this prospective study twenty-five patients were included who were scanned for pulmonary nodule follow-up. Image acquisition was performed at routine dose and three reduced dose levels in a single session by decreasing mAs-values with 45%, 60% and 75%. Tube voltage was fixed at 120 kVp for patients ≥ 80 kg and 100 kVp for patients < 80 kg. Data were reconstructed with filtered back projection (FBP), iDose(4) (levels 1,4,6) and IMR (levels 1-3). All noncalcified solid pulmonary nodules ≥ 4 mm identified by two radiologists in consensus served as the reference standard. Subsequently, nodule volume was measured with CAD software and compared to the reference consensus. The numbers of true-positives, false-positives and missed pulmonary nodules were evaluated as well as the sensitivity.Median effective radiation dose was 2.2 mSv at routine dose and 1.2, 0.9 and 0.6 mSv at respectively 45%, 60% and 75% reduced dose. A total of 28 pulmonary nodules were included. With FBP at routine dose, 89% (25/28) of the nodules were correctly identified by CAD. This was similar at reduced dose levels with FBP, iDose(4) and IMR. CAD resulted in a median number of false-positives findings of 11 per scan with FBP at routine dose (93% of the CAD marks) increasing to 15 per scan with iDose(4) (95% of the CAD marks) and 26 per scan (96% of the CAD marks) with IMR at the lowest dose level.CAD can identify pulmonary nodules at submillisievert dose levels with FBP, hybrid and model-based IR. However, the number of false-positive findings increased using hybrid and especially model-based IR at submillisievert dose while dose reduction did not affect the number of false-positives with FBP.

    View details for DOI 10.1016/j.ejrad.2015.12.003

    View details for Web of Science ID 000368276000005

    View details for PubMedID 26781139

  • Finding the optimal dose reduction and iterative reconstruction level for coronary calcium scoring JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY Willemink, M. J., den Harder, A. M., Foppen, W., Schilham, A. M., Rienks, R., Laufer, E. M., Nieman, K., de Jong, P. A., Budde, R. P., Nathoe, H. M., Leiner, T. 2016; 10 (1): 69-75


    To assess the maximally achievable computed tomography (CT) dose reduction for coronary artery calcium (CAC) scoring with iterative reconstruction (IR) by using phantom-experiments and a systematical within-patient study.Our local institutional review-board approved this study and informed consent was obtained from all participants. A phantom and patient study were conducted with 30 patients (23 men, median age 55.0 (52.0-56.0) years) who underwent 256-slice electrocardiogram-triggered CAC-scoring at four dose levels (routine, 60%, 40%, and 20%-dose) in a single session. Tube-voltage was 120 kVp, tube-current was lowered to achieve stated dose levels. Data were reconstructed with filtered back-projection (FBP) and three IR levels. Agatston, volume and mass scores were determined with validated software and compared using Wilcoxon signed ranks-tests. Subsequently, patient reclassification was analyzed.The phantom study showed that Agatston scores remained nearly stable with FBP between routine-dose and 40%-dose and increased substantially at lower dose. Twenty-three patients (77%) had coronary calcifications. For Agatston scoring, one 40%-dose and six 20%-dose FBP reconstructions were not interpretable due to noise. In contrast, with IR all reconstructions were interpretable. Median Agatston scores increased with FBP from 26.1 (5.2-192.2) at routine-dose to 60.5 (11.6-251.7) at 20% dose. However, IR lowered Agatston scores to 22.9 (5.9-195.5) at 20%-dose and strong IR (level 7) with Agatston reclassifications in 15%.IR allows for CAC-scoring radiation dose reductions of up to 80% resulting in effective doses between 0.15 and 0.18 mSv. At these dose-levels, reclassification-rates remain within 15% if the highest IR-level is applied.

    View details for DOI 10.1016/j.jcct.2015.08.004

    View details for Web of Science ID 000369115100009

    View details for PubMedID 26342405

  • Dual energy CT to reveal pseudo leakage of frozen elephant trunk. Journal of cardiovascular computed tomography van Hamersvelt, R. W., de Jong, P. A., Dessing, T. C., Leiner, T., Willemink, M. J. 2016


    In this case report dual energy CT information was used to reveal a pseudo leakage of a frozen elephant trunk stent. Different materials, which could not be distinguished based on attenuation number, were distinguished with the use of material decomposition algorithms using DECT acquisitions. By using material decomposition imaging, the DECT system proved that in this case the extraluminal densities were not caused by leakage but by a Teflon Felt supported suture.

    View details for DOI 10.1016/j.jcct.2016.11.001

    View details for PubMedID 27863922

  • Dose reduction with iterative reconstruction for coronary CT angiography: a systematic review and meta-analysis BRITISH JOURNAL OF RADIOLOGY den Harder, A. M., Willemink, M. J., de Ruiter, Q. M., de Jong, P. A., Schilham, A. M., Krestin, G. P., Leiner, T., Budde, R. P. 2016; 89 (1058)


    To investigate the achievable radiation dose reduction for coronary CT angiography (CCTA) with iterative reconstruction (IR) in adults and the effects on image quality.PubMed and EMBASE were searched, and original articles concerning IR for CCTA in adults using prospective electrocardiogram triggering were included. Primary outcome was the effective dose using filtered back projection (FBP) and IR. Secondary outcome was the effect of IR on objective and subjective image quality.The search yielded 1616 unique articles, of which 10 studies (1042 patients) were included. The pooled routine effective dose with FBP was 4.2 mSv [95% confidence interval (CI) 3.5-5.0]. A dose reduction of 48% to a pooled effective dose of 2.2 mSv (95% CI 1.3-3.1) using IR was reported. Noise, contrast-to-noise ratio and subjective image quality were equal or improved in all but one study, whereas signal-to-noise ratio was decreased in two studies with IR at reduced dose.IR allows for CCTA acquisition with an effective dose of 2.2 mSv with preserved objective and subjective image quality.

    View details for DOI 10.1259/bjr.20150068

    View details for Web of Science ID 000368422100002

    View details for PubMedID 26562096

  • Do carotid MR surface coils affect PET quantification in PET/MR imaging? EJNMMI physics Willemink, M. J., Eldib, M., Leiner, T., Fayad, Z. A., Mani, V. 2015; 2: A34-?

    View details for DOI 10.1186/2197-7364-2-S1-A34

    View details for PubMedID 26956291

  • Achievable dose reduction using iterative reconstruction for chest computed tomography: A systematic review EUROPEAN JOURNAL OF RADIOLOGY den Harder, A. M., Willemink, M. J., de Ruiter, Q. M., Schilham, A. M., Krestin, G. P., Leiner, T., de Jong, P. A., Budde, R. P. 2015; 84 (11): 2307-2313


    Iterative reconstruction (IR) allows for dose reduction with maintained image quality in CT imaging. In this systematic review the reported effective dose reductions for chest CT and the effects on image quality are investigated.A systematic search in PubMed and EMBASE was performed. Primary outcome was the reported local reference and reduced effective dose and secondary outcome was the image quality with IR. Both non contrast-enhanced and enhanced studies comparing reference dose with reduced dose were included.24 studies were included. The median number of patients per study was 66 (range 23-200) with in total 1806 patients. The median reported local reference dose of contrast-enhanced chest CT with FBP was 2.6 (range 1.5-21.8) mSv. This decreased to 1.4 (range 0.4-7.3) mSv at reduced dose levels using IR. With non contrast-enhanced chest CT the dose decreased from 3.4 (range 0.7-7.8) mSv to 0.9 (range 0.1-4.5) mSv. Objective mage quality and diagnostic confidence and acceptability remained the same or improved with IR compared to FBP in most studies while data on diagnostic accuracy was limited.Radiation dose can be reduced to less than 2 mSv for contrast-enhanced chest CT and non contrast-enhanced chest CT is possible at a submillisievert dose using IR algorithms.

    View details for DOI 10.1016/j.ejrad.2015.07.011

    View details for Web of Science ID 000363265600038

    View details for PubMedID 26212557

  • Improving head and neck CTA with hybrid and model-based iterative reconstruction techniques CLINICAL RADIOLOGY Niesten, J. M., van der Schaaf, I. C., Vos, P. C., Willemink, M. J., Velthuis, B. K. 2015; 70 (11): 1252-1259


    To compare image quality of head and neck computed tomography angiography (CTA) reconstructed with filtered back projection (FBP), hybrid iterative reconstruction (HIR) and model-based iterative reconstruction (MIR) algorithms.The raw data of 34 studies were simultaneously reconstructed with FBP, HIR (iDose(4), Philips Healthcare, Best, the Netherlands), and with a prototype version of a MIR algorithm (IMR, Philips Healthcare). Objective (contrast-to-noise ratio [CNR], vascular contrast, automatic vessel analysis [AVA], stenosis grade) and subjective image quality (ranking at level of the circle of Willis, carotid bifurcation, and shoulder) of the five reconstructions were compared using repeated-measures analysis of variance (ANOVA) and post-hoc analysis.Vascular contrast was significantly higher in both the circle of Willis and carotid bifurcation with both levels of MIR compared to the other reconstruction methods (all p<0.0001). The CNR was highest for high MIR, followed by low MIR, high HIR, mid HIR and FBP (p<0.001 except low MIR versus high HIR; p>0.33). AVA showed most complete carotids in both MIR-levels, followed by high HIR (p>0.08), mid HIR (p<0.023) and FBP (p<0.010), vertebral arteries completeness was similar (p=0.40 and p=0.06). Stenosis grade showed no significant differences (p=0.16). High HIR showed the best subjective image quality at the circle of Willis and carotid bifurcation level, followed by mid HIR. At shoulder level, low MIR and high HIR were ranked best, followed by high MIR.Objectively, MIR significantly improved the overall image quality, reduced image noise, and improved automated vessel analysis, whereas FBP showed the lowest objective image quality. Subjectively, the highest level of HIR was considered superior at the level of the circle of Willis and the carotid bifurcation, and along with the lowest level of MIR for the origins of the neck arteries at shoulder level.

    View details for DOI 10.1016/j.crad.2015.06.095

    View details for Web of Science ID 000361904300014

    View details for PubMedID 26227475

  • Coronary calcium scores are systematically underestimated at a large chest size: A multivendor phantom study JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY Willemink, M. J., Abramiuc, B., den Harder, A. M., van der Werf, N. R., de Jong, P. A., Budde, R. P., Wildberger, J. E., Vliegenthart, R., Willems, T. P., Greuter, M. J., Leiner, T. 2015; 9 (5): 415-421


    To evaluate the effect of chest size on coronary calcium score (CCS) as assessed with new-generation CT systems from 4 major vendors.An anthropomorphic, small-sized (300 × 200 mm) chest phantom containing 100 small calcifications (diameters, 0.5-2.0 mm) was evaluated with and without an extension ring on state-of-the-art CT systems from 4 vendors. The extension ring was used to mimic a patient with a large chest size (400 × 300 mm). Image acquisition was repeated 5 times with small translations and/or rotations. Routine clinical acquisition and reconstruction protocols for small and large patients were used. CCS was quantified as Agatston and mass scores with vendor software.The small-sized phantom resulted in median (interquartiles) Agatston scores of 10 (9-35), 136 (123-146), 34 (30-37), and 87 (85-89) for Philips, GE, Siemens, and Toshiba, respectively. Mass scores were 4 mg (3-9 mg), 23 mg (21-27 mg), 8 mg (8-9 mg), and 20 mg (20-20 mg), respectively. Adding the extension ring resulted in reduced Agatston scores for all vendors (17%-48%) and mass scores for 2 vendors (11%-49%). Median Agatston scores decreased to 9 (5-10), 79 (60-80), 27 (24-32), and 45 (29-53) units, and median mass scores remained similar for Philips at 4 mg (4-6 mg) and Siemens at 8 mg (7-8 mg) and decreased for the other vendors to 13 mg (11-14 mg) and 10 mg (8-13 mg), respectively.This multivendor phantom study showed that CCS can be underestimated up to 50% (49%-66%) for Agatston scores and 49% (36%-59%) for mass scores at a larger chest size, which may be relevant for women and large patients. However, CCS underestimation by chest size differs considerably by vendor.

    View details for DOI 10.1016/j.jcct.2015.03.010

    View details for Web of Science ID 000361930700006

    View details for PubMedID 25980948

  • Prognostic value of heart valve calcifications for cardiovascular events in a lung cancer screening population INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING Willemink, M. J., Takx, R. A., Isgum, I., de Koning, H. J., Oudkerk, M., Mali, W. P., Budde, R. P., Leiner, T., Vliegenthart, R., de Jong, P. A. 2015; 31 (6): 1243-1249


    To assess the prognostic value of aortic valve and mitral valve/annulus calcifications for cardiovascular events in heavily smoking men without a history of cardiovascular disease. Heavily smoking men without a cardiovascular disease history who underwent non-contrast-enhanced low-radiation-dose chest CT for lung cancer screening were included. Non-imaging predictors (age, smoking status and pack-years) were collected and imaging-predictors (calcium volume of the coronary arteries, aorta, aortic valve and mitral valve/annulus) were obtained. The outcome was the occurrence of cardiovascular events. Multivariable Cox proportional-hazards regression was used to calculate hazard-ratios (HRs) with 95% confidence interval (CI). Subsequently, concordance-statistics were calculated. In total 3111 individuals were included, of whom 186 (6.0%) developed a cardiovascular event during a follow-up of 2.9 (Q1-Q3, 2.7-3.3) years. If aortic (n = 657) or mitral (n = 85) annulus/valve calcifications were present, cardiovascular event incidence increased to 9.0% (n = 59) or 12.9% (n = 11), respectively. HRs of aortic and mitral valve/annulus calcium volume for cardiovascular events were 1.46 (95% CI, 1.09-1.84) and 2.74 (95% CI, 0.92-4.56) per 500 mm(3). The c-statistic of a basic model including age, pack-years, current smoking status, coronary and aorta calcium volume was 0.68 (95% CI, 0.63-0.72), which did not change after adding heart valve calcium volume. Aortic valve calcifications are predictors of future cardiovascular events. However, there was no added prognostic value beyond age, number of pack-years, current smoking status, coronary and aorta calcium volume for short term cardiovascular events.

    View details for DOI 10.1007/s10554-015-0664-4

    View details for Web of Science ID 000357125600016

    View details for PubMedID 25962863

  • Incidental necropsy finding of a quadricuspid aortic valve CARDIOVASCULAR PATHOLOGY van Rijswijk, J. W., Willemink, M. J., Kluin, J., Vink, A. 2015; 24 (4): 258-259


    Quadricuspid aortic valve is a rare congenital cardiac malformation often associated with abnormal valve function. In this article, we present a case of quadricuspid aortic valve only diagnosed at the time of post-mortem examination.

    View details for DOI 10.1016/j.carpath.2015.02.002

    View details for Web of Science ID 000355449100012

    View details for PubMedID 25754175

  • New Applications of Cardiac Computed Tomography Dual-Energy, Spectral, and Molecular CT Imaging JACC-CARDIOVASCULAR IMAGING Danad, I., Fayad, Z. A., Willemink, M. J., Min, J. K. 2015; 8 (6): 710-723


    Computed tomography (CT) has evolved into a powerful diagnostic tool, and it is impossible to imagine current clinical practice without CT imaging. Because of its widespread availability, ease of clinical application, superb sensitivity for the detection of coronary artery disease, and noninvasive nature, CT has become a valuable tool within the armamentarium of cardiologists. In the past few years, numerous technological advances in CT have occurred, including dual-energy CT, spectral CT, and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging tool that permits accurate plaque characterization, assessment of myocardial perfusion, and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging.

    View details for DOI 10.1016/j.jcmg.2015.03.005

    View details for Web of Science ID 000356560600013

    View details for PubMedID 26068288

  • Interscan variation of semi-automated volumetry of subsolid pulmonary nodules EUROPEAN RADIOLOGY Scholten, E. T., de Jong, P. A., Jacobs, C., van Ginneken, B., van Riel, S., Willemink, M. J., Vliegenthart, R., Oudkerk, M., de Koning, H. J., Horeweg, N., Prokop, M., Mali, W. P., Gietema, H. A. 2015; 25 (4): 1040-1047


    We aimed to test the interscan variation of semi-automatic volumetry of subsolid nodules (SSNs), as growth evaluation is important for SSN management.From a lung cancer screening trial all SSNs that were stable over at least 3 months were included (N = 44). SSNs were quantified on the baseline CT by two observers using semi-automatic volumetry software for effective diameter, volume, and mass. One observer also measured the SSNs on the second CT 3 months later. Interscan variation was evaluated using Bland-Altman plots. Observer agreement was calculated as intraclass correlation coefficient (ICC). Data are presented as mean (± standard deviation) or median and interquartile range (IQR). A Mann-Whitney U test was used for the analysis of the influence of adjustments on the measurements.Semi-automatic measurements were feasible in all 44 SSNs. The interscan limits of agreement ranged from -12.0 % to 9.7 % for diameter, -35.4 % to 28.6 % for volume and -27.6 % to 30.8 % for mass. Agreement between observers was good with intraclass correlation coefficients of 0.978, 0.957, and 0.968 for diameter, volume, and mass, respectively.Our data suggest that when using our software an increase in mass of 30 % can be regarded as significant growth.• Recently, recommendations regarding subsolid nodules have stressed the importance of growth quantification. • Volumetric measurement of subsolid nodules is feasible with good interscan agreement. • Increase of mass of 30 % can be regarded as significant growth.

    View details for DOI 10.1007/s00330-014-3478-1

    View details for Web of Science ID 000351226500016

    View details for PubMedID 25413965

  • Hybrid and Model-Based Iterative Reconstruction Techniques for Pediatric CT AMERICAN JOURNAL OF ROENTGENOLOGY den Harder, A. M., Willemink, M. J., Budde, R. P., Schilham, A. M., Leiner, T., de Jong, P. A. 2015; 204 (3): 645-653


    OBJECTIVE. Radiation exposure from CT examinations should be reduced to a minimum in children. Iterative reconstruction (IR) is a method to reduce image noise that can be used to improve CT image quality, thereby allowing radiation dose reduction. This article reviews the use of hybrid and model-based IRs in pediatric CT and discusses the possibilities, advantages, and disadvantages of IR in pediatric CT and the importance of radiation dose reduction for CT of children. CONCLUSION. IR is a promising and potentially highly valuable technique that can be used to substantially reduce the amount of radiation in pediatric imaging. Future research should determine the maximum achievable radiation dose reduction in pediatric CT that is possible without a loss of diagnostic image quality.

    View details for DOI 10.2214/AJR.14.12590

    View details for Web of Science ID 000351598800048

    View details for PubMedID 25714298

  • Intravenous contrast injection significantly affects bone mineral density measured on CT EUROPEAN RADIOLOGY Pompe, E., Willemink, M. J., Dijkhuis, G. R., Verhaar, H. J., Hoesein, F. A., de Jong, P. A. 2015; 25 (2): 283-289


    The objective is to evaluate the effect of intravenous contrast media on bone mineral density (BMD) assessment by comparing unenhanced and contrast-enhanced computed tomography (CT) examinations performed for other indications.One hundred and fifty-two patients (99 without and 53 with malignant neoplasm) who underwent both unenhanced and two contrast-enhanced (arterial and portal venous phase) abdominal CT examinations in a single session between June 2011 and July 2013 were included. BMD was evaluated on the three examinations as CT-attenuation values in Hounsfield Units (HU) in the first lumbar vertebra (L1).CT-attenuation values were significantly higher in both contrast-enhanced phases, compared to the unenhanced phase (p < 0.01). In patients without malignancies, mean ± standard deviation (SD) HU-values increased from 128.8 ± 48.6 HU for the unenhanced phase to 142.3 ± 47.2 HU for the arterial phase and 147.0 ± 47.4 HU for the portal phase (p < 0.01). In patients with malignancies, HU-values increased from 112.1 ± 38.1 HU to 126.2 ± 38.4 HU and 130.1 ± 37.3 HU (p < 0.02), respectively. With different thresholds to define osteoporosis, measurements in the arterial and portal phase resulted in 7-25% false negatives.Our study showed that intravenous contrast injection substantially affects BMD-assessment on CT and taking this into account may improve routine assessment of low BMD in nonquantitative CT.• Routine CT may gain a role in bone attenuation measurements for osteoporosis • Contrast media injection has substantial influence on CT-derived bone density • Contrast-enhanced CT leads to underestimation of osteoporosis compared to unenhanced CT • Adjusting for contrast injection phase may improve CT screening protocols for osteoporosis.

    View details for DOI 10.1007/s00330-014-3408-2

    View details for Web of Science ID 000351225800001

    View details for PubMedID 25187384

  • Quantification of coronary artery calcium in nongated CT to predict cardiovascular events in male lung cancer screening participants: Results of the NELSON study JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY Takx, R. A., Isgum, I., Willemink, M. J., van der Graaf, Y., de Koning, H. J., Vliegenthart, R., Oudkerk, M., Leiner, T., de Jong, P. A. 2015; 9 (1): 50-57


    To evaluate the incremental prognostic value of the number and maximum volume of coronary artery calcifications over modified Agatston score strata, age, pack-years, and smoking status for predicting cardiovascular events.A total of 3559 male current and former smokers received a CT examination for lung cancer screening. Smoking characteristics, patient demographics, and physician-diagnosed cardiovascular events were collected. Images were acquired without electrocardiography gating on 16-slice CT scanners. The association between the presence of both fatal and nonfatal cardiovascular events and the predictors was quantified using Cox proportional hazard analysis.Median follow-up period was 2.9 years. Incident cardiovascular events occurred in 186 participants. Adjusted hazard ratios for modified Agatston score strata of 1 to 10, 11 to 100, 101 to 400, and >400 were 3.39 (95% confidence interval [CI], 1.20-9.59), 6.52 (95% CI, 2.73-15.60), 6.58 (95% CI, 2.75-15.78), and 12.58 (95% CI, 5.42-29.16), respectively. Moreover, comparing the models with and without modified Agatston score strata to the model with age, pack-years, and smoking status yielded a significantly better net reclassification improvement (NRI; 27.3%; P < .0001). Adding the number of calcifications to the model with age, pack-years, smoking status, and modified Agatston score strata resulted in a slightly better NRI (1.68%; P = .0490) with a hazard ratio of 1.13 (95% CI, 1.05-1.21) per 10 calcifications. The incremental prognostic information contained in the volume of the largest calcification was not statistically significant (NRI, 0.14%; P = .3458).Cardiovascular event rate increased with higher numbers of calcified lesions. The number but not maximum volume of calcifications has independent, although minimal, prognostic value over age, pack-years, smoking status, and modified Agatston score strata in our population.

    View details for DOI 10.1016/j.jcct.2014.11.006

    View details for Web of Science ID 000349743000007

    View details for PubMedID 25533223

  • Coronary Artery Calcification Scoring with State-of-the-Art CT Scanners from Different Vendors Has Substantial Effect on Risk Classification RADIOLOGY Willemink, M. J., Vliegenthart, R., Takx, R. A., Leiner, T., Budde, R. P., Bleys, R. L., Das, M., Wildberger, J. E., Prokop, M., Buls, N., De Mey, J., Schilham, A. M., de Jong, P. A. 2014; 273 (3): 695-702


    To determine the intervendor variability of Agatston scoring determined with state-of-the-art computed tomographic (CT) systems from the four major vendors in an ex vivo setup and to simulate the subsequent effects on cardiovascular risk reclassification in a large population-based cohort.Research ethics board approval was not necessary because cadaveric hearts from individuals who donated their bodies to science were used. Agatston scores obtained with CT scanners from four different vendors were compared. Fifteen ex vivo human hearts were placed in a phantom resembling an average human adult. Hearts were scanned at equal radiation dose settings for the systems of all four vendors. Agatston scores were quantified semiautomatically with software used clinically. The ex vivo Agatston scores were used to simulate the effects of different CT scanners on reclassification of 432 individuals aged 55 years or older from a population-based study who were at intermediate cardiovascular risk based on Framingham risk scores. The Friedman test was used to evaluate overall differences, and post hoc analyses were performed by using the Wilcoxon signed-rank test with Bonferroni correction.Agatston scores differed substantially when CT scanners from different vendors were used, with median Agatston scores ranging from 332 (interquartile range, 114-1135) to 469 (interquartile range, 183-1381; P < .05). Simulation showed that these differences resulted in a change in cardiovascular risk classification in 0.5%-6.5% of individuals at intermediate risk when a CT scanner from a different vendor was used.Among individuals at intermediate cardiovascular risk, state-of the-art CT scanners made by different vendors produced substantially different Agatston scores, which can result in reclassification of patients to the high- or low-risk categories in up to 6.5% of cases.

    View details for DOI 10.1148/radiol.14140066

    View details for Web of Science ID 000345515100008

    View details for PubMedID 25153157

  • Computed Tomography Radiation Dose Reduction: Effect of Different Iterative Reconstruction Algorithms on Image Quality JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Willemink, M. J., Takx, R. A., de Jong, P. A., Budde, R. P., Bleys, R. L., Das, M., Wildberger, J. E., Prokop, M., Buls, N., De Mey, J., Leiner, T., Schilham, A. M. 2014; 38 (6): 815-823


    We evaluated the effects of hybrid and model-based iterative reconstruction (IR) algorithms from different vendors at multiple radiation dose levels on image quality of chest phantom scans.A chest phantom was scanned on state-of-the-art computed tomography scanners from 4 vendors at 4 dose levels (4.1 mGy, 3.0 mGy, 1.9 mGy, and 0.8 mGy). All data were reconstructed with filtered back projection (FBP) and reduced-dose data also with IR (iDose4, Adaptive Iterative Dose Reduction 3D, Adaptive Statistical Iterative Reconstruction, Sinogram-Affirmed Iterative Reconstruction, prototype Iterative Model Reconstruction, and Veo). Computed tomography numbers and noise were measured in the spine and lungs. Signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were calculated and differences were analyzed with the Friedman test.For all vendors, radiation dose reduction with FBP resulted in significantly increased noise levels (≤148%) as well as decreased SNR (≤57%) and CNR (≤58%) (P < 0.001). Conversely, IR resulted in decreased noise levels (≤48%) as well as increased SNR (≤94%) and CNR (≤94%). The SNRs and CNRs of the model-based algorithms at 80% reduced dose were similar to reference-dose FBP.Hybrid IR algorithms have the potential to reduce radiation dose with 27% to 54% and model-based IR algorithms with up to 80%.

    View details for Web of Science ID 000345430200002

    View details for PubMedID 24983438

  • The impact of CT radiation dose reduction and iterative reconstruction algorithms from four different vendors on coronary calcium scoring EUROPEAN RADIOLOGY Willemink, M. J., Takx, R. A., de Jong, P. A., Budde, R. P., Bleys, R. L., Das, M., Wildberger, J. E., Prokop, M., Buls, N., De Mey, J., Schilham, A. M., Leiner, T. 2014; 24 (9): 2201-2212


    To analyse the effects of radiation dose reduction and iterative reconstruction (IR) algorithms on coronary calcium scoring (CCS).Fifteen ex vivo human hearts were examined in an anthropomorphic chest phantom using computed tomography (CT) systems from four vendors and examined at four dose levels using unenhanced prospectively ECG-triggered protocols. Tube voltage was 120 kV and tube current differed between protocols. CT data were reconstructed with filtered back projection (FBP) and reduced dose CT data with IR. CCS was quantified with Agatston scores, calcification mass and calcification volume. Differences were analysed with the Friedman test.Fourteen hearts showed coronary calcifications. Dose reduction with FBP did not significantly change Agatston scores, calcification volumes and calcification masses (P > 0.05). Maximum differences in Agatston scores were 76, 26, 51 and 161 units, in calcification volume 97, 27, 42 and 162 mm(3), and in calcification mass 23, 23, 20 and 48 mg, respectively. IR resulted in a trend towards lower Agatston scores and calcification volumes with significant differences for one vendor (P < 0.05). Median relative differences between reference FBP and reduced dose IR for Agatston scores remained within 2.0-4.6%, 1.0-5.3%, 1.2-7.7% and 2.6-4.5%, for calcification volumes within 2.4-3.9%, 1.0-5.6%, 1.1-6.4% and 3.7-4.7%, for calcification masses within 1.9-4.1%, 0.9-7.8%, 2.9-4.7% and 2.5-3.9%, respectively. IR resulted in increased, decreased or similar calcification masses.CCS derived from standard FBP acquisitions was not affected by radiation dose reductions up to 80%. IR resulted in a trend towards lower Agatston scores and calcification volumes.In this ex vivo study, radiation dose could be reduced by 80% for coronary calcium scoring. Iterative reconstruction resulted in a trend towards lower Agatston scores and calcification volumes. Caution should be taken for coronary calcium scoring with iterative reconstruction.

    View details for DOI 10.1007/s00330-014-3217-7

    View details for Web of Science ID 000340519200020

    View details for PubMedID 24889996

  • Dose reduction for coronary calcium scoring with hybrid and model-based iterative reconstruction: an ex vivo study INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING den Harder, A. M., Willemink, M. J., Bleys, R. L., de Jong, P. A., Budde, R. P., Schilham, A. M., Leiner, T. 2014; 30 (6): 1125-1133


    To determine the influence of dose reduction on coronary calcium scoring using hybrid and model-based iterative reconstruction (IR) techniques.Fifteen ex vivo hearts were scanned in a phantom representing an average adult person at routine dose and three levels of dose reduction; 27, 55 and 82% reduced-dose, respectively. All images were reconstructed using filtered back-projection (FBP), hybrid IR (iDose4, levels 1, 4 and 7) as well as model-based IR iterative model reconstruction (IMR, levels 1, 2 and 3). Agatston, mass and volume scores found with iDose4 and IMR were compared to FBP reconstruction (routine dose) as well as objective image quality.With FBP calcium scores remained unchanged at 82% reduced dose. With IR Agatston scores differed significantly at routine dose, using IMR level 3 and iDose4 level 7, and at 82% reduced dose, using IMR levels 1-3 and iDose4 level 7. The maximum median difference was 5.3%. Mass remained unchanged at reduced dose levels while volume was significantly lower at 82% reduced dose with IMR (maximum median difference 5.0%). Objective image quality improved with IR, at 82% reduced dose the CNR of iDose4 level 7 was similar to the reference dose CNR, and IMR levels 1-3 resulted in an even higher CNR.Calcium scores were not affected by radiation-dose reduction with FBP and low levels of hybrid IR. Objective image quality increased significantly using hybrid and model-based IR. Therefore low level hybrid IR has the potential to reduce radiation-dose of coronary calcium scoring with up to 82%.

    View details for DOI 10.1007/s10554-014-0434-8

    View details for Web of Science ID 000339901400017

    View details for PubMedID 24794292

  • Cardiac valve calcifications on low-dose unenhanced ungated chest computed tomography: inter-observer and inter-examination reliability, agreement and variability EUROPEAN RADIOLOGY van Hamersvelt, R. W., Willemink, M. J., Takx, R. A., Eikendal, A. L., Budde, R. P., Leiner, T., Mol, C. P., Isgum, I., de Jong, P. A. 2014; 24 (7): 1557-1564


    To determine inter-observer and inter-examination variability for aortic valve calcification (AVC) and mitral valve and annulus calcification (MC) in low-dose unenhanced ungated lung cancer screening chest computed tomography (CT).We included 578 lung cancer screening trial participants who were examined by CT twice within 3 months to follow indeterminate pulmonary nodules. On these CTs, AVC and MC were measured in cubic millimetres. One hundred CTs were examined by five observers to determine the inter-observer variability. Reliability was assessed by kappa statistics (κ) and intra-class correlation coefficients (ICCs). Variability was expressed as the mean difference ± standard deviation (SD).Inter-examination reliability was excellent for AVC (κ = 0.94, ICC = 0.96) and MC (κ = 0.95, ICC = 0.90). Inter-examination variability was 12.7 ± 118.2 mm(3) for AVC and 31.5 ± 219.2 mm(3) for MC. Inter-observer reliability ranged from κ = 0.68 to κ = 0.92 for AVC and from κ = 0.20 to κ = 0.66 for MC. Inter-observer ICC was 0.94 for AVC and ranged from 0.56 to 0.97 for MC. Inter-observer variability ranged from -30.5 ± 252.0 mm(3) to 84.0 ± 240.5 mm(3) for AVC and from -95.2 ± 210.0 mm(3) to 303.7 ± 501.6 mm(3) for MC.AVC can be quantified with excellent reliability on ungated unenhanced low-dose chest CT, but manual detection of MC can be subject to substantial inter-observer variability. Lung cancer screening CT may be used for detection and quantification of cardiac valve calcifications.• Low-dose unenhanced ungated chest computed tomography can detect cardiac valve calcifications. • However, calcified cardiac valves are not reported by most radiologists. • Inter-observer and inter-examination variability of aortic valve calcifications is sufficient for longitudinal studies. • Volumetric measurement variability of mitral valve and annulus calcifications is substantial.

    View details for DOI 10.1007/s00330-014-3191-0

    View details for Web of Science ID 000337041900015

    View details for PubMedID 24816936

  • The impact of a new model-based iterative reconstruction algorithm on prosthetic heart valve related artifacts at reduced radiation dose MDCT INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING Sucha, D., Willemink, M. J., de Jong, P. A., Schilham, A. M., Leiner, T., Symersky, P., Budde, R. P. 2014; 30 (4): 785-793


    To assess the impact of hybrid iterative reconstruction (IR) and novel model-based iterative reconstruction (IMR) and dose reduction on prosthetic heart valve (PHV) related artifacts and objective image quality. One transcatheter and two mechanical PHVs were embedded in diluted contrast-gel, inserted in an anthropomorphic phantom and imaged stationary with retrospectively ECG-gated computed tomography. Eight acquisitions were obtained of each PHV at 120 kV, 600 mAs (routine), 300 and 150 mAs (reduced dose). Data were reconstructed with filtered back projection (FBP), IR and IMR. Hypodense and hyperdense artifact volumes were quantified using two threshold filters. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated. Artifact volumes differed significantly between reconstruction algorithms for all PHVs (P < 0.005). Compared to FBP, IR decreased overall hypodense and hyperdense artifact volumes; at 150 mAs by 53 and 20 % (IR) and 67 and 23 % (IMR), respectively and significantly increased SNR and CNR at all doses (P < 0.012). Even at reduced dose, IMR resulted in higher image quality than routine dose FBP and IR. Iterative reconstruction and particularly IMR significantly reduce PHV-related artifacts and improve objective image quality in non-pulsatile conditions, even in reduced-dose images. Also, this study suggests that IMR allows for more radiation dose reduction in comparison to hybrid IR while maintaining high image quality.

    View details for DOI 10.1007/s10554-014-0379-y

    View details for Web of Science ID 000334446300014

    View details for PubMedID 24474347

  • Small Irregular Pulmonary Nodules in Low-Dose CT: Observer Detection Sensitivity and Volumetry Accuracy AMERICAN JOURNAL OF ROENTGENOLOGY Xie, X., Willemink, M. J., de Jong, P. A., van Ooijen, P. M., Oudkerk, M., Vliegenthart, R., Greuter, M. J. 2014; 202 (3): W202-W209


    The purpose of this study is to evaluate observer detection and volume measurement of small irregular solid artificial pulmonary nodules on 64-MDCT in an anthropomorphic thoracic phantom.Forty in-house-made solid pulmonary nodules (lobulated and spiculated; actual volume, 5.1-88.4 mm3; actual CT densities, -51 to 157 HU) were randomly placed inside an anthropomorphic thoracic phantom with pulmonary vasculature. The phantom was examined on two 64-MDCT scanners, using a scan protocol as applied in lung cancer screening. Two independent blinded observers screened for pulmonary nodules. Nodule volume was evaluated semiautomatically using dedicated software and was compared with the actual volume using an independent-samples t test. The interscanner and interobserver agreement of volumetry was assessed using Bland-Altman analysis.Observer detection sensitivity increased along with increasing size of irregular nodules. Sensitivity was 100% when the actual volume was at least 69 mm3, regardless of specific observer, scanner, nodule shape, and density. Overall, nodule volume was underestimated by (mean±SD) 18.9±11.8 mm3 (39%±21%; p<0.001). The relative interscanner difference of volumetry was 3.3% (95% CI, -33.9% to 40.4%). The relative interobserver difference was 0.6% (-33.3% to 34.5%).Small irregular solid pulmonary nodules with an actual volume of at least 69 mm3 are reliably detected on 64-MDCT. However, CT-derived volume of those small nodules is largely underestimated, with considerable variation.

    View details for DOI 10.2214/AJR.13.10830

    View details for Web of Science ID 000332510900003

    View details for PubMedID 24555615

  • Coronary Artery Assessment on Electrocardiogram-Gated Thoracoabdominal Multidetector Computed Tomographic Angiography for Aortic Evaluation JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Willemink, M. J., Meijs, M. F., Cramer, M. J., Thijssen, A. S., Moll, F. L., de Jong, P. A., Leiner, T., Budde, R. P. 2014; 38 (2): 185-189


    The objective of this study was to evaluate coronary image quality, stenosis grade, and diagnostic confidence in patients undergoing electrocardiogram-gated thoracoabdominal multidetector computed tomographic angiography (CTA) for aortic evaluation.Seventy-five consecutive patients underwent retrospectively electrocardiogram-gated thoracoabdominal CTA reconstructed at each 12.5% of the R wave to R wave (R-R) interval. Two observers in consensus scored the coronary arteries per segment (15-segment American Heart Association model) for image quality, stenosis grade, and stenosis-assessment confidence.Nondiagnostic image quality prohibited coronary evaluation in 14 patients. In the remaining patients, 2% of segments was scored absent, 24% was scored nondiagnostic, 12% was scored diagnostically limited, and 61% was scored at least acceptable. Acceptable or higher image quality was seen in 82% of the proximal and middle segments. Significant stenosis (>50%) was seen in 57% of the patients. Stenosis-severity scoring confidence was moderate to high in 79% of 673 assessable segments.Electrocardiogram-gated thoracoabdominal CTA allows concomitant assessment of the proximal and middle coronary arteries and may serve as a combined tool for aortic-disease workup. Aortic CTA showed significant coronary artery stenosis in 57% of the patients evaluated for aortic pathology.

    View details for Web of Science ID 000336726400007

    View details for PubMedID 24625611

  • The effect of iterative reconstruction on quantitative computed tomography assessment of coronary plaque composition INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING Takx, R. A., Willemink, M. J., Nathoe, H. M., Schilham, A. M., Budde, R. P., de Jong, P. A., Leiner, T. 2014; 30 (1): 155-163


    To compare coronary plaque size and composition as well as degree of coronary artery stenosis on coronary Computed Tomography angiography (CCTA) using three levels of iterative reconstruction (IR) with standard filtered back projection (FBP). In 63 consecutive patients with a clinical indication for CCTA 55 coronary plaques were analysed. Raw data were reconstructed using standard FBP and levels 2, 4 and 6 of a commercially available IR algorithm (iDose(4)). CT attenuation and noise were measured in the aorta and two coronary arteries. Both signal-to-noise-ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The amount of lipid, fibrous and calcified plaque components and mean cross-sectional luminal area were analysed using dedicated software. Image noise was reduced by 41.6% (p < 0.0001) and SNR and CNR in the aorta were improved by 73.4% (p < 0.0001) and 72.9% (p < 0.0001) at IR level 6, respectively. IR improved objective image quality measures more in the aorta than in the coronary arteries. Furthermore, IR had no significant effect on measurements of plaque volume and cross-sectional luminal area. The application of IR significantly improves objective image quality, and does not alter quantitative analysis of coronary plaque volume, composition and luminal area.

    View details for DOI 10.1007/s10554-013-0293-8

    View details for Web of Science ID 000330342800017

    View details for PubMedID 24046026

  • [The future of the CT scan; will CT replace conventional radiography?]. Nederlands tijdschrift voor geneeskunde Willemink, M. J., den Harder, A. M., de Jong, P. A., Leiner, T. 2014; 158: A7438-?


    The number of CT scans being made has increased over the past few years. New CT technology has been developed to reduce the individual patient radiation dose. By using this technology it is possible to make CT scans with a radiation dose approaching conventional X-rays, which means that in the future radiation dose may not form a limitation to making CT scans. The indication for CT scans will broaden, and low-dose CT scans will increasingly replace conventional radiography.

    View details for PubMedID 25139648

  • Inter- and intrascanner variability of pulmonary nodule volumetry on low-dose 64-row CT: an anthropomorphic phantom study BRITISH JOURNAL OF RADIOLOGY Xie, X., Willemink, M. J., Zhao, Y., de Jong, P. A., van Ooijen, P. M., Oudkerk, M., Greuter, M. J., Vliegenthart, R. 2013; 86 (1029)


    To assess inter- and intrascanner variability in volumetry of solid pulmonary nodules in an anthropomorphic thoracic phantom using low-dose CT.Five spherical solid artificial nodules [diameters 3, 5, 8, 10 and 12 mm; CT density +100 Hounsfield units (HU)] were randomly placed inside an anthropomorphic thoracic phantom in different combinations. The phantom was examined on two 64-row multidetector CT (64-MDCT) systems (CT-A and CT-B) from different vendors with a low-dose protocol. Each CT examination was performed three times. The CT examinations were evaluated twice by independent blinded observers. Nodule volume was semi-automatically measured by dedicated software. Interscanner variability was evaluated by Bland-Altman analysis and expressed as 95% confidence interval (CI) of relative differences. Intrascanner variability was expressed as 95% CI of relative variation from the mean.No significant difference in CT-derived volume was found between CT-A and CT-B, except for the 3-mm nodules (p<0.05). The 95% CI of interscanner variability was within ±41.6%, ±18.2% and ±4.9% for 3, 5 and ≥8 mm nodules, respectively. The 95% CI of intrascanner variability was within ±28.6%, ±13.4% and ±2.6% for 3, 5 and ≥8 mm nodules, respectively.Different 64-MDCT scanners in low-dose settings yield good agreement in volumetry of artificial pulmonary nodules between 5 mm and 12 mm in diameter. Inter- and intrascanner variability decreases at a larger nodule size to a maximum of 4.9% for ≥8 mm nodules.The commonly accepted cut-off of 25% to determine nodule growth has the potential to be reduced for ≥8 mm nodules. This offers the possibility of reducing the interval for repeated CT scans in lung cancer screenings.

    View details for DOI 10.1259/bjr.20130160

    View details for Web of Science ID 000324102800004

    View details for PubMedID 23884758

  • Pediatric Chest Computed Tomography at a Radiation Dose Approaching a Chest Radiograph AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Willemink, M. J., de Jong, P. A. 2013; 188 (5): 626-627

    View details for Web of Science ID 000324106200025

    View details for PubMedID 23992595

  • Re: Willemink MJ, van Es HW, Helmhout PH, et al. The effects of dynamic isolated lumbar extensor training on lumbar multifidus functional cross-sectional area and functional status of patients with chronic nonspecific low back pain. Spine 2012;37:E1651-8 Response SPINE Willemink, M. J., van Es, H. W., Helmhout, P. H., Kelder, J. C., van Heesewijk, J. M. 2013; 38 (18): 1611–12

    View details for DOI 10.1097/BRS.0b013e31829e3ccb

    View details for Web of Science ID 000330365000024

    View details for PubMedID 23759812

  • Computer-Aided Segmentation and Volumetry of Artificial Ground-Glass Nodules at Chest CT AMERICAN JOURNAL OF ROENTGENOLOGY Scholten, E. T., Jacobs, C., van Ginneken, B., Willemink, M. J., Kuhnigk, J., van Ooijen, P. M., Oudkerk, M., Mali, W. P., de Jong, P. A. 2013; 201 (2): 295-300


    The purpose of this study was to investigate a new software program for semiautomatic measurement of the volume and mass of ground-glass nodules (GGNs) in a chest phantom and to investigate the influence of CT scanner, reconstruction filter, tube voltage, and tube current.We used an anthropomorphic chest phantom with eight artificial GGNs with two different CT attenuations and four different volumes. CT scans were obtained with four models of CT scanner at 120 kVp and 25 mAs with a soft and a sharp reconstruction filter. On the 256-MDCT scanner, the tube current-exposure time product and tube voltage settings were varied. GGNs were measured with software that automatically segmented the nodules. Absolute percentage error (APE) was calculated for volume, mass, and density. Wilcoxon signed rank, Mann-Whitney U, and Kruskal-Wallis tests were used for analysis.Volume and mass did not differ significantly from the true values. When measurements were expressed as APE, the error range was 2-36% for volume and 5-46% for mass, which was significantly different from no error. We did not find significant differences in APE between CT scanners with filters for lower tube current for volume or lower tube voltage for mass.Computer-aided segmentation and mass and volume measurements of GGNs with the prototype software had promising results in this study.

    View details for DOI 10.2214/AJR.12.9640

    View details for Web of Science ID 000322225400042

    View details for PubMedID 23883209

  • Iterative reconstruction techniques for computed tomography Part 1: Technical principles EUROPEAN RADIOLOGY Willemink, M. J., de Jong, P. A., Leiner, T., de Heer, L. M., Nievelstein, R. A., Budde, R. P., Schilham, A. M. 2013; 23 (6): 1623-1631


    To explain the technical principles of and differences between commercially available iterative reconstruction (IR) algorithms for computed tomography (CT) in non-mathematical terms for radiologists and clinicians.Technical details of the different proprietary IR techniques were distilled from available scientific articles and manufacturers' white papers and were verified by the manufacturers. Clinical results were obtained from a literature search spanning January 2006 to January 2012, including only original research papers concerning IR for CT.IR for CT iteratively reduces noise and artefacts in either image space or raw data, or both. Reported dose reductions ranged from 23 % to 76 % compared to locally used default filtered back-projection (FBP) settings, with similar noise, artefacts, subjective, and objective image quality.IR has the potential to allow reducing the radiation dose while preserving image quality. Disadvantages of IR include blotchy image appearance and longer computational time. Future studies need to address differences between IR algorithms for clinical low-dose CT.• Iterative reconstruction technology for CT is presented in non-mathematical terms. • IR reduces noise and artefacts compared to filtered back-projection. • IR can improve image quality in routine-dose CT and lower the radiation dose. • IR's disadvantages include longer computation and blotchy appearance of some images.

    View details for DOI 10.1007/s00330-012-2765-y

    View details for Web of Science ID 000319270800020

    View details for PubMedID 23314600

  • Iterative reconstruction does not substantially delay CT imaging in an emergency setting. Insights into imaging Willemink, M. J., Schilham, A. M., Leiner, T., Mali, W. P., de Jong, P. A., Budde, R. P. 2013; 4 (3): 391-397


    To evaluate the effects of iterative reconstruction (IR) on reconstruction time and speed in two commonly encountered acquisition protocols in an emergency setting: pulmonary CT angiography (CTA) and total body trauma CT.Twenty-five patients underwent a pulmonary CTA for evaluation of pulmonary embolisms and 15 patients underwent a total body CT after a traumatic event on a 256-slice CT. Images were reconstructed with filtered back-projection (FBP) and two IR levels. Reconstruction time and speed were quantified using custom written software.Mean reconstruction time delays for pulmonary CTAs were 10 ± 10 s and 12 ± 12 s for IR levels 2 and 4, respectively, and 44 ± 8 s and 45 ± 7 s for total body trauma CTs for IR levels 1 and 6, respectively. Mean reconstruction times and speeds for pulmonary CTAs were 26 ± 7 s, 36 ± 9 s and 38 ± 12 s, and 26.7 ± 5.6 slices/s, 18.7 ± 2.3 slices/s and 18.0 ± 2.8 slices/s for FBP, IR levels 2 and 4, respectively. For total body trauma CTs these values were 87 ± 15 s, 132 ± 17 s and 132 ± 18 s, and 20.1 ± 1.6 slices/s, 13.2 ± 0.8 slices/s and 13.2 ± 0.6 slices/s for FBP, IR levels 1 and 6, respectively.IR does not result in clinically important CT image reconstruction delays in an emergency setting. No substantial differences in reconstruction time and speed were found between different IR levels.• IR delayed total pulmonary CTA reconstruction with 10-12 s and total-body trauma CT with 44-45 s • IR is not substantially delaying reconstruction in emergency CT imaging • Reconstruction time and speed are similar for different levels of IR.

    View details for DOI 10.1007/s13244-013-0226-z

    View details for PubMedID 23417822

  • Iterative reconstruction techniques for computed tomography part 2: initial results in dose reduction and image quality EUROPEAN RADIOLOGY Willemink, M. J., Leiner, T., de Jong, P. A., de Heer, L. M., Nievelstein, R. A., Schilham, A. M., Budde, R. P. 2013; 23 (6): 1632-1642


    To present the results of a systematic literature search aimed at determining to what extent the radiation dose can be reduced with iterative reconstruction (IR) for cardiopulmonary and body imaging with computed tomography (CT) in the clinical setting and what the effects on image quality are with IR versus filtered back-projection (FBP) and to provide recommendations for future research on IR.We searched Medline and Embase from January 2006 to January 2012 and included original research papers concerning IR for CT.The systematic search yielded 380 articles. Forty-nine relevant studies were included. These studies concerned: the chest(n = 26), abdomen(n = 16), both chest and abdomen(n = 1), head(n = 4), spine(n = 1), and no specific area (n = 1). IR reduced noise and artefacts, and it improved subjective and objective image quality compared to FBP at the same dose. Conversely, low-dose IR and normal-dose FBP showed similar noise, artefacts, and subjective and objective image quality. Reported dose reductions ranged from 23 to 76 % compared to locally used default FBP settings. However, IR has not yet been investigated for ultra-low-dose acquisitions with clinical diagnosis and accuracy as endpoints.Benefits of IR include improved subjective and objective image quality as well as radiation dose reduction while preserving image quality. Future studies need to address the value of IR in ultra-low-dose CT with clinically relevant endpoints.• Iterative reconstruction improves image quality of CT images at equal acquisition parameters. • IR preserves image quality compared to normal-dose filtered back-projection. • The reduced radiation dose made possible by IR is advantageous for patients. • IR has not yet been investigated with clinical diagnosis and accuracy as endpoints.

    View details for DOI 10.1007/s00330-012-2764-z

    View details for Web of Science ID 000319270800021

    View details for PubMedID 23322411

  • Iterative reconstruction improves evaluation of native aortic and mitral valves by retrospectively ECG-gated thoracoabdominal CTA EUROPEAN RADIOLOGY Willemink, M. J., Habets, J., de Jong, P. A., Schilham, A. M., Mali, W. P., Leiner, T., Budde, R. P. 2013; 23 (4): 968-974


    To compare native aortic (AV) and mitral valve (MV) image quality on limited-dose retrospectively ECG-gated CTA of the thoracoabdominal aorta reconstructed with iterative reconstruction (IR) and filtered back projection (FBP).Fifty patients underwent routine care retrospectively ECG-gated thoracoabdominal limited-dose 256-slice CTA. At 30 % (systole) and 75 % (diastole) of the R-R interval AV and MV were reconstructed using FBP and IR. Objective image quality [density and noise (SD of density measurement)] was measured. Two independent observers scored subjective valve image quality using four-point Likert scales.IR significantly decreased image noise, but did not alter the aorta and interventricular septum density. Interobserver variability was moderate to good. Valve image quality was scored at least moderate in most cases. IR scored one or two Likert scale points higher than FBP in 10 (first observer) and 27 (second observer) scores. Conversely, IR scored one Likert scale point lower than FBP in 1 (first observer) and 4 (second observer) scores.Limited-dose retrospectively ECG-gated thoracoabdominal CTA enables moderate to excellent evaluation of AV and MV in most patients, in addition to the primary diagnostic question. Image quality is further improved by IR.

    View details for DOI 10.1007/s00330-012-2673-1

    View details for Web of Science ID 000316331200011

    View details for PubMedID 23064676

  • The Effects of Computed Tomography with Iterative Reconstruction on Solid Pulmonary Nodule Volume Quantification PLOS ONE Willemink, M. J., Borstlap, J., Takx, R. A., Schilham, A. M., Leiner, T., Budde, R. P., de Jong, P. A. 2013; 8 (2)


    The objectives of this study were to evaluate the influence of iterative reconstruction (IR) on pulmonary nodule volumetry with chest computed tomography (CT).Twenty patients (12 women and 8 men, mean age 61.9, range 32-87) underwent evaluation of pulmonary nodules with a 64-slice CT-scanner. Data were reconstructed using filtered back projection (FBP) and IR (Philips Healthcare, iDose(4)-levels 2, 4 and 6) at similar radiation dose. Volumetric nodule measurements were performed with semi-automatic software on thin slice reconstructions. Only solid pulmonary nodules were measured, no additional selection criteria were used for the nature of nodules. For intra-observer and inter-observer variability, measurements were performed once by one observer and twice by another observer. Algorithms were compared using the concordance correlation-coefficient (pc) and Friedman-test, and post-hoc analysis with the Wilcoxon-signed ranks-test with Bonferroni-correction (significance-level p<0.017).Seventy-eight nodules were present including 56 small nodules (volume<200 mm(3), diameter<8 mm) and 22 large nodules (volume≥200 mm(3), diameter≥8 mm). No significant differences in measured pulmonary nodule volumes between FBP, iDose(4)-levels 2, 4 and 6 were found in both small nodules and large nodules. FBP and iDose(4)-levels 2, 4 and 6 were correlated with pc-values of 0.98 or higher for both small and large nodules. Pc-values of intra-observer and inter-observer variability were 0.98 or higher.Measurements of solid pulmonary nodule volume measured with standard-FBP were comparable with IR, regardless of the IR-level and no significant differences between measured volumes of both small and large solid nodules were found.

    View details for DOI 10.1371/journal.pone.0058053

    View details for Web of Science ID 000315519000179

    View details for PubMedID 23460924

  • The Effects of Dynamic Isolated Lumbar Extensor Training on Lumbar Multifidus Functional Cross-Sectional Area and Functional Status of Patients With Chronic Nonspecific Low Back Pain SPINE Willemink, M. J., van Es, H. W., Helmhout, P. H., Diederik, A. L., Kelder, J. C., van Heesewijk, J. P. 2012; 37 (26): E1651-E1658


    A prospective single-arm trial.To investigate whether dynamic isolated resistance training of global lumbar extensor muscles leads to changes in lumbar multifidus (LM) morphology in terms of cross-sectional muscle, and, if so, whether these changes are associated with observed changes in self-experienced functional status of chronic nonspecific low back pain (CNSLBP).LM morphology is associated with the recurrence of CNSLBP.Sixteen male patients underwent a dynamic isolated resistance-training program for the lower back muscles of approximately 10 sessions in 12 weeks. In the next 12 weeks, frequency of training was tailored to the patients' need. Participants underwent lumbar magnetic resonance imaging at baseline (T0), after 12 weeks (T12), and after 24 weeks (T24). Functional cross-sectional area was obtained by analyzing the magnetic resonance images. Functional status was assessed using the patient-specific functional scale, Roland-Morris disability questionnaire, and global perceived effect scale.Roland-Morris disability questionnaire and patient-specific functional scale scores showed significant and clinically relevant improvements between baseline and T12, with 44% and 39%, respectively. Between T12 and T24, these scores did not change significantly. Seven participants (44%) reported clinically relevant improvements in global perceived effect at T12. At T24, 1 more participant reported a relevant global perceived effect improvement, whereas 2 participants (13%) reported worsening of their condition. The magnetic resonance imaging analysis showed minor nonsignificant changes in functional cross-sectional area.Our study shows that 10 weeks of dynamic isolated training of the lumbar extensors, once a week, leads to clinically relevant improvements in functional status of men with CNSLBP, without accompanying improvements in functional cross-sectional area of LM. These findings suggest that improvement in LM morphology is not a critical success factor in restoring functional status of patients with CNSLBP, at least in the short term (6 mo).

    View details for DOI 10.1097/BRS.0b013e318274fb2f

    View details for Web of Science ID 000312396300009

    View details for PubMedID 23023592

  • Systematic Error in Lung Nodule Volumetry: Effect of Iterative Reconstruction Versus Filtered Back Projection at Different CT Parameters AMERICAN JOURNAL OF ROENTGENOLOGY Willemink, M. J., Leiner, T., Budde, R. P., de Kort, F. P., Vliegenthart, R., van Ooijen, P. M., Oudkerk, M., de Jong, P. A. 2012; 199 (6): 1241-1246


    Iterative reconstruction potentially can reduce radiation dose compared with filtered back projection (FBP) for chest CT. This is especially important for repeated CT scanning, as is the case in patients with indeterminate lung nodules. It is currently unknown whether absolute nodule volumes measured with iterative reconstruction are comparable to those measured with FBP. We compared nodule volumes measured with iterative reconstruction and FBP at different CT parameters.An anthropomorphic chest phantom was scanned using a 256-MDCT scanner at various tube voltages and tube current-time products. Raw data were reconstructed using FBP or a commercially available iterative reconstruction algorithm. Five inserted nodules with 100 HU radiodensity and different sizes (3, 5, 8, 10, and 12 mm) were measured by two observers using semiautomatic software. Volumetric nodule measurements were performed using thin-slice reconstructions.For very small nodules (volume, 14.1 mm(3); diameter, 3 mm), FBP and iterative reconstruction measurements exhibited large errors and overestimated the nodule size by up to 160%. For larger nodules (volume, ≥ 65.4 mm(3); diameter, ≥ 5 mm), CT underestimated the actual size, but errors were small (within 25%) and remained small when the tube voltage and tube current-time product were reduced, even without iterative reconstruction.In a phantom model, no clinically relevant differences beyond reported interscan variation levels between lung nodule volumes were measured in nodules 5 mm or larger at reduced tube voltage and tube current-time product, with radiation dose reductions up to 90.6% for both FBP and iterative reconstruction, suggesting that it is safe to convert FBP protocols to iterative reconstruction and reduce tube voltage and tube current-time product for lung nodule follow-up. CT appears to slightly underestimate actual nodule volume.

    View details for DOI 10.2214/AJR.12.8727

    View details for Web of Science ID 000311408400027

    View details for PubMedID 23169714

  • The effect of iterative reconstruction on computed tomography assessment of emphysema, air trapping and airway dimensions EUROPEAN RADIOLOGY Mets, O. M., Willemink, M. J., de Kort, F. P., Mol, C. P., Leiner, T., Oudkerk, M., Prokop, M., de Jong, P. A. 2012; 22 (10): 2103-2109


    To determine the influence of iterative reconstruction (IR) on quantitative computed tomography (CT) measurements of emphysema, air trapping, and airway wall and lumen dimensions, compared to filtered back-projection (FBP).Inspiratory and expiratory chest CTs of 75 patients (37 male, 38 female; mean age 64.0 ± 5.7 years) were reconstructed using FBP and IR. CT emphysema, CT air trapping and airway dimensions of a segmental bronchus were quantified using several commonly used quantification methods. The two algorithms were compared using the concordance correlation coefficient (p (c)) and Wilcoxon signed rank test.Only the E/I-ratio(MLD) as a measure of CT air trapping and airway dimensions showed no significant differences between the algorithms, whereas all CT emphysema and the other CT air trapping measures were significantly different at IR when compared to FBP (P < 0.001).The evaluated IR algorithm significantly influences quantitative CT measures in the assessment of emphysema and air trapping. However, the E/I-ratio(MLD) as a measure of CT air trapping, as well as the airway measurements, is unaffected by this reconstruction method. Quantitative CT of the lungs should be performed with careful attention to the CT protocol, especially when iterative reconstruction is introduced.• New techniques in CT allow numerous quantitative measurements of lung function. • Iterative reconstruction influences quantitative CT measurements of emphysema and air trapping. • Expiratory-to-inspiratory ratio of mean lung density and airway measurements are unaffected by iterative reconstruction. • Quantitative lung-CT should be performed with careful attention to the CT protocol.

    View details for DOI 10.1007/s00330-012-2489-z

    View details for Web of Science ID 000308237500006

    View details for PubMedID 22618522

  • CT evaluation of chronic thromboembolic pulmonary hypertension CLINICAL RADIOLOGY Willemink, M. J., van Es, H. W., Koobs, L., Morshuis, W. J., Snijder, R. J., van Heesewijk, J. P. 2012; 67 (3): 277-285


    The educational objectives of this article are to provide an overview of the computed tomography (CT) findings in chronic thromboembolic pulmonary hypertension. This article reviews the key imaging findings at CT in patients with chronic thromboembolic pulmonary hypertension. After reading this article, the reader should have an improved awareness of the condition, its imaging features, and the CT imaging features associated with surgically accessible disease.

    View details for DOI 10.1016/j.crad.2011.09.012

    View details for Web of Science ID 000300808100011

    View details for PubMedID 22119298

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