Clinically Valuable Quality Control for PET/MRI Systems:Consensus Recommendation From the HYBRID Consortium

International audienceQuality control (QC) of medical imaging devices is essential to ensure their proper function and to gain accurate and quantitative results. Therefore, several international bodies have published QC guidelines and recommendations for a wide range of imaging modalities to ensure adequate performance of the systems. Hybrid imaging systems such as positron emission tomography/computed tomography (PET/CT) or PET/magnetic resonance imaging (PET/MRI), in particular, present additional challenges caused by differences between the combined modalities. However, despite the increasing use of this hybrid imaging modality in recent years, there are no dedicated QC recommendations for PET/MRI. Therefore, this work aims at collecting information on QC procedures across a European PET/MRI network, presenting quality assurance procedures implemented by PET/MRI vendors and achieving a consensus on PET/MRI QC procedures across imaging centers. Users of PET/MRI systems at partner sites involved in the HYBRID consortium were surveyed about local frequencies of QC procedures for PET/MRI. Although all sites indicated that they perform vendor-specific daily QC procedures, significant variations across the centers were observed for other QC tests and testing frequencies. Likewise, variations in available recommendations and guidelines and the QC procedures implemented by vendors were found. Based on the available information and our clinical expertise within this consortium, we were able to propose a minimum set of PET/MRI QC recommendations including the daily QC, cross-calibration tests, and an image quality (IQ) assessment for PET and coil checks and MR image quality tests for MRI. Together with regular checks of the PET-MRI alignment, proper PET/MRI performance can be ensured

Medical physics and imaging-a timely perspective

Radiolog

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

BACKGROUND: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Advanced quantification for fully-integrated PET/MRI : implementing MRI-based attenuation correction in clinical routine

Diese Arbeit beschäftigt sich mit Aspekten der Magnet Resonanz Tomographie (MRT) basierten Schwächungskorrektur (MR-AC). In drei Teilstudien werden Herausforderungen im Kontext der Qualtiätskontrolle, der Standard MR-AC für die Ganzkörper-Bildgebung und der MR-AC für neuro-onkologische Untersuchungen behandelt. Die Anwendbarkeit routinemäßiger Bildqualitätstest in PET/MRT Systemen wurde im ersten Teil untersucht. Es konnte gezeigt werden, dass bei Verwendung spezifischer Aufnahmeprotokolle das Standard-NEMA-Bildqualitätsphantom in allen heute verfügbaren PET/MRT-Systemen verwendet werden kann. Im zweiten Teil wurde die Reproduzierbarkeit der Standard MR-AC evaluiert. Die Ergebnisse zeigen eine gute, und klinisch ausreichende Reproduzierbarkeit der Standard MR-AC im Fall von Aufnahmen, welche nicht durch größere Bildartefakte gestört sind. Zusätzlich wurde ein Verfahren zur Extraktion einer patientenspezifischen Fett-freien Masse (LBM) aus den MR-AC Daten entwickelt. Hier konnte eine ausgezeichnete Übereinstimmung mit Standard Messungen der Körper-zusammensetzung gezeigt werden. Dieses Verfahren kann zukünftig für eine patientenspezifische LBM basierte Korrektur der SUV Werte verwendet werden. Im dritten Teil wurde eine neue Atlas-basierte MR-AC Technik an Neuroonkologischen Untersuchungen getestet und mit den aktuell verfügbaren MR-AC Methoden verglichen. Es konnte gezeigt werden, dass mit der Atlas-basierten Methode die quantitative Genauigkeit im Vergleich zu den aktuell implementierten Methoden verbessert werden konnte. Dies gilt vor allem für quantitative Messungen in der Nähe von knöchernen Strukturen. Zusammenfassend wurden wichtiger Faktoren, die die quantitative PET/MRI-Bildgebung beeinflussen, untersucht. Die Ergebnisse dieser Arbeit sind wichtige Grundlagen für die standardisierte Implementierung der PET/MRT Bildgebung in die klinische Praxis.Several aspects related to magnetic resonance imaging (MRI) based attenuation correction (MR-AC) in clinical positron emission tomography / magnet resonance imaging (PET/MRI) are addressed as part of this thesis. These aspects include: (1) challenges related to routine quality control (QC) measures, (2) the evaluation of the standard Dixon-based MR-AC approach for whole-body imaging, and (3) the assessment of MR-AC approaches in terms of quantitative accuracy for neuro-oncological examinations. The applicability of routine image quality testing for PET/MRI is evaluated in part 1 of this thesis. It could be shown, that a standard NEMA image quality phantom can be employed for QC of PET/MRI systems. However, such phantom examinations require specific acquisition protocols and adjustments in order to provide valuable and reproducible results. In part 2, the reproducibility of the standard Dixon-based MR-AC method was assessed. The results showed a high frequency of image artefacts. However, in the absence of major image distortions, a good and clinically sufficient reproducibility of the standard MR-AC method has been demonstrated. A secondary outcome of this study was a method to extract a patient specific lean body mass (LBM) from the MR-AC data. This approach showed an excellent agreement with standard body composition measurements, and, thus, could be used for a patient specific LBM based SUV correction in the future. In part 3, a new atlas-based AC method was tested and compared to standard available MR-AC methods. For neuro-oncological PET/MRI examinations, quantitative accuracy was improved compared to currently available MR-AC methods. When using the atlas based method, this improvement was particularly present for activity distributions near bony structures. In summary, important challenges to quantitative PET/MRI have been identified and addressed, that help improve the quality of fully-integrated PET/MRI for clinical routine.submitted by Ivo Florian RauschZusammenfassung in deutscher SpracheAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMedizinische Universität Wien, Dissertation, 2017OeBB(VLID)221767

Journal of Labelled Compounds and Radiopharmaceuticals / Manganese in PET imaging: Opportunities and challenges

Several radionuclides of the transition metal manganese are known and accessible. Three of them, 51Mn, 52mMn, and 52gMn, are positron emitters that are potentially interesting for positron emission tomography (PET) applications and, thus, have caught the interest of the radiochemical/radiopharmaceutical and nuclear medicine communities. This minireview provides an overview of the production routes and physical properties of these radionuclides. For medical imaging, the focus is on the longerliving 52gMn and its application for the radiolabelling of molecules and other entities exhibiting long biological halflives, the imaging of manganesedependent biological processes, and the development of bimodal PET/magnetic resonance imaging (MRI) probes in combination with paramagnetic natMn as a contrast agent.(VLID)510263

Personalizing Medicine Through Hybrid Imaging and Medical Big Data Analysis

Medical imaging has evolved from a pure visualization tool to representing a primary source of analytic approaches toward in vivo disease characterization. Hybrid imaging is an integral part of this approach, as it provides complementary visual and quantitative information in the form of morphological and functional insights into the living body. As such, non-invasive imaging modalities no longer provide images only, but data, as stated recently by pioneers in the field. Today, such information, together with other, non-imaging medical data creates highly heterogeneous data sets that underpin the concept of medical big data. While the exponential growth of medical big data challenges their processing, they inherently contain information that benefits a patient-centric personalized healthcare. Novel machine learning approaches combined with high-performance distributed cloud computing technologies help explore medical big data. Such exploration and subsequent generation of knowledge require a profound understanding of the technical challenges. These challenges increase in complexity when employing hybrid, aka dual- or even multi-modality image data as input to big data repositories. This paper provides a general insight into medical big data analysis in light of the use of hybrid imaging information. First, hybrid imaging is introduced (see further contributions to this special Research Topic), also in the context of medical big data, then the technological background of machine learning as well as state-of-the-art distributed cloud computing technologies are presented, followed by the discussion of data preservation and data sharing trends. Joint data exploration endeavors in the context of in vivo radiomics and hybrid imaging will be presented. Standardization challenges of imaging protocol, delineation, feature engineering, and machine learning evaluation will be detailed. Last, the paper will provide an outlook into the future role of hybrid imaging in view of personalized medicine, whereby a focus will be given to the derivation of prediction models as part of clinical decision support systems, to which machine learning approaches and hybrid imaging can be anchored.(VLID)473888

Radiation exposure levels of routine SPECT/CT imaging protocols.

AIMS To assess incremental and total patient exposure from clinical SPECT/CT imaging by means of effective dose estimations with regards to different protocols and SPECT/CT systems. MATERIALS AND METHODS Consecutive patient exposure levels were documented prospectively from SPECT/CT operations at three European imaging centers. Documentation included the volume-weighted computed tomography (CT) dose index, the CT dose length product (DLP) and the amount of applied radiopharmaceutical. SPECT/CT examinations were categorized regionally into head, neck, myocardium, thorax, abdomen, extremities and whole-body. Effective dose from the CT (EDCT) was estimated from the DLP using gender specific conversion factors. EDSPECT was estimated from the injected activity levels and corresponding conversion factors (ICRP 106). RESULTS This study included 678 SPECT/CT examinations. EDCT per indication and EDSPECT per tracer ranged from 0.01mSv to 7.4mSv and from 1.1mSv to 12.2mSv, respectively. In general, EDSPECT contributed most to overall patient exposure. Total EDSPECT/CT averaged across all protocol categories was 6.7mSv. CONCLUSION Total patient exposure from clinical SPECT/CT is 7mSv on average. Individual dose levels vary with the clinical indication and on-site protocol parameters

Technical and instrumentational foundations of PET/MRI

This paper highlights the origins of combined positron emission tomography (PET) and magnetic resonance imaging (MRI) whole-body systems that were first introduced for applications in humans in 2010. This text first covers basic aspects of each imaging modality before describing the technical and methodological challenges of combining PET and MRI within a single system. After several years of development, combined and even fullyintegrated PET/MRI systems have become available and made their way into the clinic. This multi-modality imaging system lends itself to the advanced exploration of diseases to support personalized medicine in a long run. To that extent, this paper provides an introduction to PET/MRI methodology and important technical solutions