401 research outputs found
Schwingungseigenschaften der Ossikel und der Cochlea und deren Bedeutung fĂŒr unser Gehör
Zusammenfassung: Untersuchungen der Bewegungen von Trommelfell und SteigbĂŒgel belegen, dass in den höheren Frequenzen komplexe, rĂ€umliche Vibrationsmuster auftreten, bei denen sich die einzelnen Elemente in sehr unterschiedlichen rĂ€umlichen Richtungen und in sehr unterschiedlichen Phasenlagen bewegen. Am SteigbĂŒgel sind eine kolbenförmige Bewegung sowie eine Rotation um die kurze und lange SteigbĂŒgelachse zu unterscheiden. Im Gegensatz zu den kolbenförmigen Schwingungen fĂŒhren Rotationsbewegungen nicht zu einer Nettovolumenverschiebung der cochleĂ€ren FlĂŒssigkeit in einem gewissen Abstand von der FuĂplatte. Deshalb wird aufgrund der gĂ€ngigen Theorie des Hörens angenommen, dass solche Kippbewegungen keinen Einfluss auf das Gehör haben. In einer Reihe von Studien wurde jedoch qualitativ gezeigt, dass auch Kippbewegungen zu cochleĂ€rer AktivitĂ€t fĂŒhren können. Weitere Forschung ist notwendig, um diesen Effekt zu quantifiziere
Development and external validation of a multivariable [Ga]Ga-PSMA-11 PET-based prediction model for lymph node involvement in men with intermediate or high-risk prostate cancer
PURPOSE
To develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [Ga]Ga-PSMA-11 PET.
METHODS
A consecutive sample of intermediate to high-risk prostate cancer (PCa) patients undergoing [Ga]Ga-PSMA-11 PET, extended pelvic lymph node dissection (ePLND), and radical prostatectomy (RP) at two tertiary referral centers were retrospectively identified. The training cohort comprised 173 patients (treated between 2013 and 2017), the validation cohort 90 patients (treated between 2016 and 2019). Three models for LNI prediction were developed and evaluated using cross-validation. Optimal risk-threshold was determined during model development. The best performing model was evaluated and compared to available conventional and multiparametric magnetic resonance imaging (mpMRI)-based prediction models using area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA).
RESULTS
A combined model including prostate-specific antigen, biopsy Gleason grade group, [Ga]Ga Ga-PSMA-11 positive volume of the primary tumor, and the assessment of the [Ga]Ga-PSMA-11 report N-status yielded an AUC of 0.923 (95% CI 0.863-0.984) in the external validation. Using a cutoff of ââ„â17%, 44 (50%) ePLNDs would be spared and LNI missed in one patient (4.8%). Compared to conventional and MRI-based models, the proposed model showed similar calibration, higher AUC (0.923 (95% CI 0.863-0.984) vs. 0.700 (95% CI 0.548-0.852)-0.824 (95% CI 0.710-0.938)) and higher net benefit at DCA.
CONCLUSIONS
Our results indicate that information from [Ga]Ga-PSMA-11 may improve LNI prediction in intermediate to high-risk PCa patients undergoing primary staging especially when combined with clinical parameters. For better LNI prediction, future research should investigate the combination of information from both PSMA PET and mpMRI for LNI prediction in PCa patients before RP
The sodium iodide symporter (NIS) as theranostic gene: its emerging role in new imaging modalities and non-viral gene therapy
Cloning of the sodium iodide symporter (NIS) in 1996 has provided an opportunity to use NIS as a powerful theranostic transgene. Novel gene therapy strategies rely on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of therapeutic radionuclides. This review highlights the remarkable progress during the last two decades in the development of the NIS gene therapy concept using selective non-viral gene delivery vehicles including synthetic polyplexes and genetically engineered mesenchymal stem cells. In addition, NIS is a sensitive reporter gene and can be monitored by high resolution PET imaging using the radiotracers sodium [ 124 I]iodide ([ 124 I]NaI) or [ 18 F]tetrafluoroborate ([ 18 F]TFB). We performed a small preclinical PET imaging study comparing sodium [ 124 I]iodide and in-house synthesized [ 18 F]TFB in an orthotopic NIS-expressing glioblastoma model. The results demonstrated an improved image quality using [ 18 F]TFB. Building upon these results, we will be able to expand the NIS gene therapy approach using non-viral gene delivery vehicles to target orthotopic tumor models with low volume disease, such as glioblastoma
In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma
CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination and poor prognosis. We evaluated the novel CXCR4 probe [(68)Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [(68)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [(68)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [(18)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34(+) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [(68)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases
Optimum imaging strategies for advanced prostate cancer: ASCO guideline
PURPOSE Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups. METHODS An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naĂŻve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared $ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality. RESULTS A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles. RECOMMENDATIONS One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario
The maximum standardized uptake value in patients with recurrent or persistent prostate cancer after radical prostatectomy and PSMA-PET-guided salvage radiotherapy-a multicenter retrospective analysis
Purpose This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) prior to salvage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort.Methods Patients who underwent (68) Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS.Results Two hundred thirty-five patients with a median follow-up (FU) of 24 months were included in the final cohort. Two-year and 4-year BRFS for all patients were 68% and 56%. The presence of LR was associated with favorable BRFS (p = 0.016). Presence of NR was associated with unfavorable BRFS (p = 0.007). While there was a trend for SUVmax values >= median (p = 0.071), SUVmax values >= 75% quartile in LR were significantly associated with unfavorable BRFS (p = 0.022, HR: 2.1, 95%CI 1.1-4.6). SUVmax value in NR was not significantly associated with BRFS. SUVmax in LR stayed significant in multivariate analysis (p = 0.030). Sensitivity analysis with patients for who had a FU of > 12 months (n = 197) confirmed these results.Conclusion The non-invasive biomarker SUVmax can prognosticate outcome in patients undergoing sRT and recurrence confined to the prostatic fossa in PSMA-PET. Its addition might contribute to improve risk stratification of patients with recurrent PCa and to guide personalized treatment decisions in terms of treatment intensification or de-intensification. This article is part of the Topical Collection on Oncology-Genitourinary
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Head-to-head intra-individual comparison of biodistribution and tumor uptake of 68Ga-FAPI and 18F-FDG PET/CT in cancer patients
PURPOSE : FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of 68Ga- FAPI versus standard-of-care 18F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. MARERILA AND METHODS : This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both 68Ga-FAPI and 18F-FDG PET/CT within a median time interval of 10 days (range 1â89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). RESULTS : A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. 68Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for 68Ga-FAPI than 18F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, 68Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases. CONCLUSION : Quantitative tumor uptake is comparable between 68Ga-FAPI and 18F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for 68Ga-FAPI. Thus, 68Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological 18F-FDG uptake.Open Access funding by Projekt DEAL.http://link.springer.com/journal/259am2022Nuclear Medicin
PET/MR imaging of bone lesions - implications for PET quantification from imperfect attenuation correction
PURPOSE: Accurate attenuation correction (AC) is essential for quantitative analysis of PET tracer distribution. In MR, the lack of cortical bone signal makes bone segmentation difficult and may require implementation of special sequences. The purpose of this study was to evaluate the need for accurate bone segmentation in MR-based AC for whole-body PET/MR imaging.
METHODS: In 22 patients undergoing sequential PET/CT and 3-T MR imaging, modified CT AC maps were produced by replacing pixels with values of >100 HU, representing mostly bone structures, by pixels with a constant value of 36 HU corresponding to soft tissue, thereby simulating current MR-derived AC maps. A total of 141 FDG-positive osseous lesions and 50 soft-tissue lesions adjacent to bones were evaluated. The mean standardized uptake value (SUVmean) was measured in each lesion in PET images reconstructed once using the standard AC maps and once using the modified AC maps. Subsequently, the errors in lesion tracer uptake for the modified PET images were calculated using the standard PET image as a reference.
RESULTS: Substitution of bone by soft tissue values in AC maps resulted in an underestimation of tracer uptake in osseous and soft tissue lesions adjacent to bones of 11.2â±â5.4 % (range 1.5-30.8 %) and 3.2â±â1.7 % (range 0.2-4 %), respectively. Analysis of the spine and pelvic osseous lesions revealed a substantial dependence of the error on lesion composition. For predominantly sclerotic spine lesions, the mean underestimation was 15.9â±â3.4 % (range 9.9-23.5 %) and for osteolytic spine lesions, 7.2â±â1.7 % (range 4.9-9.3 %), respectively.
CONCLUSION: CT data simulating treating bone as soft tissue as is currently done in MR maps for PET AC leads to a substantial underestimation of tracer uptake in bone lesions and depends on lesion composition, the largest error being seen in sclerotic lesions. Therefore, depiction of cortical bone and other calcified areas in MR AC maps is necessary for accurate quantification of tracer uptake values in PET/MR imaging
Proceedings of the International Cancer Imaging Society (ICIS) 16th Annual Teaching Course
Table of contents
O1 Tumour heterogeneity: what does it mean?
Dow-Mu Koh
O2 Skeletal sequelae in adult survivors of childhood cancer
Sue Creviston Kaste
O3 Locoregional effects of breast cancer treatment
Sarah J Vinnicombe
O4 Imaging of cancer therapy-induced CNS toxicity
Giovanni Morana, Andrea Rossi
O5 Screening for lung cancer
Christian J. Herold
O6Risk stratification of lung nodules
Theresa C. McLoud
O7 PET imaging of pulmonary nodules
Kirk A Frey
O8 Transarterial tumour therapy
Bernhard Gebauer
O9 Interventional radiology in paediatric oncology
Derek Roebuck
O10 Image guided prostate interventions
Jurgen J. FĂŒtterer
O11 Imaging cancer predisposition syndromes
Alexander J. Towbin
O12Chest and chest wall masses
Thierry AG Huisman
O13 Abdominal masses: good or bad?
Anne MJB Smets
O14 Hepatobiliary MR contrast: enhanced liver MRI for HCC diagnosis and management
Giovanni Morana
O15 Role of US elastography and multimodality fusion for managing patients with chronic liver disease and HCC
Jeong Min Lee
O16 Opportunities and challenges in imaging metastatic disease
Hersh Chandarana
O17 Diagnosis, treatment monitoring, and follow-up of lymphoma
Marius E. Mayerhoefer, Markus Raderer, Alexander Haug
O18 Managing high-risk and advanced prostate cancer
Matthias Eiber
O19 Immunotherapy: imaging challenges
Bernhard Gebauer
O20 RECIST and RECIST 1.1
Andrea Rockall
O21 Challenges of RECIST in oncology imaging basics for the trainee and novice
Aslam Sohaib
O22 Lymphoma: PET for interim and end of treatment response assessment: a usersâ guide to the Deauville Score
Victoria S Warbey
O23 Available resources
Hebert Alberto Vargas
O24 ICIS e-portal and the online learning community
Dow-Mu Koh
O25 Benign lesions that mimic pancreatic cancer
Jay P Heiken
O26 Staging and reporting pancreatic malignancies
Isaac R Francis, Mahmoud, M Al-Hawary, Ravi K Kaza
O27 Intraductal papillary mucinous neoplasm
Giovanni Morana
O28 Cystic pancreatic tumours
Mirko DâOnofrio
O29 Diffusion-weighted imaging of head and neck tumours
Harriet C. Thoeny
O30 Radiation injury in the head and neck
Ann D King
O31 PET/MR of paediatric brain tumours
Giovanni Morana, Arnoldo Piccardo, Maria Luisa GarrĂš, Andrea Rossi
O32 Structured reporting and beyond
Hebert Alberto Vargas
O33 Massachusetts General Hospital experience with structured reporting
Theresa C. McLoud
O34 The oncologistâs perspective: what the oncologist needs to know
Nick Reed
O35 Towards the cure of all children with cancer: global initiatives in pediatric oncology
Carlos Rodriguez-Galindo
O36 Multiparametric imaging of renal cancers
Hersh Chandarana
O37 Linking imaging features of renal disease and their impact on management strategies
Hebert Alberto Vargas
O38 Adrenals, retroperitoneum and peritoneum
Isaac R Francis, Ashish P Wasnik
O39 Lung and pleura
Stefan Diederich
O40 Advances in MRI
Jurgen J. FĂŒtterer
O41 Advances in molecular imaging
Wim J.G. Oyen
O42 Incorporating advanced imaging, impact on treatment selection and patient outcome
Cheng Lee Chaw, Nicholas van As
S1 Combining ADC-histogram features improves performance of MR diffusion-weighted imaging for Lymph node characterisation in cervical cancer
Igor Vieira, Frederik De Keyzer, Elleke Dresen, Sileny Han, Ignace Vergote, Philippe Moerman, Frederic Amant, Michel Koole, Vincent Vandecaveye
S2 Whole-body diffusion-weighted MRI for surgical planning in patients with colorectal cancer and peritoneal metastases
R Dresen, S De Vuysere, F De Keyzer, E Van Cutsem, A DâHoore, A Wolthuis, V Vandecaveye
S3 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extra capsular extension of prostate cancer.
P. Pricolo ([email protected]), S. Alessi, P. Summers, E. Tagliabue, G. Petralia
S4 Generating evidence for clinical benefit of PET/CT â are management studies sufficient as surrogate for patient outcome?
C. Pfannenberg, B. GĂŒckel, SC SchĂŒle, AC MĂŒller, S. Kaufmann, N. Schwenzer, M. Reimold,C. la Fougere, K. Nikolaou, P. Martus
S5 Heterogeneity of treatment response in skeletal metastases from breast cancer with 18F-fluoride and 18F-FDG PET
GJ Cook, GK Azad, BP Taylor, M Siddique, J John, J Mansi, M Harries, V Goh
S6 Accuracy of suspicious breast imagingâcan we tell the patient?
S Seth, R Burgul, A Seth
S7 Measurement method of tumour volume changes during neoadjuvant chemotherapy affects ability to predict pathological response
S Waugh, N Muhammad Gowdh, C Purdie, A Evans, E Crowe, A Thompson, S Vinnicombe
S8 Diagnostic yield of CT IVU in haematuria screening
F. Arfeen, T. Campion, E. Goldstraw
S9 Percutaneous radiofrequency ablation of unresectable locally advanced pancreatic cancer: preliminary results
DâOnofrio M, Ciaravino V, Crosara S, De Robertis R, Pozzi Mucelli R
S10 Iodine maps from dual energy CT improve detection of metastases in staging examinations of melanoma patients
M. Uhrig, D. Simons, H. Schlemmer
S11Can contrast enhanced CT predict pelvic nodal status in malignant melanoma of the lower limb?
Kate Downey
S12 Current practice in the investigation for suspected Paraneoplastic Neurological Syndromes (PNS) and positive malignancy yield.
S Murdoch, AS Al-adhami, S Viswanathan
P1 Technical success and efficacy of Pulmonary Radiofrequency ablation: an analysis of 207 ablations
S Smith, P Jennings, D Bowers, R Soomal
P2 Lesion control and patient outcome: prospective analysis of radiofrequency abaltion in pulmonary colorectal cancer metastatic disease
S Smith, P Jennings, D Bowers, R Soomal
P3 Hepatocellular carcinoma in a post-TB patient: case of tropical infections and oncologic imaging challenges
TM Mutala, AO Odhiambo, N Harish
P4 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extracapsular extension of prostate cancer
P. Pricolo, S. Alessi, P. Summers, E. Tagliabue, G. Petralia
P5 What a difference a decade makes; comparison of lung biopsies in Glasgow 2005 and 2015
M. Hall, M. Sproule, S. Sheridan
P6 Solid pseudopapillary tumour of pancreas: imaging features of a rare neoplasm
KY Thein, CH Tan, YL Thian, CM Ho
P7 MDCT - pathological correlation in colon adenocarcinoma staging: preliminary experience
S De Luca, C Carrera, V Blanchet, L AlarcĂłn, E Eyheremnedy
P8 Image guided biopsy of thoracic masses and reduction of pneumothorax risk: 25Â years experience
B K Choudhury, K Bujarbarua, G Barman
P9 Tumour heterogeneity analysis of 18F-FDG-PET for characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1
GJ Cook, E Lovat, M Siddique, V Goh, R Ferner, VS Warbey
P10 Impact of introduction of vacuum assisted excision (VAE) on screen detected high risk breast lesions
L Potti, B Kaye, A Beattie, K Dutton
P11 Can we reduce prevalent recall rate in breast screening?
AA Seth, F Constantinidis, H Dobson
P12 How to reduce prevalent recall rate? Identifying mammographic lesions with low Positive Predictive Value (PPV)
AA Seth ([email protected]), F Constantinidis, H Dobson
P13 Behaviour of untreated pulmonary thrombus in oncology patients diagnosed with incidental pulmonary embolism on CT
R. Bradley, G. Bozas, G. Avery, A. Stephens, A. Maraveyas
P14 A one-stop lymphoma biopsy service â is it possible?
S Bhuva, CA Johnson, M Subesinghe, N Taylor
P15 Changes in the new TNM classification for lung cancer (8th edition, effective January 2017)
LE Quint, RM Reddy, GP Kalemkerian
P16 Cancer immunotherapy: a review of adequate imaging assessment
G GonzĂĄlez Zapico, E Gainza Jauregui, R Ălvarez Francisco, S Ibåñez Alonso, I Tavera Bahillo, L MĂșgica Ălvarez
P17 Succinate dehydrogenase mutations and their associated tumours
O Francies, R Wheeler, L Childs, A Adams, A Sahdev
P18 Initial experience in the usefulness of dual energy technique in the abdomen
SE De Luca, ME Casalini Vañek, MD Pascuzzi, T Gillanders, PM Ramos, EP Eyheremendy
P19 Recognising the serious complication of Richterâs transformation in CLL patients
C Stove, M Digby
P20 Body diffusion-weighted MRI in oncologic practice: truths, tricks and tips
M. Nazar, M. Wirtz, MD. Pascuzzi, F. Troncoso, F. Saguier, EP. Eyheremendy
P21 Methotrexate-induced leukoencephalopathy in paediatric ALL Patients
D.J. Quint, L. Dang, M. Carlson, S. Leber, F. Silverstein
P22 Pitfalls in oncology CT reporting. A pictorial review
R Rueben, S Viswanathan
P23 Imaging of perineural extension in head and neck tumours
B Nazir, TH Teo, JB Khoo
P24 MRI findings of molecular subtypes of breast cancer: a pictorial primer
K Sharma, N Gupta, B Mathew, T Jeyakumar, K Harkins
P25 When cancer canât wait! A pictorial review of oncological emergencies
K Sharma, B Mathew, N Gupta, T Jeyakumar, S Joshua
P26 MRI of pancreatic neuroendocrine tumours: an approach to interpretation
D Christodoulou, S Gourtsoyianni, A Jacques, N Griffin, V Goh
P27 Gynaecological cancers in pregnancy: a review of imaging
CA Johnson, J Lee
P28 Suspected paraneoplastic neurological syndromes - review of published recommendations to date, with proposed guideline/flowchart
JA Goodfellow, AS Al-adhami, S Viswanathan
P29 Multi-parametric MRI of the pelvis for suspected local recurrence of prostate cancer after radical prostatectomy
R Bradley
P30 Utilisation of PI-RADS version 2 in multi-parametric MRI of the prostate; 12-months experience
R Bradley
P31 Radiological assessment of the post-chemotherapy liver
A Yong, S Jenkins, G Joseph
P32 Skeletal staging with MRI in breast cancer â what the radiologist needs to know
S Bhuva, K Partington
P33 Perineural spread of lympoma: an educational review of an unusual distribution of disease
CA Johnson, S Bhuva, M Subesinghe, N Taylor
P34 Visually isoattenuating pancreatic adenocarcinoma. Diagnostic imaging tools.
C Carrera, A Zanfardini, S De Luca, L AlarcĂłn, V Blanchet, EP Eyheremendy
P35 Imaging of larynx cancer: when is CT, MRI or FDG PET/CT the best test?
K Cavanagh, E Lauhttp://deepblue.lib.umich.edu/bitstream/2027.42/134651/1/40644_2016_Article_79.pd
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