Fabrício Guimarães Gonçalves1, Luis Octavio Tierradentro-Garcia2, Jorge Du Ub Kim2, Alireza Zandifar2, Adarsh Ghosh2, Angela N Viaene3, Dmitry Khrichenko2, Savvas Andronikou2,4, Arastoo Vossough2,4. 1. Department of Radiology, Division of Neuroradiology, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA. goncalves.neuroradio@gmail.com. 2. Department of Radiology, Division of Neuroradiology, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA. 3. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. 4. Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Abstract
BACKGROUND: Medulloblastoma, a high-grade embryonal tumor, is the most common primary brain malignancy in the pediatric population. Molecular medulloblastoma groups have documented clinically and biologically relevant characteristics. Several authors have attempted to differentiate medulloblastoma molecular groups and histology variants using diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. However, literature on the use of ADC histogram analysis in medulloblastomas is still scarce. OBJECTIVE: This study presents data from a sizable group of pediatric patients with medulloblastoma from a single institution to determine the performance of ADC histogram metrics for differentiating medulloblastoma variants and groups based on both histological and molecular features. MATERIALS AND METHODS: In this retrospective study, we evaluated the distribution of absolute and normalized ADC values of medulloblastomas. Tumors were manually segmented and diffusivity metrics calculated on a pixel-by-pixel basis. We calculated a variety of first-order histogram metrics from the ADC maps, including entropy, minimum, 10th percentile, 90th percentile, maximum, mean, median, skewness and kurtosis, to differentiate molecular and histological variants. ADC values of the tumors were also normalized to the bilateral cerebellar cortex and thalami. We used the Kruskal-Wallis and Mann-Whitney U tests to evaluate differences between the groups. We carried out receiver operating characteristic (ROC) curve analysis to evaluate the areas under the curves and to determine the cut-off values for differentiating tumor groups. RESULTS: We found 65 children with confirmed histopathological diagnosis of medulloblastoma. Mean age was 8.3 ± 5.8 years, and 60% (n = 39) were male. One child was excluded because histopathological variant could not be determined. In terms of medulloblastoma variants, tumors were classified as classic (n = 47), desmoplastic/nodular (n = 9), large/cell anaplastic (n = 6) or as having extensive nodularity (n = 2). Seven other children were excluded from the study because of incomplete imaging or equivocal molecular diagnosis. Regarding medulloblastoma molecular groups, there were: wingless (WNT) group (n = 7), sonic hedgehog (SHH) group (n = 14) and non-WNT/non-SHH (n = 36). Our results showed significant differences among the molecular groups in terms of the median (P = 0.002), mean (P = 0.003) and 90th percentile (P = 0.002) ADC histogram metrics. No significant differences among the various medulloblastoma histological variants were found. CONCLUSION: ADC histogram analysis can be implemented as a complementary tool in the preoperative evaluation of medulloblastoma in children. This technique can provide valuable information for differentiating among medulloblastoma molecular groups. ADC histogram metrics can help predict medulloblastoma molecular classification preoperatively.
BACKGROUND: Medulloblastoma, a high-grade embryonal tumor, is the most common primary brain malignancy in the pediatric population. Molecular medulloblastoma groups have documented clinically and biologically relevant characteristics. Several authors have attempted to differentiate medulloblastoma molecular groups and histology variants using diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. However, literature on the use of ADC histogram analysis in medulloblastomas is still scarce. OBJECTIVE: This study presents data from a sizable group of pediatric patients with medulloblastoma from a single institution to determine the performance of ADC histogram metrics for differentiating medulloblastoma variants and groups based on both histological and molecular features. MATERIALS AND METHODS: In this retrospective study, we evaluated the distribution of absolute and normalized ADC values of medulloblastomas. Tumors were manually segmented and diffusivity metrics calculated on a pixel-by-pixel basis. We calculated a variety of first-order histogram metrics from the ADC maps, including entropy, minimum, 10th percentile, 90th percentile, maximum, mean, median, skewness and kurtosis, to differentiate molecular and histological variants. ADC values of the tumors were also normalized to the bilateral cerebellar cortex and thalami. We used the Kruskal-Wallis and Mann-Whitney U tests to evaluate differences between the groups. We carried out receiver operating characteristic (ROC) curve analysis to evaluate the areas under the curves and to determine the cut-off values for differentiating tumor groups. RESULTS: We found 65 children with confirmed histopathological diagnosis of medulloblastoma. Mean age was 8.3 ± 5.8 years, and 60% (n = 39) were male. One child was excluded because histopathological variant could not be determined. In terms of medulloblastoma variants, tumors were classified as classic (n = 47), desmoplastic/nodular (n = 9), large/cell anaplastic (n = 6) or as having extensive nodularity (n = 2). Seven other children were excluded from the study because of incomplete imaging or equivocal molecular diagnosis. Regarding medulloblastoma molecular groups, there were: wingless (WNT) group (n = 7), sonic hedgehog (SHH) group (n = 14) and non-WNT/non-SHH (n = 36). Our results showed significant differences among the molecular groups in terms of the median (P = 0.002), mean (P = 0.003) and 90th percentile (P = 0.002) ADC histogram metrics. No significant differences among the various medulloblastoma histological variants were found. CONCLUSION: ADC histogram analysis can be implemented as a complementary tool in the preoperative evaluation of medulloblastoma in children. This technique can provide valuable information for differentiating among medulloblastoma molecular groups. ADC histogram metrics can help predict medulloblastoma molecular classification preoperatively.
Authors: Yoon-Jae Cho; Aviad Tsherniak; Pablo Tamayo; Sandro Santagata; Azra Ligon; Heidi Greulich; Rameen Berhoukim; Vladimir Amani; Liliana Goumnerova; Charles G Eberhart; Ching C Lau; James M Olson; Richard J Gilbertson; Amar Gajjar; Olivier Delattre; Marcel Kool; Keith Ligon; Matthew Meyerson; Jill P Mesirov; Scott L Pomeroy Journal: J Clin Oncol Date: 2010-11-22 Impact factor: 44.544
Authors: Margaret C Thompson; Christine Fuller; Twala L Hogg; James Dalton; David Finkelstein; Ching C Lau; Murali Chintagumpala; Adekunle Adesina; David M Ashley; Stewart J Kellie; Michael D Taylor; Tom Curran; Amar Gajjar; Richard J Gilbertson Journal: J Clin Oncol Date: 2006-03-27 Impact factor: 44.544
Authors: Paul A Northcott; David J H Shih; John Peacock; Livia Garzia; A Sorana Morrissy; Thomas Zichner; Adrian M Stütz; Andrey Korshunov; Jüri Reimand; Steven E Schumacher; Rameen Beroukhim; David W Ellison; Christian R Marshall; Anath C Lionel; Stephen Mack; Adrian Dubuc; Yuan Yao; Vijay Ramaswamy; Betty Luu; Adi Rolider; Florence M G Cavalli; Xin Wang; Marc Remke; Xiaochong Wu; Readman Y B Chiu; Andy Chu; Eric Chuah; Richard D Corbett; Gemma R Hoad; Shaun D Jackman; Yisu Li; Allan Lo; Karen L Mungall; Ka Ming Nip; Jenny Q Qian; Anthony G J Raymond; Nina T Thiessen; Richard J Varhol; Inanc Birol; Richard A Moore; Andrew J Mungall; Robert Holt; Daisuke Kawauchi; Martine F Roussel; Marcel Kool; David T W Jones; Hendrick Witt; Africa Fernandez-L; Anna M Kenney; Robert J Wechsler-Reya; Peter Dirks; Tzvi Aviv; Wieslawa A Grajkowska; Marta Perek-Polnik; Christine C Haberler; Olivier Delattre; Stéphanie S Reynaud; François F Doz; Sarah S Pernet-Fattet; Byung-Kyu Cho; Seung-Ki Kim; Kyu-Chang Wang; Wolfram Scheurlen; Charles G Eberhart; Michelle Fèvre-Montange; Anne Jouvet; Ian F Pollack; Xing Fan; Karin M Muraszko; G Yancey Gillespie; Concezio Di Rocco; Luca Massimi; Erna M C Michiels; Nanne K Kloosterhof; Pim J French; Johan M Kros; James M Olson; Richard G Ellenbogen; Karel Zitterbart; Leos Kren; Reid C Thompson; Michael K Cooper; Boleslaw Lach; Roger E McLendon; Darell D Bigner; Adam Fontebasso; Steffen Albrecht; Nada Jabado; Janet C Lindsey; Simon Bailey; Nalin Gupta; William A Weiss; László Bognár; Almos Klekner; Timothy E Van Meter; Toshihiro Kumabe; Teiji Tominaga; Samer K Elbabaa; Jeffrey R Leonard; Joshua B Rubin; Linda M Liau; Erwin G Van Meir; Maryam Fouladi; Hideo Nakamura; Giuseppe Cinalli; Miklós Garami; Peter Hauser; Ali G Saad; Achille Iolascon; Shin Jung; Carlos G Carlotti; Rajeev Vibhakar; Young Shin Ra; Shenandoah Robinson; Massimo Zollo; Claudia C Faria; Jennifer A Chan; Michael L Levy; Poul H B Sorensen; Matthew Meyerson; Scott L Pomeroy; Yoon-Jae Cho; Gary D Bader; Uri Tabori; Cynthia E Hawkins; Eric Bouffet; Stephen W Scherer; James T Rutka; David Malkin; Steven C Clifford; Steven J M Jones; Jan O Korbel; Stefan M Pfister; Marco A Marra; Michael D Taylor Journal: Nature Date: 2012-08-02 Impact factor: 49.962
Authors: David T W Jones; Natalie Jäger; Marcel Kool; Thomas Zichner; Barbara Hutter; Marc Sultan; Yoon-Jae Cho; Trevor J Pugh; Volker Hovestadt; Adrian M Stütz; Tobias Rausch; Hans-Jörg Warnatz; Marina Ryzhova; Sebastian Bender; Dominik Sturm; Sabrina Pleier; Huriye Cin; Elke Pfaff; Laura Sieber; Andrea Wittmann; Marc Remke; Hendrik Witt; Sonja Hutter; Theophilos Tzaridis; Joachim Weischenfeldt; Benjamin Raeder; Meryem Avci; Vyacheslav Amstislavskiy; Marc Zapatka; Ursula D Weber; Qi Wang; Bärbel Lasitschka; Cynthia C Bartholomae; Manfred Schmidt; Christof von Kalle; Volker Ast; Chris Lawerenz; Jürgen Eils; Rolf Kabbe; Vladimir Benes; Peter van Sluis; Jan Koster; Richard Volckmann; David Shih; Matthew J Betts; Robert B Russell; Simona Coco; Gian Paolo Tonini; Ulrich Schüller; Volkmar Hans; Norbert Graf; Yoo-Jin Kim; Camelia Monoranu; Wolfgang Roggendorf; Andreas Unterberg; Christel Herold-Mende; Till Milde; Andreas E Kulozik; Andreas von Deimling; Olaf Witt; Eberhard Maass; Jochen Rössler; Martin Ebinger; Martin U Schuhmann; Michael C Frühwald; Martin Hasselblatt; Nada Jabado; Stefan Rutkowski; André O von Bueren; Dan Williamson; Steven C Clifford; Martin G McCabe; V Peter Collins; Stephan Wolf; Stefan Wiemann; Hans Lehrach; Benedikt Brors; Wolfram Scheurlen; Jörg Felsberg; Guido Reifenberger; Paul A Northcott; Michael D Taylor; Matthew Meyerson; Scott L Pomeroy; Marie-Laure Yaspo; Jan O Korbel; Andrey Korshunov; Roland Eils; Stefan M Pfister; Peter Lichter Journal: Nature Date: 2012-08-02 Impact factor: 49.962
Authors: Marcel Kool; Jan Koster; Jens Bunt; Nancy E Hasselt; Arjan Lakeman; Peter van Sluis; Dirk Troost; Netteke Schouten-van Meeteren; Huib N Caron; Jacqueline Cloos; Alan Mrsić; Bauke Ylstra; Wieslawa Grajkowska; Wolfgang Hartmann; Torsten Pietsch; David Ellison; Steven C Clifford; Rogier Versteeg Journal: PLoS One Date: 2008-08-28 Impact factor: 3.240