Min Zhou1,2, Yue Zhou1,3, Huijun Liao1, Benjamin C Rowland1, Xiangquan Kong2, Nils D Arvold4, David A Reardon5, Patrick Y Wen5, Alexander P Lin1, Raymond Y Huang6. 1. Center for Clinical Spectroscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2. Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 3. Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 4. St Luke's Radiation Oncology Associates, St Luke's Regional Cancer Center, and Whiteside Institute for Clinical Research/University of Minnesota Duluth, Duluth, Minnesota, USA. 5. Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. 6. Department of Radiology, Brigham and Women's Hospital, Harvard Medical College, Boston, Massachusetts, USA.
Abstract
Background: Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2HG) in gliomas that can be detected by MRS. We examined the diagnostic accuracy of 2HG single-voxel spectroscopy (SVS) and chemical shift imaging (CSI) in both newly diagnosed and posttreatment settings. Methods: Long echo time (97 ms) SVS and CSI were acquired in 85 subjects, including a discovery cohort of 39 patients who had postoperative residual or recurrent glioma with confirmed IDH-mutation status and 6 normal volunteers, a prospective preoperative validation cohort of 24 patients with newly diagnosed brain mass, and a prospective recurrent-lesion validation cohort of 16 previously treated IDH-mutant glioma patients with suspected tumor recurrence. The optimal thresholds for both methods in diagnosing IDH status were determined by receiver operating characteristic analysis in the discovery cohort and then applied to the 2 validation cohorts to assess the diagnostic performance. Results: The optimal 2HG/creatine thresholds of SVS and 75th percentile CSI for IDH mutations were 0.11 and 0.23, respectively. When applied to the validation sets, the sensitivity, specificity, and accuracy in distinguishing IDH-mutant gliomas in the preoperative cohort were 85.71%, 100.00%, and 94.12% for SVS, and 100.00%, 69.23%, and 81.82% for CSI, respectively. In the recurrent-lesion cohort, the sensitivity, specificity, and accuracy for discriminating IDH-positive recurrent gliomas were 40.00%, 62.50%, and 53.85% for SVS, and 66.67%, 100.00%, and 86.67% for CSI, respectively. Conclusions: 2HG MRS provides diagnostic utility for IDH-mutant gliomas both preoperatively and at time of suspected tumor recurrence. SVS has a better diagnostic performance for untreated IDH-mutant gliomas, whereas CSI demonstrates greater performance in identifying recurrent tumors.
Background: Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2HG) in gliomas that can be detected by MRS. We examined the diagnostic accuracy of 2HG single-voxel spectroscopy (SVS) and chemical shift imaging (CSI) in both newly diagnosed and posttreatment settings. Methods: Long echo time (97 ms) SVS and CSI were acquired in 85 subjects, including a discovery cohort of 39 patients who had postoperative residual or recurrent glioma with confirmed IDH-mutation status and 6 normal volunteers, a prospective preoperative validation cohort of 24 patients with newly diagnosed brain mass, and a prospective recurrent-lesion validation cohort of 16 previously treated IDH-mutant gliomapatients with suspected tumor recurrence. The optimal thresholds for both methods in diagnosing IDH status were determined by receiver operating characteristic analysis in the discovery cohort and then applied to the 2 validation cohorts to assess the diagnostic performance. Results: The optimal 2HG/creatine thresholds of SVS and 75th percentile CSI for IDH mutations were 0.11 and 0.23, respectively. When applied to the validation sets, the sensitivity, specificity, and accuracy in distinguishing IDH-mutant gliomas in the preoperative cohort were 85.71%, 100.00%, and 94.12% for SVS, and 100.00%, 69.23%, and 81.82% for CSI, respectively. In the recurrent-lesion cohort, the sensitivity, specificity, and accuracy for discriminating IDH-positive recurrent gliomas were 40.00%, 62.50%, and 53.85% for SVS, and 66.67%, 100.00%, and 86.67% for CSI, respectively. Conclusions: 2HG MRS provides diagnostic utility for IDH-mutant gliomas both preoperatively and at time of suspected tumor recurrence. SVS has a better diagnostic performance for untreated IDH-mutant gliomas, whereas CSI demonstrates greater performance in identifying recurrent tumors.
Authors: Patrick Y Wen; David R Macdonald; David A Reardon; Timothy F Cloughesy; A Gregory Sorensen; Evanthia Galanis; John Degroot; Wolfgang Wick; Mark R Gilbert; Andrew B Lassman; Christina Tsien; Tom Mikkelsen; Eric T Wong; Marc C Chamberlain; Roger Stupp; Kathleen R Lamborn; Michael A Vogelbaum; Martin J van den Bent; Susan M Chang Journal: J Clin Oncol Date: 2010-03-15 Impact factor: 44.544
Authors: David Capper; Hanswalter Zentgraf; Jörg Balss; Christian Hartmann; Andreas von Deimling Journal: Acta Neuropathol Date: 2009-10-02 Impact factor: 17.088
Authors: Daniel J Brat; Roel G W Verhaak; Kenneth D Aldape; W K Alfred Yung; Sofie R Salama; Lee A D Cooper; Esther Rheinbay; C Ryan Miller; Mark Vitucci; Olena Morozova; A Gordon Robertson; Houtan Noushmehr; Peter W Laird; Andrew D Cherniack; Rehan Akbani; Jason T Huse; Giovanni Ciriello; Laila M Poisson; Jill S Barnholtz-Sloan; Mitchel S Berger; Cameron Brennan; Rivka R Colen; Howard Colman; Adam E Flanders; Caterina Giannini; Mia Grifford; Antonio Iavarone; Rajan Jain; Isaac Joseph; Jaegil Kim; Katayoon Kasaian; Tom Mikkelsen; Bradley A Murray; Brian Patrick O'Neill; Lior Pachter; Donald W Parsons; Carrie Sougnez; Erik P Sulman; Scott R Vandenberg; Erwin G Van Meir; Andreas von Deimling; Hailei Zhang; Daniel Crain; Kevin Lau; David Mallery; Scott Morris; Joseph Paulauskis; Robert Penny; Troy Shelton; Mark Sherman; Peggy Yena; Aaron Black; Jay Bowen; Katie Dicostanzo; Julie Gastier-Foster; Kristen M Leraas; Tara M Lichtenberg; Christopher R Pierson; Nilsa C Ramirez; Cynthia Taylor; Stephanie Weaver; Lisa Wise; Erik Zmuda; Tanja Davidsen; John A Demchok; Greg Eley; Martin L Ferguson; Carolyn M Hutter; Kenna R Mills Shaw; Bradley A Ozenberger; Margi Sheth; Heidi J Sofia; Roy Tarnuzzer; Zhining Wang; Liming Yang; Jean Claude Zenklusen; Brenda Ayala; Julien Baboud; Sudha Chudamani; Mark A Jensen; Jia Liu; Todd Pihl; Rohini Raman; Yunhu Wan; Ye Wu; Adrian Ally; J Todd Auman; Miruna Balasundaram; Saianand Balu; Stephen B Baylin; Rameen Beroukhim; Moiz S Bootwalla; Reanne Bowlby; Christopher A Bristow; Denise Brooks; Yaron Butterfield; Rebecca Carlsen; Scott Carter; Lynda Chin; Andy Chu; Eric Chuah; Kristian Cibulskis; Amanda Clarke; Simon G Coetzee; Noreen Dhalla; Tim Fennell; Sheila Fisher; Stacey Gabriel; Gad Getz; Richard Gibbs; Ranabir Guin; Angela Hadjipanayis; D Neil Hayes; Toshinori Hinoue; Katherine Hoadley; Robert A Holt; Alan P Hoyle; Stuart R Jefferys; Steven Jones; Corbin D Jones; Raju Kucherlapati; Phillip H Lai; Eric Lander; Semin Lee; Lee Lichtenstein; Yussanne Ma; Dennis T Maglinte; Harshad S Mahadeshwar; Marco A Marra; Michael Mayo; Shaowu Meng; Matthew L Meyerson; Piotr A Mieczkowski; Richard A Moore; Lisle E Mose; Andrew J Mungall; Angeliki Pantazi; Michael Parfenov; Peter J Park; Joel S Parker; Charles M Perou; Alexei Protopopov; Xiaojia Ren; Jeffrey Roach; Thaís S Sabedot; Jacqueline Schein; Steven E Schumacher; Jonathan G Seidman; Sahil Seth; Hui Shen; Janae V Simons; Payal Sipahimalani; Matthew G Soloway; Xingzhi Song; Huandong Sun; Barbara Tabak; Angela Tam; Donghui Tan; Jiabin Tang; Nina Thiessen; Timothy Triche; David J Van Den Berg; Umadevi Veluvolu; Scot Waring; Daniel J Weisenberger; Matthew D Wilkerson; Tina Wong; Junyuan Wu; Liu Xi; Andrew W Xu; Lixing Yang; Travis I Zack; Jianhua Zhang; B Arman Aksoy; Harindra Arachchi; Chris Benz; Brady Bernard; Daniel Carlin; Juok Cho; Daniel DiCara; Scott Frazer; Gregory N Fuller; JianJiong Gao; Nils Gehlenborg; David Haussler; David I Heiman; Lisa Iype; Anders Jacobsen; Zhenlin Ju; Sol Katzman; Hoon Kim; Theo Knijnenburg; Richard Bailey Kreisberg; Michael S Lawrence; William Lee; Kalle Leinonen; Pei Lin; Shiyun Ling; Wenbin Liu; Yingchun Liu; Yuexin Liu; Yiling Lu; Gordon Mills; Sam Ng; Michael S Noble; Evan Paull; Arvind Rao; Sheila Reynolds; Gordon Saksena; Zack Sanborn; Chris Sander; Nikolaus Schultz; Yasin Senbabaoglu; Ronglai Shen; Ilya Shmulevich; Rileen Sinha; Josh Stuart; S Onur Sumer; Yichao Sun; Natalie Tasman; Barry S Taylor; Doug Voet; Nils Weinhold; John N Weinstein; Da Yang; Kosuke Yoshihara; Siyuan Zheng; Wei Zhang; Lihua Zou; Ty Abel; Sara Sadeghi; Mark L Cohen; Jenny Eschbacher; Eyas M Hattab; Aditya Raghunathan; Matthew J Schniederjan; Dina Aziz; Gene Barnett; Wendi Barrett; Darell D Bigner; Lori Boice; Cathy Brewer; Chiara Calatozzolo; Benito Campos; Carlos Gilberto Carlotti; Timothy A Chan; Lucia Cuppini; Erin Curley; Stefania Cuzzubbo; Karen Devine; Francesco DiMeco; Rebecca Duell; J Bradley Elder; Ashley Fehrenbach; Gaetano Finocchiaro; William Friedman; Jordonna Fulop; Johanna Gardner; Beth Hermes; Christel Herold-Mende; Christine Jungk; Ady Kendler; Norman L Lehman; Eric Lipp; Ouida Liu; Randy Mandt; Mary McGraw; Roger Mclendon; Christopher McPherson; Luciano Neder; Phuong Nguyen; Ardene Noss; Raffaele Nunziata; Quinn T Ostrom; Cheryl Palmer; Alessandro Perin; Bianca Pollo; Alexander Potapov; Olga Potapova; W Kimryn Rathmell; Daniil Rotin; Lisa Scarpace; Cathy Schilero; Kelly Senecal; Kristen Shimmel; Vsevolod Shurkhay; Suzanne Sifri; Rosy Singh; Andrew E Sloan; Kathy Smolenski; Susan M Staugaitis; Ruth Steele; Leigh Thorne; Daniela P C Tirapelli; Andreas Unterberg; Mahitha Vallurupalli; Yun Wang; Ronald Warnick; Felicia Williams; Yingli Wolinsky; Sue Bell; Mara Rosenberg; Chip Stewart; Franklin Huang; Jonna L Grimsby; Amie J Radenbaugh; Jianan Zhang Journal: N Engl J Med Date: 2015-06-10 Impact factor: 91.245
Authors: Charles Gasparovic; Tao Song; Deidre Devier; H Jeremy Bockholt; Arvind Caprihan; Paul G Mullins; Stefan Posse; Rex E Jung; Leslie A Morrison Journal: Magn Reson Med Date: 2006-06 Impact factor: 4.668
Authors: Changho Choi; Jack M Raisanen; Sandeep K Ganji; Song Zhang; Sarah S McNeil; Zhongxu An; Akshay Madan; Kimmo J Hatanpaa; Vamsidhara Vemireddy; Christie A Sheppard; Dwight Oliver; Keith M Hulsey; Vivek Tiwari; Tomoyuki Mashimo; James Battiste; Samuel Barnett; Christopher J Madden; Toral R Patel; Edward Pan; Craig R Malloy; Bruce E Mickey; Robert M Bachoo; Elizabeth A Maher Journal: J Clin Oncol Date: 2016-10-31 Impact factor: 44.544
Authors: M J van den Bent; J S Wefel; D Schiff; M J B Taphoorn; K Jaeckle; L Junck; T Armstrong; A Choucair; A D Waldman; T Gorlia; M Chamberlain; B G Baumert; M A Vogelbaum; D R Macdonald; D A Reardon; P Y Wen; S M Chang; A H Jacobs Journal: Lancet Oncol Date: 2011-04-05 Impact factor: 41.316
Authors: Lenny Dang; David W White; Stefan Gross; Bryson D Bennett; Mark A Bittinger; Edward M Driggers; Valeria R Fantin; Hyun Gyung Jang; Shengfang Jin; Marie C Keenan; Kevin M Marks; Robert M Prins; Patrick S Ward; Katharine E Yen; Linda M Liau; Joshua D Rabinowitz; Lewis C Cantley; Craig B Thompson; Matthew G Vander Heiden; Shinsan M Su Journal: Nature Date: 2009-12-10 Impact factor: 49.962
Authors: D Williams Parsons; Siân Jones; Xiaosong Zhang; Jimmy Cheng-Ho Lin; Rebecca J Leary; Philipp Angenendt; Parminder Mankoo; Hannah Carter; I-Mei Siu; Gary L Gallia; Alessandro Olivi; Roger McLendon; B Ahmed Rasheed; Stephen Keir; Tatiana Nikolskaya; Yuri Nikolsky; Dana A Busam; Hanna Tekleab; Luis A Diaz; James Hartigan; Doug R Smith; Robert L Strausberg; Suely Kazue Nagahashi Marie; Sueli Mieko Oba Shinjo; Hai Yan; Gregory J Riggins; Darell D Bigner; Rachel Karchin; Nick Papadopoulos; Giovanni Parmigiani; Bert Vogelstein; Victor E Velculescu; Kenneth W Kinzler Journal: Science Date: 2008-09-04 Impact factor: 47.728
Authors: Changho Choi; Sandeep K Ganji; Ralph J DeBerardinis; Kimmo J Hatanpaa; Dinesh Rakheja; Zoltan Kovacs; Xiao-Li Yang; Tomoyuki Mashimo; Jack M Raisanen; Isaac Marin-Valencia; Juan M Pascual; Christopher J Madden; Bruce E Mickey; Craig R Malloy; Robert M Bachoo; Elizabeth A Maher Journal: Nat Med Date: 2012-01-26 Impact factor: 53.440
Authors: Chong Hyun Suh; Ho Sung Kim; Ji Eun Park; Seung Chai Jung; Choong Gon Choi; Dong-Cheol Woo; Ho Beom Lee; Sang Joon Kim Journal: Radiol Imaging Cancer Date: 2020-07-31
Authors: Guodong Weng; Piotr Radojewski; Sulaiman Sheriff; Claus Kiefer; Philippe Schucht; Roland Wiest; Andrew A Maudsley; Johannes Slotboom Journal: Magn Reson Med Date: 2022-03-28 Impact factor: 3.737