Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures

Leland S. Hu; Fulvio D’Angelo; Taylor M. Weiskittel; Francesca P. Caruso; Shannon P. Fortin Ensign; Mylan R. Blomquist; Matthew J. Flick; Lujia Wang; Christopher P. Sereduk; Kevin Meng-Lin; Gustavo De Leon; Ashley Nespodzany; Javier C. Urcuyo; Ashlyn C. Gonzales; Lee Curtin; Erika M. Lewis; Kyle W. Singleton; Timothy Dondlinger; Aliya Anil; Natenael B. Semmineh; Teresa Noviello; Reyna A. Patel; Panwen Wang; Junwen Wang; Jennifer M. Eschbacher; Andrea Hawkins-Daarud; Pamela R. Jackson; Itamar S. Grunfeld; Christian Elrod; Gina L. Mazza; Sam C. McGee; Lisa Paulson; Kamala Clark-Swanson; Yvette Lassiter-Morris; Kris A. Smith; Peter Nakaji; Bernard R. Bendok; Richard S. Zimmerman; Chandan Krishna; Devi P. Patra; Naresh P. Patel; Mark Lyons; Matthew Neal; Kliment Donev; Maciej M. Mrugala; Alyx B. Porter; Scott C. Beeman; Todd R. Jensen; Kathleen M. Schmainda; Yuxiang Zhou; Leslie C. Baxter; Christopher L. Plaisier; Jing Li; Hu Li; Anna Lasorella; C. Chad Quarles; Kristin R. Swanson; Michele Ceccarelli; Antonio Iavarone; Nhan L. Tran

doi:10.1038/s41467-023-41559-1

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures

Leland S. Hu, Fulvio D’Angelo, Taylor M. Weiskittel, Francesca P. Caruso, Shannon P. Fortin Ensign, Mylan R. Blomquist, Matthew J. Flick, Lujia Wang, Christopher P. Sereduk, Kevin Meng-Lin, Gustavo De Leon, Ashley Nespodzany, Javier C. Urcuyo, Ashlyn C. Gonzales, Lee Curtin, Erika M. Lewis, Kyle W. Singleton, Timothy Dondlinger, Aliya Anil, Natenael B. SemminehTeresa Noviello, Reyna A. Patel, Panwen Wang, Junwen Wang, Jennifer M. Eschbacher, Andrea Hawkins-Daarud, Pamela R. Jackson, Itamar S. Grunfeld, Christian Elrod, Gina L. Mazza, Sam C. McGee, Lisa Paulson, Kamala Clark-Swanson, Yvette Lassiter-Morris, Kris A. Smith, Peter Nakaji, Bernard R. Bendok, Richard S. Zimmerman, Chandan Krishna, Devi P. Patra, Naresh P. Patel, Mark Lyons, Matthew Neal, Kliment Donev, Maciej M. Mrugala, Alyx B. Porter, Scott C. Beeman, Todd R. Jensen, Kathleen M. Schmainda, Yuxiang Zhou, Leslie C. Baxter, Christopher L. Plaisier, Jing Li, Hu Li, Anna Lasorella, C. Chad Quarles, Kristin R. Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan L. Tran

Cancer Systems Imaging

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Original language	English (US)
Article number	6066
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-41559-1
State	Published - Dec 2023

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-023-41559-1

Cite this

Hu, L. S., D’Angelo, F., Weiskittel, T. M., Caruso, F. P., Fortin Ensign, S. P., Blomquist, M. R., Flick, M. J., Wang, L., Sereduk, C. P., Meng-Lin, K., De Leon, G., Nespodzany, A., Urcuyo, J. C., Gonzales, A. C., Curtin, L., Lewis, E. M., Singleton, K. W., Dondlinger, T., Anil, A., ... Tran, N. L. (2023). Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures. Nature communications, 14(1), Article 6066. https://doi.org/10.1038/s41467-023-41559-1

Hu, LS, D’Angelo, F, Weiskittel, TM, Caruso, FP, Fortin Ensign, SP, Blomquist, MR, Flick, MJ, Wang, L, Sereduk, CP, Meng-Lin, K, De Leon, G, Nespodzany, A, Urcuyo, JC, Gonzales, AC, Curtin, L, Lewis, EM, Singleton, KW, Dondlinger, T, Anil, A , Semmineh, NB, Noviello, T, Patel, RA, Wang, P, Wang, J, Eschbacher, JM, Hawkins-Daarud, A, Jackson, PR, Grunfeld, IS, Elrod, C, Mazza, GL, McGee, SC, Paulson, L, Clark-Swanson, K, Lassiter-Morris, Y, Smith, KA, Nakaji, P, Bendok, BR, Zimmerman, RS, Krishna, C, Patra, DP, Patel, NP, Lyons, M, Neal, M, Donev, K, Mrugala, MM, Porter, AB, Beeman, SC, Jensen, TR, Schmainda, KM, Zhou, Y, Baxter, LC, Plaisier, CL, Li, J, Li, H, Lasorella, A, Quarles, CC, Swanson, KR, Ceccarelli, M, Iavarone, A & Tran, NL 2023, 'Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures', Nature communications, vol. 14, no. 1, 6066. https://doi.org/10.1038/s41467-023-41559-1

@article{b3779dd5138e4e969d0eae87c462cb40,

title = "Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures",

abstract = "Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.",

author = "Hu, {Leland S.} and Fulvio D{\textquoteright}Angelo and Weiskittel, {Taylor M.} and Caruso, {Francesca P.} and {Fortin Ensign}, {Shannon P.} and Blomquist, {Mylan R.} and Flick, {Matthew J.} and Lujia Wang and Sereduk, {Christopher P.} and Kevin Meng-Lin and {De Leon}, Gustavo and Ashley Nespodzany and Urcuyo, {Javier C.} and Gonzales, {Ashlyn C.} and Lee Curtin and Lewis, {Erika M.} and Singleton, {Kyle W.} and Timothy Dondlinger and Aliya Anil and Semmineh, {Natenael B.} and Teresa Noviello and Patel, {Reyna A.} and Panwen Wang and Junwen Wang and Eschbacher, {Jennifer M.} and Andrea Hawkins-Daarud and Jackson, {Pamela R.} and Grunfeld, {Itamar S.} and Christian Elrod and Mazza, {Gina L.} and McGee, {Sam C.} and Lisa Paulson and Kamala Clark-Swanson and Yvette Lassiter-Morris and Smith, {Kris A.} and Peter Nakaji and Bendok, {Bernard R.} and Zimmerman, {Richard S.} and Chandan Krishna and Patra, {Devi P.} and Patel, {Naresh P.} and Mark Lyons and Matthew Neal and Kliment Donev and Mrugala, {Maciej M.} and Porter, {Alyx B.} and Beeman, {Scott C.} and Jensen, {Todd R.} and Schmainda, {Kathleen M.} and Yuxiang Zhou and Baxter, {Leslie C.} and Plaisier, {Christopher L.} and Jing Li and Hu Li and Anna Lasorella and Quarles, {C. Chad} and Swanson, {Kristin R.} and Michele Ceccarelli and Antonio Iavarone and Tran, {Nhan L.}",

note = "Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-41559-1",

language = "English (US)",

volume = "14",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures

AU - Hu, Leland S.

AU - D’Angelo, Fulvio

AU - Weiskittel, Taylor M.

AU - Caruso, Francesca P.

AU - Fortin Ensign, Shannon P.

AU - Blomquist, Mylan R.

AU - Flick, Matthew J.

AU - Wang, Lujia

AU - Sereduk, Christopher P.

AU - Meng-Lin, Kevin

AU - De Leon, Gustavo

AU - Nespodzany, Ashley

AU - Urcuyo, Javier C.

AU - Gonzales, Ashlyn C.

AU - Curtin, Lee

AU - Lewis, Erika M.

AU - Singleton, Kyle W.

AU - Dondlinger, Timothy

AU - Anil, Aliya

AU - Semmineh, Natenael B.

AU - Noviello, Teresa

AU - Patel, Reyna A.

AU - Wang, Panwen

AU - Wang, Junwen

AU - Eschbacher, Jennifer M.

AU - Hawkins-Daarud, Andrea

AU - Jackson, Pamela R.

AU - Grunfeld, Itamar S.

AU - Elrod, Christian

AU - Mazza, Gina L.

AU - McGee, Sam C.

AU - Paulson, Lisa

AU - Clark-Swanson, Kamala

AU - Lassiter-Morris, Yvette

AU - Smith, Kris A.

AU - Nakaji, Peter

AU - Bendok, Bernard R.

AU - Zimmerman, Richard S.

AU - Krishna, Chandan

AU - Patra, Devi P.

AU - Patel, Naresh P.

AU - Lyons, Mark

AU - Neal, Matthew

AU - Donev, Kliment

AU - Mrugala, Maciej M.

AU - Porter, Alyx B.

AU - Beeman, Scott C.

AU - Jensen, Todd R.

AU - Schmainda, Kathleen M.

AU - Zhou, Yuxiang

AU - Baxter, Leslie C.

AU - Plaisier, Christopher L.

AU - Li, Jing

AU - Li, Hu

AU - Lasorella, Anna

AU - Quarles, C. Chad

AU - Swanson, Kristin R.

AU - Ceccarelli, Michele

AU - Iavarone, Antonio

AU - Tran, Nhan L.

PY - 2023/12

Y1 - 2023/12

N2 - Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

AB - Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

UR - http://www.scopus.com/inward/record.url?scp=85172828207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85172828207&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-41559-1

DO - 10.1038/s41467-023-41559-1

M3 - Article

C2 - 37770427

AN - SCOPUS:85172828207

SN - 2041-1723

VL - 14

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 6066

ER -

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this