Consensus recommendations for MRI and PET imaging of primary central nervous system lymphoma: guideline statement from the International Primary CNS Lymphoma Collaborative Group (IPCG)

Ramon F Barajas^{1

2

3}, Letterio S Politi^{4

5}, Nicoletta Anzalone⁶, Heiko Schöder⁷, Christopher P Fox⁸, Jerrold L Boxerman⁹, Timothy J Kaufmann¹⁰, C Chad Quarles¹¹, Benjamin M Ellingson^{12

13}, Dorothee Auer^{14

15

16}, Ovidiu C Andronesi¹⁷, Andres J M Ferreri¹⁸, Maciej M Mrugala^{19

20}, Christian Grommes^{21

22}, Edward A Neuwelt^{23

24

25

26}, Prakash Ambady^{23

24}, James L Rubenstein^{27

28

29}, Gerald Illerhaus³⁰, Motoo Nagane³¹, Tracy T Batchelor³², Leland S Hu³³

Affiliations

¹ Department of Radiology, Neuroradiology Section, Oregon Health & Science University, Portland Oregon, USA.
² Advanced Imaging Research Center, Oregon Health & Science University, Portland, Oregon, USA.
³ Knight Cancer Institute Translational Oncology Program, Oregon Health & Science University, Portland, Oregon, USA.
⁴ Humanitas University and Humanitas Research and Clinical Center - IRCCS, Milan, Italy.
⁵ Boston Children's Hospital, Boston, Massachusetts, USA.
⁶ Neuroradiology Unit, IRCCS San Raffaele Hospital and Vita-Salute University, Milan, Italy.
⁷ Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
⁸ Department of Clinical Haematology, Nottingham University Hospitals NHS Trust, School of Medicine, University of Nottingham, Nottingham, UK.
⁹ Department of Diagnostic Imaging, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.
¹⁰ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹¹ Department of Neuroimaging Research & Barrow Neuroimaging Innovation Center, Barrow Neurological Institute, Phoenix, Arizona, USA.
¹² UCLA Brain Tumor Imaging Laboratory (BTIL), Departments of Radiological Sciences and Psychiatry, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, California, USA.
¹³ Departments of Radiological Sciences, Psychiatry, and Biobehavioral Sciences, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, California, USA.
¹⁴ Versus Arthritis Pain Centre, University of Nottingham, Nottingham, UK.
¹⁵ NIHR Nottingham Biomedical Research Centre, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
¹⁶ Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, UK.
¹⁷ A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
¹⁸ Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁹ Department of Medicine, Division of Hematology and Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona, USA.
²⁰ Department of Neurology, Mayo Clinic, Phoenix, Arizona, USA.
²¹ Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
²² Department of Neurology, Weill Cornell Medical School, New York, New York, USA.
²³ Blood-Brain Barrier Program, Oregon Health & Science University, Portland, Oregon, USA.
²⁴ Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
²⁵ Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA.
²⁶ Portland Veterans Affairs Medical Center, Portland, Oregon, USA.
²⁷ Division of Hematology/Oncology, University of California, San Francisco, California, USA.
²⁸ Department of Medicine, University of California, San Francisco, California, USA.
²⁹ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.
³⁰ Clinic of Hematology, Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany.
³¹ Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan.
³² Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³³ Department of Radiology, Neuroradiology Division, Mayo Clinic, Phoenix, Arizona, USA.

PMID: 33560416
PMCID: PMC8248856
DOI: 10.1093/neuonc/noab020

Consensus recommendations for MRI and PET imaging of primary central nervous system lymphoma: guideline statement from the International Primary CNS Lymphoma Collaborative Group (IPCG)

Ramon F Barajas et al. Neuro Oncol. 2021.

. 2021 Jul 1;23(7):1056-1071.

doi: 10.1093/neuonc/noab020.

Authors

Affiliations

¹ Department of Radiology, Neuroradiology Section, Oregon Health & Science University, Portland Oregon, USA.
² Advanced Imaging Research Center, Oregon Health & Science University, Portland, Oregon, USA.
³ Knight Cancer Institute Translational Oncology Program, Oregon Health & Science University, Portland, Oregon, USA.
⁴ Humanitas University and Humanitas Research and Clinical Center - IRCCS, Milan, Italy.
⁵ Boston Children's Hospital, Boston, Massachusetts, USA.
⁶ Neuroradiology Unit, IRCCS San Raffaele Hospital and Vita-Salute University, Milan, Italy.
⁷ Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
⁸ Department of Clinical Haematology, Nottingham University Hospitals NHS Trust, School of Medicine, University of Nottingham, Nottingham, UK.
⁹ Department of Diagnostic Imaging, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.
¹⁰ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹¹ Department of Neuroimaging Research & Barrow Neuroimaging Innovation Center, Barrow Neurological Institute, Phoenix, Arizona, USA.
¹² UCLA Brain Tumor Imaging Laboratory (BTIL), Departments of Radiological Sciences and Psychiatry, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, California, USA.
¹³ Departments of Radiological Sciences, Psychiatry, and Biobehavioral Sciences, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, California, USA.
¹⁴ Versus Arthritis Pain Centre, University of Nottingham, Nottingham, UK.
¹⁵ NIHR Nottingham Biomedical Research Centre, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
¹⁶ Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, UK.
¹⁷ A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
¹⁸ Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁹ Department of Medicine, Division of Hematology and Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona, USA.
²⁰ Department of Neurology, Mayo Clinic, Phoenix, Arizona, USA.
²¹ Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
²² Department of Neurology, Weill Cornell Medical School, New York, New York, USA.
²³ Blood-Brain Barrier Program, Oregon Health & Science University, Portland, Oregon, USA.
²⁴ Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
²⁵ Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA.
²⁶ Portland Veterans Affairs Medical Center, Portland, Oregon, USA.
²⁷ Division of Hematology/Oncology, University of California, San Francisco, California, USA.
²⁸ Department of Medicine, University of California, San Francisco, California, USA.
²⁹ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.
³⁰ Clinic of Hematology, Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany.
³¹ Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan.
³² Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³³ Department of Radiology, Neuroradiology Division, Mayo Clinic, Phoenix, Arizona, USA.

PMID: 33560416
PMCID: PMC8248856
DOI: 10.1093/neuonc/noab020

Abstract

Advanced molecular and pathophysiologic characterization of primary central nervous system lymphoma (PCNSL) has revealed insights into promising targeted therapeutic approaches. Medical imaging plays a fundamental role in PCNSL diagnosis, staging, and response assessment. Institutional imaging variation and inconsistent clinical trial reporting diminishes the reliability and reproducibility of clinical response assessment. In this context, we aimed to: (1) critically review the use of advanced positron emission tomography (PET) and magnetic resonance imaging (MRI) in the setting of PCNSL; (2) provide results from an international survey of clinical sites describing the current practices for routine and advanced imaging, and (3) provide biologically based recommendations from the International PCNSL Collaborative Group (IPCG) on adaptation of standardized imaging practices. The IPCG provides PET and MRI consensus recommendations built upon previous recommendations for standardized brain tumor imaging protocols (BTIP) in primary and metastatic disease. A biologically integrated approach is provided to addresses the unique challenges associated with the imaging assessment of PCNSL. Detailed imaging parameters facilitate the adoption of these recommendations by researchers and clinicians. To enhance clinical feasibility, we have developed both "ideal" and "minimum standard" protocols at 3T and 1.5T MR systems that will facilitate widespread adoption.

Keywords: MRI; PCNSL; PET; imaging; primary central nervous system lymphoma.

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Figures

**Fig. 1**
Biophysical features characterized by conventional and advanced physiologic MRI techniques. Shown are 6 MRI techniques that are commonly employed in neuro-oncologic imaging, along with their respective corresponding tumor phenotypes. T2-weighted (T2W) signal is typically used to define vasogenic edema. T1-weighted post-contrast enhancement (T1 + C) shows areas of disrupted blood-brain barrier (BBB). Dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) define microvascular volume as an indicator of tumor-related angiogenesis. Dynamic contrast-enhanced (DCE) MRI measures of vascular permeability (K^trans). Diffusion-weighted imaging apparent diffusion coefficient (ADC) correlates with cellular density and proliferative indices and can aid in distinguishing tumor from vasogenic edema. Diffusion tensor imaging (DTI) fractional anisotropy (FA) measures the integrity of white matter tracts, which can be used to identify regions of tumor infiltration.

**Fig. 2**
Challenges of bidirectional measurements of primary central nervous system lymphoma (PCNSL) tumor burden. (A) A single-rounded PCNSL mass lends itself to straightforward bidirectional measurement (yellow lines). (B) These bidirectional measurements can also be applied to multiple discrete masses. However, bidirectional measurements become more challenging with varied imaging patterns, such as with (C) heterogeneous enhancement, (D) linear ependymal enhancement, (E) leptomeningeal enhancement (arrows), and (F) linear perivascular enhancement (arrows). These varied imaging patterns would be more amenable to measurement using volumetric-based approaches to define tumor burden. Abbreviations: ADC, apparent diffusion coefficient; CBV, cerebral blood volume; DCE, dynamic contrast-enhanced; DSC, dynamic susceptibility contrast; PCNSL, primary central nervous system lymphoma.

**Fig. 3**
Typical morphologic and physiologic MRI appearance of PCNSL. PCNSL classically appears as a diffuse often periventricular enhancing mass (top left). T2-weighted imaging is often heterogenous but frequently demonstrates a mass like hypointense component (top middle) within enhancing regions. Increasing tumor cellularity is associated with decreasing T2 and ADC hypointensity (top right). Likewise, the degree of angiogenesis is reflected by DSC and DCE perfusion MRI sequences. CBV (bottom left) and K^trans (bottom right) are quite heterogenous in PCNSL and may be reflective of tumor aggressiveness.

**Fig. 4**
Demographic distribution of IPCG survey response. The IPCG imaging subcommittee surveyed members to determine clinical imaging practices for the evaluation of PCNSL at institutions across the world. About 147 institutions were invited to participate in this electronic survey. A 20% response rate was received from institutions delineated on the map from North America (N = 11), Europe (N = 17), and India (N = 1). Abbreviations: IPCG, International PCNSL Collaborative Group; PCNSL, primary central nervous system lymphoma.

See this image and copyright information in PMC

References

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Consensus recommendations for MRI and PET imaging of primary central nervous system lymphoma: guideline statement from the International Primary CNS Lymphoma Collaborative Group (IPCG)

Affiliations

Consensus recommendations for MRI and PET imaging of primary central nervous system lymphoma: guideline statement from the International Primary CNS Lymphoma Collaborative Group (IPCG)

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical