Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI.
Purpose:To evaluate intrinsic susceptibility (IS) MRI for the identification of cycling hypoxia, and the assessment of its extent and spatial distribution, in head and neck squamous cell carcinoma (HNSCC) xenografts and patients.Experimental Design:Quantitation of the transverse relaxation rate, R2*, which is sensitive to paramagnetic deoxyhemoglobin, using serial IS-MRI acquisitions, was used to monitor temporal oscillations in levels of paramagnetic deoxyhemoglobin in human CALRxenografts and patients with HNSCC at 3T. Autocovariance and power spectrum analysis of variations in R2* was performed for each imaged voxel, to assess statistical significance and frequencies of cycling changes in tumor blood oxygenation. Pathologic correlates with tumor perfusion (Hoechst 33342), hypoxia (pimonidazole), and vascular density (CD31) were sought in the xenografts, and dynamic contrast-enhanced (DCE) MRI was used to assess patient tumor vascularization. The prevalence of fluctuations within patient tumors, DCE parameters, and treatment outcome were reported.Results:Spontaneous R2* fluctuations with a median periodicity of 15 minutes were detected in both xenografts and patient tumors. Spatially, these fluctuations were predominantly associated with regions of heterogeneous perfusion and hypoxia in the CALRxenografts. In patients, R2* fluctuations spatially correlated with regions of lymph nodes with low Ktransvalues, typically in the vicinity of necrotic cores.Conclusions:IS-MRI can be used to monitor variations in levels of paramagnetic deoxyhemoglobin, associated with cycling hypoxia. The presence of such fluctuations may be linked with impaired tumor vasculature, the presence of which may impact treatment outcome.Clin Cancer Res; 23(15); 4233-41. ©2017 AACR.
CR-UK and EPSRC Cancer Imaging Centre, London, United Kingdom.|Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Rafal
R
Panek
Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Liam
L
Welsh
CR-UK and EPSRC Cancer Imaging Centre, London, United Kingdom.|Institute of Cancer Research, London, United Kingdom.
Lauren C J
LCJ
Baker
CR-UK and EPSRC Cancer Imaging Centre, London, United Kingdom.|Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Maria A
MA
Schmidt
Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Kee H
KH
Wong
CR-UK and EPSRC Cancer Imaging Centre, London, United Kingdom.|Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Angela M
AM
Riddell
CR-UK and EPSRC Cancer Imaging Centre, London, United Kingdom.|Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Dow-Mu
DM
Koh
Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Alex
A
Dunlop
Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Dualta
D
Mcquaid
CR-UK and EPSRC Cancer Imaging Centre, London, United Kingdom.|Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
James A
JA
d'Arcy
Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Shreerang A
SA
Bhide
Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Kevin J
KJ
Harrington
Royal Marsden Hospital, London, United Kingdom.
Christopher M
CM
Nutting
Royal Marsden Hospital, London, United Kingdom.
Georgina
G
Hopkinson
Royal Marsden Hospital, London, United Kingdom.
Cheryl
C
Richardson
Institute of Cancer Research, London, United Kingdom.
Carol
C
Box
Institute of Cancer Research, London, United Kingdom.
Suzanne A
SA
Eccles
CR-UK and EPSRC Cancer Imaging Centre, London, United Kingdom. martin.leach@icr.ac.uk.|Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Martin O
MO
Leach
CR-UK and EPSRC Cancer Imaging Centre, London, United Kingdom.|Institute of Cancer Research, London, United Kingdom.
Simon P
SP
Robinson
Institute of Cancer Research, London, United Kingdom.|Royal Marsden Hospital, London, United Kingdom.
Kate L
KL
Newbold
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000627:therapeutic use; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D009593:Nitroimidazoles / Q000008:administration & dosage; D011836:Radiation Tolerance / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D003287:Contrast Media; D009593:Nitroimidazoles; C033815:pimonidazole