The Relationship Between Functional Parameters Derived from Diffusion-Weighted MRI and 18F-Fluorodeoxyglucose PET/CT in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-analysis

Abstract

Introduction

Over the past decade, a mechanistic hypothesis emerged linking limited water diffusivity (often reflecting densely packed, actively dividing tumor cells) to elevated glucose uptake in head and neck cancer.

Objective

A systematic search of MEDLINE via PubMed identified eligible studies assessing the correlation between apparent diffusion coefficients from diffusion-weighted MRI and standardized uptake values from 18F-fluorodeoxyglucose PET/CT in head and neck cancer. Weighted correlation coefficients (ρ) were computed using Fisher Z transformations, and 95% confidence intervals (CIs) were calculated. Heterogeneity was evaluated with Higgins's inconsistency index, and potential publication bias was evaluated by visually inspecting funnel plots.

Results

A total of 25 articles, encompassing 790 patients, were systematically appraised to summarize the available evidence regarding the relationship between functional parameters in head and neck cancer. Thirteen studies, involving 367 patients and reporting a statistically significant inverse correlation between functional parameters, were summarized in the forest plot; the pooled correlation coefficient estimate was ρ = −0.55 (95% CI: −0.624 to −0.473; P < 0.05), with low heterogeneity. A further 12 studies were systematically reviewed for qualitative analysis due to the absence of significant relationships.

Conclusion

The correlations observed in some studies between apparent diffusion coefficients and standardized uptake values may provide insights to develop metrics for evaluating treatment efficacy and predicting clinical outcomes in head and neck cancer. However, not all studies confirmed this result, possibly due to factors such as molecular characteristics or clinical settings.

Keywords

head and neck squamous cell carcinoma - diffusion-weighted magnetic resonance imaging - positron emission tomography and computed tomography - apparent diffusion coefficient

Authors' Contributions

LMG: conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, validation, writing – original draft; MR: data curation, resources; LB: visualization, resources; RB: formal analysis, resources; MP: resources; DC: validation; FDG: resources, writing – review & editing, supervision.

Data Availability Statement

Data supporting the results of this study are available upon a reasonable request from the corresponding author.

Publikationsverlauf

Eingereicht: 18. Januar 2025

Angenommen: 10. Juni 2025

Artikel online veröffentlicht:
16. Oktober 2025

• References

• 1 Colevas AD, Yom SS, Pfister DG. et al. NCCN Guidelines Insights: Head and neck cancers, version 1.2018. J Natl Compr Canc Netw 2018; 16 (05) 479-490
• 2 Schwartz SM. Epidemiology of Cancer. Clin Chem 2024; 70 (01) 140-149
• 3 Caudell JJ, Gillison ML, Maghami E. et al. NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022. J Natl Compr Canc Netw 2022; 20 (03) 224-234
• 4 Verdonck-de Leeuw I, Dawson C, Licitra L. et al. European Head and Neck Society recommendations for head and neck cancer survivorship care. Oral Oncol 2022; 133: 106047
• 5 Wang J, Takashima S, Takayama F. et al. Head and neck lesions: characterization with diffusion-weighted echo-planar MR imaging. Radiology 2001; 220 (03) 621-630
• 6 Rumboldt Z, Gordon L, Gordon L, Bonsall R, Ackermann S. Imaging in head and neck cancer. Curr Treat Options Oncol 2006; 7 (01) 23-34
• 7 Cacicedo J, Navarro A, Del Hoyo O. et al. Role of fluorine-18 fluorodeoxyglucose PET/CT in head and neck oncology: the point of view of the radiation oncologist. Br J Radiol 2016; 89 (1067): 20160217
• 8 Fruehwald-Pallamar J, Czerny C, Mayerhoefer ME. et al. Functional imaging in head and neck squamous cell carcinoma: correlation of PET/CT and diffusion-weighted imaging at 3 Tesla. Eur J Nucl Med Mol Imaging 2011; 38 (06) 1009-1019
• 9 Rasmussen JH, Nørgaard M, Hansen AE. et al. Feasibility of multiparametric imaging with PET/MR in head and neck Squamous cell carcinoma. J Nucl Med 2017; 58 (01) 69-74
• 10 Surov A, Stumpp P, Meyer HJ. et al. Simultaneous (18)F-FDG-PET/MRI: Associations between diffusion, glucose metabolism and histopathological parameters in patients with head and neck squamous cell carcinoma. Oral Oncol 2016; 58: 14-20
• 11 Çolak E, Bayraktaroğlu S, Akagündüz Ö, Savaş R, Esassolak M. Correlation of ADC values measured using 3T diffusion-weighted MRI and SUVs from fluorodeoxyglucose PET/CT in head and neck squamous cell carcinomas. Gülhane Tip Derg 2020; 62 (02) 72-79
• 12 Freihat O, Zoltán T, Pinter T. et al. Correlation between Tissue Cellularity and Metabolism Represented by Diffusion-Weighted Imaging (DWI) and 18F-FDG PET/MRI in Head and Neck Cancer (HNC). Cancers (Basel) 2022; 14 (03) 847
• 13 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62 (10) 1006-1012
• 14 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. J Clin Epidemiol 2021; 134: 178-189
• 15 Deng S, Wu Z, Wu Y. et al. Meta-Analysis of the Correlation between Apparent Diffusion Coefficient and Standardized Uptake Value in Malignant Disease. Contrast Media Mol Imaging 2017; 2017: 4729547
• 16 Boellaard R, Delgado-Bolton R, Oyen WJGG. et al; European Association of Nuclear Medicine (EANM). FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging 2015; 42 (02) 328-354
• 17 Whiting PF, Rutjes AWS, Westwood ME. et al; QUADAS-2 Group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011; 155 (08) 529-536
• 18 van Aert RCM. Meta-analyzing partial correlation coefficients using Fisher's z transformation. Res Synth Methods 2023; 14 (05) 768-773
• 19 Hinkle DE, Wiersma W, Jurs SG. Applied statistics for the behavioral sciences 1988;682
• 20 Melsen WG, Bootsma MCJ, Rovers MM, Bonten MJM. The effects of clinical and statistical heterogeneity on the predictive values of results from meta-analyses. Clin Microbiol Infect 2014; 20 (02) 123-129
• 21 Kanters S. Fixed- and Random-Effects Models. Methods Mol Biol 2022; 2345: 41-65
• 22 Gawlitza M, Purz S, Kubiessa K. et al. In vivo correlation of glucose metabolism, cell density and microcirculatory parameters in patients with head and neck cancer: Initial results using simultaneous PET/MRI. PLoS One 2015; 10 (08) e0134749
• 23 Martins EBL, Chojniak R, Kowalski LP, Nicolau UR, Lima ENP, Bitencourt AGV. Diffusion-weighted MRI in the assessment of early treatment response in patients with squamous-cell carcinoma of the head and neck: Comparison with morphological and PET/CT findings. PLoS One 2015; 10 (11) e0140009
• 24 Surov A, Meyer HJ, Wienke A. Correlation between apparent diffusion coefficient (ADC) and cellularity is different in several tumors: a meta-analysis. Oncotarget 2017; 8 (35) 59492-59499
• 25 Aramburu Núñez D, Lopez Medina A, Mera Iglesias M. et al. Multimodality functional imaging using DW-MRI and ¹⁸F-FDG-PET/CT during radiation therapy for human papillomavirus negative head and neck squamous cell carcinoma: Meixoeiro Hospital of Vigo Experience. World J Radiol 2017; 9 (01) 17-26
• 26 Leifels L, Purz S, Stumpp P. et al. Associations between 18F-FDG-PET, DWI, and DCE parameters in patients with head and neck squamous cell carcinoma depend on tumor grading. Contrast Media Mol Imaging 2017; 2017: 5369625
• 27 Dang HD, Chen Y, Shi XH. et al. [Correlations of ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging Parameters with the Pathological Differentiation of Head and Neck Squamous Cell Carcinoma and Their Diagnostic Efficiencies]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2018; 40 (02) 242-249
• 28 Cheng Y, Bai L, Shang J. et al. Preliminary clinical results for PET/MR compared with PET/CT in patients with nasopharyngeal carcinoma. Oncol Rep 2020; 43 (01) 177-187
• 29 Zhang L, Song T, Meng Z. et al. Correlation between apparent diffusion coefficients and metabolic parameters in hypopharyngeal squamous cell carcinoma: A prospective study with integrated PET/MRI. Eur J Radiol 2020; 129: 109070
• 30 Garau LM, Manca G, Bola S, Aringhieri G, Faggioni L, Volterrani D. Correlation between 18F-FDG PET/CT and diffusion-weighted MRI parameters in head and neck squamous cell carcinoma at baseline and after chemo-radiotherapy. A retrospective single institutional study. Oral Radiol 2022; 38 (02) 199-209
• 31 Paudyal R, Grkovski M, Oh JH. et al. Application of community detection algorithm to investigate the correlation between imaging biomarkers of tumor metabolism, hypoxia, cellularity, and perfusion for precision radiotherapy in head and neck squamous cell carcinomas. Cancers (Basel) 2021; 13 (15) 3908
• 32 Bülbül HM, Bülbül O, Sarıoğlu S, Özdoğan Ö, Doğan E, Karabay N. Relationships Between DCE-MRI, DWI, and ¹⁸F-FDG PET/CT Parameters with Tumor Grade and Stage in Patients with Head and Neck Squamous Cell Carcinoma. Mol Imaging Radionucl Ther 2021; 30 (03) 177-186
• 33 Gupta T, Maheshwari G, Kannan S, Nair S, Chaturvedi P, Agarwal JP. Systematic review and meta-analysis of randomized controlled trials comparing elective neck dissection versus sentinel lymph node biopsy in early-stage clinically node-negative oral and/or oropharyngeal squamous cell carcinoma: Evidence-base for practice and implications for research. Oral Oncol 2022; 124: 105642
• 34 de Koekkoek-Doll PK, Roberti S, Smit L. et al. ADC Values of Cytologically Benign and Cytologically Malignant 18 F-FDG PET-Positive Lymph Nodes of Head and Neck Squamous Cell Carcinoma. Cancers (Basel) 2022; 14 (16) 4019
• 35 Wongsa P, Nantasuk M, Singhnoi S. et al. Assessing the variability and correlation between SUV and ADC parameters of head and neck cancers derived from simultaneous PET/MRI: A single-center study. J Appl Clin Med Phys 2023; 24 (05) e13928
• 36 Choi SH, Paeng JC, Sohn CH. et al. Correlation of 18F-FDG uptake with apparent diffusion coefficient ratio measured on standard and high b value diffusion MRI in head and neck cancer. J Nucl Med 2011; 52 (07) 1056-1062
• 37 Nakajo M, Nakajo M, Kajiya Y. et al. FDG PET/CT and diffusion-weighted imaging of head and neck squamous cell carcinoma: comparison of prognostic significance between primary tumor standardized uptake value and apparent diffusion coefficient. Clin Nucl Med 2012; 37 (05) 475-480
• 38 Nakamatsu S, Matsusue E, Miyoshi H, Kakite S, Kaminou T, Ogawa T. Correlation of apparent diffusion coefficients measured by diffusion-weighted MR imaging and standardized uptake values from FDG PET/CT in metastatic neck lymph nodes of head and neck squamous cell carcinomas. Clin Imaging 2012; 36 (02) 90-97
• 39 Varoquaux A, Rager O, Lovblad KO. et al. Functional imaging of head and neck squamous cell carcinoma with diffusion-weighted MRI and FDG PET/CT: quantitative analysis of ADC and SUV. Eur J Nucl Med Mol Imaging 2013; 40 (06) 842-852
• 40 Ng SH, Lin CY, Chan SC. et al. Clinical utility of multimodality imaging with dynamic contrast-enhanced MRI, diffusion-weighted MRI, and 18F-FDG PET/CT for the prediction of neck control in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiation. PLoS One 2014; 9 (12) e115933
• 41 Covello M, Cavaliere C, Aiello M. et al. Simultaneous PET/MR head-neck cancer imaging: Preliminary clinical experience and multiparametric evaluation. Eur J Radiol 2015; 84 (07) 1269-1276
• 42 Han M, Kim SY, Lee SJ, Choi JW. The Correlations Between MRI Perfusion, Diffusion Parameters, and 18F-FDG PET Metabolic Parameters in Primary Head-and-Neck Cancer: A Cross-Sectional Analysis in Single Institute. Medicine (Baltimore) 2015; 94 (47) e2141
• 43 Huedo-Medina TB, Sánchez-Meca J, Marín-Martínez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I2 index?. Psychol Methods 2006; 11 (02) 193-206
• 44 Shen G, Ma H, Liu B, Ren P, Kuang A. Correlation of the apparent diffusion coefficient and the standardized uptake value in neoplastic lesions: a meta-analysis. Nucl Med Commun 2017; 38 (12) 1076-1084
• 45 Driessen JP, Caldas-Magalhaes J, Janssen LM. et al. Diffusion-weighted MR imaging in laryngeal and hypopharyngeal carcinoma: association between apparent diffusion coefficient and histologic findings. Radiology 2014; 272 (02) 456-463
• 46 Minn H, Joensuu H, Ahonen A, Klemi P. Fluorodeoxyglucose imaging: a method to assess the proliferative activity of human cancer in vivo. Comparison with DNA flow cytometry in head and neck tumors. Cancer 1988; 61 (09) 1776-1781
• 47 Surov A, Meyer HJ, Winter K, Richter C, Hoehn AK. Histogram analysis parameters of apparent diffusion coefficient reflect tumor cellularity and proliferation activity in head and neck squamous cell carcinoma. Oncotarget 2018; 9 (34) 23599-23607
• 48 Varoquaux A, Rager O, Dulguerov P, Burkhardt K, Ailianou A, Becker M. Diffusion-weighted and PET/MR Imaging after Radiation Therapy for Malignant Head and Neck Tumors. Radiographics 2015; 35 (05) 1502-1527
• 49 Grueneisen J, Beiderwellen K, Heusch P. et al. Correlation of standardized uptake value and apparent diffusion coefficient in integrated whole-body PET/MRI of primary and recurrent cervical cancer. PLoS One 2014; 9 (05) e96751
• 50 Kużdżał B, Moszczyński K, Żanowska K. et al. Correlation between 18-FDG standardized uptake value and tumor grade in patients with resectable non-small cell lung cancer. Transl Cancer Res 2023; 12 (12) 3530-3537
• 51 Abubakar ZA, Akepati NKR, Bikkina P. Correlation of Maximum Standardized Uptake Values in 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography Scan with Immunohistochemistry and Other Prognostic Factors in Breast Cancer. Indian J Nucl Med 2019; 34 (01) 10-13
• 52 Li D, Wang Y, Liu W. et al. The Correlation between ¹⁸F-FDG PET/CT Imaging SUVmax of Preoperative Colon Cancer Primary Lesions and Clinicopathological Factors. J Oncol 2021; 2021: 4312296
• 53 Maman A, Sahin A, Ayan AK. The Relationship of SUV Value in PET-CT with Tumor Differentiation and Tumor Markers in Gastric Cancer. Eurasian J Med 2020; 52 (01) 67-72
• 54 Chan DLH, Pavlakis N, Schembri GP. et al. Dual somatostatin receptor/FDG PET/CT imaging in metastatic neuroendocrine tumours: Proposal for a novel grading scheme with prognostic significance. Theranostics 2017; 7 (05) 1149-1158
• 55 Singer AD, Pattany PM, Fayad LM, Tresley J, Subhawong TK. Volumetric segmentation of ADC maps and utility of standard deviation as measure of tumor heterogeneity in soft tissue tumors. Clin Imaging 2016; 40 (03) 386-391
• 56 Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015; 517 (7536): 576-582