The Evaluation of D-glucose Weighted Chemical Exchange Saturation Transfer (gluceoCEST)-Based Dynamic Glucose Enhanced(DGE) Magnetic Resonance Imaging（MRI） in Brain Tumor
Phase: EARLY_PHASE1
Conditions: Magnetic Resonance Imaging
Sponsor: Zhujiang Hospital

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The Evaluation of D-glucose Weighted Chemical Exchange 
Saturation Transfer (glucoCEST)-Based Dynamic Glucose 
Enhanced(DGE) Magnetic Resonance Imaging（MRI） in 
Brain Tumor 
 
 
 
 
 
 
 
 
 
Main research unit: Zhujiang Hospital of Southern Medical University 
Principal investigator: Zhibo Wen 
Participating units and persons in charge: 
Statistical Analysis Unit: 
Scheme version: 4.0 
Scheme version date: December 27, 2019 

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Confidentiality statement 
The ownership of all information contained in this study protocol belong to the investigator of the 
project. It is provided only for review by the ERC and relevant agencies. It is prohibitive that 
disclose any information to third parties unrelated to the study without the written consent of the 
Principal Investigator (PI). 
 
 

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Catalog 
 
 
Abstract ......................................................................................................................................................... 4 
Background ................................................................................................................................................. 6 
Materials and Methods ............................................................................................................................ 7 
Patients: ............................................................................................................................................... 7 
Inclusion Criteria: .............................................................................................................................. 7 
Exclusion Criteria............................................................................................................................... 7 
Methods ................................................................................................................................................... 8 
 .................................................................................................................................................................... 8 
Methods of DGE ............................................................................................................................... 8 
Statistic Analysis ......................................................................................................................................... 9 
Statistic tools: SPSS 23.0 ................................................................................................................. 9 
Basic principles: ................................................................................................................................. 9 
Missing data: ...................................................................................................................................... 9 
Description statistics: ....................................................................................................................... 9 
Baseline data analysis: ..................................................................................................................... 9 
Analysis of influencing factors: ................................................................................................... 10 
Ethical considerations ............................................................................................................................. 10 
References: ................................................................................................................................................. 10 
  
 
 

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Abstract 
Subject 
Application of glucose CEST MR imaging in brain tumors 
Sponsor 
Department of Imaging Diagnosis, Zhujiang Hospital, Southern Medical 
University 
Research Institutes 
Zhujiang Hospital, Southern Medical University 
Principal 
Investigator 
Zhibo Wen 
Purpose 
Whether glucose CEST MR imaging is superior to gadolinium contrast 
agents based MR imaging in brain tumors 
Hypothesis 
Glucose CEST MR imaging is more effective than gadolinium contrast 
imaging in the diagnosis of brain tumors 
Design 
Clinical trial 
Sample Capacity 
100 
Inclusion and 
Exclusion Criteria 
Minimum Age: 
18 Years   
Maximum Age: 
75 Years 
Criteria:  
Inclusion Criteria: 
(1) Patient must have a brain mass consistent with a primary brain tumor 
or metastatic brain tumor(2) able to give consent (3) willingness to 
participate in this  
Exclusion Criteria: 

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1) presence of any ferromagnetic implant (cardiac pacemakers, aneurysm 
clip, etc.) (2) pregnancy (3) claustrophobia or anxiety disorder (4) history 
of vertigo (5) persons with diabetes mellitus (self-report or HbA1C >= 
6.5%) (6) Sickle cell disease (7) persons taking prescription medicine for 
hypertension (8) blood iron deficiency (Hb concentration < 11 g/dL or Hct 
< 32%) (9) If volunteering for MRI: history of kidney disease and/or 
eGFR < 60. (10) Middle-ear disorder (11) double vision (12) Seizure 
disorder (13)Multiple myeloma (14) Solid organ transplant (15) History of 
severe hepatic disease/liver transplant/pending liver transplant 
Interference 
MR Imaging based on DGE 
Measure 
The area of hyperintense and the AUC between 2-5min of DGE 
Patients 
brain tumor patient treated at Zhujiang Hospital of Southern Medical 
University 
Statistical Method 
Differential test and Consistency analysis were used for statistical analysis 
 
 
 

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Background 
The priority treatment of brain tumor is surgical resection. Recurrent malignant glioma is the most 
common and highly malignant primary brain tumor in adults. It mainly includes the pleomorphic 
glioblastoma (GBM) and anaplastic astrocytoma (AA). The average survival period of GBM is 
only 14.6 months [1], while the average lifetime of AA is only 2 to 3 years [1, 2]. Residual tumor 
and highly recurrence rate is the main reason. Besides, the feasibility of reoperation is extremely 
low. Moreover, progression-free survival (6-month progression-free survival (6M-PFS)) was only 
15-21% of patients with recurrent glioma. The response rate of conventional chemotherapy was 
less than 15% in patients with recurrent glioma [1, 2]. Therefore, accurate clinical assessment of 
tumor scope is of great significance for GBM expansion surgery to remove the potential tumor 
immersed area and improve the survival rate of patients. 
Recently, natural D-glucose suggested as a potential biodegradable contrast agent. The feasibility 
of using D-glucose for dynamic perfusion imaging explored to detect malignant brain tumors 
based on the breakdown of blood brain barrier (BBB)[3]. Our study try to evaluate the feasibility 
of dynamic glucose enhanced(DGE) magnetic resonance imaging（MRI）in brain tumor, which 
based on D-glucose weighted chemical exchange saturation transfer (glucoCEST). 
In 2015, Xiang Xu et al. first demonstrated the feasibility of DGE MRI in four normal volunteers 
and three glioma patients [4]. Routinely, D-glucose was used in human biochemical studies. The 
objective of this study was to evaluate the feasibility of DGE for visualizing BBB permeability in 
brain tumor models and to compare it with GBCA-based DCE for visualizing BBB permeability. 
With glucose CEST MR imaging, we attempt to accurately predict the grade of brain glioma and 
to evaluate the infiltration range of tumor cells in the edema zone around glioma, so as to provide 
a more sufficient basis for the formulation of surgical resection plan for patients. 
 

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Materials and Methods 
Patients: 
 Brain tumor patient treated at Zhujiang Hospital of Southern Medical University. 
Minimum Age: 
18 Years   
Maximum Age: 
75 Years 
Inclusion Criteria: 
(1) Patient must have a brain mass consistent with a primary brain tumor or metastatic brain 
tumor(2) able to give consent (3) willingness to participate in this  
Exclusion Criteria: 
(1)Presence of any ferromagnetic implant (cardiac pacemakers, aneurysm clip, etc.) (2) Pregnancy 
(3) Claustrophobia or anxiety disorder (4) History of vertigo (5) Persons with diabetes mellitus 
(self-report or HbA1C >= 6.5%) (6) Sickle cell disease (7) Persons taking prescription medicine 
for hypertension (8) Blood iron deficiency (Hb concentration < 11 g/dL or Hct < 32%) (9) If 
volunteering for MRI: history of kidney disease and/or eGFR < 60. (10) Middle-ear disorder (11) 
double vision (12) Seizure disorder (13) Multiple myeloma (14) Solid organ transplant (15) 
History of severe hepatic disease/liver transplant/pending liver transplant. 
 
 
 
 

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Methods 
 
 
 
 
 
 
 
 
 
 
 
Methods of DGE 
Time-resolved glucose signal changes were detected using chemical exchange saturation transfer 
(glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response 
to an intravenous bolus of D-glucose. Starting the dynamic glucose scan, 3mimutes later, a brief 
hyperglycemic state was established by intravenous infusion of hospital-grade D50 glucose (D50, 
25 g of dextrose in 50 mL of water sterile solution), followed by 20 mL of saline solution in 1 arm. 
The glucose infusion was performed using a power injector at an infusion rate of 0.2 mL/s, 
corresponding to total infusion times of 250 seconds. Performing dynamic contrast enhancement 
based on Gd-DTPA in 30 minutes later, which was used for comparison as golden standard. Dose 
of agent is ccording to the proportion of 0.2ml/kg body weight. The Gd-DTPA infusion was 
performed using a power injector at an infusion rate of 3 mL/s, followed by 20 mL of saline 
solution in 1 arm. 
Brain tumor patients 
Meets Inclusion and 
Exclusion Criteria 
DGE and convention MR Imaging 
Statistic and analysis 
Post-procession and measurement 
Result and conclusion 

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Statistic Analysis 
Statistic tools: SPSS 23.0  
Basic principles:  
All statistical inferences were tested by bilateral tests, the test level of statistical significance was 
set at 0.05, and the confidence interval of parameters was estimated by 95% confidence interval. 
The parametric method is used as far as possible. When the data does not meet the parametric 
method conditions, the data transformation method can be used to make it meet the conditions. If 
the data still does not meet the parameter method conditions, the non-parametric method can be 
considered. 
Missing data:  
The case data that did not meet the statistical requirements were excluded. 
 Description statistics:  
The mean, standard deviation and confidence interval are given for measurement data. The 
minimum, maximum, P25, median and P75 are given if necessary. The mean and standard 
deviation of the trip value were calculated from paired measurement data. Median and mean rank 
are given when nonparametric methods are used. The enumeration data give the frequency 
distribution and the corresponding percentages. Rank data give frequency distributions and 
corresponding percentages, as well as median and mean rank. The positive rate, positive number 
and the number of cases in the denominator were given in qualitative data. 
Baseline data analysis:  
Descriptive analysis of baseline data, including baseline levels of endogenous glucose CEST in 
brain tissue. 

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Analysis of influencing factors:  
Motion artifacts have a certain image for CEST value measurement, which may lead to 
measurement error. 
Ethical considerations 
This clinical study must under the Helsinki Declaration and the relevant Chinese regulations on 
clinical research. The clinical study plan, informed consent and other data should be submitted to 
the ethics committee for approval before the starting. During the clinical study, the modification of 
clinical study plan and the informed documents can’t be performed before approved by the ethics 
committee. The investigator take care of the rights and safety of the subject and ensures the 
subject's privacy. 
 
 
References: 
[1]. Stupp, R., et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N 
Engl J Med, 2005. 352(10): p. 987-96. 
[2]. Curran, W.J., et al., Recursive partitioning analysis of prognostic factors in three Radiation Therapy  
Oncology Group malignant glioma trials. J Natl Cancer Inst, 1993. 85(9): p. 704-10. 
[3]. Xu, X., et al., Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier 
break down and increased blood volume in brain cancer. Magn Reson Med, 2015. 74(6): p. 1556-63. 
[4]. Xu, X., et al., Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First 
Results in Glioma Patients. Tomography, 2015. 1(2): p. 105-114.