High-resolution Multi-parametric Magnetic Resonance Imaging for Focal Epilepsy
Phase: NA
Conditions: Epilepsies, Partial
Sponsor: Chinese University of Hong Kong

1 
Study protocol (version 1.1), 18 Aprial 2024  
 
 
Scientific title  
High-resolution multi-parametric Magnetic Resonance Imaging for Focal Epilepsy  
 
 
 
 
Research protocol 
Version 1.1 
Date: 18 April 2024  
NCT Number:  
 
 

2 
Study protocol (version 1.1), 18 Aprial 2024  
Scientific basis 
Focal epilepsy refers to having seizures arising from a specific part of the brain1. In these patients, 
workup in magnetic resonance imaging is often necessary as patients with structural lesions have a 
much higher rate of seizures, ranging from 10% to 26% at 1 year and from 29% to 48% at 5 years2,3. 
However, there is also a subgroup of patients who has epilepsy not adequately controlled by anti-
epileptics with unrevealing first MRI study, a dedicated MRI protocol may reveal positive lesion in 
30-65% of the cases2,4-6. In these patients, several tricks can be applied to increase the detection 
rate. First, the used of a high-resolution MRI on a high-field scanner could be helpful, which can be 
increased the sensitivity up to 90%7. The use of 7T-MRI in further picking up subtle lesions in patients 
presenting with epilepsy has been investigated8, further affirming the role of high resolution MRI 
imaging. Secondly, the use of dedicated sequences, such as T1-weighted inversion recovery 
sequences9 which allow better distinction of grey and white matter, could also reveal subtle lesions 
such as polymicrogyria or Type 1 focal cortical dysplasia.  
Our study is therefore aimed to apply the findings to the local settings, and specifically to investigate 
if T1-weighted inversion recovery sequences provides additional benefit in picking up more subtle 
lesions in patienst who had an initial first negative MRI.  
Reference:  
1. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, 
Mathern GW, Moshé SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM. ILAE 
classification of the epilepsies: Position paper of the ILAE Commission for Classification and 
Terminology. Epilepsia. 2017 Apr;58(4):512-521. doi: 10.1111/epi.13709. Epub 2017 Mar 8. PMID: 
28276062; PMCID: PMC5386840. 
2. Bernasconi A, Cendes F, Theodore WH, Gill RS, Koepp MJ, Hogan RE, Jackson GD, Federico P, Labate A, 
Vaudano AE, Blümcke I, Ryvlin P, Bernasconi N. Recommendations for the use of structural magnetic 
resonance imaging in the care of patients with epilepsy: A consensus report from the International 
League Against Epilepsy Neuroimaging Task Force. Epilepsia. 2019 Jun;60(6):1054-1068. doi: 
10.1111/epi.15612. Epub 2019 May 28. PMID: 31135062. 
3. Krumholz A, Wiebe S, Gronseth GS, et al. Evidence‐based guideline: management of an unprovoked 
first seizure in adults: report of the Guideline Development Subcommittee of the American Academy 
of Neurology and the American Epilepsy Society. Neurology. 2015;84:1705–13 
4. Kokkinos V, Kallifatidis A, Kapsalaki EZ, Papanikolaou N, Garganis K. Thin isotropic FLAIR MR images at 
1.5T increase the yield of focal cortical dysplasia transmantle sign detection in frontal lobe epilepsy. 
Epilepsy Res. 2017;132:1–7. 
5. Mellerio C, Labeyrie MA, Chassoux F, et al. 3T MRI improves the detection of transmantle sign in type 
2 focal cortical dysplasia. Epilepsia. 2014;55:117–22. 
6. Knake S, Triantafyllou C, Wald LL, et al. 3T phased array MRI improves the presurgical evaluation in 
focal epilepsies: a prospective study. Neurology. 2005;65:1026–31. 
7. Ahmed R, Rubinger L, Go C, Drake JM, Rutka JT, Carter Snead O, Widjaja E. Utility of additional 
dedicated high-resolution 3T MRI in children with medically refractory focal epilepsy. Epilepsy Res. 
2018 Jul;143:113-119. doi: 10.1016/j.eplepsyres.2018.01.002. PMID: 29398181. 
8. De Ciantis A, Barba C, Tassi L, Cosottini M, Tosetti M, Costagli M, Bramerio M, Bartolini E, Biagi L, 
Cossu M, Pelliccia V, Symms MR, Guerrini R. 7T MRI in focal epilepsy with unrevealing conventional 
field strength imaging. Epilepsia. 2016 Mar;57(3):445-54. doi: 10.1111/epi.13313. Epub 2016 Jan 18. 
PMID: 26778405. 
9. Hou P, Hasan KM, Sitton CW, Wolinsky JS, Narayana PA. Phase-sensitive T1 inversion recovery 
imaging: A time-efficient interleaved technique for improved tissue contrast in neuroimaging. AJNR 
Am J Neuroradiol. 2005;26:1432–8. 
 

3 
Study protocol (version 1.1), 18 Aprial 2024  
Study protocol 
This study will be a prospective cohort model comparing baseline MRI and high-resolution MRI in 
delineation of focal abnormalities accounting for epilepsy.  
 
Patient recruitment 
Inclusion: Consecutive patients with drug-resistant focal epilepsy fulfilling the following criteria –  
1. Diagnosis of focal epilepsy with a probable site identified, as defined by concordant results from 
any TWO of the following:  
- 
Clinical seminology compatible with focal epilepsy.  
- 
Electroencephalopathy pointing towards a specific site for focal epilepsy.  
- 
Postive ictal brain scintigraphy with SPECT-CT correlation. 
AND  
2. Previous MRI (at least one study with protocol tailored for epilepsy) which did not reveal 
accountable focal lesion.  
AND  
3. Able to consent for MRI examination (if patient under age of 18, consent for MRI will be 
obtained from guardian). Patients will be provided information leaflets to read on, and written 
consent before taking part in this study and MRI examination.  
 
Exclusion:  
- 
Patients who are contraindicated to magnetic resonance imaging (such as due to underlying 
MRI incompatible metallic implants) 
- 
Patients who cannot cooperate for MRI scanning.  
- 
Patients show are unable to provide informed consent.  
 
Sample size calculation 
There is no previous studies available specifically on the use of inversion recovery sequences.  
Based on previous paper by deSantis et al. with use of 7T MRI the pickup rate of MRI on patients 
with preivous negative MRI would be around 30%. We prudently estimate that as the current MRI, 
the pick up rate would be lower than an even-higher resolution 7T MRI and approximately at half of 
previous study quoted (i.e. 15%), and a 5% false negative rate on patients who actually had lesions 
on previous baseline MRI. With a 80% statistical power and two-tail alpha = 0.05, approximately 22 
patients who needs to have both MRI done and undergone surgery. And assuming that only 1/3 of 
patients who had workup will undergo surgery, approximately 66 patients are required.  
 
MRI scanning 

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Study protocol (version 1.1), 18 Aprial 2024  
Patient will be scheduled to be scanned at the Siemens Prisma 3T MRI scanner at MRI facility, the 
Chinese University of Hong Kong. The scanning protocol consists of the following staple sequences 
for evaluation of focal epilepsy:  
- 
Axial, Coronal and Sagittal (left and Right) 2D T1-weighted inversion recovery sequences 
focusing on site of lesion.  
- 
3D FLAIR T2-weighted MRI whole brain with multi-planar reconstruction (MPR).  
- 
3D T1-weighted Sagittal MPRAGE (Magnetization Prepared - RApid Gradient Echo) with 
MPR.  
 
The following sequences will be applied optionally depending on the site of clinical suspicion and 
whether dedicated mapping will be required:  
- 
Diffuse tensor imaging of whole brain (DTI)  
- 
Functional MRI (fMRI) for mapping of specific cortical function close to the suspected site of 
lesion.  
- 
Oblique coronal T2-weighted sequences of the hippocampus if suspected hippocampal 
sclerosis.  
- 
Thin-cut dedicated T2-weighted or proton-density weighted images.  
 
Contrast injection is usually not required unless otherwise clinically needed (e.g. for scanning of 
additional clinical inidcations).  
The basic sequences will take approximately 30minutes, and the optional sequences (if needed) 
would be variable, the whole protocol will be completed within 1 hour.  
All high-resolution MRIs performed under this study will be reported by board-certified radiologist 
and be available on patient’s electronic health records (ePR).  
 
Image interpretation 
The baseline MRI of the patients will be retrospectively reviewed, while the MRI performed in this 
study will also be reviewed by two different radiologists. Radiologists are not blinded to the clinical 
history and site of clinical suspicion but are blinded to the subsequent surgical findings and 
outcomes.  
The localization of the site of epilepsy will be pointed out according to a five-point confidence scale 
(1: very unlikely, 2: unlikely, 3: equivocal/ suspicious, 4: likely, 5: highly likely).  
A likelihood score of 3 or above would indicate a positive imaging study.  
 
Statistical analysis protocol 
The primary outcome of the study is the sensitivity and specificity of the baseline MRI (bMRI) and 
the high-resolution MRI (hrMRI) studies, based on the standard of surgical findings on patients who 
underwent either intracranial EEG or surgical resection. Each of the sensitivity and specificity of the 

5 
Study protocol (version 1.1), 18 Aprial 2024  
two tiers of MRI studies (baseline MRI and high-resolution MRI) will be compared with use of 
contingency table and chi-square test.  
The secondary outcomes would include the following:  
- 
Number of cases with true positive, and false positive findings on bMRI or hrMRI; and 
descriptive statistics of findings in patients who had MRI but did not undergo surgery.  
- 
Inter-observer and Intra-observer agreement for findings on bMRI or hrMRI by kappa 
statistics.  
 
Handling and Storage of personal data 
Images of MRI sequences with multiplanar reconstruction will be uploaded to patient's electronic 
patient records for clinical use, as well as purpose of surgical navigation planning by co-investigators 
performing operation. The research sequences will be stored in the database, while study images 
and reports will be available in the patient’s electronic patient records.   
All MRI scans will be stored in the picture archiving and communication system of Gerald Choa 
Neuroscience Center/ Prince of Wales Hospital. These images can be viewed on HA clinical 
workstations for the purpose of providing clinical care. Radiologist with training in Head and Neck or 
Neuroradiology will issue a formal radiology report regrading in the examinations, the report will be 
available on the ePR system.  
The MRI data will be anonymized and encrypted before research analysis, which will also be done in 
HA clinical workstations. MRI scan data after anonymization will be stored in CUHK MRI data 
repository, with only non-identifiable patient particulars (age, sex, disease status) retained 
(informed consent obtained from patient prior to scanning). Use of selected images for publication 
purposes will be anticipated, patient particulars will be removed prior to exporting from HA clinical 
workstations.  
 
Compliance with Guidelines of Good Clinical Practice by International conference on 
harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH-
GCP) and Declaration of Helsinki 
This clinical trial is conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory 
requirement(s). 
This trial offers additional diagnostic benefit without known added clinical risk on top of usual 
clinical care. The rights, safety, and well-being of the trial subjects are the most important 
considerations and will be prevailed in the current study. No non-clinical use of product is involved in 
this study. The radiological examination subjects underwent are provided by qualified medical 
practitioners with adequate training in radiology.  
All clinical trial information should be recorded, handled, and stored in a way that allows its accurate 
reporting, interpretation and verification.