Tag Archives: MRI

Progress in Imaging Epilepsy

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Magnet resonance imaging (MRI), is frequently used, along with other data, to generate a diagnosis of epilepsy.   The MRI is a noninvasive imaging tool that scans the structure of the whole brain to identify abnormalities.  The MRI, alone, gives no information on physiological and pathological functions, only structure.  Fortunately, adjuncts and variants of the MRI and related techniques used to image epilepsy record changes in biological function.  Progress in imaging epilepsy improve diagnostic accuracy as well as expand understanding of epilepsy.  This blog will discuss progress in imaging epilepsy.

Progress in Imaging Epilepsy – MRI-related

MRI dependent imaging include 1) functional MRI and associated improvements,  2) diffusion MRI and 3) 1H-magnetic resonance spectroscopic imaging (MRSI).   The original MRI, using magnetic fields, detects subtle changes in brain structure, e.g. volume and contour differences in neuronal clusters particularly when newer technical adjustments are utilized (1).  Thus MRI imaging successfully identified differences in brains of normal individuals and those with temporal lobe epilepsy (1).  It is equally useful in detecting tumors and areas of traumatic brain injury.

1)  Functional MRI and advancements. 

The functional MRI (fMRI), a variant of the MRI, is also a non invasive technique.  It tracks blood oxygen levels in the brain.  The method relies on the observation that active neurons (e.g. those involved in brain-related activities such as thinking) consume more oxygen than quiescent neurons.  Thus, areas of high blood oxygen use pinpoint sites of activated functional neurons.  This technique succeeded in mapping areas involved in cognition, stress, and emotions (1).  Therefore, combining an EEG with a fMRI improves location of epileptogenic neurons triggering and supporting a seizure.  Such information is especially important in ablation surgery for drug-resistant patients with severe epilepsy (1).  fMRI is successfully used to follow the path of propagation of the seizure throughout the brain, providing evidence on how one part of the brain influences another during epilepsy progression (1).

2)  Diffusion-weighted MRI/Diffusion Tensor MRI.  

These imaging techniques measure tissue water movement in cells and surrounding space in the brain.  Each technique does it slightly differently with the oldest of the two as the diffusion-weighted MRI (3).  These techniques are advantageous in the diagnosis of pediatric epilepsy (4) and assessment of acute stroke(3) .  Research results using this imaging track and define the connectivity between neurons during brain-related activities, expanding knowledge of brain physiology (3).

3)  1H-magnetic resonance spectroscopic imaging (MRSI).

This is an old technique that is generating renewed interest due to its enhanced magnetic resonance sensitivity (5).  MRSI detects substances whose molecular components contain high amounts of 1H protons.  The main substances are N-acetyl-aspartate (NAA), creatine, and choline.  Results of numerous studies show that the ratio of NAA to creatine provides information on abnormal neuronal activity associated with oxidative stress.  This imaging opens up research on the relation between oxidative stress and neurotransmitters such as GABA (gamma amino butyric acid), a neurotransmitter implicated in epilepsy (5).

Progress in Imaging Epilepsy – Radioactive Imaging.

In contrast to the MRI, PET and SPECT are invasive imaging methods that inject radioactive substances to study brain activity in disease.

1)  PET stands for Positron Emission Tomography.

This imaging technique employs a positron emitting chemical (tracer) such as a radioactive variant of glucose (fluorodeoxyglucose).  Active neurons and auxiliary cells take up the sugar thus highlighting an area of brain activity.  This is used to identify tumors which are more metabolically active than normal tissue.  PET is also valuable in tracing blood flow in metabolic regions during a seizure.  While capture of a seizure during a PET scan is rare, measurement of activity between seizures is more likely and provides important information.  Here, areas of low metabolism (hypometabolism) indicate sites of epileptic origin and are useful aids in surgical ablations (1).

The PET also uses radioactive analogues of neurotransmitters to uncover changes in brain receptor activity in epilepsy (6).  Additionally, PET imaging reveals an increase in a specific marker of brain inflammation, the translocator protein (TSPO).  TSPO is elevated in epilepsy (7).  Its elevation indicates that auxiliary cells (glial cells) are active and contributing to brain inflammation (8).  See earlier blog on the role of inflammation in epilepsy (Neuroinflammation of Epilepsy – new diagnostic tools)

2)  SPECT stands for Single photon emission computed tomography. 

This  imaging technique is similar to PET but differs in that the radioactive tracers emit a different type of radiation.  Gamma rays are detected by SPECT.  For epilepsy diagnosis, SPECT is used secondarily to PET (9).  It is considered important for surgical candidates with drug resistant epilepsy in which no structural lesions are found.  This technique is highly successful in localization of  the site of seizure origin in pediatric epilepsy (10).

Progress in Imaging Epilepsy – Magnetoencephalography

Magnetoencephalography (MEG) differs radically from the above discussed techniques.  Specifically, it does not use magnetism or radioactivity to “shake up or interact with” with molecules in brain to define structure and function (11).  Rather, the MEG detects magnetic fields generated or given off from nerves after they transmit their signal (termed postsynaptic activity).  Because magnetic waves are received without distortion, the location of epileptogenic foci are more accurately identified.   MEG is considered an advanced version of the EEG.  Similar to the EEG, it is non invasive.  However, the EEG records electrical activity without the ability to assign origin to such activity.  In contrast, the MEG accurately locates the origin of abnormal nerve activity.  MEG associated with PET or MRI data is of great assistance in surgical ablations for severe epilepsy (11).  Additionally, findings from this technique suggest the existence of connectivity between several areas of the brain during seizures, expanding understanding of the complexity of epilepsy (1).  

Conclusions

This blog describes a number of sophisticated imaging techniques and methods used to assist with the diagnosis of epilepsy, illustrating progress in imaging epilepsy.  These include variations of the classic MRI, radioactive imaging and an upgraded version of the EEG.  The majority of these methods provide critical data to pinpoint epileptogenic foci for surgical ablations in cases of drug-resistant severe epilepsy.  Although accessed less frequently for research, the insights that have been gained thus far are invaluable.   These techniques offer potential for deeper understanding of the pathology of epilepsy and hence better therapy and a possible cure.

References http://pubmed

1.  Goodman AM, Szaflarski JP. Recent Advances in Neuroimaging of Epilepsy.  Neurotherapeutics. 2021 Apr;18(2):811-826. doi: 10.1007/s13311-021-01049-y.

2.   Chang C, Huang C, Zhou N, Li SX, Ver Hoef L, Gao Y. The bumps under the hippocampus. Hum Brain Mapp . 2018 Jan;39(1):472-490.  doi: 10.1002/hbm.238563. 

3.  Ranzenberger LR, Das JM, Snyder T.  Diffusion Tensor Imaging  StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. 2023 Nov 12.

4   Szmuda M, Szmuda T, Springer J et al., Diffusion tensor tractography imaging in pediatric epilepsy – A systematic review.  Neurol Neurochir Pol . 2016;50(1):1-6.  doi: 10.1016/j.pjnns.2015.10.003. 

5 Pan JW, Kuzniecky RI Utility of magnetic resonance spectroscopic imaging for human epilepsy. .Quant Imaging Med Surg. 2015 Apr;5(2):313-22. doi: 10.3978/j.issn.2223-4292.2015.01.036.

6.  Sarikaya I. PET studies in epilepsy.  Am J Nucl Med Mol Imaging. 2015 Oct 12;5(5):416-30. eCollection 2015.

7.  Galovic, M, Koepp, M. Advances of molecular imaging in epilepsy. Curr Neurol Neurosci Rep  2016 Jun;16(6):58.  doi: 10.1007/s11910-016-0660-7.

8.  Zhang L, Hu K, Shao T, Hou L, Zhang S, Ye W, Josephson L, Meyer JH, Zhang MR, Vasdev N, Wang J, Xu H, Wang L, Liang SH Recent developments on PET radiotracers for TSPO and their applications in neuroimaging.  .Acta Pharm Sin B. 2021 Feb;11(2):373-393. doi: 10.1016/j.apsb.2020.08.006.

9.  Cendes F, Theodore WH, Brinkmann BH, Sulc V, Cascino GD.Neuroimaging of epilepsy. Handb Clin Neurol. 2016;136:985-1014. doi: 10.1016/B978-0-444-53486-6.00051-X.

10.  Juhász C, John F.Utility of MRI, PET, and ictal SPECT in presurgical evaluation of non-lesional pediatric epilepsy.Seizure. 2020 Apr;77:15-28. doi: 10.1016/j.seizure.2019.05.008. 


11.  Pan R, Yang C, Li Z, Ren J, Duan Y. Magnetoencephalography-based approaches to epilepsy classification.  Front Neurosci. 2023 Jul 12;17:1183391. doi: 10.3389/fnins.2023.1183391

Assessment 7 – Value of Diagnostics for Epilepsy

Diagnostics, , , ,

Epilepsy is a disease defined by the presence of two or more seizures, separated by more than 24 hours.  However, in order to identify the appropriate anti-seizure drug for seizure suppression, a diagnosis of epilepsy is more complicated than the definition implies.  There are 4 sources of potentially valid information that together should yield the most accurate diagnosis.  The diagnostics for epilepsy are:

a) seizure history provided by the patient;

b) digital data from an electroencephalogram (EEG) which records seizure activity or, in the absence of a seizure, the presence of abnormal discharges;   

c) analysis from magnetic resonance imaging (MRI) showing presence of a tumor, scar tissue, or abnormal anatomical lesions related to site of seizure origin;

d) genetic assessment matching one or more of the known genetic errors associated with specific types of epilepsy.

What is the value of the information gathered from these sources?

1. Seizure History

Seizure history is important but can be lacking in specifics.  This is because many patients have little to no recollection of their seizures.  This starting point for a diagnosis is not particularly helpful in identifying the epilepsy type and thus, it is not helpful at all in selection of the appropriate antiseizure medication.

2.  EEG

The EEG was developed over a century ago.  Electrodes, placed on the scalp, record summated electrical activity primarily from the outer portion of the brain (the cortex).  Electrodes are precisely positioned to receive defined recognizable brain wave activity.  The EEG recording itself generally takes 20 minutes but considerable time is required to position the electrodes and also to remove them.  During the actual recording, procedures such as light stimulation or hyperventilation are used to “evoke” a seizure.

Advantages of diagnostics for epilepsy: 

Whereas the EEG usually does not record a seizure in progress, its ability to detect abnormal discharges, (called interictal epileptogenic discharges or IEDs), is significant because the presence of IEDs have been found to signal a high risk of having a future seizure.  The EEG many record local IEDs (expressed in one hemisphere) or general IEDs (expressed in the entire brain). This information contributes to a more accurate diagnosis and hence is one clear benefit of the EEG.  Additionally, the EEG is helpful in monitoring the progress of seizure suppression with drugs or surgery. Anti-seizure drugs has previously been discussed (Assessment 6 – Epilepsy Medication – Need to Know Information)

Limitations of Diagnostics for Epilepsy: 

As revealed by years of intracranial recording (surgical implantation of electrodes) in patients with epilepsy, it is apparent that the EEG has limitations.  Its short duration, lack of sensitivity and tendency for over interpretation are some of its limitations.  It has also failed to identify the multiday cyclic nature of epileptic activity. 

The short duration of the EEG test fails to capture the majority of  in-progress seizures and many patients show no evidence of IEDs.  Although in a hospital setting, the EEG may be used continually for several days, this is not routinely practiced.  To avoid obtaining incorrect data, technical expertise is required for electrode placement.  Despite this, sensitivity is diminished due to distance of the electrodes (on the scalp) from the origin of the brain activity (somewhere in the brain) and the inability of electrodes to record all brain wave activity but only a sampling of those reaching the outer layer of the brain.

3.  MRI

The MRI is one of several imaging techniques with success in identifying abnormalities in the brain in persons with epilepsy (see https://medlineplus.gov/mriscans.html ) for details on MRI imaging.  In cases of epilepsies resistant to drug, surgical protocols require prior imaging procedures.

Imaging techniques include the MRI, the positron emission tomography (PET) and MRI spectrometry, to name a few.  The MRI uses magnetic energy to define the location of structures in the brain.  The stronger the magnet, the better the resolution of the individual structures in the brain.  The PET scan adds to the MRI with the use of a radioactive tracer.  This tracer localizes to areas of high metabolism as in tumor or indicates areas of low metabolism as in epileptic lesions.  The MRI spectrometry is a supplemental test only.  It measures brain compounds known to indicate the presence of a seizure lesion.  Abnormal levels of specific compounds add to MRI data of structural changes, pinpointing a epileptic lesion.

Advantages of Diagnostics for Epilepsy: 

The MRI in association with other imaging tools (PET, Spectrometry) provide essential information for epilepsy patients resistant to drug therapy.  These patients may be candidates for surgical therapy.  High quality data from imaging techniques assist with accurate surgery but only facilities with extensive experience in imaging and treating patients whose epilepsy is not suppressed with antiseizure drugs, produce these desired outcomes.

Limitations of Diagnostics for Epilepsy: 

Outpatient use of the MRI technology generally contributes little to the initial diagnosis of epilepsy.  Most clinics lack expertise on recognition of epileptogenic lesions and additionally do not employ the optimal MRI protocols to capture these lesions.  Technologists may also lack the clinical information to alert them to the reason for the MRI and hence fail to seek expert help.  

4.  Genetic Analysis

Epilepsy is considered to have a heritable component.  Identification of the genes involved in epilepsy should provide greater understanding of this disease and lead to better therapy.  The International League Against Epilepsy Consortium on Complex Epilepsies initiated a large analysis (meta-analysis) of the genome (DNA content) of persons with epilepsy compared to controls.  The most recent work (2018) included over 15,000 epilepsy cases and over 29,000 controls.  This study identified 16 different chromosome locations that relate with confidence to epilepsy.  These chromosome positions reveal many genes already associated with epilepsy such as the ion channels on nerve cells but also importantly, many new genes not previously identified as a cause of epilepsy.

Advantages of Diagnostics for Epilepsy: 

Routine genomic testing in epilepsy could be a step closer to precision medicine. Genomic testing would allow for a precise diagnosis, and a more rational selection of anti-seizure medication.  This type of testing opens the door for discovery of novel drugs and has potential to determine exactly which genes play a role in specific types of epilepsy.

Limitations of Diagnostics for Epilepsy: 

Analysis of genomic-wide testing is complicated and the variety of different forms of epilepsy are equally complex.  To date, most of the identified genes are “associated with genetic generalized epilepsy” (ILAE Consortium).  Considerable research commitment will be needed to unravel the genetic influence on epilepsy and then to reveal how the environment interacts with these genes.

Summary

There exists 4 different types of information (patient assessment, EEG, MRI, genetic analysis) that should provide an accurate diagnosis of epilepsy.  Unfortunately, their limitations outweigh their assets.  Thus, a diagnosis of epilepsy may be absent, delayed or incorrect and consequently, antiseizure therapy may be inappropriate.