Joon Yul Choi1, Rasim Boyacioglu2, Stephen Jones3, Ken Sakaie3, Ingmar Blümcke1,4, Imad Najm1, Mark Griswold2, Dan Ma5, and Zhong Irene Wang1
1Epilepsy Center / Neurological Institute, Cleveland Clinic, Cleveland, OH, United States, 2Radiology, Case Western Reserve University, Cleveland, OH, United States, 3Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, 4Neuropathology, University of Erlangen, Erlangen, Germany, 5Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States
Synopsis
We investigate in this study
quantitative T1 and T2 values as potential biomarkers of
tissue properties in epilepsy patients with focal cortical dysplasia (FCD) using
a novel high-resolution 3D magnetic resonance fingerprinting (MRF) technique. We
first investigated the quantitative T1 and T2 values in various
Brodmann areas to verify the sensitivity of MRF in probing tissue properties of
the human cortex. We then investigated the MRF T1 and T2
values in different subtypes of FCD lesions, which were higher than their
corresponding cortical regions in the controls.
INTRODUCTION
Focal cortical dysplasia (FCD) is one
of the most common underlying pathologies for medically intractable epilepsies1.
Although a fair percentage of FCD lesions can be visually appreciated on
conventional MRI, it is challenging to distinguish subtle FCD lesions from normal
brain tissues, partly due to a lack of sensitive and specific MRI measurements.
Recent studies have shown that FCD causes abnormalities in both cyto- and
myelo-architectures of the cortex2,3. Here, we investigated
quantitative T1 and T2 values as potential biomarkers of
tissue properties in epilepsy patients with FCD using a novel high-resolution
3D magnetic resonance fingerprinting (MRF) technique4. We also investigated quantitative T1
and T2 values among Brodmann areas (BA) to test the sensitivity of
MRF variation across the cortex. METHODS
MRI acquisition: A 3D
whole-brain MRF scan was acquired from 10 healthy subjects and 8 patients with
medically intractable epilepsy and histopathologically confirmed FCD (6 FCD type
II and 2 MCD, i.e., malformation of cortical development) in a Siemens 3T
Prisma scanner (FOV=300x300x144 mm3, 1.2 mm3 isotropic
voxel, scan time=10.4 minutes)4,5. T1 and T2
maps were then generated based on the direct matching of the data to a predefined
dictionary4. T1-weighted (T1w) images were synthesized
from the MRF maps. The routine clinical 3D T1w MPRAGE scan was
additionally obtained, followed by the 3D MRF scan.
Cortical maps: The
cortical surface of the MRF T1 map was retrieved using the Freesurfer
pipeline6. In the first step, surface maps of T1w MPRAGE
were generated from “recon all”. Synthesized T1w images from MRF were
co-registered to the T1w MPRAGE images using automatic registration
(bbregister) and manual registration (tkregisterfv). The cortical surface maps
of T1 values were then obtained using the registration information
and mri_vol2surf. The sampling was performed at 2 mm depth from the pial
surface.
MRF values in Brodmann areas:
The synthesized MRF T1w images of patients and normal controls were
segmented into gray matter (GM), white matter (WM) and cerebral spinal fluid (CSF)
using FSL7, and normalized to MNI space using SyN in ANTs8.
The warping information was directly applied to the T1 and T2
maps. The GM masks were applied on the Brodmann atlas (MRIcro)9 to
calculate the average T1 and T2 values for a given BA.
MRF values in FCD lesion:
For the FCD cases, a ROI was drawn for each lesion manually. The same ROIs were
applied to normal subjects to compare the matrices with FCD patients at the
same cortical locations. GM masks were applied on the ROIs to extract the T1
and T2 values of the GM component of the lesions/normal cortices.RESULTS
Figure 1 shows five
representative lateral and mesial surface R1 (1/T1) maps
from five individual control subjects. For better visualization, we plotted R1
maps instead of T1 maps as myelin-rich structure has higher R1
values. Our data clearly visualized a pattern of higher R1 value in the
sensorimotor and visual cortex for all five subjects at an individual level.
Figure
2 shows the mean and standard deviation of the T1 and T2 values
from 11 BA. The quantitative value changes among different regions are in good
agreement with previous literature10. Highlighted are the T1
and T2 values in BAs 3 (primary somatosensory
cortex) and 17 (primary visual), which are lower than those in BAs 8
and 9 (frontal), corresponding to the different cytoarchitecture of these
cortices. BA 29 (retrosplenial) has low T2 value, due to its rich
myelin content.
MRF results on a patient
with FCD type IIa is shown in Figure 3, with arrows indicating the location of
the lesion on the MRF T1w images. Visual inspection of the T1
and T2 maps shows: (1) the anterior aspect of the right superior
temporal gyrus had higher T1 and T2 values compared to the contralateral side (mean
GM T1: lesion=1597 ms and contralateral side=1567 ms, mean GM T2:
lesion=78 ms and contralateral side=72 ms); (2) the T1 map in the lesional
region had “speckled” appearance, which likely came from higher variation
within both the GM and WM components of the lesion (std of GM T1:
lesion=119 ms and contralateral side=111 ms, std of GM T2: lesion=8
ms and contralateral side=7 ms); (3) the MRF T1w image showed
blurring of the GM-WM junction, a typical characteristic for FCD. This patient
underwent stereotactic-EEG, which confirmed seizure onset from the lesion
location. Resection rendered the patient seizure-free (follow up=2 months). Preliminary
analyses from all 8 FCDs showed an increase in T1 of the GM
component of the lesions compared to normal controls (Figure 4). When examining
FCD subtypes, the T1 increase of the lesions was more marked for
patients with MCD (T1 14% higher than normal subjects), and less so
for patients with type II (T1 3% higher than normal subjects). T2
value of the GM component of the lesions increased slightly on a group level.
CONCLUSION
Our results demonstrate
the sensitivity of using multi-parametric MRF results at 3T to differentiate
cortical regions with different cyto- or myelo-architecture. We showed the feasibility
to use the T1 and T2 values obtained from 3D MRF protocol
for characterization of FCD lesions on individual/group levels.Acknowledgements
This study is supported by NIH R01
NS109439.References
[1] Bernasconi
A, Bernasconi N, Bernhardt BC. et al. Advances in MRI for
"cryptogenic" epilepsies. Nat Rev Neurol. 2011;7:99–108.
[2] Lutti A, Dick
F, Sereno MI. et al. Using high‐resolution quantitative mapping of R1
as an index of cortical myelination. Neuroimage 2014;93:176–188.
[3] Waehnert
MD, Dinse J, Schäfer A, et al. A subject‐specific framework for
in vivo myeloarchitectonic analysis using high resolution quantitative
MRI. Neuroimage 2016;125:94–107.
[4] Ma D, Gulani V, Seiberlich
N. et al. Magnetic resonance fingerprinting. Nature. 2013;
14;495(7440):187-192.
[5] Ma D, Jones SE,
Deshmane A. et al. Development of high resolution 3D MR fingerprinting for
detection and characterization of epileptic lesions. J Magn Reson Imaging.
2019; 49(5):1333-1346.
[6] Dale AM, Fischi B,
Sereno MI. Cortical surface-based analysis. Segmentation and surface
reconstruction. Neuroimage. 1999; 9(2):179-194.
[7] Zhang Y, Brady M, Smith, S.
Segmentation of brain MR images through a hidden Markov random field model and
the expectation-maximization algorithm. IEEE Trans Med Imag, 20(1):45-57, 2001.
[8] Avants B and Gee JC. Geodesic
estimation for large deformation anatomical shape averaging and interpolation.
Neuroimage. 2004;23 Suppl 1:S139-50.
[9] Tzourio-Mazoyer
N, Landeau B, Papathanassiou D. Automated anatomical labeling of
activations in SPM using a macroscopic anatomical parcellation of the MNI MRI
single-subject brain. Neuroimage. 2002;15(1):273-289.
[10] Marques
JP, Khabipova D, Gruetter R. Studying cyto and myeloarchitecture of
the human cortex at ultra-high field with quantitative imaging:
R1, R2* and magnetic susceptibility. Neuroimage. 2017;147:152-163.