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Clinical Research
DOI: 10.1016/j.neucir.2018.06.004
Perfusion MRI grading diffuse gliomas: Impact of permeability parameters on molecular biomarkers and survival
Utilidad de la RM perfusión en la gradación de los gliomas difusos: relación entre parámetros de permeabilidad, marcadores moleculares y supervivencia
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Amaya Hilarioa,
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amayahilario@yahoo.es

Corresponding author.
, Aurelio Hernandez-Lainb, Juan Manuel Sepulvedac, Alfonso Lagaresd, Angel Perez-Nuñezd, Ana Ramosa
a Department of Radiology, Neuroradiology Section, Universitary Hospital 12 de Octubre, Madrid, Spain
b Department of Neuropathology, Universitary Hospital 12 de Octubre, Madrid, Spain
c Department of Medical Oncology, Universitary Hospital 12 de Octubre, Madrid, Spain
d Department of Neurosurgery, Universitary Hospital 12 de Octubre, Madrid, Spain
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Received 20 December 2017, Accepted 01 June 2018
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Table 1. Results of the correlation study performed between DSC and DCE perfusion parameters.
Table 2. ROC curve analysis of permeability parameters for differentiation between high- and low-grade gliomas.
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Abstract
Background and purpose

Our objectives were: (1) compare dynamic susceptibility-weighted (DSC) and dynamic contrast-enhanced (DCE) permeability parameters, (2) evaluate diagnostic accuracy of DSC and DCE discriminating high- and low-grade tumors, (3) analyze relationship of permeability parameters with overall (OS) and progression-free survival (PFS) and (4) assess differences in high-grade tumors classified according to molecular biomarkers.

Materials and methods

49 patients with histologically proved diffuse gliomas underwent DSC and DCE imaging. Parametric maps of cerebral blood volume (CBV), CBV-leakage corrected, volume transfer coefficient (Ktrans), fractional volume of the extravascular extracellular space (EES) (Ve), fractional blood plasma volume (Vp) and rate constant between EES and blood plasma (Kep) were calculated. High-grade gliomas were also classified according to isocitrate dehydrogenase (IDH), alpha-thalassemia/mental retardation syndrome X-linked (ATRX) and O6-methylguanine-dna-methyltransferase promoter methylation (MGMT) status.

Results

There is correlation between parameters leakage, Ktrans and Vp. ROC curve analysis showed significance in both Ktrans and Ve for glioma grading. Threshold value of 0.075 for Ve generated the best combination of sensitivity (80%) and specificity (75%) in tumor gradation. Leakage was the only permeability parameter related to OS (P=0.006) and PFS (0.012); with prolonged survival for leakage values lower than 1.2. IDH-mutated high-grade tumors showed lower leakage and Ktrans values. High-grade tumors with loss of ATRX presented lower leakage and Vp values.

Conclusions

Both DSC and DCE permeability parameters serve as non-invasive method for glioma grading. Leakage was the unique permeability parameter related to survival and the best discriminating high-grade gliomas classified according to IDH and ATRX status.

Keywords:
Brain
Glioma
Neoplasms
Perfusion
Permeability
Abbreviations:
ATRX
AUC
CBV
DCE
DSC
DWI
EES
HR
IDH
IQR
Kep
Ktrans
MGMT
MRI
OS
PFS
ROC
ROI
Vp
Ve
WHO
Resumen
Introducción y objetivos

1) Evaluar la utilidad de los parámetros de permeabilidad para clasificar gliomas de alto y bajo grado; 2) Analizar diferencias de permeabilidad de glioblastomas clasificados según marcadores moleculares; 3) Analizar la relación de la permeabilidad con la supervivencia global (SG) y libre de progresión (SLP), y 4) Comparar parámetros de perfusión T1 y T2*.

Material y métodos

Cuarenta y nueve pacientes con gliomas difusos confirmados histológicamente fueron estudiados con perfusión T1 y T2*. Calculamos los mapas paramétricos del volumen sanguíneo cerebral (CBV), CBV-leakage corregido, constante de permeabilidad (Ktrans), fracción de volumen vascular (Vp), fracción de volumen del espacio intersticial (Ve) y coeficiente de extracción (Kep). El análisis histológico se basó en criterios OMS 2007 y los glioblastomas se clasificaron según mutación de genes isocitrato deshidrogenasa (IDH), Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) y metilguanidina-ADN metiltransferasa (MGMT).

Resultados

Incluimos 28 varones y 21 mujeres (16-78 años). Los gliomas se clasificaron en 41 tumores de alto grado y 8 de bajo grado. Leakage se correlacionó con SG y SLP; y mostró correlación lineal con Ktrans y Vp. Los gliomas de alto y de bajo grado mostraron diferencias en los valores de leakage, Ktrans, Vp y Ve. Leakage fue el parámetro que mejor discriminó los glioblastomas clasificados según mutación IDH y ATRX.

Conclusión

La perfusión T1 y T2* sirven para clasificar a los gliomas difusos en función del grado tumoral. Leakage se relaciona con la SG y SLP y es el parámetro que mejor discrimina glioblastomas clasificados en función de IDH y ATRX.

Palabras clave:
Cerebro
Gliomas
Neoplasias
Perfusión
Permeabilidad

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