MULTIMODAL MRI AND OVERALL DIAGNOSTIC ACCURACY IN NON-ENHANCING BRAIN

GLIOMAS

S. Gaudino, V. Lorusso, M. Caulo *, A. Tartaro *, T. Tartaglione, G.M. Di Lella, C. Colosimo

Dept. of Bio-imaging and Radiological Sciences, Policlinico “A. Gemelli” Catholic University of Rome – ITALY*ITAB - Istituto di Tecnologie Avanzate Biomediche,“G. d’Annunzio” University, Chieti-Pescara – ITALY

simona.gaudino@rm.unicatt.it

Introduction

Gliomas account for more than 70% of primary brain tumors and they present considerably heterogeneous neuropathological, genetic and clinical feature

WHO grade II and III gliomas represent a heterogeneous group of tumors, also regarding their potential of malignant transformation

With conventional MRI the assessment of gliomas grade may be limited, potentially affecting therapeutic decision making

Contrast enhancement reflects only disruption of the blood-brain-barrier (BBB) and not tumor angiogenesis

In fact 14-45% of non-enhancing supratentorial gliomas are malignant and 20% of low grade gliomas enhance after gadolinium (e.g. pilocytic astrocytomas)

Introduction

These limits could be overcome by integrating morphological information with “functional” MR techniques

Diffusion WI: information on lesion cellular content Perfusion WI: degree of perfusion generally reflects

the degree of microvascularity or neovascularity (angiogenesis) of the tumoral lesion

MR Spectroscopy: information related to the metabolic aspects of the tumor

J Magn Reson Imaging (1999) 9:53–60 Neuroradiology (2008) 50:759–767Neuroradiology (2002) 44:371–381

Purpose

The aim of this study was to assess the contribution of diffusion weighted imaging (DWI), perfusion weighted imaging (PWI) and magnetic resonance spectroscopy (MRS) to the diagnostic work-up of Non-Enhancing Gliomas (NEGs)

Materials and methods We reviewed MRI studies of 31 Patients with

histopathologically confirmed brain gliomas with no CE on MRI, collected from two Italian University Hospitals

Only 22 Pts who have not undergone chemotherapy or radiotherapy before MRI examination were included in the study (15 males, 7 females; age range 19 to 81 year; mean ages 46.6 years)

13 Patients were studied with a 1.5 T and 9 with a 3 T system, using pre-contrast conventional MRI and multi-planar post-Gd T1-w images

All pts underwent DWI (b 0-1000) and PWI (dynamic first-passage gadolinium-enhanced gradient-echo sequence)

12 pts underwent MRS (MV, TE 144)

Materials and methods Two neuroradiologists evaluated for each lesions: signal intensity,

margins, the presence of cysts, hemorrhage, edema ROI, varying from 20 mm2 to 60 mm2, were positioned in the area of

maximum and minimum signal intensity (SI) on T2-w images. In these area ADC values, rCBV and rMTT values were calculated. Minimum ADC value and highest rCBV values were also measured. Cho/Cr (area and height), Cho/NAA (area and height) , Lip/Cr (height), Lac/Cr (height) were measured in the focus of highest rCBV

rCBV, rMTT and ADC normalized between tumor and healthy tissue

Pts were divided in two group: LGG and HGG All data obtained were summarized as the mean ± standard deviation Statistical analysis: Student t-test, chi-squared test, ROC curves (SPSS

version 19, MedCalc v10.2)

Materials and methodsSampling areas

The highest (1) and lowest (2) area of signal intensity on T2 FSE axial image

The ADC value in these two areas The area of lowest ADC value (3)

The rCBV and rMTT values of areas 1, 2 and 3 and the values of highest CBV (and its relative MTT) within the lesion (4)

1 2

Signal intensity values

12

3

ADC values

1

23

4

CBV, MTT values

On the area 4 we calcolated Cho/Cr (area and height), Cho/NAA (area and height) , Lip/Cr (height), Lac/Cr (height)

Results-1Of 22 gliomas : 13 Astro: 9 WHO grade II, 4 WHO grade III 9 ODG: 8 WHO grade II, one WHO grade III

In total : 17 grade II and 5 grade III

Morphological assessment: SI was homogeneous in 10 pts (8grade II, two grade III), Margins were ill-defined in most of the gliomas (16/22),

edema was evident in 6 lesions Only one lesion showed cystic component and one

necrosis (both grade II)

Age Histology GradeSignal

Intensity Margin CystNecro

sisHemorrh

age Edema27 Astro II WHO L Homogen Ill-def 0 0 0 038 Astro II WHO L Homogen Well-def 0 0 0 071 Astro II WHO L Homogen Ill-def 0 0 0 033 Astro II WHO L Inhomogen Well-def YES 0 0 024 Astro II WHO L Inhomogen Ill-def 0 0 0 060 Astro II WHO L Homogen Ill-def 0 0 0 032 Astro II WHO L Inhomogen Ill-def 0 0 0 027 Astro II WHO L Homogen Well-def 0 0 0 019 Astro II WHO L Homogen Well-def 0 0 0 YES59 ODG II WHO L Inhomogen Ill-def 0 0 0 YES31 ODG II WHO L Inhomogen Well-def 0 0 0 060 ODG II WHO L Inhomogen Ill-def 0 0 0 029 ODG II WHO L Homogen Ill-def 0 0 0 YES62 ODG II WHO L Inhomogen Ill-def 0 0 0 068 ODG II WHO L Homogen Ill-def 0 0 0 YES70 ODG II WHO L Inhomogen Ill-def 0 YES 0 YES47 ODG II WHO L Inhomogen Ill-def 0 0 0 039 Astro III WHO H Inhomogen Ill-def 0 0 0 YES43 Astro III WHO H Homogen Ill-def 0 0 0 078 Astro III WHO H Inhomogen Ill-def 0 0 0 058 Astro III WHO H Homogen Well-def 0 0 0 039 ODG III WHO H Inhomogen Yes 0 0 0 0

Results-1

HistologyrCBV in Low T2

rCBV in High T2

rCBV in Low ADC

ADC in Low T2

Astro II WHO 0,48 0,48 0,48 1,31Astro II WHO 2,20 2,20 2,20 1,48Astro II WHO 1,00 1,00 1,00 1,14Astro II WHO 1,69 0,77 1,69 1,26Astro II WHO 2,06 0,74 2,06 1,12Astro II WHO 0,35 0,35 0,35 0,82Astro II WHO 1,40 1,06 1,44 1,00Astro II WHO 0,42 0,42 0,42 0,00Astro II WHO 0,67 0,67 0,67 1,60ODG II WHO 1,80 0,69 0,92 1,25ODG II WHO 1,30 1,05 1,14 1,50ODG II WHO 1,70 1,27 1,67 1,18ODG II WHO 1,06 0,97 1,06 1,35ODG II WHO 1,20 1,13 1,33 1,00ODG II WHO 0,13 0,32 0,13 2,00ODG II WHO 2,60 1,33 2,60 1,02ODG II WHO 0,61 0,70 0,65 1,17Astro III WHO 1,70 0,11 1,88 1,60Astro III WHO 1,14 1,14 1,14 0,88Astro III WHO 2,01 0,29 2,01 1,06Astro III WHO 4,26 4,26 4,26 1,06ODG III WHO 1,64 0,52 1,10 1,32

Average 1,43 0,98 1,37 1,18Average II WHO 1,22 0,90 1,17 1,24Average III WHO 2,15 1,26 2,08 1,03

The average rCBV was: in the areas of low T2 SI =1,42 In the areas of high T2 SI = 0.98 In the areas of low ADC =1,37

ADC values in areas of low T2 SI =1,18

grade II: rCBV low T2 SI =1,22 high T2 SI = 0,90 low ADC =1,17ADC= 1.24

grade III: rCBV low T2 SI =2,15 high T2 SI = 1,25 low ADC =2,08ADC= 1.03

Results-2Histology

Cho/Cr area

Cho/NAA area

Cho/Cr height

Cho/NAAheight Lip/Cr height

Lac/Cr height

Astro II WHO 1,39 1,44 1,31 1,52 0,07 0,05Astro II WHO 1,35 0,93 1,11 1,08 0,06 0,06Astro II WHO 3,25 4,73 4,20 1,36 4,20 Astro II WHO Astro II WHO Astro II WHO 2,14 1,39 1,56 1,29 0,08 0,04Astro II WHO 1,63 1,25 1,73 2,07 0,06 0,04Astro II WHO 3,24 2,14 2,49 2,59 0,15 0,03Astro II WHO 1,49 1,31 1,43 1,98 0,35 0,03ODG II WHO ODG II WHO ODG II WHO 1,65 0,82 1,25 1,40 0,07 0,05ODG II WHO ODG II WHO ODG II WHO 1,48 2,34 1,13 2,25 0,05 0,04ODG II WHO 3,14 3,17 2,05 3,93 0,69 0,02ODG II WHO 4,19 4,93 2,98 4,36 0,25 0,14Astro III WHO Astro III WHO Astro III WHO Astro III WHO 1,67 10,53 1,67 3,10 1,36 0,07ODG III WHO

Average 2,22 2,91 1,91 2,24 0,62 0,05Average II WHO 2,27 2,22 1,93 2,17 0,55 0,05Average III WHO 1,67 10,53 1,67 3,10 1,36 0,07

Results-3Between grade II and grade III gliomas The difference in age and gender is not statistically significant There are no significant differences for signal intensity, cysts, necrosis,

hemorrhages or edema There was a significant difference in rCBV between grade II and III

(comparing all gliomas grade II vs III, and between ODG II and Astro III) in the areas of low T2 and low ADC

When SI was inhomogeneous in 12/12 pts the lowest ADC value resulted in the area of low T2 SI

Regarding MRS: the only variable that gave a significant p was Cho/NAA (area) but only one subject was in the high grade group

GROUPSrCBV in T2 Low

rMTT in T2 Low

rCBV in T2 High

rMTT in T2 High

rCBV in Low ADC

rMTT in Low ADC

Astro II/ODG II 0,330897775 0,278399498 0,348170405 0,338972 0,45354292 0,289554

Grade II vs III 0,020814802 0,353588683 0,208954425 0,355797 0,024443249 0,354925

ODG II vs Astro III 0,067583759 0,467230475 0,234793326 0,382297 0,041047381 0,447417

Results-3

Criterion Sensitivity 95% CI Specificity 95% CI +LR -LR>1.06 * 100.00 48.0 - 100.0 47.06 23.0 - 72.1 1.89 0.00

Criterion Sensitivity 95% CI Specificity 95% CI +LR -LR>1.06 * 100.00 48.0 - 100.0 47.06 23.0 - 72.1 1.89 0.00

An high probability for a gliomas to be a high-grade lesion was associated with a rCBV tumor/normal tissue ratio of >1.89 both in low T2 SI and low ADC

Case-1M 33 ys

L-deep lesion. Inhomogeneous SI, well-defined margins, cystic component

DWI,PWI, MRS deponed for LGG

Astro II

Case-2M 44 ys

ODG II

L-frontal lesion. Inhomogeneous SI, necrosis, ill-defined margins

Areas of low ADCHigh rCBVNo MRS

Case-3M 70 ys

R-parietal lesion. Inhomogeneous SI, ill-defined margins, necrosisPWI MRS deposed for HGG

T2-Cho/Cr(A) T2-Cho/NAA(A)T2-Cho/Cr(H) T2-Cho/NAA(H) T2-Lip/Cr(H) T2-Lac/Cr(H)

3,136 3,166 2,046 3,930 0,690 0,022 ODG II

Astro grade II with foci of grade III

Case-4M 43 ys

Conclusions The lack of contrast enhancement on MR studies of brain

gliomas does not always couple with a low grade tumor, and up to 25% of HGG are faintly or completely non-enhancing

Accurate tumor grading is essential for a rational therapeutic approach

In conventional MR imaging, reported values for accurate grading of gliomas varies from 55% to 83.3%*

DWI, PWI, and MRS provide useful data for tumor evaluation and grading

Neuroradiology (1994) 36:308–310

Our case series confirmed the correspondence between low T2 SI, low ADC values and increased rCBV within inhomogeneous gliomas

In grade III ADC values were slightly lower respect to grade II, without a threshold value to separate grade II from grade III lesions

The relevance of increased Cho/NAA (area) in HGG undoubtedly needs further investigation

Our results suggest that rCBV measurement may be more accurate than DWI and MRS in the identification of high-grade gliomas

Doubtless, the combination of PWI, DWI and MRS with conventional MRI increases the diagnostic accuracy in differentiating high from low-grade NEGs

Conclusions

Thank You for Your attention

Our acknowledgments to P Mattei & C Schiarelli MD