a. di gaeta, a.a. diano, p. vassallo, e. capobianco, m. muto neuroradiology unit

A. di Gaeta, A.A. Diano, P. Vassallo,

E. Capobianco, M. Muto Neuroradiology unit

A.O.R.N. “A. CARDARELLI” - Napoli

Single voxel spectroscopy in the follow-up of

low grade gliomas

• From january 2003 until november 2009 we studied • 24 low-grade astrocytoma with six years follow-up24 low-grade astrocytoma with six years follow-up

16 hemisferic astrocytoma 2 gliomatosis 2 pylocitic astrocytoma (FCP) 2 trunk glioma 2 well differenziated oligodendrogliomas

In 9 lesions we performed hystopathologic analysis

• surgery in six• stereotactic biopsy in three

METHODS

• sequences sequences for volume sampling- PRESS (point resolved spectroscopy)

The most clinically sequence used for its speedy and better S/R ratio(Pattany and all AJNR 27:1070-1073,May 2006)

• technique usedtechnique used“SINGLE VOXEL” (SVS)

Easily available in the majority of RM systems , rapid acquisition (5min.), but narrow study fieldnarrow study field even if better than multivoxel (Brandao Lara A. “MR spectroscopy of the brain “ pag 164 2002) in posterior fossa ,in sovrasellar region and in regionsadjacent to skull base.The decision of which sequences(SVS or multivoxel ) and which parameters ( TE or TR)to use depends on the location of the lesion and the choice of the brain metabolites the investigator wants to evaluate Sundgren P.C. Mr spectroscopy in radiation injury AJNR 30:1469-1476 sep 2009

- RM magnet 1,5T, “head-coil” square , basic sequences (SE T1, T2 e flair) with and without contrast

Standard RM

spectroscopy

SPECTROSCOPIC DATA EVALUATION

• Spectrum visual analysis (peak height)

• Ratio NAA (marker neuronal integrity)/Cho ( increase in high grade tumors)

• Ratio NAA/Cr (reduced in high grade tumors )

• Ratio Cho/Cr (increase in high grade tumors)

• Lactate and lipids evidence (ratio Lactate/Cr)

Intermediate echo time (135) ideal to evaluate lactate and choline peaks(Brandao Lara A “MR Spectroscopy of the brain” pag 5 ,2002 Lippincott)

SPECTROSCOPIC DATA EVALUATION

NAA/Cho = 1,8831NAA/Cr = 1,7935Cho/Cr = 0,9523

ASTROCITOMA “LOW-GRADE spectrum example”

Case 31R.M., femm a.28NAA/Cho = 0,4525NAA/Cr = 0,5023Cho/Cr = 1,6574

Evaluation criteria

Ratio NAA/Cho

Lip/Lac peak

remarks

more than 20% variations in

comparition to first examination

Appearing or increase in

comparition to first examination

To remember that low grade gliomas spectrum could be similar to normal parenchyma (Brandao Lara A. pag 142 ;2002)

Only in cases not treated

Doesnt exist a real cut-off value of NAA/Cho ratio (Cha AJNR 27:475-487, March 2006) .Indeed it is possible only differenziate tumour lesion from pseudotumoral lesion.(Majos “Proton MR spectroscopy improves discrimination between tumor and pseudotumoral lesion in solid brain masses AJNR 30:544-551, March 2009) that is 0.5 82 % diagnostic accuracy

we have not evaluated lipids and lactate in treated gliomas because their values are always elevated and don’t show a good correlation with histologic grade of the lesion .

Lipids are present almost exclusively in high grade gliomas whereas lactate could be found in both low grade and

high grade gliomas.(Xiaojuan Li AJNR 26:760-769, April 2005)

PRELIMINAR GENERAL CONSIDERATIONS

The use of NAA/Cho ratio allowed a correct retrospective classification in 80% of the cases in differenziating

recurrent tumour from radiation injury with SVS(singleVoxel spectroscopy)

Schlemmer HP,Bachert P, Herfarth K Proton Mr spectroscopicevaluation of suspicious brain lesion after stereotactic

radiotherapy AJNR 2001;22 :1316-1324

The most effective method of spectrum evaluation in SVS is the NAA/

Cho ratio.MR Spectroscopy in radiation injury Sundgren P.C.AJNR 30:1469-

1476 september 2009

A correlative study between spettroscopy and perfusion(CBF) show a good care sampling of the metabolites in more hyperfused areas ( higher Cho and increased lipids-lactate/creatina ratio ) in the high grade lesions in comparition to low grade lesions .(Chawla AJNR 28:1683-1689, October 2007)

Also a MET– PET correlative study has shown a good reliability showing the turn over a more aggressive behaviour ( metionina high uptake) in comparision to a more quiescent behaviour (low uptake).(Kato “Analysis of C-methionine uptake in low-grade gliomas and correlation with proliferative activity” AJNR 29 :1867-1871, 2007)

Morever has been demonstrated that the low TE (30) myoinositol sampling has shown a remarkable accuracy in discerning low grade gliomas (high MI/Cr ratio ) from high grade gliomas(MI/Cr low ratio)

(Castillo M AJNR 21:1645-1649, 2000)

RELATED PAPERS OF TURNING OF LOW GRADE LESIONS TO HIGH GRADE LESIONS

A good correlation of trasformation from grade 2 gliomas to grade 3 anaplastic astrocytoma was found monitoring a gradual increase of the choline and the creatine (Majos Eur Radiology 13(3):582-591, March 2003)

Some examples Some examples

6°6° examination 17/03/2006 30 30 months later months later

4°4° spectroscopic examination 13/05/2005

NAA/Cho = 0,3876NAA/Cr = 0,6070Cho/Cr = 1,5495

NAA/Cho = 0,2764NAA/Cr = 0,5208Cho/Cr = 1,883

NAA/Cho = 0,1414NAA/Cr = 0,2873Cho/Cr = 2,9500

1 spectroscopic examination 01/09/2003

TE 135

TE 35

TE 135

4° examination - 29/12/2006 – 3a. e 10m.after 3a. e 10m.after 1°examination 1°examination

NAA/Cho = 0,0871NAA/Cr = 0,2626Cho/Cr = 3,0188

NAA/Cho = 0,1535NAA/Cr = 0,4509Cho/Cr = 2,3057

1°1° spectroscopic examination - 16/02/2003

NAA/Cho > 20%

1° examination - 19/01/2006

NAA/Cho = 0,8306NAA/Cr = 0,8127Cho/Cr = 0,9705

4° esame - 26/02/2007 – 13 months after first examination

NAA/Cho = 0,6491NAA/Cr = 0,6968Cho/Cr = 1,0733

“LOW-GRADE” astrocytoma spectroscopic follow-up

Case N.95. S.G. 30 a. 1° examination january 2005

CT performed for seizure after minor trauma ( face injury playing soccer)

2° examination (six months later). june 2005june 2005. RM spectroscopy

NAA/Cho = 0,4538NAA/Cr = 0,8505Cho/Cr = 1,8741

“LOW-GRADE” ASTROCYTOMA SPECTROSCOPIC FOLLOW’UP

“LOW-GRADE”astrocytoma spectroscopic follow-up

3° examination ( 4 months later)October 2005October 2005

NAA/Cho = 0,1999NAA/Cr = 0,4130Cho/Cr = 2,0656

4° examination 2months later2months later(december 2005)(december 2005)

NAA/Cho = 0,4680NAA/Cr = 0,8297Cho/Cr = 1,7726

NAA/Cho = 0,3522NAA/Cr = 0,7553Cho/Cr = 2,1445

NAA/Cho = 0,2511NAA/Cr = 0,5712Cho/Cr = 2,2747

5° examination 3 months later (March 2006). Voxel positioned at the core months later (March 2006). Voxel positioned at the core lesion lesion

ASTROCITOMA “LOW-GRADE”spectroscopy follow-up

NAA/Cho = 0,4538NAA/Cr = 0,8505Cho/Cr = 1,8741

NAA/Cho = 0,2511NAA/Cr = 0,5712Cho/Cr = 2,2747

1° spectroscopic examination june june 20052005

4° spectroscopic examination 99 months later (March months later (March 2006)2006)

NAA/Cho > 20% Lip

FUNCTIONAL MRI” april 2006

surgery

Hystologic data :•Macroscopic report: “fragments of whitish, homogenous… tissue ”

•Microscopic report : “glial tumour fairly cellular, mainly microcistic, composed by monomorfe cells, ”

•Diagnosis: Oligoastrocitoma (grado II WHO)

1° spectroscopic control after surgery. january january 20072007

2° spectroscopic control after surgery. April 2007 2007

3° spectroscopic control after surgery. April 2009 2009

4° spectroscopic control after surgery. Nov 2009 2009

OLIGODENDROGLIOMA spectroscopy follow-upCase 106. D’A.G. A. 43 women. Operated 4 years before : “oligondendroglioma well differenziated” 1°1° spectroscopic examination 05/01/2006NAA/Cho = 0,1551NAA/Cr = 0,3696Cho/Cr = 2,3825

OLIGODENDROGLIOMA spectroscopy follow-up 2°2° spectroscopic examination 12/05/2006. 55 months later

NAA/Cho = 0,2320NAA/Cr = 0,5166Cho/Cr = 2,2263

OLIGODENDROGLIOMA spectroscopy follow-up 3°3°spectroscopic examination 16/01/2007. 7 months.later 1 year after 1° spectrum

NAA/Cho = 0,2047NAA/Cr = 0,6040Cho/Cr = 2,9497

NAA/Cho = 0,1551NAA/Cr = 0,3696Cho/Cr = 2,3825

NAA/Cho = 0,2320NAA/Cr = 0,5166Cho/Cr = 2,2263

1°1° MRs 05/01/2006

2°2° MRs 5 months later

3°3° MRs 1 year laterNAA/Cho = 0,2047NAA/Cr = 0,6040Cho/Cr = 2,9497

4°4°examination 18/06/2008. 117 months later 2 years and half from 1 spectrumOLIGODENDROGLIOMA spectroscopy follow-up

5°5°examination 30/09/2008. 33months later2 years and half from 1° spectrumOLIGODENDROGLIOMA spectroscopy follow-up

Results Results In 20 patients good correlation between

variation of NAA/Cho ratio and appearing or increase of lipid/lactate peaks and clinical-morfologic pattern (stable or progressive)

In 4 hemisferic operated astrocytomas and in a trunk glioma irradiated: disagreement between clinical-morphological pattern (in stable resolution) and spectroscopic pattern (persistent inversion of the NAA/Cho e Cho/Cr ratio)

In 2 of these patients restart of the disease at the subsequent controls

The appearing of a spectroscopic alteration could anticipate of about 1-2months contrast enhancment with standard RM(Brandao Lara A. “MR Spectroscopy of the Brain” pag 158. Lippincott)

Conclusions Conclusions

2 are the more interesting clinical applications of the spectroscopic SVS follow-up of the brain neoplasm

• “surveallance” of the not operated lesionsnot operated lesions and possibility of evaluate an initial “turn turn ” from “low-grade” to high grade lesions.

• evaluation after surgery and sometimes after RT of the beginning of the neoplastic relapse

• But the effort to separate tumor recurrence from pure radiation damage might be more problematic when using SVS compared with using multivoxel spectroscopy .Sundgren P.C. Mr spectroscopy in radiation injury AJNR 30:1469-1476 September 2009

Thank you