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A. di Gaeta, A.A. Diano, P. Vassallo, E. Capobianco, M. Muto Neuroradiology unit

Single voxel spectroscopy in the follow-up of low grade gliomas. A. di Gaeta, A.A. Diano, P. Vassallo, E. Capobianco, M. Muto Neuroradiology unit A.O.R.N. “A. CARDARELLI” - Napoli. From january 2003 until november 2009 we studied 24 low-grade astrocytoma with six years follow-up.

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A. di Gaeta, A.A. Diano, P. Vassallo, E. Capobianco, M. Muto Neuroradiology unit

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  1. Single voxel spectroscopy in the follow-up of low grade gliomas A. di Gaeta, A.A. Diano, P. Vassallo,E. Capobianco, M. Muto Neuroradiology unit A.O.R.N. “A. CARDARELLI” - Napoli

  2. From january 2003 until november 2009 we studied • 24 low-grade astrocytoma with six years follow-up • surgery in six • stereotactic biopsy in three In 9 lesions we performed hystopathologic analysis • 16 hemisferic astrocytoma • 2 gliomatosis • 2 pylocitic astrocytoma (FCP) • 2 trunk glioma • 2 well differenziated oligodendrogliomas

  3. METHODS Standard RM • RM magnet 1,5T, “head-coil” square , basic sequences (SE T1, T2 e flair) with and without contrast spectroscopy • sequences for volume sampling • PRESS (pointresolvedspectroscopy) • The mostclinicallysequenceused for itsspeedy and better S/R ratio(Pattany and all AJNR 27:1070-1073,May 2006) • techniqueused • “SINGLE VOXEL” (SVS) • Easilyavailable in the majority of RM systems , rapidacquisition (5min.), butnarrowstudyfieldevenifbetterthanmultivoxel (Brandao Lara A. “MR spectroscopy of the brain “ pag 164 2002) in posterior fossa ,in sovrasellarregion and in regionsadjacent to skull base. • The decision of whichsequences(SVS or multivoxel ) and whichparameters ( 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. Mrspectroscopy in radiationinjury AJNR 30:1469-1476 sep 2009

  4. 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)

  5. SPECTROSCOPIC DATA EVALUATION NAA/Cho = 1,8831 NAA/Cr = 1,7935 Cho/Cr = 0,9523

  6. ASTROCITOMA “LOW-GRADE spectrum example” Case 31 R.M., femm a.28 NAA/Cho = 0,4525 NAA/Cr = 0,5023 Cho/Cr = 1,6574

  7. Evaluation criteria remarks Ratio NAA/Cho more than 20% variations in comparition to first examination Lip/Lac peak Appearing or increase in comparition to first examination Only in cases not treated To remember that low grade gliomas spectrum could be similar to normal parenchyma (Brandao Lara A. pag 142 ;2002)

  8. PRELIMINAR GENERAL CONSIDERATIONS • 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)

  9. 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(single • Voxel spectroscopy) • Schlemmer HP,Bachert P, Herfarth K Proton Mr spectroscopic • evaluation 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

  10. RELATED PAPERS OF TURNING OF LOW GRADE LESIONS TO HIGH GRADE LESIONS • 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) • 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) • 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) • 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)

  11. Some examples

  12. 1 spectroscopic examination 01/09/2003 TE 35 NAA/Cho = 0,1414 NAA/Cr = 0,2873 Cho/Cr = 2,9500 4°spectroscopicexamination 13/05/2005 TE 135 NAA/Cho = 0,2764 NAA/Cr = 0,5208 Cho/Cr = 1,883 6°examination 17/03/2006 30 monthslater TE 135 NAA/Cho = 0,3876 NAA/Cr = 0,6070 Cho/Cr = 1,5495

  13. 1° spectroscopic examination - 16/02/2003 NAA/Cho = 0,1535 NAA/Cr = 0,4509 Cho/Cr = 2,3057 4°examination - 29/12/2006 – 3a. e 10m.after 1°examination NAA/Cho > 20% NAA/Cho = 0,0871 NAA/Cr = 0,2626 Cho/Cr = 3,0188

  14. 1° examination - 19/01/2006 NAA/Cho = 0,8306 NAA/Cr = 0,8127 Cho/Cr = 0,9705 4° esame - 26/02/2007 – 13 months after first examination NAA/Cho = 0,6491 NAA/Cr = 0,6968 Cho/Cr = 1,0733

  15. “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)

  16. “LOW-GRADE” ASTROCYTOMA SPECTROSCOPIC FOLLOW’UP 2° examination (six months later). june 2005. RM spectroscopy NAA/Cho = 0,4538 NAA/Cr = 0,8505 Cho/Cr = 1,8741

  17. “LOW-GRADE”astrocytoma spectroscopic follow-up 3° examination ( 4 months later) October 2005 NAA/Cho = 0,1999 NAA/Cr = 0,4130 Cho/Cr = 2,0656

  18. 4° examination2months later (december 2005) NAA/Cho = 0,4680 NAA/Cr = 0,8297 Cho/Cr = 1,7726 NAA/Cho = 0,3522 NAA/Cr = 0,7553 Cho/Cr = 2,1445

  19. ASTROCITOMA “LOW-GRADE”spectroscopy follow-up 5° examination3 months later (March 2006). Voxel positioned at the core lesion NAA/Cho = 0,2511 NAA/Cr = 0,5712 Cho/Cr = 2,2747

  20. 1° spectroscopic examination june 2005 NAA/Cho = 0,4538 NAA/Cr = 0,8505 Cho/Cr = 1,8741 NAA/Cho > 20% Lip 4° spectroscopic examination 9months later (March 2006) NAA/Cho = 0,2511 NAA/Cr = 0,5712 Cho/Cr = 2,2747

  21. FUNCTIONAL MRI” april 2006

  22. 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)

  23. 1° spectroscopic control after surgery. january 2007

  24. 2° spectroscopic control after surgery. April 2007

  25. 3° spectroscopic control after surgery. April 2009

  26. 4° spectroscopic control after surgery. Nov 2009

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

  28. OLIGODENDROGLIOMA spectroscopy follow-up 2° spectroscopic examination 12/05/2006. 5 months later NAA/Cho = 0,2320 NAA/Cr = 0,5166 Cho/Cr = 2,2263

  29. OLIGODENDROGLIOMA spectroscopy follow-up 3°spectroscopic examination 16/01/2007. 7 months.later 1 year after 1° spectrum NAA/Cho = 0,2047 NAA/Cr = 0,6040 Cho/Cr = 2,9497

  30. 1° MRs 05/01/2006 NAA/Cho = 0,1551 NAA/Cr = 0,3696 Cho/Cr = 2,3825 2° MRs 5 months later NAA/Cho = 0,2320 NAA/Cr = 0,5166 Cho/Cr = 2,2263 3° MRs 1 year later NAA/Cho = 0,2047 NAA/Cr = 0,6040 Cho/Cr = 2,9497

  31. OLIGODENDROGLIOMA spectroscopy follow-up 4°examination 18/06/2008. 17 months later 2 years and half from 1 spectrum

  32. OLIGODENDROGLIOMA spectroscopy follow-up 5°examination 30/09/2008. 3months later2 years and half from 1° spectrum

  33. 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)

  34. Conclusions 2 are the more interesting clinical applications of the spectroscopic SVS follow-up of the brain neoplasm • “surveallance” of the notoperatedlesions and possibility of evaluate an initial “turn ” from “low-grade” to high grade lesions. • evaluationaftersurgery and sometimesafter RT of the beginning of the neoplastic relapse • But the effort to separate tumorrecurrence from pure radiationdamagemight be more problematicwhenusing SVS compared with usingmultivoxelspectroscopy .Sundgren P.C. Mrspectroscopy in radiationinjury AJNR 30:1469-1476 September 2009

  35. Thank you

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