SYMPOSIUM NEURORADIOLOGICUM BOLOGNA 2010 INTRACRANIAL MASSES WITH PERILESIONAL EDEMA : DIFFERENTIAL DIAGNOSIS WITH PERFUSION-CT D. Gadda, P. Simonelli, G. Villa, V. Scardigli, D. Petacchi, C. Pandolfo, M. Moretti, S. Chiti, G.P. Giordano Careggi University Hospital - Florence - Neuroradiology

PERILESIONAL EDEMA Commonly associated with an intracranial mass Generated by vasogenic effects in the cerebral parenchyma surrounding the mass for lack or absence of blood-brain barrier (BBB) inside the lesion Extrusion of fluids into the extravascular space (“wet brain”) around the mass Careggi University Hospital - Florence - Neuroradiology

PERILESIONAL EDEMA On Computed Tomography (CT): - area of low density for the increased fluid content - not clear differentiation with areas of compressive ischemia - possible presence of neoplastic cells and tumoral neo-angiogenesis inside the perilesional edema surrounding high grade gliomas (Kelly PJ et al: Imaging- based stereotaxic serial biopsies in untreated intracranial glial neoplasms; J. Neurosurg.1987 Jun;66(6):865-74 ) Careggi University Hospital - Florence - Neuroradiology

MASS WITH PERILESIONAL EDEMA Frequently discovered or suspected on a non-enhanced CT (NECT) scan performed for the onset of stable or rapidly progressive neurological symptoms To complete the baseline imaging before MRI a supplementary contrast-enhanced CT (CECT) scan is generally indicated: a mass with perilesional edema is generally contrast-enhancing Careggi University Hospital - Florence - Neuroradiology

MASS WITH PERILESIONAL EDEMA - Neoplastic or not? - If not , is it an abscess? - Are there contraindications for steroids administration ( abscess, lymphoma ) ? - If a neoplasm is suspected, is it primitive (glioma versus lymphoma for neurosurgical strategy) or metastatic (need to search for a primitive tumor when unknown) ? Careggi University Hospital - Florence - Neuroradiology

MASS WITH PERILESIONAL EDEMA - Contrast-enhancement alone not specific for differential diagnosis - Need for advanced neuroimaging techniques - CT : Perfusion CT - MRI : Perfusion MRI, DWI, DTI, Spectroscopy Careggi University Hospital - Florence - Neuroradiology

GLIOBLASTOMA Most frequent and aggressive primitive intra-axial neoplasm (astrocytic tumors WHO Grade IV) 50-60% of astrocytic neoplasms, 20,3% CNS neoplasms (Central Brain Tumor Registry of the United States - 2007 ) Average survival 14 wks NS+Steroids ( Walker MD et al: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas : a co-operative clinical trial;JNeurosurg 1978;49:333-43 ) , 1 yr NS+CT+RT Careggi University Hospital - Florence - Neuroradiology

GLIOBLASTOMA Perfusion imaging: either glioblastomas and their surrounding tissue and perilesional edema show areas of increased rCBV for neo-angiogenesis ( Lehmann P et al: Dynamic contrast-enhanced T2*-weighted MR imaging: a brain-oedema study;JNeuroradiol2009 May 36 (2):88-92 ) Careggi University Hospital - Florence - Neuroradiology

PRIMARY CNS LYMPHOMA 4-7% primitive cerebral neoplasms Conventional imaging : difficult d.d. vs GBM or metastases Perfusion imaging : generally low rCBV, high permeability ( Schramm P et al: Dynamic CT perfusion imaging of intra-axial brain tumours: differentiation of high-grade gliomas from primary CNS lymphomas . European Radiology, vol 20, number 10, 2482-2490, online May 2010) Careggi University Hospital - Florence - Neuroradiology

MENINGIOMA Perfusion imaging may help to differentiate meningiomas from intra-axial tumors in cases of uncertainty on conventional imaging : high rCBV and permeability in meningiomas ( Hakyemez B et al: Meningiomas with conventional MRI findings resembling intraaxial tumors: can perfusion-weighted MRI be helpful in differentiation? Neuroradiology. 2006 Oct;48(10):695-702. Epub 2006 Aug 1 .) (Cianfoni A, Cha S, Bradley WG, Dillon WP, Wintermark M. Quantitative measurement of blood-brain barrier permeability using perfusion-CT in extra-axial brain tumors J Neuroradiol. 2006 Jun;33(3):164-8.) Careggi University Hospital - Florence - Neuroradiology

CEREBRAL ABSCESS Conventional imaging : difficult d.d. vs tumors with cystic or necrotic content Perfusion imaging : generally low rCBV for the solid portions of abscesses, high rCBV for tumors Careggi University Hospital - Florence - Neuroradiology

PERFUSION CT (PCT) - Information about regional microvascular density (CBV), permeability (PS) and blood flow (CBF) - Diagnostic and prognostic role when the possible presence of tumoral neo-angiogenesis is suspected - A few-minutes additional time to a CECT study is needed Careggi University Hospital - Florence - Neuroradiology

PERFUSION CT (PCT) Careggi University Hospital - Florence - Neuroradiology

STUDY PURPOSE Investigating the possible utility of Perfusion Computed Tomography (PCT) in the differential diagnosis of the newly-diagnosed intracranial solitary masses with perilesional edema Careggi University Hospital - Florence - Neuroradiology

MATERIALS AND METHODS Retrospective evaluation. 22 consecutive pts with newly diagnosed solitary masses and PCT prior to surgery or stereotactic biopsy Pathology: 10 Glioblastomas (GBM), 5 non-anaplastic meningiomas, 2 lymphomas, 4 abscesses and 1 metastasis from testicular choriocarcinoma Careggi University Hospital - Florence - Neuroradiology

MATERIALS AND METHODS PCT performance: - 4-slices multidetector CT scanner - 40 ml c.m. 370mg/mL Iodine - injection in 18-gauge i.v. line, flow 4 mL/sec - 45 dynamic scans, 1/sec, 2cm thick coverage area - 80 kVp, 108 mAs - PCT followed by CECT of the whole brain Careggi University Hospital - Florence - Neuroradiology

MATERIALS AND METHODS PCT post-processing: - two-compartmental model (Patlak analysis) for Cerebral Blood Volume (CBV) and Permeability Surface Area Product (PS) maps - maximum-slope model for Mean Transit Time (MTT) and Time to Peak (TTP) maps - CBV, PS, MTT values normalized to contralateral NAWM (rCBV, rPS, rMTT) - TTP difference in sec with contralateral NA Careggi University Hospital - Florence - Neuroradiology

MATERIALS AND METHODS PCT measurements: - circular ROI placed on the solid portions of the lesion for CBV-PS, manual ROI for MTT-TTP - maximum measurements of rCBV and rPS, mean values of rMTT and TTP were considered - rCBV and rPS measurements of the lesion and of the perilesional edema (PE rCBV and rPS) Careggi University Hospital - Florence - Neuroradiology

MATERIALS AND METHODS Statistics:: Receiver operating characteristics (ROC) analyses to compute the area under the curve (AUC) for each parameter in the differential diagnoses between biologically aggressive neoplasms (BAN: GBM, Lymphomas, Metastases) versus slow-growing tumors (grade I-II neoplasms) and non-neoplastic conditions (abscesses). ROC analyses to assess which PCT parameters had the highest predictive value for GBM, meningioma, abscess and lymphoma. Careggi University Hospital - Florence - Neuroradiology

RESULTS : BAN vs non-BAN Lesion rCBV Mean (SD) rPS rMTT TTP Edema BIOLOGICALLY AGGRESSIVE NEOPLASMS (BAN) (13 ) 4.6 (2.35) 16.87 (6.84) 1.08 (0.26) 2.13 (5.28) 1.13 (0.24) 3.81 (2.38) NON-BAN ( 9 ) 6.91 (4.58) 30.05 (21.42) 1.35 (0.33) 6.96 (5.37) 0.91 (0.31) 3.20 (2.01) P-value (Student’s t-test) 0.19 0.10 0.0495 0.0491 0.083 0.53 Area Under Curve (AUC) 0.658 0.692 0.821 0.842 0.731 0.462 Careggi University Hospital - Florence - Neuroradiology

RESULTS : GBM vs non-GBM Lesion rCBV Mean (SD) rPS rMTT TTP Edema GLIOBLASTOMAS (GBM) (10 ) 4.71 (1.99) 15.63 (6.39) 1.04 (0.11) 0.49 (1.82) 1.19 (0.20) 4.28 (2.52) NON-GBM ( 12 ) 6.25 (4.41) 27.79 (19.02) 1.32 (0.37) 7.12 (6.18) 0.91 (0.29) 2.97 (1.8) P-value (Student’s t-test) 0.29 0.056 0.029 0.003 0.02 0.17 Area Under Curve (AUC) 0.583 0.708 0.817 0.904 0.812 0.667 Careggi University Hospital - Florence - Neuroradiology

RESULTS : MENINGIOMAS Lesion rCBV Mean (SD) rPS rMTT TTP Edema MENINGIOMAS (5 ) 10.19 (2.7) 43.94 (18.32) 1.38 (0.42) 6.56 (6.1) 0.73 (0.17) 3.47 (1.83) NON-MENINGIOMAS ( 17 ) 4.18 (2.42) 15.89 (6.95) 1.14 (0.26) 3.38 (5.6) 1.13 (0.24) 3.59 (2.35) P-value (Student’s t-test) 0.0001 0.02 0.14 0.28 0.002 0.92 Area Under Curve (AUC) 0.976 0.988 0.735 0.759 0.912 0.576 Careggi University Hospital - Florence - Neuroradiology

RESULTS : LYMPHOMAS Lesion rCBV Median rPS rMTT TTP Edema LYMPHOMAS (2 ) 2.1 23.94 1.48 11.3 0.76 2.72 NON-LYMPHOMAS ( 20 ) 5.65 18.28 1.11 1.9 1.06 3.26 P-value (Mann-Whitney test) 0.08 0.56 0.20 0.1 0.42 Area Under Curve (AUC) 0.875 0.625 0.775 0.850 0.675 Careggi University Hospital - Florence - Neuroradiology

RESULTS : LYMPH vsINTRA-AXIAL 0.600 1.0 0.900 0.833 0.800 Area Under Curve (AUC) 0.45 0.02 0.07 0.13 0.17 P-value (Mann-Whitney test) 3.24 1.24 0.9 1.06 15.02 3.54 NON-LYMPH INTRA-AXIAL ( 15 ) 2.72 0.76 11.3 1.48 23.94 2.1 LYMPHOMAS (2 ) Edema rPS Median rCBV Lesion TTP rMTT Careggi University Hospital - Florence - Neuroradiology

RESULTS : ABSCESSES Lesion rCBV Median rPS rMTT TTP Edema ABSCESSES (4 ) 1.81 12.99 1.23 7.6 1.07 2.39 NON-ABSCESSES ( 18 ) 5.65 20.27 1.08 1.25 1.04 3.26 P-value (Mann-Whitney test) 0.06 0.10 0.13 0.12 0.49 0.34 Area Under Curve (AUC) 0.806 0.764 0.743 0.750 0.611 0.653 Careggi University Hospital - Florence - Neuroradiology

GLIOBLASTOMA LYMPHOMA NON-ANAPLASTIC MENINGIOMA ABSCESS

GLIOBLASTOMA rCBV = 5.48 LYMPHOMA rCBV = 1.07 NON-ANAPLASTIC MENINGIOMA rCBV = 13.97 ABSCESS rCBV = 1.21

GLIOBLASTOMA rPS = 22.12 LYMPHOMA rPS = 21.86 NON-ANAPLASTIC MENINGIOMA rPS = 37.91 ABSCESS rPS = 17.31 2b

GLIOBLASTOMA rMTT = 1.02 LYMPHOMA rMTT = 1.82 NON-ANAPLASTIC MENINGIOMA rMTT = 1.3 ABSCESS rMTT = 1.68

GLIOBLASTOMA TTP = - 0.9 LYMPHOMA TTP = 18.6 NON-ANAPLASTIC MENINGIOMA TTP = 3.6 ABSCESS TTP = 12.1

GLIOBLASTOMA Edema rCBV = 1.34 LYMPHOMA Edema rCBV = 0.71 ABSCESS Edema rCBV = 0.95 NON-ANAPLASTIC MENINGIOMA Edema rCBV = 0.8

CONCLUSIONS PCT useful in d.d. intracranial masses with edema - TTP, MTT are the best predictors for BAN and GBM Careggi University Hospital - Florence - Neuroradiology

CONCLUSIONS PCT useful in d.d. intracranial masses with edema - TTP, MTT are the best predictors for BAN and GBM lesional rCBV is a good predictor for meningioma, lymphoma, abscess Careggi University Hospital - Florence - Neuroradiology

CONCLUSIONS PCT useful in d.d. intracranial masses with edema - TTP, MTT are the best predictors for BAN and GBM lesional rCBV is a good predictor for meningioma, lymphoma, abscess rCBV of the perilesional edema is a good predictor for GBM, meningioma, lymphoma Careggi University Hospital - Florence - Neuroradiology

CONCLUSIONS PCT useful in d.d. intracranial masses with edema - TTP, MTT are the best predictors for BAN and GBM lesional rCBV is a good predictor for meningioma, lymphoma, abscess rCBV of the perilesional edema is a good predictor for GBM, meningioma, lymphoma - lesional rPS good predictor for meningioma Careggi University Hospital - Florence - Neuroradiology

CONCLUSIONS PCT useful in d.d. intracranial masses with edema - TTP, MTT are the best predictors for BAN and GBM lesional rCBV is a good predictor for meningioma, lymphoma, abscess rCBV of the perilesional edema is a good predictor for GBM, meningioma, lymphoma - lesional rPS good predictor for meningioma measurement of permeability of perilesional edema is not useful Careggi University Hospital - Florence - Neuroradiology

LIMITATIONS - limited number of cases Careggi University Hospital - Florence - Neuroradiology

LIMITATIONS - limited number of cases lack of malignant neoplasms such as lymphomas ( 2 cases) and metastases ( 1 case) Careggi University Hospital - Florence - Neuroradiology

LIMITATIONS - limited number of cases lack of malignant neoplasms such as lymphomas ( 2 cases) and metastases ( 1 case) absence of grade III-IV meningiomas , low-grade ggliomas, oligodendrogliomas or other malignant masses Careggi University Hospital - Florence - Neuroradiology

YOU !! THANK Azienda Ospedaliero-Universitaria di Careggi - Firenze Neuroradiologia

YOU !! THANK Azienda Ospedaliero-Universitaria di Careggi - Firenze Neuroradiologia